PATENT DOCUMENT

Abstract:
The invention provides devices, systems and methods for tissue approximation and repair at treatment sites. The devices, systems and methods of the invention will find use in a variety of therapeutic procedures, including endovascular, minimally-invasive, and open surgical procedures, and can be used in various anatomical regions, including the abdomen, thorax, cardiovascular system, heart, intestinal tract, stomach, urinary tract, bladder, lung, and other organs, vessels, and tissues. The invention is particularly useful in those procedures requiring minimally-invasive or endovascular access to remote tissue locations, where the instruments utilized must negotiate long, narrow, and tortuous pathways to the treatment site. In addition, many of the devices and systems of the invention are adapted to be reversible and removable from the patient at any point without interference with or trauma to internal tissues.

Full Description:
CROSS-REFERENCES TO RELATED APPLICATIONS  
       [0001]     This application is a divisional of, and claims the benefit of priority from co-pending U.S. patent application Ser. No. 10/441,531 (Attorney Docket No. 020489-001400US), filed May 19, 2003, which is a continuation-in-part of U.S. patent application Ser. No. 09/894,463 now U.S. Pat. No. 6,752,813 (Attorney Docket No. 020489-000400US) filed Jun. 27, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09/544,930 now U.S. Pat. No. 6,629,534 (Attorney Docket No. 020489-000110US) filed Apr. 7, 2000, which claims the benefit of prior U.S. Provisional Patent Application No. 60/128,690, filed on Apr. 9, 1999 under 37 CFR §1.78(a), the full disclosures of which are hereby incorporated herein by reference. This application is related to U.S. patent application Ser. No. 10/441,753 (Attorney Docket No. 020489-001200US), U.S. patent application Ser. No. 10/441,508 (Attorney Docket No. 020489-001500US), and U.S. patent application Ser. No. 10/441,687, now U.S. Pat. No. 7,226,467 (Attorney Docket No. 020489-001700US), all of which were filed on the same day as the parent application U.S. patent application Ser. No. 10/441,531 (Attorney Docket No. 020489-001400US), the full disclosures of which are incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     1. Field of the Invention  
         [0003]     The present invention relates generally to medical methods, devices, and systems. In particular, the present invention relates to methods, devices, and systems for the endovascular, percutaneous or minimally invasive surgical treatment of bodily tissues, such as tissue approximation or valve repair. More particularly, the present invention relates to repair of valves of the heart and venous valves.  
         [0004]     Surgical repair of bodily tissues often involves tissue approximation and fastening of such tissues in the approximated arrangement. When repairing valves, tissue approximation includes coapting the leaflets of the valves in a therapeutic arrangement which may then be maintained by fastening or fixing the leaflets. Such coaptation can be used to treat regurgitation which most commonly occurs in the mitral valve.  
         [0005]     Mitral valve regurgitation is characterized by retrograde flow from the left ventricle of a heart through an incompetent mitral valve into the left atrium. During a normal cycle of heart contraction (systole), the mitral valve acts as a check valve to prevent flow of oxygenated blood back into the left atrium. In this way, the oxygenated blood is pumped into the aorta through the aortic valve. Regurgitation of the valve can significantly decrease the pumping efficiency of the heart, placing the patient at risk of severe, progressive heart failure.  
         [0006]     Mitral valve regurgitation can result from a number of different mechanical defects in the mitral valve or the left ventricular wall. The valve leaflets, the valve chordae which connect the leaflets to the papillary muscles, the papillary muscles or the left ventricular wall may be damaged or otherwise dysfunctional. Commonly, the valve annulus may be damaged, dilated, or weakened, limiting the ability of the mitral valve to close adequately against the high pressures of the left ventricle.  
         [0007]     The most common treatments for mitral valve regurgitation rely on valve replacement or repair including leaflet and annulus remodeling, the latter generally referred to as valve annuloplasty. A recent technique for mitral valve repair which relies on suturing adjacent segments of the opposed valve leaflets together is referred to as the “bow-tie” or “edge-to-edge” technique. While all these techniques can be very effective, they usually rely on open heart surgery where the patient&#39;s chest is opened, typically via a sternotomy, and the patient placed on cardiopulmonary bypass. The need to both open the chest and place the patient on bypass is traumatic and has associated high mortality and morbidity.  
         [0008]     For these reasons, it would be desirable to provide alternative and additional methods, devices, and systems for performing the repair of mitral and other cardiac valves. Such methods, devices, and systems should preferably not require open chest access and be capable of being performed either endovascularly, i.e., using devices which are advanced to the heart from a point in the patient&#39;s vasculature remote from the heart or by a minimally invasive approach. Further, such devices and systems should provide features which allow repositioning and optional removal of a fixation device prior to fixation to ensure optimal placement. Still more preferably, the methods, devices, and systems would be useful for repair of tissues in the body other than heart valves. At least some of these objectives will be met by the inventions described hereinbelow.  
         [0009]     2. Description of the Background Art  
         [0010]     Minimally invasive and percutaneous techniques for coapting and modifying mitral valve leaflets to treat mitral valve regurgitation are described in PCT Publication Nos. WO 98/35638; WO 99/00059; WO 99/01377; and WO 00/03759.  
         [0011]     Maisano et al. (1998)  Eur. J. Cardiothorac. Surg.  13:240-246; Fucci et al. (1995)  Eur. J. Cardiothorac. Surg.  9:621-627; and Umana et al. (1998)  Ann. Thorac. Surg.  66:1640-1646, describe open surgical procedures for performing “edge-to-edge” or “bow-tie” mitral valve repair where edges of the opposed valve leaflets are sutured together to lessen regurgitation. Dec and Fuster (1994)  N. Engl. J. Med.  331:1564-1575 and Alvarez et al. (1996)  J. Thorac. Cardiovasc. Surg.  112:238-247 are review articles discussing the nature of and treatments for dilated cardiomyopathy.  
         [0012]     Mitral valve annuloplasty is described in the following publications. Bach and Bolling (1996)  Am. J. Cardiol.  78:966-969; Kameda et al. (1996)  Ann. Thorac. Surg.  61:1829-1832; Bach and Bolling (1995)  Am. Heart J.  129:1165-1170; and Bolling et al. (1995) 109:676-683. Linear segmental annuloplasty for mitral valve repair is described in Ricchi et al. (1997)  Ann. Thorac. Surg.  63:1805-1806. Tricuspid valve annuloplasty is described in McCarthy and Cosgrove (1997)  Ann. Thorac. Surg.  64:267-268; Tager et al. (1998)  Am. J. Cardiol.  81:1013-1016; and Abe et al. (1989)  Ann. Thorac. Surg.  48:670-676.  
         [0013]     Percutaneous transluminal cardiac repair procedures are described in Park et al. (1978)  Circulation  58:600-608; Uchida et al. (1991)  Am. Heart J.  121: 1221-1224; and Ali Khan et al. (1991)  Cathet. Cardiovasc. Diagn.  23:257-262.  
         [0014]     Endovascular cardiac valve replacement is described in U.S. Pat. Nos. 5,840,081; 5,411,552; 5,554,185; 5,332,402; 4,994,077; and 4,056,854. See also U.S. Pat. No. 3,671,979 which describes a catheter for temporary placement of an artificial heart valve.  
         [0015]     Other percutaneous and endovascular cardiac repair procedures are described in U.S. Pat. Nos. 4,917,089; 4,484,579; and 3,874,338; and PCT Publication No. WO 91/01689.  
         [0016]     Thoracoscopic and other minimally invasive heart valve repair and replacement procedures are described in U.S. Pat. Nos. 5,855,614; 5,829,447; 5,823,956; 5,797,960; 5,769,812; and 5,718,725.  
       BRIEF SUMMARY OF THE INVENTION  
       [0017]     The invention provides devices, systems and methods for tissue approximation and repair at treatment sites. The devices, systems and methods of the invention will find use in a variety of therapeutic procedures, including endovascular, minimally-invasive, and open surgical procedures, and can be used in various anatomical regions, including the abdomen, thorax, cardiovascular system, heart, intestinal tract, stomach, urinary tract, bladder, lung, and other organs, vessels, and tissues. The invention is particularly useful in those procedures requiring minimally-invasive or endovascular access to remote tissue locations, where the instruments utilized must negotiate long, narrow, and tortuous pathways to the treatment site. In addition, many of the devices and systems of the invention are adapted to be reversible and removable from the patient at any point without interference with or trauma to internal tissues.  
         [0018]     In preferred embodiments, the devices, systems and methods of the invention are adapted for fixation of tissue at a treatment site. Exemplary tissue fixation applications include cardiac valve repair, septal defect repair, vascular ligation and clamping, laceration repair and wound closure, but the invention may find use in a wide variety of tissue approximation and repair procedures. In a particularly preferred embodiment, the devices, systems and methods of the invention are adapted for repair of cardiac valves, and particularly the mitral valve, as a therapy for regurgitation. The invention enables two or more valve leaflets to be coapted using an “edge-to-edge” or “bow-tie” technique to reduce regurgitation, yet does not require open surgery through the chest and heart wall as in conventional approaches. Using the devices, systems and methods of the invention, the mitral valve can be accessed from a remote surgical or vascular access point and the two valve leaflets may be coapted using endovascular or minimally invasive approaches. While less preferred, in some circumstances the invention may also find application in open surgical approaches as well. According to the invention, the mitral valve may be approached either from the atrial side (antegrade approach) or the ventricular side (retrograde approach), and either through blood vessels or through the heart wall.  
         [0019]     The devices, systems and methods of the invention are centered on variety of devices which may be used individually or in a variety of combinations to form interventional systems. In preferred embodiments, the interventional system includes a multi-catheter guiding system, a delivery catheter and an interventional device. Each of these components will be discussed herein.  
         [0020]     In an exemplary embodiment, the invention provides a fixation device having a pair of distal elements (or fixation elements), each distal element having a free end and an engagement surface for engaging the tissue, wherein the distal elements are moveable between a first position for capturing the tissue and a second position for fixing the tissue. Preferably, the engagement surfaces are spaced apart in the first position and are closer together and generally face toward each other in the second position. The fixation device is preferably delivered to a target location in a patient&#39;s body by a delivery catheter having an elongated shaft, a proximal end and a distal end, the delivery catheter being configured to be positioned at the target location from a remote access point such as a vascular puncture or cut-down or a surgical penetration. In a preferred embodiment, the target location is a valve in the heart.  
         [0021]     The fixation device is preferably delivered with the distal elements in a delivery position configured to minimize the profile of the device. When approaching the mitral valve from the atrial side, some embodiments of the fixation device allow the device to be delivered with the free ends of the distal elements pointing in a generally proximal direction forming an angle of less than about 90°, preferably less than about 20°, relative to the longitudinal axis of the delivery device shaft. In this position the engagement surfaces are facing generally toward each other, being disposed at an angle of less than about 180°, and preferably less than about 40°, relative to each other. For ventricular approaches, in the delivery position the free ends of the distal elements are pointing in a generally distal direction and form an angle of less than about 90°, preferably less than about 20° relative to the longitudinal axis of the delivery device shaft. In this position, the engagement surfaces are facing generally toward each other, usually being disposed at an angle of less than about 180°, and preferably less than about 90°, relative to each other. Alternatively, in some ventricular approaches, it may be preferred to have the free ends of the fixation elements pointing in a generally proximal direction and the engagement surfaces facing away from each other in the delivery position.  
         [0022]     In order to provide for the reversibility and removability of the devices and systems of the invention, the distal elements preferably are movable to an inverted position that minimizes entanglement and interferences with surrounding tissues should the device be desired to be withdrawn. In mitral repair applications, this is particularly important due to the presence of chordae tendonae, valve leaflets and other tissues with which devices may become entangled. For approaches from the atrial side of the mitral valve, in the inverted position, the free ends will be pointing in a generally distal direction relative to the catheter shaft and the engagement surfaces will be facing generally away from each other, usually being disposed at an angle of more than about 180°, and preferably more than 270°, relative to each other. For ventricular approaches to the valve, in the inverted position the free ends will be pointing in a distal direction relative to the catheter shaft and the engagement surfaces will be facing generally toward each other, usually being disposed at an angle of less than about 180°, and preferably less than 90°, relative to each other.  
         [0023]     In the open position, the engagement surfaces of the distal elements preferably form an angle of up to 180° relative to each other so as to maximize the area in which to capture the valve leaflets or other target tissue. The distal elements are preferably movable to a closed position in which the engagement surfaces engage each other or form an angle as small as 0° relative to each other. The distal elements are configured to be adjusted to and left permanently in any of various positions between the open and closed positions to allow for fixation of tissues of various thickness, geometry, and spacing.  
         [0024]     In a preferred embodiment, the fixation device of the invention will further include at least one proximal element (or gripping element). Each proximal element and distal element will be movable relative to each other and configured to capture tissue between the proximal element and the engagement surface of the distal element. Preferably, the distal elements and proximal elements are independently movable but in some embodiments may be movable with the same mechanism. The proximal element may be preferably biased toward the engagement surface of the fixation element to provide a compressive force against tissue captured therebetween.  
         [0025]     In another aspect, the invention provides a fixation device for engaging tissue comprising a coupling member configured for coupling a catheter and a pair of distal elements connected to the coupling member, each distal element having an engagement surface for engaging the tissue. The distal elements are moveable between an open position wherein the distal elements extend radially outwardly facing the engagement surfaces toward a first direction, and an inverted position wherein the distal elements have rotated away from the first direction facing the engagement surfaces radially outwardly.  
         [0026]     In a further aspect, the distal elements of the invention are adapted to receive a suture passed through the target tissue. For example, implant pledgets may be detachably mounted to the distal elements so as to be positionable against a surface of tissue engaged by the distal elements. A suture may then be passed through the tissue and implant pledget, which are supported by the distal element. The implant pledgets are then detached from the distal elements, which may be withdrawn from the site, and the suture is tensioned and secured to the target tissue. The delivery catheter, in this embodiment, will further include a movable fixation tool or penetration element for penetrating the target tissue and the implant pledget. A suture is coupled to the penetration element and preferably an anchor is attached to the suture. The penetration element is movable relative to the catheter to penetrate the target tissue and the implant pledget, bringing with it the suture and anchor. The anchor is configured to deploy into an expanded configuration so as to securely engage the implant pledget opposite the target tissue, retaining the suture therein. For the mitral valve, an implant pledget and suture may be similarly deployed in both leaflets, and the sutures secured to one another to coapt the leaflets. Thus, in this embodiment, the distal elements are used to deliver implant pledgets and secure them to the target tissue, but are not themselves deployed at the site as in other embodiments. However, following deployment of the implant pledgets and associated sutures, the distal elements must be withdrawn from the body. For this purpose, the distal elements are movable to an inverted position like the embodiments described above to facilitate withdrawing the device without interference or injury to surrounding tissues.  
         [0027]     In some applications such as the repair of the mitral valve, the fixation device is adapted to be detached from the delivery catheter and left permanently in the patient. In such applications, it is often desirable to promote tissue growth around the fixation device. For this purpose, some or all of the components of the fixation device are preferably covered with a covering or coating to promote tissue growth. In one embodiment, a biocompatible fabric cover is positioned over the distal elements and/or the proximal elements. The cover may optionally be impregnated or coated with various therapeutic agents, including tissue growth promoters, antibiotics, anti-clotting, blood thinning, and other agents. Alternatively or in addition, some or all of the fixation element and/or covering may be comprised of a bioerodable, biodegradable or bioabsorbable material so that it may degrade or be absorbed by the body after the repaired tissues have grown together.  
         [0028]     The distal elements and proximal elements will be configured to provide high retention force so that the fixation device remains securely fastened to the target tissue throughout the cardiac cycle. At the same time, the distal and proximal elements will be configured to minimize trauma to the tissue engaged by them. This allows the fixation device to be removed from the tissue after initial application without creating clinically significant injury to the tissue. In order to enhance retention without creating significant trauma, the proximal elements and/or the distal elements may have friction-enhancing features on their surfaces that engage the target tissue. Such friction-enhancing features may include barbs, bumps, grooves, openings, channels, surface roughening, coverings, and coatings, among others. Optionally, magnets may be present in the proximal and/or distal elements. Preferably the friction-enhancing features and the magnets will be configured to increase the retention force of the distal and proximal elements on the tissue, while not leaving significant injury or scarring if the device is removed.  
         [0029]     The distal and proximal elements may further have a shape and flexibility to maximize retention force and minimize trauma to the target tissue. In a preferred embodiment, the engagement surfaces of the distal elements have a concave shape configured to allow the proximal elements, along with the target tissue, to be nested or recessed within the distal elements. This increases the surface area of the tissue engaged by the distal elements and creates a geometry of tissue engagement that has a higher retention force than a planar engagement surface. To minimize trauma, the longitudinal edges as well as the free ends of the distal elements are preferably curved outwardly away from the engagement surface so that these edges present a rounded surface against the target tissue. The distal elements and/or the proximal elements may also be flexible so that they deflect to some degree in response to forces against the tissue engaged thereby, reducing the chances that the tissue will tear or bruise in response to such forces.  
         [0030]     The fixation device will include an actuation mechanism for moving the distal elements between the open, closed, and inverted positions. A variety of actuation mechanisms may be used. In an exemplary embodiment, a coupling member connects the fixation device to the delivery catheter, and a stud is slidably coupled to the coupling member. In a “push to close/pull to open” embodiment, the distal elements are pivotably coupled to the stud and the actuation mechanism comprises a pair of link members connected between the distal elements and the coupling member, whereby sliding the stud relative to the coupling member pivots the distal elements inwardly or outwardly into the various positions. Alternatively, in a “push to open/pull to close” embodiment, the distal elements are pivotably coupled to the coupling member and the links connected between the distal elements and the stud.  
         [0031]     The fixation device of the invention preferably includes a coupling member that is detachably connectable to the delivery catheter. The coupling member may have various constructions, but in an exemplary embodiment comprises an outer member having an axial channel, the outer member being coupled to one of either the distal elements or the actuation mechanism. An inner member extends slidably through the axial channel and is coupled to the other of either the distal elements or the actuation mechanism. The delivery catheter will be configured to detachably connect to both the inner member and the outer member. In one embodiment, the delivery catheter has a tubular shaft and an actuator rod slidably disposed in the tubular shaft. The junction of the outer member with the tubular shaft comprises a joining line, which may have a variety of shapes including sigmoid curves. The actuator rod extends from the delivery catheter through the axial channel in the outer member to maintain its connection with the tubular shaft. The actuator rod may be connected to the inner member by various connection structures, including threaded connections. By detachment of the actuator rod from the inner member and retraction of the actuator rod back into the tubular shaft, the outer member is released from the tubular shaft to allow deployment of the fixation device.  
         [0032]     In a preferred embodiment, the fixation device further includes a locking mechanism that maintains the distal elements in a selected position relative to each other. Because the ideal degree of closure of the fixation device may not be known until it is actually applied to the target tissue, the locking mechanism is configured to retain the distal elements in position regardless of how open or closed they may be. While a variety of locking mechanisms may be used, in an exemplary embodiment the locking mechanism comprises a wedging element that is movable into frictional engagement with a movable component of the fixation device to prevent further movement of the distal elements. In embodiments utilizing the actuation mechanism described above, the component with which the wedging element engages may be the coupling member or the stud slidably coupled thereto. In one embodiment, the stud passes through an aperture in the coupling member that has a sloping sidewall, and the wedging element comprises a barbell disposed between the sidewall and the stud.  
         [0033]     The fixation device preferably also includes an unlocking mechanism for releasing the locking mechanism, allowing the distal elements and proximal elements to move. In one embodiment, the unlocking mechanism comprises a harness coupled to the wedging element of the locking mechanism to reduce frictional engagement with the movable component of the fixation device. In an exemplary embodiment, the harness is slidably coupled to the coupling member and extends around the wedging element of the locking mechanism, whereby the harness can be retracted relative to the coupling member to disengage the wedging element from the stud.  
         [0034]     In a further aspect, the invention provides an interventional system comprising a tubular guide having a proximal end, a distal end and a channel therebetween, the distal end of the tubular guide being deflectable about a first axis; a delivery catheter positionable through the channel, the delivery catheter having a flexible shaft with a proximal end, a distal end, a lumen therebetween, and an actuation element movably disposed in the lumen; and a fixation device having a coupling member releasably coupled to the distal end of the shaft, a first distal element movably coupled to the coupling member, and a first proximal element movable relative to the distal element, the first distal element being releasably coupled to the actuation element and movable therewith, the first distal element and the first proximal element being adapted to engage tissue therebetween.  
         [0035]     The delivery device of the invention is adapted to allow the user to deliver the fixation device to the target site from a remote access point, whether through endovascular or surgical approaches, align the device with the target tissue, and to selectively close, open, invert, lock or unlock the distal element. In some embodiments, the delivery device will have a highly flexible, kink resistant, torsionally stiff shaft with minimal elongation and high compressive strength. The delivery device will also have the movable components and associated actuators to move the distal elements between the open, closed, and inverted positions, to move the proximal elements into engagement with the target tissue, to unlock the locking mechanism, and to detach the distal element from the delivery catheter. In a preferred embodiment, the delivery device comprises a delivery catheter having an elongated shaft which has an inner lumen. The distal end of the shaft is configured for detachable connection to the coupling member of the fixation device. An actuator rod is slidably disposed in the inner lumen and is adapted for detachable coupling to the stud or other component of the fixation device that moves the distal elements. A plurality of tubular guides, preferably in the form of metallic or polymeric coils, extend through the inner lumen of the shaft and are typically fixed to the shaft near its proximal and distal ends but are unrestrained therebetween, providing a highly flexible and kink-resistant construction. Lines for actuating the proximal elements and the unlocking mechanism of the fixation device extend through these tubular guides and are detachably coupled to the proximal element and unlocking mechanisms. These and other aspects of delivery catheters suitable for use in the present invention are described in copending application Ser. No. 10/441,687, Attorney Docket No. 020489-001700US, filed on the same day as the present application, which has been incorporated herein by reference.  
         [0036]     The delivery catheter may additionally include a tether that is detachably coupled to a portion of the fixation device for purposes of retrieval of the device following detachment from the delivery catheter. The tether may be a separate flexible filament extending from the delivery catheter to the fixation device, but alternatively may be a line coupled to either the unlocking mechanism or the proximal element and used also for actuating those components. In either case, the tether will be detachable from the fixation device so that it may be detached once the device has been deployed successfully.  
