Patent ID: 12257148

DETAILED DESCRIPTION OF THE EMBODIMENTS

FIG.1is a schematic illustration of a fully-assembled valve prosthesis10, in accordance with an embodiment of the present invention. Valve prosthesis10comprises a collapsible inner support structure12that serves as a proximal fixation member, and a collapsible outer support structure14that serves as a distal fixation member. Outer and inner support structures14and12may be initially formed separately and then joined together, as shown, or may be formed as one integrated structure, i.e., not formed separately and then joined together. For some applications, outer and inner support structures14and12are joined together prior to implantation of prosthesis10(during a manufacturing process, or by a healthcare worker prior to implantation), while for other applications, the outer and inner support structures are coupled to one another during an implantation procedure. For some applications, outer support structure14is constructed from a plurality of separate pieces, which are joined to inner support structure12using standard manufacturing means, such as welding, gluing, or suturing (configuration not shown), such that the functionality of outer support structure14is attained.

Valve prosthesis10is configured to be placed in a native diseased valve of a subject, such as a native stenotic aortic or pulmonary valve, using a minimally-invasive approach, such as a beating heart transapical procedure, such as described hereinbelow with reference toFIGS.5A-8Aor with reference toFIGS.16A-H, or a retrograde transaortic procedure, such as described hereinbelow with reference toFIGS.9A-G. As used in the present application, including in the claims, a “native semilunar valve” is to be understood as including: (a) native semilunar valves that include their native leaflets, and (b) native semilunar valves, the native leaflets of which have been surgically excised or are otherwise absent.

Reference is made toFIG.2A, which is a schematic illustration of collapsible outer support structure14prior to assembly with inner support structure12, in accordance with an embodiment of the present invention. Outer support structure14is shaped so as to define a plurality of distal diverging strut supports20, from which a plurality of proximal engagement arms22extend radially outward in a proximal direction. Typically, the engagement arms have a shape that is generally upwardly concave, such as described hereinbelow with reference toFIG.17.

Although three strut supports20and engagement arms22are shown in the figures, for some applications valve prosthesis10comprises fewer or more supports and/or arms, such as two supports and two arms. It is noted that approximately 90% of humans have exactly three aortic sinuses. The three supports and/or arms provided in most embodiments correspond to these three aortic sinuses. For implantation in the approximately 10% of patients that have exactly two aortic sinuses, prosthesis10typically includes exactly two supports and/or arms.

Engagement arms22are typically configured to be at least partially disposed within aortic sinuses of the subject, and, for some applications, to engage and/or rest against floors of the aortic sinuses, and to apply an axial force directed toward a left ventricle of the subject. Engagement arms22meet one another at respective junctures24. For applications in which each of engagements arms22is fabricated as a separate piece, the engagement arms are mechanically engaged to one another where they meet at respective junctures24. For some applications, engagement arms22meet one another without actually touching one another, and instead meet via an area defined at each respective juncture24. Typically, the engagement arms are configured to define respective peaks at junctures24(or peak complexes, as described hereinbelow with reference toFIG.3E), and respective troughs26between each two of the peaks (or trough complexes, as described hereinbelow with reference toFIG.3E).

Outer support structure14comprises a suitable material that allows mechanical deformations associated with crimping and expansion of valve prosthesis10, such as, but not limited to, nitinol or a stainless steel alloy (e.g., AISI 316). Outer support structure14is fabricated from a single piece or from a plurality of parts that are coupled together (e.g., by suturing). For some applications, placement of engagement arms22within the aortic sinuses prevents “device migration,” i.e., undesired retrograde movement of valve prosthesis10that may result from fluid forces applied to the valve. For some applications, engagement arms22are coated with a flexible material (e.g., polyester, biocompatible, synthetic, and/or pericardium).

Strut supports20and engagement arms22may be formed as one integrated structure (as shown), or, alternatively, may be initially formed separately and then joined to one another. For example, the strut support and arms may be mechanically interlocked or sutured together, or coupled by other means. Typically, the strut support and arms are joined prior to implantation.

Reference is made toFIG.2B, which is a schematic illustration of collapsible inner support structure12prior to assembly with outer support structure14, in accordance with an embodiment of the present invention. For some applications, inner support structure12is shaped so as to define a plurality of distal diverging inner struts30, and a bulging proximal skirt32that extends from the struts. A proximal portion34of proximal skirt32is configured to engage a left ventricular outflow tract (LVOT) of the subject and/or periannular tissue at the top of the left ventricle. A relatively narrow throat section36of proximal skirt32is configured to be positioned at a valvular annulus of the subject, and to engage the native valve leaflets. Inner support structure12comprises, for example, nitinol, a stainless steel alloy, another metal, or another biocompatible material.

Reference is again made toFIG.1. Inner and outer support structures12and14are assembled together by placing outer support structure14over inner support structure12, such that outer strut supports20are aligned with, and typically support, respective inner struts30, and engagement arms22are placed over a portion of proximal skirt32. Inner struts30and outer strut supports20together function as commissural posts. Typically, such assembly is performed prior to implantation of prosthesis10, such as during manufacture of the prosthesis; alternatively, such assembly is performed in vivo during an implantation procedure, or prior to implantation by a healthcare worker.

Valve prosthesis10typically comprises a prosthetic distal valve104, which typically comprises a pliant material105coupled to strut supports20and/or inner struts30. Pliant material105of valve104is configured to collapse inwardly (i.e., towards a longitudinal axis of valve prosthesis10) during diastole, in order to inhibit retrograde blood flow, and to open outwardly during systole, to allow blood flow through the prosthesis. For some applications, when in an open position, valve104assumes a diverging shape that causes blood to flow therethrough with pressure recovery at a distal outlet of the valve, for example using techniques described in one or more of the above-mentioned patent application publications to Schwammenthal et al. For other applications, the shape of the valve does not cause such pressure recovery. For example, an angle between the pliant material105and a central longitudinal axis of prosthesis10may be too great to cause pressure recovery. In this latter case, the large angle may serve exclusively, or at least in part, to help provide axial fixation of prosthesis10to the native valve complex. Regardless of whether pressure recovery is achieved, the angle between pliant material105and the central longitudinal axis of prosthesis10typically inhibits migration of the device in an upstream direction.

