Patent Publication Number: US-9421004-B2

Title: Method of closing an opening in a wall of the heart

Description:
This application is a continuation of application Ser. No. 14/101,112, filed Dec. 9, 2013, now U.S. Pat. No. 9,089,313, which is a continuation of application Ser. No. 13/477,404, filed May 22, 2012, now U.S. Pat. No. 8,603,108, which is a continuation of application Ser. No. 11/880,265, filed on Jul. 20, 2007, now U.S. Pat. No. 8,197,496, which is a continuation of application Ser. No. 10/810,990, filed Mar. 26, 2004, now U.S. Pat. No. 7,780,683, which is a continuation of application Ser. No. 09/904,790, filed on Jul. 13, 2001, now U.S. Pat. No. 6,712,804, which is a divisional of application Ser. No. 09/444,904, filed on Nov. 22, 1999, now U.S. Pat. No. 6,290,674, which is a continuation-in-part of application Ser. No. 09/399,521, filed Sep. 20, 1999, now U.S. Pat. No. 6,231,561. 
     The present invention relates to methods and devices for closing a body lumen, tissue opening, or cavity and, in particular, for closing an atrial septal defect. 
    
    
     BACKGROUND OF THE INVENTION 
     Embolic stroke is the nation&#39;s third leading killer for adults, and is a major cause of disability. There are over 700,000 strokes per year in the United States alone. Of these, roughly 100,000 are hemoragic, and 600,000 are ischemic (either due to vessel narrowing or to embolism). The most common cause of embolic stroke emanating from the heart is thrombus formation due to atrial fibrillation. Approximately 80,000 strokes per year are attributable to atrial fibrillation. Atrial fibrillation is an arrhythmia of the heart that results in a rapid and chaotic heartbeat that produces lower cardiac output and irregular and turbulent blood flow in the vascular system. There are over five million people worldwide with atrial fibrillation, with about four hundred thousand new cases reported each year. Atrial fibrillation is associated with a 500 percent greater risk of stroke due to the condition. A patient with atrial fibrillation typically has a significantly decreased quality of life due, in part, to the fear of a stroke, and the pharmaceutical regimen necessary to reduce that risk. 
     For patients who develop atrial thrombus from atrial fibrillation, the clot normally occurs in the left atrial appendage (LAA) of the heart. The LAA is a cavity which looks like a small finger or windsock and which is connected to the lateral wall of the left atrium between the mitral valve and the root of the left pulmonary vein. The LAA normally contracts with the rest of the left atrium during a normal heart cycle, thus keeping blood from becoming stagnant therein, but often fails to contract with any vigor in patients experiencing atrial fibrillation due to the discoordinate electrical signals associated with AF. As a result, thrombus formation is predisposed to form in the stagnant blood within the LAA. 
     Blackshear and Odell have reported that of the 1288 patients with non-rheumatic atrial fibrillation involved in their study, 221 (17%) had thrombus detected in the left atrium of the heart. Blackshear J L, Odell J A., Appendage Obliteration to Reduce Stroke in Cardiac Surgical Patients With Atrial Fibrillation. Ann Thorac. Surg., 1996.61(2):755-9. Of the patients with atrial thrombus, 201 (91%) had the atrial thrombus located within the left atrial appendage. The foregoing suggests that the elimination or containment of thrombus formed within the LAA of patients with atrial fibrillation would significantly reduce the incidence of stroke in those patients. 
     Pharmacological therapies for stroke prevention such as oral or systemic administration of warfarin or the like have been inadequate due to serious side effects of the medications and lack of patient compliance in taking the medication. Invasive surgical or thorascopic techniques have been used to obliterate the LAA, however, many patients are not suitable candidates for such surgical procedures due to a compromised condition or having previously undergone cardiac surgery. In addition, the perceived risks of even a thorascopic surgical procedure often outweigh the potential benefits. See Blackshear and Odell, above. See also Lindsay B D., Obliteration of the Left Atrial Appendage: A Concept Worth Testing, Ann Thorac. Surg., 1996.61(2):515. 
     Despite the various efforts in the prior art, there remains a need for a minimally invasive method and associated devices for reducing the risk of thrombus formation in the left atrial appendage. 
     Other conditions which would benefit from a tissue aperture closure catheter are tissue openings such as an atrial septal defect. In general, the heart is divided into four chambers, the two upper being the left and right atria and the two lower being the left and right ventricles. The atria are separated from each other by a muscular wall, the interatrial septum, and the ventricles by the interventricular septum. 
     Either congenitally or by acquisition, abnormal openings, holes or shunts can occur between the chambers of the heart or the great vessels (interatrial and interventricular septal defects or patent ductus arteriosus and aorthico-pulmonary window respectively), causing shunting of blood through the opening. The ductus arteriosus is the prenatal canal between the pulmonary artery and the aortic arch which normally closes soon after birth. The deformity is usually congenital, resulting from a failure of completion of the formation of the septum, or wall, between the two sides during fetal life when the heart forms from a folded tube into a four-chambered, two unit system. 
     These deformities can carry significant sequelae. For example, with an atrial septal defect, blood is shunted from the left atrium of the heart to the right, producing an over-load of the right heart. In addition to left-to-right shunts such as occur in patent ductus arteriosus from the aorta to the pulmonary artery, the left side of the heart has to work harder because some of the blood which it pumps will recirculate through the lungs instead of going out to the rest of the body. The ill effects of these lesions usually cause added strain on the heart with ultimate failure if not corrected. 
     Previous extracardiac (outside the heart) or intracardiac septal defects have required relatively extensive surgical techniques for correction. To date the most common method of closing intracardiac shunts, such as atrial-septal defects and ventricular-septal defects, entails the relatively drastic technique of open-heart surgery, requiring opening the chest or sternum and diverting the blood from the heart with the use of a cardiopulmonary bypass. The heart is then opened, the defect is sewn shut by direct suturing with or without a patch of synthetic material (usually of Dacron, Teflon, silk, nylon or pericardium), and then the heart is closed. The patient is then taken off the cardiopulmonary bypass machine, and then the chest is closed. 
     In place of direct suturing, closures of interauricular septal defects by means of a mechanical prosthesis have been disclosed. 
