EP4175589A1

EP4175589A1 - Heart valve prostheses and related methods

Info

Publication number: EP4175589A1
Application number: EP21749406.1A
Authority: EP
Inventors: Paul Spence; Anthony Paolitto
Original assignee: Invalve Therapeutics Inc
Current assignee: Invalve Therapeutics Inc
Priority date: 2020-07-01
Filing date: 2021-07-01
Publication date: 2023-05-10
Also published as: CN116568240A; WO2022006375A1

Abstract

Prosthetic valves for treating blood flow regurgitation through a native heart valve can include a body including an inlet portion and an outlet portion having a first limb and a second limb, and defining a flow passage having an inlet in the inlet portion, a first outlet in the first limb and a second outlet in the second limb, a flow control device disposed in the flow passage within the inlet portion, and a clip connector coupled to the body. The prosthetic valve is configured to be disposed in a native valve of a heart that has been clipped to create a first flow control portion and a second flow control portion, with the inlet disposed in an atrium of the heart, and with the first outlet and the second outlet disposed in the ventricle of the heart, with the limbs configured to be disposed in the flow control portions in substantially sealing relationship with the first leaflet and the second leaflet. The prosthetic valve is further configured to permit blood to flow from the atrium to the ventricle through the flow passage, and to substantially prevent blood to flow from the ventricle to the atrium though the flow passage or between the body and the leaflets during systole of the heart. The clip connector is configured to be selectively coupled to the clip and to resist displacement of the body towards the atrium during systole.

Description

HEART VALVE PROSTHESES AND RELATED METHODS

Cross-Reference to Related Applications

[0001] This application claims priority to U.S. Provisional Patent Application Serial No.

63/046,841, entitled “Mitral Valve Protheses and Related Methods,” filed on July 1, 2020, the disclosure of which is incorporated by reference herein in its entirety.

[0002] This application is also related to U.S. Patent No. 10,912,646, entitled “Methods,

Apparatus and Devices to Treat Heart Valves” (“the ‘646 Patent”), the disclosure of which is incorporated by reference herein in its entirety.

Background

[0003] Heart valve incompetence, in various forms and affecting various valves of the heart (e.g., the aortic valve, tricuspid valve, pulmonary valve and mitral valve), has led to a growing area of research and development designed to improve heart valve functionality.

Although any one or more of these native heart valves may be compromised due, for example, to congenital disorders or, more often, disease conditions, the mitral valve has received particular attention. Regurgitation of blood flow through a heart valve, such as a mitral valve, involves the backward flow of blood through the valve when the valve is supposed to be fully closed (i.e., full coaptation of the native leaflets). A diseased or otherwise compromised mitral valve will often allow regurgitated blood flow from the left ventricle into the left atrium during cardiac systole. This causes the amount of blood ejected from the left ventricle during cardiac systole to be reduced, leading to less than optimal "ejection fraction" for the patient. Thus, the patient may experience a lower quality of life due to this inefficiency of their heart or, worse, a life-threatening condition.

[0004] Surgical techniques as well as transvascular or catheter-based techniques for treatment of mitral valve incompetence have been developed and, for example, include mitral annuloplasty, attachment of the native anterior mitral leaflet to the native posterior mitral leaflet, chordal replacement and even complete mitral valve replacement. Similar approaches have been developed for treatment of tricuspid valve incompetence.

[0005] In many cases, mitral valve regurgitation is related not to congenital defects in the mitral valve leaflets but to changes in the coaptation of the leaflets over time due to heart disease. In these situations, the native mitral leaflets are often relatively normal, but they nevertheless fail to prevent regurgitation of blood from the left ventricle into the left atrium during cardiac systole. Instead of the native anterior and posterior leaflets properly mating or coapting together completely during cardiac contraction or systole, one or more gaps between the native leaflets cause mitral regurgitation. Similar issues are encountered with tricuspid valves.

[0006] A current, commonly used technique for reducing mitral valve regurgitation is an edge-to-edge approximation or repair procedure that involves the attachment of the native mitral valve anterior leaflet to the native mitral valve posterior leaflet using a clip structure. The use of the edge to edge mitral repair procedure is increasing rapidly to treat mitral regurgitation. Abbott has the MitraClip™ on the market and Edwards has recently introduced the PASCAL device. The MitraClip™ fastens or clips the anterior mitral leaflet to the posterior mitral leaflet, while the PASCAL performs the same function with the addition of a material between the native leaflets providing certain advantages for the procedure.

[0007] MitraClip™ procedures currently use about two clips per procedure and mitral regurgitation remains in many patients who undergo treatment. The native anterior and posterior mitral leaflets have gaps between them in systole resulting in persistent mitral regurgitation even after clipping them together. Clinical studies show improved patient outcomes with the clip but many patients remain quite ill and require ongoing strict medical supervision. Abbott has also developed the TriClip™ for clipping the native leaflets of tricuspid valves.

[0008] The ‘646 Patent discloses devices attached to an edge-to-edge mitral clipping device to prevent any residual leak. These devices and methods sealed the space between the native mitral leaflets in systole and allowed for filling of the left ventricle in diastole. Some devices were fixed in shape and others had moving components or leaflets that closed the residual gap in systole and allowed blood to enter the LV in diastole.

[0009] One particularly promising variation disclosed in the ‘646 Patent was a bileaflet valve that could be positioned and attached to the edge to edge clip. A number of variations on this solution are shown including (but not limited to) FIGS. 5 - 11, 15 - 29 and 35 of the ‘646 Patent, also included herein.

[0010] Each of these variations requires the development of a new type of valve - generally a bileaflet valve that fills the gap between the native leaflets in systole and moves to allow blood to enter the left ventricle (LV) in diastole. This valve will require considerable testing and development before it is available for clinical use. There is no such similar bileaflet device on the market. So, there is a development risk and a regulatory risk that this new device may fail. It is also possible that a bi-leaflet device may not be widely welcomed by physicians who have been accustomed to tri-leaflet valves for more than 50 years.

[0011] The tri-leaflet stented valve is proven effective and safe. It has been the mainstay of surgical tissue valves for over 50 years and millions of valves with a tri-leaflet construction have been implanted in patients with very good long-term outcomes. In the last decade hundreds of thousands of stented valves carrying three leaflets have been successfully used in patients who have received catheter based heart valve replacement procedures. It would be very useful to consider using two proven technologies (the edge to edge device and the tri-leaflet stented valve) to treat mitral regurgitation. The combination of these will reduce time to market and as well as regulatory and adoption risk, in addition to clinical advantage.

[0012] Many doctors are now very accomplished in performing the mitral clipping procedure (bringing the anterior and posterior leaflets together with a clip such as the MitraClip™) and the tricuspid clipping procedure (which can have several variations on bringing together the anterior, septal, and/or posterior leaflets with a clip such as the MitraClip™). They are also confident in the reliability and with their ability to deliver a stented valve. Building a device that takes advantage on these proven implants and skill sets will be well received by doctors and safer for patients who have doctors performing a familiar procedure.

[0013] It would be useful to further address these and other problems or challenges associated with heart valve incompetence.

Summary

[0014] In some embodiments, a prosthetic valve includes a body including an inlet portion and an outlet portion having a first limb and a second limb, and defining a flow passage having an inlet in the inlet portion, a first outlet in the first limb and a second outlet in the second limb, a flow control device disposed in the flow passage within the inlet portion and configured to permit fluid flow through the flow passage in a first direction from the inlet to the first outlet and the second outlet, and to inhibit fluid flow through the flow passage in a second direction, opposite to the first direction, and a clip connector coupled to the body. The prosthetic valve is configured to be disposed in a native valve of a heart in which a first leaflet has been coupled to a second leaflet by a clip, defining a first flow control portion between the first leaflet, the second leaflet and the clip and defining a second flow control portion between the first leaflet, the second leaflet and the clip, with the inlet disposed in an atrium of the heart, and with the first outlet and the second outlet disposed in the ventricle of the heart. The first limb is configured to be disposed in the first flow control portion in substantially sealing relationship with the first leaflet and the second leaflet, and the second limb configured to be disposed in the second flow control portion in substantially sealing relationship with the first leaflet and the second leaflet. The prosthetic valve is further configured to permit blood to flow from the atrium to the ventricle through the inlet, the flow control device, the fluid passage, and the first outlet and the second outlet, during diastole of the heart, and to substantially prevent blood to flow from the ventricle to the atrium though the flow passage or between the body and the leaflets during systole of the heart. The clip connector is configured to be selectively coupled to the clip and to resist displacement of the body towards the atrium during systole.

[0015] In other embodiments, a prosthetic valve has a body including an inlet portion and an outlet portion and defining a flow passage having an inlet in the inlet portion and an outlet portion, a flow control device disposed in the flow passage within the inlet portion and configured to permit fluid flow through the flow passage in a first direction from the inlet to the outlet, and to inhibit fluid flow through the flow passage in a second direction, opposite to the first direction, and a clip connector coupled to the body. The prosthetic valve is configured to be disposed in a native valve of a heart in which a first leaflet has been coupled to a second leaflet by a clip, defining a flow control portion between the first leaflet, the second leaflet and the clip, with the inlet disposed in an atrium of the heart, and with the first outlet disposed in the ventricle of the heart. The outlet portion configured to be disposed in the flow control portion in substantially sealing relationship with the first leaflet and the second leaflet. The prosthetic valve is configured to permit blood to flow from the atrium to the ventricle through the inlet, the flow control device, the fluid passage, and the outlet, during diastole of the heart, and to substantially prevent blood to flow from the ventricle to the atrium though the flow passage or between the body and the leaflets during systole of the heart. The clip connector is configured to be selectively coupled to the clip and to resist displacement of the body towards the atrium during systole. [0016] Additional features, aspects and/or advantages will be recognized and appreciated upon further review of a detailed description of the illustrative embodiments taken in conjunction with the accompanying drawings.

Brief Description of the Drawings

[0017] FIG. 1 A is a schematic view illustrating a system constructed in accordance with one illustrative embodiment.

[0018] FIG. IB is a schematic perspective view of a native left atrium and mitral valve, similar to FIG. 1 A, but illustrating installation of the catheter delivered selective occlusion device. [0019] FIG. 1C is a schematic perspective view similar to FIG. IB, but illustrating the membrane of the selective occlusion device in place over the frame structure.

[0020] FIG. 2A is a cross-sectional view taken transversely through the selective occlusion device along line 2A-2A of FIG. 3 A when the heart cycle is in systole.

[0021] FIG. 2B is a cross-sectional view similar to FIG. 2A, during the systole phase of the heart cycle, but taken along line 2B-2B of FIG. 3 A.

[0022] FIG. 2C is a cross-sectional view similar to FIG. 2B, but illustrating the native mitral valve and the selective occlusion device while in the diastole phase of the heart cycle.

[0023] FIG. 3 A is a top view of the native mitral valve and the selective occlusion device while the heart is in the systole phase.

[0024] FIG. 3B is a top view similar to FIG. 3 A, but illustrating the device and native mitral valve while the heart is in the diastole phase.

[0025] FIG. 4A is a perspective view of the device as shown in the previous figures, with the membrane of the device removed for clarity, and showing only the frame structure in solid lines.

[0026] FIG. 4B is a perspective view similar to FIG. 4A, but illustrating the membrane applied to the frame structure of the device.

[0027] FIG. 5A is a schematic perspective view, partially sectioned similar to FIG. 1 A, but illustrating a catheter-based or transcatheter delivery and implantation system constructed in accordance with another embodiment.

[0028] FIG. 5B is a view similar to FIG. 5A, but illustrating a subsequent step in the method, in which the native mitral leaflets have been captured and clipped together. [0029] FIG. 5C is a sectional view similar to FIGS. 5A and 5B, but illustrating the frame of the selective occlusion device implanted and attached to the clip structure, with the flexible membrane removed for clarity.

[0030] FIG. 5D is a view similar to FIG. 5C, but illustrating the flexible membrane of the device in place on the frame structure.

[0031] FIG. 6A is a perspective view of the frame structure and attached clip structure shown in FIGS. 5A through 5C.

[0032] FIG. 6B is a perspective view similar to FIG. 6A, but illustrating another embodiment of a collapsible and expandable frame structure.

[0033] FIG. 7A is a cross sectional view of the native mitral valve and selective occlusion device of FIG. 6B, with the heart in the diastole phase.

[0034] FIG. 7B is a cross sectional view similar to FIG. 7A, but illustrating the selective occlusion device and the mitral valve when the heart is in the systole phase.

[0035] FIG. 8 is a side view with the heart in cross-section at the location of the native mitral valve, illustrating the selective occlusion device of FIGS. 7A and 7B, with the membrane in broken lines for clarity, and the device implanted.

[0036] FIG. 9 is a perspective view illustrating another embodiment of a selective occlusion device, showing the frame structure in solid lines and the flexible membrane in broken lines for clarity.

[0037] FIG. 10A is a schematic perspective view similar to FIGS. 1 A and 5A, but illustrating another embodiment of a catheter-based system for delivering and implanting a selective occlusion device coupled with a pre-installed mitral valve leaflet clip structure.

[0038] FIG. 10B is a view similar to FIG. 10A, but illustrating a subsequent step during the method.

[0039] FIG. IOC is a perspective view, with the heart sectioned at the native mitral valve, illustrating the implantation of the selective occlusion device, but with the flexible membrane removed for clarity.

[0040] FIG. 11 A is a perspective view showing another alternative embodiment of a selective occlusion device with the flexible membrane removed for clarity.

[0041] FIG. 1 IB is a perspective view showing another alternative embodiment of a selective occlusion device with the flexible membrane removed for clarity. [0042] FIG. 11C is a front top perspective view of the device of FIGS. 11 A or 1 IB implanted in the native mitral valve.

[0043] FIG. 1 ID is a front view of the device in FIGS. 11 A through 11C.

[0044] FIG. 1 IE is a transverse cross section of FIG. 1 ID.

[0045] FIG. 12A is a perspective view of another alternative embodiment of a selective occlusion device implanted in the native mitral valve, which is shown in cross-section similar to previous figures.

[0046] FIG. 12B is a cross-sectional view of the heart, taken at the native mitral valve, and showing the selective occlusion device of FIG. 12A in side elevation.

[0047] FIG. 12C is a view similar to FIG. 12B, but illustrating another alternative embodiment of a selective occlusion device implanted in a native mitral valve.

[0048] FIG. 12D is another view similar to FIG. 12C, but illustrating another alternative embodiment of a selective occlusion device implanted in the native mitral valve.

[0049] FIG. 13 A is a transverse cross-sectional view taken through the mitral valve and generally through one of the selective occlusion elements of FIGS. 12A through 12D, to show sealing during systole.

[0050] FIG. 13B is a view similar to FIG. 13 A, but showing the selective occlusion element and the mitral valve when the heart is in the diastole phase.

[0051] FIG. 13C is a view similar to FIG. 13B, but showing another embodiment of the selective occlusion element.

[0052] FIG. 14A is a perspective view of another alternative embodiment of a selective occlusion device and mitral valve clip structure.

[0053] FIG. 14B is a perspective view of another alternative embodiment of a selective occlusion device and mitral valve clip structure.

[0054] FIG. 14C is a perspective view of another alternative embodiment of a selective occlusion device and mitral valve clip structure.

[0055] FIG. 15A is a perspective view of another alternative embodiment of a selective occlusion device with the flexible membrane of the device broken away for clarity.

[0056] FIG. 15B is a perspective view similar to FIG. 15 A, but further illustrating a flexible membrane on the frame structure.

[0057] FIG. 15C is a side elevational view of the selective occlusion device shown in

FIGS. 15A and 15B with the flexible membrane removed for clarity. [0058] FIG. 15D is a side elevation view similar to FIG. 15C, but illustrating the flexible membrane applied to the frame structure.

[0059] FIG. 15E is a top view of the device shown in FIGS. 15A through 15D, but illustrating the membrane cross-sectioned to show the membrane shape in the expanded or filled condition when the heart is in the systole phase.

[0060] FIG. 16A is a perspective view of a system and of the heart, similar to FIG. 5 A, but illustrating another alternative embodiment of a catheter-based system and method for implanting a selective occlusion device and a clip structure in the native mitral valve.

[0061] FIG. 16B is a perspective view similar to FIG. 16A, but illustrating a subsequent step in the method.

[0062] FIG. 16C is a view similar to FIG. 16B, but illustrating another subsequent step in the method.

[0063] FIG. 16D is a perspective view illustrating the implanted selective occlusion device in the mitral valve of the patient.

[0064] FIG. 17A is a side cross-sectional view of the native mitral valve and of the selective occlusion device of FIGS. 16A through 16D being implanted and secured to the mitral valve clip structure.

[0065] FIG. 17B is a side cross-sectional view similar to FIG. 17 A, but illustrating a subsequent step in the method.

[0066] FIG. 17C is a side cross-sectional view similar to FIG. 17B, but illustrating another subsequent step in the method in which the apparatus is fully implanted.

[0067] FIG. 18A is a cross sectional view of the selective occlusion device, as shown in

FIGS. 16A through 16D and 17A through 17C, with the device and mitral valve shown when the heart is in the diastole phase.

[0068] FIG. 18B is a view similar to FIG. 18 A, but illustrating the device and the native mitral valve when the heart is in the systole phase.

[0069] FIG. 19 is a top view schematically illustrating a representation for the shape of the selective occlusion device when implanted in a native mitral valve having an anatomical curvature.

[0070] FIG. 20 is a perspective view of a selective occlusion device constructed in accordance with another alternative embodiment. [0071] FIG. 21 A is a side cross-sectional view taken generally lengthwise along a central portion of the device shown in FIG. 20.

[0072] FIG. 21B is a top view of the device shown in FIG. 21 A.

[0073] FIG. 21C is a cross-sectional view of the device shown in FIG. 21B.

[0074] FIG. 22A is a perspective view of a catheter-based system and method according to another alternative embodiment being performed on a native mitral valve, shown in a schematic cross-sectioned portion of the heart.

[0075] FIG. 22B is a view similar to FIG. 22A, but illustrating a subsequent step in the method.

[0076] FIG. 22C is a view similar to FIG. 22B, but illustrating another subsequent step in the method.

[0077] FIG. 22D is a perspective view illustrating the fully implanted apparatus in the native mitral valve, resulting from the method shown in FIGS. 22 A through 22C.

[0078] FIG. 22E is a view similar to FIG. 22D, but illustrating an alternative frame structure attached to the selective occlusion device.

[0079] FIG. 22F is a view similar to FIG. 22E, but illustrating another alternative frame structure.

[0080] FIG. 22G is a view similar to FIG. 22F, but illustrating another alternative frame structure.

[0081] FIG. 23 A is a cross-sectional view of a native mitral valve and another embodiment of a heart valve repair apparatus, shown with the heart in the systole phase.

[0082] FIG. 23B is a view similar to FIG. 23 A, but illustrating the apparatus and the mitral valve when the heart is in the diastole phase.

[0083] FIG. 24 is a side cross-sectional view of another alternative embodiment of a heart valve repair apparatus implanted in a native mitral valve.

[0084] FIG. 25A is a cross-sectional view of another alternative embodiment of a heart valve repair apparatus.

[0085] FIG. 25B is a cross-sectional view of another alternative embodiment of a heart valve repair apparatus implanted in a native mitral valve.

[0086] FIG. 26A is another alternative embodiment of a selective occlusion device shown in cross-section. [0087] FIG. 26B is a schematic view illustrating the device of FIG. 26A implanted in a native mitral valve.

[0088] FIG. 26C is a perspective view illustrating the device of FIGS. 26A and 26B implanted in a native mitral valve.

[0089] FIG. 26D is a cross-sectional view of another alternative heart valve repair apparatus implanted in a native mitral valve.

[0090] FIG. 26E is a cross-sectional view of another alternative heart valve repair apparatus implanted in a native mitral valve.

[0091] FIG. 27A is a perspective view of another alternative selective occlusion device.

[0092] FIG. 27B is a lengthwise cross-sectional view of the device shown in FIG. 27A, schematically illustrating blood flow during the systole phase of the heart.

[0093] FIG. 27C is a transverse cross-sectional view illustrating the device of FIGS. 27A and 27B during systole.

[0094] FIG. 28A is a perspective view illustrating another alternative embodiment of another apparatus including a selective occlusion device together with a mitral valve clip structure. [0095] FIG. 28B is a lengthwise cross-sectional view illustrating the device and clip structure shown in FIG. 28A.

[0096] FIG. 28C is a transverse cross-sectional view illustrating the device of FIGS. 28 A and 28B.

[0097] FIG. 29A is a cross-sectional view of a selective occlusion device and clip structure schematically illustrating blood flow between the interior membrane wall surfaces during the heart systole phase.

[0098] FIG. 29B is a cross sectional view of the apparatus of FIG. 29A implanted in the native mitral valve and illustrating the device and the mitral valve when the heart is in the systole phase.

[0099] FIG. 30 is a perspective view illustrating the mitral valve in cross-section and the fully implanted selective occlusion device and clip structure.

[0100] FIG. 31 is a perspective view of another alternative embodiment illustrating a prosthetic heart valve and leaflet clip structures.

[0101] FIG. 32A is a side elevational view of the prosthetic heart valve of FIG. 31, partially fragmented to show the prosthetic heart valve and leaflet clip structures. [0102] FIG. 32B is a side elevational view with the native heart valve in cross-section, illustrating an initial portion of the implantation procedure associated with the prosthetic heart valve of FIGS. 31 and 32 A.

[0103] FIG. 32C is a view similar to FIG. 32B, but illustrating a subsequent step in the method.

[0104] FIG. 32D is a view similar to FIG. 32C, but illustrating a subsequent step in the method.

[0105] FIG. 32E is a view similar to FIG. 32D, but illustrating the fully implanted prosthetic heart valve clipped to the native heart valve leaflets and expanded into an implanted condition.

[0106] FIG. 33 is a perspective view of another alternative embodiment of a prosthetic heart valve and native leaflet clip structure.

[0107] FIG. 34A is a side elevational view of the prosthetic heart valve illustrated in

FIG. 33.

[0108] FIG. 34B is a view of the prosthetic heart valve of FIG. 34A implanted in a native heart valve.

[0109] FIG. 35 A is a cross sectional view similar to FIG. 29B, but illustrating another illustrative embodiment of a heart valve repair apparatus implanted in a mitral valve and showing the systole phase of the heart cycle.

[0110] FIG. 35B is a cross sectional view similar to FIG. 35 A, but illustrating the apparatus and mitral valve when the heart cycle is in the diastole phase.

[0111] FIGS. 36A and 36B are illustrations of the anatomy of a native mitral valve and native tricuspid valve, respectively.

[0112] FIG. 37A is a schematic illustration of a native mitral valve.

[0113] FIGS. 37B to 37D are schematic illustrations of a native mitral valve after a clipping procedure with one more clips engaged with the native leaflets.

[0114] FIGS. 38A to 38F are schematic illustration of a native tricuspid valve after a clipping procedure with one or more clips engaged with the native leaflets.

[0115] FIGS. 39A and 39B are schematic illustrations of a prosthetic valve according to an embodiment, in side view and top view, respectively. [0116] FIGS 40A and 40B are schematic illustrations of the prosthetic valve of FIGS. 39A and 39B, shown disposed in a native mitral valve, in side view and top view, respectively.

[0117] FIG. 41 is a flow chart of a method of delivery of the prosthetic valve of FIGS. 39A and 39B, according to an embodiment.

[0118] FIGS. 42A and 42B are a perspective partial view, a partial cross-sectional side view of a prosthetic valve according to an embodiment.

[0119] FIG. 42C is a perspective view of the prosthetic valve of FIGS. 42A and 42B shown disposed in a native mitral valve.

[0120] FIGS. 42D to 42F are partial end cross-sectional views showing variants of the clip connector of the prosthetic valve of FIGS. 42A to 42C.

[0121] FIG. 43 is a partial cross-sectional side view of a prosthetic valve according to an embodiment.

[0122] FIG. 44 is a partial cross-sectional side view of a prosthetic valve according to an embodiment.

[0123] FIGS. 45A to 45C are partial cross-sectional side views of a prosthetic valve according to an embodiment, illustrating a process for expanding a limb of the prosthetic valve. [0124] FIGS. 46A to 46C are top, side, and partial cross-sectional side views, respectively, of a prosthetic valve according to an embodiment.

[0125] FIGS. 47A to 47D are top, side, end, and exploded end views of a prosthetic valve, according to an embodiment, disposed in a native mitral valve.

[0126] FIG. 48 is a top of a flow control device similar to that of the prosthetic valve of

FIGS. 47A to 47D, according to an embodiment.

[0127] FIGS. 49A and 49B are a top view and a side view, respectively, of a prosthetic valve, according to an embodiment.

[0128] FIG. 50 is a side view of a prosthetic valve, according to an embodiment.

[0129] FIGS. 51 A and 5 IB are a top view and a partial cross-sectional end view, respectively, of a prosthetic valve, according to an embodiment.

[0130] FIG. 51C to 5 IF are perspective views of a components of the flow control device of the prosthetic valve of FIGS. 51A and 51B.

[0131] FIGS. 52A and 52B are schematic illustrations of a prosthetic valve according to an embodiment, in side view and top view, respectively. [0132] FIGS 53A and 53B are schematic illustrations of the prosthetic valve of FIGS. 52A and 52B, shown disposed in a native mitral valve, in side view and top view, respectively.

[0133] FIG. 54 is a flow chart of a method of delivery of the prosthetic valve of FIGS. 52A and 52B, according to an embodiment.

