Abstract:
A method for closing a patent foramen ovale in the heart tissue of a patient may include percutaneously advancing a connector applicator to the patent foramen ovale, registering the connector applicator with the patent foramen ovale, deploying connectors into heart tissue to close the patent foramen ovale; and percutaneously removing the connector applicator from the heart. One or more anchors may be used to register the connector applicator with the patent foramen ovale. The connector applicator may include a driver having a longitudinal passage therein, where at least part of at least one connector is positioned within said passage.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates generally to a system for closing a patent foramen ovale in heart tissue. 
       BACKGROUND 
       [0002]    Referring to  FIG. 1 , a patent foramen ovale (PFO)  2  is a flap-like opening in the wall  4  between the left atrium  6  and the right atrium  8  of the heart  10 . That opening typically closes at or shortly after birth. However, in an estimated 20-25% of people, the PFO  2  remains open into adulthood. The PFO  2  allows blood clots in the bloodstream to bypass the natural filtering mechanism of the lungs, which can lead to stroke. A person with a PFO  2  is generally asymptomatic, and generally does not know he or she has a PFO  2  until after a stroke. In addition, research suggests a correlation between PFO  2  and migraine, the mechanism of which is still unknown. 
         [0003]    Currently, patients having a known PFO  2  are treated in one of two ways. The patient may be prescribed blood thinners such as coumadin, to reduce the risk of clot formation. However, this course of treatment requires lifelong dependence on that medication, which does nothing to close the opening between the atria. Alternately, a device may be placed through the PFO  2  and then unfurled like a tent on each side of the PFO  2 . Such a device may include a material such as polyester stretched over a wire frame, or stuffed inside a wire mesh. However, such devices can expose a significant amount of metal to the bloodstream, which is considered undesirable. 
     
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0004]      FIG. 1  is a cross-section view of a heart. 
           [0005]      FIG. 2  is a perspective view of an exemplary connector applicator. 
           [0006]      FIG. 3  is a perspective view of an exemplary housing that forms part of the connector applicator of  FIG. 2 . 
           [0007]      FIG. 4  is a side view of the housing of  FIG. 3 . 
           [0008]      FIG. 5  is a cross-section view of the housing of  FIG. 4  along the line A-A of  FIG. 4 . 
           [0009]      FIG. 6  is a perspective of an exemplary driver that forms part of the connector applicator of  FIG. 2 . 
           [0010]      FIG. 7  is a side view of the driver of  FIG. 6 . 
           [0011]      FIG. 8  is a cross-section view of the driver of  FIG. 6  along the line A-A of  FIG. 6 . 
           [0012]      FIG. 9  is a cross-section view of the driver of  FIG. 6  along the line B-B of  FIG. 6 . 
           [0013]      FIG. 9A  is the cross-section view of  FIG. 9 , showing a connector in a splayed configuration. 
           [0014]      FIG. 10  is a cross-section view of the driver of  FIG. 6  along the line C-C of  FIG. 6 . 
           [0015]      FIG. 11  is a cross-section view of the driver of  FIG. 6  along the line D-D of  FIG. 6 . 
           [0016]      FIG. 12  is a cross-section view of the driver of  FIG. 6  along the line E-E of  FIG. 6 . 
           [0017]      FIG. 12A  is the cross-section view of  FIG. 12 , showing a connector beginning to close. 
           [0018]      FIG. 13  is a cross-section view of the driver of  FIG. 6  along the line F-F of  FIG. 6 . 
           [0019]      FIG. 13A  is the cross-section view of  FIG. 13 , showing a connector in a closed configuration. 
           [0020]      FIG. 14  is a cross-section view of the driver of  FIG. 6  along the line G-G of  FIG. 6 . 
           [0021]      FIG. 15  is a cross-section view of the driver of  FIG. 6  along the line H-H of  FIG. 6 . 
           [0022]      FIG. 16  is a perspective view of an exemplary step of closing a PFO. 
           [0023]      FIG. 17  is a perspective view of an exemplary step of closing a PFO. 
           [0024]      FIG. 18  is a perspective view of an exemplary step of closing a PFO. 
           [0025]      FIG. 19  is a perspective view of an exemplary step of closing a PFO. 
           [0026]      FIG. 19A  is a cross-section view of an exemplary tube that is connected to the connector applicator of  FIG. 2 . 
           [0027]      FIG. 19B  is a front view of an exemplary connector used in conjunction with the connector applicator of  FIG. 2 . 
           [0028]      FIG. 19C  is a top view of a number of connectors of  FIG. 19B  interconnected by an exemplary backbone. 
