Patent Description:
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.

Dilation 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. Document <CIT>, a document falling under Article <NUM>(<NUM>) EPC, discloses an apparatus for use in a heart of a subject, the apparatus comprising: a frame assembly (<NUM>) transluminally advanceable to the heart, and comprising: an inner frame (<NUM>) that defines: a tubular portion (<NUM>) that defines a longitudinal lumen (<NUM>) therethrough, and an upstream support portion (<NUM>), coupled to the tubular portion (<NUM>); and an outer frame (<NUM>) that: is coupled to the inner frame (<NUM>), circumscribes the tubular portion (<NUM>), and defines a plurality of flanges (<NUM>) that are coupled to the tubular portion (<NUM>); and a plurality of prosthetic valve leaflets (<NUM>), coupled to the tubular portion (<NUM>), and disposed within the lumen (<NUM>), wherein: the frame assembly (<NUM>): has a compressed state for transluminal delivery to the heart, and has an expanded state, in which: the upstream support portion (<NUM>) extends radially outward from the tubular portion (<NUM>), the flanges (<NUM>) extend radially outward from the tubular portion (<NUM>) and toward the upstream support portion (<NUM>), the tubular portion (<NUM>) has a transverse cross-sectional area, and the frame assembly (<NUM>) defines a toroidal space (<NUM>) between the flanges (<NUM>), the upstream support portion (<NUM>), and the tubular portion (<NUM>), the toroidal space (<NUM>) circumscribing the tubular portion (<NUM>). Document <CIT> discloses an implantable prosthetic valve having a radially collapsible and radially expandable annular frame (<NUM>) comprising an annular main body (<NUM>) that defines a lumen through the main body, a ventricular anchor that is coupled to a ventricular end portion of the main body and an atrial portion that is coupled to the main body and extended radially away from the main body, wherein the atrial portion comprises a set of radially extending arms and one of the arms comprises a serpentine or coiled segment.

The claimed invention is defined by an apparatus for use in a heart of a subject as defined by independent claim <NUM>. Further developments of the claimed invention can be gathered from the dependent claims.

Reference is made to <FIG> and <FIG>, which are schematic illustrations of an implant <NUM> for use with a native valve of a heart of a subject, in accordance with some applications of the invention. Implant <NUM> comprises a frame assembly <NUM> that has an upstream end <NUM>, a downstream end <NUM>, and a central longitudinal axis ax1 therebetween. Frame assembly <NUM> comprises a valve frame <NUM> that comprises a tubular portion <NUM> that has an upstream end <NUM> and a downstream end <NUM>, and is shaped to define a lumen <NUM> through the tubular portion from the upstream end to the downstream end. Tubular portion <NUM> circumscribes axis ax1, and thereby defines lumen <NUM> along the axis. Valve frame <NUM> further comprises an upstream support portion <NUM>, extending from upstream end <NUM> of tubular portion <NUM>. Frame assembly <NUM> further comprises at least one leg <NUM>, coupled to valve frame <NUM> at (e.g., via) a coupling point <NUM>, and having a tissue-engaging flange <NUM>.

Typically, and as described hereinbelow, leg <NUM> is part of an outer frame (or "leg frame") <NUM>, and frames <NUM> and <NUM> define respective coupling elements <NUM> and <NUM>, which are fixed with respect to each other at coupling points <NUM>. Typically, frames <NUM> and <NUM> are coupled to each other only at coupling points <NUM> (e.g., only via the fixation of coupling elements <NUM> and <NUM> with respect to each other).

Implant <NUM> further comprises a valve member <NUM> (e.g., one or more prosthetic leaflets) disposed within lumen <NUM>, and configured to facilitate one-way liquid flow through the lumen from upstream end <NUM> to downstream end <NUM> (e.g., thereby defining the orientation of the upstream and downstream ends of tubular portion <NUM>). <FIG> shows implant <NUM> in a fully-expanded state, in which frame assembly <NUM> is in a fully-expanded state. <FIG> shows an exploded view of frame assembly <NUM> in its fully-expanded state. <FIG> show respective states of implant <NUM>, which will be discussed in more detail hereinbelow with respect to the implantation of the implant and the anatomy in which the implant is implanted. <FIG> shows implant <NUM> in a compressed state (in which frame assembly <NUM> is in a compressed state), for percutaneous delivery of the implant to the heart of the subject. Typically, in the compressed state, leg <NUM> (including flange <NUM> thereof) is in a constrained-flange state in which the flange is generally parallel with axis ax1. Further typically, in the compressed state, upstream support portion <NUM> is generally tubular, collinear with tubular portion <NUM> (e.g., extending collinearly from the tubular portion), and disposed around axis ax1.

<FIG> shows a state of implant <NUM> in which tissue-engaging flange <NUM> of each leg <NUM> extends radially away from axis ax1 (e.g., radially away from tubular portion <NUM>). <FIG> shows a state of implant <NUM> in which upstream-support portion <NUM> extends radially away from axis ax1 (and thereby radially away from tubular portion <NUM>). <FIG> shows a state of implant <NUM> in which both flange <NUM> and portion <NUM> extend away from axis ax1. In the fully-expanded state (<FIG>) both upstream support portion <NUM> and flange <NUM> extend radially away from axis ax1. Typically, frame assembly <NUM> is biased (e.g., shape-set) to assume its fully-expanded state, which is shown in <FIG>. Transitioning of implant <NUM> between the respective states is typically controlled by delivery apparatus, such as by constraining the implant in a compressed state within a delivery tube and/or against a control rod, and selectively releasing portions of the implant to allow them to expand.

In the compressed state of frame assembly <NUM>, tubular portion <NUM> has a diameter d1, and in the expanded state, the tubular portion has a diameter d2 that is greater that diameter d1. For some applications, diameter d1 is <NUM>-<NUM>, (e.g., <NUM>-<NUM>) and diameter d2 is <NUM>-<NUM>, (e.g., <NUM>-<NUM>). For some applications, and as shown, in its expanded state tubular portion <NUM> bulges slightly in its middle (e.g., is slightly barrel-shaped). For such applications, values of diameter d2 are the average diameter along the tubular portion. Similarly, values for the cross-sectional area of the tubular portion are the average cross-sectional area along the tubular portion. This also applies to other implants described herein, mutatis mutandis.

Frame assembly <NUM> is configured such that increasing the diameter of tubular portion <NUM> (e.g., from d1 to d2) causes longitudinal movement of flange <NUM> away from coupling point <NUM>. In the same way, reducing the diameter of tubular portion <NUM> (e.g., from d2 to d1) causes longitudinal movement of flange <NUM> toward coupling point <NUM>. 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 flange <NUM> away from coupling point <NUM> means increasing a distance, measured parallel with longitudinal axis ax1, between flange <NUM> and coupling point <NUM>. An example of such a configuration is described in more detail with respect to <FIG>.

Similarly reference to an element being "upstream of" (or "above") or "downstream of" (or "below") another element refers to its relative position along the central longitudinal axis of the implant ("upstream" and "downstream" being defined by the direction in which the implant facilitates blood flow).

Thus, expansion of tubular portion <NUM> from its compressed state toward its expanded state (i) increases a circumferential distance between each of coupling points <NUM> and its adjacent coupling points (e.g., between each of outer-frame coupling elements <NUM> and its adjacent outer-frame coupling elements) (e.g., from d8 to d9), and (ii) moves legs <NUM> in a longitudinally upstream direction with respect to the tubular portion.

Typically, frame assembly <NUM> is configured such that increasing the diameter of tubular portion <NUM> also causes longitudinal movement of upstream support portion <NUM> toward coupling point <NUM>, e.g., as described in more detail with respect to <FIG>. Typically, frame assembly <NUM> is configured such that increasing the diameter of tubular portion <NUM> also causes longitudinal movement of upstream end <NUM> of tubular portion <NUM> toward coupling point <NUM>. In the same way, reducing the diameter of tubular portion <NUM> causes longitudinal movement of upstream end <NUM> away from coupling point <NUM>.

For some applications, upstream support portion <NUM> comprises a plurality of arms <NUM> that each extends radially outward from tubular portion <NUM> (e.g., from upstream end <NUM> of the tubular portion). Arms <NUM> are typically flexible. For some such applications, arms <NUM> are coupled to tubular portion <NUM> such that each arm may deflect independently of adjacent arms during implantation (e.g., due to anatomical topography).

For some applications, upstream support portion <NUM> comprises a plurality of barbs <NUM> that extend out of a downstream surface of the upstream support portion. For example, each arm <NUM> may comprise one or more of barbs <NUM>. Barbs <NUM> press into tissue upstream of the native valve (e.g., into the valve annulus), thereby inhibiting downstream movement of implant <NUM> (in addition to inhibition of downstream movement provided by the geometry of upstream support portion <NUM>).

One or more surfaces of frame assembly <NUM> are covered with a covering <NUM>, which typically comprises a flexible sheet, such as a fabric, e.g., comprising polyester. Typically, covering <NUM> covers at least part of tubular portion <NUM>, typically lining an inner surface of the tubular portion, and thereby defining lumen <NUM>.

Further typically, upstream support portion <NUM> is covered with covering <NUM>, e.g., extending between arms <NUM> to form an annular shape. It is hypothesized that this reduces a likelihood of paravalvular leakage. For such applications, excess covering <NUM> may be provided between arms <NUM> of upstream support portion <NUM>, so as to facilitate their independent movement. Although <FIG> shows covering <NUM> covering an upstream side of upstream support portion <NUM>, the covering typically additionally (or alternatively) covers the downstream side of the upstream support portion. For example, covering <NUM> may extend over the tips of arms <NUM> and down the outside of the arms, or a separate piece of covering may be provided on the downstream side of the upstream support portion.

Alternatively, each arm <NUM> may be individually covered in a sleeve of covering <NUM>, thereby facilitating independent movement of the arms.

For some applications, at least part of legs <NUM> (e.g., flanges thereof) is covered with covering <NUM>.

Typically, frame assembly <NUM> comprises a plurality of legs <NUM> (e.g., two or more legs, e.g., <NUM>-<NUM> legs, such as <NUM>-<NUM> legs, such as <NUM>-<NUM> legs), arranged circumferentially around valve frame <NUM> (e.g., around the outside of tubular portion <NUM>). Typically, frame assembly <NUM> comprises a plurality of coupling points <NUM> at which the legs are coupled to valve frame <NUM>.

As described in more detail hereinbelow (e.g., with reference to <FIG>), each leg <NUM> is typically coupled to a coupling point <NUM> via a strut <NUM>. For some applications, each leg <NUM> is coupled to a plurality of (e.g., two) coupling points <NUM> via a respective plurality of (e.g., two) struts <NUM>. For some such applications, frame assembly <NUM> is arranged such that, in the expanded state of the frame assembly, leg <NUM> is disposed, circumferentially with respect to tubular portion <NUM>, between two struts, and each of the two struts are disposed, circumferentially with respect to the tubular portion, between the leg and a respective coupling point <NUM>.

