Valve prosthesis configured for deployment in annular spacer

Description

FIELD OF THE INVENTION

Embodiments of the present disclosure relate in general to valve replacement. More specifically, embodiments of the present disclosure relate to prosthetic valves for replacement of an atrioventricular valve.

BACKGROUND

Dilation of the annulus of the mitral valve prevents the valve leaflets from fully coapting when the valve is closed. Regurgitation of blood from the ventricle into the atrium results in increased total stroke volume and decreased cardiac output, and ultimate weakening of the ventricle secondary to a volume overload and a pressure overload of the atrium. Dilation of the annulus is sometimes treated by implanting a prosthetic mitral valve at a patient's native mitral valve.

SUMMARY

For some embodiments of the present disclosure, one or more guide members (e.g., wires, sutures, or strings) is configured to be anchored to respective commissures of a native atrioventricular valve of a patient, and each guide member facilitates the advancement therealong of respective commissural anchors. The commissural anchors are shaped so as to define a plurality of barbs or prongs which are expandable to restrict proximal movement of the anchors following their deployment. The guide members facilitate advancement of a collapsible prosthetic valve support (e.g., a skirt) which serves as a base for and receives a collapsible prosthetic mitral valve which is subsequently coupled to the support. The support includes a proximal annular element, or ring, and a distal cylindrical element. The cylindrical element is configured to push aside and press against the native leaflets of the native valve, and the proximal annular element is shaped so as to define one or more holes for sliding the valve support along the one or more guide members. The proximal annular element is configured to be positioned along the annulus of the native valve.

The collapsible prosthetic valve is configured for implantation in and/or at least partial replacement (e.g., full replacement) of the native atrioventricular valve of the patient, such as a native mitral valve or a native tricuspid valve. The valve support and the prosthetic valve are configured to assume collapsed states for minimally-invasive delivery to the diseased native valve, such as by percutaneous or transluminal delivery using one or more catheters. For some embodiments, the valve support and the prosthetic valve are implanted during an open-heart procedure.

The prosthetic valve support is shaped so as to define a downstream skirt. The downstream skirt is configured to be placed at native valve, such that the downstream skirt passes through the orifice of the native valve and extends toward, and, in some embodiments partially into, a ventricle. The downstream skirt in some embodiments additionally pushes aside and presses against the native leaflets of the native valve, which are left in place during and after implantation of the prosthetic valve support and/or the prosthetic valve.

The proximal annular element has upper and lower surfaces. For some embodiments of the present disclosure, one or more, e.g., a plurality of, tissue anchors are coupled to the lower surface and facilitate anchoring of the proximal annular element to the annulus of the native valve. For some embodiments, the one or more anchors include at least first and second commissural anchors that are configured to be implanted at or in the vicinity of the commissures of the native valve.

The cylindrical element of the valve support has first and second ends and a cylindrical body disposed between the first and second ends. The first end of the cylindrical element is coupled to the annular element while the second end defines a free end of the cylindrical element. For some embodiments of the present disclosure, the cylindrical element of the valve support is invertible such that (1) during a first period, the second end and the cylindrical body of the cylindrical element are disposed above the annular element (e.g., in the atrium of the heart), and (2) during a second period, the second end and the cylindrical body of the cylindrical element are disposed below the annular element (e.g., in the ventricle of the heart).

For some embodiments, techniques are applied to facilitate sealing of the interface between the valve support and the native valve, and/or the interface between the prosthetic valve and the native valve. For example, a sealing balloon may be placed on a valve-facing, lower side of the annular element of the valve support, the sealing balloon being configured to be inflated such that the balloon seals the interface between the valve support and the native valve. Alternatively or additionally, commissural helices are wrapped around chordae tendineae of the patient in order to facilitate sealing of the valve commissures around the valve support and/or around the valve. Further alternatively or additionally, the valve commissures are grasped by grasping elements that act in order to facilitate sealing of the commissures around the valve support and/or around the valve. For some embodiments, one or more of the aforementioned sealing elements facilitates anchoring of the prosthetic valve to the native valve in addition to facilitating sealing.

For some embodiments, the prosthetic valve includes an expandable frame (e.g., a wire frame), and a sealing material (such as latex) is disposed on the outer surface of the frame so as to form webbing between at least some of the struts of the wire frame, and to provide sealing between the wire frame and the native valve.

For some embodiments, an invertible prosthetic valve support is used to support a prosthetic valve. In some embodiments, a sealing element is disposed circumferentially around a surface of the invertible prosthetic valve support that is initially an inner surface of the invertible prosthetic valve support. The invertible prosthetic valve support is anchored to the native valve, and is subsequently inverted. Subsequent to the inversion of the invertible prosthetic valve support, the sealing element is disposed on the outer surface of the invertible prosthetic valve support and acts to seal the interface between the outer surface and the native valve.

In accordance with some embodiments of the present disclosure, an apparatus may include a prosthetic valve support configured to be placed at an annulus of a native atrioventricular valve of a patient, the prosthetic valve support defining an annular element that defines an inner cross-sectional area thereof; an expandable prosthetic valve configured to be placed into a ventricle of the patient, the prosthetic valve including: an expandable frame; and prosthetic valve leaflets coupled to the expandable frame; the expandable frame of the prosthetic valve being configured such that when the frame is in a non-constrained state thereof, a cross-sectional area of the frame, along at least a given portion of a length of the frame, is greater than the cross-sectional area defined by the annular element of the prosthetic valve support, the prosthetic valve thereby being couplable to the prosthetic valve support at any location along the portion, responsively to radial forces acted upon the valve support by the expandable frame, by the expandable frame being expanded when the location along the portion is aligned with the annular element of the prosthetic valve support.

For some embodiments, the valve support is collapsible for transcatheter delivery.

For some embodiments, the native atrioventricular valve includes a mitral valve, and the prosthetic valve includes three prosthetic leaflets.

For some embodiments, the annular element of the valve support is asymmetrically shaped.

For some embodiments, the annular element is shaped to define a hole, and a center of the hole is disposed asymmetrically with respect to an outer perimeter of the annular element.

For some embodiments, the frame includes proximally-facing protrusions at a distal end thereof, the protrusions being configured to prevent proximal migration of the valve into an atrium.

For some embodiments, the protrusions are disposed at an angle from the frame of more than 40 degrees.

For some embodiments, the protrusions are disposed at an angle from the frame of less than 80 degrees.

For some embodiments, a length of each of the protrusions is less than 5 mm.

For some embodiments, the frame includes a single proximally-facing protrusion corresponding to each native valve leaflet of the valve, each of the protrusions having a width of less than 1 mm.

For some embodiments, the protrusions are disposed in a sinusoidal configuration such that the protrusions conform with a saddle shape of the patient's native annulus.

For some embodiments, the protrusions are configured to prevent the native leaflets from interfering with a left ventricular outflow tract of the patient.

For some embodiments, the frame includes first and second sets of one or more protrusions, each set of protrusions configured to ensnare a respective native leaflet of the native valve of the patient, the first set of protrusions being disposed within a first circumferential arc with respect to a longitudinal axis of the prosthetic valve, on a first side of a distal end of the frame, the second set of protrusions being disposed within a second circumferential are with respect to the longitudinal axis of the prosthetic valve, on a second side of the distal end of the frame, the first and second sets being disposed so as to provide first and second gaps therebetween at the distal end of the frame, at least one of the gaps having a circumferential arc of at least 20 degrees, the apparatus further including one or more valve guide members configured to be delivered to one or more commissures of the native valve, and to guide the valve such that the first and second circumferential arcs are aligned with respective leaflets of the native valve and such that the first and second gaps are aligned with respective commissures of the native valve.

For some embodiments, the at least one of the gaps has a circumferential arc of at least 60 degrees.

For some embodiments, the first circumferential arc defines an angle of between 25 degrees and 90 degrees about the longitudinal axis of the prosthetic valve.

For some embodiments, the second circumferential arc defines an angle of between 25 degrees and 90 degrees about the longitudinal axis of the prosthetic valve.

For some embodiments, the first circumferential arc defines an angle of between 45 degrees and 75 degrees about the longitudinal axis of the prosthetic valve.

For some embodiments, the second circumferential arc defines an angle of between 45 degrees and 75 degrees about the longitudinal axis of the prosthetic valve.

For some embodiments, the expandable frame of the prosthetic valve is configured such that when the frame is in a non-constrained state thereof the frame has a maximum diameter of less than 25 mm.

For some embodiments, the expandable frame of the prosthetic valve is configured such that when the frame is in a non-constrained state thereof the frame has a maximum diameter of more than 15 mm.

For some embodiments, the expandable frame of the prosthetic valve is configured such that when the frame is in a non-constrained state thereof the frame has a maximum diameter of less than 20 mm.

For some embodiments, the expandable frame of the prosthetic valve is configured such that when the frame is in a non-constrained state thereof, a cross-sectional area of the frame at a proximal end of the frame is greater than a cross-sectional area of the frame at a distal end of the frame.

For some embodiments, the expandable frame of the prosthetic valve is configured such that when the frame is in the non-constrained state thereof the frame defines a frustoconical shape.

For some embodiments, the expandable frame of the prosthetic valve is configured such that when the frame is in the non-constrained state thereof the frame defines a trumpet shape.

In accordance with some embodiments of the present disclosure, a method may include placing a prosthetic valve support at an annulus of a native atrioventricular valve of a patient, the prosthetic valve support defining an annular element that defines an inner cross-sectional area thereof; placing into a ventricle of the patient, an expandable prosthetic valve, the prosthetic valve including an expandable frame, and prosthetic valve leaflets coupled to the expandable frame, the expandable frame of the prosthetic valve being configured such that when the frame is in a non-constrained state thereof, a cross-sectional area of the frame, along at least a given portion of a length of the frame, is greater than the cross-sectional area defined by the annular element of the prosthetic valve support; determining a location anywhere along the portion at which to couple the expandable valve the prosthetic valve support; and in response thereto, aligning the location along the portion of the expandable frame with the annular element of the prosthetic valve support; and coupling the expandable valve to the prosthetic valve support at the location, responsively to radial forces acted upon the valve support by the expandable frame, by facilitating expansion of the expandable frame, when the location along the portion is aligned with the annular element of the prosthetic valve support.

For some embodiments, placing the valve support at the annulus includes transcatheterally placing the valve support at the annulus in a collapsed state.

For some embodiments, the native atrioventricular valve includes a mitral valve, and placing the prosthetic valve into the ventricle includes placing into the ventricle a prosthetic valve that includes three prosthetic leaflets.

For some embodiments, placing the prosthetic valve support at the annulus includes placing an asymmetrically-shaped prosthetic valve support at the annulus.

For some embodiments, placing the prosthetic valve support at the annulus includes placing at the annulus an annular element that is shaped to define a hole, a center of the hole being disposed asymmetrically with respect to an outer perimeter of the annular element, the annular element being placed such that a center of the hole is disposed asymmetrically with respect to the annulus.

For some embodiments, the frame includes proximally-facing protrusions at a distal end thereof, the protrusions being configured to prevent proximal migration of the valve into an atrium, and coupling the expandable valve to the prosthetic valve support includes preventing proximal migration of the valve by coupling the valve to the valve support such that the leaflets are disposed at least partially between the protrusions and the valve support.

For some embodiments, coupling the expandable valve to the prosthetic valve support includes preventing the native leaflets from interfering with a left ventricular outflow tract of the patient.

For some embodiments, coupling the expandable valve to the prosthetic valve support includes allowing movement of the leaflets with respect to the frame while preventing the proximal migration of the valve.

For some embodiments, the frame includes first and second sets of one or more protrusions, each set of protrusions configured to ensnare a respective native leaflet of the native valve of the patient, the first set of protrusions being disposed within a first circumferential arc with respect to a longitudinal axis of the prosthetic valve, on a first side of a distal end of the frame, the second set of protrusions being disposed within a second circumferential arc with respect to the longitudinal axis of the prosthetic valve, on a second side of the distal end of the frame, the first and second sets being disposed so as to provide first and second gaps therebetween at the distal end of the frame, at least one of the gaps having a circumferential arc of at least 20 degrees, the method further including guiding the valve such that the first and second circumferential arcs are aligned with respective leaflets of the native valve and such that the first and second gaps are aligned with respective commissures of the native valve.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame to a maximum diameter of less than 25 mm.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame to a maximum diameter of more than 15 mm.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame to a maximum diameter of less than 20 mm.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame such that a cross-sectional area of the frame at a proximal end of the frame is greater than a cross-sectional area of the frame at a distal end of the frame.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame such that the frame defines a frustoconical shape.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame such that the frame defines a trumpet shape.

In accordance with some embodiments of the present disclosure, a method may include determining an indication of an area defined by an annulus of a native atrioventricular valve of a patient; selecting a prosthetic valve support by determining that the prosthetic valve support defines an annular element that defines an inner cross-sectional area that is less than the area defined by the annulus; placing the prosthetic valve support at the annulus of the native atrioventricular valve; placing into a ventricle of the patient, an expandable prosthetic valve, the prosthetic valve including an expandable frame, and prosthetic valve leaflets coupled to the expandable frame; coupling the expandable valve to the prosthetic valve support at the location, responsively to radial forces acted upon the valve support by the expandable frame, by facilitating expansion of the expandable frame, a cross-sectional area defined by the expandable frame of the prosthetic valve being limited by the cross-sectional area defined by the annular element of the prosthetic valve support, such as to facilitate sealing of the native valve with respect to the prosthetic valve by facilitating closing of leaflets of the native valve around the prosthetic valve, upon deployment of the prosthetic valve.

For some embodiments, facilitating closing of leaflets of the native valve around the prosthetic valve includes facilitating sealing of the native valve at commissures of the native valve.

For some embodiments, facilitating closing of leaflets of the native valve around the prosthetic valve includes facilitating closing of the leaflets of the native valve around an outer surface of the expandable frame.

For some embodiments, placing the valve support at the annulus includes transcatheterally placing the valve support at the annulus in a collapsed state.

For some embodiments, placing the prosthetic valve support at the annulus includes placing an asymmetrically-shaped prosthetic valve support at the annulus.

For some embodiments, coupling the expandable valve to the prosthetic valve support includes preventing the native leaflets from interfering with a left ventricular outflow tract of the patient.

For some embodiments, coupling the expandable valve to the prosthetic valve support includes allowing movement of the leaflets with respect to the frame while preventing proximal migration of the valve.

For some embodiments, the frame includes first and second sets of one or more protrusions, each set of protrusions configured to ensnare a respective native leaflet of the native valve of the patient, the first set of protrusions being disposed within a first circumferential arc with respect to a longitudinal axis of the prosthetic valve, on a first side of a distal end of the frame, the second set of protrusions being disposed within a second circumferential arc with respect to the longitudinal axis of the prosthetic valve, on a second side of the distal end of the frame, the first and second sets being disposed so as to provide first and second gaps therebetween at the distal end of the frame, at least one of the gaps having a circumferential arc of at least 20 degrees, the method further including guiding the valve such that the first and second circumferential arcs are aligned with respective leaflets of the native valve and such that the first and second gaps are aligned with respective commissures of the native valve.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame to a maximum diameter of less than 25 mm.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame to a maximum diameter of more than 15 mm.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame to a maximum diameter of less than 20 mm.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame such that the frame defines a frustoconical shape.

For some embodiments, facilitating expansion of the frame includes facilitating expansion of the frame such that the frame defines a trumpet shape.

In accordance with some embodiments of the present disclosure, a method may include placing a prosthetic valve support at an annulus of a native atrioventricular valve of a patient; placing a prosthetic valve into a ventricle of the patient, the prosthetic valve including protrusions at a distal end thereof; ensnaring one or more native leaflets of the native valve of the patient with the protrusions; and coupling the prosthetic valve to the native valve, by sandwiching native leaflets of the native valve between the protrusions and the valve support, by pulling the prosthetic valve proximally with respect to the valve support, and while the native leaflets are sandwiched between the protrusions and the valve support, coupling the prosthetic valve to the valve support, by facilitating radial expansion of the prosthetic valve such that the prosthetic valve is held in place with respect to the valve support responsively to radial forces acted upon the valve support by the prosthetic valve.

In accordance with some embodiments of the present disclosure, a method may include determining an indication of an area defined by an annulus of a native atrioventricular valve of a patient; selecting a prosthetic valve to be placed in the native valve by determining that the valve defines a cross-sectional area that is less than 90% of the area defined by the annulus; and deploying the prosthetic valve at the native valve, the selecting of the prosthetic valve facilitating sealing of the native valve with respect to the prosthetic valve by facilitating closing of leaflets of the native valve around the prosthetic valve, upon deployment of the prosthetic valve.

For some embodiments, selecting the prosthetic valve includes selecting a prosthetic valve having a material disposed on an outer surface thereof.

For some embodiments, selecting the prosthetic valve includes selecting a prosthetic valve having a material that prevents tissue growth disposed on an outer surface thereof.

For some embodiments, selecting the prosthetic valve includes selecting a prosthetic valve having a material that promotes tissue growth disposed on an outer surface thereof.

For some embodiments, selecting the prosthetic valve to be placed in the native valve includes determining that the valve defines a cross-sectional area that is less than 80% of the area defined by the annulus.

For some embodiments, selecting the prosthetic valve to be placed in the native valve includes determining that the valve defines a cross-sectional area that is less than 60% of the area defined by the annulus.

In accordance with some embodiments of the present disclosure, an apparatus may include one or more valve support guide members configured to be delivered to one or more commissures of a native atrioventricular valve of a patient; one or more valve support anchors configured to be anchored to the one or more commissures of the native valve; a prosthetic valve support advanceable toward the native valve along the one or more valve support guide members and anchored to the native valve at at least the one or more commissures; and a prosthetic valve configured to be coupled to the valve support.

For some embodiments, the valve support is collapsible for transcatheter delivery and expandable to contact the native atrioventricular valve.

For some embodiments, the one or more valve support anchors are configured to be anchored to the one or more commissures from ventricular surfaces thereof.

For some embodiments, the one or more valve support guide members includes one valve support guide member that is looped through first and second commissures of the atrioventricular valve in a manner in which a looped portion of the valve support guide member is disposed in a ventricle of the patient and first and second free ends of the valve support guide member are accessible from a site outside a body of the patient.

For some embodiments, the one or more valve support anchors includes first and second tissue anchors, the first and second tissue anchors being configured to be anchored to respective first and second commissures of the atrioventricular valve of the patient.

For some embodiments, the one or more valve support anchors each include one or more radially-expandable prongs, and the one or more prongs are disposed within a sheath in a compressed state prior to the anchoring, and exposed from within the sheath in order to expand and facilitate anchoring of the valve support anchor to the respective commissures.

For some embodiments, the prosthetic valve includes two or more prosthetic leaflets.

For some embodiments, the native atrioventricular valve includes a mitral valve, and the prosthetic valve includes three prosthetic leaflets.

For some embodiments, the valve support guide members are removable from the patient following the anchoring of the prosthetic valve support at the atrioventricular valve.

For some embodiments, the valve support is shaped so as to define a distal portion which is configured to push aside, at least in part, native leaflets of the valve of the patient.

For some embodiments, the one or more valve support anchors are advanceable along the one or more valve support guide members.

For some embodiments, the valve support is shaped so as to define one or more holes, the one or more holes being configured to facilitate slidable passage therethrough of a respective one of the one or more valve support guide members.

For some embodiments, the prosthetic valve is shaped so as to define one or more snares configured to ensnare one or more native leaflets of the native valve of the patient.

For some embodiments, the one or more valve support anchors includes one or more ventricular anchors, and the apparatus further includes one or more atrial anchors, each atrial anchor being configured to be advanced toward an atrial surface of the valve support and anchor in place the valve support in a vicinity of a respective one of the ventricular anchors.

For some embodiments, the apparatus includes one or more delivery lumens, and: each one of the one or more valve support anchors is removably coupled to a distal end of a respective delivery lumen, the delivery lumen is configured to facilitate advancement of the one or more anchors along the one or more guide members, and the delivery lumen is decoupled from the anchor following the anchoring of the anchor to the one or more commissures.

For some embodiments, the one or more valve support guide members are removable from the body of the patient following the advancement of the one or more anchors along the one or more guide members.

For some embodiments, the valve support is shaped so as to define one or more holes, the one or more holes are configured to facilitate slidable passage therethrough of a respective one of the one or more delivery lumens, and the one or more delivery lumens are decoupleable from the respective valve support anchor following the anchoring of the valve support to at least the one or more commissures.

For some embodiments, the one or more delivery lumens are removable from the body of the patient following the anchoring of the valve support to at least the one or more commissures.

For some embodiments, the valve support includes an annular element and a generally cylindrical element coupled to the annular element, the generally cylindrical element being configured to push aside native leaflets of the native valve, the cylindrical element has first and second ends and a cylindrical body that is disposed between the first and second ends.

For some embodiments, the apparatus includes one or more annular element tissue anchors, the annular element has an upper surface and a lower surface, and the lower surface is coupled to the one or more annular element tissue anchors, the one or more annular element tissue anchors being configured to puncture tissue of a native annulus of the native valve of the patient.

For some embodiments, one or more annular element tissue anchors includes a plurality of annular element tissue anchors positioned around the lower surface of the annular element.

For some embodiments, the one or more annular element tissue anchors includes a first commissural anchor configured to puncture tissue of the native valve at a first commissure thereof, and a second commissural anchor configured to puncture tissue of the native valve at a second commissure thereof.

For some embodiments, each anchor of the one or more annular element tissue anchors includes a distal pointed tip and one or more radially-expandable prongs, the prongs being configured to expand and facilitate anchoring of the anchor and restrict proximal motion of the annular element tissue anchor.

For some embodiments, the apparatus includes one or more prosthetic valve guide members reversibly couplable to the cylindrical element in a vicinity of the second end of the cylindrical element, the prosthetic valve guide members being configured to facilitate advancement of the prosthetic valve therealong and toward the valve support.

For some embodiments, the first end of the cylindrical element is coupled to the annular element, during a first period, the second end of the cylindrical element is disposed above the annular element in a manner in which the body of the cylindrical element is disposed above the annular element, and the cylindrical element is invertible in a manner in which, during a second period, the second end of the cylindrical element is disposed below the annular element and the body of the cylindrical element is disposed below the annular element.

For some embodiments, during the first period, the second end of the cylindrical element is disposed in an atrium of a heart of the patient and the annular element is positioned along an annulus of the native valve, the prosthetic valve is advanceable along the one or more prosthetic valve guide members into a ventricle of the heart of the patient, and in response to advancement of the prosthetic valve into the ventricle, the one or more prosthetic valve guide members are pulled into the ventricle and pull the second end and the body of the cylindrical element into the ventricle to invert the cylindrical element.

In accordance with some embodiments of the present disclosure, a method may include advancing one or more valve support guide members toward one or more commissures of a native atrioventricular valve of a patient; advancing along the one or more valve support guide members one or more valve support tissue anchors toward the one or more commissures; anchoring the one or more valve support tissue anchors to the one or more commissures; anchoring a prosthetic valve support at the native atrioventricular valve by anchoring the prosthetic valve support at at least the one or more commissures; and coupling a prosthetic valve to the prosthetic valve support.

For some embodiments, the method includes removing the one or more valve support guide members following the anchoring of the prosthetic valve support at the native atrioventricular valve.

For some embodiments, advancing the one or more valve support guide members toward the one or more commissures includes advancing one guide member and looping the one guide member through first and second commissures of the native atrioventricular valve in a manner in which a looped portion of the guide member is disposed in a ventricle of the patient and first and second free ends of the guide member are accessible from a site outside a body of the patient.

For some embodiments, anchoring the one or more valve support anchors includes anchoring the one or more valve support anchors to ventricular surface of the respective commissures of the native valve.

For some embodiments, anchoring the one or more valve support anchors includes anchoring first and second tissue anchors to respective first and second commissures of the native valve.

For some embodiments, advancing along the one or more valve support guide members the one or more valve support tissue anchors includes advancing the one or more valve support tissue anchors within a sheath, and anchoring the one or more valve support tissue anchors includes exposing the one or more valve support anchors from within the sheath and facilitating radial expansion of one or more radially-expandable prongs of the one or more anchors.

For some embodiments, coupling the prosthetic valve to the prosthetic valve support includes coupling a prosthetic valve having two or more leaflets.

For some embodiments, the native atrioventricular valve includes a mitral valve of the patient, and coupling the prosthetic valve to the prosthetic valve support includes coupling a prosthetic valve having three leaflets.

For some embodiments, anchoring the prosthetic valve support includes pushing aside, at least in part, native leaflets of the valve of the patient by at least a portion of the support.

For some embodiments, the prosthetic valve support is coupled to one or more annulus tissue anchors, and anchoring the prosthetic valve support includes pushing the one or more annulus tissue anchors into tissue of an annulus of the native valve.

For some embodiments, coupling the prosthetic valve to the prosthetic valve support includes ensnaring one or more native leaflets of the native valve of the patient by a portion of the prosthetic valve.

For some embodiments, the one or more valve support anchors includes one or more ventricular anchors, and the method further includes advancing one or more atrial anchors to an atrial surface of the valve support, and anchoring in place the valve support in a vicinity of a respective one of the ventricular anchors.

For some embodiments, the method includes advancing the valve support along the one or more valve support guide members prior to the anchoring of the valve support.

For some embodiments, the valve support is shaped so as to define one or more holes, and advancing the valve support along the one or more valve support guide members includes threading the one or more valve support guide members through the one or more holes of the valve support and sliding the valve support along the one or more guide members.

For some embodiments, the method includes removing the one or more valve support guide members from a body of the patient following the anchoring of the valve support.

For some embodiments, the valve support includes: an annular element, and a generally cylindrical element having first and second ends and a cylindrical body that is disposed between the first and second ends, the first end being coupled to the annular element; and anchoring of the valve support, including anchoring the valve support in a manner in which: the annular element is positioned along an annulus of the native valve, the second end of the cylindrical element is disposed above the annular element in an atrium of a heart of the patient, and the body of the cylindrical element is disposed above the annular element.

For some embodiments, the method includes, following the anchoring, inverting the cylindrical element to pull the second end of the cylindrical element below the annular element and into a ventricle of the heart, in a manner in which the body of the cylindrical element is disposed below the annular element and pushes aside one or more native leaflets of the valve of the patient.

For some embodiments, inverting the cylindrical element includes advancing the prosthetic valve along one or more prosthetic valve guide members reversibly coupled to the cylindrical element in a vicinity of the second end thereof, advancing the prosthetic valve includes advancing the prosthetic valve into the ventricle to pull the prosthetic valve guide members and the second end of the cylindrical element into the ventricle, and the method further includes following the advancing of the prosthetic valve into the ventricle, pulling proximally the prosthetic valve such that a proximal portion of the valve contacts the valve support.

For some embodiments, pulling the prosthetic valve proximally includes ensnaring the one or more leaflets of the valve by a portion of the prosthetic valve.

For some embodiments, advancing the one or more valve support anchors includes: providing a respective delivery lumen coupled at a distal end thereof to each one of the one or more anchors, advancing each delivery lumen along a respective one of the one or more valve support guide members, facilitating anchoring of each one of the one or more anchors to the one or more commissures by the respective delivery lumen, and decoupling the delivery lumen from each one of the one or more valve support anchors following the anchoring of the one or more valve support anchors.

For some embodiments, the method includes removing the one or more valve support guide members from a body of the patient following the anchoring of each one of the one or more valve support anchors to the one or more commissures.

For some embodiments, the method includes advancing the prosthetic valve support along the one or more delivery lumens prior to the anchoring the support at the native atrioventricular valve.

For some embodiments, the valve support is shaped so as to define one or more holes, and advancing the valve support along the one or more delivery lumens includes threading the one or more delivery lumens through the one or more holes of the valve support and sliding the valve support along the one or more delivery lumens.