Pliant material105comprises a flexible supple material, such as an inert biological material, e.g., pericardium sheet or any medically safe elastomer, such as, but not limited to, polyester, polymer, a metallic material/alloy, polyurethane, latex, or synthetic rubber. For some applications, pliant material105is coupled to strut supports20and/or inner struts30by sewing, such as described hereinbelow with reference toFIG.4. For example, pliant material105may be sewn onto outer diverging strut supports20. Valve104comprises a single piece or multiple pieces of pliant material105(e.g., leaflets) joined together to give a desired shape, typically a distally diverging shape. For some applications, the pliant material and support structures are coupled to one another in a single-step procedure (e.g., by sewing all the pieces together); alternatively, the pliant material and support structures are coupled to one another in a plurality of sequential steps.

Typically, valve prosthesis10further comprises a graft covering106which is coupled to proximal skirt32, such as by sewing the covering within the skirt (configuration shown inFIG.1) or around the skirt (configuration not shown). Inner support structure12thus defines a central structured body for flow passage that proximally terminates in a flared inlet (proximal skirt32) that is configured to be seated within an LVOT immediately below an aortic annulus/aortic valve. For some applications, graft covering106is coupled at one or more sites to pliant material105.

FIGS.2C and2Dare schematic illustrations of alternative configurations of a portion of valve prosthesis10, in accordance with respective embodiments of the present invention. In these configurations, inner support structure12and outer support structure14are replaced by an element38, which is shaped so as to define first and second portions40and42. First portions40serve as support structures, each of which functionally corresponds to a pair of strut support20and inner strut30, described hereinabove with reference toFIGS.2A and2B. Pliant material105is coupled to support structures40. Second portions42are bent in a proximal direction, such that proximal portions of the second portions define respective engagement arms22.

In the configuration shown inFIG.2C, two second portions42extend from the distal end of each first portion40. In the configuration shown inFIG.2D, element38is shaped so as to define two shoulders44that extend laterally from each first portion40. A single second portion42extends from each of shoulders44.

Reference is again made toFIG.1. In an embodiment of the present invention, inner support structure12is shaped so as to define one or more barbs120, which are configured to pierce or protrude into the ventricular side of the aortic annulus, as described hereinbelow with reference toFIGS.7A-E. For some applications, one or more of inner struts30is shaped so as to define a respective barb, while for other applications, another element of valve prosthesis10is shaped so as to define the one or more barbs, such as proximal skirt32. For some applications, barbs120are oriented parallel to a longitudinal axis of valve prosthesis10, while for other applications, barbs120are oriented to form an angle with respect to the longitudinal axis, such as between about-20 degrees (i.e., slanted towards a central axis of the native valve) and about +89 degrees (i.e., slanted away from the central axis of the native valve), such as between about −5 and about +30 degrees. For some applications, barbs120are set at the desired angle by heat-setting.

Reference is made toFIG.2E, which is a schematic illustration of another configuration of collapsible outer support structure14prior to assembly with inner support structure12, in accordance with an embodiment of the present invention. Inter-strut support elements17are coupled between adjacent ones of distal diverging strut supports20, and typically serve to help maintain a desired distance between each of strut supports20. For example, if a force is applied that would bring closer or separate two of the strut supports, the inter-strut support element between the strut supports would tend to reduce such a deformation. For some applications, one or more of support elements17is shaped so as to define a kink or curved section19, which deforms slightly in response to force applied to element17.

Reference is made toFIGS.3A-E, which are schematic illustrations of additional configurations of outer support structure14, in accordance with respective embodiments of the present invention. In the configurations shown inFIGS.3A-B, outer support structure14is shaped so as to define one or more native valve support elements122. These support elements apply pressure to an outer (downstream) surface of the native valve when engagement arms22are positioned in the aortic sinuses, so as to hold the native leaflets in place against proximal skirt32. In the configuration shown inFIG.3A, the area defined by engagement arms22and support elements122is open, while in the configuration shown inFIG.3B, a covering124is provided in this area. The covering generally may help capture calcific, thrombotic, or other material which might be dislodged from the native valve or the surrounding tissue, and may comprise, for example, polyester. In the configuration shown inFIG.3C, covering124is provided without support elements122.

In the configuration shown inFIG.3D, each of engagement arms22comprises or is shaped so as to define at least one extension element23that extends from the engagement arm. The engagement arms and extension elements are configured such that the engagement arms engage and/or rest against the floors of the aortic sinuses via the extension elements. For some applications, such as shown inFIG.3D, exactly one extension element23extends from each of engagement arms22, while for other applications, more than one extension element23extends from each engagement arm (configuration not shown). Although engagement arms22are shown inFIG.3Das curving down toward the sinus floors, for some applications the engagement arms are shaped so as to remain above the native commissures (for example, the engagement arms collectively may be annular in shape), or to curve down less than is shown inFIG.3D.

In the configuration shown inFIG.3E, each of engagement arms22is shaped so as to define a plurality of troughs25and local peaks27, rather than a single trough26, as shown inFIG.2A. In addition, each of engagement arms22is shaped so as to define a plurality of peaks29and local troughs31, rather than a single peak at each of junctures24, as shown inFIG.2A. (Outer support structure14may include both, only one of, or neither of the features described in the preceding two sentences.) As used in the present application, including in the claims, a “trough complex” means a portion of an engagement arm that extends downwards between respective “peak complexes.” Each “trough complex” includes n local troughs25and n−1 local peaks29, where n is greater than or equal to one. Each “peak complex” includes m local peaks29and m−1 local troughs31, where m is greater than or equal to one. It is noted that the portion of a peak complex that is at a juncture may define a local trough (configuration not shown). In addition, although the peak and trough complexes shown inFIG.3Eare generally symmetrical, non-symmetrical arrangements are also within the scope of the present invention.