For some applications, a plurality of (e.g., two) legs are coupled to each coupling point <NUM> via a respective plurality of (e.g., two) struts <NUM>. For some such applications, frame assembly <NUM> is arranged such that, in the expanded state of the frame assembly, coupling point <NUM> is disposed, circumferentially with respect to tubular portion <NUM>, between two struts <NUM>, and each of the two struts are disposed, circumferentially with respect to the tubular portion, between the coupling point and a respective leg <NUM>.

For some applications, frame assembly <NUM> comprises an outer frame (e.g., a leg frame) <NUM> that circumscribes tubular portion <NUM>, comprises (or defines) the plurality of legs <NUM> and the plurality of struts <NUM>, and is coupled to valve frame <NUM> at the plurality of coupling points <NUM>, such that the plurality of legs are distributed circumferentially around the tubular portion. For such applications, outer frame <NUM> comprises a ring <NUM> that is defined by a pattern of alternating peaks <NUM> and troughs <NUM>, and that typically circumscribes tubular portion <NUM>. For example, the ring may comprise struts <NUM>, extending between the peaks and troughs. Peaks <NUM> are longitudinally closer to upstream end <NUM> of tubular portion <NUM> than to downstream end <NUM>, and troughs <NUM> are longitudinally closer to the downstream end than to the upstream 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 ax1 or 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, peaks <NUM> are closer than troughs <NUM> to upstream end <NUM>, and troughs <NUM> are closer than peaks <NUM> to downstream end <NUM>. For applications in which frame <NUM> comprises ring <NUM>, each leg <NUM> is coupled to the ring (or defined by frame <NUM>) at a respective trough <NUM>.

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

For applications in which frame assembly <NUM> has a plurality of coupling points <NUM>, the coupling points (and therefore coupling elements <NUM> and <NUM>) are disposed circumferentially around the frame assembly (e.g., around axis ax1), typically on a transverse plane that is orthogonal to axis ax1. This transverse plane is illustrated by the position of section A-A in <FIG>. Alternatively, coupling points <NUM> may be disposed at different longitudinal heights of frame assembly <NUM>, e.g., such that different flanges <NUM> are positioned and/or moved differently to others. Typically, coupling points <NUM> (and therefore coupling elements <NUM> and <NUM>) are disposed longitudinally between upstream end <NUM> and downstream end <NUM> of frame assembly <NUM>, but not at either of these ends. Further typically, coupling points <NUM> are disposed longitudinally between upstream end <NUM> and downstream end <NUM> of tubular portion <NUM>, but not at either of these ends. For example, the coupling points may be more than <NUM> (e.g., <NUM>-<NUM>) both from end <NUM> and from end <NUM>. It is hypothesized that this advantageously positions the coupling points at a part of tubular portion <NUM> that is more rigid than end <NUM> or end <NUM>.

It is to be noted that leg <NUM> is typically expandable into its expanded state (e.g., a released-flange state) such that flange <NUM> extends away from axis ax1, independently of increasing the diameter of tubular portion <NUM> (e.g., as shown in <FIG> & <FIG>). Similarly, upstream support portion <NUM> is typically expandable into its expanded state (e.g., a released-arm state) such that it (e.g., arms <NUM> thereof) extends away from axis ax1, independently of increasing the diameter of tubular portion <NUM> (e.g., as shown in <FIG>). The state shown in <FIG> may be considered to be an intermediate state. Therefore, implant <NUM> is typically configured such that legs <NUM> (e.g., flanges <NUM> thereof) and upstream support portion <NUM> are expandable such that they both extend away from axis ax1, while retaining a distance d3 therebetween. This distance is subsequently reducible to a distance d4 by expanding tubular portion <NUM> (e.g., shown in <FIG>).

For some applications, while tubular portion <NUM> remains in its compressed state, flange <NUM> can extend away from axis ax1 over <NUM> percent (e.g., <NUM>-<NUM> percent, such as <NUM>-<NUM> percent) of the distance that it extends from the axis subsequent to the expansion of the tubular portion. For example, for applications in which implant <NUM> comprises a flange on opposing sides of the implant, a span d15 of the flanges while tubular portion <NUM> is in its compressed state may be at least <NUM> percent (e.g., <NUM>-<NUM> percent, such as <NUM>-<NUM> percent) as great as a span d16 of the flanges subsequent to the expansion of the tubular portion. For some applications, span d15 is greater than <NUM> and/or less than <NUM> (e.g., <NUM>-<NUM>). For some applications, span d16 is greater than <NUM> and/or less than <NUM> (e.g., <NUM>-<NUM>). It is to be noted that flange <NUM> is effectively fully expanded, with respect to other portions of leg <NUM> and/or with respect to tubular portion <NUM>, before and after the expansion of the tubular portion.

Similarly, for some applications, while tubular portion <NUM> remains in its compressed state, upstream support portion <NUM> (e.g., arms <NUM>) can extend away from axis ax1 over <NUM> percent (e.g., <NUM>-<NUM> percent) of the distance that it extends from the axis subsequent to the expansion of the tubular portion. That is, for some applications, a span d17 of the upstream support portion while tubular portion <NUM> is in its compressed state may be at least <NUM> percent (e.g., <NUM>-<NUM> percent) as great as a span d18 of the upstream support portion subsequent to the expansion of the tubular portion. For some applications, span d17 is greater than <NUM> (e.g., greater than <NUM>) and/or less than <NUM> (e.g., <NUM>-<NUM>). For some applications, span d18 is greater than <NUM> and/or less than <NUM> (e.g., <NUM>-<NUM>, such as <NUM>-<NUM>). It is to be noted that upstream support portion <NUM> is effectively fully expanded, with respect to tubular portion <NUM>, before and after the expansion of the tubular portion.

It is to be noted that when tubular portion <NUM> is expanded, flanges <NUM> typically translate radially outward from span d15 to span d16 (e.g., without deflecting). Typically, upstream support portion <NUM> behaves similarly (e.g., arms <NUM> translated radially outward from span d17 to span d18, e.g., without deflecting). That is, an orientation of each flange <NUM> and/or each arm <NUM> with respect to tubular portion <NUM> and/or axis ax1 is typically the same in the state shown in <FIG> as it is in the state shown in <FIG>. Similarly, for some applications an orientation of each flange <NUM> with respect to upstream support portion <NUM> (e.g., with respect to one or more arms <NUM> thereof) is the same before and after expansion of tubular portion <NUM>.

For some applications, increasing the diameter of tubular portion <NUM> from d1 to d2 causes greater than <NUM> and/or less than <NUM> (e.g., <NUM>-<NUM>, such as <NUM>-<NUM> or <NUM>-<NUM>) of longitudinal movement of flange <NUM> away from coupling point <NUM>. For some applications, increasing the diameter of tubular portion <NUM> from d1 to d2 causes greater than <NUM> and/or less than <NUM> (e.g., <NUM>-<NUM>, such as <NUM>-<NUM> or <NUM>-<NUM>) of longitudinal movement of upstream support portion <NUM> toward coupling point <NUM>. For some applications, distance d3 is <NUM>-<NUM>. For some applications, distance d4 is <NUM>-<NUM> (e.g., <NUM>-<NUM>). For some applications, increasing the diameter of tubular portion <NUM> from d1 to d2 reduces the distance between the upstream support portion and flanges <NUM> by more than <NUM> and/or less than <NUM>, such as <NUM>-<NUM> (e.g., <NUM>-<NUM>, such as <NUM>-<NUM> or <NUM>-<NUM>). For some applications, the difference between d3 and d4 is generally equal to the difference between d1 and d2. For some applications, the difference between d3 and d4 is more than <NUM> and/or less than <NUM> times (e.g., <NUM>-<NUM> times, such as about <NUM> times) greater than the difference between d1 and d2.

For some applications, flanges <NUM> curve such that a tip of each flange is disposed at a shallower angle with respect to inner region <NUM> of upstream support portion <NUM>, than are portions of leg <NUM> that are closer to downstream end <NUM> of frame assembly <NUM>. For some such applications, a tip of each flange may be generally parallel with inner region <NUM>. For some such applications, while tubular portion <NUM> is in its expanded state, a tip portion <NUM> of each flange <NUM> that extends from the tip of the flange at least <NUM> along the flange, is disposed within <NUM> of upstream support portion <NUM>. Thus, for some applications, while tubular portion <NUM> is in its expanded state, for at least <NUM> percent (e.g., <NUM>-<NUM> percent, or at least <NUM> percent) of span <NUM> of upstream support portion <NUM>, the upstream support portion is disposed within <NUM> of a flange <NUM>.

For some applications, in the absence of any obstruction (such as tissue of the valve or covering <NUM>) between flange <NUM> and upstream support portion <NUM>, increasing the diameter of tubular portion <NUM> from d1 to d2 causes the flange and the upstream support portion to move past each other (e.g., the flange may move between arms <NUM> of the upstream support portion), such that the flange is closer to the upstream end of implant <NUM> than is the upstream support portion, e.g., as shown hereinbelow for frame assemblies <NUM> and <NUM>, mutatis mutandis. (For applications in which upstream support portion <NUM> is covered by covering <NUM>, flanges <NUM> typically don't pass the covering. For example, in the absence of any obstruction, flanges <NUM> may pass between arms <NUM>, and press directly against covering <NUM>. ) It is hypothesized that for some applications this configuration applies greater force to the valve tissue being sandwiched, and thereby further facilitates anchoring of the implant. That is, for some applications, distance d3 is smaller than the sum of distance d5 and a distance d14 (described with reference to <FIG>). For some applications, increasing the diameter of tubular portion <NUM> from d1 to d2 advantageously causes flanges <NUM> and upstream support portion <NUM> to move greater than <NUM> and/or less than <NUM> (e.g., greater than <NUM> and/or less than <NUM>, e.g., <NUM>-<NUM>, such as about <NUM>) with respect to each other (e.g., toward each other and then past each other).

For some applications, in the expanded state of frame assembly <NUM>, upstream support portion <NUM> has an inner region (e.g., an inner ring) <NUM> that extends radially outward at a first angle with respect to axis ax1 (and typically with respect to tubular portion <NUM>), and an outer region (e.g., an outer ring) <NUM> that extends, from the inner region, 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. For example, for some applications inner region <NUM> extends radially outward at an angle alpha_1 of <NUM>-<NUM> degrees (e.g., <NUM>-<NUM> degrees) with respect to axis ax1, and outer region <NUM> extends radially outward at an angle alpha_2 of <NUM>-<NUM> degrees (e.g., <NUM>-<NUM> 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 portion <NUM>, and the portion of axis ax1 that extends in an upstream direction from the level of frame assembly <NUM> at which the respective region begins to extend radially outward.

