Abstract:
The present invention provides a device which is adapted to press together the septum primum and the septum secundum between the atrial chambers to close any tunnel in the septum. The device in its preferred form has two clamping members, one on each side of the septum and a central connector which connects the two clamping members and passes through the tunnel. The device is configured to conform to the anatomy such that the tunnel is not substantially deformed by the device. The central connector, in its preferred form has two wires that are spaced apart so that the wires are proximate the lateral sides of the tunnel. The spacing allows the device to be centered at an appropriate location.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application is a divisional application of U.S. application Ser. No. 11/008,539 filed Dec. 4, 2004, now abandoned; and claims priority to provisional patent application 60/528,022 filed Dec. 9, 2003, which is incorporated by reference herein. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to devices and methods which are used to close septal openings. In particular, this invention is directed to devices and methods which are used to close a patent foramen ovale (PFO) in the septum between the left atrium and right atrium. 
     2. Background Information 
     A PFO, illustrated in  FIGS. 1 and 2 , is a persistent, one-way, usually flap-like opening in the wall between the right atrium and left atrium of the heart. Because left atrial (LA) pressure is normally higher than right atrial (RA) pressure, the flap usually stays closed. Under certain conditions, however, right atrial pressure can exceed left atrial pressure which creates the possibility that blood could pass from the right atrium to the left atrium and allow blood clots to enter the systemic circulation. It is desirable that this circumstance be reduced. 
     The foramen ovale serves a desired purpose when a fetus is gestating in utero. Since blood is oxygenated through the umbilical chord, and not through the developing lungs, the circulatory system of a heart in a fetus allows the blood to flow through the foramen ovale as a physiologic conduit for right-to-left shunting. After birth, with the establishment of pulmonary circulation, the increased left atrial blood flow and pressure results in functional closure of the foramen ovale. This functional closure is subsequently followed by anatomical closure of the two over-lapping layers of tissue the septum secundum  14  and septum primum  15 . However, a PFO has been shown to persist in a number of adults. 
     The presence of a PFO is generally considered to have no therapeutic consequence in otherwise healthy adults. However, patients suffering a stroke or transient ischemic attack (TIA) in the presence of a PFO and without another cause of ischemic stroke paradoxical embolism via a PFO is considered in the diagnosis. While there is currently no proof for a cause-effect relationship, many studies have confirmed a strong association between the presence of a PFO and the risk for paradoxical embolism or stroke. In addition, there is good evidence that patients with PFO and paradoxical embolism are at increased risk for future, recurrent cerebrovascular events. 
     Accordingly, patients with an increased future risk are considered for prophylactic medical therapy to reduce the risk of a recurrent embolic event. These patients are commonly treated with oral anticoagulants, which have the potential for adverse side effects, such as hemorrhaging, hematoma, and interactions with a variety of other drugs. The use of these drugs can alter a person&#39;s recovery and necessitate adjustments in a person&#39;s daily living pattern. 
     In certain cases, such as when anticoagulation is contraindicated, surgery may be necessary or desirable to close the PFO. The surgery would typically include suturing a PFO closed by attaching the septum secundum to the septum primum. This sutured attachment can be accomplished with either an interrupted or a continuous stitch and is a common way a surgeon shuts a PFO under direct visualization. 
     Umbrella devices and a variety of other similar mechanical closure designs, developed initially for percutaneous closure of atrial septal defects (ASDs), have been used in some instances to close PFOs. These devices have the potential to allow patients to avoid the potential side effects often associated with anticoagulation therapies and the risks of invasive surgery. However, umbrella devices and the like which are designed for ASDs are not optimally suited for use as a PFO closure device. 
     Currently available designs of septal closure devices present drawbacks, including that the implantation procedure is technically complex. Additionally, there are not insignificant complication rates due to thrombus, fractures of the components, conduction system disturbances, perforations of heart tissue, and residual leaks. Many devices have high septal profile and may include large masses of foreign material which may lead to unfavorable body adaptation of a device. Since ASD devices are designed to occlude a hole, many lack anatomic conformability to the PFO flap-like anatomy. That is, when inserting an ASD into the heart to close a PFO, the narrow opening and the thin flap may form impediments to proper deployment. Even if an occlusive seal is formed, the device may be deployed in the heart on an angle which could leave some components not securely seated against the septum. Finally, some septal closure devices are complex to manufacture, which may result in lack of consistency in product performance. 
