Prosthetic valve with aligned inner and outer frames

Embodiments of the present disclosure are directed to prosthetic valves and methods of use thereof. In one implementation, an expandable prosthetic valve for implantation within a native mitral valve may be provided. The prosthetic valve may be expandable from a radially contracted state to a radially expanded state. The prosthetic valve may include an expandable outer frame and an inner frame with tissue anchors extending therefrom. The outer and inner frames may be configured and interconnected such that ventricular ends of the inner and outer frames are substantially aligned when the frames are in the radially expanded state and are not substantially aligned when the frames are in the radially contracted state.

FIELD OF THE INVENTION

Some embodiments of the present invention relate in general to valve replacement. More specifically, some embodiments of the present invention relate to prosthetic valves for replacement of a cardiac valve.

BACKGROUND

Ischemic heart disease causes regurgitation of a heart valve by the combination of ischemic dysfunction of the papillary muscles, and the dilatation of the ventricle that is present in ischemic heart disease, with the subsequent displacement of the papillary muscles and the dilatation of the valve annulus.

Dilatation of the annulus of the 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.

SUMMARY OF THE INVENTION

For some embodiments of the present invention, an implant is provided having a tubular portion, an upstream support portion and one or more flanges. The implant is percutaneously deliverable to a native heart valve in a compressed state, and is expandable at the native valve. The implant and its delivery system facilitate causing the upstream support portion and the flanges to protrude radially outward from the tubular portion without expanding the tubular portion. Expansion of the tubular portion brings the upstream support portion and the flanges closer together, for securing the implant at the native valve by sandwiching tissue of the native valve between the upstream support portion and the flanges.

In accordance with an embodiment of the present invention, an apparatus is provided for use with a native valve that is disposed between an atrium and a ventricle of a heart of a subject, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the tubular portion defining a plurality of valve-frame coupling elements disposed circumferentially around the longitudinal axis; a plurality of prosthetic leaflets, coupled to the frame, disposed within the lumen, and arranged to provide unidirectional flow of blood from an upstream end of the lumen to a downstream end of the lumen; an outer frame: including a ring defined by a pattern of alternating peaks and troughs, the peaks being longitudinally closer to the upstream end than to the downstream end, and the troughs being longitudinally closer to the downstream end than to the upstream end, and the pattern of the ring having an amplitude longitudinally between the peaks and the troughs, including a plurality of legs, each of the legs coupled to the ring at a respective trough, and shaped to define a plurality of outer-frame coupling elements, each of the outer-frame coupling elements (i) coupled to the ring at a respective peak, and (ii) fixed with respect to a respective valve-frame coupling element, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and the fixation of the outer-frame coupling elements to the valve-frame coupling elements is such that compression of the tubular portion from the expanded state toward the compressed state such that the valve-frame coupling elements pull the outer-frame coupling elements radially inward: (i) reduces a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements, and (ii) increases the amplitude of the pattern of the ring.

In an embodiment, the ring circumscribes the tubular portion.

In an embodiment, the valve-frame coupling elements are disposed circumferentially around the longitudinal axis between the upstream end and the downstream end but not at the upstream end nor at the downstream end.

In an embodiment, the upstream support portion includes one or more fabric pockets disposed circumferentially, each pocket of the one or more pockets having an opening that faces a downstream direction.

In an embodiment, the outer frame is coupled to the valve frame only via the fixation of the outer-frame coupling elements to the respective valve-frame coupling elements.

In an embodiment, the apparatus further includes an upstream support portion that includes a plurality of arms that extend radially from the tubular portion, and the upstream support portion has (i) a constrained-arm state, and (ii) a released-arm state in which the arms extend radially outward from the tubular portion, each leg has a tissue-engaging flange that has (i) a constrained-flange state, and (ii) a released-flange state in which the flange extends radially outward from the tubular portion, and the apparatus has an intermediate state in which (i) the tubular portion is in its compressed state, (ii) the upstream support portion is in its released-arm state, and (iii) the legs are in their released-flange state.

In an embodiment, the apparatus includes an implant that includes the valve frame, the leaflets, and the outer frame, and the apparatus further includes a tool: including a delivery capsule dimensioned (i) to house and retain the implant in a compressed state of the implant in which (a) the tubular portion is in its compressed state, (b) the upstream support portion is in its constrained-arm state, and (c) the legs are in their constrained-flange state, and (ii) to be advanced percutaneously to the heart of the subject while the implant is housed and in its compressed state, and operable from outside the subject to: transition the implant from its compressed state into the intermediate state while retaining the tubular portion in its compressed state, and subsequently, expand the tubular portion toward its expanded state.

In an embodiment, the tool is operable from outside the subject to transition the implant from its compressed state into the intermediate state by (i) releasing the legs into their released-flange state, while retaining the tubular portion in its compressed state, and (ii) subsequently, releasing the upstream support portion into its released-arm state, while retaining the tubular portion in its compressed state.

In an embodiment, the tool is operable from outside the subject to transition the implant from its compressed state into the intermediate state by (i) releasing the upstream support portion into its released-arm state, while retaining the tubular portion in its compressed state, and (ii) subsequently, releasing the legs into their released-flange state, while retaining the tubular portion in its compressed state.

In an embodiment, the fixation of the outer-frame coupling elements to the valve-frame coupling elements is such that, when the apparatus is in its intermediate state, expansion of the tubular portion from its compressed state toward its expanded state moves the flanges longitudinally away from the valve-frame coupling elements.

In an embodiment, the fixation of the outer-frame coupling elements to the valve-frame coupling elements is such that, when the apparatus is in its intermediate state, expansion of the tubular portion from a compressed state toward an expanded state reduces the amplitude of the pattern of the ring and passes the flanges between the arms.

In an embodiment, the upstream support portion further includes a covering that covers the arms to form an annular shape in the released-arm state, and, when the apparatus is in its intermediate state, expansion of the tubular portion from its compressed state toward its expanded state presses the flanges onto the covering.

In an embodiment, in the compressed state of the tubular portion, a downstream end of each leg of the tubular portion is longitudinally closer than the valve-frame coupling elements to the downstream end, and the flange of each leg is disposed longitudinally closer than the valve-frame coupling elements to the upstream end.

In an embodiment, in the expanded state of the tubular portion, the downstream end of each leg is longitudinally closer than the valve-frame coupling elements to the downstream end, and the flange of each leg is disposed longitudinally closer than the valve-frame coupling elements to the upstream end.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve of a heart of a subject is provided, the apparatus having an implant that includes: a valve frame that includes a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the tubular portion having an upstream end, a downstream end, a longitudinal length therebetween, and a diameter transverse to the longitudinal axis; a valve member, coupled to the tubular portion, disposed within the lumen, and arranged to provide unidirectional upstream-to-downstream flow of blood through the lumen; an upstream support portion, coupled to the tubular portion; and an outer frame, coupled to the tubular portion, and including a tissue-engaging flange, and: the implant has a first state and a second state, in both the first state and the second state, (i) the upstream support portion extends radially outward from the tubular portion, and (ii) the tissue-engaging flange extends radially outward from the tubular portion, and the tubular portion, the upstream support portion, and the outer frame are arranged such that transitioning of the implant from the first state toward the second state: increases the diameter of the tubular portion by a diameter-increase amount, decreases the length of the tubular portion by a length-decrease amount, and moves the flange a longitudinal distance toward or toward-and-beyond the upstream support portion, the distance being greater than the length-decrease amount.

In an embodiment of the present invention, the tubular portion, the upstream support portion, and the outer frame may be arranged such that the longitudinal distance is more than 20 percent greater than the length-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, and the outer frame may be arranged such that the longitudinal distance is more than 30 percent greater than the length-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, and the outer frame may be arranged such that the longitudinal distance is more than 40 percent greater than the length-decrease amount.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve that is disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis; a plurality of prosthetic leaflets, coupled to the frame, disposed within the lumen, and arranged to provide unidirectional flow of blood from an upstream end of the lumen to a downstream end of the lumen; an outer frame, including: a ring defined by a pattern of alternating peaks and troughs: the peaks being longitudinally closer than the troughs to the upstream end, the peaks being fixed to respective sites of the tubular portion at respective coupling points disposed circumferentially around the longitudinal axis, and the pattern of the ring having an amplitude longitudinally between the peaks and the troughs; and a plurality of legs, each of the legs coupled to the ring at a respective trough, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and the fixation of the peaks to the respective sites of the tubular portion is such that compression of the tubular portion from the expanded state toward the compressed state such that the respective sites of the tubular portion pull the peaks radially inward via radially-inward tension on the coupling points: (i) reduces a circumferential distance between each of the coupling points and its adjacent coupling points, and (ii) increases the amplitude of the pattern of the ring.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the peaks to the respective sites of the tubular portion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve that is disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the valve frame defining a plurality of valve-frame coupling elements disposed circumferentially around the longitudinal axis; a plurality of prosthetic leaflets, coupled to the frame, disposed within the lumen, and arranged to provide unidirectional flow of blood from an upstream end of the lumen to a downstream end of the lumen; an outer frame: including a ring defined by a pattern of alternating peaks and troughs, the peaks being longitudinally closer to the upstream end than to the downstream end, and the troughs being longitudinally closer to the downstream end than to the upstream end, and the pattern of the ring having an amplitude longitudinally between the peaks and the troughs, including a plurality of legs, each of the legs coupled to the ring at a respective trough, and shaped to define a plurality of outer-frame coupling elements, each of the outer-frame coupling elements (i) coupled to the ring at a respective peak, and (ii) fixed with respect to a respective valve-frame coupling element, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and the fixation of the outer-frame coupling elements with respect to the valve-frame coupling elements is such that compression of the tubular portion from the expanded state toward the compressed state (i) pulls the outer-frame coupling elements radially inward via radially-inward pulling of the valve-frame coupling elements on the outer-frame coupling elements, (ii) reduces a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements, and (iii) increases the amplitude of the pattern of the ring, without increasing a radial gap between the valve frame and the ring by more than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the outer-frame coupling elements to the respective valve-frame coupling elements.

