WO2009140268A1

WO2009140268A1 - Medical device for constricting tissue or a bodily orifice, for example a mitral valve

Info

Publication number: WO2009140268A1
Application number: PCT/US2009/043612
Authority: WO
Inventors: Jon Dahlgren; Doug Goertzen; Daniel Gelbart
Original assignee: Kardium Inc.
Priority date: 2008-05-13
Filing date: 2009-05-12
Publication date: 2009-11-19
Also published as: US20090287304A1; US20110022166A1; US9744038B2

Abstract

A medical device system may include an implantable device and a tool operable to implant the device. The implantable device (115) is positionable in a cavity of a bodily organ (e.g., a heart) and operable to constrict a bodily orifice (e.g., mitral valve). The device may include tissue anchors (107) that are implanted in the annulus of the orifice. The tissue anchors may be guided into position by an intravascularly or percutaneous Iy deployed anchor guide frame of the tool. Constriction of the orifice may be accomplished via a variety of structures, for example by cinching a flexible cable (111) attached to implanted tissue anchors. The device may be used to approximate the septal and lateral (clinically referred to as anterior and posterior) annulus of the mitral valve in order to move the posterior leaflet anteriorly and the anterior leaflet posteriorly and thereby improve leaflet coaptation and eliminate mitral regurgitation.

Description

MEDICAL DEVICE FOR CONSTRICTING TISSUE OR A BODILY ORIFICE,

FOR EXAMPLE A MITRAL VALVE

BACKGROUND

Field This disclosure is generally related to percutaneous or minimally invasive surgery, and more particularly to percutaneously deployed medical devices suitable for constricting tissue or a bodily orifice such as a mitral valve

Description of the Related Art

Cardiac surgery was initially undertaken only by performing a sternotomy, a type of incision in the center of the chest, which separates the sternum (chest bone) to allow access to the heart. In the previous several decades, more and more cardiac operations are performed using a percutaneous technique, which is a medical procedure where access to inner organs or other tissue is gained via a catheter. Percutaneous surgeries benefit patients by reducing surgery risk, complications, and recovery time. However, the use of percutaneous technologies also raises some particular challenges. Medical devices used in percutaneous surgery need to be deployed via narrow tubes called catheter sheaths, which significantly increase the complexity of the device structure. As well, doctors do not have direct visual contact with the medical tools used once they are placed within the body, and positioning the tools correctly and operating the tools successfully can often be very challenging.

One example of where percutaneous medical techniques are starting to be used is in the treatment of a heart disorder called mitral regurgitation. Mitral regurgitation is a condition in which blood flows backward from the left ventricle into the left atrium. The mitral apparatus is made up of four major structural components and includes the annulus, the two leaflets, the chordae and the papillary muscles. Improper function of any one of these structures or in combination can lead to mitral regurgitation. Annular dilation is a major component in the pathology of mitral regurgitation regardless of causes and is manifested in mitral regurgitation related to dilated cardiomyopathy and chronic mitral regurgitation due to ischemia. The mitral valve is intended to prevent the undesired flow of blood from the left ventricle into the left atrium when the left ventricle contracts. In a normal mitral valve, the geometry of the mitral valve ensures the cusps overlay each other to preclude the regurgitation of blood during left ventricular contraction and thereby prevent elevation of pulmonary vascular pressures and resultant symptoms of shortness of breath. Studies of the natural history of mitral regurgitation have found that totally asymptomatic patients with severe mitral insufficiency usually progress to severe disability within 5 years.

At present treatment consists of either mitral valve replacement or repair. Both methods require open heart surgery. Replacement can be performed with either mechanical or biological valves and is particularly suitable when one of the mitral cusps has been severely damaged or deformed. The mechanical valve carries the risk of thromboembolism and requires anticoagulation with all of its potential hazards, whereas the biological prosthesis suffers from limited durability. Another hazard with replacement is the risk of endocarditis. These risks and other valve related complications are greatly diminished with valve repair. Mitral valve repair is theoretically possible if the mitral valve leaflets are structurally normal but fail to appropriately coapt because of annular dilatation and/or papillary muscle dysfunction. Various surgical procedures have been developed to improve coaptation of the leaflet and to correct the deformation of the mitral valve annulus and retain the intact natural heart valve function. These procedures generally involve reducing the circumference of the posterior mitral leaflet annulus (lateral annulus) where most of the dilatation occurs. The annulus of the anterior leaflet (septal annulus) does not generally dilate because it is anchored to the fibrous skeleton at the base of the heart. Such techniques, known as mitral annuloplasty, typically suture a prosthesis around the base of the valve leaflets shortening the lateral annulus to reshape the mitral valve annulus and minimize further dilation. Different types of mitral annuloplasty prostheses have been developed for use in such surgery. In general, such prostheses are annular or partially annular shaped and may be formed from rigid or flexible material. Mitral valve surgery requires an extremely invasive approach that includes a chest wall incision, cardiopulmonary bypass, cardiac and pulmonary arrest, and an incision on the heart itself to gain access to the mitral valve. Such a procedure is expensive, requires considerable time, and is associated with high morbidity and mortality. Due to the risks associated with this procedure, many of the sickest patients are denied the potential benefits of surgical correction of mitral regurgitation. In addition, patients with moderate, symptomatic mitral regurgitation are denied early intervention and undergo surgical correction only after the development of cardiac dysfunction. Furthermore, the effectiveness of such procedures is difficult to assess during the procedure and may not be known until a much later time. Hence, the ability to make adjustments to or changes in the prosthesis function to obtain optimum effectiveness is extremely limited. Correction at a later date would require another open heart procedure.

In an attempt to treat mitral regurgitation without the need for cardiopulmonary bypass and without opening the chest, percutaneous approaches have been devised to repair the valve or place a correcting apparatus for correcting the annulus relaxation. Such approaches make use of devices which can be generally grouped into two types:

-devices deforming (mainly shortening) the coronary sinus -devices pulling together two anchor points in order to affect the mitral valve, one of the anchor points can be the coronary sinus (typically using a wire that is pulled and secured).

Neither approach emulates the current "gold standard" in mitral valve repair - annuloplasty using a ring the completely encircles the mitral valve. Both approaches suffer from several problems as a result of attempting to reshape the mitral annulus using an alternative method. Devices that deform the coronary sinus, while suitable for percutaneous procedures, are not effective in controlling the leakage of the mitral valve as the forces are not applied from the correct opposite sides of the valve, which are the lateral annulus and the septal annulus. The devices of the second type are not easily adapted to a percutaneous procedure. In order to achieve shortening in the direction connecting the lateral annulus to the septal annulus the anchor points have to be located along this line, so pulling them together will affect the desired direction of shortening. Pulling applied along a different direction will distort the mitral valve but will not achieve the optimal approximation of the two leaflets.