         [0037]     The system of the invention may additionally include a guide that facilitates introduction and navigation of the delivery catheter and fixation device to the target location. The guide is preferably tubular with a channel extending between its proximal and distal ends in which the delivery catheter and fixation device may be slidably positioned. The distal end of the guide is steerable, usually being deflectable about at least one axis, and preferably about two axes. The guide will have a size, material, flexibility and other characteristics suitable for the application in which it is being used. For mitral valve repair, the guide is preferably configured to be introduced in a femoral vein and advanced through the inferior vena cava into the heart, across a penetration in the interatrial septum, and into alignment with the mitral valve in the left atrium. Alternatively, the guide may be configured for introduction in a femoral, axillary, or brachiocephalic artery and advancement through the aorta and aortic valve into the ventricle where it is steered into alignment with the mitral valve. In a further alternative, the guide may be configured for introduction through a puncture or incision in the chest wall and through an incision in the wall of the heart to approach the mitral valve.  
         [0038]     In an exemplary embodiment, the guide comprises a multi-catheter guiding system which has two components, including an inner tubular member or inner guide catheter and an outer tubular member or outer guide catheter. The inner tubular member has a distal end deflectable about a first axis. The outer tubular member has a distal end deflectable about a second axis. Further, the inner tubular member may be rotatable relative to the outer tubular member about its longitudinal axis. Mobility in additional directions and about additional axes may optionally be provided. Additional aspects of guides usable in the system of the invention are described in pending application Ser. No. 10/441,508, Attorney Docket No. 020489-001500US, which has been incorporated herein by reference.  
         [0039]     The invention further provides methods of performing therapeutic interventions at a tissue site. In one embodiment, the method includes the steps of advancing an interventional tool having a proximal end, a distal end and a fixation device near the distal end to a location within a patient&#39;s body, wherein the fixation device includes a pair of distal elements each having a free end and an engagement surface; moving the distal elements to an open position wherein the free ends are spaced apart; positioning the distal elements such that the engagement surfaces engage tissue at the tissue site; and detaching the fixation device from the interventional tool. Preferably, the method further includes the step of inverting the distal elements to an inverted position wherein the free ends point generally in a distal direction. In some embodiments, the engagement surfaces will face generally away from each other in the inverted position, while in other embodiments, the engagement surfaces will face generally toward each other in the inverted position.  
         [0040]     In an exemplary embodiment, the tissue site comprises first and second leaflets, and the step of moving the distal elements comprises coapting the leaflets. The leaflets may be part of a variety of tissue structures, but are preferably part of a cardiac valve such as the mitral valve. In antegrade approaches, the step of advancing will usually include inserting the fixation device through a valve annulus, e.g. from an atrium of the heart to a ventricle of the heart. In such approaches, the method may further include a step of withdrawing the fixation device through the valve annulus with the fixation device in the inverted position. Retrograde approaches are also provided, in which the step of advancing will include the step of passing the fixation device through a ventricle of the heart into an atrium of the heart. The step of advancing may further comprise transluminally positioning the fixation device through a blood vessel into the heart, and may include inserting the fixation device through an interatrial septum of the heart. Alternatively, the step of advancing may comprise inserting the device through a surgical penetration in a body wall.  
         [0041]     The method may further include moving the distal elements to a closed position after the step of positioning, the free ends of the distal element being closer together in the closed position with the engagement surfaces facing generally toward each other. In addition, the method may include a step of deploying a proximal element on the fixation device toward each engagement surface to as to capture tissue therebetween. Before the step of inverting, the proximal elements are retracted away from the engagement surfaces. The method optionally includes a step of locking the distal elements in a desired position, and may further include a step of unlocking the distal elements so that they are movable again.  
         [0042]     In a further aspect, a method according to the invention comprises advancing a catheter having a proximal end, a distal end and a fixation device near the distal end to a location within a body, wherein the fixation device includes a pair of distal elements each having an engagement surface; moving the distal elements to an open position wherein the distal elements extend radially outwardly facing the engagement surfaces toward a direction other than radially outwardly; and moving the distal elements to an inverted position wherein the engagement surfaces face radially outwardly.  
         [0043]     In still another aspect, the invention provides a method for fixing tissues together comprising advancing a catheter having a proximal end, a distal end and a fixation device disposed near the distal end to a location near the tissues, wherein the fixation device includes a pair of distal elements each having a removable implant pledget; moving the distal elements so that each implant pledget engages one of the tissues; penetrating each tissue and engaged implant pledget and passing a tie therethrough; fastening the ties to fix the tissues together; and removing the fixation device leaving the implant pledget in place.  
         [0044]     In an additional aspect of the invention, kits for performing an intervention at a tissue site in a patient&#39;s body include a fixation device and Instructions for Use setting forth the steps of using the fixation device according to the methods of the invention. The fixation device may be as described in any of the various examples set forth herein. The kits may further include a delivery tool or catheter for delivering the fixation device to the tissue site, as well as a tubular guide through which the delivery tool or catheter may be positioned.  
         [0045]     Other aspects of the nature and advantages of the invention are set forth in the detailed description set forth below, taken in conjunction with the drawings. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0046]      FIG. 1  illustrates the left ventricle and left atrium of the heart during systole.  
         [0047]      FIG. 2A  illustrates free edges of leaflets in normal coaptation, and  FIG. 2B  illustrates the free edges in regurgitative coaptation.  
         [0048]      FIG. 3A-3C  illustrate grasping of the leaflets with a fixation device, inversion of the distal elements of the fixation device and removal of the fixation device, respectively.  
         [0049]      FIG. 4  illustrates the position of the fixation device in a desired orientation relative to the leaflets.  
         [0050]      FIGS. 5A-5B ,  6 A- 6 B illustrate exemplary embodiments of coupling mechanisms of the instant application.  
         [0051]      FIGS. 7A-7D  illustrate an embodiment of a fixation device in various positions.  
         [0052]      FIGS. 8A-8B  illustrate an embodiment of the fixation device wherein some or all of the components are molded as one part.  
         [0053]      FIG. 9  illustrates another embodiment of the fixation device of the present invention.  
         [0054]      FIGS. 10A-10B ,  11 A- 11 B,  12 A- 12 B,  13 A- 13 B,  14 - 16  illustrate embodiments of a fixation device in various possible positions during introduction and placement of the device within the body to perform a therapeutic procedure.  
         [0055]      FIGS. 17A-17C  illustrate a covering on the fixation device wherein the device is in various positions.  
         [0056]      FIG. 18  illustrates an embodiment of the fixation device including proximal elements and a locking mechanism.  
         [0057]      FIG. 19  provides a cross-sectional view of the locking mechanism of  FIG. 18 .  
         [0058]      FIGS. 20-21  provide a cross-sectional view of the locking mechanism in the unlocked and locked positions respectively.  
         [0059]      FIGS. 22A-22B  illustrate a variation of the fixation device to facilitate capture of more widely-separated leaflets or other tissue flaps.  
         [0060]     FIGS.  23 ,  24 A- 24 B illustrate another embodiment of a locking mechanism.  
         [0061]     FIGS.  25 ,  26 A- 26 B illustrate yet another embodiment of a locking mechanism.  
         [0062]      FIGS. 27-28  illustrate an additional embodiment of the fixation device wherein separation of couplers rotate the distal elements around pins.  
         [0063]      FIGS. 29-30  illustrate the fixation device of  FIGS. 27-28  with additional features such as barbs and bumpers.  
         [0064]      FIG. 31  illustrates an embodiment of the fixation device having engagement surfaces with a serrated edge and wherein the fixation device is mounted for a ventricular approach to a mitral valve.  
         [0065]      FIGS. 32-34  illustrate an additional embodiment of the fixation device which allows tissue to be grasped between the distal elements and the proximal elements while in an arrangement wherein the distal elements are parallel to each other.  
         [0066]      FIGS. 35-39 ,  40 A- 40 D,  41 - 42 ,  43 A- 43 C illustrate another embodiment of the fixation device wherein the fixation device includes distal elements having implant pledgets.  
         [0067]      FIGS. 44A-44B ,  45 - 46  illustrate another embodiment of the fixation device wherein the distal elements are comprised of a semi-rigid material having a folded shape.  
         [0068]      FIG. 47  is a perspective view of an embodiment of a delivery catheter for a fixation device.  
         [0069]      FIG. 48  illustrates an embodiment of a fixation device coupled to the distal end of a delivery catheter.  
         [0070]      FIG. 49  illustrates a portion of the shaft of a delivery catheter and a fixation device which is coupleable with the catheter.  
         [0071]      FIGS. 50-52  are cross-sectional views of embodiments of the shaft of the delivery catheter.  
         [0072]      FIGS. 52A-52B  illustrate embodiments of the nose of the shaft of the delivery catheter.  
         [0073]      FIG. 53A-53C  illustrate various arrangements of lock lines engaging release harnesses of a locking mechanism.  
         [0074]      FIGS. 54A-54B  illustrate various arrangements of proximal element lines engaging proximal elements of a fixation device.  
         [0075]      FIG. 55  illustrates an embodiment of the handle of the delivery catheter.  
         [0076]      FIG. 56  is a cross-sectional view of the main body of the handle.  
         [0077]      FIG. 57  illustrates an embodiment of a lock line handle.  
         [0078]      FIG. 57A  illustrates the lock line handle of  FIG. 57  positioned within a semi-tube which is disposed within the sealed chamber.  
         [0079]      FIGS. 58A-58B  illustrate a mechanism for applying tension to lock lines.  
         [0080]     FIGS.  59 ,  59 A- 59 B illustrate features of the actuator rod control and handle.  
         [0081]      FIG. 60  is a perspective view of an embodiment of a multi-catheter guiding system of the present invention, and an interventional catheter positioned therethrough.  
         [0082]      FIG. 61A  illustrates a primary curvature in an outer guide catheter.  
         [0083]      FIG. 61B  illustrates a secondary curvature in an inner guide catheter.  
         [0084]      FIGS. 61C-61D  illustrate example movement of an inner guide catheter through angle thetas.  
         [0085]      FIG. 62A  is a perspective side view of a multi-catheter guiding system having an additional curve in the outer guide catheter.  
         [0086]      FIG. 62B  illustrates lifting of the outer guide catheter due to the additional curve of  FIG. 62A .  
         [0087]      FIGS. 63A-63D  illustrate a method of using the multi-catheter guiding system for accessing the mitral valve.  
         [0088]      FIGS. 64A-64D  illustrate curvature of a guide catheter of the present invention by the actuation of one or more pullwires.  
         [0089]      FIG. 64E  illustrates attachment of a pullwire to a tip ring.  
         [0090]      FIGS. 65A-65I  illustrate embodiments of the present invention comprising sections constructed with the inclusion of braiding or coil.  
         [0091]      FIGS. 66A-66C  illustrate a keying feature of the present invention.  
         [0092]      FIGS. 67A-67B  are perspective views of a guide catheter including a series of articulating members.  
         [0093]      FIG. 68  illustrates embodiments of the handles.  
         [0094]      FIG. 69  illustrates the handles of  FIG. 68  with a portion of the housing removed.  
         [0095]      FIG. 70  illustrates steering mechanisms within a handle.  
         [0096]      FIG. 71  illustrates attachment of a pullwire to a disk.  
         [0097]      FIGS. 72A-72B  illustrate a hard stop peg restricting rotation of a disk.  
         [0098]      FIGS. 73A-73C  illustrates a portion of a hard stop gear assembly.  
         [0099]      FIGS. 74A-74F  illustrate a ball restricting rotation of a disk.  
         [0100]      FIG. 75  illustrates an embodiment of a friction assembly.  
         [0101]      FIG. 76  illustrates an embodiment of an interventional system of the present invention.  
         [0102]      FIG. 76A  illustrates an embodiment of a hemostatic valve for use with the present invention.  
         [0103]      FIG. 76B  illustrates an embodiment of a fixation device introducer.  
         [0104]      FIG. 77  illustrates another embodiment of an interventional system of the present invention.  
         [0105]      FIGS. 78-80  illustrate an embodiment of a stabilizer base for use with the present invention.  
         [0106]      FIG. 81  illustrates a kit constructed in accordance with the principles of the present invention 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0000]     I. Cardiac Physiology  
         [0107]     The left ventricle LV of a normal heart H in systole is illustrated in  FIG. 1 . The left ventricle LV is contracting and blood flows outwardly through the tricuspid (aortic) valve AV in the direction of the arrows. Back flow of blood or “regurgitation” through the mitral valve MV is prevented since the mitral valve is configured as a “check valve” which prevents back flow when pressure in the left ventricle is higher than that in the left atrium LA. The mitral valve MV comprises a pair of leaflets having free edges FE which meet evenly to close, as illustrated in  FIG. 1 . The opposite ends of the leaflets LF are attached to the surrounding heart structure along an annular region referred to as the annulus AN. The free edges FE of the leaflets LF are secured to the lower portions of the left ventricle LV through chordae tendinae CT (referred to hereinafter as the chordae) which include plurality of branching tendons secured over the lower surfaces of each of the valve leaflets LF. The chordae CT in turn, are attached to the papillary muscles PM which extend upwardly from the lower portions of the left ventricle and intraventricular septum IVS.  
         [0108]     A number of structural defects in the heart can cause mitral valve regurgitation. Regurgitation occurs when the valve leaflets do not close properly allowing leakage from the ventricle into the atrium. As shown in  FIG. 2A , the free edges of the anterior and posterior leaflets normally meet along a line of coaptation C. An example of a defect causing regurgitation is shown in  FIG. 2B . Here an enlargement of the heart causes the mitral annulus to become enlarged, making it impossible for the free edges FE to meet during systole. This results in a gap G which allows blood to leak through the valve during ventricular systole. Ruptured or elongated chordae can also cause a valve leaflet to prolapse since inadequate tension is transmitted to the leaflet via the chordae. While the other leaflet maintains a normal profile, the two valve leaflets do not properly meet and leakage from the left ventricle into the left atrium will occur. Such regurgitation can also occur in patients who have suffered ischemic heart disease where the left ventricle does not contract sufficiently to effect proper closure.  
         [0000]     II. General Overview  
         [0109]     The present invention provides methods and devices for grasping, approximating and fixating tissues such as valve leaflets to treat cardiac valve regurgitation, particularly mitral valve regurgitation. The present invention also provides features that allow repositioning and removal of the device if so desired, particularly in areas where removal may be hindered by anatomical features such as chordae CT. Such removal would allow the surgeon to reapproach the valve in a new manner if so desired.  
         [0110]     Grasping will preferably be atraumatic providing a number of benefits. By atraumatic, it is meant that the devices and methods of the invention may be applied to the valve leaflets and then removed without causing any significant clinical impairment of leaflet structure or function. The leaflets and valve continue to function substantially the same as before the invention was applied. Thus, some minor penetration or denting of the leaflets may occur using the invention while still meeting the definition of “atraumatic”. This enables the devices of the invention to be applied to a diseased valve and, if desired, removed or repositioned without having negatively affected valve function. In addition, it will be understood that in some cases it may be necessary or desirable to pierce or otherwise permanently affect the leaflets during either grasping, fixing or both. In some of these cases, grasping and fixation may be accomplished by a single device. Although a number of embodiments are provided to achieve these results, a general overview of the basic features will be presented herein. Such features are not intended to limit the scope of the invention and are presented with the aim of providing a basis for descriptions of individual embodiments presented later in the application.  
         [0111]     The devices and methods of the invention rely upon the use of an interventional tool that is positioned near a desired treatment site and used to grasp the target tissue. In endovascular applications, the interventional tool is typically an interventional catheter. In surgical applications, the interventional tool is typically an interventional instrument. In preferred embodiments, fixation of the grasped tissue is accomplished by maintaining grasping with a portion of the interventional tool which is left behind as an implant. While the invention may have a variety of applications for tissue approximation and fixation throughout the body, it is particularly well adapted for the repair of valves, especially cardiac valves such as the mitral valve. Referring to  FIG. 3A , an interventional tool  10 , having a delivery device, such as a shaft  12 , and a fixation device  14 , is illustrated having approached the mitral valve MV from the atrial side and grasped the leaflets LF. The mitral valve may be accessed either surgically or by using endovascular techniques, and either by a retrograde approach through the ventricle or by an antegrade approach through the atrium, as described above. For illustration purposes, an antegrade approach is described.  
         [0112]     The fixation device  14  is releasably attached to the shaft  12  of the interventional tool  10  at its distal end. When describing the devices of the invention herein, “proximal” shall mean the direction toward the end of the device to be manipulated by the user outside the patient&#39;s body, and “distal” shall mean the direction toward the working end of the device that is positioned at the treatment site and away from the user. With respect to the mitral valve, proximal shall refer to the atrial or upstream side of the valve leaflets and distal shall refer to the ventricular or downstream side of the valve leaflets.  
         [0113]     The fixation device  14  typically comprises proximal elements  16  (or gripping elements) and distal elements  18  (or fixation elements) which protrude radially outward and are positionable on opposite sides of the leaflets LF as shown so as to capture or retain the leaflets therebetween. The proximal elements  16  are preferably comprised of cobalt chromium, nitinol or stainless steel, and the distal elements  18  are preferably comprised of cobalt chromium or stainless steel, however any suitable materials may be used. The fixation device  14  is coupleable to the shaft  12  by a coupling mechanism  17 . The coupling mechanism  17  allows the fixation device  14  to detach and be left behind as an implant to hold the leaflets together in the coapted position.  
         [0114]     In some situations, it may be desired to reposition or remove the fixation device  14  after the proximal elements  16 , distal elements  18 , or both have been deployed to capture the leaflets LF. Such repositioning or removal may be desired for a variety of reasons, such as to reapproach the valve in an attempt to achieve better valve function, more optimal positioning of the device  14  on the leaflets, better purchase on the leaflets, to detangle the device  14  from surrounding tissue such as chordae, to exchange the device  14  with one having a different design, or to abort the fixation procedure, to name a few. To facilitate repositioning or removal of the fixation device  14  the distal elements  18  are releasable and optionally invertible to a configuration suitable for withdrawal of the device  14  from the valve without tangling or interfering with or damaging the chordae, leaflets or other tissue.  FIG. 3B  illustrates inversion wherein the distal elements  18  are moveable in the direction of arrows  40  to an inverted position. Likewise, the proximal elements  16  may be raised, if desired. In the inverted position, the device  14  may be repositioned to a desired orientation wherein the distal elements may then be reverted to a grasping position against the leaflets as in  FIG. 3A . Alternatively, the fixation device  14  may be withdrawn (indicated by arrow  42 ) from the leaflets as shown in  FIG. 3C . Such inversion reduces trauma to the leaflets and minimizes any entanglement of the device with surrounding tissues. Once the device  14  has been withdrawn through the valve leaflets, the proximal and distal elements may be moved to a closed position or configuration suitable for removal from the body or for reinsertion through the mitral valve.  
         [0115]      FIG. 4  illustrates the position of the fixation device  14  in a desired orientation in relation to the leaflets LF. This is a short-axis view of the mitral valve MV from the atrial side, therefore, the proximal elements  16  are shown in solid line and the distal elements  18  are shown in dashed line. The proximal and distal elements  16 ,  18  are positioned to be substantially perpendicular to the line of coaptation C. The device  14  may be moved roughly along the line of coaptation to the location of regurgitation. The leaflets LF are held in place so that during diastole, as shown in  FIG. 4 , the leaflets LF remain in position between the elements  16 ,  18  surrounded by openings  0  which result from the diastolic pressure gradient. Advantageously, leaflets LF are coapted such that their proximal or upstream surfaces are facing each other in a vertical orientation, parallel to the direction of blood flow through mitral valve MV. The upstream surfaces may be brought together so as to be in contact with one another or may be held slightly apart, but will preferably be maintained in the vertical orientation in which the upstream surfaces face each other at the point of coaptation. This simulates the double orifice geometry of a standard surgical bow-tie repair. Color Doppler echo will show if the regurgitation of the valve has been reduced. If the resulting mitral flow pattern is satisfactory, the leaflets may be fixed together in this orientation. If the resulting color Doppler image shows insufficient improvement in mitral regurgitation, the interventional tool  10  may be repositioned. This may be repeated until an optimal result is produced wherein the leaflets LF are held in place.  
         [0116]     Once the leaflets are coapted in the desired arrangement, the fixation device  14  is then detached from the shaft  12  and left behind as an implant to hold the leaflets together in the coapted position. As mentioned previously, the fixation device  14  is coupled to the shaft  12  by a coupling mechanism  17 .  FIGS. 5A-5B ,  6 A- 6 B illustrate exemplary embodiments of such coupling mechanisms.  FIG. 5A  shows an upper shaft  20  and a detachable lower shaft  22  which are interlocked at a joining line or mating surface  24 . The mating surface  24  may have any shape or curvature which will allow or facilitate interlocking and later detachment. A snuggly fitting outer sheath  26  is positioned over the shafts  20 ,  22  to cover the mating surface  24  as shown.  FIG. 5B  illustrates detachment of the lower shaft  22  from the upper shaft  20 . This is achieved by retracting the outer sheath  26 , so that the mating surface  24  is exposed, which allows the shafts  20 ,  22  to separate.  
         [0117]     Similarly,  FIG. 6A  illustrates a tubular upper shaft  28  and a detachable tubular lower shaft  30  which are interlocked at a mating surface  32 . Again, the mating surface  32  may have any shape or curvature which will allow or facilitate interlocking and later detachment. The tubular upper shaft  28  and tubular lower shaft  30  form an outer member having an axial channel. A snuggly fitting rod  34  or inner member is inserted through the tubular shafts  28 ,  30  to bridge the mating surface  32  as shown.  FIG. 6B  illustrates detachment of the lower shaft  30  from the upper shaft  28 . This is achieved by retracting the rod  34  to a position above the mating surface  32  which in turn allows the shafts  28 ,  30  to separate. Other examples of coupling mechanisms are described and illustrated in commonly assigned U.S. Pat. No. 6,752,813 (Attorney Docket No. 020489-000400US), incorporated herein by reference for all purposes.  
