Patent Publication Number: US-2019183639-A1

Title: Transcatheter Mitral Valve: Off-Center Valve Design

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of the filing date of U.S. Provisional Patent Application No. 62/607,493, filed Dec. 19, 2017, the disclosure of which is hereby incorporated by reference herein. 
    
    
     BACKGROUND OF THE DISCLOSURE 
     The present disclosure relates to prosthetic heart valves and, in particular, to collapsible prosthetic mitral valves. 
     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 must first be 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 For self-expanding valves, on the other hand, the stent automatically expands as the sheath covering the valve is withdrawn. 
     Two challenges that arise when designing and implanting transcatheter mitral valves are left ventricular outflow tract (LVOT) obstruction and electrical conduction problems. Both problems may occur when a prosthetic mitral valve extends too far into the left ventricle and/or at too much of an angle with respect to the longitudinal axis of the native mitral valve annulus. LVOT obstruction may occur when the physical structure of the mitral valve is positioned in the path of blood flowing from the left ventricle to the aorta through the aortic valve. Electrical conduction problems may occur when a metallic stent frame of a prosthetic mitral valve physically contacts the septum wall separating the left and right ventricles. For these and other reasons, there is still room for improvement in the design and transcatheter implantation of prosthetic mitral valves. 
     BRIEF SUMMARY 
     According to one aspect of the disclosure, a collapsible and expandable prosthetic mitral valve includes a stent having an inflow end, an outflow end, and a first central longitudinal axis extending from the inflow end to the outflow end in an expanded condition of the prosthetic mitral valve. A valve assembly is disposed within the stent. A flange is formed of a braided mesh and has a body portion coupled to the stent and a flared portion adjacent the inflow end of the stent. A second central longitudinal axis extends through the flared portion in the expanded condition of the prosthetic mitral valve. The first central longitudinal axis is offset from the second central longitudinal axis. 
     According to another aspect of the disclosure, a method of implanting a prosthetic mitral valve includes introducing a delivery device to a native mitral valve annulus while the prosthetic mitral valve is maintained in a collapsed condition by the delivery device. The prosthetic mitral valve is transitioned into an expanded condition so that a stent of the prosthetic mitral valve is positioned within the native mitral valve annulus to implant the prosthetic mitral valve. The stent includes a valve assembly disposed therein. Upon the transition, a flared portion of a flange of the prosthetic mitral valve contacts an atrial side of the native mitral valve annulus, the flange being formed of a braided mesh and having a body portion coupled to the stent. Upon implantation of the prosthetic mitral valve, the native mitral valve annulus has a first central longitudinal axis, and the stent has a second central longitudinal axis offset from the first central longitudinal axis. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         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 a side view of the prosthetic heart valve of  FIG. 4A  rotated about its longitudinal axis. 
         FIG. 4C  is a highly schematic longitudinal cross-section of the prosthetic heart valve of  FIG. 4A . 
         FIG. 4D  is an enlarged, isolated perspective view of an anchor feature of the prosthetic heart valve of  FIG. 4A . 
         FIG. 4E  is a side view of the prosthetic heart valve of  FIG. 4A  in a stage of manufacture. 
         FIG. 4F  is a highly schematic longitudinal cross-section of the prosthetic heart valve of  FIG. 4A  in a collapsed condition. 
         FIG. 4G  is a highly schematic representation of the prosthetic heart valve of  FIG. 4A  implanted into a native mitral valve annulus. 
         FIG. 4H  is a highly schematic bottom view of the outflow end of the prosthetic heart valve of  FIG. 4A . 
         FIG. 4I  is a highly schematic bottom view of the outflow end of a prosthetic heart valve according to another aspect of the disclosure. 
         FIG. 5A  is a side view of a prosthetic heart valve according to a further aspect of the disclosure. 
         FIG. 5B  is a side view of the prosthetic heart valve of  FIG. 5A  rotated about its longitudinal axis. 
         FIG. 5C  is a highly schematic top view of the inflow end of the prosthetic heart valve of  FIG. 5A . 
         FIG. 5D  is a highly schematic bottom view of the outflow end of the prosthetic heart valve of  FIG. 5A . 
         FIG. 5E  is a highly schematic longitudinal cross-section of the prosthetic heart valve of  FIG. 5A  in the expanded condition. 
         FIG. 5F  is a highly schematic longitudinal cross-section of the prosthetic heart valve of  FIG. 5A  in the collapsed condition. 
         FIG. 5G  is a highly schematic representation of the prosthetic heart valve of  FIG. 5A  implanted into a native mitral valve annulus. 
         FIG. 5H  is an enlarged, highly schematic cross-section of a portion of the flange of the prosthetic heart valve of  FIG. 5A . 
         FIG. 6A  is a side view of a prosthetic heart valve according to yet another aspect of the disclosure. 
         FIG. 6B  is a side view of the prosthetic heart valve of  FIG. 6A  rotated about its longitudinal axis. 