Thus, there is a need for methods and apparatus that enable the ability to create a full ring mitral annuloplasty via a percutaneous or intravascular procedure.

BRIEF SUMMARY The subject of the present application is a medical device with enhanced capabilities for percutaneous deployment and annulus cinching and a superior method for constricting tissue or a bodily orifice, such as the mitral valve, tricuspid valve, or aortic valve via such device. The device may enable methods that enable a complete ring to be anchored to tissue and may enable reduction of the circumference of said ring during installation or at a later time. Reference throughout this specification is made to cardiac surgery, but the methods and apparatus described herein may also be used in gastric surgery, bowel surgery, or other surgeries in which tissue may be drawn together. The methods and apparatus described herein may also be used to draw or hold tissue not part of an orifice or annulus together. The methods and apparatus described herein may be used in minimally invasive surgery as well as intravascular or percutaneous surgery. Other advantages will become apparent from the teaching herein to those of skill in the art.

A medical device system operable to constrict an orifice in tissue may be summarized as including an implant including a plurality of tissue anchors, each of the tissue anchors physically configured to be physically releasably guided along respective guide members of a guide frame to respective locations about a periphery of an orifice in a tissue and implanted in the tissue at least proximate the respective locations, the tissue anchors when implanted moveable with respect to one another between an unretracted configuration in which the tissue anchors are radially spaced relatively apart from one another and a retracted configuration in which the tissue anchors are radially spaced relatively toward one another with respect to the unretracted configuration; and a number of connectors that physically couple at least some of the tissue anchors to one another such that a distance between at least some pairs of the tissue anchors is selectively adjustable to radially contract the tissues anchors inwardly from the unretracted configuration toward the retracted configuration to constrict the orifice in the tissue.

At least one of the tissue anchors of the implant may include a plurality of resilient barbs and may further include a tool that comprises the guide frame and a constriction tube that protectively retains the barbs of the tissue anchor in a compressed configuration until released from the constriction tube. At least one of the tissue anchors may be a helical tissue anchor. The number of connectors of the implant may include a flexible cable that couples each of the tissue anchors to one another. The implant may further include a fastener that receives a portion of the flexible cable and is selectively operable to secure the flexible cable in a tensioned state. The implant may further include a spreader structure that fixes a distance between a pair of the tissue anchors such that the distance between the pair of the tissue anchors does not change between an untensioned state and the tensioned state of the flexible cable. The number of connectors of the implant may include at least one shape memory material connectors, the at least one shape memory material connector responsive to a stimulus to change a distance between at least one pair of the tissue anchors. The number of connectors of the implant may include at least one spring coupled across at least one pair of the tissue anchors and a retainer that changes a physical state in response to a stimulus, wherein the retainer retains the spring in an extended configuration until the retainer changes state responsive to the stimulus wherein the spring returns to an unextended configuration to change a distance between the pair of the tissue anchors. At least one of the number of connectors may be responsive to a magnetic field externally applied with respect to a body.

The medical device system may further include a tool comprising the guide frame, wherein the guide members include a plurality of guide rails along which respective ones of the tissue anchors traverse. The guide rails may be physically configured to retain the respective tissue anchors at least until the tissues anchors are implanted in the tissue. The guide rails may each include a change in curvature at which point the respective tissue anchor is releasable from the guide rail. The tool may further include a cap that removably retains at least a tip of the tissue anchors before the tissue anchors are implanted in the tissue. The implant and the guide frame may be compressible between a compressed configuration and an uncompressed configuration, the implant and guide frame sized and dimensioned when in the compressed configuration to be deliverable by a catheter and sized and dimensioned when in the uncompressed configuration to contact various portions of the tissue. The tissue anchor guide frame may include at least one anatomical structure engagement structure that adjusts at least one of an orientation or a position of the implant on physical engagement with an anatomical structure. The tool may further include a plurality of push tubes, each of the push tubes having at least one lumen, and a plurality of release members movable received by the at least one lumen of respective ones of the push tubes, wherein each of the release members releasably engages a respective one of the tissue anchors before the tissue anchor is implanted in the tissue. The tool may further include a plurality of guide wires, each of the guide wires movable received by the at least one lumen of a respective one of the push tubes, wherein each of the guide wires provides a releasable physically path for a respective one of the tissue anchors to the respective location on the tissue for implantation. Each of the guide wires may include a change in a radius of curvature proximate at which point the guide wire releases the respective one of the tissue anchors.

A method of operating a medical device system to constrict an orifice in tissue may be summarized as including positioning a tool having a guide frame with a plurality of guide members such that distal ends of the guide members are at least proximate respective locations about a periphery of an orifice in a tissue internally within a body; advancing a plurality of tissue anchors of an implant along respective ones of the guide members to be at least proximate respective ones of the respective locations about the periphery of the orifice in the tissue; implanting the tissue anchors in the tissue at least proximate the respective locations; and reducing a distance between at one pair of the tissue anchors to constrict the orifice in the tissue.

The method may further include advancing the tissue anchors with respect to a constriction tube to expose a plurality of barbs on each of the tissue anchors, and wherein implanting the tissue anchors in the tissue at least proximate the respective locations comprises implanting the tissue anchors in the tissue to a depth sufficient to locate the barbs in the tissue. The tissue anchors may be helical tissue anchors and implanting the tissue anchors in the tissue at least proximate the respective locations may include rotating the helical tissue anchor with respect to the tissue. Reducing a distance between at one pair of the tissue anchors to constrict the orifice in the tissue may include tensioning a flexible member that physically couples at least two of the tissue anchors together. Reducing a distance between at one pair of the tissue anchors to constrict the orifice in the tissue may further include fixing the distance between the at least one pair of the tissue anchors after tensioning the flexible member. Reducing a distance between at one pair of the tissue anchors to constrict the orifice in the tissue may include applying an external stimulus to a connection member that couples at least one pair of the tissue anchors together, where the external stimulus reduces a length of the connection member. The method may further include selectively releasing the tissue anchors from respective ones of the guide members. Selectively releasing the tissue anchors from respective ones of the guide members may include retracting a release member of the tool while maintaining in a fixed position a push tube of the tool which movably receives the release member to physically uncouple at least one of the tissue anchors from the tool.