For some applications in which implant <NUM> is configured to be placed at an atrioventricular valve (e.g., a mitral valve or a tricuspid valve) of the subject, region <NUM> is configured to be placed against the upstream surface of the annulus of the atrioventricular valve, and region <NUM> is configured to be placed against the walls of the atrium upstream of the valve.

For some applications, outer region <NUM> is more flexible than inner region <NUM>. For example, and as shown, each arm <NUM> may have a different structure in region <NUM> than in region <NUM>. It is hypothesized that the relative rigidity of region <NUM> provides resistance against ventricular migration of implant <NUM>, while the relative flexibility of region <NUM> facilitates conformation of upstream support portion <NUM> to the atrial anatomy.

For some applications, two or more of arms <NUM> are connected by a connector (not shown), reducing the flexibility, and/or the independence of movement of the connected arms relative to each other. For some applications, arms <NUM> are connected in particular sectors of upstream support portion <NUM>, thereby making these sectors more rigid than sectors in which the arms 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 upstream support portion <NUM> on the aortic sinus.

For some applications, and as shown, coupling points <NUM> are disposed closer to downstream end <NUM> of frame assembly <NUM> than are flanges <NUM>, or is upstream support portion <NUM>.

As described in more detail with respect to <FIG>, the movement of flange <NUM> away from coupling point <NUM> (and the typical movement of upstream support portion <NUM> toward the coupling point) facilitates the sandwiching of tissue of the native valve (e.g., leaflet and/or annulus tissue) between the flange and the upstream support portion, thereby securing implant <NUM> at the native valve.

Typically, in the compressed state of tubular portion <NUM>, a downstream end of each leg <NUM> is longitudinally closer than valve-frame coupling elements <NUM> to downstream end <NUM>, and flange <NUM> of each leg is disposed longitudinally closer than the valve-frame coupling elements to upstream end <NUM>. Typically, this is also the case in the expanded state of tubular portion <NUM>.

<FIG> show structural changes in frame assembly <NUM> during transitioning of the assembly between its compressed and expanded states, in accordance with some applications of the invention. <FIG> each 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> shows a leg <NUM> and struts <NUM> (e.g., a portion of outer frame <NUM>), and illustrates the structural changes that occur around outer frame <NUM>. <FIG> shows a portion of valve frame <NUM>, and illustrates the structural changes that occur around the valve frame. <FIG> shows valve frame <NUM> as a whole. In each of <FIG>, state (A) illustrates the structure while frame assembly <NUM> (and in particular tubular portion <NUM>) is in its compressed state, and state (B) illustrates the structure while the frame assembly (and in particular tubular portion <NUM>) is in its expanded state.

<FIG> shows structural changes in the coupling of legs <NUM> to coupling point <NUM> (e.g., structural changes of outer frame <NUM>) during the transitioning of frame assembly <NUM> (and in particular tubular portion <NUM>) between its compressed and expanded states. Each leg <NUM> is coupled to valve frame <NUM> via at least one strut <NUM>, which connects the leg to coupling point <NUM>. Typically, each leg <NUM> is coupled to valve frame <NUM> via a plurality of struts <NUM>. A first end <NUM> of each strut <NUM> is coupled to leg <NUM>, and a second end <NUM> of each strut is coupled to a coupling point <NUM>. As described hereinabove, for applications in which frame <NUM> comprises ring <NUM>, each leg <NUM> is coupled to the ring at a respective trough <NUM>. Ring <NUM> may comprise struts <NUM>, extending between the peaks and troughs, with each first end <NUM> at (or close to) a trough <NUM>, and each second end <NUM> at (or close to) a peak <NUM>.

In the compressed state of frame assembly <NUM> (and in particular of tubular portion <NUM>), each strut <NUM> is disposed at a first angle in which first end <NUM> is disposed closer than second end <NUM> to the downstream end of the frame assembly. Expansion of frame assembly <NUM> (and in particular of tubular portion <NUM>) toward its expanded state causes strut <NUM> to deflect to a second angle. This deflection moves first end <NUM> away from the downstream end of frame assembly <NUM>. That is, in the expanded state of frame assembly <NUM>, first end <NUM> is further from the downstream end of the frame assembly than it is when the frame assembly is in its compressed state. This movement is shown as a distance d5 between the position of end <NUM> in state (A) and its position in state (B). This movement causes the above-described movement of flanges <NUM> away from coupling points <NUM>. As shown, flanges <NUM> typically move the same distance d5 in response to expansion of frame assembly <NUM>.

For applications in which outer frame <NUM> comprises ring <NUM>, 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 ax1 of frame assembly <NUM>, and the transition between the compressed and expanded states may be described as follows: In the compressed state of frame assembly <NUM> (and in particular of tubular portion <NUM>), the pattern of ring <NUM> has an amplitude d20. In the expanded state frame assembly <NUM> (and in particular of tubular portion <NUM>), the pattern of ring <NUM> has an amplitude d21 that is lower than amplitude d20. Because (i) it is at peaks <NUM> that ring <NUM> is coupled to valve frame <NUM> at coupling points <NUM>, and (ii) it is at troughs <NUM> that ring <NUM> is coupled to legs <NUM>, this reduction in the amplitude of the pattern of ring <NUM> moves legs <NUM> (e.g., flanges <NUM> thereof) longitudinally further from the downstream end of the frame assembly. The magnitude of this longitudinal movement (e.g., the difference between magnitudes d20 and d21) is equal to d5.

Typically, distance d5 is the same distance as the distance that flange <NUM> moves away from coupling point <NUM> during expansion of the frame assembly. That is, a distance between flange <NUM> and the portion of leg <NUM> that is coupled to strut <NUM>, typically remains constant during expansion of the frame assembly. For some applications, the longitudinal movement of flange <NUM> away from coupling point <NUM> is a translational movement (e.g., a movement that does not include rotation or deflection of the flange).

For some applications, a distance d6, measured parallel to axis ax1 of frame assembly <NUM>, between coupling point <NUM> and first end <NUM> of strut <NUM> while assembly <NUM> is in its compressed state, is <NUM>-<NUM>. For some applications, a distance d7, measured parallel to axis ax1, between coupling point <NUM> and first end <NUM> of strut <NUM> while assembly <NUM> is in its expanded state, is <NUM>-<NUM> (e.g., <NUM>-<NUM>).

For some applications, amplitude d20 is <NUM>-<NUM> (e.g., <NUM>-<NUM>). For some applications, amplitude d21 is <NUM>-<NUM> (e.g., <NUM>-<NUM>).

For some applications, and as shown, in the expanded state, first end <NUM> of strut <NUM> is disposed closer to the downstream end of frame assembly <NUM> than is coupling point <NUM>. For some applications, in the expanded state, first end <NUM> of strut <NUM> is disposed further from the downstream end of frame assembly <NUM> than is coupling point <NUM>.

For applications in which frame assembly <NUM> comprises a plurality of legs <NUM> and a plurality of coupling points <NUM> (e.g., for applications in which the frame assembly comprises outer frame <NUM>) expansion of the frame assembly increases a circumferential distance between adjacent coupling points <NUM>, and an increase in a circumferential distance between adjacent legs <NUM>. <FIG> shows such an increase in the circumferential distance between adjacent coupling points <NUM>, from a circumferential distance d8 in the compressed state to a circumferential distance d9 in the expanded state. For some applications, distance d8 is <NUM>-<NUM>. For some applications, distance d9 is <NUM>-<NUM>.

For some applications, in addition to being coupled via ring <NUM> (e.g., struts <NUM> thereof) legs <NUM> are also connected to each other via connectors <NUM>. Connectors <NUM> allow the described movement of legs <NUM> during expansion of frame assembly <NUM>, but typically stabilize legs <NUM> relative to each other while the frame assembly is in its expanded state. For example, connectors <NUM> may bend and/or deflect during expansion of the frame assembly.

<FIG> show structural changes in valve frame <NUM> during the transitioning of frame assembly <NUM> between its compressed and expanded states. Tubular portion <NUM> of valve frame <NUM> is defined by a plurality of cells <NUM>, which are defined by the repeating pattern of the valve frame. When frame assembly <NUM> is expanded from its compressed state toward its expanded state, cells <NUM> (i) widen from a width d10 to a width d11 (measured orthogonal to axis ax1 of the frame assembly), and (ii) shorten from a height d12 to a height d13 (measured parallel to axis ax1 of the frame assembly). This shortening reduces the overall height (i.e., a longitudinal length between upstream end <NUM> and downstream end <NUM>) of tubular portion <NUM> from a height d22 to a height d23, and thereby causes the above-described longitudinal movement of upstream support portion <NUM> toward coupling points <NUM> by a distance d14 (shown in <FIG>). For some applications, and as shown, coupling points <NUM> are disposed at the widest part of each cell.

Due to the configurations described herein, the distance by which flanges <NUM> move with respect to (e.g., toward, or toward-and-beyond) upstream support portion <NUM> (e.g., arms <NUM> thereof), is typically greater than the reduction in the overall height of tubular portion <NUM> (e.g., more than <NUM> percent greater, such as more than <NUM> percent greater, such as more than <NUM> percent greater). That is, implant <NUM> comprises:.

As shown in the figures, valve frame <NUM> is typically coupled to outer frame <NUM> by coupling between (i) a valve-frame coupling element <NUM> defined by valve frame <NUM>, and (ii) an outer-frame coupling element <NUM> defined by outer frame <NUM> (e.g., an outer-frame coupling element is coupled to end <NUM> of each strut). Typically, elements <NUM> and <NUM> are fixed with respect to each other. Each coupling point <NUM> is thereby typically defined as the point at which a valve-frame coupling element and a corresponding outer-frame coupling element <NUM> are coupled (e.g., are fixed with respect to each other). For some applications, and as shown, elements <NUM> and <NUM> are eyelets configured to be coupled together by a connector, such as a pin or a stitch (e.g., a suture). The fixing of elements <NUM> and <NUM> with respect to each other may be achieved by welding, soldering, crimping, stitching (e.g., suturing), gluing, or any other suitable technique.

Typically, and as shown, valve-frame coupling elements <NUM> are defined by tubular portion <NUM>, and are disposed circumferentially around central longitudinal axis ax1. Outer-frame coupling elements <NUM> are coupled to ring <NUM> (or defined by frame <NUM>, such as by ring <NUM>) at respective peaks <NUM>.

