Tissue grasping devices and related methods

Abstract

To provide a suitable tissue grasping device and a related method.SOLUTION: A clip for securing cusps of a heart or venous valve includes a hub having a pair of entanglement-resistant spring-biased outer arms coupled to a lower end of the hub and a pair of entanglement-resistant spring-biased inner arms adjacent the outer arms and coupled to an upper end of the hub. A delivery catheter may be used to position the valve clip adjacent the target valve while the outer and inner arms are biased in an open position relative to one another. After the leaflet is located between the opened outer and inner arms, the biasing force may be released to allow the clip to self-close over the leaflet.SELECTED DRAWING: Figure 2B

Description

[Technical Field]

[0001] (Citation of Related Application) This application claims the benefit of U.S. Provisional Application No. 62 / 361,953 (filed July 13, 2016, Attorney Docket No. 52206-703.101), the entire contents of which are incorporated herein by reference.

[0002] BACKGROUND OF THE INVENTION 1. FIELD OF THE INVENTION The present invention relates generally to medical methods, devices, and systems. In particular, the present invention relates to methods, devices, and systems for endovascular, percutaneous, or minimally invasive surgical treatment of body tissues, such as tissue approximation or valve repair. More specifically, the present invention relates to methods and devices for repair of mitral and tricuspid heart valves, venous valves, and other tissue structures through minimally invasive and other procedures. [Background technology]

[0003] Surgical repair of bodily tissues often involves tissue approximation and fastening of such tissue in an approximation arrangement. When repairing a valve, tissue approximation often involves coapting the valve leaflets in a treatment arrangement, which can then be maintained by fastening or fixating the leaflets. Such fixation of the leaflets can be used to treat regurgitation, which most commonly occurs in the mitral valve.

[0004] Mitral regurgitation is characterized by the backflow of blood from the left ventricle of the heart through a dysfunctional mitral valve into the left atrium. During a normal cycle of cardiac contraction (systole), the mitral valve acts as a check valve to prevent the flow of oxygenated blood back into the left atrium. In this way, oxygenated blood is pumped through the aortic valve into the aorta. Valve regurgitation significantly reduces the heart's pumping efficiency and can put patients at risk for serious, progressive heart failure.

[0005] Mitral regurgitation can result from several different mechanical defects in the mitral valve or left ventricular wall. The valve leaflets, the valve tendons connecting the leaflets to the papillary muscles, the papillary muscles themselves, or the left ventricular wall can be damaged or otherwise dysfunctional. Generally, the annulus can be damaged, dilated, or weakened, limiting the ability of the mitral valve to close properly against high left ventricular pressures during systole.

[0006] The most common treatments for mitral valve regurgitation rely on valve replacement or valve repair, including leaflet and annulus remodeling, the latter generally referred to as valvuloplasty. One technique for mitral valve repair, which relies on suturing adjacent segments of opposing valve leaflets together, is called the "bow-tie" or "incision" technique. While all these techniques can be effective, they usually rely on open-heart surgery, in which the patient's chest is opened, typically via a sternotomy, and the patient undergoes cardiopulmonary bypass. The need to both open the chest and place the patient on bypass is traumatic and associated with high mortality and morbidity.

[0007] In some patients, fixation devices can be placed in the heart using minimally invasive techniques. The fixation device can hold adjacent segments of the opposing valve leaflets together and reduce mitral regurgitation. One such device used to clip the anterior and posterior leaflets of the mitral valve together is the MitraClip® fixation device sold by Abbott Vascular (Santa Clara, California, USA).

[0008] Fixation devices, such as the MitraClip® leaflet fixation device, often include a clip designed to grasp and hold the valve tissue as the clip arms are moved, positioned against the tissue at the treatment site, and then closed against the tissue. Such clips are designed to be closed into a final position and then mechanically locked in that position for continued gripping of the tissue.

[0009] Additionally, the act of grasping and closing into final position tightens the leaflets and potentially the annulus. Given that the MitraClip® is a relatively rigid device with mechanically locked steel (Elgiloy®) arms, the natural dilation and contraction of the annulus is altered.

[0010] Furthermore, to achieve prolapse and remove or reposition the device, it is required to flex the device at extreme angles (to the point of inversion) and release the grip. This extreme movement and deformation of the fixation device components before device deployment, during positioning, closure, and prolapse can lead to weakening and premature degradation of the fixation device. In addition, this makes the device extremely complex with multiple components and contributes to the relatively large overall size of the device and, therefore, a correspondingly large delivery system (approximately 24 Fr for the MitraClip® fixation device). This large catheter size inflicts additional trauma on the patient. By comparison, typical transseptal introducer sheaths are 8.5 Fr to 12 Fr (inner diameter) and 9 Fr to 16 Fr (outer diameter).

[0011] Some tissue fixation procedures require that the fixation device maintain some flexibility and mobility, allowing a range of physiological movement, even after the device is properly deployed and the target tissue is properly fixed in the desired position. This can increase the risk of premature failure of the device's complex locking mechanism, as continued deformation of the flexing components (e.g., from the continuous opening and closing of the valve leaflets) leads to undesirable degradation of the device.

[0012] Depending on the valve anatomy and disease state, there may generally be variations in coaptation length and dissimilarity in leaflet shape (e.g., dissimilarity between the anterior and posterior mitral leaflets). However, current devices and the market-leading MitraClip® fixation device are offered in only one size. This can pose a challenge for surgeons when presented with various valve sizes, coaptation lengths, fragility, and various functional and degenerative valve defects to be treated.

[0013] The ability to escape and reposition is an important safety consideration for the majority of medical devices. The current market-leading MitraClip® fixation device possesses these attributes to some extent because it allows for escape and repositioning. However, this presents a safety risk where tissue or the delivery mechanism can sometimes become caught in the barbs of the tissue-grasping features.

[0014] Finally, visualization during and after the procedure plays a critical role in the successful delivery and outcome of the device. Current state-of-the-art devices rely on fluoroscopy and transesophageal echocardiography (TEE). TEE primarily requires general anesthesia and adds significant risk to the elderly and frail patient population in whom this type of repair procedure is typically performed.

[0015] For at least these aforementioned reasons, there remains a need for: a) Simpler Devices with Fewer Components: Alternative and / or additional methods, devices, and systems for tissue fixation that may provide the beneficial resilience and durability of flexing components without the increased safety and manufacturing risks associated with multiple and complex components. b) Non-locking devices: The need for simpler devices to eliminate the procedural risks associated with locking the device and the risks associated with failure of the locking mechanism after deployment. c) Elastic and stretchable devices: the need for devices that gently tighten the annulus (or cusps) while preserving some natural expansion and contraction of the annulus (or cusps). d) Smaller Catheter Size / Profile: Considering that most patients undergoing these procedures may be elderly and frail with multiple comorbidities, there is also a need to create delivery devices much smaller than 24Fr, reducing the risks associated with vascular access. e) Multiple Device Sizes: Providing such methods, devices, and systems in a manner that does not limit the tissue grasping capabilities of the fixation device. For example, to accommodate short coaptation lengths and / or weak cusps, there may be a need for the ability to grasp beyond the coaptation region of the cusps while conforming to the shape and length of the cusps. f) Tangle-Free Design: The current market-leading MitraClip® fixation device has exposed barbs on both sides of the tissue-grasping features. Tendons, tissue, and the device delivery mechanism can become trapped by such exposed barbs. Therefore, there is a need to improve the safety of device extrication and repositioning, further reducing the risk of tissue or the delivery mechanism becoming stuck within the device during the procedure. g) Visualization: There is a need for improved visualization and feedback to perform the procedure safely and successfully with minimal trauma to the patient. h) Regional anesthesia: The ideal procedure would be under regional anesthesia without the use of general anesthesia. This mitigates the higher risks associated with general anesthesia. At least some of the embodiments disclosed below are directed to these ends.

[0016] (2. Description of Background Art) Minimally invasive and percutaneous techniques for coapting and correcting mitral valve leaflets and treating mitral valve regurgitation are described in PCT Publication Nos. WO 98 / 35638, WO 99 / 00059, WO 99 / 01377, and WO 00 / 03759, WO 2000 / 060995, and WO 2004 / 103162. 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. Thorne. Surg. 66:1640-1646 describe open techniques for performing "edge-to-edge" or "bow-tie" mitral valve repair, in which the edges of opposing leaflets are sutured together to reduce regurgitation. Dec and Fuster (1994) N. Engl. J. Med. 331:1564-1575 and Alvarez et al. (1996) J. Thorne. Cardiovasc. Surg. 112:238-247 are review articles discussing the nature and treatment of dilated cardiomyopathy.

[0017] Mitral valve repair is described in the following publications: Bach and Bolling (1996) Am. J. Cardiol. 78:966-969, Kameda et al. (1996) Ann. Thorne. Surg. 61:1829-1832, Bach and Bolling (1995) Am. Heart J. 129:1165-1170, and Bolling et al. (1995) 109:676-683. Linear segmental valvuloplasty for mitral valve repair is described in Ricchi et al. (1997) Ann. Thorne. Surg. 63:1805-1806. Tricuspid valvuloplasty is described in McCarthy and Cosgrove (1997) Ann. Thorne. Surg. 64:267-268, Tager et al. (1998) Am. J. Cardiol. 81:1013-1016, and Abe et al. (1989) Ann. Thorne. Surg. 48:670-676.

[0018] 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. Endovascular heart valve replacement is described in U.S. Patent Nos. 5,840,081, 5,411,552, 5,554,185, 5,332,402, 4,994,077, and 4,056,854. U.S. Patent No. 3,671,979 describes a catheter for temporary placement of a prosthetic heart valve.

[0019] Other percutaneous and endovascular cardiac repair procedures are described in US Pat. Nos. 4,917,089, 4,484,579, and 3,874,338, and PCT Publication No. WO 91 / 01689.

[0020] Laparoscopic and other minimally invasive heart valve repair and replacement procedures are described in U.S. Patent Nos. 5,855,614, 5,829,447, 5,823,956, 5,797,960, 5,769,812, and 5,718,725.

[0021] MitraClip® devices, systems, and methods for engaging tissue are described in US Pat. Nos. 8,057,493 and 7,226,467.

[0022] U.S. Patent Publication No. 2015 / 0257883 is of particular interest to the present application, the principal inventor of which is the inventor herein. [Prior art documents] [Patent documents]

[0023] [Patent Document 1] International Publication No. 98 / 35638 [Patent Document 2] U.S. Patent No. 5,840,081 [Patent Document 3] U.S. Patent No. 4,917,089 [Patent Document 4] U.S. Patent No. 5,855,614 Summary of the Invention [Means for solving the problem]

[0024] (Summary of the Invention) The present invention provides devices, systems, and methods for tissue access and repair at a treatment site. The devices, systems, and methods of the present invention find use in a variety of therapeutic procedures, including endovascular, minimally invasive, and open procedures, and can be used in a variety of anatomical regions, including the abdomen, chest, cardiovascular system, heart, intestinal tract, stomach, urinary tract, bladder, lungs, and other organs, vessels, and tissues. The present invention is particularly useful in those procedures requiring minimally invasive or endovascular access to remote tissue locations, especially those in which utilized instruments must navigate long, narrow, tortuous paths to the treatment site. In addition, many of the devices and systems of the present invention are adapted to be reversible and removable from the patient at any point without interference with or trauma to internal tissue.

[0025] In preferred embodiments, the devices, systems, and methods of the present invention are adapted for fixation of tissue at a treatment site. Exemplary tissue fixation applications include heart valve repair, septal defect repair, vascular ligation and clamping, laceration repair, and wound closure, although the present invention may find use in a wide variety of tissue approximation and repair procedures. In particularly preferred embodiments, the devices, systems, and methods of the present invention are adapted for repair of heart valves, particularly mitral valves, as a treatment for regurgitation. The present invention allows two or more valve leaflets to be coapted using an "incisal" or "bowtie" technique to reduce regurgitation, without requiring open surgery through the chest and heart wall as in conventional approaches. In addition, the position of the leaflets may vary in an affected mitral valve depending on the type and extent of disease, such as calcification, prolapse, or flail. These types of disease may result in one leaflet being more mobile (e.g., more difficult to capture) than the other, and therefore more difficult to grasp symmetrically in the same grasp as the other leaflet. Features of the present invention allow the fixation device to be adapted to meet the challenges of unpredictable target tissue geometry and provide a more robust grip on the tissue once it is captured. Additionally, the present invention optionally incorporates visualization techniques, allowing the device placement procedure to be performed without the use of general anesthesia.

[0026] The devices, systems, and methods of the present invention focus on various devices that can be used individually or in various combinations to form an interventional system. In a preferred embodiment, the interventional system includes a multi-catheter guidance system, a delivery catheter, and an interventional device. Each of these components will be discussed herein.

[0027] In an exemplary embodiment, the present invention provides a fixation device having a pair of outer arms (or fixation elements), each outer arm having a free end and an engagement surface for engaging tissue, the outer arms movable between a first position for capturing tissue and a second position for fixating tissue. Preferably, the engagement surfaces are spaced apart in the first position and closer together in the second position, generally facing toward each other. The fixation device is preferably delivered to a target location within a patient's body by a delivery catheter having an elongate 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 incision or a surgical penetration. In a preferred embodiment, the target location is a valve within the heart.

[0028] A particular advantage of the present invention is its ability to coapt the leaflets of the mitral valve (or any other tissue with which it is used) in a parallel or perpendicular relationship. In other words, the leaflets can be captured, drawn together, and fixed so that their proximal upstream faces are positioned parallel to one another and generally aligned with the direction of flow through the valve at the coaptation point. In some embodiments of the fixation device, the use of a sufficiently rigid outer arm, a highly frictional and compressible inner arm, and a passive closure mechanism allows the leaflets to be grasped in a spaced apart relationship and then drawn together in a coapted relationship while keeping the leaflets perpendicular (aligned with blood flow) to achieve an optimal coaptation configuration.