The method may further include selectively releasing the tissue anchors from respective ones of the guide members at or after the tissue anchors have passed a bend in the guide members. The method may further include percutaneously delivering the guide frame and the implant into the body in a compressed configuration.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, identical reference numbers identify similar elements or acts. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes of various elements and angles are not drawn to scale, and some of these elements are arbitrarily enlarged and positioned to improve drawing legibility. Further, the particular shapes of the elements as drawn, are not intended to convey any information regarding the actual shape of the particular elements, and have been solely selected for ease of recognition in the drawings.

Figure 1 is a schematic diagram of a medical device system according to one illustrated embodiment, including an implantable device and a tool with a control handle, tissue anchors, and anchor guide mechanism that is operable to implant the implantable device. Figure 2 is a cutaway diagram of a heart showing an implantable medical device implanted in tissue therein according to one illustrated embodiment, the implantable device percutaneously placed in a left atrium of the heart.

Figure 3 is a diagram showing an example of a helical tissue anchor. Figure 4A is an isometric partial view showing an example of a multi-barbed tissue anchor with resilient barbs retained by constriction tube.

Figure 4B is an isometric partial view showing an example of a multi-barbed anchor with the resilient barbs free of the constriction tube and exposed.

Figure 5A is front elevational view showing a tissue helical anchor embedded in tissue according to one illustrated embodiment.

Figure 5B is front elevational view showing a barbed tissue anchor embedded in tissue according to one illustrated embodiment. Figure 6A is an elevational view showing a tissue anchor movably received on a guided member according to one illustrated embodiment.

Figure 6B is an elevational view showing a tissue anchor movable received on a guided rail according to another illustrated embodiment.

Figures 7A-7C are sequential elevational views showing a helical tissue anchor movably received on a guided member penetrating tissue at three successive intervals of time according to one illustrated embodiment.

Figures 8A and 8B are sequential elevational views showing a multi-barbed tissue anchor movably received on a guided member penetrating tissue at two successive intervals of time according to one illustrated embodiment.

Figure 9 is an isometric view of an anchor guide frame according to one illustrated embodiment.

Figure 10 is a side elevational view of an anchor guide frame compressed into a sheath according to one illustrated embodiment. Figure 11 is an isometric view of an expanded anchor guide frame according to one illustrated embodiment.

Figure 12 is an isometric view showing a distal end of the medical device system according to one illustrated embodiment

Figure 13 is a cutaway diagram of a heart showing an example of tissue anchors secured in a mitral valve annulus. Figure 14 is a cutaway diagram of a heart showing an example of tissue anchors and a cable used to constrict a mitral valve annulus.

Figures 15A and 15B are cross-sectional views of a tool to secure a cable of an implantable device that constricts a bodily orifice at two successive intervals of time illustrating a time prior to cutting the cable and a time when the cable is being cut according to one illustrated embodiment.

Figures 16A and 16B are sequential isometric views showing a portion of a catheter with side slots according to one illustrated embodiment

Figure 17 is a cross-sectional partial view of a mechanism according to one illustrated embodiment for holding a tissue anchor captive

Figures 18A and 18B are successive side elevational views of a mechanism according to one illustrated embodiment for restricting a tissue anchor from release until the tissue anchor is fully embedded in tissue

DETAILED DESCRIPTION In the following description, certain specific details are set forth in order to provide a thorough understanding of various embodiments of the invention. However, one skilled in the art will understand that the invention may be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments of the invention.

Unless the context requires otherwise, throughout the specification and claims which follow, the word "comprise" and variations thereof, such as, "comprises" and "comprising" are to be construed in an open, inclusive sense, that is as "including, but not limited to." Reference throughout this specification to "one embodiment" or

"an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. It should also be noted that the term "or" is generally employed in its sense including "and/or" unless the content clearly dictates otherwise.

The headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed invention.

Overview of Device and Orifice Constriction Methods

Various embodiments of medical apparatus which are percutaneously or intravascularly deployed and may be used for constricting a bodily orifice are described herein.

Figure 1 shows a medical device system 100 including an implantable device 115 and tool 116 to implant the implantable device 115, according to one illustrated embodiment.

The tool 115 of the medical device system 100 may be used to deploy the implantable device 115 having tissue anchors 107 and a flexible cable 111. The tissue anchors 107 may be secured to the annulus of an orifice and the flexible cable 111 may be used to constrict the orifice by pulling the anchors 107 inward. The tool 116 of the medical device system 100 comprises a flexible anchor guide frame 108 that may be used to guide tissue anchors 107 of the implantable device to target positions on the orifice annulus. The anchor guide frame 108 may be made of a material such as Nitinol. The anchor guide frame 108 shown in Figure 1 is comprised of three guide members, for instance guide wires 112, - one guide member for each of the tissue anchors 107 shown. The guide frame 108 may include a different number of guide members (e.g., guide wires or guide rails) if more tissue anchors are desired. The guide members 112 shown preferably have hinges 113 and may be connected with small loops 109. The hinges 113 and loops 109 enable the guide frame 108 to fold up to fit inside a catheter and to expand to extend across an orifice. Both the hinges 113 and loops 109 may be replaced by other mechanisms or structures that enable bending or compression. The tool 116 of the medical device system 100 typically has an articulation mechanism 106 (e.g., a plurality of articulation joints) that enables correctly orienting the anchor guide frame 108 during deployment of tissue anchors 107. The articulation mechanism 106 is preferably able to bend in any direction. The tool 116 of the medical device system 100 may include control knobs 103 and 104 which may be used to control the bending of the articulation mechanism 106 via cables that are carried in the long flexible tube 105.

The tool 116 of the medical device system 100 may include a long flexible tube 105 which extends from the articulation mechanism 106 to a medical device control mechanism 114 located at a proximal end of the catheter. Control mechanism 114 may include control knobs 103 and 104, elongated release members (e.g., rods or wires) 101 , push tubes 102, and guide wires 112. Additional controls may be included in other embodiments. The flexible tube 105 may have multiple lumens. Multi-lumen push tubes 102, guide members (e.g. , guide wires) 112, release members 101 , cable 111 , and other mechanisms may be carried in flexible tube 105. In the illustrated embodiment, each push tube 102 has two lumens. A guide wire 112 is carried in a first lumen and a release member 101 is carried in a second lumen. Anchors 107 are attached at distal tips of release members 101. The tissue anchor 107 may be inserted into the annulus of an orifice by advancing the push tube 102 along the guide member 112 and advancing or rotating the release member 101 carried in the push tube 102 at the same rate. The tissue anchor 107 may advance past the hinge 113 and embed into the annulus of the orifice to be constricted while in an unretracted configuration. Once the tissue anchor 107 is embedded, the release member 101 attached to the anchor may be retracted while the push tube 102 is held in place in a retracted configuration. Retraction of the release member 101 causes the tissue anchor 107 to detach from the distal tip of the release member 101 and remain embedded in the tissue at least proximate a desired location. Other embodiments may use different methods and/or structures to release the tissue anchors 107.

