Patent Publication Number: US-11382750-B2

Title: Prosthetic mitral valve

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 15/796,184, filed Oct. 27, 2017, now U.S. Pat. No. 10,441,421 which claims the benefit of the filing date of U.S. Provisional Application No. 62/457,374, filed Feb. 10, 2017, and U.S. Provisional Application No. 62/414,125, filed Oct. 28, 2016, the disclosures of which are incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     The present disclosure relates to heart valve replacement and, in particular, to collapsible prosthetic heart valves. More particularly, the present disclosure relates to collapsible prosthetic heart valves for use in the mitral valve annulus. 
     Prosthetic heart valves that are collapsible to a relatively small circumferential size can be delivered into a patient less invasively than valves that are not collapsible. For example, a collapsible valve may be delivered into a patient via a tube-like delivery apparatus such as a catheter, a trocar, a laparoscopic instrument, or the like. This collapsibility can avoid the need for a more invasive procedure such as full open-chest, open-heart surgery. 
     Collapsible prosthetic heart valves typically take the form of a valve structure mounted on a stent. There are two types of stents on which the valve structures are ordinarily mounted: a self-expanding stent and a balloon-expandable stent. To place such valves into a delivery apparatus and ultimately into a patient, the valve is generally first collapsed or crimped to reduce its circumferential size. 
     When a collapsed prosthetic valve has reached the desired implant site in the patient (e.g., at or near the annulus of the patient&#39;s heart valve that is to be replaced by the prosthetic valve), the prosthetic valve can be deployed or released from the delivery apparatus and re-expanded to full operating size. For balloon-expandable valves, this generally involves releasing the entire valve, assuring its proper location, and then expanding a balloon positioned within the valve stent. For self-expanding valves, on the other hand, the stent automatically expands as the sheath covering the valve is withdrawn. 
     SUMMARY OF THE INVENTION 
     In some embodiments, a prosthetic heart valve having an inflow end and an outflow end includes a stent having a collapsed condition, an expanded condition, and a plurality of cells arranged in circumferential rows. The stent has an anterior side configured and arranged to be disposed adjacent an anterior native valve leaflet and a posterior side configured and arranged to be disposed adjacent a posterior native valve leaflet. A valve assembly having a plurality of leaflets is disposed within the stent and a flange is disposed about the stent, the flange having a flared portion adjacent the inflow end of the prosthetic heart valve and a body portion extending from the flared portion to the outflow end. The flange extends between a first set of attachment points adjacent the inflow end and a second set of attachment points adjacent the outflow end. 
     In some embodiments, a prosthetic heart valve having an inflow end and an outflow end includes a stent having a collapsed condition, an expanded condition, and a plurality of cells arranged in circumferential rows. The stent has an anterior side configured and arranged to be disposed adjacent an anterior native valve leaflet and a posterior side configured and arranged to be disposed adjacent a posterior native valve leaflet. A valve assembly having a plurality of leaflets is disposed within the stent and a flange is disposed about the stent, the flange being asymmetric about a longitudinal axis such that a posterior side of the flange has a different shape than an anterior side of the flange. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Various embodiments of the present disclosure are described herein with reference to the drawings, wherein: 
         FIG. 1  is a highly schematic cutaway representation of a human heart showing various delivery approaches; 
         FIG. 2  is a highly schematic representation of a native mitral valve and associated cardiac structures; 
         FIG. 3A  is a side view of a prosthetic heart valve according to the prior art; 
         FIG. 3B  is a highly schematic longitudinal cross-section of the prosthetic heart valve of  FIG. 3A ; 
         FIG. 4A  is a side view of a prosthetic heart valve according to an aspect of the disclosure; 
         FIG. 4B  is an isolated perspective view of an anchor feature of the prosthetic heart valve of  FIG. 4A ; 
         FIG. 4C  is a side view of the prosthetic heart valve of  FIG. 4A  in a stage of manufacture; 
         FIG. 4D  is a highly schematic longitudinal cross-section of the prosthetic heart valve of  FIG. 4A  in a collapsed condition; 
         FIG. 4E  is a highly schematic representation of the prosthetic heart valve of  FIG. 4A  implanted into a native mitral valve annulus; 
         FIG. 5A  is a side view of a prosthetic heart valve according to a further aspect of the disclosure; 
         FIG. 5B  is a schematic profile view of the prosthetic heart valve of  FIG. 5A ; 
         FIG. 5C  is a schematic profile view of a variant of the prosthetic heart valve of  FIG. 5A  having a covering layer; 
         FIG. 5D  is a schematic profile view of another variant of the prosthetic heart valve of  FIG. 5A  having a covering layer; 
         FIG. 6A  is a side view of a prosthetic heart valve according to yet another aspect of the disclosure; 
         FIG. 6B  is a schematic top view of the prosthetic heart valve of  FIG. 6A ; 
         FIG. 6C  is a schematic top view of a variant of the prosthetic heart valve of  FIG. 6A  having an oval flange; 
         FIG. 6D  is a side view of a prosthetic heart valve according to yet another aspect of the disclosure; 
         FIG. 6E  is a schematic side view of a prosthetic heart valve according to yet another aspect of the disclosure; 
         FIG. 7A  is a schematic side view of a prosthetic heart valve according to yet another aspect of the disclosure; 
         FIG. 7B  is a schematic side view of a prosthetic heart valve according to yet another aspect of the disclosure; 
         FIG. 7C  is a schematic side view of a prosthetic heart valve according to yet another aspect of the disclosure; and 
         FIG. 8  is a schematic side view showing flanges of different profiles disposed on a stent. 