         FIG. 6C  is a bottom perspective view of the outflow end of the prosthetic heart valve of  FIG. 6A . 
         FIG. 6D  is a highly schematic top view of the inflow end of the prosthetic heart valve of  FIG. 6A . 
         FIG. 6E  is a highly schematic bottom view of the outflow end of the prosthetic heart valve of  FIG. 6A . 
         FIG. 6F  is a highly schematic longitudinal cross-section of the prosthetic heart valve of  FIG. 6A  in a collapsed condition. 
         FIG. 6G  is a highly schematic representation of the prosthetic heart valve of  FIG. 6A  implanted into a native mitral valve annulus. 
         FIG. 7A  is a highly schematic bottom view of the outflow end of a prosthetic heart valve according to another aspect of the disclosure. 
         FIG. 7B  is a side view of a prosthetic heart valve according to a further aspect of the disclosure incorporating features of the prosthetic heart valve of  FIG. 7A . 
         FIG. 7C  is a side view of the prosthetic heart valve of  FIG. 7B  rotated about its longitudinal axis. 
         FIG. 7D  is a highly schematic top view of the inflow end of the prosthetic heart valve of  FIG. 7B . 
         FIG. 7E  is a highly schematic bottom view of the outflow end of the prosthetic heart valve of  FIG. 7B . 
         FIG. 7F  is a highly schematic longitudinal cross-section of the prosthetic heart valve of  FIG. 7B  in the expanded condition. 
         FIG. 7G  is a highly schematic longitudinal cross-section of the prosthetic heart valve of  FIG. 7B  in the collapsed condition. 
         FIG. 7H  is a highly schematic representation of the prosthetic heart valve of  FIG. 7B  implanted into a native mitral valve annulus. 
         FIG. 8A  is a side view of a prosthetic heart valve according to another aspect of the disclosure. 
         FIG. 8B  is a highly schematic top view of the inflow end of the prosthetic heart valve of  FIG. 8A . 
         FIG. 8C  is a highly schematic representation of the prosthetic heart valve of  FIG. 8A  implanted into a native valve annulus. 
         FIG. 9A  is a highly schematic top view of the inflow end of a prosthetic heart valve according to yet another aspect of the disclosure. 
         FIG. 9B  is a highly schematic representation of the prosthetic heart valve of  FIG. 9A  implanted into a native valve annulus. 
     
    
    
     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 properly 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 properly 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 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 of 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 of 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 to interfere with atrial function in the native valve annulus. 
     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”). 
       FIG. 4A  is a side view of a prosthetic heart valve  400  in accordance with one embodiment of the disclosure.  FIG. 4B  shows prosthetic heart valve  400  rotated approximately 180 degrees about its longitudinal axis compared to  FIG. 4A . 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 for replacement of 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. 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 illustrated, cells  454  are generally diamond shaped. 
     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 valve assembly  460  having three leaflets  462  attached to a cylindrical cuff  464 . It should be understood that although native mitral valve  130  has two leaflets  136 ,  138 , prosthetic heart valve  400  may have three leaflets, 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 . Because prosthetic heart valve  400  has three leaflets  462 , it also has three CAFs  466 , which provide points of attachment for adjacent leaflets  462  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  that hook under native mitral valve leaflets  136 ,  138  to help prevent prosthetic heart valve  400  from migrating into left atrium  122 . 
     A single anchor arm  470  is shown in  FIG. 4D . 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 formed of 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 stage of manufacture in  FIG. 4E  to better illustrate the attachment of anchor arms  470  to prosthetic heart valve  400 . After valve assembly  460  and cuff  464  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. 4E , anchor arms  470  may be positioned within and/or adjacent to a selected cell  454  of stent  450  and connected to the prosthetic heart valve  400 , for example by suturing the body portion  471  of anchor arm  470  to the struts  452  defining the perimeter of selected cell  454 . 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 , 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. 4F , prosthetic heart valve  400  may be transitioned to the collapsed condition, with free end portions  474  of anchor arms  470  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 the site of 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 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. 4G . 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 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 cells  454 . Although the use of nine cells  454  is merely an example, the use of an odd number of cells  454  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. For example, it is preferable, although not necessary, to use two anchor arms  470  for each of the two native mitral valve leaflets to better distribute the forces caused by hooking or clamping native the mitral valve leaflets between anchor arms  470  and stent  450 . With nine substantially equally-sized cells  454 , or any other odd number of similarly sized cells, symmetry in the positioning of anchor arms  470  is difficult to achieve.  FIG. 4H  shows prosthetic heart valve  400  as viewed from outflow end  412 . It should be understood that although stent  450  is illustrated as a regular nine-sided polygon (with each side representing a single cell  454 ), this representation is for purposes of clarity only and prosthetic heart valve  400 , including stent  450 , may take a substantially cylindrical shape when in the expanded condition. As shown in  FIG. 4H , two anchor arms  470   a  and  470   b  may be coupled to stent  450  at adjacent cells  454 , for example on cells  454  on either side of a CAF  466 . The remaining two anchor arms  470   c  and  470   d  cannot be placed on adjacent cells  454  diametrically opposed to anchor arms  470   a  and  470   b  so as to maintain the symmetry of anchor arms  470 . When positioning two pairs of anchor arms on substantially diametrically opposed portions of stent  450 , it is preferable to maintain the symmetry of the anchor arms relative to at least one plane P 1  dividing prosthetic heart valve  400 . As shown in  FIG. 4H , for a stent having nine substantially similarly-sized cells, this symmetry may be achieved by coupling the other pair of anchor arms  470   c  and  470   d  to stent  450  at two cells  454  that are separated by one cell  454 . When implanting prosthetic heart valve  400 , it is preferable to hook anchor arms  470   a  and  470   b  under the posterior leaflet  136  of native mitral valve  130 , with anchor arms  470   c  and  470   d  hooked under the anterior leaflet  138  of native mitral valve  130 . With this configuration, one CAF  466  abuts posterior leaflet  136  and two CAFs abut anterior leaflet  138 . 
