WO2018083493A1

WO2018083493A1 - Annuloplasty prosthesis and related methods

Info

Publication number: WO2018083493A1
Application number: PCT/GB2017/053326
Authority: WO
Inventors: Paolo DE SCISCIO; Jacob BRUBERT
Original assignee: Cambridge Enterprise Limited
Priority date: 2016-11-04
Filing date: 2017-11-06
Publication date: 2018-05-11

Abstract

An annuloplasty prosthesis comprises: a frame; and wherein at least a portion of the frame is capable of reversibly transitioning between a rigid mode and a flexible mode, thereby allowing the device to change its shape.

Description

ANNULOPLASTY PROSTHESIS AND RELATED METHODS

DESCRIPTION BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to devices for repair of cardiac valves via transcatheter methods. More particularly, it relates to methods and apparatus for transcatheter implantation of an annuloplasty prosthesis. The devices can comprise multiple anchoring elements coupled to an annular support such that deployment of said anchoring elements secures the prosthesis to the native annular tissue. In preferred embodiments, at least a portion of the annular support comprises material capable of transitioning between soft and rigid states. In so doing, the prosthesis can be manipulated during deployment such that the degree of annular area reduction is determined intraoperatively.

Description of Prior Technology Cardiac valves serve to maintain functional unidirectional flow of blood within the heart. Valve dysfunction may occur as a result of cardiovascular disease (i.e. heart failure) or degenerative valve changes (i.e. calcification). In particular, dilatation or narrowing of the valvular apparatus may lead to insufficiency (leak) or blockage (stenosis), respectively. Accordingly, a number of devices have been developed to treat the various forms of valvular heart disease. With respect to the atrioventricular valves of the heart, annuloplasty rings are commonly employed to augment the native anatomy. Generally, an annuloplasty repair aims to achieve maximal leaflet coaptation area during systole by reducing the annular diameter (i.e. the anteroposterior diameter) while supporting the posterior annulus against dilatation. This may be achieved via attachment to all aspects of the valve (anterior and posterior leaflets in the case of the mitral valve) or a portion of the valve. Annuloplasty devices can be further divided into rigid, semi-rigid or flexible, planar or saddle-shaped, and adjustable or non-adjustable. Said design changes are achieved through a combination of material selection and geometry. Examples are seen in US Patent No. 4,042,979 to Angell, 4,290, 151 to Massana, 5,061,277 to Carpentier & Lane, 6,217,610 to Carpentier et al, and 6, 187,040 to Wright, the contents of which are hereby incorporated by reference. Variations in design result from the need to address a number of contributing factors leading to valvular regurgitation. In particular, rigid devices are desirable in the setting of severe dilatation and limited annular motion. The fixed nature of the device enables the operator to remodel the annulus to a predetermined geometry. Flexible designs aim to maintain the three-dimensional contour of the native annulus. As a result they serve more so to limit further dilatation.

Differences in geometry between the tricuspid and mitral valves have led to location-specific devices. Briefly, the mitral valve comprises a posterior and anterior leaflet, the posterior leaflet accounting for two-thirds of the valvular circumference. The leaflet free edges are tethered to the left ventricle by the subvalvular chordae-papillary apparatus preventing valvular prolapse during systole. The mitral leaflets attach to a saddle-shaped annulus at the atrioventricular junction. During left ventricular contraction the annulus undergoes a sphincter motion to facilitate leaflet coaptation. In particular, as annular height increases relative to the commissural width, peak leaflet stress decreases becoming maximally attenuated at a height-to-width ratio exceeding 0.20. Accordingly, a rigid prosthesis with a planar geometry may restrict widening of the annulus during diastolic relaxation resulting in limited ventricular filling. To address this, a number of predetermined rigid saddle-shaped devices have been developed including US patent no. 6,858,039 to McCarthy, incorporated herein by reference.

Conventionally, valvular annuloplasty has been performed via open heart surgery with cardiopulmonary bypass during which the prosthesis is manually sutured to the annular wall. Open mitral repair is inherently invasive requiring the patient's heart to be stopped. In contrast, less invasive transcatheter techniques enable devices to be deployed while the heart continues to beat. A number of mitral repair devices have recently been adapted for transcatheter delivery. Percutaneous annuloplasty refers to indirect or direct techniques performed using standard catheter-based methods. US patent no. 7,591,826 to Alferness & Kaye details an indirect approach, specifically implantation of a device within the neighboring coronary sinus. Comprised of two self-expanding nitinol anchors with a nitinol curvilinear connecting segment, the device is positioned within the coronary sinus transmitting tension to the posterior and lateral mitral annulus. As a further example, US patent no. 6,890,353 to Cohn et al. utilizes nitinol rods to achieve a similar annular compression via the coronary sinus. US patent no. 8,845,723 to Spence et al. and US patent no. 6,986,775 to Morales & Starksen et al. exemplify the direct approach through percutaneous mechanical cinching. This method utilizes a retrograde transventricular approach to deliver pledget sutures along the medial and lateral aspects of the posterior annulus. When cinched together the plication sutures draw the annulus inward increasing leaflet coaptation. The plication suture technique for mitral repair was first described by Burr et al. in 1977 (The Journal of Thoracic and Cardiovascular Surgery, vol. 73, No. 4, pp. 589-595). In addition to mechanical plication, US patent no. 8,328,798 to Witzel et al. and US patent no. 8,974,445 to Warnking et al. specify a percutaneous energy-mediated cinching approach whereby the annular tissue is heated leading to scarring.

US patent no. 8,758,372 to Cartledge et al. and US patent no. 7,361,190 to Shaoulian et al. are among the first to describe an adjustable percutaneous annuloplasty prosthesis. In each case, a complete D-shaped prosthesis is surgically implanted with transcatheter adjustment made via mechanical rotation of a tightening element and radiofrequency stimulation of the shape memory alloy, respectively. While the ability to adjust the prosthesis size and shape in response to realtime loading pressures is advantageous, initial surgical implantation imparts significant risk to the patient. US patent no. 8,518,107 to Tsukashlma, et al. addresses this limitation by incorporating a plurality of segments that cooperate with each other to facilitate transcatheter delivery wherein the prosthesis is adapted from an initial elongated configuration to a D-shaped annular geometry. Direct linear access via transapical delivery is required to enable the delivery system to manipulate the annulus in the anter-posterior dimension. Late adjustment, defined as change to the prosthesis shape and/or size, is achieved via internal or external application of radiofrequency stimulation. An example of a percutaneously-deployed incomplete annuloplasty ring is described by US patent no. 8,608,797 to Gross & Gross wherein a transseptal approach is used to deliver a modified C-shape semi-rigid prosthesis that is mechanically adjusted during implantation.

Significantly, all of the aforementioned devices have a fixed geometry once deployment is initiated. A method to overcome this is detailed in US patent publication no. 2012/0109289 to Boiling et al. wherein annulus gripping elements are adjustable between a first (delivery) configuration and a second (deployed) configuration. Accordingly, by coupling the annular support structure and gripping elements, the prosthesis may be adjusted between the two configurations prior to detachment from the delivery apparatus.

As with surgical annuloplasty devices, each of the aformentioned percutaneous prostheses address one requirement for valve annuloplasty to the detriment of another. In adjustable iterations, the degree of radial reduction is limited to a predetermined shape. Together with an inability to directly size the prosthesis (as in surgical implantation), adjustable percutaneous devices may lead to under- or over- sizing. Procedural complexity presents another disadvantage when compared to other transcatheter technologies, for example transcatheter aortic valve replacement using a transfemoral approach. US patent no. 8,608,797 to Gross & Gross requires the operator to deploy a dozen anchors independently. Moreover, the transseptal approach requires significant experience given the risk of damage to adjacent anatomical structures and frequent distortion of the atrial and interatrial septum in mitral regurgitation.

In the setting of mitral regurgitation, it is foreseeable that an annuloplasty recipient may require valve implantation in the future. Implanting a prosthetic valve within an annuloplasty ring can be problematic due to the mismatch between the geometries of the respective devices. Whereas surgical valve replacement enables excision of the annuloplasty ring prior to valve implantation, the transcatheter valve is deployed within said ring. In this case, the non-circular geometry of the annuloplasty prosthesis, specifically devices for the mitral position, may interfere with transcatheter valve placement, deployment and/or functioning. While there are devices capable of adjusting size postoperatively, they do not expand or change shape appropriately to accommodate a transcatheter mitral valve.

In view of the limitations associated with previously known techniques for percutaneous annuloplasty of the mitral valve, herein is disclosed a device comprising: multiple anchoring elements coupled to an annular support. Deployment of said anchoring elements secures the prosthesis to the native annular tissue, with at least a portion of the annular support being adaptable to facilitate transcatheter delivery, annular remodelling and postoperative shape change.

SUMMARY OF THE INVENTION

According to one aspect of the invention, there is provided an annuloplasty prosthesis comprising: a frame; and wherein at least a portion of the frame is capable of reversibly transitioning between a rigid mode and a flexible mode, thereby allowing the device to change its shape. The reversibility from rigid to a flexible mode makes it possible adjust or even remove the prosthesis after it has been deployed: the prosthesis can be set in place and left in the rigid mode, and then when it needs to be adjusted it can be transitioned to the flexible mode to enable the adjustment.

Said prosthesis can have a first, relatively compact, configuration to enable it to be delivered to the desired location and a second, less compact, configuration when deployed and in use, and wherein the prosthesis can transition between the two configurations when said portion is in the flexible mode. This allows the prosthesis to be delivered in a compact state, e.g. via a catheter, and thereafter be arranged into a fuller, deployed arrangement. The initial delivery can be done in the rigid mode, to prevent accidental deployment, and the transition to flexible mode can be initiated when the prosthesis reaches the deployment site. Alternatively, the prosthesis may be transitioned to flexible mode before it reaches the deployment site.