For some applications, respective extension elements23, described hereinabove with reference toFIG.3D, extend from one or more of the troughs of a trough complex, and/or from elsewhere along the trough complex.

FIG.3Fis a schematic illustration of an additional configuration of outer support structure14, in accordance with an embodiment of the present invention. In this embodiment, outer support structure14, in addition to defining proximal engagement arms22, is shaped so as to define a plurality of inner engagement arms33. The inner engagement arms are configured to pass through the valvular annulus. Typically, troughs35of inner engagement arms33are configured to engage the LVOT and/or periannular tissue at the top of the left ventricle. For some applications, each of inner engagement arms33is shaped so as to define one or more barbs37, which are configured to pierce or protrude into the ventricular side of the aortic annulus. Typically, during an implantation procedure, inner engagement arms33are released from an overtube, trocar, or catheter prior to the release of proximal skirt32therefrom, such as described hereinbelow with reference toFIGS.7A-C,9A-G, and16A-H. The fixation provided by inner engagement arms33holds prosthesis10in place until the implantation procedure is complete, such that blood flow against skirt32does not dislodge the prosthesis during the implantation procedure.

FIG.3Gis a schematic illustration of a fully-assembled valve prosthesis that includes inner engagement arms33ofFIG.3F, in accordance with an embodiment of the present invention.FIG.7E, described hereinbelow, shows prosthesis10in situ having the configuration shown inFIG.3F.

For some applications, the features shown in one or more ofFIGS.2A-Band3A-G are combined. For example, valve support elements122and/or covering124may be provided for arms22ofFIG.3E. Other such combinations of features are within the scope of the present invention.

Reference is now made toFIGS.4A-C, which are schematic illustrations of configurations for coupling pliant material105to inner struts30of inner support structure12and to strut supports20of outer support structure14, in accordance with respective embodiments of the present invention.

In the configuration shown inFIG.4A, valve104comprises a plurality of segments of pliant material105, pairs of which are coupled together at respective interfaces between one of inner struts30and one of strut supports20. Inner strut30is shaped so as to define an elongated slit130. During manufacture of valve prosthesis10, edges of two pieces of pliant material105are inserted through slit130such that a portion of each of the pieces of pliant material is sandwiched between inner strut30and strut support20. The inner strut and strut support are tightly coupled together, such as by passing one or more sutures132through holes134defined by inner strut30and strut support20. Sutures132typically couple the strut and strut support together such that pliant material105is supported on both sides thereof, thereby forming a strain relief which reduces stresses on the leaflets of valve104at the sutures. The relatively large surface areas of inner strut30and strut support20distribute the stress applied at pliant material105, so that this stress is not applied primarily around holes134. Typically, the edges of slit130are rounded in order to avoid damage to pliant material105.

In the configuration shown inFIGS.4B-C, portions136of graft covering106(including, optionally, pericardium or any suitable supple synthetic or biological material) are inserted through slit130, between the edges of the slit and the two pieces of pliant material. The portions of the graft covering reduce friction between the pliant material and inner strut30. As can be seen inFIG.4C, portions136of graft covering106are typically integral with the rest of graft covering106(which is sewn to skirt32). Graft covering106(including, optionally, pericardium or any suitable supple synthetic or biological material) is thus shaped so as to define distally protruding portions136.

FIGS.4D and4Eare side-view schematic illustrations of two configurations for coupling pliant material105to graft covering106, and reducing leaflet stress during valve opening (FIG.4D) or valve closure (FIG.4E), in accordance with respective embodiments of the present invention. In both of these configurations, graft covering106is sewn to a cord107, such that a portion of pliant material105is held between the cord and the graft covering. Cord107passes through a hole108(FIG.4C) passing through or near one of the commissural posts (configuration not shown).

Reference is now made toFIGS.5A-8A, which illustrate apparatus and a method for implanting valve prosthesis10in a native stenosed valve140of a heart142, in accordance with respective embodiments of the present invention.

FIGS.5A-Cillustrate an overtube or trocar150and the initial steps of the implantation method, in accordance with respective embodiments of the present invention. Overtube or trocar150is placed over a dilator154. As shown inFIG.5A, overtube or trocar150is typically inserted through an apex156of heart142, and advanced into a left ventricle157where its motion is terminated, or through left ventricle157until the distal end of dilator154passes native aortic valve leaflets158. For example, apex156may be punctured using a standard Seldinger technique, and a guidewire may be advanced into an ascending aorta160. Optionally, native aortic valve140is partially dilated to about 15-20 mm (e.g., about 16 mm), typically using a standard valvuloplasty balloon catheter. (In contrast, full dilation would be achieved utilizing dilation of 20 mm or more.) Overtube or trocar150is advanced into the ascending aorta. Overtube or trocar150is pushed beyond aortic valve140such that the distal end of overtube or trocar150is located above the highest point of native aortic valve140. Dilator154is removed while overtube or trocar150remains in place with its distal end located above aortic valve140, as shown inFIG.5B. It is to be understood that the procedure may be modified so that overtube or trocar150is placed within the left ventricle and remains within the left ventricle throughout the entire implantation procedure. Valve prosthesis10is advanced through the distal end of overtube or trocar150into ascending aorta160distal to native leaflets158, as shown inFIG.5C. Typically, to facilitate this advancement, prior to the implantation procedure valve prosthesis10is loaded into a delivery tube202, such as described hereinbelow with reference toFIGS.12A-13D. During the implantation procedure, delivery tube202is advanced through overtube or trocar150, thereby advancing the valve prosthesis through the overtube or trocar.