     The teachings provided above in connection with prosthetic heart valve  400  may be applied to a stent that is similar to stent  450 , but that has an even number of cells. For example,  FIG. 4I  shows a prosthetic heart valve  400 ′ that incorporates a stent  450 ′ having two circumferential rows of twelve cells  454 ′ having substantially equal sizes. Similar to the illustration of  FIG. 4H , stent  450 ′ in  FIG. 4I  is shown as a regular twelve-sided polygon for purposes of clarity only, and prosthetic heart valve  400 ′ and stent  450 ′ may be substantially cylindrical when in the expanded condition. The use of a stent  450 ′ having an even number of substantially similarly sized cells  454 ′ makes it easier to couple a first pair of anchor arms  470   a ′ and  470   b ′ to a first side of stent  450 ′ and a second pair of anchor arms  470   c ′ and  470   d ′ to a diametrically-opposed second side of stent  450 ′ while maintaining the symmetry of the anchor arms  470   a ′- 470   d ′ relative to two planes P 2 , P 3 . In other words, the circumferential spacing between anchor arms  470   a ′ and  470   b ′ may be substantially equal to the spacing between anchor arms  470   c ′ and  470   d ′, while the circumferential spacing between anchor arms  470   a ′ and  470   c ′ may be substantially equal to the spacing between anchor arms  470   b ′ and  470   d ′. When prosthetic heart valve  400 ′ is implanted, this symmetry about two planes P 2 , P 3  may provide for a more uniform distribution of forces than prosthetic heart valves exhibiting such symmetry in less than two planes (such as prosthetic heart valve  400  described above). In addition, the twelve-cell configuration may provide for more uniform expansion of the stent compared to the nine-cell configuration. 
     While prosthetic heart valve  400  may be used as shown and described above in connection with  FIGS. 4A-I , 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. Flange  580  may facilitate the anchoring of heart valve  500  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  FIGS. 5A-D , 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 cylindrical or tubular geometry and may be configured to be circumferentially disposed around a portion of stent  450  and/or valve assembly  460 . Flange  580  may be coupled to stent  450  (and optionally to valve assembly  460  and/or cuff  464 ) by sutures, for example. Flange  580  may be alternatively or additionally connected to stent  450  via ultrasonic welds, glue, adhesives, or other suitable means. When coupled to stent  450 , body portion  582  of flange  580  is nearer outflow end  512  and flared portion  584  is nearer inflow end  510 . When 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. 5C , flared portion  584  may have a diameter D 1  that is greater than the diameter D 2  of body portion  582  when prosthetic heart valve  500  is in the expanded condition. In addition, the distance which flared portion  584  extends radially outwardly from longitudinal axis L may increase nearer inflow end  510 . 
     Flange  580  may be preset to take the illustrated trumpet shape in the absence of external forces. As with stent  450  and anchor arms  470 , 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 ( FIGS. 5A-E ) to the collapsed condition ( FIG. 5F ) and maintained in the collapsed condition by a surrounding sheath of a delivery device. Anchors  470  may flip and point toward outflow end  512  as described in connection with  FIG. 4F , and flange  580  may collapse radially inwardly and become substantially cylindrical and/or significantly less flared than in the expanded condition. The body  582  of flange  580  may be positioned between anchor arms  470  and the remainder of stent  450 . 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 , may be 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  470  revert to the preset shape as described in connection with  FIG. 4F , capturing native mitral valve leaflets  136 ,  138  between anchor arms  470  and corresponding portions of stent  450 . Flange  580  also transitions from the collapsed condition to the expanded condition, assuming its preset shape shown in  FIG. 5G . When implanted and in the expanded condition, flange  580  provides a large surface area to help anchor prosthetic valve  500  within native valve annulus VA, and may be particularly effective at resisting movement of prosthetic heart valve  500  toward left ventricle  124 . Specifically, flange  580  has an expanded diameter that is too large to pass through native valve annulus VA. Because flange  580  is coupled to stent  450 , 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  470  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 native valve annulus VA. In particular, as shown in  FIG. 5H , flange  580  may be formed with an outer layer  580   a  and an inner layer  580   b , for example by folding one portion of braided wires  586  over another portion of braided wires  586 . A fabric layer  588 , such as a polyester fabric, may be inserted or sandwiched between outer layer  580   a  and inner layer  580   b . Fabric 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 native mitral valve annulus VA. Although flange  580  is described as being folded over onto itself, alternative configurations may be suitable for holding fabric layer  588 , for example by weaving or braiding two separate layers of braided wires  586  together. In a variation hereof, a single fabric layer  588  may be applied to the outside surface of flange  580 , 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 native valve annulus VA. 