     
    
    
     DETAILED DESCRIPTION 
     Blood flows through the mitral valve from the left atrium to the left ventricle. As used herein, the term “inflow end,” when used in connection with a prosthetic mitral heart valve, refers to the end of the heart valve closest to the left atrium when the heart valve is implanted in a patient, whereas the term “outflow end,” when used in connection with a prosthetic mitral heart valve, refers to the end of the heart valve closest to the left ventricle when the heart valve is implanted in a patient. Also, as used herein, the terms “substantially,” “generally,” and “about” are intended to mean that slight deviations from absolute are included within the scope of the term so modified. Generally, materials described as being suitable for components in one embodiment of the disclosure may also be suitable for similar or identical components described in other embodiments. 
       FIG. 1  is a highly schematic cutaway representation of human heart  100 . The human heart includes two atria and two ventricles: right atrium  112  and left atrium  122 , and right ventricle  114  and left ventricle  124 . Heart  100  further includes aorta  110  and aortic arch  120 . Disposed between left atrium  122  and left ventricle  124  is mitral valve  130 . Mitral valve  130 , also known as the bicuspid valve or left atrioventricular valve, is a dual-flap valve that opens as a result of increased pressure in left atrium  122  as it fills with blood. As atrial pressure increases above that of left ventricle  124 , mitral valve  130  opens and blood passes into left ventricle  124 . Blood flows through heart  100  in the direction shown by arrows “B”. 
     A dashed arrow, labeled “TA”, indicates a transapical approach for implanting a prosthetic heart valve, in this case to replace the mitral valve. In transapical delivery, a small incision is made between the ribs and into the apex of left ventricle  124  to deliver the prosthetic heart valve to the target site. A second dashed arrow, labeled “TS”, indicates a transseptal approach for implanting a prosthetic heart valve in which the valve is passed through the septum between right atrium  112  and left atrium  122 . Other approaches for implanting a prosthetic heart valve are also possible. 
       FIG. 2  is a more detailed schematic representation of native mitral valve  130  and its associated structures. As previously noted, mitral valve  130  includes two flaps or leaflets, posterior leaflet  136  and anterior leaflet  138 , disposed between left atrium  122  and left ventricle  124 . Cord-like tendons, known as chordae tendineae  134 , connect the two leaflets  136 ,  138  to the medial and lateral papillary muscles  132 . During atrial systole, blood flows from higher pressure in left atrium  122  to lower pressure in left ventricle  124 . When left ventricle  124  contracts in ventricular systole, the increased blood pressure in the chamber pushes leaflets  136 ,  138  to close, preventing the backflow of blood into left atrium  122 . Since the blood pressure in left atrium  122  is much lower than that in left ventricle  124 , leaflets  136 ,  138  attempt to evert to the low pressure regions. Chordae tendineae  134  prevent the eversion by becoming tense, thus pulling on leaflets  136 ,  138  and holding them in the closed position. 
       FIGS. 3A and 3B  are a side view and a longitudinal cross-sectional view of prosthetic heart valve  300  according to the prior art. Prosthetic heart valve  300  is a collapsible prosthetic heart valve designed to replace the function of the native mitral valve of a patient (see native mitral valve  130  of  FIGS. 1-2 ). Generally, prosthetic valve  300  has a substantially cylindrical shape with inflow end  310  and outflow end  312 . When used to replace native mitral valve  130 , prosthetic valve  300  may have a low profile so as not cause obstruction of the left ventricle outflow tract. 
     Prosthetic heart valve  300  may include stent  350 , which may be formed from biocompatible materials that are capable of self-expansion, such as, for example, shape-memory alloys including nitinol. Stent  350  may include a plurality of struts  352  that form cells  354  connected to one another in one or more annular rows around the stent. Cells  354  may all be of substantially the same size around the perimeter and along the length of stent  350 . Alternatively, cells  354  near inflow end  310  may be larger than the cells near outflow end  312 . Stent  350  may be expandable to provide a radial force to assist with positioning and stabilizing prosthetic heart valve  300  in the native valve annulus. 
     Prosthetic heart valve  300  may also include a substantially cylindrical valve assembly  360  including a plurality of leaflets  362  ( FIG. 3B ) attached to a cuff  364  ( FIG. 3A ). Leaflets  362  replace the function of native mitral valve leaflets  136  and  138  described above with reference to  FIG. 2 . That is, leaflets  362  coapt with one another to function as a one-way valve. The valve assembly  360  of prosthetic heart valve  300  may include two or three leaflets, but it should be appreciated that prosthetic heart valve  300  may have more than three leaflets. Both cuff  364  and leaflets  362  may be wholly or partly formed of any suitable biological material, such as bovine or porcine pericardium, or polymers, such as polytetrafluoroethylene (PTFE), urethanes and the like. Valve assembly  360  may be secured to stent  350  by suturing to struts  352  or by using tissue glue, ultrasonic welding, or other suitable methods. 
     When prosthetic heart valve  300  is implanted in a patient, for example at the annulus of native mitral valve  130 , it is biased towards an expanded condition, providing radial force to anchor the valve in place. However, if the radial force is too high, damage may occur to heart tissue. If, instead, the radial force is too low, the heart valve may move from its implanted position, for example, into either left ventricle  124  or left atrium  122 , requiring emergency surgery to remove the displaced valve. The potential for such movement may be heightened in mitral valve applications, particularly if a low profile valve is used. 
