Abstract:
The present invention provides methods and devices for closing two overlapping layers of tissue in a mammalian heart, for example a patent foramen ovale (PFO). The closure devices may take a number of different forms and may be retrievable. In some embodiments, a device is sized and shaped to extend from septum secundum, into the left atrium, through septum primum, and into the right atrium, such that the first and second ends cooperate to provide a compressive force to the overlapping layers of tissue. In some embodiments, the closure devices may be delivered with a catheter capable of puncturing mammalian tissue.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This Application is a Divisional of U.S. patent application Ser. No. 10/341,802, entitled Patent Foramen Ovale (PFO) Closure Method and Device, filed Jan. 14, 2003, and incorporated herein by this reference. 
     
    
     FIELD OF THE INVENTION  
       [0002]     The invention relates to occlusion devices and methods for the closure of physical anomalies, like septal apertures, such as patent foramen ovale and other septal and vascular defects.  
       BACKGROUND OF THE INVENTION  
       [0003]     A patent foramen ovale (PFO) as shown in  FIG. 1 , is a persistent, one-way, usually flap-like opening in the wall between the right atrium  10  and left atrium  12  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 functional closure is subsequently followed by anatomical closure of the two over-lapping layers of tissue: septum primum  14  and septum secundum  16 . However, a PFO has been shown to persist in a number of adults.  
         [0004]     The cause of ischemic stroke remains cryptogenic (of unknown origin) in approximately 40% of cases. Especially in young patients, 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.  
         [0005]     The presence of a PFO has no therapeutic consequence in otherwise healthy adults. In contrast, patients suffering a stroke or transient ischemic attack (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 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.  
         [0006]     In certain cases, such as when anticoagulation is contraindicated, surgery may be used to close the PFO. To suture a PFO closed requires attachment of septum secundum to septum primum with either an interrupted or a continuous stitch, which is the common way a surgeon shuts the PFO under direct visualization.  
         [0007]     Nonsurgical closure of PFOs has become possible with the advent of 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.  
         [0008]     Currently available designs of septal closure devices, however, present such drawbacks as technical complexity of implantation procedure, high complication rates (thrombus, fractures, conduction system disturbances, perforations, residual leaks), high septal profile, large masses of foreign material, and lack of anatomic conformability especially to the PFO flap-like anatomy, as most were originally designed to close ASD&#39;s, which are true holes. Additionally, some septal closure devices are complex to manufacture, which can result in lack of consistency in product performance.  
       SUMMARY OF THE INVENTION  
       [0009]     In one aspect, the present invention provides a method of closing two overlapping layers of tissue in a mammalian heart, e.g., a patent foramen ovale (PFO), using a closure device that applies a compressive force to at least one of the layers of tissue. The closure device may be retrievable, such that it may be removed after a period of time sufficient to allow the overlapping layers of tissue to fuse together. If necessary to sufficiently close the length of the layers of tissue, multiple closure devices may be administered. The closure devices may be delivered with a catheter capable of puncturing mammalian tissue in at least one location.  
         [0010]     The closure device of the present invention may take a number of different forms. For example, the closure device may have first and second ends, both of which may be capable of puncturing mammalian tissue. The device may be a structure such as a ring with a gap, a folded ring, at least one grappling hook member joined to at least one curved arm by a joinder member, opposed grappling hook members joined by a central connecting member, a grappling hook member and a central connecting member, or a closure device anchor joined to a structure of sufficient diameter to hold the device in place against the overlapping layers of tissue. In some embodiments of the present invention, the closure device is sized and shaped such that it extends from septum secundum in the left atrium, into the left atrium, through septum primum, into the right atrium, and to septum secundum in the right atrium. Some retrievable devices include elongate tethers to facilitate their removal. Each of these devices has certain advantages, and one skilled in the art will be capable of selecting the device appropriate for a given application.  
         [0011]     The ends of the closure device may also take a number of different forms. For example, at least one end may form a disc or a closure device anchor, such as a coil, hook, or corkscrew. These end structures help to maintain the device in place. One of the ends, for example the second end, may take the form of a knot or a structure similarly capable of holding the device in place and applying a sufficient compressive force to the overlapping layers of tissue. In some embodiments, the end structure may be adjusted to alter the compressive force applied to the overlapping layers of tissue. As previously mentioned, either or both of the first and second ends may be capable of puncturing mammalian tissue. In some embodiments, the first end of the device is a septal puncture needle.  