     U.S. Pat. No. 3,874,388 to King, et al. relates to a shunt defect closure system including a pair of opposed umbrella-like elements locked together in a face to face relationship and delivered by means of a catheter, whereby a defect is closed. U.S. Pat. No. 5,350,399 to Erlebacher, et al. relates to a percutaneous arterial puncture seal device also including a pair of opposed umbrella-like elements and an insertion tool. 
     U.S. Pat. No. 4,710,192 to Liotta, et al. relates to a vaulted diaphragm for occlusion in a descending thoracic aorta. 
     U.S. Pat. No. 5,108,420 to Marks relates to an aperture occlusion device consisting of a wire having an elongated configuration for delivery to the aperture, and a preprogrammed configuration including occlusion forming wire segments on each side of the aperture. 
     U.S. Pat. No. 4,007,743 to Blake relates to an opening mechanism for umbrella-like intravascular shunt defect closure device having foldable flat ring sections which extend between pivotable struts when the device is expanded and fold between the struts when the device is collapsed. 
     Notwithstanding the foregoing, there remains a need for a transluminal method and apparatus for correcting intracardiac septal defects, which enables a patch to placed across a septal defect to inhibit or prevent the flow of blood therethrough. 
     SUMMARY OF THE INVENTION 
     The present invention provides a closure catheter and methods for closing an opening in tissue, a body lumen, hollow organ or other body cavity. The catheter and methods of its use are useful in a variety of procedures, such as treating (closing) wounds and naturally or surgically created apertures or passageways. Applications include, but are not limited to, atrial septal defect closure, patent ductus arteriosis closure, aneurysm isolation and graft and/or bypass anostomosis procedures. 
     There is provided in accordance with one aspect of the present invention a method of closing an opening in a wall of the heart. The method comprises the steps of advancing a catheter through the opening, and deploying at least two suture ends from the catheter and into tissue adjacent the opening. The catheter is retracted from the opening, and the suture ends are drawn toward each other to reduce the size of the opening. The opening is thereafter secured in the reduced size. 
     In one embodiment, the advancing step comprises advancing the catheter through an atrial septal defect. The deploying step comprises deploying at least four suture ends. Preferably, each suture end is provided with a tissue anchor, and the deploying step comprises advancing the tissue anchors into tissue adjacent the opening. The securing step comprises knotting the sutures, clamping the sutures, adhesively bonding the sutures and/or the tissue to retain the opening in the reduced size. 
     In accordance with another aspect of the present invention, there is provided an atrial septal closure catheter. The catheter comprises an elongate flexible body, having a proximal end and a distal end, and a longitudinal axis extending therebetween. At least two supports are provided on the distal end, the supports moveable from a first position in which there are substantially parallel with the axis, and a second position in which they are inclined with respect to the axis. A control is provided on the proximal end for moving the supports from the first position to the second position. In one embodiment, the supports incline radially outwardly in the proximal direction when the supports are in the second position. 
     Preferably, the closure catheter comprises at least four supports, and each support carries at least one anchor. Each anchor is preferably provided with an anchor suture. 
     In accordance with a further aspect of the present invention, there is provided a method for closing an opening in a wall of the heart. The method comprises the steps of providing a catheter having at least three tissue anchors thereon, each tissue anchor having a suture secured thereto. The catheter is advanced to the opening in the wall of the heart, and the anchors are inclined outwardly from the axis of the catheter to aim the anchors at tissue surrounding the opening. The anchors are deployed into tissue surrounding the opening, and the sutures are manipulated to reduce the size of the openings. 
     In one embodiment, the deploying the anchors step comprises deploying the anchors in a proximal direction. In another embodiment, the deploying the anchors step comprises deploying the anchors in a distal direction. 
     In accordance with a further aspect of the present invention, there is provided a closure catheter for closing an atrial septal defect. The catheter comprises an elongate flexible tubular body, having a proximal end and a distal end, and a longitudinal axis extending therebetween. At least two anchor supports are provided on the distal end, the anchor supports moveable between an axial position in which they are substantially parallel with the longitudinal axis, and an inclined position in which they are inclined laterally away from the axis. A control is provided on the proximal end, for moving the anchor supports between the axial and the inclined positions. Each anchor support has a proximal end and a distal end, and the distal end is pivotably secured to the catheter so that the proximal end moves away from the axis when the anchor support is moved into the inclined position. 
     In one embodiment, the closure catheter further comprises an anchor in each of the anchor supports. Preferably, from about four to about 10 anchor supports are each provided with an anchor. Each anchor is preferably connected to a suture. 
     In one embodiment, a retention structure is removably carried by the distal end of the catheter or slideably carried by the suture. The retention structure is adapted to be distally advanced such that it constricts around the sutures, thereby securing them in a desired position. In one embodiment, the retention structure comprises a slideable knot, such as a Prusik knot. 
     Further features and advantages of the present invention will become apparent to those of skill in the art in view of the detailed description of preferred embodiments which follows, when considered together with the attached drawings and claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWING 
         FIG. 1  is an anterior illustration of a heart, with the proximal parts of the great vessels. 
         FIG. 2  is a schematic cross section through the heart with a transeptal catheter deployed through the septum and a closure catheter extending into the LAA. 
         FIG. 3A  is an enlarged perspective view of the distal end of a closure catheter in accordance with the present invention. 
         FIG. 3B  is a cross section taken along the lines  3 B- 3 B of  FIG. 3A . 
         FIG. 4  is a partial cross-sectional view of a tissue anchor and introducer, positioned within an anchor guide in accordance with the present invention. 
         FIG. 5  is an exploded view of a tissue anchor and introducer in accordance with one aspect of the invention. 
         FIG. 6A  is a schematic illustration of a tissue anchor and introducer advancing into a tissue surface. 
         FIG. 6B  is an illustration as in  FIG. 6A , with the anchor positioned within the tissue and the introducer partially retracted. 
         FIG. 6C  is an illustration as in  FIG. 6B , with the introducer fully refracted and the anchor positioned within the tissue. 
         FIG. 7  shows a schematic view of a closure catheter disposed within the opening of the LAA. 