     Nitinol (an alloy of nickel and titanium) is known to be used in medical devices because of its biocompatablity and, especially, its unique properties. Nitinol is a member of a class of materials which exhibit shape memory characteristics. Specifically, nitinol has the ability to “remember” a shape and, after being deformed, will return to that shape once a certain temperature is reached. Hence, nitinol has been used to create medical devices that have a desired configuration in the body, e.g., a vena cava filter. The device is deformed into a delivery configuration (generally a reduced profile for delivery through a catheter). Once the device is delivered to the desired site, the nitinol changes configuration into the desired shape upon achieving a certain temperature. This is generally considered thermal responsive shape memory. Nitinol, and other materials, also exhibit superelastic shape memory. In this case, the nitinol can be restrained in a delivery configuration and then will return to the desired configuration as the device leaves the delivery catheter. Of course, some devices can be a combination of thermally induced shape memory and superelastic shape memory. 
     The present invention is designed to address these and other deficiencies of the prior art septal closure devices. 
     SUMMARY OF THE INVENTION 
     The present invention provides a device which is adapted to press together the septum primum and the septum secundum between the atrial chambers to close any tunnel in the septum. The device in its preferred form has two clamping members, one on each side of the septum and a central connector which connects the two clamping members and passes through the tunnel. The device is configured to conform to the anatomy such that the tunnel is not substantially deformed by the device. The central connector, in its preferred form has two wires that are spaced apart so that the wires are proximate the lateral sides of the tunnel. The spacing allows the device to be centered at an appropriate location. 
     In a preferred form of the device, the clamping members are spirals which are formed from nitinol. The spirals may be constructed of wire, or alternatively, may be constructed of nitinol sheets which have been cut or shaped to form the spirals. The spirals may circle around more or less than 360 degrees and may have the a helical form. In one preferred embodiment the connector may be attached to the inner end of the wire that forms the spiral, in another, the connector may be attached to the outer end of the wire that forms the spiral. Of course, depending on the desired configuration, the connector may be connected to the inner location on one side of the device and the outer location on the other side of the device. 
     The clamping member may be a spiral or some other structure or configuration which secures the septum together. For example, a plurality of wires may be used which could be spread out along the septum to provide the desired clamping force. Other shapes and orientations could be used which would spread the clamping force over a sufficient surface area to accomplish the desired effect. 
     The connecting member may be two or more wires which are configured to spread apart in the PFO tunnel. The spacing of the wires is sized to center the device in the desired clamping location in the septum. In one preferred embodiment, the wires are joined at ends and bow apart from each other to fit within the PFO tunnel. Alternatively, the wires may form an S-shaped curve to improve the centering location. Other shapes and configurations are possible. 
     In an alternate form the connecting member may be formed of thin wires that are wound into a helix (e.g., in the shape of a coil spring). The connecting member may have one or more helically wound wires that form the connecting member. The resultant connector may be shaped in the same manner as the other embodiments. In other embodiments, the connecting member may have an abrasive surface so that a healing response may be stimulated by the abrasive surface. Additionally, the abrasive surface may be directionally oriented. That is, if one were to feel the surface of the wire in one direction, the wire would feel smooth and in the other direction, the wire would feel abrasive or rough. 
     In still other embodiments, the connecting member may include a film which extends between the connecting wires. The film may be comprised of and/or impregnated with biological and/or bioresorbable material. In another embodiment a joint may be formed at a location along the length of the connecting member. The joint reduces the trauma of the closure device within the PFO. The device may also have a hook or some other piercing element to maintain the PFO closure device in the desired location. Of course, each of the configurations could be used in combination. 