         [0012]     The closure device may be formed of any of several materials, such as flexible polymer materials, bioabsorbable materials, shape memory materials, metals, noble metals, or swellable foams. In particular embodiments, the device includes nitinol. Some of the devices are formed from a single piece of material, while others are formed from multiple pieces of material joined together.  
         [0013]     Some closure devices according to the present invention are intended to puncture septum primum upon insertion into the heart. For example, such a device may be inserted into the right atrium of the heart and puncture septum primum to enter the left atrium of the heart. At this point, the first end of the device may simply be deployed into the left atrium, or the first end of the device may be deployed into the left atrium and at least partially puncture septum secundum. In those embodiments where the first end of the device at least partially punctures septum secundum, the first end may be embedded in septum secundum or may completely puncture septum secundum such that the first end extends into the right atrium. The second end of the device may then be positioned against septum secundum in the right atrium, thereby providing a compressive force to the septal tissues. In other embodiments, the second end is also positioned in the left atrium while another portion of the device, such as a fold, is positioned in the right atrium, thereby compressing the septal tissues between the device.  
         [0014]     Alternatively, some closure devices according to the present invention are intended to be inserted between the overlapping layers of tissue, e.g. through the PFO tunnel, to enter the left atrium. In these embodiments, the first end of the device is then deployed in the left atrium and the second end of the device is deployed in the right atrium, thereby providing a compressive force to the septal tissue. As discussed above, at least one of the ends of the device may partially puncture septum secundum.  
         [0015]     These and other features will become readily apparent from the following detailed description wherein embodiments of the invention are shown and described by way of illustration. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0016]      FIG. 1  is a diagrammatic sectional view of a Patent Foramen Ovale (PFO);  
         [0017]      FIG. 2  is a view in side elevation of the PFO closure device with mechanical anchors of the present invention;  
         [0018]      FIGS. 3   a ,  3   b  and  3   c  illustrate the steps in the deployment of the PFO closure device of  FIG. 2 ;  
         [0019]      FIG. 4  is a view in side elevation of a second embodiment of the PFO closure device with mechanical anchors of the present invention;  
         [0020]      FIGS. 5   a ,  5   b  and  5   c  illustrate the steps in the deployment of the PFO closure device of  FIG. 4 ;  
         [0021]      FIG. 6  is a view in side elevation of a catheter and septal puncture needle used to pierce septum primum;  
         [0022]      FIG. 7  is a view in side elevation of a needle anchor for PFO closure;  
         [0023]      FIG. 8  is a view in side elevation of a suture and anchor used for PFO closure;  
         [0024]      FIG. 9  is a diagram of multiple anchor placement for PFO closure;  
         [0025]      FIGS. 10   a ,  10   b  and  10   c  illustrate the steps in the deployment of a rivet and suture type of PFO closure device;  
         [0026]      FIGS. 11   a ,  11   b ,  11   c  and lid illustrate the steps in the deployment of a removable PFO closure device;  
         [0027]      FIGS. 12   a ,  12   b  and  12   c  illustrate the steps in the deployment of a multiple hook PFO closure device;  
         [0028]      FIG. 13  is a view in side elevation of an alternative structure of the second embodiment of the PFO closure device with mechanical anchors of the present invention;  
         [0029]      FIG. 14  is a view in side elevation of an alternative structure of the second embodiment of the PFO closure device with mechanical anchors of the present invention; and  
         [0030]      FIGS. 15   a ,  15   b , and  15   c  are an end face view from the right atrium, an end face view from the left atrium, and a side elevation view, respectively, of the deployed alternative structure of the second embodiment of the PFO closure device with mechanical anchors of the present invention.  
     
    
     DETAILED DESCRIPTION  
       [0031]     Referring to  FIGS. 2 and 3 , a PFO closure device with mechanical anchors indicated generally at  18  includes opposed grappling hook members  20  and  22  connected by a central connecting member  24 . When the PFO closure device  18  is deployed, the grappling hook members  20  and  22  each include two or more curved hooks. In  FIGS. 2 and 3 , three curved hooks  26 ,  28  and  30  form the grappling hook member  20  and three curved hooks  32 ,  34  and  36  form the grappling hook member  22 . As shown in  FIG. 2 , the grappling hooks  26 ,  28 ,  30 ,  32 ,  34 , and  36  extend radially from the central connecting member  24 . The grappling hooks of grappling hook members  20  and  22  have the same geometry but are rotated such that each grappling hook of grappling hook member  20  is situated precisely between two opposed grappling hooks of grappling hook member  22 . The angle between any two grappling hooks of grappling hook members  20  and  22  may be determined by the formula 360°/(number of hooks per grappling hook member). To fit within a catheter, these hooks may all be straightened outwardly and compressed to lie along the longitudinal axis of the central connecting member  24 . In this form, the PFO closure device extends longitudinally within a catheter  38 .  