Figure 2 shows an implantable device implanted in a portion of a heart to constrict a bodily orifice, for example a mitral valve of the heart, according to one illustrated embodiment.

A portion of the medical device system 100 may be percutaneously and/or intravascular^ inserted into a portion of a heart 212, for example in a left atrium 206 of the heart 212. In this example, a flexible anchor guide frame 214 and implantable device of the medical device system 100 are delivered via a catheter 202 inserted via the inferior vena cava 204 and penetrating the transatrial septum 213 from a right atrium 203. The catheter 202 is preferably under 8 mm in diameter.

The flexible anchor guide frame 214 expands after being delivered via the catheter 202 into a shape that preferably enables the tissue anchors 207 of the implantable device to be delivered to the desired respective positions on the mitral annulus 209. The flexible anchor guide frame 214 may be moved into the correct orientation by adjusting a shape of an articulation mechanism 205, advancing or retracting flexible tube 201 , or rotating flexible tube 201. The flexible anchor guide frame 214 preferably has an overall shape that enables the frame to take on a desired orientation within a cavity by conforming to the shape or being affected by the movement of anatomical features. Such a property is known as "self-locating". Minimal insertion force and operator guidance is typically needed to properly position the anchor guide mechanism. The flexible anchor guide frame 214 may also have specific features which cause the flexible anchor guide frame 214 to orient correctly based on the position of an anatomical feature, such as the mitral valve leaflets 211. An example of such a feature is alignment fin 215. Alignment fin 215 is attached rigidly to flexible anchor guide frame 214 and shaped so that it may be deflected to a particular orientation by an anatomical feature, such as mitral valve leaflets 211. As the flexible anchor guide frame 214 is advanced toward an anatomical feature, such as the mitral valve annulus 209, the shape or motion of an anatomical feature, such as the mitral valve leaflets 211 , may cause alignment fin 215, and thus attached flexible anchor guide frame 214, to rotate or translate to a desired orientation or location. The tissue anchors 207 may be inserted into the annulus 209 by advancing the push tubes 216 along the guide members (e.g., guide wires or rails) 112. The tissue anchors 207 may advance past the bend 208 and embed into the annulus 209. The embedded tissue anchors 207 may then be released from the push tubes 216. The flexible cable 210 connecting the tissue anchors 207 may then be tightened and secured to constrict the mitral annulus 209.

Figure 3 shows an example of a tissue anchor according to one illustrated embodiment.

The tissue anchor 301 has a helical structure with sharp tip 303, and hence is denominated as a helical tissue anchor 301. Loop 302 may be used to connect to a structure to hold the tissue anchor 301 to a release rod. Loop 302 may also be used to attach tissue anchor 301 to a cable used for cinching the annulus of a bodily orifice.

Figures 4A and 4B show an example of a tissue anchor according to one illustrated embodiment. In particular, Figure 4A shows the tissue anchor 403 in a compressed configuration, while Figure 4B shows the tissue anchor 406 in an expanded configuration. The tissue anchors 403, 406 comprise multiple barbs 408, which may be resilient. The multiple barbs 408 may be compressed into constriction tube 404 as shown for tissue anchor 403. Compression of barbs 408 into constriction tube 404 enables the anchor to move more readily through a catheter and also to be inserted more readily into tissue without causing damage to the tissue.

Tissue anchor 403 may include a hole 409 that may be used to attach the anchor to a cable 401 used for cinching the annulus of a bodily orifice. Constriction tube 404 may include a slot 402 to allow anchor 403 to be ejected from constriction tube 404 in the case where hole 409 is mounted on a protruding flange.

Tissue anchor 406 may include a hole 407 that may be used to connect said anchor to release rod 405. Release rod 405 may be carried in a lumen of push tube 410. If constriction tube 404 is extended over hole 407 as shown for anchor 403, release rod 405 is held captive in hole 407 by the wall of tube 404. If constriction tube 404 is retracted so as to not cover hole 407, as shown for tissue anchor 406, release rod 405 is not held captive in hole 407 and said tissue anchor may become disconnected from constriction tube 404 and release rod 405.

Tissue anchor 406 may be disconnected from release rod 405 and barbs 408 may be uncompressed by retracting constriction tube 404 relative to the release rod 405 and tissue anchor 406. Retracting constriction tube 404 past the tips of barbs 408 causes said barbs to be released and resiliently expand. Retracting constriction tube 404 past hole 407 may release tissue anchor 406.

Figures 5A and 5B show examples of two types of tissue anchors embedded in tissue.

In particular, Figure 5A shows a helical anchor 501 embedded in tissue 502. The helical tissue anchor 501 is embedded in tissue 502 by rotating the helical tissue anchor 501 about is longitudinal axis. Figure 5B shows a multi-barbed anchor 505 embedded in tissue 502. The multi-barbed tissue anchor 505 is embedded in tissue 502 by pushing the anchor into the tissue. Barbs 504 provide resistance to restrict the tissue anchor 505 from being extracted.

Figures 6A and 6B show examples of tissue anchors guided by a guide member in the form of a guide rail.

In particular, Figure 6A shows a multi-lumen push tube 600 that may slide over a guide rail 601. Tissue anchor 602 may be temporarily attached to multi-lumen push tube 600 by constriction tube 606 and a release rod (not shown). Sliding push tube 600 along guide rail 601 enables tissue anchor 602 to be controllably delivered to a location proximate to guide rail 601. Tissue anchor 602 may be constructed or oriented in such a way that tissue anchor tip 607 slides along or very near to guide rail 601. Such orientation or construction enables the tip to be protected from obstructions in the catheter or body that may dull the tip. Also, such orientation or construction protects areas of tissue proximate the guide rail from inadvertent, damaging contact with the sharp tip 607 of tissue anchor 602.