     Another potential issue with prosthetic heart valves is inadequate sealing between the prosthetic valve and the native tissue. For example, if prosthetic heart valve  300  is implanted at the annulus of mitral valve  130  in a patient, improper or inadequate sealing may result in blood flowing from left ventricle  124  into left atrium  122 , even if leaflets  362  of valve assembly  360  are working properly. This may occur, for example, if blood flows in a retrograde fashion between the outer perimeter of prosthetic heart valve  300  and the native tissue at the site of implantation. This phenomenon is known as perivalvular (or paravalvular) leak (“PV leak”). 
     In addition to anchoring and perivalvular leakage, there are other considerations when forming a prosthetic heart valve for mitral applications. For example, the replacement valve may need to accommodate irregular or large mitral valve annuli without damaging nearby native structures or affecting electrical signals. Additionally, the replacement valve may address the location and position of the left ventricular outflow tract and try to limit obstruction of it. The replacement valve should also be simple to use and the ability of the valve to anchor within the native annulus should be easy and repeatable. 
     Other considerations may include the anchoring or securement of the posterior leaflet. Because of the relatively small size and location of the posterior leaflet in some patients, it may be difficult to visualize and capture the leaflet with an anchor. It would also be beneficial to reduce the risk of migration of the valve. Additionally, it would be beneficial to secure the native leaflets so that they do not obstruct blood flow, for example, into the left ventricular outflow tract or the aorta. 
       FIG. 4A  is a side view of a prosthetic heart valve  400  in accordance with one embodiment of the disclosure. Prosthetic heart valve  400  may be similar or identical to prosthetic heart valve  300  in certain respects. For example, prosthetic heart valve  400  is collapsible and expandable and designed to replace a native mitral valve, having a substantially cylindrical shape with an inflow end  410  and an outflow end  412 . It should be understood that prosthetic heart valve  400  is not limited to replacement of mitral valves, and may be used to replace other heart valves. Prosthetic heart valve  400  may include stent  450 , which may be similar to stent  350 , having a plurality of struts  452  that form cells  454  connected to one another in one or more annular rows around stent  450 . Stent  450  includes two annular rows of cells  454  of substantially similar size and shape, with nine cells in each row. As illustrated, cells  454  are generally diamond shaped. However, it should be understood that a different number of rows of cells  454 , as well as a different number of cells  454  per row, may be suitable. As discussed in relation to stent  350 , stent  450  may be formed from a shape memory alloy, such as nitinol. The struts  452  forming stent  450  may have a diameter of between about 0.020 inches (0.51 mm) and about 0.025 inches (0.64 mm), although other dimensions may be suitable. Forming stent  450  from struts  452  of a relatively large diameter may provide increased stiffness to stent  450 , which may provide certain benefits, such as minimizing the deflection of commissure attachment features (CAFs)  466  during normal operation of prosthetic heart valve  400 . On the other hand, forming stent  450  from struts  452  of a relatively small diameter may provide increased flexibility to stent  450 , which may provide certain benefits, such as the capability to be collapsed to a smaller profile during delivery. 
     Prosthetic heart valve  400  may also include a valve assembly having three leaflets  462  attached to a cylindrical cuff  464  similar to that shown and described with reference to  FIGS. 3A-B . It should be understood that although native mitral valve  130  has two leaflets  136 ,  138 , prosthetic heart valve  400  may have three leaflets  462 , or more or fewer than three leaflets, provided that the leaflets act to allow one-way antegrade blood flow through the prosthetic heart valve  400 , but obstruct retrograde blood flow through the prosthetic heart valve. Prosthetic heart valve  400  may have the same number of leaflets  462  as CAFs  466 , each CAF providing a point of attachment for adjacent leaflets to stent  450 . It should be understood that prosthetic heart valve  400  may alternatively include a pair of prosthetic leaflets and a corresponding pair of CAFs. 
     As with stent  350 , stent  450  may be expandable to provide a radial force to assist with positioning and stabilizing prosthetic heart valve  400  in the native mitral valve annulus. However, prosthetic valve  400  includes additional securement features in the form of anchor arms  470  to help prevent prosthetic heart valve  400  from migrating into left atrium  122 . Anchor arms  470  may be separately attachable such that they hook under native mitral valve leaflets  136 ,  138  or may be cut directly into the stent  450 , for example, via laser cutting. 
     A single anchor arm  470  is shown in  FIG. 4B . Anchor arm  470  may be formed of a single wire  472  bent or otherwise formed into a body portion  471  having a substantially diamond shape. Wire  472  is preferably a shape-memory alloy such as nitinol. In one example, wire  472  is formed of nitinol having a diameter of about 0.015 inches (0.38 mm). As with struts  452  of stent  450 , the diameter of wire  472  may be increased to provide increased stiffness or decreased to provide increased flexibility. Although the shape of body portion  471  may vary, it preferably corresponds to the geometry of a single cell  454  of stent  450 . Wire  472  has two free end portions  474  that extend adjacent and substantially parallel to one another, and that are curved or hooked so as to lie at a spaced distance radially outward from body portion  471 . Preferably, the tip  476  of each free end portion  474  is blunt and/or rounded to reduce the likelihood of tips  476  damaging the native tissue hooked by anchor arm  470 . In addition or alternatively, a blunted and/or rounded end cap  478  may be assembled over or onto the tips  476  of free end portions  474  and fixed to tips  476 , for example by welding, to provide an atraumatic tissue contact surface. 