For some embodiments, the method includes removing the one or more delivery lumens from a body of the patient following the anchoring the support at the atrioventricular valve.

In accordance with some embodiments of the present disclosure, an apparatus may include a valve support for receiving a prosthetic valve, the valve support including: an annular element configured to be positioned along a native annulus of a native atrioventricular valve of a patient; and a flexible generally cylindrical element configured to be positioned in the native atrioventricular valve of the patient and to push aside native leaflets of the native valve, the cylindrical element having first and second ends and a cylindrical body that is disposed between the first and second ends, and: the first end of the cylindrical element is coupled to the annular element, during a first period, the second end of the cylindrical element is disposed above the annular element in a manner in which the body of the cylindrical element is disposed above the annular element, and the cylindrical element is invertible in a manner in which, during a second period, the second end of the cylindrical element is disposed below the annular element and the body of the cylindrical element is disposed below the annular element.

For some embodiments, the cylindrical element includes a flexible wireframe covered by a fabric.

For some embodiments, the valve support is collapsible for transcatheter delivery and expandable to contact the native atrioventricular valve.

For some embodiments, the annular element has an upper surface and a lower surface, the lower surface is coupled to one or more annular element tissue anchors configured to puncture tissue of the native annulus of the patient.

For some embodiments, the one or more annular element tissue anchors includes a plurality of annular element tissue anchors positioned around the lower surface of the annular element.

For some embodiments, the one or more annular element tissue anchors includes a first commissural annular element tissue anchor configured to puncture tissue of the native valve at a first commissure thereof, and a second commissural annular element tissue anchor configured to puncture tissue of the native valve at a second commissure thereof.

For some embodiments, the apparatus includes one or more valve support guide members configured to be delivered to one or more commissures of the native atrioventricular valve of the patient, the one or more valve support guide members are configured to facilitate advancement of the valve support toward the native valve.

For some embodiments, the valve support is shaped so as to define one or more holes, the one or more holes configured to facilitate slidable passage therethrough of a respective one of the one or more valve support guide members.

For some embodiments, the apparatus includes one or more valve support tissue anchors configured to be advanceable along the one or more valve support guide members and anchored to the one or more commissures of the valve.

For some embodiments, the valve support guide members are removable from the patient following the anchoring of the valve support at the atrioventricular valve.

For some embodiments, the one or more valve support anchors are configured to be anchored to the one or more commissures from ventricular surfaces thereof prior to advancement of the valve support.

For some embodiments, the one or more valve support tissue anchors includes first and second valve support tissue anchors, the first and second valve support tissue anchors being configured to be anchored to respective first and second commissures of the atrioventricular valve of the patient.

For some embodiments, the one or more valve support tissue anchors each include one or more radially-expandable prongs, and the one or more prongs are disposed within a sheath in a compressed state prior to the anchoring and exposed from within the sheath in order to expand and facilitate anchoring of the anchor to the respective commissures.

For some embodiments, the apparatus includes the prosthetic valve, and the prosthetic valve is couplable to the valve support.

For some embodiments, during the first period, the second end of the cylindrical element is disposed in an atrium of a heart of the patient and the annular element is positioned along an annulus of the native valve, the prosthetic valve is advanceable along the one or more prosthetic valve guide members into a ventricle of the heart of the patient, and in response to advancement of the prosthetic valve into the ventricle, the one or more prosthetic valve guide members are pulled into the ventricle and pull the second end of the cylindrical element into the ventricle to invert the cylindrical element.

For some embodiments, the prosthetic valve is collapsible for transcatheter delivery and expandable when exposed from within a delivery catheter.

For some embodiments, the prosthetic valve includes two or more prosthetic leaflets.

For some embodiments, the native atrioventricular valve includes a mitral valve, and the prosthetic valve includes three prosthetic leaflets.

For some embodiments, the prosthetic valve guide members are removable from the patient following the anchoring of the prosthetic valve at the atrioventricular valve.

For some embodiments, the prosthetic valve is shaped so as to define one or more snares configured to ensnare one or more native leaflets of the native valve of the patient.

In accordance with some embodiments of the present disclosure, a method may include advancing toward a native atrioventricular valve of a heart of a patient, a valve support including: an annular element, and a generally cylindrical element having first and second ends and a cylindrical body that is disposed between the first and second ends, the first end being coupled to the annular element; anchoring the annular element to an annulus of the native atrioventricular valve, following the anchoring, the second end of the cylindrical element is disposed above the annular element in an atrium of the heart, in a manner in which the body of the cylindrical element is disposed above the annular element; and following the anchoring, inverting the cylindrical element to pull the second end of the cylindrical element below the annular element and into a ventricle of the heart, in a manner in which the body of the cylindrical element is disposed below the annular element and pushes aside one or more native leaflets of the valve of the patient.

For some embodiments, anchoring the annular element to the annulus of the native atrioventricular valve includes: advancing one or more valve support anchors that are distinct from the valve support toward one or more commissures of the heart, and anchoring the annular element to the annulus using the one or more positioning anchors.

For some embodiments, the annular element is coupled to one or more annular element tissue anchors, and anchoring the annular element includes pushing the one or more annular element tissue anchors into tissue of the annulus.

For some embodiments, inverting the cylindrical element includes advancing a prosthetic valve along one or more valve guide members reversibly coupled to the cylindrical element in a vicinity of the second end thereof, advancing the prosthetic valve includes advancing the prosthetic valve into the ventricle to pull the guide members and the second end of the cylindrical element into the ventricle, and the method further includes following the advancing of the prosthetic valve into the ventricle, pulling proximally the prosthetic valve such that a proximal portion of the valve contacts the valve support.

For some embodiments, pulling the prosthetic valve proximally includes ensnaring the one or more leaflets of the valve by a portion of the prosthetic valve.

For some embodiments, the valve support is collapsible for transcatheter delivery and expandable to contact the native atrioventricular valve.

For some embodiments, the one or more annular element tissue anchors includes a plurality of annular element tissue anchors positioned around the lower surface of the annular element.

For some embodiments, the apparatus includes one or more valve support tissue anchors that are distinct from the valve support and are configured to be advanceable along the one or more valve support guide members and anchored to the one or more commissures of the valve.

For some embodiments, the one or more valve support guide members are removable from the patient following the anchoring of the valve support at the atrioventricular valve.

For some embodiments, the one or more valve support tissue anchors are configured to be anchored to the one or more commissures from ventricular surfaces thereof prior to advancement of the valve support.

For some embodiments, the valve support further includes a flexible generally cylindrical element coupled to the annular element and configured to be positioned in the native atrioventricular valve of the patient and to push aside native leaflets of the native valve, the cylindrical element having first and second ends and a cylindrical body that is disposed between the first and second ends.

For some embodiments, the cylindrical element includes a flexible wireframe covered by a fabric.

For some embodiments, the apparatus includes the prosthetic valve, and the prosthetic valve is couplable to the valve support.

For some embodiments, during the first period, the second end of the cylindrical element is disposed in an atrium of a heart of the patient, the prosthetic valve is advanceable along the one or more prosthetic valve guide members into a ventricle of the heart of the patient, and in response to advancement of the prosthetic valve into the ventricle, the one or more prosthetic valve guide members are pulled into the ventricle and pull the second end of the cylindrical element into the ventricle to invert the cylindrical element.

In accordance with some embodiments of the present disclosure, an apparatus may include one or more valve support guide members configured to be delivered to one or more commissures of a native atrioventricular valve of a patient; a prosthetic valve support configured to be advanced toward the native valve along the one or more valve support guide members and placed at the native valve; a prosthetic valve configured to be coupled to the valve support; and one or more sealing elements configured to facilitate sealing of an interface between the prosthetic valve support and the native valve.

For some embodiments, the sealing element includes a balloon disposed circumferentially around an outer surface of the prosthetic valve support.

For some embodiments, the sealing element includes one or more helices that are configured to facilitate sealing of commissures of the native valve with respect to the valve support by being wrapped around chordae tendineae of the native valve.

For some embodiments, the sealing element includes grasping elements that are configured to facilitate sealing of commissures of the native valve with respect to the valve support by grasping the commissures.

For some embodiments, the sealing element is configured to facilitate anchoring of the support to the native valve.

For some embodiments, the valve support is collapsible for transcatheter delivery and expandable to contact the native atrioventricular valve.

For some embodiments, the prosthetic valve includes two or more prosthetic leaflets.

For some embodiments, the native atrioventricular valve includes a mitral valve, and the prosthetic valve includes three prosthetic leaflets.

For some embodiments, the valve support guide members are removable from the patient following coupling of the prosthetic valve to the valve support.

For some embodiments, the valve support is shaped so as to define a distal portion which is configured to push aside, at least in part, native leaflets of the valve of the patient.

For some embodiments, the apparatus further includes: a guide wire configured to be advanced, via the native atrioventricular valve, into a ventricle of the patient, and coupled to an inner wall of the patient's ventricle; and a valve support guide member tube coupled to the guide wire, and a distal portion of the valve support guide member is configured to loop through the valve support guide member tube, such that, in response to the valve support guide member being pushed distally, portions of the valve support guide member are pushed to respective commissures of the native valve.

For some embodiments, the prosthetic valve is shaped so as to define one or more protrusions configured to ensnare one or more native leaflets of the native valve of the patient.

For some embodiments, the protrusions are disposed in a sinusoidal configuration such that the protrusions conform with a saddle shape of the patient's native annulus.

For some embodiments, the protrusions are configured to prevent the native leaflets from interfering with a left ventricular outflow tract of the patient, by sandwiching the leaflets between the protrusions and the prosthetic valve support.

For some embodiments, the valve support includes: a first end that is configured to be placed on an atrial side of a native atrioventricular valve of a patient; and a second end that is configured, during a first period, to be disposed inside the patient's atrium, above the first end of the valve support, the valve support being at least partially invertible in a manner in which, during a second period, the second end of the valve support is disposed at least partially inside a ventricle of the patient, below the first end of the valve support.

For some embodiments, the valve support includes an annular element and a generally cylindrical element coupled to the annular element, the generally cylindrical element being configured to push aside native leaflets of the native valve, and the cylindrical element has first and second ends and a cylindrical body that is disposed between the first and second ends.

For some embodiments, the sealing element includes a balloon disposed underneath the annular element and configured to facilitate sealing of an interface between the annular element and the native valve.

For some embodiments, the apparatus further includes one or more prosthetic valve guide members, the prosthetic valve guide members being configured to facilitate advancement of the prosthetic valve therealong and toward the valve support.

In accordance with some embodiments of the present disclosure, an apparatus may include a prosthetic valve support configured to be advanced toward a native atrioventricular valve of a patient and placed at the native valve; a prosthetic valve configured to be coupled to the valve support, the prosthetic valve being shaped so as to define first and second sets of one or more protrusions, each set of protrusions configured to ensnare a respective native leaflet of the native valve of the patient, the first set of protrusions being disposed within a first circumferential arc with respect to a longitudinal axis of the prosthetic valve, on a first side of a distal end of the prosthetic valve, the second set of protrusions being disposed within a second circumferential arc with respect to the longitudinal axis of the prosthetic valve, on a second side of the distal end of the prosthetic valve, the first and second sets being disposed so as to provide first and second gaps therebetween at the distal end of the prosthetic valve, at least one of the gaps having a circumferential arc of at least 20 degrees; and one or more valve guide members configured to be delivered to one or more commissures of the native valve, and to guide the valve such that the first and second circumferential arcs are aligned with respective leaflets of the native valve and such that the first and second gaps are aligned with respective commissures of the native valve.

For some embodiments, the at least one of the gaps has a circumferential are of at least 60 degrees.

For some embodiments, the first circumferential arc defines an angle of between 25 degrees and 90 degrees about the longitudinal axis of the prosthetic valve.

For some embodiments, the second circumferential arc defines an angle of between 25 degrees and 90 degrees about the longitudinal axis of the prosthetic valve.

For some embodiments, the first circumferential arc defines an angle of between 45 degrees and 75 degrees about the longitudinal axis of the prosthetic valve.

For some embodiments, the second circumferential arc defines an angle of between 45 degrees and 75 degrees about the longitudinal axis of the prosthetic valve.

In accordance with some embodiments of the present disclosure, a method may include determining an area defined by an annulus of a native atrioventricular valve of a patient; selecting a prosthetic valve to be placed in the native valve by determining that the valve defines a cross-sectional area that is less than 90% of the area defined by the annulus; and deploying the prosthetic valve at the native valve, the selecting of the prosthetic valve facilitating sealing of the native valve with respect to the prosthetic valve by facilitating closing of leaflets of the native valve around the prosthetic valve, upon deployment of the prosthetic valve.

For some embodiments, selecting the prosthetic valve includes selecting a prosthetic valve having a material disposed on an outer surface thereof.

For some embodiments, selecting the prosthetic valve includes selecting a prosthetic valve having a material that prevents tissue growth disposed on an outer surface thereof.

For some embodiments, selecting the prosthetic valve includes selecting a prosthetic valve having a material that promotes tissue growth disposed on an outer surface thereof.

In accordance with some embodiments of the present disclosure, an apparatus may include a valve support for receiving a prosthetic valve, the valve support including: a first end that is configured to be placed on an atrial side of a native atrioventricular valve of a patient; and a second end that is configured, during a first period, to be disposed inside the patient's atrium, above the first end of the valve support, the valve support being at least partially invertible in a manner in which, during a second period, the second end of the cylindrical element is disposed at least partially inside a ventricle of the patient, below the first end of the valve support.

For some embodiments, the valve support includes a flexible wireframe covered by a fabric.

For some embodiments, the valve support is collapsible for transcatheter delivery and expandable to contact the native atrioventricular valve.

For some embodiments, the valve support defines a surface that is an inner surface of the valve support during the first period, and an outer surface of the valve support during the second period, and the apparatus further includes a sealing material that is disposed on the surface, such that during the second period the sealing material facilitates sealing between the valve support and the native valve.

For some embodiments, the first end includes a coupling element configured to couple the valve support to tissue of the native valve on the atrial side of the native valve.

For some embodiments, the first end is shaped to define barbs that are configured to couple the valve support to tissue of the native valve on the atrial side of the native valve.

For some embodiments, the valve support includes: an annular element configured to be positioned along a native annulus of the native atrioventricular valve; and a flexible generally cylindrical element configured to be positioned in the native atrioventricular valve of the patient and to push aside native leaflets of the native valve, the first end of the cylindrical element defining the first end of the valve support, and the first end of the cylindrical element being coupled to the annular element.

For some embodiments, the apparatus further includes one or more valve support guide members configured to be delivered to one or more commissures of the native atrioventricular valve of the patient, and the one or more valve support guide members are configured to facilitate advancement of the valve support toward the native valve.

For some embodiments, the apparatus further includes one or more prosthetic valve guide members reversibly couplable to the cylindrical element in a vicinity of the second end of the cylindrical element, the prosthetic valve guide members being configured to facilitate advancement of the prosthetic valve therealong and toward the valve support.

For some embodiments, the apparatus further includes the prosthetic valve, and the prosthetic valve is couplable to the valve support.

For some embodiments, during the first period, the second end of the cylindrical element is disposed in an atrium of a heart of the patient and the annular element is positioned along an annulus of the native valve, the prosthetic valve is advanceable along the one or more prosthetic valve guide members into a ventricle of the heart of the patient, and in response to advancement of the prosthetic valve into the ventricle, the one or more prosthetic valve guide members are pulled into the ventricle and pull the second end of the cylindrical element into the ventricle to invert the cylindrical element.

For some embodiments, the apparatus further includes one or more sealing elements configured to facilitate sealing of an interface between the prosthetic valve support and the native valve.

For some embodiments, the sealing element includes a balloon disposed circumferentially around a surface of the prosthetic valve support.

For some embodiments, the sealing element includes one or more helices that are configured to facilitate scaling of commissures of the native valve with respect to the valve support by being wrapped around chordae tendineae of the native valve.

For some embodiments, the sealing element is configured to facilitate anchoring of the support to the native valve.

For some embodiments, the apparatus further includes the prosthetic valve, and the prosthetic valve is couplable to the valve support.

For some embodiments, the prosthetic valve is collapsible for transcatheter delivery and expandable when exposed from within a delivery catheter.

For some embodiments, the prosthetic valve includes two or more prosthetic leaflets.

For some embodiments, the native atrioventricular valve includes a mitral valve, and the prosthetic valve includes three prosthetic leaflets.

For some embodiments, the prosthetic valve is shaped so as to define one or more protrusions configured to ensnare one or more native leaflets of the native valve of the patient.

For some embodiments, the protrusions are disposed in a sinusoidal configuration such that the protrusions conform with a saddle shape of the patient's native annulus.

In accordance with some embodiments of the present disclosure, an apparatus may include a guide wire configured to be advanced into a patient's ventricle via a native atrioventricular valve of the patient, and coupled to an inner wall of the patient's ventricle; a valve support guide member tube coupled to the guide wire; a valve support guide member, a distal portion of the valve support guide member looping through the valve support guide member tube, such that, in response to the valve support guide member being pushed distally, portions of the valve support guide member are pushed to respective commissures of the native valve; a prosthetic valve support configured to be advanced toward the commissures of the native valve along the valve support guide member portions; and a prosthetic valve configured to be coupled to the valve support.

For some embodiments, first and second free ends of the valve support guide member are accessible from a site outside a body of the patient.

For some embodiments, the valve support includes: an annular element configured to be positioned along a native annulus of the native atrioventricular valve; and a generally cylindrical element configured to be positioned in the native atrioventricular valve of the patient and to push aside native leaflets of the native valve, the cylindrical element being coupled to the annular element, at a first end of the cylindrical element.

For some embodiments, the valve support is shaped so as to define one or more holes, the one or more holes configured to facilitate slidable passage therethrough of respective portions of the portions of the valve support guide member.

For some embodiments, the guide member is configured to facilitate advancement of the prosthetic valve therealong and toward the valve support.

For some embodiments, the prosthetic valve is collapsible for transcatheter delivery and expandable when exposed from within a delivery catheter.

For some embodiments, the prosthetic valve includes two or more prosthetic leaflets.

For some embodiments, the native atrioventricular valve includes a mitral valve, and the prosthetic valve includes three prosthetic leaflets.

For some embodiments, the guide member is removable from the patient following the coupling of the prosthetic valve to the valve support.

For some embodiments, the prosthetic valve is shaped so as to define one or more protrusions configured to ensnare one or more native leaflets of the native valve of the patient.

For some embodiments, the protrusions are disposed in a sinusoidal configuration such that the protrusions conform with a saddle shape of the patient's native annulus.

For some embodiments, the apparatus further includes one or more sealing elements configured to facilitate sealing of an interface between the prosthetic valve support and the native valve.

For some embodiments, the sealing element includes a balloon disposed circumferentially around a surface of the prosthetic valve support.

For some embodiments, the scaling element includes grasping elements that are configured to facilitate sealing of commissures of the native valve with respect to the valve support by grasping the commissures.

For some embodiments, the sealing element is configured to facilitate anchoring of the support to the native valve.

In accordance with some embodiments of the present disclosure, an apparatus may include one or more valve guide members configured to be delivered to one or more commissures of a native atrioventricular valve of a patient; a prosthetic valve configured to be advanced to be advanced toward the native valve along the one or more valve guide members and placed at the native valve at at least the one or more commissures; and one or more proximally-facing grasping elements that are configured to facilitate sealing of commissures of the native valve with respect to the valve by: being inserted into a ventricle of the patient; and being pulled proximally and being closed around tissue in a vicinity of the commissures.

For some embodiments, the grasping elements include two surfaces that are hingedly coupled to one another, and that are configured to facilitate the sealing of the commissures of the native valve with respect to the prosthetic valve by being closed about the hinge with respect to one another.

In accordance with some embodiments of the present disclosure, a method may include advancing one or more valve support guide members toward one or more commissures of a native atrioventricular valve of a patient; placing a prosthetic valve support at the native atrioventricular valve by advancing the valve support along the one or more valve support guide members; coupling a prosthetic valve to the prosthetic valve support; and facilitating sealing of an interface between the prosthetic valve support and the native valve by deploying a sealing element in a vicinity of the interface.

In accordance with some embodiments of the present disclosure, a method may include placing a first end of a prosthetic valve support on an atrial side of a native atrioventricular valve of a patient, such that a second end of the valve support is disposed, during a first period, inside the patient's atrium, above the first end of the valve support; and subsequent to the placing of the valve support, inverting at least a portion of the valve support such that, during a second period, the second end of the valve support is disposed at least partially inside a ventricle of the patient, below the first end of the valve support.

In accordance with some embodiments of the present disclosure, a method may include advancing a guide wire, via a native atrioventricular valve, into a ventricle of the patient, a valve support guide member tube being coupled to the guide wire; coupling a distal end of the guide wire to an inner wall of the patient's ventricle; and causing portions of a valve support guide member to be pushed to respective commissures of the native valve, by pushing the guide member distally, a distal portion of the valve support guide member looping through the valve support guide member tube; advancing a prosthetic valve support toward the commissures of the native valve along the valve support guide member portions; and coupling a prosthetic valve to the valve support.

In accordance with some embodiments of the present disclosure, a method may include advancing one or more valve guide members toward one or more commissures of a native atrioventricular valve of a patient; placing a prosthetic valve at the native atrioventricular valve by advancing the valve along the one or more valve guide members; and facilitating sealing of commissures of the native valve with respect to the valve by: inserting into a ventricle of the patient one or more grasping elements that are coupled to the prosthetic valve; pulling the grasping elements proximally; and closing the grasping elements around tissue in a vicinity of the commissures.

The present disclosure will be more fully understood from the following detailed description of embodiments thereof, taken together with the drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-B are schematic illustrations of advancement of one or more guide members toward respective commissures of a mitral valve, in accordance with some embodiments of the present disclosure;

FIGS. 1C-D are schematic illustrations of the advancement and deployment of commissural anchors via the guide members, in accordance with some embodiments of the present disclosure;

FIGS. 2A-D are schematic illustrations of the advancement of a prosthetic valve support toward a native atrioventricular valve of a patient, in accordance with some embodiments of the present disclosure;

FIGS. 2E-F are schematic illustrations of locking of the prosthetic valve support at the native valve, in accordance with some embodiments of the present disclosure;

FIGS. 2G-K are schematic illustrations of the advancement of a prosthetic valve and the coupling of the prosthetic valve to the valve support, in accordance with some embodiments of the present disclosure;

FIGS. 3A-B are schematic illustrations of the advancement of a prosthetic valve support toward a native atrioventricular valve of a patient, the valve support including a sealing balloon, in accordance with some embodiments of the present disclosure;

FIGS. 3C-D are schematic illustrations of locking of the prosthetic valve support at the native valve, the valve support including the sealing balloon, in accordance with some embodiments of the present disclosure;

FIGS. 4A-C are schematic illustrations of a valve support being used with commissural helices that facilitate anchoring and/or sealing of the valve support, in accordance with some embodiments of the present disclosure;

FIGS. 5A-D are schematic illustrations of grasping elements being used to anchor and/or provide sealing of a prosthetic valve, in accordance with some embodiments of the present disclosure;

FIGS. 6A-B are schematic illustrations of a prosthetic valve that includes a sealing material, in accordance with some embodiments of the present disclosure;

FIGS. 7A-F are schematic illustrations of a guide wire delivery system, in accordance with some embodiments of the present disclosure;

FIGS. 8A-C are schematic illustrations of a valve support that has a cylindrical element that is invertible, in accordance with some embodiments of the present disclosure;

FIGS. 9A-D are schematic illustrations of the advancement of an invertible prosthetic valve support toward a native atrioventricular valve of a patient, in accordance with some embodiments of the present disclosure;

FIG. 9E is a schematic illustration of inversion of the invertible prosthetic valve support at the native valve, in accordance with some embodiments of the present disclosure;

FIGS. 9F-H are schematic illustrations of the advancement of a prosthetic valve and the coupling of the prosthetic valve to the invertible valve support, in accordance with some embodiments of the present disclosure;

FIG. 10 is a schematic illustration of a prosthetic valve, the cross-sectional area of which is smaller than the area defined by the patient's native valve annulus, in accordance with some embodiments of the present disclosure;

FIGS. 11A-D are schematic illustrations of a prosthetic valve that defines protrusions from portions of the distal end of the valve, in accordance with some embodiments of the present disclosure;

FIGS. 12A-C are schematic illustrations of a prosthetic valve that defines distal protrusions that are disposed sinusoidally around the circumference of the valve, in accordance with some embodiments of the present disclosure;

FIGS. 13A-E are schematic illustrations of respective configurations of a frame of a prosthetic valve, in accordance with some embodiments of the present disclosure;

FIGS. 14A-D are schematic illustrations of respective configurations of a prosthetic valve support, in accordance with some embodiments of the present disclosure;

FIGS. 15A-E are schematic illustrations of respective steps of a procedure for deploying a prosthetic valve, in accordance with some embodiments of the present disclosure;

FIGS. 16A-H are schematic illustrations of respective steps of an alternative procedure for deploying a prosthetic valve, in accordance with some embodiments of the present disclosure;

FIGS. 17A-C are schematic illustrations of leaflets of a prosthetic valve, in accordance with some embodiments of the present disclosure;

FIGS. 18A-B are schematic illustrations of a valve support coupled to a plurality of tissue anchors, in accordance with some embodiments of the present disclosure;

FIGS. 19A-D are schematic illustrations of the valve support of FIGS. 18A-B being implanted in the native valve of the patient and facilitating implantation of a prosthetic valve, in accordance with some embodiments of the present disclosure; and

FIGS. 20A-B are schematic illustrations of a prosthetic valve and a prosthetic valve support deployed, respectively, at a tricuspid valve, and at an aortic valve, in accordance with some embodiments of the present disclosure.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Reference is now made to FIGS. 1A-B, which are schematic illustrations of a system 20 for replacing an atrioventricular valve 5 of a patient including one or more guide members 21a and 21b which are advanced toward first and second commissures 8 and 10 of valve 5 of a heart 2 of the patient, in accordance with some embodiments of the present disclosure. For some embodiments, guide members 21a and 21b include distinct guide members. Alternatively (as shown in FIGS. 7A-F), only one guide member is looped through commissures 8 and 10 in a manner in which the guide member defines a looped portion between commissures 8 and 10 (i.e., a portion of the guide member that is disposed in a ventricle 6 of heart 2), and first and second free ends which are disposed and accessible at a site outside the body of the patient. For such embodiments, the guide member defines portions 21a and 21b.

It is noted that for embodiments in which valve 5 is the patient's mitral valve, first and second commissures 8 and 10 are the anterior and posterior commissures. For embodiments in which valve 5 is the patient's tricuspid valve (which includes three commissures), the first and second commissures may be the anterior and posterior commissures of the tricuspid valve.

For some embodiments, guide members 21a and 21b include guide wires having a diameter of 0.035 inches.

The transcatheter procedure in some embodiments begins with the advancing of a semi-rigid guide wire into a right atrium 4 of the patient. The semi-rigid guide wire provides a guide for the subsequent advancement of a sheath 25 therealong and into the right atrium. Once sheath 25 has entered the right atrium, the semi-rigid guide wire is retracted from the patient's body. Sheath 25 in some embodiments includes a 13-20 F sheath, although the size may be selected as appropriate for a given patient. Sheath 25 is advanced through vasculature into the right atrium using a suitable point of origin in some embodiments determined for a given patient. For example: sheath 25 may be introduced into the femoral vein of the patient, through an inferior vena cava, into the right atrium, and into the left atrium transseptally, in some embodiments through the fossa ovalis; sheath 25 may be introduced into the basilic vein, through the subclavian vein to the superior vena cava, into the right atrium, and into the left atrium transseptally, in some embodiments through the fossa ovalis; or sheath 25 may be introduced into the external jugular vein, through the subclavian vein to the superior vena cava, into the right atrium, and into the left atrium transseptally, in some embodiments through the fossa ovalis.