FIGS.6A-Bshow an implantation of valve prosthesis10in ascending aorta160, in accordance with an embodiment of the present invention. As mentioned above with reference toFIGS.5A-C, the distal end of overtube or trocar150is positioned past native valve leaflets158. The distal end of valve prosthesis10is advanced out of overtube or trocar150until engagement arms22exit overtube or trocar150and snap or spring open, as shown inFIG.6A. Overtube or trocar150is gently pulled back until engagement arms22are brought into aortic sinuses164. For some applications, overtube or trocar150and/or valve prosthesis10are gently rotated as indicated by arrows166in order to align engagement arms22with respective aortic sinuses164. Although not typically necessary, fluoroscopic, ultrasound, or other surgical imaging techniques may be used to aid in this positioning. Overtube or trocar150and valve prosthesis10are pulled back slightly, such that engagement arms22are positioned within respective aortic sinuses164, as shown inFIG.6B. (Although engagement arms22are shown inFIG.6Bas being in contact with the sinus floors, for some applications the engagement arms do not come in contact with the sinus floors, such as described hereinbelow with reference toFIG.7B.) Typically, valve prosthesis10is configured such that when engagement arms22are placed properly within aortic sinuses164, outer strut supports20are aligned with commissures170(see, for example,FIG.8A), thus preventing any possible obstruction of coronary ostia116by valve prosthesis10. At this point in the implantation procedure, the distal end of valve prosthesis10is free of overtube or trocar150, and the proximal end of prosthesis10remains in overtube or trocar150.

For some applications, the use of imaging techniques is not necessary. The careful pulling back of valve prosthesis10, without application of excessive force, generally causes each of engagement arms22to automatically self-align with a respective aortic sinus164, because outer support structure14, particularly engagement arms22, generally matches the three-dimensional shape of aortic valve140. If one of engagement arms22comes in contact with a commissure170during the careful pulling back of the prosthesis, the arm slides down the slope of the leaflet into the aortic sinus. Typically, arms22are evenly distributed around valve prosthesis10with a separation of 120 degrees between arms, such that all three arms naturally fall into place in respective sinuses upon even just one of the engagement arms achieving proper alignment with a sinus. This natural alignment generally occurs even if the sinuses themselves are not perfectly distributed at 120 degrees from one another.

This alignment process generally ensures positioning of the prosthetic leaflets within the aortic sinuses, thus exposing the prosthetic leaflets to natural blood vortex formation in the aortic sinuses, which contributes to early closure of the prosthetic leaflets, thus reducing closing volume (i.e., leakage through the prosthetic leaflets before fully closing), as well as promoting low-impact closure of the prosthetic leaflets, which typically reduces leaflet wear.

For some applications, a correct rotational disposition of the prosthesis with respect to the aortic valve site is determined by the surgeon based on tactile feedback.

Reference is now made toFIGS.7A-E, which illustrate valve prosthesis10in situ upon completion of the implantation procedure, in accordance with respective embodiments of the present invention. After valve prosthesis10is placed properly within native stenosed valve140, as described hereinabove with reference toFIGS.5A-6B, the proximal end of valve prosthesis10is released from overtube or trocar150, by withdrawing overtube or trocar150. Proximal skirt32snaps or springs open to at least partially engage, with its proximal portion34, the left-ventricular side of native valve140, including at least a portion of an inner surface of an LVOT180. As a result, valve prosthesis10forms an axial engagement system above and below native valve annulus182of native valve140, which axially sandwiches a native valve complex (as defined hereinbelow with reference toFIG.15) from the aortic and left-ventricular sides thereof. Native valve leaflets158are captured between proximal skirt32and engagement arms22, typically without applying force along the longitudinal axis of the leaflets, in order to avoid shortening of the length of the leaflets, or forced bending, crimping, or folding over of the leaflets. For some applications, barbs120, if provided, pierce aortic annulus182on the left-ventricular side of native valve140, while for other applications, the barbs are blunt, in which case they generally protrude into the tissue of the aortic annulus, without piercing the tissue. For some applications, support structure14is configured to elevate native valve leaflets158from within the aortic sinuses.

In the embodiment shown inFIG.7A, upon the completion of the implantation of prosthesis10, engagement arms22are positioned within aortic sinuses164, such that the ends of the engagement arms touch the floors of the sinuses. Although the ends of the engagement arms are shown touching approximately the radial center of the floors of the sinuses, for some applications, the ends of the engagement arms touch the floors further from leaflets158or closer to the leaflets, or touch the body of the leaflets, the roots of the leaflets, or the transition between the sinuses and the leaflet roots. Alternatively, the engagement arms are shorter, such as shown inFIG.7B, such that they do not reach the floors of the sinuses. Further alternatively, for some applications prosthesis10does not comprise arms22, as shown inFIG.7C.

In the embodiment shown inFIG.7D, prosthesis10has been implanted after the native valve leaflets have been excised, in accordance with an embodiment of the present invention.

The embodiment illustrated inFIG.7Eshows valve prosthesis10in situ having the configuration of outer support structure14described hereinabove with reference toFIG.3F.

For some applications, barbs120are coated or otherwise provided with a surface property for enhancing their attachment to tissue of aortic annulus182. Graft covering106of proximal skirt32also helps prevent regurgitation and device migration.

For some applications, the positioning of arms22prior to the opening of proximal skirt32prevents native valve leaflets158from opening more than a predetermined desired amount. The support provided by arms22to the valve leaflets limits the subsequent opening of the leaflets by the proximal skirt. The desired amount of opening is determined at least in part by the angle between arms22and a central longitudinal axis of the prosthesis (shown, for example, as angle .theta. inFIG.7A). Typically, the angle is between about 1 and about 89 degrees, such as between about 10 and about 60 degrees, such as 25 degrees, or between about 25 and about 65 degrees. Typically, the angle is predetermined. For some applications, the fixation members of prosthesis10are configured to prevent opening of the native leaflets to their maximum diameter.

