Patent Publication Number: US-2023149163-A1

Title: Transcatheter mitral valve prosthesis

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 14/046,606 (Attorney Docket No. 42194-703.401, U.S. Pat. No. ______), filed Oct. 4, 2013; which is a divisional of U.S. patent application Ser. No. 13/096,572 (Attorney Docket No. 42194-703.201, U.S. Pat. No. 8,579,964), filed Apr. 28, 2011; which claims the benefit of U.S. Provisional Patent Applications Nos. 61/414,879 (Attorney Docket No. 42194-703.103) filed Nov. 17, 2010; 61/393,860 (Attorney Docket No. 42194-703.102) filed Oct. 15, 2010; and 61/331,799 (Attorney Docket No. 42194-703.101) filed May 5, 2010; the entire contents of which are incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     Field of the Invention 
     The present invention generally relates to medical devices and methods, and more particularly relates to the treatment of valve insufficiency, such as mitral insufficiency, also referred to as mitral regurgitation. The use of prosthetic valves delivered by traditional surgical implantation methods, or by less invasive percutaneous catheter or minimally invasive transapical methods are one possible treatment for valvar insufficiency. 
     The heart of vertebrate animals is divided into four chambers, and is equipped with four valves (the mitral, aortic, pulmonary and tricuspid valves) that ensure that blood pumped by the heart flows in a forward direction through the cardiovascular system. The mitral valve of a healthy heart prevents the backflow of blood from the left ventricle into the left atrium of the heart, and comprises two flexible leaflets (anterior and posterior) that close when the left ventricle contracts. The leaflets are attached to a fibrous annulus, and their free edges are tethered by subvalvular chordae tendineae to papillary muscles in the left ventricle to prevent them from prolapsing into the left atrium during the contraction of the left ventricle. 
     Various cardiac diseases or degenerative changes may cause dysfunction in any of these portions of the mitral valve apparatus, causing the mitral valve to become abnormally narrowed or dilated, or to allow blood to leak (i.e. regurgitate) from the left ventricle back into the left atrium. Any such impairments compromise cardiac sufficiency, and can be debilitating or life threatening. 
     Numerous surgical methods and devices have accordingly been developed to treat mitral valve dysfunction, including open-heart surgical techniques for replacing, repairing or reshaping the native mitral valve apparatus, and the surgical implantation of various prosthetic devices such as annuloplasty rings to modify the anatomy of the native mitral valve. More recently, less invasive transcatheter techniques for the delivery of replacement mitral valve assemblies have been developed. In such techniques, a prosthetic valve is generally mounted in a crimped state on the end of a flexible catheter and advanced through a blood vessel or the body of the patient until the valve reaches the implantation site. The prosthetic valve is then expanded to its functional size at the site of the defective native valve. 
     While these devices and methods are promising treatments for valvar insufficiency, they can be difficult to deliver, expensive to manufacture, or may not be indicated for all patients. Therefore, it would be desirable to provide improved devices and methods for the treatment of valvar insufficiency such as mitral insufficiency. At least some of these objectives will be met by the devices and methods disclosed below. 
     2. Description of the Background Art 
     By way of example, PCT international patent number PCT/US2008/054410 (published as PCT international publication no. WO2008/103722), the disclosure of which is hereby incorporated by reference, describes a transcatheter mitral valve prosthesis that comprises a resilient ring, a plurality of leaflet membranes mounted with respect to the ring so as to permit blood flow therethrough in one direction, and a plurality of tissue-engaging positioning elements movably mounted with respect to the ring and dimensioned to grip the anatomical structure of the heart valve annulus, heart valve leaflets, and/or heart wall. Each of the positioning elements defines respective proximal, intermediate, and distal tissue engaging regions cooperatively configured and dimensioned to simultaneously engage separate corresponding areas of the tissue of an anatomical structure, and may include respective first, second, and third elongate tissue-piercing elements. The valve prosthesis may also include a skirt mounted with respect to the resilient ring for sealing a periphery of the valve prosthesis against a reverse flow of blood around the valve prosthesis. 
     PCT international patent number PCT/US2009/041754 (published as PCT international publication no. WO2009/134701), the disclosure of which is hereby incorporated by reference, describes a prosthetic mitral valve assembly that comprises an anchor or outer support frame with a flared upper end and a tapered portion to fit the contours of the native mitral valve, and a tissue-based one-way valve mounted therein. The assembly is adapted to expand radially outwardly and into contact with the native heart tissue to create a pressure fit, and further includes tension members anchoring the leaflets of the valve assembly to a suitable location on the heart o function as prosthetic chordae tendineae. 
     Also known in the prior art are prosthetic mitral valve assemblies that utilize a claw structure for attachment of the prosthesis to the heart (see, for example, U.S. patent application publication no. US2007/0016286 to Hermann et al., the disclosure of which is hereby incorporated by reference), as are prosthetic mitral valve assemblies that rely on the application of axial rather than radial clamping forces to facilitate the self-positioning and self-anchoring of the prosthesis with respect to the native anatomical structure. 
     Another method which has been proposed as a treatment of mitral valve regurgitation is the surgical bow tie method, which recently has been adapted into a minimally invasive catheter based treatment where an implant is used to clip the valve leaflets together. This procedure is more fully disclosed in the scientific and patent literature, such as in U.S. Pat. No. 6,629,534 to St. Goar et al., the entire contents of which are incorporated herein by reference. 
     Other relevant publications include U.S. Patent Publication No. 2011/0015731 to Carpentier et al. 
     BRIEF SUMMARY OF THE INVENTION 
     The present invention generally relates to medical devices and methods, and more particularly prosthetic valves used to treat mitral regurgitation. While the present disclosure focuses on the use of a prosthetic valve for treating mitral regurgitation, this is not intended to be limiting. The prosthetic valves disclosed herein may also be used to treat other body valves including other heart valves or venous valves. Exemplary heart valves include the aortic valve, the triscupsid valve, or the pulmonary valve. 
     In embodiments of the present subject matter, transcatheter mitral valve prostheses and transcatheter methods and systems of deploying the same are provided. In certain embodiments, fire mitral valve prosthesis comprises a tissue-type prosthetic one-way valve structure comprising a plurality of leaflets affixed within a self-expanding or expandable anchor (i.e. frame) portion having a geometry that expands into a low profile atrial skirt region, an annular region dimensioned to generally conform to a native mitral valve annulus, a ventricular skirt region that displaces the native mitral valve leaflets, and a plurality of leaflet commissures extending into the sub-annular ventricular space (i.e. in the direction of the outflow of blood through the prosthesis) and configured to optimize the efficiency of the prosthetic valve structure and the load distribution on the leaflets thereof The anchor portion may also in preferred embodiments be asymmetrical along its longitudinal axis, with the atrial skirt region, the annular region and/or the ventricular skirt region having differently configured anterior and posterior aspects in order to facilitate close accommodation of the asymmetrical contours and features of a typical native mitral valve apparatus. This asymmetry may result inherently from the structural configuration of the anchor portion as discussed further below, and/or as a consequence of shaping or forming steps employed during the manufacturing process. 
     The prosthetic valve structure in preferred embodiments may comprise a bicuspid or tricuspid valve in order, in part, to simplify manufacture of the mitral valve prosthesis, but as would be readily apparent to those of skill in the art, other configurations are possible. The leaflets may be fabricated from a single piece or from multiple pieces of standard biologic prosthetic materials, such as cryo- or chemically-preserved pericardium (e.g. bovine, equine, porcine, caprine, kangaroo), or from standard suitable synthetic prosthetic materials (e.g. fiber-reinforced matrix materials) well known in the art, and may be sewn or otherwise adhered to the anchor to form the valve leaflets in any standard suitable manner. 
     To optimize prosthetic valve efficiency and the load distribution on the prosthetic leaflets, the commissures extend generally axially in a cantilevered fashion downstream into the sub-annular space, and are capable of flexing radially and laterally along their axial lengths to distribute the forces associated with blood flow through the prosthetic valve structure. In some embodiments, the commissures define (when the mitral valve prosthesis is in an expended state) a somewhat frustoconical aperture that narrows along the forward direction of blood flow in order to aid in the closure of the prosthetic valve structure during contraction of the ventricle. To further optimize efficiency and load distribution on the leaflets, the commissures may be shaped and dimensioned so as to provide for the attachment of the leaflets along arcuate seams, and may also be made selectively flexible at different points or zones along their axial length through, for example, the addition or deletion of reinforcing struts, or through variation of the thickness of the commissures in selected regions. 
     The anchor portion of the mitral valve prosthesis is preferably fabricated from a single piece of metallic material that has been cut so as to permit the mitral valve prosthesis to be compressed into a compact, generally tubular delivery configuration, and expanded into the deployment configuration further described herein. In self-expanding embodiments, the anchor portion of the mitral valve prosthesis may be fabricated from a shape memory alloy (SMA) such as the nickel-titanium alloy nitinol, and in expandable embodiments, the anchor portion may be fabricated from any metallic material, such as chromium alloy or stainless steel, that is suitable for implantation into the body. In some embodiments, the metallic material may be of a single thickness throughout entirety of the anchor portion, and in others may vary in thickness so as to facilitate variations in the radial force that is exerted by the anchor portion in specific regions thereof, to increase or decrease the flexibility of the anchor portion in certain regions, and/or to control the process of compression in preparation for deployment and the process of expansion during deployment. 
     When deployed, the atrial skirt region of the mitral valve prosthesis extends generally radially outwards so as to lie flat against and cover the atrial surface of the native mitral valve annulus, and to anchor the mitral valve prosthesis against at least a portion of the adjoining atrial surface of the heart. The atrial skirt region has a low axial profile (extending only slightly into the atrium of the heart) in order to minimize potentially thrombogenic turbulence in blood flow, and in preferred embodiments, may be covered with standard biologic or synthetic prosthetic materials of the sort described above in order to seal the atrial skirt region against the atrial surface and to facilitate the funnelling of atrial blood through the mitral valve prosthesis. In some embodiments, the atrial skirt region further comprises atrial barbs or prongs to further facilitate the anchoring of the deployed prosthesis to the atrial heart surface. To facilitate the orientation and alignment of the mitral valve prosthesis within the native mitral valve upon deployment, particularly in embodiments where the anchor portion is longitudinally asymmetrical, the atrial skirt region of the anchor portion of the mitral valve prosthesis may preferably further comprise an alignment structure that may be differentiated (such as by angiography, computed tomography, etc.) from the remainder of the atrial skirt region and thereby used as an orientation guide during deployment. Most preferably, the alignment structure may comprise an elongation of the anterior aspect of the atrial skirt region configured to expand radially to accommodate the aortic root portion of the atrial surface. 
     The annular region of the mitral valve prosthesis is dimensioned, as noted above, to generally conform to and anchor against a native mitral valve annulus when deployed. In preferred embodiments, the deployed annular region may define a generally D-shaped annulus suitable for fitting the contours of a typical native mitral valve, and may be covered with standard biologic or synthetic prosthetic materials of the sort previously described to seal the annular region against the native mitral valve annulus. 