[0029] A particular advantage of the present invention is its ability to coapt the leaflets of the mitral valve (or any other tissue with which it is used) in a parallel or perpendicular relationship while grasping along the anatomical contours of the leaflets. In other words, the leaflets can be captured, drawn together, and secured so that their proximal upstream surfaces are positioned parallel to one another and generally aligned with the direction of flow through the valve at the coaptation point, while additionally grasping along the anatomical contours away from coaptation. In some embodiments of the fixation device, the use of sufficiently flexible outer arms, highly frictional and compressible inner arms, and a passive closure mechanism allows the leaflets to be grasped in a spaced apart relationship and then drawn together in a coapted relationship while keeping the leaflets perpendicular (aligned with blood flow) to achieve an optimal coaptation configuration.

[0030] A particular advantage of the present invention is its ability to coapt the leaflets of the mitral valve (or any other tissue with which it is used) in a leaflet-shaped, proximal anatomical relationship while grasping in line with the anatomical contours of the leaflets. In other words, the leaflets can be captured, drawn together, and secured, thus preserving their natural anatomical shape. In some embodiments of the fixation device, the use of sufficiently flexible outer arms, highly frictional and compressible inner arms, and a passive closure mechanism allows the leaflets to be grasped in a spaced apart relationship and then drawn together in a coapted relationship while keeping the leaflets perpendicular (aligned with blood flow) to achieve an optimal coaptation configuration.

[0031] The fixation device is preferably delivered with the outer arms 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 outer arms facing generally proximally, 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 generally face toward each other and are disposed at an angle of less than about 180°, preferably less than about 40°, relative to each other. For the ventricular approach, in the delivery position, the free ends of the outer arms face generally distally, 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 generally face toward each other and are disposed at an angle of less than about 180°, preferably less than about 90°, relative to each other. Alternatively, in some ventricular approaches, it may be preferable to have the free ends of the fixation elements facing generally proximally in the delivery position and the engagement surfaces facing away from each other.

[0032] To provide for reversibility and removability of the devices and systems of the present invention, the leaflets are lifted from the sufficiently flexible outer arm using sutures or wires, effectively mimicking inversion of the outer arm, which minimizes entanglement and interference with surrounding tissue when it is desired to remove the device. In mitral valve repair applications, this is particularly important due to the presence of chordae tendineae, valve leaflets, and other tissues with which the device can become entangled. For an approach from the atrial side of the mitral valve (in the simulated inverted position), the sutures or wires are positioned at an angle greater than about 180°, preferably greater than 270°, relative to each other. For a ventricular approach to the valve in the simulated inverted position, the sutures or wires will be oriented distally relative to the catheter shaft, with the engaging surfaces generally facing toward each other and typically positioned at an angle less than about 180°, preferably less than 90°, relative to each other.

[0033] In the open position, the engagement surfaces of the outer arms preferably form an angle of up to 180° relative to one another to maximize the area within which to capture the valve leaflets or other target tissue. The outer arms are preferably flexible to a closed position in which the engagement surfaces engage one another or form an angle as small as 0° relative to one another. The outer arms are flexible and configured to be permanently left in any of a variety of positions while exerting an opposing compressive force on the inner arms to enable fixation of tissues of various thicknesses, geometries, and spacings.

[0034] A particular advantage of the present invention is that both the outer and inner arms are sufficiently superelastic and flexible to impart a permanent and gentle (non-traumatic) reaction force to the tissue while allowing slight movement to match a) the anatomical shape of the leaflet and b) the physiological forces on the leaflet.

[0035] A particular advantage of the present invention is that both the outer and inner arms are sufficiently superelastic, stretchable, and flexible to provide gentle therapeutic clamping to the valve annulus (directly or via the leaflets) while preserving some natural expansion during diastole and supporting natural contraction of the annulus during systole, in response to capturing the leaflets in an open state into a closed final configuration. This gentle clamping to the annulus potentially promotes positive remodeling of the annulus, particularly in dilated annuli of enlarged hearts. In addition, it preserves natural annular expansion during diastole, which in turn increases the valve orifice area for enhanced blood flow from the atrium to the ventricle during diastole. While the valve clips of the present invention may be less traumatic and more flexible than the MitraClip® device, the clips are still sufficiently robust to firmly grip and secure the valve leaflets, so they can function as desired to improve flow control through the treated valve.

[0036] Another particular advantage of the present invention is that the frictional elements (barbs) are positioned internally along the longitudinal axis of the arm body and are confined by continuous, rigid lateral surfaces. Unlike the MitraClip® device, the barbs are not exposed along the sides. This is advantageous because it significantly reduces the risk of entanglement of chordae tendineae, valve leaflets, and other tissues with which the device may become entangled. Furthermore, this feature reduces the risk of entanglement of sutures or wires or other such delivery catheter elements that may potentially come into contact with the fixation device.

[0037] In preferred embodiments, the fixation device of the present invention will further include at least one inner arm (or grasping element) and one outer arm (or joining element). Each inner arm and outer arm will be movable relative to one another and configured to capture tissue between the engagement surfaces of the inner and outer arms. Preferably, the outer and inner arms are independently movable, but in some embodiments may be movable using the same mechanism. The inner arm is preferably biased toward the engagement surface of the fixation element, or vice versa, to provide a compressive force against tissue captured therebetween.

[0038] In another aspect, the present invention provides a fixation device comprising a coupling element configured for coupling to a catheter and a pair of outer arms connected to the coupling element, each outer arm carrying an engagement surface for grasping tissue.

[0039] In some applications, such as mitral valve repair, 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. To this end, some or all of the components of the fixation device are preferably covered with a cover or coating to promote tissue growth. In one embodiment, a biocompatible fabric cover is positioned over the outer arm and / or inner arm. The cover may optionally be impregnated or coated with various therapeutic agents, including tissue growth promoters, antibiotics, anticoagulants, blood thinners, and other agents. Alternatively, or in addition, some or all of the fixation elements and / or cover may be comprised of a bioerodible, biodegradable, or bioabsorbable material, so that it can degrade or be absorbed by the body after the repaired tissue has grown with it.

[0040] In some applications, such as mitral valve repair, the fixation device is adapted to be detached from the delivery catheter and temporarily left in the patient. In such applications, it is often desirable to provide a hemocompatible and biocompatible surface while not encouraging tissue growth around the fixation device. To this end, some or all of the components of the fixation device are preferably covered with a cover or coating to promote hemocompatibility without tissue growth. In one embodiment, a biocompatible textile cover is positioned over the outer arm and / or inner arm. The cover may optionally be impregnated or coated with various therapeutic agents, including tissue growth inhibitors, antibiotics, anticoagulants, blood thinners, and other agents. Alternatively, or in addition, some or all of the fixation elements and / or cover may be comprised of a bioerodible, biodegradable, or bioabsorbable material, so that it can degrade or be absorbed by the body after the repaired tissue has grown in.

[0041] The outer and inner arms will be configured to provide a sufficiently 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 inner arms will be configured to minimize any acute trauma to the tissue engaged by them. This allows the fixation device to be removed from the tissue after initial application without producing clinically significant injury to the tissue. To enhance retention without producing significant trauma, the inner and / or outer arms may have friction-enhancing features on their surfaces that engage the target tissue. Such friction-enhancing features may include barbs, protrusions, grooves, openings, channels, roughening, covers, and coatings, among others. Preferably, the friction-enhancing features will be configured to increase the retention force of the distal and inner arms against the tissue when the device is removed without leaving significant injury or scarring.

[0042] The outer and inner arms may further have a shape and flexibility to maximize retention and minimize trauma to the target tissue. In a preferred embodiment, the engagement surface of the outer arm has a concave shape configured to allow the inner arm to nest or retract within the outer arm, along with the target tissue. This increases the surface area of ​​the tissue engaged by the outer arm, creating a tissue engagement geometry with higher retention than a flat engagement surface. To minimize trauma, the longitudinal edges and free ends of the outer arm preferably curve outward away from the engagement surface, so that these edges present a rounded surface to the target tissue. The outer and / or inner arms may also be flexible so that they deflect to some extent in response to forces against the tissue engaged thereby, reducing the likelihood that the tissue will tear or be damaged in response to such forces.

[0043] The fixation device will include an actuation mechanism for moving the outer arms between open, closed, and inverted positions. A variety of actuation mechanisms can be used. In an exemplary embodiment, a suture or string or wire or lever controllable by the user through the delivery system handle can be used to raise and lower the outer or inner arms and capture the leaflets.

[0044] The fixation device of the present invention preferably includes a coupling member that is removably connectable to the delivery catheter. While the coupling member can have a variety of configurations, in an exemplary embodiment, it comprises a flexible rod, wire, or stylet of sufficient tensile strength that slidably extends coaxially from the handle to the fixation device. When desired, the user operates a handle safety release mechanism that allows retraction of the coupling member. This, in turn, slides the coupling member from the engagement element between the delivery system and the fixation device. The delivery catheter will be configured to removably connect to both the coupling member and the fixation device. In one embodiment, the delivery catheter has a round bore through the elongate member and a rod / wire / stylet slidably disposed within the bore of the elongate member. The junction of the coupling member, elongate member, and fixation device comprises mating surfaces that can have various shapes, including S-curves or angled or flat surfaces. The rod / wire / stylet extends from the delivery catheter through an axial channel in the outer member to maintain its connection with the fixation device. The rod / wire / stylet may be connected by a variety of connection structures, including threaded connections. Removal and retraction of the rod / wire / stylet back into the delivery catheter uncouples the delivery catheter and allows deployment of the fixation device.

[0045] The delivery devices of the present invention deliver interventional devices to target locations within the body. Such interventional devices include, among other things, fixation devices or any device that accesses tissue, such as a valve leaflet. The delivery devices and systems direct the interventional device to the target location through a minimally invasive approach, such as through the patient's vasculature, and provide for manipulation of the interventional device at the target location, such as to access tissue. Optionally, the delivery devices and systems may provide for decoupling of the interventional device, allowing it to remain as an implant.

[0046] In one aspect of the present invention, a delivery device is provided that includes an elongate, flexible shaft, preferably suitable for introduction through tortuous pathways within the body. The elongate shaft has a proximal end, a distal end, and a main lumen therebetween. Included within the delivery device is at least one elongate body, particularly at least one flexible tubular guide, extending through the main lumen. In some embodiments, the tubular guide is fixed to the shaft proximal to the proximal end and proximal to the distal end, and is unconstrained relative to the shaft therebetween so as to be laterally movable within the main lumen. Alternatively, the tubular guide may be unconstrained only at the distal portion of the shaft, providing greater flexibility in that portion.

[0047] In some embodiments, there are two flexible tubular guides. However, three, four, five, six, or more flexible guides may alternatively be present. The tubular guides may be made of any suitable material that provides lateral flexibility while providing strength under compression, such as metal or polymer coils. Additionally, other elongate bodies, such as cylindrical rods, wires, sutures, stylets, etc., may also be present to provide additional tensile strength. In some embodiments, the main lumen is occupied by a fluid, and thus the elongate body is surrounded by such a fluid.

[0048] In certain aspects of the invention, the delivery device includes an actuating element movably disposed within at least one of the flexible tubular guides and extending between a proximal end and a distal end. The actuating element is adapted for coupling with a movable component of the interventional element, such that movement of the actuating element moves the movable component. Such interventional elements are typically removably coupled to the distal end of the shaft. The movable component can have any of a variety of functions, including grasping, approximating, cutting, ablation, stapling, or otherwise engaging tissue. In one embodiment, the movable component provides tissue approximation, such as coaptation of valve leaflets. In preferred embodiments, the interventional element has first and second tissue-engaging elements adapted to engage tissue therebetween. Thus, in these embodiments, the actuating element is used to move the tissue-engaging elements to engage tissue. Additionally, in some embodiments, the shaft and interventional element are adapted for positioning through a blood vessel.

[0049] In some aspects of the present invention, a system is provided for approximating tissue to a treatment site. In some embodiments, the system includes an elongate, flexible shaft having a proximal end, a distal end, a main lumen therebetween, and at least one flexible tubular guide extending through the main lumen. Again, in preferred embodiments, the tubular guide is fixed to the shaft proximal to the proximal end and proximal to the distal end, and is unconstrained within at least a portion of the main lumen therebetween so as to be laterally movable within the main lumen. In some embodiments, the system also includes an actuating element movably disposed within the tubular guide and an approximation device coupled to the distal end of the shaft, the approximation device having first and second engagement elements for engaging tissue therebetween, at least one of the engagement elements being movable and coupled to the actuating element.

[0050] The delivery device of the present invention is adapted to enable a user to deliver a fixation device to a target site from a remote access point (whether through an endovascular or surgical approach), align the device with the target tissue, and selectively close, open, invert, lock, or unlock the outer arms. The delivery device will preferably have a highly flexible, kink-resistant, torsionally stiff shaft with minimal elongation and high tensile and compressive strength. The delivery device will also have movable components and associated actuators used to move the arms between lowered and raised positions, move the arms into engagement with the target tissue, and detach the outer arms from the delivery catheter. Multiple tubular guides, preferably in the form of metal coils or plastic or multi-lumen tubes with a low coefficient of friction, extend through the inner lumen of the shaft and are secured to the shaft adjacent its proximal and distal ends but are unconstrained therebetween, providing a highly flexible and kink-resistant structure. Lines for actuating the inner arms and unlocking mechanisms of the fixation device extend through these tubular guides and are removably coupled to the inner arms and unlocking mechanisms.

[0051] The delivery catheter may additionally include a tether consisting of a suture or wire or flexible rod that is removably coupled to a portion of the fixation device for purposes of retrieval of the device following removal from the delivery catheter. The tether may be a separate flexible filament extending from the delivery catheter to the fixation device, or alternatively, may be a line coupled to either the unlocking mechanism or inner arm and also used to actuate those components. In either case, the tether is detachable from the fixation device so that it can be removed once the device has been successfully deployed.