Figure 6B shows a single-lumen push tube 603 that may slide over guide rail 601. Helical tissue anchor 604 also may slide over guide rail 601 and may be temporarily attached to single-lumen push tube 603 by latch mechanism 609. Latch mechanism 609 may be fastened to tissue anchor 604 by a friction fitting that is released under sufficient axial force. This assembly enables tissue anchor 604 to be controllably delivered to a location proximate to guide rail 601. Tissue anchor 604 may be constructed or oriented in such a way that tissue anchor tip 608 slides along or very near to guide rail 601. Such orientation or construction enables the tip of the tissue anchor 604 to be protected from obstructions in the catheter or body that may dull the tip. Also, such orientation or construction protects areas of tissue proximate the guide rail 601 from inadvertent, damaging contact with the sharp tip of tissue anchor 608. While Figures 6A and 6B show examples of two particular types of tissue anchors being guided by a rail, it will be apparent to those skilled in the art that many other types of tissue anchors could also be deployed with the aid of a guide rail as well.

Figures 7A-7C sequentially illustrates deployment of a helical tissue anchor implanted or embedded in tissue according to one illustrated embodiment.

In particular, Figure 7A shows a helical tissue anchor 702 partially deployed into tissue 708. The location that tissue anchor 702 enters the tissue may be determined by the position of a guide member, for instance guide rail 704. Bend 707 in guide rail 704 may be positioned at the approximate location where the tissue anchor 702 is to be deployed into the tissue. Bend 707 in guide rail 704 may comprise a hinge, a flexure, or one of many other joints. Tissue anchor 702 is deployed by rotating push tube 703. The rotation of tissue anchor 702 at the position of the bend 707 causes tissue anchor 702 to spiral off guide rail 704 and into tissue 708. Figure 7B shows the helical tissue anchor 705 fully deployed into tissue 708, but still connected to latch mechanism 709. In the fully deployed position, helical tissue anchor 705 may no longer wrap around guide rail 704. When still connected to latch mechanism 709, the helical tissue anchor 705 may be readily retracted by counter-rotating push tube 703. Figure 7C shows the helical tissue anchor 706 fully deployed into tissue 708 and disconnected from to latch mechanism 709. Latch mechanism 709 may become disconnected from tissue anchor 706 by retracting push tube 703 or releasing latch mechanism 709 with the addition of another cable to trigger a release mechanism. Figures 8A and 8B sequentially show deployment of a multi- barbed tissue anchor in tissue according to one illustrated embodiment.

In particular, Figure 8A shows a multi-barbed tissue anchor 805 fully inserted into tissue 804, but still encapsulated or retained by constriction tube 809. The location that the multi-barbed tissue anchor 805 enters the tissue may be determined by the position of a guide member, for instance guide rail 803. A bend 810 in guide rail 803 may be positioned at the approximate location where the multi-barbed tissue anchor 805 is to be deployed into the tissue 804. The bend 810 in guide rail 803 may be constructed using a hinge, a flexure, or one of many other methods. The multi-barbed tissue anchor 805 is deployed by advancing push tube 802 over guide rail 803. If encapsulated or retained by constriction tube 809, multi-barbed tissue anchor 805 may be readily retracted by retracting push tube 802.

Figure 8B shows the multi-barbed tissue anchor 808 fully inserted into tissue 804, but disconnected from constriction tube 811 and release member 806. The multi-barbed tissue anchor 808 is preferably retracted slightly before release member 806 is disconnected in order to cause barbs 807 to expand. The multi-barbed tissue anchor 808 may be disconnected from release member 806 and barbs 807 may be expanded by retracting constriction tube 809 relative to the release member 806 and multi-barbed tissue anchor 808. Retracting constriction tube 811 past the tips of barbs 807 causes the resilient barbs to be released and expand.

Figure 9 shows an example of an anchor guide frame of a tool according to one illustrated embodiment.

An anchor guide frame 901 is used to guide tissue anchors of the implant device to correct insertion or anchor points or locations. The anchor guide frame 901 shown comprises three guide members, for instance rails 905, but said guide frame may comprise more or fewer guide members. The anchor guide frame 901 embodiment illustrated shows all guide rails 905 connected at the bottom of the guide frame 901. An anchor guide frame is not required to have all guide members connected together, although it is often preferable to do so to create a guide frame that enables tissue anchors to be positioned relative to each other and to anatomical features. Thus, an anchor guide frame may have multiple disconnected groups of connected guide wires.

The anchor guide frame 901 preferably is capable of folding to enable delivery via a catheter. Guide members (e.g., guide wires or rails) 905 may be hinged at bends 902 and guide connection point 904 to enable folding. Loop 903 facilitates folding and also acts as a spring to enable unfolding of the anchor guide frame 901.

Guide members 905 may be formed to have respective bends 906 when no external forces are being applied. When guide members 905 are carried in a catheter with an articulation mechanism shaped into a curve as shown in Figure 2, the forces exerted on the guide member by the catheter and articulation mechanism will cause bend 906 to align with the curve in the articulation mechanism. Such alignment causes anchor guide frame 901 to rotate to a desired position relative to the catheter orientation. Bend 906 may also be formed to assist in curving the articulation mechanism in a particular way. An anchor guide frame may also contain additional features which use anatomical features or movement to assist in orientation of said anchor guide mechanism or guide frame 901. An example of such a feature is an alignment fin 907. Alignment fin 907 is attached rigidly to flexible anchor guide frame 901 and shaped so that the alignment fin 907 may be deflected by an anatomical feature, such as mitral valve leaflets, to a particular orientation. As the flexible anchor guide frame 901 is advanced toward an anatomical feature, such as the mitral valve annulus, the shape or motion of an anatomical feature, such as the mitral valve leaflets, may cause alignment fin 907, and thus flexible anchor guide frame 901 , to rotate to a desired orientation.

Figure 10 shows an anchor guide frame folded for delivery inside a catheter according to one illustrated embodiment.

An anchor guide frame including guide members (e.g., guide wires or rails)1004 may be folded inside a catheter 1001. Hinges 1006 and loop 1007 enhance folding of the anchor guide mechanism. In the embodiment illustrated, tissue anchors 1003 fit between the guide members 1004 in the folded configuration. Protective anchor cap 1005 holds and covers the sharp tips of tissue anchors 1003 and may ensure that the tips do not catch or embed on the sides of catheter 1001. Protective anchor cap 1005 may be held in place by control wire 1002

Figure 11 shows an anchor guide frame in an expanded configuration according to one illustrated embodiment.