As shown (e.g., in <FIG>), valve frame <NUM> (e.g., tubular portion <NUM> thereof) and outer frame <NUM> (e.g., ring <NUM> thereof) are arranged in a close-fitting coaxial arrangement, in both the expanded and compressed states of frame assembly <NUM>. Ignoring spaces due to the cellular structure of the frames, a radial gap d19 between valve frame <NUM> (e.g., tubular portion <NUM> thereof) and outer frame <NUM> (e.g., ring <NUM> thereof) is typically less than <NUM> (e.g., less than <NUM>), in both the compressed and expanded states, and during the transition therebetween. This is facilitated by the coupling between frames <NUM> and <NUM>, and the behavior, described hereinabove, of frame <NUM> in response to changes in the diameter of tubular portion <NUM> (e.g., rather than solely due to delivery techniques and/or tools). For some applications, more than <NUM> percent (e.g., more than <NUM> percent) of ring <NUM> is disposed within <NUM> of tubular portion <NUM> in both the compressed and expanded states, and during the transition therebetween. For some applications, more than <NUM> percent (e.g., more than <NUM> percent) of outer frame <NUM>, except for flanges <NUM>, is disposed within <NUM> of tubular portion <NUM> in both the compressed and expanded states, and during the transition therebetween.

The structural changes to frame assembly <NUM> (e.g., to outer frame <NUM> thereof) are described hereinabove as they occur during (e.g., as a result of) expansion of the frame assembly (in particular tubular portion <NUM> thereof). This is the natural way to describe these changes because, as described hereinbelow with respect to <FIG>, assembly <NUM> is in its compressed state during percutaneous delivery to the implant site, and is subsequently expanded. However, the nature of implant <NUM> may be further understood by describing structural changes that occur during compression of the frame assembly (e.g., a transition from the expanded state in <FIG> to the intermediate state in <FIG>), in particular tubular portion <NUM> thereof (including if tubular portion <NUM> were compressed by application of compressive force to the tubular portion, and not to frame <NUM> except via the tubular portion pulling frame <NUM> radially inward). Such descriptions may also be relevant because implant <NUM> is typically compressed (i.e., "crimped") soon before its percutaneous delivery, and therefore these changes may occur while implant <NUM> is in the care of the operating physician.

For some applications, the fixation of peaks <NUM> to respective sites of tubular portion <NUM> is such that compression of the tubular portion from its expanded state toward its compressed state such that the respective sites of the tubular portion pull the peaks radially inward via radially-inward tension on coupling points <NUM>: (i) reduces a circumferential distance between each of the coupling points and its adjacent coupling points (e.g., from d9 to d8), and (ii) increases the amplitude of the pattern of ring <NUM> (e.g., from d21 to d20).

For some applications, the fixation of outer-frame coupling elements <NUM> to valve-frame coupling elements <NUM> is such that compression of tubular portion <NUM> from its expanded state toward its 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 (e.g., from d9 to d8), and (ii) increases the amplitude of the pattern of ring <NUM> (e.g., from d21 to d20).

For some applications, the fixation of peaks <NUM> to the respective sites of tubular portion <NUM> is such that compression of the tubular portion from its expanded state toward its 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 coupling points <NUM> and its adjacent coupling points (e.g., from d9 to d8), and (iii) increases the amplitude of the pattern of ring <NUM> (e.g., from d21 to d20), without increasing radial gap d19 between valve frame <NUM> (e.g., tubular portion <NUM> thereof) and the ring by more than <NUM>.

For some applications, the fixation of outer-frame coupling elements <NUM> with respect to valve-frame coupling elements <NUM> is such that compression of tubular portion <NUM> from its expanded state toward its compressed state (i) pulls outer-frame coupling elements <NUM> radially inward via radially-inward pulling of valve-frame coupling elements <NUM> on outer-frame coupling elements <NUM>, (ii) reduces a circumferential distance between each of the outer-frame coupling elements and its adjacent outer-frame coupling elements (e.g., from d9 to d8), and (iii) increases the amplitude of the pattern of ring <NUM> (e.g., from d21 to d20), without increasing radial gap d19 between valve frame <NUM> (e.g., tubular portion <NUM> thereof) and the ring by more than <NUM>.

Reference is made to <FIG>, which are schematic illustrations of implantation of implant <NUM> at a native valve <NUM> of a heart <NUM> of a subject, in accordance with some applications of the invention. Valve <NUM> is shown as a mitral valve of the subject, disposed between a left atrium <NUM> and a left ventricle <NUM> of the subject. However, implant <NUM> may be implanted at another heart valve of the subject, mutatis mutandis. Similarly, although <FIG> show implant <NUM> being delivered transseptally via a sheath <NUM>, the implant may alternatively be delivered by any other suitable route, such as transatrially, or transapically.

Implant <NUM> is delivered, in its compressed state, to native valve <NUM> using a delivery tool <NUM> that is operable from outside the subject (<FIG>). Typically, implant <NUM> is delivered within a delivery capsule <NUM> of tool <NUM>, which retains the implant in its compressed state. A transseptal approach, such as a transfemoral approach, is shown. Typically, implant <NUM> is positioned such that at least flanges <NUM> are disposed downstream of the native valve (i.e., within ventricle <NUM>). At this stage, frame assembly <NUM> of implant <NUM> is as shown in <FIG>.

Subsequently, flanges <NUM> are allowed to protrude radially outward, as described hereinabove, e.g., by releasing them from capsule <NUM> (<FIG>). For example, and as shown, capsule <NUM> may comprise a distal capsule-portion <NUM> and a proximal capsule-portion <NUM>, and the distal capsule-portion may be moved distally with respect to implant <NUM>, so as to expose flanges <NUM>. At this stage, frame assembly <NUM> of implant <NUM> is as shown in <FIG>.

Subsequently, implant <NUM> is moved upstream, such that upstream support portion <NUM>, in its compressed state, is disposed upstream of leaflets <NUM> (i.e., within atrium <NUM>). For some applications, the upstream movement of implant <NUM> causes flanges <NUM> to engage leaflets <NUM>. However, because of the relatively large distance d3 provided by implant <NUM> (described hereinabove), for some applications it is not necessary to move the implant so far upstream that flanges <NUM> tightly engage leaflets <NUM> and/or pull the leaflets upstream of the valve annulus. Upstream support portion <NUM> is then allowed to expand such that it protrudes radially outward, as described hereinabove, e.g., by releasing it from capsule <NUM> (<FIG>). For example, and as shown, proximal capsule-portion <NUM> may be moved proximally with respect to implant <NUM>, so as to expose upstream support portion <NUM>. At this stage, frame assembly <NUM> of implant <NUM> is as shown in <FIG>, in which: (i) distance d3 exists between upstream support portion <NUM> and flanges <NUM>, (ii) the flanges have span d15, (iii) the upstream support portion has span d17, and (iv) tubular portion <NUM> has diameter d1.

Typically, expansion of frame assembly <NUM> is inhibited by distal capsule-portion <NUM> (e.g., by inhibiting expansion of tubular portion <NUM>), and/or by another portion of delivery tool <NUM> (e.g., a portion of the delivery tool that is disposed within lumen <NUM>).

Subsequently, implant <NUM> is allowed to expand toward its expanded state, such that tubular portion <NUM> widens to diameter d2, and the distance between upstream support portion <NUM> and flanges <NUM> reduces to distance d4 (<FIG>). This sandwiches tissue of valve <NUM> (typically including annular tissue and/or leaflets <NUM>) between upstream support portion <NUM> and flanges <NUM>, thereby securing implant <NUM> at the valve. <FIG> shows delivery capsule <NUM> having been removed from the body of the subject, leaving implant <NUM> in place at valve <NUM>.

As described hereinabove, implant <NUM> is configured such that when tubular portion <NUM> is expanded, flanges <NUM> and upstream support portion <NUM> move a relatively large distance toward each other. This enables distance d3 to be relatively large, while distance d4 is sufficiently small to provide effective anchoring. As also described hereinabove, implant <NUM> is configured such that flanges <NUM> and upstream support portion <NUM> can extend radially outward a relatively large distance while tubular portion <NUM> remains compressed. It is hypothesized that for some applications, these configurations (independently and/or together) facilitate effective anchoring of implant <NUM>, by facilitating placement of a relatively large proportion of valve tissue (e.g., leaflets <NUM>) between the flanges and the upstream support portion prior to expanding tubular portion <NUM> and sandwiching the valve tissue.

It is further hypothesized that the relatively great radially-outward extension of flanges <NUM> and upstream support portion <NUM> prior to expansion of tubular portion <NUM>, further facilitates the anchoring/sandwiching step by reducing radially-outward pushing of the valve tissue (e.g., leaflets <NUM>) during the expansion of the tubular portion, and thereby increasing the amount of valve tissue that is sandwiched.

It is yet further hypothesized that this configuration of implant <NUM> facilitates identifying correct positioning of the implant (i.e., with upstream support portion <NUM> upstream of leaflets <NUM> and flanges <NUM> downstream of the leaflets) prior to expanding tubular portion <NUM> and sandwiching the valve tissue.

As shown in <FIG>, for some applications, in the expanded state of frame assembly <NUM>, implant <NUM> defines a toroidal space <NUM> between flanges <NUM> and upstream support portion <NUM> (e.g., a space that is wider than distance d4). For example, space <NUM> may have a generally triangular cross-section. It is hypothesized that for some such applications, in addition to sandwiching tissue of the native valve between upstream support portion <NUM> and flanges <NUM> (e.g., the tips of the flanges), space <NUM> advantageously promotes tissue growth therewithin (e.g., between leaflet tissue and covering <NUM>), which over time further secures implant <NUM> within the native valve.

Reference is now made to <FIG>, which is a schematic illustration of a step in the implantation of implant <NUM>, in accordance with some applications of the invention.

<FIG> show an implantation technique in which flanges <NUM> are expanded prior to upstream support portion <NUM>, for some applications the upstream support portion is expanded prior to the flanges. <FIG> shows a step in such an application.

Reference is again made to <FIG>. As noted hereinabove, implant <NUM> may be implanted by causing flanges <NUM> to radially protrude before causing upstream support portion <NUM> to radially protrude, or may be implanted by causing the upstream support portion to protrude before causing the flanges to protrude. For some applications, implant <NUM> is thereby configured to be deliverable in a downstream direction (e.g., transseptally, as shown, or transapically) or in an upstream direction (e.g., transapically or via the aortic valve). Thus, for some applications, 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 implant <NUM> is responsively prepared for the chosen delivery route (e.g., by loading the implant into an appropriate delivery tool).

It is to be noted that for some applications, downstream delivery of implant <NUM> may be performed by expanding flanges <NUM> first (e.g., as shown in <FIG>) or by expanding upstream support portion <NUM> first (e.g., as shown in <FIG>). Similarly, for some applications upstream delivery of implant <NUM> may be performed by upstream support portion <NUM> first, or by expanding flanges <NUM> first.