       FIG. 6A  is a side view of prosthetic heart valve  600  in accordance with a further embodiment of the disclosure.  FIG. 6B  illustrates prosthetic heart valve  600  rotated approximately 90 degrees about its longitudinal axis compared to  FIG. 6A . Prosthetic heart valve  600  may be similar to prosthetic heart valve  300  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 having three leaflets attached to a cylindrical cuff, in substantially the same manner as described above in connection with prosthetic heart valve  400 . 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  652  forming two circumferential rows of cells  653   a ,  653   b . CAFs  666  may be included near outflow end  612 . First row of cells  653   a  is disposed adjacent outflow end  612  and includes fully symmetric cells  654  alternating with second cells  655 . Fully symmetric cells  654  may be substantially diamond-shaped and include four substantially straight struts  654   a - d  of equal length. Cells  654  are fully symmetric in that they are symmetric about a vertical line extending from the intersection of struts  654   a  and  654   b  to the intersection of struts  654   c  and  654   c , and about a horizontal line extending from the intersection of struts  654   a  and  654   c  to the intersection of struts  654   b  and  654   d . Cells  655  may include a pair of substantially straight struts  655   a ,  655   b  which form a V-shape attached to two substantially curved struts  655   c ,  655   d . Cells  655  are partially symmetric in that they are symmetric only about a vertical line extending from the intersection of struts  655   a  and  655   b  to the intersection of struts  655   c  and  655   d . Engaging arms  670  may be nested within each cell  655 . Engaging arms  670  may be pivotably connected to cells  655  and configured to engage portions of heart tissue (e.g., native mitral valve leaflets) when prosthetic heart valve  600  is deployed in a patient, similar to anchor arms  470  described above. Second row of cells  653   b  may include a plurality of asymmetric cells  656  formed by two struts shared with cells from first row  653   a  (e.g., struts  654   c  and  655   d  or struts  654   d  and  655   c ) and two substantially straight struts  656   a ,  656   b . Second row of cells  653   b  may also include a plurality of fully symmetric cells  657  substantially similar or identical to fully symmetric cells  654 . 
     As shown in  FIGS. 6A-E , stent  650  is formed of two rows of cells, each row having twelve cells and is thus referred to as a twelve-cell configuration. The considerations regarding the placement of engaging arms  670  around the circumference of stent  650  are similar to those described above with respect to the placement of anchor arms  470 ′ on twelve-cell stent  450 ′. In particular, first row of cells  653   a  may include two sets of three fully symmetric cells  654  on diametrically opposing portions of stent  650 . Between each set of fully symmetric cells  654  may be another set of three cells, each set including two partially symmetric cells  655  having engaging arms  670  nested therein with a fully symmetric cell  654  positioned between the two partially symmetric cells  655 . Because stent  650  has an even number of cells in first circumferential row  653   a , in this case twelve, engaging arms  670  may be positioned symmetrically relative to two planes P 4 , P 5 , each bisecting prosthetic heart valve  600 . 
     Each engaging arm  670  may be formed of a shape-memory alloy, and is preferably formed from the same material as stent  650 . For example, stent  650  and engaging arms  670  may be formed from a single tube of Nitinol, for example by laser cutting. Engaging arms  670  may include two substantially parallel struts  670   a ,  670   b  connected to one another by rounded strut  670   c . Engaging arms  670  may be shape set, for example by heat setting, so that in the absence of external forces, the free end of engaging arm  670  defined by strut  670   c  is positioned radially outwardly from the partially symmetric cell  655  in which the engaging arm is nested. However, forces may be applied to engaging arms  670  and to prosthetic heart valve  600  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. 6F , prosthetic heart valve  600  may be transitioned to the collapsed condition, with engaging arms  670  constrained so that each engaging arm is positioned substantially within a surface defined by the partially symmetric cell  655  in which the engaging arm is nested. In other words, when in the collapsed condition shown in  FIG. 6F , engaging arms  670  do not protrude a significant distance radially outwardly from stent  650 . Prosthetic heart valve  600  may be held in the collapsed condition by the delivery device as it is delivered to native mitral valve  130 . When in a desired position relative to native mitral valve  130 , prosthetic heart valve  600  may be released from the delivery device. As constraining forces are removed from prosthetic heart valve  600 , it begins to transition to the expanded condition, while engaging arms  670  move to their preset shape projecting radially outwardly from the rest of stent  650 . Once engaging arms  670  are in their preset shape, prosthetic heart valve  600  may be pulled (or pushed) toward left atrium  122  until engaging arms  670  hook under native mitral valve leaflets  136 ,  138 , as shown in  FIG. 6G . The rounded configuration of strut  670   c  may reduce the likelihood of trauma to native tissue captured by engaging arms  670 . When hooked around native mitral valve leaflets  136 ,  138 , engaging arms  670  help anchor prosthetic heart valve  600  within native valve annulus VA and resist its migration into left atrium  122 . 