         FIG. 8  is a schematic illustration of the opening of the LAA as in  FIG. 7 , with the anchor guides in an inclined orientation. 
         FIG. 9  is a schematic illustration as in  FIG. 8 , with tissue anchors deployed from the anchor guides. 
         FIG. 10  is a schematic illustration as in  FIG. 9 , with the anchor guides retracted into an axial orientation. 
         FIG. 11  is a schematic illustration as in  FIG. 10 , with the closure catheter retracted and the LAA drawn closed using the tissue anchors. 
         FIG. 11A  is a schematic illustration of the distal tip of a deployment catheter, having an anchor suture loop with a slideable retention structure thereon. 
         FIG. 11B  is a schematic illustration of a simplified Prusik knot, utilized as a component of the retention structure shown in  FIG. 11A . 
         FIG. 11C  is an enlargement of the retention structure shown in  FIG. 11A . 
         FIG. 12  is a perspective view of a closure catheter in accordance with the present invention positioned within a tissue aperture, such as an atrial septal defect. 
         FIG. 13  is a side elevational partial cross-section of the catheter of  FIG. 12 , in an anchor deployment orientation within the aperture. 
         FIG. 14  is a side elevational partial cross-section as in  FIG. 13 , with the deployment catheter withdrawn from the aperture. 
         FIG. 15  is a side elevational cross section through the aperture, which has been closed in accordance with the present invention. 
         FIG. 16  is a perspective view of a closure catheter in accordance with the present invention, carrying an aperture patch. 
         FIG. 17  is a cross-sectional view through the catheter of  FIG. 16 , shown deploying a patch across a tissue aperture. 
         FIGS. 18A-18G  are alternate tissue anchors for use with the closure catheter of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     For simplicity, the present invention will be described primarily in the context of a left atrial appendage closure procedure. However, the device and methods herein are readily applicable to a wider variety of closure or attachment procedures, and all such applications are contemplated by the present inventors. For example, additional heart muscle procedures such as atrial septal defect closure and patent ductus arteriosis closure are contemplated. Vascular procedures such as isolation or repair of aneurysms, anastomosis of vessel to vessel or vessel to prosthetic tubular graft (e.g., PTFE or Dacron tubes, with or without wire support structures as are well known in the art) joints may also be accomplished using the devices of the present invention. Attachment of implantable prostheses, such as attachment of the annulus of a prosthetic tissue or mechanical heart valve may be accomplished. A variety of other tissue openings, lumens, hollow organs and surgically created passageways may be closed, patched or reduced in volume in accordance with the present invention. For example, an opening in a tissue plane may be closed or patched, such as by attaching a fabric or tissue sheet across the opening. In one specific application, the device of the present invention is used to anchor a fabric patch to close an atrial septal defect. The target aperture or cavity may be accessed transluminally (e.g., vascular catheter or endoscope) or through solid tissue, such as transmural, percutaneous or other approach. The present invention may also be used in an open surgical procedure such as to close the left atrial appendage during open heart surgery to correct or address a different condition. In another example, the device is advanced through the percutaneous opening and used to close a vascular puncture such as a femoral artery access site for a PTA or other diagnostic or therapeutic interventional procedure. Adaptation of the devices and methods disclosed herein to accomplish procedures such as the foregoing will be apparent to those of skill in the art in view of the disclosure herein. 
     Referring to  FIG. 1 , a heart  10  is illustrated to show certain portions including the left ventricle  12 , the left atrium  14 , the left atrial appendage (LAA)  16 , the pulmonary artery  18 , the aorta  20 , the right ventricle  22 , the right atria  24 , and the right atrial appendage  26 . As is understood in the art, the left atrium  14  is located above the left ventricle  12  and the two are separated by the mitral valve (not illustrated). The LAA  16  is normally in fluid communication with the left atrium  14  such that blood flows in and out of the LAA  16  as the heart  10  beats. 
     In accordance with the present invention, a closure catheter  38  is advanced through the heart and into the LAA. In general, the closure catheter  38  is adapted to grasp tissue surrounding the opening to the LAA, and retract it radially inwardly to reduce the volume of and/or close the LAA. The LAA is thereafter secured in its closed orientation, and the closure catheter  38  is removed. Specific aspects of one embodiment of the closure catheter in accordance with the present invention are described in greater detail below. 
     The LAA may be accessed through any of a variety of pathways as will be apparent to those of skill in the art. Transeptal access, as contemplated by  FIG. 2 , may be achieved by introducing a transeptal catheter through the femoral or jugular vein, and transluminally advancing the catheter into the right atrium. Once in the right atrium, a long hollow needle with a preformed curve and a sharpened distal tip is forcibly inserted through the fossa ovalis. A radiopaque contrast media may then be injected through the needle to allow visualization and ensure placement of the needle in the left atrium, as opposed to being in the pericardial space, aorta, or other undesired location. 
     Once the position of the needle in the left atrium is confirmed, the transeptal catheter is advanced into the left atrium. The closure catheter  38  may then be advanced through the transeptal catheter  30 , and steered or directed into the left atrial appendage. Alternative approaches include venous transatrial approaches such as transvascular advancement through the aorta and the mitral valve. In addition, the devices of the present invention can be readily adapted for use in an open heart surgical procedure, although transluminal access is presently preferred. 
     Thus, referring to  FIG. 2 , a transeptal catheter  30  has a proximal end  32  and a distal end  34 . The distal end  34  of the transeptal catheter  30  has breached the septum  40  of the patient&#39;s heart  10  and is disposed adjacent the opening  42  of the patient&#39;s LAA  16 . The distal end  36  of a closure catheter  38  extends from the distal end  34  of the transeptal catheter  30  and into the LAA  16 . 
     At the proximal end  46  of the transeptal catheter  30 , a luer connector coupled to a hemostasis valve  48  prevents the egress of blood from a central lumen of the transeptal catheter  30 . The proximal end  50  of the closure catheter  38  extends proximally from the hemostasis valve  48 . Additional details concerning the use and design of transeptal access catheters are well known in the art and will not be discussed further herein. 