     The ventricular skirt region expands when deployed in the ventricular space generally radially outwards against the native mitral valve, but not so far as to obstruct the left ventricular outflow tract, nor to contact the ventricular wall. To anchor the mitral valve prosthesis against the displaced native leaflets in the ventricular space, the maximal radial displacement of the fully deployed ventricular skirt region is selected to be slightly greater than the circumference of the native mitral valve. In preferred embodiments, the ventricular skirt region also comprises ventricular and/or native leaflet barbs or prongs to further anchor the deployed prosthesis thereto. Most preferably, the ventricular skirt region is asymmetrical and the prongs thereof comprise two trigonal anchoring tabs located in the anterior aspect of the ventricular skirt region for anchoring against the fibrous trigones on either side of the anterior leaflet of the native mitral valve, and one posterior ventricular anchoring tab located in the posterior aspect of the ventricular skirt region for anchoring over the posterior leaflet of the native mitral valve. Associated with these tabs are deployment control regions as described in further detail below. 
     The ventricular skirt region may also in some embodiments be covered with standard biologic or synthetic prosthetic materials of the sort previously described in order to seal the ventricular skirt region against the displaced native leaflets, and thereby to funnel ventricular blood (during contraction of the ventricle) towards the prosthetic valve structure to assist in the closure thereof during contraction of the ventricle. 
     The combined 3-zone anchoring of the mitral valve prosthesis against the atrial surface, the native valve annulus, and the displaced native leaflets (supplemented, in preferred embodiments by a fourth zone of anchoring from the trigonal and posterior ventricular anchoring) in the ventricular space prevents the prosthesis from migrating or dislodging from within the native valve annulus during the contraction of the atrium or the ventricle, and lessens the anchoring pressure that is required to be applied in any given anchoring zone as compared to a prosthesis that is anchored in only a single anchoring zone, or in any combination of these four anchoring zones. The consequent reduction in radial force required to be exerted against the native structures in each zone minimizes the risk of obstruction or impingement of the nearby aortic valve or aortic root caused by the displacement of the native mitral valve apparatus. The combined 3 or 4-zone anchoring of the mitral valve prosthesis also facilitates the positioning and/or re-positioning of the mitral valve prosthesis as described below. 
     To deploy the mitral valve prosthesis within the native mitral valve apparatus, the prosthesis is first compacted and loaded into a suitably-adapted conventional catheter delivery system of the sort well known to those of skill in the art. Preferably, to facilitate later deployment, the commissures and associated prosthetic valve structure of the prosthesis are captured within an inner lumen of the catheter delivery system, and the remaining portions of the anchor region are captured within a secondary outer lumen of the catheter delivery system. The loaded mitral valve prosthesis may then be delivered (typically either transseptally or transapically) in its compacted form into the left atrium of the heart using a conventional catheter delivery system. The prosthesis is releasably attached to the catheter delivery system via its commissures, and shielded by the (preferably dual-lumen) delivery sheath thereof during transit into the atrial space. Once the prosthesis has been guided into the left atrium, the delivery sheath of the catheter delivery system is retracted as described below in order to permit expansion of the various regions of the prosthesis to proceed. Of course, in self-expanding embodiments, expansion of the prosthesis will occur spontaneously upon retraction of the delivery sheath, and in expandable embodiments, a catheter inflation structure such as a balloon is required to effect the expansion. 
     Deployment of the mitral valve prosthesis may proceed differently depending upon the features of the particular embodiment of the prosthesis being deployed. For example, in asymmetrical embodiments that comprise trigonal anchoring tabs and a posterior ventricular anchoring tab in the ventricular skirt region (as well as, preferably, an alignment structure in the atrial region), these tabs may preferably be deployed before deployment of the remaining portions of the ventricular skirt regions in order to facilitate the anchoring of these tabs against the native fibrous trigones and posterior leaflet, respectively. 
     In the first general deployment step, the atrial skirt region of the mitral valve prosthesis is permitted to expand by retracting the corresponding portion of the catheter delivery sheath (or is balloon-expanded following the retraction of the corresponding portion of the delivery sheath) within the left atrium of the heart, and the expanded atrial skirt region is then positioned over the atrial surface of the native mitral valve and anchored against at least a portion of the adjoining atrial surface of the heart. In preferred embodiments where the atrial skirt region comprises an alignment structure, this first general deployment step may be further broken down into two sub-steps, wherein the catheter delivery sheath is first retracted only so far as to permit expansion of the alignment structure (so that it may be visualized to facilitate manipulation of the delivery system in such a way as to orient the mitral valve prosthesis into a desired position), and then, once initial alignment of the prosthesis appears to be satisfactory, further retracted to permit the expansion, positioning and anchoring of the remaining portions of the atrial skirt region. In embodiments where the alignment structure comprises an elongation of the anterior aspect of the atrial skirt region, such initial alignment comprises the rotation and/or alignment of the alignment structure so that it is situated adjacent the aortic root and between the fibrous trigones of the native anterior leaflet. 
     Next, the annular region of the prosthesis is permitted to expand by further retraction of the catheter delivery sheath so as to engage the native mitral valve annulus (i.e. to contact the native valve annulus throughout at least a majority thereof) in order to create a second anchoring zone and to create a suitable opening for blood flow through the prosthetic valve structure. 
     Then, in embodiments that comprise trigonal anchoring tabs and a posterior ventricular anchoring tab in the ventricular skirt region, the catheter delivery sheath is further retracted so far as to permit the tabs to expand while the remainder of the ventricular skirt region of the prosthesis, including the deployment control regions of the tabs, remain sheathed. With the deployment control regions still retained within the delivery system and the atrial skirt region anchored against the atrial surface, the tabs project radially outward to facilitate engagement with the corresponding features of the native mitral valve. The posterior ventricular anchoring tab is aligned in the middle of the posterior leaflet of the mitral valve where there is an absence of chordae attachments to the posterior leaflet, and passed over the posterior leaflet to seat between the posterior leaflet and the ventricular wall. The two trigonal anchoring tabs are positioned on either side of the anterior leaflet with their heads positioned at the fibrous trigones. Slight rotation and realignment of the prosthesis can occur at this time. 
     Once the assembly has been satisfactorily positioned and the tabs aligned, the catheter delivery sheath may be further retracted to permit expansion of the remaining portions of the ventricular skirt region to secure the prosthesis within the mitral apparatus and seal the mitral annulus. Complete retraction of the outer catheter delivery sheath releases the ventricular skirt region and allows the anchoring tabs to proximate their anchoring location. As the prosthesis expands, the trigonal tabs anchor against the fibrous trigones, capturing the native anterior leaflet and chordae between the tabs and the anterior surface of the prosthetic valve assembly, and the posterior ventricular tab anchors between the ventricular wall and the posterior leaflet, capturing the posterior leaflet between the posterior anchoring tab and the posterior surface of the prosthetic valve assembly. The remaining portions of the ventricular skirt region expand out against the native mitral valve leaflets and adjacent anatomy, thereby creating a sealing funnel within the native leaflets and displacing the native leaflets from the prosthetic commissures to avoid obstruction of the prosthetic valve function. With the commissures of the prosthesis still captured within the delivery system, very minor adjustments may still made to ensure accurate positioning, anchoring and sealing. 
     In embodiments that do not comprise trigonal anchoring tabs and a posterior ventricular anchoring tab in the ventricular skirt region, the retraction of the catheter delivery sheath from the ventricular skirt region may, of course, be performed in one step after the atrial skirt and annular regions of the prosthesis have been initially anchored, to permit the ventricular skirt region of the prosthesis to expand against the native mitral valve, and to additionally anchor the prosthesis against the displaced native leaflets in the ventricular space. Optionally, the mitral valve prosthesis, which is still at this point releasably attached to the catheter delivery system via its commissures, may be driven slightly further downstream into ventricular space to create a greater seating force as between the atrial skirt region and atrial surface of the heart, and to provide additional purchase for any ventricular and/or native leaflet barbs or prongs that may be present in the ventricular skirt region. In embodiments where one or more of the atrial skirt region, the annular region and the ventricular skirt region are covered with a suitable biologic or synthetic prosthetic material, a seal may also be formed between the respective regions of the prosthesis and the associated zone of the native mitral valve apparatus. 
     Finally, once satisfactory positioning of the prosthesis has been achieved, the commissures are released from the catheter delivery system, allowing the catheter delivery system to be withdrawn, and leaving the mitral valve prosthesis in place as a functional replacement for the native mitral valve apparatus. Upon release of the commissures, the prosthesis may further undergo a final stage of foreshortening and seating as any remaining pressure exerted by the delivery system is released. The atrial skirt region may recoil slightly from this release in pressure, pulling the prosthesis slightly further up in to the left atrium, and thereby further seating the ventricular skirt region, including any associated barbs, prongs or tabs. In embodiments that comprise trigonal anchoring tabs, the seating thereof pulls the captured anterior leaflet tightly against the prosthesis, thereby avoiding or minimizing obstruction of the Left Ventricular Outflow Tract (LVOT), and firmly seats the ventricular skirt region in the annulus to prevent paravalvular leakage. Once final deployment is complete, the delivery system is retracted and removed. 
     In a first aspect of the present invention, a method of anchoring a prosthetic valve in a patient&#39;s heart comprises providing the prosthetic valve, wherein the prosthetic valve comprises an anchor having an atrial skirt, an annular region, a ventricular skirt, and a plurality of valve leaflets, wherein the anchor has a collapsed configuration for delivery to the heart and an expanded configuration for anchoring with the heart, and positioning the prosthetic valve in the patient&#39;s heart. The method also comprises expanding the atrial skirt radially outward so as to lie over a superior surface of the patient&#39;s native mitral valve, anchoring the atrial skirt against a portion of the atrium, and radially expanding the annular region of the anchor to conform with and to engage the native mitral valve annulus. The method also comprises radially expanding the ventricular skirt thereby displacing the native mitral valve leaflets radially outward. 
     At least a portion of the prosthetic valve may be covered with tissue or a synthetic material. Positioning the prosthetic valve may comprise transseptally delivering the prosthetic valve from the right atrium to the left atrium of the heart, or transapically delivering the prosthetic valve from a region outside the heart to the left ventricle of the heart. 
     Expanding the atrial skirt may comprise slidably moving a restraining sheath away from the atrial skirt thereby allowing radial expansion thereof. The atrial skirt may self-expand when the restraining sheath is removed therefrom. The method may further comprise applying a force on the prosthetic valve to ensure that the atrial skirt engages the superior surface of the mitral valve. The atrial skirt may comprise a plurality of barbs, and expanding the atrial skirt may comprise anchoring the barbs into the superior surface of the mitral valve. Expanding the atrial skirt may comprise sealing the atrial skirt against the superior surface of the native mitral valve. 
     Radially expanding the annular region may comprise slidably moving a restraining sheath away from the annular region thereby allowing radial expansion thereof. The annular region may self-expand when the restraining sheath is removed therefrom. Radially expanding the annular region may comprise asymmetrically expanding the annular region such that an anterior portion of the annular region is substantially flat, and a posterior portion of the annular region is cylindrically ,  shaped. 