     The device, in its preferred form, is adapted to be delivered through a catheter into the atria. The device is constrained into a delivery profile and introduced into a catheter for delivery to the heart. Once the catheter is located at the desired delivery site, the device is deployed into the site and changes shape into the desired configuration. The shape change could be a result of a thermally induced shape change or a change due to the superelastic character of the material. Once in the delivery location, the catheter is withdrawn. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a front elevational view from the left atrium of the atrial septum with patent foramen ovale (PFO); 
         FIG. 2  is a cross-sectional view of the atrial septum of  FIG. 1 ; 
         FIG. 3  is a bottom plan view of the double spiral patent foramen ovale closure clamp of the present invention showing the connecting central loop; 
         FIG. 4  is a view in side elevation of the double spiral PFO closure clamp of  FIG. 3 ; 
         FIG. 5  A- 5 G show the steps for inserting the double spiral PFO closure clamp of  FIGS. 3 and 4 ; 
         FIG. 6  is a front elevational view from the left atrium of the double spiral PFO closure clamp in place with the central loop in the PFO channel; 
         FIG. 7  is a cross-sectional view of the atrial septum and double spiral PFO closure clamp of  FIG. 5 ; 
         FIG. 8  is a perspective view of a jig for forming the double spiral PFO closure clamp of the present invention; and 
         FIG. 9  is a top plan view of the jig of  FIG. 7  with spiral sections of the double spiral PFO closure clamp of the present invention wound thereon. 
         FIG. 10  is a view in side elevation of a second embodiment of the double spiral PFO closure clamp of the present invention; 
         FIG. 11  is a front elevational view from the right atrium of the double spiral PFO closure clamp of  FIG. 10 ; 
         FIG. 12  is a front elevational view from the left atrium of the double spiral PFO closure clamp of  FIG. 10 ; 
         FIG. 13  is a view in front elevation of a second embodiment of a central connector for a PFO closure clamp of  FIG. 10 ; 
         FIGS. 14A and 14B  are a plan view and a view in side elevation, respectively of a jig for forming the double spiral PFO closure clamp of  FIG. 10  with the central connector of  FIG. 13 ; 
         FIGS. 15A and 15B  are a plan are a plan view and a side elevation view, respectively, of the jig of  FIGS. 14A and 14B  with the left atrial spiral section of the double spiral PFO closure clamp of  FIG. 10  and with one half of the central connector of  FIG. 13  formed thereon; 
         FIGS. 16A and 16B  are a plan view and a view in side elevation, respectively, of the jig of  FIGS. 14A and 14B  with the right atrial spiral section of the double spiral PFO closure clamp of  FIG. 10  and with one half of the central connector of  FIG. 13  formed thereon; 
         FIGS. 17A and 17B  are a plan view and a side elevation view, respectively, of an expanded double spiral PFO closure clamp of  FIG. 10  with one half of the central connector for  FIG. 13 ; 
         FIGS. 18A and 18B  are alternative embodiments of a center joint of the present invention using helically wound wire; 
         FIGS. 19A-19F  are alternative embodiments of a center joint of the present invention using special surface preparations; 
         FIG. 20  is an alternative embodiment of a center joint of the present invention using a membrane; 
         FIGS. 21A and 21B  are alternative embodiments of a center joint of the present invention using a flexible joint; and 
         FIGS. 22A and 22B  are alternative embodiments of a center joint of the present invention in which piercing wires are used to secure the device at the desired location. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     With reference to  FIGS. 1 and 2 , the atrial septum  10  divides the left atrium and right atrium of the heart. The patent foramen ovale (PFO) channel  12  extends between the left and right atria and is closed by a flap  14  and  15 . Due to the overlap of the septum primum over the septum secundum, the PFO channel or tunnel extends substantially parallel to the surface of the atrial septum. The anatomical structure presents a problem when attempts are made to use conventional septal occluders with opposed, spaced, parallel sections (possibly spiral) are joined by a straight wire or bridge which is substantially perpendicular to the planes of engagement between the sections and the atrial septum. The straight wire or bridge deforms the channel  12  and often prevents proper closure even when the septum primum and the septum secundum are biased toward one another by the spiral sections of the occluder. 
     Referring to  FIGS. 3-7 , the double spiral PFO closure clamp of the present invention indicated generally at  16  includes a left atrial spiral section  18  and an opposed right atrial spiral section  20  which are joined by an inclined central loop  22 . The loops of each spiral extend progressively outward from the base loop in different planes, and the innermost loops  26  of the two spiral sections  18  and  20  are connected by the inclined central loop  22 . The outermost free ends  28  of the base loops  24  are provided with protective balls  30 . 