The prosthesis can be an annuloplasty ring, either a mitral valve annuloplasty ring or a tricuspid valve annuloplasty ring. Existing mitral and tricuspid rings are not adjustable after deployment of the ring, which is a significant drawback. The annuloplasty ring can be a continuous ring, or have two ends that may be connected to form a continuous ring. Alternatively, the two ends may remain unconnected so that the annuloplasty ring is an incomplete ring. As such, it will be clear that the term 'ring' should not be construed to require a continuous loop. Nor does it require a perfect circular shape.

The frame can further comprises elements which are not capable of reversibly transitioning between a rigid and flexible mode. Such elements may include, for example, anchoring elements for attaching the prosthesis to surrounding tissue.

The portion of the frame that can undergo the transition can comprises a core of the frame. As such, the transition will affect the overall properties of the frame as a whole. The core can be surrounded by an encapsulating layer. The transitioning portion can be capable of reversibly transitioning between a rigid and flexible mode due to a change in the properties of the core. As such, the encapsulating layer can help contain the core material, if that material transitions to a fluid state in the flexible mode.

The transitioning portion of the frame can be configured to undergo the transition in mode under the influence of an external stimulus. Such a stimulus could be an electric field or the provision of heat, for example.

The material properties of the core can be such that the core undergoes a solid to liquid phase transition, wherein said rigid mode corresponds to the core being solid and said flexible mode corresponds to said core being liquid. For example, the core can undergo the solid to liquid phase transition at a temperature of from 35°C to 80°C, more preferably from 40°C to 70°C, and even more preferably from 45°C to 60°C. In these temperature ranges, the transition can be triggered within the human or animal body, without causing permanent heat damage to the surrounding tissues.

The encapsulation layer can comprise fluoropolymers, in particular polytetrafluoroethylene (PTFE) or expanded PTFE (ePTFE) or fluorinated ethylene propylene (FEP) or ethylene- tetrafluoroethylene (ETFE), polysiloxanes, polyurethanes, polybutylenes, and/or styrenic thermoplastic elastomers, in paticular poly(styrene-block- isobutylene-blockstyrene) (SIBS) liquid silicone rubbers, silicone rubbers with peroxide, acetoxy, oxime, amine or platinum cures, natural or synthetic isoprene type rubbers, or paralyene C.

The transitioning portion can comprise a eutectic alloy, in particular a quaternary bismuth alloy, ethylene butyl acrylate copolymer, ethylene methyl acrylate copolymer, ethylene acrylic acid copolymer, ethylene methacrylic acid copolymer, polybutylene, poly(epsilon-caprolactone), thermoplastic polyolefin elastomer/plastomer, thermoplastic polyurethane elastomer, polyamide, polylactic acid, poly(n-isopropylacrylamide) and/or cellulose acetate butyrate.

The transitioning portion can have a Young's modulus greater than zero and up to 200 GPa in the rigid mode, preferably between 0.5 GPa and 150 GPa, more preferably between 5 GPa and 100 GPa, and/or a Shore A hardness greater than 50, preferably greater than 75, more preferably greater than 100, and/or a tensile strength greater than 10 MPa, preferably greater than 20 MPa, more preferably greater than 30 MPa. These properties allow the prosthesis to fulfil its structural function when deployed. The portion can have a dynamic viscosity less than 10 Pa.s in the flexible mode, preferably less than 0.1 Pa.s, more preferably less than 0.01 Pa.s. This allows the prosthesis to be easily reshaped or reconfigured. A ratio of Young's moduli of said portion in the rigid and flexible modes (Erigid/Efl_exibie) is preferably greater than 10, more preferably greater than 100.

The prosthesis preferably retains its shape when transitioning from the flexible mode to the rigid mode. Further the prosthesis can preferably be transitioned into the rigid mode from different shapes in the flexible mode. This allows the prosthesis to be conformed to the surround tissue in situ and then set into the rigid mode to give the best possible fit.

The prosthesis can further comprise anchoring elements for attaching the prosthesis to adjacent tissue, and may further comprise supports, such as ribs, attached to the anchoring elements. The ribs may each comprise a sheath for housing the anchoring elements until the prosthesis is deployed, at which point the anchors can be triggered to extend out of the ribs (for example via a spring loading or hydraulic action mechanism). The ribs can extend through the encapsulating layer and into said core, such that a change in rigidity of the core directly affects the mobility of the ribs.

The sheath of each support can extend outside of the frame. In that case, each sheath can be configured to retract within the frame to expose the anchoring elements. Alternatively, the sheath of each support can be provided within the frame of the prosthesis. In that case, the prosthesis can further comprise a trigger for releasing the anchoring elements from within the sheaths, so that the anchoring elements move out of the sheaths. The anchoring element or anchoring elements within each sheath are preferably moveable independently of anchoring elements in other sheaths, so that if one sheath fails to deploy its anchoring elements, the other sheaths are not affected.

According to another aspect of the invention, there is provided a method of using the prosthesis discussed above, the method comprising: causing the prosthesis to undergo transition from one of the rigid or flexible modes to the other. Such transition might occur when preparing the prosthesis for use, before a medical procedure.

According to another aspect of the invention, there is provided a method of inserting the prosthesis discussed above into a human or animal body, the method comprising: causing the prosthesis to undergo transition from the rigid mode to the flexible mode; shaping the prosthesis into a deployed configuration; and causing the prosthesis to undergo transition from the flexible mode to the rigid mode. As such, the prosthesis can be set into a rigid mode to perform its function, whilst being easy to deploy by virtue of the flexible mode.

The method may comprise inserting the prosthesis into the human or animal body either before or after the step of causing the prosthesis to undergo transition from the rigid mode to the flexible mode.

According to another aspect of the invention, there is provided a method of adjusting, the prosthesis discussed above in a human or animal body, the method comprising: causing the prosthesis to undergo transition from the rigid mode to the flexible mode; and adjusting the prosthesis, optionally including removing the prosthesis from the human or animal body. As such, the reversibility of the rigid/flexible mode transition enables the possibility of the deployed prosthesis being subsequently adjusted, either to correct an error in deployment or to account for further changes in the surrounding tissue.

In any of the methods discussed above, the step of causing the prosthesis to undergo transition from the rigid mode to the flexible mode can comprise heating said portion of the prosthesis. The source of heat can be external to a surrounding body, internal to a surrounding body but separated from the frame, or in direct contact with the frame.

According to another aspect of the invention there is provided a device, such as a catheter, for delivering a prosthesis as discussed above to a desired location within a human or animal body, the device comprising: a transition inducer for inducing a transition in said portion of the prosthesis frame between the rigid mode and the flexible mode, or vice versa. As such the triggering of the transition can be easily achieved during the deployment of the prosthesis. The transition inducer can be a heater, either a direct (i.e. radiative or conductive) heater or an indirect heater such as an electromagnetic field generator for causing induction heating by inducing eddy currents in said portion of the prosthesis frame, thereby heating said portion of the frame.

The distal end of the device can comprise a plurality of struts configured to expand and retract in a radial direction, and at least one of the struts can be provided with a portion for gripping the prosthesis. The portion for gripping can be an eyelet with protruding edges configured to engage with a projecting portion of a support member of the prosthesis. As a result of this arrangement, the prosthesis can be held firmly and pushed into place on the surrounding tissue, thereby allowing the prosthesis to be conformed to the local tissue geometry and/or for the anchoring members to be firmly deployed. The device can further comprise a realignment wire arranged to guide the projecting portion of the supporting member to the eyelet by pulling the projecting portion to the eyelet when the wire is tightened and the struts are radially expanded. This allows for the proper positioning of the prosthesis on the device once the struts have been radially expanded.

According to another aspect of the invention there is provided a method of using the delivery device, the method comprising: configuring the delivery device and prosthesis so that the prosthesis is held in at least one strut portion for gripping the prosthesis; using the delivery device to position the prosthesis in the desired location; activating anchoring elements of the prosthesis to hold the prosthesis in the desired location; removing the delivery device so as to leave the prosthesis in the desired location. According to this method, the delivery device holds the prosthesis strongly enough to position it in place, but after the prosthesis is fixed via the anchoring elements into the tissue the delivery device can be decoupled from the prosthesis to allow the delivery device to be removed (i.e. because the prosthesis is held more strongly by the anchoring elements than by the delivery device).

One implementation of the present invention provides methods for transcatheter delivery of an implantable prosthesis for repair of a heart valve. In general, said methods include fixation of a prosthesis to the native annular tissue with subsequent remodelling to reduce the annular area. The prosthesis may comprise multiple anchoring elements, coupled to the prosthesis frame wherein deployment of said anchoring elements secures the prosthesis to the native annulus. In preferred embodiments, at least a portion of the prosthesis frame comprises material capable of transitioning between a soft and rigid state. Accordingly, the prosthesis in its soft state may be configured to conform to the geometry of the native annulus. Subsequent remodeling by manipulation of the delivery apparatus changes the annular area - the degree of reduction being determined in real-time under the guidance of three-dimensional echocardiography. Thereafter, transition to a rigid state maintains the remodeled geometry. In some embodiments, the prosthesis is capable of reversibly transitioning between soft and rigid states. In so doing, and following reversion to the soft state from the rigid state, the prosthesis may be adapted postoperatively to further reshape the annulus and/or accommodate a second prosthesis therein.