     The ventricular skirt may further comprise a trigonal anchoring tab on an anterior portion of the ventricular skirt, and radially expanding the ventricular skirt may comprise anchoring the trigonal anchoring tab against a first fibrous trigon on a first side of the anterior leaflet of the native mitral valve. The native anterior leaflet and adjacent chordae tendineae may be captured between the trigonal anchoring tab and an anterior surface of the anchor. The ventricular skirt may further comprise a second trigonal anchoring tab on the anterior portion of the ventricular skirt, and wherein radially expanding the ventricular skirt may comprise anchoring the second trigonal anchoring tab against a second fibrous trigon opposite the first fibrous trigon. The native anterior leaflet and adjacent chordae tendineae may be captured between the second trigonal anchoring tab and an anterior surface of the anchor. The ventricular skirt may further comprise a posterior ventricular anchoring tab on a posterior portion of the ventricular skirt. Radially expanding the ventricular skirt may comprise anchoring the posterior ventricular anchoring tab over a posterior leaflet of the native mitral valve to seat between the posterior leaflet and a ventricular wall of the heart. Radially expanding the ventricular skirt may comprise slidably moving a restraining sheath away from the ventricular skirt thereby allowing radial expansion thereof. The ventricular skirt may self-expand when the restraining sheath is removed therefrom. 
     The ventricular skirt may comprise a plurality of barbs, and expanding the ventricular skirt may comprise anchoring the barbs into heart tissue. The prosthetic valve may comprise a plurality of prosthetic valve leaflets, and radially expanding the ventricular skirt may comprise displacing the native mitral valve leaflets radially outward thereby preventing interference of the native mitral valve leaflets with the prosthetic valve leaflets. Radially expanding the ventricular skirt may comprise displacing the native mitral valve leaflets radially outward without contacting a ventricular wall, and without obstructing a left ventricular outflow tract. Radially expanding the ventricular skirt may comprise asymmetrically expanding the ventricular skirt such that an anterior portion of the ventricular skirt is substantially flat, and a posterior portion of the ventricular skirt is cylindrically shaped. 
     The atrial skirt may comprise an alignment element, and the method may comprise aligning the alignment element relative to the patient&#39;s valve. The valve may comprise a mitral valve, and aligning may comprise aligning the alignment element with an aortic root and disposing the alignment between two fibrous trigones of an anterior leaflet of the mitral valve. Aligning may comprise rotating the prosthetic valve. The prosthetic valve may comprise a plurality of prosthetic leaflets coupled to one or more commissures, and the method may comprise releasing the commissures from a delivery catheter. The prosthetic valve may comprise a tricuspid leaflet configuration. 
     The prosthetic valve may have an open configuration in which the prosthetic valve leaflets are disposed away from one another, and a closed configuration in which the prosthetic valve leaflets engage one another. Blood flows freely through the prosthetic valve in the open configuration, and retrograde blood flow across the prosthetic valve is substantially prevented in the closed configuration. The method may comprise reducing or eliminating mitral regurgitation. The prosthetic valve may comprise a therapeutic agent, and the method may comprise eluting the therapeutic agent from the prosthetic valve into adjacent tissue. 
     In another aspect of the present invention, a prosthetic cardiac valve comprises an anchor having an atrial skirt, an annular region, and a ventricular skirt. The anchor has a collapsed configuration for delivery to the heart and an expanded configuration for anchoring the prosthetic cardiac valve to a patient&#39;s heart. The prosthetic valve also comprises a plurality of prosthetic valve leaflets, each of the leaflets having a first end and a free end, wherein the first end is coupled with the anchor and the free end is opposite of the first end. The prosthetic cardiac valve has an open configuration in which the free ends of the prosthetic valve leaflets are disposed away from one another to allow antegrade blood-flow therepast, and a closed configuration in which the free ends of the prosthetic valve leaflets engage one another and substantially prevent retrograde bloodflow therepast. 
     At least a portion of the atrial skirt may be covered with tissue or a synthetic material. The atrial skirt may further comprise a plurality of barbs coupled thereto, the plurality of barbs adapted to anchor the atrial skirt into a superior surface of the patient&#39;s mitral valve. The atrial skirt may comprise a collapsed configuration and an expanded configuration. The collapsed configuration may be adapted for delivery to the patient&#39;s heart, and the expanded configuration may be radially expanded relative to the collapsed configuration and adapted to lie over a superior surface of the patient&#39;s native mitral valve, thereby anchoring the atrial skirt against a portion of the atrium. The atrial skirt may self-expand from the collapsed configuration to the radially expanded configuration when unconstrained, The atrial skirt may comprise one more radiopaque markers. The atrial skirt may comprise a plurality of axially oriented struts connected together with a connector element thereby forming a series of peaks and valleys. Some of the peaks and valleys may extend axially outward further than the rest of the atrial skirt, thereby forming an alignment element. 
     At least a portion of the annular region may be covered with tissue or a synthetic material. The annular region may have a collapsed configuration and an expanded configuration. The collapsed configuration may be adapted for delivery to the patient&#39;s heart, and the expanded configuration may be radially expanded relative to the collapsed configuration and adapted to conform with and to engage the native mitral valve annulus. The annular region may self-expand from the collapsed configuration to the expanded configuration when unconstrained. The annular region may comprise an asymmetrically D-shaped cross-section having a substantially flat anterior portion, and a cylindrically shaped posterior portion. The annular region may comprise a plurality of axially oriented struts connected together with a connector element thereby forming a series of peaks and valleys. One or more of the axially oriented struts may comprise one or more suture holes extending therethrough, the suture holes sized to receive a suture. 
     At least a portion of the ventricular skirt may be covered with tissue or a synthetic material. The ventricular skirt may comprise an asymmetrically D-shaped cross-section having a substantially flat anterior portion, and a cylindrically shaped posterior portion. The ventricular skirt may have a collapsed configuration and an expanded configuration. The collapsed configuration may be adapted for delivery to the patient&#39;s heart, and the expanded configuration may be radially expanded relative to the collapsed configuration and adapted to displace the native mitral valve leaflets radially outward. The ventricular skirt may self-expand from the collapsed configuration to the expanded configuration when unconstrained. 
     The ventricular skirt may further comprise a trigonal anchoring tab disposed on an anterior portion of the ventricular skirt. The trigonal anchoring tab may be adapted to being anchored against a first fibrous trigon on a first side of an anterior leaflet of the patient&#39;s mitral valve. Thus, the anterior leaflet and adjacent chordae tendineae may be captured between the trigonal anchoring tab and an anterior surface of the anchor. The ventricular skirt may further comprise a second trigonal anchoring tab that may be disposed on the anterior portion of the ventricular skirt. The second trigonal anchoring tab may be adapted to being anchored against a second fibrous trigon opposite the first fibrous trigon, such that the anterior leaflet and adjacent chordae tendineae are captured between the second trigonal anchoring tab and the anterior surface of the anchor. The ventricular skirt may further comprise a posterior ventricular anchoring tab disposed on a posterior portion of the ventricular skirt. The posterior ventricular anchoring tab may be adapted to being anchored over a posterior leaflet of the patient&#39;s mitral valve, such that the posterior ventricular anchoring tab is seated between the posterior leaflet and a ventricular wall of the patient&#39;s heart. The ventricular skirt may further comprise a plurality of barbs coupled thereto, and that may be adapted to anchor the ventricular skirt into heart tissue. The ventricular skirt may comprise a plurality of struts connected together with a connector element thereby forming a series of peaks and valleys. The one or more struts may comprise one or more suture holes extending therethrough, and that may be sized to receive a suture. 
     The plurality of prosthetic valve leaflets may comprise a tricuspid leaflet configuration. At least a portion of the one or more prosthetic valve leaflets may comprise tissue or a synthetic material. One or more of the plurality of prosthetic valve leaflets may be disposed over one or more commissure posts or struts that are radially biased inward relative to the ventricular skirt. The one or more commissure posts or struts may comprise one or more suture holes extending therethrough and that may be sized to receive a suture. The one or more prosthetic valve leaflets may be coupled to a commissure post or strut having a commissure tab adapted to releasably engage the commissure post or strut with a delivery device. 
     The prosthetic cardiac valve may further comprise an alignment element coupled to an anterior portion of the anchor. The alignment element may be adapted to be aligned with an aortic root of the patient&#39;s heart and disposed between two fibrous trigones of an anterior leaflet of the patient&#39;s mitral valve. The alignment element may be coupled with the atrial skirt. The prosthetic cardiac valve may further comprise a therapeutic agent coupled thereto, and adapted to being controllably eluted therefrom. 
     In still another aspect of the present invention, a delivery system for delivering a prosthetic cardiac valve to a patient&#39;s heart comprises an inner guidewire shaft having a lumen extending therethrough and adapted to slidably receive a guidewire, and a hub shaft concentrically disposed over the inner guidewire shaft. The delivery system also comprises a bell shaft slidably and concentrically disposed over the hub shaft, a sheath slidably and concentrically disposed over the bell shaft, and a handle near a proximal end of the delivery system. The handle comprises an actuator mechanism adapted to advance and retract the bell shaft and the sheath. 
     The system may further comprise the prosthetic cardiac valve which may be housed in the sheath in a radially collapsed configuration. The prosthetic cardiac valve may comprise an anchor having an atrial skirt, an annular region, and a ventricular skirt. The prosthetic valve may also comprise a plurality of prosthetic valve leaflets. Each of the leaflets may have a first end and a free end. The first end may be coupled with the anchor and the free end may be opposite of the first end. The prosthetic cardiac valve may have an open configuration in which the free ends of the prosthetic valve leaflets are disposed away from one another to allow antegrade bloodflow therepast. The valve may have a closed configuration in which the free ends of the prosthetic valve leaflets engage one another and substantially prevent retrograde blood flow therepast. 
     Proximal retraction of the sheath relative to the bell shaft may remove a constraint from the prosthetic cardiac valve thereby allowing the prosthetic cardiac valve to self-expand into engagement with the patient&#39;s native heart tissue. The prosthetic cardiac valve may be releasably coupled with the hub shaft, and proximal retraction of the bell shaft relative to the hub shaft may release the prosthetic cardiac valve therefrom. The actuator mechanism may comprise a rotatable wheel. The system may further comprise a tissue penetrating distal tip coupled to the hub shaft. The tissue penetrating distal tip may be adapted to pass through and expand an incision in the patient&#39;s heart. The system may further comprise a pin lock mechanism releasably coupled with the handle. The pin lock mechanism may limit proximal retraction of the sheath. 
     These and other embodiments are described in further detail in the following description related to the appended drawing figures. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the drawings, like reference numerals designate like or similar steps or components. 
         FIG.  1    is a schematic illustration of the left ventricle of a heart showing blood flow during systole with arrows. 
         FIG.  2    is a schematic illustration of the left ventricle of a heart having prolapsed leaflets in the mitral valve. 
         FIG.  3    is a schematic illustration of a heart in a patient suffering from cardiomyopathy where the heart is dilated and the leaflets do not meet. 
         FIG.  3 A  shows, normal closure of the leaflets. 
         FIG.  3 B  shows abnormal closure in the dilated heart. 
         FIG.  4    illustrates mitral valve regurgitation in the left ventricle of a heart having impaired papillary muscles. 