         [0118]     In a preferred embodiment, mating surface  24  (or mating surface  32 ) is a sigmoid curve defining a male element and female element on upper shaft  20  (or upper shaft  28 ) which interlock respectively with corresponding female and male elements on lower shaft  22  (or lower shaft  30 ). Typically, the lower shaft is the coupling mechanism  17  of the fixation device  14 . Therefore, the shape of the mating surface selected will preferably provide at least some mating surfaces transverse to the axial axis of the a mechanism  19  to facilitate application of compressive and tensile forces through the coupling mechanism  17  to the fixation device  14 , yet causing minimal interference when the fixation device  14  is to be released from the upper shaft.  
         [0000]     III. Fixation Device  
         [0119]     A. Introduction and Placement of Fixation Device  
         [0120]     The fixation device  14  is delivered to the valve or the desired tissues with the use of a delivery device. The delivery device may be rigid or flexible depending on the application. For endovascular applications, the delivery device comprises a flexible delivery catheter which will be described in later sections. Typically, however, such a catheter comprises a shaft, having a proximal end and a distal end, and a fixation device releasably attached to its distal end. The shaft is usually elongate and flexible, suitable for intravascular introduction. Alternatively, the delivery device may comprise a shorter and less flexible interventional instrument which may be used for trans-thoracic surgical introduction through the wall of the heart, although some flexibility and a minimal profile will generally be desirable. A fixation device is releasably coupleable with the delivery device as illustrated in  FIG. 3A . The fixation device may have a variety of forms, a few embodiments of which will be described herein.  
         [0121]      FIGS. 7A-7D  illustrate an embodiment of a fixation device  14  in various positions or configurations.  FIG. 7A  illustrates the fixation device  14  in a closed configuration for delivery through the patient&#39;s vasculature and, in this example, through the mitral valve. The fixation device  14  includes a coupling member  19  which allows detachment of the fixation device  14  for implantation. In this example, the coupling member  19  is shown to include the lower shaft  22  and mating surface  24  of  FIGS. 5A-5B , and therefore the coupling member  19  would function similarly as described above. The fixation device  14  also includes a pair of opposed distal elements  18 , each distal element  18  having an engagement surface  50  facing inwardly toward the opposed distal element  18  in the closed configuration. Distal elements  18  preferably comprise elongate arms  53 , each arm having a proximal end  52  rotatably connected to the coupling member  19  and a free end  54 . Suitable connections for arms  53  to coupling member  19  include pins, living hinges, or other known rotational connection mechanisms. In the closed configuration of  FIG. 7A , free ends  54  point in a first direction such that the arms  53  and engagement surfaces  50  are nearly parallel to each other and to an axis  21 , and preferably are angled slightly inwardly toward each other. In a preferred embodiment, when tissue is not present between arms  53 , the arms  53  may be closed until free ends  54  either touch each other or engage shaft  12  when fixation device  14  is attached thereto, thereby minimizing the profile of the fixation device  14  for passage through a delivery device.  
         [0122]      FIGS. 7B-7C  illustrate the fixation device  14  in an open position wherein the engagement surfaces  50  are disposed at a separation angle  56  apart, wherein the separation angle  56  is typically up to approximately 180 degrees, preferably up to 90-180 degrees, and arms  53  are disposed generally symmetrically relative to axis  21 . The arms  53  may be moveable to the open position by a variety of actuation mechanisms. For example, a plunger or actuator rod may be advanced through the coupling member  19 , as indicated by arrow  62 , so as to engage a spring or spring loaded actuation mechanism  58  which is attached to the distal elements  18 . By exerting a force against the actuation mechanism  58 , the distal elements  18  are rotated relative to coupling member  19 . The distal elements  18  may be held in this open position by the actuator rod against the resistance provided by the spring of the actuation mechanism  58  which biases the distal elements  18  toward the closed position of  FIG. 7A  when the distal elements  18  are less than 180 degrees apart. The spring loading of the actuation mechanism  58  resists outward movement of the actuation mechanism  58  and urges the device  14  towards the closed position.  
         [0123]     In this embodiment, proximal elements  16  comprise resilient loop-shaped wire forms biased outwardly and attached to the coupling member  19  so as to be biased to an open position shown in  FIG. 7C  but moveable rotationally inwardly when arms  53  are closed. The wire forms may be flexible enough to be rigidly attached to coupling member  19  and resiliently deflectable inwardly, or they may be attached by a rotational coupling such as a pin or living hinge. In use, leaflets LF are positioned between the proximal elements  16  and distal elements  18 . Once, the leaflets LF are positioned between the proximal and distal elements  16 ,  18 , the distal elements  18  may be closed, compressing the leaflets between engagement surfaces  50  and proximal elements  18 . Depending upon the thickness of the leaflets, the arrangements of the leaflets, the position of the fixation device on the leaflets and other factors, the arms  53  may be maintained in the open position of  FIG. 7B , moved to the fully closed position of  FIG. 7A , or placed in any of various positions in between so as to coapt the leaflets LF and hold them in the desired position with the desired degree of force. In any case, the fixation device  14  will remain in place as an implant following detachment from the delivery catheter.  
         [0124]     In some situations, as previously mentioned, it may be desirable to reopen the fixation device  14  following initial placement. To reopen the device  14 , the actuator rod may be readvanced or reinserted through the coupling member  19  and readvanced to press against the actuation mechanism  58 , as previously indicated by arrow  62  in  FIG. 7B . Again, such advancement applies a force against the actuation mechanism  58  in the manner described above thus moving arms  53  outwardly to release force against leaflets and move engagement surfaces  50  away from proximal elements  16 . The leaflets are then free to move relative to fixation device  14 . The fixation device  14  may then be repositioned as desired and the actuator rod retracted to reclose the distal elements  18  to coapt the leaflets.  
         [0125]     Under some circumstances, it may be further desirable to withdraw the fixation device  14  back through the valve or completely from the patient following initial insertion through the valve. Should this be attempted with the clip in the closed or open positions illustrated in  FIGS. 7A-7C , there may be a risk that arms  53  could interfere or become entangled with the chordae, leaflets or other tissues. To avoid this, the fixation element  14  is preferably adapted for inversion of arms  53  so that free ends  54  point in a second direction, opposite to the first direction in which the free ends  54  pointed in the closed position, each arm  53  forming an obtuse angle relative to axis  21  as illustrated in  FIG. 7D . The arms  53  may be rotated so that the engagement surfaces  50  are disposed at a separation angle  56  of up to 360 degrees, and preferably at least up to 270 degrees. This may be accomplished by exerting a force against actuation mechanism  58  with a push rod or plunger extending through coupling member  19  as described above. In this embodiment, once the distal elements  18  have rotated beyond 180 degrees apart, the spring loading of the actuation mechanism  58  biases the distal elements  18  toward the inverted position. The spring loading of the actuation mechanism  58  resists outward movement of the actuation mechanism  58  and urges the device  14  towards the inverted position.  
         [0126]     With arms  53  in the inverted position, engagement surfaces  50  provide an atraumatic surface deflect tissues as the fixation device is withdrawn. This allows the device to be retracted back through the valve annulus without risk of injury to valvular and other tissues. In some cases, once the fixation device  14  has been pulled back through the valve, it will be desirable to return the device to the closed position for withdrawal of the device from the body (either through the vasculature or through a surgical opening).  
         [0127]     The embodiment illustrated in  FIGS. 7A-7D  is assembled from separate components composed of biocompatible materials. The components may be formed from the same or different materials, including but not limited to stainless steel or other metals, Elgiloy®, nitinol, titanium, tantalum, metal alloys or polymers. Additionally, some or all of these components may be made of bioabsorbable materials that will be absorbed by surrounding tissues or will dissolve into the bloodstream following implantation. It has been found that in mitral valve repair applications the fixation devices of the invention are completely surrounded by tissue within a few months of implantation, after which the devices could dissolve or be absorbed without negative impact to the repair.  
         [0128]     In a further embodiment, some or all of the components may be molded as one part, as illustrated in  FIGS. 8A-8B . Here, the coupling member  19 , distal elements  18  and actuation mechanism  58  of the fixation device  14  are all molded from a polymer material as one moveable piece.  FIG. 8A  shows the fixation device  14  in the open position. Advancement of an actuator rod  64  rotates the distal elements  18  relative to the coupling member  19  by a living hinge or by elastic deformation of the plastic at the point of connection between the elements  18  and the coupling member  19 . Typically, this point of connection comprises a thinner segment of polymer to facilitate such bending. Likewise, the actuation mechanism  58  coupled to the distal elements  18  in the same manner.  FIG. 8B  shows the fixation device  14  in the inverted position.  
         [0129]      FIG. 9  illustrates another embodiment of a fixation device  14 . Here, the fixation device  14  is shown coupled to a shaft  12  to form an interventional tool  10 . The fixation device  14  includes a coupling member  19  and a pair of opposed distal elements  18 . The distal elements  18  comprise elongate arms  53 , each arm having a proximal end  52  rotatably connected to the coupling member  19  and a free end  54 . The free ends  54  have a rounded shape to minimize interference with and trauma to surrounding tissue structures. Preferably, each free end  54  defines a curvature about two axes, one being an axis  66  perpendicular to longitudinal axis of arms  53 . Thus, the engagement surfaces  50  have a cupped or concave shape to surface area in contact with tissue and to assist in grasping and holding the valve leaflets. This further allows arms  53  to nest around the shaft  12  in the closed position to minimize the profile of the device. Preferably, arms  53  are at least partially cupped or curved inwardly about their longitudinal axes  66 . Also, preferably, each free end  54  defines a curvature about an axis  67  perpendicular to axis  66  or the longitudinal axis of arms  53 . This curvature is a reverse curvature along the most distal portion of the free end  54 . Likewise, the longitudinal edges of the free ends  54  may flare outwardly. Both the reverse curvature and flaring minimize trauma to the tissue engaged therewith.  
         [0130]     In a preferred embodiment suitable for mitral valve repair, the transverse width across engagement surfaces  50  (which determines the width of tissue engaged) is at least about 2 mm, usually 3-10 mm, and preferably about 4-6 mm. In some situations, a wider engagement is desired wherein the engagement surfaces  50  are larger, for example about 2 cm, or multiple fixation devices are used adjacent to each other. Arms  53  and engagement surfaces  50  are configured to engage a length of tissue of about 4-10 mm, and preferably about 6-8 mm along the longitudinal axis of arms  53 . Arms  53  further include a plurality of openings to enhance grip and to promote tissue ingrowth following implantation.  
         [0131]     The valve leaflets are grasped between the distal elements  18  and proximal elements  16 . In some embodiments, the proximal elements  16  are flexible, resilient, and cantilevered from coupling member  19 . The proximal elements are preferably resiliently biased toward the distal elements. Each proximal element  16  is shaped and positioned to be at least partially recessed within the concavity of the distal element  18  when no tissue is present. When the fixation device  14  is in the open position, the proximal elements  16  are shaped such that each proximal element  16  is separated from the engagement surface  50  near the proximal end  52  of arm  53  and slopes toward the engagement surface  50  near the free end  54  with the free end of the proximal element contacting engagement surface  50 , as illustrated in  FIG. 9 . This shape of the proximal elements  16  accommodates valve leaflets or other tissues of varying thicknesses.  
         [0132]     Proximal elements  16  include a plurality of openings  63  and scalloped side edges  61  to increase grip on tissue. The proximal elements  16  optionally include frictional accessories, frictional features or grip-enhancing elements to assist in grasping and/or holding the leaflets. In preferred embodiments, the frictional accessories comprise barbs  60  having tapering pointed tips extending toward engagement surfaces  50 . It may be appreciated that any suitable frictional accessories may be used, such as prongs, windings, bands, barbs, grooves, channels, bumps, surface roughening, sintering, high-friction pads, coverings, coatings or a combination of these. Optionally, magnets may be present in the proximal and/or distal elements. It may be appreciated that the mating surfaces will be made from or will include material of opposite magnetic charge to cause attraction by magnetic force. For example, the proximal elements and distal elements may each include magnetic material of opposite charge so that tissue is held under constant compression between the proximal and distal elements to facilitate faster healing and ingrowth of tissue. Also, the magnetic force may be used to draw the proximal elements  16  toward the distal elements  18 , in addition to or alternatively to biasing of the proximal elements toward the distal elements. This may assist in deployment of the proximal elements  16 . In another example, the distal elements  18  each include magnetic material of opposite charge so that tissue positioned between the distal elements  18  is held therebetween by magnetic force.  
         [0133]     The proximal elements  16  may be covered with a fabric or other flexible material as described below to enhance grip and tissue ingrowth following implantation. Preferably, when fabrics or coverings are used in combination with barbs or other frictional features, such features will protrude through such fabric or other covering so as to contact any tissue engaged by proximal elements  16 .  
         [0134]     In an exemplary embodiment, proximal elements  16  are formed from metallic sheet of a spring-like material using a stamping operation which creates openings  63 , scalloped edges  61  and barbs  60 . Alternatively, proximal elements  16  could be comprised of a spring-like material or molded from a biocompatible polymer. It should be noted that while some types of frictional accessories that can be used in the present invention may permanently alter or cause some trauma to the tissue engaged thereby, in a preferred embodiment, the frictional accessories will be atraumatic and will not injure or otherwise affect the tissue in a clinically significant way. For example, in the case of barbs  60 , it has been demonstrated that following engagement of mitral valve leaflets by fixation device  14 , should the device later be removed during the procedure barbs  60  leave no significant permanent scarring or other impairment of the leaflet tissue and are thus considered atraumatic.  
         [0135]     The fixation device  14  also includes an actuation mechanism  58 . In this embodiment, the actuation mechanism  58  comprises two link members or legs  68 , each leg  68  having a first end  70  which is rotatably joined with one of the distal elements  18  at a riveted joint  76  and a second end  72  which is rotatably joined with a stud  74 . The legs  68  are preferably comprised of a rigid or semi-rigid metal or polymer such as Elgiloy®, cobalt chromium or stainless steel, however any suitable material may be used. While in the embodiment illustrated both legs  68  are pinned to stud  74  by a single rivet  78 , it may be appreciated, however, that each leg  68  may be individually attached to the stud  74  by a separate rivet or pin. The stud  74  is joinable with an actuator rod  64  (not shown) which extends through the shaft  12  and is axially extendable and retractable to move the stud  74  and therefore the legs  68  which rotate the distal elements  18  between closed, open and inverted positions. Likewise, immobilization of the stud  74  holds the legs  68  in place and therefore holds the distal elements  18  in a desired position. The stud  74  may also be locked in place by a locking feature which will be further described in later sections.  
         [0136]     In any of the embodiments of fixation device  14  disclosed herein, it may be desirable to provide some mobility or flexibility in distal elements  18  and/or proximal elements  16  in the closed position to enable these elements to move or flex with the opening or closing of the valve leaflets. This provides shock absorption and thereby reduces force on the leaflets and minimizes the possibility for tearing or other trauma to the leaflets. Such mobility or flexibility may be provided by using a flexible, resilient metal or polymer of appropriate thickness to construct the distal elements  18 . Also, the locking mechanism of the fixation device (described below) may be constructed of flexible materials to allow some slight movement of the proximal and distal elements even when locked. Further, the distal elements  18  can be connected to the coupling mechanism  19  or to actuation mechanism  58  by a mechanism that biases the distal element into the closed position (inwardly) but permits the arms to open slightly in response to forces exerted by the leaflets. For example, rather than being pinned at a single point, these components may be pinned through a slot that allowed a small amount of translation of the pin in response to forces against the arms. A spring is used to bias the pinned component toward one end of the slot.  
         [0137]      FIGS. 10A-10B ,  11 A- 11 B,  12 A- 12 B,  13 A- 13 B, and  FIGS. 14-16  illustrate embodiments of the fixation device  14  of  FIG. 9  in various possible positions during introduction and placement of the device  14  within the body to perform a therapeutic procedure.  FIG. 10A  illustrates an embodiment of an interventional tool  10  delivered through a catheter  86 . It may be appreciated that the interventional tool  10  may take the form of a catheter, and likewise, the catheter  86  may take the form of a guide catheter or sheath. However, in this example the terms interventional tool  10  and catheter  86  will be used. The interventional tool  10  comprises a fixation device  14  coupled to a shaft  12  and the fixation device  14  is shown in the closed position.  FIG. 10B  illustrates a similar embodiment of the fixation device of  FIG. 10A  in a larger view. In the closed position, the opposed pair of distal elements  18  are positioned so that the engagement surfaces  50  face each other. Each distal element  18  comprises an elongate arm  53  having a cupped or concave shape so that together the arms  53  surround the shaft  12  and optionally contact each other on opposite sides of the shaft. This provides a low profile for the fixation device  14  which is readily passable through the catheter  86  and through any anatomical structures, such as the mitral valve. In addition,  FIG. 10B  further includes an actuation mechanism  58 . In this embodiment, the actuation mechanism  58  comprises two legs  68  which are each movably coupled to a base  69 . The base  69  is joined with an actuator rod  64  which extends through the shaft  12  and is used to manipulate the fixation device  14 . In some embodiments, the actuator rod  64  attaches directly to the actuation mechanism  58 , particularly the base  69 . However, the actuator rod  64  may alternatively attach to a stud  74  which in turn is attached to the base  69 . In some embodiments, the stud  74  is threaded so that the actuator rod  64  attaches to the stud  74  by a screw-type action. However, the rod  64  and stud  74  may be joined by any mechanism which is releasable to allow the fixation device  14  to be detached from shaft  12 .  
         [0138]      FIGS. 11A-11B  illustrate the fixation device  14  in the open position. In the open position, the distal elements  18  are rotated so that the engagement surfaces  50  face a first direction. Distal advancement of the stud  74  relative to coupling member  19  by action of the actuator rod  64  applies force to the distal elements  18  which begin to rotate around joints  76  due to freedom of movement in this direction. Such rotation and movement of the distal elements  18  radially outward causes rotation of the legs  68  about joints  80  so that the legs  68  are directly slightly outwards. The stud  74  may be advanced to any desired distance correlating to a desired separation of the distal elements  18 . In the open position, engagement surfaces  50  are disposed at an acute angle relative to shaft  12 , and are preferably at an angle of between 90 and 180 degrees relative to each other. In one embodiment, in the open position the free ends  54  of arms  53  have a span therebetween of about 10-20 mm, usually about 12-18 mm, and preferably about 14-16 mm.  
         [0139]     Proximal elements  16  are typically biased outwardly toward arms  53 . The proximal elements  16  may be moved inwardly toward the shaft  12  and held against the shaft  12  with the aid of proximal element lines  90  which can be in the form of sutures, wires, nitinol wire, rods, cables, polymeric lines, or other suitable structures. The proximal element lines  90  may be connected with the proximal elements  16  by threading the lines  90  in a variety of ways. When the proximal elements  16  have a loop shape, as shown in  FIG. 11A , the line  90  may pass through the loop and double back. When the proximal elements  16  have an elongate solid shape, as shown in  FIG. 11B , the line  90  may pass through one or more of the openings  63  in the element  16 . Further, a line loop  48  may be present on a proximal element  16 , also illustrated in  FIG. 11B , through which a proximal element line  90  may pass and double back. Such a line loop  48  may be useful to reduce friction on proximal element line  90  or when the proximal elements  16  are solid or devoid of other loops or openings through which the proximal element lines  90  may attach. A proximal element line  90  may attach to the proximal elements  16  by detachable means which would allow a single line  90  to be attached to a proximal element  16  without doubling back and would allow the single line  90  to be detached directly from the proximal element  16  when desired. Examples of such detachable means include hooks, snares, clips or breakable couplings, to name a few. By applying sufficient tension to the proximal element line  90 , the detachable means may be detached from the proximal element  16  such as by breakage of the coupling. Other mechanisms for detachment may also be used. Similarly, a lock line  92  may be attached and detached from a locking mechanism by similar detachable means.  
         [0140]     In the open position, the fixation device  14  can engage the tissue which is to be approximated or treated. The embodiment illustrated in  FIGS. 9-11  is adapted for repair of the mitral valve using an antegrade approach from the left atrium. The interventional tool  10  is advanced through the mitral valve from the left atrium to the left ventricle. The distal elements  18  are oriented to be perpendicular to the line of coaptation and then positioned so that the engagement surfaces  50  contact the ventricular surface of the valve leaflets, thereby grasping the leaflets. The proximal elements  16  remain on the atrial side of the valve leaflets so that the leaflets lie between the proximal and distal elements. In this embodiment, the proximal elements  16  have frictional accessories, such as barbs  60  which are directed toward the distal elements  18 . However, neither the proximal elements  16  nor the barbs  60  contact the leaflets at this time.  
         [0141]     The interventional tool  10  may be repeatedly manipulated to reposition the fixation device  14  so that the leaflets are properly contacted or grasped at a desired location. Repositioning is achieved with the fixation device in the open position. In some instances, regurgitation may also be checked while the device  14  is in the open position. If regurgitation is not satisfactorily reduced, the device may be repositioned and regurgitation checked again until the desired results are achieved.  
         [0142]     It may also be desired to invert the fixation device  14  to aid in repositioning or removal of the fixation device  14 .  FIGS. 12A-12B  illustrate the fixation device  14  in the inverted position. By further advancement of stud  74  relative to coupling member  19 , the distal elements  18  are further rotated so that the engagement surfaces  50  face outwardly and free ends  54  point distally, with each arm  53  forming an obtuse angle relative to shaft  12 . The angle between arms  53  is preferably in the range of about 270 to 360 degrees. Further advancement of the stud  74  further rotates the distal elements  18  around joints  76 . This rotation and movement of the distal elements  18  radially outward causes rotation of the legs  68  about joints  80  so that the legs  68  are returned toward their initial position, generally parallel to each other. The stud  74  may be advanced to any desired distance correlating to a desired inversion of the distal elements  18 . Preferably, in the fully inverted position, the span between free ends  54  is no more than about 20 mm, usually less than about 16 mm, and preferably about 12-14 mm. In this illustration, the proximal elements  16  remain positioned against the shaft  12  by exerting tension on the proximal element lines  90 . Thus, a relatively large space may be created between the elements  16 ,  18  for repositioning. In addition, the inverted position allows withdrawal of the fixation device  14  through the valve while minimizing trauma to the leaflets. Engagement surfaces  50  provide an atraumatic surface for deflecting tissue as the fixation device is retracted proximally. It should be further noted that barbs  60  are angled slightly in the distal direction (away from the free ends of the proximal elements  16 ), reducing the risk that the barbs will catch on or lacerate tissue as the fixation device is withdrawn.  