     With continued reference to  FIGS. 3-7 , in a preferred embodiment, the spirals that are disposed on each side of the septum and press against the septum with sufficient force to stabilize the device in the desired location. As illustrated, inner loops are connected and the outer loops are configured to compress against the septum. In an alternative configuration, not illustrated, the outer loops may be connected and the inner loops may be configured to press against the septum. In each embodiment, the center joint is configured to connect the loops and, according to several embodiments, the center joint is configured to center the device in the desired delivery location because the center joint is configured to spread out within the PFO tunnel and, as a result, become centered within the PFO tunnel. 
     The ball  30  of the right atrial spiral section  20  may be grasped and drawn into a protective sheath. As the free end  28  of the right atrial spiral section is drawn inwardly into the protective sheath, the coils of the spiral section straighten as they are drawn into the sheath until the inclined central loop  22  is reached. Then as the central loop enters the sheath, the sides of the central loop are compressed together, and as the central loop is enclosed by the sheath and moves inwardly, it draws the loops of the left atrial spiral section  18 , beginning with the innermost loop  26 , as a straight section into the sheath. 
       FIG. 5A  shows the double spiral PFO closure clamp in straightened form enclosed by sheath  32 . The tip of the sheath may be curved to assist the recovery of the curved loops of the double spiral PFO closure clamp. Here, the sheath is inserted through the PFO channel  12  from the right atrium into the left atrium, and the left atrium, and in  FIG. 5B , a wire  34  connected within the sheath to the free end  28  of spiral section  20  forces the spiral section  18  out of the sheath so that it is deployed in the left atrium. Subsequently, as shown in  FIG. 5C , the sheath and wire  34  are withdrawn toward the right atrium to draw the spiral section  18  against the atrial septum  10 . 
     In  FIG. 5D , after the inclined central loop  22  has been positioned within the sheath  32  in the PFO channel  12 , the sheath is withdrawn to deploy and seat the inclined central loop in the PFO channel. Then, as shown in  FIG. 5E , the wire  34  ejects the spiral section  20  into the right atrium against the atrial septum. In  FIG. 5F , the wire  34  is released from the free end of the spiral section  20 , and in  FIG. 5G , the sheath  32  and wire  34  are withdrawn. 
     The spiral sections  18  and  20  are formed to be urged toward one another. Also, since the loops of each opposed spiral section  18  and  20  are in different planes and since the inclined central loop  22  joins the innermost loops  26  of each spiral section, the spiral section  18  will draw the spiral section  20  against the atrial septum once it is deployed from sheath  32 . 
       FIGS. 6 and 7  show the double spiral PFO closure clamp  16  in place with the inclined central loop  22  seated in the PFO channel. The spiral sections  18  and  20  are not aligned but are offset so that the inclined central loop follows the PFO channel and does not deform the channel  12 . However, enough of the two spiral sections overlap so that the septum primum and the septum secundum are engaged thereby and biased to a closed position. 
     Since the inclined central loop  22  which joins the spiral sections  18  and  20  is seated in the PFO channel, it prevents shift or rotation of the spiral sections which might occur if a straight non-looped joined piece was used between the spiral sections. 
       FIGS. 8 and 9  disclose a jig  36  used to manufacture the double spiral PFO closure clamp  16 . The jig includes two stepped cone shaped sections  38  and  40  which are each used to form one of the spiral sections  18  or  20  and one half of the inclined central loop  22 . Each stepped cone shaped section includes a plurality of arcuate sections  42 , 44 ,  46 , and  48  of progressively decreasing size which terminate at a small, circular projection  50 . The front faces  52 ,  54 ,  56 , and  58  of each of the arcuate sections is flat and supports an inclined mandrel  60  having an arcuate side  62 . The arcuate side  62  faces left on the cone shaped section  38  and right on the cone shaped section  40 . The front faces  52  and  58  support projecting pins  64  and  66  respectively positioned above and below the arcuate side of the mandrel  60 . 
