Patent foramen ovale (PFO) closure method and device

[0001] 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.

[0002] 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.

[0003] 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.

[0004] 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.

[0005] 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.

[0006] 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's, which are true holes. Additionally, some septal closure devices are complex to manufacture, which can result in lack of consistency in product performance.

[0007] 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.

[0008] 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.

[0009] 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.

[0010] 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.

[0011] 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.

[0012] 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.

[0013] 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.

[0029] 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.

[0030] 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. 3a, 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. 3c, 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.

[0031] 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.

[0032] 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.

[0033] 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. 5a, 5b and 5c, 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. 5b, 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. 5c, 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.

[0034] 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. 15a and 15b). Septum primum and septum secundum are thus compressed between the pointed ends and at least one of the folds of the device (FIG. 15c).

[0035] 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.

[0036] 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.

[0037] 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.

[0038] 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. 10c, 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.

[0039] 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.

[0040] 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.

[0041] 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.

[0042] A rivet design suture system 60 is shown in FIGS. 10a, 10b and 10c. 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. 10b to compress the two septa together. The suture 62 can then be knotted with knot 68, as shown in FIG. 10c, 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. 10c, 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.

[0043] 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. 11a–11d. 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.

[0044] 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. 11b), 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. 11c). 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. 11d) 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. 11d.

[0045] 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.