         [0143]     Once the fixation device  14  has been positioned in a desired location against the valve leaflets, the leaflets may then be captured between the proximal elements  16  and the distal elements  18 .  FIGS. 13A-13B  illustrate the fixation device  14  in such a position. Here, the proximal elements  16  are lowered toward the engagement surfaces  50  so that the leaflets are held therebetween. In  FIG. 13B , the proximal elements  16  are shown to include barbs  60  which may be used to provide atraumatic gripping of the leaflets. Alternatively, larger, more sharply pointed barbs or other penetration structures may be used to pierce the leaflets to more actively assist in holding them in place. This position is similar to the open position of  FIGS. 11A-11B , however the proximal elements  16  are now lowered toward arms  53  by releasing tension on proximal element lines  90  to compress the leaflet tissue therebetween. At any time, the proximal elements  16  may be raised and the distal elements  18  adjusted or inverted to reposition the fixation device  14 , if regurgitation is not sufficiently reduced.  
         [0144]     After the leaflets have been captured between the proximal and distal elements  16 ,  18  in a desired arrangement, the distal elements  18  may be locked to hold the leaflets in this position or the fixation device  14  may be returned to or toward a closed position. Such locking will be described in a later section.  FIG. 14  illustrates the fixation device  14  in the closed position wherein the leaflets (not shown) are captured and coapted. This is achieved by retraction of the stud  74  proximally relative to coupling member  19  so that the legs  68  of the actuation mechanism  58  apply an upwards force to the distal elements  18  which in turn rotate the distal elements  18  so that the engagement surfaces  50  again face one another. The released proximal elements  16  which are biased outwardly toward distal elements  18  are concurrently urged inwardly by the distal elements  18 . The fixation device  14  may then be locked to hold the leaflets in this closed position as described below.  
         [0145]     As shown in  FIG. 15 , the fixation device  14  may then be released from the shaft  12 . As mentioned, the fixation device  14  is releasably coupleable to the shaft  12  by coupling member  19 .  FIG. 15  illustrates the coupling structure, a portion of the shaft  12  to which the coupling member  19  of the fixation device  14  attaches. As shown, the proximal element lines  90  may remain attached to the proximal elements  16  following detachment from shaft  12  to function as a tether to keep the fixation device  14  connected with the catheter  86 . Optionally, a separate tether coupled between shaft  12  and fixation device  14  may be used expressly for this purpose while the proximal element lines  90  are removed. In any case, the repair of the leaflets or tissue may be observed by non-invasive visualization techniques, such as echocardiography, to ensure the desired outcome. If the repair is not desired, the fixation device  14  may be retrieved with the use of the tether or proximal element lines  90  so as to reconnect coupling member  19  with shaft  12 .  
         [0146]     In an exemplary embodiments, proximal element lines  90  are elongated flexible threads, wire, cable, sutures or lines extending through shaft  12 , looped through proximal elements  16 , and extending back through shaft  12  to its proximal end. When detachment is desired, one end of each line may be released at the proximal end of the shaft  12  and the other end pulled to draw the free end of the line distally through shaft  12  and through proximal element  16  thereby releasing the fixation device.  
         [0147]      FIG. 16  illustrates a released fixation device  14  in a closed position. As shown, the coupling member  19  remains separated from the shaft  12  of the interventional tool  10  and the proximal elements  16  are deployed so that tissue (not shown) may reside between the proximal elements  16  and distal elements  18 .  
         [0148]     While the above described embodiments of the invention utilize a push-to-open, pull-to-close mechanism for opening and closing distal elements  18 , it should be understood that a pull-to-open, push-to-close mechanism is equally possible. For example, distal elements  18  may be coupled at their proximal ends to stud  74  rather than to coupling member  19 , and legs  68  may be coupled at their proximal ends to coupling member  19  rather than to stud  74 . In this example, when stud  74  is pushed distally relative to coupling member  19 , distal elements  18  would close, while pulling on stud  74  proximally toward coupling member  19  would open distal elements  18 .  
         [0149]     B. Covering on Fixation Device  
         [0150]     The fixation device  14  may optionally include a covering. The covering may assist in grasping the tissue and may later provide a surface for tissue ingrowth. Ingrowth of the surrounding tissues, such as the valve leaflets, provides stability to the device  14  as it is further anchored in place and may cover the device with native tissue thus reducing the possibility of immunologic reactions. The covering may be comprised of any biocompatible material, such as polyethylene terepthalate, polyester, cotton, polyurethane, expanded polytetrafluoroethylene (ePTFE), silicon, or various polymers or fibers and have any suitable form, such as a fabric, mesh, textured weave, felt, looped or porous structure. Generally, the covering has a low profile so as not to interfere with delivery through an introducer sheath or with grasping and coapting of leaflets or tissue.  
         [0151]      FIGS. 17A-17C  illustrate a covering  100  on the fixation device  14  wherein the device  14  is in various positions.  FIG. 17A  shows the covering  100  encapsulating the distal elements  18  and the actuation mechanism  58  while the device  14  is in the open position. Thus, the engagement surfaces  50  are covered by the covering  100  which helps to minimize trauma on tissues and provides additional friction to assist in grasping and retaining tissues.  FIG. 17B  shows the device  14  of  FIG. 17A  in the inverted position. The covering  100  is loosely fitted and/or is flexible or elastic such that the device  14  can freely move to various positions and the covering  100  conforms to the contours of the device  14  and remains securely attached in all positions.  FIG. 17C  shows the device  14  in the closed position. Thus, when the fixation device  14  is left behind as an implant in the closed position, the exposed surfaces of the device  14  are substantially covered by the covering  100 . It may be appreciated that the covering  100  may cover specific parts of the fixation device  14  while leaving other parts exposed. For example, the covering  100  may comprise sleeves that fit over the distal elements  18  and not the actuation mechanism  58 , caps that fit over the distal ends  54  of the distal elements  18  or pads that cover the engagement surfaces  50 , to name a few. It may be appreciated that, the covering  100  may allow any frictional accessories, such as barbs, to be exposed. Also, the covering  100  may cover the proximal elements  16  and/or any other surfaces of the fixation device  14 . In any case, the covering  100  should be durable to withstand multiple introduction cycles and, when implanted within a heart, a lifetime of cardiac cycles.  
         [0152]     The covering  100  may alternatively be comprised of a polymer or other suitable materials dipped, sprayed, coated or otherwise adhered to the surfaces of the fixation device  14 . Optionally, the polymer coating may include pores or contours to assist in grasping the tissue and/or to promote tissue ingrowth.  
         [0153]     Any of the coverings  100  may optionally include drugs, antibiotics, anti-thrombosis agents, or anti-platelet agents such as heparin, COUMADIN® (Warfarin Sodium), to name a few. These agents may, for example, be impregnated in or coated on the coverings  100 . These agents may then be delivered to the grasped tissues surrounding tissues and/or bloodstream for therapeutic effects.  
         [0154]     C. Fixation Device Locking Mechanisms  
         [0155]     As mentioned previously, the fixation device  14  optionally includes a locking mechanism for locking the device  14  in a particular position, such as an open, closed or inverted position or any position therebetween. It may be appreciated that the locking mechanism includes an unlocking mechanism which allows the device to be both locked and unlocked.  FIGS. 18-21  illustrate an embodiment of a locking mechanism  106 . Referring to  FIG. 18 , in this embodiment, the locking mechanism  106  is disposed between the coupling member  19  and the base  69  of the actuation mechanism  58 . The base  69  is fixedly attached to the stud  74  which extends through the locking mechanism  106 . The stud  74  is releasably attached to the actuator rod  64  which passes through the coupling member  19  and the shaft  12  of the interventional tool  10 . The base  69  is also connected to the legs  68  of the actuation mechanism  58  which are in turn connected to the distal elements  18 .  
         [0156]      FIG. 18  also illustrates the proximal elements  16 , which in this embodiment straddle the locking mechanism and join beneath the locking mechanism  106 . The proximal elements  16  are shown supported by proximal element lines  90 . The proximal elements  16  are raised and lowered by manipulation of the proximal element lines  90 . In addition, lock lines  92  are shown connected with a release harness  108  of the locking mechanism  106 . The lock lines  92  are used to lock and unlock the locking mechanism  106  as will be described below. The proximal element lines  90  and lock lines  92  may be comprised of any suitable material, typically wire, nitinol wire, cable, suture or thread, to name a few. In addition, the proximal element lines  90  and/or lock lines  92  may include a coating, such as parylene. Parylene is a vapor deposited pinhole free protective film which is conformal and biocompatible. It is inert and protects against moisture, chemicals, and electrical charge.  
         [0157]      FIG. 19  provides a front view of the locking mechanism  106  of  FIG. 18 . However, here the proximal elements  16  are supported by a single proximal element line  90  which is through both of the proximal elements  16 . In this arrangement both of the elements are raised and lowered simultaneously by action of a single proximal element line  90 . Whether the proximal elements  16  are manipulated individually by separate proximal element lines  90  or jointly by a single proximal element line  90 , the proximal element lines  90  may extend directly through openings in the proximal elements and/or through a layer or portion of a covering  100  on the proximal elements, or through a suture loop above or below a covering  100 .  
         [0158]      FIGS. 20-21  illustrate the locking mechanism  106  showing the locking mechanism  106  in the unlocked and locked positions respectively. Referring to  FIG. 20 , the locking mechanism  106  includes one or more wedging elements, such as rolling elements. In this embodiment, the rolling elements comprise a pair of barbells  110  disposed on opposite sides of the stud  74 , each barbell having a pair of generally cylindrical caps and a shaft therebetween. The barbells  110  and the stud  74  are preferably comprised of cobalt chromium or stainless steel, however any suitable material may be used. The barbells  110  are manipulated by hooked ends  112  of the release harness  108 . When an upwards force is applied to the harness  108  by the lock line  92  (illustrated in  FIG. 18 ), the hooked ends  112  raise the barbells  110  against a spring  114 , as shown in  FIG. 20 . This draws the barbells  110  up along a sidewall or sloping surface  116  which unwedges the barbells  110  from against the stud  74 . In this position, the stud  74  is free to move. Thus, when the lock line  92  raises or lifts the harness  108 , the locking mechanism  106  is in an unlocked position wherein the stud  74  is free to move the actuation mechanism  58  and therefore the distal elements  18  to any desired position. Release of the harness  108  by the lock line  92  transitions the locking mechanism  106  to a locked position, illustrated in  FIG. 21 . By releasing the upwards force on the barbells  110  by the hooked ends  112 , the spring  114  forces the barbells  110  downwards and wedges the barbells  110  between the sloping surface  116  and the stud  74 . This restricts motion of the stud  74 , which in turn locks the actuation mechanism  58  and therefore distal elements  18  in place. In addition, the stud  74  may include one or more grooves  82  or indentations which receive the barbells  110 . This may provide more rapid and positive locking by causing the barbells  110  to settle in a definite position, increase the stability of the locking feature by further preventing movement of the barbells  110 , as well as tangible indication to the user that the barbell has reached a locking position. In addition, the grooves  82  may be used to indicate the relative position of the distal elements  18 , particularly the distance between the distal elements  18 . For example, each groove  82  may be positioned to correspond with a 0.5 or 1.0 mm decrease in distance between the distal elements  18 . As the stud  74  is moved, the barbells  110  will contact the grooves  82 ; by counting the number of grooves  82  that are felt as the stud  74  is moved, the user can determine the distance between the distal elements  18  and can provide the desired degree of coaptation based upon leaflet thickness, geometry, spacing, blood flow dynamics and other factors. Thus, the grooves  82  may provide tactile feedback to the user.  
         [0159]     The locking mechanism  106  allows the fixation device  14  to remain in an unlocked position when attached to the interventional tool  10  during grasping and repositioning and then maintain a locked position when left behind as an implant. It may be appreciated, however, that the locking mechanism  106  may be repeatedly locked and unlocked throughout the placement of the fixation device  14  if desired. Once the final placement is determined, the lock line  92  and proximal element lines  90  are removed and the fixation device is left behind.  
         [0160]     FIGS.  23 ,  24 A- 24 B illustrate another embodiment of a locking mechanism  106 . Referring to  FIG. 23 , in this embodiment, the locking mechanism  106  is again disposed between the coupling member  19  and the base  69  of the actuation mechanism  58 . The base  69  is connected to the stud  74  which extends through the locking mechanism  106 , and connects to an actuator rod which extends through the coupling member  19  and the shaft  12  of the interventional tool  10 . The base  69  is also connected to the legs  68  of the actuation mechanism  58  which are in turn connected to the distal elements  18 .  FIG. 23  also illustrates the proximal elements  16  which manipulate the locking mechanism  106  in this embodiment. The locking mechanism  106  comprises folded leaf structures  124  having overlapping portions  124   a ,  124   b , each folded structure  124  being attached to a proximal element  16 . In  FIG. 23  and  FIG. 24A , the folded structures  124  are shown without the remainder of the locking mechanism  106  for clarity. Proximal elements  16  are flexible and resilient and are biased outwardly. The folded leaf structures  124  include holes  125  ( FIG. 24B ) in each overlapping portion  124   a ,  124   b  so that the stud  74  passes through the holes  125  of the portions  124   a ,  124   b  as shown. The locking mechanism includes slots into which ends  123  of the folded leaf structures  124  are fixed. When the proximal elements  16  are in an undeployed position, as in  FIG. 23 , the folded leaf structures  124  lie substantially perpendicular to the stud  74  so that the holes  125  in each overlapping portion are vertically aligned. This allows the stud  74  to pass freely through the holes and the locking mechanism  106  is considered to be in an unlocked position.  
         [0161]     Deployment of the proximal elements  16 , as shown in  FIG. 24A , tilts the folded leaf structures  124  so as to be disposed in a non-perpendicular orientation relative to the stud  74  and the holes  125  are no longer vertically aligned with one another. In this arrangement, the stud  74  is not free to move due to friction against the holes of the folded leaf structure  124 .  FIG. 24B  provides a larger perspective view of the folded structures  124  in this position. Thus, the locking mechanism  106  is considered to be in a locked position. This arrangement allows the fixation device  14  to maintain an unlocked position during grasping and repositioning and then maintain a locked position when the proximal elements  16  are deployed and the fixation device  14  is left behind as an implant. It may be appreciated, however, that the locking mechanism  106  may be repeatedly locked and unlocked throughout the placement of the fixation device  14  if desired.  
         [0162]     FIGS.  25 ,  26 A- 26 B illustrate another embodiment of a locking mechanism  106 . Referring to  FIG. 25 , in this embodiment, the locking mechanism  106  is again disposed between the coupling member  19  and the base  69  of the actuation mechanism  58 . And, the base  69  is connected to the stud  74  which extends through the locking mechanism  106  and connects to an actuator rod which extends through the coupling member  19  and the shaft of the interventional tool  10 .  FIG. 25  illustrates the proximal elements  16  which manipulate the locking mechanism  106  in this embodiment. The locking mechanism  106  comprises C-shaped structures  128 , each C-shaped structure  128  attached to a proximal element  16 . The C-shaped structures  128  hook around the stud  74  so that the stud  74  passes through the “C” of each structure  128  as shown in  FIGS. 26A-26B . As shown, the structures  128  cross each other and the “C” of each structure  128  faces each other. A spring  130  biases the C-shaped structures into engagement with one another. When the proximal elements are in an undeployed position, as in  FIG. 26A , the C-shaped structures  128  are urged into an orientation more orthogonal to the axial direction defined by stud  74 , thus bringing the “C” of each structure  128  into closer axial alignment. This allows the stud  74  to pass freely through the “C” of each structure  128 . Deployment of the proximal elements  16  outwardly urges the C-shaped structures into a more angular, non-orthogonal orientation relative to stud  74  causing the sidewalls of the “C” of each structure  128  to engage stud  74  more forcefully. In this arrangement, the stud  74  is not free to move due to friction against the “C” shaped structures  128 .  
         [0163]     D. Additional Embodiments of Fixation Devices  
         [0164]      FIGS. 22A-22B  illustrate a variation of the fixation device  14  described above in which the distal and proximal elements  16 ,  18  on each side of the fixation device are movable laterally toward and away from each other to facilitate capture of more widely-separated leaflets or other tissue flaps. The coupling member  19  is bifurcated into two resilient and flexible branches  19 A,  19 B which are biased outwardly into the position shown in  FIG. 22A , but which are movable to the position shown in  FIG. 22B . As an alternative, branches  19 A,  19 B may be more rigid members connected to coupling member  19  by pins or hinges so as to be pivotable toward and away from each other. Each of proximal elements  16  and distal elements  18  are coupled at their proximal ends to one branch  19 A or  19 B of the coupling member  19 . Legs  68  are coupled at their proximal ends to base  69 , and therefore stud  74 , and at their distal ends to distal elements  18 , as described above. Translation of stud  74  distally or proximally relative to coupling member  19  opens or closes distal elements  18  as in formerly described embodiments. A collar  131  is slidably disposed over coupling member  19  and has an annular groove  133  on its inner wall configured to slide over and frictionally engage detents  135  on branches  19 A,  19 B. A sheath  137  is positioned coaxially over shaft  12  and is slidable relative thereto to facilitate pushing collar  131  distally over coupling member  19 .  
         [0165]     In use, the embodiment of  FIGS. 22A-22B  is introduced with distal and proximal elements  16 ,  18  in the closed position. Collar  131  is pushed distally against, but not over, detents  135  so that branches  19 A,  19 B are disposed together and fixation device  14  has a minimal profile. When the user is ready to capture the target tissue (e.g. valve leaflets), sheath  137  is retracted so that collar  131  slides proximally over coupling member  19 . This allows branches  19 A,  19 B to separate into the position of  FIG. 22A . Actuator  64  is pushed distally so as to open distal elements  18 . Tension is maintained on proximal element lines  90  (not shown in  FIGS. 22A-22B ) so that proximal elements  16  remain separated from distal elements  18 . When tissue is positioned between the proximal and distal elements, tension is released on proximal element lines  90  allowing the tissue to be captured between the proximal and distal elements. Sheath  137  may then be advanced distally so that collar  131  urges branches  19 A,  19 B back together. Sheath  137  is advanced until groove  133  in collar  131  slides over detents  135  and is frictionally maintained thereon as shown in  FIG. 22B . Sheath  137  may then be retracted from collar  131 . Distal elements  18  may be closed, opened or inverted by advancing or retracting stud  74  via actuator  64 , as in the embodiments described above. It should be understood that the embodiment of  FIGS. 22A-22B  preferably includes a locking mechanism as described above, which has been omitted from the figures for clarity.  
         [0166]     In a further alternative of the embodiment of  FIGS. 22A-22B , fixation device  14  may be configured to allow for independent actuation of each of the lateral branches  19 A,  19 B and/or distal elements  18 . In an exemplary embodiment, shaft  12  and coupling member  19  may be longitudinally split into two identical halves such that a first branch  19 A may be drawn into collar  131  independently of a second branch  19 B. Similarly, actuator shaft  64  may be longitudinally split so that each half can slide independently of the other half, thus allowing one of distal elements  18  to be closed independently of the other distal element  18 . This configuration permits the user to capture one of the valve leaflets between one of the distal and proximal elements  16 ,  18 , then draw the corresponding branch  19 A into the collar  131 . The fixation device  14  may then be repositioned to capture a second of the valve leaflets between the other proximal and distal elements  16 ,  18 , after which the second branch  19 B may be drawn into collar  131  to complete the coaptation. Of course, the closure of distal elements  18  may occur either before or after branches  19 A,  19 B are drawn into collar  131 .  
         [0167]      FIGS. 27-28  illustrate an additional embodiment of the fixation device  14 . As shown in  FIG. 27 , the fixation device  14  includes a coupling member  19  which couples the device  14  to the shaft  12  of the interventional tool  10 . Here, the device  14  also includes a top coupler  150  attached to coupling member  19  and a bottom coupler  152  attached to the stud  74  so that the two couplers are axially moveable relative to one another. The distal elements  18  are rotatably attached to the top coupler  150  by upper pins  156  and rotatably attached to the bottom coupler  152  by lower pins  160 . When the bottom coupler  152  is advanced, the pins  156 ,  160  are drawn apart. The upper pins  156  are disposed within slots  158  as shown. When the bottom coupler  152  is advanced distally relative to top coupler  150 , pins  156 ,  160  are drawn apart. Angling of the slots  158  causes the distal elements  18  to rotate toward the coupling member  19  as the pins  156 ,  160  are drawn apart. Relative movement of the couplers  150 ,  152  may be achieved by any suitable mechanism including sliding or threading.  
         [0168]      FIG. 28  illustrates the fixation device  14  in the closed position. Here, the device  14  has a low profile (width in the range of approximately 0.140-0.160 inches orthogonal to the axial direction defined by shaft  12 /stud  74 ) so that the device  14  may be easily passed through a catheter and through any tissue structures. To open the device  14  the bottom coupler  152  is then retracted or the couplers  150 ,  152  brought toward one another to rotate the distal elements  18  outward. The components of the fixation device  14  may be formed from stainless steel or other suitable metal, such as by machining, or formed from a polymer, such as by injection molding. In addition, portions of the fixation device  14 , particularly the distal elements  18 , may be covered with a covering such as described above, to promote tissue ingrowth, reduce trauma, enhance friction and/or release pharmacological agents. Alternatively, the device  14  may have a smooth surface which prevents cellular adhesion thereby reducing the accumulation of cells having potential to form an emboli.  