         [0032]     To deploy the PFO closure device  18 , the catheter  38  is inserted from the right atrium  10  through the PFO tunnel, i.e. between septum primum  14  and septum secundum  16 , into the left atrium  12 . As shown in  FIG. 3   a , the grappling hook member  20  is deployed into the left atrium. Next, as shown in  FIG. 3b , the catheter  38  is drawn back into the right atrium and the grappling hooks  26 ,  28  and  30  are drawn back and embedded in the left sides of septum primum and septum secundum. The central connecting member  24  extends at an angle through the PFO tunnel permitting septum primum and septum secundum to be drawn to the closed position and secured by the grappling hooks  26 ,  28  and  30 . Finally, as shown in  FIG. 3   c , the catheter  38  is drawn back to permit the grappling hook member  22  to deploy, and grappling hooks  32 ,  34  and  36  pierce the right side of septum primum and septum secundum.  
         [0033]     The grappling hook members  20  and  22  may be formed of flexible, spring-like, bioabsorbable polymer material so as to permit movement from the compressed straight shape to the curved hook shapes following deployment from the catheter  38 . The central connecting member  24  may also be formed of bioabsorbable material, such as an absorbable suture material, so the device will ultimately leave no foreign substance in either atrium. Alternatively, the grappling hook members  20  and  22  may be formed of spring metal or of a shape memory material, such as nitinol. When the PFO closure device is not formed of bioabsorbable material, it is possible to form the device with only the grappling hook member  20  and a central connecting member  24  so that the device is repositionable and retrievable. When the device is made of a bioabsorbable material or is not intended to be retrievable, the ends of grappling hooks  26 ,  28 ,  30 ,  32 ,  34  and  36  may further include a barb to maintain the device in the septal tissue. In some embodiments, the grappling hook members  20  and  22  serve as tissue scaffolds, and are covered with a vascular material, such as polyester, biological tissue, bioresorbable polymer, or spongy polymeric material.  
         [0034]     As shown in  FIG. 3 , the closure device will conform, at least to some extent, to the septal tissue that it compresses. The extent of this conformance depends upon the material from which the device was formed: a device formed of a spring metal or shape memory material will conform to the surrounding septal tissue to a lesser extent than one formed of a flexible, bioabsorbable polymer material.  
         [0035]      FIG. 4  shows a second embodiment of a PFO closure device with mechanical anchors indicated generally at  40 . This device, when deployed, forms a ring hook design that terminates in two opposed, pointed ends  42  and  44 . The device may be straightened to pass through a catheter  38 . To deploy the device as shown in  FIGS. 5   a ,  5   b  and  5   c , the catheter is caused to pierce septum primum  14  and enter the left atrium where the pointed end  42  is deployed. Then, as shown in  FIG. 5   b , the catheter is drawn back through septum primum to draw the device through septum primum and embed the pointed end  42  in the left side of septum secundum. Finally, as shown in  FIG. 5   c , the catheter is withdrawn to fully deploy the PFO closure device and the pointed end  44  is embedded in the right side of septum secundum to compress septum primum and septum secundum together. As shown in  FIGS. 4 and 5 , the ring PFO closure device  40 , when deployed, may include a gap that is slightly smaller than the thickness of septum secundum into which it is embedded. In some embodiments, the opposed ends  42  and  44  of the deployed PFO closure device  40  contact each other or overlap.  
         [0036]     As shown in  FIGS. 13 and 14 , closure device  40  may take alternative forms. For example, closure devices  90  and  100  are formed as partial rings terminating in two pointed ends  92  and  94  or  102  and  104  and having at least one fold therebetween. Closure devices  90  and  100  are deployed in a manner similar to that described above and shown in  FIG. 5 . When deployed, the pointed ends  92  and  94  or  102  and  104  puncture the surface of septum secundum exposed in the left atrium and at least one of the folds contacts the surface of septum secundum exposed in the right atrium ( FIGS. 15   a  and  15   b ). Septum primum and septum secundum are thus compressed between the pointed ends and at least one of the folds of the device ( FIG. 15   c ).  
         [0037]     Multiple PFO closure devices  40 ,  90  or  100  can be inserted until the physician is satisfied with the resultant PFO closure. Again, the PFO closure devices may be formed of flexible, bioabsorbable polymer material, spring metal, other spring-like non-bioabsorbable material, or shape memory material. The choice of material will affect the degree to which the device conforms to the surrounding septal tissue. As shown in  FIGS. 4, 13 , and  14 , the PFO closure device may be a monolithic structure.  