There is further provided, in accordance with an embodiment of the present invention, an apparatus for use with a native valve that is disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis; a plurality of prosthetic leaflets, coupled to the frame, disposed within the lumen, and arranged to provide unidirectional flow of blood from an upstream end of the lumen to a downstream end of the lumen; an outer frame, including: a ring defined by a pattern of alternating peaks and troughs: the peaks being longitudinally closer than the troughs to the upstream end, the peaks being fixed to respective sites of the tubular portion at respective coupling points disposed circumferentially around the longitudinal axis, and the pattern of the ring having an amplitude longitudinally between the peaks and the troughs; and a plurality of legs, each of the legs coupled to the ring at a respective trough, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and the fixation of the peaks to the respective sites of the tubular portion is such that compression of the tubular portion from the expanded state toward the compressed state (i) pulls the peaks radially inward via radially-inward pulling of the respective sites of the tubular portion on the peaks, (ii) reduces a circumferential distance between each of the coupling points and its adjacent coupling points, and (iii) increases the amplitude of the pattern of the ring, without increasing a radial gap between the valve frame and the ring by more than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the peaks to the respective sites of the tubular portion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the tubular portion having an upstream end, a downstream end, and defining a plurality of valve-frame coupling elements disposed circumferentially around the longitudinal axis between the upstream end and the downstream end but not at the upstream end nor at the downstream end; a plurality of prosthetic leaflets, disposed within the lumen, and arranged to provide unidirectional flow of blood through the lumen; an outer frame: including a ring defined by a pattern of alternating peaks and troughs, the peaks being longitudinally closer to the upstream end than to the downstream end, and the troughs being longitudinally closer to the downstream end than to the upstream end, including a plurality of legs, each of the legs coupled to the ring at a respective trough, and shaped to define a plurality of outer-frame coupling elements, each of the outer-frame coupling elements (i) coupled to the ring at a respective peak, and (ii) fixed with respect to a respective valve-frame coupling element at a respective coupling point, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and expansion of the tubular portion from the compressed state toward the expanded state (i) increases a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements, and (ii) moves the plurality of legs in a longitudinally upstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the outer-frame coupling elements to the respective valve-frame coupling elements.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a valve frame, including a tubular portion that circumscribes a longitudinal axis of the valve frame so as to define a lumen along the axis, the tubular portion having an upstream end and a downstream end; a plurality of prosthetic leaflets, disposed within the lumen, and arranged to provide unidirectional flow of blood through the lumen; an outer frame, including: a ring defined by a pattern of alternating peaks and troughs: the peaks being longitudinally closer than the troughs to the upstream end, the peaks being fixed to respective sites of the tubular portion at respective coupling points disposed circumferentially around the longitudinal axis between the upstream end and the downstream end but not at the upstream end nor the downstream end; and a plurality of legs, each of the legs coupled to the ring at a respective trough, and: the tubular portion has (i) a compressed state in which the tubular portion has a compressed diameter, and (ii) an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and expansion of the tubular portion from the compressed state toward the expanded state (i) increases a circumferential distance between each of the coupling points and its adjacent coupling points, and (ii) moves the plurality of legs in a longitudinally upstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame only via the fixation of the peaks to the respective sites of the tubular portion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve of a heart of a subject is provided, the apparatus including: a frame assembly, having an upstream end and a downstream end, and a central longitudinal axis therebetween, and including: a valve frame, including: a tubular portion having an upstream end and a downstream end, and shaped to define a lumen therebetween, and an upstream support portion, extending from the upstream end of the tubular portion; and at least one leg, coupled to the valve frame at a coupling point, and having a tissue-engaging flange; and a valve member disposed within the lumen, and configured to facilitate one-way liquid flow through the lumen from the upstream end of the tubular portion to the downstream end of the tubular portion, and the frame assembly: has a compressed state, for percutaneous delivery to the heart, in which the tubular portion has a compressed diameter, is biased to assume an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and is configured such that increasing the diameter of the tubular portion toward the expanded diameter causes longitudinal movement: of the upstream support portion toward the coupling point, and of the tissue-engaging flange away from the coupling point.

In an embodiment: the apparatus includes an implant that includes the frame assembly and the valve member, and the apparatus further includes a tool: including a delivery capsule dimensioned (i) to house and retain the implant in the compressed state, and (ii) to be advanced percutaneously to the heart of the subject while the implant is housed and in the compressed state, and operable from outside the subject to facilitate an increase of the diameter of the tubular portion from the compressed diameter toward the expanded diameter such that the increase of the diameter actuates longitudinal movement: of the upstream support portion toward the coupling point, and of the tissue-engaging flange away from the coupling point.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes longitudinal movement of the upstream end of the tubular portion toward the coupling point.

In an embodiment, the coupling point is disposed closer to the downstream end of the frame assembly than are either the tissue-engaging flange or the upstream support portion.

In an embodiment, in the expanded state of the frame assembly, the leg extends away from the central longitudinal axis.

In an embodiment, the expanded state of the frame assembly may be a fully-expanded state of the frame assembly, the leg is expandable into an expanded state of the leg, independently of increasing the diameter of the tubular portion, and in the expanded state of the leg, the leg extends away from the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, the leg extends away from the central longitudinal axis, and in the compressed state of the frame assembly, the leg is generally parallel with the central longitudinal axis.

In an embodiment, the frame assembly may be configured such that the longitudinal movement of the tissue-engaging flange away from the coupling point is a translational movement of the tissue-engaging flange that does not include rotation of the tissue-engaging flange.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes 1-20 mm of longitudinal movement of the tissue-engaging flange away from the coupling point.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes 1-20 mm of longitudinal movement of the upstream support portion toward the coupling point.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state reduces a distance between the upstream support portion and the tissue-engaging flange by 5-30 mm.

In an embodiment, the frame assembly may be configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state moves the tissue-engaging flange longitudinally past the upstream support portion.

In an embodiment, the tubular portion may be defined by a plurality of cells of the valve frame, and increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state: includes (i) increasing a width, orthogonal to the longitudinal axis of the frame assembly, of each cell, and (ii) reducing a height, parallel with the longitudinal axis of the frame assembly, of each cell, and causes longitudinal movement of the upstream support portion toward the coupling point by reducing a height, parallel with the longitudinal axis of the frame assembly, of the tubular portion, by reducing the height of each cell.

In an embodiment, the leg is disposed on an outside of the tubular portion.

In an embodiment, the at least one leg includes a plurality of legs, the coupling point includes a plurality of coupling points, and the frame assembly includes a leg frame that circumscribes the tubular portion, includes the plurality of legs, and is coupled to the valve frame at the plurality of coupling points, such that the plurality of legs is distributed circumferentially around the tubular portion.

In an embodiment, the plurality of coupling points is disposed circumferentially around the frame assembly on a transverse plane that is orthogonal to the longitudinal axis of the frame assembly.

In an embodiment, the plurality of legs may be coupled to the valve frame via a plurality of struts, each strut having a first end that is coupled to a leg of the plurality of legs, and a second end that is coupled to a coupling point of the plurality of coupling points, in the compressed state of the frame assembly, being disposed at a first angle in which the first end is disposed closer to the downstream end of the frame assembly than is the second end, and being deflectable with respect to the coupling point of the plurality of coupling points, such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes the strut to deflect to a second angle in which the first end is disposed further from the downstream end of the frame assembly than is the first end in the compressed state of the frame assembly.

In an embodiment, the leg frame may be structured such that each leg of the plurality of legs is coupled to two struts of the plurality of struts, and two struts of the plurality of struts are coupled to each coupling point of the plurality of coupling points.

In an embodiment, the leg may be coupled to the valve frame via a strut, the strut having a first end that is coupled to the leg, and a second end that is coupled to the coupling point, in the compressed state of the frame assembly, being disposed at a first angle in which the first end is disposed closer to the downstream end of the frame assembly than is the second end, and being deflectable with respect to the coupling point, such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes the strut to deflect to a second angle in which the first end is disposed further from the downstream end of the frame assembly than is the first end in the compressed state of the frame assembly.

In an embodiment, the at least one leg includes at least a first leg and a second leg.

In an embodiment, the first leg and the second leg are both coupled to the valve frame at the coupling point.

In an embodiment, the first leg may be coupled to the coupling point via a respective first strut, and the second leg is coupled to the coupling point via a respective second strut.

In an embodiment, the first and second legs, the first and second struts, and the coupling point are arranged such that, in the expanded state of the frame assembly: the coupling point is disposed, circumferentially with respect to the tubular portion, between the first strut and the second strut, the first strut is disposed, circumferentially with respect to the tubular portion, between the coupling point and the first leg, and the second strut is disposed, circumferentially with respect to the tubular portion, between the coupling point and the second leg.

In an embodiment, the coupling point includes at least a first coupling point and a second coupling point.

In an embodiment, the leg is coupled to the valve frame at the first coupling point and at the second coupling point.

In an embodiment, the leg may be coupled to the first coupling point via a respective first strut, and to the second coupling point via a respective second strut.

In an embodiment, the first and second legs, the first and second struts, and the coupling point are arranged such that, in the expanded state of the frame assembly: the leg is disposed, circumferentially with respect to the tubular portion, between the first strut and the second strut, the first strut is disposed, circumferentially with respect to the tubular portion, between the leg and the first coupling point, and the second strut is disposed, circumferentially with respect to the tubular portion, between the leg and the second coupling point.

In an embodiment, in the expanded state of the frame assembly, the upstream support portion extends radially outward from the tubular portion.

In an embodiment, the expanded state of the frame assembly is a fully-expanded state of the frame assembly, the upstream support portion is expandable into an expanded state of the upstream support portion, independently of increasing the diameter of the tubular portion, and in the expanded state of the upstream support portion, the upstream support portion extends radially outward from the tubular portion.

In an embodiment, in the compressed state of the frame assembly, the upstream support portion is generally tubular, collinear with the tubular portion, and disposed around the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, an inner region of the upstream support portion extends radially outward from the tubular portion at a first angle with respect to the tubular portion, and an outer region of the upstream support portion extends, from the inner region of the upstream support portion, further radially outward from the tubular portion at a second angle with respect to the tubular portion, the second angle being smaller than the first angle.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve of a heart of a subject is provided, the apparatus including a frame assembly, having an upstream end and a downstream end, and a central longitudinal axis therebetween, and including: a valve frame, including: a tubular portion having an upstream end and a downstream end, and shaped to define a lumen therebetween, and an upstream support portion, extending from the upstream end of the tubular portion; and at least one leg, coupled to the valve frame at a coupling point, and having a tissue-engaging flange; and a valve member disposed within the lumen, and configured to facilitate one-way liquid flow through the lumen from the upstream end of the tubular portion to the downstream end of the tubular portion, and the frame assembly: has a compressed state, for percutaneous delivery to the heart, in which the tubular portion has a compressed diameter, is biased to assume an expanded state in which the tubular portion has an expanded diameter that is greater than the compressed diameter, and is configured such that reducing the diameter of the tubular portion toward the compressed diameter causes longitudinal movement of the upstream support portion away from the coupling point, and of the tissue-engaging flange toward the coupling point.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve of a heart of a subject is provided, the apparatus including a frame assembly, having an upstream end and a downstream end, and a central longitudinal axis therebetween, including: a valve frame, including: a tubular portion having an upstream end and a downstream end, and shaped to define a lumen therebetween, and an upstream support portion, extending from the upstream end of the tubular portion; and at least one leg, coupled to the valve frame at a coupling point, and having a tissue-engaging flange; and a valve member disposed within the lumen, and configured to facilitate one-way liquid flow through the lumen from the upstream end of the tubular portion to the downstream end of the tubular portion, and the frame assembly: has a compressed state, for percutaneous delivery to the heart, is intracorporeally expandable into an expanded state in which a diameter of the tubular portion is greater than in the compressed state, and is configured such that increasing the diameter of the tubular portion by expanding the frame assembly toward the expanded state causes longitudinal movement of the tissue-engaging flange away from the coupling point.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve of a heart of a subject is provided, the apparatus including a frame assembly, having an upstream end and a downstream end, and a central longitudinal axis therebetween, and including: an inner frame including an inner-frame tubular portion that circumscribes the central longitudinal axis, has an upstream end and a downstream end, and defines a channel therebetween, the inner frame defining a plurality of inner-frame couplings disposed circumferentially at a longitudinal location of the inner frame, an outer frame including an outer-frame tubular portion that coaxially circumscribes at least a portion of the inner-frame tubular portion, the outer frame defining a plurality of outer-frame couplings disposed circumferentially at a longitudinal location of the outer frame, and a plurality of connectors, each connector connecting a respective inner-frame coupling to a respective outer-frame coupling; a liner, disposed over at least part of the inner-frame tubular portion; and a plurality of prosthetic leaflets, coupled to the inner-frame tubular portion and disposed within the channel, and: the frame assembly: (i) is compressible by a radially-compressive force into a compressed state in which the inner frame is in a compressed state thereof and the outer frame is in a compressed state thereof, (ii) is configured, upon removal of the radially-compressive force, to automatically expand into an expanded state thereof in which the inner frame is in an expanded state thereof and the outer frame is in an expanded state thereof, in the expanded state of the frame assembly, the prosthetic leaflets are configured to facilitate one-way fluid flow, in a downstream direction, through the channel, and the connection of the inner-frame couplings to the respective outer-frame couplings is such that expansion of the frame assembly from the compressed state to the expanded state causes the inner-frame tubular portion to slide longitudinally in a downstream direction with respect to the outer-frame tubular portion.