         [0169]     Optionally, the fixation device  14  may include tissue retention features such as barbs  170  and/or bumpers  172 , illustrated in  FIGS. 29-30 . The barbs  170  may extend from the engagement surfaces  50  of the distal elements  18 , as shown, and may be present in any number and any arrangement. Thus, the barbs  170  will engage the leaflets or tissue during grasping to assist in holding the tissue either by frictional engagement, minor surface penetration or by complete piercing of the tissue, depending on the length and shape of the barbs  170  selected. Alternatively or in addition, bumpers  172  may extend from the distal elements  18 . As shown in  FIG. 29 , each bumpers  172  may extend from the proximal end  52  of the distal element  18  and curve toward the free end  54  of the distal element  18 . Or, as shown in  FIG. 30 , each bumper  172  may extend from the free end  54  and curve toward the proximal end  52 . Bumpers  172  are preferably constructed of a resilient metal or polymer and may have any of various geometries, including a solid thin sheet or a loop-shaped wire form. The bumpers  172  may help to actively engage and disengage tissue from the barbs  170  during opening and closing of the fixation device  14 . Further, to assist in grasping a tissue, the engagement surfaces  50  may have any texture or form to increase friction against the grasped tissue. For example, the surfaces  50  may include serrations, scales, felt, barbs, polymeric frictional elements, knurling or grooves, to name a few.  
         [0170]      FIG. 31  illustrates the engagement surface  50  having a serrated edge  174  to improve grip on tissue engaged.  FIG. 31  also illustrates an embodiment of the fixation device  14  mounted on an interventional tool  10  or delivery catheter for ventricular approach to the mitral valve. Here the device  14  is mounted on the shaft  12  with the engagement surfaces  50  facing distally relative to shaft  12  (and facing upstream relative to the mitral valve). Thus, when the mitral valve is approached from the ventricular side, the engagement surfaces  50  can be pressed against the downstream surfaces of the valve without passing through the valve. It may be appreciated that any of the embodiments of the fixation device  14  described herein may be mounted on shaft  12  in this orientation for approach to any valve or tissue, including embodiments that include both proximal and distal elements.  
         [0171]     It may be appreciated that when the fixation device  14  is mounted on the shaft  12  in orientation illustrated in  FIG. 31 , the position of the distal elements and the proximal elements are reversed. In such instances it is useful to keep in mind that the distal elements contact the distal surface or downstream surface of the leaflets and the proximal elements contact the proximal surface or upstream surface of the leaflets. Thus, regardless of the approach to the valve and the relative position of the proximal and distal elements on the fixation device, the proximal and distal elements remain consistent in relation to the valve.  
         [0172]      FIGS. 32-34  illustrate an additional embodiment of the fixation device  14 . As shown in  FIG. 32 , the fixation device  14  includes a coupling member  19 , proximal elements  16  and distal elements  18  which are each connected to a set of base components  186 . The distal elements  18  are connected to the base components  186  (top base component  186   a  and a bottom base component  186   b ) by extension arms  188 . In this embodiment, each distal element  18  is connected by two extension arms  188  in a crossed arrangement so that one extension arm  188  connects the distal element  18  to the top base component  186   a  and the other extension arm  188 ′ connects the distal element  18  to the bottom base component  186   b . The top base component  186   a  can be separated from the bottom base component  186   b  by any suitable method which may be torque driven, spring driven or push/pull. Increasing the separation distance between the base components  186  draws the distal elements  18  inwards toward the base components  186 , as shown in  FIG. 33 . This allows the tissue to be grasped between the distal elements  18  and proximal elements  16  while in an arrangement wherein the distal elements  18  are parallel to each other. This may prevent inconsistent compression of the tissue and may better accommodate tissues or leaflets of varying thicknesses. As shown in  FIG. 34 , the distal elements  18  may be drawn together and the proximal elements  16  may be retracted to form a low profile fixation device  14 .  
         [0173]      FIGS. 35-39 ,  40 A- 40 D,  41 - 42 ,  43 A- 43 C illustrate another embodiment of the fixation device  14 . In this embodiment, the device  14  is deliverable in the inverted position and moveable to the open position for grasping of the tissue.  FIG. 35  illustrates the fixation device  14  in the inverted position. The fixation device  14  includes a shaft  198 , proximal elements  16  and distal elements  18 . Each distal element  18  has a proximal end  52  rotatably connected to the shaft  198  and a free end  54 . The fixation device  14  also includes an actuator rod  204 , a base  202  and a pair of deployment arms  200  attached to the base  202  as shown. In the inverted position, the extender  204  is extended and deployment arms  200  are disposed between the actuator rod  204  and the distal elements  18 . As shown in  FIG. 36 , the actuator rod  204  may be retracted so that the deployment arms  200  press against the distal elements  18 , rotating the distal elements  18  from the inverted position to the open position. The angle of the distal elements  18  may be adjusted by retracting or extending the actuator rod  204  various distances. As shown in  FIG. 37 , further retraction of the actuator rod  204  raises the distal elements  18  further.  
         [0174]     In the open position, tissue or leaflets may be grasped between the distal elements  18  and proximal elements  16 .  FIG. 38  illustrates the proximal elements  16  in their released position wherein the tissue or leaflet would be present therebetween. Hereinafter, the tissue will be referred to as leaflets. In this embodiment, each distal element  18  includes an implant pledget  210 , typically press-fit or nested within each distal element  18 . The implant pledgets  210  will be attached to the leaflets by ties, such as sutures or wires, and will be used to hold the leaflets in desired coaptation. The implant pledgets  210  will then be separated from the fixation device  14  and will remain as an implant.  
         [0175]     To attach the implant pledgets  210  to the leaflets, the leaflets and implant pledgets  210  are punctured by fixation tools  220 , as shown in  FIG. 39 . The fixation tools  220  extend from the catheter  86 , pass through the leaflets and puncture the implant pledgets  210 . Thus, the pledgets  210  are comprised of a puncturable material, such as structural mesh. The fixation tools  220  are used to deliver an anchor  222  as illustrated in larger view in  FIGS. 40A-40D .  FIG. 40A  shows the fixation tool  220  including a sleeve  224  surrounding the fixation tool  220  and an anchor  222  loaded therebetween. In this embodiment, the anchor includes one or more flaps  228  which are held within the sleeve  224 . It may be appreciated that the anchor  222  may have any suitable form. Additional exemplary embodiments of anchors are provided in commonly assigned U.S. Pat. No. 6,752,813 (Attorney Docket No. 020489-000400US) incorporated herein for all purposes. A suture  226  is attached to the anchor  222  and extends through the sleeve  224  or on the outside of the sleeve  224 , as shown, to the catheter  86 . The fixation tools  220  are advanced so that the anchor  222  passes through the leaflet (not shown) and the pledget  210 , as shown in  FIG. 41 .  
         [0176]     Referring now to  FIG. 40B , the sleeve  224  is then retracted to expose the flaps  228  which releases the anchor  222  from the confines of the sleeve  224 . The flaps  228  extend radially outwardly, illustrated in  FIG. 40C , by spring loading, shape memory or other self-expanding mechanism. Thus, the flaps  228  are positioned against the distal side of the pledget  210 , the suture  226  passing through the pledget  210  and the leaflet, as shown in  FIG. 41 . At this point, the pledgets  210  can be removed from the distal elements  18 . By extending the actuator rod  204  distally, the base  202  draws the deployment arms  200  distally which returns the distal elements  18  to the inverted position, as shown in  FIG. 42 . Since the pledgets  210  have been pierced by the fixation tools  220  and the anchors  222  have been deployed, the pledgets  210  and the leaflets disengage from distal elements  18  and remain in position. The proximal elements  16  may also be returned to their initial position as shown, using any of various mechanisms as have been described above in connection with other embodiments. Referring now to  FIG. 40D , the fixation tool  220  is then removed while the anchor  222  remains in place with suture  226  attached.  
         [0177]     The implant pledgets  210  are then separated from the fixation device  14  and left behind to maintain coaptation of the leaflets in the desired position.  FIGS. 43A-43C  illustrate the implant pledgets  210  from various perspective views.  FIG. 43A  provides a perspective top view showing that the pledgets  210  are connected by a link  230  that allows the pledgets  210  to be released from one side of the fixation device  14 . In addition, the sutures  226  are fixed together, either by knot tying or placement of a suture fastener  232  as shown. It may be appreciated that the suture fastener  232  may have any suitable form. Additional exemplary embodiments of suture fasteners  232  are provided in commonly-assigned U.S. Pat. No. 7,048,754 (Attorney Docket No. 020489-000500US), which is incorporated herein by reference for all purposes.  FIG. 43B  provides a perspective bottom view showing the anchor  222  positioned against the bottom side of the pledget  210 . Likewise,  FIG. 43C  provides a perspective side view also showing the anchor  222  positioned against the bottom side of the pledget  210 .  
         [0178]      FIGS. 44A-44B ,  45 - 46  illustrate another embodiment of the fixation device  14 . As shown in  FIG. 44A , the fixation device  14  is mounted on the shaft  12  and is comprised of distal elements  18  and a retention clip  36  comprised of a semi-rigid material having a folded shape. The material may be any suitable material providing rigidity with recoiling properties such as various metals or plastics. The folded shape is such that a fold  252  is directed distally and free ends  254  are directed proximally toward the distal elements  18 . Penetration elements  256  are disposed near the free ends  254  and directed toward the shaft  12 . In addition, an opening  258  is located near the fold  252 , as illustrated in  FIG. 44B  which provides a perspectives view of the device  14 . Referring back to  FIG. 44A , the fold  252  is attached to an actuator rod  74  which passes through the shaft  12  and an arrow-shaped structure  260  is disposed on the shaft  12  between the free ends  254 , proximal to the opening  258 , as shown. In this arrangement, the fixation device  14  is advanced through the valve so that the distal elements  18  are disposed below the leaflets. The device may then be retracted proximally to capture the leaflets within the distal elements  18 . As shown in  FIG. 45 , retraction of the actuator rod  74  draws the retention clip  36  toward the distal elements  18  so that the sloping sides of the arrow-shaped structure  260  force the free ends  254  outward, away from the shaft  12 . Further retraction of actuator rod  74  results in the sloping sides of arrow shaped structure  260  falling into the opening  258  in retention clip  36 , causing retention clip  36  to recoil back to the closed position as shown in  FIG. 46 , with the free ends  254  extending through the distal elements  18 . This allows the penetration elements  256  to penetrate the leaflets (not shown) to secure engagement therewith. The actuator rod  74  is then detached from the retention clip  36  and shaft  12  is detached from distal elements  18  which are left in place to hold the leaflets in a coapted arrangement.  
         [0179]     It may be appreciated that the foregoing embodiment may also include proximal elements  16  configured to be positioned on the upstream side of the valve leaflets to assist in the capture and fixation. Such proximal elements may be mounted to shaft  12  so as to be removed following fixation of the leaflets, or the proximal elements may be connected to distal elements  18  and/or retention clip  36  to be implanted therewith.  
         [0180]     In further embodiments, the proximal elements may be manipulated to enhance gripping. For example, the proximal elements may be lowered to grasp leaflets or tissue between the proximal and distal elements, and then the proximal elements may be moved to drag the leaflets or tissue into the fixation device. In another example, the proximal elements may be independently lowered to grasp the leaflets or tissue. This may be useful for sequential grasping. In sequential grasping, one proximal element is lowered to capture a leaflet or tissue portion between the proximal and distal elements. The fixation device is then moved, adjusted or maneuvered to a position for grasping another leaflet or tissue portion between another set of proximal and distal elements. In this position, the second proximal element is then lowered to grasp this other leaflet or tissue portion.  
         [0000]     IV. Delivery Device  
         [0181]     A. Overview of Delivery Device  
         [0182]      FIG. 47  provides a perspective view of an embodiment of a delivery device or delivery catheter  300  which may be used to introduce and position a fixation device as described above. The delivery catheter  300  includes a shaft  302 , having a proximal end  322  and a distal end  324 , and a handle  304  attached to the proximal end  322 . A fixation device (not shown) is removably coupleable to the distal end  324  for delivery to a site within the body, typically for endovascular delivery to the mitral valve. Thus, extending from the distal end  324  is a coupling structure  320  for coupling with a fixation device. Also extending from the distal end  324  is an actuator rod  64 . The actuator rod  64  is connectable with the fixation device and acts to manipulate the fixation device, typically opening and closing the distal elements. Such coupling to a fixation device is illustrated in  FIG. 48 .  
         [0183]      FIG. 48  illustrates an embodiment of a fixation device  14  coupled to the distal end  324  of the delivery catheter  300 . The shaft  302  is shown having a nose  318  near its distal end  324 . In this embodiment, the nose  318  has a flanged shape. Such a flanged shape prevents the nose  318  from being retracted into a guiding catheter or introducer as will be discussed in later sections. However, it may be appreciated that the nose  318  may have any shape including bullet, rounded, blunt or pointed, to name a few. Extending from the nose  318  is a compression coil  326  through which the coupling structure  320  and actuator rod  64  pass. The actuator rod  64  is coupleable, as shown, with the stud  74  of the fixation device  14 . Such coupling is illustrated in  FIG. 49 .  
         [0184]      FIG. 49  illustrates a portion of the shaft  302  of the delivery catheter  300  and a fixation device  14  which is coupleable with the catheter  300 . Passing through the shaft  302  is the actuator rod  64 . In this embodiment, the actuator rod  64  comprises a proximal extremity  303  and a distal extremity  328 , the distal extremity  328  of which is surrounded by a coil  330 . The proximal extremity  303  is typically comprised of stainless steel, nitinol, or Elgiloy®, to name a few, and may have a diameter in the range of 0.010 in. to 0.040 in., preferably 0.020 in. to 0.030 in., more preferably 0.025 in., and a length in the range of 48 to 72 in. The distal extremity  328  may be tapered, is typically comprised of stainless steel, nitinol, or Elgiloy®, to name a few, and may have a diameter in the range of 0.011 to 0.025 in and a length in the range of 4 to 12 in. Such narrowing increases flexibility of the distal end  324  of the actuator rod  64 . The actuator rod  64  further comprises a joiner  332  which is attached to the distal extremity  328 . The joiner  332  is removably attachable with stud  74  of the fixation device  14 . In this embodiment, the joiner  332  has internal threads which mate with external threads on the stud  74  of the fixation device  14 . As described previously, the stud  74  is connected with the distal elements  18  so that advancement and retraction of the stud  74 , by means of the actuator rod  64 , manipulates the distal elements. Likewise, the coupling member  19  of the fixation device  14  mates with the coupling structure  320  of the catheter  300 . Thus, the coupling member  19  and coupling structure  320  function as previously described in relation to  FIGS. 6A-6B .  
         [0185]     Referring back to  FIG. 48 , the fixation device  14  may also include a locking mechanism which includes a release harness  108 , as previously described in relation to  FIGS. 18-21 . Lock lines  92  are connected with the release harness  108  to lock and unlock the locking mechanism  106  as previously described. The lock lines  92  extend through the shaft  302  of the delivery catheter  300  and may connect with the release harness  108  in various arrangements as will be illustrated in later sections. Similarly, proximal element lines  90  extend through the shaft  302  of the delivery catheter  300  and connect with the proximal elements  16 . The proximal elements  16  are raised and lowered by manipulation of the proximal element lines  90  as previously described. The proximal element lines  90  may connect with the proximal elements  16  in various arrangements as will be illustrated in later sections.  
         [0186]     Referring back to  FIG. 47 , the handle  304  attached to the proximal end  322  of the shaft  302  is used to manipulate the coupled fixation device  14  and to optionally decouple the fixation device  14  for permanent implantation. As described, the fixation device  14  is primarily manipulated by the actuator rod  64 , proximal element lines  90  and lock lines  92 . The actuator rod  64  manipulates the distal elements  18 , the proximal element lines  90  manipulate the proximal elements  16  and the lock lines  92  manipulate the locking mechanism. In this embodiment, the actuator rod  64  may be translated (extended or retracted) to manipulate the distal elements  18 . This is achieved with the use of the actuator rod control  314  which will be described in later sections. The actuator rod  64  may also be rotated to engage or disengage the threaded joiner with the threaded stud  74 . This is achieved with the use of the actuator rod handle  316  which will also be described in later sections. Further, the proximal element lines  90  may be extended, retracted, loaded with various amounts of tension or removed with the use of the proximal element line handle  312 . And, the lock lines  92  may be may be extended, retracted, loaded with various amounts of tension or removed with the use of the lock line handle  310 . Both of these handles  310 ,  312  will be described in more detail in later sections. The actuator rod handle  316 , actuator rod control  314 , proximal element line handle  312  and lock line handle  310  are all joined with a main body  308  within which the actuator rod  64 , proximal element lines  90  and lock lines  92  are guided into the shaft  302 . The handle  304  further includes a support base  306  connected with the main body  308 . The main body  308  is slideable along the support base  306  to provide translation of the shaft  302 . Further, the main body  308  is rotatable around the support base  306  to rotate the shaft.  
         [0187]     B. Delivery Catheter Shaft  
         [0188]      FIG. 50  illustrates a cross-sectional view of the delivery catheter shaft  302  of  FIG. 47 . In this embodiment, the shaft  302  has a tubular shape with inner lumen  348  and is comprised of a material which provides hoop strength while maintaining flexibility and kink resistance, such as a braided laminated material. Such material may include stainless steel braided or coiled wire embedded in a polymer such as polyurethane, polyester, Pebax, Grilamid TR55, and AESNO to name a few. To provide further support and hoop strength, a support coil  346  is disposed within the lumen  348  of shaft  302  as illustrated in  FIG. 50 .  
         [0189]     Passing through the support coil  346  are a variety of elongated bodies, including tubular guides and cylindrical rods. For example, one type of tubular guide is a compression coil  326  extending through lumen  348  from the proximal end  322  to the distal end  324  of the shaft  302 , and the actuator rod  64  extends through the compression coil  326 . Therefore, the compression coil typically has a length in the range of 48 to 60 in. and an inner diameter in the range of 0.020 to 0.035 in. to allow passage of the actuator rod  64  therethrough. The actuator rod  64  is manipulable to rotate and translate within and relative to the compression coil  326 . The compression coil  326  allows lateral flexibility of the actuator rod  64  and therefore the shaft  302  while resisting buckling and providing column strength under compression. The compression coil may be comprised of 304V stainless steel to provide these properties.  
         [0190]     To provide additional tensile strength for the shaft  302  and to minimize elongation, a tension cable  344  may also pass through the support coil  346 . The tension cable  344  extends through lumen  348  from the proximal end  322  to the distal end  324  of the shaft  302 . Therefore, the tension cable  344  typically has a diameter in the range of 0.005 in. to 0.010 in. and a length in the range of 48 to 60 in. In preferred embodiments, the tension cable  344  is comprised of 304V stainless steel.  
         [0191]     In addition, at least one lock line shaft  341  having a tubular shape may be present having a lock line lumen  340  through which lock lines  92  pass between the lock line handle  310  and the locking mechanism  106 . The lock line shaft  341  extends through lumen  348  from the proximal end  322  to the distal end  324  of the shaft  302 . Therefore, the lock line shaft  341  typically has a length in the range of 48 to 60 in., an inner diameter in the range of 0.016 to 0.030 in., and an outer diameter in the range of 0.018 to 0.034 in. In preferred embodiments, the lock line shaft  341  is comprised of a 304V stainless steel coil however other structures or materials may be used which provide kink resistance and compression strength.  
         [0192]     Similarly, at least one proximal element line shaft  343  having a tubular shape may be present having a proximal element line lumen  342 . Proximal element lines  90  pass through this lumen  342  between the proximal element line handle  312  and the proximal elements  16 . Thus, the proximal element line shaft  343  extends through lumen  348  from the proximal end  322  to the distal end  324  of the shaft  302 . Therefore, the proximal element line shaft  343  typically has a length in the range of 48 to 60 in., an inner diameter in the range of 0.016 to 0.030 in., and an outer diameter in the range of 0.018 to 0.034 in. In preferred embodiments, the proximal element line shaft  343  is comprised of a 304V stainless steel coil however other structures or materials may be used which provide kink resistance and compression strength.  
         [0193]     In this embodiment, the elongated bodies (compression coil  326  enclosed actuator rod  64 , tension cable  344 , lock line shaft  342 , proximal element line shaft  343 ) each “float” freely in inner lumen  348  within the support coil  346  and are fixed only at the proximal end  322  and distal end  324  of shaft  302 . The lumen  348  is typically filled and flushed with heparinized saline during use. Alternatively or in addition, the lumen  348  may be filled with one or more fillers, such as flexible rods, beads, extruded sections, gels or other fluids. Preferably the fillers allow for some lateral movement or deflection of the elongated bodies within lumen  348  but in some cases may restrict such movement. Typically, the elongated bodies are fixed at the proximal and distal ends of the shaft and are free to move laterally and rotationally therebetween. Such freedom of movement of the elongated bodies provides the shaft  302  with an increased flexibility as the elongated bodies self-adjust and reposition during bending and/or torqueing of the shaft  302 . It may be appreciated that the elongated bodies may not be fixed at the proximal and distal ends. The elongated bodies are simply unconstrained relative to the shaft  302  in at least one location so as to be laterally moveable within the lumen  348 . Preferably the elongated bodies are unrestrained in at least a distal portion of the catheter, e.g. 5-15 cm from the distal end  324 , so as to provide maximum flexibility in the distal portion.  
         [0194]     It may be appreciated, however, that alternate shaft  302  designs may also be used. For example, referring to  FIG. 51 , in this embodiment the shaft  302  again has a tubular shape with an inner lumen  348  and a support coil  346  disposed within the lumen  348  of shaft  302 . Filling the inner lumen  348  within the support coil  346  is an extrusion  334  having lumens through which pass a variety of elongated bodies, including the compression coil  326  enclosed actuator rod  64 , tension cable  344 , lock line shafts  342 , and proximal element line shafts  343 , as shown. The support coil  346  and elongated bodies may have the same geometries and be comprised of the same materials as described above in relation to  FIG. 50 .  
         [0195]     Alternatively, as shown in  FIG. 52 , the shaft  302  may include an internal partition  350  to create multiple lumens within the shaft  302 . For example, the partition  350  may have a central lumen  352  for passage of the actuator rod  64 , optionally surrounded by the compression coil  326 . In addition, the partition  350  may also create at least one lock line lumen  340  for passage of a lock line  92  and at least one proximal element line lumen  341  for passage of a proximal element line  90 . Optionally, each of the lumens defined by partition  350  may be lined with a kink-resistant element, such as a coil as in previous embodiments.  