         FIGS.  5 A- 5 B  illustrate the mitral valve. 
         FIG.  6    illustrates a bottom, partial cross-sectional view of an exemplary prosthetic mitral valve. 
         FIG.  7    is a perspective view of the anchor portion of the prosthetic mitral valve seen in  FIG.  6   . 
         FIG.  8 A  is a perspective view of a prosthetic mitral valve. 
         FIG.  8 B  is a top view from the atrium of the prosthetic valve in  FIG.  8 A . 
         FIG.  9 A  illustrates a perspective view of the prosthetic valve in  FIG.  8 A  from the atrium. 
         FIG.  9 B  illustrates a perspective view of the prosthetic valve in  FIG.  8 A  from the ventricle. 
         FIG.  10    illustrates the prosthetic valve of  FIG.  8 A  uncovered and unrolled in a flat pattern. 
         FIG.  11    is a side view of a delivery device for implantation of a prosthetic valve. 
         FIG.  12    is a perspective exploded view of a proximal portion of the delivery device in  FIG.  11   . 
         FIG.  13    is a perspective exploded view of a distal portion of the delivery device in  FIG.  11   . 
         FIG.  14    is a cross-section of the a proximal portion of the delivery device in  FIG.  11   . 
         FIGS.  15 A- 15 C  are cross-sectional views of a distal portion of the delivery device in  FIG.  11   . 
         FIG.  16    is a side view of another exemplary embodiment of a delivery device for implantation of a prosthetic valve. 
         FIG.  17    is a perspective view of the delivery device in  FIG.  16   . 
         FIG.  18    is a perspective exploded view of the delivery device in  FIG.  16   . 
         FIGS.  19 A- 19 B  are side views of the delivery device in  FIG.  16    during various stages of operation. 
         FIG.  20    illustrates a distal portion of the delivery device in  FIG.  16    that is adapted to engage a portion of a prosthetic valve. 
         FIG.  21    illustrates engagement of the delivery device in  FIG.  16    with the prosthetic valve of  FIG.  8 A . 
         FIGS.  22 A- 22 G  illustrate an exemplary method of transapically delivering a prosthetic mitral valve. 
         FIGS.  23 A- 23 G  illustrate an exemplary method of transseptally delivering a prosthetic mitral valve. 
         FIG.  24    illustrates a prosthetic mitral valve implanted in the mitral space. 
         FIG.  25    illustrates a bottom view of a mitral valve implanted in the mitral space looking upward from the left ventricle. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Specific embodiments of the disclosed device, delivery system, and method will now be described with reference to the drawings. Nothing in this detailed description is intended to imply that any particular component, feature, or step is essential to the invention. 
     Cardiac Anatomy. The left ventricle LV of a normal heart H in systole is illustrated in  FIG.  1   . The left ventricle LV is contracting and blood flows outwardly through the aortic valve AV, a tricuspid valve in the direction of the arrows. Bach flow of blood or “regurgitation” through the mitral valve MV is prevented since the mitral valve is configured as a “check valve” which prevents back flow when pressure in the left ventricle is higher than that in the left atrium LA, The mitral valve MV comprises a pair of leaflets having free edges FE which meet evenly to close, as illustrated in  FIG.  1   . The opposite ends of the leaflets LF are attached to the surrounding heart structure along an annular region referred to as the annulus AN. The free edges FE of the leaflets LF are secured to the lower portions of the left ventricle LV through chordae tendineae CT (also referred to herein as the chordae) which include a plurality of branching tendons secured over the lower surfaces of each of the valve leaflets LF. The chordae CT in turn, are attached to the papillary muscles PM which extend upwardly from the lower portions of the left ventricle and interventricular septum IVS. 
     Referring now to  FIGS.  2 - 4   , a number of structural defects in the heart can cause mitral prolapse since inadequate tension is transmitted to the leaflet via the chordae. While the other leaflet maintains a normal profile, the two valve leaflets do not properly meet and leakage from the left ventricle LV into the left atrium LA will occur, as shown by the arrow. 
     Regurgitation also occurs in the patients suffering from cardiomyopathy where the heart is dilated and the increased size prevents the valve leaflets LF from meeting properly, as shown in  FIG.  3   . The enlargement of the heart causes the mitral annulus to become enlarged, making it impossible for the free edges FE to meet during systole. The free edges of the anterior and posterior leaflets normally meet along a line of coaptation C as shown in  FIG.  3 A , but a significant gap G can be left in patients suffering from cardiomyopathy, as shown in  FIG.  3 B . 
     Mitral valve regurgitation can also occur in patients who have suffered ischemic heart disease where the functioning of the papillary muscles PM is impaired, as illustrated in  FIG.  4   . As the left ventricle LV contracts during systole, the papillary muscles PM do not contract sufficiently to effect proper closure, The leaflets LF 1  and LF 2  then prolapse, as illustrated, Leakage again occurs from the left ventricle LV to the left atrium LA, as shown by the arrow. 
       FIG.  5 A  more clearly illustrates the anatomy of a mitral valve MV which is a bicuspid valve having an anterior side ANT and a posterior side POST. The valve includes an anterior (aortic) leaflet AL and a posterior (mural) leaflet PL. Chordae tendineae CT couple the valve leaflets AL, PL with the antero-lateral papillary muscle ALPM and the postero-medial papillary muscle PMPM. The valve leaflets AL, PL join one another along a line referred to as the antero-lateral commissure ALC and the posterior-medial commissure PMC. The annulus AN circumscribes the valve leaflets, and two regions adjacent an anterior portion of the annulus, on opposite sides of the anterior leaflet are referred to as the left fibrous trigone LFT and also the right fibrous trigone RFT. These areas are indicted by generally by the solid triangles.  FIG.  5 B  more clearly illustrates the left and right fibrous trigones, LFT, RFT. 
     While various surgical techniques as well as implantable devices have been proposed and appear to be promising treatments for mitral regurgitation, surgical approaches can require a lengthy recovery period, and implantable devices have varying clinical results. Therefore, there still is a need for improved devices and methods for treating mitral regurgitation. While the embodiments disclosed herein are directed to an implantable prosthetic mitral valve for treating mitral regurgitation, one of skill in the art will appreciate that this is not intended to be limiting, and the device and methods disclosed herein may also be used to treat other cardiac valves such as the tricuspid valve, aortic valve, pulmonary valve, etc, as well as other valves in the body such as venous valves. 
     Prosthetic Valve. Prosthetic valves have been surgically implanted in the heart as a treatment for mitral regurgitation. Some of these valves have been valves harvested from animals such as porcine valves, and others have been prosthetic mechanical valves with or without a tissue covering. More recently, minimally invasive catheter technology has been used to deliver prosthetic valves to the heart, These valves typically include an anchor for securing the valve to the patients heart, and a valve mechanism, either a mechanical valve, a valve with animal tissue, or combinations thereof. The prosthetic valve once implanted, takes over for malfunctioning native valve, thereby reducing or eliminating valvar insufficiency. While some of these valves appear promising, there still is a need for improved valves. The following discloses exemplary embodiments of a prosthetic valve, a delivery system for the prosthetic valve, and methods of delivering the valve that overcome some of the challenges associated with existing prosthetic valves. 
     Referring now to  FIGS.  6 - 7   , exemplary embodiments of a mitral valve prosthesis generally designated with reference numeral  10  comprise tricuspid tissue-type prosthetic one-way valve structure  12  comprising leaflets  14  affixed within self-expanding or expandable anchor portion  16  having a geometry that expands into low profile atrial skirt region  18 , annular region  20 , ventricular skirt region  22 , and a plurality of leaflet commissures  24  (also referred to herein as commissure posts) extending axially in a cantilevered fashion downstream into the sub-annular space defined by ventricular skirt region  22 .  FIG.  6    shows a partial cross-section of the valve  10  from the patient&#39;s left ventricle looking upward toward the right atrium. The atrial skirt region  18  is anchored to a lower portion of the right atrium  19 . The valve leaflets  14  have an open position (not illustrated) and a closed position illustrated in  FIG.  6   . In the open position, the leaflets  14  are displaced away from one another to allow blood flow therepast, and in the closed position, the leaflets  14  engage one another to close the valve and prevent retrograde blood flow therepast. The valve commissures  24  may be configured to optimize the efficiency of the prosthetic valve structure  12  and the load distribution on the leaflets  14  by providing for the attachment of the leaflets  14  along arcuate seams  28  (best seen in  FIG.  7   ), and by being made selectively flexible at different points or zones along their axial length through the addition/deletion of reinforcing struts. 
       FIG.  7    shows a perspective view of the anchor portion  16  of the valve  10  which has been formed from a series of interconnected struts. The atrial skirt region  18  forms an annular flanged region on the anchor to help secure an upper portion of the prosthetic valve in the atrium, and the annular region  20  is a cylindrical region for anchoring the valve along the native valve annulus. The ventricular skirt region  22  similarly is cylindrically shaped and helps anchor a lower portion of the valve in the patients left ventricle, Any portion, or all of the anchor may be covered with tissue such as pericardium or other tissues disclosed herein, or a synthetic material such as Dacron or ePTFE may be used to cover the anchor. The covering helps to seal the anchor to the native valve, and this helps funnel blood into and through the prosthetic valve, rather than around the valve. In some embodiments, the anchor may remain uncovered. The prosthetic valve has an expanded configuration and a collapsed configuration. The collapsed configuration has a low profile cylindrical shape that is suitable for mounting on a delivery system and delivery is preferably made either transluminally on a catheter, or transapically through the heart wall. The expanded configuration (as illustrated) allow the prosthetic valve to be anchored into a desired position. 
       FIG.  8 A  illustrates a perspective view of a preferred embodiment of a prosthetic mitral valve with optional coverings removed to allow visibility of the anchor struts.  FIG.  8 B  illustrates a top view of the prosthetic valve in  FIG.  8 A  from the atrium looking down into the ventricle. The valve  800  includes an asymmetrical expanded anchor portion having a D-shaped cross-section. As shown, the anchor portion generally comprises anterior  802  and posterior  804  aspects along the longitudinal axis thereof, as well as atrial  806 , annular  808  and ventricular  810  regions that correspond generally to the atrial skirt  18 , annular  20  and ventricular skirt  22  regions of the embodiment described above in  FIGS.  6 - 7   . Commissures (also referred to herein as commissure posts)  813  also correspond generally to the leaflets  14  of the embodiment in  FIGS.  6 - 7   . The prosthetic valve  800  has a collapsed configuration and an expanded configuration. The collapsed configuration is adapted to loading on a shaft such as a delivery catheter for transluminal delivery to the heart, or on a shaft for transapical delivery through the heart wall. The radially expanded configuration is adapted to anchor the valve to the patient&#39;s native heart adjacent the damaged valve. In order to allow the valve to expand from the collapsed configuration to the expanded configuration, the anchor portion of the valve may be fabricated from a self-expanding material such as a nickel titanium alloy like nitinol, or it may also be made from spring temper stainless steel, or a resilient polymer. In still other embodiments, the anchor may be expandable with an expandable member such as a balloon. In preferred embodiments, the anchor is fabricated by laser cutting, electrical discharge machining (EDM), or photochemically etching a tube. The anchor may also be fabricated by photochemically etching a flat sheet of material which is then rolled up with the opposing ends welded together. 