[0134] FIGS. 55A to 55C are side perspective, top, and top perspective view of a prosthetic valve according to an embodiment, disposed in a centrally-clipped mitral valve.

[0135] FIGS. 56A and 56B are top views of a prosthetic valve according to an embodiment, disposed in a centrally clipped mitral valve, and FIGS. 56C to 561 illustrate mechanisms and procedures for securing the prosthetic valve to the clip in the mitral valve.

[0136] FIGS. 57A and 57B are top and end views, respectively, of a prosthetic valve according to an embodiment, shown disposed in an eccentrically-clipped mitral valve.

[0137] FIGS. 58A and 58B are top and end views, respectively, of a prosthetic valve according to an embodiment, shown disposed in an eccentrically-clipped mitral valve.

[0138] FIGS. 59A and 59B are top and end views, respectively, of a prosthetic valve according to an embodiment, shown disposed in an eccentrically-clipped mitral valve.

[0139] FIGS. 60A and 60B are perspective top and side views, respectively, of a prosthetic valve according to an embodiment, shown disposed in an eccentrically-clipped mitral valve.

[0140] FIGS. 60C and 60D are perspective top views of the prosthetic valve of FIGS. 60A and 60B, illustrating alternative heart tissue tethers.

[0141] FIG. 61 A is a top view of a prosthetic valve according to an embodiment, shown disposed in an eccentrically-clipped mitral valve, and FIG. 6 IB is a top perspective view of the clip of FIG. 61 A.

[0142] FIG. 62 is a top view of a prosthetic valve according to an embodiment, shown disposed in a mitral valve clipped with two eccentrically-placed clips.

[0143] FIGS. 63 is a top view of a prosthetic valve according to an embodiment, shown disposed in a tricuspid valve clipped with two clips in a triple orifice clipping procedure.

[0144] FIGS. 64A and 64B are top and top perspective views, respectively, of a prosthetic valve according to an embodiment, shown in FIG. 64A disposed in a tricuspid valve clipped with three clips. [0145] FIG. 65A is a cross-sectional perspective view of a delivery system for clips and for the prosthetic valve of FIGS. 64A and 64B, and FIGS. 65B to 65D illustrate delivery of the clips to the tricuspid valve resulting in the clipped tricuspid valve shown in FIG. 64A [0146] FIG. 66 is a top view of a prosthetic valve according to an embodiment, shown disposed in a tricuspid valve that has been clipped with three clips in a bicuspidization procedure. [0147] FIGS. 67A to 67C illustrate a heart tissue tether for a clip, and a process for delivering and deploying the tether and the clip.

Detailed Description

[0148] The detailed description herein serves to describe non-limiting embodiments or examples involving various inventive concepts and uses reference numbers for ease of understanding these examples. Common reference numbers between the figures refer to common features and structure having the same or similar functions, as will be understood. While various figures will have common reference numbers referring to such common features and structure, for purposes of conciseness, later figure descriptions will not necessarily repeat a discussion of these features and structure.

[0149] Referring first to FIG. 1 A, a native heart 10 is shown and includes a left atrium 12, a left ventricle 14, and a native mitral valve 16, which controls blood flow from the left atrium 12 to the left ventricle 14. The tricuspid valve 18 is also shown in communication with the right ventricle 19. The mitral valve 16 includes an anterior leaflet 16a, a posterior leaflet 16b and a native valve annulus 16c. When the mitral valve 16 is functioning properly, it will open to allow blood flow from the left atrium 12 into the left ventricle 14 during the diastole portion of the heart cycle. When the heart 10 contracts during systole, the anterior and posterior native mitral leaflets 16a, 16b will fully coapt or engage with one another to stop any blood flow in the reverse direction into the left atrium 12 and blood in the left ventricle 14 will be ejected efficiently and fully through the aortic valve (not shown). A catheter 20 carries a collapsed selective occlusion device 22 along a guide wire 24. In this illustrative procedure, the catheter 20 is delivered transeptally across the inter-atrial septum 12a. It will be appreciated that any other transcatheter approach, or other surgical approaches of various levels of invasiveness, may be used instead. The patient may or may not be on bypass and the heart may or may not be beating during the procedure. As further shown in FIG. 1A, the native mitral leaflets 16a, 16b are supported by chordae tendineae 26 attached to papillary muscles 28. As schematically illustrated in FIG. 1 A, the anterior and posterior native mitral leaflets 16a, 16b may not properly coapt or engage with one another when the heart cycle is in systole. Insufficient coaptation of the leaflets 16a, 16b leads to blood flow out of the left ventricle 14 in a backward direction, or in regurgitation, through the mitral valve 16 into the left atrium 12 instead of fully through the aortic valve (not shown).

[0150] Now referring to FIG. 1 A in conjunction with FIGS. IB and 1C, the selective occlusion device 22 has been fully extruded or extended from the distal end 20a of the catheter 20, and transformed from the collapsed position or condition shown in FIG. 1 A within the catheter 20, to the expanded condition shown in FIGS. IB and 1C. As further shown in FIGS. IB and 1C, the selective occlusion device 22 comprises a collapsible and expandable frame structure 30. The frame structure 30 is comprised of a curved frame member 32 generally extending across the native mitral valve 16 while being supported or stabilized at the native annulus 16c. The selective occlusion device 22 is formed in a manner allowing it to be collapsed for delivery as shown in FIG. 1 A, but expanded to the exemplary form shown in FIGS. IB and 1C. This may be accomplished in many ways. For example, the frame structure 30 may be comprised of flexible polymers, metals such as super-elastic or shape memory metals or other materials. The selective occlusion device 22 may, for example, expand into a preformed shape through the use of shape memory materials. The frame structure 30 may be covered partially or completely by fabrics such as the Dacron, Teflon and/or other covering materials such as used in the manufacture of prosthetic cardiac valves or other implants. More specifically, the frame structure 30 includes a curved frame member 32 which, in this embodiment, and/or other embodiments, extends from one commissure to the other. The frame member 32 may instead extend from other portions of the heart tissue generally located at the annulus region. At opposite ends, the frame structure 30 is supported by respective first and second non-penetrating annulus connectors 34, 36. As an example of a non-penetrating annulus connector, these connectors are configured with respective upper and lower connector elements 34a, 34b and 36a, 36b. These connector elements 34a, 34b and 36a, 36b respectively sandwich or capture annulus tissue therebetween at each commissure. The connector elements 34a, 34b and 36a, 36b are each shown as "butterfly-type" connectors that may be slipped or inserted into place with native leaflet tissue sandwiched or secured therebetween. It will be appreciated that other tissue trapping connectors may be used instead, and/or other penetrating or non-penetrating connectors. Non-penetrating connectors are advantageous because they cause no damage that would otherwise occur due to penetrating connectors, and they allow for position adjustment. The frame structure 30 further includes first and second membrane support members 38, 40 at opposite ends configured to be located in the left ventricle 14 to support a flexible membrane 44 in a slightly open condition. Together with the frame structure 30, the flexible membrane 44 forms a selective occlusion device that works in conjunction with the native mitral valve leaflets 16a, 16b to control blood flow through the mitral valve 16. The flexible membrane 44, in this embodiment acts as a prosthetic heart valve by moving in coordination with the leaflets 16a, 16b as will be described below. In other embodiments, the selective occlusion device need not have any moving part that moves in conjunction with the leaflets 16a, 16b. The flexible membrane 44 is secured at opposite portions of the frame structure 30 to the support members 38, 40 in any suitable manner, such as adhesive, mechanical securement, suturing, fasteners, etc. As further shown, a considerable portion at a lower margin of the flexible membrane 44 is not attached to the frame structure 30. The membrane support members 38, 40 are short, curved members and remaining membrane portions at the lower margin of the flexible membrane 44 are not directly attached to any frame portion. This allows the flexible membrane to billow, expand or inflate outward as will be discussed further below during systole to engage with the native leaflets 16a, 16b and prevent regurgitation of blood flow in a reverse direction through the mitral valve 16 when the heart cycle is in systole.

[0151] The flexible membrane 44 may be formed of various types of thin, flexible materials. For example, the materials may be natural, synthetic or bioengineered materials. Materials may include valve tissue or pericardial tissue from animals, such as cows and pigs, or other sources. Synthetic materials such as ePTFE, Dacron, Teflon or other materials or combinations of materials may be used to construct the flexible membrane 44. Flexibility of the frame structure 30 together with the flexibility of the flexible membrane 44 provides for operation of the selective occlusion device 22 and the manners contemplated herein, and may also help prevent failure due to fatigue from repeated cycling movement of the selective occlusion device 22 in the heart 10. It will be appreciated that FIG. IB shows the flexible membrane 44 removed for a clear view of the frame structure 30, and in this FIG. the flexible membrane 44 is in broken lines, while in FIG. 1C the flexible membrane 44 is shown in solid lines, with the heart cycle in systole and the flexible membrane 44 fully engaging the native leaflets 16a, 16b to reduce regurgitation of blood flow through the mitral valve 16. The flexible membrane 44 may be sutured to the frame structure 30 using techniques employed by the prosthetic heart valve industry for the manufacture of prosthetic aortic and mitral valves. The frame may be made from one or more layers of material, such as super-elastic or shape memory material and the membrane 44 may be suitably secured. One manner may be trapping the flexible membrane 44 between layers of the frame structure 30. To retain the membrane 44 in place, fabric covering(s) (not shown) over a metallic frame may aid in attaching the membrane 44 to the frame structure 30.

[0152] FIGS. 2A, 2B and 2C are transverse cross-sections through the selective occlusion device 22 and the mitral valve 16 shown in FIGS. 1 A through 1C. FIG. 2A illustrates the device 22 in a cross section along line 2A-2A of FIG. 3 A, while FIG. 2B shows the selective occlusion device 22 in cross section along line 2B-2B of FIG. 3A, with each of these two FIGS showing the heart cycle in systole. FIGS. 3 A and 3B are top views respectively showing the systole and diastole conditions, but not illustrating the hinge 32a that may be provided to assist with folding during delivery. FIG. 2C is similar to FIG. 2B but showing the selective occlusion device 22 when the heart cycle is in diastole. In systole (FIGS. 2A, 2B and 3 A), which is when the native mitral valve 16 is supposed to fully close to prevent blood flow back into the left atrium 12, the pressurized blood will flow through the open end 45 of the flexible membrane and be prevented from flowing through the closed end 47, at least to any substantial degree. As will be appreciated from a review of some embodiments, a small vent may be provided in the flexible membrane. Because the flexible membrane billows or expands outwardly in the direction of the arrows shown in FIG. 2B, the native mitral leaflets 16a, 16b will seal against or coapt with the flexible membrane 44 to prevent blood flow regurgitation. In this manner, native mitral leaflets 16a, 16b that would not otherwise properly seal together or coapt will seal in systole against the flexible membrane 44. To ensure coaptation, one or more portions of the flexible membrane 44 adjacent to frame structure 30 will move away from the adjacent frame structure into contact with the native leaflet(s) 16a, 16b. In other words, only a portion of the lower margin of the flexible membrane 44 is affixed to frame structure 30. As further shown in FIG. 2B, there may be extra membrane material adjacent the membrane support members 38, 40 to allow for the expanded membrane condition. As further shown in FIGS. 2C and 3B, when the heart cycle is in diastole and blood flow needs to occur from the left atrium 12 into the left ventricle 14 (during the filling portion of the heart cycle), the blood will push past the flexible membrane 44 and the flexible membrane 44 will move into a collapsed or contracted condition while the native mitral leaflets 16a, 16b move apart or away from each other in the opposite direction to facilitate blood flow in the direction of the arrows. The arch-shaped membrane support members 38, 40 maintain a separation between lower margins or edges of the flexible membrane 44 to force blood to fill the inside or interior of the membrane 44 during systole through the open end 45, causing the membrane 44 to expand or billow outward so that the membrane 44 fills the gap between the native mitral valve leaflets 16a, 16b. The arch-shaped or curved support members 38, 40, and/or other portions of the frame structure 30, may be formed using a central wire and a fabric cover around the wire. Other constructions are possible as well, such as using soft, sponge-like material, and fabrics in conjunction with more structurally supportive material such as metal and/or plastic. The filling and emptying of the flexible membrane 44 through the open end 45 can ensure that there is washing or rinsing of the underside of the membrane 44 with each heartbeat to prevent clot formation, and any resulting embolization of clot material.

[0153] FIGS. 4A and 4B are respectively similar to FIGS. IB and 1C, but illustrate the selective occlusion device 22 isolated from the native mitral valve 16 (FIGS. IB and 1C).

[0154] FIGS. 5A through 5D illustrate another embodiment of a selective occlusion device

22a. As previously stated, all like reference numerals between the various embodiments and FIGS refer to like structure and function except to the extent described herein. Some reference numerals will have a suffix modification such as a letter (e.g., "22a"), or a prime mark (e.g., 90'), indicating a modification to the like structure which will be discussed and/or apparent from a review of the drawings. To be more concise, redundant descriptions of like structure and function between the various FIGS will not be made or will be kept to a minimum. This embodiment is particularly suited to achieve beneficial effects for those mitral valve repairs involving clipping or otherwise securing one native leaflet margin to another. It will be appreciated, though, that clips or other anchors (herein generically referred to as clip structures) may be applied to only one leaflet margin, and more than one clip or anchor may be used. Often, mitral valve repair is made with a clip structure 50 having first and second clip elements 50a, 50b movable toward each other from an open condition to a closed position. The clip structure 50 is typically applied in a transcatheter procedure using a suitable catheter assembly 52. A representative and illustrative clip structure 50 is shown in these FIGS for clipping together margins of the native leaflets 16a, 16b near a central location of each margin. The beginning of the procedure is shown in FIG. 5A with the catheter assembly 52 directed transeptally into the left atrium 12 through the inter-atrial septum 12a and into the mitral valve 16 and to the left ventricle 14. A portion of the margin of each leaflet 16a,

16b is captured by the clip structure 50 and then clipped and firmly secured together as shown in FIG. 5B. At least one of the elements 50a, 50b moves toward the other in a clipping or clamping action to change from an open condition to a closed condition. A wire, suture or other tensile member or connector 54 is coupled to the clip structure 50. At or near the end of the clipping step of the method, a selective occlusion device 22a in the form of a frame structure 30a and flexible membrane 44a (FIG. 5D) is introduced through the catheter or catheters 52 in a manner similar to the method described above with respect to the first embodiment. The selective occlusion device 22a is guided by the suture, wire or other tensile member 54 affixed and extending from the clip structure 50.

[0155] As further shown in FIG. 5C, this embodiment of the device 30a, 44a includes two sections 60, 62. This embodiment advantageously utilizes the clip structure 50 as an anchoring mechanism for assisting with securing the device 30a, 44a in place and implanted as a selective occlusion device 22a in the native mitral valve 16. The two sections 60, 62 are employed in a manner described above in connection with the single section embodiment of the device 30, 44.

As will be appreciated from a review of FIGS. 5C and 5D, a modified frame structure 30a is employed to support a modified flexible membrane 44a. More specifically, the flexible membrane 44a includes corresponding sections 44al and 44a2. These may be formed from one or more distinct pieces of membrane material. In addition, third and fourth membrane support members 64, 66 are provided to support the flexible membrane sections 44al and 44a2 in manners similar and analogous to the manner that support members 38, 40 support and function in the first illustrative embodiment discussed above. An arc-shaped frame member 32 is shown similar to the first embodiment spanning across the native valve 16. Vertical support members 65, 67 extend from the frame member 32 and couple with the membrane support members 64, 66. As another option, the frame member 32 may be eliminated and the vertical members 65, 67 or other structure could be joined together in the central region of the device 22a.

[0156] As further shown best in FIG. 5C, the suture or wire 54 couples the clip structure

50 to the frame structure 30a, such as by using a crimp element or other securement 68 generally at hinge 32a. It will be appreciated that other securement methods and structures may be used instead to secure the clip structure 50 to the frame structure 30a. The clip structure 50 and the frame structure 30a may take other forms than the illustrative forms shown and described herein. Use of the clip structure 50 securing the frame structure 30a in addition to the non-penetrating and/or other connectors such as generally at the native annulus 16c provides for an overall secure implant. The clip structure 50 and one or more annulus connectors will provide opposing forces that firmly secure the frame structure 30a and flexible membrane 44a generally therebetween. The two separate selective occlusion or flow control sections 44al, 44a2 are separated from each other by the clip structure 50. The attachment of the selective occlusion device 22a to the native mitral valve 16 may be a direct connection between the flexible membrane 44a and the native leaflets 16a, 16b (see below). Another option is that instead of the single arch-type frame member 32, the two side-by-side sections 60, 62 of the frame structure 30a may be otherwise coupled together near the center of the selective occlusion device 22a to avoid the need for a continuous frame member 32 spanning across the native mitral valve 16. Still further modifications are possible, while retaining advantages of a clip structure used in combination with a selective occlusion device. For example, the selective occlusion device may be configured as a frame structure and flexible membrane affixed around a continuous perimeter portion of the frame structure.

[0157] FIGS. 6A and 6B illustrate additional embodiments of selective occlusion devices

22b and 22c. In these FIGS the flexible membrane 44a is shown in broken lines so that the respective frame structures 30b, 30c are more clearly shown. In the illustrative embodiment of FIG. 6A, the central hinge has been eliminated and the suture or wire 54 extends directly through the frame member 32. As with all embodiments, the devices 22b, 22c and any associated components, such as the frame structures 30b, 30c, may be made flexible enough and foldable into a collapsed condition for catheter delivery purposes. Again, a crimp element (not shown) or any other fixation manner may be used to secure the wire or suture 54 in tension against the frame structure 30b, 30c. FIG. 6B illustrates an embodiment of the selective occlusion device 22c slightly different from the embodiment of FIG. 6 A in that the flexible membrane 44a, shown in broken lines, is folded inwardly at the region of the clip structure 50. As shown in FIG. 6A, and as one additional option, the flexible membrane 44a may be more distinctly attached to the frame members as shown by the broken lines extending upwardly against the vertical frame members 65, 67.

[0158] FIGS. 7A and 7B are top views illustrating selective occlusion device 22c, such as shown in FIG. 6B having separate sections 44a 1 and 44a2 secured in place and implanted within a native mitral valve 16. FIG. 7A shows the selective occlusion device 22c when the heart cycle is in diastole, and FIG. 7B shows the selective occlusion device 22c when the heart cycle is in systole. The function of a multi-section apparatus, such as with devices 22a, 22b, 22c, is similar to the function of the single section selective occlusion device 22 discussed above in connection with the first illustrative embodiment, except that with the native mitral valve itself separated into two sections by the clip structure 50, the separate flexible membrane sections 44al and 44a2 independently function to contract or collapse in diastole (FIG. 7A) and billow, expand or inflate outwardly in systole (FIG. 7B) due to the forceful introduction of blood flow when the heart cycle is in systole. The effect or result is similar to that described above in connection with, for example, FIGS. 3 A and 3B, but with the dual effect of correcting any misalignment or lack of coaptation between the native mitral leaflets 16a, 16b on each side of the clip structure 50. In this manner, blood flow is allowed in diastole as shown in FIG. 7 A past the native mitral leaflets 16a, 16b which have spread or expanded outwardly and also past the two section flexible membrane 44a which has collapsed inwardly or away from the native mitral leaflets 16a, 16b. Reverse or regurgitated blood flow is at least reduced, if not reduced to essentially zero (prevented), during systole as the flexible membrane 44a expands or inflates to contact or engage the native mitral leaflets 16a, 16b creating a fluid seal.

[0159] FIG. 8 shows a side view of the selective occlusion device 22c shown in FIG. 7B, but with the flexible membrane 44a shown in broken lines for clarity. The selective occlusion device 22c is securely implanted in the mitral valve 16 between annulus connectors 34, 36 generally at an upper location and a clip structure 50 at a lower location. Again, different connector and/or clip configurations may be used than those shown and described, and different numbers of connectors and clip structures may be used. The clip structure or structures may be secured to each leaflet 16a, 16b simultaneously as shown, or may be secured separately to a single leaflet 16a and/or 16b. Although the tensile member 54 is shown to have a particular length to connect between the clip structure 50 and the frame member 32, a tensile member or other type of connection of any necessary longer or shorter extent may be used instead. In some cases, the clip structure 50 may be directly affixed to the frame structure 30.

[0160] FIG. 9 illustrates a selective occlusion device 22d constructed according to an illustrative embodiment, in which an alternatively configured frame structure 30d is used and coupled with a flexible membrane 44 (shown in broken lines for clarity. Particularly, lower supporting members 70, 72, 74, 76 have a different configuration for guiding the shape of the flexible membrane 44. The flexible membrane 44 may be securely attached to the lower supporting members 70, 72, 74, 76 along their entire lengths, or along a portion of their lengths, or not at all if they are otherwise held in place during diastole in a suitable manner. The lower margins of the flexible membrane 44 are allowed to billow or expand outwardly and may be detached from the lower supporting members 70, 72, 74, 76 along at least substantial portions to allow this expanding or billowing action to take place. In addition, the entire frame structure 30d and/or only the lower supporting members 70, 72, 74, 76 may be highly flexible to allow this expansion or billowing action to take place when the heart cycle is in systole, as previously described.

[0161] FIGS. 10A, 10B and IOC show another illustrative embodiment in which a transcatheter system 52 is used and, specifically, a clip structure capturing device 80 is used to help secure the selective occlusion device 22a in place. This may be particularly useful when applying a selective occlusion device such as according to the present disclosure to a previously implanted mitral clip structure 50. The clip structure 50 may be of any type or configuration. In cases where the clip structure 50 has failed to properly repair the mitral valve 16, or the mitral valve function has degraded over time, despite the clip repair procedure, this embodiment assists with the capturing of the previously implanted clip structure 50 and implantation of a selective occlusion device, such as frame structure 30a and flexible membrane 44a. In this regard, and as shown in FIGS. 10A and 10B, a lasso or suture loop device 81 is deployed from a catheter 82 and captures the clip structure 50 with assistance from a guide device 83. The suture, wire or other tensile member 54 that extends upwardly through the mitral valve 16 may be a part of the suture loop device 81 in this embodiment and may then be used as generally described above to guide and securely affix selective occlusion device 22a, to the clip structure 50, as shown in FIG. IOC. For clarity, the flexible membrane 44a has not been shown in FIG. IOC.

[0162] FIGS. 11 A and 1 IB illustrate two additional embodiments of selective occlusion devices 22e, 22f, without showing the flexible membranes, that may be used to prevent blood flow regurgitation through a heart valve such as, by way of example, the mitral valve 16. In these embodiments, a flexible membrane 44a (FIGS. 11C through 1 IE) may be secured over a frame structure 90, 90' from one end to the other, such as between two non-penetrating annulus connectors or, in other embodiments, penetrating connector portions 92, 94, 92', 94'. Advantageously, there are two spaced apart elongate frame members 96, 98 extending between the connectors 92, 94, 92', 94', each having an upward bend or hump 100, 102 creating a recessed space. As shown in FIG. 11C the flexible membrane 44a is carried on this frame structure 90, 90' and may be secured to the frame members 96, 98 along all or some of the lengths thereof. This can leave a desired portion of the flexible membrane 44a at the lower margin of the frame structures 90, 90' unsecured and able to expand or billow in outward direction during systole, generally as described above in prior described embodiments or in later described embodiments. This outward expansion or billowing action will allow the flexible membrane 44a to better contact or engage the natural leaflet tissue during systole to prevent regurgitation of blood flow. This will also allow for more exchange of blood beneath or within the flexible membrane to prevent blood stagnation and the resulting possibility of clotting which may embolize and cause stroke or other complications. The humps 100, 102 in each of the lower, spaced apart support members 96, 98 accommodate the clip structure 50 and generally receive that portion of the mitral valve 16 fastened together at the A2/P2 junction. A central connection element, such as a hole 104, is provided in a central frame member 105 and allows a wire, suture or other tensile member 54 to attach the frame structure 90, 90' to the clip structure 50. The central frame member connects the annulus connectors 92, 94 and 92’, 94’ together and arches over and across the mitral valve 16 in a manner similar to frame member 32. Suitable configurations of the frame structure 90, 90' may be used, such as any of those previously described, for accommodating one or more clip structures and forming a plurality of separate flexible membrane sections, for example, with one section on each side of a clip structure 50. FIGS. 11 A and 1 IB also show another way of attaching a frame structure generally at the native annulus 16c with one or more holes 106, 108, 110, 112 to engage with a suitable fixation element or anchor 114 (FIG. 1 ID). The embodiment of FIG. 1 ID includes two additional fixation holes 116, 118 for receiving fasteners. In some embodiments such as shown in FIG. 1 ID, penetrating anchors may be used, such as rivets, T-bars, pledgets, or other fixation elements, although the benefits of non-penetrating connectors in accordance with this disclosure would be desirable, such as for purposes of allowing self-adjustment and reduced tissue damage.