     Referring to  FIGS. 2 and 3 , the closure catheter  38  thus has a proximal end  50 , a distal end  36 , and an elongate flexible tubular body  52  extending therebetween. The axial length of the closure catheter  38  can be varied, depending upon the intended access point and pathway. For a femoral vein-transeptal approach, the closure catheter  38  generally has an axial length within the range of from about 100 cm to about 140 cm, and, in one embodiment, about 117 cm. 
     The outside diameter of the flexible body  52  can also be varied, depending upon the number of internal lumen and other functionalities as will be understood by those of skill in the art. In one embodiment, the outside diameter is about 12 FR (0.156 inches), and closure catheters are contemplated to have OD&#39;s generally within the range of from about 0.078 inches to about 0.250 inches. Diameters outside of the above range may also be used, provided that the functional consequences of the diameter are acceptable for the intended application of the catheter. 
     For example, the lower limit of the outside diameter for tubular body  52  in a given application will be a function of the number of fluid or other functional lumen contained within the catheter. In addition, tubular body  52  must have sufficient pushability to permit the catheter to be advanced to its target location within the heart without buckling or undesirable bending. The ability of the tubular body  52  to transmit torque may also be desirable, such as in embodiments in which the tissue anchor deployment guides are not uniformly circumferentially distributed about the distal end  36  of the catheter. Optimization of the outside diameter of the catheter, taking into account the flexibility, pushability and torque transmission characteristics can be accomplished through routine experimentation using conventional catheter design techniques well known to those of skill in the art. 
     The flexible body  52  can be manufactured in accordance with any of a variety of known techniques. In one embodiment, the flexible body  52  is extruded from any of a variety of materials such as HDPE, PEBAX, nylon, polyimide, and PEEK. Alternatively, at least a portion or all of the length of tubular body  52  may comprise a spring coil, solid walled hypodermic needle or other metal tubing, or braided reinforced wall, as are known in the art. 
     The proximal end  50  of the closure catheter  38  is provided with a manifold  51 , having a plurality of access ports. Generally, manifold  51  is provided with an access port  53  which may be used as a guidewire port in an over the wire embodiment, and a deployment wire port  57 . Additional access ports such as a contrast media introduction port  55 , or others may be provided as needed, depending upon the functional requirements of the catheter. 
     The tubular body  52  has at least a first actuator lumen  54 , for axially movably receiving an actuator  56 . Actuator  56  extends between a proximal end  64  at about the proximal end of the closure catheter, and a distal end  66  at or near the distal end  36  of the closure catheter  38 . The distal end  66  of the actuator  56  is secured to a cap  68 . In the illustrated embodiment, the actuator lumen  54  is in communication with the access port  53  to permit the actuator  56  to extend proximally therethrough. 
     Actuator  56  can have a variety of forms, depending upon the construction of the anchor supports  62  on the distal end  36  of the closure catheter  38 . In general, the catheter in the area of the anchor supports  62  should have a crossing profile of no more than about 14 French for transluminal advancement and positioning. However, the anchor supports must then be capable of directing tissue anchors into the wall of the cavity or lumen which may have an inside diameter on the order of about 1.5 cm to about 3 cm in the case of the LAA in an average adult. The device of the present invention can be readily scaled up or down depending upon the intended use, such as to accommodate a 5 cm to 10 cm cavity in GI tract applications or 5 mm to about 2 cm for vascular applications. For this purpose, the anchor supports are preferably moveable between a reduced cross sectional orientation and an enlarged cross sectional orientation to aim at, and, in some embodiments, contact the target tissue surface. 
     One convenient construction to accomplish the foregoing is for each anchor support  62  to take the form of a lever arm structure which is pivotably connected at one end to the catheter body. This construction permits inclination of the anchor support throughout a continuous range of outside diameters which may be desirable to aim the anchor and accommodate different treatment sites and/or normal anatomical variation within the patient population. 
     A laterally moveable anchor support can be moved between an axial orientation and an inclined orientation in a variety of ways. One convenient way is through the use of a pull wire or other actuator which increases the diameter of the deployment zone of the catheter in response to an axial shortening of fixed length moveable segments as disclosed in more detail below. For this construction, the actuator will be under pulling tension during actuation. Any of a variety of structures such as polymeric or metal single or multiple strand wires, ribbons or tubes can be used. In the illustrated embodiment, the actuator  56  comprises stainless steel tube, having an outside diameter of about 0.025 inches. 
     A pull wire can alternatively be connected to the radially outwardly facing surface and preferably near the distal end of each anchor support, and each anchor support is hingably attached at its proximal end to the catheter. Proximal traction on the pull wire will cause the anchor support to incline radially outwardly in the distal direction, and toward the target tissue. 
     In an alternate construction, the anchor support is inclined under a compressive force on the actuator  56 . For example, the embodiment described in detail below can readily be converted to a push actuated system by axially immovable fixing the distal end of the anchor guide assembly to the catheter and slideably pushing the proximal end of the anchor guide assembly in the distal direction to achieve axial compression as will become apparent from the discussion below. 
     Push wire actuators have different requirements, than pull actuator systems, such as the ability to propagate a sufficient compressive force without excessive compression bending or friction. Thus, solid core wires or tubular structures may be preferred, as well as larger outside diameters compared to the minimum requirements in a pull actuated system. Thus, the inside diameter of the actuator lumen  57  may be varied, depending upon the actuator system design. In the illustrated embodiment, the actuator lumen  57  has an ID of about 0.038 inches, to slideably accommodate the 0.025 inch OD actuator  56 . 
     A radially outwardly directed force on the anchor supports  62  can be provided by any of a variety of alternative expansion structures, depending upon desired performance and construction issues. For example, an inflatable balloon can be positioned radially inwardly from a plurality of hingably mounted anchor supports  62 , and placed in communication with actuator lumen  54  which may be used as an inflation lumen. Any of a variety of balloon materials may be used, ranging in physical properties from latex for a highly compliant, low pressure system to PET for a noncompliant high pressure and consequently high radial force system, as is understood in the balloon angioplasty arts. 
     The tubular body  52  may additionally be provided with a guidewire lumen  57 , or a guidewire lumen  57  may extend coaxially throughout the length of a tubular actuator  56  as in the illustrated embodiment. 