In accordance with an embodiment of the present invention, an apparatus for use with a native valve disposed between an atrium and a ventricle of a heart of a subject is provided, the apparatus including: a tubular portion, having an upstream portion that includes an upstream end, and a downstream portion that includes a downstream end, and shaped to define a lumen between the upstream portion and the downstream portion; a plurality of prosthetic leaflets, disposed within the lumen, and arranged to provide unidirectional flow of blood from the upstream portion to the downstream portion; an annular upstream support portion: having an inner portion that extends radially outward from the upstream portion, and including one or more fabric pockets disposed circumferentially around the inner portion, each pocket of the one or more pockets having an opening that faces a downstream direction.

In an embodiment, the upstream support portion includes (i) a plurality of arms that extend radially outward from the tubular portion, and (ii) a covering, disposed over the plurality of arms, each arm has (i) a radially-inner part at the inner portion of the upstream support portion, and (ii) a radially-outer part at the outer portion of the upstream support portion, at the inner portion of the upstream support portion, the covering is closely-fitted between the radially-inner parts of the arms, and at the outer portion of the upstream support portion, the pockets are formed by the covering being loosely-fitted between the radially-outer parts of the arms.

In an embodiment, the upstream support portion includes (i) a plurality of arms that extend radially outward from the tubular portion, and (ii) a covering, disposed over the plurality of arms, each arm has (i) a radially-inner part at the inner portion of the upstream support portion, and (ii) a radially-outer part at the outer portion of the upstream support portion, the radially-outer part being more flexible than the radially-inner part.

In an embodiment, the upstream support portion includes (i) a plurality of arms that extend radially outward from the tubular portion, and (ii) a covering, disposed over the plurality of arms, each arm has (i) a radially-inner part at the inner portion of the upstream support portion, and (ii) a radially-outer part at the outer portion of the upstream support portion, at the outer portion of the upstream support portion, the pockets are formed by each arm curving to form a hook shape.

In an embodiment, each pocket may be shaped and arranged to billow in response to perivalvular flow of blood in an upstream direction.

In an embodiment, the apparatus may be configured to be transluminally delivered to the heart and implanted at the native valve by expansion of the apparatus, such that the upstream support portion is disposed in the atrium and the tubular portion extends from the upstream support portion into the ventricle, and each pocket is shaped and arranged such that perivalvular flow of blood in an upstream direction presses the pocket against tissue of the atrium.

In accordance with an embodiment of the present invention, an apparatus is provided including a plurality of prosthetic valve leaflets; and a frame assembly, including: a tubular portion defined by a repeating pattern of cells, the tubular portion extending circumferentially around a longitudinal axis so as to define a longitudinal lumen, the prosthetic valve leaflets coupled to the inner frame and disposed within the lumen; an outer frame, including a plurality of legs, distributed circumferentially around the tubular portion, each leg having a tissue-engaging flange; an upstream support portion that includes a plurality of arms that extend radially outward from the tubular portion; and a plurality of appendages, each having a first end that defines a coupling element via which the tubular portion is coupled to the outer frame, and a second end; and the frame assembly defines a plurality of hubs, distributed circumferentially around the longitudinal axis on a plane that is transverse to the longitudinal axis, each hub defined by convergence and connection of, (i) two adjacent cells of the tubular portion, (ii) an arm of the plurality of arms, and (iii) an appendage of the plurality of appendages.

In an embodiment, each hub has six radiating spokes, two of the six spokes being part of a first cell of the two adjacent cells, two of the six spokes being part of a second cell of the two adjacent cells, one of the six spokes being the arm, and one of the six spokes being the second end of the appendage.

In an embodiment, the appendages are in-plane with the tubular portion.

In an embodiment, the appendages are in-plane with the outer frame.

In accordance with an embodiment of the present invention, a method for use with a native valve of a heart of a subject is provided, the method including percutaneously advancing to heart, an implant: including a valve frame, a valve member disposed within a lumen defined by the valve frame, and at least one leg, coupled to the valve frame at a coupling point, and having an upstream end, a downstream end, and a central longitudinal axis therebetween; positioning the implant within the heart such that a tissue-engaging flange of the leg is disposed downstream of the valve, and thereafter causing the flange to protrude radially outward from the axis; subsequently, while an upstream support portion of the valve frame is disposed upstream of the valve, causing the upstream support portion to protrude radially outward from the axis, such that tissue of the valve is disposed between the upstream support portion and the flange; and subsequently, sandwiching the tissue between the upstream support portion and the flange by reducing a distance between the upstream support portion and the flange by causing longitudinal movement (i) of the upstream support portion toward the coupling point, and (ii) of the tissue-engaging flange away from the coupling point.

In an embodiment, causing the longitudinal movement (i) of the upstream support portion toward the coupling point, and (ii) of the tissue-engaging flange away from the coupling point, includes causing the longitudinal movement by increasing a diameter of the lumen.

In accordance with an embodiment of the present invention, a method for use with a native valve of a heart of a subject is provided, the method including percutaneously advancing to heart, an implant: including a valve frame, a valve member disposed within a lumen defined by the valve frame, and at least one leg, coupled to the valve frame at a coupling point, and having an upstream end, a downstream end, and a central longitudinal axis therebetween; positioning the implant within the heart such that an upstream support portion of the valve frame is disposed upstream of the valve, and thereafter causing the upstream support portion to protrude radially outward from the axis; subsequently, while a tissue-engaging flange of the leg is disposed downstream of the valve, causing the tissue-engaging flange to protrude radially outward from the axis, such that tissue of the valve is disposed between the upstream support portion and the flange; and subsequently, sandwiching the tissue between the upstream support portion and the flange by reducing a distance between the upstream support portion and the flange by causing longitudinal movement (i) of the upstream support portion toward the coupling point, and (ii) of the tissue-engaging flange away from the coupling point.

In an embodiment, causing the longitudinal movement (i) of the upstream support portion toward the coupling point, and (ii) of the tissue-engaging flange away from the coupling point, includes causing the longitudinal movement by increasing a diameter of the lumen.

In accordance with an embodiment of the present invention, a method for use with a native valve of a heart of a subject is provided, the method including: percutaneously advancing an implant to the heart, the implant having an upstream end, a downstream end, and a central longitudinal axis therebetween, and including a tubular portion, an upstream support portion, and a plurality of tissue-engaging flanges; positioning the implant within the heart such that the upstream support portion is disposed upstream of the valve, positioning the implant within the heart such that the tissue-engaging flanges are disposed downstream of the valve, without increasing a diameter of the tubular portion: causing the upstream support portion to extend radially outward from the axis so as to have a first support-portion span, and causing the flanges to extend radially outward from the axis so as to have a first flange span; and subsequently, causing the upstream support portion and the flanges move toward each other by at least 5 mm by increasing a diameter of the tubular portion such that: the upstream support portion extends radially outward so as to have a second support-portion span, the first support-portion span being at least 40 percent as great as the second support-portion span, and the flanges extend radially outward so as to have a second flange span, the first flange span being at least 30 percent as great as the second flange span.

There is further provided, in accordance with an application of the present invention, a method for use with a native valve of a heart of a subject, the method including: percutaneously advancing an implant to the heart, the implant: having an upstream end, a downstream end, and a central longitudinal axis therebetween, and including a tubular portion, an upstream support portion, and a plurality of tissue-engaging flanges; positioning the implant within the heart such that the upstream support portion is disposed upstream of the valve, positioning the implant within the heart such that the tissue-engaging flanges are disposed downstream of the valve, without increasing a diameter of the tubular portion: causing the upstream support portion to extend radially outward from the axis, and causing the flanges to extend radially outward from the axis so as to have a first flange span; and subsequently, by increasing a diameter of the tubular portion: causing the upstream support portion and the flanges move toward each other by at least 5 mm, causing the upstream support portion to move further radially outward from the axis, and causing each flange of the plurality of flanges to translate radially outward so as to have a second flange span that is greater than the first flange span.

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

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made toFIGS. 1A-Band2A-E, which are schematic illustrations of an implant20(alternatively, “prosthetic valve20”) for use with a native valve of a heart of a subject, in accordance with some embodiments of the invention. Prosthetic valve20comprises a frame assembly22that has an upstream end24(alternatively, “atrial end24”), a downstream end26(alternatively, “ventricular end26”), and a central longitudinal axis ax1therebetween. The term “atrial end” may refer to an end of a given feature configured to be situated closest to an atrium of the heart when prosthetic valve20is implanted therein. For example, inFIGS. 1A, 1B, 2A-E, and4A-F, the atrial end of prosthetic valve20may be the top end of prosthetic valve20. Similarly, the term “ventricular end” may refer to an end of a given feature configured to be situated closest to a ventricle of the heart when prosthetic valve20is implanted therein. For example, inFIGS. 1A, 1B, 2A-E, and4A-F, the ventricular end of prosthetic valve20may be the bottom end of prosthetic valve20. Frame assembly22comprises a valve frame30(alternatively “inner frame30”) that comprises a tubular portion32(alternatively, “inner frame tubular portion32”) that has an atrial end34and a ventricular end36, and is shaped to define a lumen38through the inner frame tubular portion32from the atrial end to the ventricular end. As illustrated inFIGS. 1A and 1B, inner frame tubular portion32may also include one or more projections28, which extend from ventricular end36of inner frame tubular portion32. Inner frame tubular portion32circumscribes axis ax1, and thereby defines lumen38along the axis. Inner frame30further comprises an atrial support portion40, extending from atrial end34of inner frame tubular portion32. Frame assembly22further comprises at least one leg50(alternatively, “ventricular anchor support50”), coupled to inner frame30at (e.g., via) a coupling point52, and having a tissue-engaging flange54(alternatively, “outer frame tissue anchor54”).

In some embodiments, and as described hereinbelow, ventricular anchor support50is part of an outer frame60, and frames30and60define respective coupling elements31and61, which are fixed with respect to each other at coupling points52. As illustrated inFIG. 1A, inner frame30may be positioned at least partially within outer frame60. In some embodiments, frames30and60are coupled to each other only at coupling points52(e.g., only via the fixation of coupling elements31and61with respect to each other).

Prosthetic valve20further comprises a valve member58(e.g., one or more prosthetic leaflets) disposed within lumen38, and configured to facilitate one-way liquid flow through the lumen from atrial end34to ventricular end36(e.g., thereby defining the orientation of the atrial and ventricular ends of inner frame tubular portion32).FIG. 1Ashows prosthetic valve20in a fully-expanded state (alternatively, “radially expanded state”), in which frame assembly22is in a radially expanded state.FIG. 1Bshows an exploded view of frame assembly22in its radially expanded state.FIGS. 2A-Eshow respective states of prosthetic valve20, which will be discussed in more detail hereinbelow with respect to the implantation of the prosthetic valve and the anatomy in which the prosthetic valve is implanted.FIG. 2Ashows prosthetic valve20in a compressed state (alternatively, “radially contracted state”), in which frame assembly22is in a radially contracted state for percutaneous delivery of the prosthetic valve to the heart of the subject. In some embodiments, in the radially contracted state, ventricular anchor support50(including outer frame tissue anchor54thereof) is in a constrained-anchor state in which the outer frame tissue anchor is generally parallel with axis ax1. Further, in the radially contracted state, atrial support portion40is generally tubular, collinear with inner frame tubular portion32(e.g., extending collinearly from the inner frame tubular portion), and disposed around axis ax1.