An anchor guide frame 1112 may self expand after exiting catheter 1111. In particular, the anchor guide frame 1112 may be formed of a resilient material or a shape memory material such as Nitinol. Loop 1106 may be formed to cause the anchor guide frame 1112 to expand. Hinges 1105 facilitate separation of guide members 1104 by about 20 mm to 45 mm. In the illustrated embodiment, tissue anchors 1109 are held within the volume encompassed by anchor guide frame 1112 which ensures the tissue anchors 1109 do not accidentally impinge tissue. Also, the tips of the tissue anchors are held captive within protective anchor cap 1110. The tips of the tissue anchors may be released by advancing control wire 1103 and thereby also advancing anchor cap 1110. The tips of the tissue anchors are no longer held captive if anchor cap 1110 is advanced sufficiently to a point past the tips of the tissue anchors. As guide members 1104 curve away from anchor cap 1110, advancing tissue anchors 1109 causes the tips of the tissue anchors to move away from and avoid anchor cap 1110.

Articulation mechanism 1107 (e.g., articulation joints) of the tool is shown in a curved configuration or state. Articulation mechanism 1107 may be curved using wires (not shown) that are carried on opposing sides relative to a longitudinal axis of the articulation mechanism and fixed to the distal end of the articulation mechanism 1107. Tensioning one wire causes the articulation mechanism 1107 to arc in the direction of the side of the articulation mechanism on which the tensioned wire is carried in. For some situations, it is desirable to cause gaps between articulation links or articulation joints to open at different rates. For example, when inserting articulation mechanism 1107 into the left atrium, it may be preferable to cause the distal links, such as articulation link or joint 1113 and articulation link or joint 1114, to separate or bend prior to or more than the proximal articulation links or joints, such as articulation link or joint 1115 and articulation link or joint 1116. One embodiment to enable such an attribute is to insert springs, as indicated by 1108 and 1102, with varying spring constant k between the links or articulation joints. To cause the distal end of articulation mechanism 1107 to bend first, the distal links should be forced apart by springs with a higher spring constant than the springs between the proximal links. Another embodiment for enabling unequal separation of articulation links or joints is to control the shape of the guide members 1104 that are routed through the articulation mechanism 1107. The guide members should have a preformed bend with a decreasing radius of curvature in the area from proximal articulation link or joint 1115 to distal articulation link or joint 1114. Figure 12 shows a configuration of tissue anchors and push tubes at a distal tip of a medical device system according to one illustrated embodiment. For the sake of clarity, Figure 12 omits guide members and anchor guide frame that would typically be located at the distal tip of the medical device system.

An articulation mechanism 1204 may include multiple lumens 1208 through which push tubes 1202 are carried. In this particular embodiment, three lumens 1208 are shown, but other embodiments may comprise more or less. Push tubes 1202 may also include multiple lumens. In this particular embodiment, each push tube 1202 has a lumen 1201 in which a guide member (e.g., guide wire or rail) may be carried and a second lumen that carries a release member (e.g., rod or wire) (not shown) which is connected to the tissue anchors 1209. Constriction tubes 1205 may be mated into or onto the distal end of the second lumen. All tissue anchors may be connected by a flexible cable 1207. The flexible cable 1207 may also be carried within a separate lumen within the articulation mechanism 1204. Lumens 1203 are used to carry cables that control the curvature of the articulation mechanism 1204.

Figure 13 shows a cross section of a heart with an anchor guide frame according to one illustrated embodiment positioned within a left atrium of the heart. An anchor guide frame 1303 is shown self-located on a mitral annulus 1304 within the left atrium. The tissue anchor deployment sites 1301 are preferably located on the mitral annulus and coincident with bends in the guide members (e.g., guide wires or rails) 1302. While Figure 13 shows three guide members 1302 and tissue deployment sites 1301 for simplicity; in many cases more deployment sites and guide members are desirable. In such cases, it is a simple matter to add additional guide members and anchor deployment sites to the illustrated embodiment.

An alignment fin 1305 may fit between mitral valve leaflets 1306. The movement and anatomical structure of the mitral valve leaflets 1306 exert force on alignment fin 1305 and assist in orienting the anchor guide frame 1303 correctly Figure 14 shows a cross section of a heart with an installed assembly capable of constricting a mitral valve annulus according to one illustrated embodiment.

Tissue anchors 1401 , 1402, and 1403 are shown fully deployed on the mitral annulus 1406. Tissue anchors 1401-1403 may be connected by a flexible cable 1405. Other mechanisms for connecting tissue anchors 1401 , 1402, 1403 are possible. For example, rigid members, preferably with adjustable length (e.g., turn-buckles), may be used to connect the tissue anchors 1401-1403. Flexible cable 1405 may slide through holes on the tissue anchors 1401 , 1402, 1403.

Flexible cable 1405 may pass through a hollow spreader bar 1404. Hollow spreader bar 1404 provides support to keep tissue anchors 1401 and 1403 from moving closer together when flexible cable 1405 is shortened. Such support reduces undesired forces being applied to an aortic valve 1407 of the heart.

Reducing a distance between pairs of the tissue anchors 1401 , 1402 and 1402, 1403 causes an anterior-posterior (A-P) annular dimension of the mitral valve to reduce and improves leaflet coaptation. Several methods may be used to reduce the distance between two or more pairs of tissue anchors 1401 , 1402 and 1402, 1403. A first method is to shorten the cable during the installation procedure by routing the flexible cable 1405 through fastener 1408, pulling the cable manually to be as tight as desired and crimping fastener 1408. Fastener 1408 may also be constructed using a one way clutch so that the flexible cable 1405 can only be pulled through in one direction, in which case crimping is not required. A second method of reducing tissue anchor separation (i.e., distance between two successive tissue anchors) is to include shortening actuator 1409 between two tissue anchors. In the case where shortening actuator 1409 is included, flexible cable 1405 is split and attached to either end of the shortening actuator. One embodiment of shortening actuator 1409 contains an element that is capable of changing length as a response to a stimulus such as changes in an external magnetic field or heating induced by a changing magnetic field. The element capable of changing lengths may be made of a highly magnetostrictive alloy such as Terfenol-D or from a Shape Memory Alloy (SMA) such as specially treated Nitinol. Embodiment of such actuators are described in US11/902,199. The element capable of changing lengths may be made of a spring under tension (e.g., in an extended configuration) encapsulated in a retainer material that changes state in response to a stimulus (e.g., melts under low heat and solidifies at body temperature - such as a thermoplastic polymer). Current induced in a loop by an external magnetic field may be channeled through the spring. The current may heat the spring which will cause the polymer to soften and the spring length to contract to an unextended configuration. The contraction of the spring can be used to reduce the separation of the tissue anchors. Embodiments of such actuators are described in US11 /905,771. A closed, electrically conducting loop is required if shortening actuator 1409 is to be responsive to heating or energy induced by a changing magnetic field. Such a loop may be achieved by using an electrically conductive material for flexible cable 1405 and ensuring an electrical contact between both ends of flexible cable 1405 that are connected to shortening actuator 1409. Figures 15A and 15B show a tool and fastener used to tighten and secure a cable according to one illustrated embodiment.