     The tubular body  52  may additionally be provided with a deployment lumen  58 , for axially movably receiving one or more deployment elements  60  such as a wire, or suture for deploying one or more tissue anchors  90  into the target tissue  110 . Deployment force for deploying the tissue anchors  90  can be designed to be in either the distal or proximal direction, and many of the considerations discussed above in connection with the actuator  56  and corresponding actuator lumen  54  apply to the deployment system as well. In the illustrated embodiment, deployment of the tissue anchors  90  is accomplished by proximal retraction on the deployment element  60  which, in turn, retracts deployment wire  106 . Pushability is thus not an issue, and common suture such as 0.008 inch diameter nylon line may be used. For this embodiment, deployment lumen  58  has an inside diameter of about 0.038 inches. The deployment lumen  58  can be sized to receive either a single deployment element  60 , or a plurality of deployment elements  106  such as a unique suture for each tissue anchor. 
     The distal end  36  of the closure catheter  38  is provided with one or more anchor supports  62 , for removably carrying one or more tissue anchors. Preferably, two or more anchor supports  62  are provided, and, generally, in a device intended for LAA closure, from about 3 to about 12 anchor supports  62  are provided. In the illustrated embodiment, six anchor supports  62  are evenly circumferentially spaced around the longitudinal axis of the closure catheter  38 . 
     Each anchor support  62  comprises a surface  63  for slideably retaining at least one tissue anchor, and permitting the tissue anchor to be aimed by manipulation of a control on the proximal end  50  of the closure catheter  38 . Specific details of one embodiment of the anchor support  62  having a single anchor therein will be discussed below. Multiple anchors, such as two or three or more, can also be carried by each anchor support for sequential deployment. 
     The anchor supports  62  are movable between an axial orientation and an inclined orientation, in response to manipulation of a proximal control. The proximal control can take any of a variety of forms, such as slider switches or levers, rotatable levers or knobs, or the like, depending upon the desired performance. For example, a rotatable knob control can permit precise control over the degree of inclination of the anchor supports  62 . A direct axial slider control, such as a knob or other grip directly mounted to the actuator  56  will optimize tactile feedback of events such as the anchor supports  62  coming into contact with the target tissue. 
     Each of the illustrated anchor supports  62  comprises at least a proximal section  70 , a distal section  72 , and a flex point  74 . See  FIG. 4 . The distal end  73  of each distal section  72  is movably connected to the catheter body or the cap  68 . In this embodiment, proximal retraction of the actuator  56  shortens the axial distance between the proximal end  71  of the proximal section  70  and the distal end  73  of distal section  72 , forcing the flex point  74  radially outwardly from the longitudinal axis of the closure catheter  38 . In this manner, proximal retraction of the actuator  56  through a controlled axial distance will cause a predictable and controlled increase in the angle between the proximal and distal sections  70  and  72  of the anchor support  62  and the longitudinal axis of the catheter. This is ideally suited for aiming a plurality of tissue anchors at the interior wall of a tubular structure, such as a vessel or the left atrial appendage. 
     Referring to  FIG. 4 , there is illustrated an enlarged detailed view of one anchor support  62  in accordance with the present invention. The proximal section  70  and distal section  72  preferably comprise a tubular wall  76  and  78  joined at the flex point  74 . In one embodiment, the proximal section  70  and distal section  72  may be formed from a single length of tubing, such as by laser cutting, photolithography, or grinding to separate the proximal section  70  from the distal section  72  while leaving one or two or more integrally formed hinges at flex point  74 . Any of a variety of polymeric or metal tubing may be utilized for this purpose, including stainless steel, Nitinol or other super-elastic alloys, polyimide, or others which will be appreciated by those of skill in the art in view of the disclosure herein. 
     In the illustrated six tube embodiment, the proximal section  70  and distal section  72  are formed from a length of PEEK tubing having an inside diameter of about 0.038 inches, an outside diameter of about 0.045 inches and an overall length of about 1.4 inches. In general, if more than six anchor supports  62  are used, the diameter of each will be commensurately less than in the six tube embodiment for any particular application. When the proximal section  70  and the distal section  72  are coaxially aligned, a gap having an axial length of about 0.030 is provided therebetween. In the illustrated embodiment, the proximal section  70  and distal section  72  are approximately equal in length although dissimilar lengths may be desirable in certain embodiments. The length of the portion of the anchor support  62  which carries the tissue anchor  90  is preferably selected for a particular procedure or anatomy so that the anchor support  62  will be inclined at an acceptable launch angle when the deployment end of the anchor support  62  is brought into contact with the target tissue  110 . Lengths from the hinge to the deployment end of the anchor support  62  within the range of from about 0.5 cm to about 1.5 cm are contemplated for the LAA application disclosed herein. 
     For certain applications, the proximal section  70  is at least about 10% and preferably at least about 20% longer than the distal section  72 . For example, in one device adapted for the LAA closure application, the proximal section  70  in a six anchor device has a length of about 0.54 inches, and the distal section  72  has a length of about 0.40 inches. Each anchor support has an OD of about 0.045 inches. As with previous embodiments, the functional roles and/or the dimensions of the proximal and distal sections can be reversed and remain within the scope of the present invention. Optimization of the relative lever arm lengths can be determined for each application taking into account a variety of variables such as desired device diameter, target lumen or tissue aperture diameter, launch angle and desired pull forces for aiming and deployment. 
     The proximal end  71  of the proximal section  70  and distal end  73  of distal section  72  are movably secured to the closure catheter  38  in any of a variety of ways which will be apparent to those of skill in the art in view of the disclosure herein. In the illustrated embodiment, each anchor support  62  comprises a four segment component which may be constructed from a single length of tubing by providing an intermediate flex point  74 , a proximal flex point  80  and a distal flex point  82 . Distal flex point  82  provides a pivotable connection between the anchor support  62  and a distal connection segment  84 . The distal connection segment  84  may be secured to the distal end of actuator  56  by any of a variety of techniques, such as soldering, adhesives, mechanical interfit or others, as will be apparent to those of skill in the art. In the illustrated embodiment, the distal connection segment  84  is secured to the distal end  66  of the actuator  56  by adhesive bonding. 