In some embodiments of the present disclosure, sheath 25 is advanced through the inferior vena cava of the patient and into the right atrium using a suitable point of origin in some embodiments determined for a given patient.

Sheath 25 is advanced distally until sheath 25 reaches the interatrial septum. For some embodiments, a resilient needle and a dilator (not shown) are advanced through the sheath and into the heart. In order to advance the sheath transseptally into the left atrium, the dilator is advanced to the septum, and the needle is pushed from within the dilator and is allowed to puncture the septum to create an opening that facilitates passage of the dilator and subsequently the sheath therethrough and into the left atrium. The dilator is passed through the hole in the septum created by the needle. In some embodiments, the dilator is shaped to define a hollow shaft for passage along the needle, and the hollow shaft is shaped to define a tapered distal end. This tapered distal end is first advanced through the hole created by the needle. The hole is enlarged when the gradually increasing diameter of the distal end of the dilator is pushed through the hole in the septum.

The advancement of sheath 25 through the septum and into the left atrium is followed by the extraction of the dilator and the needle from within sheath 25.

FIGS. 1C-D and 2A-B show advancement of one or more tissue anchors 30a and 30b (alternatively, “tissue anchor bases 30a and 30b”) along guide members 21a and 21b, respectively. Tissue anchor bases 30a and 30b include a flexible, biocompatible material (e.g., nitinol) and include one or more (e.g., a plurality of) radially-expandable prongs 32 (alternatively, “leaves 32”) which may include, e.g., barbs. Each tissue anchor base 30a and 30b is reversibly coupled to a respective delivery mechanism, such as delivery lumen 27a and 27b. Each delivery lumen 27 slides around a respective guide member 21. A respective surrounding sheath 26a and 26b surrounds each delivery lumen 27a and 27b and around tissue anchor bases 30a and 30b at least in part in order to compress and prevent expansion of the leaves 32 of tissue anchor bases 30a and 30b.

As shown in FIG. 1D, the distal ends of lumens 27a and 27b are reversibly coupled to ribbed crimping structures 34. As described hereinbelow, tissue anchor bases 30a and 30b are anchored to ventricular surfaces of commissures 8 and 10. Following the anchoring, ribbed crimping structures 34 extend from tissue anchor bases 30a and 30b through commissures 8 and 10, respectively, and toward the atrial surfaces of commissures 8 and 10. Ribbed crimping structures 34 are configured to facilitate anchoring of a valve support (described hereinbelow) to the atrial surfaces of commissures 8 and 10. Tissue anchor bases 30 and crimping structures 34 may together constitute a tissue anchor 35, which may be configured to anchor a valve support (via engagement of the valve support with crimping structures 34) to the ventricular surfaces of commissures 8 and 10 (via anchor bases 30).

Anchor bases 30a and 30b, ribbed crimping structures 34, and the distal ends of surrounding sheaths 26a and 26b are advanced into ventricle 6. Subsequently, anchor bases 30a and 30b are pushed distally from within sheaths 26a and 26b, (or sheaths 26a and 26b are pulled proximally with respect to anchor bases 30a and 30b) to expose anchor bases 30a and 30b. As anchor bases 30a and 30b are exposed from within sheaths 26a and 26b, leaves 32 are free to expand and splay outward, as shown in FIG. 1D. Leaves 32 expand such that anchor bases 30a and 30b assume a flower shape. Leaves 32, collectively in their expanded state, create a larger surface area to engage tissue than in their compressed states. Following the exposing of anchor bases 30a and 30b, sheaths 26a and 26b are extracted.

As shown in FIG. 2B, lumens 27a and 27b are pulled proximally so that leaves 32 of anchor bases 30a and 30b engage respective ventricular surface of commissures 8 and 10. Leaves 32 create a large surface area which restricts proximal motion of anchor bases 30a and 30b from commissures 8 and 10, respectively.

For some embodiments, following the anchoring of anchor bases 30a and 30b to commissures 8 and 10, respectively, guide members 21a and 21b are removed from the body of the patient.

Reference is now made to FIGS. 2C-F, which are schematic illustrations of the advancement of a prosthetic valve support 40 (alternatively, “annular spacer 40”) along lumens 27a and 27b, in accordance with some embodiments of the present disclosure. In such a manner, lumens 27a and 27b function as spacer guide members. As illustrated in FIG. 2D, spacer 40 may be annular, with a spacer opening 47 extending therethrough. Spacer 40 is collapsible and includes a proximal annular element 44 (alternatively, “wall 44”) and a distal cylindrical element 42 (alternatively, “cylindrical skirt 42”). As illustrated in FIG. 2D, in some embodiments wall 44 may be substantially flattened or planar, thus rendering wall 44 disc-shaped. As also illustrated in FIG. 2D, an outer diameter of cylindrical skirt 42 may be smaller than an outer diameter of disc-shaped wall 44. Spacer opening 47 may extend through disc-shaped wall 44 and cylindrical skirt 42. Thus, spacer opening 47 may define an inner diameter of disc-shaped wall 44 and cylindrical skirt 42. Spacer 40 is configured to assume a collapsed state (e.g., surrounded by a sheath or overtube 50 shown in FIG. 2C) for minimally-invasive delivery to the diseased native valve, such as by percutaneous or transluminal delivery using one or more catheters. FIG. 2C and the other figures show spacer 40 in an expanded state after delivery in right atrium 4 and advancement toward the native valve. As shown in FIG. 2D, spacer 40 is shaped so as to define one or more (e.g., two, as shown in View A) holes 46a and 46b for slidable advancement of spacer 40 along lumens 27a and 27b, respectively. That is, prior to introduction of spacer 40 into the body of the patient, lumens 27a and 27b are threaded through holes 46a and 46b, respectively, and spacer 40 is slid along lumens 27a and 27b. Spacer 40 is slid by pushing elements 52a and 52b which surround delivery lumens 27a and 27b, respectively.

It is to be noted that spacer 40 is slid along lumens 27a and 27b by way of illustration and not limitation. That is, for some embodiments, following the anchoring of tissue anchor bases 30a and 30b to commissures 8 and 10, respectively, guide members 21a and 21b are not removed from the body of the patient, but rather lumens 27a and 27b are removed (e.g., by being decoupled from crimping structures 34) leaving behind tissue anchor bases 30a and 30b and guide members 21a and 21b. Guide members 21a and 21b may then be threaded through holes 46a and 46b, respectively, and spacer 40 is slid along guide members 21a and 21b. In such a manner, guide members 21a and 21b function as spacer guide members.

Spacer 40 includes a collapsible flexible support stent 48, which is at least partially covered by a covering 49. Spacer 40 is configured to be placed at native valve 5, such that cylindrical skirt 42 passes through the orifice of the native valve and extends towards, and, in some embodiments partially into, ventricle 6 (as shown in FIG. 2E). Since cylindrical skirt 42 may be configured to sit within the orifice of the native valve, spacer 40 may be configured such that spacer opening 47 (which defines the inner diameter of cylindrical skirt 42) may have a smaller diameter than the native valve orifice. For example, as illustrated in FIG. 2E, spacer 40 may be configured such that spacer opening 47 may have a smaller diameter than native annulus 11. Cylindrical skirt 42 in some embodiments pushes aside and presses against native leaflets of native valve 5 at least in part, which are left in place during and after implantation of the central valve section 80. Disc-shaped wall 44 is configured to be placed around a native annulus 11 of the native valve, and to extend at least partially into an atrium 4 such that disc-shaped wall 44 rests against the native annulus. Disc-shaped wall 44 is in some embodiments too large to pass through the annulus, and may, for example, have an outer diameter of between 30 and 60 mm.

For some embodiments, collapsible support stent 48 includes a plurality of struts. As illustrated in FIG. 2D, stent 48 may include struts 48a positioned within disc-shaped wall 44 and struts 48b positioned within cylindrical skirt 42. The struts may include, for example, a metal such as nitinol or stainless steel. For some embodiments, stent 48 includes a flexible metal, e.g., nitinol, which facilitates compression of spacer 40 within a delivery sheath or overtube 50. For some embodiments, covering 49 includes a fabric, such as a woven fabric, e.g., Dacron. Covering 49 is in some embodiments configured to cover at least a portion of cylindrical skirt 42, and at least a portion of disc-shaped wall 44. The covering may include a single piece, or a plurality of pieces sewn together. Disc-shaped wall 44 may be configured to at least partially obstruct blood flow therethrough due, at least in part, to the presence of stent 48 and/or due to the arrangement of covering 49 upon stent 48.

As shown in FIG. 2D, pushing elements 52a and 52b are each coupled to locking crimping elements 64a and 64b, respectively. Locking crimping elements 64a and 64b are disposed adjacently, proximally to holes 46a and 46b respectively of spacer 40. These techniques enable the surgeon to readily bring crimping elements 64a and 64b to the appropriate sites along disc-shaped wall 44, without the need for excessive imaging, such as fluoroscopy.

FIG. 2E shows spacer 40 prior to implantation at annulus 11. As shown, ribbed crimping structures 34 project away from tissue anchor bases 30a and 30b, through commissures 8 and 10, and toward atrium 4. Spacer 40 is advanced along lumens 27a and 27b toward structures 34 by being pushed by pushing elements 52a and 52b and locking crimping elements 64a and 64b.

In FIG. 2F, spacer 40 is further pushed by pushing elements 52a and 52b and locking crimping elements 64a and 64b such that holes 46a and 46b of spacer 40 advance around ribbed crimping structures 34. As holes 46a and 46b are advanced around ribbed crimping structures 34, locking crimping elements 64a and 64b advance over and surround ribbed crimping elements 34 to lock in place spacer 40 from an atrial surface of valve 5.

Responsively to the placement of spacer 40 at native valve 5, cylindrical skirt 42 is positioned partially within ventricle 6 and native leaflets 12 and 14 of native valve 5 are pushed aside.

As shown in section A-A, ribbed crimping structures 34 of tissue anchors 35 are shaped so as to define a plurality of male couplings. Locking crimping elements 64a and 64b each include a cylindrical element having an inner lumen that is shaped so as to surround a respective ribbed crimping structure 34. Each inner lumen of locking crimping elements 64a and 64b is shaped so as to define female couplings to receive the male couplings of ribbed crimping structure 34. The female couplings of locking crimping element 64 are directioned such that they facilitate distal advancement of locking crimping element 64 while restricting proximal advancement of locking crimping element 64. When the female couplings of locking crimping element 64 receive the male couplings of ribbed crimping structure 34, spacer 40 is locked in place from an atrial surface of valve 5. It is to be noted that for some embodiments, ribbed crimping elements 34 include female couplings, and locking crimping elements 64 include male couplings.

Reference is now made to FIGS. 2G-K which are schematic illustrations of the coupling of a central valve section 80 to spacer 40, in accordance with some embodiments of the present disclosure. Spacer 40 receives the central valve section 80 within spacer opening 47 and functions as a docking station. Thus, the docking station is a coupling element that provides coupling between two other elements (in this case, between annulus 11 and central valve section 80.)

Following the placement of spacer 40 at annulus 11, pushing elements 52a and 52b and sheath or overtube 50 are removed from the body of the patient, leaving behind lumens 27a and 27b, as shown in FIG. 2G.

As shown in FIG. 2G, a guide wire 72 is advanced toward ventricle 6 and facilitates the advancement of an overtube 70 through sheath 25 and the positioning of a distal end of overtube 70 within ventricle 6. Overtube 70 facilitates the advancement of central valve section 80 in a compressed state, toward spacer 40.

FIG. 2H shows partial deployment of central valve section 80 within ventricle 6 of heart 2. Central valve section 80 is shown including an expandable frame 79 including a plurality of stent struts 79a by way of illustration and not limitation. The wireframe of central valve section 80 includes a flexible metal, e.g., nitinol or stainless steel. It is to be noted that the wireframe of central valve section 80 is covered by a covering (not shown for clarity of illustration) including a braided mesh or in a fabric such as a woven fabric, e.g., Dacron. The covering is in some embodiments configured to cover at least a portion of the frame. The covering may include a single piece, or a plurality of pieces sewn together. Expandable frame 79 is in some embodiments self-expandable, although the scope of the present disclosure includes using a prosthetic valve that includes a balloon expandable frame, mutatis mutandis.

Following the partial deployment of central valve section 80 in ventricle 6, overtube 70 is pulled proximally to pull central valve section 80 proximally such that cylindrical skirt 42 and/or disc-shaped wall 44 of spacer 40 surrounds a proximal portion of central valve section 80. Central valve section 80 may be configured to expand such that central valve section 80, in particular cylindrical portion 86 thereof, is held in place with respect to spacer 40 responsively to radial forces acted upon spacer 40 by central valve section 80. Because spacer 40 and central valve section 80 are configured to be implanted separately and to engage one another within the body, spacer 40 and central valve section 80 may be separable such that the features can be disengaged (e.g. by contracting central valve section 80 and removing it from spacer 40. In addition, and as illustrated in FIG. 2J, an outer diameter of cylindrical portion 86 of the central valve section may be smaller than the diameter of native annulus 11 due, at least in part, to the engagement between expanded cylindrical portion 86 and spacer 40.

Central valve section 80 includes a plurality of distal protrusions 84 (e.g., snares). As illustrated in FIGS. 2I and 2J, protrusions 84 are configured to extend radially outward beyond cylindrical skirt 42 of the annular spacer. When central valve section 80 is pulled proximally, as described hereinabove, protrusions 84 ensnare and engage the native leaflets of the atrioventricular valve. By the ensnaring of the native leaflets, protrusions 84 sandwich the native valve between protrusions 84 and spacer 40. Such ensnaring helps further anchor central valve section 80 to the native atrioventricular valve. The scope of the present disclosure includes using any sort of protrusions (e.g., hooks) that protrude from the distal end of expandable frame 79 of central valve section 80 and that are configured such that the native valve is sandwiched between the protrusions and spacer 40. In some embodiments, the protrusions cause sandwiching of the native valve leaflets, such that the leaflets do not interfere with the left ventricular outflow tract (LVOT).

For some embodiments, protrusions 84 are such as to (a) prevent proximal migration of the central valve section into the patient's atrium, while (b) allowing movement of the native leaflets with respect to the frame of the central valve section. For example, the protrusions may have the aforementioned functionalities by having lengths of less than 5 mm, and/or by a total width of each set of protrusions corresponding to respective leaflets of the native valve being less than 5 mm. For example, the central valve section may include a single protrusion corresponding to each leaflet of the native valve, the width of each of the single protrusions being less than 1 mm. Thus, the central valve section may be stopped from proximally migrating into the atrium, by the protrusions preventing the distal end of the central valve section from migrating further proximally than edges of native leaflets of the valve. Furthermore, the protrusions may allow movement of the native leaflets with respect to the frame of the central valve section by not generally squeezing the native leaflets between the protrusions and the frame of the central valve section. For some embodiments, by allowing movement of the native leaflets with respect to the frame of the central valve section, sealing of the native leaflets against the outer surface of the frame of the central valve section is facilitated, in accordance with the techniques described hereinbelow with reference to FIG. 10. In some embodiments, spacer 40 prevents the central valve section from migrating distally into the patient's ventricle.

For some embodiments, during the procedure, the central valve section is pulled back proximally with respect to the annular spacer, as described hereinabove. The central valve section is pulled back to a position with respect to the annular spacer that is such that protrusions 84 prevent the native leaflets from interfering with the LVOT, by sandwiching the native leaflets between the protrusions and the annular spacer, and/or by anchoring ends of the native leaflets as described hereinabove. The central valve section is then deployed at this position.

For some embodiments, protrusions are disposed on the central valve section on the sides of the central valve section that are adjacent to the anterior and posterior leaflets of the native valve, and the central valve section does not includes protrusions on the portions of the central valve section that are adjacent to the commissures of the native valve, as described with reference to FIGS. 11A-D. For some embodiments, the protrusions are disposed in a sinusoidal configuration in order to conform with the saddle shape of the native valve, as described hereinbelow with reference to FIGS. 12A-C.

Additionally, as shown in FIG. 2J, central valve section 80 includes one or more (e.g., a plurality, as shown) coupling elements 81 at the proximal end of central valve section 80. Overtube 70, which facilitates the advancement of central valve section 80, is reversibly coupled to central valve section 80, via coupling elements 81.

Central valve section 80 is configured for implantation in and/or at least partial replacement of a native atrioventricular valve 5 of the patient, such as a native mitral valve or a native tricuspid valve. Central valve section 80 is configured to assume a collapsed state for minimally-invasive delivery to the diseased native valve, such as by percutaneous or transluminal delivery using one or more catheters. FIG. 2J shows central valve section 80 in an expanded state after delivery to the native valve.

Reference is now made to FIG. 2K which shows a bird's-eye view of central valve section 80. Central valve section 80 further includes a plurality of valve leaflets 82, which may be artificial or tissue-based. The leaflets are in some embodiments coupled to an inner surface of the central valve section. Leaflets 82 are coupled, e.g., sewn, to expandable frame 79 and/or to the covering. For embodiments in which the central valve section is configured to be implanted at the native mitral valve, the central valve section in some embodiments includes three leaflets 82a, 82b, and 82c, as shown in FIG. 2K.

Reference is now made to FIGS. 3A-D, which are schematic illustrations of the advancement of spacer 40 toward native atrioventricular valve 5 of a patient, the annular spacer including a sealing balloon 90, in accordance with some embodiments of the present disclosure. The steps shown in FIGS. 3A-C are generally similar to those shown in FIGS. 2C-F. For some embodiments, sealing balloon 90 is disposed on the valve-facing, lower side of disc-shaped wall 44 of the annular spacer. FIG. 3D shows spacer 40, the spacer having been implanted at annulus 11. In some embodiments, at this stage, balloon 90 is inflated, as shown in the transition from FIG. 3C to FIG. 3D. The balloon is inflated via an inflation lumen 92, shown in FIG. 3C, for example. For some embodiments, the balloon seals the interface between the spacer and native annulus 11, thereby reducing retrograde blood flow from ventricle 6 into atrium 4, relative to retrograde blood flow in the absence of a sealing balloon. For some embodiments, the balloon is inflated prior to the placement of the prosthetic support at annulus 11.

Reference is now made to FIGS. 4A-C, which are schematic illustrations of spacer 40 being used with commissural helices 100a and 100b that facilitate anchoring and/or sealing of the spacer, in accordance with some embodiments of the present disclosure. For some embodiments, commissural helices are used as an alternative or in addition to tissue anchor bases 30a and 30b and/or other anchoring elements described herein, in order to facilitate the anchoring of spacer 40.

Commissural helices 100a and 100b are in some embodiments placed at commissures 8 and 10 in a generally similar technique to that described with reference to tissue anchor bases 30a and 30b. In some embodiments, each helix 30a and 30b is reversibly coupled to a respective delivery lumen 27a and 27b. As described above, each delivery lumen 27 slides around a respective guide member 21, and a respective surrounding sheath 26a and 26b surrounds each delivery lumen 27a and 27b.

Commissural helices 100a and 100b (optionally, ribbed crimping structures 34), and the distal ends of surrounding sheaths 26a and 26b are advanced into ventricle 6. The helices are pushed out of the distal ends of surrounding sheaths 26a and 26b. Subsequently, the helices are rotated proximally such that the helices wrap around at least some chordae tendineae 102 of the patient. Following the advancement of the helices out of sheaths 26a and 26b, the sheaths are extracted. For some embodiments the helices are conical helices (as shown), and the wider end of the conical helix is disposed at the proximal end of the helix.

Subsequent to the placement of commissural helices 100a and 100b around the chordae tendineae, spacer 40 is placed at annulus 11, in accordance with the techniques described hereinabove, and as shown in FIG. 4B. Subsequently, central valve section 80 is coupled to spacer 40, in accordance with the techniques described hereinabove, and as shown in FIG. 4C.

In some embodiments, commissural helices 100a and 100b facilitate sealing of native commissures 8 and 10, thereby reducing retrograde blood flow via the commissures, relative to retrograde blood flow in the absence of the helices. Further in some embodiments, the sealing of the native commissures facilitates anchoring of the spacer to native valve 5.

Reference is now made to FIGS. 5A-D, which are schematic illustrations of grasping elements 106a and 106b being used to anchor central valve section 80, in accordance with some embodiments of the present disclosure. For some embodiments, guide members 21a and 21b are advanced toward first and second commissures 8 and 10 of valve 5 of the patient, as described hereinabove. Grasping elements 106a and 106b are reversibly coupled to distal ends of delivery lumen 27a and 27b, the delivery lumens being advanced over respective guide members, as described hereinabove. For some embodiments, the guiding members and the grasping elements are advanced toward the patient's commissures via surrounding sheaths 26a and 26b, the surrounding sheaths being generally as described hereinabove. The grasping elements are in some embodiments placed distally to the commissures in a proximally-facing configuration, as shown in FIG. 5A. For example, as shown, the grasping elements may be configured to be proximally facing due to the coupling of the grasping elements to the guide members.

Subsequent to the placement of grasping elements 106a and 106b distally to native commissures 8 and 10, central valve section 80 is advanced toward native valve 5, as shown in FIG. 5B. For example, the central valve section may be advanced over delivery lumens 27a and 27b, as shown. The central valve section is placed at the native valve and, subsequently, the grasping elements are retracted proximally toward commissures 8 and 10, as shown in the transition from FIG. 5B to FIG. 5C. For some embodiments, the grasping elements are coupled to central valve section 80 via coupling tubes 107a and 107b, the coupling tubes being coupled to the sides of the central valve section, as shown. The grasping elements are closed such that the native commissures are grasped and sealed by the grasping elements, as shown in FIG. 5D. In some embodiments, the grasping elements define two surfaces that are hingedly coupled to each other. For example, the grasping elements may include forceps, as shown. The grasping elements are closed by closing the surfaces about the hinge, with respect to one another.

In some embodiments, grasping elements 106a and 106b facilitate sealing of native commissures 8 and 10, thereby reducing retrograde blood flow via the commissures, relative to retrograde blood flow in the absence of the grasping elements. Further in some embodiments, the sealing of the native commissures facilitates anchoring of the central valve section to native valve 5.

Although not shown, for some embodiments, spacer 40 is used in addition to grasping elements 106a and 106b, in order to anchor central valve section 80 to native valve 5. For some embodiments, the grasping elements are used to anchor and/or provide sealing for spacer 40 (instead of, or in addition to, being used to anchor central valve section 80, as shown). For such embodiments, generally similar techniques are used to those described with respect to the use of the grasping elements for anchoring the central valve section, mutatis mutandis.

Reference is now made to FIGS. 6A-B, which are schematic illustrations of central valve section 80, the central valve section including a sealing material 110 on an outer surface of the central valve section, in accordance with some embodiments of the present disclosure. For some embodiments, central valve section 80 is used in conjunction with spacer 40, as described hereinabove. The techniques for implanting central valve section 80 as shown in FIGS. 6A-B are generally similar to those described hereinabove. In some embodiments, sealing material 110 seals the interface between the central valve section and native valve 5. The scaling material reduces retrograde blood flow from ventricle 6 into atrium 4, relative to retrograde blood flow in the absence of the sealing material. In some embodiments, the sealing material is composed of latex, dacron, and/or any other suitable biocompatible material. The sealing material is in some embodiments placed around at least a portion of expandable frame 79 of the central valve section so as to form a webbing between struts 79a of the expandable frame.

Reference is now made to FIGS. 7A-F, which are schematic illustrations of a guide wire delivery system, in accordance with some embodiments of the present disclosure. As described hereinabove (e.g., with reference to FIGS. 2C-F), for some embodiments, guide members 21a and 21b, function as spacer guide members, by spacer 40 being slid along guide members 21a and 21b. For some embodiments, only one guide member 21 is looped through commissures 8 and 10 in a manner in which the guide member defines a looped portion between commissures 8 and 10 (i.e., a portion of the guide member that is disposed in a ventricle 6 of heart 2), and first and second free ends, which are disposed and accessible at a site outside the body of the patient. For such embodiments, the guide member defines portions 21a and 21b.

For some embodiments, an anchor base 302 is advanced toward the vicinity of apex 304 of heart 2, via sheath 25, and is anchored to the vicinity of the apex, as shown in FIG. 7A. A guidewire 306 extends proximally from the anchor base 302. Guide member 21 passes through a guide member tube 320, the guide member tube being coupled to guidewire 306. Guide member 21 is pushed distally. Guide member tube 320 is unable to advance distally over guidewire 306, due to the coupling of the guide member tube to the guidewire. Therefore, the pushing of guide member 21 distally, causes portions 21a and 21b to spread apart from one another and to be pushed against commissures 8 and 10 of native valve 5. Portions 21a and 21b are then used to guide spacer 40 to the commissures, as shown in FIGS. 7B-C, using generally similar techniques to those described hereinabove, except for the differences described hereinbelow.

As shown in FIG. 7B, spacer 40 is slid over guide member portions 21a and 21b, by pushing elements 52a and 52b. Since the guide member portions are positioned at commissures 8 and 10, the guide member portions guide the distal ends of pushing elements 52a and 52b, such that the pushing elements push the spacer against the commissures, as shown in FIG. 7C.

Subsequent to the placement of spacer 40 at the native valve, central valve section 80 is coupled to spacer 40. For some embodiments, pushing elements 52a and 52b continue to push the spacer against the native valve, during the coupling of the central valve section to the spacer. As described hereinabove, overtube 70 is advanced into ventricle 6, as shown in FIG. 7D. FIG. 7E shows central valve section having been partially deployed in the ventricle. Following the partial deployment of central valve section 80 in ventricle 6, overtube 70 is pulled proximally to pull central valve section 80 proximally such that cylindrical skirt 42 and/or disc-shaped wall 44 of spacer 40 surrounds a proximal portion of central valve section 80. Central valve section 80 may be configured to expand such that central valve section 80 is held in place with respect to spacer 40 responsively to radial forces acted upon spacer 40 by central valve section 80. During the pulling back of overtube 70, pushing elements 52a and 52b push spacer 40 against the central valve section, thereby providing a counter force against which overtube 70 is pulled back. For some embodiments, the pushing of the spacer against the commissures is such that it is not necessary to use anchors for anchoring the spacer to the native valve during the coupling of the central valve section to the spacer. Alternatively, in addition to the pushing elements providing a counter force against which the central valve section is pulled, anchors are used to anchor the spacer to the native valve during the coupling of the central valve section to the spacer.

As described hereinabove, central valve section 80 includes a plurality of distal protrusions 84. When central valve section 80 is pulled proximally, as described hereinabove, protrusions 84 ensnare and engage the native leaflets of the atrioventricular valve. By the ensnaring of the native leaflets, protrusions 84 sandwich the native valve between protrusions 84 and spacer 40. Such ensnaring helps further anchor central valve section 80 to the native atrioventricular valve.

For some embodiments, as described hereinabove, protrusions 84 are such as to (a) prevent proximal migration of the central valve section into the patient's atrium, while (b) allowing movement of the native leaflets with respect to the frame of the central valve section. For example, the protrusions may have the aforementioned functionalities by having lengths of less than 5 mm and/or by a total width of each set of protrusions corresponding to respective leaflets of the native valve being less than 5 mm. For example, the central valve section may include a single protrusion corresponding to each leaflet of the native valve, the width of each of the single protrusions being less than 1 mm. Thus, the central valve section may be stopped from proximally migrating into the atrium, by the protrusions preventing the distal end of the central valve section from migrating further proximally than edges of native leaflets of the valve. Furthermore, the protrusions may allow movement of the native leaflets with respect to the frame of the central valve section by not generally squeezing the native leaflets between the protrusions and the frame of the central valve section. For some embodiments, by allowing movement of the native leaflets with respect to the frame of the central valve section, sealing of the native leaflets against the outer surface of the frame of the central valve section is facilitated, in accordance with the techniques described hereinbelow with reference to FIG. 10.