[0163] FIGS. 12A and 12B illustrate another illustrative embodiment of a selective occlusion device 22g. Rather than employing a flexible membrane, this apparatus includes at least one rigid occlusion element 120. This embodiment is more specifically configured to operate in conjunction with mitral valve leaflets 16a, 16b that have been affixed together at a central location along their margins with a clip structure 50 such as a clip structure previously described. Therefore, two selective occlusion elements 120 are provided for reasons analogous to the two section flexible membrane embodiments described herein. The selective occlusion elements 120 are "rigid" in use within the mitral valve 16 in that they are static and need not flex inwardly or outwardly to engage and disengage the native mitral leaflets 16a, 16b during the systole and diastole portions of the heart cycle. Instead, these disk-shaped elements 120 retain their shape and are sized and located in the native mitral valve 16 such that the native mitral leaflets 16a, 16b engage the elements 120 during systole and disengage the elements 120 during diastole. This selective or cyclical interaction is shown in FIGS. 13 A and 13B, to be described further below. The device 22g shown in FIGS. 12A and 12B includes a frame structure 30e that is configured to extend generally across the native mitral valve 16, with a frame member 32 and hinge 32a as generally described in previous embodiments, along with non-penetrating annulus connectors 34, 36 as also previously described. Further, the clip structure 50 is secured to the frame structure 30e with a crimp element 68 and a suture, wire or other tensile member 54, such as in one of the previously described manners. In this way, the first and second rigid, selective occlusion elements 120 are respectively disposed on opposite sides of the native mitral valve 16 and on opposite sides of the clip structure 50 to selectively include the openings in the native mitral valve 16 formed when the clip structure 50 is affixed to each leaflet 16a, 16b bringing central portions of the two leaflet margins together either in direct contact with each other or in contact with a spacer (not shown) disposed between the movable clip elements. In this embodiment, the frame structure 30e is formed with a curved or arch-type frame member 32 configured to extend over the native mitral valve 16 in the left atrium 12.

[0164] The selective occlusion device 22g is shown when the heart cycle is in systole in

FIGS. 12A, 12B and 13A. The native anterior and posterior mitral valve leaflets 16a, 16b are shown being forced inwardly toward each other. There is no blood leak or regurgitation because the static occlusion elements 120 fill any residual gap between the anterior and posterior leaflets 16a, 16b. The elements 120 do not need to be of the depicted shape. Any shape of space filling would be sufficient if the gap between the two leaflets 16a, 16b is filled by the elements 120. The best shape could be determined at least partly by studying the shape of the gap between the native mitral valve leaflets 16a, 16b in systole after a clip structure 50 has been applied. The optimal shape for the elements 120 for a particular patient anatomy may even be custom manufactured for that patient with rapid manufacturing techniques. Advantages of using rigid/static element(s) 120 include their ability to withstand repeated cycling forces perhaps better than a design that relies on one or more moving valve elements that may be more susceptible to fatigue.

[0165] FIG. 12B more particularly shows a cut away view of the mitral valve 16 from commissure to commissure. At the commissures, the anchors or connectors 34, 36 are shown on each side - both above and below the leaflets 16a, 16b. Centrally, there is a clip structure 50 or other attachment that anchors to the mitral valve leaflets 16a, 16b either individually or together.

A tensile or other connecting member 54 extends up from the clip attachment component 50 and attaches to the frame member 32 which extends across the valve 16 from commissure to commissure.

[0166] The frame structure 30e can be constructed of a metal material such as stainless steel or Nitinol. Nitinol or other shape memory or super-elastic material may be preferred as this can be collapsed for delivery via a catheter device inside the heart, and then expanded inside the heart for implantation.

[0167] The element(s) 120 may be constructed in a number of ways and have various shapes. They could be composed of a frame of metal such as Nitinol that could be collapsed for catheter delivery. The metal frame could be covered by a plastic material or other artificial material like silicone or Teflon or polyurethane. Animal or human pericardium and animal or human heart valve material or any of the materials typically used for heart valve leaflet construction could be used to cover the frame structure 30e. A synthetic material or bioengineered material could also be used to cover the frame structure 30e.

[0168] The inside of the static occlusion elements 120 could be hollow. Or, a bladder or sac could be inside to fill the hollow interior space of the element(s) 120. The bladder could be filled with air or any gas or a liquid such as saline, sterile water, blood, antibiotic or antiseptic fluid, polymer or curable fluid material. The use of a bladder to fill the inside of the element 120 could eliminate the need or reduce the need for a frame associated with the element 120.

[0169] The selective occlusion device 22g has commissural and leaflet attachments to anchor it in position. It would also be possible to create this apparatus without a leaflet attachment. For example, the attachment could be at the commissures only. It would not be necessary to have a clip structure 50 and a member connected to the frame member 32. In this case there would not need to be two occluding elements 120. A single occlusion element 120 could be used to fill any gap between the two leaflets 16a, 16b. The shape of course would be different - likely an oval surface to extend between the commissures. The frame of such an element could be similar to that previously shown and described in connection with the first embodiment or another configuration.

[0170] FIG. 12C shows another illustrative embodiment or variation of a selective occlusion device 22h mounted inside the heart to the native mitral valve 16. There are two selective occluding elements 120 attached to a frame structure 30f. The frame structure 30f is engaged with a clip structure 50 that is attaching the anterior and posterior leaflets 16a, 16b together centrally, e.g., near the A2/P2 junction. The frame structure 30f is stabilized by connectors 34, 36 at the commissures and annulus region 16c of the valve 16.

[0171] The embodiment of FIG. 12C is similar to that shown in FIGS. 12A and 12B. The difference here is that the support frame member 32 is not located above the elements 120 but below the elements 120. In other embodiments the support frame member 32 is located above the selective occlusion device and been directed to the left atrium. In this embodiment, the supporting frame member 32 is biased downward and toward the left ventricle, generally below the mitral valve 16. Also, in this embodiment, the frame member 32 can be directly connected to the clip structure 50 that attaches the two leaflets 16a, 16b and the frame structure 30f together. This may allow a procedure where the entire device is implanted at one time. The clip structure 50, with the selective occlusion device elements 120 coupled to frame structure 3 Of, could be delivered by a catheter (not shown). The clip structure 50 (with or without exposing the rest of the device) could be extruded outside the delivery catheter inside the heart 10. The clip structure 50 may then be closed on the native mitral valve anterior and posterior leaflets 16a, 16b. The remainder of the selective occlusion device 22h could be then released from the delivery catheter - placing the entire device in position. This may simplify the procedure to one step.

[0172] It is also important to note that in prior embodiments the frame structure has been above the clip structure 50, and in this embodiment, the frame structure 30f is below. It is also possible to have both an upper and a lower support frame structure (such as by combining two arc shaped supports in one device). It would also be possible to join upper and lower arc support or frame members, so the support or frame structure is a complete loop or circle. This may provide further structural strength to the system. [0173] FIG. 12D is a side elevational view schematically illustrating another illustrative embodiment of a selective occlusion device 22i including first and second rigid or static selective occlusion elements 120 coupled with a frame structure 30g. In this embodiment, the rigid selective occlusion elements 120 are directly coupled to the frame structure 30g, which may be a frame member 32 coupled with the clip structure 50. As in previous embodiments, the clip structure 50 may directly couple respective margins of the anterior and posterior mitral leaflets 16a, 16b, or may couple these leaflet margins together against an intermediate spacer (not shown). This may be used to correctly orient and locate the rigid selective occlusion elements 120 on opposite sides of the clip structure 50 and within the side-by-side openings of the native mitral valve 16 created by the central clip structure 50. Optionally, additional connectors 122, 124 shown in broken lines may be used to help secure the rigid selective occlusion elements 120 in place at the commissures of the mitral valve 16.

[0174] FIGS. 13 A and 13B schematically illustrate, in cross section, the functioning of the rigid, selective occlusion elements 120 shown in FIGS. 12A through 12D. Specifically, when the heart cycle is in systole the native mitral leaflets 16a, 16b will close against the rigid selective occlusion elements 120 to provide a fluid seal against regurgitation of blood flow. As shown in FIG. 13B, during diastole, the mitral valve leaflets 16a, 16b will spread apart and disengage from the rigid selective occlusion elements 120 to allow blood flow from the left atrium 12 into the left ventricle 14 between the rigid selective occlusion elements 120 and the respective native leaflets 16a, 16b. The one or more elements 120 fill any gap between the anterior and posterior leaflets 16a, 16b. When mitral regurgitation occurs due to failure of complete leaflet coaptation, the leaflets 16a, 16b are frequently pulled apart from each other in the plane of the valve 16 (here left- right). However, the situation may become more complex because the leaflets 16a, 16b tend to be pulled down into the ventricle 14 as well as apart from each other as mitral regurgitation becomes more severe over time. So, an up/down gap may also occur with one leaflet 16a or 16b sitting at a higher plane than the other leaflet 16a, 16b.

[0175] The advantage to a convexly curved outer surface of the element(s) 120 is that this surface can be shaped to adapt to a wide variety of defects that may occur between the anterior and posterior leaflets 16a, 16b. An outer, convexly curved surface of the element(s) 120 can accommodate leaflet gaps that are in the plane of the valve 16 (left right in the Figure) and perpendicular to the plane of the valve 16 (up and down in the Figure). [0176] The selective occlusion device 22g is symmetric on each side. The elements 120 could also be constructed so that they are asymmetrical, i.e., not identical on opposite sides. For example, the posterior leaflet 16b may be more retracted into the left ventricle 14 than the anterior leaflet 16a. It may be useful to have adjustments in the element 120 on the side facing the posterior leaflet 16b to fill the gap left by a retracted posterior leaflet 16b. The element 120 may be constructed to be more prominent on the side of the element 120 adjacent to the posterior leaflet 16b than on the side adjacent or facing the anterior leaflet 16a. One or more elements 120 may be adjustable in shape, such as by an adjustable level of inflation to a hollow interior of the element 120 or other method, to accommodate any need to fill a gap between the leaflets 16a, 16b that would otherwise cause regurgitation.

[0177] Custom made or custom size elements 120 could also be made depending on the shape of the gap. A gap could be determined by echocardiography or CT and appropriately sized and shaped filling elements 120 could be selected based on measurements obtained with imaging. The valve defect that needs repair may be more shaped as a cylinder and a cylinder or pyramid- cylinder shape may be better to stop blood regurgitation than a lens or disc shape for the element(s) 120.

[0178] The margins of the element(s) 120 facing the oncoming flow of blood from the left atrium 12 has a tapering surface. This will allow the blood to flow smoothly into the left ventricle and avoid blood damage or hemolysis and to promote complete and unimpeded filling of the left ventricle 14. The edge of the element(s) 120 inside the left ventricle 14 also demonstrates a taper similar to the inflow region of the element(s) 120. When the heart begins to contract, blood will be ejected back toward the element(s) 120 and the native leaflets 16a, 16b will begin to move toward the element(s) 120 to produce a complete seal - preventing regurgitation of blood during systole.

[0179] An additional option is provided and illustrated in FIG. 13C. The rigid selective occlusion element(s) 120 may be formed in a fluid efficient manner, such as a teardrop shape or other hemodynamic shape to prevent undesirable blood flow patterns and damage or hemolysis as the blood flows past the elements 120 in between the element 120 and the respective mitral leaflets 16a, 16b.

[0180] FIGS. 14A, 14B and 14C illustrate additional embodiments of selective occlusion devices 22j, 22k, 221 that utilize rigid or static selective occlusion elements 120. These elements 120 function as discussed above in connection with FIGS. 12A through 12D and FIGS. 13A, 13B. In FIG. 14A the rigid or static selective occlusion elements 120 are coupled to a frame structure 30h that is secured along top margins of the elements 120. At each end of the frame structure 30h respective commissure connectors 126, 128 are provided that include connecting elements which operate the same as the butterfly type elements previously described by sandwiching mitral tissue or other heart tissue therebetween. Additional securement is provided by the clip structure 50 and a suitable tensile element or other connector 54, such as also previously described.

[0181] FIG. 14B illustrates an embodiment of a selective occlusion device 22k in the form of rigid or static elements 120 that are again generally disc shaped and secured together by a frame member 32’, a tensile element or connector 54 and a connected clip structure 50.

[0182] FIG. 14C illustrates an embodiment of a selective occlusion device 221 in which the rigid selective occlusion elements 120 are secured together by fabric or other structure 129, and further secured through a tensile member or other connector 54 to a clip structure 50 which secures the selective occlusion device 221 to the native mitral valve 16 through a clipping action as previously described.

[0183] FIGS. 15A through 15E illustrate another embodiment of a selective occlusion device 22m including a flexible membrane 44a and a frame structure 30i. The flexible membrane 44a is secured to frame structure 30i that is also preferably flexible for reasons such as previously described. This embodiment is similar to previous embodiments utilizing flexible membranes 44a in conjunction with a mitral valve clip structure 50, but includes a central reinforced area such as a fabric area 130 allowing the native leaflet margin tissue to be a clipped against the reinforced fabric area 130 directly. The clip structure 50 is shown in broken lines in FIG. 15E. In this alternative, the native mitral tissue is not directly contacting abutting native mitral tissue but instead contacts and is secured against the reinforced central fabric area 130 of the flexible membrane 44a. This fabric or other reinforcing material 130 may, for example, be useful in situations where the remainder of the flexible membrane is formed from more delicate material such as biologic material. Annulus connectors 132, 134 are provided and rest against an upper portion of the annulus 16c as generally shown in other Figures, such that the clip structure 50 (not shown in this embodiment) secures the selective occlusion device 22m to the reinforced, central area 130 from below, and the annulus connectors 132, 134 secure the selective occlusion device 22m from above by bearing against or otherwise coupling to the native annulus 16c. [0184] FIGS. 16A through 16D illustrate another illustrative embodiment of a transcatheter delivered selective occlusion device 22n combined with a clip structure 50. Again, the clip structure 50 is used to affix a lower central margin portion of one leaflet 16a to a lower central margin portion of the opposing leaflet 16b, generally as previously described. Again, this clipping action may be for purposes of clipping the anterior leaflet 16a directly in contact with the posterior leaflet 16b at the central location, or clipping the anterior and posterior leaflets 16a, 16b against an intermediate spacer. In this embodiment, the selective occlusion device is coupled with the clip structure 50 delivered through one or more catheters 52. As shown in FIGS. 16A and 16B, the catheter assembly 52 is delivered transeptally into the left atrium 12 and downwardly through the native mitral valve 16 although other approaches may be used instead in the various embodiments. The clip structure 50 is extruded from the catheter assembly distal end and, in the open condition shown in FIG. 16A captures the leaflet margin portions as shown in FIG. 16B and is actuated to move one or both clip elements 50a, 50b together into the position shown in FIG. 16C to secure the central leaflet margin portions together. The remaining portion of the selective occlusion device 22n is then extruded from the distal end of the catheter assembly 52 as shown in FIG. 16C. As shown in FIG. 16D the selective occlusion device 22n, which may be, as illustrative examples, of the type shown in FIG. 16D or any of the types otherwise shown and described herein, or even other configurations contemplated hereby, self-expands into the mitral valve location. Operation of the selective occlusion device 22n may be generally as described herein, and securement of the device 22n occurs generally between the clip structure 50 and respective annulus connectors 132, 134. Specifically, as previously discussed, the annulus connectors 132, 134 provide a downward force for securing the device 22n generally at the annulus 16c, while the clip structure 50 provides an upward force to generally secure the selective occlusion device 22n therebetween in place in the native mitral valve 16.

[0185] FIGS. 17A through 17C illustrate an embodiment of an apparatus for transcatheter delivery and implantation. In this embodiment, the clip structure 50 is delivered below the mitral valve 50 generally as previously described, and the selective occlusion device 22n is delivered to a location above the native mitral valve 16. The selective occlusion device 22n is inserted into the mitral valve 16 and between the native leaflets 16a, 16b, and also between the clip elements as shown in the method proceeding from FIG. 17A to 17B. Once in position as shown in FIG. 17B, at least one of the clip elements is moved toward the other clip element to clip or clamp the leaflet margins together, as previously described, and also to clamp a lower central portion of the selective occlusion device 22n and, particularly, the flexible membrane 44a in this embodiment, such that the leaflet margins are secured together at the same time as the selective occlusion device 22n is secured and implanted in place within the native mitral valve 16. As shown in FIG. 17C, the selective occlusion device 22n is fully extruded from the catheter assembly, whereupon it self- expands into position in the native mitral valve 16 and functions as otherwise generally discussed herein. More particularly, FIGS. 18A and 18B illustrate the diastole and systole portions, respectively, of the heart cycle with the apparatus secured in place as described in connection with FIGS. 17A through 17C. In FIG. 18 A, during diastole, blood flow is allowed between the native mitral leaflets 16a, 16b and the flexible membrane 44a, while in systole the flexible membrane 44a, in each section, fills with blood and thereby expands or inflates as the mitral leaflets 16a, 16b move toward one another and against the flexible membrane 44a to form a fluid seal preventing regurgitation of blood flow from the left ventricle 14 into the left atrium 12 of the heart 10.

[0186] FIG. 19 is an anatomical view from above the native mitral valve 16 with the selective occlusion device 22n superimposed to show another representation for the configuration in which the selective occlusion device 22n is curved and flexes in accordance with the natural curvature of the mitral valve 16.

[0187] FIGS. 20, 21 A, 21B and 21C illustrate another embodiment for a selective occlusion device 22o and apparatus (combining the device 22o with a clip structure 50), in which the selective occlusion device 22o is configured generally as a two section device, but with the sections in fluid communication as best shown in FIG. 21 A. A clip structure 50 is secured to the selective occlusion device 22o at a position between respective open ends 140, 142 of the sections. The clip structure 50 is used in the same manner as previously described. The flexible membrane 44b is supported by a flexible but strong frame structure 143, which may be formed in any manner contemplated herein, such as for allowing transcatheter delivery and implantation. The open ends 140, 142 are defined by hoop or ring portions 145, 147 of the frame structure 143. The hollow interior 144 of a flexible membrane 44b receives blood flow in the systole portion of the heart cycle and fluid communication between the two openings 140, 142 ensures better rinsing or washing during the heart cycle to reduce the chances of blood clots.

[0188] FIGS. 22A through 22D illustrate another embodiment of an apparatus for transcatheter delivery and implantation of a clip structure 50 coupled with a selective occlusion device 22p. A difference with this embodiment is that the clip structure 50 clips the native mitral leaflets 16a, 16b against a central or intermediate spacer 150, instead of directly into contact with each other. The procedure is generally shown in FIGS. 22A through 22C in which the clip structure 50 is first extruded from the transeptally directed catheter assembly 52 generally at a location below the mitral leaflets 16a, 16b. The leaflets 16a, 16b are captured against the intermediate spacer 150, as shown in FIG. 22B. The leaflets 16a, 16b are secured firmly against the spacer 150 as shown in FIG. 22C by moving at least one of the clip elements 50a, 50b toward the other. In this embodiment, each clip element 50a, 50b is moved toward the central or intermediate spacer 150 to clamp leaflet tissue against the spacer 150. The selective occlusion device 22p, in this illustrative embodiment, is already secured to the clip structure 50 when it is extruded from the catheter assembly 52 as illustrated in FIG. 22C whereupon the selective occlusion device 22p self-expands into the implanted condition shown in FIG. 22D. It will be appreciated that the selective occlusion device 22p may be extruded and implanted as a separate component, as well as coupled to the clip structure 50 in a suitable manner, instead of being extruded in an already assembled form from the catheter or catheters 52.

[0189] FIG. 22E illustrates another embodiment, similar to that shown in FIG. 22D, but further illustrating respective annulus connectors 154, 156 as part of the selective occlusion device 22p in the form of frame members that bear against heart tissue generally at the annulus 16c in the left atrium 12 and, additionally or optionally, frame members or connectors 158, 160 (shown in broken lines) coupled with the selective occlusion device 22p and located in the left ventricle 14 abutting the annulus 16c from below. Use of both sets of annulus connectors 154, 156, 158, 160 results in sandwiching the heart tissue therebetween for better securement.

[0190] FIG. 22F illustrates another embodiment of a device 22q, similar to FIG. 22E, but illustrating a single annular connector 164 generally encircling the native mitral valve 16 formed as part of the selective occlusion device and anchoring the selective occlusion device 22q in the native mitral valve 16 securely, preventing rocking in any direction but allowing flexibility. As with all embodiments, the frame members may be formed of any desired material, such as flexible wire-like materials formed from polymers and/or flexible metals including super-elastic or shape memory materials. This can help achieve overall goals of the embodiments of flexibility for collapsed delivery and improved operation during implanted use, as well as resistance against failure due to fatigue in this application involving continuous cycling in the heart. [0191] FIG. 22G illustrates another embodiment of a device 22r. The selective occlusion device 22r may be as described in connection with any other embodiment, but for illustrative purposes, is shown with a hollow flexible membrane 44b, while the frame structure has been modified as shown. The frame structure includes a generally annular frame member 170 such as described and shown in connection with FIG. 22F, but including raised portions 170a, 170b relative to other portions. The raised portions 170a, 170b are configured to be located adjacent and above the commissures of the native mitral valve 16 and are connected with a central frame member 32 extending generally across the native mitral valve 16 and formed as part of the selective occlusion device 22r such as with another connecting frame member 172. Such frame members at the annulus, as with all embodiments, may be above the annulus, below the annulus, or frame members/connectors may be above and below the annulus to sandwich tissue therebetween.

[0192] FIGS. 23A and 23B schematically illustrate a selective occlusion device 22s coupled with a central clip 50 including a spacer 150 implanted in a mitral valve 16. FIG. 23 A illustrates the device 22s and the mitral valve 16 when the heart cycle is in systole, while FIG. 23B illustrates the mitral valve 16 and the selective occlusion device 22s when the heart is in diastole. The frame structure includes respective hoops or rings 180, 182 as shown in solid lines in FIG. 23A and broken lines in FIG. 23B. These define the openings 140, 142. A benefit of this frame configuration is that the frame will not contact the commissures during repeated heart cycling. The device, like other embodiments allows blood flow from the left atrium to the left ventricle in diastole but prevents blood flow during systole.

[0193] FIG. 24 is a cross-sectional view schematically illustrating the mitral valve 16 and the implanted selective occlusion device 22s, coupled with a central clip structure 50 such as at a coupling 183. The selective occlusion device 22s is of a type with a hollow interior 144 having two fluid communicating sections 184, 186 and respective first and second openings 140, 142 and a closed end 188. Fluid communication between sections 184, 186 allows for better rinsing and washing action and reduced chance of clotting.

[0194] FIGS. 25A and 25B are schematic views of a selective occlusion device 22t, 22F including a flexible membrane 44b, 44b’ with FIGS. 25 A and 25B showing the selective occlusion devices 22t, 22F when the heart cycle is in systole. The difference between the two devices 22t, 22F is that the flexible membrane 44b’ is integrated into the spacer 150 of the clip structure 50, while the flexible membrane 44b is not. Flexible membrane 44b and/or another portion, such as a frame portion, of device 22t may be otherwise coupled to clip structure 50 such as in the manner shown in FIG. 24 or another suitable manner.

[0195] FIGS. 26A, 26B and 26C schematically illustrate another illustrative embodiment of an apparatus including a central clip structure 50 (FIG. 26B) and a selective occlusion device 22u. The selective occlusion device 22u, as with previous devices shown and described herein, is a hollow fluid communicating structure having a flexible membrane 44b and allowing blood flow into the hollow interior 144 defined by the flexible membrane 44b in systole, as shown in FIG.

26B and 26C. In diastole, the flexible membrane 44b collapses inwardly, as previously shown and described, to allow blood flow past the selective occlusion device 22u and between the native mitral leaflets 16a, 16b from the left atrium 12 into the left ventricle 14. In this embodiment, the orientation of openings 140, 142 and shape of the device 22u force blood flow, in systole, toward the commissure regions as shown by the arrows. These forces help retain the device 22u in place, in addition to any other securement such as the clip structure 50. In this way, rocking of the device 22u may be reduced and the device 22u can be more stable during implantation and use. These inlets 140, 142 are angled acutely away from the central clip structure 50 as shown in FIG. 26B. [0196] FIG. 26D illustrates another embodiment of a selective occlusion device 22v in which a suitable baffle structure 190 is provided within the selective occlusion device 22v for directing blood flow outwardly as shown by the arrows toward the connecting locations between the device 22v and the mitral annulus 16c. This helps to produce securement force and stabilization of the device 22v in the implanted condition. A single opening 192 is provided for in flow during systole and the device 22v includes a closed end 194 and a hollow interior 195, such that the device 22v fills with blood during systole and collapses to expel the blood during diastole as previously shown and described. A frame structure 196 is provided to support a flexible membrane 44b, generally as previously described, except that the frame structure is shaped and configured differently so as to form the single opening 192 defined by a hoop or ring frame member 197. It will be appreciated that the shapes and configurations of these structures may be modified from those shown in these illustrative examples.

[0197] FIG. 26E is an embodiment of a device 22w that may be configured as previous embodiments have been described, in terms of the selective occlusion device 22w, but which includes a generally annular or circular frame 200 structure that is a flat element for securing the apparatus in place in the mitral valve 16. The frame structure 200 is shown to rest and/or be secured in the left atrium 12 abutting against heart tissue generally proximate the mitral annulus 16c. However, it will be appreciated that such a structure could be secured in other manners, and that an additional lower support may be provided to sandwich heart tissue therebetween.

[0198] FIGS. 27A through 27C illustrate another embodiment of a selective occlusion device 22x which may be constructed in accordance with previous described embodiments, but including at least one small vent 202 opposite to the two openings 140, 142 of the flexible membrane 44b. The vent 202 is not large enough to result in any significant regurgitation or leakage of blood in systole. To the extent that the vent 202 does not allow any significant regurgitation of blood, this end of the flexible membrane is closed while the opposite end includes at least one and, in this embodiment two openings 140, 142. Otherwise, this embodiment of the flexible membrane 44b operates and functions for purposes and in ways as previously shown and described. One or more vents 202 may, for example, provide a pressure relief to reduce the forces against the device 22x during high pressure systole portions of the heart cycle.