     The atrial skirt portion  816  forms a flanged region that helps to anchor the prosthetic valve to the atrium, above the mitral valve. The atrial skirt includes a plurality of triangular fingers which extend radially outward from the anchor to form the flange. The posterior  804  portion of the atrial skirt  816  is generally round or circular, while a portion of the anterior  802  part of the atrial skirt  816  is flat. Thus, the atrial skirt region preferably has a D-shaped cross-section. This allows the prosthetic valve to conform to the patient&#39;s cardiac anatomy without obstructing other portions of the heart, as will be discussed below. Each triangular finger is formed from a pair of interconnected struts. The triangular fingers of the atrial skirt generally are bent radially outward from the central axis of the prosthetic valve and lie in a plane that is transverse to the valve central axis. In some embodiments, the atrial skirt lies in a plane that is substantially perpendicular to the central axis of the valve. The anterior portion  802  of the atrial skirt  806  optionally includes an alignment element  814  which may be one or more struts which extend vertically upward and substantially parallel to the prosthetic valve. The alignment element  814  may include radiopaque markers (not illustrated) to facilitate visualization under fluoroscopy. The alignment element helps the physician to align the prosthetic valve with the native mitral valve anatomy, as will be discussed later. 
     Disposed under the atrial skirt region is the annular region  820  which also has a collapsed configuration for delivery, and an expanded configuration for anchoring the prosthetic valve along the native valve annulus. The annular region is also comprised of a plurality of interconnected struts that form a series of cells, preferably closed. Suture holes  821  in some of the struts allow tissue or other coverings (not illustrated) to be attached to the annular region. Covering all or a portion of the anchor with tissue or another covering helps seal the anchor against the heart valve and adjacent tissue, thereby ensuring that blood is funneled through the valve, and not around it. The annular region may be cylindrical, but in preferred embodiments has a posterior portion  804  which is circular, and an anterior portion  802  which is flat, thereby forming a D-shaped cross-section. This D-shaped cross-section conforms better to the native mitral valve anatomy without obstructing blood flow in other areas of the heart. 
     The lower portion of the prosthetic valve includes the ventricular skirt region  828 . The ventricular skirt region also has a collapsed configuration for delivery, and an expanded configuration for anchoring. It is formed from a plurality of interconnected struts that form a series of cells, preferably closed, that can radially expand. The ventricular skirt in the expanded configuration anchors the prosthetic valve to the ventricle by expanding against the native mitral valve leaflets. Optional barbs  823  in the ventricular skirt may be used to further help anchor the prosthetic valve into the ventricular tissue, Barbs may optionally also be included in the atrial skirt portion as well as the annular region of the anchor. Additionally, optional suture holes  821  in the ventricular skirt may be used to help suture tissue or another material to the ventricular skirt region, similarly as discussed above. The anterior  802  portion of the ventricular skirt may be flat, and the posterior  804  portion of the ventricular skirt may be circular, similarly forming a D-shaped cross-section to anchor and conform to the native anatomy without obstructing other portions of the heart. Also, the lower portions of the ventricular skirt serve as deployment control regions since the lower portions can remain sheathed thereby constraining the ventricular skirt from radial expansion until after the optional ventricular trigonal tabs and posterior tab have expanded, as will be explained in greater detail below. 
     The ventricular skirt portion may optionally also include a pair of ventricular trigonal tabs  824  on the anterior portion of the anchor (only 1 visible in this view) for helping to anchor the prosthetic valve as will be discussed in greater detail below. The ventricular skirt may also optionally include a posterior tab  826  on a posterior portion  804  of the ventricular skirt for anchoring the prosthetic valve to a posterior portion of the annulus. The trigonal tabs  824  or the posterior tab  826  are tabs that extend radially outward from the anchor, and they are inclined upward in the upstream direction. 
     The actual valve mechanism is formed from three commissures posts (also referred to as commissures)  813  which extend radially inward toward the central axis of the anchor in a funnel or cone like shape. The commissures  813  are formed from a plurality of interconnected struts that create the triangular shaped commissures. The struts of the commissures may include one or more suture holes  821  that allow tissue or a synthetic material to be attached to the commissures. In this exemplary embodiment, the valve is a tricuspid valve, therefore it includes three commissures  813 . The tips of the commissures may include a commissure tab  812  (also referred to as a tab) for engaging a delivery catheter. In this embodiment, the tabs have enlarged head regions connected to a narrower neck, forming a mushroom-like shape. The commissures may be biased in any position, but preferably angle inward slightly toward the central axis of the prosthetic valve so that retrograde blood flow forces the commissures into apposition with one another to close the valve, and antegrade blood flow pushes the commissures radially outward, to fully open the valve.  FIG.  8 B  is a top view illustrating the prosthetic valve of  FIG.  8 A  from the atrial side, and shows the preferred D-shaped cross-section. 
       FIG.  9 A  illustrates the prosthetic mitral valve of  FIGS.  8 A- 8 B  with a covering  870  coupled to portions of the anchor with suture  872 . This view is taken from an atrial perspective. In this embodiment, the covering is preferably pericardium which may come from a number of sources as disclosed elsewhere in this specification. In alternative embodiments, the covering may be a polymer such as Dacron polyester, ePTFE, or another synthetic material. The covering is preferably disposed over the annular region  820  and the ventricular skirt region  828 , and in some embodiments the anterior ventricular trigonal  824  tabs and the ventricular posterior tab  830  may also be covered with the same or a different material. The covering helps seal the anchor against the adjacent tissue so that blood funnels through the valve mechanism. In this embodiment, the atrial skirt is left uncovered, as well as tabs  824 ,  830 . Additionally, radiopaque markers  814   a  form a portion of the alignment element and facilitate visualization of the prosthetic valve under fluoroscopy which is important during alignment of the valve. 
       FIG.  9 B  is a perspective view of the prosthetic mitral valve seen in  FIG.  9 A , as seen from the ventricle. The struts of the valve commissures are covered with the same material or a different material as the annular and ventricular regions as discussed above, thereby forming the tricuspid valve leaflets  813 .  FIG.  9 B  shows the valve in the closed configuration where the three leaflets are engaged with one another preventing retrograde blood flow. Commissure tabs  812  remain uncovered and allow the commissures to be coupled with a delivery device as will be explained below. The prosthetic valve in  FIGS.  9 A- 9 B  may be sterilized so they are suitable for implantation in a patient using methods known in the art. 
       FIG.  10    illustrates the prosthetic valve of  FIG.  9 A  with the covering removed, and the remaining anchor unrolled and flattened out. The prosthetic valve  800  is formed from a plurality of interconnected struts. For example, the atrial skirt region  806  includes a plurality of interconnected struts that form a series of peaks and valleys. The flat anterior region  802  of the prosthetic valve has its peaks and valleys axially offset from those of the remaining portion of the atrial skirt, and this region becomes a part of the alignment element  814 . Radiopaque markers  814   a  are disposed on either side of the offset peaks and valleys and help with visualization during implantation of the valve. An axially oriented connector joins the struts of the skirt region  806  with the struts of the annular region  808 . The annular region is also comprised of a plurality of axially oriented and interconnected struts that form peaks and valleys. Connector struts couple struts of the annular region with the struts of the ventricular region  810 . The ventricular region also includes a plurality of interconnected struts that form peaks and valleys. Additionally, the struts form the leaflet commissures  813 , the ventricular skirt  828 , as well as the trigonal and posterior tabs  824 ,  830 . Suture holes  821  are disposed along the struts of the annular region as well as the ventricular region to allow attachment of a cover such as pericardium or a polymer such as Dacron or ePTFE. Barbs  823  are disposed along the ventricular skirt  828  to help anchor the prosthetic valve to adjacent tissue. Commissure tabs or tabs  812  are disposed on the tips of the commissures  813  and may be used to releasably couple the prosthetic valve with a delivery system as will be described below. One of skill in the art will appreciate that a number of strut geometries may be used, and additionally that strut dimensions such as length, width, thickness, etc. may be adjusted in order to provide the anchor with the desired mechanical properties such as stiffness, radial crush strength, commissure deflection, etc. Therefore, the illustrated geometry is not intended to be limiting. 
     Once the flat anchor pattern has been formed by EDM, laser cutting, photochemical etching, or other techniques known in the art, the anchor is radially expanded into a desired geometry. The anchor is then heat treated using known processes to set the shape. Thus, the anchor may be loaded onto a delivery catheter in a collapsed configuration and constrained in the collapsed configuration with a constraining sheath. Removal of the constraining sheath will allow the anchor to self-expand into its unbiased pre-set shape. In other embodiments, an expandable member such as a balloon may be used to radially expand the anchor into its preferred expanded configuration. 
     Delivery Systems.  FIGS.  11 - 15 C  show a delivery apparatus  1124  fashioned to deliver a prosthetic mitral valve to the heart transapically. However, one of skill in the art will appreciate that the delivery system may be modified and relative motion of the various components adjusted to allow the device to be used to deliver a prosthetic mitral valve transseptally. The delivery apparatus is generally comprised of a handle  1101  that is the combination of a handle section  1102  and a handle section  1103  (best seen in  FIG.  12   ), as well as a flexible tip  1110  that can smoothly penetrate the apex of the heart, and a sheath catheter  1109  which houses several additional catheters that are designed to translate axially and will be described in detail below. 
     The handle  1101  includes a female threaded leer adaptor  1113  which connects to a Tuohy Borst adaptor  1114  in order to provide a hemostatic seal with a 0.035″ diameter guide wire (not shown). The female threaded leer adaptor  1113  is in threaded contact with the proximal section of the handle  1101  through a threaded port  1131  (best seen in  FIG.  12   ). 
     As can be seen in  FIG.  11   , the handle  1101  provides location for the control mechanisms used to position and deploy a prosthetic mitral valve. The handle  1101  provides housing for a thumbwheel  1106  that can be accessed through a window  1137  that appears on both the top and bottom of the handle  1101 . The thumbwheel  1106  internally mates with a threaded insert  1115  (best seen in  FIG.  12   ) that actuates the sheath catheter  1109 , and the mechanics of this interaction will be explained in detail below. 
       FIG.  11    also shows a deployment thumbwheel  1104  that provides linear translation to a deployment catheter  1120  (best seen in  FIG.  12   ) when turned, since the turning motion of the deployment thumbwheel  1104  acts as a power screw, pushing the peg  1128  forward and distally from the user. The mechanics behind the peg  1128  will be further detailed below. The thumbwheel lock  1105  provides a security measure against unwanted rotation of the deployment thumbwheel  1104  by acting as a physical barrier to rotation. In order to turn the deployment thumbwheel  1104  the user must push forward the thumbwheel lock  1105 , disengaging it from two slots  1147  (seen in  FIG.  12   ) in the deployment thumbwheel  1105 . 
     As can also be seen in  FIG.  11   , a bleed valve  1108  and fluid line  1107  are connected to an internal mechanism in the distal portion of the handle  1101 , which provides a hemostatic seal for the sheath catheter  1109 . The details of this connection will be described below. 