           [0029]      FIG. 20  is a perspective view of an exemplary step of closing a PFO. 
           [0030]      FIG. 21  is a perspective view of an exemplary step of closing a PFO. 
           [0031]      FIG. 22  is a perspective view of an exemplary step of closing a PFO. 
           [0032]      FIG. 23  is a perspective view of an exemplary step of closing a PFO. 
           [0033]      FIG. 24  is a perspective view of an exemplary step of closing a PFO. 
           [0034]      FIG. 25  is a perspective view of an exemplary step of closing a PFO. 
           [0035]      FIG. 26  is a perspective view of an exemplary step of closing a PFO. 
           [0036]      FIG. 27  is a perspective view of an exemplary step of closing a PFO. 
       
    
    
       [0037]    The use of the same reference symbols in different figures indicates similar or identical items. 
       DETAILED DESCRIPTION 
       [0038]    Referring to  FIG. 2 , a connector applicator  12  includes a driver  14  movable relative to a housing  16 . The housing  16  may be substantially tubular. Alternately, the housing  16  may be shaped in any other suitable manner. The housing  16  is substantially rigid. Alternately, at least part of the housing  16  may be flexible. The housing  16  may be fabricated from any suitable material. A plurality of connectors  18  are held by the connector applicator  12 . 
         [0039]    Referring also to  FIGS. 3-4 , slots  20  may be defined in the housing  16 . The slots  20  are aligned with the connectors  18  held by the connector applicator  12  in order to allow the connectors  18  to be deployed through those slots  20 , as described in greater detail below. The slots  20  may extend far enough around the circumference of the housing  16  to allow the connectors  18  to splay before closing, where the connectors  18  are configured to splay. Each slot  20  is as least as wide as the corresponding connector  18  is thick, to allow the corresponding connector  18  to be deployed through that slot  20 . Referring to  FIG. 5 , the housing  16  includes a lumen  22  therethrough. That lumen may be any suitable shape. As one example, the lumen  22  may include two straight, substantially-perpendicular sides opposite one another, and two arcuate sides opposite each other, where each arcuate side is a portion of the circumferential shell of the housing  16 . As a result, two walls  26  may be located both proximally and distally to each slot  20 , where each wall  26  may be a generally solid region between the straight side of the lumen  22  and the shell of the housing  16 . Consequently, each slot  20  may be a bay-like area within the housing  16 , where the walls  26  restrain the connector  18  that is located in the slot from moving substantially in the longitudinal direction during deployment. 
         [0040]    Referring to  FIGS. 6-7 , the driver  14  has a shape that varies in cross-section along at least part of its length. The driver  14  includes a generally longitudinal passage  24  defined therein. The longitudinal passage  24  may divide the driver  14  into two or more parts. That is, the driver  14  may include one or more physically-separate components. In such an embodiment, the different portions of the driver  14  can be driven by pulling them at the same rate with separate cables (one attached to each portion), a single cable attached to all of the portions, or any other suitable mechanism or mechanisms attached to one or all portions. Alternatively, the spaced-apart portions of the driver  14  can be joined together at the side to the right of the ‘H’ label in  FIG. 7 , such that the driver  14  could be driven by pulling a single cable or other mechanism attached to the driver  14 . At least part of at least one connector  18  is positioned within the longitudinal passage  24 . The driver  14  is shaped such that it is movable relative to at least one connector  18  to change the shape of that connector  18 . Each connector  18  is held within a corresponding slot  20  in the housing  16  that maintains the connector  18  in substantially the same longitudinal position during the motion of the driver  14 . As a result, as the driver  14  is moved relative to the connector  18 , the cross-section of the driver  14  that engages the connector  18  changes, causing the connector  18  to change shape.  FIGS. 8-15  show the cross-section of the longitudinal passage  24  at various points along the driver  14  identified in  FIG. 7 . These figures, and the effects of the changing cross-section on the connectors  18 , are described in greater detail below. Optionally, at least part of the driver  14  may be coated with a biocompatible lubricant such as sodium stearate. Optionally, at least two connectors  18  may be connected by a backbone  19 , referring to  FIG. 19C . The backbone  19  may be flexible, rigid, or configured in any other suitable manner. The backbone can be made of the same material as the connectors  18 , or of any other suitable material, such as suture or metal wire. Advantageously, all connectors  18  are interconnected by the backbone  19 . 