[0199] FIGS. 28A through 28C illustrate another embodiment of an apparatus comprised of a central clip structure 50 and the previously described selective occlusion device 22p. In this embodiment, the clip structure 50 includes a central gripping structure 210 which may have tines or other knurled, roughened or frictional surfaces. This will assist with clamping and retaining mitral leaflet margin tissue between the respective clip elements 50a, 50b and the selective occlusion device 22p. The clip structure 50 is secured to the selective occlusion device 22p, such as via the central gripping element 210. FIGS. 28B and 28C further illustrate that the selective occlusion device 22p operates in the same manner, for example, as described above with fluid communication between two generally adjacent openings 140, 142 for increased washing and rinsing.

[0200] FIGS. 29A, 29B and 30 illustrate the apparatus shown in FIGS. 28A through 28C in operation after being implanted in the mitral valve 16. Specifically, blood enters the selective occlusion device 22p through the open ends 140, 142 and fills the interior 144 defined by the flexible membrane 44b, whereupon the flexible membrane 44b expands or inflates to engage in contact with the native mitral leaflets 16a, 16b forming a fluid seal that prevents regurgitation of blood flow during systole (FIGS. 29A and 29B). This is shown in FIG. 29B with the anatomy of the mitral valve 16 further shown and the native leaflet tissue contacting the outside surfaces of the flexible membrane 44b during systole.

[0201] FIG. 31 illustrates another embodiment showing an expandable prosthetic heart valve 220, which may be comprised of a generally cylindrical outer or peripheral frame structure 222 and coupled with interior prosthetic leaflets 224 that open and close to control blood flow therethrough. This is different from the other versions of a selective occlusion device which have at least one movable valve element (e.g., the flexible membrane that operates in conjunction with a native mitral leaflet), in that this prosthetic heart valve 220 does not operate in conjunction with the native leaflet to control blood flow. Instead, the prosthetic leaflets 224 control blood flow through the prosthetic valve 220. Coupled to the frame structure 222 are clip structures 50 or elements that directly couple the expandable prosthetic heart valve 220 to heart valve leaflets, such as the mitral valve leaflets 16a, 16b as previously shown and described. FIG. 32A is a side elevational view partially fragmented to show the internal stent structure 226 exposed underneath an outer covering 230, which may be natural, synthetic, biologic, bioengineered, or any other suitable medical grade material useful for cardiac devices of this type.

[0202] FIGS. 32B through 32E illustrate the succession of steps used to implant the prosthetic valve 220 of FIGS. 31 and 32A. In particular, this apparatus may be implanted through a transcatheter procedure, or a more invasive procedures such as a surgical procedure or keyhole type or other less invasive procedure. The collapsed or folded apparatus 220 is inserted between the mitral valve leaflets 16a, 16b as shown in FIG. 32B, the clip structures 50 are used to capture the lower margins of the mitral leaflets 16a, 16b (FIG. 32C) and clamp them as shown in FIG.

32D. The expandable prosthetic heart valve 220 is then expanded against the native mitral leaflets 16a, 16b as shown in FIG. 32E to secure the implanted prosthetic heart valve 220 in place within the native mitral valve 16. The prosthetic leaflets 224 then open and close, respectively during diastole and systole to allow and prevent the flow of blood through the prosthetic heart valve 220. [0203] FIG. 33 illustrates another embodiment, similar to the previous embodiment shown in FIG. 32, but adding an upper flange element 236 that helps secure the prosthetic heart valve 220 by stabilizing the heart valve 220 within the left atrium 12. In this regard the flange 236 is mounted above the native mitral valve 16. The flange 236 may abut against heart tissue in the lower portion of the left atrium 12. FIG. 34A is a side elevational view of the prosthetic heart valve 220 shown in FIG. 33. FIG. 34B is an illustration of the prosthetic heart valve 220 shown secured in place within the native mitral valve 16.

[0204] FIGS. 35 A and 35B show another embodiment of a selective occlusion device 22y mounted in a native mitral valve 16, as viewed in cross section. This embodiment includes a flexible membrane 44c with an open end facing the left ventricle 14, as in other embodiments, and receiving blood flow from below when the heart cycle is in systole (FIG. 35 A). In this portion of the heart cycle, the flexible membrane 44c expands against the native leaflets 16a, 16b to reduce regurgitation as previously discussed. In diastole, the flexible membrane collapses and expels the blood therein (FIG. 35B). Blood then travels in the reverse direction, generally, through the mitral valve 16 by flowing between the native leaflets 16a, 16b and outer surfaces of the collapsed membrane 44c. A difference between this embodiment and others is that multiple clip structures 50 are used to secure the selective occlusion device 22y directly to the leaflets 16a, 16b. The leaflets 16a, 16b are not clipped to each other. It will be appreciated that even further clip structures 50 may be used in this embodiment as well as others. In this embodiment, a clip structure 50 secures one side of the flexible membrane 44c to the anterior leaflet 16a and another clip structure 50 secures the flexible membrane 44c to the posterior leaflet 16b.

[0205] As described above with reference to FIGS. 31 to 34B, the flow of blood through a native valve can be controlled by a prosthetic valve that is engaged with the native valve apparatus by coupling the prosthetic valve to, and between, each of the native leaflets, e.g. by a clip that engages each leaflet and fixes it with respect to the frame of the prosthetic valve. Prosthetic valves, such as those used in transcatheter aortic valve implantation (“TAVI”) or transcatheter aortic valve replacement (“TAVR”) procedures, have proven to be reliable and effective.

Prosthetic valves such as the CoreValve Evolut valve offered by Medtronic and the Sapien valve offered by Edwards Lifesciences are representative. They have metal stent or frame bodies, which may be balloon-expandable (e.g. cobalt chromium) or self-expanding (e.g. Nitinol) that support a tri-leaflet prosthetic valve set (typically formed of animal tissue such as pericardium or native animal leaflets).

[0206] As described in more detail in the following embodiments, prosthetic valves can also be used to control the flow of blood through a native heart valve on which an edge-to-edge approximation procedure is performed (e.g. with a clip such as the MitraClip™ or PASCAL), which procedure alters the native valve orifice between the native valve leaflets. For ease of illustration and explanation in the following description, the native valve is a mitral valve, i.e. a bileaflet valve with an anterior leaflet and a posterior leaflet, but the devices and procedures described below can also be used, or adapted for use, with other native valves, such as the tricuspid, that have three native leaflets.

[0207] For reference, FIG. 36A illustrates a native mitral valve MV, with a posterior leaflet PL and anterior leaflet AL. The posterior leaflet PL has three segments or scallops: PI (anterior or medial scallop); P2 (middle scallop); and P3 (posterior or lateral scallop). The anterior leaflet AL has three corresponding segments: A1 (anterior segment); A2 (middle segment); and A3 (posterior segment). The corresponding segments or scallops of the anterior leaflets coapt with each other to prevent retrograde flow through the valve (from the left ventricle LV into the left atrium LA) during systole - in FIG. 36 A, the leaflets are shown coapted, i.e. they are in the position they assume during systole. The two leaflets AL and PL meet at two commissures - the posteromedial commissure PMC and the anterolateral commissure ALC. The leaflets extend from the mitral valve’s annulus, MVA (not shown in FIG. 36A).

[0208] For further reference, FIG. 36B illustrates a native tricuspid valve MV, with a posterior leaflet PL, an anterior leaflet AL, and a septal leaflet SL. In FIG. 36B, the leaflets are shown coapted, i.e. they are in the position they assume during systole. The leaflets meet at three commissures: the anterior leaflet AL meets the septal leaflet SL at the anteroseptal commissure ASC; the septal leaflet SL and the posterior leaflet PL meet at the posteroseptal commissure PSC, and the posterior leaflet PL meets the anterior leaflet AL at the anteroposterior leaflet APC.

[0209] For further reference, a native mitral valve MV is shown schematically in

FIG. 37A. In this figure, the edges of the leaflets AL and PL are shown in solid lines when the heart is in systole, i.e. the leaflet edges are coapted against each other and (for a competent native valve) block retrograde blood flow, and are shown in dashed lines with the heart is in diastole, i.e. the leaflets are spaced, permitting antegrade blood flow from the left atrium LA to the left ventricle LV.

[0210] FIGS. 37B to 37D schematically illustrate a native mitral valve MV on which an edge-to-edge approximation is performed with one or more clips. As shown in FIG. 37B, a single clip CL has been disposed centrally to approximate the edges of the anterior leaflet AL and posterior leaflet PL at their respective A2 and P2 segments. This has created two flow control portions through which blood can flow during diastole - FCP1, which is bounded by the anterior leaflet AL, posterior leaflet PL, clip CL, and posteromedial commissure PMC, and FCP2, which is bounded by the anterior leaflet AL, posterior leaflet PL, clip CL, and anterolateral commissure ALC. Similarly, as shown in FIG. 37C, a single clip CL has been disposed off-center in the native leaflets. Two flow control portions - FCP1 and FCP2 - are created, but they are of substantially different sizes. In the extreme case of off-center or eccentric clipping, the smaller flow control portion (e.g. FCP1 in FIG. 37C) may be of insignificant or negligible size to warrant treatment.

As such, a single, larger flow control portion may result with the placement of a single clip CL.

As shown in FIG. 37D, two clips have been disposed spaced from each other to approximate the edges of the anterior leaflet AL and posterior leaflet PL. This has created three flow control portions through which blood can flow during diastole - FCP1, which is bounded by the anterior leaflet AL, posterior leaflet PL, clip CL, and posteromedial commissure PMC; FCP2, which is bounded by the anterior leaflet AL, posterior leaflet PL, clip CL, and anterolateral commissure ALC; and FCP3, which is bounded by the anterior leaflet AL, posterior leaflet PL, and the two clips CL.

[0211] FIGS. 38A to 38F schematically illustrate a native tricuspid valve TV on which an edge-to-edge approximation is performed. FIGS. 38A and 38B illustrate a native tricuspid valve TV on which a “triple orifice” clipping technique has been performed with two clips CL (such as the TriClip™ - FIG. 38A illustrates tricuspid valve TV during systole, and FIG. 38B illustrates tricuspid valve TV during diastole. One clip CL joins the anterior leaflet AL and the septal leaflet SL, while the other clip CL joins the posterior leaflet PL and the septal leaflet SL. This clipping procedure has created three flow control portions through which blood can flow during diastole - FCP1, which is bounded by the anterior leaflet AL, posterior leaflet PL, septal leaflet SL, both clips CL, and anteroposterior commissure APC; FCP2, which is bounded by the anterior leaflet AL, septal leaflet SL, one clip CL, and anteroseptal commissure ASC; and FCP3, which is bounded by the posterior leaflet PL, septal leaflet SL, one clip CL, and posteroseptal commissure PSC.

[0212] FIGS. 38C and 38D illustrate a native tricuspid valve TV on which a

“bicuspidization” clipping technique has been performed with two or more clips CL - FIG. 38C illustrates tricuspid valve TV during systole, and FIG. 38D illustrates tricuspid valve TV during diastole. All of the clips CL joins the anterior leaflet AL and the septal leaflet SL. This clipping procedure has created one large flow control portion through which blood can flow during diastole - FCP1, which is bounded by the anterior leaflet AL, posterior leaflet PL, septal leaflet SL, one of the clips CL, anteroposterior commissure APC, and posteroseptal commissure PSC.

[0213] FIGS. 38E and 38F illustrate a native tricuspid valve TV on which a “three clip variant” clipping technique has been performed with three clips CL - FIG. 38E illustrates tricuspid valve TV during systole, and FIG. 38F illustrates tricuspid valve TV during diastole. One clip CL joins the anterior leaflet AL and the septal leaflet SL, one joins the joins the septal leaflet SL and posterior leaflet PL, and one joins the posterior leaflet PL and the anterior leaflet AL. This clipping procedure also creates one large flow control portion through which blood can flow during diastole - FCP1, which is similar to, but smaller than, the opening of the native tricuspid valve before the clipping procedure. Thus, the flow control portion FCP 1 is bounded by the anterior leaflet AL, posterior leaflet PL, and septal leaflet SL, but instead of being bounded by the three native commissures, it is bounded by the three clips CL.

[0214] As discussed above, the goal of an edge-to-edge approximation procedure, using one or more clips (such as the MitraClip™, TriClip™, or PASCAL) is to repair a native valve that is not adequately preventing retrograde flow during systole, i.e. is experiencing regurgitation. The clipping procedure can reduce, or ideally eliminate, such regurgitation. However, experience has shown that regurgitation can still occur in one or more of the flow control portions FCP created by the clipping procedure, either immediately after the procedure or over time (e.g. with expansion of the heart and correspondingly the size of the annulus of the native valve, or retraction of the native leaflets). In the embodiments described above, a selective occlusion device may be disposed in the one or more regurgitant flow control portions to reduce or eliminate regurgitation. The selective occlusion device may be engaged with the clip(s) to maintain, or aid in maintaining, the device in the desired position with respect to the native valve and the flow control portions. The selective occlusion device may also be supported with respect to the native valve with the aid of one or more structures that engage with the annulus of the native valve and/or other structure of the native valve apparatus. In embodiments described below, a prosthetic valve may be disposed in the one or more regurgitant flow control portions. Devices and systems incorporating such prosthetic valves may employ similar structures and techniques for engaging with the clip and/or the native valve apparatus to maintain the prosthetic valve(s) in position.

[0215] An embodiment of a prosthetic valve 100 is illustrated schematically in a side view and top view, respectively, in FIGS. 39A and 39B. In the following description, some of the reference numbers use are the same as those in the preceding description. The reference numbers used below are intended to be internally consistent, so no correspondence of structures or functions for elements with the same reference number in the preceding and following description should be inferred. As shown in FIGS. 39A and 39B, prosthetic valve 100 includes a body 110 with an inlet portion 112, a transition portion 113, and an outlet portion 114. Outlet portion 114 includes a first limb 116 and a second limb 117, and may optionally include a third limb 118.

Body 110 defines a flow passage 130 therethrough that includes a flow control passage 132 in the inlet portion 112, a branching or transition passage 133 in transition portion 113, a first limb passage 134 in the first limb 116 and a second limb passage 136 in second limb 117, and may optionally include a third limb passage 138 in optional third limb 118.

[0216] All of the portions of the flow passage 130 are in fluid communication with each other and can conduct fluid, e.g. blood, from an inlet 131 at the entrance to the flow passage 130, through the flow control passage 132, through the transition passage 133, and through the first limb passage 134 out of a first outlet 135 at the exit to the first limb passage 134, the second limb passage 136 out of a second outlet 137 at the exit to the second limb passage 136, and optionally through the optional third limb passage 138 and out of a third outlet 139 at the exit to the optional third limb passage 138.

[0217] Flow through the flow passage 130, and in particular through flow control passage

132, is controlled by flow control device 160. Flow control device 160 can be constructed, and function, similar to known prosthetic valves described above, and may be implemented as a tri leaflet valve with three leaflets. Other valve constructions may be suitable, including valves with fewer than three leaflets, which may coapt against fixed structures in the valve in addition to, or instead of, coapting against other leaflet(s), as described in more detail below in particular embodiments. As shown schematically in FIGS. 39A to 40B, flow control device 160 may be cylindrical, with a circular cross section. Flow control device 160 may be mounted to inlet portion 112 of body 110 and disposed so that all flow through flow control passage 132 must pass through flow control device 160. Flow control device 160 is configured to permit fluid to flow therethrough in the direction from the inlet 131 to the outlets 135, 137, and optionally 139, but to prevent fluid to flow in the opposite direction.

[0218] It is well known that tissue valves can fail, and it is also known that this problem can be solved by delivering another tissue-based stent valve inside a failed valve. Thus, it is contemplated that if flow control device 160 fails, a new tri-leaflet valve can be placed inside flow control device 160.

[0219] Prosthetic valve 100 also includes a clip connector 170 that is part of, or coupled to, body 110, and is configured to engage with a clip such as those described above, and thereby to retain prosthetic valve 100 in operative relationship with a native heart valve to which the clip is attached. In particular, clip connector 170 is configured to carry fluid dynamic load applied to prosthetic valve 100 during the cardiac cycle of the heart to the clip CL and thence to the native leaflets, annulus, and surrounding heart tissue to resist displacement of the prosthetic valve. The largest loads to be carried tend to be during systole, and the displacement to be resisted is towards the atrium of the heart.

[0220] Clip connector can be implemented in a variety of configurations, including those described above in connection with numerous embodiments of selective occlusion devices to couple a frame structure (which can be analogized to body frame 120 and/or to annulus connector 180) to a clip structure, for example in FIGS. 5C-5D (with a tensile member 54), FIGS. 12C-12D (frame member 32 connected directly to the clip 50), FIGS. 14A-14C (with a rod-like connector 54), FIGS. 15A-15E and FIGS. 27A-27C (with the clip directly engaging a reinforced central fabric area 130 of the flexible membrane 44a or 44b).

[0221] Prosthetic valve 100 is shown disposed in a native heart valve in a side view and top view, respectively, in FIGS. 40A and 40B. Note that for convenience of illustration, prosthetic valve 100 is shown in FIGS. 40A and 40B without the optional third limb 118 and associated third limb passage 138 and third outlet 139, and the native heart valve is illustrated as a mitral valve MV. Mitral valve MV is shown with the anterior leaflet AL and posterior leaflet PL joined by a clip CL in an edge-to-edge approximation, similar to the mitral valve MV shown in FIG. 37B. Thus, mitral valve MV has two flow control portions - FCP1 and FCP2 - defined between the clip, the leaflets, and the commissures of the mitral valve MV.

[0222] As shown in FIGS. 40A and 40B, prosthetic valve 100 can be disposed in mitral valve MV with inlet 131 disposed in the left atrium LA and the first outlet 135 and second outlet 137 disposed in the left ventricle LV. First limb 116 is shown disposed in flow control portion FCP1, and second limb 117 is shown disposed in flow control portion FCP2. Clip connector 170 is engaged with clip CL. Optional annulus connector 180 can be engaged with mitral valve annulus MVA. When prosthetic valve 100 is disposed in mitral valve MV, it is operable to reduce or eliminate regurgitation through flow control portions FCP1 and/or FCP2, i.e. to prevent retrograde flow of blood from the left ventricle to the left atrium during systole, but to allow blood to flow freely through prosthetic valve 100 from left atrium LA to left ventricle LV during diastole.

[0223] As noted above, prosthetic valve 100 can be used with other native heart valves, including the other atrioventricular valve, the tricuspid valve. For example, a prosthetic valve with the optional third limb may be useful for a tricuspid valve on which a triple orifice clipping technique has been used, with each of the three limbs being disposable in each of the three resulting flow control portions, respectively. However, in some instances it may be preferable to use a prosthetic valve that does not include the third limb in such a tricuspid valve, disposing each of two limbs in two of the three flow control portions, and allowing the third flow control portion to function only with the native leaflets.

[0224] The height of inlet portion 112 of body 100, or the collective height of inlet portion

112 and transition portion 113, may be of any suitable distance, though it is desirable that it not be so large that the inflow of blood into inlet 131 is impeded, i.e. sufficient room is left above and around inlet 131 inside the atrium of the heart for blood to freely enter.

[0225] The absolute and relative sizes (cross-sectional areas) of the flow control passage

132 (and flow control device 160) and of the first limb passage 134 and second limb passage 136 (and optional third limb passage 138) can be varied to optimize function, to match the anatomy, cardiac capacity, etc. of the heart, or to account for other relevant factors.

[0226] Each of the first limb 116 and the second limb 117 may be configured so that outer surfaces thereof engage in a substantially sealing relationship with the anterior leaflet and the posterior leaflet and thereby to reduce or prevent the flow of blood therebetween, during at least a portion of the pumping cycle of the heart. In some embodiments, each of the first limb and the second limb may be sized (e.g. perimeter) and configured (e.g. cross-sectional shape is circular, elliptical, ovoid, etc.) to substantially fill, or over-fill (stretch) the corresponding flow control passage, maintaining the edges of the leaflets in sealing relationship with the outer surfaces of the first limb and the second limb throughout the cardiac cycle, thus preventing flow between the limbs and the leaflets from the atrium to the ventricle during diastole and from the ventricle to the atrium during systole. In this configuration, substantially all blood flow from the atrium to the ventricle during diastole is therefore carried through the prosthetic valve (and thus through the flow control device), and blood flow from the ventricle to the atrium during systole (regurgitation) is substantially prevented (by the flow control device 160). This configuration offers several benefits. First, the native leaflets would move little or not at all during the cardiac cycle, which should reduce wear resulting from repetitive contact between the leaflets and the outer surfaces of the limbs of the prosthetic valve (there is little momentum on the native leaflet during impact with the limbs). The native leaflets are pliable and will tend to fill any irregular shapes or defects in closure. Second, complete valve sealing, i.e. prevention of regurgitation, should be assured. Finally, the heart tends to deteriorate over time in patients needing valve repair or replacement.

For such patients, regurgitation should not occur again as the prosthetic valve assumes virtually full responsibility for the function of the native valve, and the residual valve tissue will be able to fill any gaps that may occur as the heart dilates (or alternatively any gaps that may occur as the valve leaflets retract with disease progression). These benefits are particularly applicable for a native valve to which an edge-to-edge clip has been applied. After the clip is applied the total opening size of the valve is limited to the area of the resultant flow control portion(s), which is a smaller area than that of the original opening of the native valve. Thus, the surface or orifice area that must be occluded by a valve is reduced and the load on the prosthetic valve is reduced. In many instances the clip can securely hold the load created by cardiac contraction, highest during systole.

[0227] In another configuration, the limbs could be sized to be smaller than the flow control portions, allowing a gap to be formed during diastole and permitting some of the blood flowing from the atrium to the ventricle to flow through the gap (in addition to the blood flowing through the flow passage and the flow control device). The limbs are preferable sized so that during systole the leaflets can sealingly engage the limbs’ outer surface and prevent retrograde flow between the limbs and the leaflets.

[0228] The limbs of prosthetic valve 100 are shown schematically in FIGS. 39B and 40B as being elliptical in cross section. This is because the flow control portions of the native valve that result from leaflet clipping are likely to be oval or slit like. By shaping the limbs with a corresponding cross-section, they can better follow the shape of the flow control portions and fill the leak space. In some embodiments, the cross-sectional shape of the limbs may be rounder (circular or oval) near the clip with a teardrop (more V-shaped) extension toward the commissures. Although the limbs are shown schematically in FIGS. 39B and 40B as being approximately linear, or symmetrically arranged about a center line through the clip, as can be seen in FIG. 36A, there is a natural curve to the coaptation line of the native mitral valve leaflets. When looking down on the mitral valve with the anterior leaflet above, there is a upward curve to the line of closure. To conform to this anatomy, in some embodiments the limbs of the prosthetic valve could be arranged to follow the curve of the coaptation line.

[0229] Limbs 116, 117 (and optionally 118) are shown schematically in FIGS. 39B and

40B as being straight and being parallel with each other. However, in some embodiments the limbs may be straight but may be non-parallel, and may be angled towards or away from each other. In other embodiments they may not be straight, but may instead be arcuate, and thus the outlet portion 114 of body 110 may have a horseshoe shape, similar to the shape of the device shown in FIG. 26B. Similarly, although the space between limbs 116, 117 (and optionally 118) is illustrated as rectangular in the schematic illustrations in FIGS. 39A and 40A, this space can be arcuate or curved with a large radius of curvature, or may be sharper (more V shaped).

[0230] Limbs 116, 117 (and optionally 118) are shown schematically in FIGS. 39A to 40B as being generally tubular in shape. However, in some embodiments it may be useful for the limbs to flare outwardly (larger perimeter) towards their respective outlets, as this may encourage more blood to enter the flow passage 130 during systole and urge closed the leaflets of the flow control device 160. Thus, the outlet ends of the limbs could have a trumpet bell shape, for example.

[0231] Although limbs 116, 117 (and optionally 118) are shown schematically in FIGS.

39B and 40B as having ends (i.e. at outlets 135, 137 (and optionally 139)) that are flat, i.e. linear and orthogonal to a central vertical axis of prosthetic valve 100, in other embodiments the ends of the limbs can be of any other configuration, including angled and / or arcuate, provided that they can be reliably positioned in the native valve so that preferably the entirety of the outlets are below the locations where the native leaflets are sealingly engaged with the limbs 116, 117 (and optionally 188). The outlets may also have an outflow perimeter that is not planar but rather a scalloped perimeter. For instance, the portion of the outflow perimeter that engages the anterior leaflet may extend deeper within the ventricle than the corresponding portion that engages the posterior leaflet. As such, the upward surge of blood during systole will first come into contact with this deeper extending portion of the outlet and may ensure better systolic filling of the prosthetic valve 100. [0232] Body 110 can be constructed with materials and techniques similar to known prosthetic heart valves such as those discussed above. For example, body 110 can have a body frame 120 formed of wires, struts, mesh, braids, or other suitable constructions, in metal (such as cobalt chrome, stainless steel, shape memory metals such as Nitinol, etc.), polymer, or other suitable material. Body frame 120 can be formed in a single, unitary piece formed in a Y shape, or it could be constructed by separate pieces that are joined together, e.g. one piece for each of the inlet portion 112, transition portion 113, first limb 116, second limb 117, and (optionally) third limb 118. In embodiments in which the body frame 120 is formed in separate pieces, the pieces could be delivered and implanted separately to make delivery easier, and then coupled together in place in the heart valve. As described in more detail below with reference to specific embodiments, body frame 120 does not necessarily extend to the outlet portion 114 of body 110. For example, a stiff graft (such as Dacron, Teflon etc. with or without coatings) could be used with no frame or with minimal frame.