     Internal mechanics of the delivery apparatus  1124  are illustrated in detail in  FIG.  12   , and the following descriptions will reveal the interactions between individual components, and the manner in which those components combine in order to achieve a prosthetic heart valve delivery apparatus. 
     As seen in  FIG.  12   , a handle section  1103  and handle section  1102  combine to create a handle  1101  that forms the basis of the delivery apparatus  1124 . In order to advance the sheath catheter  1109  during valve loading, or retract the sheath catheter  1109  during deployment, a rotatable thumbwheel  1106  is in threaded contact (internal threads  1129  seen in  FIG.  14   ) with a threaded insert  1115  (external threads  1130  of  FIG.  13   ) that translates linearly along the axis of the delivery apparatus, from a proximal position to a distal position. The sheath catheter  1109  is in mating contact with the threaded insert  1115  and is fastened through the use of a collar  1117  that aligns and mates the collar with the insert. The collar  1117  is fastened with screws  1116  (best seen in DETAIL A in  FIG.  14   ) to the threaded insert  1115  and contains a fluid port  1142  (best seen in DETAIL A in  FIG.  14   ) that provides location for the fluid line  1117  so that hemostasis can be maintained between the patient and delivery apparatus. An O-ring  1118  (best seen in DETAIL A in  FIG.  14   ) seals the stationary catheter  1119  (best seen in  FIG.  14   ) against the sheath catheter  1109 . The fluid line  1107  also provides a means of visually locating the sheath catheter  1109  with respect to position, as a slot  1138  in the handle  1101  allows the fluid line  1107  to translate with the sheath catheter  1109  (through a hole  1151  (best seen in DETAIL A in  FIG.  14   ) during operation, and this translation is highly visible. In order to prevent rotation of the threaded insert during translation, a flat face  1164  has been machined onto both sides of the threaded insert  1115 . The flat faces  1164  remain in contact with bosses  1139  and  1140  that are located on both handle section  1102  and handle section  1103  so that the bosses  1139  and  1140  act to grip the threaded insert  1115  and prevent rotation. A textured pattern  1155  allows the user to easily turn the thumbwheel  1106  in the surgical field. Detents  1141  (best seen in  FIG.  14   ) locate flanges  63  (seen in  FIG.  14   ) on the thumbwheel  1116  in order to allow for rotation. 
     The manner in which individual catheters (there are four catheters) move with respect to each other is illustrated in  FIG.  12   . Sheath catheter  1109  provides housing for the stationary catheter  1119 , which in turn provides housing for the movable hub catheter  1120 . The hub catheter  1120  translates linearly with respect to the nose catheter  1121  which can also be translated with respect to each previous catheter, and the handle  1101 . The stationary catheter  1119  is mated to a handle section  1103  in an internal bore  1150  which also forms a seal between the stationary catheter  1119  and the hub catheter  1120 . The distal portion of the stationary catheter  1119  is formed in the shape of a bell  1122  (see DETAIL A in  FIG.  15 A ) which acts as a housing to retain the hub capture  1123  (seen in DETAIL A in  FIG.  15 A ). 
     As previously stated a thumbwheel lock  1105  prevents rotation of the deployment thumbwheel  1104 . In order to provide a seating force that keeps the thumbwheel lock  1105  in a locked position until manipulated, a spring  1125  is housed in an internal bore  62  (best seen in  FIG.  14   ) and abuts against a shoulder  1161  (best seen in  FIG.  14   ) that is located inside the thumbwheel lock  1105 . This spring  1125  maintains the leading edge  1149  of the thumbwheel lock  1105  in a locked position within the two slots  1147  of the deployment thumbwheel  1104 . Gripping texture  1154  is provided on the thumbwheel lock  1105  for ease of use. In order to locate and retain the thumbwheel lock  1105  inside of the handle  1101 , a slot  1135  has been provided in both a handle section  1102  and a handle section  1103 . 
     As shown in  FIG.  12   , a sliding block  1127  is housed inside of flat parallel faces  1134  which appear on the inside of the handle  1101 . This sliding block  1127  is in mating contact with hub catheter  1120  and is the physical mechanism that linearly actuates the catheter. A spring  1126  is mounted on an external post  1159  and abuts against a shoulder  1133  that is located on the distal end of the sliding block  1127 . This spring  1126  forces a peg  1128  (located inside a thru-hole  1156  of  FIG.  14   ) into contact with the proximal edge of an angled slot  1148  that is cut into the deployment thumbwheel  1104 . The deployment thumbwheel  1104  is contained between a shoulder  1136  and a snap ring (not shown), both of which are features of the handle  1101 . Gripping texture  1153  on the deployment thumbwheel  1104  allows the user to easily rotate the thumbwheel in a clockwise direction, actuating the peg  1128  to ride distally along the slot  1148  and move the sliding block  1127 , which pushes the hub catheter  1120  and hub  1123  (best seen in DETAIL A of  FIG.  15 A ) forward and out of the bell  1122  (seen in DETAIL A of  FIG.  15 A ). A slot  1132  appears in a handle section  1102  and a handle section  1103  and prevents the peg  1128  from translating beyond a desired range. 
     A nose catheter  1121  extends from a Tuohy Borst adaptor  1114  on the proximal end of the handle  1101 , and internally throughout the handle and the respective catheters (sheath catheter  1109 , stationary catheter  1119 , and hub catheter  1120 ), terminating inside the rigid insert  1112  (seen in  FIG.  15 A ) of the flexible tip  1110  (seen in  FIG.  15 A ) that abuts with the distal end of the sheath catheter  1109 . 
       FIG.  13    displays an exploded view of the tip section of the delivery apparatus  1124 , and shows the relation between prosthetic mitral valve  1165  and the internal and external catheters. When crimped and loaded, the prosthetic mitral valve  1165  is encased between the internal surface of the sheath catheter  1109  and the external surface of the nose catheter  1121 . In order to capture and anchor the prosthetic mitral valve  1165  within the delivery apparatus  1124 , three commissure tabs  1160  (circumferentially spaced at 120.degree. apart) appearing on the proximal end of the prosthetic mitral valve  1165  provide points of contact between the valve and three slots  1143  (seen in  FIG.  15 A ) that are machined into the outer surface of the hub  1123  (circumferentially spaced at 120.degree. apart). After first advancing the hub catheter  1120  ( FIG.  15 A ) by rotating the deployment thumbwheel  1104  (seen in  FIG.  12   ) clockwise, the three commissure tabs  1160  can be captured within the three slots  1143  (seen in  FIG.  15 A ). The hub  1123  can then be retracted into the bell  1122  by releasing the deployment thumbwheel  1104  (seen in  FIG.  12   ). In this position the prosthetic mitral valve  1165  is anchored to the delivery apparatus  1124 , and further crimping of the valve will allow the sheath catheter  1109  to be advanced over the valve. 
       FIGS.  15 A- 15 C  further detail the manner in which loading of the prosthetic mitral valve  1165  (seen in  FIG.  13   ) into the delivery apparatus  1124  can be achieved. Initially, the flexible tip  1110  is abutted against the distal edge  1157  of the sheath catheter  1109 . The flexible tip  1110  is comprised of a rigid insert  1112 , and a soft and flexible tip portion  1111  which is over-molded onto the rigid insert  1112 . The shoulder  1145  and tapered face  1146  of the rigid insert  1112  act to guide and locate the distal edge  1157  of the sheath catheter  1109 , so that the catheter may rest against and be stiffened by the flexible tip  1110 , and be more easily introduced into the apex of the heart. 
     An initial position from which loading can be achieved is illustrated in  FIG.  15 A . As a first step in the loading of a prosthetic mitral valve  1165  (seen in  FIG.  13   ) into the delivery apparatus  1124 , the sheath catheter  1109  is withdrawn by rotation of the thumbwheel  1106  in a clockwise direction. The distal edge  1157  of the sheath catheter  1109  is retracted until it passes the distal edge of the bell  1122 , as illustrated in DETAIL A of  FIG.  15 B . As a second step in the loading of a prosthetic mitral valve  1165  (seen in  FIG.  13   ) into the delivery apparatus  1124 , the hub  1123  is advanced from beneath the bell  1122  by clockwise turning of the deployment thumbwheel  1104  (seen in  FIG.  12   ), as illustrated in DETAIL A of  FIG.  15 C . The deployment thumbwheel may only be turned once the thumbwheel lock  1105  (see  FIG.  12   ) has been set in the forward position, disengaging it from contact with the thumbwheel. Advancement of the hub  1123  uncovers three slots  1143  into which three commissure tabs  1160  of the prosthetic mitral valve  1165  (seen in  FIG.  13   ) will fit and be anchored. After anchoring of the commissure tabs  1160  into the slots  1143  by retraction of the hub  1123  has been achieved, a third step in the loading of a prosthetic mitral valve  1165  (seen in  FIG.  13   ) into the delivery apparatus  1124  may be performed. The prosthetic mitral valve  1165  (seen in  FIG.  13   ) can be crimped down to a minimum diameter by a loading mechanism (not shown), and then the sheath cannula  1109  can be advanced forward so as to cover the valve, by rotation of the thumbwheel  1106  in a counter-clockwise direction. The delivery apparatus  1124  and prosthetic mitral valve  1165  are then ready for deployment. 
       FIGS.  16 - 19 B  illustrate another exemplary embodiment of a delivery device for implanting a prosthetic valve in the heart transapically. However, one of skill in the art will appreciate that the delivery system may be modified and relative motion of the various components adjusted to allow the device to be used to deliver a prosthetic transseptally. The delivery apparatus is generally comprised of a handle  1601  that is the combination of two halves ( 1610  and  1635 ), as well as a tip  1603  that can smoothly penetrate the apex of the heart, and a flexible sheath  1602  which is comprised of concentric catheters that are designed to translate axially and will be described detail below. 
     The handle  1601  includes a handle cap  1611  which connects to a female threaded luer adaptor  1612  in order to provide a sealable exit for a 0.035″ diameter guide-wire (not shown). The handle cap  1611  is attached to the handle  1601  with threaded fasteners  1613 . The female threaded luer adaptor  1612  is in threaded contact with the handle cap  1611  through a tapped port, and when fully inserted squeezes against an o-ring ( 1636  best seen in  FIG.  18   ) which seals against the outer diameter of a guide-wire catheter ( 1621  best seen in  FIG.  18   ). 
     As can be seen in  FIG.  17   , the handle  1601  provides location for the control mechanisms used to position and deploy a prosthetic mitral valve. The handle  1601  provides housing for a thumbwheel  1616  that can be accessed through a window  1606  that appears on both the top and bottom of the handle  1601 . The thumbwheel  1616  internally mates with a threaded insert ( 1627  in  FIG.  18   ) that actuates the sheath catheter  1604 , and the mechanics of this interaction will be explained in detail below. 
       FIG.  17    also shows a first hemostasis tube  1617  that is inserted internally through a slot  1605 , and that mates with a first hemp-port through a hole ( 1625  and  1626  in  FIG.  18    respectively). The first hemostasis tube  1617  allows for fluid purging between internal catheters. The position of the first hemostasis tube  1617  along the slot  1605  provides a visual cue as to the position of the sheath catheter  1604 , and relative deployment phase of a prosthetic mitral valve (not shown). The relationship between the connection of the first hemostasis tube  1617  and the sheath catheter  1604  will be described below. 