[0052] In some embodiments, the delivery device further includes an actuating element movably disposed within one of the at least one flexible tubular guides and a fixation device coupled to the distal end of the shaft and adapted for positioning within the cardiac chamber. Typically, the fixation device is releasably coupled to the shaft. In some embodiments, the fixation device has at least one inner arm and at least one outer arm adapted to engage the valve leaflets therebetween, and at least one of the inner and outer arms is movable and coupled to the actuating element. Alternatively, or in addition, the actuating element includes a flexible line, such as a locking line or an inner or outer arm line.

[0053] The system may further include first and second flexible tubular guides extending through the main lumen from the proximal end to the distal end. The first and second tubular guides are preferably secured to the shaft proximal to the proximal end and proximal to the distal end and are unconstrained within at least a portion of the main lumen therebetween so as to be laterally movable within the main lumen. Further, a first movable element extends through the first tubular guide and a second movable element is movably disposed within the second tubular guide.

[0054] The system may still further include an actuator handle connected to a proximal end of the shaft, the actuator handle having a body, and first, second, and third actuating elements movably coupled thereto, the first, second, and third actuating elements coupled to the first, second, and third movable elements.

[0055] The system of the present invention may additionally include a guide that facilitates the 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, within which the delivery catheter and fixation device can be slidably positioned. The distal end of the guide is steerable, typically deflectable about at least one axis, 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 into the femoral vein and advanced through the inferior vena cava into the heart, across a penetration in the atrial septum, and into alignment with the mitral valve in the left atrium.

[0056] Alternatively, the guide may be configured to be introduced into the brachiocephalic or axillary or jugular vein (neck / shoulder access) and advanced through the superior vena cava into the heart, across a penetration in the atrial septum, and into alignment with the mitral valve in the left atrium.

[0057] Alternatively, the guide may be configured for introduction into the femoral, axillary, or brachiocephalic artery and advancement through the aorta and aortic valve into a 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.

[0058] In an exemplary embodiment, the guide comprises a two-component multi-catheter guidance system including an inner tubular member or inner guide catheter and an outer tubular member or outer guide catheter. The outer tubular member has a distal end that is deflectable about an axis. The inner tubular member has a distal end that is deflectable about an additional axis. Additionally, the distal end of the inner tubular member may be angularly deflectable. Mobility in additional directions and about additional axes may optionally be provided.

[0059] The present invention also provides a method of performing a therapeutic intervention at a tissue site. In one embodiment, the method includes advancing an interventional tool having a proximal end, a distal end, and a fixation device proximate the distal end to a location within a patient's body, the fixation device including a pair of outer arms each having a free end and an engagement surface; moving the outer arms to an open position, the free ends being spaced apart; positioning the outer arms so that the engagement surfaces engage tissue at the tissue site; and removing the fixation device from the interventional tool. Preferably, the method further includes decoupling the cusps from the outer arms to allow for escape or to retry the procedure.

[0060] At least one embodiment of the present disclosure relates to a tissue grasping device including a base section, a first outer arm having a free end and a fixed end coupled to the base and a first inner arm having a free end and a fixed end coupled to the base, followed by a second outer arm and a second inner arm similarly coupled to the base in a modular manner, wherein tissue is grasped between the distal and proximal arms, the distal and proximal arms being formed from an elastic-plastic material or a viscous material or a shape-memory material configured to exhibit superelasticity in a physiological environment, and the base being formed from an elastic / plastic material or a shape-memory material configured to exhibit superelasticity in a physiological environment.

[0061] At least one embodiment of the present disclosure relates to a tissue fixation system configured for endovascular delivery and for use in joining mitral (or tricuspid) valve tissue during a mitral (or tricuspid) valve procedure, the system including a tissue grasping device including a base section, a first outer arm having a free end and a fixed end coupled to the base and a first proximal arm having a free end and a fixed end coupled to the base, followed by a second outer arm and a second proximal arm similarly coupled to the base in a modular manner, wherein tissue is grasped between the distal and proximal arms, the distal and proximal arms being formed from a shape memory material configured to exhibit superelasticity in a physiological environment, and the base being formed from an elastic / plastic material or a shape memory material configured to exhibit superelasticity in a physiological environment.

[0062] At least one embodiment of the inner or outer arm has barbs contained within smooth outer edges on both sides of the barbs to limit the risk of tissue or delivery mechanism getting stuck in the barbs, and the barbs are formed from an elastic-plastic or viscous or shape-memory material configured to exhibit superelasticity in a physiological environment.

[0063] At least one embodiment of a fixation device delivery system provides a standalone or dedicated probe built into the delivery system that incorporates an active ultrasound probe, the probe being retractable, translatable, rotatable, steerable, and having at least one or more features, including but not limited to, 2D imaging, Doppler, 3D imaging, 4D imaging, multi-modality imaging features, with or without the use of ultrasound markers or contrast agents, synchronization or desynchronization to limit physiological artifacts (e.g., but not limited to, caused by heartbeat and breathing), and aids in assisting, identifying, and navigating before, during, and after the procedure.

[0064] At least one embodiment of the fixation device delivery system provides a standalone or dedicated probe built into the delivery system that incorporates a passive ultrasound probe, which is retractable, translatable, rotatable, steerable, and has at least one or more multi-modality imaging enabling features, such as, but not limited to, 2D imaging, Doppler, 3D imaging, 4D imaging, with or without the use of ultrasound markers or contrast agents, synchronous or desynchronized to limit physiological artifacts (e.g., but not limited to, caused by heartbeat and breathing), and to help assist, identify, and navigate before, during, and / or after the procedure.

[0065] At least one embodiment of the fixation device delivery system provides a standalone or dedicated probe built into the delivery system that incorporates an active optical coherence tomography (OCT) probe, which is retractable, translatable, rotatable, steerable, and has at least one or more enabling features, such as, but not limited to, 2D imaging, Doppler, 3D imaging, 4D imaging, multi-modality imaging features, with or without the use of OCT markers or contrast agents, synchronization or desynchronization to limit physiological artifacts (e.g., but not limited to, caused by heartbeat and breathing), and aids in assisting, identifying, and navigating before, during, and / or after the procedure.

[0066] At least one embodiment of the fixation device delivery system provides a standalone or dedicated probe built into the delivery system that incorporates a passive optical coherence tomography (OCT) probe, which is retractable, translatable, rotatable, steerable, and has at least one or more features, including, but not limited to, 2D imaging, Doppler, 3D imaging, 4D imaging, multi-modality imaging features, with or without the use of OCT markers or contrast agents, synchronization or desynchronization to limit physiological artifacts (e.g., but not limited to, caused by heartbeat and breathing), and aids in assisting, identifying, and navigating before, during, and / or after the procedure.

[0067] At least one embodiment of a fixation device delivery system provides a standalone or dedicated probe built into the delivery system that incorporates an active optical camera-based imaging system stored inside a balloon that can be filled with a fluid (gas or liquid) that allows visualization when the balloon is either in contact with or near the target tissue, and the probe is retractable, translatable, rotatable, steerable, and has at least one or more enabling features, such as, but not limited to, 2D imaging, Doppler, 3D imaging, 4D imaging, multi-modality imaging features, with or without the use of optical markers or contrast agents, synchronization or desynchronization to limit physiological artifacts (e.g., but not limited to, caused by heartbeat and breathing), and to help assist, identify, and navigate before, during, and / or after the procedure.

[0068] At least one embodiment of a fixation device delivery system provides a standalone or dedicated probe built into the delivery system that incorporates a passive optical camera-based imaging system (e.g., but not limited to, a fiber optic imaging system) stored inside a balloon that can be filled with a fluid (gas or liquid) that allows visualization when the balloon is either in contact with or near the target tissue, and the probe is retractable, translatable, rotatable, steerable, and has at least one or more features, including, but not limited to, 2D imaging, Doppler, 3D imaging, 4D imaging, multi-modality imaging features, with or without the use of optical markers or contrast agents, synchronized or desynchronized to limit physiological artifacts (e.g., but not limited to, caused by heartbeat and breathing), and to help assist, identify, and navigate before, during, and / or after the procedure.

[0069] At least one embodiment of a fixation device delivery system provides a standalone or dedicated probe built into the delivery system that incorporates an active sensor / transducer / actuator system, the probe being retractable, translatable, rotatable, steerable, and having at least one or more enabling features, such as, but not limited to, pressure, strain, stress, ECG, EMG, 2D imaging, Doppler, 3D imaging, 4D imaging, multi-modality imaging features, with or without the use of markers or contrast agents, synchronization or desynchronization to limit physiological artifacts (e.g., but not limited to, caused by heart rate and breathing), and to help assist, identify, and navigate before, during, and / or after the procedure.

[0070] At least one embodiment of a fixation device delivery system provides a standalone or dedicated probe built into the delivery system that incorporates a passive sensor / transducer / actuator system (e.g., but not limited to, an RFID-based system), which is retractable, translatable, rotatable, steerable, and has at least one or more enabling features, such as, but not limited to, pressure, strain, stress, ECG, EMG, 2D imaging, Doppler, 3D imaging, 4D imaging, multi-modality sensing / transducing features, with or without the use of markers or contrast agents, synchronization or desynchronization to limit physiological artifacts (e.g., but not limited to, caused by heart rate and breathing), and to help assist, identify, and navigate before, during, and / or after the procedure.

[0071] At least one embodiment of the fixation device delivery system provides for a device that is coated to enhance biocompatibility and tissue interface, and the coating can be with a metal (e.g., but not limited to, titanium, tantalum, gold, platinum, iridium, tungsten, or combinations thereof), and / or ceramic, and / or polymer, such as, but not limited to, fluoropolymers (PTFE, PFA, FEP, ECTFE, ETFE), parylene, polyester, PER, polypropylene, PEEK, PVDF, HDPE, LDPE, UHMWPE, phosphorylcholine, hydroxyapatite, CaP, THV, biodegradable materials (polylactic acid, polyglycolic acid), polydioxanone, poly(ε-caprolactone), polyanhydrides, poly(orthoesters), copoly(ether-esters), polyamides, polylactones, poly(propylene fumarate), and / or combinations thereof, and these coatings can be hydrophilic or hydrophobic.

[0072] At least one embodiment of the fixation device delivery system provides for a device that is coated to enhance biocompatibility and tissue interface; the coating can be with a metal (e.g., but not limited to, titanium, tantalum, gold, platinum, iridium, tungsten, or combinations thereof), and / or ceramic, and / or polymer, such as, but not limited to, fluoropolymers (PTFE, PFA, FEP, ECTFE, ETFE), parylene, polyester, PER, polypropylene, PEEK, PVDF, HDPE, LDPE, UHMWPE, phosphorylcholine, hydroxyapatite, CaP, THV, and bioerodible materials such as biodegradable materials (polylactic acid, polyglycolic acid), polydioxanone, poly(ε-caprolactone), polyanhydrides, poly(orthoesters), copoly(ether-esters), polyamides, polylactones, poly(propylene fumarate), and / or combinations thereof; these coatings can be hydrophilic or hydrophobic.

[0073] At least one embodiment of the present disclosure relates to a method for grasping tissue, the method including the steps of: positioning a tissue grasping device adjacent to a target tissue, the tissue grasping device being formed from a shape memory material and including a base section, a first arm, and a second arm, each arm having a first end coupled to the base section and a free end extending from the base section, the first and second arms being positioned opposite one another; and moving the tissue grasping device from a pre-deployed configuration toward a deployed configuration, the first and second arms being configured to elastically flex in a distal direction toward a relaxed configuration as the tissue grasping device is moved from the pre-deployed configuration toward the deployed configuration.

[0074] At least one embodiment of the present disclosure relates to a method for manufacturing a tissue grasping device, the method including the steps of cutting one or more structural features into a strip or sheet of shape memory alloy feedstock, the one or more structural features including a plurality of slotted recesses disposed at one or more locations away from a side edge of the feedstock, and thermosetting one or more bending features into the feedstock.

[0075] In a first specific aspect, a valve clip according to the present invention includes a hub, a first pair of leaflet capture arms including a first inner arm and a first outer arm coupled to the hub, and a second pair of leaflet capture inner arms including a second inner arm and a second outer arm coupled to the hub, wherein the outer and inner arms are biased apart to create a leaflet capture space therebetween and are configured to self-close over the valve leaflets when released after the leaflets have been captured.

[0076] The hub is typically configured for removably mounting to the deployment shaft, and at least some of the leaflet capture arms are typically formed as leaf springs. The outer surface of each inner arm is positioned adjacent to the inner surface of each outer arm, and the lower end of each arm is coupled to the hub, with the lower end of each inner arm typically being above the lower end of each outer arm. The terms "inferior" and "superior" are defined relative to the patient anatomy in which the valve clip will be implanted. For example, when implanted within a mitral valve, superior refers to the side of the clip facing the atrium, and inferior refers to the side of the clip facing the ventricle. When implanted within a vein, superior will refer to the upstream direction, while inferior refers to the downstream direction.

[0077] The spring-biased outer and inner arms are configured to be "released" to initially capture a pair of leaflets and then self-close over the leaflets after the leaflets are captured. By "released" we mean that the individual arms can be bent or biased so that they are moved from their normal unbiased configuration, i.e., when they are free of deformation due to the application of an external force.

[0078] In certain embodiments, at least some of the outer and inner arms of the valve clip are formed as "leaf springs" with a resilient base and less elastic (more rigid) valve gripping elements. The resilient base typically provides most or all of the elasticity or bending capacity of the leaf spring structure and is configured so that it can be attached directly or indirectly to a hub. The valve gripping elements (e.g., but not limited to, barbs), in contrast, will typically undergo little or no bending when deployed over the leaflets of the target valve. Typically, all of the outer and inner arms will have the configuration as described.