[0233] The construction of limbs 116, 117, and (optionally) 118 could vary. In some embodiments, the portion of the body frame 120 in the limbs can be configured with a stent frame, with the potential for body covering 122 and/or body lining 123 to include, or the addition of, padding (formed of materials such as silicone and pericardium). It may be useful to make the limbs more complaint so that the limbs move with each heartbeat and reduce the wear when leaflet tissues contact the device. Thus, any or all of the limbs could be constructed similar to the arrangements described above for pseudo-valves, such as the embodiments shown in FIGS. 5D, 7A-B, 15A-E, or 18A-B. In such embodiments, the limbs can be constructed with a frame that allows the superimposed biologically compatible covering (such as pericardium) to move back and forth with each cardiac cycle. In other embodiments, the limbs could be constructed similar to the occlusion devices shown in FIGS. 13A-B and FIGS. 25A-B, in which the occlusion device is rigid or static, and the native leaflets moves toward the limbs to seal against leak and prevent wear. [0234] In some embodiments, the limbs of prosthetic valve can be configured to have their shapes be adjustable to improve the seal between the limbs and the native leaflets. For example, oval shaped balloons or oval shaped stents could be introduced to shape the limbs after the prosthetic valve 100 has been placed in the native valve. Such an approach could also be useful if the body covering 122 and/or body lining 123 on (or in) a limb wears out. A new body lining 123 could be applied from inside the limb, delivered through the flow passage 130 on a stent or a frame. This approach would be particularly useful if the limb is constructed with a segment in which there is little or no frame material.

[0235] Flow control device 160 is coupled to, and supported by, body frame 120 in inlet portion 112, or may optionally form some or all of the inlet portion of the body frame 120, and be coupled to the transition portion 113.

[0236] Body frame 120 can be covered on the outside with a body covering 122 and/or on the inside with a body lining 123, each of which may be formed from any suitable material that is biocompatible, sufficiently impermeable to fluids such as blood to form the flow passage 130 and maintain fluid within (or outside of) flow passage 130, and atraumatic to native valve tissue (leaflets, chordae, heart chamber walls, etc.) that contact the body 120. Suitable materials can include animal pericardium and synthetic materials such as Dacron (the latter material may be more suitable for covering areas of the body 120 that do not contact heart tissue as it can be somewhat abrasive).

[0237] Body covering 122 and/or body lining 123 may cover or line the entirety of body

120, or may be discontinuous, and cover only portions of body 120. Each may also be attached continuously to each area of body frame 120 that it covers or lines, but may also be attached around the periphery or margins of selected areas on the body 120, but not attached within those areas. This construction can allow blood to pass between, for example, struts in the body frame 120 and expand/balloon out the body covering 122 and/or body lining 123 so that it gently contacts the native valve leaflets. The native leaflets would contact against material of body covering 122 and/or body lining 123 (for example pericardium) that is backed by blood within flow passage 130 rather than against a solid portion of body frame 120. Body frame 120 could be formed with struts that are widely spaced in the region of contact to ensure the body covering 122 and/or body lining 123 will be expanded by blood. This could reduce considerably wear on native leaflet tissues.

[0238] As shown in FIG. 39A (but omitted from FIG. 40 A for ease of illustration), body

110 can also include an outlet cuff 124 at the outflow ends of the limbs 116 and 117 (and optionally, not shown, on limb 118) that includes padding material to reduce the risk of injury to cardiac tissue that may contact those portions of the body 120 during the cardiac cycle. Such padding material could be any useful biocompatible material. Silicone, polyurethane, bio polymers or bio-elastomers, Dacron, PTFE (Teflon) fabrics (often used in rolled or folded form in the sewing cuff of prosthetic valve sewing rings) are suitable options that are commonly used in valve structures. Such padding or damage reducing materials could be added to any part of prosthetic valve 100.

[0239] In some embodiments, features may be included in the flow passage 130 to guide the flow of fluid (e.g. blood) through prosthetic valve 100. For example, it may be useful to urge the fluid towards the lateral walls of flow passage 130, e.g. in the transition passage 133, similar to the flow diversion performed by the baffle 190 in FIG. 26D above. As described in connection with FIG. 26D, the force of the fluid flow directed to the sides of the prosthetic valve 100 may reduce the risk of rocking. It may alternatively, or additionally, be useful to mix the fluid (e.g. blood) flowing through flow passage 130, such as with a spiral component disposed in the transition passage 133, similar to the manner described with reference to FIG. 26D above. Mixing the fluid around a spiral may reduce the rocking on the prosthetic valve 100 by dissipating the energy and directing the flow centrally to the flow control component 160. Structure to perform the flow diversion and/or mixing is shown schematically in FIG. 39A as optional flow diverter / mixer 150 (flow diverter / mixer is omitted from FIG. 40A for ease of illustration).

[0240] Although clip CL is described above with reference to FIGS. 36A to 40B as being a commercially-available edge-to-edge leaflet clip such as the MitraClip or PASCAL, and prosthetic valve 100 being configured to engaged with such a clip after it has been used to clip the native leaflets, in some embodiments the clip CL may be configured differently than such commercially-available clips, and/or may be included as part of a system with prosthetic valve device 100 and configured to be delivered sequentially or concurrently with prosthetic valve 100 as part of a total valve repair / replacement procedure. As described above, prosthetic valve 100 is configured to be anchored to the clip CL, which in turn is coupled to the tissue of the anterior leaflet AL and posterior leaflet PL, and prosthetic valve 100 will carry a considerable fluid dynamic load during systole that must in turn be carried by the clip and the leaflets. Thus, an enlarged clip anchor may be useful. For example, the clip could be composed of two or three paddles (instead of the single paddle of the PASCAL and MitraClip™ device) to increase the area of the leaflets engaged by the clip. This allows the dynamic load to be distributed more evenly over a larger leaflet area (and over a greater number of underlying chordae tendineae that are attached to the engaged leaflet portions). [0241] Rather than relying on the clip connector (and thus clip CL, native valve leaflets, or other native valve tissue) to carry all of the fluid dynamic loads imposed on the prosthetic valve, in some embodiments those loads can be carried in part by other structures without putting the clip or the native leaflets in the load path. Thus, in some embodiments prosthetic valve can include an optional annulus connector 180 and/or an optional heart tissue tether 190.

[0242] As shown in FIGS. 39A to 40B, optional annulus connector 180 may be part of, or coupled to, body 110, and is configured to engage with an annulus (and/or other nearby tissue, including the atrial wall, the native leaflets, and/or the chordae tendineae) of a native heart valve to enhance the stability of the prosthetic valve 100 when placed in the native heart valve, e.g. to inhibit lateral rocking of the prosthetic valve, and or displacement away from the annulus towards the atrium (during systole) or the ventricle (during diastole). Annulus connector 180 may be implement similarly to annulus connectors described above with reference to various embodiments of selective occlusion devices, including: FIG. 22E (with annulus connectors 154 and 152 configured as elongate frame members that extend longitudinally from the frame of the selective occlusion device and can engage a peripheral portion of the mitral valve annulus, with connector 154 engageable with tissue on the atrial side of the annulus and connector 158 engageable with tissue on the ventricle side of the annulus); FIG. 22F (with a single circular annulus connector 164 coupled to the frame of the selective occlusion device and engageable with substantially the entire periphery of the atrial surface of the annulus, thus preventing rocking in any direction but allowing flexibility - this configuration could also be used for engagement with the ventricle side of the annulus); FIG. 26E (similar to FIG. 22F, but the with the circular annulus connector configured as a frame structure 200 that is a flat element that may be secured to the atrium side of the annulus, and may alternatively or additionally have a similar structure that may be secured to the ventricle side of the annulus). Annulus connector 180 may be configured with non-tissue penetrating members or with tissue penetrating members.

[0243] As shown in FIGS. 39A to 40B, one or more optional heart tissue tethers 190 may be coupled to body 110, clip connector 170, clip CL, and/or annulus connector 180. For ease of illustration, not all options are shown in all of the figures. Heart tissue tethers 190 may be elongate tension members implemented as metal wires, polymer sutures (of monofilament or braided construction), or other suitable, biocompatible materials with sufficient tensile strength to carried the desired portion of the fluid dynamic loads imposed on prosthetic valve 100. Each such tether may include a suitable anchoring mechanism by which the free end of the tether (opposite to the end connected to prosthetic valve 100) may be secured to the heart tissue. Such a tether anchor 192 can include any known mechanisms for securing tethers or sutures to tissue, including cardiac tissues, such as pins, screws, clips, suture loops, or enlarged structures (pledgets, disks) that may be disposed on the opposite side of a tissue wall from the body of the tether. The heart tissue tether(s) 190 could be coupled to heart tissue that includes various locations / structures in the ventricle, such as the apex of the ventricle, the ventricular septum, any other wall of the ventricle, one or more of the papillary muscles, one or more or the chordae tendineae, and/or the annulus of the native valve.

[0244] Prosthetic valve 100 may be delivered to and positioned in the native valve, and secured to the clip CL by the clip connector, to the annulus (and/or nearby tissue) by the annulus connectors, and or to other heart tissue by the heart tissue tether(s) in various methods and sequences. The delivery, positioning, and/or securement may also be performed as part of an integrated procedure with an edge-to-edge approximation procedure with clip(s) CL, sequentially after an edge-to-edge approximation during the same interventional process, or as a separate procedure on a patient who has previously been subjected to an edge-to-edge approximation procedure. Some options are described with reference to the method 200 shown in the flow chart in FIG. 41. At 201, one or more clips CL may optionally be delivered to the native valve, and used to clip the native leaflet for edge-to-edge approximation. As described above, this procedure can create two flow control portions, each bounded by the native leaflets, the (or a) clip, and a commissure of the native valve. As noted above, 201 may have been previously performed in a separate procedure, or may be performed as part of the same procedure as the subsequent portions of method 200. At 202, the clipped native valve can be evaluated for leakage or regurgitation, and a determination made as to whether any such leakage or regurgitation was sufficiently severe to warrant usage of prosthetic valve 100. At 203, the extent of the leakage or regurgitation, the size of the flow control portions, and/or other relevant clinical information could be determined (e.g. through imaging) to enable selection of a suitable prosthetic valve (e.g. size of the limbs 116, 117 (or optionally 118). At 204, the prosthetic valve 100 is delivered to the native valve, such as by known endovascular techniques, using a delivery catheter. At 205, the prosthetic valve 100 is disposed in the native valve with the inlet 131 of flow passage 130 disposed in the atrium of the heart, with the first limb 116 of body 110 of prosthetic valve 100 disposed in the first flow control portion FCP1, with the first outlet 135 of the flow passage 130 disposed in the ventricle of the heart, and with the second limb 117 of body 110 of prosthetic valve 100 disposed in the second flow control portion FCP2, with the second outlet 137 of the flow passage 130 disposed in the ventricle of the heart. At 206, clip connector 170 is coupled to clip(s) CL that are clipped to the native leaflets. In integrated procedures, clip connector 170 may be coupled to clip(s) CL before clip(s) CL are clipped to the native leaflets for the edge-to-edge approximation.

[0245] Optionally, at 207 annulus connector(s) 180 may be engaged with the native annulus (on the ventricle side and/or atrial side), and/or adjacent tissue. Although in the flow chart of FIG. 41 207 is shown as being after 206, in some embodiments the annulus connector(s) 180 may be engaged with the native annulus first, i.e. with the prosthetic valve in position in the native valve, and then the clip connector 170 may be coupled to clip(s) CL. Also optionally, at 208, one or more heart tissue tether(s) 190 may be engaged with cardiac tissue in one or more locations in the heart. Further optionally, at the completion of the method 200, or in a subsequent procedure, if some blood regurgitation is identified, and determined to arise from insufficient seal between the native leaflets in the flow control portion(s) of the native valve and the limb(s) 116, 117, then at 210, one or both of the limbs 116, 117 of prosthetic valve 100 may be further, or re-, dilated to reshape or increase the perimeter of the limb(s) and improve the seal with the native leaflets, as described in more detail below.

[0246] A prosthetic valve according to an embodiment is shown in FIGS. 42A-42C.

Prosthetic valve 300 includes a body 310 with an inlet portion 312, transition portion 313, and outlet portion 314, with first limb 316 and second limb 317. Body frame 320 includes elongate, longitudinal struts 321a extending from the inlet 360 to the first outlet 335 and second outlet 337 on the outer sides of the body 320, and a U-shaped elongate strut 321b between first limb 316 and second limb 317, interconnected with a series of hoops or rings 321c. Body 310 further includes an outlet cuff 324 at the outlet end of each limb. Body 310 includes body covering 322 over the entire outer surface of body 310. Body 310 defines a flow passage 330 between inlet 331 and first outlet 335 and second outlet 337, including flow control passage 332, transition passage 333, first limb passage 334, and second limb passage 336.

[0247] Prosthetic valve 300 further includes a clip connector 370, which in this embodiment is implemented as a web 371 of material extending between first limb 316 and second limb 317, and which can be captured between the paddles of a clip CL and the native leaflets of the mitral valve MV. Embodiments and uses of various clips CL are described below. [0248] FIG. 42D illustrates a clip CL having a first paddle or clip member PI, a second paddle or clip member P2, and a spacer SP. Anterior leaflet AL is captured between first paddle PI and a first tissue gripper TGI movable relative to paddle PI to allow insertion of anterior leaflet AL free margin therebetween. Posterior leaflet PL is captured between a second paddle P2 and a second tissue gripper TG2 in a similar manner. Independent leaflet capture is achieved by selectively operating first paddle PI and first tissue gripper TGI to engage a first (e.g. anterior) leaflet, or second paddle PI and second tissue gripper TG2 to engage a second (e.g. posterior) leaflet, as is the case with current PASCAL and latest generation MitraClip™ devices. Captured leaflets may be retained between a tissue gripper TGI, TG2 and a respective cooperating paddle PI, P2 even with the paddle in an open position relative to the opposite paddle, or with the paddle spaced away from the spacer SP. As illustrated in FIG. 42D, paddles PI, P2 of clip CL are shown in a fully closed position with captured tissue of anterior leaflet AL and posterior leaflet PL in an approximated spatial relationship.

[0249] Web 371 of clip connector 370 of prosthetic valve 300 may be fabricated by multiple plies of textile material (as illustrated) or in a laminate configuration to enhance its structural strength. Spacer SP is configured with an appropriately sized slot to engage web 371 and secure it in a reliable manner and withstand the dynamic load applied to prosthetic valve 300 during the cardiac cycle. Clip CL may be designed in a manner that closing of clip CL may impart an additional web-clamping load across the slot in spacer SP. FIG. 42E illustrates a variant for the coupling of web 371 of clip connector 370 to clip CL. Clip CL is configured with a pair of barbed members BM. Web 371 is of sufficient thickness and structural integrity to be penetrated by a series of barbs BR of barbed members BM to allow secure coupling of prosthetic valve 300 to clip CL. Structural stiffness and spacing of barbed members BM, and orientation of barbs BR allow insertion of web 371 in one direction and resist retraction of in the opposite direction.

Alternatively, similar to tissue TGI, TG2, barbed members BM may be movable and operable between an open configuration to receive web 371 and a closed position to secure web 371 therewithin. Such closed position may coincide with a final closed position of clip CL.

[0250] FIG. 42F illustrates a further variant for coupling web 371 of clip connector 370 between a spacer SP and a captured leaflet (e.g. anterior leaflet AL). Tissue gripper TGI is configured with a second series of barbs BR on the opposite side of the barbs BR used to capture anterior leaflet AL. Spacer SP is configured with a similar series of barbs BR. Inserting web 371 between spacer SP barbs BR and tissue gripper TGI and closing clip CL will securely couple prosthetic valve 300 to clip CL. The insertion of web 371 is facilitated by having paddle PA and tissue gripper TGI engaged with anterior leaflet AL, but with the latter being selectively positioned in paddle PI in its open position spaced away from spacer SP.

[0251] Prosthetic valve 300 further includes annulus connector 380 (not shown in FIG.

42A for ease of illustration). In this embodiment, annulus connector includes a first arm 381 and second arm 383. First arm 381 is an arcuate, elongate rod or strut coupled to inlet portion 312 of body 310 and extending laterally and downwardly, and terminates at its distal end in a first annulus anchor 382, which is a transverse, arcuate, elongate rod or strut sized and oriented to engage the annulus of the native valve, e.g. mitral valve annulus MVA of mitral valve MV, as shown in FIG. 42C. (Note that FIGS. 42B and 42C illustrate slight different implementations of annulus connector 380 - in FIG. 42B, first arm 381 and second arm 383 are coupled to inlet portion 312, whereas in FIG. 42C first arm 381 and second arm 383 are coupled to first limb 316 and second limb 317.) Second arm 383 is a mirror image of first arm 381, and terminates in a second annulus anchor 384, which is a mirror image of first annulus anchor 382. In THE embodiment of FIG. 42B, annulus connector 380 is configured to engage with the upper, atrial side of the mitral valve annulus MVA, but in the embodiment of FIG. 42C, it is instead configured to engage with the lower, ventricle side of the mitral valve annulus MVA, or the prosthetic valve 300 could include two annulus connectors, one on each side of the annulus.

[0252] Prosthetic valve further includes a flow control device 360, which in this implementation is a tri-leaflet valve, disposed in flow control passage 322 and coupled to body frame 320 in the inlet portion 312 of body 110. Blood flow through prosthetic valve is shown with arrows, i.e. blood can flow from the left atrium LA, into inlet 331, into flow control passage 332, through flow control device 360, into transition passage 333, into both first limb passage 334 and second limb passage 336, and out of first outlet 335 and second outlet 337 into left ventricle LV. This blood flow would take place during the diastolic portion of the cardiac cycle. During the systolic portion, the flow control device 360 would prevent blood flow in the opposite direction, from the left ventricle LV to the left atrium LA. [0253] A prosthetic valve according to another embodiment is shown in FIG. 43.

Prosthetic valve 400 in FIG. 43 is similar to prosthetic valve 300 in FIGS. 42A to 42C - the following description focuses on differences of interest, and omits details that are common. A clip and annulus connector are shown in phantom for reference. This embodiment has a variation in construction that may reduce native leaflet wear.

[0254] Prosthetic valve 400 includes a body frame 420 that is formed with different structures in different portions. In the inlet portion 412, transition portion 413 and parts of first limb 416 and second limb 417, body frame 420 is implemented with a wire mesh construction with diamond-shaped cells, such as by using laser-cut tubing, as is commonly used for the stents or bodies of prosthetic valves. However, in the portion of first limb 416 and second limb 417 that are to be disposed in the flow control portions of the clipped valve, and thus in contact with the edges of the native leaflets, there is less structure to body 410. In particular, the stent-like structure of the limbs have a gap in the leaflet-contact area 416a of the first limb 416 and leaflet contact area 417a of the second limb 417, and the gap is spanned by a small number of wires (or slender rods) 42 Id that link the stent-like portions. The wires can be preferentially arranged to be adjacent to laterally inside and outside edges of the limbs, so that when the prosthetic valve 400 is disposed in a mitral valve, the wires are adjacent to the clip and to the valves commissures, i.e. are away from the native leaflets, to minimize direct contact with the native leaflets. Additional wires or other supporting structures may be added as need to maintain the shape of the limbs in the leaflet contact areas. The outlet end of each limb may be formed with structure other than a stent frame, e.g. a simple circle or oval of wire.

[0255] The entire body frame 420 is covered with a body covering 422, which in this embodiment is fabricated with pericardium tissue. Body covering 422 is affixed to the stent-like portions of the body frame, i.e. above and below the leaflet contact areas of the limbs, but may not be attached to the underlying wires in the leaflet contact area. Thus, the native leaflets’ engagement with the body covering 422 in the leaflet contact area imposes less stress and wear on the tissue of the native leaflets because the body covering 422 is backed only by blood in the first limb passage 434 and second limb passage 436.

[0256] A prosthetic valve according to another embodiment is shown in FIG. 44.

Prosthetic valve 500 in FIG. 44 is similar to prosthetic valve 300 in FIGS. 42A to 42C - the following description focuses on differences of interest, and omits details that are common. A clip and annulus connector are shown in phantom for reference. FIG. 44 illustrates an alternative approach to holding prosthetic valve 500 in correct spatial relationship with the flow control portions FCP, i.e. the spatial relationship is maintained with an annulus connector, and a clip connector is not used. This embodiment has another variation in construction that may reduce native leaflet wear. Whereas typical stent mounted prosthetic valves are covered completely or partially by a fabric such as Dacron, prosthetic valve 500 includes a body covering 522 that has two portions - body covering inlet portion 522a and body covering limb portion 522b - each formed of different materials. Body covering limb portion 522b, which is the portion of body covering 522 that would contact the native leaflets during use, is formed of pericardium or similar biological material. Such biological material is less prone to wearing the native leaflets than the fabric material covering the remainder of prosthetic valve 500.

[0257] A prosthetic valve according to another embodiment is shown in FIGS. 45A to

45C. Prosthetic valve 600 in FIGS. 45A to 45C is similar to prosthetic valve 300 in FIGS. 42A to 42C - the following description focuses on differences of interest, and omits details that are common. A clip and annulus connector are shown in phantom for reference. This embodiment is used to illustrate a procedure that can be used to address leakage between a limb of the prosthetic valve and the native leaflets.

[0258] To be effective in preventing mitral regurgitation, the native leaflets should sealingly engage the limbs of the prosthetic valve. It is well known that as the heart deteriorates in heart failure, the native leaflets can become more distracted, and regurgitation can increase. It is envisioned that native leaflet distraction could become sufficiently large that the native leaflets no longer sealingly engage the limbs of the prosthetic valve. This potential issue can be addressed by a procedure in which one or more of first limb 616 and second limb 617 may be expanded to a larger perimeter after prosthetic valve 600 has been delivered. Such a procedure can be performed in conjunction with the procedure in which prosthetic valve 600 is delivered and deployed, e.g. by evaluating the sealing of the native leaflets to first limb 616 and second limb 617, such as by measuring the presence and severity of regurgitation, and the using the procedure to address any such regurgitation. Alternatively, the procedure can be performed separately, for example well after the initial procedure to deliver and deploy prosthetic valve 600 has been performed and deterioration of the heart causes the onset of, or increase in, regurgitation. [0259] The procedure to reshape or increase the perimeter of first limb 616 and/or second limb 617 can be accomplished in several ways. First, as shown in FIG. 45B, a catheter C having an expandable balloon B on which is disposed a balloon-expandable stent ST (e.g. constructed of stainless steel or cobalt chrome) can be delivered to the native valve and into second limb passage 636 of second limb 617 (via flow control passage 632, flow control device 660, and transition passage 633). Balloon B can then be inflated, expanding stent ST into engagement with - and then expanding - the second limb portion of body frame 620. The resulting condition of prosthetic valve 600 is shown in FIG. 45C, with stent ST in place in second limb 617. The dashed line if FIG. 45C shows the original size of second limb 617, the arrows indicate the expansion by stent ST, and the solid line illustrates the new, expanded size of second limb 617.

[0260] Another approach to expanding the perimeter of, for example, second limb 617 that can result in the condition shown in FIG. 45C, is to use a stent ST that is self-expanding (e.g. one formed from shape memory material such as Nitinol), and deliver it to second limb 617 with a catheter (not shown) with a delivery lumen from which stent ST can be discharged into position.

A benefit of using a self-expanding stent is that, as is well known, such stents can be retrieved (e.g. via the delivery catheter before deployment is complete, or via a retrieval catheter if already deployed) if the deliver is unsatisfactory or the stent fails.

[0261] A third approach to expanding the perimeter of, for example, second limb 617 that can result in the condition shown in FIG. 45C, is to omit the stent ST and use the balloon B on catheter C directly to further expand the perimeter of the portion of body frame 620 in second limb 617 from the perimeter with which it was initially delivered and deployed, e.g. if that portion of body frame 120 is constructed of expandable material such as stainless steel or cobalt chrome (rather than from a shape memory material).

[0262] A prosthetic valve according to another embodiment is shown in FIGS. 46A to

46C. Prosthetic valve 700 in FIGS. 46A to 46C is similar to prosthetic valve 300 in FIGS. 42A to 42C - the following description focuses on differences of interest, and omits details that are common. This embodiment is used to illustrate that prosthetic valve 700 can have a relatively short axial height (especially within the left atrium) and a considerably larger inlet diameter flow control passage.

[0263] Prosthetic valve 700 has a body 710 with an inlet portion 712, transition portion

713, and outlet portion 714 (with first limb 716 and second limb 717). Body 710 defines a flow passage that includes a flow control passage 732, a transition passage 733, a first limb passage 734, and a second limb passage 736, and extends between an inlet 731 and a first outlet 735 and a second outlet 737. A flow control device 760 is disposed in flow control passage 732. As can be seen in FIGS. 46B and 46C, flow control device 760 has a relatively short axial height (i.e. in along its central, longitudinal axis). The entire body is also has a relatively short axial height, between inlet 731 and first outlet 735 and second outlet 735. Thus, when prosthetic valve 700 is disposed in a native valve, such as the mitral valve between left atrium LA and left ventricle LV, as shown in FIG. 46B, inlet 731 is disposed in left atrium LA but leaves ample clearance from the walls of the atrium to allow good blood flow into flow control device 750. First outlet 735 and second outlet 737 are disposed in left ventricle LV, but do not project far into the ventricle, and thus minimize contact with portions of the native valve apparatus or the ventricle wall. As shown in FIGS. 46A to 46C, flow control device 760 also has a large diameter relative to the overall size of prosthetic valve 700, as do first outlet 735 and second outlet 737 (and the flow passage between inlet 731 and the outlets), thus providing a large flow area for blood to pass through prosthetic valve 700 from left atrium LA to left ventricle LV during diastole, as indicated by the arrows in FIGS. 46B and 46C.