     The proximal flex point  80  in the illustrated embodiment separates the proximal section  70  from a proximal connection segment  86 , which is attached to the catheter body  52 . In this construction, proximal axial retraction of the actuator  56  with respect to the tubular body  52  will cause the distal connection segment  84  to advance proximally towards the proximal connection segment  86 , thereby laterally displacing the flex point  74  away from the longitudinal axis of the closure catheter  38 . As a consequence, each of the proximal section  70  and the distal section  72  are aimed at an angle which is inclined outwardly from the axis of the closure catheter  38 . 
     In general, each flex point  80 ,  82  includes a hinge  81 ,  83  which may be, as illustrated, a strip of flexible material. The hinges  81  and  83  are preferably positioned on the inside radius of the flex points  80 ,  82 , respectively, for many construction materials. For certain materials, such as Nitinol or other superelastic alloys, the hinges  81  and  83  can be positioned at approximately 90.degree. or 180.degree. or other angle around the circumference of the tubular anchor guide from the inside radius of the flex point. 
     A tissue anchor  90  is illustrated as positioned within the distal section  72 , for deployment in a generally proximal direction. Alternatively, the anchor  90  can be loaded in the proximal section  70 , for distal deployment. A variety of tissue anchors can be readily adapted for use with the closure catheter  38  of the present invention, as will be appreciated by those of skill in the art in view of the disclosure herein. In the illustrated embodiment, the tissue anchor  90  comprises a tubular structure having a body  92 , and one or more barbs  94 . Tubular body  92  is coaxially movably disposed about an introducer  96 . Introducer  96  has a proximal section  98 , and a sharpened distal tip  100  separated by an elongate distal section  102  for slideably receiving the tissue anchor  90  thereon. 
     The tissue anchor  90  in the illustrated embodiment comprises a tubular body  92  having an axial length of about 0.118 inches, an inside diameter of about 0.017 inches and an outside diameter of about 0.023 inches. Two or more barbs  94  may be provided by laser cutting a pattern in the wall of the tube, and bending each barb  94  such that it is biased radially outwardly as illustrated. The tissue anchor  90  may be made from any of a variety of biocompatible metals such as stainless steel, Nitinol, Elgiloy or others known in the art. Polymeric anchors such as HDPE, nylon, PTFE or others may alternatively be used. For embodiments which will rely upon a secondary closure structure such as staples, sutures or clips to retain the LAA or other cavity closed, the anchor may comprise a bioabsorbable or dissolvable material so that it disappears after a period of time. An anchor suture  108  is secured to the anchor. 
     In one embodiment of the invention, the introducer  96  has an axial length of about 0.250 inches. The proximal section  98  has an outside diameter of about 0.023 inches and an axial length of about 0.100 inches. The distal section  102  has an outside diameter of about 0.016 inches and an axial length of about 0.150 inches. The outside diameter mismatch between the proximal section  98  and the distal section  102  provides a distally facing abutment  104 , for supporting the tubular body  92  of tissue anchor  90 , during the tissue penetration step. A deployment wire (e.g., a suture)  106  is secured to the proximal end  98  of the introducer  96 . The introducer  96  may be made in any of a variety of ways, such as extrusion or machining from stainless steel tube stock. 
     Referring to  FIGS. 6A-6C , introduction of the tissue anchor  90  into target tissue  110  is illustrated following inclination of the anchor support  62  with respect to the longitudinal axis of the closure catheter  38 . Proximal retraction of the deployment wire  106  causes the tissue anchor  90  and introducer  96  assembly to travel axially through the distal section  72 , and into the tissue  110 . Continued axial fraction on the deployment wire  106  causes the longitudinal axis of the introducer  96  to rotate, such that the introducer  96  becomes coaxially aligned with the longitudinal axis of the proximal section  70 . Continued proximal traction on the deployment wire  106  retracts the introducer  96  from the tissue anchor  90 , leaving the tissue anchor  90  in place within the tissue. The anchor suture  108  remains secured to the tissue anchor  90 , as illustrated in  FIG. 6C . 
     In use, the closure catheter  38  is percutaneously introduced into the vascular system and transluminally advanced into the heart and, subsequently, into the left atrial appendage using techniques which are known in the art. Referring to  FIG. 7 , the distal end  36  of the closure catheter  38  is positioned at about the opening of the LAA  16 , and the position may be confirmed using fluoroscopy, echocardiography, or other imaging. The actuator  56  is thereafter proximally retracted, to incline the anchor supports  62  radially outwardly from the longitudinal axis of the closure catheter  38 , as illustrated in  FIG. 8 . Preferably, the axial length of the proximal section  70  of each anchor support  62 , in combination with the angular range of motion at the proximal flex point  80 , permit the flex point  74  to be brought into contact with the tissue surrounding the opening to the LAA. In general, this is preferably accomplished with the distal section  72  inclined at an angle within a range of from about 45.degree. to about 120.degree. with respect to the longitudinal axis of the closure catheter  38 . Actuator  56  may be proximally retracted until the supports  62  are fully inclined, or until tactile feedback reveals that the anchor supports  62  have come into contact with the surrounding tissue  110 . 
     Following inclination of the anchor supports  62 , the deployment wire  106  is proximally retracted thereby advancing each of the tissue anchors  90  into the surrounding tissue  110  as has been discussed. See  FIG. 9 . The anchor supports  62  are thereafter returned to the first, axial position, as illustrated in  FIG. 10 , for retraction from the left atrial appendage. Proximal retraction on the anchor sutures  108  such as through a tube, loop or aperture will then cause the left atrial appendage wall to collapse as illustrated in  FIG. 11 . Anchor sutures may thereafter be secured together using any of a variety of conventional means, such as clips, knots, adhesives, or others which will be understood by those of skill in the art. Alternatively, the LAA may be sutured, pinned, stapled or clipped shut, or retained using any of a variety of biocompatible adhesives. 
     In one embodiment, a single suture  108  is slideably connected to a plurality of anchors such that proximal retraction of the suture  108  following deployment of the anchors draws the tissue closed in a “purse string” fashion. A similar technique is illustrated in FIGS. 31A and 31B in U.S. Pat. No. 5,865,791 to Whayne, et al., the disclosure of which is incorporated in its entirety herein by reference. 