Subsequent to the placement of the central valve section at the native valve, sheath 25, overtube 70, pushing elements 52a and 52b, guide member 21, anchor base 302, and guidewire 306 are removed from the patient's body, as shown in FIG. 7F, which shows the central valve section in its deployed state. For some embodiments, in order to remove guide member 21 from the patient's body, guide member portions 21a and 21b are decoupled from guide member tube 320. For example, the guide member portions may be coupled to the guide member tube via threading, the guide member portions being decoupled from the guide member tube by unscrewing the guide member portions from the guide member tube.

Reference is now made to FIGS. 8A-C which are schematic illustrations of a system 120 including an invertible spacer 140, in accordance with some embodiments of the present disclosure. Invertible spacer 140 is identical to spacer 40 described herein, with the exception that the cylindrical skirt 142 of the spacer 140 is invertible, as is described hereinbelow. Additionally, the method of advancing toward and implanting spacer 140 at annulus 11 is identical to the methods of advancing toward and implanting spacer 40 at annulus 11, as described hereinabove.

Spacer 140 includes a disc-shaped wall 144 (that is identical to disc-shaped wall 44 described hereinabove) and a cylindrical skirt 142. Cylindrical skirt 142 has a first end 150, a second end 152, and a cylindrical body 153 disposed between first and second ends 150 and 152. Cylindrical skirt 142 is attached to disc-shaped wall 144 at first end 150 of cylindrical skirt 142.

During and following implantation of spacer 140 at annulus 11, as shown in FIG. 8A, cylindrical skirt 142 is disposed above disc-shaped wall 144 in a manner in which second end 152 and cylindrical body 153 are disposed above disc-shaped wall 144 and within atrium 4. One or more elongate guide members 146a and 146b are reversibly coupled to cylindrical skirt 142 in a vicinity of second end 152. Elongate guide members 146a and 146b facilitate (a) advancement of central valve section 80 therealong and toward spacer 140, and (b) inversion of cylindrical skirt 142 toward ventricle 6 when at least a portion of central valve section 80 is deployed within ventricle 6 (as shown in FIG. 8B).

The configuration of spacer 140 as shown in FIG. 8A (i.e., the configuration in which cylindrical skirt 142 is disposed within atrium 4) eliminates the obstruction of native valve 5 and of leaflets 12 and 14 by any portion of spacer 140. In this manner, spacer 140 may be implanted at valve 5 while valve 5 resumes its native function and leaflets 12 and 14 resume their natural function (as shown by the phantom drawing of leaflets 12 and 14 in FIG. 8A which indicates their movement). This atrially-inverted configuration of spacer 140 reduces and even eliminates the amount of time the patient is under cardiopulmonary bypass. Only once central valve section 80 is delivered and coupled to spacer 140 and cylindrical skirt 142 is thereby ventricularly-inverted, native leaflets 12 and 14 are pushed aside (FIG. 8B).

FIG. 8B shows the inversion of cylindrical skirt 142 by the partial positioning and deployment of central valve section 80 within ventricle 6. Elongate guide members 146a and 146b are reversibly coupled to central valve section 80 and extend within overtube 70. Following the full deployment of central valve section 80 and the coupling of central valve section 80 to spacer 140, elongate guide members 146a and 146b are decoupled from central valve section 80 and from cylindrical skirt 142. For example, a cutting tool may be used to decouple elongate members 146a and 146b from the spacer 140. Alternatively, elongate members 146a and 146b may be looped through the cylindrical skirt 142, such that both ends of each elongate member 146a and 146b remain outside of the patient's body. The operating physician decouples elongate members 146a and 146b from spacer 140 by releasing one end of each of elongate members 146a and 146b and pulling on the other end, until elongate members 146a and 146b are drawn from spacer 140 and removed from within the body of the patient.

FIG. 8C shows central valve section 80 coupled to spacer 140. Central valve section 80 is identical to the central valve section described hereinabove.

Reference is now made to FIGS. 9A-E, which are schematic illustrations of the advancement of an invertible spacer 300 toward a native atrioventricular valve of a patient, and inversion of the spacer, in accordance with some embodiments of the present disclosure. Spacer 300 is used to anchor central valve section 80 to native valve 5 in a generally similar manner to that described with reference to spacer 40.

During an exemplary procedure, anchor base 302 is advanced toward the vicinity of apex 304 of heart 2, via sheath 25, and is anchored to the vicinity of the apex, as shown in FIG. 8A. A guidewire 306 extends proximally from the anchor base. A distal tensioning element 308 (e.g., a plunger) is advanced over guidewire 306 into ventricle 6, and spacer 300 is advanced out of the distal end of sheath 25, as shown in FIG. 9B. A first end 310 of spacer 300 (which at this stage is the distal end of the spacer), includes barbs 314 (shown in FIG. 9B), or other anchoring elements for anchoring the first end of the spacer to tissue of native valve 5. Spacer 300 is pushed distally such that the barbs are pushed into the native valve tissue, thereby anchoring the first end of the spacer to the native valve, as shown in FIG. 9C. A plurality of wires 309 pass from distal tensioning element 308 to a proximal tensioning element 311 (shown in FIG. 9D), via a second end 312 of spacer 300 (which at this stage is the proximal end of the spacer). For some embodiments, a sealing element 316 is disposed circumferentially around a surface of the invertible spacer that is initially an inner surface of the invertible spacer (a shown in FIGS. 8A-D). For example, the sealing material may be latex, dacron, or another suitable biocompatible sealing material.

Subsequent to the anchoring of first end 310 of spacer 300 to native valve tissue (as shown in FIG. 9C), distal tensioning element 308 is further advanced distally into ventricle 6, and proximal tensioning element 311 is advanced toward the ventricle. As shown in the transition from FIG. 9D-F, as the proximal tensioning element passes through the spacer, wires 309 cause spacer 300 to invert, by pulling second end 312 of the spacer through first end 310 of the spacer. Subsequent to the inversion of the spacer, sealing material 316 is disposed circumferentially around the outside of the spacer, thereby providing a seal at the interface between spacer 300 and native valve 5.

Reference is now made to FIGS. 9G-H, which are schematic illustrations of the deployment of central valve section 80 and the coupling of the central valve section to invertible spacer 300, in accordance with some embodiments of the present disclosure.

The deployment of central valve section 80 is generally similar to the techniques described hereinabove with reference to FIGS. 2H-J. The central valve section is partially deployed in ventricle 6, via overtube 70. Following the partial deployment of central valve section 80 in ventricle 6, overtube 70 is pulled proximally (as shown in FIG. 8G) to pull central valve section 80 proximally such that spacer 300 surrounds a proximal portion of central valve section 80, as shown in FIG. 8H. Central valve section 80 may be configured to expand such that central valve section 80 is held in place with respect to spacer 300 responsively to radial forces acted upon spacer 300 by central valve section 80.

As described hereinabove, for some embodiments, central valve section 80 includes a plurality of distal protrusions 84. When central valve section 80 is pulled proximally, protrusions 84 ensnare and engage the native leaflets of the atrioventricular valve. By the ensnaring of the native leaflets, protrusions 84 sandwich the native valve between protrusions 84 and spacer 300. Such ensnaring helps further anchor central valve section 80 to the native atrioventricular valve.

For some embodiments, as described hereinabove, protrusions 84 are such as to (a) prevent proximal migration of the central valve section into the patient's atrium, while (b) allowing movement of the native leaflets with respect to the frame of the central valve section. For example, the protrusions may have the aforementioned functionalities by having lengths of less than 5 mm, and/or by a total width of each set of protrusions corresponding to respective leaflets of the native valve being less than 5 mm. For example, the central valve section may include a single protrusion corresponding to each leaflet of the native valve, the width of each of the single protrusions being less than 1 mm. Thus, the central valve section may be stopped from proximally migrating into the atrium, by the protrusions preventing the distal end of the central valve section from migrating further proximally than edges of native leaflets of the valve. Furthermore, the protrusions may allow movement of the native leaflets with respect to the frame of the central valve section by not generally squeezing the native leaflets between the protrusions and the frame of the central valve section. For some embodiments, by allowing movement of the native leaflets with respect to the frame of the central valve section, sealing of the native leaflets against the outer surface of the frame of the central valve section is facilitated, in accordance with the techniques described hereinbelow with reference to FIG. 10.

Additionally, as shown in FIG. 9H, and as described hereinabove, central valve section 80 includes one or more coupling elements 81 (for example, a plurality of coupling elements, as shown) at the proximal end of central valve section 80. Overtube 70, which facilitates the advancement of central valve section 80, is reversibly coupled to central valve section 80, via coupling elements 81.

Subsequent to the coupling of central valve section 80 to spacer 300, overtube 70, distal and proximal tensioning elements 308 and 311, and wires 309 are removed from the patient's body, via sheath 25. In some embodiments, wires 309 are cut, in order to facilitate the removal of the wires from the patient's body. Guidewire 306 and anchor base 302 are removed from the patient's body by detaching the anchor base from apex 304, and withdrawing the anchor base and the guidewire, via sheath 25.

Reference is now made to FIG. 10, which is a schematic illustration of central valve section 80, for placing inside atrioventricular valve 5 of the patient, in accordance with some embodiments of the present disclosure. The expandable frame 79 of the central valve section has a diameter d, and a corresponding cross-sectional area. Native annulus 11, which is in some embodiments saddle-shaped, defines an area A, as shown. For some embodiments, area A, which is defined by the native annulus is measured, e.g., using a measuring ring. A central valve section is chosen to be placed in the annulus, the cross-sectional area of the central valve section being less than 90% (e.g., less than 80%, or less than 60%) of area A. For some embodiments, diameter d of the central valve section is less than 25 mm, e.g., less than 20 mm, and/or more than 15 mm, e.g., 15-25 mm. For some embodiments, placing a central valve section inside the native valve with the dimensions of the native valve annulus and the central valve section as described, facilitates sealing of the central valve section with respect to the native valve, by the native valve leaflets closing around the outer surface of the central valve section.

For some embodiments, a spacer 40 that includes disc-shaped wall 44 (e.g., as shown in FIGS. 14A-C) is chosen to be placed at the annulus, the disc-shaped wall defining an inner cross-sectional area that is less than 90% (e.g., less than 80%, or less than 60%) of area A. Central valve section 80 is deployed at the native valve by coupling the central valve section to the spacer at the location, responsively to radial forces acted upon the spacer by the expandable frame, by facilitating expansion of the expandable frame, as described herein. The cross-sectional area defined by the expandable frame of the central valve section, upon expansion of the expandable frame, is limited by the cross-sectional area defined by the disc-shaped wall of the spacer to less than 90% (e.g., less than 80%, or less than 60%) of area A. For some embodiments, placing a spacer at the annulus with the dimensions of the native valve annulus and spacer 40, as described, facilitates sealing of the central valve section with respect to the native valve, by the native valve leaflets closing around the outer surface of the central valve section.

In some embodiments, placing a central valve section inside the native valve with the dimensions of the native valve annulus, the central valve section 80, and/or spacer 40 as described in the above paragraphs, facilitates sealing of the central valve section with respect to the native valve. For some embodiments, the sealing is facilitated by the native leaflets being pushed against, and closing against, the outer surface of the frame of the central valve section during systole, in a similar manner to the manner in which native valve leaflets coapt during systole, in a healthy mitral valve. In some embodiments, as the diameter of the central valve section is increased, the length of the native leaflets that is pushed against the outer surface of the central valve section during systole is increased, thereby enhancing the sealing of the native leaflets with respect to the frame of the central valve section. However, beyond a given diameter, as the diameter of the central valve section is increased, the native valve leaflets are pushed apart at the commissures, thereby causing retrograde leakage of blood through the commissures. Therefore, in accordance with some embodiments of the present disclosure, central valve section 80, and/or spacer 40 are chosen such that the cross-sectional area of the central valve section when expanded inside the spacer is less than 90% (e.g., less than 80%, or less than 60%) of area A. Thus the spacer facilitates sealing of the central valve section with respect to the native valve, by the native valve leaflets closing around the outer surface of the central valve section, while not causing retrograde leakage of blood through the commissures.

For some embodiments, in order to facilitate the sealing of the native valve around the outer surface of the central valve section, a material is placed on the outer surface of the central valve section in order to provide a sealing interface between the central valve section and the native valve. For example, a smooth material that prevents tissue growth (e.g., polytetrafluoroethylene (PTFE), and/or pericardium) may be placed on the outer surface of the central valve section. Alternatively or additionally, a material that facilitates tissue growth (such as dacron) may be placed on the outer surface of the central valve section, in order to (a) act as a sealing interface between the native valve and the central valve section, and (b) facilitate tissue growth around the central valve section to facilitate anchoring and/or sealing of the central valve section.

Reference is now made to FIGS. 11A-D, which are schematic illustrations of central valve section 80, in accordance with some embodiments of the present disclosure. For some embodiments, protrusions 84 are disposed on the central valve section on portions 400 of the central valve section that are placed adjacent to the anterior and posterior leaflets of the native valve, and the central valve section does not include protrusions on portions 402 of the central valve section that are placed adjacent to the commissures of the native valve.

FIGS. 11B-D show bottom views (i.e., views of the distal ends) of respective configurations of central valve section 80 and protrusions 84. The protrusions converge from the proximal ends 404 of the protrusion to the distal ends 406 of the protrusions. The protrusions are configured such as to ensnare chordae tendineae, and to pull the chordae tendineae toward each other when the central valve section is pulled proximally, due to the convergence of the snares with respect to each other. FIG. 11D shows the central valve section deployed at native valve 5. As shown, the protrusions ensnare chordae tendineae 102 of the patient. The protrusions facilitate sealing and anchoring of the central valve section with respect to the native valve by pulling the chordae tendinae toward each other, as described. As described hereinabove, for some embodiments the central valve section does not define protrusions 84 on portions 402 that are placed next to the native commissures, e.g., commissure 8, shown in FIG. 11D.

For some embodiments, as described hereinabove, protrusions 84 are such as to (a) prevent proximal migration of the central valve section into the patient's atrium, while (b) allowing movement of the native leaflets with respect to the frame of the central valve section. For example, the protrusions may have the aforementioned functionalities by having lengths of less than 5 mm, and/or by a total width of each set of protrusions corresponding to respective leaflets of the native valve being less than 5 mm. For example, the central valve section may include a single protrusion corresponding to each leaflet of the native valve, the width of each of the single protrusions being less than 1 mm. Thus, the central valve section may be stopped from proximally migrating into the atrium, by the protrusions preventing the distal end of the central valve section from migrating further proximally than edges of native leaflets of the valve. Furthermore, the protrusions may allow movement of the native leaflets with respect to the frame of the central valve section by not generally squeezing the native leaflets between the protrusions and the frame of the central valve section. For some embodiments, by allowing movement of the native leaflets with respect to the frame of the central valve section, sealing of the native leaflets against the outer surface of the frame of the central valve section is facilitated, in accordance with the techniques described hereinabove with reference to FIG. 10.

For some embodiments, a first set of protrusions 84 from the distal end of central valve section 80 are disposed within a first circumferential arc with respect to a longitudinal axis of the central valve section, on a first side of the distal end of the central valve section, the first side of the distal end being configured to be placed adjacent to the anterior leaflet of the native valve. A second set of protrusions are disposed within a second circumferential arc with respect to a longitudinal axis of the central valve section, on a second side of the distal end of the central valve section, the second side of the distal end being configured to be placed adjacent to the posterior leaflet of the native valve.

The first and second sets of protrusions are disposed so as to provide first and second gaps therebetween at the distal end of the central valve section. In some embodiments, at least one of the gaps between the two sets of protrusions has a circumferential arc of at least 20 degrees (e.g., at least 60 degrees, or at least 100 degrees), and/or less than 180 degrees (e.g., less than 140 degrees), e.g., 60-180 degrees, or 100-140 degrees. Further in some embodiments, one or both of the first and second circumferential arcs defines an angle of at least 25 degrees (e.g., at least 45 degrees), and/or less than 90 degrees (e.g., less than 75 degrees), e.g., 25-90 degrees, or 45-75 degrees.

Valve section guide members (e.g., guide members 21a and 21b, and/or delivery lumen 27a and 27b, as described hereinabove) are delivered to commissures of the native valve, and guide the central valve section such that the first and second circumferential arc are aligned with respective leaflets of the native valve and such that the first and second gaps are aligned with respective commissures of the native valve.

Reference is now made to FIGS. 12A-C, which are schematic illustrations of central valve section 80, the central valve section defining distal protrusions 84 that are disposed sinusoidally around the circumference of the central valve section, in accordance with some embodiments of the present disclosure. For some embodiments the protrusions are shaped sinusoidally, in order to conform with the saddle-shape of native valve annulus 11, thereby facilitating the sandwiching of the native valve leaflets between the protrusions and spacer 40. As shown, the peaks of the sinusoid that is defined by the protrusions is disposed on portions 402 that are placed next to the native commissures and the troughs of the sinusoid is placed on portions of the central valve section that are placed in the vicinity of the centers of the anterior and posterior leaflets of the native valve. As shown in FIG. 12C, for some embodiments the distal end of the central valve section defines a sinusoidal shape.

Reference is now made to FIGS. 13A-E, which are schematic illustrations of respective configurations of expandable frame 79 of central valve section 80, in accordance with some embodiments of the present disclosure. As described hereinabove, for some embodiments, central valve section 80 defines distal protrusions 84 that are configured to facilitate sandwiching of the native valve leaflets between the protrusions and spacer 40. For some embodiments, tips of the distal protrusions are shaped so as to prevent the tips from piercing, and/or otherwise damaging, tissue of the native leaflets. For example, the tips of the protrusions may be curved, as shown in FIG. 13A. Or, the distal tips of the protrusions may be shaped as balls, as shown in FIG. 13, and/or a different rounded shape. For some embodiments, the distal tip of each of the protrusions is joined to the distal tip of an adjacent protrusion by an arch 410, as shown in FIGS. 13C and 13D.

For some embodiments, the protrusions are configured to be distally-facing during the insertion of central valve section 80 into the subject's left ventricle. For example, the central valve section may be inserted through overtube 70 (shown in FIG. 7E, for example). The central valve section is crimped during the insertion of the central valve section through the overtube, and the protrusions are constrained in their distally-facing configurations by the overtube. The protrusions are pre-shaped such that in the resting state of the protrusions, the protrusions assume proximally-facing configurations, as shown in FIG. 13D, for example. Thus, upon emerging from overtube 70, the protrusions assume proximally-facing configurations. For some embodiments, when the protrusions assume the proximally-facing configurations, the protrusions are disposed at an angle theta (FIG. 13D) from expandable frame 79 of more than 40 degrees (e.g., more than 50 degrees), and/or less than 80 degrees (e.g., less than 70 degrees).

In some embodiments, protrusions 84 are coupled to frame 79 of central valve section 80 at joints 412. For some embodiments, joints 412 are thinner than portions of the protrusions and of the frame surrounding the joints, as shown in FIG. 13D. For some embodiments, the thinness of the joints with respect to the surrounding portions facilitates the crimping of the protrusions into distally-facing configuration during the insertion of the central valve section into the heart.

For some embodiments, barbs 416 extend from a proximal portion of expandable frame 79 of central valve section 80, as shown in FIG. 13E. For example, the barbs may be configured to anchor the central valve section to the native valve by piercing tissue of the native valve. Alternatively or additionally, the barbs may be configured to anchor the central valve section to the spacer 40, by becoming coupled to portions of the spacer. For some embodiments the barbs protrude from the top-central corner of respective cells of expandable frame 79. In some embodiments, when the central valve section is crimped, the barbs fit within gaps of respective cells of the expandable frame, and do not substantially increase the crimping profile of the central valve section, relative to a generally similar central valve section that does not include barbs.

For some embodiments, the barbs are not generally used for coupling central valve section 80 to spacer 40. Rather, the central valve section is coupled to the spacer by virtue of radial expansion of the central valve section against disc-shaped wall 44 of the spacer. Barbs 416 are used to prevent central valve section from migrating distally into the patient's left ventricle, and/or to prevent spacer 40 from migrating proximally into the subject's left atrium.

For some embodiments (not shown), barbs protrude from coupling elements 81 of central valve section 80, the barbs being generally similar in shape and function to that described with reference to barbs 416. For some embodiments (not shown), radially-inwardly facing barbs 45 protrude from disc-shaped wall 44 of spacer 40, as shown in FIG. 14D. As described with reference to barbs 416, the barbs that protrude from disc-shaped wall 44 may facilitate coupling of the central valve section to the spacer. Alternatively or additionally, the barbs that protrude from disc-shaped wall 44 are used to prevent central valve section from migrating distally into the patient's left ventricle, and/or to prevent spacer 40 from migrating proximally into the subject's left atrium.

For some embodiments, a proximal end of expandable frame 79 of central valve section 80 defines a larger cross-section area than more distal portions of the expandable frame. For example, the expandable frame may have a frustoconical shape, the walls of the expandable frame diverging from a distal end of the frame to a proximal end of the frame. Alternatively, the expandable frame may have a trumpet shape (i.e., the frame may be generally tubular, with a dilated proximal end). For some embodiments, the larger cross-sectional area of the proximal end of the frame prevents the central valve section from migrating distally into the patient's left ventricle, and/or prevents spacer 40 from migrating proximally into the subject's left atrium.

Reference is now made to FIGS. 14A-D, which are schematic illustrations of respective configurations of spacer 40, in accordance with some embodiments of the present disclosure. As described hereinabove, for some embodiments, the spacer includes a proximal disc-shaped wall 44 and a distal cylindrical skirt 42 (e.g., as shown in FIG. 2D). Alternatively, the spacer does not include a distal cylindrical element. For example, the spacer may only include disc-shaped wall 44. As described hereinabove, disc-shaped wall 44 is configured to be placed around native annulus 11 of the native valve, and to extend at least partially into atrium 4 such that disc-shaped wall 44 rests against the native annulus. Disc-shaped wall 44 is in some embodiments too large to pass through the annulus, and may, for example, have an outer diameter of between 30 and 60 mm.

FIGS. 14A-D show disc-shaped wall 44 of spacer 40 in respective configurations, in accordance with some embodiments of the present disclosure. For some embodiments, the disc-shaped wall is D-shaped, as shown in FIG. 14A. Alternatively or additionally, the disc-shaped wall has a generally round shape, as shown in FIGS. 14B-C. For some embodiments the disc-shaped wall is asymmetrical. For example, FIG. 14B shows a generally rounded disc-shaped wall that is wider on a first side 420 of the element than on a second side 422 of the element. In some embodiments, the wider side of the disc-shaped wall is placed on the anterior side of the native annulus. In accordance with some embodiments, the disc-shaped wall is symmetrical, asymmetrical, oval, round, defines a hole that is centered with respect to the disc-shaped wall, and/or defines a hole that is off-center with respect to the disc-shaped wall. For some embodiments, the stiffness of the disc-shaped wall varies around the circumference of the disc-shaped wall.

For some embodiments, disc-shaped wall 44 is asymmetrical, as shown in FIG. 14B. In some embodiments, the asymmetry of the disc-shaped wall is such that the center of the hole defined by the disc-shaped wall is disposed asymmetrically (i.e., off-center) with respect to the center of the disc-shaped wall, as defined by the outer perimeter of the disc-shaped wall. For some embodiments, the asymmetric disposition of the center of the hole defined by the disc-shaped wall is such that when the central valve section is placed inside the disc-shaped wall, the longitudinal axis of the central valve section is disposed asymmetrically (i.e., off-center) with respect to the center of the disc-shaped wall, as defined by the outer perimeter of the disc-shaped wall. In some embodiments, the disc-shaped wall is shaped such that, when the disc-shaped wall is placed on the patient's mitral annulus, and the central valve section is expanded inside the disc-shaped wall, the longitudinal axis of the central valve section is disposed in the vicinity of the location at which the patient's native leaflets coapt (this location being off-center with respect to the patient's native mitral annulus).

For some embodiments (not shown), radially-inwardly facing barbs 45 protrude from disc-shaped wall 44 of spacer 40, as shown in FIG. 14D. As described with reference to barbs 416 shown protruding from central valve section 80 in FIG. 13E, the barbs that protrude from disc-shaped wall 44 may facilitate coupling of the central valve section to the spacer. Alternatively or additionally, the barbs that protrude from disc-shaped wall 44 are used to prevent central valve section from migrating distally into the patient's left ventricle, and/or to prevent spacer 40 from migrating proximally into the subject's left atrium. For some embodiments, some or all of barbs 102 are curved. In some embodiments, the curved barbs curve away from the plane of disc-shaped wall 44, such that, when implanted, barbs 102 point into the patient's atrium.

In some embodiments, the disc-shaped wall includes support stent 48, the stent being covered at least in part with covering 49, e.g., fabric. In some embodiments, the upper surface of disc-shaped wall 44 is covered with fabric, for example, in order to provide a generally smooth surface for coming into contact with the patient's blood flow. Further in some embodiments, the lower surface of the disc-shaped wall (i.e., the side of the disc-shaped wall that is placed in contact with the native annulus) is not covered with fabric, for example, in order to reduce a crimped volume (or cross-sectional area) of the disc-shaped wall, relative to the volume of the disc-shaped wall if the lower surface of the disc-shaped wall were covered in fabric. In some embodiments, a thickness of the fabric layer is less than 0.2 mm, e.g., less than 0.1 mm, or less than 0.05 mm.

For some embodiments, the side of the disc-shaped wall that is placed in contact with the native annulus is covered with the fabric, the fabric being configured to facilitate coupling of the disc-shaped wall to the native annulus, by facilitating fibrosis at the interface between the disc-shaped wall and the native annulus. For some embodiments, the upper surface of the disc-shaped wall is not covered with fabric. For example, the upper surface may not be covered in fabric in order to reduce a crimped volume (or cross-sectional area) of the disc-shaped wall, relative to the volume of the disc-shaped wall if the upper surface of the disc-shaped wall were covered in fabric.

For some embodiments, disc-shaped wall 44 is not covered with fabric, and/or is not configured to form a seal against frame 79 of central valve section 80. For some embodiments, the disc-shaped wall is configured to allow leakage of blood between the disc-shaped wall and frame 79 of central valve section 80. For example, the disc-shaped wall may be configured to allow leakage of blood through the interface between the disc-shaped wall and the frame of the central valve section, in order to accommodate a flow of blood between the patient's atrium and the patient's ventricle that is greater than can be accommodated by blood flowing through the leaflets of the central valve section.

Reference is now made to FIGS. 15A-E, which are schematic illustrations of respective steps of a procedure for deploying a central valve section, in accordance with some embodiments of the present disclosure. As described hereinabove and hereinbelow (for example, with reference to FIGS. 2A-K, 7A-F, 8A-C, 9A-H, and 16A-G), for some procedures, spacer 40 is placed on the valve annulus and, subsequently, central valve section 80 is inserted into the subject's left ventricle through the spacer. Alternatively, any of the procedures described herein (for example, procedures described with reference to FIGS. 2A-K, 7A-F, 8A-C, 9A-H, and 16A-G) may be performed by first placing the central valve section inside the subject's left ventricle, and, subsequently, deploying the spacer at the annulus. For example, FIGS. 15A-E show a procedure in which the central valve section is placed inside the subject's left ventricle, and, subsequently, the spacer is deployed at the annulus.

As shown in FIG. 15A, for some embodiments, central valve section 80 is placed in the subject's ventricle, before spacer 40 is placed at the native valve. The central valve section is in some embodiments placed in the left ventricle in an undeployed state, via overtube 70. Subsequently, the spacer is placed at the native valve using pushing elements, as shown in FIG. 15B. For some embodiments, three pushing elements 52a, 52b, and 52c are used to push the spacer against the native valve, as shown in FIG. 15B.

Subsequent to the placement of spacer 40 at the native valve, central valve section 80 is coupled to spacer 40. For some embodiments, pushing elements 52a, 52b, and 52c continue to push the spacer against the native valve, during the coupling of the central valve section to the spacer. FIG. 15C shows central valve section having been partially deployed in the ventricle.