FIG. 2Bshows a state of prosthetic valve20in which outer frame tissue anchor54of each ventricular anchor support50extends radially away from axis ax1(e.g., radially away from inner frame tubular portion32).FIG. 2Cshows a state of prosthetic valve20in which atrial support portion40extends radially away from axis ax1(and thereby radially away from inner frame tubular portion32).FIG. 2Dshows a state of prosthetic valve20in which both outer frame tissue anchor54and atrial support portion40extend away from axis ax1. In the radially expanded state (FIGS. 1A-B) both atrial support portion40and outer frame tissue anchor54extend radially away from axis ax1. In some embodiments, frame assembly22is biased (e.g., shape-set) to assume its radially expanded state, which is shown inFIG. 2E. Transitioning of prosthetic valve20between the respective states may be controlled by delivery apparatus, such as by constraining the prosthetic valve in a radially contracted state within a delivery tube and/or against a control rod, and selectively releasing portions of the prosthetic valve to allow them to expand.

In the radially contracted state of frame assembly22, inner frame tubular portion32has a diameter d1, and in the radially expanded state, the inner frame tubular portion has a diameter d2that is greater that diameter d1. For some embodiments, diameter d1is 4-15 mm, (e.g., 5-11 mm) and diameter d2is 20-50 mm, (e.g., 23-33 mm). Frame assembly22is configured such that increasing the diameter of inner frame tubular portion32(e.g., from d1to d2) causes longitudinal movement of outer frame tissue anchor54away from coupling point52. In the same way, reducing the diameter of inner frame tubular portion32(e.g., from d2to d1) causes longitudinal movement of outer frame tissue anchor54toward coupling point52. It is to be noted that the term “longitudinal movement” (including the specification and the claims) means movement parallel with central longitudinal axis ax1. Therefore longitudinal movement of outer frame tissue anchor54away from coupling point52means increasing a distance, measured parallel with longitudinal axis ax1, between outer frame tissue anchor54and coupling point52. An example of such a configuration is described in more detail with respect toFIG. 3A.

Thus, expansion of inner frame tubular portion32from its radially contracted state toward its radially expanded state (i) increases a circumferential distance between each of coupling points52and its adjacent coupling points (e.g., between each of outer-frame coupling elements61and its adjacent outer-frame coupling elements) (e.g., from d8to d9), and (ii) moves ventricular anchor support50in a longitudinally atrial direction with respect to the inner frame tubular portion. The term “atrial direction” may refer to a direction extending upstream from prosthetic valve20, towards an atrium of the heart. For example, inFIGS. 4A-4F, an “atrial direction” may refer to a direction extending upwards from prosthetic valve20towards atrium6. Similarly, the term “ventricular direction” may refer to a direction extending downstream from prosthetic valve20, towards a ventricle of the heart. For example, inFIGS. 4A-4F, a “ventricular direction” may refer to a direction extending downwards from prosthetic valve20towards ventricle8.

In some embodiments, frame assembly22is configured such that increasing the diameter of inner frame tubular portion32also causes longitudinal movement of atrial support portion40toward coupling point52, e.g., as described in more detail with respect toFIGS. 3B-C. In some embodiments, frame assembly22is configured such that increasing the diameter of inner frame tubular portion32also causes longitudinal movement of atrial end34of inner frame tubular portion32toward coupling point52. In the same way, reducing the diameter of inner frame tubular portion32causes longitudinal movement of atrial end34away from coupling point52.

For some embodiments, atrial support portion40comprises a plurality of inner frame tissue anchors46that each extends radially outward from inner frame tubular portion32(e.g., from atrial end34of the inner frame tubular portion). Inner frame tissue anchors46are flexible. For some such embodiments, inner frame tissue anchors46are coupled to inner frame tubular portion32such that each inner frame tissue anchor may deflect independently of adjacent inner frame tissue anchors46during implantation (e.g., due to anatomical topography).

For some embodiments, atrial support portion40comprises a plurality of barbs48that extend out of a ventricular surface of the atrial support portion. For example, each inner frame tissue anchor46may comprise one or more of barbs48. Barbs48press into tissue on an atrial side of the native valve (e.g., into the valve annulus), thereby inhibiting movement of prosthetic valve20in a ventricular direction (in addition to inhibition of movement in a ventricular direction provided by the geometry of atrial support portion40).

One or more surfaces of frame assembly22are covered with a covering23, which comprises a flexible sheet, such as a fabric, e.g., comprising polyester. In some embodiments, covering23covers at least part of inner frame tubular portion32, lining an inner surface of the inner frame tubular portion, and thereby defining lumen38.

Further, atrial support portion40is covered with covering23, e.g., extending between inner frame tissue anchors46to form an annular shape. It is hypothesized that this reduces a likelihood of paravalvular leakage. For such embodiments, excess covering23may be provided between inner frame tissue anchors46of atrial support portion40, so as to facilitate their independent movement. AlthoughFIG. 1Ashows covering23covering an atrial side of atrial support portion40, the covering additionally (or alternatively) covers the ventricular side of the atrial support portion. For example, covering23may extend over the tips of inner frame tissue anchors46and down the outside of the inner frame tissue anchors, or a separate piece of covering may be provided on the ventricular side of the atrial support portion.

Alternatively, each inner frame tissue anchor46may be individually covered in a sleeve of covering23, thereby facilitating independent movement of the inner frame tissue anchors.

For some embodiments, at least a portion of ventricular anchor support50(e.g., outer frame tissue anchors54thereof) is covered with covering23.

In some embodiments, frame assembly22comprises a plurality of ventricular anchor supports50(e.g., two or more ventricular anchor supports, e.g., 2-16 ventricular anchor supports, such as 4-12 ventricular anchor supports, such as 6-12 ventricular anchor supports), arranged circumferentially around inner frame30(e.g., around the outside of inner frame tubular portion32). In some embodiments, frame assembly22comprises a plurality of coupling points52at which the ventricular anchor supports are coupled to inner frame30.

As described in more detail hereinbelow (e.g., with reference toFIG. 3A), each ventricular anchor support50may be coupled to a coupling point52via a strut70. For some embodiments, each ventricular anchor support50is coupled to a plurality of (e.g., two) coupling points52via a respective plurality of (e.g., two) struts70. For some such embodiments, frame assembly22is arranged such that, in the radially expanded state of the frame assembly, ventricular anchor support50is disposed, circumferentially with respect to inner frame tubular portion32, between two struts, and each of the two struts are disposed, circumferentially with respect to the inner frame tubular portion, between the ventricular anchor support and a respective coupling point52.

For some embodiments, a plurality of (e.g., two) ventricular anchor supports50are coupled to each coupling point52via a respective plurality of (e.g., two) struts70. For some such embodiments, frame assembly22is arranged such that, in the radially expanded state of the frame assembly, coupling point52is disposed, circumferentially with respect to inner frame tubular portion32, between two struts70, and each of the two struts are disposed, circumferentially with respect to the inner frame tubular portion, between the coupling point and a respective ventricular anchor support50.

For some embodiments, frame assembly22comprises an outer frame60that circumscribes inner frame tubular portion32, comprises (or defines) the plurality of ventricular anchoring supports50and the plurality of struts70, and is coupled to inner frame30at the plurality of coupling points52, such that the plurality of ventricular anchoring supports are distributed circumferentially around the inner frame tubular portion. For such embodiments, outer frame60comprises a ring66that is defined by a pattern of alternating peaks64and troughs62, and that circumscribes inner frame tubular portion32. For example, the ring may comprise struts70, extending between the peaks and troughs. Peaks64are longitudinally closer to atrial end34of inner frame tubular portion32than to ventricular end36, and troughs62are longitudinally closer to the ventricular end than to the atrial end. (It is to be noted that throughout this patent application, including the specification and the claims, the term “longitudinally” means with respect to longitudinal axis ax1. For example, “longitudinally closer” means closer along axis ax1(whether positioned on axis ax1or lateral to axis ax1), and “longitudinal movement” means a change in position along axis ax1(which may be in additional to movement toward or away from axis ax1). Therefore, peaks64are closer than troughs62to atrial end34, and troughs62are closer than peaks64to ventricular end36. As illustrated inFIG. 1B, outer frame60may include multiple rings66(e.g. two rings66) which are connected by ventricular anchoring supports50. Rings66and ventricular anchor supports50may form an annular outer frame tubular portion65. Annular outer frame tubular portion65may have an atrial end67and a ventricular end69, and may circumscribe axis ax1. As also illustrated inFIG. 1B, outer frame tissue anchors54may extend from annular outer frame tubular portion65. For embodiments in which frame60comprises ring66, each ventricular anchor support50is coupled to the ring (or defined by frame60) at a respective trough62.

In the embodiment shown, the peaks and troughs are defined by ring66having a generally zig-zag shape. However, the scope of the invention includes ring66having another shape that defines peaks and troughs, such as a serpentine or sinusoid shape.

For embodiments in which frame assembly22has a plurality of coupling points52, the coupling points (and therefore coupling elements31and61) are disposed circumferentially around the frame assembly (e.g., around axis ax1), in some embodiments on a transverse plane that is orthogonal to axis ax1. This transverse plane is illustrated by the position of section A-A inFIG. 2B. Alternatively, coupling points52may be disposed at different longitudinal heights of frame assembly22, e.g., such that different outer frame tissue anchors54are positioned and/or moved differently to others. In some embodiments, coupling points52(and therefore coupling elements31and61) are disposed longitudinally between atrial end24and ventricular end26of frame assembly22, but not at either of these ends. Further in some embodiments, coupling points52are disposed longitudinally between atrial end34and ventricular end36of inner frame tubular portion32, but not at either of these ends. For example, the coupling points may be more than 3 mm (e.g., 4-10 mm) both from end34and from end36. It is hypothesized that this advantageously positions the coupling points at a part of inner frame tubular portion32that is more rigid than end34or end36.

It is to be noted that ventricular anchor support50is expandable into its radially expanded state (e.g., a released-anchor state) such that outer frame tissue anchor54extends away from axis ax1, independently of increasing the diameter of inner frame tubular portion32(e.g., as shown inFIGS. 2B & 2D). Similarly, atrial support portion40is expandable into its radially expanded state (e.g., a released-anchor state) such that it (e.g., inner frame tissue anchors46thereof) extends away from axis ax1, independently of increasing the diameter of inner frame tubular portion32(e.g., as shown inFIGS. 2C & 2D). The state shown inFIG. 2Dmay be considered to be an intermediate state. Therefore, prosthetic valve20is configured such that ventricular anchor supports50(e.g., outer frame tissue anchors54thereof) and atrial support portion40are expandable such that they both extend away from axis ax1, while retaining a distance d3therebetween. This distance is subsequently reducible to a distance d4by expanding inner frame tubular portion32(e.g., shown inFIG. 2E).

For some embodiments, while inner frame tubular portion32remains in its radially contracted state, outer frame tissue anchor54can extend away from axis ax1over 40 percent (e.g., 40-80 percent, such as 40-70 percent) of the distance that it extends from the axis subsequent to the expansion of the inner frame tubular portion. For example, for embodiments in which prosthetic valve20comprises a outer frame tissue anchor54on opposing sides of the prosthetic valve, a span d15of the outer frame tissue anchors while inner frame tubular portion32is in its radially contracted state may be at least 40 percent (e.g., 40-80 percent, such as 40-70 percent) as great as a span d16of the outer frame tissue anchors subsequent to the expansion of the inner frame tubular portion. For some embodiments, span d15is greater than 15 mm and/or less than 50 mm (e.g., 20-30 mm). For some embodiments, span d16is greater than 30 mm and/or less than 60 mm (e.g., 40-50 mm). It is to be noted that outer frame tissue anchor54is effectively fully radially expanded, with respect to other portions of ventricular anchor support50and/or with respect to inner frame tubular portion32, before and after the expansion of the inner frame tubular portion.