According to another implementation of the invention, there is provided a method for transcatheter delivery of the prosthesis wherein the device exists between an elongated (sheathed) configuration, an expanded (partially deployed) configuration and a remodeled (deployed) configuration. A further aspect of the invention relates to a method for initial expansion of the prosthesis from the elongated (sheathed) configuration to a geometry that conforms to the native anatomy. A further aspect of the invention relates to a method for prosthesis remodeling from the partially deployed configuration to a final dimension.

Preferably, the prosthesis is advanced to a position within the native annulus using a retrograde approach. In some embodiments, the prosthesis in its soft state is adapted via catheter foreshortening/elongation. In other embodiments, the prosthesis in its soft state is adapted via balloon inflation/deflation. In yet further embodiments, the prosthesis in its soft state is adapted via steerable or moveable grips. In each case, the prosthesis remains reversibly tethered to the delivery apparatus until transitioned to a rigid state. In preferred embodiments, the prosthesis is delivered within a sheath having an outer diameter of from 4 mm to 12 mm, more preferably from 5 mm to 10 mm, more preferably from 6 mm to 8 mm. Once deployed and in its rigid state, the prosthesis is a diameter of from 15 mm to 45 mm, more preferably between from 20 mm to 40 mm, more preferably from 25 mm to 35 mm. The prosthesis may form a complete or incomplete ring structure.

The prosthesis can further comprise anchoring elements extending from, and located equidistant along the inferior aspect of the prosthesis, having a free end that penetrates the annular tissue and preferably one element that resists retraction once engaged with said tissue. Deployment of said anchoring elements secures the prosthesis to the annular wall. Preferably, each anchoring element is independently operated.

In some embodiments, the prosthesis can be delivered to the site of implantation with the anchoring elements in their deployed configuration. In other embodiments, the prosthesis may comprise a plurality of independent cavities containing the anchoring elements therein. In this case, anchoring elements are restrained within their respective channel via mechanical methods. Accordingly, anchoring elements are deployed by retraction of the restraint. In yet further embodiments, the prosthesis comprises a network of interconnected cavities. In this case, hydraulic linear actuators may be used to deploy the anchoring elements. Accordingly, the network comprises at least one delivery port wherein at least one delivery tube attaches to said delivery port. The cavity is sealed by detachment of the delivery tube from the delivery port.

An advantage of the present invention is the provision of an apparatus and method for direct annuloplasty.

Another advantage of the present invention is the provision of an annuloplasty device with the capacity to transition between soft and rigid states wherein, in the soft state and once secured to the native annulus, reduction of the annular area may be determined in vivo by real-time imaging.

Still another advantage of the present invention is the provision of an annuloplasty device having a structure that can change configuration in a second procedure to further repair the valvular apparatus and/or accommodate a second device therein.

Additional features and advantages of the present invention will be obtained by reference to the detailed description and accompanying drawings which set forth exemplary embodiments as realized in the claims hereof:

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described below, by way of non-limiting example only with reference to the accompanying Figures, in which:

FIGS. 1A-1B are orthographic views detailing the anatomy of the mitral valve as a site for device implantation according to one embodiment of the present invention;

FIG. 2 is an orthographic view detailing an embodiment of the prosthesis positioned within the native mitral annulus; FIGS. 3A-3G are orthographic views detailing configurations of a complete D-shaped annuloplasty prosthesis according to one embodiment of the present invention;

FIGS. 4A-4B are superior views detailing further embodiments of the prosthesis of FIG. 2 configured as an incomplete annuloplasty;

FIGS. 5A-5C are isometric views detailing yet further embodiments of the prosthesis of FIG. 2 configured to the saddle-shape of the healthy annulus of FIG. IB;

FIGS. 6A-6C are isometric views detailing radial remodelling of the prostheses of FIG. 4 to accommodate a second prosthesis therein;

FIGS. 7A-7B are orthographic and isometric views detailing the elements comprising the prosthesis of FIG. 2 according to one embodiment of the invention; FIGS. 8A-8D are orthographic and isometric views detailing yet another embodiment of the mechanisms for deployment of the anchoring elements;

FIGS. 9A-9C are orthographic views detailing mechanisms for deployment of the anchoring elements according to one embodiment of the invention; FIG. 10A-10B are orthographic and isometric views detailing an interconnected network of cavities comprising the anchoring elements according to one embodiment of the invention;

FIGS. 11A-11E are orthographic views detailing embodiments of the anchoring elements;

FIGS. 12A-12L are orthographic views detailing an exemplary method for implantation of the prosthesis according to one embodiment of the invention;

FIG. 13 details a delivery catheter comprising the delivery apparatus of FIG. 12 according to one embodiment of the invention;

FIGS. 14A-14C detail the distal member of the delivery apparatus of FIG. 13;

FIGS. 15A-15F are isometric views illustrating the sequence for deployment of the prosthesis of FIG. 5 according to one embodiment of the invention; and

FIGS. 16A-16C are orthographic views detailing the body and proximal member of the delivery apparatus of FIG. 13 according to one embodiment of the invention.

DETAILED DESCRIPTION OF PREFERRED EMB ODEVIENT S

The present invention relates to methods for transcatheter repair of a heart valve. The illustrative examples serve to describe preferred embodiments of the present invention without limitation of said invention. Although the description below focuses, for consistency and clarity, on the application of the invention to repair the mitral valve, the invention may be applied to other structures within the human body, in particular the tricuspid valve. In each case, benefits arise from the ability to deliver the prosthesis and determine its shape in vivo using a catheter - relative to prior art for surgical and transcatheter annuloplasty, respectively. Although the specifics of how such functionality might be exploited will differ by application, the underlying benefits provided by the invention are the same and are readily appreciated by those skilled in the art.

In general, the embodiments disclosed herein describe transcatheter methods for augmenting the annulus of a heart valve using a prosthesis that initially conforms to the native tissue and is thereafter remodelled and set in place. In this context, 'transcatheter' is intended to mean that the prosthesis (or the relevant parts of the prosthesis) may be delivered to a given site in the body using a catheter, preferably via endovascular access. Accordingly, said prosthesis exists in a first configuration to enable it to fit within a delivery catheter and a second configuration that permits apposition of the prosthesis to the native annulus. The delivery and deployed configurations are taken to be different with the prosthesis existing in either state as determined by the material properties of the prosthesis and mechanical manipulation by the delivery catheter. 'Conforms' is intended to mean that the prosthesis may take the form of an adjacent structure when in direct contact and pressed against said structure. The term 'remodel', used interchangeably with 'adjust', refers to a change in the dimensions of the prosthesis wherein the geometry of the prosthesis is altered. As detailed in subsequent sections, the ability to conform and remodel is in part a function of the material properties of at least one portion of the prosthesis wherein said portion may transition from a soft to a rigid state. By way of example, this may be achieved with a fast curing polymer or a eutectic alloy that undergoes phase transition using methods compatible with human tissue.

With reference to FIGS. 1A-1B, the mitral apparatus 100 (depicted in coronal and plan views) comprises the left atrial wall 110, annulus 112, leaflets 114a and 114b, chordae tendineae 116, 116a, 116b, papillary muscles 118 and left ventricular wall 120. Specifically, the anterior 114a and posterior 114b leaflets are separated by the anterolateral and posteromedial commissures 122a, 122b, respectively. The posterior leaflet is narrower and extends across two-thirds of the left atrioventricular junction within the left ventricular inlet. Anatomically, the posterior leaflet is divided into a lateral 124a, central 124b and medial 124c segment, clinically termed PI, P2 and P3, respectively. Similarly, the semicircular anterior leaflet is divided into three regions 126a, 126b, 126c corresponding to Al, A2, A3, respectively. The annulus 112 refers to the discontinuous fibrous junction separating the left atria 119 and left ventricle 121. The fibrous trigones of the left and non-coronary cusps of the aortic valve exist in continuity with the anterior leaflet forming a region of fibrous annulus. The remaining two-thirds of the annulus is muscular tissue. This distribution enables the annulus to function as a sphincter whereby contraction of adjacent myocardial fibers and expansion of the aortic root accentuates the saddle- shaped (hyperbolic paraboloid) geometry, increasing the available leaflet area for coaptation. Consequently, dilatation of the annulus, specifically the muscular region (as in the case of heart failure), reduces leaflet coaptation leading to mitral regurgitation. FIG. IB illustrates the mitral annulus as eight regions: 1 : Center of trigones (Saddle Horn) 130, 2: Right trigone 132, 3 : Posterior commissure 122b, 4: P3 scallop 124c, 5: Center of posterior annulus (P2 Scallop) 124b, 6: PI scallop 124a, 7: Anterior commissure 122a, 8: Left trigone

134. With reference to the anatomy of FIG. IB, FIG. 2 depicts the prosthesis 200 configured along the eight regions of the mitral annulus wherein the prosthesis 200 initially assumes the geometry of the dilated annulus 112 and is thereafter remodeled via catheter manipulation to reduce regurgitation as required. The prosthesis 200 may take a number of geometric forms to achieve a reduction in regurgitation, preferably the saddle-shape of the healthy mitral annulus.

Regardless of the geometric form, preferred embodiments of the prosthesis comprise a first material capable of transitioning from a soft to a rigid state. The first material may be encapsulated within a second material. The second material may be nonporous, particularly if the soft state of the first material is a liquid state.