Following the partial deployment of central valve section 80 in ventricle 6, overtube 70 is pulled proximally to pull central valve section 80 proximally such that disc-shaped wall 44 of spacer 40 surrounds a proximal portion of central valve section 80, as shown in FIG. 15D. Central valve section 80 may be configured to expand such that central valve section 80 is held in place with respect to spacer 40 responsively to radial forces acted upon spacer 40 by central valve section 80. During the pulling back of overtube 70, pushing elements 52a, 52b, and 52c push spacer 40 against the central valve section, thereby providing a counter force against which overtube 70 is pulled back. For some embodiments, the pushing of the spacer against the commissures is such that it is not necessary to use anchors for anchoring the spacer to the native valve during the coupling of the central valve section to the spacer. Alternatively, in addition to the pushing elements providing a counter force against which the central valve section is pulled, anchors are used to anchor the spacer to the native valve during the coupling of the central valve section to the spacer.

It is noted with reference to FIG. 15D that, in some embodiments, disc-shaped wall 44 of spacer 40 defines an inner cross-sectional area thereof. As described hereinabove, central valve section 80 includes expandable frame 79, and prosthetic leaflets 82. The expandable frame of the central valve section is configured such that when the frame is in a non-constrained state thereof, the cross-sectional area of the frame, along at least a given portion L (shown in FIG. 15D) of the length of the frame, is greater than the inner cross-sectional area defined by the disc-shaped wall of the spacer. In some embodiments, during a central valve section deployment procedure, a location anywhere along portion L at which to couple the expandable central valve section to the spacer is selected. In response thereto, the location along the portion of the expandable frame is aligned with the disc-shaped wall of the spacer. The expandable central valve section is then coupled to the spacer at the location, responsively to radial forces acted upon the spacer by the expandable frame, by facilitating expansion of the expandable frame, when the location along the portion is aligned with the disc-shaped wall of the spacer.

As described hereinabove, for some embodiments, expandable frame 79 of central valve section 80 has a frustoconical shape. For some embodiments, the central valve section is coupled to spacer 40 responsively to radial forces acted upon the spacer by the expandable frame, when a given location along portion L is aligned with disc-shaped wall 44 of the spacer. For some embodiments, the portion immediately proximal to the given location along portion L has a greater cross-sectional area than the frame at the given location, due to the frustoconical shape of the expandable frame. In some embodiments, the greater cross-sectional area of the portion immediately proximal to the given location along portion L relative to the cross-sectional area of the frame at the given location, reduces distal migration of the central valve section toward the subject's left ventricle.

For some embodiments, the location along portion L at which to couple central valve section 80 to spacer 40 is selected, based upon a distance D between protrusions 84 and disc-shaped wall 44 that would result from coupling the central valve section to the disc-shaped wall at that location. For example, the location along portion L at which to couple central valve section 80 to spacer 40 may be selected, such that distance D is such as to anchor the central valve section to the patient's native valve by squeezing the patient's native valve leaflets between the protrusions and the disc-shaped wall, and/or by ensnaring the patient's chordae tendinae between the protrusions and the disc-shaped wall. Alternatively or additionally, the location along portion L at which to couple central valve section 80 to spacer 40 may be selected, such that distance D is such that protrusions 84 (a) prevent proximal migration of the central valve section into the patient's atrium, while (b) allowing movement of the native leaflets with respect to the frame of the central valve section. In some embodiments, the location along portion L is selected such that distance D is such that the central valve section may be stopped from proximally migrating into the atrium, by the protrusions preventing the distal end of the central valve section from migrating further proximally than edges of native leaflets of the valve, while the protrusions allow movement of the native leaflets with respect to the frame of the central valve section by not generally squeezing the native leaflets between the protrusions and the frame of the central valve section. For some embodiments, by allowing movement of the native leaflets with respect to the frame of the central valve section sealing of the native leaflets against the outer surface of the frame of the central valve section is facilitated, in accordance with the techniques described hereinabove with reference to FIG. 10.

Subsequent to the placement of the central valve section at the native valve, overtube 70, and pushing elements 52a, 52b, and 52c are removed from the patient's body, as shown in FIG. 15E, which shows the central valve section in its deployed state.

Reference is now made to FIGS. 16A-G, which are schematic illustrations of respective steps of an alternative procedure for deploying central valve section 80, in accordance with some embodiments of the present disclosure. As described hereinabove, with reference to FIGS. 7A-F, for some embodiments, a looped guide member 21 is looped through commissures 8 and 10 in a manner in which the guide member defines a looped portion between commissures 8 and 10. For some embodiments, the looped guide member has steering functionality. The steering functionality of the looped guide member is used to guide the guide member to the commissures, and/or to guide other portions of the apparatus to the native valve and/or to ventricle 6. The looped guide member is in some embodiments advanced toward ventricle 6 over guidewire 306, e.g., as described hereinabove with reference to FIG. 7A.

In some embodiments, as shown in FIG. 16A, portions 21a and 21b of the looped guide member are independently manipulable. The portions of the looped guide member are manipulated (e.g., expanded and contracted) so as to guide the looped guide member to the subject's native valve, by pushing against inner surfaces of the subject's heart, as shown in FIG. 16A.

FIG. 16B shows the looped guide member looped through commissures 8 and 10 of the subject's native valve. When the looped guide member is disposed at the native valve, the guide member is used to guide and to anchor spacer 40, as described hereinbelow.

As shown in FIG. 16C, for some embodiments, looped guide member 21 is coupled to spacer 40 via coupling wires 500 and coupling mechanisms 502. For example, as shown, the coupling mechanism may include an anchor. A suture 504, or a different looped element, protrudes from the bottom surface of disc-shaped wall 44 of spacer 40 and is anchored by the anchor. Thus, when looped guide member 21 is pushed distally into ventricle 6, the spacer is pulled against the annulus of the native valve by coupling wires 500 pulling on the spacer.

In some embodiments, coupling mechanisms 502, which are used to couple looped guide member 21 to spacer 40 are detachable coupling mechanisms. For example, as shown, the coupling mechanism may include an anchor that defines an opening 506 through which suture 504 is inserted. The opening is closed by a closing member 508, such as a rod, or a wire. In order to detach the guide member from the spacer, closing member 508 is opened (e.g., by being pulled proximally) such that suture 504 is released through opening 506.

Subsequent to the placement of spacer 40 at the native valve, central valve section 80 is placed in ventricle 6, by advancing overtube 70 into the ventricle, as shown in FIG. 16D. FIG. 16E shows central valve section having been partially deployed in the ventricle. Following the partial deployment of central valve section 80 in ventricle 6, overtube 70 is pulled proximally to pull central valve section 80 proximally such that disc-shaped wall 44 of spacer 40 surrounds a proximal portion of central valve section 80, as shown in FIGS. 16E-F. Central valve section 80 may be configured to expand such that central valve section 80 is held in place with respect to spacer 40 responsively to radial forces acted upon spacer 40 by central valve section 80.

During the pulling back of overtube 70, looped guide member 21 is pushed distally, thereby pulling spacer 40 against the native annulus and providing a counter force against which overtube 70 is pulled back. For some embodiments, pulling of the spacer against the native annulus is such that it is not necessary to use anchors for anchoring the spacer to the native valve during the coupling of the central valve section to the spacer. Alternatively, in addition to the pulling of the spacer against the native annulus providing a counter force against which the central valve section is pulled, anchors are used to anchor the spacer to the native valve during the coupling of the central valve section to the central valve section.

FIG. 16G shows central valve section 80 and spacer 40 coupled to the native valve. At this stage, coupling mechanism 502 is in some embodiments detached from the spacer. For example, as shown, closing member 508 is pulled, such that opening 506 is opened, and suture 504 is released through the opening. Subsequently, looped guide member 21, and overtube 70 are removed from the subject's body, as shown in FIG. 16H, which shows the central valve section in its deployed state.

As described with reference to FIGS. 16A-H, for some embodiments, central valve section 80 is coupled to a native valve, by (a) placing spacer 40 on an atrial side of the native annulus, (b) placing the central valve section inside the ventricle, and then, simultaneously, (c) pulling the central valve section toward the atrium, and pulling the spacer toward the ventricle.

Reference is now made to FIGS. 17A-C, which are schematic illustrations of leaflets 82 of central valve section 80, in accordance with some embodiments of the present disclosure. FIG. 17A shows the leaflets before the leaflets are sutured to expandable frame 79 of the central valve section. As shown, in this state, the leaflets have a diameter D1, and the leaflets are not fully closed. FIG. 17B shows the leaflets when the leaflets have been sutured to expandable frame 79 of the central valve section. The expandable frame constrains the leaflets, such that the leaflets define a diameter D2, which is smaller than diameter D1, thereby closing the leaflets. FIG. 17C shows the leaflets subsequent to the deployment of central valve section 80 inside spacer 40, the spacer constraining the expansion of the central valve section. Due to the spacer constraining the central valve section, the valve leaflets are constrained so as define a diameter D3, which is smaller than diameter D2.

In some embodiments, valve leaflets 82 are selected to be used in central valve section 80, the leaflets being sized such that both at diameter D2 (when the leaflets are constrained by expandable frame 79 but are not constrained by spacer 40) and at diameter D3 (when the leaflets are constrained by both expandable frame 79 and spacer 40), the valve leaflets fully coapt.

Reference is now made to FIGS. 18A-B which are schematic illustrations of a system 220 including a spacer 240 including a disc-shaped wall 244 and a cylindrical skirt 242 and one or more (e.g., a plurality, as shown, of) tissue anchor bases 230, in accordance with some embodiments of the present disclosure. Disc-shaped wall 244 has an upper surface 241 and a lower surface 243. Tissue anchor bases 230 are coupled to lower surface 234 of the disc-shaped wall. Tissue anchor bases 230 are shaped so as to define a pointed distal tip 234 and one or more (e.g., three, as shown) radially-expandable leaves 232. Leaves 232 include a flexible metal, e.g., nitinol or stainless steel, and have a tendency to expand radially. Tissue anchor bases 230 facilitate coupling of spacer 240 to annulus 11 of native valve 5, such as the mitral valve or the tricuspid valve. Tissue anchor bases 230 are in some embodiments distributed approximately evenly around lower surface 243 of disc-shaped wall 244. For some embodiments, one or more tissue anchor bases 230 are disposed at a location of disc-shaped wall that is configured to be positioned adjacently to commissures 8 and 10 of valve 5.

Reference is now made to FIGS. 19A-D which are schematic illustrations of spacer 240 being implanted at valve 5 and the subsequent coupling of central valve section 80 to spacer 240. Spacer 240 is advanced toward native valve 5 by pushing elements 52a and 52b, as described hereinabove with respect to spacer 40 with reference to FIGS. 2D-F. In response to the pushing force to spacer 240 by pushing elements 52a and 52b, tissue anchor bases 230 are pushed into tissue of annulus 11 of valve 5. The pushing force by elements 52a and 52b is sufficient to implant each one of the plurality of tissue anchor bases that are distributed around lower surface 243 of disc-shaped wall 244.

FIG. 19A shows initial penetration of tissue of annulus 11 by pointed distal tip 234 of anchor base 230. In FIG. 19B, the initial force of the tissue on leaves 232 pushes inwardly leaves 232. Finally, in FIG. 19C, leaves 232 expand within tissue of annulus 11 to assume a flower shape and a larger surface area to restrict proximal motion of anchor base 230 and thereby anchor spacer 240 in tissue of annulus 11. As shown in FIGS. 19A-C, the cylindrical element of spacer 240 pushes aside native leaflets 12 and 14 of valve 5.

In FIG. 19D, central valve section 80 is coupled to spacer 240, in a manner as described hereinabove.

It is noted that, in general, central valve section 80 is self-expandable. When the central valve section is deployed (i.e., when the central valve section self-expands) inside the subject's heart, the expansion of the central valve section is in some embodiments constrained by spacer 40. Further in some embodiments, the expansion of the central valve section is not constrained by the native annulus.

For some embodiments, by constraining the expansion of the central valve section with the spacer, the deployed cross-sectional area of the central valve section may be fixed at a given area, by using a spacer that defines a hole having the given cross-sectional area. As described hereinabove with reference to FIG. 10, for some embodiments, the area defined by the native annulus is measured, and the cross-sectional area of the central valve section that is to be deployed in the valve is selected based upon the measured area of the native annulus. Alternatively or additionally, spacer 40 is selected based upon the measured area of the native annulus.

For example, a spacer may be selected such that the spacer constrains the expansion of the central valve section, when the cross-sectional area of the central valve section is less than 90% (e.g., less than 80%, or less than 60%) of the area defined by the native annulus. As described hereinabove, for some embodiments, placing a central valve section inside the native valve with the dimensions of the native valve annulus and the central valve section being as described, facilitates sealing of the central valve section with respect to the native valve, by the native valve leaflets closing around the outer surface of the central valve section.

For some embodiments, the expansion of central valve section 80 against spacer 40 couples the central valve section to the spacer, and/or couples the central valve section and the spacer to the native mitral valve. In some embodiments, the expansion of the central valve section against the spacer couples the central valve section to the spacer, and sandwiching of the native valve leaflets between protrusions from the distal end of the central valve section and the spacer couples the central valve section and the spacer to the native valve.

Reference is now made to FIGS. 1A-D, 2A-K, 3A-D, 4A-C, 5A-D, 6A-B, 7A-F, 8A-C, 9A-H, 10, 11A-D, and 12A-C. It is to be noted that spacer 40 may be invertible as described hereinabove with respect to spacer 140 and spacer 300, with reference to FIGS. 8A-C, and 9A-H. It is to be further noted that spacer 140 and spacer 300 may be used in conjunction with one or more of the elements for facilitating sealing of the native valve with respect to a spacer or a central valve section that is described with reference to FIGS. 3A-D, 4A-C, 5A-D, and 6A-B. For example, spacer 140 and spacer 300 may be used with sealing balloon 90, commissural anchors 100a and 100b, grasping elements 106a and 106b, and/or sealing material 110. It is still further noted that spacer 140 and spacer 300 may be implanted using a guide member that defines a looped portion between commissures 8 and 10, as described with reference to FIGS. 7A-F. It is further noted that any of the embodiments described herein can be used in conjunction with central valve sections having configurations as described with reference to FIGS. 10-12C.

The systems described herein are advanced toward valve 5 in a transcatheter procedure, as shown. It is to be noted, however, that the systems described herein may be advanced using any suitable procedure, e.g., minimally-invasively (e.g., via a transeptal, a transatrial, a transapical, and/or a transaortic approach), or using an open-heart procedure. It is to be further noted that spacers and prosthetic valves herein may be used to replace native mitral valves or native tricuspid valves.

Reference is now made to FIGS. 20A-B, which are schematic illustrations of spacer 40 and central valve section 80 coupled respectively to a tricuspid valve, and to an aortic valve, in accordance with some embodiments of the present disclosure. For some embodiments, spacer 40 and central valve section 80 are deployed at a tricuspid valve and/or at an aortic valve using generally similar techniques to those described herein with reference to the deployment of the spacer and the central valve section at the mitral valve, mutatis mutandis.

It will be appreciated by persons skilled in the art that the present disclosure is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present disclosure includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.

Claims

1. A prosthetic heart valve, comprising: an annular spacer configured to engage a native heart valve, the annular spacer comprising: a cylindrical skirt having an upstream end and a downstream end opposite from the upstream end, wherein a spacer opening extends through the cylindrical skirt between the upstream end and downstream end thereof, anda disc-shaped wall situated about a portion of the cylindrical skirt and extending radially outward from the cylindrical skirt; anda central valve section configured for disposal within the spacer opening of the annular spacer, the central valve section having: a hollow valve section body configured to support a valve prosthesis therein, andat least one anchoring protrusion configured to extend radially outward from the valve section body, the at least one anchoring protrusion being configured to prevent the central valve section from moving axially relative to the annular spacer,wherein the central valve section is configured to: expand radially within the heart from a delivery configuration into an at least partially-expanded configuration while at least a portion of the central valve section is situated outside of the spacer opening of the annular spacer, andmove into the spacer opening, while the central valve section remains in the at least partially-expanded configuration, until the at least one anchoring protrusion contacts the downstream end of the cylindrical skirt, andwherein the cylindrical skirt of the annular spacer is configured to be inverted such that a first end of the cylindrical skirt is situated upstream of the disc-shaped wall after deployment of the annular spacer within the native heart valve, the first end of the cylindrical skirt being the downstream end of the cylindrical skirt when the cylindrical skirt is in a non-inverted configuration.
2. The prosthetic heart valve of claim 1, wherein the disc-shaped wall of the annular spacer is situated about the upstream end of the cylindrical skirt, andthe at least one anchoring protrusion is connected to a downstream end of the valve section body.
3. The prosthetic heart valve of claim 1, wherein the disc-shaped wall of the annular spacer is configured to contact an atrial side of the native heart valve and to secure the central valve section relative to an annulus of the native heart valve, andthe cylindrical skirt of the annular spacer is configured to extend at least partially into a ventricle of the heart.
4. The prosthetic heart valve of claim 1, wherein the at least one anchoring protrusion is configured to extend through the downstream end of the spacer opening.
5. The prosthetic heart valve of claim 1, wherein the disc-shaped wall comprises: a support stent having a plurality of struts, anda covering arranged upon the support stent, the covering being configured to obstruct blood flow.
6. The prosthetic heart valve of claim 1, wherein the valve section body includes a flexible wire frame formed at least partially of a plurality of struts intersecting at strut junctions, andwherein when the central valve section is disposed within the spacer opening of the annular spacer, at least one strut junction of the flexible wire frame is situated in an upstream direction from the upstream end of the cylindrical skirt.
7. The prosthetic heart valve of claim 6, wherein the at least one anchoring protrusion is connected to a strut junction along a downstream end of the flexible wire frame.
8. The prosthetic heart valve of claim 1, wherein the at least one anchoring protrusion is configured to extend radially outward beyond an outer diameter of the downstream end of the cylindrical skirt when the central valve section is disposed within the spacer opening of the annular spacer.
9. The prosthetic heart valve of claim 1, wherein the central valve section has a greater axial length than the annular spacer.
10. A prosthetic heart valve, comprising: an annular spacer configured to engage a native heart valve, the annular spacer comprising: a cylindrical skirt having an upstream end and a downstream end opposite from the upstream end, wherein a spacer opening extends through the cylindrical skirt between the upstream end and downstream end thereof, anda disc-shaped wall situated about a portion of the cylindrical skirt and extending radially outward from the cylindrical skirt,wherein the cylindrical skirt is configured to be inverted such that a first end of the cylindrical skirt is situated upstream of the disc-shaped wall after deployment of the annular spacer within the native heart valve, the first end of the cylindrical skirt being the downstream end of the cylindrical skirt when the cylindrical skirt is in a non-inverted configuration; anda central valve section configured for disposal within the spacer opening of the annular spacer, the central valve section having: a hollow valve section body configured to support a valve prosthesis therein, andat least one anchoring protrusion configured to extend radially outward from the valve section body, the at least one anchoring protrusion being configured to prevent the central valve section from moving axially relative to the annular spacer,wherein the central valve section is configured for deployment into the heart separately from the annular spacer.
11. The prosthetic heart valve of claim 10, wherein the disc-shaped wall of the annular spacer is situated about the upstream end of the cylindrical skirt, andthe at least one anchoring protrusion is connected to a downstream end of the valve section body.
12. The prosthetic heart valve of claim 10, wherein the disc-shaped wall of the annular spacer is configured to contact an atrial side of the native heart valve and to secure the central valve section relative to an annulus of the native heart valve, andthe cylindrical skirt of the annular spacer is configured to extend at least partially into a ventricle of the heart.
13. The prosthetic heart valve of claim 10, wherein the at least one anchoring protrusion is configured to extend through the downstream end of the spacer opening.
14. The prosthetic heart valve of claim 10, wherein the disc-shaped wall comprises: a support stent having a plurality of struts, anda covering arranged upon the support stent, the covering being configured to obstruct blood flow.
15. The prosthetic heart valve of claim 10, wherein the valve section body includes a flexible wire frame formed at least partially of a plurality of struts intersecting at strut junctions, andwherein when the central valve section is disposed within the spacer opening of the annular spacer, at least one strut junction of the flexible wire frame is situated in an upstream direction from the upstream end of the cylindrical skirt.
16. The prosthetic heart valve of claim 15, wherein the at least one anchoring protrusion is connected to a strut junction along a downstream end of the flexible wire frame.
17. The prosthetic heart valve of claim 10, wherein the at least one anchoring protrusion is configured to extend radially outward beyond an outer diameter of the downstream end of the cylindrical skirt when the central valve section is disposed within the spacer opening of the annular spacer.
18. The prosthetic heart valve of claim 10, wherein the central valve section has a greater axial length than the annular spacer.
19. The prosthetic heart valve of claim 10, wherein the central valve section is configured to: expand radially within the heart from a delivery configuration into a deployed configuration while the central valve section is situated outside of the spacer opening of the annular spacer, andmove into the spacer opening, while the central valve section remains in the deployed configuration, until the at least one anchoring protrusion contacts the downstream end of the cylindrical skirt.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent application Ser. No. 16/740,659, filed Jan. 13, 2020, now U.S. Pat. No. 10,925,595, which is a continuation of U.S. patent application Ser. No. 16/040,831, filed Jul. 20, 2018, which issued as U.S. Pat. No. 10,531,872 on Jan. 14, 2020, which is a continuation of U.S. patent application Ser. No. 15/691,032, filed Aug. 30, 2017, which issued as U.S. Pat. No. 10,512,456 on Dec. 24, 2019, which is a continuation of U.S. patent application Ser. No. 14/689,608, filed Apr. 17, 2015, which issued as U.S. Pat. No. 9,763,657 on Sep. 19, 2017, which is a continuation of U.S. patent application Ser. No. 13/811,308, filed Mar. 7, 2013, which issued as U.S. Pat. No. 9,017,399 on Apr. 28, 2015, which is a U.S. national stage entry under 35 U.S.C. § 371 of International Application No. PCT/IL2011/000582, filed Jul. 21, 2011, which claims priority and is a continuation-in-part of: (a) U.S. patent application Ser. No. 12/840,463, filed Jul. 21, 2010; (b) U.S. patent application Ser. No. 13/033,852, filed Feb. 24, 2011, which is a continuation-in-part of U.S. patent application Ser. No. 12/840,463, filed Jul. 21, 2010; and claims priority from U.S. Provisional Patent Application No. 61/492,449, filed Jun. 2, 2011. All of the above-referenced applications are incorporated herein by reference.

US Referenced Citations (1171)