Reference is again made toFIG.7A. For some applications, prosthetic distal valve104is coupled to strut supports20and/or inner struts30of prosthesis10(see, for example,FIG.1), such that at least 50% of an axial length of the prosthetic leaflets is distal to native valve leaflets158. In other words, if prosthetic distal valve104has an axial length L1, a portion L2of length L1that is distal to leaflets158is greater than a portion L3of length L1that is proximal to leaflets158.

FIG.8Ashows valve prosthesis10in situ upon completion of the implantation procedure, as viewed from ascending aorta160, upon placement of engagement arms22within respective aortic sinuses164, in accordance with an embodiment of the present invention. In this embodiment, engagement arms22are positioned within aortic sinuses164, such that the ends of the engagement arms touch the floors of the sinuses, for example as described hereinabove with reference toFIG.7A.

FIG.8Bshows valve prosthesis10in situ upon completion of the implantation procedure, in accordance with an embodiment of the present invention. In this embodiment, junctures24between pairs of engagement arms22ride above respective native commissures170, without impinging on the commissures (i.e., touching or pushing the commissures). In other words, there is a gap between each of junctures24and its respective native commissure170. Engagement arms22are positioned within aortic sinuses164, such that the ends of the engagement arms touch the floors of the sinuses. In this embodiment, the number of engagement arms22is typically equal to the number of aortic sinuses164of the native valve, and the engagement arms are radially separated by approximately equal angles. The three-dimensional shape of engagement arms22causes the ends of the engagement arms to find the lowest point of reach within the floors of the sinuses, thereby enabling self-alignment of prosthesis10with the native aortic valve site and commissures170.

A length L (parallel to a longitudinal axis of prosthesis10) between (a) each juncture24and (b) the contact point of respective engagement arm22to the sinus floor is typically greater than about 6 mm, e.g., greater than about 10 mm, or than about 13 mm. For some applications, length L is between about 10 and about 18 mm, e.g., about 13 mm.

In typical human subjects, the native valve complex has three native commissures170, which define respective commissural high points, and three respective sinus low points. Prosthesis10is configured to match these high and low points. Such matching enables axial anchoring, without forced bending, crimping, or folding over of the leaflets, and without impinging on the commissures. In this way, prosthesis10embraces the leaflets, rather than squeezing them.

For some applications, engagement arms22are generally aligned with the native leaflets, thereby avoiding local deformation, and distributing force over a larger contiguous area of the leaflet surface.

FIG.8Cshows valve prosthesis10in situ upon completion of the implantation procedure, in accordance with an embodiment of the present invention. In this embodiment, junctures24between pairs of engagement arms22ride above respective native commissures170, impinging on the commissures (i.e., touching or pushing the commissures). Engagement arms22are positioned within aortic sinuses164, such that the ends of the engagement arms do not reach the floors of the sinuses (such as described hereinabove with reference toFIG.7B). The three-dimensional shape of junctures24causes the junctures to align with commissures170, thereby enabling self-alignment of prosthesis10with the native aortic valve site and commissures170. In an embodiment (not shown), junctures24apply axial force to (i.e., push) the commissures, and engagement arms22apply axial force to aortic sinuses164.

Reference is made toFIGS.9A-G, which schematically illustrate a retrograde transaortic approach for implanting valve prosthesis10, in accordance with an embodiment of the present invention. Prior to the implantation procedure, prosthesis10is positioned in a retrograde delivery catheter250, as shown inFIG.9G. A retrograde delivery catheter tube251of catheter250holds engagement arms22, and a delivery catheter cap252holds proximal skirt32.

The implantation procedure begins with the transaortic insertion of a guidewire190into left ventricle157, as shown inFIG.9A. Optionally, stenotic aortic valve140is partially dilated to about 15-20 mm (e.g., about 16 mm), typically using a standard valvuloplasty balloon catheter. (In contrast, full dilation would be achieved by using a balloon catheter with a diameter of 20 mm or more.) Retrograde delivery catheter250is advanced over guidewire190into ascending aorta160towards native aortic valve140, as shown inFIG.9A. As shown inFIG.9B, retrograde delivery catheter250is advanced over guidewire190until delivery catheter cap252passes through native aortic valve140partially into left ventricle157. As also shown inFIG.9B, retrograde delivery catheter tube251is pulled back (in the direction indicated by an arrow255), while a device stopper254(shown inFIG.9G) prevents valve prosthesis10within tube251from being pulled back with tube251, so that engagement arms22are released and flare out laterally into the sinuses. At this stage of the implantation procedure, proximal skirt32of prosthesis10remains in delivery catheter cap252.

As shown inFIG.9C, at the next step of the implantation procedure, delivery catheter cap252is pushed in the direction of the apex of the heart (as shown by an arrow257), using a retrograde delivery catheter cap shaft253that passes through tube251and prosthesis10. This advancing of cap252frees proximal skirt32to snap or spring open, and engage the inner surface of LVOT180. Barbs120, if provided, pierce or protrude into the aortic annulus on the left-ventricular side of the native valve. Retrograde delivery catheter tube251is further pulled back until the rest of valve prosthesis10is released from the tube, as shown inFIG.9D.

Retrograde delivery catheter tube251is again advanced over shaft253toward the apex of the heart, until tube251rejoins cap252, as shown inFIG.9E. Retrograde delivery catheter250and guidewire190are withdrawn from left ventricle157, and then from ascending aorta160, leaving prosthesis10in place, as shown inFIG.9F.