Fastener 1507 may be used to tighten or secure cables being used to constrict a bodily orifice. Typically prior to attachment of fastener 1507, tissue anchors have been implanted or placed in the tissue, and a flexible cable has been connected to the tissue anchors. Cable end 1504 and cable end 1503 are typically carried in catheter sheath 1505 and routed outside the body. Cable end 1504 and cable end 1503 may be the two ends of one flexible cable. The portion of the cable not shown loops around the orifice to be constricted and is attached to the implanted tissue anchors used to secure the cable to the orifice. Cable end 1504 may be fed into hole 1511 and locked by ferrule 1510 while fastener 1507 is still outside the body. Cable end 1503 may be routed through taper lock 1509 while fastener 1507 is still outside the body.

Fastener 1507 may be attached to fastener positioning tube 1506. Cable end 1503 may be inserted through slot 1502 and into fastener positioning tube 1506. Fastener 1507 and fastener positioning tube 1506 may be inserted into catheter sheath 1505 and advanced until fastener 1507 is proximate an annulus of the orifice to be constricted. Cable end 1503 may be pulled in a direction away from fastener 1507, causing the cable to pull through taper lock 1509 and constrict the orifice. While the cable is being tightened and secured, fastener 1507 may be held by fastener positioning tube 1506. Taper lock 1509 restricts cable end 1503 from being pulled out the right side (as illustrated in Figures 15A, 15B) of fastener 1507. Taper lock 1509 may have teeth 1515 to grip cable end 1503. Taper lock 1509 may have a longitudinal slot to enable compression of taper lock 1509 and constriction around cable end 1503. Spring 1508 may force taper lock 1509 into a conical hole 1514, causing the force taper lock 1509 to tighten around cable end 1503.

When the orifice has been sufficiently constricted, cable end 1503 may be severed using cable cutting tube 1501. Cable cutting tube 1501 comprises a sharpened end 1516. In particular, Figure 15A shows cable cutting tube 1501 in a retracted position. The cable cutting tube may slide inside of fastener positioning tube 1506. Figure 15B shows cable cutting tube 1512 in the cable cutting position, physically engaging the cable 1513. Cable cutting tube 1512 may sever cable end 1513 by forcing cable end 1513 against the end of slot 1516. The cable end may be severed in other ways, including using a hot tip to melt through the cable.

Figures 16A and 16B show a catheter with grooves, or side slots, and a mechanism for securing cables or wires in said side slots according to one illustrated embodiment. In particular, Figure 16A shows catheter 1604 with cables 1601 held within longitudinal groove 1603 on the inner surface of the tube wall by tube 1602. The longitudinal groove 1603 has a cross sectional shape that enables tube 1602 to be held captive. Figure 16 shows a circular groove (i.e., arcuate cross-section), but other shapes may be used. Tube 1602 carries cables 1601. Tube 1602 could also carry wires or tubes. When tube 1602 is removed by pulling it out the end, as shown in Figure 16B by catheter 1607, cables 1605 are free to move into the central area of the tube. Tube 1602 can be reinserted over cables 1605 to again constrain them in groove 1603.

Although Figures 16A and 16B show catheter 1604 and catheter 1607 with only one groove 1603, it is possible to have many such grooves in a catheter and to secure a plurality of wires and tubes in said grooves. One of the reasons for securing cables or wires in grooves, or side slots, is to eliminate tangling of cables or wires during medical procedures.

Figure 17 shows a mechanism for holding a tissue anchor captive according to one illustrated embodiment Tissue anchor 1703 may be held captive in constriction tube 1706 of the tool by release member 1704. Constriction tube 1706 may be inserted and secured to a distal end of one lumen of push tube 1701. Constriction tube 1706 may be held captive in the lumen by one or more ribs 1705.

Tissue anchor 1703 may be released from constriction tube 1706 by retracting push tube 1701 and constriction tube 1706 relative to release member 1704. As the distal end of constriction tube 1706 clears hole 1707, tip of release member 1708 will pop out of hole 1707 and tissue anchor 1703 will no longer be held captive.

Lumen 1702 of push tube 1701 may be used to slide over a guide member.

Figures 18A and 18B show a mechanism for restricting a tissue anchor from release until anchor is fully embedded in tissue according to one illustrated embodiment

An additional benefit is provided if the tool to implant the implantable device for constricting a bodily orifice does not release tissue anchors of the implantable device until the tissue anchors are fully embedded in the tissue. It is possible to achieve this benefit by adding an additional latch

1806, 1810 to the tool.

In particular, Figure 18A shows a tissue anchor 1802 prior to deployment. The tissue anchor 1802 may not be released from constriction tube 1805 by retracting push tube 1803 and constriction tube 1805 relative to release member 1804 because latch 1806 in an engaged or locked position extends into a notch 1801.

Figure 18B shows the tissue anchor 1808 fully deployed into tissue 1812. As tissue anchor 1808 was deployed into tissue 1812, the surface of tissue 1812 causes lever 1811 to bend. When lever 1811 is bent, latch 1810 clears notch 1813. Once latch 1810 clears notch 1813, tissue anchor 1808 may be released from constriction tube 1809

The various embodiments described above can be combined to provide further embodiments. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference, in their entirety. Aspects of the invention can be modified, if necessary, to employ systems, circuits and concepts of the various patents, applications and publications to provide yet further embodiments of the invention.

These and other changes can be made to the invention in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the invention to the specific embodiments disclosed in the specification and the claims, but should be construed to include all medical treatment devices in accordance with the claims. Accordingly, the invention is not limited by the disclosure, but instead its scope is to be determined entirely by the following claims.

