Abstract:
Devices for and methods of closing a patent foramen ovale (PFO), thus reducing or eliminating blood flow through the defect The device is formed from a tubular structure having split ends, such that, after insertion, struts defined by the split ends pivot in a radial direction away from the tube, thereby securing the device within the septal defect. Methods include inserting the device as a tubular structure into the PFO and causing the struts to extend radially away from the central axis of the device.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional of U.S. application Ser. No. 11/102,884 filed Apr. 8, 2005, now abandoned which claims priority to U.S. Provisional Application 60/561,544, filed Apr. 9, 2004, the entire contents of both application are incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     The invention relates to devices and methods for closing defects such as a patent foramen ovale (PFO). 
     A PFO is a persistent, one-way, usually flap-like opening in the wall between the right atrium and left atrium of the heart. Since left atrial (LA) pressure is normally higher than right atrial (RA) pressure, the flap typically stays closed. Under certain conditions, however, RA pressure can exceed LA pressure, creating the possibility for right to left shunting that can allow blood clots to enter the systemic circulation. 
     In utero, the foramen ovale serves 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 closure is typically followed by anatomical closure of the two over-lapping layers of tissue, septum primum and septum secundum. However, a PFO has been shown to persist in a significant minority of adults. 
     The presence of a PFO has no therapeutic consequence in otherwise healthy adults, however, patients suffering a stroke or TIA in the presence of a PFO and without another cause of ischemic stroke are considered for prophylactic medical therapy to reduce the risk of a recurrent embolic event. These patients can be treated with oral anticoagulants, but such drugs have the potential for adverse side effects such as hemorrhaging, hematoma, and interactions with other drugs. In certain cases, such as when the use of anticoagulation drugs is contraindicated, surgery may be used to suture a PFO closed. Suturing a PFO requires attachment of septum secundum to septum primum with a stitch (continuous or interrupted), which is the common way a surgeon shuts the PFO under direct visualization. 
     Non-surgical closure of PFOs has become possible with umbrella devices and a variety of other similar mechanical closure designs developed initially for percutaneous closure of atrial septal defects (ASD). These devices allow patients to avoid the potential side effects often associated with anticoagulation therapies. 
     SUMMARY OF THE INVENTION 
     Embodiments of the invention include devices and methods for closing a septal defect, including a PFO. In one embodiment, the device includes a tubular structure having dimensions suitable for insertion into a catheter, and slits extending from one or both ends that define struts that can pivot away from the rest of the tube to provide desirable anchoring of the device within a septal defect. The slits can be spaced at regular or irregular intervals along the tube circumference, and can have different lengths. A slit extending from one end of the tube can be aligned or offset with respect to a corresponding slit extending from the other end. The configuration of slits can be designed to optimize the distribution of clamping forces provided by the struts defined by the slits. In some embodiments, prior to insertion into the body, struts defined by slits from one end can overlap or touch corresponding struts defined by slits from the other end. The device can further include a recovery wire attached to one or more struts, such that tension applied to the recovery wire can enable the device to be retracted into the catheter. 
     The device is preferably made from a polymer with shape memory properties, and can also include a means for causing the struts to extend radially when released from the catheter into the body. The means can include a tissue scaffold attached to at least one of the struts, and/or a tensioner, such as an elastic band or string. The tissue scaffold can be made of a bioresorbable material, a flexible biocompatible material capable of promoting tissue growth, a polyester fabric, a Teflon-based material, a polyurethane, a metallic mesh, polyvinyl alcohol, an extracellular matrix, a synthetic bioabsorbable polymeric scaffold, collagen, and combinations thereof. At an axially central portion, the device can further include whiskers to provoke an inflammatory response, a collar including a sponge-like material, a drug coating, or an anticoagulant. 
     Benefits of certain embodiments can include atraumatic shape, good conformity to the anatomy (especially when used for a PFO), small diameter delivery sheath, no permanent foreign material, ease of manufacturing, cost effectiveness, and overall simplicity. Other features and advantages will become apparent from the following detailed description and drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of a tube with slits used to form a closure device. 
         FIG. 2  is a perspective view of the tube of  FIG. 1  with the ends shown split extending outwardly. 
         FIGS. 3 and 4  are a perspective view and front elevational view, respectively, of an embodiment with three struts and whiskers and/or sponge material. 
         FIGS. 5 and 6  are side and front (through line  6 - 6  of  FIG. 5 ) views of the device of  FIGS. 3 and 4 , shown positioned in the PFO. 
         FIG. 7  is a perspective view of an alternative embodiment to  FIG. 3  with a tissue scaffold. 