     Prosthetic heart valve  400  is shown at a possible intermediate stage of manufacture in  FIG. 4C  to better illustrate the attachment of anchor arms  470  to prosthetic heart valve  400 . After cuff  464  and leaflets  462  have been attached to stent  450 , anchor arms  470  may be coupled to prosthetic heart valve  400  at desired locations around stent  450 . As shown in  FIG. 4C , anchor arms  470  may be positioned within and/or adjacent to a selected cell  454   a  of stent  450  and connected to the prosthetic heart valve  400 , for example by suturing body portion  471  of anchor arm  470  to the struts  452  defining the perimeter of selected cell  454   a . The sutures coupling anchor arms  470  to prosthetic heart valve  400  may additionally pass through cuff  464 . Forces applied to free end portions  474  are transmitted to the body portion  471  of anchor arm  470 . With the above-described configuration of anchor arm  470  and its attachment to cell  454   a , those transmitted forces are distributed over a larger area of stent  450 , providing better reinforcement than if free end portions  474  were sewn or otherwise directly connected to stent  450  without the use of body portion  471 . 
     As noted above, wire  472  forming anchor arms  470  is preferably made from a shape-memory alloy. By using a shape-memory alloy, the shape of anchor arms  470  may be set, for example by heat setting, to take the illustrated shape in the absence of applied forces. However, forces may be applied to anchor arms  470  and to prosthetic heart valve  400  generally to reduce the radial size and/or bulk of the prosthetic heart valve when in the collapsed condition, which may facilitate intravascular (or other minimally invasive) delivery of the prosthetic heart valve via a delivery device (not shown). For example, as shown in  FIG. 4D , prosthetic heart valve  400  may be transitioned to the collapsed condition, with free end portions  474  of anchor arms  470  being distorted or “flipped” to point toward outflow end  412  rather than inflow end  410 . Prosthetic heart valve  400  may be maintained in the collapsed condition, for example by a surrounding sheath of a delivery device (not shown), as prosthetic heart valve  400  is delivered to native mitral valve  130 . When in a desired position relative to native mitral valve  130 , prosthetic heart valve  400  may be released from the delivery device. As the constraining forces are removed from prosthetic heart valve  400 , it begins to transition to the expanded condition, while anchor arms  470  move to their preset shape. Since anchor arms  470  are shape-set so that their free end portions  474  point toward inflow end  410 , anchor arms  470  revert to that shape when released from the delivery device. As the free end portions  474  of anchor arms  470  transition from pointing toward outflow end  412  to pointing toward inflow end  410 , native mitral valve leaflets  136 ,  138  are captured between the free end portions  474  and the body of stent  450 , as shown in  FIG. 4E . When hooked around native mitral valve leaflets  136 ,  138 , anchor arms  470  help anchor prosthetic heart valve  400  within native valve annulus VA and are particularly effective at resisting migration of the prosthetic heart valve into left atrium  122 . Distorting or flipping the anchor arms  470  while prosthetic heart valve  400  is maintained in the collapsed condition may reduce the profile of the collapsed valve, although prosthetic heart valve  400  may alternatively be put in the collapsed condition without distorting or flipping anchor arms  470 . 
     As described above, the stent  450  of prosthetic heart valve  400  may include two circumferential rows of annular cells  454 , with each row containing nine such cells. Although the use of nine cells  454  per row is merely an example, the use of an odd number of cells  454  per row in prosthetic heart valves for replacing native mitral valve  130  may cause difficulty in creating symmetry in the positioning of anchor arms  470  on the prosthetic heart valve. 
     While prosthetic heart valve  400  may be used as shown and described above in connection with  FIGS. 4A-E , a prosthetic heart valve may be provided with additional anchoring and/or sealing elements. For example,  FIGS. 5A-D  illustrate a prosthetic heart valve  500  that essentially comprises prosthetic heart valve  400  with a flange  580  coupled thereto. This embodiment has many elements that perform functions analogous to like-numbered elements of the previous embodiment, these elements having a leading digit of “5” instead of a “4”, so that elements  500 ,  510 ,  512 ,  550 ,  552 ,  554 ,  566 , and the like are analogous to previously-described elements  400 ,  410 ,  412 ,  450 ,  452 ,  454 ,  466 , etc. It will be noted that stent  550  is similar to stent  450 , but includes a plurality of anchor arms  570  extending therefrom. In one embodiment, a pair of anchor arms  570  may be provided on a portion of the stent  550 , for example, on the anterior side thereof, as is further described in later embodiments, additionally or alternatively, a plurality of anchor arms  570  may be disposed circumferentially around the stent  550  as shown in  FIG. 5 . 
     Additionally, prosthetic heart valve  500  includes flange  580  to facilitate the anchoring of the heart valve within native mitral valve annulus  130  and the prevention of PV leak. Flange  580  may be formed of a material braided to create various shapes and/or geometries to engage tissue. As shown in  FIG. 5A , flange  580  includes a plurality of braided strands or wires  586  arranged in three-dimensional shapes. In one example, wires  586  form a braided metal fabric that is resilient, collapsible and capable of heat treatment to substantially set a desired shape. One class of materials which meets these qualifications is shape-memory alloys, such as nitinol. Wires  586  may comprise various materials other than nitinol that have elastic and/or memory properties, such as spring stainless steel, tradenamed alloys such as Elgiloy® and Hastelloy®, CoCrNi alloys (e.g., tradename Phynox), MP35N®, CoCrMo alloys, or a mixture of metal and polymer fibers. Depending on the individual material selected, the strand diameter, number of strands, and pitch may be altered to achieve the desired shape and properties of flange  580 . 