Claims

1. A medical device system operable to constrict an orifice in tissue, comprising: an implant comprising: a plurality of tissue anchors, each of the tissue anchors physically configured to be physically releasably guided along respective guide members of a guide frame to respective locations about a periphery of an orifice in a tissue and implanted in the tissue at least proximate the respective locations, the tissue anchors when implanted moveable with respect to one another between an unretracted configuration in which the tissue anchors are radially spaced relatively apart from one another and a retracted configuration in which the tissue anchors are radially spaced relatively toward one another with respect to the unretracted configuration; and a number of connectors that physically couple at least some of the tissue anchors to one another such that a distance between at least some pairs of the tissue anchors is selectively adjustable to radially contract the tissues anchors inwardly from the unretracted configuration toward the retracted configuration to constrict the orifice in the tissue.

2. The medical device system of claim 1 wherein at least one of the tissue anchors of the implant includes a plurality of resilient barbs and further comprising: a tool that comprises the guide frame and a constriction tube that protectively retains the barbs of the tissue anchor in a compressed configuration until released from the constriction tube.

3. The medical device system of claim 1 wherein at least one of the tissue anchors is a helical tissue anchor.

4. The medical device system of claim 1 wherein the number of connectors of the implant includes a flexible cable that couples each of the tissue anchors to one another.

5. The medical device system of claim 4 wherein the implant further comprises a fastener that receives a portion of the flexible cable and is selectively operable to secure the flexible cable in a tensioned state.

6. The medical device system of claim 5 wherein the implant further comprises a spreader structure that fixes a distance between a pair of the tissue anchors such that the distance between the pair of the tissue anchors does not change between an untensioned state and the tensioned state of the flexible cable.

7. The medical device system of claim 1 wherein the number of connectors of the implant includes at least one shape memory material connectors, the at least one shape memory material connector responsive to a stimulus to change a distance between at least one pair of the tissue anchors.

8. The medical device system of claim 1 wherein the number of connectors of the implant includes at least one spring coupled across at least one pair of the tissue anchors and a retainer that changes a physical state in response to a stimulus, wherein the retainer retains the spring in an extended configuration until the retainer changes state responsive to the stimulus wherein the spring returns to an unextended configuration to change a distance between the pair of the tissue anchors.

9. The medical device system of claims 7 or 8 wherein at least one of the number of connectors is responsive to a magnetic field externally applied with respect to a body.

10. The medical device system of claim 1 , further comprising: a tool comprising the guide frame, wherein the guide members include a plurality of guide rails along which respective ones of the tissue anchors traverse.

11. The medical device system of claim 10 wherein the guide rails are physically configured to retain the respective tissue anchors at least until the tissues anchors are implanted in the tissue

12. The medical device system of claim 10 wherein the guide rails each include a change in curvature at which point the respective tissue anchor is releasable from the guide rail.

13. The medical device system of claim 10 wherein the tool further comprises a cap that removably retains at least a tip of the tissue anchors before the tissue anchors are implanted in the tissue.

14. The medical device system of claim 10 wherein the implant and the guide frame are compressible between a compressed configuration and an uncompressed configuration, the implant and guide frame sized and dimensioned when in the compressed configuration to be deliverable by a catheter and sized and dimensioned when in the uncompressed configuration to contact various portions of the tissue.

15. The medical device system of claim 10 wherein the tissue anchor guide frame includes at least one anatomical structure engagement structure that adjusts at least one of an orientation or a position of the implant on physical engagement with an anatomical structure.

16. The medical device system of claim 10 wherein the tool further comprises a plurality of push tubes, each of the push tubes having at least one lumen, and a plurality of release members movable received by the at least one lumen of respective ones of the push tubes, wherein each of the release members releasably engages a respective one of the tissue anchors before the tissue anchor is implanted in the tissue.

17. The medical device system of claim 16 wherein the tool further comprises a plurality of guide wires, each of the guide wires movable received by the at least one lumen of a respective one of the push tubes, wherein each of the guide wires provides a releasable physically path for a respective one of the tissue anchors to the respective location on the tissue for implantation.

18. The medical device system of claim 17 wherein each of the guide wires includes a change in a radius of curvature proximate at which point the guide wire releases the respective one of the tissue anchors.

19. A method of operating a medical device system to constrict an orifice in tissue, the method comprising: positioning a tool having a guide frame with a plurality of guide members such that distal ends of the guide members are at least proximate respective locations about a periphery of an orifice in a tissue internally within a body; advancing a plurality of tissue anchors of an implant along respective ones of the guide members to be at least proximate respective ones of the respective locations about the periphery of the orifice in the tissue; implanting the tissue anchors in the tissue at least proximate the respective locations; and reducing a distance between at one pair of the tissue anchors to constrict the orifice in the tissue.

20. The method of claim 19, further comprising: advancing the tissue anchors with respect to a constriction tube to expose a plurality of barbs on each of the tissue anchors, and wherein implanting the tissue anchors in the tissue at least proximate the respective locations comprises implanting the tissue anchors in the tissue to a depth sufficient to locate the barbs in the tissue.

21. The method of claim 19 wherein the tissue anchors are helical tissue anchors and implanting the tissue anchors in the tissue at least proximate the respective locations comprises rotating the helical tissue anchor with respect to the tissue.

22. The method of claim 19 wherein reducing a distance between at one pair of the tissue anchors to constrict the orifice in the tissue comprises tensioning a flexible member that physically couples at least two of the tissue anchors together.

23. The method of claim 22 wherein reducing a distance between at one pair of the tissue anchors to constrict the orifice in the tissue further comprises fixing the distance between the at least one pair of the tissue anchors after tensioning the flexible member.

24. The method of claim 19 wherein reducing a distance between at one pair of the tissue anchors to constrict the orifice in the tissue comprises applying an external stimulus to a connection member that couples at least one pair of the tissue anchors together, where the external stimulus reduces a length of the connection member.

25. The method of claim 19, further comprising: selectively releasing the tissue anchors from respective ones of the guide members.

26. The method of claim 25 wherein selectively releasing the tissue anchors from respective ones of the guide members comprises retracting a release member of the tool while maintaining in a fixed position a push tube of the tool which movably receives the release member to physically uncouple at least one of the tissue anchors from the tool.

27. The method of claim 19, further comprising: selectively releasing the tissue anchors from respective ones of the guide members at or after the tissue anchors have passed a bend in the guide members.

28. The method of claim 19, further comprising: percutaneously delivering the guide frame and the implant into the body in a compressed configuration.