Similarly, for some embodiments, while inner frame tubular portion32remains in its radially contracted state, atrial support portion40(e.g., inner frame tissue anchors46) can extend away from axis ax1over 30 percent (e.g., 30-70 percent) of the distance that it extends from the axis subsequent to the expansion of the inner frame tubular portion. That is, for some embodiments, a span d17of the atrial support portion while inner frame tubular portion32is in its radially contracted state may be at least 30 percent (e.g., 30-70 percent) as great as a span d18of the atrial support portion subsequent to the expansion of the inner frame tubular portion. For some embodiments, span d17is greater than 16 mm (e.g., greater than 20 mm) and/or less than 50 mm (e.g., 30-40 mm). For some embodiments, span d18is greater than 40 mm and/or less than 65 mm (e.g., 45-56 mm, such as 45-50 mm). It is to be noted that atrial support portion40is effectively fully radially expanded, with respect to inner frame tubular portion32, before and after the expansion of the inner frame tubular portion.

It is to be noted that when inner frame tubular portion32is radially expanded, outer frame tissue anchors54translate radially outward from span d15to span d16(e.g., without deflecting). In some embodiments atrial support portion40behaves similarly (e.g., inner frame tissue anchors46translated radially outward from span d17to span d18, e.g., without deflecting). That is, an orientation of each outer frame tissue anchor54and/or each inner frame tissue anchor46with respect to inner frame tubular portion32and/or axis ax1is the same in the state shown inFIG. 2Das it is in the state shown inFIG. 2E. Similarly, for some embodiments an orientation of each outer frame tissue anchor54with respect to atrial support portion40(e.g., with respect to one or more inner frame tissue anchors46thereof) is the same before and after expansion of inner frame tubular portion32.

For some embodiments, increasing the diameter of inner frame tubular portion32from d1to d2causes greater than 1 mm and/or less than 20 mm (e.g., 1-20 mm, such as 1-10 mm or 5-20 mm) of longitudinal movement of outer frame tissue anchor54away from coupling point52. For some embodiments, increasing the diameter of inner frame tubular portion32from d1to d2causes greater than 1 mm and/or less than 20 mm (e.g., 1-20 mm, such as 1-10 mm or 5-20 mm) of longitudinal movement of atrial support portion40toward coupling point52. For some embodiments, distance d3is 7-30 mm. For some embodiments, distance d4is 0-15 mm (e.g., 2-15 mm). For some embodiments, increasing the diameter of inner frame tubular portion32from d1to d2reduces the distance between the atrial support portion and outer frame tissue anchors54by more than 5 mm and/or less than 30 mm, such as 5-30 mm (e.g., 10-30 mm, such as 10-20 mm or 20-30 mm). For some embodiments, the difference between d3and d4is generally equal to the difference between d1and d2. For some embodiments, the difference between d3and d4is more than 1.2 and/or less than 3 times (e.g., 1.5-2.5 times, such as about 2 times) greater than the difference between d1and d2.

For some embodiments, outer frame tissue anchors54curve such that a tip of each outer frame tissue anchor54is disposed at a shallower angle with respect to inner region42of atrial support portion40, than are portions of ventricular anchor support50that are closer to ventricular end26of frame assembly22. For some such embodiments, a tip of each outer frame tissue anchor may be generally parallel with inner region42. For some such embodiments, while inner frame tubular portion32is in its radially expanded state, a tip portion55of each outer frame tissue anchor54that extends from the tip of the outer frame tissue anchor at least 2 mm along the outer frame tissue anchor, is disposed within 2 mm of atrial support portion40. Thus, for some embodiments, while inner frame tubular portion32is in its radially expanded state, for at least 5 percent (e.g., 5-8 percent, or at least 8 percent) of span18of atrial support portion40, the atrial support portion is disposed within 2 mm of an outer frame tissue anchor54.

For some embodiments, in the absence of any obstruction (such as tissue of the valve or covering23) between outer frame tissue anchor54and atrial support portion40, increasing the diameter of inner frame tubular portion32from d1to d2causes the outer frame tissue anchor54and the atrial support portion to move past each other (e.g., the outer frame tissue anchor54may move between inner frame tissue anchors46of the atrial support portion), such that the outer frame tissue anchor54is closer to the atrial end of prosthetic valve20than is the atrial support portion, e.g., as shown hereinbelow for frame assemblies122and222, mutatis mutandis. (For embodiments in which atrial support portion40is covered by covering23, outer frame tissue anchors54do not pass the covering. For example, in the absence of any obstruction, outer frame tissue anchors54may between inner frame tissue anchors46, and press directly against covering23.) It is hypothesized that for some embodiments this configuration applies greater force to the valve tissue being sandwiched, and thereby further facilitates anchoring of the prosthetic valve. That is, for some embodiments, distance d3is smaller than the sum of distance d5and a distance d14(described with reference toFIG. 3C). For some embodiments, increasing the diameter of inner frame tubular portion32from d1to d2advantageously causes outer frame tissue anchors54and atrial support portion40to move greater than 3 mm and/or less than 25 mm (e.g., greater than 5 mm and/or less than 15 mm, e.g., 5-10 mm, such as about 7 mm) with respect to each other (e.g., toward each other and then past each other).

In some embodiments, in the radially expanded state of frame assembly22, atrial support portion40has an inner region (e.g., an inner ring)42that extends radially outward at a first angle with respect to axis ax1(and with respect to inner frame tubular portion32), and an outer region (e.g., an outer ring)44that extends, from the inner region, further radially outward from the inner frame tubular portion at a second angle with respect to the inner frame tubular portion, the second angle being smaller than the first angle. For example, for some embodiments inner region42extends radially outward at an angle alpha_1 of 60-120 degrees (e.g., 70-110 degrees) with respect to axis ax1, and outer region44extends radially outward at an angle alpha_2 of 5-70 degrees (e.g., 10-60 degrees) with respect to axis ax1.

It is to be noted that angles alpha_1 and alpha_2 are measured between the respective region support portion40, and the portion of axis ax1that extends in an atrial direction from the level of frame assembly22at which the respective region begins to extend radially outward.

For some embodiments in which prosthetic valve20is configured to be placed at an atrioventricular valve (e.g., a mitral valve or a tricuspid valve) of the subject, region42is configured to be placed against the atrial surface of the annulus of the atrioventricular valve, and region44is configured to be placed against the walls of the atrium upstream of the valve.

For some embodiments, outer region44is more flexible than inner region42. For example, and as shown, each inner frame tissue anchor46may have a different structure in region44than in region42. It is hypothesized that the relative rigidity of region42provides resistance against ventricular migration of prosthetic valve20, while the relative flexibility of region44facilitates conformation of atrial support portion40to the atrial anatomy.

For some embodiments, two or more of inner frame tissue anchors46are connected by a connector (not shown), reducing the flexibility, and/or the independence of movement of the connected inner frame tissue anchors relative to each other. For some embodiments, inner frame tissue anchors46are connected in particular sectors of atrial support portion40, thereby making these sectors more rigid than sectors in which the inner frame tissue anchors are not connected. For example, a relatively rigid sector may be provided to be placed against the posterior portion of the mitral annulus, and a relatively flexible sector may be provided to be placed against the anterior side of the mitral annulus, so as to reduce forces applied by atrial support portion40on the aortic sinus.

For some embodiments, and as shown, coupling points52are disposed closer to ventricular end26of frame assembly22than are outer frame tissue anchors54, or is atrial support portion40.

As described in more detail with respect toFIGS. 4A-F, the movement of outer frame tissue anchor54away from coupling point52(and the typical movement of atrial support portion40toward the coupling point) facilitates the sandwiching of tissue of the native valve (e.g., leaflet and/or annulus tissue) between the outer frame tissue anchor54and the atrial support portion, thereby securing prosthetic valve20at the native valve.

In some embodiments, in the radially contracted state of inner frame tubular portion32, a ventricular end of each ventricular anchor support50is longitudinally closer than valve-frame coupling elements31to ventricular end36, and outer frame tissue anchor54of each ventricular anchor support50is disposed longitudinally closer than the valve-frame coupling elements to atrial end34. In some embodiments, this is also the case in the radially expanded state of inner frame tubular portion32.

FIGS. 3A-Cshow structural changes in frame assembly22during transitioning of the assembly between its radially contracted and radially expanded states, in accordance with some embodiments of the invention.FIGS. 3A-Ceach show a portion of the frame assembly, the structural changes thereof being representative of the structural changes that occur in other portions of the frame assembly.FIG. 3Ashows a ventricular anchor support50and struts70(e.g., a portion of outer frame60), and illustrates the structural changes that occur around outer frame60.FIG. 3Bshows a portion of inner frame30, and illustrates the structural changes that occur around the inner frame.FIG. 3Cshows inner frame30as a whole. In each ofFIGS. 3A-C, state (A) illustrates the structure while frame assembly22(and in particular inner frame tubular portion32) is in its radially contracted state, and state (B) illustrates the structure while the frame assembly (and in particular inner frame tubular portion32) is in its radially expanded state.

FIG. 3Ashows structural changes in the coupling of ventricular anchoring supports50to coupling point52(e.g., structural changes of outer frame60) during the transitioning of frame assembly22(and in particular inner frame tubular portion32) between its radially contracted and radially expanded states. Each ventricular anchor support50is coupled to inner frame30via at least one strut70, which connects the ventricular anchoring support to coupling point52. In some embodiments, each ventricular anchor support50is coupled to inner frame30via a plurality of struts70. A first end72of each strut70is coupled to ventricular anchor support50, and a second end74of each strut is coupled to a coupling point52. As described hereinabove, for embodiments in which frame60comprises ring66, each ventricular anchor support50is coupled to the ring at a respective trough62. Ring66may comprise struts70, extending between the peaks and troughs, with each first end72at (or close to) a trough62, and each second end74at (or close to) a peak64. As depicted inFIGS. 1B and 3A, first end72may form the ventricular end69of outer frame tubular portion65.

In the radially contracted state of frame assembly22(and in particular of inner frame tubular portion32), each strut70is disposed at a first angle in which first end72is disposed closer than second end74to the ventricular end of the frame assembly. Expansion of frame assembly22(and in particular of inner frame tubular portion32) toward its radially expanded state causes strut70to deflect to a second angle. This deflection moves first end72away from the ventricular end of frame assembly22. That is, in the radially expanded state of frame assembly22, first end72is further from the ventricular end of the frame assembly than it is when the frame assembly is in its radially contracted state. This movement is shown as a distance d5between the position of end72in state (A) and its position in state (B). This movement causes the above-described movement of outer frame tissue anchors54away from coupling points52. As shown, outer frame tissue anchors54move the same distance d5in response to expansion of frame assembly22. Since outer frame tissue anchors54and first end72(i.e., ventricular end69) move the same distance d5in response to expansion of frame assembly22, the axial distance (i.e., the distance along axis ax1) between outer frame tissue anchors54and first end72(i.e., ventricular end69) may remain constant between the radially expanded state and the radially contracted state of annular outer frame60.

For embodiments in which outer frame60comprises ring66, the pattern of alternating peaks and troughs may be described as having an amplitude longitudinally between the peaks and troughs, i.e., measured parallel with central longitudinal axis ax1of frame assembly22, and the transition between the radially contracted and radially expanded states may be described as follows: In the radially contracted state of frame assembly22(and in particular of inner frame tubular portion32), the pattern of ring66has an amplitude d20. In the radially expanded state frame assembly22(and in particular of inner frame tubular portion32), the pattern of ring66has an amplitude d21that is lower than amplitude d20. Because (i) it is at peaks64that ring66is coupled to inner frame30at coupling points52, and (ii) it is at troughs62that ring66is coupled to ventricular anchoring supports50, this reduction in the amplitude of the pattern of ring66moves ventricular anchoring supports50(e.g., outer frame tissue anchors54thereof) longitudinally further from the ventricular end of the frame assembly. The magnitude of this longitudinal movement (e.g., the difference between magnitudes d20and d21) is equal to d5.