Number	Name	Date	Kind
3874388	King et al.	Apr 1975	A
4222126	Boretos et al.	Sep 1980	A
4261342	Aranguren Guo	Apr 1981	A
4340091	Skelton et al.	Jul 1982	A
4423525	Vallana et al.	Jan 1984	A
4853986	Allen	Aug 1989	A
4892541	Abnso	Jan 1990	A
4972494	White et al.	Nov 1990	A
5108420	Marks	Apr 1992	A
5201757	Heyn et al.	Apr 1993	A
5314473	Godin	May 1994	A
5405378	Strecker	Apr 1995	A
5443500	S gwart	Aug 1995	A
5607444	Lam	Mar 1997	A
5607470	Milo	Mar 1997	A
5647857	Anderson et al.	Jul 1997	A
5713948	Uflacker	Feb 1998	A
5716417	Girard et al.	Feb 1998	A
5741297	Simon	Apr 1998	A
5765682	Bley et al.	Jun 1998	A
5776140	Cottone	Jul 1998	A
5868777	Lam	Feb 1999	A
5873906	Lau et al.	Feb 1999	A
5954766	Zadno-Azizi et al.	Sep 1999	A
5957949	Leonhardt et al.	Sep 1999	A
5961549	Nguyen et al.	Oct 1999	A
5980565	Jayaraman	Nov 1999	A
6010530	Goicoechea	Jan 2000	A
6019787	Richard et al.	Feb 2000	A
6042607	Williamson, IV et al.	Mar 2000	A
6074417	Peredo	Jun 2000	A
6120534	Ruiz	Aug 2000	A
6113612	Swanson et al.	Sep 2000	A
6126686	Badylak et al.	Oct 2000	A
6152937	Peterson et al.	Nov 2000	A
6165183	Kuehn et al.	Dec 2000	A
6165210	Lau et al.	Dec 2000	A
6187020	Zegdi et al.	Feb 2001	B1
6193745	Fogarty et al.	Feb 2001	B1
6254609	Vrba et al.	Jul 2001	B1
6264700	Kilcoyne et al.	Jul 2001	B1
6287339	Vazquez et al.	Sep 2001	B1
6312465	Griffin et al.	Nov 2001	B1
6332893	Mortier et al.	Dec 2001	B1
6334873	Lane et al.	Jan 2002	B1
6346074	Roth	Feb 2002	B1
6350278	Lenker et al.	Feb 2002	B1
6352561	Leopold et al.	Mar 2002	B1
6391036	Berg et al.	May 2002	B1
6402780	Williamson, IV et al.	Jun 2002	B2
6409755	Viba	Jun 2002	B1
6419696	Ortiz et al.	Jul 2002	B1
6428550	Vargas et al.	Aug 2002	B1
6440164	DiMatteo et al.	Aug 2002	B1
6454799	Schreck	Sep 2002	B1
6458153	Bailey et al.	Oct 2002	B1
6511491	Grudem et al.	Jan 2003	B2
6530952	Vesely	Mar 2003	B2
6540782	Snyders	Apr 2003	B1
6551350	Thornton et al.	Apr 2003	B1
6558396	Inoue	May 2003	B1
6558418	Carpentier et al.	May 2003	B2
6569196	Vesely	May 2003	B1
6602263	Swanson et al.	Aug 2003	B1
6616675	Evard et al.	Sep 2003	B1
6652556	VanTassel et al.	Nov 2003	B1
6669724	Park et al.	Dec 2003	B2
6682558	Tu et al.	Jan 2004	B2
6699256	Logan et al.	Mar 2004	B1
6716244	Kiaco	Apr 2004	B2
6719781	Kim	Apr 2004	B1
6730118	Spenser et al.	May 2004	B2
6730121	Ortiz et al.	May 2004	B2
6733525	Yang et al.	May 2004	B2
6752813	Goldfarb et al.	Jun 2004	B2
6755857	Peterson et al.	Jun 2004	B2
6764518	Godin	Jul 2004	B2
6767362	Schreck	Jul 2004	B2
6797002	Spence et al.	Sep 2004	B2
6821297	Snyders	Nov 2004	B2
6830585	Artof et al.	Dec 2004	B1
6830638	Boylan et al.	Dec 2004	B2
6893460	Spenser et al.	May 2005	B2
6926715	Hauck et al.	Aug 2005	B1
6939370	Hartley et al.	Sep 2005	B2
6960217	Bolduc	Nov 2005	B2
6964684	Ortiz et al.	Nov 2005	B2
6974476	McGuckin, Jr. et al.	Dec 2005	B2
7011681	Vesely	Mar 2006	B2
7018406	Seguin et al.	Mar 2006	B2
7041132	Quijano et al.	May 2006	B2
7074236	Rabkin et al.	Jul 2006	B2
7077861	Spence	Jul 2006	B2
7101395	Tremulis et al.	Sep 2006	B2
7101396	Artof et al.	Sep 2006	B2
7137184	Schreck	Nov 2006	B2
7172625	Shu et al.	Feb 2007	B2
7198646	Figulla et al.	Apr 2007	B2
7201772	Schwammenthal et al.	Apr 2007	B2
7226467	Lucatero et al.	Jun 2007	B2
7226477	Cox	Jun 2007	B2
7261686	Couvillon, Jr.	Aug 2007	B2
7288097	Séguin	Oct 2007	B2
7288111	Holloway et al.	Oct 2007	B1
7316716	Egan	Jan 2008	B2
7329279	Haug et al.	Feb 2008	B2
7336213	Hyde et al.	Feb 2008	B2
7351256	Hojeibane et al.	Apr 2008	B2
7374573	Gabbay	May 2008	B2
7377938	Sarac et al.	May 2008	B2
7381218	Schreck	Jun 2008	B2
7381219	Salahieh et al.	Jun 2008	B2
7404824	Webler et al.	Jul 2008	B1
7422603	Lane	Sep 2008	B2
7429269	Schwammenthal et al.	Sep 2008	B2
7442204	Schwammenthal et al.	Oct 2008	B2
7445630	Lashinski et al.	Nov 2008	B2
7455677	Vargas et al.	Nov 2008	B2
7455688	Furst et al.	Nov 2008	B2
7462162	Phan et al.	Dec 2008	B2
7481838	Carpentier et al.	Jan 2009	B2
7510575	Spenser et al.	Mar 2009	B2
7513909	Lane et al.	Apr 2009	B2
7524331	Birdsall	Apr 2009	B2
7527646	Rahdert et al.	May 2009	B2
7556632	Zadno	Jul 2009	B2
7556646	Yang et al.	Jul 2009	B2
7563267	Goldfarb et al.	Jul 2009	B2
7563273	Goldfarb et al.	Jul 2009	B2
7582111	Krolik et al.	Sep 2009	B2
7585321	Cribler et al.	Sep 2009	B2
7597711	Drews et al.	Oct 2009	B2
7608091	Goldfarb et al.	Oct 2009	B2
7611534	Kapadia et al.	Nov 2009	B2
7621948	Herrmann et al.	Nov 2009	B2
7625403	Krivoruchko et al.	Dec 2009	B2
7632302	Vreeman et al.	Dec 2009	B2
7635329	Goldfarb et al.	Dec 2009	B2
7646528	Styrc	Jan 2010	B2
7655015	Goldfarb et al.	Feb 2010	B2
7682380	Thornton et al.	Mar 2010	B2
7708775	Rowe et al.	May 2010	B2
7717952	Case et al.	May 2010	B2
7717955	Lane et al.	May 2010	B2
7731741	Eidenschink	Jun 2010	B2
7731742	Schlick et al.	Jun 2010	B2
7736388	Goldfarb et al.	Jun 2010	B2
7748389	Salahieh et al.	Jul 2010	B2
7753922	Starksen	Jul 2010	B2
7753949	Lamphere et al.	Jul 2010	B2
7758595	Allen et al.	Jul 2010	B2
7758632	Hojeibane et al.	Jul 2010	B2
7758640	Vesely	Jul 2010	B2
7771467	Svensson	Aug 2010	B2
7771469	Liddicoat	Aug 2010	B2
7776083	Vesely	Aug 2010	B2
7780726	Seguin	Aug 2010	B2
7799069	Bailey et al.	Sep 2010	B2
7803181	Furst et al.	Sep 2010	B2
7811296	Goldfarb et al.	Oct 2010	B2
7811316	Kalmann et al.	Oct 2010	B2
7824442	Salahieh et al.	Nov 2010	B2
7837645	Bessler et al.	Nov 2010	B2
7837727	Goetz et al.	Nov 2010	B2
7842081	Yadin	Nov 2010	B2
7850725	Vardi et al.	Dec 2010	B2
7871432	Bergin	Jan 2011	B2
7871436	Ryan et al.	Jan 2011	B2
7887583	Macoviak	Feb 2011	B2
7892281	Seguin et al.	Feb 2011	B2
7896915	Guyenot et al.	Mar 2011	B2
7914544	Nguyen et al.	Mar 2011	B2
7914569	Nguyen et al.	Mar 2011	B2
7927370	Webler et al.	Apr 2011	B2
7942927	Kaye et al.	May 2011	B2
7947072	Yang et al.	May 2011	B2
7947075	Goetz et al.	May 2011	B2
7951195	Antonsson et al.	May 2011	B2
7955375	Agnew	Jun 2011	B2
7955377	Melsheimer	Jun 2011	B2
7955384	Rafiee et al.	Jun 2011	B2
7959666	Salahieh et al.	Jun 2011	B2
7959672	Salahieh et al.	Jun 2011	B2
7967833	Sterman et al.	Jun 2011	B2
7967857	Lane	Jun 2011	B2
7981151	Rowe	Jul 2011	B2
7981153	Fogarty et al.	Jul 2011	B2
7992567	Hirotsuka et al.	Aug 2011	B2
7993393	Carpentier et al.	Aug 2011	B2
8002825	Letac et al.	Aug 2011	B2
8002826	Seguin	Aug 2011	B2
8016877	Seguin et al.	Sep 2011	B2
8016882	Macoviak et al.	Sep 2011	B2
8021420	Dolan	Sep 2011	B2
8021421	Fogarty et al.	Sep 2011	B2
8025695	Fogarty et al.	Sep 2011	B2
8029518	Goldfarb et al.	Oct 2011	B2
8029557	Sobino-Serrano et al.	Oct 2011	B2
8029564	Johnson et al.	Oct 2011	B2
8034104	Carpentier et al.	Oct 2011	B2
8038720	Wallace et al.	Oct 2011	B2
8043360	McNamara et al.	Oct 2011	B2
8048138	Sullivan et al.	Nov 2011	B2
8048140	Purdy	Nov 2011	B2
8048153	Salahieh et al.	Nov 2011	B2
8052592	Goldfarb et al.	Nov 2011	B2
8052741	Bruszewski et al.	Nov 2011	B2
8052749	Salahieh et al.	Nov 2011	B2
8057493	Goldfarb et al.	Nov 2011	B2
8057532	Hoffman	Nov 2011	B2
8057540	Letac et al.	Nov 2011	B2
8062355	Figulla et al.	Nov 2011	B2
8062359	Marquez et al.	Nov 2011	B2
8070708	Rottenberg et al.	Dec 2011	B2
8070800	Lock et al.	Dec 2011	B2
8070802	Lamphere et al.	Dec 2011	B2
8070804	Hyde et al.	Dec 2011	B2
8075611	Millwee et al.	Dec 2011	B2
8080054	Rowe	Dec 2011	B2
8083793	Lane et al.	Dec 2011	B2
D652927	Braido et al.	Jan 2012	S
D653341	Braido et al.	Jan 2012	S
8092518	Schreck	Jan 2012	B2
8092520	Quadri	Jan 2012	B2
8092521	Figulla et al.	Jan 2012	B2
8105377	Liddicoat	Jan 2012	B2
8109996	Stacchino et al.	Feb 2012	B2
8118866	Herrmann et al.	Feb 2012	B2
8133270	Kheradvar et al.	Mar 2012	B2
8136218	Milwee et al.	Mar 2012	B2
8137398	Tuval et al.	Mar 2012	B2
8142494	Rahdert et al.	Mar 2012	B2
8142496	Berreklouw	Mar 2012	B2
8142497	Friedman	Mar 2012	B2
8147504	Ino et al.	Apr 2012	B2
8157853	Laske et al.	Apr 2012	B2
8157860	McNamara et al.	Apr 2012	B2
8163008	Wilson et al.	Apr 2012	B2
8163014	Lane et al.	Apr 2012	B2
D660433	Braido et al.	May 2012	S
D660967	Braido et al.	May 2012	S
8167852	Bloom et al.	May 2012	B2
8167894	Miles et al.	May 2012	B2
8167932	Bourang et al.	May 2012	B2
8167935	McGuckin, Jr. et al.	May 2012	B2
8172896	McNamara et al.	May 2012	B2
8172898	Alferness et al.	May 2012	B2
8177836	Lee et al.	May 2012	B2
8182528	Salahieh et al.	May 2012	B2
8211169	Lane et al.	Jul 2012	B2
8216256	Raschdorf, Jr. et al.	Jul 2012	B2
8216301	Bonhoeffer et al.	Jul 2012	B2
8221492	Case et al.	Jul 2012	B2
8221493	Boyle et al.	Jul 2012	B2
8226710	Nguyen et al.	Jul 2012	B2
8231670	Salahieh et al.	Jul 2012	B2
8142492	Forster et al.	Aug 2012	B2
8236045	Benichou et al.	Aug 2012	B2
8236049	Rowe et al.	Aug 2012	B2
8252042	McNamara et al.	Aug 2012	B2
8252051	Chau et al.	Aug 2012	B2
8252052	Salahieh et al.	Aug 2012	B2
8257390	Carley et al.	Sep 2012	B2
8267988	Hamer et al.	Sep 2012	B2
8277501	Chalekian et al.	Oct 2012	B2
8287591	Keidar et al.	Oct 2012	B2
8298280	Yadin et al.	Oct 2012	B2
8303653	Bonhoeffer et al.	Nov 2012	B2
8308798	Pintor et al.	Nov 2012	B2
8313525	Tuval et al.	Nov 2012	B2
8317853	Agnew	Nov 2012	B2
8317855	Gregorich et al.	Nov 2012	B2
8323335	Rowe et al.	Dec 2012	B2
8328868	Paul et al.	Dec 2012	B2
8337541	Quadri et al.	Dec 2012	B2
8343174	Goldfarb et al.	Jan 2013	B2
8343213	Salahieh et al.	Jan 2013	B2
8348999	Kheradvar et al.	Jan 2013	B2
8366767	Zhang	Feb 2013	B2
8372140	Hoffman et al.	Feb 2013	B2
8377119	Drews et al.	Feb 2013	B2
8398708	Meiri et al.	Mar 2013	B2
8403981	Forster et al.	Mar 2013	B2
8403983	Quadri et al.	Mar 2013	B2
8408214	Spenser et al.	Apr 2013	B2
8414644	Quadri et al.	Apr 2013	B2
8425593	Braido et al.	Apr 2013	B2
8430934	Das	Apr 2013	B2
8444689	Zhang	May 2013	B2
8449599	Chau et al.	May 2013	B2
8449625	Campbell et al.	May 2013	B2
8454686	Alkhatib	Jun 2013	B2
8460365	Haverkost et al.	Jun 2013	B2
8474460	Barrett et al.	Jul 2013	B2
8500821	Sobrino-Serrano et al.	Aug 2013	B2
8512400	Tran et al.	Aug 2013	B2
8539662	Stacchino et al.	Sep 2013	B2
8545544	Spenser et al.	Oct 2013	B2
8551160	Figulla et al.	Oct 2013	B2
8551181	Dolan	Oct 2013	B2
8562672	Bonhoeffer et al.	Oct 2013	B2
8568475	Nguyen et al.	Oct 2013	B2
8579964	Lane et al.	Nov 2013	B2
8579965	Bonhoeffer et al.	Nov 2013	B2
8585755	Chau et al.	Nov 2013	B2
8585756	Bonhoeffer et al.	Nov 2013	B2
8591460	Wilson et al.	Nov 2013	B2
8591570	Revuelta et al.	Nov 2013	B2
8623075	Murray, III et al.	Jan 2014	B2
8623080	Fogarty et al.	Jan 2014	B2
8628569	Benichou et al.	Jan 2014	B2
8628570	Seguin	Jan 2014	B2
8628571	Hacohen et al.	Jan 2014	B1
8652203	Quadri et al.	Feb 2014	B2
8652204	Quill et al.	Feb 2014	B2
8657872	Seguin	Feb 2014	B2
8663322	Keranen	Mar 2014	B2
8673020	Sobrino-Serrano et al.	Mar 2014	B2
8679174	Ottma et al.	Mar 2014	B2
8685086	Navia et al.	Apr 2014	B2
8696742	Pintor et al.	Apr 2014	B2
8728155	Montorfano et al.	May 2014	B2
8734507	Keranen	May 2014	B2
8747460	Tuval et al.	Jun 2014	B2
8771345	Tuval et al.	Jul 2014	B2
8784472	Eldenschink	Jul 2014	B2
8784479	Antonsson et al.	Jul 2014	B2
8784481	Alkhatib et al.	Jul 2014	B2
8795355	Alkhatib	Aug 2014	B2
8795356	Quadri et al.	Aug 2014	B2
8795357	Yohanan et al.	Aug 2014	B2
8801776	House et al.	Aug 2014	B2
8808366	Braido et al.	Aug 2014	B2
8840663	Salahieh et al.	Sep 2014	B2
8840664	Karapetian et al.	Sep 2014	B2
8845722	Gabbay	Sep 2014	B2
8852261	White	Oct 2014	B2
8852272	Gross et al.	Oct 2014	B2
8870948	Erzberger et al.	Oct 2014	B1
8870949	Rowe	Oct 2014	B2
8870950	Hacohen	Oct 2014	B2
8876800	Behan	Nov 2014	B2
8894702	Quadri et al.	Nov 2014	B2
8900294	Paniagua et al.	Dec 2014	B2
8900295	Migliazza et al.	Dec 2014	B2
8906083	Obermiller et al.	Dec 2014	B2
8911455	Quadri et al.	Dec 2014	B2
8911489	Ben-Muvhar	Dec 2014	B2
8911493	Rowe et al.	Dec 2014	B2
8932343	Alkhatib et al.	Jan 2015	B2
8945177	Dell et al.	Feb 2015	B2
8961595	Alkhatib	Feb 2015	B2
8979922	Jayasinhe et al.	Mar 2015	B2
8986370	Annest	Mar 2015	B2
8986373	Chau et al.	Mar 2015	B2
8986375	Garde et al.	Mar 2015	B2
8992599	Thubrikar et al.	Mar 2015	B2
8992604	Gross et al.	Mar 2015	B2
8998982	Richter et al.	Apr 2015	B2
9005273	Salahieh et al.	Apr 2015	B2
9011468	Ketai et al.	Apr 2015	B2
9011527	Li et al.	Apr 2015	B2
9017399	Gross et al.	Apr 2015	B2
D730520	Braido et al.	May 2015	S
D730521	Braido et al.	May 2015	S
9023100	Quadri et al.	May 2015	B2
9034032	McLean et al.	May 2015	B2
9034033	McLean et al.	May 2015	B2
9039757	McLean et al.	May 2015	B2
D732666	Nguyen et al.	Jun 2015	S
9050188	Schweich, Jr. et al.	Jun 2015	B2
9060858	Thornton et al.	Jun 2015	B2
9072603	Tuval et al.	Jul 2015	B2
9084676	Chau et al.	Jul 2015	B2
9095434	Rowe	Aug 2015	B2
9125740	Morriss et al.	Aug 2015	B2
9119719	Zipory et al.	Sep 2015	B2
9125738	Figulla et al.	Sep 2015	B2
9132006	Spenser et al.	Sep 2015	B2
9132009	Hacohen et al.	Sep 2015	B2
9138312	Tuval et al.	Sep 2015	B2
9155619	Liu et al.	Oct 2015	B2
9173659	Bodewadt et al.	Nov 2015	B2
9173738	Murray, III et al.	Nov 2015	B2
9180009	Majkrzak et al.	Nov 2015	B2
9220594	Braido et al.	Dec 2015	B2
9226820	Braido et al.	Jan 2016	B2
9226839	Kariniemi et al.	Jan 2016	B1
9232995	Kovalsky et al.	Jan 2016	B2
9241790	Lane et al.	Jan 2016	B2
9241791	Braido et al.	Jan 2016	B2
9241792	Benichou et al.	Jan 2016	B2
9241794	Braido et al.	Jan 2016	B2
9248014	Lane et al.	Feb 2016	B2
9277994	Miller et al.	Mar 2016	B2
9289290	Alkhatib et al.	Mar 2016	B2
9289291	Gorman, III et al.	Mar 2016	B2
9295550	Nguyen et al.	Mar 2016	B2
9295551	Straubinger et al.	Mar 2016	B2
9295552	McLean et al.	Mar 2016	B2
9301836	Buchbinder et al.	Apr 2016	B2
9320591	Bolduc	Apr 2016	B2
D755384	Pesce et al.	May 2016	S
9326852	Spenser	May 2016	B2
9326876	Acosta et al.	May 2016	B2
9345573	Nyuli et al.	May 2016	B2
9358107	Nguyen et al.	Jun 2016	B2
9387078	Gross et al.	Jul 2016	B2
9393110	Levi et al.	Jul 2016	B2
9421098	Gifford, III et al.	Aug 2016	B2
9427303	Liddy et al.	Aug 2016	B2
9427316	Schweich, Jr. et al.	Aug 2016	B2
9439757	Wallace et al.	Sep 2016	B2
9445893	Vaturi	Sep 2016	B2
9463102	Kelly	Oct 2016	B2
9474599	Keranen	Oct 2016	B2
9474638	Robinson et al.	Oct 2016	B2
9480559	Vidlund et al.	Nov 2016	B2
9492273	Wallace et al.	Nov 2016	B2
9498314	Behan	Nov 2016	B2
9532870	Cooper et al.	Jan 2017	B2
9554897	Lane et al.	Jan 2017	B2
9554899	Granada et al.	Jan 2017	B2
9561103	Granada et al.	Feb 2017	B2
9566152	Schweich, Jr. et al.	Feb 2017	B2
9572665	Lane et al.	Feb 2017	B2
9597182	Straubinger et al.	Mar 2017	B2
9629716	Seguin	Apr 2017	B2
9662203	Sheahan et al.	May 2017	B2
9681952	Hacohen	Jun 2017	B2
9717591	Chau et al.	Aug 2017	B2
9743932	Amplatz et al.	Aug 2017	B2
9763657	Hacohen et al.	Sep 2017	B2
9763817	Roeder	Sep 2017	B2
9770256	Cohen et al.	Sep 2017	B2
D800908	Hariton et al.	Oct 2017	S
9788941	Hacohen	Oct 2017	B2
9895226	Harari et al.	Feb 2018	B1
9974651	Hariton et al.	May 2018	B2
10010414	Cooper et al.	Jul 2018	B2
10076415	Metchik et al.	Sep 2018	B1
10105222	Metchik et al.	Oct 2018	B1
10111751	Metchik et al.	Oct 2018	B1
10123873	Metchik et al.	Nov 2018	B1
10130475	Metchik et al.	Nov 2018	B1
10136993	Metchik et al.	Nov 2018	B1
10149761	Granada et al.	Dec 2018	B2
10154906	Granada et al.	Dec 2018	B2
10159570	Metchik et al.	Dec 2018	B1
10182908	Tubishevitz et al.	Jan 2019	B2
10226341	Gross et al.	Mar 2019	B2
10231837	Metchik et al.	Mar 2019	B1
10238493	Metchik et al.	Mar 2019	B1
10245143	Gross et al.	Apr 2019	B2
10245144	Metchik et al.	Apr 2019	B1
10292816	Raanani et al.	May 2019	B2
10299927	McLean et al.	May 2019	B2
10321995	Christianson et al.	Jun 2019	B1
10322020	Lam et al.	Jun 2019	B2
10327895	Lozonschi et al.	Jun 2019	B2
10335278	McLean et al.	Jul 2019	B2
10357360	Hariton et al.	Jul 2019	B2
10376361	Gross et al.	Aug 2019	B2
10390952	Hariton et al.	Aug 2019	B2
10426610	Hariton et al.	Oct 2019	B2
10463487	Hariton et al.	Nov 2019	B2
10463488	Hariton et al.	Nov 2019	B2
10507105	Hariton et al.	Dec 2019	B2
10507108	Delgado et al.	Dec 2019	B2
10507109	Metchik et al.	Dec 2019	B2
10512456	Hacohen et al.	Dec 2019	B2
10517719	Miller et al.	Dec 2019	B2
10524792	Hernandez et al.	Jan 2020	B2
10524910	Hammer et al.	Jan 2020	B2
10531872	Hacohen	Jan 2020	B2
10548731	Lashinski et al.	Feb 2020	B2
10575948	Iamberger et al.	Mar 2020	B2
10595992	Chambers	Mar 2020	B2
10595997	Metchik et al.	Mar 2020	B2
10610358	Vidlund et al.	Apr 2020	B2
10631871	Goldfarb et al.	Apr 2020	B2
10646342	Marr et al.	May 2020	B1
10667908	Hariton et al.	Jun 2020	B2
10667912	Dixon et al.	Jun 2020	B2
10682227	Hariton et al.	Jun 2020	B2
10695177	Hariton et al.	Jun 2020	B2
10702385	Hacohen	Jul 2020	B2
10722360	Hariton et al.	Jul 2020	B2
10758342	Chau et al.	Sep 2020	B2
10758344	Hariton et al.	Sep 2020	B2
10799345	Hariton et al.	Oct 2020	B2
10813760	Metchik et al.	Oct 2020	B2
10820998	Marr et al.	Nov 2020	B2
10842627	Delgado et al.	Nov 2020	B2
10849748	Hariton et al.	Dec 2020	B2
10856972	Hariton et al.	Dec 2020	B2
10856975	Hariton et al.	Dec 2020	B2
10856978	Straubinger et al.	Dec 2020	B2
10864078	Hariton et al.	Dec 2020	B2
10874514	Dixon et al.	Dec 2020	B2
10881511	Hariton et al.	Jan 2021	B2
10888422	Hariton et al.	Jan 2021	B2
10888425	Delgado et al.	Jan 2021	B2
10888644	Ratz et al.	Jan 2021	B2
10905548	Hariton et al.	Feb 2021	B2
10905549	Hariton et al.	Feb 2021	B2
10905552	Dixon et al.	Feb 2021	B2
10905554	Cao	Feb 2021	B2
10918483	Metchik et al.	Feb 2021	B2
10925595	Hacohen	Feb 2021	B2
10925732	Delgado et al.	Feb 2021	B2
10945843	Delgado et al.	Mar 2021	B2
10945844	McCann et al.	Mar 2021	B2
10959846	Marr et al.	Mar 2021	B2
10973636	Hariton et al.	Apr 2021	B2
10993809	McCann et al.	May 2021	B2
11065114	Raanani et al.	Jul 2021	B2
11083582	McCann et al.	Aug 2021	B2
11147672	McCann et al.	Oct 2021	B2
11179240	Delgado et al.	Nov 2021	B2
11291545	Hacohen	Apr 2022	B2
11291546	Gross et al.	Apr 2022	B2
11291547	Gross et al.	Apr 2022	B2
11304806	Hariton et al.	Apr 2022	B2
11389297	Franklin et al.	Jul 2022	B2
20010005787	Oz et al.	Jun 2001	A1
20010021872	Bailey et al.	Sep 2001	A1
20010056295	Solem	Dec 2001	A1
20020013571	Goldfarb et al.	Jan 2002	A1
20020032481	Gabbay	Mar 2002	A1
20020099436	Thornton et al.	Jul 2002	A1
20020151970	Garrison et al.	Oct 2002	A1
20020177894	Acosta et al.	Nov 2002	A1
20030036791	Philipp et al.	Feb 2003	A1
20030050694	Yang et al.	Mar 2003	A1
20030060875	Wittens	Mar 2003	A1
20030069635	Cartledge et al.	Apr 2003	A1
20030074052	Besselink	Apr 2003	A1
20030074059	Nguyen et al.	Apr 2003	A1
20030083742	Spence et al.	May 2003	A1
20030105519	Fasol et al.	Jun 2003	A1
20030158578	Pantages et al.	Aug 2003	A1
20040010272	Manetakis et al.	Jan 2004	A1
20040030382	St. Goar et al.	Feb 2004	A1
20040039414	Carley et al.	Feb 2004	A1
20040039436	Spenser et al.	Feb 2004	A1
20040093060	Seguin et al.	May 2004	A1
20040122503	Campbell et al.	Jun 2004	A1
20040122514	Fogarty et al.	Jun 2004	A1
20040133267	Lane	Jul 2004	A1
20040143315	Bruun et al.	Jul 2004	A1
20040176839	Huynh et al.	Sep 2004	A1
20040186558	Pavcnik et al.	Sep 2004	A1
20040186565	Schreck	Sep 2004	A1
20040186566	Hindrichs et al.	Sep 2004	A1
20040210244	Vargas et al.	Oct 2004	A1
20040210304	Seguin et al.	Oct 2004	A1
20040220593	Greenhalgh	Nov 2004	A1
20040225354	Allen et al.	Nov 2004	A1
20040236354	Seguin	Nov 2004	A1
20040249433	Freitag	Dec 2004	A1
20040260389	Case et al.	Dec 2004	A1
20040260394	Douk et al.	Dec 2004	A1
20050004668	Aklog et al.	Jan 2005	A1
20050021056	St. Goar et al.	Jan 2005	A1
20050027305	Shiu et al.	Feb 2005	A1
20050027348	Case et al.	Feb 2005	A1
20050038494	Eldenschink	Feb 2005	A1
20050055086	Stobie	Mar 2005	A1
20050075726	Svanidze et al.	Apr 2005	A1
20050075731	Artof et al.	Apr 2005	A1
20050080430	Wright, Jr. et al.	Apr 2005	A1
20050080474	Andreas et al.	Apr 2005	A1
20050085900	Case et al.	Apr 2005	A1
20050137681	Shoemaker et al.	Jun 2005	A1
20050137686	Salahieh et al.	Jun 2005	A1
20050137688	Salahieh et al.	Jun 2005	A1
20050137689	Salahieh et al.	Jun 2005	A1
20050137690	Selahleh et al.	Jun 2005	A1
20050137691	Salahieh et al.	Jun 2005	A1
20050137692	Haug et al.	Jun 2005	A1
20050137693	Haug et al.	Jun 2005	A1
20050137695	Salahieh et al.	Jun 2005	A1
20050137697	Salahieh et al.	Jun 2005	A1
20050137699	Salahieh et al.	Jun 2005	A1
20050143809	Salahieh et al.	Jun 2005	A1
20050149160	McFerran	Jul 2005	A1
20050164443	Linder et al.	Jul 2005	A1
20050182486	Gabbay	Aug 2005	A1
20050197695	Stacchino et al.	Sep 2005	A1
20050203549	Realyvasquez	Sep 2005	A1
20050203618	Sharkawy et al.	Sep 2005	A1
20050216079	MaCoviak	Sep 2005	A1
20050234508	Cummins et al.	Oct 2005	A1
20050240200	Bergheim	Oct 2005	A1
20050251251	Cribier	Nov 2005	A1
20050256566	Gabbay	Nov 2005	A1
20050267573	Macoviak et al.	Dec 2005	A9
20060004439	Spenser et al.	Jan 2006	A1
20060004469	Sokel	Jan 2006	A1
20060015171	Armstrong	Jan 2006	A1
20060020275	Goldfarb et al.	Jan 2006	A1
20060020327	Lashinski et al.	Jan 2006	A1
20060020333	Lashinski	Jan 2006	A1
20060030863	Fields et al.	Feb 2006	A1
20060041189	Vancalllie	Feb 2006	A1
20060047297	Case	Mar 2006	A1
20060052867	Revuelta	Mar 2006	A1
20060089627	Burnett et al.	Apr 2006	A1
20060111773	Rittgers et al.	May 2006	A1
20060116750	Hebert et al.	Jun 2006	A1