         [0038]     A PFO may also be closed with one or more sutures. As used in the art and indicated in the Figures, “suture” refers to a single connection used to hold two pieces of material or tissue together and need not be a continuous stitch. However, to suture a PFO closed has conventionally required the attachment of septum secundum to septum primum with a continuous stitch. This need for a continuous stitch can be eliminated by implanting sutures across the PFO using implantable suture anchors. As shown in  FIGS. 6 and 7 , a catheter  46  is used to puncture septum primum and then septum secundum. In the case of septum primum, the puncture creates a hole through which the catheter can pass; in the case of septum secundum, the puncture may be a depression that does not pass through septum secundum. A single puncture may be made in septum secundum as shown in  FIGS. 6-8 , or, as subsequently described and shown in  FIG. 9 , multiple punctures may be made. These punctures are made using a sharp pointed needle tip  48 . Following puncture to a desired depth, the catheter  46  surrounding the needle  48  is withdrawn and the needle component returns (most likely via shape memory) to its predetermined anchor-shape.  
         [0039]     The anchors are most likely fabricated from a shape memory alloy, such as nitinol, although they could be made from a flexible, bioabsorbable polymer or a noble metal, each having their own advantage—no long term implant issues with bioabsorbable anchors and excellent radiopacity with anchors fabricated from a noble metal, such as platinum-iridium. The remainder of the suture may be formed of any suitable material, including wire, polymeric materials, and bioabsorbable materials.  
         [0040]     The suturing method includes using a standard septal puncture technique to locate and puncture septum primum. Following this, several approaches exist. One would be that the septal puncture needle would be withdrawn from the catheter and the suturing system then delivered through the catheter (the septal needle catheter would maintain position across septum primum during the exchange). Alternatively, a wire could be placed through the septal needle catheter to maintain position and the suture system could be delivered over the wire, or the septal puncture needle could become part of the suture system. Following delivery of the suture system, the proximal end of the suture may then be tied off so as to secure the system in place and keep the PFO closed. As described below for the rivet design suture system and shown in  FIG. 10   c , the proximal end of the suture may be formed into a knot, i.e. the end of the suture may be formed into a structure having a diameter larger than that of the catheter used to puncture septum primum so as to ensure that the suture system remains in place. Other suitable structures for the proximal end of the suture include, but are not limited to, coils, spirals, and other adjustable mechanisms. This structure should apply sufficient compression to hold septum primum and septum secundum together. The structure may be adjustable, such that the level of compression may be altered as necessary. Multiple sutures may be inserted until the physician is satisfied with the PFO closure.  
         [0041]     In  FIG. 8 , a suture  50  is delivered through the septal needle catheter following the removal of the needle. A suture catheter  52  enters the left atrium through the septal needle catheter, is pulled back against septum secundum, setting the needle tip(s)  54  deep within it or through it, if it is thin enough. The tip could be either radiopaque, echogenic, or both, to be visible by x-ray (fluoroscopy) and/or cardiac echo. Once proper position is determined, the constricting system (a hypotube or a series of con-axial hypotubes in the embodiment where multiple needles are simultaneously delivered) is withdrawn, allowing the suture anchor  56  to form into a pre-determined shape tissue anchor, most likely via shape memory properties. The anchor  56  on the end of the suture  50  has been embedded in septum secundum and expands to anchor the suture, which passes through septum primum once the suture catheter is removed. The anchor shape can be one of many different options, including but not limited to a coil, hook, corkscrew, or grappling hook.  
         [0042]     In those cases where a true puncture through septum secundum can be made, an anchor can be placed entirely in the right atrium, leaving nothing but suture in the left atrium. These anchors may be short strips or cylindrical rods made from a metallic or polymeric material that is biostable or bioabsorbable, or a piece of swellable foam, such as Ivalon.  
         [0043]     In another embodiment, the septal needle catheter crosses septum secundum in multiple locations simultaneously. In this embodiment, the final result, as seen from the left atrium in an end face view of septum primum and septum secundum, would be as shown in  FIG. 9 , where a plurality of spaced anchors  58  engage septum secundum.  