         FIGS. 8 and 9  are further embodiments of a closure device, and  FIGS. 10 and 11  are perspective views of the device of  FIG. 8  with the addition of a connector and shown in vivo. 
         FIGS. 12-16  are views of another embodiment of the present invention. 
         FIGS. 17-23  are views of another embodiment shown with and without a tissue scaffold. 
     
    
    
     DETAILED DESCRIPTION 
     The present invention includes embodiments of a closure device for a PFO, atrial septal defect (ASD), or other suitable defect, preferably formed from a single tube with cuts made to produce the final device shape. The device can have struts that extend radially outwardly from a central portion, or loops that extend from the central portion and back to the central portion, preferably in a plane that is parallel to the defect (such as the PFO tunnel). 
     Referring to  FIG. 1 , in one embodiment a closure device is made from a single polymer tube  10  by providing slits  12 ,  14  at both ends and setting a desired shape, such as by thermo-mechanical treatment, to produce a design as shown in  FIG. 2 . This treatment can include heating or other thermal steps, and mechanical steps, such as folding back the struts. 
     This device has a first set of struts  16   a ,  16   b  and a second set of struts  18   a ,  18   b  at the opposite end. A center portion  20  is between the ends and typically has no cuts. As shown in  FIG. 2 , a recovery wire  22  and lug  24  can optionally be provided at a proximal end (right atrium in case of use for a PFO) and coupled to struts  16   a ,  16   b . The device can be collapsed and loaded into a delivery sheath by grabbing the lug and bringing the split ends on a proximal side back together. 
     The device is formed back into a tube for deployment via a catheter. Upon deployment, the occluder reverts to its designed shape due to elastic recovery of the polymer, shape memory recovery, or/and the use of strings, springs, or elastic sheet (tensile elements). Even though tensile elements may be thinner than the frame, they can produce much higher forces than the frame itself, thus assisting the frame in its recovery. This is possible because the primary mode of deformation is in tension, while the frame deformation mode is in bending and torsion. Tensile elements also provide a way for centering so the occluder can be positioned properly in a wide defect. 
     Without a wire and a lug or other method to grab the struts at the proximal end, if the proximal end needed to be withdrawn back into a catheter, the struts would fold over the outside of the central portion, thereby increasing the cross-sectional profile. This may be acceptable, but a smaller profile would be obtained by pulling the ends of the struts back into the tubular shape. At the distal end where struts  18   a ,  18   b  are (the left atrial end in case of use in a PFO), a pulling action of the device back into a catheter would naturally urge the struts back into the tubular configuration. 
     The number of radially extending parts (struts) formed from each end of a tube could be greater than two, such as any number from 3 to 10. Using many more struts, such as more than 10, may be possible but could be impractical because there could be a considerable decrease in their stiffness due to the decrease in thickness. More struts at each end may be possible with appropriate materials. 
       FIGS. 3 and 4  show a closure device  30  with 3 slits made at each end of a tube to form three struts  32   a - 32   c ,  34   a - 34   c  at each end of the tube. Small strips, referred to here as whiskers  36 , made of the same material as the tube or some other materials can be attached to the central portion  38 , or material can be partially shaved from the center region  38  of the tube. These whiskers can produce an inflammatory response and speed up the healing process. The whiskers can have a drug coating, such as with an anti-coagulant, or can be made of a drug that is slowly dissolved. Rather than the whiskers as shown, a collar with a foam or sponge-like material, such as polyvinyl alcohol, can be used, and can include an anti-coagulant. 
       FIGS. 5 and 6  show the embodiment of  FIGS. 3 and 4  as deployed in a PFO tunnel. As indicated here, struts  32   a  and  34   a  have ends that contact septum primum  50 , and struts  32   b  and  34   b  have ends that contact septum secundum  52 . Struts  32   c  and  34   c  are not shown in  FIG. 5 , but as indicated in  FIG. 6 , they could be positioned against septum primum or septum secundum. These struts cooperate to provide a compressive clamping force to the PFO. 
     Center portion  38  can extend through the PFO tunnel and can be at an acute angle A relative to a downward vertical direction. This is an example of how the configuration can conform well to the anatomy. 
     As shown in top view  FIG. 4 , the struts can be formed so that they are evenly distributed circumferentially. Generally, the struts can be equally spaced by 360°/n in the circumferential direction, where n is the number of struts; for 3 struts, each strut is at 120° relative to adjacent struts. The struts at one end can be offset by (360°/n)/2 from the struts at the other end. 