[0264] Similar to prosthetic valve 300, prosthetic valve 700 includes a clip connector 770 which is configured from a structural web 771 extending from and spanning between first limb 716 and second limb 717 of valve 700. Clip connector 770 is couplable to clip CL in a variety of ways as previously described in FIGS. 42D to 42F. Once coupled with clip CL, web 771 of clip connector 770 is engaged between opposing paddles or clip members of clip CL and also between the captured portions of opposed and approximated native leaflets (e.g. anterior leaflet AL and posterior leaflet PL in mitral valve MV).

[0265] A prosthetic valve according to another embodiment is shown in FIGS. 47A to

47D. Prosthetic valve 800 in FIGS. 47A to 47D is similar to prosthetic valve 700 in FIGS. 46A to 46C - the following description focuses on differences of interest, and omits details that are common. This embodiment is used to illustrate structures for coupling prosthetic valve 800 to clip CL.

[0266] Prosthetic valve 800 has a clip connector 870 that transfers fluid dynamic loads imposed on prosthetic valve 800 to clip CL via an axial clip post 873. Axial clip post in turn is connected to body frame 820 by two paths: via three radial valve struts 872 coupled between axial clip post 873 and the upper rim of the frame of flow control device 860 (which may be coupled to, or a portion of, body frame 820); and via a U-shaped crotch strut 874 coupled between axial clip post 873 and the portion of body frame 820 between first limb 816 and second limb 817. Body frame 820 includes outlet portions 825 (which may be short sections of stent structures) at the outlet ends of first limb 816 and second limb 817, to maintain first outlet 835 and second outlet 837 open. Crotch strut 874 can be coupled to outlet portions 825. Axial clip post 873 is coupled to clip CL via any suitable mechanical joint, such tongue-and-groove, a barbed fitting, a snap fit, etc. As such, prosthetic valve 800 may be coupled to clip CL: i) after clip CL has been previously and fully deployed (i.e. both leaflets of a target native valve have been captured by clip CL); ii) after clip CL has been partially deployed with only one of the native leaflets captured between a central spacer and a first clip member (such as between spacer SP and paddle PI of clip CL shown in FIGS. 42D to 42F), and prior to capturing a second native leaflet between the central spacer and a second clip member (such as second paddle P2 shown in FIGS. 42D to 42F; or iii) prior to leaflet capture by clip CL (i.e. prosthetic valve 800 and clip CL forming a device assembly prior to delivery to the patient’s target heart valve). A releasable mechanical joint may also be used, thereby allowing prosthetic valve 800 to be decoupled from clip CL and replaced by a different size or configuration of prosthetic valve if a surgical intervention warrants such replacement.

[0267] Radial valve struts 872 are configured and arranged to be disposed below the coaptation line of the leaflets 862 of flow control device 860 as best seen in FIGS. 47 A (leaflets 862 shown open, during diastole) and 47B (leaflets 862 are shown coapted, during systole, and radial valve struts 872 are shown in phantom). In an alternative embodiment, shown in FIG. 48, a prosthetic valve 900 includes radial valve struts 972 that are configured and arranged to be disposed above the coaptation line of the leaflets 962 of flow control device 960. In both embodiments, radial valve struts 872 and 972 can be securely coupled to the frame of the flow control device, and do not interfere with the operation of the leaflets of the flow control device - thus, these designs facilitate the use of already-developed prosthetic valves for the flow control device, rather than requiring re-engineering of their design.

[0268] Prosthetic valve 800 is shown in an end view disposed in native mitral valve MV in an delivered position and in an exploded view, respectively, in FIGS. 47C and 47D. Clip CL is shown in FIG. 47D with its paddles PI, P2 open, and the relationship of native leaflets AL and PL and the clip connector 870 with clip CL is clearly seen. Spacer SP is of a suitable size and volume to advantageously allow configuration of a mechanical joint, or other suitable interface, to appropriately engage a clip connector 870 of prosthetic valve 800. The latter can be achieved with either or both of paddles PI, P2 in their open spaced apart position, or with paddles PI, P2 in a closed position and proximate to spacer SP.

[0269] A prosthetic valve according to another embodiment is shown in FIGS. 49A to

49B. Prosthetic valve 1000 in FIGS. 49A and 49B is similar to prosthetic valve 300 in FIGS. 42A to 42C - the following description focuses on differences of interest, and omits details that are common. This embodiment illustrates an alternative design for an annulus connector.

[0270] As shown in FIGS. 49A and 49B, prosthetic valve 1000 includes a body frame

1020 that integrates with a clip connector 1070 and an annulus connector 1080. In contrast to clip connector 870 of prosthetic valve 800 in FIGS. 47A to 47D, the load path for clip connector 1070 is only through crotch strut 1074. Outlet portions 1025 of body frame 1020 are wire hoops or rings, and each is coupled on its laterally inner side to a lower end of crotch strut 1074 and on their laterally outer side to a body frame side strut 1026 running axially along a laterally outer side of body 1010. Each body frame side strut 1026 is coupled at its upper end to the frame of flow control device 1060 and/or to annulus connector 1080.

[0271] Annulus connector 1080 includes first arm 1081 and second arm 1083, each extending from the frame of flow control device 1060 and/or upper end of a corresponding body frame side strut 1026, and having at their distal ends first annulus anchor 1082 and second annulus anchor 1084, respectively. In this embodiment, annulus connector 1080 engages the atrium side of mitral valve annulus MVA. However, alternatively, or in addition, annulus connector could include arms that extend through the commissures of the mitral valve and have annulus anchors disposed to engage the ventricle side of mitral valve annulus MVA. First annulus anchor 1082 and/or second annulus anchor 1084 may include tissue piercing members, such as barbs, for enhancing securement to heart tissue.

[0272] A prosthetic valve according to another embodiment is shown in FIG. 50.

Prosthetic valve 1100 in FIG. 50 is similar to prosthetic valve 1000 in FIGS. 49A and 49B, but includes an annulus connector 1180 that engages both the atrium and ventricle sides of mitral valve annulus MVA. [0273] As shown in FIG. 50, prosthetic valve 1100 includes a body frame that includes outlet portions 1125, each coupled on its laterally inner side to a lower end of crotch strut 1174 and on their laterally outer side to a body frame side strut 1126 running axially along a laterally outer side of body 1110. Each body frame side strut 1126 is coupled at its upper end to the frame of flow control device 1160. Annulus connector 1180 includes two first annulus anchors 1182 and two second annulus anchors 1184 extending from a respective body frame side strut 1126. One first annulus anchor 1182 engages the atrium side of mitral valve annulus MVA and the other first annulus anchor 1182 engages the ventricle side of mitral valve annulus MVA. Similarly, one second annulus anchor 1184 engages the atrium side of mitral valve annulus MVA and the other second annulus anchor 1184 engages the ventricle side of mitral valve annulus MVA.

[0274] Clip connector 1170 includes a transverse strut 1175, coupled at its ends to the two body frame outlet portions 1125, and coupled at its center to clip CL. Unlike some of the previous embodiments, transverse strut 1175 can be disposed on the ventricle side of clip CL, and even below the level of the captured native leaflet free margin within clip CL.

[0275] A prosthetic valve according to another embodiment is shown in FIGS. 51 A and

5 IB in a top view and a partial cross-sectional end view, respectively. Prosthetic valve 1200 includes a non-standard flow control device 1260 that can provide better blood flow through prosthetic valve 1200. Flow control device 1260 can be used with any of the prosthetic valve embodiments described above, e.g. prosthetic valves 300, 400, 500, 600, 700, 800, 900, 1000, and 1100, instead of a standard tri-leaflet design.

[0276] As shown in FIGS. 51 A and 5 IB, and in more detail in a perspective views in

FIGS. 51C and 5 ID, flow control device 1260 includes a stent frame 1261 supporting two conventional leaflets 1262, each subtending one third of the circumference of the flow control device 1260. However, instead of being adjacent to each other, and joined at a commissure, the leaflets 1262 are spaced apart, disposed diametrically opposite each other, and aligned with first limb 1216 and second limb 1217, and correspondingly with first limb passage 1234 and second limb passage 1236. Rather than coapting against each other, leaflets 1262 coapt against static half-cusps 1265, each subtending one sixth of the circumference of the flow control device 1260 and disposed between leaflets 1262. Flow control device 1265 is shown in FIG. 51C in the configuration it assumes during systole, i.e. with the tissue leaflets 1262 coapted against the static half-cusps 1265. Flow control device 1260 is shown in FIG. 5 ID with the tissue leaflets omitted for clarity of illustration of the static half-cusps 1265.

[0277] As also shown in more detail in FIGS. 5 ID to 5 IF, each static half-cusp 1265 includes a static cusp frame 1266 and a static cusp membrane 1267 supported on static cusp frame 1266. Both the leaflets 1262 and the static cusp membrane 1267 may be formed from tissue such as pericardium. Static cusp frame 1266 may be formed of the same material as the main frame of flow control device 1260, e.g. stainless steel, cobalt chrome, or Nitinol. As shown in FIGS. 5 IB and 5 ID to 5 IF, static cusp frames 1266 may be coupled to axial clip post 1273 of clip connector 1270. Variations in the construction of the static half-cusp assembly are possible, including draping or encapsulating frame 1266 with a suitable biopolymer membrane, for example silicone poly(urethane urea) formulation. Alternatively, the volume delimited by the static cusp frame 1266, static cusp membrane 1267 and stent frame 1261 may include a collapsible open-cell foam polycarbonate urethane draped by a pericardium or biopolymer membrane. Alternatively, the static half cusps may be constructed to include a biopolymer, biocompatible, or bioengineered material capable of maintaining its shape and geometry in use, and suitable to resist calcification, withstand stresses and strains of the cardiac cycle, and that is non-thrombogenic. Such materials are also suitable for the movable cusps in prosthetic valves 300, 400, 500, 600, 700, 800, 900, 1000, and 1100, instead of the more commonly used animal pericardium. One example of a prosthetic valve using such biopolymer material is the Tria Valve produced Foldax Inc.

[0278] In operation of flow control device 1260, during diastole leaflets 1262 are open, collapsed against the periphery of flow control device, i.e. as shown FIG. 51 A. Blood can flow from the left atrium LA into inlet 1231, through the apertures between leaflets 1262 and static half-cusps 1265, and into first limb passage 1234 and second limb passage 1236. As is apparent from FIG. 51 A, the alignment of leaflets 1262 with the limb passages provides a smooth, relatively straight flow path. During systole, leaflets 1262 coapt and seal against static cusp membranes 1267, blocking retrograde blood flow or regurgitation, similar to the coaptation of leaflets in a tri -leaflet valve. In configurations of prosthetic valve 1200 having limb passages 1234, 1236 that are not diametrically opposite as illustrated in FIG. 51 A, alignment of leaflets 1262 can be tailored to align with limb passages by varying the amount that the static half-cusps 1265 each subtend the circumference of the flow control device 1260. For example, in an embodiment having a first limb 1216 and a second limb 1217 angularly oriented 160 degrees apart relative to clip CL, a first static half cusp 1265 can be configured to subtend one-ninth of the circumference and a second half cusp 1265 configured to subtend two-ninths of the circumference such that the resulting alignment of leaflets 1262 is in register with the limb passages 1234, 1236. [0279] The prosthetic valve embodiments described above include a single flow control device to control the flow through two (or more) flow control portions of a clipped native valve, by incorporating a bifurcated flow control passage with two (or more) limb passages extending through two (or more) limbs, each preferably sealingly engaging the native leaflets in a respective flow control portions. In the following prosthetic valve embodiments, a separate flow control device is used to control the flow through each flow control portion of a clipped native valve.

Thus, for a clipped native valve with two flow control portions through which it is desired to control flow with a prosthetic valve (rather than relying only on the function of the clipped native leaflets founding the flow control portion), a prosthetic valve includes two flow control devices. For a clipped native valve with a single flow control portion, or with multiple flow control portions but for which it is necessary or desirable to address regurgitation through only one of the flow control portions, the prosthetic valve includes a single flow control device. Other structures and functions described for the prosthetic valve embodiments above are also applicable to the embodiments described below, and additional structures or functions are included in the embodiments described below, as will be made clear from the following description. In general, the same reference numbering scheme is used for the preceding and following embodiments, for ease of reference, and unless otherwise apparent from the detailed description below, any structure in the following embodiments that corresponds to structure in the embodiments above can include all of the same details of design and implementation, and all of the same options and alternatives, as described above.

[0280] An embodiment of a prosthetic valve 2000 is illustrated schematically in a side view and top view, respectively, in FIGS. 52A and 52B. Prosthetic valve 2000 includes a body 2010 with an inlet portion 2012 and an outlet portion 2014. Body 2010 defines a flow passage 2030 therethrough that includes a flow control passage 2032 in the inlet portion 2012 and an outlet passage 2034 in the outlet portion 2014.

[0281] The portions of the flow passage 2030 are in fluid communication with each other and can conduct fluid, e.g. blood, from an inlet 2031 at the entrance to the flow control passage, through the flow control passage 2032 and through the outlet passage 2034 out of an outlet 2035 at the lower end of body 2010.

[0282] Flow through the flow passage 2030, and in particular through flow control passage

2032, is controlled by flow control device 2060. Flow control device 2060 can be constructed, and function, similar to any of the flow control devices described above for other embodiments. As shown schematically in FIGS. 52A to 53B, flow control device 2060 may be cylindrical, with a circular cross section. Flow control device 2060 may be mounted to inlet portion 2012 of body 2010 and disposed so that all flow through flow control passage 2032 must pass through flow control device 2060. Flow control device 2060 is configured to permit fluid to flow therethrough in the direction from the inlet 2031 to the outlet 2035, but to prevent fluid to flow in the opposite direction.

[0283] It is well known that tissue valves can fail, and it is also known that this problem can be solved by delivering another tissue-based stent valve inside a failed valve. Thus, it is contemplated that if flow control device 2060 fails, a new tri-leaflet valve can be placed inside flow control device 2060.

[0284] Prosthetic valve 2000 also includes a clip connector 2070 that is part of, or coupled to, body 2010, and is configured to engage with a clip such as those described above, and thereby to retain prosthetic valve 2000 in operative relationship with a native heart valve to which the clip is attached. In particular, clip connector 2070 is configured to carry fluid dynamic load applied to prosthetic valve 2000 during the cardiac cycle of the heart to the clip CL and thence to the native leaflets, annulus, and surrounding heart tissue to resist displacement of the prosthetic valve. The largest loads to be carried tend to be during systole, and the displacement to be resisted is towards the atrium of the heart.

[0285] Clip connector can be implemented in a variety of configurations, including those described above, as well as additional variations describe in more detail below. As describe above, clip CL can be any of the commercially available designs, or can be customized or modified specifically for use with prosthetic valve 2000. For example, as described in more detail below for specific embodiments, clip CL can have a spacer (similar to the spacer of the PASCAL clip) disposed between the paddles of the clip, and the spacer can be configured to fill or occlude a portion of the space between the native leaflets of a clipped native valve in a clipping procedure, thus reducing the size of, or filling a portion of, the native valve orifice area. The spacer can be configured and sized to increase a resulting flow control portion (e.g. adjacent to a commissure between the native leaflets) relative to clipping the same native valve with a clip not having a spacer, and whereby the paddles are proximally disposed to each other.

[0286] As shown schematically in FIGS. 52A to 53B, prosthetic valve 2000 may include a second body 2010’ and associated flow control device 2060’, which can also be coupled to the clip connector 2070, and may also have an optional annulus connector 2080’ (or be coupled to the same annulus connector 2080). Body 2010’ may be identical in structure and function to body 2010, including a flow passage 2030’ with inlet 203 , flow control passage 2032’, outlet passage 2034’, and outlet 2035’. Body 2010’ may have a body frame 2020’, etc. A prosthetic valve 2000 with both body 2010 and 2010’ may be used to control blood flow in a clipped native valve having two flow control portions needing regurgitation reduction - body 2010 can be disposed in a first flow control portion FCP1 and body 2010’ can be disposed in a second flow control portion FCP2, as shown in FIGS. 53A and 53B.

[0287] Prosthetic valve 2000 is shown disposed in a native heart valve in a side view and top view, respectively, in FIGS. 53 A and 53B. Note that for convenience of illustration the native heart valve is illustrated as a mitral valve MV. Note also that prosthetic valve 2000 is illustrated with the optional second body 2010’ disposed in one of the two flow control portions of clipped mitral valve MV. Mitral valve MV is shown with the anterior leaflet AL and posterior leaflet PL joined by a clip CL in an edge-to-edge approximation, similar to the mitral valve MV shown in FIG. 37B. Thus, mitral valve MV has two flow control portions - FCP1 and FCP2 - defined between the clip, the leaflets, and the commissures of the mitral valve MV. As discussed above with reference to FIGS. 37A to 38F, there are many possible arrangements of clips on either the mitral valve or tricuspid valve, creating one, two, or three flow control portions - prosthetic valve 2000 may be used with any of those clipped valve configurations to address regurgitation in one or two of the flow control portions.

[0288] As shown in FIGS. 53A and 53B, prosthetic valve 2000 can be disposed in mitral valve MV with inlets 2031 and 2031 ’ disposed in the left atrium LA and outlets 2035 and 2035’ disposed in the left ventricle LV. Body 2010 is shown disposed in flow control portion FCP1, and body 2010’ is shown disposed in flow control portion FCP2. Clip connector 2070 is engaged with clip CL. Optional annulus connectors 2080 and 2080’ can be engaged with mitral valve annulus MVA. Similarly, optional heart tissue tether(s) 2090 can be engaged with heart tissue, e.g. in the left ventricle LV. When prosthetic valve 2000 is disposed in mitral valve MV, it is operable to reduce or eliminate regurgitation through flow control portions FCP1 and/or FCP2, i.e. to prevent retrograde flow of blood from the left ventricle to the left atrium during systole, but to allow blood to flow freely through prosthetic valve 2000 from left atrium LA to left ventricle LV during diastole.

[0289] The height of inlet portion 2012 of body 2000, may be of any suitable distance, though it is desirable that it not be so large that the inflow of blood into inlet 2031 is impeded, i.e. sufficient room is left above and around inlet 2031 inside the atrium of the heart for blood to freely enter.

[0290] Each of body 2010 and 2010’ may be configured so that outer surfaces thereof engage in a substantially sealing relationship with the anterior leaflet AL and the posterior leaflet PL and thereby to reduce or prevent the flow of blood therebetween, during at least a portion of the pumping cycle of the heart. In some embodiments, each of the first body 2010 and the second body 2010’ may be sized (e.g. perimeter) and configured (e.g. cross-sectional shape is circular, elliptical, ovoid, etc.) to substantially fill, or over-fill (stretch) the corresponding flow control portion, maintaining the edges of the leaflets in sealing relationship with the outer surfaces of the first body 2010 and the second body 2010’ throughout the cardiac cycle, thus preventing flow between the outlet portions and the leaflets from the atrium to the ventricle during diastole and from the ventricle to the atrium during systole. In this configuration, substantially all blood flow from the atrium to the ventricle during diastole is therefore carried through the prosthetic valve (and thus through the flow control devices 2060, 2060’), and blood flow from the ventricle to the atrium during systole (regurgitation) is substantially prevented (by the flow control devices 2060 and 2060’). This configuration offers several benefits. First, the native leaflets would move little or not at all during the cardiac cycle, which should reduce wear resulting from repetitive contact between the leaflets and the outer surfaces of the bodies of the prosthetic valve (there is little momentum on the native leaflet during impact with the outlet portions). The native leaflets are pliable and will tend to fill any irregular shapes or defects in closure. Second, complete valve sealing, i.e. prevention of regurgitation, should be assured. Finally, the heart tends to deteriorate over time in patients needing valve repair or replacement. For such patients, regurgitation should not occur again as the prosthetic valve assumes virtually full responsibility for the function of the native valve, and the residual valve tissue will be able to fill any gaps that may occur as the heart dilates (or alternatively any gaps that may occur as the valve leaflets retract with disease progression). These benefits are particularly applicable for a native valve to which an edge-to- edge clip has been applied. After the clip is applied the total opening size of the valve is limited to the area of the resultant flow control portion(s), which is a smaller area than that of the original opening of the native valve. Thus, the surface or orifice area that must be occluded by a valve is reduced and the load on the prosthetic valve is reduced. In many instances the clip can securely hold the load created by cardiac contraction, highest during systole.

[0291] In another configuration, the bodies 2010, 2010’ could be sized to be smaller than the flow control portions, allowing a gap to be formed during diastole and permitting some of the blood flowing from the atrium to the ventricle to flow through the gap (in addition to the blood flowing through the flow passage and the flow control device). The bodies 2010, 2010’ are preferable sized so that during systole the leaflets can sealingly engage the bodies’ outer surface and prevent retrograde flow between the limbs and the leaflets.

[0292] The bodies 2010, 2010’ of prosthetic valve 2000 are shown schematically in

FIGS. 52B and 53B as being circular in cross section, whereas the flow control portions of the native valve that result from leaflet clipping may be oval or slit like, as shown in FIG. 53B for ease of illustration. However, shaping the bodies with a corresponding cross-section could better follow the shape of the flow control portions and fill the leak space. In some embodiments, the cross-sectional shape of the bodies, at least in the leaflet-contacting areas, could be more elliptical, or with a teardrop (more V-shaped) shape, with the narrower portion oriented toward the commissures. Although the bodies are shown schematically in FIGS. 52B and 53B as being approximately linear, or symmetrically arranged about a center line through the clip, as can be seen in FIG. 36A, there is a natural curve to the coaptation line of the native mitral valve leaflets. When looking down on the mitral valve with the anterior leaflet above, there is a upward curve to the line of closure. To conform to this anatomy, in some embodiments the bodies of the prosthetic valve could be arranged to follow the curve of the coaptation line (i.e. curve formed by the leaflet free margins of opposed mitral or tricuspid leaflets during systole).

[0293] Bodies 2010, 2010’ are shown schematically in FIGS. 52B and 53B as being straight and being parallel with each other. However, in some embodiments with two bodies, the bodies may be straight but may be non-parallel, and may be angled towards or away from each other. In other embodiments they may not be straight, but may instead be arcuate. [0294] Bodies 2010, 2010’ are shown schematically in FIGS. 52A to 53B as being generally tubular in shape. However, in some embodiments it may be useful for the bodies to flare outwardly (larger perimeter) towards their respective outlets, as this may encourage more blood to enter the flow passage 2030 during systole and urge closed the leaflets of the flow control devices 160, 160’. Thus, the outlet ends of the bodies 2010, 2010’ could have a trumpet bell shape, for example.

[0295] Although bodies 2010, 2010’ are shown schematically in FIGS. 52B and 53B as having ends (i.e. at outlets 2035, 2035’) that are flat, i.e. linear and orthogonal to a central vertical axis of prosthetic valve 2000, in other embodiments the ends of the bodies 2010, 2010’ can be of any other configuration, including angled and / or arcuate, provided that they can be reliably positioned in the native valve so that preferably the entirety of the outlets are below the locations where the native leaflets are sealingly engaged with the bodies 2010, 2010’. The outlets may also have an outflow perimeter that is not planar but rather a scalloped perimeter. For instance, the portion of the outflow perimeter that engages the anterior leaflet AL may extend deeper within the ventricle than the corresponding portion that engages the posterior leaflet PL. As such, the upward surge of blood during systole will first come into contact with this deeper extending portion of the outlet and may ensure better systolic filling of the prosthetic valve 2000.

[0296] Each of body 2010, 2010’ can be constructed with materials and techniques similar to known prosthetic heart valves such as those discussed above. In the following description, only body 2010 is describe for simplicity, but all discussion is equally applicable to body 2010’. Body 2010 can have a body frame 2020 formed of wires, struts, mesh, braids, or other suitable constructions, in metal (such as cobalt chrome, stainless steel, shape memory metals such as Nitinol, etc.), polymer, or other suitable material. Body frame 2020 can be formed in a single, unitary piece, or it could be constructed by separate pieces that are joined together, e.g. one piece for each of the inlet portion 2012 and a separate piece for outlet portion 2014. In embodiments in which the body frame 2020 is formed in separate pieces, the pieces could be delivered and implanted separately to make delivery easier, and then coupled together in place in the heart valve. As described in more detail below with reference to specific embodiments, body frame 2020 does not necessarily extend to the outlet portion 2014 of body 2010. For example, a stiff graft (such as Dacron, Teflon etc. with or without coatings) could be used with no frame or with minimal frame. [0297] The construction of bodies 2010, 2010’ could vary. In some embodiments, the portion of the body frame 2020 in the outlet portion 2014 can be configured with a stent frame, with the potential for body covering 2022 and/or body lining 2023 to include, or the addition of, padding (formed of materials such as silicone and pericardium). It may be useful to make the outlet portion 2014 more complaint so that the outlet portion moves with each heartbeat and reduces the wear when leaflet tissues contact the device. Thus, outlet portion 2014 could be constructed similar to the arrangements described above for pseudo-valves, such as the embodiments shown in FIGS. 5D, 7A-B, 15A-E, or 18A-B. In such embodiments, the outlet portion can be constructed with a frame that allows the superimposed biologically compatible covering (such as pericardium) to move back and forth with each cardiac cycle. In other embodiments, the outlet portion 2014 could be constructed similar to the occlusion devices shown in FIGS. 13A-B and FIGS. 25A-B, in which the occlusion device is rigid or static, and the native leaflets moves toward the limbs to seal against leak and prevent wear.