     As can also be seen in  FIG.  17   , a second hemostasis tube  1614  is inserted into the handle  1601  and mated to a second hemp-port ( 1629  in  FIG.  18   ) in order to allow fluid purging between internal catheters, and details of this insertion will be described below. Finally, a pin lock  1608  provides a security measure against premature release of a prosthetic mitral valve, by acting as a physical barrier to translation between internal mechanisms. Pin lock prongs  1615  rely on spring force to retain the pin lock  1608  in the handle  1601 , and a user must first pull out the pin lock  1608  before final deployment of a prosthetic valve. 
       FIG.  17    also shows how the handle  1601  is fastened together by use of threaded fasteners and nuts ( 1607  and  1639  of  FIG.  18    respectively), and countersunk locator holes  1609  placed throughout the handle length. 
     internal mechanisms of the delivery system are illustrated in detail in  FIG.  18   , and the following descriptions will reveal the interactions between individual components, and the manner in which those components combine in order to create a system that is able to deliver a prosthetic mitral valve preferably transapically. 
     As seen in  FIG.  18   , the flexible sheath  1602  is comprised of four concentrically nested catheters. In order from smallest to largest in diameter, the concentrically nested catheters will be described in detail. The innermost catheter is a guide-wire catheter  1621  that runs internally throughout the entire delivery system, beginning at the tip  1603  and terminating in the female threaded luer adaptor  1612 . The guide-wire catheter  1621  is composed of a lower durometer, single lumen Pebax extrusion and is stationary. It provides a channel through which a guide-wire (not shown) can communicate with the delivery system. The next catheter is the hub catheter  1622  which provides support for the hub  1620  and is generally comprised of a higher durometer, single lumen PEEK extrusion. The hub catheter  1622  is in mating connection with both the hub  1622  at the distal end, and a stainless steel support rod  1634  at the proximal end. The stainless steel support rod  1634  is held fixed by virtue of a stopper  1637  that is encased in the handle  1601 . The hub catheter  1622  is stationary, and provides support and axial rigidity to the concentrically nested catheters. The next catheter is the bell catheter  1624 , which provides housing to the hub  1620  and is generally comprised of a medium durometer, single lumen Pebax extrusion, including internal steel braiding and lubricious liner, as well as a radiopaque marker band (not shown). The bell catheter  1624  translates axially, and can be advanced and retracted with respect to the hub  1620 . The bell catheter  1624  is in mating connection with the second Nemo-port  1629  at the proximal end, and hemostasis between the bell catheter  1624  and the stainless steel support rod  1634  can be achieved by purging the second hemostasis tube  1614 . The bell catheter  1624  is bumped up to a larger diameter  1623  on the distal end in order to encapsulate the hub  1620 . The outermost and final catheter is the sheath catheter  1604  which provides housing for a prosthetic mitral valve (not shown), and which is able to penetrate the apex of the heart (not shown), by supporting and directing a tip  1603  and assisting in the dilation of an incision in the heart wall muscle. The sheath catheter  1604  is generally comprised of a medium durometer, single lumen Pebax extrusion, including internal steel braiding and lubricious liner, as well as radiopaque marker band (not shown). The sheath catheter  1604  translates axially, and can be advanced and retracted with respect to the hub  1620 . The sheath catheter  1604  is in mating connection with the first hemp-port  1625  at the proximal end, and hemostasis between the sheath catheter  1604  and the bell catheter  1624  can be achieved by purging the first hemostasis tube  1617 . 
     As seen in  FIG.  18   , the proximal end of the sheath catheter  1604  is in mating contact with a first hemo-port  1625 . The first hemo-port is in mating contact with a threaded insert  1627 , and an o-ring  1638 , which is entrapped between the first hemo-port  1625  and the threaded insert  1627  in order to compress against the bell catheter  1624 , creating a hemostatic seal. As the thumbwheel  1616  is rotated, the screw insert  1627  will translate, and the sheath catheter  1624  can be retracted or advanced by virtue of attachment. In order to provide adequate stiffness to dilate heart wall tissue, the distal edge of the sheath catheter  1604  will abut against a shoulder  1618  located on the tip  1603 . This communication allows the tip  1603  to remain secure and aligned with the sheath catheter  1604  during delivery, and creates piercing stiffness. 
       FIG.  18    also details the mechanism through which the bell catheter  1624  can be retracted or advanced with respect to the hub  1620 . The thumbwheel  1616  can be rotated to such an extent that the screw insert  1627  will be brought into contact with two pins  1628  that are press fit into the second hemo-port  1629 . As the bell catheter  1624  is in mating contact with the second hemo-port  1629 , further rotation of the thumbwheel  1616  will cause the second hemo-port  1629  to translate and press against a spring  1633  by virtue of connection to a second hemo-port cap  1632 . This advancement will cause the bumped larger diameter section  1623  of the bell catheter  1624  to be retracted from the hub  1620 . As the thumbwheel  1616  is rotated in the opposite direction, restoring force produced by the spring  1633  will cause the second hemo-port  1629  to be pushed in the opposite direction, drawing the bumped larger diameter section  1623  of the bell catheter  1624  back over the hub  1620 , an action that is necessary during the initial loading of a valve prosthesis. 
       FIG.  18    further details the manner in which hemostasis is achieved between the stainless steel support rod  1634  and the bell catheter  1624 . An o-ring  1631  is compressed between the second hemo-port  1629  and the second hemo-port cap  1632 , creating a seal against the stainless steel support rod  1634 , Hemostasis between the bell catheter  1624  and the stainless steel support rod  1634  can be achieved by purging the second hemostasis tube  1614 , which is in communication with the void to be purged through a slot and hole  1630 . 
     The deployment process and actions necessary to activate the mechanisms responsible for deployment are detailed in  FIGS.  19 A- 19 B . When performed in the reverse order, these actions also necessitate the first loading of a valve (not shown) prior to surgery. 
     As seen in  FIG.  19 A , manipulation of the thumbwheel  1616  will provide translational control of the sheath catheter  1604 . In order to effect the deployment of a heart valve (not shown), the user must withdraw the sheath catheter  1604  from contact with the shoulder  1618  of the tip  1603  until it passes the larger diameter section  1623  of the bell catheter  1624 . A heart valve (not shown) will reside concentrically above the guide-wire catheter  1621  in the position indicated by the leader for  1621  in  FIG.  19 A , similarly as to the embodiment illustrated in  FIG.  13   . The sheath catheter  1604  can be withdrawn until the screw insert  1627  comes into contact with the pin lock  1608 . The pin lock  1608  must then be removed before further travel of the screw insert  1627  can be achieved. 
     As seen in  FIG.  19 B , the pin lock  1608  is removed from the handle  1601  in order to allow further translation of the sheath catheter  1604 . When the sheath catheter  1604  is fully retracted, the larger diameter section  1623  of the bell catheter  1624  is also fully retracted, which completely frees the heart valve (not shown) from the delivery system. Three hub slots  1619 , spaced circumferentially at 120.degree. from each other provide the anchoring mechanism and physical link between delivery system and heart valve. Once the larger diameter section  1623  of the bell catheter  1624  has been withdrawn, the hub slots  1619  become uncovered which allows the heart valve anchor (not shown) to fully expand. 
       FIG.  20    illustrates a distal portion of the delivery device in  FIG.  16   . Three hub slots  1619  are slidably disposed distally relative to the large diameter tip  1623  of bell catheter  1624 . These slots allow engagement with a prosthetic valve. The valve may be releasable held by the slots by disposing the commissure tabs or tabs  812  of the prosthetic valve into slots  1619  and then retracting the slots  1619  under tip  1623  of bell catheter  1624 . The prosthetic valve may be released from the delivery catheter by advancing the slots distally relative to the bell catheter so that the loading anchors or tabs  812  may self-expand out of and away from slots  1619  when the constraint of tip  1623  on bell catheter  1624  has been removed. 
       FIG.  21    illustrates a prosthetic mitral valve  800  (as discussed above with reference to  FIG.  8 A ) with the anchor tabs  812  disposed in the hub slots (not visible), and bell catheter  1623  advanced thereover. Thus, even though most of the prosthetic valve  800  has self-expanded into its expanded configuration, the valve commissures remain in a collapsed configuration with the tabs  812  captured in slots  1619 . Once the constraint provided by bell catheter  1623  has been removed from the slots  1619 , the tabs  812  may self-expand out of slots  1619 , the commissures will open up to their unbiased position. The prosthetic valve is then disconnected and free from the delivery device. 
     Transapical Delivery Methods.  FIGS.  22 A- 22 G  illustrate an exemplary method of transapically delivering a prosthetic mitral valve. This embodiment may use any of the prosthetic valves described herein, and may use any of the delivery devices described herein,  FIG.  22 A  illustrates the general transapical pathway that is taken with entry into the heart at the apex  2202 , through the left ventricle  2204 , across the mitral valve  2206  and into the left atrium  2208 . The aortic valve  2210  remains unaffected. Transapical delivery methods have been described in the patent and scientific literature, such as in International PCT Publication No. WO2009/134701, the entire contents of which are incorporated herein by reference. 
     In  FIG.  22 B  a delivery device  2214  is introduced through an incision in the apex  2202  and over a guidewire GW through the ventricle  2204 , past the mitral valve  2206  with a distal portion of the delivery device  2214  disposed in the atrium  2208 . The delivery device has a rounded tip  2212 . that is configured to pass through and dilate the incision, and can be advanced through the heart without causing unwanted trauma to the mitral valve  2206  or adjacent tissue. Suture  2216  may be stitched around the delivery device  2214  at the apex  2202  using a purse string stitch or other patterns known in the art in order to prevent excessive bleeding and to help hold the delivery device in position. 
     In  FIG.  22 C , the outer sheath  2214   a  of the delivery device  2214  is retracted proximally relative to the prosthetic mitral valve  2220  (or the prosthetic mitral valve is advanced distally relative to the outer sheath  2214   a ) to expose the alignment element  2218  and a portion of the atrial skirt region  2222  on the prosthetic mitral valve  2220  which allows the atrial skirt region  2222  to begin to partially radially expand outward and flare open. Alignment element  2218  may include a pair of radiopaque markers  2218   a  which facilitate visualization under fluoroscopy. The physician can then align the alignment element so that the radiopaque markers  2218   a  are disposed on either side of the anterior mitral valve leaflet. Delivery device  2214  may be rotated in order to help align the alignment element. The alignment element is preferably situated adjacent the aortic root and between the fibrous trigones of the native anterior leaflet. 
     In  FIG.  22 D  once alignment has been obtained, the sheath  2214   a  is further retracted proximally, allowing radial expansion of the atrial skirt  2222  which flares outward to form a flange, Proximal retraction of the delivery device  2214  and prosthetic valve  2220  seat the atrial skirt  2222  against an atrial surface adjacent the mitral valve  2206  thereby anchoring the prosthetic valve in a first position. 