     Depending upon the size and anatomical forces working on the aperture or lumen to be closed, anywhere from 2 to about 12 or more anchors may be spaced around the circumference of the opening using any of the deployment catheters disclosed herein. Preferably, from about 3 to about 8 anchors, and, in one “purse string” embodiment, six anchors are utilized in the context of closing an atrial septal defect. However, the precise number and position of the anchors surrounding an atrial septal defect or other aperture can be varied depending upon the anatomy, and clinical judgment as will be apparent to those of skill in the art. 
     Referring to  FIGS. 11A-11C  the distal end  36  of a deployment catheter is schematically illustrated following deployment of a plurality of anchors  90 . Only two anchors are illustrated for simplicity. An anchor suture  108  extends in a loop  113 , and slideably carries each of the anchors  90 . A retention structure  109  is slideably carried by first and second portions of the anchor suture  108 , such that distal advancement of the retention structure  109  along the suture  108  causes the loop  113  formed by the distal portion of anchor suture  108  and retention structure  109  to decrease in circumference, such as would be accomplished during a reduction of the size of the tissue aperture or lumen. 
     Preferably, the retention structure  109  may be advanced distally along the suture  108  to close the loop  113  such as by proximally retracting the suture  108  into the deployment catheter and contacting the retention structure  109  against a distal surface  69  which may be on the cap  68  or other aspect of the distal end  36  of the catheter. In the illustrated embodiment, the retention structure  109  includes a first Prusik knot  115  and a second Prusik knot  117 , slideably carried on the suture  108 . The first and second Prusik knots  115 ,  117  are secured together such as by a square knot  119 . Any of a variety of other knots, links or other connections may alternatively be utilized. 
     The foregoing closure techniques may be accomplished through the closure catheter, or through the use of a separate catheter. The closure catheter may thereafter be proximally retracted from the patient, and the percutaneous and vascular access sites closed in accordance with conventional puncture closure techniques. 
     In accordance with a further aspect of the present invention, the closure catheter  38  with modifications identified below and/or apparent to those of skill in the art in view of the intended application, may be utilized to close any of a variety of tissue apertures. These include, for example, atrial septal defects, ventricle septal defects, patent ductus arteriosis, patent foreman ovale, and others which will be apparent to those of skill in the art. Tissue aperture closure techniques will be discussed in general in connection with  FIGS. 12-17 . 
     Referring to  FIG. 12 , there is schematically illustrated a fragmentary view of a tissue plane  120  such as a septum or other wall of the heart. Tissue plane  120  contains an aperture  122 , which is desirably closed. The closure catheter  38  is illustrated such that at least a portion of the distal end  36  extends through the aperture  122 . Although the present aspect of the invention will be described in terms of a retrograde or proximal tissue anchor advancement from the back side of the tissue plane, the anchor deployment direction can readily be reversed by one of ordinary skill in the art in view of the disclosure herein, and the modifications to the associated method would be apparent in the context of a distal anchor advancement embodiment. In general, the proximal anchor advancement method, as illustrated, may desirably assist in centering of the catheter within the aperture, as well as permitting positive traction to be in the same direction as anchor deployment. 
     Closure catheter  38  is provided with a plurality of anchor supports  62  as have been described previously herein. In an embodiment intended for atrial septal defect closure, anywhere within the range of from about 3 to about 12 anchor supports  62  may be utilized. 
     Referring to  FIG. 13 , each anchor support  62  comprises a proximal section  70 , a distal section  72 , and a hinge or flex point  74  therebetween as has been previously discussed. At least one anchor  90  is carried by each anchor support  62 , such as within the tubular distal section  72  in the context of a proximal deployment direction embodiment. Anchor  90  is connected to an anchor suture  108  as has been discussed. In the illustrated embodiment, the anchor suture  108  extends along the outside of the anchor support  62  and into the distal opening of a lumen in tubular body  52 . The anchor sutures  108  may, at some point, be joined into a single element, or distinct anchor sutures  108  may extend throughout the length of the catheter body to the proximal end thereof 
     As shown in  FIG. 13 , the anchor support  62  is advanced from a generally axially extending orientation to an inclined orientation to facilitate deployment of the anchor  90  into the tissue plane  120  adjacent aperture  122 . Preferably, the geometry of the triangle defined by distal section  72 , proximal section  70  and the longitudinal axis of the catheter is selected such that the plurality of anchors  90  will define a roughly circular pattern which has a greater diameter than the diameter of aperture  122 . Thus, the length of proximal section  70  will generally be greater than the approximate radius of the aperture  122 . 
     In general, for atrial septal defect applications, the circle which best fits the anchor deployment pattern when the distal section  72  is inclined to its operative angle will have a diameter within the range of from about 0.5 centimeters to about 3 centimeters. Dimensions beyond either end of the foregoing range may be desirable to correct defects of unusual proportions. In addition, it is not necessary that the anchors define a circular pattern when deployed into the tissue plane  120 . Non-circular patterns such as polygonal, elliptical, oval or other, may be desirable, depending upon the nature of the aperture  122  to be closed. 
       FIG. 13  illustrates the anchors  90  partially deployed into or through the tissue plane  120 . In general, the anchors  90  may either be designed to reside within the tissue plane  120  such as for locations of the aperture  120  which are adjacent relatively thick tissues. Alternatively, the tissue anchor  90  may be designed to reside on one side of the tissue plane  120 , and attached to a suture which extends through the tissue plane  120  as illustrated in  FIGS. 14 and 15 . 
     Referring to  FIG. 14 , the closure catheter  38  is illustrated as returned to the generally axial orientation and proximally retracted through the aperture  122  following deployment of a plurality of tissue anchors  90 . The anchor sutures  108  may thereafter be proximally refracted from the proximal end of the closure catheter  38 , thereby drawing the tissue surrounding aperture  122  together to close the aperture. The anchor sutures  108  may thereafter be secured together in any of a variety of manners, such as by clamping, knotting, adhesives, thermal bonding or the like. 