By existing in a generally soft (or malleable) state on deployment, at least a portion of the prosthesis may conform to the dilated geometry of a diseased mitral valve and/or may be remodeled to a desired state in vivo. A transition, such as a phase shift (i.e. a change in state of matter, such as from liquid to solid), to a rigid (hard) state maintains the prosthesis in a permanent or semi-permanent geometry. In other words, the prosthesis can retain its shape or geometry as it transitions from the soft to rigid mode, so that the rigid prosthesis can have whatever shape has been created in the soft mode. This allows the prosthesis to be conformed to the desired geometry in situ.

Transition from a soft to a rigid state, or across a spectrum of malleable to nonmalleable, may be initiated by internal or external stimuli. In some embodiments, the method for initiating transition from a soft to a rigid state may be the removal of a continuous stimulus required to maintain the prosthesis in its soft state. In preferred embodiments, the application of a stimulus initiates the phase transition. In each case, 'internal stimuli' refers to any suitable stimulus acting within the prosthesis, for example chemical additives. 'External stimuli' refers to any suitable stimulus applied from outside the prosthesis, for example heat, an electric current or an electromagnetic field. In preferred embodiments, heat-induced phase transition (i.e. change in state of matter) should occur at temperatures compatible with human tissue, preferably within 35°C to 80°C, more preferably within 40°C to 70°C, more preferably within 45°C to 60°C.

The mechanism for initiating transition may be embedded within the delivery system for the prosthesis (e.g. a delivery catheter and associated instrumentation, discussed in more detail below). In some embodiments, conductive wires may be embedded in, or form one of the layers of the encapsulating coating wherein direct current results in heating of the encapsulated material. Said conductive wires may be insulated from the environment external to the device, including contact with the blood, to limit heat transfer to biological tissue. By way of example and not limitation, the conductive wires may comprise copper, stainless steel, nitinol or gold.

In yet further embodiments, a source of energy may be applied via non-contact methods from within the body, preferably within the delivery system. In yet further embodiments, a source of energy may be applied via non-contact methods from outside the body, such as by using a wire coil to produce an electromagnetic field. In both cases, an electromagnetic field may be generated with the net effect being induction of eddy currents within the prosthesis. In some embodiments, the encapsulated material may not be a conductor appropriate for direct inductive heating. Accordingly, one aspect of the prosthesis may include a conductive element in direct contact with the encapsulated material, wherein an electromagnetic field induces eddy currents and/or hysteresis in the conductive element adjacent to the target material. In that scenario, the target material is heated by the conductive element, giving rise to indirect inductive heating of the target material.

In preferred embodiments, all components of the encapsulated material, if comprised of more than one element, transition to a rigid state at one temperature. By way of example and not limitation, the encapsulated material may comprise a fast curing polymer such as hydrophilic siloxanes, a eutectic alloy with low melting temperature such as a quaternary bismuth alloy, or a polymer with a low melting temperature such as ethylene butyl acrylate copolymer, ethylene methyl acrylate copolymer, ethylene acrylic acid copolymer, ethylene methacrylic acid copolymer, polybutylene, poly epsilon caprolacton, thermoplastic polyolefin elastomer/plastomer, thermoplastic polyurethane elastomer, polyamide, polylactic acid, poly(n- isopropylacrylamide) and/or cellulose acetate butyrate. Combinations of the aforementioned components, or other materials may be used to achieve the desired thermal, mechanical and electrical properties. In preferred embodiments, the properties of the encapsulated material of the prosthesis, in its rigid state, may include an elastic modulus greater than zero and up to 200 GPa, preferably between 0.5 GPa and 150 GPa, more preferably between 5GPa and 100 GPa, Shore A hardness greater than 50, preferably greater than 75, more preferably greater than 100, and/or a tensile strength greater than 10 MPa, preferably greater than 20 MPa, more preferably greater than 30 MPa. In its soft state, the properties of the prosthesis may include a dynamic viscosity less than 10 Pa.s, preferably less than 0.1 Pa.s, more preferably less than 0.01 Pa.s. The ratio of elastic moduli in the rigid and flexible states (E_ng,d/Eflexibie) may be greater than 10, preferably greater than 100. The thickness of the encapsulated material may be between 7 to 1 mm, preferably 6 to 3 mm, more preferably 5 to 4 mm. With respect to positioning the prosthesis, it may be desirable to select a material that may be visualized under fluoroscopy, for example a bismuth-based alloy. Alternatively, visualization markers may be added on or within the encapsulating material or anchoring elements, preferably in line with the commissures as a prominent site for alignment during deployment. Additional markers positioned along the prosthesis may serve to guide prosthesis deployment or reshaping in the presence of disease recurrence. The markers may comprise precious metals, polymers, minerals or other appropriate materials.

In preferred embodiments, the dimensions of the remodeled prosthesis approximate those of the healthy mitral annulus as quantified by Dwivedi et al (Echo Research and Practice, December 2014, pp41-50, DOI: 10.1530/ERP-14-0050). and hereby incorporated by reference. Accordingly, the remodeled prosthesis may have an anteroposterior diameter of 20 to 40 mm and a commissural diameter of 30 to 50 mm. The saddle geometry may be defined by a height to commissural width ratio of 20-25%. The benefits of a saddle-shaped annuloplasty prosthesis arise from a uniform annular force distribution, compared to planar rings, leading to a relative reduction of forces in the commissural chords thus improving leaflet coaptation geometry and leaflet stress distribution.

FIG. 3A is an orthographic view of a prosthesis 200 according to one embodiment of the invention. The prosthesis 200 is an annuloplasty ring. As can be seen, the frame of the remodeled prosthesis is configured to form a complete D-shape (as such, it will be understood that an annuloplasty 'ring' is not required to be circular in shape and indeed, as further illustrated below, may not even be a complete loop). As a means of reducing the delivery profile, the prosthesis

200 may be contained within the delivery catheter in an incomplete linear geometry and assembled within the heart to form a complete D-shape geometry. Accordingly, FIGS. 3B-3C depict embodiments of the invention wherein the prosthesis 200 is configured to form a complete

D-shape by articulation of its proximal end 210b to a connecting element 212 on its distal end

210a, generally positioned along the anterior aspect of the annulus. In some embodiments, as in

FIG. 3B, the prosthesis frame may have ends 210a, 210b configured as an interlocking joint 216 within the connecting element 212. In further embodiments, as in FIG. 3C, the proximal free end 210b may comprise a magnetic plate 218 allowing for magnetic coupling with the connecting element 212 of the distal end 210a, having a strength that aligns and maintains an articulation throughout the cardiac cycle but may be detached when subjected to dilative forces, such as in the case of transcatheter mitral valve replacement. It may be desirable for the anterior aspect of the prosthesis to be shortened to allow for a change in the annular area index prior to rigid transition. Accordingly, in some embodiments, the connecting element 212 is configured to receive and hold the distal free end 210a, preferably without contact between proximal and distal free ends 210a, 210b. FIG. 3D depicts connecting element 212 of the distal end 210a wherein said connecting element 212 has a plurality of teeth 220 that resist retraction. In further embodiments, as in FIG. 3E, the proximal free end 210b is tethered to the connecting element 212 by a suture or wire 222 that may be tightened during deployment to draw said proximal free end 210b closer to the distal free end 210a. In yet further embodiments, as in FIG. 3F, the free ends 210a, 210b may overlap and interlock during remodeling wherein the configuration of the overlapping and interlocking aspects are maintained by transition to a rigid state. In yet further embodiments, as in FIG. 3G, the free ends of the prosthesis 210a, 210b may be connected by a compressive spring made of a coil or helical wire 224. Accordingly, in its soft state, the prosthesis 200 may be adapted such that the free ends are drawn towards each other. Transition to a rigid state prevents expansion in so far as the mechanical strength of the prosthesis 200 is greater than the restoring force of the spring 224.

FIGS. 4A-4B are orthographic views of the prosthesis 200 according to further embodiments of the invention wherein the remodeled prosthesis is configured to form an incomplete configuration. FIG. 4A depicts the prosthesis configured to form an incomplete D-shape having free ends 211a, 211b that do not connect. The distance between the free ends may be less than 50% of the commissural width, preferably less than 30%, more preferably less than 15%. In other embodiments, as in FIG. 4B, the incomplete structure takes the form of a C configuration. In each case, the circumference of the prosthesis relative to the circumference of the native annulus is 0.5 to 0.9, preferably 0.55 to 0.85, more preferably 0.6 to 0.8. FIGS. 5A-5C depict further embodiments of the invention wherein the prosthesis 200 is configured to form a saddle-shape consistent with a healthy mitral annulus. The height of the anterior horn ha of the prosthesis is expressed as the height-to-commissural width ratio. In some embodiments, the height of the anterior horn ha is 12-28%), preferably 15-25%), more preferably

18-22%). Similarly, the height of the posterior horn hp of the prosthesis may be expressed as the height-to-commissural width ratio. Accordingly, the posterior aspect has a height hp of 6-22%, preferably 9-19%, more preferably 12-16%. In preferred embodiments the anterior height ha is at least 10% greater than the posterior height hp. In some embodiments, in particular the prostheses of FIG. 5B-5C having an incomplete structure, the saddle shape may be formed using only the posterior horn.