Reference is now made to <FIG>, which is a schematic illustration of implant <NUM>, in the state and position shown in <FIG>, in accordance with some applications of the invention. For some applications, while implant <NUM> is in the state and position shown in <FIG>, leaflets <NUM> of valve <NUM> are able to move, at least in part in response to beating of the heart. Frame (A) shows leaflets <NUM> during ventricular systole, and frame (B) shows the leaflets during ventricular diastole. For some such applications, blood is thereby able to flow from atrium <NUM> to ventricle <NUM>, between leaflets <NUM> and implant <NUM>. It is hypothesized that this advantageously facilitates a more relaxed implantation procedure, e.g., facilitating retaining of implant <NUM> in this state and position for a duration of greater than <NUM> minutes. During this time, imaging techniques may be used to verify the position of implant <NUM>, and/or positioning of leaflets <NUM> between upstream support portion <NUM> and flanges <NUM>.

Reference is made to <FIG> and <FIG>, which are schematic illustrations of frame assemblies <NUM> and <NUM> of respective implants, in accordance with some applications of the invention. Except where noted otherwise, frame assemblies <NUM> and <NUM> are typically identical to frame assembly <NUM>, mutatis mutandis. Elements of frame assemblies <NUM> and <NUM> share the name of corresponding elements of frame assembly <NUM>. Additionally, except where noted otherwise, the implants to which frame assemblies <NUM> and <NUM> belong are similar to implant <NUM>, mutatis mutandis.

Frame assembly <NUM> comprises (i) a valve frame <NUM> that comprises a tubular portion <NUM> and an upstream support portion <NUM> that typically comprises a plurality of arms <NUM>, and (ii) an outer frame (e.g., a leg frame) <NUM> that circumscribes the valve frame, and comprises a plurality of legs <NUM> that each comprise a tissue-engaging flange <NUM>. Typically, outer frame <NUM> comprises a ring <NUM> to which legs <NUM> are coupled. Ring <NUM> is defined by a pattern of alternating peaks and troughs, the peaks being fixed to frame <NUM> at respective coupling points <NUM>, e.g., as described hereinabove for frame assembly <NUM>, mutatis mutandis.

Whereas arms <NUM> of frame assembly <NUM> are shown as extending from upstream end <NUM> of tubular portion <NUM>, arms <NUM> and <NUM> of frame assemblies <NUM> and <NUM>, respectively, extend from sites further downstream. (This difference may also be made to frame assembly <NUM>, mutatis mutandis. ) Tubular portions <NUM>, <NUM> and <NUM> are each defined by a repeating pattern of cells that extends around the central longitudinal axis. Typically, and as shown, tubular portions <NUM>, <NUM> and <NUM> are each defined by two stacked, tessellating rows of cells. In the expanded state of each tubular portion, these cells are typically narrower at their upstream and downstream extremities than midway between these extremities. For example, and as shown, the cells may be roughly diamond or astroid in shape. In frame assembly <NUM>, each arm <NUM> is attached to and extends from a site <NUM> that is at the upstream extremity of cells of the upstream row. In contrast, in frame assemblies <NUM> and <NUM>, each arm <NUM> or <NUM> is attached to and extends from a site <NUM> (assembly <NUM>) or <NUM> (assembly <NUM>) that is at the connection between two adjacent cells of the upstream row (alternatively described as being at the upstream extremity of cells of the downstream row).

It is hypothesized by the inventors that this lower position of the arms, while maintaining the length of the lumen of the tubular portion, advantageously reduces the distance that the tubular portion (i.e., the downstream 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 arms reduces radial compression of the tubular portion by movement of the heart, due to greater rigidity of the tubular portion at sites <NUM> and <NUM> (which is supported by two adjacent cells) than at site <NUM> (which is supported by only one cell).

As shown, in the expanded state of frame assemblies <NUM>, <NUM> and <NUM>, the legs (<NUM>, <NUM> and <NUM>, respectively) are circumferentially staggered with the arms of the upstream support portion (<NUM>, <NUM> and <NUM>, respectively). This allows the legs to move in an upstream direction between the arms during expansion of the tubular portion (<NUM>, <NUM> and <NUM>, respectively), facilitating application of greater sandwiching force on tissue of the native valve. The lower position of the arms of assemblies <NUM> and <NUM> includes circumferentially shifting the position of the arms by the width of half a cell. In order to maintain the circumferential staggering of the arms and legs, rings <NUM> and <NUM> (and thereby legs <NUM> and <NUM>) are circumferentially shifted correspondingly. As a result, whereas the peaks of ring <NUM> generally align with connections between adjacent cells of the downstream row of cells of tubular portion <NUM> (and are fixed to these sites), the peaks of rings <NUM> and <NUM> are generally aligned midway between these sites (i.e., at spaces of the cellular structure of the tubular portion). Appendages <NUM> (for assembly <NUM>) or <NUM> (for assembly <NUM>) facilitate fixing of the peak with respect to the tubular structure.

For assembly <NUM>, appendages <NUM> are defined by valve frame <NUM> (e.g., by tubular portion <NUM> thereof) and extend (in a downstream direction) to the peaks of ring <NUM>, to which they are fixed. For example, each appendage <NUM> may define a valve-frame coupling element <NUM> that is fixed to a respective outer-frame coupling element <NUM> defined by outer frame <NUM>. Typically, appendages <NUM> extend from sites <NUM>. Typically, appendages <NUM> are integral with tubular portion <NUM> and/or in-plane with the tubular portion (e.g., are part of its tubular shape).

For assembly <NUM>, appendages <NUM> are defined by outer frame <NUM>, and extend (e.g., in an upstream direction) from the peaks of ring <NUM>. Typically, appendages <NUM> extend to sites <NUM>, to which they are fixed. For example, each appendage <NUM> may define an outer-frame coupling element <NUM> that is fixed to a respective valve-frame coupling element <NUM> defined by valve frame <NUM> (e.g., by tubular portion <NUM> thereof). Typically, appendages <NUM> are integral with outer frame <NUM> and/or in-plane with adjacent portions of outer frame <NUM>, such as ring <NUM>.

Therefore, frame assembly <NUM> defines a hub at site <NUM>, and frame assembly <NUM> defines a hub at site <NUM>. For some applications, apparatus therefore comprises:.

Reference is made to <FIG>, which are schematic illustrations of an implant <NUM> comprising a frame assembly <NUM>, in accordance with some applications of the invention. Except where noted otherwise, frame assembly <NUM> is identical to frame assembly <NUM>, and implant <NUM> is identical to the implant to which frame assembly <NUM> belongs, mutatis mutandis. <FIG> is a side-view of implant <NUM>, and <FIG> is an isometric bottom-view of the implant.

Frame assembly <NUM> comprises (i) a valve frame <NUM> that comprises a tubular portion <NUM> and an upstream support portion <NUM> that typically comprises a plurality of arms <NUM>, and (ii) an outer frame (e.g., a leg frame) <NUM> that circumscribes the valve frame, and comprises a plurality of legs <NUM> that each comprise a tissue-engaging flange <NUM>. Typically, outer frame <NUM> comprises a ring <NUM> to which legs <NUM> are coupled. Ring <NUM> is defined by a pattern of alternating peaks and troughs, the peaks being fixed to frame <NUM> at respective coupling points <NUM>, e.g., as described hereinabove for frame assembly <NUM> and/or frame assembly <NUM>, mutatis mutandis.

Frame assembly <NUM> comprises an annular upstream support portion <NUM> that has an inner portion <NUM> that extends radially outward from the upstream portion (e.g., the upstream end) of tubular portion <NUM>. Upstream support portion <NUM> further comprises one or more fabric pockets <NUM> disposed circumferentially around inner portion <NUM>, each pocket of the one or more pockets having an opening that faces a downstream direction (i.e., generally toward the downstream end of implant <NUM>). In the figures, upstream support portion <NUM> has a single toroidal pocket <NUM> that extends circumferentially around inner portion <NUM>.

Typically, a covering <NUM> (e.g., similar to covering <NUM>, described hereinabove, mutatis mutandis) is disposed over arms <NUM>, thereby forming pocket <NUM>. Further typically, arms <NUM> are shaped to form pocket <NUM> from covering <NUM>. For example, and as shown, arms <NUM> may curve to form a hook-shape.

For some applications, portion <NUM> has a plurality of separate pockets <NUM>, e.g., separated at arms <NUM>. For some such applications, covering <NUM> is loosely-fitted (e.g., baggy) between radially-outward parts of arms <NUM>, e.g., compared to inner portion <NUM>, in which the covering is more closely-fitted between radially-inward parts of the arms.

<FIG> shows implant <NUM> implanted at native valve <NUM>. Pocket <NUM> is typically shaped and arranged to billow in response to perivalvular flow <NUM> of blood in an upstream direction. If ventricular systole forces blood in ventricle <NUM> between implant <NUM> and native valve <NUM>, that blood inflates pocket <NUM> and presses it (e.g., covering <NUM> and/or the radially-outward part of arm <NUM>) against tissue of atrium <NUM> (e.g., against the atrial wall), thereby increasing sealing responsively. It is hypothesized by the inventors that the shape and orientation of pocket <NUM> (e.g., the hook-shape of arms <NUM>) facilitates this pressing radially-outward in response to the pocket's receipt of upstream-flowing blood.

Pocket(s) <NUM> may be used in combination with any of the implants described herein, mutatis mutandis.

Reference is now made to <FIG>, which is a schematic illustration of a frame assembly <NUM> of an implant, in accordance with some applications of the invention. Except where noted otherwise, frame assembly <NUM> is typically identical to frame assembly <NUM>, mutatis mutandis. Elements of frame assembly <NUM> share the name of corresponding elements of frame assembly <NUM>. Additionally, except where noted otherwise, the implant to which frame assembly <NUM> belongs is similar to implant the other implants described herein (e.g., implant <NUM>), mutatis mutandis. <FIG> shows frame assembly <NUM> in an expanded state (e.g., in the absence of external deforming forces, such as those provided by a delivery tool during implantation, or by heart tissue after implantation).

Frame assembly <NUM> comprises (i) a valve frame (e.g., an inner frame) <NUM> that comprises a tubular portion <NUM> and an upstream support portion <NUM> that typically comprises a plurality of radial arms <NUM>, and (ii) an outer frame (e.g., a leg frame) <NUM> that circumscribes the valve frame, and comprises a plurality of legs <NUM> that each comprise a tissue-engaging flange <NUM>. Typically, outer frame <NUM> comprises a ring <NUM> to which legs <NUM> are coupled. Ring <NUM> is defined by a pattern of alternating peaks and troughs, the peaks being fixed to frame <NUM> at respective coupling points <NUM>, e.g., as described hereinabove for frame assemblies <NUM> and <NUM>, mutatis mutandis. Tubular portion <NUM> has a diameter d26 (corresponding to diameter d2 of implant <NUM>), and a transverse cross-sectional area that is a function of diameter d26.