[0298] In some embodiments, the outlet portion 2014 of prosthetic valve 2000 can be configured to have its shapes be adjustable to improve the seal between the outlet portion and the native leaflets. For example, oval shaped balloons or oval shaped stents could be introduced to shape the body portion limbs after the prosthetic valve 2000 has been placed in the native valve. Such an approach could also be useful if the body covering 2022 and/or body lining 2023 on (or in) an outlet portion 2014 wears out. A new body lining 2023 could be applied from inside the body portion 2014, delivered through the flow passage 2030 on a stent or a frame. This approach would be particularly useful if the body portion 2014 is constructed with a segment in which there is little or no frame material.

[0299] Flow control device 2060 is coupled to, and supported by, body frame 2020 in inlet portion 2012, or may optionally form some or all of the inlet portion of the body frame 2020. [0300] Body frame 2020 can be covered on the outside with a body covering 2022 and/or on the inside with a body lining 2023, each of which may be formed from any suitable material that is biocompatible, sufficiently impermeable to fluids such as blood to form the flow passage 2030 and maintain fluid within (or outside of) flow passage 2030, and atraumatic to native valve tissue (leaflets, chordae, heart chamber walls, etc.) that contact the body 2020. Suitable materials can include animal pericardium and synthetic materials such as Dacron (the latter material may be more suitable for covering areas of the body 2020 that do not contact heart tissue as it can be somewhat abrasive).

[0301] Body covering 2022 and/or body lining 2023 may cover or line the entirety of body

2020, or may be discontinuous, and cover only portions body 2020. Each may also be attached continuously to each area of body frame 2020 that it covers or lines, but may also be attached around the periphery or margins of selected areas on the body 2020, but not attached within those areas. This construction can allow blood to pass between, for example, struts in the body frame 2020 and expand/balloon out the body covering 2022 and/or body lining 2023 so that it gently contacts the native valve leaflets. The native leaflets would contact against material of body covering 2022 and/or body lining 2023 (for example pericardium) that is backed by blood within flow passage 2030 rather than against a solid portion of body frame 2020. Body frame 2020 could be formed with struts that are widely spaced in the region of contact to ensure the body covering 2022 and/or body lining 2023 will be expanded by blood. This could reduce considerably wear on native leaflet tissues.

[0302] As shown in FIGS. 52A and FIG. 53A, body 2010 can also include an outlet cuff

2024 at the outflow end of outlet portion 2014 that includes padding material to reduce the risk of injury to cardiac tissue that may contact those portions of the body 120 during the cardiac cycle. Such padding material could be any useful biocompatible material. Silicone, polyurethane, bio polymers or bio-elastomers, Dacron, PTFE (Teflon) fabrics (often used in rolled or folded form in the sewing cuff of prosthetic valve sewing rings) are suitable options that are commonly used in valve structures. Such padding or damage reducing materials could be added to any part of prosthetic valve 2000.

[0303] Although clip CL may be a commercially-available edge-to-edge leaflet clip such as the MitraClip™ or PASCAL, and prosthetic valve 2000 being configured to engaged with such a clip after it has been used to clip the native leaflets, in some embodiments the clip CL may be configured differently than such commercially-available clips (for example any of the clips described above with reference to FIGS. 42D to 42F), and/or may be included as part of a system with prosthetic valve device 2000 and configured to be delivered sequentially or concurrently with prosthetic valve 2000 as part of a total valve repair / replacement procedure. As described above, prosthetic valve 2000 is configured to be anchored to the clip CL, which in turn is coupled to the tissue of the anterior leaflet AL and posterior leaflet PL, and prosthetic valve 2000 will carry a considerable fluid dynamic load during systole that must in turn be carried by the clip and the leaflets. Thus, an enlarged clip anchor may be useful. For example, the clip could be composed of two or three paddles (instead of the single paddle of the PASCAL and MitraClip™ device) to increase the area of the leaflets engaged by the clip. This allows the dynamic load to be distributed more evenly over a larger leaflet area (and over a greater number of underlying chordae tendineae that are attached to the engaged leaflet portions).

[0304] Rather than relying on the clip connector (and thus clip CL, native valve leaflets, or other native valve tissue) to carry all of the fluid dynamic loads imposed on the prosthetic valve, in some embodiments those loads can be carried in part by other structures without putting the clip or the native leaflets in the load path. Thus, in some embodiments prosthetic valve can include an optional annulus connector 2080 and/or an optional heart tissue tether 2090.

[0305] As shown in FIGS. 52A to 53B, optional annulus connector 2080 may be part of, or coupled to, body 2010, and is configured to engage with an annulus (and/or other nearby tissue, including the atrial wall, the native leaflets, and/or the chordae tendineae) of a native heart valve to enhance the stability of the prosthetic valve 2000 when placed in the native heart valve, e.g. to inhibit lateral rocking of the prosthetic valve relative to the plane of the native valve, and or displacement away from the annulus towards the atrium (during systole) or the ventricle (during diastole). Annulus connector 2080 may be implement similarly to annulus connectors described above with reference to various embodiments of selective occlusion devices and prosthetic valves. Annulus connector 2080 may be configured with non-tissue penetrating members or with tissue penetrating members. Optional body 2010’ may also have an annulus connector 2080’, or may share the same annulus connector 2080 with body 2010.

[0306] As shown in FIGS. 52A to 53B, one or more optional heart tissue tethers 2090 may be coupled to bodies 2010, 2010’, clip connector 2070, clip CL, and/or annulus connectors 2080. 2080’. For ease of illustration, not all options are shown in all of the figures. Heart tissue tethers 2090 and their heart tissue anchors 2092 may be implemented in the same manner and heart tissue tethers 190 and heart tissue anchors 192 described above for prosthetic valve 100 and other embodiments above.

[0307] Prosthetic valve 2000 may be delivered to and positioned in the native valve, and secured to the clip CL by the clip connector, to the annulus (and/or nearby tissue) by the annulus connectors, and or to other heart tissue by the heart tissue tether(s) in various methods and sequences. The delivery, positioning, and/or securement may also be performed as part of an integrated procedure with an edge-to-edge approximation procedure with clip(s) CL, sequentially after an edge-to-edge approximation during the same interventional process, or as a separate procedure on a patient who has previously been subjected to an edge-to-edge approximation procedure. Some options are described with reference to the method 2100 shown in the flow chart in FIG. 54. At 2101, one or more clips CL may optionally be delivered to the native valve, and used to clip the native leaflet for edge-to-edge approximation. As described above, this procedure can create two flow control portions, each bounded by the native leaflets, the (or a) clip, and a commissure of the native valve. As noted above, 2101 may have been previously performed in a separate procedure, or may be performed as part of the same procedure as the subsequent portions of method 2100. At 2102, the clipped native valve can be evaluated for leakage or regurgitation, and a determination made as to whether any such leakage or regurgitation was sufficiently severe to warrant usage of prosthetic valve 2000. At 2103, the extent of the leakage or regurgitation, the size of the flow control portions, and/or other relevant clinical information could be determined (e.g. through imaging) to enable selection of a suitable prosthetic valve (e.g. size of the outlet portion(s) 2014, 2014’). At 2104, the prosthetic valve 2000 is delivered to the native valve, such as by known endovascular techniques, using a delivery catheter. At 2105, the prosthetic valve 2000 is disposed in the native valve with the inlet 2031 of flow passage 2030 disposed in the atrium of the heart, with the outlet portion 2014 of body 2010 of prosthetic valve 2000 disposed in the first flow control portion FCP1, with the outlet 2035 of the outlet passage 2034 disposed in the ventricle of the heart. Optionally, for embodiments of prosthetic valve 2000 that include a second body 2010’, prosthetic valve 2000’ may be disposed with the inlet 2031’ of flow passage 2030’ disposed in the atrium of the heart, with the outlet portion 2014’ of body 2010’ disposed in the second flow control portion FCP2, with the outlet 2035’ of the outlet passage 2034’ disposed in the ventricle of the heart. At 2106, clip connector 2170 is coupled to clip(s) CL that are clipped to the native leaflets. In integrated procedures, clip connector 2170 may be coupled to clip(s) CL before clip(s) CL are clipped to the native leaflets for the edge-to-edge approximation.

[0308] Optionally, at 2107 annulus connector(s) 2180 may be engaged with the native annulus (on the ventricle side and/or atrial side), and/or adjacent tissue. Although in the flow chart of FIG. 54, 2107 is shown as being after 2106, in some embodiments the annulus connector(s) 2180, 2180’ may be engaged with the native annulus first, i.e. with the prosthetic valve in position in the native valve, and then the clip connector 2170 may be coupled to clip(s) CL. Also optionally, at 2108, one or more heart tissue tether(s) 2190 may be engaged with cardiac tissue in one or more locations in the heart. Further optionally, at the completion of the method 2100, or in a subsequent procedure, if some blood regurgitation is identified, and determined to arise from insufficient seal between the native leaflets in the flow control portion(s) of the native valve and the outlet portion(s) 2014, 2014’ of bodie(s) 2010, 2010’, then at 2110, one or both of the outlet portion(s) 2014, 2014’ may be further, or re-, dilated to reshape or increase the perimeter of the outlet portion(s) and improve the seal with the native leaflets, as described in more detail above. [0309] A prosthetic valve according to another embodiment is shown in FIGS. 55A to

55C, shown disposed in a centrally-clipped mitral valve MV. Prosthetic valve 2200 in FIGS. 55A to 55C includes two bodies, 2210 and 2210’, which are shown disposed in two flow control portions, FCP1 and FCP2, of mitral valve MV.

[0310] Prosthetic valve 2200 has a first body 2210 with an inlet portion 2212 and outlet portion 2214, and a second body 2210’ with an inlet portion 2212’ and outlet portion 2214’. Body 2210 defines a flow passage 2230 that extends between an inlet 2231 (shown disposed in left atrium LA) and an outlet 2235 (shown disposed in a left ventricle LV), and has a flow control device 2260 disposed therein. Similarly, body 2210’ defines a flow passage 2230’ that extends between an inlet 2231’ (shown disposed in left atrium LA) and an outlet 2235’ (shown disposed in a left ventricle LV), and has a flow control device 2260’ disposed therein. As noted above, prosthetic valve 2200 is disposed in a centrally-clipped mitral valve, with one body 2210, 2210’ disposed in each of flow control portions FCP1 and FCP2. Prosthetic valve 2200 is coupled to clip CL by clip connector 2270, which in this embodiment includes a transverse strut 2275 coupled between body 2210 and 2210’, and a tension member (e.g. suture) 2276 coupled between transverse strut 2275 and spacer SP of clip CL. Prosthetic valve 2200 also includes an annulus connector 2280, coupled to both bodies 2210 and 2210’, and configured similarly to the annulus connectors of several embodiments described above, in this instance engaged with the ventricle side of mitral valve annulus MVA.

[0311] FIG. 55B illustrates a variation on the portion of prosthetic valve 2200. The outlet portions of the bodies 2210, 2210’ include leaflet contact areas 2216a, 2216’ that are non-circular in cross-section, extending laterally towards the commissures of the native mitral valve, which helps to close the roughly triangular portion of the flow control passages FCP1, FCP2 that may not otherwise be filled by the bodies 2210, 2210’. These portions of leaflet contact areas 2216a, 2216a’ may be formed by “padding material” such as Dacron or pericardium to produce the desired shape on the outside of body frame 2220, 2220’.

[0312] A prosthetic valve according to another embodiment is shown in FIGS. 56A to 561, shown disposed in a centrally-clipped mitral valve MV. Prosthetic valve 2300 in FIGS. 56A, 56B, 56D, and 56E includes a single body, 2310, which is shown disposed in one of the two flow control portions, FCP1 and FCP2, of mitral valve MV. Such a prosthetic valve and procedure may be useful when only one flow control portion of a centrally-clipped mitral valve (or of clipped tricuspid valve) has unacceptable levels of regurgitation that requires treatment.

[0313] Body 2310 of prosthetic valve can be implemented in accordance with any of the options and features disclosed above. The differentiating aspects of this embodiment are the mechanisms for securing prosthetic valve 2300 into operative relationship with the mitral valve MV, using a combination of a suture-based clip connector 2370 and a suture-based heart tissue tether 2390.

[0314] Clip connector 2370 is implemented as an elongate suture 2377 with two suture crimps 2378a, 2378b slidably disposed on suture 2377. The free ends of suture 2377 are adjacent, forming a bight between them. A distal (closer to the bight) suture crimp 2378a forms with the bight a distal suture loop 2379a (best seen in FIGS. 56C to 56E). The size (perimeter) of distal loop 2379a is adjustable by sliding the distal suture crimp 2378a toward the bight (preferably the suture crimps are configured to be slidable in one direction, and to resist sliding in the other direction, so that a suture loop can be tightened around a structure, and not release). A proximal (closer to the free ends of suture 2377) suture crimp 2378b forms with the distal suture crimp 2378a a proximal suture loop 2379b. and operative to form two loops in suture 2377 and selectively shorten the length of each loop. As explained in more detail below, clip connector 2370 is configured so that distal suture loop 2379a can be disposed around clip CL and tightened by sliding distal suture crimp 2378a distally (thus securing suture 2377 to clip CL) and proximal suture loop 2379b can be disposed around body 2310 of prosthetic valve 2300 and tightened by sliding proximal suture crimp 2378b distally (thus securing body 2310 to clip CL via suture 2377). [0315] As shown in FIG. 56C, the distal end of a delivery catheter C can be inserted into the left atrium LA (using any suitable technique, e.g. transseptal delivery), and suture 2377 can be delivered out of the delivery lumen of catheter C. Suture 2377 can be delivered in looped form, i.e. by delivering the bight end from catheter C while free ends remain external to the patient’s body (e.g. at the leg, for a transfemoral delivery), and the bight end can be manipulated and maneuvered using conventional techniques. Thus, distal suture loop 2379a can be inserted through flow control portion FCP2, into left ventricle LV, then disposed over the ventricle end of clip CL, and the free ends of suture 2377 can be pulled proximally to urge the distal end of distal suture loop 2379a upwardly against the upper (atrial) end of clip CL. Distal suture crimp 2378a can then be slid distally over suture 2377 to tight distal suture loop 2379a. Alternatively, a free end of suture 2377 can be delivered from catheter C, and manipulated and maneuvered until it is in the configuration shown in FIG. 56C, and the free end externalized from the patient so that distal suture crimp can then be applied to the two free ends of the suture 2377 outside the body, and pushed down suture 2377, through catheter C, and into the position shown in FIG. 56C before being slid further down suture 2377 to tighten distal suture loop 2379a.

[0316] The same catheter C can then deliver prosthetic valve 2300, as shown in FIG. 56C, into proximal suture loop 2379b (not shown in FIG. 56C). Then, as shown in FIGS. 56D and 56E, body 2310 of prosthetic valve 2300 can be disposed in flow control portion FCP2, with the proximal loop 2379b of suture 2377 disposed around the body 2310 of prosthetic valve 2300. Proximal suture crimp 2378b can be slid distally along suture 2377 to secure proximal suture loop around body 2310, and the free ends of suture 2377 can be clipped off close to proximal suture crimp 2378b - compare FIG. 56D to 56E.

[0317] Two alternative techniques for disposing distal suture loop 2379a around clip CL are shown in FIGS. 56F to 561, contrasted to the technique shown in FIG. 56C. In the technique shown in FIGS. 56F and 56G, distal suture loop 2379a is inserted through flow control portion FCP2, into left ventricle LV, then passed upwardly through the other flow control portion FCP1 into left atrium LA. The free end of suture 2377 can then be passed through distal suture loop 2379a (e.g. external to the patient), and pulled proximally, tightening the bight of suture 2377 around clip CL and the approximated edges of the anterior leaflet AL and posterior leaflet PL. Distal suture crimp 2378a can then be slide distally to tighten distal suture loop 2379a around the clip CL and leaflet tissue. Alternatively, as with the option shown in FIG. 56C, instead of delivering the bight of suture 2377 through catheter C, a free end of suture 2377 can be delivered into the atrium, around the clip, and externalized, establishing the configuration shown in FIGS. 56F and 56G. [0318] Another technique is shown in FIGS. 56H and 561. In this technique, a free end of suture 2377 is delivered (e.g. by catheter C) into the left atrium LA, through flow control portion FCP1 into left ventricle LV, around the posterior leaflet PL side of clip CL, out of flow control portion FCP2 into the left atrium LA, over clip CL, back through flow control portion FCP1 into left ventricle LV, round the anterior leaflet AL side of clip CL, back out of flow control portion FCP2 into left atrium LA, between suture 2377 and posterior leaflet PL, and back out of left atrium LA, then externalized from the patient. Tension can be applied to the free ends of suture 2377 to tighten the knot around clip CL and the clipped portions of the native leaflets. Distal suture crimp 2378a can then be applied, and pushed down suture 2377 into left atrium LA, forming distal suture loop 2379a.

[0319] As noted above, prosthetic valve 2300 includes a heart tissue tether 2390. Since prosthetic valve 2300 is offset laterally from clip CL, the fluid dynamic forces imposed on prosthetic valve 2300 during the cardiac cycle (pushing it strongly toward the left atrium LA during systole and less strongly towards the left ventricle LV during diastole) can impose a rocking force on prosthetic valve 2300, i.e. rotating about clip CL. The upwardly-directed rocking force (created during systole) can be countered by heart tissue tether 2390. Heart tissue tether 2090 is also implemented with a suture 2393 and a suture crimp 2394. As best seen in FIGS. 56C and 56E, a suture loop 2395 of suture 2393 can be disposed around sub-annular tissue, in this instance chordae tendineae of one of the native leaflets extending between papillary muscle PM (the one closest to the flow control portion, or in this instance the posteromedial papillary muscle, which is closes to the illustrated flow control portion FCP2) and the native leaflet. Suture 2393 can be passed through flow control portion FCP2, between valve body 2310 and the mitral valve annulus MV A, e.g. near or in the valve commissure. Suture 2393 can be secured against valve body 2310 by proximal suture loop 2379b, then suture crimp 2394 can be slid distally along suture 2393 to draw valve body 2310 down (towards left ventricle LV and papillary muscle PM). The downwardly directed tension force on valve body 2310 from suture 2393 acts counter to the rocking force produced by blood pressure during systole, thus reducing or eliminating rocking of prosthetic valve 2300 about clip CL.

[0320] A prosthetic valve according to another embodiment is shown in FIGS. 57A and

57B. Prosthetic valve 2400 is shown disposed in a mitral valve MV in which a clip CL has been applied to anterior leaflet AL and posterior leaflet PL in an eccentric position, i.e. not centered. In this instance, the clip CL has been applied to the A1 and PI cusps. Thus, there is a single large flow control portion FCP1 (or there may be a very small flow control portion (not identified in the figures) between the clip and the nearer commissure). The differentiating aspect of this embodiment is the mechanism for securing prosthetic valve 2400 into operative relationship with the mitral valve MV, using a hoop coupled to clip CL.

[0321] Clip connector 2470 is implemented as a clip connector ring or hoop 2474 that is coupled to clip CL. Hoop 2474 may be collapsed or compressed into a constrained configuration rendering it suitable for catheter delivery. Clip connector hoop 2474 can be formed from self expanding material (such as Nitinol) and can be coupled to clip CL outside the patient’s body, and delivered together with clip, such as through a catheter, and disposed on the ventricle side of the anterior leaflet AL and posterior leaflet PL. The clip can be engaged with the leaflets, and the clip connector hoop 2474 can subsequently be released from the delivery catheter. Clip connector hoop 2474 can then self expand and elastically resume a unconstrained, expanded configuration (as illustrated in FIG. 57B), so that it is disposed below (on the left ventricle LV side of) the native leaflets, concentric with flow control portion FCP1. Prosthetic valve 2400 can then be delivered (e.g. by the same delivery catheter as was used to deliver the clip CL and clip connector hoop 2474) into the left atrium LA, with body 2410 disposed in flow control portion FCP1 and clip connector hoop 2474, and body 2410 can be expanded (or allowed to self-expand) into secure engagement with clip connector hoop 2474, in the configuration shown in FIGS. 57A and 57B. [0322] A prosthetic valve according to another embodiment is shown in FIGS. 58A and

58B. Prosthetic valve 2500 is also shown disposed in an eccentrically-clipped mitral valve MV. The differentiating aspect of this embodiment is the mechanism for securing prosthetic valve 2500 into operative relationship with the mitral valve MV, using a strut extending from the clip CL. [0323] Clip connector 2570 is shown with two slight variations in these figures. In FIG.

58A, clip connector 2570 includes a vertically-oriented, U-shaped clip post 2573 extending laterally from the frame of body 2510. The free end of clip post 2573 can be coupled to clip CL with any of the mechanical coupling options describe above. For example, terminal end of clip post 2573 may be inserted into a suitable configured opening 2574 in spacer of clip CL.

[0324] In FIG. 58A, clip connector 2570 includes an axial clip post 2573 that extends vertically from clip CL, and is engaged by a strut 2575 that extends laterally from the frame of body 2510. [0325] As shown in FIGS. 58A and 58B, prosthetic valve 2500 includes an annulus connector 2580, similar to that of many of the embodiments described above.

[0326] A prosthetic valve according to another embodiment is shown in FIGS. 59A and

59B. Prosthetic valve 2600 is also shown disposed in an eccentrically-clipped mitral valve MV. The differentiating aspect of this embodiment is the mechanism for securing prosthetic valve 2600 into operative relationship with the mitral valve MV, essentially combining features of prosthetic valve 2300 (FIGS. 56A to 561) and prosthetic valve 2500 (FIGS. 58A and 58B).

[0327] Clip connector 2670 includes an L-shaped axial post 2673 extending from clip CL

(similar to axial post 2573 of prosthetic valve 2500), and a distal suture loop 2678a that is coupled to post 2673 and secured around body 2610 (similar to suture 2377 of prosthetic valve 2300). [0328] As shown in FIGS. 59A and 59B, prosthetic valve 2600 includes an annulus connector 2680, similar to that of many of the embodiments described above.

[0329] Similar to prosthetic valve 2300, prosthetic valve 2600 also includes heart tissue tether 2690 disposable around chordae tendineae CT.

[0330] A prosthetic valve according to another embodiment is shown in FIGS. 60A to

60D. Prosthetic valve 2700 is also shown disposed in an eccentrically-clipped mitral valve MV. This embodiment is very similar to prosthetic valve 2300 (FIGS. 56A to 561), but has a slightly different coupling mechanism for the clip connector 2770.

[0331] Similar to clip connector 2370 of prosthetic valve 2300, clip connector 2770 includes elongate suture 2777, but with just one suture crimp, proximal suture crimp 2778b, which forms with the bight of suture 2777 a proximal suture loop 2779b, which is configured to be disposed around body 2710 of prosthetic valve 2700 and tightened by sliding proximal suture crimp 2778b distally (thus securing body 2710 to clip CL via suture 2777). In this embodiment suture 2777 has a single free end, and the other end is fixed to the atrium side of clip CL.

[0332] Similar to prosthetic valve 2300, prosthetic valve 2700 also includes heart tissue tether 2790, with a suture 2793, a suture loop 2795 disposable around chordae tendineae CT, and a suture crimp 2794. Two variations on heart tissue tether 2790 are shown in FIGS. 60C and 60D.

In the variation in FIG. 60C, heart tissue tether 2790 engages with papillary muscle PM, rather than chordae tendineae CT. Suture 2793 passes through papillary muscle PM (e.g. by piercing papillary muscle PM with a needle coupled to suture 2793 and drawing suture 2793 through). Alternatively, an anchor (screw, hook, ring, etc. - not shown) can be coupled to papillary muscle PM and suture 2793 can be coupled to, or passed through, the anchor. In the variation shown in FIG. 60D, heart tissue tether 2790 includes a tissue anchor 2792, shown schematically as a button or pledget, that can be disposed on an outer (epicardial) side of a wall of the ventricle, VW, e.g. at the ventricle’s apex, and the suture 2793 can be secured to the anchor 2792.

[0333] A prosthetic valve according to another embodiment is shown in FIGS. 61 A and

61B. Prosthetic valve 2800 is also shown disposed in an eccentrically-clipped mitral valve MV. The differentiating aspect of this embodiment is a clip that combines clipping, spacing, and occluding functions, enabling a larger flow control portion and thus a larger flow control device, with effective sealing against paravalvular leakage.

[0334] As shown in FIG. 61A, body 2810 of prosthetic valve 2800 is disposed in a flow control passage FCP1 created by clipping the posterior leaflet PL and anterior leaflet AL eccentrically (i.e. not centrally, in this instance by clipping the A1 and PI cusps). Prosthetic valve 2800 is similar to other prosthetic valves disclosed above, such as prosthetic valve 2500 shown in FIGS. 58A and 58B, and similarly includes as part of clip connector 2870 an axial clip post 2873 similar to post 2573 of prosthetic valve 2500.

[0335] The native leaflets are clipped with clip CL, shown in more detail in FIG. 61B.