     Similar to stent  450 , stent  650  of prosthetic heart valve  600  may be formed with an odd number of cells in each circumferential row rather than an even number. Stent  650 ′, shown in  FIG. 7A , is similar to stent  650  with the exception that it has two annular rows of nine cells each. With this configuration, engaging arms  670 ′ may be situated around the circumference of stent  650 ′ so that they are symmetric relative to one plane P 6 . Prosthetic heart valve  700 , shown in  FIGS. 7B-H , incorporates flange  780  with stent  650 ′. Flange  780 , and its relation to stent  650 ′, may be similar or identical to the flange  580  of prosthetic heart valve  500  and its relation to stent  450 ′. For example, flange  780  may include a plurality of braided strands or wires  786  arranged in three dimensional shapes. The body portion  782  and flared portion  784  of flange  780  may also be similar or identical to the corresponding portions of flange  580 , with body portion  782  being coupled to stent  650 ′ by sutures, for example. Similar to prosthetic heart valve  500 , the engaging arms  670 ′ of prosthetic heart valve  700  are shape-set so that, in the absence of applied forces, the body portion  782  of flange  780  is positioned between the struts  670   a ′- 670   c ′ forming engaging arms  670 ′ and the remainder of stent  650 ′. Similarly, prosthetic heart valve  700  may also include a valve assembly having three leaflets attached to a cylindrical cuff in substantially the same manner as described above in connection with prosthetic heart valves  400  and  600 . 
     Prosthetic heart valve  700  may be delivered to the implant site in the collapsed condition, shown in  FIG. 7G , and may be transitioned to the expanded condition near native mitral valve  130 . Engaging arms  670 ′ revert to the preset shape in a similar manner as described above in connection with the engaging arms of prosthetic heart valve  600 , capturing native mitral valve leaflets  136 ,  138  between engaging arms  670 ′ and corresponding portions of stent  650 ′, as shown in  FIG. 7H . Flange  780  also transitions from the collapsed condition to the expanded condition, assuming its preset shape shown in  FIG. 7H . Similar to flange  580  of prosthetic heart valve  500 , flange  780  of prosthetic heart valve  700  expands to help anchor prosthetic valve  700  within native valve annulus VA. Flange  780  may also include a fabric layer, similar to fabric layer  588 , to provide additional sealing against PV leak. As with prosthetic heart valve  500  described above, the combination of engaging arms  670 ′ and flange  780  securely anchors prosthetic heart valve  700  within native valve annuls VA and limits its migration toward either the left atrium or the left ventricle. 
       FIG. 8A  illustrates a side view of a prosthetic heart valve  800  according to another aspect of the disclosure. Prosthetic heart valve  800  may be substantially similar to prosthetic heart valves  500  and  700  in many respects. For example, prosthetic heart valve  800  may include an inflow end  810 , and outflow end  812 , and a valve portion  850  that may be substantially similar or identical to prosthetic heart valve  400  or  600 . Prosthetic heart valve  800  may include a flange portion  880  that may be substantially similar or identical to flange  580  or flange  780 . It should be understood that, in  FIG. 8A , valve portion  850  is shown with a cuff  864  attached thereto, which may be similar or identical to other cuffs described above. Further, a second cuff  865 , which may be formed of any of the cuff materials described above, may be coupled to an outer periphery of flange portion  880  and may also cover one or more anchor arms or engaging arms  870 , which may be substantially similar or identical to other anchor arms or engagement arms described herein, including engagement arms  670 . As shown best in  FIG. 8A , prosthetic heart valve  800  may include one or more retainers  866  adapted to mate with complementary structures on a delivery device, with the retainers helping to avoid unintentional decoupling of the prosthetic heart valve from the delivery device during deployment at the native valve annulus, such as the native mitral valve. 