In the context of disease recurrence, it may be advantageous to change the geometry of the prosthesis in a second procedure to further repair the valvular apparatus and/or accommodate a second device therein. Accordingly, in some embodiments the encapsulated material may be capable of transitioning from a rigid state to a soft state thereby reversing the initial transition used for implantation. Thereafter, the prosthesis may be adapted via catheter manipulation. In some embodiments, on reversal to its soft state, the prosthesis may be adapted by inflation of a balloon positioned within its lumen wherein the outer diameter of the balloon is larger than, and therefore applies a radial force to the inner surface of the prosthesis. By way of example and not limitation, FIGS. 6A-6C demonstrate remodeling of the prosthesis 200 to a circular geometry that would more appropriately conform to the outer frame of a transcatheter mitral valve deployed therein. FIG. 6A shows the prosthesis 200 being radially augmented, for example by balloon dilatation, to modify its configuration from a D-shape to a circular geometry 204. FIG. 6B shows the prosthesis 200 being radially expanded, for example by balloon dilatation, to modify its configuration from an incomplete D-shape to an incomplete circular geometry 206. FIG. 6C shows the prosthesis 200 being radially expanded, for example by balloon dilatation, to modify its configuration from an incomplete C-shape to an incomplete circular geometry 208. In each case, the principal of reversal allows for remodeling of the prosthesis via catheter manipulation.

In circumstances where a transcatheter mitral valve is implanted within the prosthesis, it may be desirable for the transcatheter valve to have an outer diameter at least equal to the internal diameter of the prosthesis 200. In so doing, the prosthesis 200 serves the function of a sealing cuff limiting paravalvular leak. By way of example and not limitation, the 35mm NeoVasc Inc. Tiara® valve has an anterior-posterior diameter of 30-34mm and a commissural width of 35- 40mm, corresponding to an orifice area of 750-1070 mm². Accordingly, the shape of the prosthesis may be adapted to assume a cross-sectional area at least 30x35mm (820 mm²) to accommodate the replacement valve.

Preferably, the prosthesis 200 is adjusted by the transcatheter valve during deployment resulting in a prosthesis 200 that conforms to the outer surface of the transcatheter valve frame. For incomplete configurations, as in FIG. 4, reversal to a soft state is sufficient to achieve expansion by deployment of the transcatheter valve therein. In contrast, complete configurations may (depending on their diameter) require a mechanism that allows the prosthesis 200 to separate at one or more points along its surface when subjected to a radial force. With reference to FIGS. 3B-3G, as detailed above having free ends 210a, 210b articulated to/within connecting element 212, the detachment force of the articulation preferably greater than the force applied by contraction of the native annulus during the cardiac cycle. By way of example and without limitation, a dovetail joint 216, a jigsaw configuration, magnet 218, suture 222 or other joint types may be employed wherein a radial force of at least 10N, preferably 15N, more preferably 20N is required to break the connection between the free ends. In yet a further embodiment, the restoring force of a compression spring may be used to expand the prosthesis, following reversal to its soft state.

In circumstances where further repair of the mitral annulus is required postoperatively, it may be desirable to reduce the dimensions of the prosthesis with respect to the anterior-posterior diameter, commissural width and/or orifice area. For incomplete configurations, as in FIG. 4, each of the aforementioned dimensions may be adapted following attachment of, and manipulation by the delivery catheter, and after the prosthesis has been re-set into the flexible state. Postoperatively, a delivery catheter may be re-engaged with the prosthesis at two or more points. The aforementioned points are preferably located at the ends of the prosthesis. Further engagements may be made between the ends of the prosthesis. Engagement between the catheter and prosthesis may be achieved mechanically or magnetically. The ends of the prosthesis may contain loops, hooks or magnets to facilitate engagement with the delivery catheter. In the same way, the anterior-posterior diameter and/or the commissural width may be adapted for a homogenous complete structure as depicted in FIG. 3A. In other embodiments having two free ends held together by a connecting element, as in FIG. 3B-3G, the aforementioned dimensions may be reduced by shortening or removal of said connecting element.

With reference to FIGS. 7A-7B, the frame of the prosthesis 200 comprises an inner core material 230 encapsulated by, as an example, an elastomer layer 232 as an encapsulating material to prevent exposure of the core material and a biocompatible exterior layer 234, preferably with properties that promote tissue growth onto the prosthesis to enhance anchorage, such as a polyethylene terephthalate exterior 234. By way of example and not limitation, the encapsulating material may comprise, fluoropoloymers, in particular poly(tetra-fluoroethylene) (PTFE), fluorinated ethylene propylene (FEP), ethylene-tetrafluoroethylene (ETFE), polysiloxanes, polyurethanes, polybutylenes, styrenic thermoplastic elastomers, in paticular poly(styrene-block- isobutylene-blockstyrene) (SIBS), liquid silicone rubbers, silicone rubbers with peroxide, acetoxy, oxime, amine or platinum cures, natural rubbers or synthetic isoprene type rubbers, or paralyene (such as paralyene C). The encapsulating layer may be formed in situ through dipping, over-moulding, condensation, or other deposition methods known to those skilled in the art. Alternatively, the encapsulated material may be injected into a pre-formed encapsulating layer, where the encapsulating layer is a tube fabricated by melt extrusion, solution extrusion, dipping, rolling or through other methods known to those skilled in the art. The biocompatible exterior layer may comprise expanded PTFE (ePTFE), polyester,poly ethylene terephthalate or SIBS, to be applied by way of suturing, melting bonding or other methods known to those skilled in the art. In each case, the encapsulating layer and the biocompatible exterior 234 take the shape of the prosthesis. .

With continued reference to FIGS. 7A-7B, the prosthesis comprises a plurality of anchoring elements 240 extending from the inferior aspect of the prosthesis 200. Said anchoring elements (in their deployed state) may extend beyond the plane of the inferior aspect of the prosthesis 200 by 0.5 to 5.0 mm, preferably 1.0 to 4.0 mm, more preferably 1.5 to 3.0 mm, with a radius of curvature between 0.3 and 3.0 mm, preferably between 0.6 and 2.7 mm, more preferably between 0.9 and 2.4 mm. The anchoring elements may be attached to the prosthesis by way of bonding, suturing or wrapping around the encapsulating material. Preferably, said attachment maintains a predetermined angle between the anchoring elements and the inferior aspect of the prosthesis frame wherein the anchoring elements do not rotate or bend relative to the prosthesis frame when anchoring to the annulus. In preferred embodiments, the anchoring elements 240 may be extensions of intermittent segments or ribs 242 positioned along the prosthesis 200. As shown in FIG. 7B, said ribs are contained within the encapsulating material 232 of the prosthesis 200 with the rib lumen in communication with the encapsulated material 230 such that said material fills the rib lumen.

With reference to FIGS. 8A-8B, part of the anchoring elements 240 may be partially contained within the prosthesis prior to deployment. FIG. 8A depicts an internal housing 310, which can be part of each rib 242, to isolate the anchoring element 240 from the encapsulated material 232. In preferred embodiments, said anchoring element 240 arises from the superior aspect of the rib, extending linearly through the rib housing 310. The remaining portion may be contained within a sheath 311 coaxial to the housing 310 wherein said sheath 311 may retract into said housing 310 (i.e. within the frame of the prosthesis) to expose the free end of the anchoring element 240. With reference to FIGS. 8A-8B, the sheath 311 may be retracted by pressing the prosthesis against the native annulus 112, thus allowing the free end of the anchoring elements 240 to penetrate into the native tissue. In some embodiments, the sheath has a lip at its proximal end such that it is constrained within the rib. The sheath 311 may have one or a plurality of lumens for each free end of the contained anchoring elements. To enhance tissue contact and stability, the sheath 311 may comprise a collar 313. In preferred embodiments, as shown in FIG. 8B, when the sheath is retracted (i.e. as the prosthesis is pressed against the native annulus 112) the anchoring element assumes the geometry of a hook as it enters the native tissue. In other embodiments, the anchoring element may remain in its linear configuration, having barbs to resist retraction.

FIGS. 8C and 8D show a complete rib 242, including the internal housing 310 and the surrounding rib structure. As can be seen the rib 242 acts as a support for the anchoring elements 240. The rib 242 may be broadly annular in shape, with a projecting portion (discussed further below). FIG 8C depicts the sheath 311 extended and anchoring elements 240 contained therein. FIG 8D depicts the sheath 311 retracted within the housing 310, and with the anchoring elements 240 in a deployed configuration.

In further embodiments of the invention, with reference to FIGS. 9A-9C, the anchoring elements 240 may be completely contained within the prosthesis prior to deployment. In other words, before deployment there is no sheath extending beyond the housing 310 (in other words, the housing 310 itself acts as a sheath for the anchoring elements). In some embodiments, the anchoring element 240 may be subjected to compressive forces to contain said anchoring element within the housing 310. Preferably, the method for applying the compressive force is reversible wherein removal of said force results in movement of the anchoring element 240 from the constrained configuration within the housing 310 to a deployed configuration extending from the inferior aspect of the encapsulating material 232. FIG. 9A depicts an anchoring element 240 having a helical spring 241 compressed within the modified anchoring channel 310 by an external sheath 330. In FIG. 9B, removal of said sheath 330 results in deployment of the anchoring element 240 according to the magnitude and direction of the restoring force of the spring 241. In a further embodiment, with reference to FIG. 9C, the compressive force is applied using a suture or wire 332 passing through an eyelet 334 in the free end 340 of the anchoring element 240, and the force can be released to deploy the anchor by removing or cutting the restraining suture or wire. In each case, the magnitude of the compressive force should be less than the yield point of the material used to form the anchoring element 240. Accordingly, the force generated by release of the constraint may be generally quantified by Hooke's law of elasticity. For anchoring elements formed of a pseudo- or super-elastic material, for example Nitinol, the linear relationship between force and displacement is only applicable within its low- strain region. The mechanism responsible for applying the compressive force may be attached to a wire or suture that traverses the length of the catheter to enable controlled release by the operator.