[0079] In other specific embodiments, adjacent outer and inner arms of the valve clip will have substantially congruent shapes. By substantially congruent, we mean that the outer and inner arms will have identical or complementary shapes and will be able to "nestate" when attached to the hub and in their unbiased configuration. Typically, when the outer and inner arms are in their unbiased configuration and accommodate a valve leaflet between them as it is captured by the valve clip, there will be a small distance or gap, typically between 0 mm and 6 mm, and preferably between 0.5 mm and 2.5 mm, between the underside of the inner arm and the upper surface of the outer arm. These gap values ​​accommodate a single leaflet of typical thickness between the inner and outer arms. In other specific embodiments in which two or more leaflets are captured between pairs of arms, these gap values ​​may be increased by a factor of two or three. While a minimum gap may exist, the spring bias of the arms may itself be sufficient to accommodate the full range of leaflet wall thicknesses.

[0080] In a first illustrated embodiment, the valve gripping elements of the valve clip will diverge from a common axis through the hub and form a V-shape when the outer and inner arms are de-energized. Typically, the resilient base is curved and the valve gripping elements are straight on both the outer and inner arms. Even more typically, the resilient base on the outer arm has an S-shaped curve selected to offset or separate the upper surface of the outer arm from the lower surface of the inner arm to provide clearance or separation and accommodate the valve leaflets as previously described. Alternatively, a spacer can be used between the arms to create space to accommodate the leaflets.

[0081] In other illustrated embodiments, the valve grasping elements are parallel to a common axis when the outer and inner arms are de-energized. In such cases, the inner arm is generally straight, but the base of the outer arm has a curve selected to separate the upper surface of the outer arm from the lower surface of the inner arm to accommodate the valve leaflets therebetween.

[0082] In a second aspect of the invention, a system for delivering a valve clip to a cardiac or venous valve may comprise any of the valve clip designs described above or elsewhere or herein, and may further comprise a deployment shaft configured to be removably attached to the hub of the valve clip.

[0083] In certain embodiments of the present systems, the deployment shaft may extend upwardly from the hub along an axis of symmetry through the hub and between the right and left lateral and medial arms.

[0084] In exemplary embodiments, the system further includes a steerable deployment catheter that is removably or fixedly coupled to the deployment shaft. In some cases, the lower end of the deployment shaft is configured to be coupled to the steerable deployment catheter. In other cases, the upper end of the deployment shaft is configured to be coupled to the steerable deployment catheter.

[0085] In still further embodiments, the steerable catheter may include imaging components to enable real-time visualization of the implantation procedure. The imaging components may include one or more of an optical imaging component, an ultrasound imaging component, an OCT imaging component, or the like. The imaging components are positioned on the deployment catheter so that they can visualize both the target anatomical valve and the valve clip as the valve clip is being manipulated for implantation across the valve leaflets. In still further embodiments, the delivery system and / or fixation device may contain radiopaque and / or echogenic mechanical indicators that change position once the leaflets are fully inserted, thereby allowing the user to confirm leaflet insertion by visualization via conventional fluoroscopy or ultrasound imaging.

[0086] In yet other embodiments of the inventive system, the steerable catheter will include a mechanism for selectively applying a biasing force to the outer and / or inner arms of the valve clip to open the arms and create a gap or space for receiving and capturing a valve leaflet. In the illustrated embodiment, a first set of tethers will be positioned on or through the delivery catheter and coupled to the outer arms, such that the tethers can be tensioned to selectively bias the outer arms into a leaflet-capturing position. A second set of tethers will typically be positioned through the delivery catheter and coupled to the inner arms, configured to selectively bias the inner arms into a leaflet-capturing position. Both sets of tethers will typically be further configured to selectively de-bias the outer and inner arms, such that the outer and inner arms are enabled to self-close against and over the leaflet to secure the leaflet for treatment of any of the conditions described herein and above.

[0087] In a third specific aspect, the present invention provides a method for clipping an anatomical valve and securing the leaflets of the valve to treat various medical conditions. For example, the leaflets of the mitral valve can be clipped to treat mitral regurgitation. In another example, the leaflets of a venous valve can be clipped to treat venous insufficiency.

[0088] The method of the present invention includes advancing a valve clip having a pair of outer arms and a pair of inner arms adjacent to a target anatomical valve. At least one of the (1) pair of outer arms and (2) pair of inner arms is biased to open a leaflet capture space or gap between the adjacent outer and inner arms. The valve clip is then positioned so that one leaflet is located or captured in the gap or space between the left outer and inner arms and another leaflet is located in the gap or space between the right outer and inner arms. The leaflets can then be secured by releasing the biasing force or tension on at least one pair of outer or inner arms such that the left and right outer and inner arms self-close over the leaflets, thus securing the leaflets together.

[0089] In certain embodiments of the methods of the present invention, both the pair of outer arms and the pair of inner arms will be initially biased to create an opening of a leaflet capture gap or space therebetween. Biasing is typically accomplished by pulling on a tether attached to at least one of the pair of outer and inner arms, with a separate tether structure typically attached to each pair of outer and inner arms. The tether can be tensioned to bias the outer and inner arms so that they move away from each other, creating a leaflet capture gap or space therebetween. After the outer and inner arms are biased open and the leaflets are captured, tension on the tether can be released so that the outer and inner arms self-close over the leaflets.

[0090] As an alternative to using tethers, the biasing step may include advancing a pair of struts or other engagement members against at least one pair of outer and inner arms. The struts may engage at least two lower arms or at least two upper arms to selectively open the lower and upper arms to a leaflet-capturing position. In some cases, the struts may engage an upper surface of each outer arm, such that advancing the strut downwardly opens the outer arm relative to the inner arm. The inner arm may optionally be configured to remain stationary as the struts are advanced. In other cases, the struts may engage an underside of each inner arm, such that advancing the strut upwardly opens the inner arm relative to the outer arm. The outer arm may optionally be configured to remain stationary as the struts are advanced.

[0091] In other embodiments of the methods herein, the positioning of the valve clip includes manipulating a delivery catheter, wherein the valve clip is releasably attached to a distal end of the delivery catheter. The positioning step may further include observing the anatomical valve and the valve clip as the valve clip is positioned by observing a mechanical valve position indicator (as described above) and / or by using an imaging component on the delivery catheter.

[0092] A particular advantage of the present invention is the multiple sizes and shapes of the fixation device. The fixation device can be configured to attach to a small section of the leaflet (where the leaflet joints form a parallel seal together) or, in a preferred embodiment, to a larger section that includes the parallel joint section of the leaflet as well as a curved contoured section. The longer contoured arms allow for easier capture of the leaflet.

[0093] Another particular advantage of the present invention is that the fixation device is lock-free through the use of super-elastic and fully flexible inner and outer arms.

[0094] Another particular advantage of the present invention is that the fixation device is made from sufficiently flexible inner and outer arms that securely, yet atraumatically, grasp tissue while allowing sufficient dynamic movement of the leaflets under physiological forces.

[0095] Another particular advantage of the present invention is that the friction elements of the medial and lateral arms are recessed and barricaded on the sides, which reduces the risk of entanglement with tendons, tissue, or the delivery system.

[0096] Another particular advantage of the present invention includes modular manufacturing and / or assembly of both the outer and inner arms. Inner and outer arm combinations of various shapes and sizes can be interchangeably manufactured and / or assembled in a modular fashion to meet the patient / user's clinical treatment needs. For example, one side of the inner and outer arms may be longer to grasp the larger anterior mitral leaflets, while a shorter inner and outer arm combination may be used to grasp the shorter posterior mitral leaflets.

[0097] Another particular advantage of the present invention is the elimination of large increased movements of the fixation device during prolapse, such as inversion of the leaflet grasping arms. This is accomplished by the use of sutures, strings, or wires to lift the leaflets away from the grasping arms.

[0098] Another particular advantage of the present invention is the relatively simple and compact size of the fixation device, which allows for the use of smaller diameter catheters, thus making deployment more atraumatic to the patient. For example, the MitraClip® device uses a 24 Fr outer diameter guide catheter. In a preferred embodiment, the present invention uses a 12 Fr outer diameter guide catheter.

[0099] Another particular advantage of the present invention is compatibility with commercially available transseptal introducer sheaths. This is achieved by making the delivery device compatible with standard commercially available fixed or steerable transseptal introducer sheaths. Some examples of commercial introducer sheath sizes include, but are not limited to, 7Fr, 7.5Fr, 8Fr, 8.5Fr, 9Fr, 9.5Fr, 10Fr, 10.5Fr, 11Fr, 11.5Fr, and 12Fr inner diameters. Some examples of commercially available introducers (not limited to these examples) include the HeartSpan Fixed Curve Braided Trans-septal Sheath and HeartSpan Steerable Sheath Introducer by Merit Medical Systems, Inc. (UT), and the DIREX by Boston Scientific Corporation (MA). TM and Zurpaz™ Steerable Sheath, and Agilis NxT by St. Jude Medical (MN). TM Includes.

[0100] Another advantage of the present invention is the potential to perform the procedure under local anesthesia, thus eliminating the risks of general anesthesia. This is achieved by incorporating visualization techniques into or in conjunction with the delivery catheter system, replacing the need for transesophageal echocardiography (TEE).