       FIG. 8B  is a top view of prosthetic heart valve  800 , looking down at the inflow end of the prosthetic heart valve, with the leaflets  862  of the prosthetic heart valve in an open condition. In the illustrated embodiment, valve portion  850  is substantially cylindrical and includes three prosthetic leaflets  862 , although more or fewer than three leaflets may be suitable, and shapes other than cylindrical may be suitable. Flange portion  880 , on the other hand, is substantially elliptical in the illustrated embodiment, the elliptical shape generally including a major axis X MAJOR  and a minor axis X MINOR . Although other shapes of flange portion  880  may be suitable, the native mitral valve  130  is typically elliptical, and thus a corresponding elliptical shape of the flange portion may better correspond with the native anatomy. As illustrated, although valve portion  850  is substantially cylindrical and flange portion  880  is substantially elliptical, the valve portion is substantially centered at the intersection of the major axis X MAJOR  and minor axis X MINOR  of the elliptical flange portion. In order to obtain this configuration, a variety of different sized connectors  890  may connect flange portion  880  to valve portion  850 . Each connector may include a first portion  892  which may be, for example, a crimp tube. One or a group of wires of flange portion  880  may be gathered and coupled to the first portion  892  of connector  890 . Each connector  890  may include a second portion  894  extending between a first end coupled to the first portion  892  of the connector and a second end coupled to valve portion  850 . The second portion  894  of connector  890  may take the form of a strand, wire, or other substantially straight member, and may be coupled at its second end to a strut or other portion of the stent of valve portion  850 . Second portion  894  may be coupled to the stent of valve portion  850  via welding, sutures, adhesives, or any other suitable connection method. In one embodiment, second portion  894  may be integral with the stent of valve portion  850 , for example by laser cutting the stent from a single tube, with the second portions of connectors  890  being cut from the same tube. It should be understood that the second portion  894  of connectors  890  may be the only structures coupling flange portion  880  to the stent of valve portion  850 . The second portions  894  of connectors  890  may have different lengths depending on their positions around the circumference of valve portion  850 . For example, the second portions  894  of connectors  890  positioned along or adjacent major axis X MAJOR  may be longer than all other second portions. On the other hand, the second portions  894  of connectors  890  positioned along or adjacent minor axis X MINOR  may be shorter than all other second portions. In some embodiments, the second portions  894  of the connectors  890  positioned on or adjacent minor axis X MINOR  may be omitted, with the first portions  892  of the connectors being directly coupled to valve portion  850 . By varying the lengths of the second portions  894  of connectors  890  so that the second portions are shortest along minor axis X MINOR  and increase in length toward major axis X MAJOR , flange portion  880  may maintain an elliptical shape while valve portion  850  may maintain a cylindrical shape and be positioned substantially at the intersection of the major and minor axes. 
       FIG. 8C  shows a highly schematic illustration of prosthetic heart valve  800  positioned within the valve annulus VA of native mitral valve  130 . The native aortic valve AV is also illustrated to show the general positional relationship between the native aortic valve and native mitral valve  130 , although the drawing is not intended to be to scale. As illustrated in  FIG. 8C , one or more engagement arms  870  may engage or hook around the native anterior leaflet  138  and posterior leaflet  136  of native mitral valve  130  to help resist migration of prosthetic heart valve  800  into the left atrium. Similarly, a top or flared portion of flange portion  880  may contact the native mitral valve annulus facing the left atrium to help resist migration of the prosthetic heart valve  800  into the left ventricle. It should be understood that, although the exterior perimeter of valve portion  850  may be spaced a distance from the interior surface of flange portion  880 , cuff  864  and/or second cuff  865  may help ensure that blood does not flow from the left atrium to the left ventricle (or vice versa) through the space between the valve portion and the flange portion. For example, second cuff  865  may be positioned on an exterior and/or interior surface of flange portion  880  and may extend so that it couples to valve portion  850  in order to help ensure that blood is only able to flow through the prosthetic valve  800  via the space between leaflets  862  when the leaflets are in an open condition, as best seen in  FIG. 8B . 
     Referring again to  FIG. 8C , although prosthetic heart valve  800  may be effective at allowing blood to flow in the antegrade direction through the valve portion  850  and restricting blood from flowing in the retrograde direction in a manner similar to a properly functioning native mitral valve, potential drawbacks may be present depending on the particular geometry and placement of prosthetic heart valve  800  in the heart. For example, as noted above, if the outflow end of one or both of valve portion  850  and flared portion  880  extend a large distance into the left ventricle, the structure may obstruct blood flowing along the LVOT through native aortic valve AV. In addition, depending on the size of prosthetic heart valve  800  and whether it is angled with respect to the longitudinal axis of native mitral valve  130  when implanted, portions of the prosthetic heart valve may contact the septum separating the left and right ventricles and interfere with electrical conduction in the tissue, which may result in heart pacing irregularities. One way to reduce the likelihood of either of these problems arising is to shift the valve portion posteriorly, as described below. 