     Such an even distribution at each end and equal offset of the two ends relative to each other can be used, but such relationships are not required. The slits at each end of the tube can be formed in one of a number of different ways, and can produce struts that have different widths. In addition, while the slits may be rather narrow as shown, such that the sum of the widths of the struts is just a little less than the circumference of the tube, the slits can be made wider so that the struts are narrower, although it is generally preferable to have wider struts to provide good support. 
       FIG. 7  is a perspective view of a device similar to that of  FIGS. 3 and 4 , but with the addition of a tissue scaffold. While preferably bioresorbable, the tissue scaffold may be formed of any flexible, biocompatible material capable of promoting tissue growth, including but not limited to polyester fabrics, Teflon-based materials such as ePTFE, polyurethanes, metallic meshes, polyvinyl alcohol (PVA), extracellular matrix (ECM), or other bioengineered material, synthetic bioabsorbable polymeric scaffolds, other natural materials (e.g. collagen), or combinations of the foregoing materials. Also, a tissue scaffold may be formed of a thin metallic film or foil. The scaffold may be attached to one or both sides of the device. The tissue scaffold or the frame can have drugs or biological agents to accelerate the defect healing process and/or decrease thrombosis. 
     Referring to  FIG. 8 , in another embodiment, the tube has four slits at each end to produce four struts at each end of the tube. As indicated above, whiskers and/or sponge material and tissue scaffolds could be added, as could a recovery wire and lug. 
     Referring to  FIG. 9 , an embodiment similar to that of  FIG. 8  is shown with the addition of elastic bands or strings  90 ,  92  extending from ends of struts at one end to ends of struts at another end. These bands can be provided for some or all of the opposing struts. As shown here, the struts can be located at the same circumferential position at each end (and not offset, unlike in  FIG. 4 ). The strings help to bend back the struts, and can also help to orient and center the device as shown below. 
     In the embodiments of  FIGS. 10 and 11 , device  100  has four struts at each end. From each of two of the struts, an elastic band  102 ,  104  extends from one strut to a corresponding strut at the opposite end of the device. The bands can provide centering and/or be inflammatory. 
       FIGS. 12-15  show another embodiment. Referring specifically to  FIG. 12 , the tube has several different slits, including two longer slits, 180° apart, at each end to form bases  120  and  122  for struts, and two shorter slits are made, offset by 90° from the longer slits, to form struts  124 ,  126 ,  128 , and  130  at one end. As also shown in  FIGS. 13 and 14 , struts  124 - 130  can be formed at one end to be offset at a circumferential angle of 90° with respect to struts at the other end, identified here as struts  132 ,  134 ,  136 , and  138 . 
     Referring to  FIG. 15 , in this side view, it is shown that the struts can be formed during manufacture such that the ends of the struts at opposite ends overlap when treated and before deployment. In other words, a distal end strut  126  and a proximal end strut  136  cross such that the end of strut  126  is closer to the proximal end than the end of proximal strut  136 . 
     This configuration may be more suitable for a polymer embodiment or for another type of material that may not have full recovery force. Nitinol, for example, has rather high recovery force and is better able to reassume its original shape after being folded into a catheter and then deployed. A polymer may not have quite as much recovery force, and therefore it can be useful to compensate partially for this by allowing struts at one end to cross the struts at the other end in the manufactured configuration. The struts will be contacting tissue that separates them, and therefore in the deployed position, the struts will be spaced part and not overlap. 
     Referring to  FIG. 16 , the tube in this case is shown with slits that are somewhat similar to that in  FIG. 12 , except that rather than the long slits being offset as in  FIG. 12 , the long slits in  FIG. 16  at opposite ends are circumferentially aligned. In this embodiment, struts  162 ,  164 ,  166  and  168  are produced at one end, with similar struts at the other end. Unlike the embodiment as shown in  FIG. 13 , in which struts  124  and  128  extend substantially parallel, struts  162  and  166  are curved to come together at an end  170 . Other struts are matched up pairwise in a similar manner, forming in effect four loops. 
     Each of these loops is preferably parallel to the defect. This allows most of the loop to be in contact with the tissue, such as one of the septa in the case of a PFO. The loop can be perpendicular to the defect, which is more like a strut that doubles back to the central portion. This configuration is possible but less desirable. 
     As shown in  FIG. 19 , the ends  170 ,  172  of these loops can be formed to be very close together or even touch when manufactured. As described above, a material with a recovery that does not fully come back into place may be compensated by bringing the ends together or overlapping as described above. 