20060122692	Gilad et al.	Jun 2006	A1
20060135964	Vesely	Jun 2006	A1
20060155357	Melsheimer	Jul 2006	A1
20060178700	Quinn	Aug 2006	A1
20060178740	Slacchino et al.	Aug 2006	A1
20060184203	Martin et al.	Aug 2006	A1
20060190036	Wendel et al.	Aug 2006	A1
20060190038	Carley et al.	Aug 2006	A1
20060195183	Navia et al.	Aug 2006	A1
20060195184	Lane et al.	Aug 2006	A1
20060201519	Frazier et al.	Sep 2006	A1
20060212111	Case et al.	Sep 2006	A1
20060216404	Seyler et al.	Sep 2006	A1
20060229708	Powell et al.	Oct 2006	A1
20060241656	Starksen et al.	Oct 2006	A1
20060241748	Lee et al.	Oct 2006	A1
20060247680	Amplatz et al.	Nov 2006	A1
20060253191	Salahieh et al.	Nov 2006	A1
20060259136	Nguyen et al.	Nov 2006	A1
20060259137	Artof et al.	Nov 2006	A1
20060271166	Thill et al.	Nov 2006	A1
20060271171	McQuinn et al.	Nov 2006	A1
20060282150	Olson et al.	Dec 2006	A1
20060287719	Rowe et al.	Dec 2006	A1
20070016286	Herrmann et al.	Jan 2007	A1
20070016288	Gurskis et al.	Jan 2007	A1
20070027528	Agnew	Feb 2007	A1
20070027549	Godin	Feb 2007	A1
20070038293	Goar et al.	Feb 2007	A1
20070038295	Case et al.	Feb 2007	A1
20070043435	Seguin	Feb 2007	A1
20070055340	Pryor	Mar 2007	A1
20070056346	Spenser et al.	Mar 2007	A1
20070078510	Ryan	Apr 2007	A1
20070112422	Dehdashtian	May 2007	A1
20070118151	Davidson	May 2007	A1
20070162103	Case et al.	Jul 2007	A1
20070162107	Haug et al.	Jul 2007	A1
20070162111	Fukamachi et al.	Jul 2007	A1
20070173932	Cali et al.	Jul 2007	A1
20070197858	Goldfarb et al.	Aug 2007	A1
20070198077	Cully et al.	Aug 2007	A1
20070198097	Zegdi	Aug 2007	A1
20070208550	Cao et al.	Sep 2007	A1
20070213810	Newhauser et al.	Sep 2007	A1
20070213813	Von Segesser et al.	Sep 2007	A1
20070219630	Chu	Sep 2007	A1
20070225759	Thommen et al.	Sep 2007	A1
20070225760	Moszner et al.	Sep 2007	A1
20070233186	Meng	Oct 2007	A1
20070233237	Krivoruchko	Oct 2007	A1
20070239272	Navia et al.	Oct 2007	A1
20070239273	Allen	Oct 2007	A1
20070244546	Francis	Oct 2007	A1
20070255400	Parravicini et al.	Nov 2007	A1
20080004688	Spenser et al.	Jan 2008	A1
20080004697	Lichtenstein et al.	Jan 2008	A1
20080051703	Thornton et al.	Feb 2008	A1
20080065011	Marchand et al.	Mar 2008	A1
20080065204	Macoviak et al.	Mar 2008	A1
20080071361	Tuval et al.	Mar 2008	A1
20080071363	Tuval et al.	Mar 2008	A1
20080071366	Tuval et al.	Mar 2008	A1
20080071369	Tuval et al.	Mar 2008	A1
20080077235	Kirson	Mar 2008	A1
20080066164	Rowe	Apr 2008	A1
20080082083	Forde et al.	Apr 2008	A1
20080082159	Tseng et al.	Apr 2008	A1
20080082166	Styrc et al.	Apr 2008	A1
20080086204	Rankin	Apr 2008	A1
20080091261	Long et al.	Apr 2008	A1
20080097595	Gabbay	Apr 2008	A1
20080132989	Snow et al.	Jun 2008	A1
20080140003	Bei et al.	Jun 2008	A1
20080147182	Righini et al.	Jun 2008	A1
20080161910	Revuelta et al.	Jul 2008	A1
20080167705	Agnew	Jul 2008	A1
20080167714	St. Goar et al.	Jul 2008	A1
20080188929	Schreck	Aug 2008	A1
20080195200	Vidlund et al.	Aug 2008	A1
20080200980	Robin et al.	Aug 2008	A1
20080208328	Antocci et al.	Aug 2008	A1
20080208332	Lamphere et al.	Aug 2008	A1
20080221672	Lamphere et al.	Sep 2008	A1
20080234814	Salahieh et al.	Sep 2008	A1
20080243245	Thambar et al.	Oct 2008	A1
20080255580	Hoffman et al.	Oct 2008	A1
20080262609	Gross et al.	Oct 2008	A1
20080269879	Sathe et al.	Oct 2008	A1
20080281411	Berreklouw	Nov 2008	A1
20080294234	Hartley et al.	Nov 2008	A1
20090005863	Goetz et al.	Jan 2009	A1
20090036966	O'Connor et al.	Feb 2009	A1
20090054969	Salahieh et al.	Feb 2009	A1
20090082844	Zacharias et al.	Mar 2009	A1
20090088836	Bishop et al.	Apr 2009	A1
20090099554	Forster et al.	Apr 2009	A1
20090099650	Bolduc et al.	Apr 2009	A1
20090105794	Ziarno et al.	Apr 2009	A1
20090112159	Slattery et al.	Apr 2009	A1
20090125098	Chuter	May 2009	A1
20090157175	Benichou	Jun 2009	A1
20090163934	Raschdorf, Jr. et al.	Jun 2009	A1
20090171363	Chocron	Jul 2009	A1
20090177278	Spence	Jul 2009	A1
20090210052	Forster et al.	Aug 2009	A1
20090222081	Linder et al.	Sep 2009	A1
20090240320	Tuval et al.	Sep 2009	A1
20090241656	Jacquemin	Oct 2009	A1
20090259306	Rowe	Oct 2009	A1
20090264859	Mas	Oct 2009	A1
20090264994	Saadat	Oct 2009	A1
20090276040	Rowe et al.	Nov 2009	A1
20090281619	Le et al.	Nov 2009	A1
20090287299	Tabor et al.	Nov 2009	A1
20090287304	Dahlgren et al.	Nov 2009	A1
20090299449	Styrc	Dec 2009	A1
20090306768	Quadri et al.	Dec 2009	A1
20090319037	Rowe et al.	Dec 2009	A1
20100022823	Goldfarb et al.	Jan 2010	A1
20100023117	Yoganathan et al.	Jan 2010	A1
20100023120	Holecek et al.	Jan 2010	A1
20100036479	Hill et al.	Feb 2010	A1
20100036484	Hariton et al.	Feb 2010	A1
20100049313	Alon et al.	Feb 2010	A1
20100069852	Kelley	Mar 2010	A1
20100076548	Konno	Mar 2010	A1
20100082094	Quadri et al.	Apr 2010	A1
20100100167	Bortlein et al.	Apr 2010	A1
20100114299	Ben Muvhar et al.	May 2010	A1
20100131054	Tuval et al.	May 2010	A1
20100137979	Tuval et al.	Jun 2010	A1
20100160958	Clark	Jun 2010	A1
20100161036	Pintor et al.	Jun 2010	A1
20100161042	Maisano et al.	Jun 2010	A1
20100174363	Castro	Jul 2010	A1
20100179643	Shalev	Jul 2010	A1
20100179648	Richter et al.	Jul 2010	A1
20100179649	Richter et al.	Jul 2010	A1
20100185277	Braido et al.	Jul 2010	A1
20100217382	Chau et al.	Aug 2010	A1
20100222810	DeBeer et al.	Sep 2010	A1
20100228285	Miles et al.	Sep 2010	A1
20100234940	Dolan	Sep 2010	A1
20100249908	Chau et al.	Sep 2010	A1
20100249917	Zhang	Sep 2010	A1
20100256737	Pollock et al.	Oct 2010	A1
20100262232	Annest	Oct 2010	A1
20100280603	Maisano et al.	Nov 2010	A1
20100280606	Naor	Nov 2010	A1
20100312333	Navia et al.	Dec 2010	A1
20100324595	Linder et al.	Dec 2010	A1
20100331971	Keranen et al.	Dec 2010	A1
20110004227	Goldfarb et al.	Jan 2011	A1
20110004296	Lutter et al.	Jan 2011	A1
20110004299	Navia et al.	Jan 2011	A1
20110015729	Jimenez et al.	Jan 2011	A1
20110015731	Carpentier et al.	Jan 2011	A1
20110022165	Oba et al.	Jan 2011	A1
20110029072	Gabbay	Feb 2011	A1
20110040374	Goetz et al.	Feb 2011	A1
20110040375	Letac et al.	Feb 2011	A1
20110046662	Moszner et al.	Feb 2011	A1
20110054466	Rothstein et al.	Mar 2011	A1
20110054598	Johnson	Mar 2011	A1
20110066233	Thornton et al.	Mar 2011	A1
20110071626	Wright et al.	Mar 2011	A1
20110077730	Fenster	Mar 2011	A1
20110084596	Taylor	Mar 2011	A1
20110082538	Dahlgren et al.	Apr 2011	A1
20110087322	Letac et al.	Apr 2011	A1
20110093063	Schreck	Apr 2011	A1
20110098525	Karmode et al.	Apr 2011	A1
20110106247	Miler et al.	May 2011	A1
20110112625	Ben-Muvhar et al.	May 2011	A1
20110112632	Chau et al.	May 2011	A1
20110118830	Liddicoat et al.	May 2011	A1
20110125257	Seguin et al.	May 2011	A1
20110125258	Centola	May 2011	A1
20110137326	Bachman	Jun 2011	A1
20110137397	Chau et al.	Jun 2011	A1
20110137409	Yang et al.	Jun 2011	A1
20110137410	Hacohen	Jun 2011	A1
20110144742	Madrid et al.	Jun 2011	A1
20110166636	Rowe	Jul 2011	A1
20110172784	Richter et al.	Jul 2011	A1
20110178597	Navia et al.	Jul 2011	A9
20110184510	Maisano et al.	Jul 2011	A1
20110190877	Lane et al.	Aug 2011	A1
20110190879	Bobo et al.	Aug 2011	A1
20110202076	Richter	Aug 2011	A1
20110208283	Rust	Aug 2011	A1
20110208293	Tabor	Aug 2011	A1
20110208298	Tuval et al.	Aug 2011	A1
20110213459	Garrison et al.	Sep 2011	A1
20110213461	Seguin et al.	Sep 2011	A1
20110218619	Benichou et al.	Sep 2011	A1
20110218620	Meiri et al.	Sep 2011	A1
20110224785	Hacohen	Sep 2011	A1
20110238159	Guyenot et al.	Sep 2011	A1
20110245911	Quill et al.	Oct 2011	A1
20110245917	Savage et al.	Oct 2011	A1
20110251675	Dwork	Oct 2011	A1
20110251676	Sweeney et al.	Oct 2011	A1
20110251678	Eidenschink et al.	Oct 2011	A1
20110251679	Wiemeyer et al.	Oct 2011	A1
20110251682	Murray, III et al.	Oct 2011	A1
20110251683	Tabor	Oct 2011	A1
20110257721	Tabor	Oct 2011	A1
20110257729	Spenser et al.	Oct 2011	A1
20110257736	Marquez et al.	Oct 2011	A1
20110257737	Fogarty et al.	Oct 2011	A1
20110261680	Tran et al.	Oct 2011	A1
20110264191	Rothstein	Oct 2011	A1
20110264196	Savage et al.	Oct 2011	A1
20110264198	Murray, III et al.	Oct 2011	A1
20110264199	Tran et al.	Oct 2011	A1
20110264200	Tran et al.	Oct 2011	A1
20110264201	Yeung et al.	Oct 2011	A1
20110264202	Murray, III et al.	Oct 2011	A1
20110264203	Dwork et al.	Oct 2011	A1
20110264206	Tabor	Oct 2011	A1
20110264208	Duffy et al.	Oct 2011	A1
20110270276	Rothstein et al.	Nov 2011	A1
20110271967	Mortier et al.	Nov 2011	A1
20110282438	Drews et al.	Nov 2011	A1
20110282439	Thill et al.	Nov 2011	A1
20110282440	Cao et al.	Nov 2011	A1
20110283514	Fogarty et al.	Nov 2011	A1
20110288634	Tuval et al.	Nov 2011	A1
20110295354	Bueche et al.	Dec 2011	A1
20110295363	Girard et al.	Dec 2011	A1
20110301688	Dolan	Dec 2011	A1
20110301701	Padala et al.	Dec 2011	A1
20110301702	Rust et al.	Dec 2011	A1
20110306916	Nitzan et al.	Dec 2011	A1
20110307049	Kao	Dec 2011	A1
20110313452	Carley et al.	Dec 2011	A1
20110313515	Quadri et al.	Dec 2011	A1
20110319989	Lane et al.	Dec 2011	A1
20110319991	Hariton et al.	Dec 2011	A1
20120010694	Lutter et al.	Jan 2012	A1
20120016468	Robin et al.	Jan 2012	A1
20120022629	Perera et al.	Jan 2012	A1
20120022633	Olson et al.	Jan 2012	A1
20120022637	Ben-Muvhar	Jan 2012	A1
20120022639	Hacohen et al.	Jan 2012	A1
20120022640	Gross et al.	Jan 2012	A1
20120035703	Lutter et al.	Feb 2012	A1
20120035713	Lutter et al.	Feb 2012	A1
20120035722	Tuval	Feb 2012	A1
20120041547	Duffy et al.	Feb 2012	A1
20120041551	Spenser et al.	Feb 2012	A1
20120046738	Lau et al.	Feb 2012	A1
20120046742	Tuval et al.	Feb 2012	A1
20120053676	Ku et al.	Mar 2012	A1
20120053682	Kovalsky et al.	Mar 2012	A1
20120053688	Fogarty et al.	Mar 2012	A1
20120059454	Millwee et al.	Mar 2012	A1
20120059458	Buchbinder et al.	Mar 2012	A1
20120065464	Ellis et al.	Mar 2012	A1
20120078237	Wang et al.	Mar 2012	A1
20120078353	Quadri et al.	Mar 2012	A1
20120078357	Conklin	Mar 2012	A1
20120083832	Delaloye et al.	Apr 2012	A1
20120083839	Letac et al.	Apr 2012	A1
20120083879	Eberhardt et al.	Apr 2012	A1
20120089223	Nguyen et al.	Apr 2012	A1
20120101570	Tuval et al.	Apr 2012	A1
20120101571	Thambar et al.	Apr 2012	A1
20120101572	Kovalsky et al.	Apr 2012	A1
20120123511	Brown	May 2012	A1
20120123529	Levi et al.	May 2012	A1
20120123530	Carpentier et al.	May 2012	A1
20120130473	Norris et al.	May 2012	A1
20120130474	Buckley	May 2012	A1
20120130475	Shaw	May 2012	A1
20120136434	Carpentier et al.	May 2012	A1
20120150218	Sandgren et al.	Jun 2012	A1
20120165915	Melsheimer et al.	Jun 2012	A1
20120165930	Gifford, III et al.	Jun 2012	A1
20120179244	Schankereli et al.	Jul 2012	A1
20120197292	Chin-Chen et al.	Aug 2012	A1
20120277845	Bowe	Nov 2012	A1
20120283824	Lutter et al.	Nov 2012	A1
20120290062	McNamara et al.	Nov 2012	A1
20120296360	Norris et al.	Nov 2012	A1
20120296418	Bonyuet et al.	Nov 2012	A1
20120300063	Majkrzak et al.	Nov 2012	A1
20120310328	Olson et al.	Dec 2012	A1
20120323316	Chau et al.	Dec 2012	A1
20120330408	Hillukkla et al.	Dec 2012	A1
20130006347	McHugo	Jan 2013	A1
20130018450	Hunt	Jan 2013	A1
20130018458	Ychanan et al.	Jan 2013	A1
20130030519	Tran et al.	Jan 2013	A1
20130035759	Gross et al.	Feb 2013	A1
20130041451	Patterson et al.	Feb 2013	A1
20130046373	Cartledge et al.	Feb 2013	A1
20130066341	Ketai et al.	Mar 2013	A1
20130066342	Dell et al.	Mar 2013	A1
20130079872	Gallagher	Mar 2013	A1
20130116779	Weber	May 2013	A1
20130116780	Miller et al.	May 2013	A1
20130123896	Bloss et al.	May 2013	A1
20130123900	Eblacas et al.	May 2013	A1
20130144381	Quadri et al.	Jun 2013	A1
20130150945	Crawford et al.	Jun 2013	A1
20130150956	Yohanan et al.	Jun 2013	A1
20130158647	Norris et al.	Jun 2013	A1
20130166017	Cartledge et al.	Jun 2013	A1
20130166022	Conklin	Jun 2013	A1
20130172978	Vidlund et al.	Jul 2013	A1
20130172992	Gross et al.	Jul 2013	A1
20130178930	Straubinger et al.	Jul 2013	A1
20130190857	Mitra et al.	Jul 2013	A1
20130190861	Chau et al.	Jul 2013	A1
20130211501	Buckley et al.	Aug 2013	A1
20130231735	Deem et al.	Sep 2013	A1
20130245742	Norris	Sep 2013	A1
20130253643	Rolando et al.	Sep 2013	A1
20130261737	Costello	Oct 2013	A1
20130261738	Clague et al.	Oct 2013	A1
20130274870	Lombardi et al.	Oct 2013	A1
20130282059	Ketai et al.	Oct 2013	A1
20130289711	Liddy et al.	Oct 2013	A1
20130289740	Liddy et al.	Oct 2013	A1
20130297013	Klima et al.	Nov 2013	A1
20130304197	Buchbinder et al.	Nov 2013	A1
20130304200	McLean et al.	Nov 2013	A1
20130310928	Morriss et al.	Nov 2013	A1
20130325114	McLean et al.	Dec 2013	A1
20130331929	Mitra et al.	Dec 2013	A1
20140000112	Braido et al.	Jan 2014	A1
20140005767	Glazier et al.	Jan 2014	A1
20140005778	Buchbinder et al.	Jan 2014	A1
20140018911	Zhou et al.	Jan 2014	A1
20140018915	Biadillah et al.	Jan 2014	A1
20140031928	Murphy et al.	Jan 2014	A1
20140046430	Shaw	Feb 2014	A1
20140052237	Lane et al.	Feb 2014	A1
20140067050	Costello et al.	Mar 2014	A1
20140067054	Chau et al.	Mar 2014	A1
20140081376	Burkart et al.	Mar 2014	A1
20140106951	Brandon	Apr 2014	A1
20140120287	Jacoby et al.	May 2014	A1
20140121749	Roeder	May 2014	A1
20140121763	Duffy et al.	May 2014	A1
20140135894	Norris et al.	May 2014	A1
20140135895	Andress et al.	May 2014	A1
20140142681	Norris	May 2014	A1
20140142688	Duffy et al.	May 2014	A1
20140148891	Johnson	May 2014	A1
20140163690	White	Jun 2014	A1
20140172069	Roeder et al.	Jun 2014	A1
20140172077	Bruchman et al.	Jun 2014	A1
20140172082	Bruchman et al.	Jun 2014	A1
20140188210	Beard et al.	Jul 2014	A1
20140188221	Chung et al.	Jul 2014	A1
20140194970	Chobotov	Jul 2014	A1
20140194981	Menk et al.	Jul 2014	A1
20140194983	Kovalsky et al.	Jul 2014	A1
20140207231	Hacohen et al.	Jul 2014	A1
20140214157	Börtlein et al.	Jul 2014	A1
20140214159	Vidlund et al.	Jul 2014	A1
20140222136	Geist et al.	Aug 2014	A1
20140222142	Kovalsky et al.	Aug 2014	A1
20140236287	Clague et al.	Aug 2014	A1
20140236289	Alkhatib	Aug 2014	A1
20140249622	Carmi et al.	Sep 2014	A1
20140257461	Robinson et al.	Sep 2014	A1
20140257467	Lane et al.	Sep 2014	A1
20140257475	Gross et al.	Sep 2014	A1
20140257476	Montorfano et al.	Sep 2014	A1
20140277358	Slazas	Sep 2014	A1
20140277409	Bortlein et al.	Sep 2014	A1
20140277411	Bortlein et al.	Sep 2014	A1
20140277412	Börtlein et al.	Sep 2014	A1
20140277418	Miller	Sep 2014	A1
20140277422	Ratz et al.	Sep 2014	A1
20140277427	Ratz et al.	Sep 2014	A1
20140296962	Cartledge et al.	Oct 2014	A1
20140296969	Tegels et al.	Oct 2014	A1
20140324164	Gross et al.	Oct 2014	A1
20140331475	Duffy et al.	Nov 2014	A1
20140336744	Tani et al.	Nov 2014	A1
20140343670	Bakis et al.	Nov 2014	A1
20140358222	Gorman, III et al.	Dec 2014	A1
20140358224	Tegels et al.	Dec 2014	A1
20140379065	Johnson et al.	Dec 2014	A1
20140379074	Spence et al.	Dec 2014	A1
20140379076	Vidlund et al.	Dec 2014	A1
20150018944	O'Connell et al.	Jan 2015	A1
20150032205	Matheny	Jan 2015	A1
20150045881	Lim	Feb 2015	A1
20150094802	Buchbinder et al.	Apr 2015	A1
20150119970	Nakayama et al.	Apr 2015	A1
20150127097	Neumann et al.	May 2015	A1
20150142100	Morriss et al.	May 2015	A1
20150142103	Vidlund	May 2015	A1
20150157457	Hacohen	Jun 2015	A1
20150157458	Thambar et al.	Jun 2015	A1
20150164640	McLean et al.	Jun 2015	A1
20150173896	Richter et al.	Jun 2015	A1
20150173897	Raanani et al.	Jun 2015	A1
20150196390	Ma et al.	Jul 2015	A1
20150196393	Vidlund et al.	Jul 2015	A1
20150216661	Hacohen et al.	Aug 2015	A1
20150238313	Ence et al.	Aug 2015	A1
20150245934	Lombardi et al.	Sep 2015	A1
20150250588	Yang et al.	Sep 2015	A1
20150272730	Melnick et al.	Oct 2015	A1
20150272731	Racchini et al.	Oct 2015	A1
20150272734	Sheps et al.	Oct 2015	A1
20150282964	Beard et al.	Oct 2015	A1
20150305903	Kitaoka	Oct 2015	A1
20150320556	Levi et al.	Nov 2015	A1
20150327994	Morriss et al.	Nov 2015	A1
20150328000	Ratz et al.	Nov 2015	A1
20150335429	Morriss et al.	Nov 2015	A1
20150351903	Morriss et al.	Dec 2015	A1
20150351904	Cooper et al.	Dec 2015	A1
20150359629	Ganesan et al.	Dec 2015	A1
20150359631	Sheahan et al.	Dec 2015	A1
20150369628	Ganesan et al.	Dec 2015	A1
20160030169	Shahriari	Feb 2016	A1
20160030171	Quijano et al.	Feb 2016	A1
20160089482	Siegenthaler	Mar 2016	A1
20160095700	Righini	Apr 2016	A1
20160100939	Amstrong et al.	Apr 2016	A1
20160106539	Buchbinder et al.	Apr 2016	A1
20160113765	Ganesan et al.	Apr 2016	A1
20160113766	Ganesan et al.	Apr 2016	A1
20160113768	Ganesan et al.	Apr 2016	A1
20160158497	Tran et al.	Jun 2016	A1
20160175095	Dienno et al.	Jun 2016	A1
20160184098	Vaturi	Jun 2016	A1
20160220367	Barrett	Aug 2016	A1
20160228247	Maimon et al.	Aug 2016	A1
20160242902	Morriss et al.	Aug 2016	A1
20160262885	Sandstrom et al.	Sep 2016	A1
20160270911	Ganesan et al.	Sep 2016	A1
20160310268	Oba et al.	Oct 2016	A1
20160310274	Gross et al.	Oct 2016	A1
20160317301	Quadri et al.	Nov 2016	A1
20160317305	Pelled et al.	Nov 2016	A1
20160324633	Gross et al.	Nov 2016	A1
20160324635	Vidlund et al.	Nov 2016	A1
20160324640	Gifford, III et al.	Nov 2016	A1
20160331525	Straubinger et al.	Nov 2016	A1
20160331526	Schweich, Jr. et al.	Nov 2016	A1
20160338706	Rowe	Nov 2016	A1
20160367360	Cartledge et al.	Dec 2016	A1
20160367368	Vdlund et al.	Dec 2016	A1
20160374802	Levi et al.	Dec 2016	A1
20170042678	Ganesan et al.	Feb 2017	A1
20170049435	Sauer et al.	Feb 2017	A1
20170056166	Ratz et al.	Mar 2017	A1
20170056171	Cooper et al.	Mar 2017	A1
20170065411	Grundeman et al.	Mar 2017	A1
20170100236	Robertson et al.	Apr 2017	A1
20170128205	Tamir et al.	May 2017	A1
20170135816	Lashinski et al.	May 2017	A1
20170189174	Braido et al.	Jul 2017	A1
20170196688	Christianson et al.	Jul 2017	A1
20170196692	Kirk et al.	Jul 2017	A1
20170209264	Chau et al.	Jul 2017	A1
20170216026	Quill et al.	Aug 2017	A1
20170224323	Rowe et al.	Aug 2017	A1
20170231757	Gassler	Aug 2017	A1
20170231759	Geist et al.	Aug 2017	A1
20170231760	Lane et al.	Aug 2017	A1
20170239048	Goldfarb et al.	Aug 2017	A1
20170325948	Wallace et al.	Nov 2017	A1
20170333183	Backus	Nov 2017	A1
20170333187	Hariton et al.	Nov 2017	A1
20180000580	Wallace et al.	Jan 2018	A1
20180014930	Hariton et al.	Jan 2018	A1
20180021129	Peterson et al.	Jan 2018	A1
20180028215	Cohen	Feb 2018	A1
20180049873	Manash et al.	Feb 2018	A1
20180055628	Patel et al.	Mar 2018	A1
20180055630	Patel et al.	Mar 2018	A1
20180098850	Rafiee et al.	Apr 2018	A1
20180116790	Ratz et al.	May 2018	A1
20180116843	Schreck et al.	May 2018	A1
20180125644	Conklin	May 2018	A1
20180132999	Perouse	May 2018	A1
20180153689	Maimon et al.	Jun 2018	A1
20180161159	Lee et al.	Jun 2018	A1
20180177594	Patel et al.	Jun 2018	A1
20180206983	Noe et al.	Jul 2018	A1
20180214263	Rolando et al.	Aug 2018	A1
20180243086	Barbarino et al.	Aug 2018	A1
20180250126	O'Connor et al.	Sep 2018	A1
20180250130	Hariton et al.	Sep 2018	A1
20180250147	Syed	Sep 2018	A1
20180256323	Hariton et al.	Sep 2018	A1
20180256325	Hariton et al.	Sep 2018	A1
20180271654	Hariton et al.	Sep 2018	A1
20180271655	Hariton et al.	Sep 2018	A1
20180289479	Hariton et al.	Oct 2018	A1
20180296333	Dixon et al.	Oct 2018	A1
20180296336	Cooper et al.	Oct 2018	A1
20180325671	Abunassar et al.	Nov 2018	A1
20180338829	Hariton et al.	Nov 2018	A1
20180344457	Gross et al.	Dec 2018	A1
20180344490	Fox et al.	Dec 2018	A1
20180353294	Calomeni et al.	Dec 2018	A1
20180360457	Ellis et al.	Dec 2018	A1
20190000613	Delgado et al.	Jan 2019	A1
20190015093	Hacohen et al.	Jan 2019	A1
20190015200	Delgado et al.	Jan 2019	A1
20190021852	Delgado et al.	Jan 2019	A1
20190053896	Adamek-Bowers et al.	Feb 2019	A1
20190060060	Chau et al.	Feb 2019	A1
20190060068	Cope et al.	Feb 2019	A1
20190060070	Groothuis et al.	Feb 2019	A1
20190069997	Ratz et al.	Mar 2019	A1
20190083261	Perszyk et al.	Mar 2019	A1
20190105153	Barash et al.	Apr 2019	A1
20190117391	Humair	Apr 2019	A1
20190175339	Vidlund	Jun 2019	A1
20190175342	Hariton et al.	Jun 2019	A1
20190183639	Moore	Jun 2019	A1
20190192295	Spence et al.	Jun 2019	A1
20190328519	Hariton et al.	Oct 2019	A1
20190336280	Naor et al.	Nov 2019	A1
20190343627	Hariton et al.	Nov 2019	A1
20190350701	Adamek-Bowers et al.	Nov 2019	A1
20190365530	Hoang et al.	Dec 2019	A1
20190388218	Vidlund et al.	Dec 2019	A1
20190388220	Vidlund et al.	Dec 2019	A1
20200000449	Goldfarb et al.	Jan 2020	A1
20200000579	Manash et al.	Jan 2020	A1
20200015964	Noe et al.	Jan 2020	A1
20200030098	Delgado et al.	Jan 2020	A1
20200054335	Hernandez et al.	Feb 2020	A1
20200060818	Geist et al.	Feb 2020	A1
20200113677	McCann et al.	Apr 2020	A1
20200113689	McCann et al.	Apr 2020	A1
20200113692	McCann et al.	Apr 2020	A1
20200138567	Marr et al.	May 2020	A1
20200163761	Hariton et al.	May 2020	A1
20200214832	Metchik et al.	Jul 2020	A1
20200237512	McCann et al.	Jul 2020	A1
20200246136	Marr et al.	Aug 2020	A1
20200246140	Hariton et al.	Aug 2020	A1
20200253600	Darabian	Aug 2020	A1
20200261094	Goldfarb et al.	Aug 2020	A1
20200306037	Siegel et al.	Oct 2020	A1
20200315786	Metchik et al.	Oct 2020	A1
20200337842	Metchik et al.	Oct 2020	A1
20210085455	Bateman et al.	Mar 2021	A1
20210093449	Hariton et al.	Apr 2021	A1
20210106419	Abunassar	Apr 2021	A1
20210113331	Quadri et al.	Apr 2021	A1
20210137680	Kizuka et al.	May 2021	A1
20210259835	Tyler, II et al.	Aug 2021	A1
20220000612	Hacohen	Jan 2022	A1