In preferred embodiments, the compressive force is released when the prosthesis is in contact with the annular tissue, wherein movement of the anchoring elements from the inferior aspect of the prosthesis will result in puncture of, and fixation to the underlying annulus. In other embodiments, the anchoring elements are released prior to prosthesis-annulus contact. In so doing, movement of the catheter facilitates puncture of, and fixation to the annulus. While the release/unsheathing of all the anchoring elements may be initiated by a single action, in preferred embodiments the anchoring elements within each sheath may be moved independently from those in other sheaths. As a result, the failure of one sheath to deploy its anchoring elements does not result in the failure of the all the anchoring elements to deploy.

In yet a further embodiment of the invention, with reference to FIGS. 10A-10B (it should be understood that FIGS. 10A-10B show internal structures otherwise not visible through the exterior surface), the anchoring elements may be deployed using hydraulic linear actuation. Accordingly, one aspect of the prosthesis comprises a channel 320 at least partially in communication with the rib housings 310. The channel 320 comprises at least one lumen with at least one port 324 wherein hydraulic fluid can be delivered to the channel 320 through said port 324, optionally via a dedicated delivery tube. In some embodiments, the channel 320 further contains a plurality of lumens each communicating with at least one rib 242 to enable independent or coupled deployment of the anchoring element(s). That is, hydraulic fluid delivered to the channel 320 can be distributed to the ribs, wherein the pressure of the hydraulic fluid can be utilized to hydraulically deploy the anchoring elements. In so far as the network of channels is filled with a liquid to facilitate hydraulic actuation of the anchoring elements, the network may be sealed by detachment of the delivery tube from the delivery port. Alternatively, detachment of the delivery tube may not seal the port 324, and thus will establish communication between the hydraulic fluid and the blood, in which case a biocompatible liquid must be used within the hydraulic network. In some embodiments, following deployment of the anchoring elements it may be desirable to replace the liquid with a hardening material to improve the mechanical properties of the prosthesis. FIGS. 11A-11E depict variations of the anchoring elements having a free end to initiate puncture of the annular tissue and at least one element to restrict retraction. By way of example and not limitation, the anchoring elements may be formed of nitinol, stainless steel, platinum, titanium, gold, polyether ether ketone or polyether block amide. The free end of the anchoring element 340 may be round, oval, triangular, tapered or curved. As shown in FIG. 11A-11E, the anchoring elements may extend perpendicular to the inferior surface of the prosthesis, the free end 340 having one or a plurality of barbs 342. The barbs may be aligned on one side of the free edge as in FIGS. 11C-11E, may be different lengths as in FIG. HE, or may be on opposing sides as in FIGS. 11A & 11B, may be evenly positioned along the anchoring element as in FIG. H ID or may be unevenly positioned along the anchoring element as in FIG. 11 A. With respect to deployment of the anchoring elements into the native tissue, either via removal of a restraint as in FIGS. 8 and 9, or linear actuation as in FIG. 10, it may be desirable for the anchoring elements to appropriate a curved (hook) configuration. In this context, the shape memory effect of nitinol may be preferred given the advantage that the anchoring element may be deformed when loaded within the housing 310, thereby reducing the profile of the anchoring channel. Irrespective of the mechanism used to deploy the anchoring elements, the force required to overcome the surface tension and compliance of the annular tissue should be greater than 0.01 N, preferably greater than 0.1 N, more preferably greater than 1 N.

The anchoring elements may be formed from a single piece of material by moulding, machining, laser cutting or other methods known to those skilled in the art. Attachment of said elements to the inferior aspect of the prosthesis, as in FIG. 7A, may be achieved through welding, gluing, sewing, weaving or melting. In the case of FIG. 7B, anchoring elements comprise ribs embedded in the encapsulating material. Accordingly, attachment may be achieved during coating of the encapsulated material (i.e. dip coating). In cases where the encapsulating material is first manufactured and subsequently filled with the encapsulated material, the ribs may be embedded via dip coating, solvent casting, injection moulding, compression moulding, sewing, or weaving. The number of anchoring elements required to fix the prosthesis to the native annulus is determined by the prosthesis diameter. In some embodiments, the number of ribs 242 containing anchoring elements 240 may be between 8 and 22, preferably 10 and 20, more preferably 12 and 18. With respect to the delivery profile, it may be desirable to position the anchoring elements equidistant along the prosthesis. Alternatively, the anchoring elements may be positioned to optimize stress distribution, which may result in distribution unevenly along the prosthesis. Thickness of the anchoring elements may also be varied to enhance delivery and/or fixation. In some embodiments, as in FIG. 8B, the anchoring elements may be contained within, or covered by a sheath. To puncture the annular tissue, the sheath may be removed. In other embodiments, the prosthesis may be moved relative to the sheath wherein the anchoring elements pierce said sheath.

In general, the prosthesis is configured for delivery to the mitral apparatus via arterial catheterisation, venous catheterisation or direct ventricular puncture. In preferred embodiments, the prosthesis is adapted from an elongated (sheathed) configuration to an expanded (partially- deployed) configuration by realignment of the prosthesis onto the delivery apparatus - the prosthesis being reversibly coupled to the delivery apparatus. The method of deployment further comprises radial expansion of the delivery apparatus, apposition of the prosthesis to the annulus and fixation of the anchoring elements to the annular tissue. Thereafter, the prosthesis and annulus are shaped by radial contraction of the delivery apparatus. To establish a saddle geometry, the anterior and/or posterior horn may be elevated if desired. The method of deployment further comprises transition to a rigid state and decoupling of the prosthesis from the delivery apparatus such that said delivery apparatus can be removed from the heart without disruption to the implant.

FIGS. 12A-12L show exemplary methods for implantation of the prosthesis according to one embodiment of the invention. This embodiment may use any one of the prostheses and delivery systems disclosed herein. For the purpose of illustration, coronal views of the interior aspect of the heart are used showing the right and left atrium 510, 512, right and left ventricle 514, 516, tricuspid and mitral valve 518, 520, right and left chordae-papillary apparatus 522, 524, aortic valve 530, superior vena cava 532, inferior vena cava 534 and the aorta 528.

FIGS. 12A-12D depict a retrograde approach with entry into the heart 500 via peripheral catheterisation, preferably femoral catheterisation, described in US patent no. 7381210 B2 to

Zarbatany et al. and incorporated herein by reference. Briefly, a guidewire 610 can be introduced into the aorta via the femoral artery using the Seldinger technique. Said guidewire 610 can be subsequently advanced through the left ventricle 516, across the mitral valve 520 and positioned in the left atrium 512. The delivery system comprising a delivery sheath 622 having a delivery apparatus 624 contained therein, can be advanced over the guidewire 610 to be positioned within the left ventricle 516. In preferred embodiments, the delivery sheath 622 and delivery apparatus 624 are operated independently. Specifically, the delivery sheath may be used to guide and align the delivery apparatus 624 to the mitral commissures 122a, 122b. Thereafter, the delivery apparatus 624 may be advanced across the mitral valve 520 into the left atrium 512 revealing the prosthesis 200. FIGS. 12C-12D illustrate expansion of the prosthesis from an elongated (sheathed) configuration 202 to an expanded (partially deployed) configuration 204 by contraction of the distal member of the delivery apparatus. Fixation of the prosthesis is achieved by deployment of the anchoring elements 240. Thereafter, catheter manipulation may be used to remodel the annulus as required.

In circumstances where it is undesirable to establish arterial access and/or direct access is preferred, a retrograde approach may be achieved via ventricular puncture. FIGS. 12E-12H depict the transapical approach, described in US patent no. 8579964 B2 to Lane et al. and incorporated herein by reference. Briefly, the delivery sheath 622 can be inserted through the cardiac apex 515 and advanced into the left ventricle 516. In some embodiments, a piercing member may be used to puncture the cardiac apex 515 creating a small opening for insertion of a guidewire 610. Catheters of increasing size can be advanced over said guidewire to dilate the access site in preparation for insertion of the delivery system. Thereafter, the delivery apparatus 624 follows the retrograde approach of FIGS. 12A-12D, advancing across the mitral valve 518 into the left atrium 512. When positioned, the prosthesis may be adapted from an elongated (sheathed) configuration 202 to an expanded (partially deployed) configuration 203 to a remodelled (deployed) configuration 204 (FIG 12H). Alternatively, FIGS. 12I-12L illustrate an antegrade transeptal approach performed via puncture of the interatrial septum, preferably at the site of the fossa ovalis 511.

FIG. 13 depicts the delivery apparatus of FIG. 12 according to one embodiment of the invention. The delivery apparatus includes a distal end 700, a body 800 and a proximal end 900. The distal end 700 can comprise struts 720, preferably metallic, adaptable in the radial direction. The body 800 can comprise a plurality of lumens (not shown) housing a plurality of wires. The proximal end 900 can comprise at least some of a stabilizer 910, a Luer port 912 (in some preferred embodiments a three-way Luer port) and an operator handle 920. In some embodiments, the distal end 700 and/or the body 800 include a radiodense marker 630 to aid guidance under fluoroscopic imaging.