       FIG. 20  shows still another embodiment. As shown here, shorter and longer axial slits are not that much different, thereby producing larger loops when ends of the struts are brought together as shown in  FIGS. 21 and 22  to create loops in a manner similar to that shown in  FIG. 17 . In this case, a tissue scaffold can also be provided in advance and during manufacture to the loops to result in the scaffold on the device as shown in  FIGS. 21 and 22 . 
     As indicated, the slits can have different widths, different numbers, and different slits can be formed with different lengths. In the case of struts, the ends of the struts contact the tissue, while in the case of the loops, as shown in  FIGS. 17 and 21 , for example, the loop may contact the tissue over a larger area, thereby producing less trauma to the patient. To reduce trauma with struts, ends of the struts can be modified, such as rounded to reduce trauma that may be provided to septum primum and septum secundum when implanted. 
     The proximal and distal end loops in  FIG. 17  are aligned, but they could be rotationally offset, preferably by 90 degrees so the ends are perpendicular to each other. This can be accomplished by changing the pattern of slits in a tube. 
     As indicated before, the device can be deployed through a catheter using generally conventionally known processes. This description relates to the use for a PFO, where the proximal side is the right atrium and the distal side is the left atrium, but the process could be used for other types of defects or treatments. 
     The occluder in its manufactured form is essentially folded back into the tubular form and inserted into a catheter. The distal end of the catheter is inserted into the left atrium where the catheter and the occluder are moved relative to each other so that the struts, loops, or other radial pieces can fan out to contact septum primum and septum secundum. This movement can be accomplished by pushing the occluder out of the catheter or retracting the catheter so that the occluder is not constrained and can fan out. At this stage, it should not be difficult to pull the device back into the catheter if necessary to remove or reposition, as the radial pieces will tend to go back into the catheter. 
     When positioning at the distal end is satisfactory, the catheter is retracted through the PFO tunnel between septum primum and septum secundum to expose the central portion, and is then moved further in the proximal direction to the device so that the catheter ceases to constrain the radial pieces from fanning out in the right atrium. As indicated above in  FIG. 2 , a recovery lug can be provided so that if the device is positioned and it is desirable to retrieve it, hooks or arms can be used to grab the lug to pull the proximal end in the right atrium back into a tubular configuration. Further distal direction movement of the catheter relative to the device will cause the distal (left atrium) end to be drawn back into the catheter. 
     As indicated before, the device can be made of nitinol or some other metal with good recovery or shape memory properties, or it can be made of a polymer. In the case of a polymer, the polymer is preferably treated to make it make it radiopaque so that it can be seen on x-ray or other imaging equipment. 
     The shape and construction of such devices can have some advantages over other PFO closure devices. It has atraumatic shape, good embolization resistance in some embodiments, and the ability to conform to the anatomy, especially in a defect tunnel due to the angled joint between the proximal and distal side. The device can be repositioned or/and removed during delivery. It has a small profile after deployment. It can be made of bioresorbable components. Certain embodiments can be used to close symmetric defects (e.g., atrial septal defects) or asymmetric defects (e.g., PFO) using two versions of the device, i.e., one with a straight center tube and one with an angled center tube. 
     Occluders as described herein can be used with anti-thrombogenic compounds, including but not limited to heparin and peptides, to reduce thrombogenicity of the occluder and/or to enhance the healing response of the septal tissue following deployment of the occluder in vivo. Similarly, the occluders described herein may be used to deliver other drugs or pharmaceutical agents (e.g., growth factors, peptides, or cells). The anti-thrombogenic compounds, drugs, and/or pharmaceutical agents may be included in the occluders of the present invention in several ways, including by incorporation into the tissue scaffold, as previously described, or as a coating, e.g. a polymeric coating, on the tube(s) forming the distal side and proximal side of the occluder. Furthermore, the occluders described herein may include cells that have been seeded within the tissue scaffold or coated upon the tube(s) forming the distal side and proximal side of the occluder. 
     In some of the embodiments, such as that of  FIG. 1 , the occluder can be unitary or even monolithic (except for coatings or other surface treatments). 
     Having described preferred embodiments of the invention, it should be apparent that various modifications may be made without departing from the spirit and scope of the invention. While the device can be made from an extruded tube, pieces of polymer or other material can also be used to make the device by applying different joining methods such as welding, gluing, etc. The strands may have circular or polygonal cross-sections. The device can also be molded. The tube cross-section may be circular or polygonal (including square and rectangular). While in most cases, each end has the same number of slits or loops, either aligned or offset, each end can be formed differently; e.g., one end could have a different number or configuration of struts.