Similarly to other frame assemblies described herein, in the expanded state of frame assembly <NUM>, legs <NUM> are circumferentially staggered with arms <NUM> of upstream support portion <NUM>. This allows the legs (e.g., flanges <NUM> thereof) to move in an upstream direction between the arms during deployment of the implant (although the presence of heart tissue typically reduces the amount by which flanges <NUM> move between arms <NUM>). <FIG> shows frame assembly <NUM> in its expanded state, in which upstream support portion <NUM> (e.g., arms <NUM>) and flanges <NUM> extend radially outward from tubular portion <NUM>, and intersect at an intersection <NUM>. Opposite intersections <NUM> define an intersect diameter d27. Typically, flanges <NUM> extend radially outward from the tubular portion and toward the upstream support portion <NUM> (i.e., outward and in an upstream direction). A toroidal space <NUM> is defined between flanges <NUM>, upstream support portion <NUM>, and tubular portion <NUM>, the toroidal space circumscribing the tubular portion.

As described hereinabove with respect to other implants, the implant to which frame assembly <NUM> belongs is secured at the native valve by sandwiching heart tissue (e.g., leaflets <NUM> and/or the valve annulus) between upstream support portion <NUM> and flanges <NUM> (e.g., within space <NUM>). Typically, leaflets <NUM> are trapped in space <NUM>. Space <NUM> is dimensioned to be sufficiently large to accommodate leaflets <NUM>, because it has been observed by the inventors that if space <NUM> is too small, the implant tends to become secured to tissue that is suboptimally close to the middle of the native valve orifice (e.g., closer to the free edges of the leaflets), and to sit in a position that is suboptimally downstream (i.e., into ventricle <NUM>). Additionally, space <NUM> is dimensioned to be sufficiently small to accommodate leaflets <NUM> snugly, because it has been observed by the inventors that if space <NUM> is sufficiently small that the leaflets fill the space well (typically folding or bunching up within the space), sandwiching forces are applied to leaflet tissue throughout space <NUM>. In contrast, if space <NUM> is too large, sandwiching forces may be applied to the leaflets only at or close to intersections <NUM>, reducing the effectiveness of anchoring, and/or increasing a likelihood of damaging the tissue at or close to the intersections.

It is hypothesized by the inventors that an optimal size of space <NUM> (i.e., a size that is sufficiently large to accommodate leaflets <NUM>, but sufficiently small to do so snugly) is achieved when the space has a cross-sectional area <NUM> that is <NUM>-<NUM> percent (e.g., <NUM>-<NUM> percent, such as <NUM>-<NUM> percent or <NUM>-<NUM> percent) of the transverse cross-sectional area of tubular portion <NUM>. It is further hypothesized that this relative size is optimal across implants that have tubular portions of different diameters. For example:.

This optimal relative size range of area <NUM> is hypothesized by the inventors to apply to implants that have tubular portions that are narrower or wider than the above examples (e.g., <NUM> or <NUM> diameter).

For some applications, implants of different diameters d26 are provided, and each of the implants has a cross-sectional area <NUM> that is <NUM>-<NUM> percent (e.g., <NUM>-<NUM> percent, such as <NUM>-<NUM> percent or <NUM>-<NUM> percent) of the transverse cross-sectional area of the tubular portion <NUM> of the implant. For example, the tubular portion <NUM> of one of the implants may have a have transverse cross-sectional area that is at least <NUM> percent (e.g., at least <NUM> percent) greater than another one of the implants.

Tubular portion <NUM> has an upstream end <NUM> and a downstream end <NUM>. Similarly to frame assembly <NUM>, arms <NUM> are attached to and extend from sites <NUM> that are downstream of upstream end <NUM>, e.g., at the connection between two adjacent cells of the upstream row of cells of tubular portion <NUM> (alternatively described as being at the upstream extremity of cells of the downstream row of cells).

Progressively lateral portions of each arm <NUM> define, respectively: (i) an ascending portion 446a that extends in an upstream direction past upstream end <NUM> of tubular portion <NUM> (e.g., by a distance d28), (ii) an arch portion 446b that curves in a downstream direction to form an arch (portion 446b may alternatively be described as being convex in an upstream direction), and (iii) a lateral portion 446c that curves in an upstream direction. For some applications, in the absence of tissue, arch portion 446b curves in the downstream direction as far as (and typically past) tips <NUM> of flanges <NUM> (i.e., at the arch portion, each arm <NUM> extends below (i.e., further downstream than) adjacent tips <NUM>). For some applications, and as shown, intersections <NUM> are generally close to where arms <NUM> begin to curve upstream.

A height d29 is the height, along the central longitudinal axis of the implant, between (i) the crest of arch portion 446b, and (ii) intersection <NUM>. For some applications, height d29 is <NUM>-<NUM> (e.g., <NUM>-<NUM>).

A height d30 is the height, along the central longitudinal axis of the implant, between (i) the crest of arch portion 446b, and (ii) site <NUM>. For some applications, height d30 is <NUM>-<NUM> (e.g., <NUM>-<NUM>).

It is to be noted, therefore, that for some applications, arms <NUM> extend (i) radially outward and above (a) upstream end <NUM> and (b) the tips of flanges <NUM>, and then (ii) further radially outward and below (a) upstream end <NUM> and/or (b) the tips of flanges <NUM> (i.e., toward the flanges). The above configuration of arm <NUM> increases the size of toroidal space <NUM> (compared to a similar arm in which d28 and/or d29 are smaller), e.g., providing an optimal cross-sectional area <NUM>, as described hereinabove. (In contrast, for example, in frame assemblies <NUM> and <NUM>, the arms do not have arch portions that extend above (i) the upstream end of the respective tubular portion, or (ii) the tips of the respective flanges. Although the lateral portions of these arms do extend upwardly, the lateral portions are radially outward of the flanges, and therefore do not increase the cross-sectional area of the toroidal space defined by these frame assemblies.

For some applications, an end 446d (i.e., the lateral extremity) of arm <NUM> is disposed further in an upstream direction than arch portion 446b.

For some applications, the outer stent frame (e.g., leg frame) <NUM> has a radial thickness d24 (i.e., a thickness measured along an axis that extends radially outward from the central longitudinal axis of the implant) that is greater than a radial thickness d25 of inner stent frame (e.g., valve frame) <NUM>. That is, the outer stent frame is radially thicker than the inner stent frame. This is typically achieved by cutting (e.g., laser cutting) the inner stent frame from a nitinol tube that has a first wall thickness (e.g., equal to d25), and cutting the outer stent frame from another nitinol tube that has a second, greater wall thickness (e.g., equal to d24). However, other methods of manufacture, including 3D printing, may be used.

For some applications, thickness d24 is at least <NUM> percent (e.g., at least <NUM> percent, such as at least <NUM> percent) and/or no more than <NUM> percent (e.g., no more than <NUM> percent) greater than thickness d25. For some applications, thickness d24 is <NUM>-<NUM> (e.g., <NUM>-<NUM>, e.g., <NUM>-<NUM>, such as <NUM>), and thickness d25 is <NUM>-<NUM> (e.g., <NUM>-<NUM>, e.g., <NUM>-<NUM>, such as <NUM>).

Having the outer stent frame (e.g., leg frame) be radially thicker than inner stent frame (e.g., valve frame) may be applied to the other frame assemblies described herein, mutatis mutandis.

There is therefore provided, in accordance with some applications of the invention, apparatus comprising:.

wherein the inner stent frame is cut from a first tube of nitinol that has a first-tube wall thickness, the outer stent frame is cut from a second tube of nitinol that has a second-tube wall thickness that is greater than the first-tube wall thickness.

Providing a frame assembly in which the outer frame has greater radial thicknesses is hypothesized by the inventors to advantageously provide (i) radially-expansive strength (and resistance to radially-inward deformation) to the portion of the frame assembly in which the prosthetic leaflets are disposed, and (ii) rigidity (and resistance to fatigue) to legs <NUM>.

For some applications, when frames <NUM> and <NUM> are separate and independent (e.g., during manufacturing, before the frames are fixed to each other), and the frames are in respective relaxed expanded states (e.g., in the absence of external deforming forces, such as if placed on a table) tubular portion <NUM> defines an inner-stent-frame relaxed expanded diameter (which is measured as an outer diameter of the tubular portion) that is greater than an outer-stent-frame relaxed expanded diameter defined by ring <NUM> (which is measured as an inner diameter of the ring). For some applications, the inner-stent-frame relaxed expanded diameter is <NUM>-<NUM> (e.g., <NUM>-<NUM>, such as <NUM>) mm greater than the outer-stent-frame relaxed expanded diameter.

Therefore, in the expanded state of frame assembly <NUM> (shown in <FIG>), frame <NUM> (e.g., ring <NUM>) constrains tubular portion <NUM> to an inner-stent-frame constrained expanded diameter that is smaller than the inner-stent-frame relaxed expanded diameter. Therefore, even in the relaxed expanded state of frame assembly <NUM> (i.e., the state shown in <FIG>), residual stress is typically present in frame <NUM> (e.g., tubular portion <NUM> thereof) and/or frame <NUM> (e.g., ring <NUM> thereof). Additionally, when the frame assembly is in its compressed state, and throughout its expansion into its expanded state, circumferential contact (and reciprocating expansive and compressive forces) is maintained between frame <NUM> and tubular portion <NUM>.

It is hypothesized by the inventors that this optional residually-stressed configuration advantageously increases the strength of the frame assembly (e.g., the tubular portion), and in particular its resistance to deformation, e.g., in response to forces applied directly to the frame assembly by tissue of the native valve, and/or applied indirectly to the frame assembly during systole when ventricular blood is forced against the prosthetic leaflets, which pull on the frame assembly.

It is to be noted that frames <NUM> and <NUM> are fixed to each other independently of any additional coupling that might be provided by the residually-stressed configuration. For example, and as described hereinabove, the frames are fixed to each other at coupling points <NUM>, e.g., by welding, soldering, crimping, stitching (e.g., suturing), gluing, or any other suitable technique. As described hereinbelow with reference to <FIG>, for some applications the frames are also fixed to each other at commissures of the implant. That is, the residually-stressed configuration is provided for strength and rigidity of the frame assembly (and for ensuring maintenance of circumferential contact between the frames), rather than for coupling of the frames to each other.