FIGS. 14A-14B depict the distal end 700 of the delivery apparatus, the distal end comprising a distal member 710 having a plurality of struts 720. In preferred embodiments, the struts arise from an external tube (not shown) within the delivery sheath 622 and extend distally to attachment sites on an internal tube 732. Radial expansion of the distal member 710 may be achieved by retraction of the internal tube 732 relative to the external tube. In other embodiments, radial expansion of the distal member 710 may be achieved by advancing the external tube relative to the internal tube 732. In the expanded state, said struts 720 of the distal member 710 may have a radius of curvature, from the perspective of the strut origin, between 5 mm and 15 mm, more preferably between 7 mm and 12 mm. In so doing, the peak outer diameter of the expanded state may be between 15 mm and 50 mm, preferably between 20 mm and 45 mm, more preferably between 25 mm and 40 mm. Radial expansion is reversible in so far as expansion does not exceed the yield point of the struts. At least one modified eyelet 722, having a protruding edge 724, is located on each strut, acting as a portion for gripping the prosthesis. Said eyelet 722 is configured to engage with and constrain a projecting portion of the ribs 242 of a prosthesis, such as shown in FIG. 7B (in which the projecting portion can be seen on the right hand side), to facilitate prosthesis alignment prior to fixation. Alignment may be achieved using at least one realignment wire 726, as in FIG. 12 J, wherein tightening of said wire pulls each rib toward its corresponding eyelet such that it engages with, and is secured to the strut. In so doing, retraction of the realignment wire 726 adjusts the elongated (sheathed) prosthesis 202 to a partially deployed configuration 203.

With ongoing reference to FIG. 14A-14B, in some embodiments at least one strut of the distal member, preferably two struts, are configured to have a groove or channel 728 running from the distal attachment to the eyelet 722. A looped wire (not shown) may be provided therein, extending to the level of the eyelets 722 on the distal member 710. Preferably, the wire loop is positioned adjacent to and in between the rib 242 and the eyelet 722 wherein the realignment wire 726 passes through the looped wire. Accordingly, retraction of the looped wire results in elevation of one aspect of the prosthesis 200 to establish the saddle geometry of FIG. 5.

As previously noted it may be desirable to embed the mechanism for initiating phase transition within the delivery system. With reference to FIG. 14C, in some embodiments, conductive wires 740 may be embedded in, or form one of the layers of the inner tube 732 wherein an electromagnetic field may be generated with the net effect being induction of eddy currents within the prosthesis. In other embodiments, the struts 720 may be formed of conductive materials wherein when in contact with the prosthesis ribs 242, direct current results in heating of the encapsulated material. FIGS. 15A-15F detail a method for deployment of the prosthesis 200 of FIG. 5 according to one embodiment of the invention. With reference to FIGS. 15A-15B, the delivery apparatus exits the delivery sheath 622 with the prosthesis 200 in its elongated delivery configuration tethered to the delivery apparatus and positioned adjacent to the catheter struts 720. To reduce the delivery profile, it may be desirable for the prosthesis 200 to be positioned proximal to the distal member within the delivery sheath 622. Regardless of orientation, preferably at least one realignment wire 726 runs through, and therefore connects the ribs 242 of the prosthesis 200 to the eyelets 722 of the catheter struts 720. FIGS. 15B-15D illustrate the arrangement of the realignment wire 726 along the prosthesis 200 during the deployment procedure. When contained within the delivery sheath 622, the realignment wire 726a, 726b may be configured to be slack to enable the prosthesis to assume an elongated configuration. Having advanced out of the delivery sheath 622 and into the left atrium 512, the realignment wire 726a, 726b may be tightened to orient the prosthesis 200 horizontal to the distal member 710. Thereafter, said catheter struts 720 may be radially expanded and the realignment wire 726 a, 726b tightened such that the ribs 242 of the prosthesis 200 engage with the eyelets 722 of the catheter struts 720 to align and secure the prosthesis 200. In so doing, the proximal and distal ends of the prosthesis 210b, 210a are pulled toward each other forming an incomplete structure.

With reference to FIGS. 15E-15F (in which it should be understood that the surrounding tissue is not shown, but present), following deployment of the anchoring elements 240, the prosthesis 200 in its soft state may be remodeled by contraction of the distal member and tightening of the realignment wire 726a, 726b such that the dimensions of the prosthesis are changed. For example, the proximal and distal ends 210b, 210a are drawn closer together. In so doing, the degree of regurgitation may be reduced. The saddle geometry of FIG. 5 may be established during or after diameter reduction by retraction of the looped wire. Following confirmation of size and position, the delivery apparatus is locked and the encapsulated material transitioned to its rigid state. The prosthesis may then be released from the distal member by removal of the realignment wire. Subsequently, the delivery apparatus may be retracted from the vasculature leaving the prosthesis secured to the mitral annulus. With continued reference to FIGS. 15E-15F, together with FIGS. 8A-8B, deployment of the anchoring elements 240 requires a puncture force above the resistance threshold of the native tissue, preferably greater than 1.0 N, more preferably greater than 1.5 N, more preferably greater than 2.0 N. In the soft state, resistance applied by the native tissue may deform the prosthesis

200 at or adjacent to the ribs 242. Accordingly, the internal ribbing of the anchoring elements 240 may engage with the eyelets 722 on the struts 720 of the distal member such that said ribs 242 are secured within said eyelets 722. In so doing, translation of the delivery apparatus applies a force in the longitudinal plane (from the perspective of the anchoring element and in opposition to resistance of the native tissue). The realignment wire 726 may be used to ensure the ribs 242 remained tethered to the struts 720. Following deployment of the anchoring elements 242, but prior to release of the ribs 242 from the eyelets 722, manipulation of the distal member, by way of contraction or expansion, thus alters the geometry of the prosthesis. In preferred embodiments, each strut-rib connection may be independently adjusted.

FIGS. 16A-16B depict the proximal end 900 of the delivery apparatus comprising a handle 920 having at least three control elements: a rotating shaft 922 for translation of the internal tube 732 or central rod, paired rotary controllers 924, 926 for tightening and release of the realignment wire 726 and at least one sliding controller 928 for elevating the prosthesis 200 to establish a saddle geometry. In some embodiments, a fourth control element 932 comprising a rotary or sliding controller may be used to retract the sheath of FIG. 8B constraining the anchoring element 240. In other embodiments, a fourth control element comprising an inflation port may be used to deploy the anchoring elements of FIG. 10.

With continued reference to FIGS. 16A-16B (and FIG. 13 and FIGS. 14A-14C), the body 800, realignment wire 726, looped wires 734, 735 and internal tube 732 of FIG. 14 enter the proximal end 900 of the delivery apparatus through the stabilizer 910 having at least one luer taper therein. The rotating shaft 922 may be directly connected to the internal tube 732 wherein rotation results in linear translation of said tube. Similarly, the free ends of the realignment wire 726a, 726b may be secured to the paired rotary controllers 924, 926 wherein rotation results in tightening of said wire. Similarly, the looped wires 734, 735 may be secured to the paired sliding controllers 928, 930 wherein translation results in retraction of said wires. In other embodiments, the control elements may be connected via intermediate members having a compression spring biased toward the delivery condition. In so doing, operation of the control elements move the intermediate members toward the deployed position. Said position may be maintained by engaging the lock on each control element 923, 925a, 925b, 929a, 929b. Alternatives to compression springs include bands or differential pulleys. In preferred embodiments, the paired rotary controllers 924, 926 contain an additional friction plate torque limiter wherein the slipping torque is set to release the realignment wire 726 immediately prior to its yield point.

FIG. 16C shows the body 800 of the delivery apparatus comprising a plurality of elongated tubular structures 730, 732, 612 forming a plurality of lumens 820, 822, 824 housing a plurality of structures, for example the internal tube 732, the realignment wire 726a, 726b, the looped wire 734a, 734b and the guidewire 610. In preferred embodiments, the realignment wire 726a, 726b run within the body 800 external to the internal tube 732 with the looped wires 734a, 734b running within the internal tube 732. In preferred embodiments, the body is flexible and non- compressible along its length having an outer diameter no greater than 11 mm, preferably no greater than 9 mm, more preferably no greater than 7 mm, and less than the inner diameter of the delivery sheath. To improve delivery and steerability, the body may have a diameter less than the distal end 700 when in its contracted state. The wall may comprise multiple layers of polymer reinforced by braided metal wire. Accordingly, the delivery apparatus may have sufficient torsional stiffness to pivot in a circular motion on its longitudinal axis to align the prosthesis during deployment, if required. Examples of a catheter body consistent with the principals of the present invention are seen in US Patent No. 4,329,994 Ato Cooper and US Patent No. 7,130,700 B2 to Gardeski & Leners, the contents of which are hereby incorporated by reference.

Detachment of the prosthesis from the distal member, following transition to a rigid state, requires release of the realignment wire 726. Accordingly, some embodiments contain within the proximal body a cutting member 940 that may be engaged to break the realignment wire 726. In this context, it may be desirable for the realignment wire 726 to be made of a high tensile strength suture, for example nylon, polyester, polytetrafluoroethylene, polypropylene, polybutester, polyglactin, polydioxanone, polytrimethylene carbonate or poliglecaprone. In other embodiments, the realignment wire 726 may be released from one of the rotary controllers 924, 926 such that the second rotary controller 926 retracts the free end of the wire 726a into the body 800 of the delivery apparatus. In yet further embodiments, the realignment wire 726 may be released from both rotary controllers 924, 926 such that it may be pulled through one of the controllers.

As noted previously, in preferred embodiments the delivery sheath and the delivery apparatus are separate devices each having their own operating handle. The inner diameter of the delivery lumen should be greater than the maximum diameter of the delivery apparatus (in its delivery configuration) but no more than 11 mm, preferably 9 mm, more preferably 7 mm; the outer diameter of the delivery sheath being no greater than 12 mm, preferably 10 mm, more preferably

8 mm. With reference to FIGS. 12A-12D and 12I-12L, the body of the delivery sheath may comprise a plurality of regions with varying strength and flexibility along its length.