     To form the double spiral PFO closure clamp  16 , an elongate length of wire is formed upon each of the cone shaped sections  38  and  40  as shown in  FIG. 9 . Each of these lengths of wire  68  and  70  are preferably formed of shape memory material such as nitinol and are annealed after being wound in place on the stepped, cone shaped sections  38  and  40 . The wire is wound clockwise on the cone shaped section  38  and counter-clockwise on the cone shaped section  40 . Each length of wire begins at starting pin  72  and extends around the projecting pin  64  and the arcuate side  62  to the projecting pin  66 . The wire extends behind the projecting pin  66  and around the circular projection  50 . At the flat face  58 , the wire drops and extends around the arcuate section  48  to the flat face  56  where the wire drops again to extend around the arcuate section  44 , and at the flat face  52 , the wire drops to extend around the arcuate section  42  to a terminal post  74 . Thus the two spiral sections  18  and  20  of  FIG. 4  are formed. Once the two wire sections are processed on the jig  36 , they are removed from the core shaped sections  38  and  40  and one is inverted and rotated relative to the other so that the inclined, arcuate wire sections formed on the mandrels  60  may be welded together to form the inclined central loop  22 . Now the free ends of each wire section which were held by the terminal pins  74  are provided with the protective balls  30 . 
     With reference to  FIGS. 10-12 , a second embodiment of the double spiral PFO closure clamp of the present invention is indicated generally at  76 . The double spiral PFO closure clamp  76  includes a right atrial spiral section  78  to contact the right side of the septum and an opposed left atrial spiral section  80  to contact the left side of the septum. These two spiral sections are joined by an inclined central loop  82  which rests in the PFO channel  12 . Unlike the offset atrial spiral sections  18  and  20  of the PFO closure clamp  16 , the atrial spiral sections  78  and  80  of the PFO closure clamp  76  are directly opposed in substantial alignment when they are deployed against the atrial septum. This is facilitated by connecting the large, outermost loop of each atrial spiral section to the inclined central loop  82 . 
     As shown by  FIG. 11 , the outermost loop  84  of the right atrial spiral section  78  is connected to the bottom of the central loop  82  at  86 , and curves upwardly over the septum and then inwardly to form the smaller inner loops of the right atrial spiral section. These inner loops terminate at an innermost free end  88  provided with a protective ball  30 . 
     To form the left atrial spiral section  80  in opposed alignment with the right atrial spiral section, the outermost loop  90  is connected to the top of the central loop  82  at  92  as shown by  FIG. 12 . The outermost loop  90  then curves downwardly over the septum and then inwardly to form the inner loops of the left atrial spiral section. These inner loops terminate at an innermost free end  94  provided with a protective ball  30 . 
     The outermost loops  84  and  90  are configured to position the left atrial spiral section and right atrial spiral section in aligned, opposed relationship. 
     Instead of connecting the two spiral sections  78  and  80  with a central loop which rests in the PFO channel, the central loop can be replaced with the double “S” shaped connector  96  of  FIG. 13 . This connector has rounded side surfaces  98  and  100  which engage the sides of the PFO channel, but the connections  86  and  92  with the outer loops  84  and  90  of the spiral sections  78  and  80  are oriented in opposite directions by the configuration of the connector. Thus forces on the connector from the spirals which would tend to cause shifting of a round central loop are offset to oppose shifting of the connector. 
       FIGS. 14A and 14B ,  15 A and  15 B,  16 A and  15 B, and  17 A and  17 B show the manner in which the double spiral PFO closure clamp  76  with the double “S” shaped connector  96  is formed. A split jig  102  is used to form both the right atrial spiral section  78  and the left atrial spiral section  80 . The jig includes two spaced stepped sections  104  and  106  having opposed arcuate steps which progressively decrease in size. Between the stepped sections are formed to form the double “S” shaped connector  96 . These forms include a pin  108  which projects adjacent to a round form  110 . This round form  110  contacts a second round form  112  which is adjacent to a second projection pin  114 . Spaced from but adjacent to the round forms  110  and  112  are two spaced arcuate forms  116  and  118 . Centered between the arcuate forms  116  and  118  is a round form  120 . Wire end retaining screws  122 , 124 , and  126  are positioned outwardly from the stepped sections  104  and  106 . 