         [0196]      FIGS. 52A-52C  illustrate embodiments of the nose  318  of the shaft  302 . In  FIG. 52A , the nose  318  comprises a tip ring  280  and a lock ring  282 . In preferred embodiments, Epoxy and PEBAX are deposited between the tip ring  280  and the lock ring  282  to bond them together. The lock ring  282  has a geometry to mate with the tip ring  280  to maintain relative alignment between the two.  FIG. 52B  illustrates another embodiment of the nose  318  of the shaft  302 . Here, the tip ring  280  is covered by a soft tip  284  to provide a more atraumatic tip and a smoother transition to the shaft.  
         [0197]     C. Lock Line Arrangements  
         [0198]     As mentioned previously, when lock lines  92  are present, the lines  92  pass through at least one lock line lumen  340  between the lock line handle  310  and the locking mechanism  106 . The lock lines  92  engage the release harnesses  108  of the locking mechanism  106  to lock and unlock the locking mechanism  106  as previously described. The lock lines  92  may engage the release harnesses  108  in various arrangements, examples of which are illustrated in  FIGS. 53A-53C . In each embodiment, two lock line lumens  340  are present within the shaft  302  of the delivery catheter  300  terminating at the nose  318 . The lumens  340  are disposed on alternate sides of the actuator rod  64  so that each lumen  340  is directed toward a release harness  108 .  
         [0199]      FIG. 53A  illustrates an embodiment wherein two lock lines  92 ,  92 ′ pass through a single lock line lumen  340  and are threaded through a release harness  108  on one side of the actuator rod  64  (the actuator rod  64  is shown without surrounding housing such as coupling structure, for clarity). The lock lines  92 ,  92 ′ are then separated so that each lock line passes on an opposite side of the actuator rod  64 . The lock lines  92 ,  92 ′ then pass through the release harness  108 ′ on the opposite side of the actuator rod  64  and continue together passing through a another single lock line lumen  340 ′. This lock line arrangement is the same arrangement illustrated in  FIG. 48 .  
         [0200]      FIG. 53B  illustrates an embodiment wherein one lock line  92  passes through a single lock line lumen  340 , is threaded through a release harness  108  on one side of the actuator rod  64 , and is returned to the lock line lumen  340 . Similarly, another lock line  92 ′ passes through another single lock line lumen  340 ′, is threaded through a different release harness  108 ′ located on the opposite side of the actuator rod  64 , and is returned to the another single lock line lumen  340 ′.  
         [0201]      FIG. 53C  illustrates an embodiment wherein both lock lines  92 ,  92 ′ pass through a single lock line lumen  340 . One lock line  92  is threaded through a release harness  108  on one side of the actuator rod  64  and is then passed through another lock line lumen  340 ′ on the opposite side of the actuator rod  64 . The other lock line  92 ′ is threaded through another release harness  108 ′ on the other side of the actuator rod  64 ′ and is then passed through the another lock line lumen  340 ′ with the previous lock line  92 .  
         [0202]     It may be appreciated that a variety of lock line arrangements may be used and are not limited to the arrangements illustrated and described above. The various arrangements allow the harnesses  108  to be manipulated independently or jointly, allow various amounts of tension to be applied and vary the force required for removal of the lock lines when the fixation device is to be left behind. For example, a single lock line passing through one or two lumens may be connected to both release harnesses for simultaneous application of tension.  
         [0203]     D. Proximal Element Line Arrangements  
         [0204]     As mentioned previously, when proximal element lines  90  are present, the lines  90  pass through at least one proximal element line lumen  342  between the proximal element line handle  312  and at least one proximal element  16 . The proximal element lines  90  engage the proximal elements  16  to raise or lower the element  16  as previously described. The proximal element lines  90  may engage the proximal elements  16  in various arrangements, examples of which are illustrated in  FIGS. 54A-54B . In each embodiment, two proximal element line lumens  342  are present within the shaft  302  of the delivery catheter  300  terminating at the nose  318 . The lumens  342  are disposed on alternate sides of the actuator rod  64  (the actuator rod  64  is shown without surrounding housing such as coupling structure, for clarity) so that each lumen  342  is directed toward a proximal element  16 .  
         [0205]      FIG. 54A  illustrates an embodiment wherein one proximal element line  90  passes through a single proximal element line lumen  342 . The proximal element line  90  is threaded through an eyelet  360  of a proximal element  16  on one side of the actuator rod  64 , passes over the actuator rod  64  and is threaded through an eyelet  360 ′ of another proximal element  16 ′ on the other side of the actuator rod  64 . The proximal element line  90  then passes through another single proximal element line lumen  342 ′. This proximal element line arrangement is the same arrangement illustrated in  FIG. 48 .  
         [0206]      FIG. 54B  illustrates an embodiment wherein one proximal element line  90  passes through a single proximal element line lumen  342 , is threaded through an eyelet  360  of a proximal element  16  on one side of the actuator rod  64 , and is returned to the proximal element line lumen  342 . Similarly, another proximal element line  90 ′ passes through another single proximal element line lumen  342 ′ on the opposite side of the actuator rod  64 , and is returned to the another single proximal element line lumen  342 ′.  
         [0207]     It may be appreciated that a variety of proximal element line arrangements may be used and are not limited to the arrangements illustrated and described above. The various arrangements allow the proximal elements to be manipulated independently or jointly, allow various amounts of tension to be applied and vary the force required for removal of the proximal element lines when the fixation device is to be left behind. For example, a single proximal element line passing through one or two lumens in shaft  302  may be used for simultaneous actuation of both proximal elements.  
         [0208]     E. Main Body of Handle  
         [0209]      FIG. 55  illustrates an embodiment of the handle  304  of the delivery catheter  300 . As mentioned previously, the actuator rod handle  316 , actuator rod control  314 , proximal element line handle  312  and lock line handle  310  are all joined with the main body  318 . The handle  304  further includes a support base  306  connected with the main body  308 . The main body  308  is slideable along the support base  306  to provide translation of the shaft  302  and the main body  308  is rotatable around the support base  306  to rotate the shaft.  
         [0210]      FIG. 56  provides a partial cross-sectional view of the main body  308  of the handle  304  depicted in  FIG. 55 . As shown, the main body  308  includes a sealed chamber  370  within which the actuator rod  64 , proximal element lines  90  and lock lines  92  are guided into the shaft  302 . The sealed chamber  370  is in fluid communication with the inner lumen  348  of shaft  302  and is typically filled with saline and flushed with heparin or heparinized saline. The sealed chamber  370  has a seal  372  along its perimeter to prevent leakage and the introduction of air to the chamber  370 . Any air in the chamber  370  may be bled from the chamber  370  by one or more luers  374  which pass through the main body  308  into the chamber  370  as illustrated in  FIG. 55 . In this embodiment, the handle  304  includes two such luers  374 , one on each side of the main body  308  (second luer symmetrically positioned on backside of main body  308  in  FIG. 55 , hidden from view). Referring now to  FIG. 56 , the sealed chamber  370  also has various additional seals, such as an actuator rod seal  376  which surrounds the actuator rod  64  where the actuator rod  64  enters the sealed chamber  370 , and a shaft seal  378  which surrounds the shaft  302  where the shaft  302  enters the sealed chamber  370 .  
         [0211]     F. Lock Line Handle and Proximal Element Line Handle  
         [0212]     As mentioned previously, the lock lines  92  may be may be extended, retracted, loaded with various amounts of tension or removed using the lock line handle  310 . Likewise, the proximal element lines  90  may be extended, retracted, loaded with various amounts of tension or removed using the proximal element line handle  312 . Both of these handles  310 ,  312  may be similarly designed to manipulate the appropriate lines  90 ,  92  passing therethrough.  
         [0213]      FIG. 57  illustrates an embodiment of a lock line handle  310  having lock lines  92  passing therethrough. The lock line handle  310  has a distal end  384 , a proximal end  382  and an elongate shaft  383  therebetween. The distal end  382  is positionable within the sealed chamber  370  so that the proximal end  382  extends out of the chamber  370 , beyond the main body  308 . The free ends of the lock lines  92  are disposed near the proximal end  382 , passing through the wall of the handle  310  near a threaded nub  390 . The handle  310  further includes a cap  388  which is positionable on the nub  309 . Internal threading with the cap  388  mates with the threading on the threaded nub  390  so that the cap  388  holds the free ends of the lock lines  92  between the cap  388  and the nub  390  and/or other portions of the handle  310  by friction. The lock lines  92  pass through a central lumen (not shown) of the elongate shaft  383 , extend through the sealed chamber  370  (as shown in  FIG. 56 ) and extend through the shaft  302  to the locking mechanism  106 .  
         [0214]     Disposed near the distal end  384  of the handle  310  is at least one wing  392 . In the embodiment of  FIG. 57 , two wings  392  are present, each wing  392  disposed on opposite sides of the elongate shaft  383 . The wings  392  extend radially outwardly and curve proximally so that a portion is parallel to the elongate shaft  383 , as shown. It may be appreciated that the wings  392  may alternatively have the shape of solid or continuous protrusions which extend radially and have a portion which is parallel to the elongate shaft  383 . The wings  392  are used to hold the lock line handle  310  in a desired position which in turn holds the lock under a desired load of tension, as will be described further below. The handle  310  also includes a finger grip  386  near the proximal end  382  which extends radially outwardly in alignment with the radial extension of the at least one wing  392 . Thus, the user may determine the orientation of the wings  392  within the sealed chamber  370  from the orientation of the finger grip  386  outside of the main body  308 . The finger grip  386  may also serve an ergonomic purpose to assist in manipulating the handle  310 .  
         [0215]     The portion of the wings  392  parallel to the elongate shaft  383  have grooves or serrations  394 . The serrations  394  are used to apply tension to the lock lines  92 . As shown in  FIG. 57A , the lock line handle  310  is positioned within a semi-tube  400  which is disposed within the sealed chamber  370 . The semi-tube  400  comprises a top half  402  and a bottom half  404 , each half  402 ,  404  having grooves or serrations  406  which mate with the serrations  394  of the wings  392 . Thus, when the wings  392  are rotated to mate the serrations  394 ,  406 , as shown in  FIG. 58A , the elongate shaft  383  is held in place. Likewise, the wings  392  may be rotated, as shown in  FIG. 58B , so that the wings  392  are disposed between the halves  402 ,  404  and the serrations  394 ,  406  are disengaged. In this position, the shaft  383  may be translated to apply or release tension in the lock lines  92 . Thus, tension in the lines  92  may be adjusted by rotating the shaft  383  to disengage the serrations  394 ,  406 , translating the shaft  383  and then rotating the shaft  383  back to reengage the serrations  394 ,  406 . Alternatively, the finger grip  386  may be pulled to apply tension to the lock lines  92 . Pulling the finger grip  386  translates the lock line handle  310  within the semi-tube  400 . Such translation is achievable due to angling of the serrations  394 ,  406  and flexibility of wings  382 . However, the angling of the serrations  394 ,  406  prevents translation in the opposite direction, i.e. by pushing the finger grip  386 . Therefore, to release tension from the lock lines  92 , the shaft  383  is rotated to disengage the serrations  394 ,  406 , allowing translation of the shaft  383 , and then the shaft  383  is rotated back to reengage the serrations  394 ,  406 .  
         [0216]     To remove the lock lines  92 , the cap  388  is removed from the threaded nub  390  exposing the free ends of the lock lines  92 . If one lock line  92  is present having two free ends, continuous pulling on one of the free ends draws the entire length of lock line  92  out of the catheter  300 . If more than one lock line  92  is present, each lock line  92  will have two free ends. Continuous pulling on one of the free ends of each lock line  92  draws the entire length of each lock line  92  out of the catheter  300 .  
         [0217]     It may be appreciated that the proximal element line handle  312  has corresponding features to the lock line handle  310  and operates in the same manner as illustrated in FIGS.  57 A,  58 A- 58 B. It may also be appreciated that other mechanisms may be used for manipulating the lock lines  92  and proximal element lines  90 , such as including buttons, springs, levers and knobs.  
         [0218]     G. Actuator Rod Control and Handle  
         [0219]     The actuator rod  64  may be manipulated using the actuator rod control  314  and the actuator rod handle  316 .  FIG. 59  provides a cross-sectional view of a portion of the handle  304  which includes the actuator rod control  314  and the actuator rod handle  316 . The actuator rod handle  316  is located at the proximal end of the handle  314 . The actuator rod handle  316  is fixedly attached to the proximal end of the actuator rod  64 . The actuator rod  64  is inserted through a collet  426  which is disposed within a holder  428  as shown. The holder  428  has external threads  434  which mate with internal threads  432  of the actuator rod control  314 . Thus, rotation of the actuator rod control  314  causes the holder  428  to translate along the actuator rod control  314  by action of the threading, as will be described in more detail below. The actuator rod control  314  is rotatably coupled with the main body  308  of the handle  304  and is held in place by a lip  430 .  
         [0220]     Referring to  FIG. 59A , the actuator rod control  314  may be manually rotated in a clockwise or counter clockwise direction, as indicated by arrow  436 . Rotation of the actuator rod control  314  translates (extends or retracts) the actuator rod  64  to manipulate the distal elements  18  of the fixation device  14 . Specifically, rotation of the actuator rod control  314  causes the external threads  434  of the adjacent holder  428  to translate along the mated internal threads  432  of the actuator rod control  314 . Rotation of the holder  428  itself is prevented by holding pins  424  which protrude from the holder  428  and nest into grooves  438  in the main body  308  of the handle  304 . As the holder  428  translates, each holding pin  424  translates along its corresponding groove  438 . Since the collet  426  is attached to the holder  428 , the collet  426  translates along with the holder  428 . To simultaneously translate the actuator rod  64 , the actuator rod  64  is removably attached to the collet  426  by a pin  422 . The pin  422  may have any suitable form, including a clip-shape which partially wraps around the collet  426  as illustrated in  FIG. 59 . Thus, rotation of the actuator rod control  314  provides fine control of translation of the actuator rod  64  and therefore fine control of positioning the distal elements  18 .  
         [0221]     Referring to  FIG. 59B , removal of the pin  422 , as shown, allows disengagement of the actuator rod handle  316  and fixedly attached actuator rod  64  from the collet  426 . Once disengaged, the actuator rod  64  may be rotated, as indicated by arrow  440 , by manually rotating the actuator rod handle  316 . As described previously, rotation of the actuator rod  64  engages or disengages the threaded joiner  332  of the delivery catheter  300  from the threaded stud  74  of the fixation device  14 . This is used to attach or detach the fixation device  14  from the delivery catheter  300 . In addition, when the actuator rod  64  is in the disengaged state, the actuator rod  64  may optionally be retracted and optionally removed from the catheter  300  by pulling the actuator rod handle  316  and withdrawing the actuator rod  64  from the handle  304 .  
         [0222]     Depending on the application, the location of the target site, and the approach selected, the devices of the invention may be modified in ways well known to those of skill in the art or used in conjunction with other devices that are known in the art. For example, the delivery catheter may be modified in length, stiffness, shape and steerability for a desired application. Likewise, the orientation of the fixation device relative to the delivery catheter may be reversed or otherwise changed. The actuation mechanisms may be changed to be driven in alternate directions (push to open, pull to close, or pull to open, push to close). Materials and designs may be changed to be, for example, more flexible or more rigid. And, the fixation device components may be altered to those of different size or shape. Further, the delivery catheter of the present invention may be used to deliver other types of devices, particularly endovascular and minimally invasive surgical devices used in angioplasty, atherectomy, stent-delivery, embolic filtration and removal, septal defect repair, tissue approximation and repair, vascular clamping and ligation, suturing, aneurysm repair, vascular occlusion, and electrophysiological mapping and ablation, to name a few. Thus, the delivery catheter of the present invention may be used for applications in which a highly flexible, kink-resistant device is desirable with high compressive, tensile and torsional strength.  
         [0000]     V. Multi-Catheter Guiding System  
         [0223]     A. Overview of Guiding System  
         [0224]     Referring to  FIG. 60 , an embodiment of a multi-catheter guiding system  1  of the present invention is illustrated. The system  1  comprises an outer guide catheter  1000 , having a proximal end  1014 , a distal end  1016 , and a central lumen  1018  therethrough, and an inner guide catheter  1020 , having a proximal end  1024 , distal end  1026  and central lumen  1028  therethrough, wherein the inner guide catheter  1020  is positioned coaxially within the central lumen  1018  of the outer guide catheter  1000 , as shown. The distal ends  1016 ,  1026  of catheters  1000 ,  1020 , respectively, are sized to be passable to a body cavity, typically through a body lumen such as a vascular lumen. Thus, the distal end  1016  preferably has an outer diameter in the range of approximately 0.040 in. to 0.500 in., more preferably in the range of 0.130 in. to 0.320 in. The central lumen  1018  is sized for the passage of the inner guide catheter  1020 ; the distal end  1026  preferably has an outer diameter in the range of approximately 0.035 in. to 0.280 in., more preferably 0.120 in to 0.200 in. The central lumen  1028  is sized for the passage of a variety of devices therethrough. Therefore, the central lumen  1028  preferably has an inner diameter in the range of approximately 0.026 in. to 0.450 in., more preferably in the range of 0.100 in. to 0.180 in.  
         [0225]      FIG. 60  illustrates an interventional catheter  1030  positioned within the inner guide catheter  1020  which may optionally be included in system  1 , however other interventional devices may be used. The interventional catheter  1030  has a proximal end  1034  and a distal end  1036 , wherein an interventional tool  1040  is positioned at the distal end  1036 . In this embodiment, the interventional tool  1040  comprises a detachable fixation device or clip. Optionally, the interventional catheter  1030  may also include a nosepiece  1042  having a stop  1043 , as shown. The stop  1043  prevents the interventional tool  1040  from entering the central lumen  1028  of the inner guide catheter  1020 . Thus, the interventional catheter  1030  may be advanced and retracted until the stop  1043  contacts the distal end  1026  of the inner guiding catheter  1020  preventing further retraction. This may provide certain advantages during some procedures. It may be appreciated that in embodiments which include such a stop  1043 , the interventional catheter  1030  would be pre-loaded within the inner guide catheter  1020  for advancement through the outer guiding catheter  1000  or both the interventional catheter  1030  and the inner guiding catheter  1020  would be pre-loaded into the outer guiding catheter  1000  for advancement to the target tissue. This is because the stop  1043  prevents advancement of the interventional catheter  1030  through the inner guiding catheter  1020 .  
         [0226]     The outer guide catheter  1000  and/or the inner guide catheter  1020  are precurved and/or have steering mechanisms, embodiments of which will be described later in detail, to position the distal ends  1016 ,  1026  in desired directions. Precurvature or steering of the outer guide catheter  1000  directs the distal end  1016  in a first direction to create a primary curve while precurvature and/or steering of the inner guide catheter  1020  directs distal end  1026  in a second direction, differing from the first, to create a secondary curve. Together, the primary and secondary curves form a compound curve. Advancement of the interventional catheter  1030  through the coaxial guide catheters  1000 ,  1020  guides the interventional catheter  1030  through the compound curve toward a desired direction, usually in a direction which will allow the interventional catheter  1030  to reach its target.  
         [0227]     Steering of the outer guide catheter  1000  and inner guide catheter  1020  may be achieved by actuation of one or more steering mechanisms. Actuation of the steering mechanisms is achieved with the use of actuators which are typically located on handles connected with each of the catheters  1000 ,  1020 . As illustrated in  FIG. 60 , handle  1056  is connected to the proximal end  1014  of the outer guide catheter  1000  and remains outside of the patient&#39;s body during use. Handle  1056  includes steering actuator  1050  which may be used to bend, arc or reshape the outer guide catheter  1000 , such as to form a primary curve. Handle  1057  is connected to the proximal end (not shown) of the inner guide catheter  1020  and may optionally join with handle  1056  to form one larger handle, as shown. Handle  1057  includes steering actuator  1052  which may be used to bend, arc or reshape the inner guide catheter  1020 , such as to form a secondary curve and move the distal end  1026  of the inner guide catheter  1020  through an angle theta, as will be described in a later section.  
         [0228]     In addition, locking actuators  1058 ,  1060  may be used to actuate locking mechanisms to lock the catheters  1000 ,  1020  in a particular position. Actuators  1050 ,  1052 ,  1058 ,  1060  are illustrated as buttons, however it may be appreciated that these and any additional actuators located on the handles  1056 ,  1057  may have any suitable form including knobs, thumbwheels, levers, switches, toggles, sensors or other devices. Other embodiments of the handles will be described in detail in a later section.  
         [0229]     In addition, the handle  1056  may include a numerical or graphical display  1061  of information such as data indicating the position the catheters  1000 ,  1020 , or force on actuators. It may also be appreciated that actuators  1050 ,  1052 ,  1058 ,  1060  and any other buttons or screens may be disposed on a single handle which connects with both the catheters  1000 ,  1020 .  
         [0230]     B. Example Positions  
         [0231]      FIGS. 61A-61D  illustrate examples of positions that the catheters  1000 ,  1020  may hold. Referring to  FIG. 61A , the outer guide catheter  1000  may be precurved and/or steered into a position which includes a primary curve  1100 . The primary curve  1100  typically has a radius of curvature  1102  in the range of approximately 0.125 in. to 1.000 in., preferably in the range of approximately 0.250 in. to 0.500 in. or forms a curve in the range of approximately 0° to 120°. As shown, when the position includes only a primary curve  1100 , the distal end  16  lies in a single plane X. An axis x, transversing through the center of the central lumen  18  at the distal end  16 , lies within plane X.  
         [0232]     Referring to  FIG. 61B , the inner guide catheter  1020  extends through the central lumen  1018  of the outer guide catheter  1000 . The inner guide catheter  1020  may be precurved and/or steered into a position which includes a secondary curve  1104 . The secondary curve  1104  typically has a radius of curvature  10600  in the range of approximately 0.050 in. to 0.750 in., preferably in the range of approximately 0.125 in. to 0.250 in. or forms a curve in the range of approximately 0° to 180°. The secondary curve  1104  can lie in the same plane as the primary curve  1100 , plane X, or it can lie in a different plane, such as plane Z as shown. In this example, plane Z is substantially orthogonal to plane X. Axis z, transversing through the center of the central lumen  1028  of the inner guide catheter  1020  at the distal end  1026 , lies within plane Z. In this example, axis x and axis z are at substantially 90 degree angles to each other; however, it may be appreciated that axis x and axis z may be at any angle in relation to each other. Also, although in this example the primary curve  1100  and the secondary curve  1104  lie in different planes, particularly in substantially orthogonal planes, the curves  1100 ,  1104  may alternatively lie in the same plane.  