FIGS.10A and10Bshow valve prosthesis10in open (systolic) and closed (diastolic) positions, respectively, in accordance with an embodiment of the present invention. For clarity of illustration, the surrounding anatomy is not shown in the figure. Collapsible pliant material105of valve104opens during systole and closes during diastole, because of the fluid forces applied thereto by the blood flow and the pressure difference between the left ventricle and the aorta. Alternatively, valve104comprises one or more rigid components, such as rigid leaflets, for example as described in U.S. Pat. No. 6,312,465 to Griffin et al. or U.S. Pat. No. 5,908,451 to Yeo, both of which are incorporated herein by reference. Although prosthesis10, including valve104, is shown in the figures as defining a single flow field therethrough, for some applications the prosthesis and valve are configured so as to define a plurality of flow fields therethrough, such as shown in several figures of the '451 patent to Yeo (e.g.,FIGS.1-3thereof).

Reference is made toFIGS.11A-D, which illustrate several configurations for axially coupling valve prosthesis10to aortic annulus182, in accordance with respective embodiments of the present invention. For clarity of illustration, these figures show a spread view of the native valve, viewed from a central axis of the native valve, with native aortic valve leaflets158cut longitudinally and pulled to the sides.

In the configuration shown inFIG.11A, proximal skirt32of valve prosthesis10is shaped so as to define a single barb120for each leaflet158, such that the barbs are generally centered with respect to the leaflets and engagement arms22. In the configuration shown inFIG.11B, the proximal skirt is shaped so as to define a pair of barbs120for each leaflet158.

In the configuration shown inFIG.11C, each engagement arm22comprises at least one proximal spike192, which typically protrudes from a most proximal region of the engagement arm (i.e., the portion of the engagement arm closest to the apex of the heart). Spikes192penetrate aortic annulus182from the aortic side, until the spikes exit the annulus on the left-ventricular side, and engage respective barbs120on the left-ventricular side.

In the configuration shown inFIG.11D, barbs120penetrate aortic annulus182from the left-ventricular side thereof, until the barbs exit the annulus on the aortic side, and are coupled to respective engagement arms22in respective sinuses. For example, the ends of the barbs may be shaped as hooks, in order to hook around proximal regions of engagement arms22.

Reference is made toFIGS.12A-G, which illustrate a holding device200for holding valve prosthesis10prior to the implantation of the prosthesis, in accordance with an embodiment of the present invention. Valve prosthesis10is loaded into delivery tube202from holding device200, as is described hereinbelow with reference toFIGS.13A-D. During an implantation procedure, delivery tube202is advanced into an overtube or trocar, such as overtube or trocar150, described hereinabove with reference toFIGS.5A-C.

FIGS.12A and12Billustrate outer and sectional views, respectively, of holding device200, in accordance with an embodiment of the present invention. For some applications, holding device200is shaped so as to define a conical portion204and a tubular portion206. Holding device200comprises, for example, plastic.

FIG.12Cshows valve prosthesis10loaded in holding device200, in accordance with an embodiment of the present invention. The proximal end of valve prosthesis10is typically fully compressed within tubular portion206, while collapsible pliant material105is in at least a partially open position within conical portion204, so as not to deform the typically delicate material of the valve. The proximal end of the prosthesis is optionally coupled to a device holder208.

FIGS.12D and12Eshow a configuration of device holder208, in accordance with an embodiment of the present invention. In this configuration, device holder208is shaped so as to define one or more female coupling openings209, to which corresponding male coupling members218of valve prosthesis10are releasably coupled. For example, proximal portion34of proximal skirt32(FIGS.1and2B) may be shaped so as to define male coupling members218. (For clarity of illustration, proximal skirt32is not shown inFIG.12E.) For some applications, the genders of the coupling elements are reversed.

FIG.12Fillustrates holding device200in storage in a jar210containing a preservation fluid212such as glutaraldehyde solution. For some applications, holding device200is held upright by a holder214. The contents of the holding device200are typically kept in preservation fluid212at all times, and jar210is sealed by a cover216.

FIG.12Gillustrates the removal of holding device200from storage jar210prior to loading valve prosthesis10into delivery tube202, in accordance with an embodiment of the present invention. Holding device200and its contents are typically washed prior to loading.

Reference is now made toFIGS.13A-D, which illustrate the loading of valve prosthesis10into delivery tube202from holding device200, in accordance with an embodiment of the present invention. As shown inFIG.13A, a distal end of a central delivery shaft222includes a device holder connector220. Device holder connector220is removably coupled to device holder208, which is coupled (e.g., fixed) to valve prosthesis10. For example, device holder connector220and device holder208may comprise mating, screw-threaded male and female connectors.

As shown inFIG.13B, retraction, to the right in the figure, of central delivery shaft222pulls valve prosthesis10, which is at least partially compressed, into delivery tube202. As shown inFIG.13C, valve prosthesis10is pulled into delivery tube202. Valve prosthesis10is placed in delivery tube202such that engagement arms22extend from delivery tube202, and thus are free to flare outwards radially, as shown inFIG.13D. (The engagement arms are constrained from flaring outwards during the initial steps of an implantation procedure by an overtube or trocar into which delivery tube202is inserted, such as overtube or trocar150, described hereinabove with reference toFIGS.5A-C.)

Although valve prosthesis10has been generally described herein as being implantable in an aortic valve, in some embodiments of the present invention the valve prosthesis is configured to be placed in another cardiac valve, such as a mitral valve, tricuspid valve, or pulmonary valve (such as described hereinbelow with reference toFIG.14), or in a venous valve. As used herein, including in the claims, “proximal” and “upstream” mean the side of the native or prosthetic valve closer to incoming blood flow, and “distal” and “downstream” mean the side of the native or prosthetic valve closer to outgoing blood flow.