     Flange  580  may include a body portion  582  terminating at an outflow end of the flange and a flared portion  584  terminating at an inflow end of the flange. Body portion  582  may be formed with a generally cylindrical or tubular geometry and may be configured to be circumferentially disposed around a portion of stent  550  and/or valve assembly  560 . Flange  580  may be coupled to stent  550  (and optionally to the leaflets and/or cuff) by sutures, for example. Flange  580  may be alternatively or additionally connected to stent  550  via a coupler, ultrasonic welds, laser welding, glue, adhesives, or other suitable means. In one particular embodiment, the wires  586  of the flange  580  are collected in marker bands and welded in groups, for example in a quantity of 12, although alternative quantities are possible. A coupler tube, formed of stainless steel, nitinol, platinum/iridium, MP35N, titanium, or the like, with corrosion resistance and suitable weld strength properties, may then be welded, for example, via a laser, to a strut  552  of the stent. As shown in the profile of  FIG. 5B , flange  580  may be connected to stent  550  at attachment position  5 P 1 , may flare out slightly to form a generally tubular body portion  582 , bulge out to form flared portion  584  and fold over itself to couple to stent  550  at attachment position  5 P 2 . At each attachment position  5 P 1 , 5 P 2  a number of strands of the wires  586  forming flange  580  may be tied or crimped together and attached to the strut  552  of stent  550 . By having multiple attachment positions (e.g.,  5 P 1  adjacent outflow end  512  and  5 P 2  adjacent inflow end  510 ) a three-dimensional structure may be formed, the structure having two portions  5 A 1 , 5 A 2  of braided material at least partially overlapping one another to form flange  580 , the two portions defining a cavity  5 C therebetween. 
     When coupled to stent  550 , body portion  582  of flange  580  is nearer outflow end  512  and flared portion  584  is nearer inflow end  510 . In the expanded condition, flared portion  584  extends a greater distance radially outwardly from the longitudinal axis L of prosthetic heart valve  500  than body portion  582 . In other words, as shown in  FIG. 5A , flared portion  584  may have a diameter  5 D 1  that is greater than the diameter  5 D 2  of body portion  582  when prosthetic heart valve  500  is in the expanded condition. In at least some examples, diameter  5 D 1  may be between 50 and 70 mm, while diameter  5 D 2  may be between 40 and 60 mm. Moreover, as shown in  FIG. 5B , flared portion  584  may radially extend a distance  5 R 1  from the stent, while body portion  582  may radially extend a distance  5 R 2  from the stent. In at least some examples, distance  5 R 1  may be between 10 and 25 mm, while distance  5 R 2  may be between 5 and 15 mm. 
     Flange  580  may be preset to take the illustrated shape in the absence of external forces. As with stent  450  and anchor arms  470  of  FIG. 4A , flange  580  may be collapsed to a decreased profile to facilitate minimally invasive delivery. For example, prosthetic heart valve  500  may be transitioned from the expanded condition to the collapsed condition and maintained in the collapsed condition by a surrounding sheath of a delivery device. 
     Prosthetic heart valve  500  may be delivered to the implant site in the collapsed condition and, when in the desired position relative to native mitral valve  130 , transitioned to the expanded condition, for example by removing the surrounding sheath of the delivery device. During the transition from the collapsed condition to the expanded condition, anchor arms  570  revert to the preset shape, capturing native mitral valve leaflets  136 ,  138  between anchor arms  570  and corresponding portions of stent  550 . Flange  580  also transitions from the collapsed condition to the expanded condition, assuming its preset shape. When implanted and in the expanded condition, flange  580  provides a large surface area to help anchor prosthetic valve  500  within the native valve annulus, and may be particularly effective at resisting movement of prosthetic heart valve  500  toward left ventricle  124 . Specifically, flange  580  is sized to have an expanded diameter that is too large to pass through the native valve annulus. Because flange  580  is coupled to stent  550 , prosthetic heart valve  500  is restricted from migrating into left ventricle  124  during normal operation of prosthetic heart valve  500 . Thus, the combination of anchor arms  570  engaged with the mitral valve leaflets, and flange  580  engaged with the tissue on the atrial side of the mitral valve annulus, helps to securely anchor prosthetic heart valve  500  within the mitral valve annulus and limits its migration toward either the left atrium or the left ventricle. 
     In addition to providing anchoring capabilities, flange  580  may improve sealing between prosthetic heart valve  500  and the native valve annulus. For example, a covering layer  588 , such as a polyester fabric or tissue, may be placed over portions  5 A 1 , 5 A 2  of flange  580  ( FIG. 5C ). Alternatively, only a portion of flange  580  may be covered with covering layer  588  (e.g., only portion  5 A 1 , only portion  5 A 2  or only a fraction of portions  5 A 1 ,  5 A 2 ). Covering layer  588  may enhance tissue ingrowth into prosthetic heart valve  500  after implantation and may also enhance the fluid seal, and thus help prevent PV leak, between the outer diameter of prosthetic heart valve  500  and the adjacent portions of the native mitral valve annulus. In a variation hereof, a covering layer  588  may be applied to the inside surface of flange  580 , or to both the outside and inside surfaces of flange  580  to improve sealing between prosthetic heart valve  500  and the native valve annulus. In another variation, shown in  FIG. 5D , portions  5 A 1 ′, 5 A 2 ′ of flange  580 ′ are disposed closer together and cavity  5 D is formed, which is smaller than cavity  5 C, resulting in a flared portion  584 ′ that is flatter than that described above. 