Reference is made to <FIG>, which are schematic illustrations of a connector <NUM> and a commissure <NUM> of a prosthetic valve, in accordance with some applications of the invention. Connector <NUM> typically comprises a flexible sheet <NUM> that is folded to define elements of the connector. Further typically, sheet <NUM> is a single, unitary sheet (e.g., cut from a single piece of stock material). <FIG> shows two perspective views of connector <NUM> (e.g., sheet <NUM> thereof) in its folded state, and <FIG> shows its unfolded state. <FIG> shows connector <NUM> fixed to frame assembly <NUM> at commissure <NUM>. Commissure <NUM> is described with respect to the implant to which frame assembly <NUM> belongs, although it may be used in combination with the other prosthetic valves described herein, and/or with other prosthetic valves, mutatis mutandis.

The implant to which frame assembly <NUM> belongs defines a plurality of commissures <NUM> at which two of the prosthetic leaflets of the implant (e.g., leaflets <NUM> or similar) meet, and are fixed to the frame assembly. At each commissure, the implant comprises a plurality of stitches (e.g., stitches) <NUM>, via which commissural portions of the two prosthetic leaflets are secured to the frame assembly. For some applications, the stitches secure the prosthetic leaflets to the inner stent frame (frame <NUM>, e.g., tubular portion <NUM> thereof) and to the outer stent frame (frame <NUM>). That is, the leaflets are not coupled to the outer stent frame merely by being fixed to the inner stent frame, which in turn is coupled to the outer stent frame. Rather, the leaflets are fixed to both frames by stitches <NUM>. Because (as described hereinabove) (i) frame <NUM> is radially thicker than frame <NUM>, and (ii) the relative diameters of the frames results in residual stress and maintained circumferential contact between frames <NUM> and <NUM>, the fixation of the leaflets to both frames advantageously provides the implant with enhanced resistance to pulling of commissures <NUM> radially inward by the prosthetic leaflets when ventricular pressure increases during ventricular systole.

For some applications, and as shown, stitches <NUM> fix the leaflets to both frames by fixing a connector <NUM> (typically comprising primarily or solely a fabric) to the two frames. Connector <NUM> is shaped to define a plurality of flaps <NUM>, and a leaflet-receptacle <NUM> comprising one or more (e.g., two) leaflet-engaging tabs <NUM>, such as a first leaflet-engaging tab 506a and a second leaflet-engaging tab 506b. For some applications, connector <NUM> is shaped to define a panel (e.g., a plate) <NUM>, tabs <NUM> protrude from of one side of the panel, and each flap <NUM> folds over a respective portion of the other side of the panel. The commissural portions of the leaflets are stitched to leaflet-engaging tabs <NUM> (e.g., to respective leaflet-engaging tabs). Flaps <NUM> are stitched to frames <NUM> and <NUM> - i.e., are fixed to the frames by stitches <NUM>. Typically, flaps <NUM> are folded over or wrapped around elements of frames <NUM> and <NUM>, and are fixed in this disposition by stitches <NUM>, thereby providing increased strength to the fixation of the leaflets to the frames (and of the frames to each other).

Typically, connector <NUM> comprises four flaps <NUM>. For some applications, and as shown, flaps <NUM> are arranged in a circuit such that each flap has two adjacent flaps around the circuit, and the fold axis ax2 of each flap is oriented at <NUM>-<NUM> degrees (e.g., <NUM>-<NUM> degrees, e.g., <NUM>-<NUM> degrees) from the fold axis of each of its adjacent flaps. For applications in which the frame to which connector <NUM> is to be connected has a cellular structure with roughly diamond-shape cells, such an arrangement facilitates attachment of the connector to the frame.

For some applications, and as shown, and as shown, connector <NUM> has four flaps arranged roughly in a diamond shape, with two upstream flaps 504a tapering away from each other in a downstream direction, and two downstream flaps 504b tapering toward each other in a downstream direction. Each upstream flap 504a is typically folded over or wrapped around an element of frame <NUM> and an element of frame <NUM>. As can be seen in <FIG>, at commissure <NUM>, elements of frame <NUM> align with elements of frame <NUM>, and flaps 504a are arranged to align with these elements of both frames. Flaps <NUM> are folded over or wrapped around these elements of both frames, and are fixed to these elements by stitches <NUM>. In the position of downstream flaps 504b, elements of frame <NUM> do not align with elements of frame <NUM>, and may even be perpendicular to them. Downstream flaps 504b are arranged to align with elements of frame <NUM>, and are folded over or wrapped around elements, but typically not over or around elements of frame <NUM>. The elements of frame <NUM>, and flaps 504b, are stitched to elements of frame <NUM>; these stitches are indicated by the reference numeral 502b, while the stitches that secure flaps over or around frame elements are indicated by the reference numeral 502a. For some applications, panel <NUM> is also stitched to elements of frame <NUM> and/or frame <NUM>; these stitches are indicated by the reference numeral 502c.

It is to be noted that frames <NUM> and <NUM> are thereby fixed to each other at commissures <NUM> (i.e., in addition to at coupling points <NUM>).

Alternatively, connector <NUM> and/or the stitches may secure the leaflets only to inner frame <NUM>, such that the leaflets are coupled to outer frame <NUM> only via inner frame <NUM>.

There is therefore provided, in accordance with some applications of the invention, a connector (e.g., connector <NUM>) comprising a flexible sheet (e.g., sheet <NUM>) that is folded to define: (i) a panel (e.g., panel <NUM>) that has a first side (e.g., side 508a), and a second side (e.g., side 508b) that is opposite the first side; (ii) a leaflet receptacle (e.g., receptacle <NUM>), disposed on the first side of the panel, and protruding in the first direction away from the panel; and (iii) a plurality of flaps (e.g., flaps <NUM>), each flap folded about a respective fold axis (e.g., axis ax2) such that at least part of each flap is disposed on the second side of the panel.

Receptacle <NUM> is configured to sandwich one or more prosthetic leaflets between leaflet-engaging tabs 506a and 506b. Typically, stitching holes <NUM> are defined in leaflet-engaging tabs <NUM> to guide the introduction of stitches which will secure the leaflets sandwiched between the tabs. For some applications, holes <NUM> are arranged into rows. For example, and as shown, each leaflet-engaging tab <NUM> may define a first row 518a of stitching holes and a second row 518b of stitching holes, the rows of one tab being aligned with the rows of the other tab. For some such applications, rows 518a and 518b diverge from each other at an angle alpha_3, typically such that that progressively downstream parts of the rows are progressively further from each other. For example, angle alpha_3 may be <NUM>-<NUM> degrees (e.g., <NUM>-<NUM> degrees, e.g., <NUM>-<NUM> degrees, such as about <NUM> degrees).

For some applications, sheet <NUM> is folded such that each leaflet-engaging tab <NUM> comprises an outer layer 520o, and an inner layer 520i that is positioned to be sandwiched between the outer layer and the one or more leaflets.

In the unfolded state of connector <NUM> (<FIG>), sheet <NUM> defines a plane (i.e., the plane of the page). In the unfolded state, sheet <NUM> defines, in the plane, (i) panel <NUM> at a medial region of sheet <NUM>, (ii) flaps <NUM>, disposed peripherally to the panel, and (iii) first and second tab portions <NUM>, also disposed peripherally from the panel. Each tab portion <NUM> includes outer layer 520o and inner layer 520i, and in the folded state, defines a respective leaflet-engaging tab <NUM>.

Typically, sheet <NUM> further defines bridging elements <NUM>, via each of which a respective tab portion <NUM> is connected to panel <NUM>. Flaps <NUM> are connected to panel <NUM> independently of the bridging elements.

In the unfolded state, tab portions <NUM> flank panel <NUM> by being disposed, in the plane, on opposing lateral sides of the panel. In the unfolded state, panel <NUM>, tab portions <NUM>, and bridging elements <NUM> are arranged in a row that defines a lateral axis ax3 in the plane, axis ax3 passing through the panel, tab portions, and bridging elements. Axis ax3 typically passes between upstream flaps 504a and downstream flaps 504b. Typically, the fold axis ax2 of each flap <NUM> is disposed at an angle alpha_4 that is <NUM>-<NUM> degrees from lateral axis ax3.

In the folded state, bridging elements <NUM> extend from respective edges of panel <NUM> and toward each other across first side 508a of the panel, and each of the leaflet-engaging tabs <NUM> protrudes from its respective bridging element away from the first side of the panel in the direction that the first side of the panel faces.

Reference is made to <FIG> and <FIG>, which are schematic illustrations of another connector <NUM> for connecting prosthetic leaflets (e.g., leaflets <NUM>) to a frame of a prosthetic valve implant, in accordance with some applications of the invention. Connector <NUM> may be used with any of the implants described herein, or with a different prosthetic valve, mutatis mutandis.

Connector <NUM> typically comprises a flexible sheet <NUM> that is folded to define elements of the connector. Further typically, sheet <NUM> is a single, unitary sheet (e.g., cut from a single piece of stock material). <FIG> shows two perspective views of connector <NUM> (e.g., sheet <NUM> thereof) in its folded state, and <FIG> shows its unfolded state. To facilitate illustration of the folding of sheet <NUM>, in <FIG> and <FIG> opposing sides of the sheet are differently shaded, e.g., as demonstrated by a corner of sheet <NUM> being curled over in <FIG> to show its reverse side.

Connector <NUM> (e.g., in its folded state) is shaped to define a plurality of flaps <NUM>, and a leaflet-receptacle <NUM> comprising one or more (e.g., two) leaflet-engaging tabs <NUM>, such as a first leaflet-engaging tab 606a and a second leaflet-engaging tab 606b. Connector <NUM> is typically shaped to define a panel (e.g., a plate) <NUM>. In the folded state, tabs <NUM> protrude from of a first side 608a of the panel, and each flap <NUM> folds over a second side 608b of the panel (e.g., a respective portion thereof). The commissural portions of leaflets <NUM> are stitched to leaflet-engaging tabs <NUM>. Flaps <NUM> are folded over or wrapped around elements of the frame of the prosthetic valve implant, e.g., as shown in <FIG>. Typically, flaps <NUM> are fixed in this disposition by stitches (not shown).

Typically, connector <NUM> comprises four flaps <NUM>, typically two upstream flaps 604a and two downstream flaps 604b. For some applications, and as shown, flaps <NUM> are arranged in a circuit such that each flap has two adjacent flaps around the circuit, and the fold axis ax4 of each flap is oriented at <NUM>-<NUM> degrees (e.g., <NUM>-<NUM> degrees, e.g., <NUM>-<NUM> degrees) from the fold axis of each of its adjacent flaps. For applications in which the frame to which connector <NUM> is to be connected has a cellular structure with roughly diamond-shape cells, such an arrangement facilitates attachment of the connector to the frame, e.g., as shown in <FIG>.