         [0044]     A rivet design suture system  60  is shown in  FIGS. 10   a ,  10   b  and  10   c . Here a suture  62  and anchor  64  are contained within a catheter  66 , which pierces both septum secundum and septum primum. The anchor  64 , which is formed of a firm material, such as a metal disc, a small hook (such as the shape memory hooks previously described), or a piece of bio-absorbable polymer, is then deployed into the left atrium, and the suture  62  and catheter  66  are then pulled back as shown in  FIG. 10   b  to compress the two septa together. The suture  62  can then be knotted with knot  68 , as shown in  FIG. 10   c , to secure the system  60  in place to keep the PFO closed, i.e. the end of the suture may be formed into a structure having a diameter larger than that of the catheter used to puncture septum primum so as to ensure that the suture system remains in place. Other suitable structures for the second end of the suture include, but are not limited to, coils, spirals, other adjustable mechanisms. As shown in  FIG. 10   c , this structure should apply sufficient compression to hold septum primum and septum secundum together. The structure may be adjustable, such that the level of compression may be altered as necessary. Multiple rivet systems can be inserted until a physician is satisfied with the PFO closure.  
         [0045]     The PFO closure device of the present invention may be formed in a manner to facilitate removal once septum primum and septum secundum are fused. An exemplary removable PFO closure device  70  is deployed in the manner illustrated by  FIGS. 11   a - 11   d . The PFO closure device  70  may be delivered by a delivery catheter or sheath  72  and includes a grappling hook member  74  joined to a curved arm  76  by an enlarged tip joinder member  78 . At least one of the grappling hook member and curved arm of the PFO closure device may be curved relative to the other. An elongate tether  80  is connected to the tip joinder member  78  and extends back through the catheter  72 . The tether  80  can be coated to minimize trauma to the veins.  
         [0046]     To deploy the removable PFO closure device  70  according to one embodiment of the invention, the grappling hook member  74  is passed through septum primum  14  ( FIG. 11   b ), and the grappling hook, when free of the catheter, curves in a manner convex relative to the surface of septum secundum and penetrates septum secundum  16  ( FIG. 11   c ). Then, the grappling hook is drawn back toward the catheter by the tether  80  to apply tension to the tissue causing septum secundum to be drawn into contact with septum primum. Then the curved arm  76  is deployed ( FIG. 11   d ) and curves in a manner concave relative to septum secundum so as to engage septum secundum as the catheter is drawn back. The compressive force applied by the grappling hook and the curved arm hold septum primum and septum secundum tightly together. The grappling hook  74  and curved arm  76  are preferably formed of shape memory material, such as nitinol, so that they respond to body temperature when deployed from the catheter  72  to form the shape shown in  FIG. 11   d.    
         [0047]     Once the PFO closure device  70  is in place, the catheter  72  is withdrawn and the free end of the tether  80  is attached to a button subcutaneously and allowed to remain in place for a period of time sufficient to allow the two septa to fuse together. Then the device is pulled through septum primum and into a recovery sheath by means of the tether  80  and removed.  
         [0048]     The PFO closure device  70  can be deployed as shown in  FIG. 11  without the tether  80  to provide a free standing device with the grappling hook  74  and arm  76  being formed to press the two septa  14  and  16  together. The device may later be removed by a removal device, which grabs the joinder member  78  and draws the device through septum primum  14  and into a removal sheath.  
         [0049]     Instead of a single opposed grappling hook  74  and curved arm  76 , the PFO closure device can include a plurality of opposed grappling hooks and curved arms radially extending in a spaced relationship from the joinder member  78 . Such a device  82  is shown in  FIG. 12 . Here, the PFO closure device includes a plurality of grappling hooks  84  and a plurality of opposed curved arms  86  which are enclosed in a delivery catheter  72 . A small hole  88  is created in septum primum  14  to permit insertion of the catheter into the left atrium and the grappling hooks  84  are deployed as shown in  FIG. 12   a . Then, the delivery catheter is drawn back to engage the hooks with both septum secundum and septum primum as shown in  FIG. 12   b . Next, as shown in  FIG. 12   c , the catheter is drawn away to release the curved arms  86 , which engage the two septa in opposed relationship to the grappling hooks  84 . The device may have many, e.g. eight, opposed grappling hooks and curved arms. As in the case of the PFO closure device  70 , the device  82  may be removed by grasping the tip joinder member  78 .  
         [0050]     The device  82  may be permanently deployed by inserting the catheter through the PFO channel between septum secundum and septum primum into the left atrium to deploy the grappling hooks  84 . Then, the catheter is withdrawn back through the PFO channel to release the curved arms  86 .  
         [0051]     Having described embodiments of the present invention, it should be apparent that the invention is capable of other and different embodiments and may be modified in various respects, all without departing from the scope of the invention as defined by the appended claims. Accordingly, the foregoing drawings and description are to be regarded as illustrative in nature and not in a restrictive or limiting sense.