       FIG. 6A  is a schematic cross-sectional view of prosthetic heart valve  600  in accordance with a further embodiment of the disclosure. Prosthetic heart valve  600  may be similar to prosthetic heart valve  500  in certain respects. For example, prosthetic heart valve  600  is collapsible and expandable and designed for replacement of a native mitral valve, having a substantially cylindrical shape with an inflow end  610  and an outflow end  612 . Prosthetic heart valve  600  may also include a valve assembly (not shown) having three leaflets attached to a cylindrical cuff in substantially the same manner as described above in connection with previously-described prosthetic valves. It should be understood that prosthetic heart valve  600  is not limited to replacement of mitral valves, and may be used to replace other heart valves. 
     Prosthetic heart valve  600  may include stent  650 , which generally extends between inflow end  610  and outflow end  612  and includes a plurality of struts forming rows of cells. CAFs (not shown) may be included near outflow end  612  for coupling the leaflets to the stent. Prosthetic heart valve  600  may also include a flange  680  similar to flange  580  described above, and formed of any of the materials described, such as braided nitinol wires. 
     In contrast to the previous embodiments, flange  680  has an asymmetric configuration about a central longitudinal axis L of prosthetic heart valve  600 . Specifically, the flange forms different shapes on the anterior and posterior sides of the prosthetic heart valve. On the posterior side, flange  680  has a flared portion  684 P and a body portion  682 P that are similar to those of  FIGS. 5A-B . It is of note that body portion  682 P may terminate before the extreme end of the outflow end  612  of the valve so as not cover all of stent  650 , and that an exposed portion  685 P of stent  650  may be formed at the outflow end  612  on the posterior side of the valve. 
     Conversely, on the anterior side of the prosthetic heart valve, flange  680  has the same or similar flared portion  684 A, but a different body portion  682 A which leaves an exposed portion  685 A of stent  650  that is much larger than exposed portion  685 P. Specifically, body portion  682 A is formed such that only about half of stent  650  is covered by flange  680  on the anterior side. In at least some examples, exposed portion  685 A of stent  650  is between about 10% and about 80% of the total length of stent  650  in the fully expanded condition, or between about 30% and about 60% of the total length of stent  650 . Additionally, the coverage of flange  680  may be determined by the location of its points of attachment to stent  650 . For example, in the example shown in  FIG. 6A , twelve attachment points are shown, six attachment points  6 P 1 - 6 P 6  near inflow end  610  and six attachment points  6 P 7 - 6 P 12  defining the extent to which flange  680  extends toward outflow end  612 . As shown in  FIG. 6A , five of the lower attachment points  6 P 7 - 6 P 11  are generally aligned in the circumferential direction of stent  650 , while the sixth attachment point  6 P 12  is disposed approximately halfway between inflow end  610  and outflow end  612 . It will be understood that the number of attachment points may be varied to include two, three, four, five, six, seven, eight, nine, ten or more attachment points, but that the attachment points on the anterior side may be intentionally misaligned with the attachment points on the posterior side of the valve to form the intended exposed portions. In some other examples, the number of attachment points in a row is equal to the number of cells in one row of the stent, each attachment point corresponding to one cell in the row. 
     The relatively large exposed portion  685 A at the anterior side of the stent permits uninterrupted blood flow and avoids obstruction of the left ventricular outflow tract. To further assist in limiting obstruction of the left ventricular outflow tract, one or more anchor arms  670  may be disposed adjacent exposed portion  685 A to retain the native valve leaflet in place during operation of the valve and further prevent the native valve leaflet from moving toward the left ventricular outflow tract. Conversely, on the posterior side, a plurality of stabilizing wires  672  may be used instead of an anchoring arm. In fact, stabilizing wires  672  may be disposed circumferentially around flange  680  at all locations. The stabilizing wires  672 , which may be in the form of a hook or a barb, push against or pierce native tissue during radial expansion to further stabilize the prosthetic heart valve. Because the posterior native leaflet and the anterior native leaflet have different sizes and geometries, the use of a combination of stabilizing wires and anchor arms may yield better anchoring than a symmetric configuration. For example, the shorter native posterior leaflet may be more easily grasped with wires  672  than with an anchor arm. 
       FIG. 6B  is a top schematic representation of prosthetic heart valve  600 . As shown, stent  650  is disposed at the center of prosthetic heart valve  600 , while flared portion  684  extends a radial distance r 1  away from stent  650  on all sides. In at least some examples, radial distance r 1  is between about 50 mm and about 70 mm Posterior body portion  682 P extends a radial distance r 2  away from stent  650  adjacent the native posterior leaflet, but does not have the same extension at the native anterior leaflet. In at least some examples, radial distance r 2  is between about 5 mm and about 25 mm adjacent the posterior leaflet. Additionally, a number of stabilizing wires  672  are circumferentially disposed around body portion  682  with the exception of the region near the left ventricular outflow tract. 