[0101] Other objects and advantages of the present invention will become apparent from the following detailed description taken in conjunction with the accompanying drawings. The present specification also provides, for example, the following items: (Item 1) A valve clip, the valve clip comprising: a hub configured to be removably attached to the deployment shaft; a first pair of leaflet capture arms including a first inner arm and a first outer arm coupled to the hub; a second pair of leaflet capture arms including a second inner arm and a second outer arm coupled to the hub; Equipped with The valve clip is configured such that the outer and inner arms are biased apart to create a leaflet capture space therebetween and, once the leaflets are captured, are released to self-close over the valve leaflets. (Item 2) Item 10. The valve clip of item 1, wherein at least some of the leaflet capture arms are formed as leaf springs. (Item 3) Item 3. The valve clip of item 2, wherein at least some of the outer and inner arms are formed as leaf springs with a resilient base attached to the hub and less resilient valve gripping elements extending from the base. (Item 4) 4. The valve clip of item 3, wherein each of the outer and inner arms is formed as a leaf spring with a resilient base attached to the hub and a less resilient valve gripping element extending from the base. (Item 5) Item 5. The valve clip of item 4, wherein the valve gripping elements diverge from a common axis to form a V-shape when the outer and inner arms are de-energized. (Item 6) Item 6. The valve clip of item 5, wherein for both the outer and inner arms, the resilient base is curved and the valve gripping elements are straight. (Item 7) 7. The valve clip of claim 6, wherein the resilient base of the outer arm has an S-shaped curve selected to separate an upper surface of the inner arm from a lower surface of the outer arm, such separation accommodating the valve leaflets. (Item 8) 8. The valve clip of claim 7, wherein the resilient base of the outer arm has an S-shaped curve selected to separate an upper surface of the inner arm from a lower surface of the outer arm, such separation accommodating the valve leaflets. (Item 9) Item 6. The valve clip of item 5, wherein the valve gripping elements are parallel to a common axis when the outer and inner arms are de-energized. (Item 10) 10. The valve clip of claim 9, wherein the inner arm is generally straight but the base of the outer arm has a curve selected to separate an upper surface of the inner arm from a lower surface of the outer arm, such separation accommodating the valve leaflets. (Item 11) 1. A system for delivering a valve clip to a cardiac or venous valve, the system comprising: The valve clip according to item 1; a deployment shaft configured to be removably attached to the hub of the valve clip; A system comprising: (Item 12) Item 12. The system of item 11, wherein the deployment shaft extends upward from the hub along a line of symmetry between the right and left lateral and medial arms. (Item 13) Item 13. The system of item 12, further comprising a steerable deployment catheter coupled to the deployment shaft. (Item 14) Item 14. The system of item 13, wherein the lower end of the deployment shaft is configured to be coupled to the steerable deployment catheter. (Item 15) Item 15. The system of item 14, wherein the upper end of the deployment shaft is configured to be coupled to the steerable deployment catheter. (Item 16) Item 14. The system of item 13, wherein the steerable deployment catheter includes an imaging component. (Item 17) Item 17. The system of item 16, wherein the imaging component comprises one or more of a mechanical tip position indicator component, an optical imaging component, an ultrasound component, and an OCT imaging component. (Item 18) Item 12. The system of item 11, further comprising a first set of tethers positioned through the delivery catheter, coupled to the outer arms, and configured to selectively bias the outer arms into a leaflet capture position. (Item 19) 20. The system of claim 18, wherein the first set of tethers is further configured to selectively de-bias the outer arms such that the outer arms self-close toward the valve leaflets. (Item 20) Item 12. The system of item 11, further comprising a second set of tethers positioned through the delivery catheter, coupled to the inner arms, and configured to selectively bias the inner arms into a leaflet capture position. (Item 21) 21. The system of claim 20, wherein the second set of tethers is further configured to selectively de-energize the inner arms such that the inner arms self-close toward the valve leaflets. (Item 22) Item 12. The system of item 11, further comprising: a first set of tethers positioned through the delivery catheter, coupled to the outer arm, and configured to selectively bias the outer arm into a leaflet capturing position; and a second set of tethers positioned through the delivery catheter, coupled to the inner arm, and configured to selectively bias the inner arm into a leaflet capturing position. (Item 23) Item 12. The system of item 11, further comprising a pair of struts reciprocally coupled to the deployment shaft, the struts engaging at least the two lower arms or the two upper arms and selectively opening the lower and upper arms to a leaflet capture position. (Item 24) 24. The system of claim 23, wherein the support strut is configured to engage an upper surface of each outer arm, and downward advancement of the support strut releases the outer arm relative to the inner arm. (Item 25) Item 24. The system of item 23, wherein the inner arm is configured to remain stationary when the strut is advanced. (Item 26) 24. The system of claim 23, wherein the strut is configured to engage an underside of each inner arm, and wherein advancing the strut upwardly releases the inner arm relative to the outer arm. (Item 27) Item 27. The system of item 26, wherein the outer arm is configured to remain stationary when the strut is advanced. (Item 28) 1. A method for clipping an anatomical valve, the method comprising: advancing a valve clip having a pair of outer arms and a pair of inner arms adjacent to the anatomical valve; (1) biasing at least one of the pair of outer arms and (2) the pair of inner arms to open a leaflet capture space between adjacent outer and inner arms; positioning the valve clip so that one leaflet is positioned within the leaflet capture space between left lateral and medial arms and another leaflet is positioned within the leaflet capture space between right lateral and medial arms; releasing the bias on the at least one pair of outer or inner arms such that the left outer and inner arms and the right outer and inner arms self-close over the leaflets and secure them; A method comprising: (Item 29) 30. The method of claim 28, further comprising lifting the inner arms from the valve leaflets and releasing the valve clip from the leaflets after initial placement to allow for repositioning or removal of the valve clip. (Item 30) 30. The method of claim 29, wherein the anatomical valve is a heart valve. (Item 31) 31. The method of claim 30, wherein the heart valve is a mitral valve. (Item 32) 32. The method of claim 31, wherein the anatomical valve is a venous valve. (Item 33) 30. The method of claim 29, wherein the biasing comprises pulling a tether attached to the at least one pair of outer or inner arms. (Item 34) Item 34. The method of item 33, wherein the biasing includes applying tension to a tether attached to each pair of outer and inner arms. (Item 35) Item 35. The method of item 34, wherein releasing the bias comprises releasing tension on the tether. (Item 36) 30. The method of claim 29, wherein the biasing comprises manipulating a delivery catheter, the valve clip being releasably attached to a distal end of the delivery catheter. (Item 37) 37. The method of claim 36, further comprising using an imaging component on the delivery catheter to observe the anatomical valve and the valve clip as the valve clip is positioned. (Item 38) 30. The method of claim 29, wherein the biasing includes advancing a pair of struts into engagement with at least the two lower arms or the two upper arms to selectively open a valve-receiving space between the lower and upper arms. (Item 39) Item 39. The method of item 38, wherein advancing the strut downwardly against the upper surface of each outer arm opens the outer arm relative to the inner arm. (Item 40) Item 39. The method of item 38, wherein advancing the strut upwardly against the underside of each inner arm opens the inner arm relative to the outer arm. (Item 41) 36. The method of claim 35, further comprising using an imaging component on the delivery catheter to observe the anatomical valve and the valve clip as the valve clip is positioned. (Item 42) Item 4. The valve clip of item 3, wherein at least one of the inner and outer arms has barbs or tissue fixation elements trapped within a side rail or barrier to resist entanglement with tendons or the delivery system. (Item 43) Item 5. The valve clip of item 4, wherein the valve grasping elements diverge from a common axis when the outer and inner arms are de-energized to form a curved shape that closely matches the natural cusp shape. (Item 44) Item 10. The valve clip of item 1, wherein the inner and outer arms are configured to capture the leaflet within a coaptation segment of the leaflet. (Item 45) Item 10. The valve clip of item 1, wherein the inner and outer arms capture the leaflets within the coapted and non-coapted segments of the leaflets. (Item 46) Item 46. The valve clip of item 45, wherein the inner and outer arms are configured to capture the leaflets within the coapted and non-coapted segments along the contours of the native leaflets and annulus. (Item 47) Item 10. The valve clip of item 1, wherein the inner and outer arms are configured to simultaneously capture the leaflets. (Item 48) Item 10. The valve clip of item 1, wherein the inner and outer arms are configured to capture the leaflets sequentially. (Item 49) Item 10. The valve clip of item 1, wherein the inner and outer arms are configured to independently capture a leaflet. (Item 50) Item 15. The system of item 14, wherein the deployment shaft is configured to be coupled to a pressure sensor. (Item 51) Item 15. The system of item 14, wherein the deployment shaft is configured to be coupled to an ultrasonic sensor. (Item 52) Item 15. The system of item 14, wherein the deployment shaft is configured to be coupled to an OCT system. (Item 53) Item 12. The system of item 11, further comprising a first set of tethers positioned through the delivery catheter, coupled to the outer arms, and configured to selectively lift the leaflets from the outer arms. (Item 54) Item 54. The system of item 53, further comprising a second set of tethers positioned through the delivery catheter, coupled to the inner arm, and configured to selectively raise and lower the inner arm relative to the outer arm. (Item 55) Item 1, wherein the size and shape of one pair of inner and outer arms are configured to capture the anterior native mitral valve leaflets, and the other pair of inner and outer arms are configured to capture the posterior native mitral valve leaflets. (Item 56) Item 1. The valve clip of item 1, wherein the size and shape of the first pair of inner and outer arms are configured to capture a first native tricuspid valve leaflet, the second pair of inner and outer arms are configured to capture a second native tricuspid valve leaflet, and the third pair of inner and outer arms are configured to capture a third native tricuspid valve leaflet. (Item 57) 2. The valve clip of claim 1, wherein the size and shape of each pair of inner and outer arms is modular for ease of manufacture and to accommodate variations in disease states of the valve. (Item 58) Item 10. The valve clip of item 1, wherein the inner and outer arms are configured to elastically deform or stretch to partially conform to the natural movement of the valve annulus with each heartbeat. (Item 59) Item 10. The valve clip of item 1, wherein the inner and outer arms are configured to elastically resist deformation of the captured leaflet with each heartbeat. (Item 60) Item 10. The valve clip of item 1, wherein the inner and outer arms are configured to tighten the captured leaflets, thereby elastically tightening the valve annulus. (Item 61) Item 12. The system of item 11, further comprising a pair of struts fixed to the deployment shaft and reciprocally coupled to the valve clip, the struts engaging at least the two lower arms or the two upper arms and selectively opening the lower and upper arms to a leaflet capture position. (Item 62) Item 62. The system of item 61, wherein the post is configured to engage an upper surface of each outer arm, and advancing the valve clip upwardly opens the outer arms relative to the inner arms. (Item 63) Item 62. The system of item 61, wherein the inner arm is configured to remain stationary when the valve clip is advanced toward the post. (Item 64) Item 62. The system of item 61, wherein the post is configured to engage an underside of each inner arm, and advancing the valve clip downwardly opens the inner arm relative to the outer arm. (Item 65) Item 12. The system of item 11, further comprising a pair of struts movably coupled to the deployment shaft and reciprocally coupled to the valve clip, the struts engaging at least the two lower arms or the two upper arms and selectively opening the lower and upper arms to a leaflet capture position. (Item 66) Item 66. The system of item 65, wherein the struts are coupled to a set of tethers and configured to engage an upper surface of each outer arm, and wherein advancing the struts downwardly releases the outer arms relative to the inner arms. (Item 67) Item 66. The system of item 65, wherein the struts are coupled to a set of tethers and configured to engage the underside of each inner arm, and wherein advancing the struts upwardly releases the inner arms relative to the outer arms. (Item 68) Item 10. The valve clip of item 1, wherein the first pair of inner and outer arms and the second pair of inner and outer arms are configured to simultaneously capture a leaflet. (Item 69) Item 10. The valve clip of item 1, wherein the first pair of inner and outer arms and the second pair of inner and outer arms are configured to capture leaflets in succession. (Item 70) Item 10. The valve clip of item 1, wherein the first pair of inner and outer arms and the second pair of inner and outer arms are configured to independently capture leaflets. (Item 71) Item 72. The valve clip of item 1, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to bias or unbias the arms. Item 10. The valve clip of item 1, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to raise or lower the arms and to lift the leaflets from the outer arms. (Item 73) Item 10. The valve clip of item 1, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to bias or de-bias the outer arms and to lift leaflets from the outer arms and disengage the valve clip from the leaflets. (Item 74) Item 1. The valve clip of item 1, wherein the outer and inner leaflet capture arms are releasably attached to a tether that can be used to bias or de-bias the arms to capture the leaflet or release the captured leaflet from the arms. (Item 75) Item 1. The valve clip of item 1, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to bias or de-bias the arms to capture or release the captured leaflets from the arms and retrieve the valve clip. (Item 76) Item 12. The valve clip of item 11, wherein the first pair of inner and outer arms and the second pair of inner and outer arms are configured to simultaneously capture a leaflet. (Item 77) Item 12. The valve clip of item 11, wherein the first pair of inner and outer arms and the second pair of inner and outer arms are configured to capture the leaflets in succession. (Item 78) Item 12. The valve clip of item 11, wherein the first pair of inner and outer arms and the second pair of inner and outer arms are configured to independently capture leaflets. (Item 79) Item 12. The valve clip of item 11, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to bias or unbias said arms. (Item 80) Item 12. The valve clip of item 11, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to raise or lower the arms and to lift the leaflets from the outer arms. (Item 81) Item 12. The valve clip of item 11, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to bias or de-bias the outer arms and to lift a leaflet from the outer arms and disengage the valve clip from the leaflet. (Item 82) Item 83. The valve clip of item 11, wherein the outer and inner leaflet capture arms are releasably attached to a tether that can be used to bias or de-bias the arms to capture the leaflet or release the captured leaflet from the arms. Item 12. The valve clip of item 11, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to bias or de-bias the arms to capture or release the captured leaflets from the arms and retrieve the valve clip. (Item 84) Item 12. The valve clip of item 11, wherein the first pair of inner and outer arms and the second pair of inner and outer arms are configured to simultaneously capture a leaflet. (Item 85) Item 12. The valve clip of item 11, wherein the first pair of inner and outer arms and the second pair of inner and outer arms are configured to capture the leaflets in succession. (Item 86) Item 12. The valve clip of item 11, wherein the first pair of inner and outer arms and the second pair of inner and outer arms are configured to independently capture leaflets. (Item 87) Item 12. The valve clip of item 11, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to bias or unbias said arms. (Item 88) Item 12. The valve clip of item 11, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to raise or lower the arms and to lift the leaflets from the outer arms. (Item 89) Item 12. The valve clip of item 11, wherein at least the outer leaflet capture arms are releasably attached to a tether that can be used to bias or de-bias the outer arms and to lift a leaflet from the outer arms and disengage the valve clip from the leaflet. (Item 90) Item 12. The valve clip of item 11, wherein the outer and inner leaflet capture arms are releasably attached to a tether that can be used to bias or de-bias the arms to capture the leaflet or release the captured leaflet from the arms. (Item 91) Item 12. The valve clip of item 11, wherein at least the lateral leaflet capture arms are releasably attached to a tether that can be used to bias or de-bias the arms to capture or release the captured leaflets from the arms and retrieve the valve clip. [Brief explanation of the drawings]