Foreign Referenced Citations (91)

Number	Date	Country
2822801	Aug 2006	CA
103974674	Aug 2014	CN
1264582	Dec 2002	EP
1637092	Mar 2006	EP
2 446 915	May 2012	EP
1768630	Jan 2015	EP
2349124	Oct 2018	EP
3583922	Dec 2019	EP
3270825	Apr 2020	EP
2485795	Sep 2020	EP
9843557	Oct 1998	WO
9930647	Jun 1999	WO
0047139	Aug 2000	WO
0162189	Aug 2001	WO
0187190	Nov 2001	WO
WO 2003020179	Mar 2003	WO
03028558	Apr 2003	WO
WO 2004028399	Apr 2004	WO
2006007401	Jan 2006	WO
WO 2006007389	Jan 2006	WO
2006054930	May 2006	WO
2006070372	Jul 2006	WO
2006089236	Aug 2006	WO
WO 2006086434	Aug 2006	WO
WO 2006116558	Nov 2006	WO
WO 2006128193	Nov 2006	WO
WO 2007047488	Apr 2007	WO
2007059252	May 2007	WO
2008013915	Jan 2008	WO
2008029296	Mar 2008	WO
2008070797	Jun 2008	WO
2008103722	Aug 2008	WO
2009033469	Mar 2009	WO
2009053497	Apr 2009	WO
2009091509	Jul 2009	WO
WO 2009091509	Jul 2009	WO
2010006627	Jan 2010	WO
WO 2010006627	Jan 2010	WO
WO 2010027485	Mar 2010	WO
WO 2010045297	Apr 2010	WO
2010073246	Jul 2010	WO
2010081033	Jul 2010	WO
2010121076	Oct 2010	WO
2011025972	Mar 2011	WO
2011069048	Jun 2011	WO
WO 2011069048	Jun 2011	WO
2011106137	Sep 2011	WO
2011111047	Sep 2011	WO
2011137531	Nov 2011	WO
2011143263	Nov 2011	WO
WO 2011144351	Nov 2011	WO
2011154942	Dec 2011	WO
2012011108	Jan 2012	WO
2012024428	Feb 2012	WO
2012036740	Mar 2012	WO
WO 2012048035	Apr 2012	WO
2012127309	Sep 2012	WO
2012177942	Dec 2012	WO
2013021374	Feb 2013	WO
2013021375	Feb 2013	WO
2013021384	Feb 2013	WO
2013059747	Apr 2013	WO
WO 2013059747	Apr 2013	WO
WO 2013072496	May 2013	WO
2013078497	Jun 2013	WO
2013128436	Jun 2013	WO
WO 2013078497	Jun 2013	WO
WO 2013114214	Aug 2013	WO
WO 2013175468	Nov 2013	WO
2014022124	Feb 2014	WO
2014121280	Aug 2014	WO
2014145338	Sep 2014	WO
WO 2014144937	Sep 2014	WO
2014164364	Oct 2014	WO
WO 2014164364	Oct 2014	WO
2015173794	Nov 2015	WO
2016093877	Jun 2016	WO
2016125160	Aug 2016	WO
WO 2016150806	Sep 2016	WO
2017223486	Dec 2017	WO
2018025260	Feb 2018	WO
2018106837	Jun 2018	WO
2018112429 41	Jun 2018	WO
2018118717	Jun 2018	WO
2018131042	Jul 2018	WO
2018131043	Jul 2018	WO
WO 2019027507	Feb 2019	WO
WO 2019195860	Oct 2019	WO
WO 20201677677	Aug 2020	WO
2021156866	Aug 2021	WO
2021186424	Sep 2021	WO

Non-Patent Literature Citations (183)

Entry
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 2009: Percutaneous Mitral Leaflet Repair: MitraClip Therapy for Mitral Regurgitation (Aug. 17, 2012) (8 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 2010: Deposition of Dr. Ivan Vesely, Ph.D. (Sep. 27, 2021) (170 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 2014: Second Declaration of Dr. Michael Sacks (Oct. 13, 2021) (28 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Patent Owner's Contingent Motion to Amend Under 37 C.F.R. § 42.121 (Oct. 13, 2021) (35 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Patent Owner's Response Pursuant to 37 C.F.R. § 42.120 (Oct. 13, 2021) (75 pages).
Fann, James I. et al., Beating Heart Catheter-Based Edge-to-Edge Mitral Valve Procedure in a Porcine Model: Efficacy and Healing Response, 110 Circulation, Aug. 2004, at 988 (6 pages).
Feldman, Ted et al., Percutaneous Mitral Repair With the MitraClip System: Safety and Midterm Durability in the Initial Everest Cohort, 54 J. Am. Coll. Cardiology, Aug. 2009, at 686 (9 pages).
Feldman, Ted et al., Percutaneous Mitral Valve Repair Using the Edge-to-Edge Technique: Six-Month Results of the Everest Phase I Clinical Trial, 46 J. Am. Coll. Cardiology, Dec. 2005, at 3134 (7 pages).
Maisano, Francesco et al., The Evolution From Surgery to Percutaneous Mitral Valve Interventions: The Role of the Edge-to-Edge Technique, 58 J. Am. Coll. Cardiology, Nov. 2011, at 2174 (9 pages).
Ando, Tomo et al., Iatrogenic Ventricular Septal Defect Following Transcatheter Aortic Valve Replacement: A Systematic Review, 25 Heart, Lung, and Circulation 968-74 (Apr. 22, 2016) (7 pages).
Batista, Randas J. V. et al., Partial Left Ventriculectomy to Treat End-Stage Heart Disease, 64 Annals Thoracic Surgery 634-38 (1997) (5 pages).
Beall, Jr., Arthur C et al., Clinical Experience with a Dacron Velour-Covered Teflon-Disc Mitral-Valve Prosthesis, 5 Annals Thoracic Surgery 402-10 (1968) (9 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 1014: Transcript of proceedings held May 20, 2021 (May 26, 2021) (21 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Exhibit 1015: Facilitate, Merriam-Webster.com, https://www. www.merriam-webster.com/dictionary/facilitate (accessed May 27, 2021) (5 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Paper 12: Petitioners' Authorized Reply to Patent Owner's Preliminary Response (May 27, 2021) (9 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Paper 13: Patent Owner's Authorized Surreply to Petitioner's Reply to Patent Owner's Preliminary Response (Jun. 4, 2021) (8 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Paper 16: Institution Decision (Jul. 20, 2021) (51 pages).
Fucci, Carlo et al., Improved Results with Mitral Valve Repair Using New Surgical Techniques, 9 Eur. J. Cardiothoracic Surgery 621-27 (1995) (7 pages).
Maisano, Francesco et al., The Edge-To-Edge Technique: A Simplified Method to Correct Mitral Insufficiency, 13 Eur. J. Cardiothoracic Surgery 240-46 (1998) (7 pages).
Poirier, Nancy et al., A Novel Repair for Patients with Atrioventricular Septal Defect Requiring Reoperation for Left Atrioventricular Valve Regurgitation, 18 Eur. J. Cardiothoracic Surgery 54-61 (2000) (8 pages).
Stone, Gregg W. et al., Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 1: Clinical Trial Design Principles, 66 J. Am. C. Cardiology 278-307 (2015) (30 pages).
Urena, Marina et al., Transseptal Transcatheter Mitral Valve Replacement Using Balloon-Expandable Transcatheter Heart Valves, JACC: Cardiovascular Interventions 1905-19 (2017) (15 pages).
An Office Action dated Jul. 27, 2022, which issued during the prosecution of U.S. Appl. No. 16/881,350.
An Office Action dated Sep. 21, 2022, which issued during the prosecution of U.S. Appl. No. 16/776,581.
An Office Action dated Jul. 20, 2022, which issued during the prosecution of U.S. Appl. No. 17/101,787.
An Office Action dated Sep. 16, 2022, which issued during the prosecution of U.S. Appl. No. 16/135,466.
An Office Action dated Aug. 1, 2022, which issued during the prosecution of European Patent Application No. 18826823.9.
European Search Report dated Sep. 6, 2022 which issued during the prosecution of Applicant's European App No. 22161862.2.
IPR2021-01051 Petitioners' Reply To Preliminary Guidance dated Aug. 2, 2022.
IPR2021-01051 Patent Owner's Sur-Reply To Petitioners' Reply To Preliminary Guidance dated Aug. 23, 2022.
An Office Action dated Aug. 5, 2022, which issued during the prosecution of U.S. Appl. No. 16/760,147.
An Office Action dated Sep. 8, 2022, which issued during the prosecution of U.S. Appl. No. 16/896,858.
An Office Action dated Jun. 6, 2018, which issued during the prosecution of UK Patent Application No. 1720803.4.
An Office Action dated Jun. 18, 2018, which issued during the prosecution of UK Patent Application No. 1800339.6.
An International Search Report and a Written Opinion both dated Jun. 20, 2018, which issued during the prosecution of Applicant's PCT/IL2018/050024.
USPTO AA dated Apr. 2, 2018 in connection with U.S. Appl. No. 14/763,004.
USPTO RR dated May 4, 2018 in connection with U.S. Appl. No. 15/872,501.
USPTO NFOA dated Jul. 26, 2018 in connection with U.S. Appl. No. 15/872,501.
USPTO NOA mailed Apr. 20, 2018 in connection with U.S. Appl. No. 15/878,206.
USPTO NFOA dated Apr. 20, 2018 in connection with U.S. Appl. No. 15/886,517.
USPTO NFOA dated Aug. 9, 2018 in connection with U.S. Appl. No. 15/899,858.
USPTO NFOA dated Aug. 9, 2018 in connection with U.S. Appl. No. 15/002,403.
USPTO NFOA dated Jun. 28, 2018 in connection with U.S. Appl. No. 29/635,658.
USPTO NFOA dated Jun. 28, 2018 in connection with U.S. Appl. No. 29/635,661.
USPTO NFOA dated Oct. 23, 2017 in connection with U.S. Appl. No. 14/763,004.
USPTO FOA dated Jan. 17, 2018 in connection with U.S. Appl. No. 14/763,004.
USPTO NFOA dated Feb. 7, 2018 in connection with U.S. Appl. No. 15/197,069.
USPTO NFOA dated Dec. 7, 2017 in connection with U.S. Appl. No. 15/213,791.
Interview Summary dated Feb. 8, 2018 in connection with U.S. Appl. No. 15/213,791.
USPTO NFOA dated Jan. 5, 2018 in connection with U.S. Appl. No. 15/541,783.
USPTO NFOA dated Feb. 2, 2018 in connection with U.S. Appl. No. 15/329,920.
Invitation to pay additional fees dated Jan. 2, 2018; PCT/IL2017/050849.
Invitation to Pay Additional Fees, dated Jun. 12, 2014; PCT/IL2014/050087.
Invitation to Pay Additional Fees, dated Sep. 28, 2017; PCT/IL2017/050873.
EESR dated Jun. 29, 2017; Appln. 11809374.9.
EESR dated Feb. 18, 2015: Appln. 12821522.5.
EPO Office Action dated Feb. 10, 2017; Appln. 12821522.5.
Great Britain Office Action dated Feb. 7, 2017; Appln. GB1613219.3.
IPRP issued Dec. 2, 2013; PCT/IL2011/000582.
IPRP issued Sep. 11, 2012; PCT/IL2011/00023.
IPRP issued Feb. 11, 2014; PCT/IL2012/000292.
IPRP issued Feb. 11, 2014 PCT/IL2012/000293.
ISR and WO mailed Dec. 5, 2011; PCT/IL11/00582.
ISR and WO mailed Mar. 17, 2014; PCT/IL13/50937.
ISR and WO mailed Oct. 13, 2011; PCT/IL11/00231.
ISR and WO mailed Feb. 6, 2013; PCT/IL2012/000292.
ISR and WO mailed Feb. 6, 2013; PCT/IL2012/000293.
ISR and WO mailed Sep. 4, 2014; PCT/IL2014/050067.
ISR and WO mailed Oct. 27, 2015; PCT/IL2015/050792.
ISR and WO mailed May 30, 2016; PCT/IL2016/050125.
Alexander Geha, et al., “Replacement of Degenerated Mitral and Aortic Bioprostheses Without Explantaton”, Ann. Thorac Surg. Jun. 2001; 72: 1509-1514.
Dominique Himbert MD; “Mitral Regurgitation and Stenosis from Bioprosthesis and Annuloplasty Failure: Transcatheter Approaches and Outcomes”. 24 pages, Oct. 28, 2013.
Saturn Project: A Novel Solution for Transcatheter Heart Valve Replacement Specifically Designed to Address Clinical Therapeutic Needs on Mitral Valve; Dec. 2016; 8 pages.
Frank Langer MD, et al; Ring plus String: “Papillary Muscle Repositioning as an Adjunctive Repair Technique for Ischemic Mitral Regurgitation”, J. Thoracic Cardiovasc. Surg. 133: 247-9, Jan. 2007.
Frank Langer MD, et al; “Ring+String Successful Repair Technique for Ischemic Mitral Regurgitation With Severe Leaflet Tethering”, Circulation 120[suppl 1]: S85-891. Sep. 2009.
Francesco Maisano, MD: “Valvetech Cardiovalve: Novel Design Feature and Clinical Update” 2015; TCR Presentation re Cardiovalve; 10 pages.
Giovanni Righini; Righini presentation EuroPCR May 2015 (Saturn)-(downloaded from: https://www.pcronline.com/Cases-resourcesimages/Resources/Course-videos-slides/2015/Cardiovascularinnovaton-pipeline-Mitral-and-tricuspid-valve-interventions).
John G Webb, et al; “Transcatheter Valve-in-Valve Implantation for Failed Bioprosthetic Heart Valves”, Circulation 2010; 1121;1848-1847; originally published online Apr. 12, 2010.
S. Willeke, et al; “Detachable shape-memory sewing ring for heart valves”, Artificial Organs, 16:294-297; 1992 (an abstract).
U.S. Appl. No. 61/283,819.
U.S. Appl. No. 61/492,449.
U.S. Appl. No. 61/515,372.
U.S. Appl. No. 61/525,281.
U.S. Appl. No. 61/537,276.
U.S. Appl. No. 61/555,160.
U.S. Appl. No. 61/588,892.
USPTO FOA dated Feb. 10, 2014; U.S. Appl. No. 13/033,852.
USPTO FOA dated Feb. 15, 2013; U.S. Appl. No. 12/840,463.
USPTO FOA dated Feb. 25, 2016; U.S. Appl. No. 14/522,987.
USPTO FOA dated Mar. 25, 2015; U.S. Appl. No. 12/840,463.
USPTO FOA dated Apr. 13, 2016; U.S. Appl. No. 14/626,267.
USPTO FOA dated May 23, 2014; U.S. Appl. No. 13/412,814.
USPTO FOA dated Jul. 18, 2013; U.S. Appl. No. 13/044,694.
USPTO FOA dated Jul. 23, 2013; U.S. Appl. No. 12/961,721.
USPTO FOA dated Sep. 12, 2013; U.S. Appl. No. 13/412,814.
USPTO NFOA dated Jan. 18, 2017; U.S. Appl. No. 14/626,267.
USPTO NFOA dated Jan. 21, 2016; U.S. Appl. No. 14/237,264.
USPTO NFOA dated Feb. 6, 2013; U.S. Appl. No. 13/412,814.
USPTO NFOA dated Feb. 7, 2017; U.S. Appl. No. 14/689,608.
USPTO NFOA dated Jun. 4, 2014; U.S. Appl. No. 12/840,463.
USPTO NFOA dated Jun. 17, 2014; U.S. Appl. No. 12/961,721.
USPTO NFOA dated Jun. 30, 2015; U.S. Appl. No. 14/522,987.
USPTO NFOA dated Jul. 2, 2014; U.S. Appl. No. 13/811,308.
USPTO NFOA dated Jul. 3, 2014; U.S. Appl. No. 13/033,852.
USPTO NFOA dated Aug. 2, 2013; U.S. Appl. No. 13/033,852.
USPTO NFOA dated Sep. 19, 2014; U.S. Appl. No. 13/044,694.
USPTO NFOA dated Nov. 8, 2013; U.S. Appl. No. 12/840,463.
USPTO NFOA dated Nov. 23, 2012; U.S. App. No. 13/033,852.
USPTO NFOA dated Nov. 27, 2015; U.S. Appl. No. 14/626,267.
USPTO NFOA dated Nov. 28, 2012; U.S. Appl. No. 12/961,721.
USPTO NFOA dated Dec. 10, 2015, U.S. Appl. No. 14/237,258.
USPTO NFOA dated Dec. 31, 2012; U.S. Appl. No. 13/044,694.
USPTO NFOA dated May 29, 2012; U.S. Appl. No. 12/840,463.
USPTO NOA dated May 20, 2016; U.S. Appl. No. 14/237,258.
USPTO NOA dated Jul. 6, 2017; U.S. Appl. No. 14/689,608.
USPTO NOA dated Aug. 18, 2017; U.S. Appl. No. 14/689,608.
USPTO NOA mailed Feb. 11, 2015; U.S. Appl. No. 13/033,852.
USPTO NOA mailed Mar. 10, 2015; U.S. Appl. No. 13/811,308.
USPTO Noa mailed Apr. 8, 2016; U.S. Appl. No. 14/237,258.
USPTO NOA mailed May 5, 2015; U.S. Appl. No. 12/840,463.
USPTO NOA dated May 10, 2016, U.S. Appl. No. 14/237,258.
USPTO NOA mailed May 22, 2017; U.S. Appl. No. 14/689,608.
USPTO NOA mailed Aug. 15, 2014; U.S. Appl. No. 13/412,814.
USPTO RR dated Jan. 20, 2016; U.S. Appl. No. 14/161,921.
USPTO RR dated Feb. 3, 2014; U.S. Appl. No. 13/811,308.
USPTO RR dated Apr. 21, 2017; U.S. Appl. No. 15/213,791.
USPTO RR dated Jul. 2, 2012; U.S. Appl. No. 13/033,852.
USPTO RR dated Aug. 13, 2012; U.S. Appl. No. 13/044,694.
USPTO RR dated Aug. 14, 2012; U.S. Appl. No. 12/961,721.
USPTO RR dated Aug. 28, 2015; U.S. Appl. No. 14/237,264.
USPTO RR dated Sep. 26, 2016; U.S. Appl. No. 14/763,004.
Sündermann, Simon H. et al., Feasibility of the Engager™ aortic transcatheter valve system using a flexible over-the-wire design, 42 European Journal of Cardio-Thoracic Surgery, Jun. 27, 2012, at e48 (5 pages).
Symetis S.A., Clinical Investigation Plan for Acurate Neo™ TA Delivery System, Protocol Jan. 2015, ver. 2, ClinicalTrials.gov Identifier NCT02950428, Sept. 8, 2015 (76 pages).
Tchetche, Didier et al., New-generation TAVI devices: description and specifications, 10 EuroIntervention (Supplement), Sep. 2014, at U90 (11 pages).
International Search Report dated Dec. 5, 2011, by the United States Patent and Trademark Office in PCT/IL2011/000582 (3 pages).
Written Opinion of the International Searching Authority dated Dec. 5, 2011, by the United States Patent and Trademark Office in PCT/IL2011/000582 (12 pages).
IPR2021-01051 Preliminary Guidance Patent Owner's Motion To Amend dated Jun. 24, 2022.
Ex Parte Quayle dated May 2, 2022, which issued during the prosecution of U.S. Appl. No. 16/879,952.
An International Search Report and a Written Opinion both dated May 3, 2022, which issued during the prosecution of Applicant's PCT/IL2021/051433.
An Office Action together with an English Summary dated May 7, 2022 which issued during the prosecution of Chinese Patent Application No. 201880058940.2.
Notice of Allowance dated May 4, 2022, which issued during the prosecution of U.S. Appl. No. 16/680,739.
An Office Action dated Jun. 28, 2022, which issued during the prosecution of U.S. Appl. No. 16/135,969.
An Office Action dated Jul. 8, 2022, which issued during the prosecution of U.S. Appl. No. 16/144,054.
IPR2021-00383 Final Written Decision dated Jul. 18, 2022.
Office Action dated Mar. 3, 2023 from the European Patent Office in Application No. 17 751 143.3.
Office Action dated Mar. 20, 2023 issued in U.S. Appl. No. 17/181,722.
U.S. Appl. No. 14/689,608, filed Apr. 17, 2015, published as 2015/0216661, issued as U.S. Pat. No. 9,763,657.
U.S. Appl. No. 15/691,032, filed Aug. 30, 2017, published as 2017/0360426, issued as U.S. Pat. No. 10,512,456.
U.S. Appl. No. 61/492,449, filed Jun. 2, 2011.
U.S. Appl. No. 12/840,463, filed Jul. 21, 2010, published as 2012/0022639, U.S. Pat. No. 9,132,009.
U.S. Appl. No. 13/033,852, filed Feb. 24, 2011, published as 2012/0022640, U.S. Pat. No. 8,992,604.
U.S. Appl. No. 13/811,308, filed Mar. 7, 2013, published as 2013/0172992, U.S. Pat. No. 9,017,399.
U.S. Appl. No. 16/040,831, filed Jul. 20, 2018, published as 2019/0015093, U.S. Pat. No. 10,531,872.
U.S. Appl. No. 16/740,659, filed Jan. 13, 2020, published as 2020/0146671, U.S. Pat. No. 10,925,595.
An Office Action dated Jan. 26, 2022, which issued during the prosecution of U.S. Appl. No. 16/888.210.
Notice of Allowance dated Jan. 31, 2022, which issued during the prosecution of U.S. Appl. No. 17/479.418.
An Office Action dated Mar. 18, 2022, which issued during the prosecution of U.S. Appl. No. 16/746,489.
Notice of Allowance dated Mar. 22, 2022, which issued during the prosecution of U.S. Appl. No. 17/366,711.
Notice of Allowance dated Mar. 4, 2022, which issued during the prosecution of U.S. Appl. No. 16/768,909.
An Office Action dated Dec. 9, 2021, which issued during the prosecution of U.S. Appl. No. 16/135,969.
An Office Action dated Jan. 24. 2022, which issued during the prosecution of U.S. Appl. No. 16/135,466.
An Office Action dated Apr. 11, 2022, which issued during the prosecution of U.S. Appl. No. 17/181,961.
IPR2021-00383 Preliminary Guidance dated Jan. 31, 2022.
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Paper 10: Decision Granting Institution Of Inter Partes Review (Dec. 10, 2021) (42 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Petitioners' Opposition to Patent Owner's Contingent Motion to Amend (Jan. 5, 2022) (32 pages).
Edwards Lifesciences Corp. v. Cardiovalve Ltd., IPR2021-00383, Petitioners' Reply to Patent Owner's Response (Jan. 5, 2022) (41 pages).
European Search Report dated Mar. 20, 2023 which issued during the prosecution of Applicant's European App No. 22204764.9.
An Office Action dated Apr. 14, 2023, which issued during the prosecution of U.S. Appl. No. 16/144,054.
An Office Action dated May 15, 2023, which issued during the prosecution of U.S. Appl. No. 16/656,790.
An Office Action dated May 16, 2023, which issued during the prosecution of U.S. Appl. No. 17/114,771.
An Office Action dated May 17, 2023, which issued during the prosecution of U.S. Appl. No. 17/466,785.
An Office Action dated May 25, 2023, which issued during the prosecution of U.S. Appl. No. 17/397,235.
An Office Action dated Sep. 29, 2022, which issued during the prosecution of U.S. Appl. No. 17/010,886.
An Office Action dated Sep. 29, 2022, which issued during the prosecution of U.S. Appl. No. 16/656,790.
An Office Action dated Nov. 2, 2022, which issued during the prosecution of U.S. Appl. No. 17/004,693.
An Office Action dated Nov. 28, 2022, which issued during the prosecution of U.S. Appl. No. 17/141,853.
An Office Action dated Oct. 19, 2022, which issued during the prosecution of U.S. Appl. No. 17/875,589.
An Office Action dated Oct. 26, 2022, which issued during the prosecution of U.S. Appl. No. 16/746,489.
U.S. Appl. No. 12/840,463, filed Jul. 21, 2010, published as 2012/0022639, issued as U.S. Pat. No. 9,132,009.
U.S. Appl. No. 13/033,852, filed Feb. 24, 2011, published as 2012/0022640, issued as U.S. Pat. No. 8,992,604.
U.S. Appl. No. 13/811,308, filed Mar. 7, 2013, published as 2013/0172992, issued as U.S. Pat. No. 9,017,399.
U.S. Appl. No. 16/040,831, filed Jul. 20, 2018, published as 2019/0015093, issued as U.S. Pat. No. 10,531,872.
U.S. Appl. No. 16/740,659, filed Jan. 13, 2020, published as 2020/0146671, issued as U.S. Pat. No. 10,925,595.

Related Publications (1)

	Number	Date	Country
	20210169467 A1	Jun 2021	US

Provisional Applications (1)

	Number	Date	Country
	61492449	Jun 2011	US

Continuations (5)

	Number	Date	Country
Parent	16740659	Jan 2020	US
Child	17181961		US
Parent	16040831	Jul 2018	US
Child	16740659		US
Parent	15691032	Aug 2017	US
Child	16040831		US
Parent	14689608	Apr 2015	US
Child	15691032		US
Parent	13811308		US
Child	14689608		US

Continuation in Parts (3)

	Number	Date	Country
Parent	13033852	Feb 2011	US
Child	13811308		US
Parent	12840463	Jul 2010	US
Child	13033852		US
Parent	12840463	Jul 2010	US
Child	PCT/IL2011/000582		US

Valve prosthesis configured for deployment in annular spacer

Information

Patent Number

Date Filed

Date Issued

Inventors

Original Assignees

Examiners

Agents

CPC

Field of Search

CPC

International Classifications

Disclaimer

Term Extension

Abstract

Description

Claims

CROSS-REFERENCES TO RELATED APPLICATIONS

US Referenced Citations (1171)

Foreign Referenced Citations (91)

Non-Patent Literature Citations (183)

Related Publications (1)

Provisional Applications (1)

Continuations (5)

Continuation in Parts (3)