Clip CL includes a spacer SP, first paddle PI, second paddle P2, and a post connector PC to which axial clip post 2873 can be secured by any suitable mechanism (as described above in more detail). As shown in FIG. 61 A, anterior leaflet is secured to clip CL between paddle P2 and spacer SP, and posterior leaflet PL is secured to clip CL between paddle PI and spacer SP. As is apparent from FIG. 61 A, spacer SP has a significant width between paddles PI and P2, such that when the native leaflets are secured to clip CL, their coapting edges are separated, rather than being close together as is the case with clips such as the MitraClip™. This spaced clipping creates a larger (longer perimeter, greater flow area) flow control portion FCP1 than if the edges of the leaflets AL, PL were clipped directly together. In turn, this enables placement of a larger diameter prosthetic valve body 2810, with a larger flow area. The edges of leaflets AL and PL can sealingly engage the V-shaped (from a top view) leaflet surface LS of spacer SP, and the side of valve body 2810 can sealingly engage valve surface VS of clip CL. Spacer SP essentially fills the triangular space between the leaflets AL, PL, the commissure (anterolateral commissure ALC), and the prosthetic valve 2800, thus also functioning as an occluder. The clipped margins of the anterior leaflet AL and posterior leaflet PL are maintained in a fixed spatial relationship relative to each other throughout the cardiac cycle. There is no blood flow through the occluder, and in between the clipped leaflet margins during any phase of the cardiac cycle. Thus, paravalvular leakage, or regurgitation, of blood between the atrium and ventricle is reduced or eliminated.

[0336] Prosthetic valve 2800 also includes an annulus connector 2880, which in this embodiment is disposed below the native annulus, resisting upwardly (towards the atrium) directed fluid dynamic forces, e.g. during systole. The differentiating aspect of this embodiment is the clip with spacer-occluder structure and function. The mechanism for securing prosthetic valve 2600 into operative relationship with the mitral valve MV, essentially combining features of prosthetic valve 2300 (FIGS. 56A to 561) and prosthetic valve 2500 (FIGS. 58A and 58B)..

[0337] A prosthetic valve according to another embodiment is shown in FIG. 62.

Prosthetic valve 2900 is shown disposed in a mitral valve that has been clipped with two spaced clips CL, creating therebetween a single, large flow control portion FCP1. Body 2910 of prosthetic valve 2900 can be secured to at least one of the clips CL, and preferably to both of the clips CL, using any of the structures and techniques described above for other embodiments. For example, as shown in FIG. 62, prosthetic valve 2900 includes a clip connector 2970 that includes a hoop 2974, similar to the hoop 2474 described above for prosthetic valve 2400 (FIGS. 57A and 57B). Hoop 2974 is preferably coupled to both clips CL thereby preventing rocking of the prosthetic valve 2900. Alternatively, clip connector 2970 could be implemented with a suture loop, such as described above for prosthetic valves 2300 (FIGS. 56A-56I), 2600 (FIGS. 59A and 59B), or 2700 (FIGS. 60A and 60B). Securing body 2910 to appropriately sized hoop 2974 in this manner prevents over-stressing or over-tensioning of the free margin lengths of anterior leaflet AL and posterior leaflet PL that are delimited between the spaced apart clips CL.

[0338] As described above, the many embodiments of prosthetic valves described above can be used to address regurgitation in mitral valves or tricuspid valves. FIGS. 63 to 66 illustrate some exemplary applications to tricuspid valves.

[0339] As shown in FIG. 63, a tricuspid valve TV has been clipped with two clips CL in a triple orifice technique (as described above with reference to FIGS. 38E and 38F, which creates three two control portions, FCP1 (the largest) and FCP2 and FCP3 (smaller)). FIG. 63 illustrates a prosthetic valve 3000 disposed in flow control portion FCP1. In FIG. 63, the heart is in systole, such that all leaflets (including the leaflets in the prosthetic valve) are in the closed position. Prosthetic valve 3000 is shown with an annulus connector 3080 engaged with an atrium side of the tri cuspid valve annulus, but in other variations the (or another) annulus connector 3080 could engage the ventricle side of the tricuspid valve annulus, and/or the prosthetic valve 3000 could include a heart tissue tether or any of the other mechanisms described above in addition to clip connectors to secure the prosthetic valve in position relative to the native valve. In addition, prosthetic valve 3000 includes a clip connector 3070, which is illustrated with axial clip posts 3073 connected to the two clips CL. However, in other variations any of the clip connector embodiments described above could be used to secure prosthetic valve 3000 to clips CL.

[0340] As shown in FIG. 64A, a tricuspid valve TV has been clipped with three clips CL in a modified triple orifice technique that produces a larger, more central flow control portion FCP1. FIG. 64 illustrates a prosthetic valve 3100 disposed in flow control portion FCP1. In FIG. 64, the heart is in systole, such that all leaflets (including the leaflets in the prosthetic valve) are in the closed position. Prosthetic valve 3100 is shown with a clip connector 3170 that includes three eyelets 3172 that project radially from body 3110, which can be engaged with sutures 3177, each of extends from a respective clip CL and which has a length from clip CL to respective eyelet 3172 by a distal suture crimp 3178a (most easily seen in FIG. 64B). Suture 3177 can conveniently be the guide wire over which each clip CL is delivered to tricuspid valve TV. The delivery process for the clips CL and the prosthetic valve 3100 is illustrated in FIGS. 65A to 65D.

[0341] As shown in FIG. 65 A, a delivery system for clips CL and prosthetic valve 3100 includes a catheter C supporting prosthetic valve 3100 for delivery through valve delivery sheath VDS. Valve delivery sheath VDS includes eyelet slots ES through which eyelets 3172 can project radially. Valve delivery sheath VDS is disposed in a lumen of clip delivery cannula CDC, through which clips CL can be delivered. Each clip CL has a delivery guidewire to which it is coupled, which in this embodiment is suture 3177 of clip connector 3170. The sutures 3177 are threaded through eyelets 3172, and clips CL are disposed at the distal end of sutures 3177, distal to eyelets 3172. Each of the three clips CL can be delivered to tricuspid valve in sequence, as shown in FIGS. 65B to 65D, each clipping an adjacent pair of leaflets (as shown in FIGS. 65B to 65D, by way of example only, the first clip CL clips anterior leaflet AL to septal leaflet SL, the second clip CL clips septal leaflet SL to posterior leaflet PL, and the third clip CL clips anterior leaflet AL to posterior leaflet AL), resulting in the clipped tricuspid valve shown in FIG. 64A. Prosthetic valve 3100 can then be delivered from valve delivery sheath VDS out of clip delivery cannula CDC, and positioned in flow control portion FCP1. The proximal end of each of suture 3177 can then be tensioned (e.g. from outside of the patient’s body) and distal suture crimps 3178a pushed over sutures 3177 and against eyelets 3172, thus securing prosthetic valve 3100 to clips CL. Suture 3177 can then be clipped or cut close to distal suture crimps 3178a, and the delivery system withdrawn from the patient.

[0342] As shown in FIG. 66, a tricuspid valve TV has been clipped with three clips CL in a “bicuspidization” clipping technique (as described above with reference to FIGS. 38C and 38D), which creates a single control portion FCP1. FIG. 66 illustrates a prosthetic valve 3200 disposed in flow control portion FCP1. In FIG. 66, the heart is in systole, such that all leaflets (including the leaflets in the prosthetic valve) are in the closed position. Prosthetic valve 3000 is shown with an annulus connector 3280 engaged with an atrium side of the tricuspid valve annulus, but in other variations the (or another) annulus connector 3280 could engage the ventricle side of the tricuspid valve annulus, and/or the prosthetic valve 3200 could include a heart tissue tether or any of the other mechanisms described above in addition to clip connectors to secure the prosthetic valve in position relative to the native valve. In addition, prosthetic valve 3200 includes a clip connector 3270, which is illustrated with an axial clip post 3273 connected to the clip CL closest to valve body 3210. However, in other variations any of the clip connector embodiments described above could be used to secure prosthetic valve 3200 to one or more of the clips CL.

[0343] As discussed above, any of the prosthetic valves embodiments described herein can include a heart tissue tether that can be between the prosthetic valve and heart tissue, such as on the ventricle side of the native atrioventricular valve, which can provide a tension force that opposes the fluid dynamic forces imposed on the prosthetic valve during systole that would tend to displace the prosthetic valve towards the atrium and/or rock the prosthetic valve with respect to the plane of the native valve. As noted in the description of prosthetic valves 100 and 2000, such heart tissue tethers can be coupled to the clip connector and/or clip (among other options).

FIGS. 67A to 67C illustrate a heart tissue tether 3390 that can be coupled between a clip CL and the ventricular apex VA of the heart, and a method for delivering the heart tissue tether 3390 and clip CL to the heart. As shown in FIG. 67A, heart tissue tether 3390 can be delivered into the left ventricle LV by a catheter C. Heart tissue tether 3390 includes a tether anchor 3392 and a suture 3393, which can serve as a guidewire during delivery of heart tissue tether 3390. In FIG. 67A, tether anchor 3392 is shown in two positions - a first position near the middle of left ventricle LV during delivery, in a delivery (closed or collapsed) configuration, disposed at the distal end of suture 3393, and a second position disposed on the epicardial surface of the ventricle apex VA, in an deployed (expanded) configuration, after passing through a puncture though ventricle apex VA, disposed at the distal end of suture 3393 (shown in dashed line for the delivered position).

[0344] In FIG. 67B, clip CL is shown in left ventricle LV after being delivered from catheter C, riding over suture 3393, which passes through a lumen in clip C, and functions as a guidewire for delivery of clip CL. Suture 3393 is not under tension, thus allowing full manipulation, positioning, and orientation of clip CL by its delivery catheter, including closing of paddles PI and P2 to engage the native leaflets.

[0345] In FIG. 67C, clip C is shown fully deployed, i.e. having clipped together the native leaflets. The free end of suture 3393 can be tensioned, and suture crimp 3394 pushed distally over suture 3393, against clip CL, and then secured to suture 3393 to fix the length of suture 3393 between ventricle apex VA and clip CL, and to provide desired tension on clip CL. At this point in the procedure, suture 3393 can be clipped or cut proximal to suture crimp 3394, and the remainder of suture 3393 withdrawn. Any of the prosthetic valves described above can then be delivered to the native valve (e.g. through catheter C) and secured to clip CL with a suitable clip connector. Heart tissue tether 3390 then serves to oppose fluid dynamic imposed on the prosthetic valve.

[0346] While various embodiments have been described herein, textually and/or graphically, it should be understood that they have been presented by way of example only, and not limitation. Likewise, it should be understood that the specific terminology used herein is for the purpose of describing particular embodiments and/or features or components thereof and is not intended to be limiting. Various modifications, changes, enhancements, and/or variations in form and/or detail may be made without departing from the scope of the disclosure and/or without altering the function and/or advantages thereof unless expressly stated otherwise. Functionally equivalent embodiments, implementations, and/or methods, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions and are intended to fall within the scope of the disclosure.

[0347] For example, while the prosthetic valves are described herein as being used with particular native valves and clip configurations, it should be understood that they have been presented by way of example only and not limitation. The embodiments and/or devices described herein are not intended to be limited to any specific implementation unless expressly stated otherwise.

[0348] Where schematics, embodiments, and/or implementations described above indicate certain components arranged and/or configured in certain orientations or positions, the arrangement of components may be modified, adjusted, optimized, etc. The specific size and/or specific shape of the various components can be different from the embodiments shown and/or can be otherwise modified, while still providing the functions as described herein. More specifically, the size and shape of the various components can be specifically selected for a desired or intended usage. Thus, it should be understood that the size, shape, and/or arrangement of the embodiments and/or components thereof can be adapted for a given use unless the context explicitly states otherwise. By way of example, in some implementations, a treatment device intended to provide treatment to an adult user may have a first size and/or shape, while a treatment device intended to provide treatment to a pediatric user may have a second size and/or shape smaller than the first size and/or shape. Moreover, the smaller size and/or shape of, for example, a pediatric treatment device may result in certain components being moved, reoriented, and/or rearranged while maintaining the desired function of the device.

[0349] Although various embodiments have been described as having particular characteristics, functions, components, elements, and/or features, other embodiments are possible having any combination and/or sub-combination of the characteristics, functions, components, elements, and/or features from any of the embodiments described herein, except mutually exclusive combinations or when clearly stated otherwise. Moreover, unless otherwise clearly indicated herein, any particular combination of components, functions, features, elements, etc. can be separated and/or segregated into independent components, functions, features, elements, etc. or can integrated into a single or unitary component, function, feature, element, etc.

[0350] Where methods described above indicate certain events occurring in certain order, the ordering of certain events may be modified. Additionally, certain of the events may be performed concurrently in a parallel process when possible, as well as performed sequentially as described above. While methods have been described as having particular steps and/or combinations of steps, other methods are possible having a combination of any steps from any of methods described herein, except mutually exclusive combinations and/or unless the context clearly states otherwise.

Claims

1. A prosthetic valve comprising: a body including an inlet portion and an outlet portion having a first limb and a second limb, and defining a flow passage having an inlet in the inlet portion, a first outlet in the first limb and a second outlet in the second limb; a flow control device disposed in the flow passage within the inlet portion and configured to permit fluid flow through the flow passage in a first direction from the inlet to the first outlet and the second outlet, and to inhibit fluid flow through the flow passage in a second direction, opposite to the first direction; and a clip connector coupled to the body, the prosthetic valve configured to be disposed in a native valve of a heart in which a first leaflet has been coupled to a second leaflet by a clip, defining a first flow control portion between the first leaflet, the second leaflet and the clip and defining a second flow control portion between the first leaflet, the second leaflet and the clip, with the inlet disposed in an atrium of the heart, and with the first outlet and the second outlet disposed in the ventricle of the heart, the first limb configured to be disposed in the first flow control portion in substantially sealing relationship with the first leaflet and the second leaflet, the second limb configured to be disposed in the second flow control portion in substantially sealing relationship with the first leaflet and the second leaflet, the prosthetic valve configured to permit blood to flow from the atrium to the ventricle through the inlet, the flow control device, the fluid passage, and the first outlet and the second outlet, during diastole of the heart, and to substantially prevent blood to flow from the ventricle to the atrium though the flow passage or between the body and the leaflets during systole of the heart, and the clip connector configured to be selectively coupled to the clip and to resist displacement of the body towards the atrium during systole.

2. The prosthetic valve of claim 1, further comprising an annulus connector coupled to the body and configured to selectively engage with an annulus of the native valve and to resist movement of the body during systole and/or diastole of the heart.

3. The prosthetic valve of claim 2, wherein the annulus connector includes a first arm extending from the body and a first annulus anchor coupled to a distal end of the first arm, the first annulus anchor configured to engage with the annulus of the native heart valve.

4. The prosthetic valve of claim 3, wherein the annulus connector includes a second arm extending from the body opposite to the first arm and a second annulus anchor coupled to a distal end of the second arm, the second annulus anchor configured to engage with the annulus of the native heart valve.

5. The prosthetic valve of claims 1 to 3, wherein the annulus connector is configured to engage an atrial side of the native valve annulus.

6. The prosthetic valve of claims 2 to 5, wherein the annulus connector is configured to engage a ventricle side of the native valve annulus.

7. The prosthetic valve of claim 1 further comprising a heart tissue tether coupled to any of the body, the clip connector or the annulus connector, and including a tether anchor configured to be secured to heart tissue, the heart tissue tether configured to transmit fluid dynamic loads imposed on the prosthetic valve during the cardiac cycle to the heart tissue to assist in maintaining the prosthetic valve in a desired position in the native heart valve.

8. The prosthetic valve of claims 1 to 7, wherein the flow control device is a tri-leaflet valve.

9. The prosthetic valve of claims 1 to 7, wherein the flow control device includes a valve frame, a first tissue leaflet coupled to the valve frame, a second tissue leaflet coupled to the frame and disposed diametrically opposite to the first tissue leaflet, each tissue leaflet subtending approximately one third of a perimeter of the valve frame, a first static half-cusp coupled to the valve frame between the first tissue leaflet and the second tissue leaflet and a second half-cusp coupled to the valve frame between the first tissue leaflet and the second tissue leaflet diametrically opposite to the first static half-cusp, each static half-cusp subtending approximately one sixth of the perimeter of the valve frame, the tissue leaflets sealingly engageable with the static half cusps to prevent fluid flow therebetween in a first direction and to permit fluid flow therebetween in a second direction, opposite to the first direction.

10. The prosthetic valve of claim 9, wherein each static half-cusp includes a static cusp frame coupled to the valve frame and a static cusp membrane supported on the static cusp frame and disposed to sealingly engage with the tissue leaflets.

11. The prosthetic valve of claim 1, wherein the outlet portion has a third limb having a third outlet, the clip is a first clip, the prosthetic valve is configured to be disposed in a native valve of a heart in which the first leaflet has been coupled to the second leaflet by the second clip, or the first leaflet has been coupled to a third leaflet by the second clip, the second clip defining in part a third flow control portion, the third limb configured to be disposed in the third flow control portion.

12. The prosthetic valve of claim 1, wherein the body includes a body covering, each of the first limb and the second limb including a leaflet contact area against which the native leaflets can sealingly engage when the limbs are disposed in the flow control portion, the body covering in at least the leaflet contact areas being formed of tissue.

13. The prosthetic valve of claim 12, wherein the body includes a body frame having a stent frame wire mesh construction for portions of the body other than the leaflet contact area, the body frame having less structural rigidity in a radial direction in the leaflet contact area so that the body covering is relatively more compliant so that it imposes less stress on native leaflets that contact the leaflet contact area.

14. The prosthetic valve of claim 1, wherein each of the first limb and the second limb includes at an outlet end thereof an outlet cuff, the outlet cuff including padding material to reduce the risk of injury to cardiac tissue that may contact the outlet ends of the limbs.

15. The prosthetic valve of claim 1, wherein the clip connector includes an axial clip post extending from the body and having a first end coupleable to the clip with a mechanical joint and a includes a plurality of radial valve struts coupled at a lower end thereof to a second end of the axial clip post and coupled at an upper thereof to a frame of the flow control device.

16. The prosthetic valve of claim 15, wherein the radial valve struts are disposed on the ventricle side of a coaptation line of tissue leaflets disposed in the flow control device.

17. A prosthetic valve comprising: a body including an inlet portion and an outlet portion and defining a flow passage having an inlet in the inlet portion and an outlet portion; a flow control device disposed in the flow passage within the inlet portion and configured to permit fluid flow through the flow passage in a first direction from the inlet to the outlet, and to inhibit fluid flow through the flow passage in a second direction, opposite to the first direction; and a clip connector coupled to the body, the prosthetic valve configured to be disposed in a native valve of a heart in which a first leaflet has been coupled to a second leaflet by a clip, defining a flow control portion between the first leaflet, the second leaflet and the clip, with the inlet disposed in an atrium of the heart, and with outlet disposed in the ventricle of the heart, the outlet portion configured to be disposed in the flow control portion in substantially sealing relationship with the first leaflet and the second leaflet, the prosthetic valve configured to permit blood to flow from the atrium to the ventricle through the inlet, the flow control device, the fluid passage, and the outlet, during diastole of the heart, and to substantially prevent blood to flow from the ventricle to the atrium though the flow passage or between the body and the leaflets during systole of the heart, and the clip connector configured to be selectively coupled to the clip and to resist displacement of the body towards the atrium during systole.

18. The prosthetic valve of claim 17, further comprising an annulus connector coupled to the body and configured to selectively engage with an annulus of the native valve and to resist movement of the body during systole and/or diastole of the heart.

19. The prosthetic valve of claim 18, wherein the annulus connector includes a first arm extending from the body and a first annulus anchor coupled to a distal end of the first arm, the first annulus anchor configured to engage with the annulus of the native heart valve.

20. The prosthetic valve of claim 19, wherein the annulus connector includes a second arm extending from the body opposite to the first arm and a second annulus anchor coupled to a distal end of the second arm, the second annulus anchor configured to engage with the annulus of the native heart valve.

21. The prosthetic valve of claims 17 to 19, wherein the annulus connector is configured to engage an atrial side of the native valve annulus.

22. The prosthetic valve of claims 17 to 19, wherein the annulus connector is configured to engage a ventricle side of the native valve annulus.

23. The prosthetic valve of claim 17 further comprising a heart tissue tether coupled to any of the body, the clip connector or the annulus connector, and including a tether anchor configured to be secured to heart tissue, the heart tissue tether configured to transmit fluid dynamic loads imposed on the prosthetic valve during the cardiac cycle to the heart tissue to assist in maintaining the prosthetic valve in a desired position in the native heart valve.

24. The prosthetic valve of claims 17 to 23, wherein the flow control device is a tri-leaflet valve.

25. The prosthetic valve of claim 17, wherein the clip is a first clip, the body is a first body, the inlet portion is a first inlet portion, the outlet portion is a first outlet portion, the flow passage is a first flow passage, the inlet is a first inlet, the outlet is a first outlet, and further comprising a second body including a second inlet portion and a second outlet portion and defining a second flow passage having a second inlet in the second inlet portion and a second outlet in the second outlet portion, wherein the prosthetic valve is configured to be disposed in a native valve of a heart in which the first leaflet has been coupled to the second leaflet by a second clip, or the first leaflet has been coupled to a third leaflet by the second clip, the second clip defining in part a second flow control portion, the second outlet portion configured to be disposed in the second flow control portion.

26. The prosthetic valve of claim 17, wherein the clip connector includes an axial clip post extending from the body and having a first end coupleable to the clip with a mechanical joint.

27. The prosthetic valve of claim 17, wherein the atrioventricular valve is a mitral valve, the first leaflet is an anterior leaflet, and the second leaflet is a posterior leaflet.

28. The prosthetic valve of claim 27, wherein the clip is coupled to a central portion of each of the anterior leaflet and the posterior leaflet, defining the first flow control portion between the anterior leaflet, the posterior leaflet, a posteromedial commissure of the mitral valve, and the clip and defining a second flow control portion between the anterior leaflet, the posterior leaflet, the anterolateral commissure of the mitral valve, and the clip, the first flow control portion and the second flow control portion having approximately equal flow areas.

29. The prosthetic valve of claim 27, wherein the clip is coupled eccentrically to the anterior leaflet and the posterior leaflet, defining the first flow control portion between the anterior leaflet, the posterior leaflet, a posteromedial commissure of the mitral valve, and the clip and defining a second flow control portion between the anterior leaflet, the posterior leaflet, the anterolateral commissure of the mitral valve, and the clip, the first flow control portion having a flow area substantially larger than a flow area of the second flow control portion.

30. A method of repairing a native atrioventricular valve having a first leaflet coupled to a second leaflet by a clip, defining a first flow control portion between the first leaflet, the second leaflet and the clip and defining a second flow control portion between the first leaflet, the second leaflet and the clip, the method comprising: delivering to the native atrioventricular valve a prosthetic valve having a body including an inlet portion and an outlet portion having a first limb and a second limb, and defining a flow passage having an inlet in the inlet portion, a first outlet in the first limb and a second outlet in the second limb, and a flow control device disposed in the flow passage within the inlet portion and configured to permit fluid flow through the flow passage in a first direction from the inlet to the first outlet and the second outlet, and to inhibit fluid flow through the flow passage in a second direction, opposite to the first direction and a clip connector coupled to the body; disposing the prosthetic valve in the native atrioventricular valve with the inlet disposed in an atrium of the heart, and with the first outlet and the second outlet disposed in the ventricle of the heart, with the first limb disposed in the first flow control portion in substantially sealing relationship with the first leaflet and the second leaflet and the second limb disposed in the second flow control portion in substantially sealing relationship with the first leaflet and the second leaflet; and coupling the clip connector to the clip.

31. The method of claim 30, wherein the prosthetic valve includes an annulus connector coupled to the body, further comprising engaging the annulus connector with an annulus of the native atrioventricular valve.

32. The method of claim 31, wherein the engaging the annulus connector includes engaging one or both of an atrium side of the native valve annulus and the ventricle side of the native valve annulus.

33. The method of claim 30, wherein the prosthetic valve includes a heart tissue tether coupled to the body and having a tissue anchor at a distal end thereof, further comprising securing the tissue anchor to heart tissue of the heart.

34. The method of claims 30 to 33, further comprising, before the delivering the prosthetic valve, delivering the clip to the native atrioventricular valve and securing the clip to the native leaflets to create the first flow control portion and the second flow control portion.

35. A method of repairing a native atrioventricular valve having a first leaflet coupled to a second leaflet by a clip, defining a flow control portion between the first leaflet, the second leaflet and the clip, the method comprising: delivering to the native atrioventricular valve a prosthetic valve having a body including an inlet portion and an outlet portion, and defining a flow passage having an inlet in the inlet portion, an outlet in the outlet portion, and a flow control device disposed in the flow passage within the inlet portion and configured to permit fluid flow through the flow passage in a first direction from the inlet to the outlet, and to inhibit fluid flow through the flow passage in a second direction, opposite to the first direction, and a clip connector coupled to the body; disposing the prosthetic valve in the native atrioventricular valve with the inlet disposed in an atrium of the heart, and with the outlet disposed in the ventricle of the heart, with the outlet portion disposed in the flow control portion in substantially sealing relationship with the first leaflet and the second leaflet; and coupling the clip connector to the clip.

36. The method of claim 35, wherein the prosthetic valve includes an annulus connector coupled to the body, further comprising engaging the annulus connector with an annulus of the native atrioventricular valve.

37. The method of claim 36, wherein the engaging the annulus connector includes engaging one or both of an atrium side of the native valve annulus and the ventricle side of the native valve annulus.

38. The method of claim 35, wherein the prosthetic valve includes a heart tissue tether coupled to the body and having a tissue anchor at a distal end thereof, further comprising securing the tissue anchor to heart tissue of the heart.

39. The method of claims 35 to 38, further comprising, before the delivering the prosthetic valve, delivering the clip to the native atrioventricular valve and securing the clip to the native leaflets to create the first flow control portion and the second flow control portion.