[0102] [Figure 1A-1] FIG. 1A-1 illustrates the left ventricle and left atrium of a human heart during systole. [Figure 1A-2] FIG. 1A-2 illustrates the free margins of the mitral valve leaflets in normal coaptation. [Figure 1A-3] FIG. 1A-3 illustrates the free margins of the mitral valve leaflets in regurgitant coaptation. [Figure 1B-1] FIG. 1B-1 illustrates the fixation device mounted in a retrograde orientation relative to the apex. [Figure 1B-2] FIG. 1B-2 illustrates the fixation device mounted in a preferred antegrade orientation relative to the apex. [Figure 2A] 2A-2H depict various embodiments of catheter-based delivery systems used to deploy fixation devices within the heart. [Figure 2B] 2A-2H depict various embodiments of catheter-based delivery systems used to deploy fixation devices within the heart. [Figure 2C] 2A-2H depict various embodiments of catheter-based delivery systems used to deploy fixation devices within the heart. [Figure 2D] 2A-2H depict various embodiments of catheter-based delivery systems used to deploy fixation devices within the heart. [Figure 2E] 2A-2H depict various embodiments of catheter-based delivery systems used to deploy fixation devices within the heart. [Figure 2F]2A-2H depict various embodiments of catheter-based delivery systems used to deploy fixation devices within the heart. [Figure 2G] 2A-2H depict various embodiments of catheter-based delivery systems used to deploy fixation devices within the heart. [Figure 2H] 2A-2H depict various embodiments of catheter-based delivery systems used to deploy fixation devices within the heart. [Figure 2I] 2I-1 and 2I-2 illustrate the distal segment of the introducer sheath when manipulated in a two-way steerable configuration. [Figure 2J] 2J-2P and 2Q-1-2Q-3 depict a preferred embodiment of an exemplary 12 Fr catheter-based delivery system used to deploy the fixation device within the heart. [Figure 2K] 2J-2P and 2Q-1-2Q-3 depict a preferred embodiment of an exemplary 12 Fr catheter-based delivery system used to deploy the fixation device within the heart. [Figure 2L] 2J-2P and 2Q-1-2Q-3 depict a preferred embodiment of an exemplary 12 Fr catheter-based delivery system used to deploy the fixation device within the heart. [Figure 2M] 2J-2P and 2Q-1-2Q-3 depict a preferred embodiment of an exemplary 12 Fr catheter-based delivery system used to deploy the fixation device within the heart. [Figure 2N] 2J-2P and 2Q-1-2Q-3 depict a preferred embodiment of an exemplary 12 Fr catheter-based delivery system used to deploy the fixation device within the heart. [Figure 2O] 2J-2P and 2Q-1-2Q-3 depict a preferred embodiment of an exemplary 12 Fr catheter-based delivery system used to deploy the fixation device within the heart. [Figure 2P]2J-2P and 2Q-1-2Q-3 depict a preferred embodiment of an exemplary 12 Fr catheter-based delivery system used to deploy the fixation device within the heart. [Figure 2Q] 2J-2P and 2Q-1-2Q-3 depict a preferred embodiment of an exemplary 12 Fr catheter-based delivery system used to deploy the fixation device within the heart. [Figure 3A] 3A, 3B-1, 3B-2, and 3C show various exemplary embodiments of fixation devices. [Figure 3B] 3A, 3B-1, 3B-2, and 3C show various exemplary embodiments of fixation devices. [Figure 3C] 3A, 3B-1, 3B-2, and 3C show various exemplary embodiments of fixation devices. [Figure 4A] 4A-4F depict the stepwise deployment of a preferred embodiment using simultaneous leaflet capture. [Figure 4B] 4A-4F depict the stepwise deployment of a preferred embodiment using simultaneous leaflet capture. [Figure 4C] 4A-4F depict the stepwise deployment of a preferred embodiment using simultaneous leaflet capture. [Figure 4D] 4A-4F depict the stepwise deployment of a preferred embodiment using simultaneous leaflet capture. [Figure 4E] 4A-4F depict the stepwise deployment of a preferred embodiment using simultaneous leaflet capture. [Figure 4F] 4A-4F depict the stepwise deployment of a preferred embodiment using simultaneous leaflet capture. [Figure 5] 5A-5D depict staged capture of the mitral valve leaflets using side-by-side capture via independent manipulation of the inner arms. [Figure 6] 6A-6D depict staged capture of the mitral valve leaflets using side-by-side capture via independent manipulation of the medial and lateral arms. [Figure 7] 7A-7F depict a stepwise escape procedure after any degree of leaflet capture by the arms. [Figure 8A] FIG. 8A illustrates the mechanism by which the outer arm is operated. [Figure 8B] FIG. 8B is a detailed illustration of the embodiment of FIG. 8B. [Figure 8C] 8A and 8B for controlling the outer arm during prolapse. This position of the suture is beneficial for removing the mitral valve leaflets from the device. [Figure 8D] FIG. 8D is a detailed view of the mechanism of FIG. 8C. [Figure 9A] FIG. 9A illustrates the mechanism for operating the inner arm. [Figure 9B] FIG. 9B is a detailed view of the mechanism of FIG. 9A. [Figure 9C] FIG. 9C shows an alternative embodiment of a mechanism for operating the inner arm. [Figure 9D] FIG. 9D shows the mechanism of FIG. 9C with the inner arm in a collapsed state. [Figure 10A] FIG. 10A illustrates another embodiment of a deployment mechanism for controlling the clip and both the inner and outer arms. [Figure 10B] FIG. 10B is a detailed illustration of the deployment mechanism of FIG. 10A with the release rod retracted. [Figure 10C] FIG. 10C depicts the release of the valve clip using the release rod of FIG. 10B. [Figure 10D] FIG. 10D is a detailed view of the release mechanism depicted in FIG. 10C. [Figure 10E] FIG. 10E depicts retraction of the delivery system after release of the valve clip. [Figure 11] 11 and 11A-11D illustrate a specific fixation device (valve clip) embodiment with isolated views of the inner and outer arms. [Figure 12] 12 and 12A-12D illustrate further embodiments of a valve clip fixation device in which the opposing arms have dissimilar lengths, with isolated views of the inner and outer arms. FIG. 12E illustrates the valve clip of FIG. 12 implanted within a mitral valve. [Figure 13A] FIG. 13A illustrates a further embodiment of a valve clip securement device in which the inner and outer arms are formed by a single piece. [Figure 13B] FIG. 13B illustrates a further embodiment of a valve clip fixation device having a spacer within the base. [Figure 13C] FIG. 13C illustrates a further embodiment of a fixation device that utilizes two arms. [Figure 13D] FIG. 13D illustrates a further embodiment of a fixation device that utilizes four arms along the coaptation length of the natural leaflet. [Figure 13E] 13E illustrates an exemplary embodiment with three pairs of inner and outer arms, for example, to capture three separate leaflets in a tricuspid valve. [Figure 13F] 13F-1 and 13F-2 illustrate a further embodiment of the base bracket 10 with contoured features that allow for easier removal of the fixation device from the delivery catheter. [Figure 13G] 13G-1-13K-2 illustrate further embodiments of release bar 16 with strut features that allow for spreading of the outer arms of the fixation device during deployment. [Figure 13H] 13G-1-13K-2 illustrate further embodiments of release bar 16 with strut features that allow for spreading of the outer arms of the fixation device during deployment. [Figure 13I] 13G-1-13K-2 illustrate further embodiments of release bar 16 with strut features that allow for spreading of the outer arms of the fixation device during deployment. [Figure 13J] 13G-1-13K-2 illustrate further embodiments of release bar 16 with strut features that allow for spreading of the outer arms of the fixation device during deployment. [Figure 13K] 13G-1-13K-2 illustrate further embodiments of release bar 16 with strut features that allow for spreading of the outer arms of the fixation device during deployment. [Figure 14]FIG. 14 illustrates a further embodiment configuration of a fixation device in which the opposing arms are of different lengths. [Figure 15] FIG. 15 illustrates a further embodiment configuration of the fixation device in which the opposing arms are at different angles. [Figure 16] FIG. 16 illustrates a further embodiment configuration of the fixation device in which the opposing arms are at different or unconstrained angles in the shape setting. [Figure 17A] FIG. 17A reproduces a MitraClip® embodiment (FIG. 11B, US Pat. No. 8,057,493, B2; page 8 / 68) showing the inner gripping arms with barbs 60 exposed on the sides. [Figure 17B] FIG. 17B illustrates an improvement to the Mitraclip® device in which the barbs 60 are repositioned within the width of the arms 60' and aligned with the tangle-resistant sides of the present invention. [Figure 18A] 18A-18E illustrate further embodiments of fixation devices that utilize a camera / optical system with various types of viewing balloons to provide visualization during deployment. [Figure 18B] 18A-18E illustrate further embodiments of fixation devices that utilize a camera / optical system with various types of viewing balloons to provide visualization during deployment. [Figure 18C] 18A-18E illustrate further embodiments of fixation devices that utilize a camera / optical system with various types of viewing balloons to provide visualization during deployment. [Figure 18D] 18A-18E illustrate further embodiments of fixation devices that utilize a camera / optical system with various types of viewing balloons to provide visualization during deployment. [Figure 18E] 18A-18E illustrate further embodiments of fixation devices that utilize a camera / optical system with various types of viewing balloons to provide visualization during deployment. [Figure 19]FIG. 19 illustrates a further embodiment of a fixation device that utilizes an OCT sensor to provide vision during deployment. [Figure 20] FIG. 20 illustrates a further embodiment of a fixation device that utilizes an ultrasound echography sensor to provide vision during deployment. DETAILED DESCRIPTION OF THE INVENTION

[0103] (Detailed Description of the Invention) (I. Cardiac Physiology) The left ventricle LV of a normal heart H during systole is illustrated in FIG. 1A-1. The left ventricle LV is contracting, and blood flows outward through the tricuspid (mitral) valve AV in the direction of the arrow. Backflow, or "regurgitation," of blood through the mitral valve MV is prevented because the mitral valve is configured as a "check valve," preventing backflow when pressure within the left ventricle is higher than that within the left atrium LA. The mitral valve MV comprises a pair of leaflets with free edges FE that meet evenly to close, as illustrated in FIG. 1A-1. Opposite ends of the leaflets LF attach to surrounding cardiac structures along an annular region referred to as the annulus AN. The free edges FE of the leaflets LF are anchored to the lower portion of the left ventricle LV through chordae tendineae CT (hereafter referred to as tendons), which comprise multiple branching tendons that wrap over and anchor the underside of each leaflet LF. The tendons CT, in turn, attach to the papillary muscles PM, which extend upward from the lower portion of the left ventricle and the interventricular septum IVS.

[0104] Several structural defects within 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 Figure 1A-2, the free edges of the anterior and posterior leaflets normally meet along the coaptation line C. An example of a defect causing regurgitation is shown in Figure 1A-3. Here, enlargement of the heart causes the mitral valve annulus to become enlarged, preventing the free edges FE from meeting during systole. This results in a gap G, which allows blood to leak through the valve during ventricular systole. Ruptured or stretched tendons can also cause a leaflet to prolapse because improper tension is transmitted to the leaflet through the tendon. While the other leaflet maintains its normal shape, two leaflets do not meet properly, and leakage from the left ventricle into the left atrium will occur. Such regurgitation can also occur in patients with ischemic heart disease, in which the left ventricle does not meet sufficiently to effect proper closure.

[0105] (II. General Overview) The present invention provides methods and devices for grasping, approximating, and securing tissue, such as valve leaflets, to treat heart valve regurgitation, particularly mitral valve regurgitation. The present invention also provides features that allow for repositioning and removal of the device, if so desired, particularly in areas where removal may be hindered by anatomical features such as tendon CT. Such removal may allow the surgeon to reapproach the valve in a new manner, if so desired.

[0106] The grasping will preferably be atraumatic, which provides several benefits. By atraumatic, we mean that the devices and methods of the present invention can be applied to the valve leaflets and then removed without causing any significant clinical disturbance of leaflet structure or function. The leaflets and valve continue to function substantially identically as before the present invention was applied. Thus, some slight penetration or indentation of the leaflets may occur using the present invention, yet still meet the definition of "atraumatic." This allows the devices of the present invention to be applied to diseased valves and, if desired, removed or repositioned without adversely affecting valve function. Additionally, it should be understood that in some cases, it may be necessary or desirable to puncture or otherwise permanently affect the leaflets during either grasping, fixation, or both. In some of these cases, grasping and fixation can be accomplished by a single device. While several 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 present invention, but are presented with the goal of providing a basis for the description of the individual embodiments presented later in the application.

[0107] The devices and methods of the present invention rely on the use of an interventional tool that is positioned proximate the desired treatment site and used to grasp the target tissue. In intravascular 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 the grasp with a portion of the interventional tool that remains as an implant. While the present invention may have a variety of applications for tissue approximation and fixation throughout the body, it is particularly well-suited for repair of valves, particularly heart valves such as the mitral and tricuspid valves.

[0108] 1B-1 and 1B-2 illustrate the fixation device in both retrograde and antegrade configurations for deployment, respectively. The fixation device is attached to a release bar 16 or 166 that is part of a distal delivery catheter 499. In both surgical methods, the placement and position of the device remain unchanged. This may allow the fixation device to be deployed using various entry points that best suit the user's needs. For purposes of illustration, the antegrade approach will primarily be described below.

[0109] 2A-2H depict various embodiments of catheter-based fixation device delivery systems that can be used to deploy fixation devices. Knobs 502 and 503 are used to position the medial (14, 22) and lateral (12, 20) arms of the fixation device at (14', 22') and (12', 20'), respectively, to fixate the two leaflets LF (arm manipulation). Each knob can be configured to manipulate either the lateral or medial arm of the device. While only a two-handle system is illustrated, the concept can be expanded to include three or more handle systems with a combination of fixed and / or steerable shaft systems.

[0110] 2A illustrates one embodiment of a delivery system utilizing a fixed curve introducer sheath in combination with a four-way steerable delivery catheter. Arm control knobs 502 and 503 are configured on the same catheter handle 508. Knobs 500 and 501 are used to steer the catheter's distal delivery shaft 499 in four directions, with each knob (500 and 501) providing two-way steering. The distal introducer sheath 498 retains a fixed curve.

[0111] 2B illustrates a further embodiment of a delivery system utilizing a fixed curve introducer sheath in combination with a two-way steerable delivery catheter. Arm control knobs 502 and 503 are configured similarly to catheter handle 508. Knob 504 is used to orient the distal delivery shaft 499 of the catheter in two directions, providing two-way steering. Distal introducer sheath 498 retains a fixed curve.

[0112] 2C illustrates a further embodiment of a delivery system utilizing a two-way steerable introducer sheath in combination with a delivery catheter. An introducer sheath handle 510 houses a two-way steering knob 505 for manipulating and steering the distal sheath 498. This is arranged in conjunction with another handle 511, which in turn holds arm operating knobs 502 and 503. Note that a pre-fabricated two-way steerable introducer sheath from Merit Medical (HeartSpan® Steerable Sheath Introducer, https: / / www.merit.com / cardiac-intervention / ep-and-crm / electrophysiology / heartspan-steerable-sheath-introducer / ) is shown as an example for illustrative purposes.

[0113] 2D illustrates a similar embodiment of a delivery system utilizing a four-way steerable introducer sheath in combination with a delivery catheter. An introducer sheath handle 510 houses two two-way steering knobs 506 and 507 for manipulating and steering the distal sheath 498 and providing four-way steerability. This is arranged in conjunction with another handle 511, which in turn holds arm operating knobs 502 and 503.

[0114] 2E illustrates a further embodiment of a delivery system utilizing a two-way steerable guide catheter in combination with a two-way steerable delivery catheter. An introducer sheath handle 510 houses a two-way steering knob 505 for manipulating and steering the distal sheath 498. This is arranged in conjunction with another handle 515, which in turn holds arm operating knobs 502, 503, as well as a knob 518 that provides two-way steering of the distal delivery shaft 499. Note that a pre-made two-way steerable introducer sheath from Merit Medical (HeartSpan® Steerable Sheath Introducer, https: / / www.merit.com / cardiac-intervention / ep-and-crm / electrophysiology / heartspan-steerable-sheath-introducer / ) is shown as an example for illustrative purposes.

[0115] 2F illustrates a further embodiment of a delivery system utilizing a two-way steerable guide catheter in combination with a four-way steerable delivery catheter. An introducer sheath handle 510 houses a two-way steering knob 505 for manipulating and steering the distal sheath 498. This is arranged in conjunction with another handle 517, which in turn holds arm manipulation knobs 502, 503, plus knobs 520 and 521, respectively, that provide two-way steering of the distal delivery shaft 499, resulting in four-way steerability. Note that a pre-fabricated two-way steerable introducer sheath from Merit Medical (HeartSpan® Steerable Sheath Introducer, https: / / www.merit.com / cardiac-intervention / ep-and-crm / electrophysiology / heartspan-steerable-sheath-introducer / ) is shown as an example for illustrative purposes.