         [0233]     Referring now to  FIG. 61C , the inner guide catheter  1020  may be further manipulated to allow the distal end  1026  to move through an angle theta  1070 . The angle theta  1070  is in the range of approximately −180° to +180°, typically in the range of −90° to +90°, possibly in the range of −60° to +60°, −45° to +45°, −30° to +30° or less. As shown, the angle theta  1070  lies within a plane Y. In particular, axis y, which runs through the center of the central lumen  1028  at the distal end  1026 , forms the angle theta  1070  with axis z. In this example, plane Y is orthogonal to both plane X and plane Z. Axes x, y, z all intercept at a point within the central lumen  1028  which also coincides with the intersection of planes X, Y, Z.  
         [0234]     Similarly,  FIG. 61D  illustrates movement of the distal end  1026  through an angle theta  1070  on the opposite side of axis z. Again, the angle theta  1070  is measured from the axis z to the axis y, which runs through the center of the central lumen  1016  at the distal end  1026 . As shown, the angle theta  1070  lies in plane Y. Thus, the primary curve  1100 , secondary curve  1104 , and angle theta  1070  can all lie in different planes, and optionally in orthogonal planes. However, it may be appreciated that the planes within which the primary curve  1100 , secondary curve  1104  and angle theta  1070  lie may be mutually dependent and therefore would allow the possibility that some of these lie within the same plane.  
         [0235]     In addition, the outer guide catheter  1000  may be pre-formed and/or steerable to provide additional curves or shapes. For example, as illustrated in  FIG. 62A , an additional curve  1110  may be formed by the outer guide catheter  1000  proximal to the primary curve  1100 . In this example, the curve  1110  provides lift or raises the distal end  1016  of the outer guide catheter  1000 , which in turn raises the distal end  1026  of the inner guide catheter  1020 . Such lifting is illustrated in  FIG. 62B . Here, the system  1  is shown prior to lifting in dashed line wherein the axis y′ passes through the intersection of axis z and axis x′. After application of curve  1110 , the distal portion of the system  1  is lifted in the direction of axis z so that axis x′ is raised to axis x″ and axis y′ is raised to axis y″. This raises distal end  1026  to a desired height.  
         [0236]     The articulated position of the multi-catheter guiding system  1  illustrated in  FIGS. 61A-61D  and  FIGS. 62A-62B  is particularly useful for accessing the mitral valve.  FIGS. 63A-63D  illustrate a method of using the system  1  for accessing the mitral valve MV. To gain access to the mitral valve, the outer guide catheter  1000  may be tracked over a dilator and guidewire from a puncture in the femoral vein, through the inferior vena cava and into the right atrium. As shown in  FIG. 63A , the outer guide catheter  1000  may be punctured through a fossa F in the interatrial septum S. The outer guide catheter  1000  is then advanced through the fossa F and curved by the primary curve  1100  so that the distal end  1016  is directed over the mitral valve MV. Again, it may be appreciated that this approach serves merely as an example and other approaches may be used, such as through the jugular vein, femoral artery, port access or direct access, to name a few. Positioning of the distal end  1016  over the mitral valve MV may be accomplished by precurvature of the outer guide catheter  1000 , wherein the catheter  1000  assumes this position when the dilator and guidewire are retracted, and/or by steering of the outer guide catheter  1000  to the desired position. In this example, formation of the primary curve  1100  moves the distal end  1016  within a primary plane, corresponding to previous plane X, substantially parallel to the valve surface. This moves the distal end  1016  laterally along the short axis of the mitral valve MV, and allows the distal end  1016  to be centered over the opening O between the leaflets LF.  
         [0237]     Referring to  FIG. 63B , the inner guide catheter  1020  is advanced through the central lumen  1018  of the outer guide catheter  1000  and the distal end  1026  is positioned so that the central lumen  1028  is directed toward the target tissue, the mitral valve MV. In particular, the central lumen  1028  is to be directed toward a specific area of the mitral valve MV, such as toward the opening O between the valve leaflets LF, so that a particular interventional procedure may be performed. In  FIG. 63B , the inner guide catheter  1020  is shown in a position which includes a secondary curve  1104  in a secondary plane, corresponding to previous plane Z. Formation of the secondary curve  1104  moves the distal end  1026  vertically and angularly between the commissures C, directing the central lumen  1028  toward the mitral valve MV. In this position an interventional device or catheter  1030  which is passed through the central lumen  1028  would be directed toward and/or through the opening O. Although the primary curve  1100  and the secondary curve  1104  may be varied to accommodate different anatomical variations of the valve MV and different surgical procedures, further adjustment may be desired beyond these two curvatures for proper positioning of the system  1 .  
         [0238]     Referring to  FIG. 63C , the distal end  1026  of the inner guide catheter  1020  may be positioned through an angle theta  1070 . This moves the distal end  1026  vertically and angularly through a theta plane, corresponding to previous plane Y. Movement of the distal end  1026  through the angle theta  1070  in either direction is shown in dashed line in  FIG. 63B . Such movement can be achieved by precurvature and/or by steering of the catheter  1020 . Consequently, the central lumen  1028  can be directed toward the mitral valve MV within a plane which differs from the secondary plane. After such movements, the inner guide catheter  1020  will be in a position so that the opening of the central lumen  1028  at the end  1016  faces the desired direction. In this case, the desired direction is toward the center of and orthogonal to the mitral valve.  
         [0239]     In some instances, it is desired to raise or lower the distal end  1026  so that it is at a desired height in relation to the mitral valve MV. This may be accomplished by precurvature and/or by steering of the outer guide catheter  1000  to form additional curve  1110 . Generally this is used to lift the distal end  1026  above the mitral MV wherein such lifting was illustrated in  FIG. 62B .  
         [0240]     When the curvatures in the catheters  1000 ,  1020  are formed by steering mechanisms, the steering mechanisms may be locked in place by a locking feature. Locking can provide additional stiffness and stability in the guiding system  1  for the passage of interventional devices or catheters  1030  therethrough, as illustrated in  FIG. 60 . The interventional catheter  1030  can be passed through the central lumen  1028  toward the target tissue, in this case the mitral valve MV. Positioning of the distal end  1026  over the opening O, as described above, allows the catheter  1030  to pass through the opening O between the leaflets LF if desired, as shown in  FIG. 63D . At this point, any desired procedure may be applied to the mitral valve for correction of regurgitation or any other disorder.  
         [0241]     C. Steering Mechanisms  
         [0242]     As described previously, the curvatures may be formed in the catheters  1000 ,  1020  by precurving, steering or any suitable means. Precurving involves setting a specific curvature in the catheter prior to usage, such as by heat setting a polymer or by utilizing a shape-memory alloy. Since the catheters are generally flexible, loading of the catheter on a guidewire, dilator obturator or other introductory device straightens the catheter throughout the curved region. Once the catheter is positioned in the anatomy, the introductory device is removed and the catheter is allowed to relax back into the precurved setting.  
         [0243]     To provide a higher degree of control and variety of possible curvatures, steering mechanisms may be used to create the curvatures and position the catheters. In some embodiments, the steering mechanisms comprise cables or pullwires within the wall of the catheter. As shown in  FIG. 64A , the outer guide catheter  1000  may include a pullwire  1120  slidably disposed in lumens within the wall of the catheter  1000  extending to the distal end  1016 . By applying tension to the pullwire  1120  in the proximal direction, the distal end  1016  curves in the direction of the pullwire  1120  as illustrated by arrow  1122 . Likewise, as shown in  FIG. 64A , placement of the pullwire  1120  along the opposite side of the catheter  1000  will allow the distal end  1016  to curve in the opposite direction, as illustrated by arrow  1124 , when tension is applied to the pullwire  1120 . Thus, referring to  FIG. 64C , diametrically opposing placement of pullwires  1120  within the walls of the catheter  1000  allows the distal end  1016  to be steered in opposite directions. This provides a means of correcting or adjusting a curvature. For example, if tension is applied to one pullwire to create a curvature, the curvature may be lessened by applying tension to the diametrically opposite pullwire. Referring now to  FIG. 64D , an additional set of opposing pullwires  1120 ′ may extend within the wall of the catheter  1000  as shown. This combination of pullwires  1120 ,  1120 ′ allows curvature of the distal end in at least four directions illustrated by arrows  1122 ,  1124 ,  1126 ,  1128 . In this example, pullwires  1120  create the primary curve  1100  of the outer guide catheter  1000  and the pullwires  1120 ′ create the lift. It may be appreciated that  FIGS. 64A-64D  also pertain to the inner guide catheter  1020 . For example, in  FIG. 64D , pullwires  1120  may create the secondary curve  1104  of the inner guide catheter  1020  and the pullwires  1120 ′ create the angle theta  1070 .  
         [0244]     Such pullwires  1120  and/or pullwires  1120 ′ and associated lumens may be placed in any arrangement, singly or in pairs, symmetrically or nonsymmetrically and any number of pullwires may be present. This may allow curvature in any direction and about various axes. The pullwires  1120 ,  1120 ′ may be fixed at any location along the length of the catheter by any suitable method, such as gluing, tying, soldering, or potting, to name a few. When tension is applied to the pullwire, the curvature forms from the point of attachment of the pullwire toward the proximal direction. Therefore, curvatures may be formed throughout the length of the catheter depending upon the locations of the points of attachment of the pullwires. Typically, however, the pullwires will be attached near the distal end of the catheter, optionally to an embedded tip ring  280 , illustrated in  FIG. 64E . As shown, the pullwire  1120  passes through an orifice  286  in the tip ring  280 , forms a loop shape and then passes back through the orifice  286  and travels back up through the catheter wall (not shown). In addition, the lumens which house the pullwires may be straight, as shown in  FIGS. 64A-64D , or may be curved.  
         [0245]     D. Catheter Construction  
         [0246]     The outer guide catheter  1000  and inner guide catheter  1020  may have the same or different construction which may include any suitable material or combination of materials to create the above described curvatures. For clarity, the examples provided will be in reference to the outer guide catheter  1000 , however it may be appreciated that such examples may also apply to the inner guide catheter  1020 .  
         [0247]     In embodiments in which the catheter is precurved rather than steerable or in addition to being steerable, the catheter  1000  may be comprised of a polymer or copolymer which is able to be set in a desired curvature, such as by heat setting. Likewise, the catheter  1000  may be comprised of a shape-memory alloy.  
         [0248]     In embodiments in which the catheter is steerable, the catheter  1000  may be comprised of one or more of a variety of materials, either along the length of the catheter  1000  or in various segments. Example materials include polyurethane, Pebax, nylon, polyester, polyethylene, polyimide, polyethylenetelephthalate(PET), polyetheretherketone (PEEK). In addition, the walls of the catheter  1000  may be reinforced with a variety of structures, such as metal braids or coils. Such reinforcements may be along the length of the catheter  1000  or in various segments.  
         [0249]     For example, referring to  FIG. 65A , the catheter  1000  may have a proximal braided segment  1150 , a coiled segment  1152  and distal braided segment  1154 . The proximal braided segment  1150  provides increased column strength and torque transmission. The coiled segment  1152  provides increased steerability. The distal braided segment  1154  provides a blend of steerability and torque/column strength. In another example, referring to  FIG. 65B , the outer guiding catheter  1000  has a proximal double-layer braided segment  1151  and a distal braided segment  1154 . Thus, the proximal double-layer segment  1151  comprises a multi-lumen tube  1160  (having steering lumens  1162  for pullwires, distal ends of the steering lumens  1162  optionally embedded with stainless steel coils for reinforcement, and a central lumen  1163 ), an inner braided layer  1164 , and an outer braided layer  1166 , as illustrated in the cross-sectional view of  FIG. 65C . Similarly,  FIG. 65D  provides a cross-sectional view of the distal braided segment  1154  comprising the multi-lumen tube  1160  and a single braided layer  1168 . In a further example, referring to  FIG. 65E , the inner guiding catheter  1020  comprises a multi-lumen tube  1160  without reinforcement at its proximal end, a single braided layer middle segment  1170  and a single braided layer distal segment  1171 . Each of the single braided layer segments  1170 ,  1171  have a multi-lumen tube  1160  and a single layer of braiding  1168 , as illustrated in cross-sectional view  FIG. 65F . However, the segments  1170 ,  1171  are comprised of polymers of differing durometers, typically decreasing toward the distal end.  
         [0250]      FIG. 65G  illustrates an other example of a cross-section of a distal section of an outer guiding catheter  1000 . Here, layer  1130  comprises 55D Pebax and has a thickness of approximately 0.0125 in. Layer  1131  comprises a 30 ppi braid and has a thickness of approximately 0.002 in. by 0.0065 in. Layer  1132  comprises 55D Pebax and has a thickness of approximately 0.006 in. Layer  1133  comprises 30 ppi braid and has a thickness of approximately 0.002 in by 0.0065 in. And finally, layer  1134  comprises Nylon 11 and includes steering lumens for approximately 0.0105 in. diameter pullwires  1120 . Central lumen  1163  is of sufficient size for passage of devices.  
         [0251]      FIGS. 65H-65I  illustrate additional examples of cross-sections of an inner guiding catheter  1020 ,  FIG. 65I  illustrating a cross-section of a portion of the distal end and  FIG. 65I  illustrating a cross-section of a more distal portion of the distal end. Referring to  FIG. 65H , layer  1135  comprises 40D polymer and has a thickness of approximately 0.0125 in. Layer  1136  comprises a 30 ppi braid and has a thickness of approximately 0.002 in. by 0.0065 in. Layer  1137  comprises 40D polymer and has a thickness of approximately 0.006 in. Layer  1138  comprises a 40 D polymer layer and has a thickness of approximately 0.0035 in. And finally, layer  1139  comprises a 55D liner. In addition, coiled steering lumens are included for approximately 0.0105 in. diameter pullwires  1120 . And, central lumen  1163  is of sufficient size for passage of devices. Referring to  FIG. 65I , layer  1140  comprises a 40D polymer, layer  1141  comprises a 35D polymer, layer  1142  comprises a braid and layer  1143  comprises a liner. In addition, coiled steering lumens  1144  are included for pullwires. And, central lumen  1163  is of sufficient size for passage of devices.  
         [0252]      FIGS. 66A-66C  illustrate an embodiment of a keying feature which may be incorporated into the catheter shafts. The keying feature is used to maintain relationship between the inner and outer guide catheters to assist in steering capabilities. As shown in  FIG. 66A , the inner guide catheter  1020  includes one or more protrusions  1400  which extend radially outwardly. In this example, four protrusions  1400  are present, equally spaced around the exterior of the catheter  1020 . Likewise, the outer guide catheter  1000  includes corresponding notches  1402  which align with the protrusions  1400 . Thus, in this example, the catheter  1000  includes four notches equally spaced around its central lumen  1018 . Thus, the inner guide catheter  1020  is able to be translated within the outer guide catheter  1000 , however rotation of the inner guide catheter  1020  within the outer guide catheter  1000  is prevented by the keying feature, i.e. the interlocking protrusions  1400  and notches  1402 . Such keying helps maintain a known correlation of position between the inner guide catheter  1020  and outer guide catheter  1000 . Since the inner and outer guide catheters  1020 ,  1000  form curvatures in different directions, such keying is beneficial to ensure that the compound curvature formed by the separate curvatures in the inner and outer guide catheters  1020 ,  1000  is the compound curvature that is anticipated. Keying may also increase stability wherein the curvatures remain in position reducing the possibility of compensating for each other.  
         [0253]      FIG. 66B  illustrates a cross-sectional view of the outer guiding catheter  1000  of  FIG. 66A . Here, the catheter  1000  includes a notched layer  1404  along the inner surface of central lumen  1018 . The notched layer  1404  includes notches  1402  in any size, shape, arrangement and number. Optionally, the notched layer  1404  may include lumens  1406 , typically for passage of pullwires  1120 . However, the lumens  1406  may alternatively or in addition be used for other uses. It may also be appreciated that the notched layer  1404  may be incorporated into the wall of the catheter  1000 , such as by extrusion, or may be a separate layer positioned within the catheter  1000 . Further, it may be appreciated that the notched layer  1404  may extend the entire length of the catheter  1000  or one or more portions of the length of the catheter  1000 , including simply a small strip at a designated location along the length of the catheter  1000 .  
         [0254]      FIG. 66C  illustrates a cross-sectional view of the inner guiding catheter  1020  of  FIG. 66A . Here, the catheter  1020  includes protrusions  1400  along the outer surface of the catheter  1020 . The protrusions  1400  may be of any size, shape, arrangement and number. It may be appreciated that the protrusions  1400  may be incorporated into the wall of the catheter  1020 , such as by extrusion, may be included in a separate cylindrical layer on the outer surface of the catheter  1020 , or the protrusions  1400  may be individually adhered to the outer surface of the catheter  1020 . Further, it may be appreciated that the protrusions  1400  may extend the entire length of the catheter  1000  or one or more portions of the length of the catheter  1020 , including simply a small strip at a designated location along the length of the catheter  1020 .  
         [0255]     Thus, the keying feature may be present along one or more specific portions of the catheters  1000 ,  1020  or may extend along the entire length of the catheters  1000 ,  1020 . Likewise, the notches  1402  may extend along the entire length of the outer guiding catheter  1020  while the protrusions  1400  extend along discrete portions of the inner guiding catheter  1000  and vice versa. It may further be appreciated that the protrusions  1400  may be present on the inner surface of the outer guiding catheter  1000  while the notches  1402  are present along the outer surface of the inner guiding catheter  1020 .  
         [0256]     Alternatively or in addition, one or more steerable portions of the catheter  1000  may comprise a series of articulating members  1180  as illustrated in  FIG. 67A . Exemplary embodiments of steerable portions of catheters comprising such articulating members  1180  are described in U.S. patent application Ser. No. 10/441,753 (Attorney Docket No. 020489-001200US) incorporated herein by reference for all purposes.  FIG. 67B  illustrates the outer guide catheter  1000  having a steerable portion comprising articulating members  1180  at its distal end  1016 .  
         [0257]     Briefly, referring to  FIG. 67A , each articulating member  1180  may have any shape, particularly a shape which allows interfitting or nesting as shown. In addition, it is desired that each member  1180  have the capability of independently rotating against an adjacent articulating member  1180 . In this embodiment, the articulating members  1180  comprise interfitting domed rings  1184 . The domed rings  1184  each include a base  1188  and a dome  1186 . The base  1188  and dome  1186  have a hollow interior which, when the domed rings  1184  are interfit in a series, forms a central lumen  1190 . In addition, the dome  1186  allows each articulating member  1180  to mate against an inner surface of an adjacent domed ring  1184 .  
         [0258]     The intermitting domed rings  1184  are connected by at least one pullwire  1120 . Such pullwires typically extend through the length of the catheter  1000  and at least one of the interfitting domed rings  1184  to a fixation point where the pullwire  1120  is fixedly attached. By applying tension to the pullwire  1120 , the pullwire  1120  arcs the series of interfitting domed rings  1184  proximal to the attachment point to form a curve. Thus, pulling or applying tension on at least one pullwire, steers or deflects the catheter  1000  in the direction of that pullwire  1120 . By positioning various pullwires  1120  throughout the circumference of the domed rings  1184 , the catheter  1000  may be directed in any number of directions.  
         [0259]     Also shown in  FIG. 67A , each interfitting domed ring  1184  may comprise one or more pullwire lumens  1182  through which the pullwires  1120  are threaded. Alternatively, the pullwires  1120  may be threaded through the central lumen  1190 . In any case, the pullwires are attached to the catheter  1000  at a position where a desired curve is to be formed. The pullwires  1120  may be fixed in place by any suitable method, such as soldering, gluing, tying, welding or potting, to name a few. Such fixation method is typically dependent upon the materials used. The articulating members  1180  may be comprised of any suitable material including stainless steel, various metals, various polymers or co-polymers. Likewise the pullwires  1120  may be comprised of any suitable material such as fibers, sutures, metal wires, metal braids, or polymer braids.  
         [0260]     E. Handles  
         [0261]     As mentioned previously, manipulation of the guide catheters  1000 ,  1020  is achieved with the use of handles  1056 ,  1057  attached to the proximal ends of the catheters  1000 ,  1020 .  FIG. 68  illustrates a preferred embodiment of handles  1056 ,  1057 . As shown, handle  1056  is attached to the proximal end  1014  of outer guide catheter  1000  and handle  1057  is attached to the proximal end  1024  of inner guide catheter  1020 . Inner guide catheter  1020  is inserted through handle  1056  and is positioned coaxially within outer guide catheter  1000 . In this embodiment, the handles  1056 ,  1057  are not linked together as shown in the embodiment illustrated in  FIG. 60 . It may be appreciated that such handles  1056 ,  1057  may alternatively be connected by external connecting rods, bars or plates or by an additional external stabilizing base. An embodiment of a stabilizing base will be described in a later section. Referring back to  FIG. 68 , interventional catheter is inserted through handle  1057  and is positioned coaxially within inner guide catheter  1020  and outer guide catheter  1000 .  
         [0262]     Each handle  1056 ,  1057  includes two steering knobs  1300   a ,  1300   b  emerging from a handle housing  1302  for manipulation by a user. Steering knobs  1300   a  are disposed on a side of the housing  1302  and steering knobs  1300   b  are disposed on a face of the housing  1302 . However, it may be appreciated that such placement may vary based on a variety of factors including type of steering mechanism, size and shape of handle, type and arrangement of parts within handle, and ergonomics to name a few.  
         [0263]      FIG. 69  illustrates the handles  1056 ,  1057  of  FIG. 68  with a portion of the housing  1302  removed to reveal the assemblies of the handles. Each knob  1300   a ,  1300   b  controls a steering mechanism which is used to form a curvature in the attached catheter. Each steering mechanism includes a hard stop gear assembly  1304  and a friction assembly  1306 . Tension is applied to one or more pullwires by action of the hard stop gear assembly to form a curve in a catheter. Tension is maintained by the friction assembly. When tension is released from the one or more pullwires the catheter returns to a straightened position.  