       FIG. 9A  illustrates a top view of prosthetic heart valve  900  looking toward the inflow end thereof. Prosthetic heart valve  900  may be substantially similar to prosthetic heart valve  800 , with the main difference being the position of the valve portion relative to the flange portion, and the configuration of the connectors that dictate this relative positioning. Similar to prosthetic valve  800 , prosthetic valve  900  may include a substantially elliptical flange portion  980  having a major axis X MAJOR  and a minor axis X MINOR . Also similar to prosthetic valve  800 , prosthetic valve  900  may include a substantially cylindrical valve portion  950  with three prosthetic leaflets  962 . However, while valve portion  950  is preferably centered in the direction of the major axis X MAJOR  of flange portion  980 , the valve portion is preferably offset in the posterior direction from the major axis of the flange portion. In other words, whereas the central longitudinal axis of valve portion  850  is substantially coaxial with the central longitudinal axis of flange portion  880 , the central longitudinal axis of valve portion  950  is posteriorly offset from the central longitudinal axis of flange portion  980 . Thus, when implanted, while the central longitudinal axis of valve portion  850  is substantially aligned with the central longitudinal axis of native mitral valve  130  as shown in  FIG. 8C , the central longitudinal axis of valve portion  950  when implanted is posteriorly offset from the central longitudinal axis of the native mitral valve, as shown in  FIG. 9B . Preferably, the central longitudinal axis of valve portion  950  is substantially parallel to the central longitudinal axis of flange portion  980 . In one embodiment, the central longitudinal axis of valve portion  950  is offset from the central longitudinal axis of flange portion  980  (and/or the central longitudinal axis of native mitral valve  130  after implantation) by a distance of between about 4 mm and about 8 mm in the posterior direction. In some embodiments, that posterior offset may be between about 5 mm and about 7 mm. In another embodiment, that posterior offset may be about 6 mm. 
     Still referring to  FIG. 9A , one way to provide the offset of valve portion  950  relative to flange portion  980  is to modify connectors  990  compared to connectors  890 . The general structure of connectors  990  may be substantially similar or identical to that of connectors  890 . For example, each connector  990  may include a first portion  992  which may connect to one or a group of wires of flange portion  980 . In one embodiment, first portion  992  that be a crimp tube that is crimped over one or a group of wires of flange portion  980 . Each connector  990  also may include a second portion  994  that may take the form of a strand, wire, or other substantially straight member, and may be coupled at a first end to first portion  992  and at a second end to a strut or other stent portion of valve portion  950 . The second portions  994  of connectors  990  may have different lengths in order to help position valve portion  950  posterior to the major axis X MAJOR . For example, the second portion  994  of one connector  990  extending along the minor axis X MINOR  on the anterior side of prosthetic valve  900  may have a large length compared to the second portion of another connector extending along the minor axis on the posterior side of the prosthetic valve. 
     In one embodiment, the second end of the second portion  994  of each connector  990  may be positioned at substantially the same location in the inflow-to-outflow direction of the valve portion  950 . In such configuration, the connectors  990  positioned near the posterior side of prosthetic heart valve  900  would extend at a greater angle relative the central longitudinal axis of the prosthetic valve compared to connectors positioned near the anterior side of the prosthetic heart valve, as shown in  FIG. 9B . In other words, anterior connectors  990  may be closer to being orthogonal to the longitudinal axis of the prosthetic heart valve  900  than are the posterior connectors. 
     Although not separately labeled, prosthetic heart valve  900  may include a first cuff on the valve portion  950  that is substantially similar or substantially identical to cuff  864  on valve portion  850 , and a second cuff on the flange portion  980  may be substantially similar or substantially identical to second cuff  865  on flange portion  880 , so that blood does not pass through prosthetic heart valve  900  other than past leaflets  962  when they are in the open condition. Further, prosthetic heart valve  900  may include engagement arms  970  that are substantially similar in most respects to engagement arms  870 . However, because valve portion  950  has a posterior offset, an anterior engagement arm  970  may be longer than a posterior engagement arm, as the native anterior leaflet  138  may be a greater distance from the valve portion  950  than is the native posterior leaflet  136  when implanted. 
     Although prosthetic heart valves  800 ,  900  are both described as having first and second cuffs on valve portions  850 ,  950  and flange portions  880 ,  980 , respectively, that help ensure blood flows only past leaflets  862 ,  962  in the open condition, additional cuffs may be provided. As described and illustrated, when prosthetic heart valves  800 ,  900  are implanted, blood may flow from the left atrium into the space between the exterior surfaces of valve portions  850 ,  950  and the interior surfaces of flange portions  880 ,  980 , although the blood cannot flow from that position into the left ventricle due to the presence of the first and/or second cuffs. In other embodiments, it may be preferable to include a substantially annular cuff or sealing member extending from an exterior circumference of the valve portion to the inflow edge of the flange portion. With such an annular cuff, blood may be prevented from entering the space between the exterior surfaces of valve portions  850 ,  950  and the interior surfaces of flange portions  880 ,  980  in the first place. 