     In the illustrated embodiment, the closure catheter  38  carries a detachable clamp  124  which may be deployed from the distal end of the closure catheter  38  such as by a push wire, to retain the anchor sutures  108 . The clamp  124  may be an annular structure with an aperture therein for receiving the anchor sutures  108 . The clamp is carried on the catheter in an “open” position and biased towards a “closed” position in which it tightens around the sutures  108 . A ring of elastomeric polymer, a relatively inelastic but tightenable loop such as a ligating band, or a shape memory metal alloy may be used for this purpose. Any of a variety of clamps, clips, adhesives, or other structures may be utilized to secure the anchor sutures  108  as will be appreciated by those of skill in the art in view of the disclosure herein. Anchor sutures  108  may thereafter be severed such as by mechanical or thermal means, and the closure catheter  38  is thereafter retracted from the treatment site. 
     Alternatively, elastic bands or other forms of the clamp may be deployed to directly clamp the tissue and hold the aperture closed. In this application, the closure catheter is used to attach a plurality of anchors spaced around the circumference of the aperture. The anchors are drawn radially inwardly towards each other by proximal traction on one or more sutures. Further proximal traction on the one or more sutures pulls the aperture edges proximally out of the tissue plane. The partially everted aperture can then be secured closed by deploying a clamp there around. As used herein, “clamp” includes all of the elastic band, ligating band, metal clips and other embodiments disclosed herein. 
     In accordance with a further aspect of the present invention, the closure catheter  38  is provided with a deployable patch  126 , as illustrated in  FIGS. 16 and 17 . The patch  126  may comprise of any of a variety of materials, such as PTFE, Dacron, or others depending upon the intended use. Suitable fabrics are well-known in the medical device art, such as those used to cover endovascular grafts or other prosthetic devices. 
     The patch  126  is preferably carried by the distal sections  72  of the anchor support  62 . In the illustrated embodiment, the tissue anchors  90  are carried within the proximal section  70  of anchor support  62 . In this manner, as illustrated in  FIG. 17 , the patch  126  is automatically unfolded and positioned across the aperture  122  as the anchor supports  62  are inclined into the anchor deployment orientation. The tissue anchor  90  may thereafter be advanced through the patch  126  and into the tissue plane  120  to tack the patch  126  against the opening  122 . Alternatively, the tissue anchors may be deployed in a pattern which surrounds but does not penetrate the tissue patch. In this embodiment, the tissue anchors are preferably connected to the tissue patch such as by a suture. The tissue anchors may also both be connected to the patch or to each other by sutures and penetrated through the patch into the target tissue. 
     Tissue anchors  90  may be deployed proximally by pulling the deployment wire  106 . Alternatively, tissue anchors  90  with or without an anchor suture  108 , may be deployed from the proximal section  70  by a push wire axially movably positioned within the proximal section  70 . Tissue anchors  90  may be carried on an introducer  96  as has been discussed previously herein. 
     The patch  126  may be retained on the distal section  72  in any of a variety of ways, such as through the use of low strength adhesive compositions, or by piercing the anchors  90  through the material of the patch  126  during the catheter assembly process. 
     The cardiac defects may be accessed via catheter through a variety of pathways. An ASD or VSD may be accessed from the arterial circuit. The catheter is introduced into the arterial vascular system and guided up the descending thoracic and/or abdominal aorta. The catheter may then be advanced into the left ventricle (LV) through the aortic outflow tract. Once in the LV, the closure anchors may be deployed in the VSD. Alternatively, once in the LV, the catheter may be directed up through the mitral valve and into the left atrium (LA). When the catheter is in the LA, it may be directed into the ASD and the anchors deployed. 
     Alternatively, an ASD or VSD may be accessed from the venous circuit. The catheter may be introduced into the venous system, advanced into the Inferior Vena Cava (IVC) or Superior Vena Cava (SVC) and guided into the right atrium (RA). The catheter may then be directed into the ASD. Alternatively, once in the RA, the catheter may be advanced through the tricuspid valve and into the right ventricle (RV) and directed into the VSD and the anchors deployed. 
     Referring to  FIGS. 18A-18G , there are illustrated a variety of tissue anchors which may be used in the tissue closure or attachment device of the present invention. Each of  FIGS. 18A and 18B  disclose an anchor having a body  92 , a distal tip  101 , and one or more barbs  94  to resist proximal movement of the anchor. An aperture  107  is provided to receive the anchor suture. The embodiments of  FIGS. 18A and 18B  can be readily manufactured such as by stamping or cutting out of flat sheet stock. 
     The anchor illustrated in  FIG. 18C  comprises a wire having a body  92  and a distal tip  101 . The wire preferably comprises a super-elastic alloy such as Nitinol or other nickel titanium-based alloy. The anchor is carried within a tubular introducer, in a straight orientation, for introduction into the tissue where the anchor is to reside. As the body  92  is advanced distally from the carrier tube, the anchor resumes its looped distal end configuration within the tissue, to resist proximal retraction on the wire body  92 . 
       FIG. 18D  illustrates a tubular anchor, which may be manufactured from a section of hypotube, or in the form of a flat sheet which is thereafter rolled about a mandrel and soldered or otherwise secured. The anchor comprises a distal tip  101 , one or more barbs  94 , and an aperture  107  for securing the anchor suture. The anchor of  FIG. 18D  may be carried by and deployed from the interior of a tubular anchor support as has been discussed. Alternatively, the anchor of  FIG. 18D  can be coaxially positioned over a central tubular or solid anchor support wire. 
       FIG. 18E  illustrates an anchor which may be formed either by cutting from tube stock or by cutting a flat sheet such as illustrated in  FIG. 18F  which is thereafter rolled about an axis and soldered or otherwise secured into a tubular body. In this embodiment, three distal tips  101  in the flat sheet stock may be formed into a single distal tip  101  in the finished anchor as illustrated in  FIG. 18E . One or more barbs  94  may be formed by slotting the sheet in a U or V-shaped configuration as illustrated. The anchor in  FIG. 18E  is additionally provided with one or more barbs  95  which resist distal migration of the anchor. This may be desirable where the anchor is implanted across a thin membrane, or in other applications where distal as well as proximal migration is desirably minimized. 
     Although the present invention has been described in terms of certain preferred embodiments, other embodiments will become apparent to those of skill in the art in view of the disclosure herein. Accordingly, the scope of the invention is not intended to be limited by the specific disclosed embodiments, but, rather, by the attached claims.