[0116] 2G illustrates a further embodiment of a delivery system utilizing a four-way steerable guide catheter in combination with a two-way steerable delivery catheter. A steerable guide catheter handle 523 houses two two-way steering knobs 529 and 528 for manipulating and four-way steering the distal sheath 498. This is arranged in conjunction with another handle 515, which in turn holds arm manipulation knobs 502, 503, plus a knob 518 that provides two-way steering of the distal delivery shaft 499. In some embodiments, the knob 518 can be configured for arm manipulation instead of delivery catheter steerability.

[0117] 2H illustrates a further embodiment of a delivery system utilizing a four-way steerable introducer sheath in combination with a two-way steerable delivery catheter. An introducer sheath handle 523 houses two two-way steering knobs 529 and 528 for manipulating and four-way steering the distal sheath 498. This is arranged in conjunction with another handle 517, which in turn holds arm manipulation knobs 502, 503, plus knobs 520 and 521, respectively, that provide two-way steering of the distal delivery shaft 499, resulting in four-way steerability.

[0118] 2I-1 and 2I-2 illustrate the movement of the distal introducer sheath 498 with a two-way steering configuration.

[0119] 2J-2Q depict a preferred embodiment of an exemplary 12 Fr custom catheter-based delivery system used to deploy the fixation device within the heart.

[0120] FIG. 2J illustrates a further embodiment of an exemplary 12 Fr delivery system similar to FIG. 2G, but utilizing a four-way steerable guide catheter in combination with a delivery catheter using custom handles 745, 747. The steerable guide catheter handle 745 houses two two-way steering knobs 529 and 528 for four-way steering of the sheath 498. The steerable guide is disposed in conjunction with a delivery catheter handle 747, which in turn holds arm manipulation knobs 502, 503, plus a knob 518 configured for arm manipulation instead of delivery catheter steerability. In a preferred embodiment, knob 502 is used to independently manipulate one inner arm, while knob 503 is used to independently manipulate the other inner arm. A third knob 518 is used to simultaneously manipulate the two outer arms.

[0121] 2K shows the distal segment of the catheter system shown in FIG. 2J. As can be seen, an exemplary 9 Fr outer diameter delivery catheter shaft 499 passes through the lumen of an exemplary 12 Fr inner diameter steerable guide catheter shaft 498.

[0122] 2L shows the steerable guide and delivery catheter handle side-by-side. Exemplary stainless steel tube 623 provides a means for supporting and mounting the steerable guide catheter handle on a suitable stand (not shown), while exemplary stainless steel tube 615 provides a means for supporting and translating the delivery catheter when inside the steerable guide handle.

[0123] 2M shows a detailed view of the delivery catheter handle with a flush port 715, which can optionally be used to measure hemodynamic pressure at the release bar 16. In addition, the figure shows an exemplary quarter-turn locking release rod knob 550. The knob 550 can be used to manipulate the release rod 18 and thereby release / deploy the fixation element.

[0124] FIG. 2N shows an exemplary distal segment of a custom delivery catheter.

[0125] Figure 2O shows details of the steerable guide handle 745 with the dilator proximal shaft 403 and quarter-turn locking dilator knob 730. In addition, the steerable guide catheter handle consists of a lockable and pinchable hemostatic valve 735. When unlocked and not pinched by the user, the hemostatic valve collapses tightly closed on itself to provide a hemostatic seal. As shown in Figure 2O, if a dilator 403 (or delivery catheter) is present, it will then close over the dilator 403 (or delivery catheter); in addition to providing a hemostatic seal, this will also restrain movement of the dilator 403 (or delivery catheter).

[0126] When locked using lock 727 as shown in Figure 2P or when pinched by the user, the hemostatic valve is opened, allowing free movement or passage of the dilator (or delivery catheter). Optional exemplary indicia 700 and 702 indicate the steerable function of knobs 520 and 528.

[0127] FIG. 2Q-1 shows a detailed view of the distal segment of the steerable guide catheter shaft 498. The shaft 498 is wire reinforced to provide the required kink resistance, torqueability, and pushability. The proximal shaft 405 is relatively stiff, while the distal steerable shaft 402 is relatively flexible, and the mid-shaft 401 provides an intermediate level of mixed stiffness. Three radiopaque markers 400 are present to enhance visualization under fluoroscopy.

[0128] 2Q-2 shows one of the exemplary markers 702. Manipulation of the corresponding knob (528 as shown in FIGS. 2O, 2P) results in exemplary steering of the distal segments 402, 401 of the steerable guide catheter shaft 498.

[0129] 3A-3C show an exemplary prototype of a fixation device type.

[0130] Figure 3A shows the first bare-bones prototype, in which the inner and outer arms are fastened using sutures and pins. Additionally, in this exemplary prototype, the inner and outer arms are contoured to allow additional grip beyond the required coaptation of the native valve. The inner and outer arms of this exemplary prototype were fabricated from Nitinol.

[0131] 3B-1 shows another exemplary embodiment of the contoured fixation device. As can be seen, this is a complete prototype of the fixation device (with inner arms 14, 22, outer arms 12, 20, base bracket 10, and fastener 24). The inner and outer arms of this exemplary prototype are made from nitinol, while the base bracket 10 and fastener 24 are made from titanium.

[0132] Figure 3B-2 shows the individual inner arms 14, 22 and outer arms 12, 20 of the fixation device shown in Figure 3B-1. Note that the outer arms of Figures 3B-1 and 3B-2 have fewer barbs or friction elements when compared to the prototype outer arms shown in Figures 3A or 3C.

[0133] 3C shows another exemplary embodiment of the contoured fixation device. As can be seen, this is a complete prototype of the fixation device (with inner arms 14, 22, outer arms 12, 20, base bracket 10, and fastener 24). The inner and outer arms of this exemplary prototype are made from nitinol, while the base bracket 10 and fastener 24 are made from titanium. Compared to the contoured prototype of the fixation device in FIGS. 3A and 3B-1, this prototype is designed primarily for the coaptation region of the native valve.

[0134] 4A-4F depict arm manipulation to be controlled, for example, by knobs 502, 503, and / or 518. Specifically, these figures illustrate a preferred stepwise deployment of the fixation device in the antegrade orientation.

[0135] Prior to insertion of the device and delivery assembly through the mitral valve, the device remains in a collapsed state inside the steerable guide catheter shaft 498, with all arms folded upwards. This is illustrated in FIG. 4A by the positions of arms 12, 20, 14, 22.

[0136] FIG. 4A shows manipulation 60 and 61 of the outer arms 12 and 20 to positions 12' and 20' after insertion of the device past the mitral valve leaflet LF.

[0137] FIG. 4B further illustrates this by showing the final position of outer arms 12 and 20 facing upward just below leaflet LF.

[0138] 4C shows repositioning of the fixation device so that the mitral valve leaflets LF are fixed by the outer arms 20 and 12. This is achieved by translating the device approximately 1 cm toward the atrium.

[0139] 4D shows the capture of the leaflet LF by movement of arms 14 and 22 to positions 14' and 22' at 62 and 63. The barbed features of the elements secure the leaflet LF to the fixation device.

[0140] FIG. 4E further illustrates the end result of the capture in which arms 14, 22, 12, and 20 effectively capture the mitral valve leaflet LF.

[0141] Figure 4F shows the deployment of the fixation device. Note that Figure 4F is the end state of all described procedures for deployment of the preferred embodiment.

[0142] 5A-5D depict arm manipulation to be controlled, for example, by knobs 502, 503, and / or 518. Specifically, these figures illustrate the stepwise deployment of the fixation device in an antegrade orientation, with inner arms 22 and 14 each independently capturing a leaflet.

[0143] FIG. 5A illustrates the preferred embodiment after its placement beneath the mitral valve leaflet LF, as previously described in FIG. 4C.

[0144] FIG. 5B depicts an independent operation 62 to lower the inner arm 22 to position 22' and capture the first leaflet LF.

[0145] FIG. 5C illustrates the advanced position of operation 62.

[0146] 5D depicts an independent actuation 63 of the second inner arm 14 to position 14', capturing the second leaflet LF. Note that the order of acts 62 and 63 can be interchanged to meet preferred user needs.

[0147] 6A-6D depict an alternative variation of independent arm manipulation for sequential capture of the leaflet LF. Specifically, these figures illustrate, for purposes of representation of ideas, the stepwise deployment of the fixation device in an antegrade orientation.

[0148] 6A illustrates manipulation 60 of outer arm 20 to position 20'. The device must now be positioned so that the cusp LF is apposed to the barbed feature of arm 20.

[0149] 6B shows the capture of the leaflet LF by the lowering 62 of the inner arm 22 to position 22'. This captures the first leaflet LF.

[0150] The result of operation 60 followed by operation 62 is shown in Figure 6C, where the device has successfully captured one leaflet LF, which also shows operation 61 to reposition outer arm 12 to position 12'.

[0151] FIG. 6D illustrates operation 63 of lowering inner arm 14 to position 14' to capture the second leaflet LF.

[0152] Note that the operation pairs (60, 62) and (61, 63) can be permuted to meet user needs.

[0153] The result of the operation depicted in Figures 6A-6D is illustrated in Figure 4E, with arms 14, 22, 12, and 20 effectively capturing the mitral valve leaflet LF.

[0154] Preferred embodiments are designed to allow the user to abort device deployment following any complications. Additionally, a prolapse maneuver may be required to correct suboptimal capture or reposition the leaflets. Examples of "prolapse" maneuvers are illustrated in Figures 7A-7F.

[0155] FIG. 7A shows an exemplary fixation device after complete capture of the mitral valve leaflet LF.

[0156] FIG. 7B shows the release of the leaflet LF by lifting the inner capture arms 22 and 14 to positions 22′ and 14′ via operations 64 and 65. FIG. 7C depicts the end result of operations 64 and 65. FIG. 7D illustrates actuations 51 and 52 of sutures 47 and 48 such that suture segments 42 and 44 are translated to positions 42′ and 44′. Note that this translation lifts the leaflet LF from outer arms 12 and 20 to position LF′. FIG. 7E shows the end result of these operations 51 and 52. FIG. 7F shows a further embodiment of operations 51 and 52 in which arms 20 and 12 are fully collapsed upward. At this stage, prolapse is complete, and the fixation device can be retracted into the atrium, away from the mitral valve. The user may choose to retry the procedure or fully retract and remove the fixation device and delivery catheter 499 through the steerable guide catheter shaft 498.

[0157] 8A-8D provide a more detailed depiction of the movement and manipulation of the fixation device, focusing on the sutures connecting the fixation device to the delivery system.

[0158] FIG. 8A illustrates the back side of the device (facing component 16) without showing inner arms 14 and 22 to avoid clutter. This depiction represents the position of all other device elements while outer arms 12 and 20 are ready to capture. Suture 95 follows the catheter tubing and elements 28 and 16, then advances through loop 98, forming segments 91 and 93. Suture 97 follows the catheter tubing and elements 28 and 16, forming segments 92 and 94. The distal ends of sutures 91 and 92 are looped through hole 30 onto release rod 18. Suture 96 also follows the front side of the catheter tubing and elements 28 and 16, which in turn advances through feature 30 to be looped through loop 98. FIG. 8B is a zoomed-in image of FIG. 8A, designated by the circle drawn around feature 30. It should be noted that the use of loop 98 may be rendered impractical by utilizing a loop at the distal end of suture 96 .

[0159] FIG. 8C depicts a further embodiment of the embodiment depicted in FIG. 8A. Here, operations 110, 111, and 112 translate suture segments 93, 94, and 98 from their original positions, as depicted in FIG. 8A. Note that operations 110 and 112 can be via knobs on the handles (e.g., knob 518), which retrieve the leaflets LF from their positions on the outer arms 12 and 20, allowing for prolapse. FIG. 8C is essentially a more detailed illustration of the preferred embodiment of FIG. 7E. FIG. 8D provides a zoomed image of the embodiment of FIG. 8C, designated by the black circle depicted around element 30. Note that in a preferred exemplary embodiment, operations 110 and 112 can be active operations of knobs on the delivery handles (e.g., simultaneous pulling of both 110 and 112 using a single knob 518), while operation 111 can be passive (e.g., application of a constant tension using a spring).

[0160] 9A-9D provide a more detailed view of the mechanisms that operate the inner arms 14 and 22. Note that the sutures and mechanisms involved in the outer arms 12 and 20 are not shown in FIGS. 9A-9D for simplicity.

[0161] FIG. 9A illustrates the fixation device prior to the action of operations 77 and 78 on sutures 75 and 76 to collapse inner arms 14 and 22. Note that suture 76 is also comprised of segments 74 and 72. Similarly, suture 75 is comprised of segments 73 and 71. The distal ends of segments 71 and 72 are looped around release rod 18 through feature 26 on deployment bar 16. FIG. 9B provides an enlarged view of the mechanism and sutures described above, designated by the circle drawn around feature 26. FIG. 9C depicts a further embodiment of the fixation device in which suture segments 71 and 73 are looped through separate suture loops 83 attached to inner arm 14. Similarly, suture segments 72 and 74 are looped through separate suture loop 82, with the sutures looped through loops 83 and 82. 9D shows the fixation device after continuation of manipulations 77 and 78 has successfully collapsed the inner arms 14 and 22. This is essential in the prolapse procedure because it allows the device to become compact for retraction. Additionally, this manipulation of raising and lowering the inner arms while keeping the outer arms lowered allows the user to make several attempts to capture the leaflets.

[0162] 10A-10E illustrate the deployment and detachment of the fixation device from the delivery system.

[0163] FIG. 10A depicts the fixation device in its final position after capturing the mitral valve leaflet LF (not shown). FIG. 10B is a zoomed image of the circular portion of FIG. 10A, designated by the circle drawn around element 30. Here, operation 180 acts on release rod 18 as it is retracted from the delivery system using, for example, release rod knob 550. The result of this operation is shown in FIG. 10C, with the fixation device effectively separated from deployment bar 16. FIG. 10D depicts the effect of operation 180 on suture segments 91 and 92, which are unlinked from the device due to removal of release rod 18 and retracted along their length up through the delivery system. Note that release of suture segments 71 and 72 occurs through the same mechanism via feature 26. The end result of release can be seen in FIG. 10E, with the device successfully implanted within the heart and the distal delivery system ready for retraction.