     A variation of prosthetic heart valve  600  is shown in  FIG. 6D  and marked as prosthetic heart valve  600 ′. Prosthetic heart valve  600 ′ includes stent  650  and flange  680 ′ and is similar to prosthetic heart valve  600  with a few exceptions. First, flange  680 ′ includes flared portion  684 P′ on the posterior side and flared portion  684 A′ on the anterior side, both of which are flatter than corresponding flared portions  684 P, 684 A and similar to that described with reference to  FIG. 5D . Additionally, body portion  682 A′ is closer to anchoring arms  670  so that a native leaflet or tissue may be grasped therebetween. Attachment point  6 P 12  is also formed closer to the outflow end  612  so that the device is more uniform along the outflow end. 
       FIG. 6C  is a top schematic representation of prosthetic heart valve  600 ′ which slightly varies from heart valve  600 . As shown, stent  650  is disposed at the center of prosthetic heart valve  600 ′, while flared portion  684 ′ extends a substantially constant radial distance r 1 ′ away from stent  650  on all sides. In at least some examples, radial distance r 1 ′ is between about 50 mm and about 70 mm. The difference in this configuration is the shape of the body portion  682 ′. Specifically, body portion  682 ′ has an oval lateral-cross-section instead of being circular, which may be a better fit for certain patients. It is also contemplated the body portion may have a D-shaped lateral-cross-section to match the shape of the native annulus to provide an improved fit. Posterior body portion  682 P′ extends a radial distance r 2 ′ away from stent  650  adjacent the native posterior leaflet, but does not have the same extension at the native anterior leaflet. In at least some examples, radial distance r 2 ′ is between about 5 mm and about 25 mm adjacent the posterior leaflet. By combining a flange  680 ′ having portions with an oval, or irregularly-shaped lateral cross-section with a circular stent (and thus, valve assembly) several benefits may be gained. First, circular stents and valve assemblies may be easier to manufacture and their operation is better understood. Thus, it may be easier to maintain this circular configuration of the stent and valve assembly while modifying the outer components (e.g., flange) depending on the intended application. Second, the assembly may be used with large annuli. Specifically, it is postulated that a valve assembly with a 29 mm diameter may provide adequate flow to most patients. Thus, for extremely large annuli, a standard 29 mm valve assembly may be used in conjunction with larger flanges as desired. This reduces the need for making valve assemblies in multiple different sizes, while allowing the prosthetic heart valve to be crimped to the smallest possible diameter. Although it is contemplated that other sized valve assemblies may be used when desired, as valves having smaller diameters reduce crimp profile, while larger valves have the benefit of increasing fluid flow. 
     Another variation of prosthetic heart valve  600  is shown in  FIG. 6E  and marked as prosthetic heart valve  600 ″. Prosthetic heart valve  600 ″ includes stent  650 ″ and flange  680 ″ and is similar to prosthetic heart valve  600  with a few exceptions. First, flange  680 ″ is limited only to a flared portion  684 ″ adjacent the atrium and does not include a body portion. Additionally, a number of arms  692  are circumferentially disposed around stent  650 ″ adjacent outflow end  612 . Arms  692  may be integrally formed with stent  650 ″ or formed of a separate metallic body that is later welded to the stent. Each of arms  692  includes a number of stabilizing wires  693  similar to those described above, except for arm  694  disposed on the anterior side, which does not include such wires. In one example, anterior arm  694  may be released first to capture a native valve leaflet between it and the rest of stent  650 ″, and arms  692  having wires  693  may be deployed sequentially thereafter. Additionally, arms  692 , 694  may be configured to transition between a first, delivery condition and a second, deployed condition, the arms in the first condition extending toward the outflow end and in the second condition extending toward the inflow end. 
       FIG. 7A  illustrates yet another example of a prosthetic heart valve  700 A having stent  750  and asymmetric flange  780 A. The flange  780 A may be formed of a braided material, such as nitinol, to create various shapes and/or geometries to engage tissue. In this example, flange  780 A is formed of two portions,  7 A 1 , 7 A 2  that are joined together. Additionally, flange  780 A is disposed closer to outflow end  712  than to inflow end  710 . Such a configuration may limit the possibility of obstructing the left ventricular outflow tract. For example, as the anchor arms, flange and atrial seal are brought closer to the outflow side of the stent, it may effectively position the prosthesis closer to the atrium, as opposed to the ventricle, making it less likely to obstruct the outflow tract. Moreover, the use of anchoring arms  770  on one side and stabilizing wires  772  on an opposite side may help in anchoring the prosthetic heart valve as described above. Anchoring arms  770  may also aid in capturing a native valve leaflet and prevent the leaflet from obstructing the left ventricular outflow tract. 
       FIG. 7B  illustrates yet another example of a prosthetic heart valve  700  having stent  750  and asymmetric flange  780 B formed of two portions  7 A 1 ′, 7 A 2 ′. In this example, flange  780 B is substantially similar to flange  780 A, except that it also includes an S-shaped curve  790  on the posterior side to sandwich the native valve annulus therein, the S-shaped curve having a number of stabilizing wires  772  disposed on an outer surface thereof. One or more anchoring arms  770  are disposed on an anterior side of the stent opposite S-shaped curve  790 . 