       FIG.  22 E  shows that further proximal retraction of sheath  2214   a  exposes and axially removes additional constraint from the prosthetic valve  2220 , thereby allowing more of the valve to self-expand. The annular region  2224  expands into engagement with the mitral valve annulus and the ventricular trigonal tabs  2226  and the posterior tab  2228  radially expand. Portions of the ventricular skirt serve as deployment control regions and prevent the entire ventricular skirt from expanding because they are still constrained. The tabs are captured between the anterior and posterior mitral valve leaflets and the ventricular wall. The posterior ventricular anchoring tab  2228  is preferably aligned in the middle of the posterior mitral valve leaflet where there is an absence of chordae attachments, and is passed over the posterior leaflet to seat between the posterior leaflet and the ventricular wall. The two ventricular trigonal anchoring tabs  2226  are positioned on either side of the anterior leaflet with their heads positioned at the fibrous trigones. Slight rotation and realignment of the prosthesis can occur at this time. As the prosthesis expands, the anterior trigonal tabs anchor against the fibrous trigones, capturing the native anterior leaflet and chordae between the tabs and the anterior surface of the prosthetic valve, and the posterior ventricular tab anchors between the ventricular wall and the posterior leaflet, capturing the posterior leaflet between the posterior anchoring tab and the posterior surface of the prosthetic valve assembly. 
       FIG.  22 F  shows that further retraction of sheath  2214   a  releases the ventricular trigonal tabs and the posterior tab and the deployment control regions of the ventricular skirt  2230  are also released and allowed to radially expand outward against the native mitral valve leaflets. 
     This creates a sealing funnel within the native leaflets and helps direct blood flow through the prosthetic mitral valve, With the commissures of the prosthesis still captured within the delivery system, very minor adjustments may still be made to ensure accurate positioning, anchoring and sealing. The prosthetic valve is now anchored in four positions. The anchor tabs  2232  are then released from the delivery device by retraction of an inner shaft, allowing the tabs to self-expand out of slots on the delivery catheter as previously discussed above and shown in  FIG.  22 G . The prosthetic valve is now implanted in the patient&#39;s heart and takes over the native mitral valve. The delivery device  2214  may then be removed from the heart by proximally retracting it and removing it from the apex incision, The suture  2216  may then be tied off, sealing the puncture site. 
     Transseptal Delivery Methods.  FIGS.  23 A- 23 G  illustrate an exemplary method of transseptally delivering a prosthetic mitral valve. This embodiment may use any of the prosthetic valves described herein, and may use any of the delivery devices described herein if modified appropriately. One of skill in the art will appreciate that relative motion of the various shafts in the delivery system embodiments disclosed above may need to be reversed in order to accommodate a transseptal approach.  FIG.  23 A  illustrates the general transseptal pathway that is taken with the delivery device passing up the vena cava  2302  into the right atrium  2304 . A transseptal puncture  2306  is created through the atrial septum, often through the foramen ovale, so that the device may be passed into the left atrium  2308 , above the mitral valve  2310  and adjacent the left ventricle  2312 . Transseptal techniques have been published in the patent and scientific literature, such as in U.S. Patent Publication No. 2004/0181238 to Zarbatany et al., the entire contents of which are incorporated herein by reference. 
     In  FIG.  23 B  a delivery device  2314  is passed over a guidewire GW through the vena cava  2302  into the right atrium  2306 . The delivery device  2314  is then transseptally passed through the atrial wall into the left atrium  2308  adjacent the mitral valve  2310 . The guidewire GW may be disposed across the mitral valve  2310  in the left ventricle  2312 . The distal tip of the delivery device typically includes a nose cone or other atraumatic tip to prevent damaging the mitral valve or adjacent tissue. 
     In  FIG.  23 C , the outer sheath  2214   a  of the delivery device  2214  is retracted proximally relative to the prosthetic mitral valve  2319 . Alternatively, a distal portion  2314   b  of the delivery device  2214  may be advanced distally relative to the prosthetic valve  2319  to expose the alignment element  2316  and a portion of the atrial skirt region  2318  on the prosthetic mitral valve  2319  which allows the atrial skirt region  2318  to begin to partially radially expand outward and flare open. Alignment element  2316  may include a pair of radiopaque markers  2316   a  which facilitate visualization under fluoroscopy. The physician can then align the alignment element so that the radiopaque markers  2316   a  are disposed on either side of the anterior mitral valve leaflet. The alignment element is preferably situated adjacent the aortic root and between the fibrous trigones of the native anterior leaflet. Delivery device  2214  may be rotated in order to help align the alignment element. 
     In  FIG.  23 D  once alignment has been obtained, the distal portion  2314   b  is further advanced distally allowing radial expansion of the atrial skirt  2318  which flares outward to form a flange. Distally advancing the delivery device  2214  and prosthetic valve  2319  seats the atrial skirt  2318  against an atrial surface adjacent the mitral valve  2310  thereby anchoring the prosthetic valve in a first position. 
       FIG.  23 E  shows that further distal advancement of distal portion  2314   b  exposes and axially removes additional constraint from the prosthetic valve  2319 , thereby allowing more of the valve to self-expand. The annular region  2320  expands into engagement with the mitral valve annulus and the ventricular trigonal tabs  2324  and the posterior tab  2322  radially expand. Portions of the ventricular skirt serve as deployment control regions since they remain constrained and thus the entire ventricular skirt cannot expand. The tabs are captured between the anterior and posterior mitral valve leaflets and the ventricular wall. The posterior ventricular anchoring tab  2322  is preferably aligned in the middle of the posterior mitral valve leaflet where there is an absence of chordae attachments, and is passed over the posterior leaflet to seat between the posterior leaflet and the ventricular wall. The two ventricular trigonal anchoring tabs  2324  are positioned on either side of the anterior leaflet with their heads positioned at the fibrous trigones. Slight rotation and realignment of the prosthesis can occur at this time. As the prosthesis expands, the anterior trigonal tabs anchor against the fibrous trigones, capturing the native anterior leaflet and chordae between the tabs and the anterior surface of the prosthetic valve, and the posterior ventricular tab anchors between the ventricular wall and the posterior leaflet, capturing the posterior leaflet between the posterior anchoring tab and the posterior surface of the prosthetic valve assembly. 
       FIG.  23 F  shows that further distal advancement of distal portion  2314   b  releases the ventricular trigonal tabs and the posterior tab and the ventricular skirt  2326  is also released and allowed to radially expand outward against the native mitral valve leaflets without engaging the ventricular wall. This creates a sealing funnel within the native leaflets and helps funnel blood flow through the prosthetic valve. With the commissures of the prosthetic valve still captured by the delivery system, very minor adjustments may still be made to ensure accurate positioning, anchoring and sealing. The prosthetic valve is now anchored in four positions. The anchor tabs  2328  are then released from the delivery device by further advancement of an inner shaft, allowing the tabs to self-expand out of slots on the delivery catheter as previously discussed above and shown in  FIG.  23 G . The prosthetic valve is now implanted in the patient&#39;s heart and takes over the native mitral valve. The delivery device  2314  may then be removed from the heart by proximally retracting it back through the atrial septum, and out of the vena cava. 
       FIG.  24    shows the prosthetic valve  2418  anchored in the mitral space after transapical or transseptal delivery. Prosthetic valve  2418  is preferably the prosthetic mitral valve illustrated in  FIG.  8 A , and delivered by methods shown in  FIGS.  22 A- 22 G  or  FIGS.  23 A- 23 G . The prosthetic valve  2418  has radially self-expanded into engagement with the mitral valve to anchor it in position without obstructing other portions of the heart including the left ventricular outflow tract such as aortic valve  2402 . The anterior trigonal tabs  2408  (only 1 seen in this view) and the posterior ventricular tab  2405  are radially expanded outward from the rest of the ventricular skirt  2410  and the anterior leaflet  2406  and posterior leaflet  2404  are captured between the respective tab and the ventricular skirt  2410  to form an anchor point. The ventricular skirt  2410  is also radially expanded outward to engage and press outwardly at least some of the chordae tendineae and papillary muscles but preferably without pressing against the ventricular wall. The annular region  2416  is expanded radially outward to engage and press against the mitral valve annulus, and the atrial skirt  2414  has also expanded outwardly to form a flange that rests on top of the mitral valve against the atrium. Thus, the prosthetic valve  2418  is anchored in four positions in the mitral space which prevents the prosthetic valve from migrating or dislodging during contraction of the heart. Moreover, using four anchor points lessens the anchoring pressure that is required to be applied in any given anchoring zone as compared to a prosthesis that is anchored in only a single anchoring zone, or in any combination of these four anchoring zones. The consequent reduction in radial force required to be exerted against the native structures in each zone minimizes the risk of obstruction or impingement of the nearby aortic valve or aortic root caused by the displacement of the native mitral valve apparatus. Valve leaflets  2420  form a tricuspid valve which opens with antegrade blood flow and closes with retrograde blood flow. Tab  2412  on a tip of the commissures  2421  (best seen in  FIG.  25   ) remains free after disengagement from the delivery device. 
       FIG.  25    illustrates the prosthetic valve  2418  of  FIG.  24    anchored in the mitral space and viewed from the left ventricle, looking upward toward the atrium. As previously mentioned, the prosthetic valve  2418  may be transapically or transseptally delivered and is preferably the prosthetic mitral valve illustrated in  FIG.  8 A , delivered by methods shown in  FIGS.  22 A- 22 G  or  FIGS.  23 A- 23 G . This view more clearly illustrates anchoring and engagement of the prosthetic mitral valve  2418  with the adjacent tissue. For example, the three valve leaflets  2420  forming the tricuspid valve are shown in the open position, allowing blood flow therepast. Additionally, the anterior trigonal tabs  2408  and the posterior ventricular tab  2405  are shown radially expanded outward into engagement with the ventricular heart tissue  2425 , The anterior portion of the prosthetic valve in between anterior trigonal tabs  2408  is approximately flat to match the corresponding flat anatomy as previously discussed above. The flat shape of the anterior portion of the prosthetic valve prevents the prosthetic valve from impinging on and obstructing adjacent anatomy such as the left ventricular outflow tract including the aortic valve.  FIG.  25    also illustrates how the ventricular skirt  2410  expands radially outward against the native mitral valve leaflets. 
     Drug Delivery. Any of the prosthetic valves may also be used as a drug delivery device for localized drug elution. The therapeutic agent may be a coated on the prosthetic valve, on the tissue covering the anchor, on both, or otherwise carried by the prosthetic valve and controllably eluted therefrom after implantation. Exemplary drugs include anti-calcification drugs, antibiotics, anti-platelet aggregation drugs, anti-inflammatory drugs, drugs which inhibit tissue rejection, anti-restenosis drugs, anti-thrombogenic drugs, thrombolytic drugs, etc. Drugs which have these therapeutic effects are well known to those of skill in the art. 
     Although the exemplary embodiments have been described in some detail for clarity of understanding and by way of example, a variety of additional modifications, adaptations and changes may be clear to those of skill in the art. One of skill in the art will appreciate that the various features described herein may be combined with one another or substituted with one another. Hence, the scope of the present invention is limited solely by the appended claims.