In some embodiments, distance d5is the same distance as the distance that outer frame tissue anchor54moves away from coupling point52during expansion of the frame assembly. That is, a distance between outer frame tissue anchor54and the portion of ventricular anchor support50that is coupled to strut70, remains constant during expansion of the frame assembly. For some embodiments, the longitudinal movement of outer frame tissue anchor54away from coupling point52is a translational movement (e.g., a movement that does not include rotation or deflection of the outer frame tissue anchor54).

For some embodiments, a distance d6, measured parallel to axis ax1of frame assembly22, between coupling point52and first end72of strut70while assembly22is in its radially contracted state, is 3-15 mm. For some embodiments, a distance d7, measured parallel to axis ax1, between coupling point52and first end72of strut70while assembly22is in its radially expanded state, is 1-5 mm (e.g., 1-4 mm).

For some embodiments, and as shown, in the radially expanded state, first end72of strut70is disposed closer to the ventricular end of frame assembly22than is coupling point52. For some embodiments, in the radially expanded state, first end72of strut70is disposed further from the ventricular end of frame assembly22than is coupling point52.

For embodiments in which frame assembly22comprises a plurality of ventricular anchoring supports50and a plurality of coupling points52(e.g., for embodiments in which the frame assembly comprises annular outer frame60) expansion of the frame assembly increases a circumferential distance between adjacent coupling points52, and an increase in a circumferential distance between adjacent ventricular anchoring supports50.FIG. 3Ashows such an increase in the circumferential distance between adjacent coupling points52, from a circumferential distance d8in the radially contracted state to a circumferential distance d9in the radially expanded state. For some embodiments, distance d8is 1-6 mm. For some embodiments, distance d9is 3-15 mm.

For some embodiments, in addition to being coupled via ring66(e.g., struts70thereof) ventricular anchoring supports50are also connected to each other via connectors78. Connectors78allow the described movement of ventricular anchoring supports50during expansion of frame assembly22, but stabilize ventricular anchoring supports50relative to each other while the frame assembly is in its radially expanded state. For example, connectors78may bend and/or deflect during expansion of the frame assembly.

FIGS. 3B-Cshow structural changes in inner frame30during the transitioning of frame assembly22between its radially contracted and radially expanded states. Inner frame tubular portion32of inner frame30is defined by a plurality of cells80, which are defined by the repeating pattern of the inner frame. When frame assembly22is radially expanded from its radially contracted state toward its radially expanded state, cells80(i) widen from a width d10to a width d11(measured orthogonal to axis ax1of the frame assembly), and (ii) shorten from a height d12to a height d13(measured parallel to axis ax1of the frame assembly). This shortening reduces the overall height (i.e., a longitudinal length between atrial end34and ventricular end36) of inner frame tubular portion32from a height d22to a height d23, and thereby causes the above-described longitudinal movement of atrial support portion40toward coupling points52by a distance d14(shown inFIG. 3C). For some embodiments, and as shown, coupling points52are disposed at the widest part of each cell.

Due to the configurations described herein, the distance by which outer frame tissue anchors54move with respect to (e.g., toward, or toward-and-beyond) atrial support portion40(e.g., inner frame tissue anchors46thereof), is greater than the reduction in the overall height of inner frame tubular portion32(e.g., more than 20 percent greater, such as more than 30 percent greater, such as more than 40 percent greater). That is, prosthetic valve20comprises: an inner frame (30) that comprises an inner frame tubular portion (32) that circumscribes a longitudinal axis (ax1) of the inner frame so as to define a lumen (38) along the axis, the inner frame tubular portion having an atrial end (34), a ventricular end (36), a longitudinal length therebetween, and a diameter (e.g., d1or d2) transverse to the longitudinal axis; a valve member (58), coupled to the inner frame tubular portion, disposed within the lumen, and arranged to provide unidirectional atrial-to-ventricular flow of blood through the lumen; an atrial support portion (40), coupled to the inner frame tubular portion; and an annular outer frame (60), coupled to the inner frame tubular portion, and comprising an outer frame tissue anchor (54), wherein: the prosthetic valve has a first state (e.g., as shown inFIG. 2DandFIG. 4D) and a second state (e.g., as shown inFIG. 2EandFIG. 4E), in both the first state and the second state, (i) the atrial support portion extends radially outward from the inner frame tubular portion, and (ii) the outer frame tissue anchor54extends radially outward from the inner frame tubular portion, and the inner frame tubular portion, the atrial support portion, and the outer frame are arranged such that transitioning of the prosthetic valve from the first state toward the second state: increases the diameter of the inner frame tubular portion by a diameter-increase amount (e.g., the difference between d1and d2), decreases the length of the inner frame tubular portion by a length-decrease amount (e.g., the difference between d22and d23), and moves the outer frame tissue anchor54a longitudinal distance with respect to (e.g., toward or toward-and-beyond) the atrial support portion (e.g., the difference between d3and d4), this distance being greater than the length-decrease amount.

As shown in the figures, inner frame30is coupled to outer frame60by coupling between (i) a valve-frame coupling element31defined by inner frame30, and (ii) an outer-frame coupling element61defined by outer frame60(e.g., an outer-frame coupling element is coupled to end74of each strut). In some embodiments, elements31and61are fixed with respect to each other. Each coupling point52is thereby defined as the point at which a valve-frame coupling element and a corresponding outer-frame coupling element61are coupled (e.g., are fixed with respect to each other). For some embodiments, and as shown, elements31and61are eyelets configured to be coupled together by a connector, such as a pin or suture. For some embodiments, elements31and61are soldered or welded together.

In some embodiments, and as shown, valve-frame coupling elements31are defined by inner frame tubular portion32, and are disposed circumferentially around central longitudinal axis ax1. Outer-frame coupling elements61are coupled to ring66(or defined by annular outer frame60, such as by ring66) at respective peaks64.

As shown (e.g., inFIGS. 2A-E), inner frame30(e.g., inner frame tubular portion32thereof) and annular outer frame60(e.g., ring66thereof) are arranged in a close-fitting coaxial arrangement, in both the radially expanded and radially contracted states of frame assembly22. Ignoring spaces due to the cellular structure of the frames, a radial gap d19between inner frame30(e.g., inner frame tubular portion32thereof) and outer frame60(e.g., ring66thereof) may be less than 2 mm (e.g., less than 1 mm), in both the radially contracted and radially expanded states, and during the transition therebetween. This is facilitated by the coupling between frames30and60, and the behavior, described hereinabove, of annular outer frame60in response to changes in the diameter of inner frame tubular portion32(e.g., rather than solely due to delivery techniques and/or tools). For some embodiments, more than 50 percent (e.g., more than 60 percent) of ring66is disposed within 2 mm of inner frame tubular portion32in both the radially contracted and radially expanded states, and during the transition therebetween. For some embodiments, more than 50 percent (e.g., more than 60 percent) of annular outer frame60, except for outer frame tissue anchors54, is disposed within 2 mm of inner frame tubular portion32in both the radially contracted and radially expanded states, and during the transition therebetween.

The structural changes to frame assembly22(e.g., to outer frame60thereof) are described hereinabove as they occur during (e.g., as a result of) expansion of the frame assembly (in particular inner frame tubular portion32thereof). This is the natural way to describe these changes because, as described hereinbelow with respect toFIGS. 4A-6, assembly22is in its radially contracted state during percutaneous delivery to the prosthetic valve site, and is subsequently radially expanded. However, the nature of prosthetic valve20may be further understood by describing structural changes that occur during compression of the frame assembly (e.g., a transition from the radially expanded state inFIG. 2Eto the intermediate state inFIG. 2D), in particular inner frame tubular portion32thereof (including if inner frame tubular portion32were radially contracted by application of compressive force to the inner frame tubular portion, and not to frame60except via the inner frame tubular portion pulling frame60radially inward). Such descriptions may also be relevant because prosthetic valve20is radially contracted (i.e., “crimped”) soon before its percutaneous delivery, and therefore these changes may occur while prosthetic valve20is in the care of the operating physician.

For some embodiments, the fixation of peaks64to respective sites of inner frame tubular portion32is such that compression of the inner frame tubular portion from its radially expanded state toward its radially contracted state such that the respective sites of the inner frame tubular portion pull the peaks radially inward via radially-inward tension on coupling points52: (i) reduces a circumferential distance between each of the coupling points and its adjacent coupling points (e.g., from d9to d8), and (ii) increases the amplitude of the pattern of ring66(e.g., from d21to d20).

For some embodiments, the fixation of outer-frame coupling elements61to valve-frame coupling elements31is such that compression of inner frame tubular portion32from its radially expanded state toward its radially contracted state such that the valve-frame coupling elements pull the outer-frame coupling elements radially inward: (i) reduces a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements (e.g., from d9to d8), and (ii) increases the amplitude of the pattern of ring66(e.g., from d21to d20).

For some embodiments, the fixation of peaks64to the respective sites of inner frame tubular portion32is such that compression of the inner frame tubular portion from its radially expanded state toward its radially contracted state (i) pulls the peaks radially inward via radially-inward pulling of the respective sites of the inner frame tubular portion on the peaks, (ii) reduces a circumferential distance between each of coupling points52and its adjacent coupling points (e.g., from d9to d8), and (iii) increases the amplitude of the pattern of ring66(e.g., from d21to d20), without increasing radial gap d19between inner frame30(e.g., inner frame tubular portion32thereof) and the ring by more than 1.5 mm.

For some embodiments, the fixation of outer-frame coupling elements61with respect to valve-frame coupling elements31is such that compression of inner frame tubular portion32from its radially expanded state toward its radially contracted state (i) pulls outer-frame coupling elements61radially inward via radially-inward pulling of valve-frame coupling elements31on outer-frame coupling elements61, (ii) reduces a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements (e.g., from d9to d8), and (iii) increases the amplitude of the pattern of ring66(e.g., from d21to d20), without increasing radial gap d19between inner frame30(e.g., inner frame tubular portion32thereof) and the ring by more than 1.5 mm.

Reference is made toFIGS. 4A-F, which are schematic illustrations of implantation of prosthetic valve20at a native valve10of a heart4of a subject, in accordance with some embodiments of the invention. Valve10is shown as a mitral valve of the subject, disposed between a left atrium6and a left ventricle8of the subject. However prosthetic valve20may be implanted at another heart valve of the subject, mutatis mutandis. Similarly, althoughFIGS. 4A-Fshow prosthetic valve20being delivered transseptally via a sheath88, the prosthetic valve may alternatively be delivered by any other suitable route, such as transatrially, or transapically.

Prosthetic valve20is delivered, in its radially contracted state, to native valve10using a delivery tool89that is operable from outside the subject (FIG. 4A). In some embodiments, prosthetic valve20is delivered within a delivery capsule90of tool89, which retains the prosthetic valve in its radially contracted state. A transseptal approach, such as a transfemoral approach, is shown. In some embodiments, prosthetic valve20is positioned such that at least outer frame tissue anchors54are disposed in a ventricular direction of the native valve (i.e., within ventricle8). At this stage, frame assembly22of prosthetic valve20is as shown inFIG. 2A.

Subsequently, outer frame tissue anchors54are allowed to protrude radially outward, as described hereinabove, e.g., by releasing them from capsule90(FIG. 4B). For example, and as shown, capsule90may comprise a distal capsule-portion92and a proximal capsule-portion94, and the distal capsule-portion may be moved distally with respect to prosthetic valve20, so as to expose outer frame tissue anchors54. At this stage, frame assembly22of prosthetic valve20is as shown inFIG. 2B.