     In yet another example, prosthetic heart valve  700 C having stent  750 C and asymmetric flange  780 C is shown in  FIG. 7C . In this example, flange  780 C is formed of a braided material that is substantially similar to flange  780 A, but is coupled to base  795 , which forms part of stent  750 C. Base  795  and flange  780 C may be formed of different materials. Specifically, base  795  may be integrally formed with the stent or later welded to the stent, and may be formed of a thicker material that is more fatigue-resistant than just a braid. Alternatively, the entire flange may be made from a laser cut stent so that all of base  795 , flange  780 C and stent  750 C are formed of the same material. A separate arm  794  may be used for sandwiching the native valve leaflet as previously described. 
     It will be understood that the shape of the flange may be modified as desired. For example,  FIG. 8  shows a stent  800  and a number of possible profiles for a flange. Flange  880 A is generally straight and extends toward inflow end  810  of the stent  800 . Flange  880 B likewise initially extends toward inflow end  810 , but has a steep curve that allows it to extend back toward outflow end  812 . Flange  880 C is the flattest of the configurations, and flange  880 D has a slight curve and extends toward outflow end  812  as shown. These and other profiles are possible. Additionally, it will be understood that the same or different profiles may be used on the anterior side and the posterior side of the device as previously described. Moreover, as shown, all of the configurations of flanges  880 A-D are shown as being attached to the stent closer to outflow end  812  than to inflow end  810 . This allows for most of the device to be seated closer to the atrium than the ventricle, reducing the risk of obstruction of the left ventricular outflow tract. 
     According to the disclosure, a prosthetic heart valve has an inflow end and an outflow end, and may include a stent having a collapsed condition, an expanded condition, and a plurality of cells arranged in circumferential rows, the stent has an anterior side configured and arranged to be disposed adjacent an anterior native valve leaflet, and a posterior side configured and arranged to be disposed adjacent a posterior native valve leaflet, a valve assembly disposed within the stent and with a plurality of leaflets, and a flange disposed about the stent, the flange has a flared portion adjacent the inflow end of the prosthetic heart valve and a body portion that extends from the flared portion to the outflow end, the flange extends between a first set of attachment points adjacent the inflow end, and a second set of attachment points adjacent the outflow end; and/or 
     the flange is formed of a braided mesh, and the body portion extends a first distance toward the outflow end on one side of the prosthetic heart valve, and extends a second distance toward the outflow end on another side of the prosthetic heart valve, the second distance being less than the first distance; and/or 
     the body portion extends over the stent to define a first exposed portion of the stent on the anterior side of the stent, and a second exposed portion of the stent on the posterior side of the stent, the first exposed portion being larger than the second exposed portion; and/or 
     the body portion extends over the stent to define a first exposed portion of the stent on the anterior side of the stent, the first exposed portion being configured and arranged to allow unimpeded blood flow through the left ventricular outflow tract; and/or 
     the body portion covers about half of the stent on an anterior side of the stent; and/or 
     the flared portion is symmetric about a longitudinal axis of the stent; and/or 
     the prosthetic heart valve further includes a cover layer disposed over at least a portion of the flange; and/or 
     the prosthetic heart valve further includes at least one anchor arm disposed adjacent the anterior side of the stent; and/or 
     the prosthetic heart valve further includes a plurality of stabilizing wires disposed adjacent a posterior side of the stent; and/or 
     the flared portion of the flange has a first diameter in an expanded condition of the flange and the body portion of the flange has a second diameter in the expanded condition of the flange, the second diameter being smaller than the first diameter; and/or 
     both the flared portion and the body portion of the flange have circular lateral cross-sections in an expanded condition of the flange; 
     the flared portion has a circular lateral cross-section in an expanded condition of the flange, and the body portion of the flange has an oval lateral cross-section in an expanded condition of the flange. 
     According to the disclosure, a prosthetic heart valve may also have an inflow end and an outflow end, a stent having a collapsed condition, an expanded condition, and a plurality of cells arranged in circumferential rows, the stent has an anterior side configured and arranged to be disposed adjacent an anterior native valve leaflet, and a posterior side configured and arranged to be disposed adjacent a posterior native valve leaflet, a valve assembly disposed within the stent and with a plurality of leaflets, and a flange disposed about the stent, the flange being asymmetric about a longitudinal axis such that a posterior side of the flange has a different shape than an anterior side of the flange; and/or 
     the flange is formed of a braided mesh and has a flared portion adjacent the inflow end of the prosthetic heart valve and a body portion extending from the flared portion to the outflow end; and/or 
     the flared portion has a same shape on the anterior side of the flange and on the posterior side of the flange, and the body portion has a different shape on the anterior side of the flange than on the posterior side of the flange; and/or 
     the body portion extends a first distance toward the outflow end on one side of the prosthetic heart valve, and extends a second distance toward the outflow end on another side of the prosthetic heart valve, the second distance being less than the first distance; and/or 
     the body portion extends over the stent to define a first exposed portion of the stent on the anterior side of the stent, and a second exposed portion of the stent on the posterior side of the stent, the first exposed portion being larger than the second exposed portion; and/or 
     the body portion extends over the stent to define a first exposed portion of the stent on the anterior side of the stent, the first exposed portion being configured and arranged to allow unimpeded blood flow through the left ventricular outflow tract; and/or 
     the prosthetic heart valve further includes at least one anchor arm disposed adjacent the anterior side of the stent, and a plurality of stabilizing wires disposed adjacent a posterior side of the stent; and/or 
     the flange is formed of at least two portions of material that overlap one another. 
     Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims. For example, any of the anchor arms described above may be integrally formed with the stent and laser cut from the stent body. In addition, features of embodiments described herein may be combined with features of other embodiments described herein without departing from the scope of the invention.