     With reference to  FIGS. 15A and 15B , the left atrial spiral section  80  and one half of the double “S” shaped connector  96  are formed by winding wire in a clockwise direction on the stepped sections  104  and  106 . Beginning at the wire end retaining screw  124 , the wire is passed around the pin  108  and across the round forms  110  and  112  and then around the form  112  and back to the round form  120 . The wire is then brought around the round form  120  and then around the arcuate form  116  to the pin  114  to form one half of the double “S” shaped connector  96 . From the pin  114 , the wire is wound in a clockwise direction from the bottom to the top of the stepped sections  104  and  106  and is then secured to the wire end retaining screw  126 . When the wire is thermal shape memory wire, it is annealed in place before the left atrial spiral section is removed from the jig  102 . 
     As shown in  FIGS. 16A and 16B , the right atrial spiral section  78  is formed in the reverse manner and is wound counter clockwise on the stepped sections  104  and  106 . Beginning at the wire end retaining screw  124 , the wire is passed around the pin  114 , the round forms  112  and  110 , the round form  120  and an arcuate form  118  to the pin  108  to form the remaining half of the double “S” shaped connector  96 . The wire is then wound in a counter clockwise direction from the bottom to the top of the stepped sections  104  and  106  and is then passed to the wire end retaining screw  126 . 
       FIGS. 17A and 17B  show the manner in which the two atrial spiral sections  78  and  80  are joined to form the double spiral PFO closure clamp  76 . The two atrial spiral sections are oriented back to back to form the double “S” shaped connector  96 , and are secured together at  128  and  130 . 
     The double spiral PFO closure clamp  76  can be straightened with a tubular delivery device for delivery and may be delivered across the PFO by catheter using a pusher wire. The left atrial spiral section  80  is delivered first into the left atrium and flattened against the septum. The central double “S” shaped connector  96  is then unsheathed in the PFO channel, and finally the right atrial spiral section  78  is released against the septum in the right atrium. 
       FIGS. 18A and 18B  illustrate another embodiment of the center joint of the present invention. In this embodiment, the center joint is constructed of wire which has been wound to form a spiral  200  that connects ends  210  and  220 . The spiral wound wire is flexible enough to accommodate a variety of anatomical configurations for the PFO tunnel. In this manner the spiral wound wire will conform to the PFO tunnel and will bend as necessary to allow the ends  210  and  220  to conform to the wall of the septum (not shown in this embodiment). The spirals US 1 DOCS 1788254V1 are illustrate in an exaggerated and open manner. Preferably the wire will be tightly close together and have a small overall diameter. Alternatively, the wire may have a thin wire strand  225  disposed in the helical wire to ensure that the spiral does not expand beyond the length of the wire strand. The wire  225  allows the center joint to be flexible and conform to the PFO tunnel without expanding beyond the longitudinal distance of the wire strand. The ends  210  and  220  are illustrated as the wire elements of the CardioSeal device more specifically described in U.S. Pat. No. 5,629,766 which is incorporated by reference into this specification. 
       FIG. 18B  illustrates another embodiment of the center joint with a pair of helically wound wires  230 ,  240  that form the center joint. Ends  245 , 247  of the device that contact the walls of the septum are illustrated as spirals. Of course, one skilled in the art would recognize the that the ends could be in a variety of configurations and dimensions, for example, spiral and CardioSeal configurations. The illustration exaggerates relative dimension of the center joint for clarity. In this embodiment, the center joint wires may also have wire strands  250 ,  252  disposed with the helically wound wire similar to the wire described in connection with  FIG. 18A . In this embodiment, the strands  250 , 252  may have a bent configuration, such as illustrated so that the center joint is disposed at the desired (e.g., centered) location. 
       FIGS. 19A-19F  illustrate various configuration of the center joint which may be used with a PFO closure device. In these illustrations, the center joint is illustrated without the ends. That is, only the portion that would be disposed within and next to the PFO tunnel is illustrated. The ends (not illustrated) would be connected at the locations identified by reference numberal  26 . In these embodiments, different treatments are provided to the wires which assist in the positioning device and healing of the septum once the device is delivered.  FIG. 19A  illustrates two wires  260 ,  262  which are configured in an oval shape and are provided with a surface treatment which roughens the surface of the wires.  FIG. 19B  illustrates a magnified view of the wire  262  and shows bumps or roughness  264  on the wire. A variety of surface treatments may cause the roughness, for example, the wire may be electro-coated with a material that has a rougher surface. Alternatively, a mechanical knurling process may be used to roughen the surface. Finally, for example, the extrusion process of the wire manufacture may be modified to create a rough surface instead of a smooth. The rough surface may be randomly rough, as illustrated, or the rough surface may have a pattern, as would be typically achieved by a knurling or extrusion process. A rough surface in the center joint may provide certain advantages, for example, the rough surface may assure the center joint stays in place. Additionally, the roughened wires may stimulate a healing response by “irritating” the PFO tunnel in a manner that stimulates the body to heal and close the PFO tunnel. 