Subsequently, prosthetic valve20is moved upstream in an atrial direction, such that atrial support portion40, in its radially contracted state, is disposed in an atrial direction of leaflets12(i.e., within atrium6). For some embodiments, the atrial movement of prosthetic valve20causes outer frame tissue anchors54to engage leaflets12. However, because of the relatively large distance d3provided by prosthetic valve20(described hereinabove), for some embodiments it is not necessary to move the prosthetic valve so far in an atrial direction that outer frame tissue anchors54tightly engage leaflets12and/or pull the leaflets in an atrial direction of the valve annulus. Atrial support portion40is then allowed to expand such that it protrudes radially outward, as described hereinabove, e.g., by releasing it from capsule90(FIG. 4D). For example, and as shown, proximal capsule-portion94may be moved proximally with respect to prosthetic valve20, so as to expose atrial support portion40. At this stage, frame assembly22of prosthetic valve20is as shown inFIG. 2D, in which: (i) distance d3exists between atrial support portion40and outer frame tissue anchors54, (ii) the outer frame tissue anchors have span d15, (iii) the atrial support portion has span d17, and (iv) inner frame tubular portion32has diameter d1.

In some embodiments, expansion of frame assembly22is inhibited by distal capsule-portion92(e.g., by inhibiting expansion of inner frame tubular portion32), and/or by another portion of delivery tool89(e.g., a portion of the delivery tool that is disposed within lumen38).

Subsequently, prosthetic valve20is allowed to expand toward its radially expanded state, such that inner frame tubular portion32widens to diameter d2, and the distance between atrial support portion40and outer frame tissue anchors54reduces to distance d4(FIG. 4E). This sandwiches tissue of valve10(including annular tissue and/or leaflets12in some embodiments) between atrial support portion40and outer frame tissue anchors54, thereby securing prosthetic valve20at the valve. As depicted inFIG. 4E, atrial support portion40, including inner frame tissue anchors46, may engage atrial tissue of the native mitral valve (i.e., may engage the native mitral valve from the atrial side) while outer frame tissue anchors may engage ventricular tissue of the native mitral valve (i.e., may engage the native mitral valve from the ventricular side).FIG. 4Fshows delivery capsule90having been removed from the body of the subject, leaving prosthetic valve20in place at valve10.

As described hereinabove, prosthetic valve20is configured such that when inner frame tubular portion32is radially expanded, outer frame tissue anchors54and atrial support portion40move a relatively large distance toward each other. This enables distance d3to be relatively large, while distance d4is sufficiently small to provide effective anchoring. As also described hereinabove, prosthetic valve20is configured such that outer frame tissue anchors54and atrial support portion40can extend radially outward a relatively large distance while inner frame tubular portion32remains radially contracted. It is hypothesized that for some embodiments, these configurations (independently and/or together) facilitate effective anchoring of prosthetic valve20, by facilitating placement of a relatively large proportion of valve tissue (e.g., leaflets12) between the outer frame tissue anchors54and the atrial support portion prior to expanding inner frame tubular portion32and sandwiching the valve tissue.

It is further hypothesized that the relatively great radially-outward extension of outer frame tissue anchors54and atrial support portion40prior to expansion of inner frame tubular portion32, further facilitates the anchoring/sandwiching step by reducing radially-outward pushing of the valve tissue (e.g., leaflets12) during the expansion of the inner frame tubular portion, and thereby increasing the amount of valve tissue that is sandwiched.

It is yet further hypothesized that this configuration of prosthetic valve20facilitates identifying correct positioning of the prosthetic valve (i.e., with atrial support portion40in an atrial direction of leaflets12and outer frame tissue anchors54in a ventricular direction of the leaflets) prior to expanding inner frame tubular portion32and sandwiching the valve tissue.

As shown inFIG. 1A, for some embodiments, in the radially expanded state of frame assembly22, prosthetic valve20defines a toroidal space49between outer frame tissue anchors54and atrial support portion40(e.g., a space that is wider than distance d4). For example, space49may have a generally triangular cross-section. It is hypothesized that for some such embodiments, in addition to sandwiching tissue of the native valve between atrial support portion40and outer frame tissue anchors54(e.g., the tips of the outer frame tissue anchors), space49advantageously promotes tissue growth therewithin (e.g., between leaflet tissue and covering23), which over time further secures prosthetic valve20within the native valve.

Reference is now made toFIG. 5, which is a schematic illustration of a step in the implantation of prosthetic valve20, in accordance with some embodiments of the invention. WhereasFIGS. 4A-Fshow an implantation technique in which outer frame tissue anchors54are radially expanded prior to atrial support portion40, for some embodiments the atrial support portion is radially expanded prior to the outer frame tissue anchors54.FIG. 5shows a step in such an embodiment.

Reference is again made toFIGS. 2A-5. As noted hereinabove, prosthetic valve20may be implanted by causing outer frame tissue anchors54to radially protrude before causing atrial support portion40to radially protrude, or may be implanted by causing the atrial support portion to protrude before causing the outer frame tissue anchors54to protrude. For some embodiments, prosthetic valve20is thereby configured to be deliverable in a ventricular direction (e.g., transseptally, as shown, or transapically) or in an in an atrial direction direction (e.g., transapically or via the aortic valve). Thus, for some embodiments, an operating physician may decide which delivery route is preferable for a given application (e.g., for a given subject, and/or based on available equipment and/or expertise), and prosthetic valve20is responsively prepared for the chosen delivery route (e.g., by loading the prosthetic valve into an appropriate delivery tool).

It is to be noted that for some embodiments, ventricular delivery of prosthetic valve20may be performed by expanding outer frame tissue anchors54first (e.g., as shown inFIGS. 4A-F) or by expanding atrial support portion40first (e.g., as shown inFIG. 5). Similarly, for some embodiments atrial delivery of prosthetic valve20may be performed by atrial support portion40first, or by expanding outer frame tissue anchors54first.

Reference is now made toFIG. 6, which is a schematic illustration of prosthetic valve20, in the state and position shown inFIG. 4D, in accordance with some embodiments of the invention. For some embodiments, while prosthetic valve20is in the state and position shown inFIG. 4D, leaflets12of valve10are able to move, at least in part in response to beating of the heart. Frame (A) shows leaflets12during ventricular systole, and frame (B) shows the leaflets during ventricular diastole. For some such embodiments, blood is thereby able to flow from atrium6to ventricle8, between leaflets12and prosthetic valve20. It is hypothesized that this advantageously facilitates a more relaxed implantation procedure, e.g., facilitating retaining of prosthetic valve20in this state and position for a duration of greater than 8 minutes. During this time, imaging techniques may be used to verify the position of prosthetic valve20, and/or positioning of leaflets12between atrial support portion40and outer frame tissue anchors54.

Reference is made toFIGS. 7A-Band8A-B, which are schematic illustrations of frame assemblies122and222of respective prosthetic valves, in accordance with some embodiments of the invention. Except where noted otherwise, frame assemblies122and222may be identical to frame assembly22, mutatis mutandis. Elements of frame assemblies122and222share the name of corresponding elements of frame assembly22. Additionally, except where noted otherwise, the prosthetic valves to which frame assemblies122and222belong are similar to prosthetic valve20, mutatis mutandis.FIG. 7Adepicts frame assembly122in the radially contracted state, whileFIG. 7Bdepicts frame assembly122in the radially expanded state. Similarly,FIG. 8Adepicts frame assembly222in the radially contracted state, whileFIG. 8Bdepicts frame assembly222in the radially expanded state. As shown inFIGS. 7A-7B and 8A-8B, inner frame tissue anchors146,246and outer frame tissue anchors154,254may be positioned substantially parallel to axis ax1when frame assembly122,222is in the radially contracted state and may deflect radially outwards away from axis ax1when frame assembly122,222expands into the radially expanded state.

Frame assembly122includes an inner frame130that includes an inner frame tubular portion132having an atrial end134and a ventricular end136. One or more projections128may extend from ventricular end136of inner frame tubular portion132. Inner frame tubular portion132may also include an atrial support portion140that may include a plurality of inner frame tissue anchors146extending from inner frame tubular portion132. Inner frame tissue anchors146may connect to inner frame tubular portion132at connection locations145, which may be situated in an intermediate portion of inner frame tubular portion132(that is, between atrial end134and ventricular end136). Inner frame tissue anchors146may include inner regions142and outer regions144. As depicted inFIG. 7B, when frame assembly122is in the radially expanded state, inner regions142may extend downwards in a ventricular direction, while outer regions144may extend upwards in an atrial direction. Frame assembly122may also include an outer frame160that circumscribes the inner frame130and which includes an outer frame tubular portion165having an atrial end167and a ventricular end169. Outer frame160may also include a plurality of ventricular anchoring supports150that each include an outer frame tissue anchor154extending from outer frame tubular portion165. As depicted inFIG. 7B, outer frame tissue anchors154may connect to outer frame tubular portion165at connection points153, and may extend radially outward to terminal ends155. Connection points153may be positioned in an intermediate portion of outer frame tubular portion165, between atrial end167and ventricular end169. As also depicted inFIG. 7B, when frame assembly122is in the radially expanded state, the entire length of outer frame tissue anchors154(i.e., the length extending from connection point153to terminal end155) may extend upward towards the atrium of the heart. In some embodiments, outer frame160includes a ring166to which ventricular anchoring supports150are coupled. Ring166is defined by a pattern of alternating peaks and troughs, the peaks being fixed to frame130at respective coupling points152, e.g., as described hereinabove for frame assembly22, mutatis mutandis.

As illustrated inFIG. 7A, when frame assembly122is in the radially contracted state, the ventricular end136of the inner frame tubular portion132may be spaced apart from the ventricular end169of the outer frame tubular portion165relative to axis ax1. In particular, ventricular end136of the inner frame tubular portion132may be positioned in a ventricular direction from the ventricular end169of the outer frame tubular portion. Atrial end134of the inner frame tubular portion132may be positioned in an atrial direction from the atrial end167of the outer frame tubular portion165. However, as illustrated inFIG. 7B, ventricular ends136,169may be configured to be substantially aligned in a common lateral plane when frame assembly122is in the radially expanded state. That is, ventricular ends136,169may be spaced at substantially the same position along axis ax1when frame assembly122is in the radially expanded state. As a result, radial expansion of prosthetic valve120may decrease the distance between ventricular end136and ventricular end169. In addition, and as also illustrated inFIGS. 7A-7B, inner frame tubular portion132may have a greater axial length than outer frame tubular portion165. For example, as illustrated inFIG. 7B, ventricular ends136,169of the inner and outer tubular frame portions132,165, respectively, may be substantially aligned, while the atrial end134of the inner frame tubular portion132may extend in an atrial direction beyond the atrial end167of the outer frame tubular portion165.

Frame assembly222includes an inner frame230that includes an inner frame tubular portion232having an atrial end234and a ventricular end236. One or more projections228may extend from ventricular end236of inner frame tubular portion232. Inner frame tubular portion232may also include an atrial support portion240that may include a plurality of inner frame tissue anchors246extending from inner frame tubular portion232. Inner frame tissue anchors246may connect to inner frame tubular portion232at connection locations245, which may be situated in an intermediate portion of inner frame tubular portion232(i.e., between atrial end234and ventricular end236). Inner frame tissue anchors246may include inner regions242and outer regions244. As depicted inFIG. 8B, when frame assembly222is in the radially expanded state, inner regions242may extend downwards in a ventricular direction, while outer regions244may extend upwards in an atrial direction. Frame assembly222may also include an outer frame260that circumscribes the inner frame and which includes an outer frame tubular portion265having an atrial end267and a ventricular end269. Outer frame260may also include a plurality of ventricular anchoring supports250that each include an outer frame tissue anchor254extending from outer frame tubular portion265. As depicted inFIG. 8B, outer frame tissue anchors254may connect to outer frame tubular portion265at connection points253, and may extend radially outward to terminal ends255. Connection points253may be positioned in an intermediate portion of outer frame tubular portion265, between atrial end267and ventricular end269. As also depicted inFIG. 8B, when frame assembly222is in the radially expanded state, the entire length of outer frame tissue anchors254(i.e., the length extending from connection points253to terminal ends255) may extend upward towards an atrium. In some embodiments, outer frame260includes a ring266to which ventricular anchoring supports250are coupled. Ring266is defined by a pattern of alternating peaks and troughs, the peaks being fixed to frame230at respective coupling points252, e.g., as described hereinabove for frame assembly22, mutatis mutandis.