     In an exemplary method of use, prosthetic heart valve  900  may be transitioned into a collapsed condition similar to that shown for valve  700  in  FIG. 7G , and loaded into a delivery device, an outer sheath of the delivery device covering the prosthetic heart valve and maintaining it in the collapsed condition. The collapsed prosthetic heart valve  900  may be passed through the patient&#39;s body (for example, through the atrial septum using a transseptal (TS) approach or through the left ventricle using a transapical (TA) approach) and positioned adjacent native mitral valve  130 . The outer sheath may be translated to allow prosthetic valve  900  to expand into the expanded condition, with flange portion  980  in contact with an atrial side of the native mitral valve annulus and valve portion  950  positioned between native anterior leaflet  138  and native posterior leaflet  136 . If engagement arms  970  are included, they may transition to a pre-set shape, such as that shown in  FIG. 9B , to hook over or otherwise engage native leaflets  136 ,  138 . As noted above, upon implantation, the central longitudinal axis of valve portion  950  is offset from, and preferably parallel to, the central longitudinal axis of native mitral valve  130 . 
     According to one embodiment of the disclosure, a collapsible and expandable prosthetic mitral valve comprises: 
     a stent having an inflow end, an outflow end, and a first central longitudinal axis extending from the inflow end to the outflow end in an expanded condition of the prosthetic mitral valve; 
     a valve assembly disposed within the stent; and 
     a flange formed of a braided mesh and having a body portion coupled to the stent and a flared portion adjacent the inflow end of the stent, a second central longitudinal axis extending through the flared portion in the expanded condition of the prosthetic mitral valve, 
     wherein the first central longitudinal axis is offset from the second central longitudinal axis; and/or 
     the first central longitudinal axis is parallel to the second central longitudinal axis; and/or 
     the flared portion is substantially elliptical in the expanded condition of the prosthetic mitral valve and includes a major axis and a minor axis; and/or 
     the first central longitudinal axis is positioned on the minor axis and is offset from the major axis; and/or 
     a plurality of connectors coupling the flared portion of the flange to the stent; and/or 
     the flared portion of the flange includes an anterior portion on a first side of the major axis and a posterior portion on a second side of the major axis, the first central longitudinal axis being positioned on the second side of the major axis; and/or 
     a first one of the connectors couples the anterior portion of the flange to an anterior portion of the stent and has a first length, and a second one of the connectors couples the posterior portion of the flange to a posterior portion of the stent and has a second length, the first length being greater than the second length; and/or 
     the stent is substantially cylindrical in the expanded condition of the prosthetic mitral valve; and/or 
     an anterior engagement arm and a posterior engagement arm each having a first end pivotably coupled to the stent and a free end extending toward the inflow end of the stent; and/or 
     the anterior engagement arm is longer than the posterior engagement arm. 
     In another embodiment of the disclosure, a method of implanting a prosthetic mitral valve comprises: 
     introducing a delivery device to a native mitral valve annulus while the prosthetic mitral valve is maintained in a collapsed condition by the delivery device; 
     transitioning the prosthetic mitral valve into an expanded condition so that a stent of the prosthetic mitral valve is positioned within the native mitral valve annulus to implant the prosthetic mitral valve, the stent including a valve assembly disposed therein, and so that a flared portion of a flange of the prosthetic mitral valve contacts an atrial side of the native mitral valve annulus, the flange being formed of a braided mesh and having a body portion coupled to the stent, 
     wherein upon implantation of the prosthetic mitral valve, the native mitral valve annulus has a first central longitudinal axis, and the stent has a second central longitudinal axis offset from the first central longitudinal axis; and/or 
     upon implantation of the prosthetic mitral valve, the second central longitudinal axis is positioned closer to a posterior leaflet of the native mitral valve than to an anterior leaflet of the native mitral valve; and/or 
     upon implantation of the prosthetic mitral valve, the first central longitudinal axis is parallel to the second central longitudinal axis; and/or 
     in the expanded condition of the prosthetic mitral valve, the flared portion is substantially elliptical and includes a major axis and a minor axis; and/or 
     the second central longitudinal axis is positioned on the minor axis and is offset from the major axis; and/or 
     a plurality of connectors couple the flared portion of the flange to the stent; and/or upon implantation of the prosthetic mitral valve, a first one of the connectors is positioned nearer an anterior leaflet of the native mitral valve than is a second one of the connectors, the first one of the connectors having a length greater than a length of the second one of the connectors; and/or 
     the stent is substantially cylindrical in the expanded condition of the prosthetic mitral valve; and/or 
     engaging a free end of an anterior engagement arm of the stent with an anterior leaflet of the native mitral valve and engaging a free end of a posterior engagement arm of the stent with a posterior leaflet of the native mitral valve, each engagement arm having a first end pivotably coupled to the stent; and/or 
     the anterior engagement arm has a first length from the first end to the free end and the posterior engagement arm has a second length form the first end of the free end that is less than the first length. 
     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, features of one embodiment of the invention may be combined with features of one or more other embodiments of the invention without departing from the scope of the invention.