Reference is made toFIG.14, which is a schematic illustration of a fully-assembled valve prosthesis300placed in a pulmonary valve310, in accordance with an embodiment of the present invention. Valve prosthesis300is generally similar to valve prosthesis10, described herein with reference toFIGS.1-13D and16A-17, with appropriate modifications, such as size, for placement in pulmonary valve310. Valve prosthesis300comprises two portions that are configured to axially sandwich the native pulmonary valve complex from right-ventricular312and pulmonary trunk314sides thereof.

Reference is made toFIG.15, which is a schematic anatomical illustration showing the location of a native valve complex, in accordance with an embodiment of the present invention. As used herein, including in the claims, the “native valve complex” includes the area demarcated by a box320, which includes native aortic valve leaflets158, native valve annulus182, subvalvular tissue322on the left-ventricular side, and the lower half of the aortic sinuses164(i.e., up to the top of box320).

Reference is made toFIGS.16A-H, which schematically illustrate another transapical technique for implanting valve prosthesis10(in addition to the transapical approach described hereinabove with reference toFIGS.5A-8A), in accordance with an embodiment of the present invention. Prior to the implantation procedure, prosthesis10is positioned in a transapical delivery catheter350, as shown inFIG.16H. A transapical delivery tube351of catheter350holds proximal skirt32, and a transapical delivery cap352holds the distal end of the valve.

The implantation procedure begins with insertion of catheter350through an apex of the heart, into left ventricle157. For example, the apex may be punctured using a standard Seldinger technique. A guidewire390is advanced through catheter350into ascending aorta160, as shown inFIG.16A. Optionally, aortic valve140is partially dilated to about 15-20 mm (e.g., about 16 mm), typically using a standard valvuloplasty balloon catheter.

Catheter350is advanced over guidewire390through native aortic valve140, into ascending aorta160. Delivery cap352is advanced further into the ascending aorta, by pushing with delivery cap shaft353. The advancement of the delivery cap releases engagement arms22, which flare out laterally, as shown inFIG.16B. Catheter350is withdrawn towards the ventricle, thereby positioning engagement arms22in the sinuses, as shown inFIG.16C. (Although engagement arms22are shown inFIG.16Cas being in contact with the sinus floors, for some applications the engagement arms do not come in contact with the sinus floors, such as described hereinabove with reference toFIG.7B.) At this stage of the implantation procedure, proximal skirt32remains in tube351.

Alternatively, catheter350is placed within an overtube (not shown), similar to overtube or trocar150(FIGS.5A-6B), and in such a configuration the engagement arms may be released either by pulling back of the overtube, or by the pushing forward of delivery end cap352.

At the next step of the implantation procedure, tube351is withdrawn in the direction of the apex of the heart. Delivery cap shaft353prevents cap352from being withdrawn with tube351(FIG.16H). As a result, proximal skirt32is freed from tube351to snap or spring open, and engage the inner surface of LVOT180. Barbs120, if provided, pierce or protrude into the aortic annulus on the left-ventricular side of the native valve. It is noted that cap352remains in place until after proximal skirt32opens. Blood flow thus cannot wash the skirt downstream during the implantation procedure.

Cap352is advanced further into the ascending aorta by pushing on delivery cap shaft353, thereby releasing the rest of valve prosthesis10from cap352, as shown inFIG.16E. Delivery tube351is advanced over shaft353through aortic valve140, until tube351rejoins cap352, as shown inFIG.16F. Delivery catheter350is withdrawn into the left ventricle, as shown inFIG.16G, and then from the heart, along with guidewire390. Prosthesis10is left in place, completing the implantation procedure.

Reference is made toFIG.17, which is a schematic illustration showing a shape of engagement arms22, in accordance with an embodiment of the present invention. In the figure, outer support structure14is shown placed on an abstract geometric form400for clarity of illustration of the shape of the structure. As can be seen, in this embodiment engagement arms22have a shape that is generally upwardly concave (except at the junctures), i.e., concave in a downstream direction. In mathematical terms, this shape can be characterized by the function z″(r)>0, where z is the height at any given point on one of engagement arms22(e.g., point P), and r is the distance from the z-axis to the given point. (It is understood that the arms may be shaped so as to include one or more relatively short sections that are upwardly convex (i.e., z″(r)<0), but that the general shape of the arms is upwardly concave.)

For some applications, engagement arms22are shaped such that at least a portion of the arms is parallel to the longitudinal axis of outer support structure14.

In en embodiment, the shape of the arms is characterized by the function z″(r)<=0, i.e., the general shapes of the arms is not upwardly concave.

As used herein, including in the claims, the “ascending aorta” includes the aortic root (sinuses) and the tubular portion above the root.

Although valve prostheses10and300have been described herein as comprising a valve, for some applications the prostheses do not comprise valves.

FIG.18is a schematic illustration of an assembled valve prosthesis support structure1800, in accordance with an alternative embodiment presented herein. Assembled valve prosthesis support structure1800comprises a collapsible inner support structure1812, which serves as a proximal fixation member, and a collapsible outer support structure1814, which serves as a distal fixation member.

FIG.19Ais a schematic illustration of collapsible outer support structure1814.FIG.19Bis a schematic illustration of collapsible inner support structure1812. Outer and inner support structures1814and1812may be initially formed separately and then joined together, as shown inFIG.18, or may be formed as one integrated structure. In one embodiment, outer and inner support structures1814and1812are joined together prior to implantation of the prosthesis (e.g., during a manufacturing process, or by a healthcare worker prior to implantation). In another embodiment, the outer and inner support structures1814and1812are coupled to one another during an implantation procedure. In one embodiment, outer support structure1814is constructed from a plurality of separate pieces, which are joined to inner support structure1812using standard manufacturing means, such as welding, gluing, or suturing, such that the functionality of outer support structure1814is attained.