     Other configurations for the wires of the center joint are possible.  FIGS. 19C and 19D  illustrate an alternative treatment of the wire.  FIG. 19C  shows the wires  270  and  272  which are adapted to be delivered into the PFO tunnel and the wires include a roughness that is different in one direction than the other. That is, if one were to run the wire between a thumb and an index finger in one direction, it would be relatively smooth and in the other direction, it would feel more rough.  FIG. 19D  illustrates the directional “quills”  275  which provide a smooth surface (downward as illustrated) and a rough surface (in the upward direction as illustrated). The direction of the quills may be configured to allow for convenient placement of the device within the PFO and for improved resistance to movement. The quills may be placed on the device in a variety of methods including a post extrusion process or directional knurling. 
     In another configuration, illustrated in  FIGS. 19E and 19F , the quills are provided having opposed direction. In this embodiment, the wires  280  and  282  have quills  284  which are directed toward the center of the center joint. Similarly, the quills  285 , on the other side of the center joint, are also directed toward the center of the center joint. This configuration may allow for improved stability within the PFO once delivered. In each of the embodiments, the healing response may be improved using roughened or quilled surfaces for the center joint. 
       FIG. 20  illustrates yet another configuration for the center joint that includes a fabric or mesh. The center joint is formed by wires  290  and  292 , a mesh or fabric  294  is secured to the wires using a variety of known techniques. The mesh itself could be a biological material that stimulates a biological response. Alternatively, the mesh may be impregnated with a chemical or biological agent that may stimulate a biological healing response. Finally, the mesh could be the vehicle to deliver an agent to the PFO tunnel. 
       FIGS. 21A and 21B  also illustrate alternative embodiments of the center joints which provide improved movement within the PFO tunnel for the center joint. Specifically, as illustrated in  FIG. 21A , a “trailer hitch” design is used to improve the ability of the wires to conform within the PFO tunnel. Wires  300 ,  310  form a single wire center joint and are connected by a “trailer hitch” connection  320 . The connection is configured to allow improved movement of the wires so that the ends (not illustrated) can conform to the septal walls without unnecessary stress. In a modification of the embodiment illustrated in  FIG. 21A  is shown in  FIG. 21B . In the embodiment illustrated, the wires  330  and  332  are joined at end  26 , which as in the other embodiments, will secure the end wire configuration that secures against septum. Similarly, the  334  and  336  are joined at the other side of the center joint. A pair of “trailer hitch” connections  338  and  340  are used to allow the movement of the wires in the center joint. The use of connection  338  and  340  may provide for sufficient flexibility to allow for thicker, more stable wires to be used as the center joint. The use of thicker, stiffer wires may allow for greater resistance from movement for the center joint. 
     In the embodiment of the invention illustrated in  FIG. 22A  the wires that form the oval connection provide a length of wire that could pierce into the septal tissue to secure the center joint in the desire location and, as a result, stabilize the PFO closure device. In the embodiment illustrated, wires  340  and  342  are joined to wires  344  and  346 , respectively. The joints  348  and  350  may be welds or other joints that allow for the reduced profile that is desirable for delivery through a catheter. The ends  352 ,  354 ,  356  and  358  are designed to pierce the septum and allow for the improved stability described above. 
     In a slightly modified configuration, the wires may be provided that are in a configuration illustrated in  FIG. 22B . In this embodiment, joints  360  and  362  provide for the connection between the wires  364 - 370 . The wires, as illustrated, have a shape that provides the greatest longitudinal width at the joint. This has the benefit of being able to keep the center joint centered within the PFO. In each of the embodiments described in connection with  FIGS. 22A and 22B , the closure device is secured by the piercing elements. The wires can be constructed of a metal or a polymer, and have a circular cross-section or some other form such as a rectangle or polygon.