         [0264]      FIG. 70  illustrates steering mechanisms within a handle wherein the housing  1302  is removed for clarity. Here, steering knob  1300   a  is attached to a hard stop gear assembly  1304  and a friction assembly (not in view) and steering knob  1300   b  is attached to a separate hard stop gear assembly  1304  and friction assembly  1306 . Steering knob  1300   a  is attached to a knob post  1318  which passes through a base  1308 , terminating in a knob gear wheel  1310 . The knob gear wheel  1310  actuates the hard stop gear assembly  1304 , thereby applying tension to one or more pullwires  1120 .  
         [0265]     The knob gear wheel  1310  is a toothed wheel that engages a disk gear wheel  1312 . Rotation of the steering knob  1300   a  rotates the knob post  1318  and knob gear wheel  1310  which in turn rotates the disk gear wheel  1312 . Rotation of the disk gear wheel  1312  applies tension to one or more pullwires extending through the attached catheter, in this example the outer guiding catheter  1000 . As shown, the outer guiding catheter  1000  passes through the base  1308 , wherein one or more pullwires  1120  extending through the catheter  1000  are attached to the disk  1314 . Such attachment is schematically illustrated in  FIG. 71 . Catheter  1000  is shown passing through base  1308 . A pullwire  1120  passing through a steering lumen  1162  in the catheter  1000  emerges from the wall of the catheter  1000 , passes through an aperture  1320  in the disk  1314  and is attached to an anchor peg  1316  on the disk  1314 . Rotation of the disk  1314  (indicated by arrow  1328 ) around disk post  1315  by action of the disk gear wheel  1312 , applies tension to the pullwire  1120  by drawing the pullwire  1120  through the aperture  1320  and wrapping the pullwire  1120  around the disk  1314  as it rotates. Additional rotation of the disk  1314  applies increasing tension to the pullwire  1120 . To limit the amount of tension applied to the pullwire  1120 , to limit curvature of the catheter and/or to avoid possible breakage of the pullwire  1120 , the rotation of the disk  1314  may be restricted by hard stop peg  1322  which is attached to the disk  1314  and extends into the base  1308 .  
         [0266]      FIGS. 72A-72B  illustrate how the hard stop peg  1322  is used to restrict rotation of disk  1314 .  FIGS. 72A-72B  provide a top view, wherein the disk  1314  is disposed on the base  1308 . The anchor peg  1316  is shown with the pullwire  1120  there attached. A groove  1326  is formed in the base  1308  beneath the disk  1314  and forms an arc shape. The hard stop peg  1322  extends from the disk  1314  into the groove  1326  in the base  1308 . Referring now to  FIG. 72B , rotation of the disk  1314  around knob post  1318 , indicated by arrow  1330 , draws the pullwire  1120  through the aperture  1320  as previously described, wrapping the pullwire  1120  around the disk  1314 . As the disk  1314  rotates, the hard stop peg  1322  follows along the groove  1326 , as shown. The disk  1314  continues rotating until the hard stop peg  1322  reaches a hard stop  1324 . The hard stop  1324  is positioned in the groove  1326  and prevents further passage of the hard stop peg  1322 . Thus, disk  1314  rotation may be restricted to any degree of rotation less than or equal to 360 degrees by positioning of the hard stop  1324 .  
         [0267]     In some instances, it is desired to restrict rotation of the disk  1314  to a degree of rotation which is more than 360 degrees. This may be achieved with another embodiment of the hard stop gear assembly  1304 . Referring now to  FIGS. 73A-73B , a portion of such a hard stop gear assembly  1304  is shown.  FIG. 73A  illustrates the base  1308  and the disk post  1315  positioned therethrough. Also shown in the base  1308  is an aperture  1334  through which the knob post  1318 , knob gear wheel  1310  and friction assembly  1306  pass, and a passageway  1336  through which the catheter  1000  passes. In this embodiment of the hard stop gear assembly  1304 , a groove  1326  is also present in an arc shape around the disk post  1315 , however a ball  1332  is positioned in the groove  1326  rather than a hard stop peg  1322 . Disk  1314  is positioned over the groove  1326  and the ball  1332  as shown in  FIG. 73B . The disk  1314 , illustrated in  FIG. 73C , has a groove  1356  in its surface which is positioned adjacent to the base  1308 , the groove  1356  having an arc shape similar to the groove  1326  in the base  1308 . The ball  1332  is not fixedly attached to the base  1308  or the disk  1314  and is therefore free to move along the channel formed by the groove  1326  in the base  1308  and the groove in the disk  1314 .  
         [0268]      FIGS. 74A-74F  illustrate how rotation of the disk  1314  may be restricted by the ball  1332  to a degree of rotation which is more than 360 degrees.  FIGS. 74A-74F  illustrate the groove  1326  in the base  1308  wherein the groove  1326  has an arc shape around disk post  1315 . The groove  1326  does not form a complete circle; a first groove end  1350   a  and a second groove end  1350   b  form a wall which prevent passage of the ball  1332 . It may be appreciated that the groove ends  1350   a ,  1350   b  may be any distance apart, shortening the length of the groove  1326  by any amount, and allowing the ball  1332  movement, and hence catheter deflection, to be adjusted to any desired amount. To begin, referring to  FIG. 74A , the ball  1332  is positioned within the groove  1326  near the first groove end  1350   a . The disk  1314  has a matching groove  1352  (shape illustrated in dashed line) including a first groove end  1354   a  and a second groove end  1354   b . The disk  1314  is positioned over the ball  1332  so that the ball  1332  is near the second groove end  1354   b.    
         [0269]     Referring now to  FIG. 74B , the disk  1314  may be rotated while the ball  1332  remains in place. Here, the disk  1314  has rotated 90 degrees, as indicated by arrow  36000  and the position of the groove ends  1354   a ,  1354   b . Referring now to  FIG. 74C , the disk  1314  may be further rotated while the ball  1332  remains in place. Here, the disk  1314  has rotated 270 degrees, as indicated by arrow  36000  and the position of the groove ends  1354   a ,  1354   b . The disk  1314  may continue rotating to 360 degrees, as shown in  FIG. 74D , indicated by arrow  36000 . Here, the first groove end  1354   a  in the disk  1314  has contacted the ball  1332  and pushes the ball  1332  along groove  1326  in the base. Referring now to  FIG. 74E , the disk  1314  may be further rotated while the ball  1332  is pushed along the groove  1326  in the base  1308  by the first groove end  1354   a  in the disk  1314 . Here, the disk  1314  is shown to have rotated 540 degrees. Referring to  FIG. 74F , the disk  1314  rotates until the ball  1332  reaches the second groove end  1350   b  of the base  1308 , providing a hard stop. In this position, the ball  1332  is held between the first groove end  1354   a  of the disk  1314  and the second groove end  1350   b  of the base  1308  and further rotation of the disk  1314  is prevented. Thus, the disk  1314  was rotated approximately 660 degrees in this example. Any maximum degree of rotation may be set by positioning of groove ends  1350   a ,  1350   b  and/or groove ends  1354   a ,  1354   b . Additionally, in some embodiments, rotation can be limited by adding more than one ball  1332  to the groove  1326 , for example, two, three, four, five, six, seven, eight, nine, ten or more balls may be used to limit travel and hence curvature.  
         [0270]     It may be appreciated that one or more pullwires  1120  are attached to the disk  1314  in a manner similar to that illustrated in  FIG. 71 . Therefore, as the disk  1314  rotates, around disk post  1315  by action of the disk gear wheel  1312 , tension is applied to the pullwire  1120  by drawing the pullwire  1120  through the aperture  1320  and wrapping the pullwire  1120  around the disk  1314  as it rotates. Additional rotation of the disk  1314  applies increasing tension to the pullwire  1120 . Restriction of rotation as described above limits the amount of tension applied to the pullwire  1120 , to limit curvature of the catheter and/or to avoid possible breakage of the pullwire  1120 .  
         [0271]     As mentioned, each steering mechanism includes at least a hard stop gear assembly  1304  and a friction assembly  1306 . As described above, tension is applied to one or more pullwires by action of the hard stop gear assembly to form a curve in a catheter. Tension is maintained by the friction assembly.  FIG. 75  illustrates an embodiment of a friction assembly  1306 . The friction assembly  1306  essentially holds a steering knob, in this example steering knob  1300   b , and the associated knob post  1318  in a rotated position. Here, rotation of the knob  1300   b  and post  1318  rotates attached knob gear wheel  1310 . The knob gear wheel  1310  actuates the hard stop gear assembly  1304 , thereby applying tension to one or more pullwires  1120 . The knob gear wheel  1310  is a toothed wheel that engages a disk gear wheel  1312 . Rotation of the steering knob  1300   b  rotates the knob post  1318  and knob gear wheel  1310  which in turn rotates the disk gear wheel  1312 . Rotation of the disk gear wheel  1312  applies tension to one or more pullwires extending through the attached catheter, in this example the outer guiding catheter  1000 .  
         [0272]     The steering knob  1300   b  and knob post  1318  are held in a rotated position by friction provided by a frictional pad  1370 . The frictional pad  1370  is positioned between ring  1372  attached to the knob post  1318  and a plate  1374  attached to the base  1308 . The knob post  1318  extends from the knob  1300   b  through the ring  1372 , the frictional pad  1370  and then the plate  1374 . The plate  1374  has internal threads which mate with threads on the knob post  1318 . As the knob post  1318  rotates, the threads on the post  1318  advance through the threads on the plate  1374 . This draws the ring  1372  closer to the plate  1374 , compressing the frictional pad  1370  therebetween. Frictional pad  1370  may be comprised of any O-ring or sheet material with desirable frictional and compressibility characteristics, such as silicone rubber, natural rubber or synthetic rubbers, to name a few. In preferred embodiments, an EPDM rubber O-ring is used. Reverse rotation of the knob post  1318  is resisted by friction of the frictional pad  1370  against the ring  1372 . The higher the compression of the frictional pad  1370  the stronger the frictional hold. Therefore, as the steering knob  1300   b  is rotated and increasing amounts of tension are applied to the pullwires  1120 , increasing amounts of friction are applied to the ring  1372  to hold the knob  1300   b  in place.  
         [0273]     Manual reverse rotation of the steering knob  1300   b  releases tension on the pullwires  1120  and draws the ring  1372  away from the plate  1374  thereby reducing the frictional load. When tension is released from the pullwires  1120  the catheter  1000  returns toward a straightened position.  
         [0274]     It may be appreciated that each handle  1056 ,  1057  includes a steering mechanism for each curve to be formed in the attached catheter. Thus, as shown in  FIG. 69 , handle  1056  includes a steering mechanism to form the primary curve  1100  in outer guiding catheter  1000  and a steering mechanism to form the additional curve  1110 . Likewise, handle  1057  includes a steering mechanism to form the secondary curve  1104  in inner guiding catheter  1020  and a steering mechanism to form the angle theta  1070 .  
         [0275]     Some curves, such as the primary curve  1100 , secondary curve  1104  and additional curve  1110  each typically vary in curvature between a straight configuration and a curved configuration in a single direction. Such movement may be achieved with single set of a hard stop gear assembly  1304  and a friction assembly  1306 . However, other curves, such as the angle theta  1070 , may be formed in two directions as shown in  FIGS. 61C-61D . Such movement is achieved with two sets of the hard stop gear assembly  1304  and the friction assembly  1306 , each set controlling curvature in a single direction.  
         [0276]      FIG. 75  illustrates the presence of an additional set of the friction assembly  1306 ′. One or more pullwires  1120 ′, such as an opposing set as illustrated in  FIG. 64D , extending within the wall of the catheter  1000  are attached to the disk  1314 ′ in the same manner as pullwires  1120  are attached to disk  1314 . The disks  1314 ,  1314 ′ are arranged so that rotation of steering knob  1300   b  in one direction applies tension to the pullwires  1120  via disk  1314  and rotation of steering knob  1300   b  in the opposite direction applies tension to the pullwires  1120 ′ via disk  1314 ′. Likewise, the additional friction assembly  1306 ′ is shown having a ring  1372 ′ attached to the knob post  1318  and a frictional pad  1370 ′ disposed between the ring  1372 ′ and the opposite side of the plate  1374 . Therefore, as rotation of the steering knob  1300   b  in the opposite direction applies tension to the pullwires  1120 ′ via disk  1314 ′, the frictional pad  1370 ′ applies tension to the ring  1372 ′ holding the knob post  1318 ′ in place.  
         [0277]     It may be appreciated that various other mechanisms may be used for tensioning and holding pullwires  1120  in place. Example mechanisms that may alternatively be used include clutches, ratchets, levers, knobs, rack and pinions, and deformable handles, to name a few.  
         [0278]     F. Interventional System  
         [0279]      FIG. 76  illustrates an embodiment of an interventional system  3  of the present invention. An embodiment of the multi-catheter guiding system  1  of the present invention is shown comprising an outer guide catheter  1000 , having a proximal end  1014  and a distal end  1016 , and an inner guide catheter  1020 , having a proximal end  1024  and a distal end  1026 , wherein the inner guide catheter  1020  is positioned coaxially within the outer guide catheter  1000 , as shown. In addition, a hemostatic valve  1090  is disposed within handle  1056  or external to handle  1056  as shown to provide leak-free sealing with or without the inner guide catheter  1020  in place. The valve  1090  also prevents back bleeding and reduces the possibility of air introduction when inserting the inner guide catheter  1020  through the outer guide catheter  1000 . An example of a hemostatic valve  1090  is illustrated in  FIG. 76A , however any suitable valve or hemostatic valve may be used to provide similar functions. In  FIG. 76A , the valve  1090  has a first end  1091 , a second end  1092  and a lumen  1093  therethrough. The inner wall of lumen  1093  is preferably tapered toward end  1091  and may further include a plurality of tapered axial channels configured to receive the protrusions  1400  on the inner guide catheter  1020 . The first end  1091  is attached to the outer guide catheter  1000  and the second end  1092  is free. Referring now back to  FIG. 76 , the distal ends  1016 ,  1026  of catheters  1000 ,  1020 , respectively, are sized to be passable to a body cavity, typically through a body lumen such as a vascular lumen.  
         [0280]     To assist in inserting the fixation device  14  through a hemostatic valve  1090 , a fixation device introducer may be used. For example, when the fixation device  14  is loaded on a delivery catheter  300  and an inner guide catheter  1020 , insertion of the fixation device  14 , delivery catheter  300  and inner guide catheter  1020  through an outer guide catheter  1000  involves passing the fixation device  14  through a hemostatic valve  1090  on the outer guide catheter  1000 . To reduce any trauma to the fixation device  14  by the hemostatic valve  1090 , a fixation device introducer may be used. An embodiment of a fixation device introducer  1420  is illustrated in  FIG. 76B . The introducer  1420  includes a loading body  1422  and an insertion endpiece  1424 . The fixation device  14  is loaded into the loading body  1422  and into the insertion endpiece  1424  to approximately the dashed line  1428 . The insertion endpiece  1424  has a split end creating individual split sections  1430 , in this embodiment, four split sections  1430 . By compressing the split sections  1430 , the endpiece  1424  forms a taper. Such a taper is then inserted through a hemostatic valve  1090 , so that the insertion endpiece  1424  creates a smooth passageway through the valve for the fixation device  14 . Once the insertion endpiece  1424  is inserted through the valve  1090 , the fixation device  14 , and attached delivery catheter  300  and inner guide catheter  1020 , may then be advanced through the fixation device introducer  1420 . The fixation device introducer  1420  also includes a hemostatic valve within the loading body  1422  to prevent any backbleeding or leakage through the introducer  1420 .  
         [0281]     Manipulation of the guide catheters  1000 ,  1020  is achieved with the use of handles  1056 ,  1057  attached to the proximal ends of the catheters  1000 ,  1020 . As shown, handle  1056  is attached to the proximal end  1014  of outer guide catheter  1000  and handle  1057  is attached to the proximal end  1024  of inner guide catheter  1020 . Inner guide catheter  1020  is inserted through handle  1056  and is positioned coaxially within outer guide catheter  1000 .  
         [0282]     An embodiment of the delivery catheter  300  of the present invention is inserted through handle  1057  and is positioned coaxially within inner guide catheter  1020  and outer guide catheter  1000 . Therefore, a hemostatic valve  1090  is disposed within handle  1057  or external to handle  1057  as shown to provide leak-free sealing with or without the delivery catheter  300  in place. The valve  1090  functions as described above. The delivery catheter  300  includes a shaft  302 , having a proximal end  322  and a distal end  324 , and a handle  304  attached to the proximal end  322 . A fixation device  14  is removably coupled to the distal end  324  for delivery to a site within the body.  
         [0283]     The outer guide catheter  1000  and/or the inner guide catheter  1020  are precurved and/or have steering mechanisms to position the distal ends  1016 ,  1026  in desired directions. Precurvature or steering of the outer guide catheter  1000  directs the distal end  1016  in a first direction to create a primary curve while precurvature and/or steering of the inner guide catheter  1020  directs distal end  1026  in a second direction, differing from the first, to create a secondary curve. Together, the primary and secondary curves form a compound curve. Advancement of the delivery catheter  300  through the coaxial guide catheters  1000 ,  1020  guides the delivery catheter  300  through the compound curve toward a desired direction, usually in a direction which will position the fixation device  14  in a desired location within the body.  
         [0284]      FIG. 77  illustrates portions of another embodiment of an interventional system  3  of the present invention. Handles  1056 ,  1057  of the multi-catheter guiding system  1  of the present invention are shown. Each handle  1056 ,  1057  includes a set of steering knobs  1300   a ,  1300   b , as shown. Manipulation of the guide catheters  1000 ,  1020  is achieved with the use of the steering knobs  1300   a ,  1300   b  attached to the proximal ends of the catheters  1000 ,  1020 . Handle  304  of the delivery catheter  300  is also shown, including the proximal element line handle  312 , the lock line handle  310 , the actuator rod control  314  and the actuator rod handle  316 , among other features. The handle  304  is supported by the support base  306  which is connected to the handle  1057 .  
         [0285]     It may be appreciated the above described systems  3  are not intended to limit the scope of the present invention. The systems  3  may include any or all of the components of the described invention. In addition, the multi-catheter guiding system  1  of the present invention may be used to introduce other delivery catheters, interventional catheters or other devices. Likewise, the delivery catheter  300  may be introduced through other introducers or guiding systems. Also, the delivery catheter  300  may be used to deliver other types of devices to a target location within the body, including endoscopic staplers, devices for electrophysiology mapping or ablation, septal defect repair devices, heart valves, annuloplasty rings and others.  
         [0286]     In addition, many of the components of the system  3  may include one or more hydrophilic coatings. Hydrophilic coatings become slippery when wet, eliminate the need for separate lubricants. Thus, such coatings may be present on the multi-catheter guiding system, delivery catheter, and fixation device, including the proximal elements and distal elements, to name a few.  
         [0287]     Further, the system  3  may be supported by an external stabilizer base  1440 , an embodiment of which is illustrated in  FIG. 78 . Stabilizer base  1440  maintains the relative positions of the outer guide, inner guide and delivery catheter during a procedure. In this embodiment, the base  1440  comprises a platform  1442  having a planar shape for positioning on or against a flat surface, such as a table or benchtop. The base  1440  further includes a pair of handle holders  1444 ,  1448 , each attached to the platform  1442  and extending upwardly from the platform  1442 , either angularly or perpendicularly. Handle holder  1444  includes a notch  1446  for holding the outer guiding catheter  1000 , as illustrated in  FIG. 79 , thereby supporting the handle  1056 .  FIG. 79  shows the handle  1056  attached to the outer guiding catheter  1000  positioned so that the proximal end  1014  of the outer guiding catheter  1000  rests in the notch  1446 . Referring back to  FIG. 78 , handle holder  1448  includes an elongate portion  1452  having a trough  1450  and a hooked end  1454 . As shown in  FIG. 80 , handle  1057  rests on the elongate portion  1452  and the handle  304  rests on hooked end  1454  so that the inner guiding catheter  1020  extends from the handle  1057  to the handle  1056  and continues on within outer guiding catheter  1000 . The handle  304  is additionally supported by support base  306 , as shown.  
         [0288]     It may be appreciated that the stabilizer base  1440  may take a variety of forms and may include differences in structural design to accommodate various types, shapes, arrangements and numbers of handles.  
         [0289]     G. Kits  
         [0290]     Referring now to  FIG. 81 , kits  1500  according to the present invention comprise any of the components described in relation to the present invention. The kits  1500  may include any of the components described above, such as the outer guide catheter  1000  including handle  1056 , the inner guide catheter  1020  including handle  1057 , the delivery catheter  300  and the fixation device  14  and instructions for use IFU. Optionally, any of the kits may further include any other system components described above, such as various interventional tools  1040 , or components associated with positioning a device in a body lumen, such as a guidewire  1202 , dilator  1206  or needle  1204 . The instructions for use IFU will set forth any of the methods as described above, and all kit components will usually be packaged together in a pouch  1505  or other conventional medical device packaging. Usually, those kit components which will be used in performing the procedure on the patient will be sterilized and maintained within the kit. Optionally, separate pouches, bags, trays or other packaging may be provided within a larger package, where the smaller packs may be opened separately to separately maintain the components in a sterile fashion.  
         [0291]     While the foregoing is a complete description of the preferred embodiments of the invention, various alternatives, substitutions, additions, modifications, and equivalents are possible without departing from the scope of the invention. For example, in many of the above-described embodiments, the invention is described in the context of approaching a valve structure from the upstream side—that is, the atrial side in the case of a mitral valve. It should be understood that any of the foregoing embodiments may be utilized in other approaches as well, including from the ventricular or downstream side of the valve, as well as using surgical approaches through a wall of the heart. Moreover, the invention may be used in the treatment of a variety of other tissue structures besides heart valves, and will find usefulness in a variety of tissue approximation, attachment, closure, clamping and ligation applications, some endovascular, some endoscopic, and some open surgical.  
         [0292]     Again, although the foregoing invention has been described in some detail by way of illustration and example, for purposes of clarity of understanding, it will be obvious that various alternatives, modifications and equivalents may be used and the above description should not be taken as limiting in scope of the invention which is defined by the appended claims.