Assembled valve prosthesis support structure1800is configured to include a valve prosthesis as described above with respect toFIG.1. The support structure1800and valve prosthesis is configured to be placed in a native diseased valve of a subject, such as a native stenotic aortic or pulmonary valve, using a minimally-invasive approach, such as a beating heart transapical procedure, such as described with reference toFIGS.5A-8A, or with reference toFIGS.16A-H, or a retrograde transaortic procedure, such as described with reference toFIGS.9A-G.

As shown inFIG.19A, outer support structure1814is shaped so as to define a plurality of distal strut supports1820, from which a plurality of proximal engagement arms1822extend radially outward in a proximal direction. Strut supports1820and engagement arms1822may be formed as one integrated structure (as shown), or, alternatively, may be initially formed separately and then joined to one another. For example, the strut supports1820and engagement arms1822may be mechanically interlocked, sutured, or coupled by other means. Typically, the strut support1820and engagement arms1822are joined prior to implantation.

Typically, engagement arms1822have a shape that is generally upwardly concave, such as described with reference toFIG.17. Engagement arms1822are typically configured to be at least partially disposed within the aortic sinuses of the subject, to engage and/or rest against floors of the aortic sinuses, and/or to apply an axial force directed toward the left ventricle of the subject. Placement of engagement arms1822within the aortic sinuses prevents “device migration,” i.e., undesired retrograde (towards the left ventricle) movement of the valve prosthesis that may result from fluid forces applied to the valve. Engagement arms1822meet one another at respective junctures1824. In one embodiment, engagement arms1822are fabricated as separate pieces and are mechanically engaged to one another at respective junctures1824. In another embodiment, engagement arms1822meet via an area defined at each respective juncture1824, and thus do not actually touch one another. Typically, the engagement arms are configured to define respective peaks at junctures1824, and respective troughs1826between each two of the peaks.

Outer support structure1814is typically formed of a suitable material that allows mechanical deformations associated with crimping and expansion of a valve prosthesis. For example, outer support structure1814may be formed of nitinol or a stainless steel alloy (e.g., AISI 316). In one embodiment, outer support structure1814is fabricated from a single piece. In another embodiment, outer support structure1814is formed of a plurality of pieces that are coupled together. In one embodiment, engagement arms1822are coated with a flexible material (e.g., polyester, other synthetic material, pericardium, and/or other biological material).

With reference toFIG.19B, inner support structure1812is shaped so as to define a plurality of distal inner strut supports1830. In one embodiment, inner support structure1812is sutured to outer support structure1814at respective strut supports1820and1830. Sutures between inner and outer support structures1812and1814allow for movement and compliance between the inner and outer support structures. Inner support structure1812also includes a proximal skirt1832that extends from the struts. A proximal portion1834of proximal skirt1832is provided in a bulging configuration to engage the left ventricular outflow tract (LVOT) of the subject and/or periannular tissue at the top of the left ventricle. A relatively narrow throat portion1836of proximal skirt1832is configured to be positioned at a valvular annulus of the subject. A flared distal portion1837of proximal skirt1832is configured to flare outward so as to engage the inner surface of the native valve leaflets. The flared distal portion1837preserves prosthesis leaflet integrity and prolongs overall valve durability by avoiding contact between the prosthesis leaflets and inner support structure1812when the prosthesis leaflets are open. Inner support structure1812may be formed of materials such as: nitinol, stainless steel alloys, other metals or metal alloys, or biocompatible materials.

In the embodiment shown inFIG.18, support structure1800has been designed to provide a more accommodating fit within bulkier, calcified native valve commissures. For example, a distance1841is created between engagement arms1822of outer support structure1814. In one embodiment, distance1841is between about 0.5 millimeters (mm) to about 8 mm; alternatively between about 1 mm to about 6 mm, or between about 3 mm and about 5 mm. Distance1841allows for the accommodation of bulkier, calcified commissures, and allows support structure1800to sit lower in the aortic root even in the face of moderate-heavy calcification. A distance1843is also created between each respective trough1826of each engagement arm1822and skirt portion1832of inner support structure1812. Distance1843allows for the accommodation of bulkier, calcified native valve leaflets. In one embodiment, distance1843is between about 1 mm to about 14 mm; alternatively between about 2 mm to about 10 mm, or between about 3 mm to about 8 mm, or between about 4 mm to about 6 mm. More specifically, depending on the size of the prosthesis, distance1843is between about 1 mm and about 10 mm; alternatively between about 1 mm to about 12 mm, or between about 1 mm to about 14 mm; alternatively, between about 2 mm and about 9 mm, or between about 2 mm to about 10 mm; alternatively between about 3 mm to about 8 mm; alternatively between about 4 mm to about 6 mm. The design of support structure1800provides a frame that can conform to the patient-specific anatomy, including variability in calcium loads, while maintaining the correct position of the support structure, and therefore ensuring proper valve function. The design of support structure1800also ensures stable implantation and localization of the valve prosthesis, and proper sealing between the prosthesis and the native valve against perivalvular leaks.

The scope of the present invention includes embodiments described in the following applications, which are assigned to the assignee of the present application and are incorporated herein by reference. In an embodiment, techniques and apparatus described in one or more of the following applications are combined with techniques and apparatus described herein:U.S. patent application Ser. No. 11/024,908, filed Dec. 30, 2004, entitled, “Fluid flow prosthetic device,” which published as US Patent Application Publication 2006/0149360;International Patent Application PCT/IL2005/001399, filed Dec. 29, 2005, entitled, “Fluid flow prosthetic device,” which published as PCT Publication WO 06/070372; and/orInternational Patent Application PCT/IL2004/000601, filed Jul. 6, 2004, entitled, “Implantable prosthetic devices particularly for transarterial delivery in the treatment of aortic stenosis, and methods of implanting such devices,” which published as PCT Publication WO 05/002466, and U.S. patent application Ser. No. 10/563,384, filed Apr. 20, 2006, in the national stage thereof, which published as US Patent Application Publication 2006/0259134.

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