Accordingly, the delivery sheath may bend without kinking at predetermined sites when pulled unilaterally. The mechanism used to bend the sheath may be housed within the sheath wall and may include a method for mechanical retraction of a wire (or suture), release of a biased spring or other methods common to those skilled in the art. Examples of a steerable sheath consistent with the principals of the present invention are seen in US Patent No. 7,037,290 B2 to Gardeski et al., and US Patent No. 8,814,824 B2 to Kauphusman et al., the contents of which are hereby incorporated by reference. The distal aspect of said sheath may be rigid such that when the sheath is bent, said distal aspect extends linearly from the bent portion. In so doing, the delivery apparatus exits the sheath with its path constrained by the rigid distal aspect. In a further embodiment, a linear rack with teeth may be embedded on the inner wall of the delivery sheath with the delivery apparatus comprising a biased pawl that engages said teeth. Alternatively a toothless ratchet may be used. In each case, the delivery apparatus is coupled to the delivery sheath wherein movement of said sheath results in movement of the delivery apparatus. Movement of the delivery apparatus relative to the delivery sheath may be controlled by the independent handle following positioning of the sheath within the left ventricle. Thereafter, the delivery apparatus may be advanced unrestricted. Retraction will require a minimum force to overcome the pawl-tooth lock.

While the invention has been described with reference to exemplary embodiments, it is understood that a variety of modifications and additions may be made, or equivalents substituted for elements thereof, without departing from the scope of the invention. Those skilled in the art will appreciate that the invention is not limited to the embodiments disclosed herein and may be adapted for use in a variety of applications including embodiments falling within the scope of the appended claims.

Claims

1. An annuloplasty prosthesis comprising:

a frame; and

wherein at least a portion of the frame is capable of reversibly transitioning between a rigid mode and a flexible mode, thereby allowing the device to change its shape.

2. The prosthesis according to claim 1, wherein said prosthesis has a first, relatively compact, configuration to enable it to be delivered to a desired location and a second, less compact, configuration when deployed and in use, and wherein the prosthesis can transition between the two configurations when said portion is in the flexible mode.

3. The prosthesis according to claim 1 or claim 2, wherein the prosthesis is an annuloplasty ring, either a mitral valve annuloplasty ring or a tricuspid valve annuloplasty ring.

4. The prosthesis according to claim 3, wherein the annuloplasty ring has two ends that may be connected to form a continuous ring, or may remain unconnected so that the annuloplasty ring is an incomplete ring.

5. The prosthesis according to any one of the preceding claims, wherein the frame further comprises elements which are not capable of reversibly transitioning between a rigid and flexible mode.

6. The prosthesis according to any one of the preceding claims, wherein said portion of the frame comprises a core of the frame.

7. The prosthesis according to claim 6, wherein said core is surrounded by an encapsulating layer.

8. The prosthesis according to claim 6 or claim 7, wherein said portion is capable of reversibly transitioning between a rigid and flexible mode due to a change in the properties of the core.

9. The prosthesis according any one of the preceding claims, wherein said portion of the frame is configured to undergo the transition in mode under the influence of an external stimulus.

10. The prosthesis according to claim 6 or any claim dependent therefrom, wherein the material properties of the core are such that the core undergoes a solid to liquid phase transition, wherein said rigid mode corresponds to the core being solid and said flexible mode corresponds to said core being liquid.

11. The prosthesis according to claim 10, wherein the material properties of the core are such that the core undergoes the solid to liquid phase transition at a temperature of from 35°C to 80°C, more preferably from 40°C to 70°C, and even more preferably from 45°C to 60°C.

12. The prosthesis according to claim 7 or any claim dependent therefrom, where the

encapsulation layer comprises fluoropolymers, in particular polytetrafluoroethylene (PTFE) or expanded PTFE (ePTFE) or fluorinated ethylene propylene (FEP) or ethylene- tetrafluoroethylene (ETFE), polysiloxanes, polyurethanes, polybutylenes, and/or styrenic thermoplastic elastomers, in paticular poly(styrene-block- isobutylene-blockstyrene) (SIBS) liquid silicone rubbers, silicone rubbers with peroxide, acetoxy, oxime, amine or platinum cures, natural or synthetic isoprene type rubbers, or paralyene C.

13. The prosthesis according to any one of the preceding claims, wherein said portion comprises a eutectic alloy, in particular a quaternary bismuth alloy, ethylene butyl acrylate copolymer, ethylene methyl acrylate copolymer, ethylene acrylic acid copolymer, ethylene methacrylic acid copolymer, polybutylene, poly(epsilon-caprolactone), thermoplastic polyolefin elastomer/plastomer, thermoplastic polyurethane elastomer, polyamide, polylactic acid, poly(n-isopropylacrylamide) and/or cellulose acetate butyrate.

14. The prosthesis according to any one of the preceding claims, wherein said portion has a Young's modulus greater than zero and up to 200 GPa in the rigid mode, preferably between 0.5 GPa and 150 GPa, more preferably between 5GPa and 100 GPa.

15. The prosthesis according to any one of the preceding claims, wherein said portion has a Shore A hardness greater than 50, preferably greater than 75, more preferably greater than 100, or a tensile strength greater than 10 MPa, preferably greater than 20 MPa, more preferably greater than 30 MPa.

16. The prosthesis according to any one of the preceding claims, wherein said portion has a dynamic viscosity less than 10 Pa.s in the flexible mode, preferably less than 0.1 Pa.s, more preferably less than 0.01 Pa.s.

17. The prosthesis according to any one of the preceding claims, wherein a ratio of Young's moduli of said portion in the rigid and flexible modes (E_ng,d/Eflexibie) is greater than 10, preferably greater than 100.

18. The prosthesis according to any one of the preceding claims, wherein the prosthesis retains its shape when transitioning from the flexible mode to the rigid mode.

19. The prosthesis according to claim 18, wherein the prosthesis can be transitioned into the rigid mode from different shapes in the flexible mode.

20. The prosthesis according to any one of the preceding claims, further comprising anchoring elements for attaching the prosthesis to adjacent tissue.

21. The prosthesis according to claim 20, further comprising supports to which the anchoring elements are attached.

22. The prosthesis according to claim 21, when appendant to claim 7, wherein the supports extend through the encapsulating layer and into said core.

23. The prosthesis according to claim 21 or 22, wherein the supports each comprise a sheath for housing the anchoring elements until the prosthesis is deployed.

24. The prosthesis according to claim 23, wherein the sheath of each support can extend outside of the frame.

25. The prosthesis according to claim 24, wherein each sheath is configured to retract within the frame to expose the anchoring elements.

26. The prosthesis according to claim 23, wherein the sheath of each support is provided within the frame.

27. The prosthesis according to claim 26, further comprising a trigger for releasing the

anchoring elements from within the sheaths, such that the anchoring elements move out of said sheaths.

28. The prosthesis according to claim 27, wherein the anchoring element or anchoring elements within each sheath are moveable independently of anchoring elements in other sheaths.

29. A method of using the prosthesis of any of claims 1 to 28, the method comprising:

causing the prosthesis to undergo transition from one of the rigid or flexible modes to the other.

30. A method of inserting the prosthesis of any of claims 1 to 28 into a human or animal body, the method comprising:

causing the prosthesis to undergo transition from the rigid mode to the flexible mode; shaping the prosthesis into a deployed configuration; and causing the prosthesis to undergo transition from the flexible mode to the rigid mode.

31. The method according to claim 30, further comprising inserting the prosthesis into the

human or animal body either before or after the step of causing the prosthesis to undergo transition from the rigid mode to the flexible mode.

32. A method of adjusting, the prosthesis of any of claims 1 to 28 in a human or animal body, the method comprising:

causing the prosthesis to undergo transition from the rigid mode to the flexible mode; and adjusting the prosthesis, optionally including removing the prosthesis from the human or animal body.

33. A method according to any one of claims 29 to 32, wherein the step of causing the prosthesis to undergo transition from the rigid mode to the flexible mode comprises heating said portion of the prosthesis.

34. A method according to claim 33, wherein the source of heat is external to the body, internal to the body but separated from the frame, or in direct contact with the frame.

35. A device for delivering a prosthesis of any of claims 1 to 28 to a desired location within a human or animal body, the device comprising:

a transition inducer for inducing a transition in said portion of the prosthesis frame between the rigid mode and the flexible mode, or vice versa.

36. The device of claim 35, wherein said transition inducer is a heater.

37. The device of claim 36, wherein said heater is a direct heater.

38. The device of claim 36, wherein said heater is an electromagnetic field generator for

inducing eddy currents in said portion of the prosthesis frame, thereby heating said portion of the frame.

39. The device of any one of claims 35 to 38, wherein the device is or comprises a catheter.

40. The device according to any one of claims 35 to 39, wherein:

a distal end of the device comprises a plurality of struts configured to expand and retract in a radial direction, and

at least one of the struts is provided with a portion for gripping the prosthesis.

41. The device according to claim 40, wherein the portion for gripping is an eyelet with protruding edges configured to engage with a projecting portion of a support member of the prosthesis.

42. The device according to claim 40, further comprising a realignment wire arranged to guide the projecting portion of the supporting member to the eyelet by pulling the projecting portion to the eyelet when the wire is tightened and the struts are radially expanded.

43. A method of using the delivery device of any of claims 41 to 43, the method comprising: configuring the delivery device and prosthesis so that the prosthesis is held in the at least one strut portion for gripping the prosthesis;

using the delivery device to position the prosthesis in the desired location;

activating anchoring elements of the prosthesis to hold the prosthesis in the desired location;

removing the delivery device so as to leave the prosthesis in the desired location..