[0164] FIG. 11 shows an example embodiment with inner (22, 14) and outer (12, 20) arm struts shaped on the outside of the fixation device. Additionally, it shows flat-patterned inner (22", 14") and outer (12", 20") arms to illustrate one method of fabricating the arms using a laser or wire EDM cut nitinol plane.

[0165] FIG. 12 shows an example of a preferred embodiment with inner (22, 122) and outer (120, 20) arm struts shaped on the outside of the fixation device. Note that the inner 122 and outer 120 arms are shorter than 22 and 20 to accommodate the shorter posterior mitral leaflets. Additionally, this shows flat-patterned inner (122") and outer (120") arms to illustrate one method of fabricating the arms using a laser or wire EDM cut nitinol flat.

[0166] 13A-13E illustrate various alternative embodiments of the fixation device. Note that any combination of these embodiments and those previously discussed may be used to address desired user needs.

[0167] 13A illustrates an embodiment in which both outer arms are formed as a single, continuous, bifurcating outer arm component 201 that grasps a cusp on either side. Similarly, both inner arms are formed as a single, continuous, bifurcating inner arm component 202 that grasps a cusp on either side.

[0168] 13B shows an example of an embodiment of the fixation device in which there is a spacer 203 between the inner arms that a) provides room for a thicker leaflet LF, b) provides additional flexibility to the inner arms, and c) provides an alternative site for removably coupling the fixation device to a delivery catheter.

[0169] 13C illustrates an example of a valve clip fixation device embodiment that has only two outer arms 204 and no inner arms designed to capture the leaflets LF. In addition, FIG. 13C shows an example of a fixation device embodiment in which there is a spacer 203 between the arms. This spacer can be used to provide clearance for tissue capture or for attachment of the fixation device to a delivery catheter.

[0170] Figure 13D illustrates a valve clip fixation device embodiment that primarily uses pairs of outer arms 136, 132 and inner arms 134, 138 to capture the leaflet LF along the native valve's coaptation line 205. In contrast to the previous embodiment, in which the capture arms diverge from the coaptation line when grasping the leaflet, the capture arms in Figures 13C and 13D are aligned parallel to the coaptation line when grasping the leaflet.

[0171] 13E shows an embodiment of the valve clip fixation device in which there are three pairs of inner and outer arms 206. This is for grasping three sets of leaflets, such as the tricuspid valve.

[0172] 13F-1 and 13F-2 show an exemplary embodiment of a base bracket 10 with a ramp feature 11 that enhances easy removal onto the fixation device upon removal of the release rod 18 during deployment.

[0173] 13G-1-13G-4 show an exemplary embodiment of a release bar 16 with two struts 17. The struts aid in spreading (or lowering) the outer arms during leaflet capture while allowing seamless removal from the fixation device during deployment.

[0174] 13H-1 and 13H-2 illustrate the function of the support posts 17. FIGS. 13H-1 and 13H-2 show back and side views, respectively, of the release bar 16 and the base bracket 10 and release rod 18 subassembly. Note that the arms are not shown for clarity. In the starting position, the base bracket 10 is in a lower position and there is a gap 54 between the support posts 17 and the base bracket 10.

[0175] 13I-1 and 13I-2, the base bracket is manipulated toward the strut 17, for example, using a wire or suture connected to one of the delivery catheter handle knobs. This manipulation results in a reduction of the gap 54.

[0176] 13J-1 and 13K-2 show partial front views of the release bar 16, release rod 18, and schematics of the outer arms 132, 136 and inner arms 134, 136. FIG. 13J-1 shows the base bracket 10 in a starting position. In this exemplary embodiment, the inner and outer arms are typically made of a superelastic material, such as Nitinol. The outer arm is shaped toward a vertical position, while the inner arm is shaped toward a horizontal position. Thus, while there is a constant bias for the outer arm to move toward the vertical position, as in FIG. 13D, the inner arm is constantly biased toward the outer arm. Furthermore, the outer arm can be made stronger compared to the inner arm, for example, by using a thicker outer arm. Furthermore, the inner arm is positioned in a raised position, for example, using the technique previously described in FIG. 9D. Thus, the outer arm is constrained only by the support post 17. In FIG. 13J-2, the base bracket 10 is manipulated upward toward the support post 17. This results in the desired lowering of the outer arms as they are pushed down against the posts 17.

[0177] 13K-1 and 13K-2 are similar to FIGS. 13J-1 and 13J-2, with the inner arms 134, 138 preset to be in a lowered position.

[0178] 13G-1-13K-2 show the post fixed to the release bar 16, it will be apparent to one skilled in the art that the post can be movable. For example, the post could be mounted on a lever arm and hinged to the release bar 16 and used to manipulate the arm with mechanical advantage using a tether.

[0179] Figure 14 shows an example of an embodiment in which the outer arms do not have barbs or friction elements. Alternatively, the inner arms may or may not have barbs or friction elements. Additionally, the length of each individual inner or outer arm may be:

[0180] The offset length can vary such that A=0-100 mm, B=0-100 mm, C=0-100 mm, D=0-100 mm, and A≧B, or B≧A, or B≠A, C≧D, or D≧C, or C≠D, B≧D, or D≧B, or B≠D, A≧C, or C≧A, or C≠A. Note that while only offset lengths are depicted, the same can apply to the individual physical lengths of the entire arm or only the section of the arm that engages the cusp. That is, each individual arm can be differently sized in thickness, length, and width.

[0181] 15 illustrates various configurations of fixation device embodiments where the final angles (Af, Bf, Cf, Df) = 0-180 degrees, and where Angle Af ≥ Angle Bf, or Angle Af ≤ Angle Bf, or Angle Af ≠ Angle Bf, Angle Cf ≥ Angle Df, or Angle Cf ≤ Angle Df, or Angle Cf ≠ Angle Df, Angle Af ≥ Angle Cf, or Angle Af ≤ Angle Cf, or Angle Af ≠ Angle Cf, Angle Bf ≥ Angle Df, or Bf ≤ Angle Df, or Angle Bf ≠ Angle Df. Note that in a preferred configuration, the inner and outer arms are elastically or superelastically biased toward each other with sufficient force to securely capture the leaflet when placed between them.

[0182] 16 illustrates various configurations of fixation device embodiments where the final angles (A, B, C, D) = 0-180 degrees, and where angle A ≥ angle B, or angle A ≤ angle B, or angle A ≠ angle B, angle C ≥ angle D, or angle C ≤ angle D, or angle C ≠ angle D, angle A ≥ angle C, or angle A ≤ angle C, or angle A ≠ angle C, angle B ≥ angle D, or angle B ≤ angle D, or angle B ≠ angle D. In preferred embodiments, the final and shape-set angles may have the following relationships: angle A ≤ angle A, angle B ≤ angle B, angle C ≤ angle C, angle D ≤ angle D, angle A ≠ angle B, angle C ≠ angle D.

[0183] FIG. 17A reproduces a MitraClip® embodiment (FIG. 11B, US Pat. No. 8,057,493 B2; page 8 / 68) showing the inner gripping arms with barbs 60 exposed on the sides.

[0184] 17B depicts a further embodiment of the present invention in which the MitraClip® external barb 60 of FIG. 17A is replaced with and redesigned with an internal barb 60′ (FIG. 17B), consistent with the present invention. In the present invention, designing the arms so that the barbs are internal to the arms rather than external to the arms further ensures that tendons, tissues, or delivery device components (e.g., sutures or wires) do not unintentionally or accidentally get caught, tangled, or structurally compromised during manipulation of the fixation device within the heart.

[0185] 18A-18C illustrate an embodiment to aid in visualization of fixation during the procedure. This is accomplished via an optical camera with a light source 800 embedded inside a balloon 802 filled with a clear liquid, such as saline or DI water. Alternatively, the in-situ camera and / or light source can be replaced with a fiber optic-based scope.

[0186] 18B shows an example of an embodiment in which the balloon is inflated through the delivery catheter lumen and optical visualization is achieved along the surface of the transparent balloon. In this embodiment, a semi-compliant or variable stiffness balloon configuration may be used. During deployment, the balloon 802 is inflated with clear saline or DI water, contacting the clip and / or tissue and providing visual feedback via the camera 800. The visual feedback can be used to plan and perform the procedure.

[0187] FIG. 18C shows an example of a porous outer balloon 804 surrounding a non-porous inner balloon 806 that surrounds an optical camera with a light source 800, the porous outer balloon displacing surrounding blood for improved visualization.

[0188] 18D shows an optical camera with a light source 800 on a retractable / steerable structure inside a balloon 808 with variable compliance. The balloon's highly compliant inner surface 812 conforms to the top surface of the clip and cusp, providing improved contact for increased visualization. The balloon's top surface 812 may be more rigid to ensure full inflation of the balloon 810 over the clip and cusp. The balloon 810 may be on a delivery catheter or implant, or as a standalone device.

[0189] 18E shows a pair of optical cameras or fiber optic sensors 820 housed in or on a balloon 822 mounted on a retractable / steerable structure 824. Alternatively, these sensors / cameras can be mounted on the steerable / retractable shaft 826.

[0190] 19 shows one or more optical coherence tomography (OCT) sensors 830 attached to the distal shaft 832 of the delivery system. These sensors 830 may be mounted in multiple units or on a retractable and / or steerable shaft 834. This would allow for high-resolution tissue and delivery device imaging during implantation.

[0191] 20 shows one or more ultrasound sensors 840 attached to the distal shaft 842 of the delivery system. These sensors 840 may be mounted in multiples or on a retractable and / or steerable shaft 844. This would allow for 2D, 3D, and Doppler modalities to be integrated to help navigate and perform the procedure.

[0192] It should be noted that any combination of the embodiments illustrated in Figures 18A-E-20 may be used as part of the present invention to accomplish visualization. In preferred embodiments, these disclosed visualization ideas should be sufficient to replace transesophageal echocardiography (TEE) and / or fluoroscopy. TEE is one of the primary reasons patients undergo general anesthesia during this procedure. Therefore, eliminating the requirement for TEE during this procedure reduces the risks associated with general anesthesia. Meanwhile, reducing fluoroscopy reduces the risks from x-rays.

[0193] Sensors and actuators that can be used in connection with the present invention are intended to improve the safety, ease of use, and effectiveness of delivery systems and fixation devices. Sensors and actuators can be used to assist and evaluate device delivery (acute) and effectiveness (acute or chronic). Sensors and actuators can be active or passive, removable, or implantable, and can provide acute or chronic physiological or non-physiological data to determine or assess patient health. Sensors and actuators can be active or passive, removable, or implantable, and can provide acute or chronic physiological or non-physiological data to determine or assess implant integrity. Functional sensors can be used for visualization, including thermal, optical, ultrasound (including ICE), OCT, and fluorescent sensors and actuators, which can be electrical, mechanical, magnetic, RF, chemical, or a combination. Sensors and actuators can be wired or wireless and can communicate with a mobile or fixed external interface. The catheter of the present invention can be used as a conduit for external sensors, such as a pressure sensor to replace a Swan-Ganz catheter. The terms sensor and actuator may be used interchangeably. The listed sensors and actuators are examples only. Any suitable metal or polymer or ceramic, organic or inorganic, flexible or rigid, matrix or material, and combinations thereof, may be used to produce the desired sensors and actuators.

[0194] All implant embodiments described herein may optionally be clad, attached, coated, or the like to improve biocompatibility and tissue interface. Suitable covers may be woven, interlocking mesh, fibrous, braided, woven, or non-woven. Coatings may be metallic, ceramic, polymeric, or a combination thereof. Suitable metallic coatings include titanium, TiN, tantalum, gold, platinum, and alloys thereof. Suitable ceramic and inorganic coatings include titanium dioxide, hydroxyapatite, CaP, and the like. Suitable polymeric coatings include fluoropolymers such as PTFE, PFA, FEP, ECTFE, ETFE, parylene, polyester, PET, polypropylene, PEEK, PVDF, HDPE, LDPE, UHMWPE, phosphorylcholine, THV, and the like. Suitable biodegradable materials include poly(lactic acid), poly(glycolic acid), polydioxanone, poly(ε-caprolactone), polyanhydrides, poly(orthoesters), copoly(ether-esters), polyamides, polylactones, poly(propylene fumarate), and combinations thereof. Such metal, ceramic, and / or polymer coatings are listed by way of example only. Any suitable metal, ceramic, polymer, and combination thereof may be used to produce the desired coating.

[0195] Below is a list of reference numbers used in this application. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4]

[0196] While many embodiments of the present disclosure have been described in detail, certain variations and modifications will be apparent to those skilled in the art, including embodiments that do not provide all of the features and benefits described herein. It will be understood by those skilled in the art that the present disclosure extends beyond the specifically disclosed embodiments to other alternative or additional embodiments and / or uses, as well as obvious modifications and equivalents thereof. In addition, while some variations have been shown and described in varying detail, other modifications that are within the scope of the present disclosure will be readily apparent to those skilled in the art based on this disclosure. It is also contemplated that various combinations or subcombinations of specific features and aspects of the embodiments may be made and still fall within the scope of the present disclosure. Thus, it should be understood that various features and aspects of the disclosed embodiments may be combined with or substituted for one another to form variable modes of the present disclosure. Therefore, it is intended that the scope of the present disclosure disclosed herein should not be limited by the specific disclosed embodiments described above. With respect to all of the above-described embodiments, the steps of any method need not be performed sequentially.

Claims

[Claim 1] Methods, devices, and systems for endovascular, percutaneous, or minimally invasive surgical treatment of body tissue, such as tissue approximation or valve repair.

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