There is therefore provided, in accordance with some applications of the invention, a connector (e.g., connector <NUM>) comprising a flexible sheet (e.g., sheet <NUM>) that is folded to define: (i) a panel (e.g., panel <NUM>) that has a first side (e.g., side 608a), and a second side (e.g., side 608b) that is opposite the first side; (ii) a leaflet receptacle (e.g., receptacle <NUM>), disposed on the first side of the panel, and protruding in a first direction away from the panel; and (iii) a plurality of flaps (e.g., flaps <NUM>), each flap folded about a respective fold axis (e.g., axis ax4) such that at least part of each flap is disposed on the second side of the panel.

Receptacle <NUM> is configured to sandwich one or more prosthetic leaflets between leaflet-engaging tabs 606a and 606b. Typically, stitching holes <NUM> are defined in leaflet-engaging tabs <NUM> to guide the introduction of stitches which will secure the leaflets sandwiched between the tabs. For some applications, holes <NUM> are arranged into rows. For example, and as shown, each leaflet-engaging tab <NUM> may define a first row 618a of stitching holes and a second row 618b of stitching holes, the rows of one tab being aligned with the corresponding rows of the other tab. For some such applications, rows 618a and 618b diverge from each other at an angle alpha _5, typically such that that progressively downstream parts of the rows are progressively further from each other. For example, angle alpha_5 may be <NUM>-<NUM> degrees (e.g., <NUM>-<NUM> degrees, e.g., <NUM>-<NUM> degrees, such as about <NUM> degrees). Downstream is defined by the direction in which the prosthetic leaflets facilitate one-way fluid flow, which itself is in part dependent on the orientation of the attachment of the leaflets to connectors <NUM>.

Typically, sheet <NUM> is folded such that each leaflet-engaging tab <NUM> comprises an outer layer 620o, and an inner layer 620i that is positioned to be sandwiched between the outer layer and the one or more leaflets. For some applications, and as further described hereinbelow, rows 618a and 618b are defined by inner layer 620i, and a third row 618c of stitching holes is defined by outer layer <NUM>, and the folding of sheet <NUM> is such that row 618c aligns with row 618a. For such applications, only row 618c is visible in the folded state. In the unfolded state, an angle alpha_7 between rows 618a and 618c is typically <NUM>-<NUM> degrees (e.g., <NUM>-<NUM> degrees, e.g., <NUM>-<NUM> degrees, e.g., <NUM>-<NUM> degrees, such as <NUM>-<NUM> degrees).

In the unfolded state of connector <NUM> (<FIG>), sheet <NUM> defines a plane (i.e., the plane of the page). In the unfolded state, sheet <NUM> defines, in the plane, (i) panel <NUM> at a medial region of sheet <NUM>, (ii) flaps <NUM>, disposed peripherally to the panel, and (iii) first and second tab portions <NUM>, also disposed peripherally from the panel. Each tab portion <NUM> includes outer layer 620o and inner layer 620i, and in the folded state, defines a respective leaflet-engaging tab <NUM>.

Sheet <NUM> further defines bridging elements <NUM>, via each of which a respective tab portion <NUM> is connected to panel <NUM>. Flaps <NUM> are connected to panel <NUM> via the bridging elements.

Typically, in the folded state, part of each flap <NUM> is disposed on first side 608a of panel <NUM>, and part of each flap is disposed on second side 608b. For example, bridging elements <NUM> are typically disposed on first side 608a, and each flap <NUM> extends from one of the bridging elements and around panel <NUM> such that part of the flap is disposed on side 608a, and part is disposed on side 608b.

In the unfolded state, tab portions <NUM> flank panel <NUM> by being disposed, in the plane, on opposing lateral sides of the panel. In the unfolded state, panel <NUM>, tab portions <NUM>, and bridging elements <NUM> are arranged in a row that defines a lateral axis ax5 in the plane, axis ax5 passing through the panel, tab portions, and bridging elements. Axis ax5 typically passes between upstream flaps 604a and downstream flaps 604b. Typically, the fold axis ax4 of each flap <NUM> is disposed at an angle alpha_6 that is <NUM>-<NUM> degrees from lateral axis ax5.

Sheet <NUM> typically further defines a lapel <NUM> that, in the unfolded state, is lateral to each tab portion <NUM>. Lapels <NUM> are described further hereinbelow.

In the folded state, bridging elements <NUM> extend from respective edges of panel <NUM> and toward each other across first side 608a of the panel, and each of the leaflet-engaging tabs <NUM> protrudes from its respective bridging element away from the first side of the panel in the direction that the first side of the panel faces.

<FIG> show steps in the folding of sheet <NUM> from the unfolded state to the folded state, in order to define connector <NUM>, in accordance with some applications of the inventions. Folds are made in downstream regions of tab portions <NUM>, e.g., the downstream edge of each layer 610o and each layer 610i is folded over to form respective folds <NUM> (<FIG>). This will provide each leaflet-engaging tab with a cushion <NUM>, described hereinbelow. Folds <NUM> may be secured by stitching.

Sheet <NUM> is folded in half along its longitudinal axis ax6, bringing tab portions <NUM> together (<FIG>). Commissural portions of two leaflets <NUM> (e.g., a first leaflet 58a and a second leaflet 58b) are introduced, such that they are sandwiched together between portions <NUM>. As shown, the positioning of the leaflets is typically such that they are disposed between the holes <NUM> of one portion <NUM>, and those of the other portion <NUM>. Holes <NUM> of row 618b of both portions <NUM> are stitched together, as indicated by reference numeral <NUM>. The stitches therefore pass through leaflets 58a and 58b, thereby securing them to connector <NUM>.

Subsequently, tab portions <NUM> are folded back against themselves, thereby defining inner layer 620i and outer layer 620o (<FIG>), and aligning rows 618c with rows 618a. Holes <NUM> of rows 618a and 618b are now hidden by outer layer 620o. Rows 618c and 618a of one tab portion <NUM>, leaflets 58a and 58b, and rows 618a and 618c of the other tab portion are then stitched together, as indicated by reference numeral <NUM>. This reinforces the connection of the leaflets to connector <NUM>. Thus, tab portions <NUM> are formed into leaflet-engaging tabs <NUM>.

Subsequent to the step shown in <FIG>, the folding in half of sheet <NUM> shown in step 13B is reversed, mutatis mutandis, moving bridging elements <NUM> away from each other and folding them against panel <NUM> (<FIG>). Typically, regions of each leaflet <NUM> that are disposed beyond row 618c become disposed between bridging elements <NUM> and panel <NUM>.

Typically, the step shown in <FIG> brings lapels <NUM> into contact with bridging elements <NUM>. The step shown in <FIG> typically causes each bridging element <NUM> to move with the bridging element <NUM> with which it is in contact, and folding with respect to outer layer 620i of leaflet-engaging tabs <NUM>. For some applications, stitches are passed through lapel <NUM>, bridging element <NUM>, leaflet <NUM>, and panel <NUM>. This stitching may be an independent step, or may be achieved when securing flaps <NUM> to the frame of the prosthetic valve, e.g., as described hereinbelow.

<FIG> shows perspective views of the state shown in <FIG>. Each leaflet <NUM> has a downstream edge <NUM>. It is to be noted that leaflet-engaging tabs <NUM> typically extend in a downstream direction beyond downstream edges <NUM>. It is to be further noted that cushions <NUM> are typically positioned such that at least part of each cushion is disposed further downstream than downstream edges <NUM>. Tabs <NUM> and/or cushions <NUM> are thereby configured to inhibit movement of the commissural portion of each leaflet <NUM> (and especially of downstream edges <NUM>) toward the frame of the prosthetic valve. It is hypothesized by the inventors that this reduces a likelihood of leaflets <NUM> becoming damaged over time due to contact with the frame.

Subsequently, connector <NUM> is secured to the frame of the prosthetic valve (<FIG>). Flaps <NUM> are folded over components of the frame of the prosthetic valve (which are shown in phantom), and secured by stitching. For some applications, some of this stitching may pass through several elements, such as flaps <NUM>, panel <NUM>, leaflets <NUM>, bridging elements <NUM>, and/or lapels <NUM>.

Although <FIG> show a particular sequence, and although some of the steps are necessarily performed before others, it is to be understood that some of the steps may be performed in a different order to that shown. For example, folds <NUM> may be folded at a later stage to that shown.

Typically, three connectors <NUM> are used to connect three leaflets <NUM> at three commissures to the frame of the prosthetic valve, to form a tri-leaflet check-valve.

Reference is again made to <FIG>. Among the advantages provided by assembling a prosthetic valve from two (e.g., concentric) frames is the ability to divide the frame elements required between the two frames, in a manner that would not be possible in a single frame, or in a manner that, if a single frame were used, would increase the size (e.g., the diameter or the length) of the implant in its compressed state. Additionally, for some applications, the use of two frames allows different sizes of the implant to be compressed ("crimped") to the same or similar diameter, and for some such applications, to be delivered using the same delivery tool (e.g., delivery tool <NUM>). For example, for implants comprising frame assembly <NUM>, an implant of a larger size may have a lumen diameter that is at least <NUM> percent greater than the lumen diameter of an implant of a smaller size (in their respective expanded states), but in their compressed states, the diameter of the implant of the larger size may be no more than <NUM> percent greater than the diameter of the implant of the smaller size.

For some applications, a delivery tool is provided for use with different sizes of the implant, e.g., with the implants provided separately. For some such applications, a kit is provided containing a delivery tool and implants of different sizes.

Claim 1:
Apparatus for use in a heart of a subject, the apparatus comprising:
a frame assembly (<NUM>) transluminally advanceable to the heart, and comprising:
an inner frame (<NUM>) that defines:
a tubular portion (<NUM>) that defines a longitudinal lumen (<NUM>) therethrough, and
an upstream support portion (<NUM>), coupled to the tubular portion (<NUM>); and
an outer frame (<NUM>) that:
is coupled to the inner frame (<NUM>),
circumscribes the tubular portion (<NUM>), and
defines a plurality of flanges (<NUM>) that are coupled to the tubular portion (<NUM>); and
a plurality of prosthetic valve leaflets (<NUM>), coupled to the tubular portion (<NUM>), and disposed within the lumen (<NUM>),
wherein:
the frame assembly (<NUM>):
has a compressed state for transluminal delivery to the heart, and
has an expanded state, in which:
the upstream support portion (<NUM>) extends radially outward from the tubular portion (<NUM>),
the flanges (<NUM>) extend radially outward from the tubular portion (<NUM>) and toward the upstream support portion (<NUM>),
the tubular portion (<NUM>) has a transverse cross-sectional area, and
the frame assembly (<NUM>) defines a toroidal space (<NUM>) between the flanges (<NUM>), the upstream support portion (<NUM>), and the tubular portion (<NUM>), the toroidal space (<NUM>) circumscribing the tubular portion (<NUM>) and having a cross-sectional area that is <NUM>-<NUM> percent of the transverse cross-sectional area of the tubular portion (<NUM>).