As illustrated inFIG. 8A, when frame assembly222is in the radially contracted state, the ventricular end236of the inner frame tubular portion may be spaced apart from the ventricular end269of the outer frame tubular portion relative to axis ax1. In particular, ventricular end236may be positioned in a ventricular direction from ventricular end269when frame assembly222is in the radially contracted state. In addition, as illustrated inFIG. 8B, ventricular ends236,269of the inner and outer frame tubular portions232,265, respectively, may be configured to be substantially aligned in a common lateral plane when frame assembly222is in the radially expanded state. That is, ventricular ends236,269may be spaced at substantially the same position along axis ax1when frame assembly222is in the radially expanded state.

Whereas inner frame tissue anchors46of frame assembly22are shown as extending from atrial end34of inner frame tubular portion32, inner frame tissue anchors146and246of frame assemblies122and222, respectively, may extend from sites further in a ventricular direction. (This difference may also be made to frame assembly22, mutatis mutandis.) Inner frame tubular portions32,132and232are each defined by a repeating pattern of cells that extends around the central longitudinal axis. In some embodiments, and as shown, inner frame tubular portions32,132and232are each defined by two stacked, tessellating rows of cells. In the radially expanded state of each inner frame tubular portion, these cells may be narrower at their atrial and ventricular extremities than midway between these extremities. For example, and as shown, the cells may be roughly diamond or astroid in shape. In frame assembly22, each inner frame tissue anchor46is attached to and extends from a site35that is at the atrial extremity of cells of the atrial row. In contrast, in frame assemblies122and222, each inner frame tissue anchor146or246is attached to and extends from a site135(assembly122) or235(assembly222) that is at the connection between two adjacent cells of the atrial row (alternatively described as being at the atrial extremity of cells of the ventricular row).

It is hypothesized by the inventors that this lower position of the inner frame tissue anchors, while maintaining the length of the lumen of the inner frame tubular portion, advantageously reduces the distance that the inner frame tubular portion (i.e., the ventricular end thereof) extends into the ventricle of the subject, and thereby reduces a likelihood of inhibiting blood flow out of the ventricle through the left ventricular outflow tract. It is further hypothesized that this position of the inner frame tissue anchors reduces radial compression of the inner frame tubular portion by movement of the heart, due to greater rigidity of the inner frame tubular portion at sites135and235(which is supported by two adjacent cells) than at site35(which is supported by only one cell).

As illustrated inFIG. 7B, when frame assembly122is in the radially expanded state, connection locations145of the inner frame tissue anchors146may be positioned in an atrial direction from the atrial end167of the outer frame tubular portion165. As a result, outer frame tubular portion165may be positioned in a ventricular direction from connection locations145and from inner frame tissue anchors146.

As depicted inFIGS. 7B and 8B, and as discussed above, ventricular end169,269of the outer frame tubular portion165,265may be substantially aligned with the ventricular end136,236of the inner frame tubular portion132,232when frame assembly122,222is expanded. Meantime, atrial end134,234of the inner frame tubular portion may132,232extend in an atrial direction beyond the atrial end167,267of the outer frame tubular165,265when frame assembly122,222is expanded. Thus, in at least some embodiments, a distance between ventricular end169,269of the outer frame tubular portion165,265and ventricular end136,236of the inner frame tubular portion132,232may be smaller than a distance between atrial end167,267of the outer frame tubular portion165,265and atrial end134,234of the inner frame tubular portion132,232.

As shown, in the radially expanded state of frame assemblies22,122, and222, the ventricular anchoring supports (50,150, and250, respectively) (and thus outer frame tissue anchors54,154,254) are circumferentially staggered with the inner frame tissue anchors (46,146, and246, respectively). This may allow the ventricular anchoring supports50to move in an atrial direction between the inner frame tissue anchors during expansion of the inner frame tubular portion (32,132and232, respectively), facilitating application of greater sandwiching force on tissue of the native valve. The lower position of the inner frame tissue anchors of assemblies122and222includes circumferentially shifting the position of the inner frame tissue anchors by the width of half a cell. In order to maintain the circumferential staggering of the inner frame tissue anchors46,146,246and outer frame tissue anchors54,154,254, rings166and266(and thereby ventricular anchoring supports150and250) are circumferentially shifted correspondingly. As a result, whereas the peaks of ring66generally align with connections between adjacent cells of the ventricular row of cells of inner frame tubular portion32(and are fixed to these sites), the peaks of rings166and266are generally aligned midway between these sites (i.e., at spaces of the cellular structure of the inner frame tubular portion). An appendages168(for assembly122) or268(for assembly222) facilitate fixing of the peak with respect to the tubular structure.

For assembly122, appendages168are defined by inner frame130(e.g., by inner frame tubular portion132thereof) and extend (in a ventricular direction) to the peaks of ring166, to which they are fixed. For example, each appendage168may define a valve-frame coupling element131that is fixed to a respective outer-frame coupling element161defined by outer frame260. In some embodiments, appendages168extend from sites135. In some embodiments, appendages168are integral with inner frame tubular portion132and/or in-plane with the inner frame tubular portion (e.g., are part of its tubular shape). As illustrated inFIG. 7B, coupling element161may be spaced apart from the atrial167and ventricular169ends of the outer frame tubular portion165, while coupling element131may be spaced apart from the atrial134and ventricular136ends of the inner frame tubular portion132. As a result, and as also illustrated inFIG. 7B, outer frame tubular portion165may have no connections to inner frame tubular portion132along ventricular end169of the outer frame tubular portion165. Additionally, inner frame tubular portion132may have no connections to outer frame tubular portion165along ventricular end136of the inner frame tubular portion132.

For assembly222, appendages268are defined by outer frame260, and extend (e.g., in an atrial direction) from the peaks of ring266. In some embodiments, appendages268extend to sites235, to which they are fixed. For example, each appendage268may define an outer frame coupling element261that is fixed to a respective inner frame coupling element231defined by inner frame230(e.g., by inner frame tubular portion232thereof). In some embodiments, appendages268are integral with outer frame260and/or in-plane with adjacent portions of outer frame260, such as ring266.

Therefore, frame assembly122defines a hub at site135, and frame assembly222defines a hub at site235. For some embodiments, apparatus therefore comprises: a plurality of prosthetic valve leaflets; and a frame assembly, comprising: an inner frame tubular portion (132or232) defined by a repeating pattern of cells, the inner frame tubular portion extending circumferentially around longitudinal axis ax1so as to define a longitudinal lumen, the prosthetic valve leaflets coupled to the inner frame and disposed within the lumen; an outer frame (160or260), comprising a plurality of ventricular anchoring supports (150or250), distributed circumferentially around the inner frame tubular portion, each support having an outer frame tissue anchor (154or254); an atrial support portion (140or240) that comprises a plurality of inner frame tissue anchors (146or246) that extend radially outward from the inner frame tubular portion; and a plurality of appendages (168or268), each having a first end that defines a coupling element (161or261) via which the inner frame tubular portion is coupled to the outer frame, and a second end; wherein the frame assembly defines a plurality of hubs (135or235), distributed circumferentially around the longitudinal axis on a plane that is transverse to longitudinal axis ax1, each hub defined by convergence and connection of, (i) two adjacent cells of the inner frame tubular portion, (ii) an inner frame tissue anchor of the plurality of inner frame tissue anchors, and (iii) an appendage of the plurality of appendages.

Reference is made toFIGS. 9A-C, which are schematic illustrations of an prosthetic valve320comprising a frame assembly322, in accordance with some embodiments of the invention. Except where noted otherwise, frame assembly322is identical to frame assembly122, and prosthetic valve300is identical to the prosthetic valve to which frame assembly122belongs, mutatis mutandis.FIG. 9Ais a side-view of prosthetic valve320, andFIG. 9Bis an isometric bottom-view of the prosthetic valve.

Frame assembly122comprises (i) an inner frame330that comprises an inner frame tubular portion332and an atrial support portion340that comprises a plurality of inner frame tissue anchors346, and (ii) an outer frame360that circumscribes the inner frame, and comprises a plurality of ventricular anchoring supports350that each comprise an outer frame tissue anchor354. In some embodiments, outer frame360comprises a ring366to which ventricular anchoring supports350are coupled. Ring366is defined by a pattern of alternating peaks and troughs, the peaks being fixed to frame330at respective coupling points352, e.g., as described hereinabove for frame assembly22and/or frame assembly122, mutatis mutandis.

Frame assembly322comprises an annular atrial support portion340that has an inner portion342that extends radially outward from the atrial portion (e.g., the atrial end) of inner frame tubular portion332. Atrial support portion340further comprises one or more fabric pockets344disposed circumferentially around inner portion342, each pocket of the one or more pockets having an opening that faces a ventricular direction (i.e., generally toward the ventricular end of prosthetic valve320). In the figures, atrial support portion340has a single toroidal pocket344that extends circumferentially around inner portion342.

In some embodiments, a covering323(e.g., similar to covering23, described hereinabove, mutatis mutandis) is disposed over inner frame tissue anchors346, thereby forming pocket344. Further in some embodiments, inner frame tissue anchors346are shaped to form pocket344from covering323. For example, and as shown, inner frame tissue anchors346may curve to form a hook-shape.

For some embodiments, portion340has a plurality of separate pockets344, e.g., separated at inner frame tissue anchors346. For some such embodiments, covering323is loosely-fitted (e.g., baggy) between radially-outward parts of inner frame tissue anchors346, e.g., compared to inner portion342, in which the covering is more closely-fitted between radially-inward parts of the inner frame tissue anchors.

FIG. 9Cshows prosthetic valve320implanted at native valve10. Pocket344is shaped and arranged to billow in response to perivalvular flow302of blood in an atrial direction. If ventricular systole forces blood in ventricle8between prosthetic valve320and native valve10, that blood inflates pocket344and presses it (e.g., covering323and/or the radially-outward part of inner frame tissue anchor346) against tissue of atrium6(e.g., against the atrial wall), thereby increasing sealing responsively. It is hypothesized by the inventors that the shape and orientation of pocket344(e.g., the hook-shape of inner frame tissue anchors346) facilitates this pressing radially-outward in response to the pocket's receipt of blood flowing in an atrial direction (that is, towards the atrium).

Pocket(s)344may be used in combination with any of the prosthetic valves described herein, mutatis mutandis.

Reference is again made toFIGS. 1A-9C. It is to be noted that unless specifically stated otherwise, the term “radially outward” (e.g., used to describe atrial support portion40and outer frame tissue anchors54) means portions of the element are disposed progressively further outward from a central point (such as longitudinal axis ax1or inner frame tubular portion32), but does not necessarily mean disposed at 90 degrees with respect to longitudinal axis ax1. For example, outer frame tissue anchors54may extend radially outward at 90 degrees with respect to longitudinal axis ax1, but may alternatively extend radially outward at a shallower angle with respect to the longitudinal axis.