         [0041]    Referring also to  FIGS. 19 and 19A , the connector applicator  12  may be connected to a tube  28  in any suitable manner. The tube  28  is advantageously flexible, and has a lumen  30  defined therein. A control wire  32  may be connected to the driver  14 , and may extend through the lumen  30  of the tube  28 . The control wire  32  may be connected to the driver  14  in any suitable manner. The application of tension to the control wire  32  causes the driver  14  to move along the lumen  22  of the housing  16  or move in any other suitable manner relative to the housing  16 , as described in greater detail below. The control wire  32  may be connected to a handle (not shown) or other structure or mechanism outside the patient, to enable control of the driver  14 . 
         [0042]    The connectors  18  may be configured in any suitable manner. As one example, referring to  FIG. 19B , at least one connector  18  may be a wire staple having a substantially straight base  34  connected at each end to a curved tine  36 . The connector  18  may be sized, and the tines  36  curved, such that the curvature of each tine  36  is substantially the same as that of the housing  16  and such that the outer surface of each tine  36  is slightly closer to the longitudinal centerline of the housing  16  than the outer surface of the housing  16 . Each connector  18  may be a staple, clip or any other suitable structure or mechanism. The connectors  18  may be all of a single or similar configuration. Alternately, at least one connector  18  may be shaped differently, fabricated from different materials, or otherwise configured differently than at least one other connector  18 . As one example, at least one connector  18  may be substantially as disclosed in U.S. patent application Ser. No. 11/093,003, “Vascular Closure System,” filed on Mar. 28, 2005, which is hereby incorporated by reference in its entirety. As another example, at least one connector may be substantially as disclosed in U.S. patent application Ser. No. 11/282,177, “Vascular Closure System Utilizing a Staple,” filed on Nov. 4, 2005, which is hereby incorporated by reference in its entirety. 
         [0043]    Referring to  FIG. 18 , at least one anchor  38  may be utilized in conjunction with the connector applicator  12 . Each anchor  38  is a mechanism movable from a first configuration having a first width to a second configuration having a second, larger width, then back to the first configuration. Each anchor  38  may be configured in any suitable manner. As one example, at least one anchor  38  may be a tubular structure having two or more slots defined therethrough, such that compression of the anchor causes the segments  48  of the anchor  38  between the slots to deform outward. At least one anchor  38  may have a blunt or soft distal end. Optionally, a soft tip fabricated from rubber, silicone or other soft biocompatible material may be connected to the distal end of at least one anchor  38 . 
         [0044]    Each anchor  38  may be connected to a corresponding tether  40 . Where the corresponding anchor  38  is originally in a substantially tubular state and/or is configured to have a lumen therethrough, the tether  40  may extend into that lumen and connect to the distal end of the anchor  38 . The tether  40  may be tensioned in order to compress the corresponding anchor  38  and cause segments  48  thereof to expand outward. At least one anchor  38  may be elastically deformable. If so, the anchor  38  is in the first configuration until the tether  40  is tensioned to deform the anchor  38  to the second configuration, and the anchor  38  remains in the second configuration until the tether  40  is released Alternately, at least one anchor  38  may be superelastically deformable. For example, such an anchor  38  may be fabricated from nickel-titanium alloy. Alternately, at least one anchor  38  may be plastically deformable. Such an anchor  38  may be substantially as disclosed in U.S. patent application Ser. No. 11/093,003. The housing  16  of the connector applicator  12  may include at least two apertures defined therein, where at least one tether  40  passes through an aperture different from at least one other tether  40 . The passage of tethers  40  through different apertures allows the connector applicator  12  to be properly located relative to the PFO  2 , as described in greater detail below. Optionally, the tethers  40  may extend through the tube  28  as well. 
         [0045]    Operation 
         [0046]    Referring to  FIG. 16 , a conventional guidewire  42  is inserted percutaneously into the patient and advanced through the vasculature to the PFO  2 . Any suitable guidewire  42  may be used. Insertion of the guidewire into the patient may be through conventional femoral artery or radial artery access, or through any other blood vessel that allows the guidewire  42  to be advanced through the vasculature to the PFO  2 . After the guidewire  42  reaches the PFO  2 , it is advanced completely through the PFO  2 . The advancement of the guidewire  42  advantageously may be performed with the assistance of a fluoroscope or other imaging device that indicates the position of the guidewire  42  in the patient. The use of such an imaging device in conjunction with a guidewire  42  is standard in the art. 
         [0047]    A conventional sheath  44  is then advanced through the vasculature, along and over the guidewire  42 . The sheath  44  is substantially tubular, and includes a lumen  46  defined therein. The sheath  44  is advantageously flexible. Any suitable sheath  44  may be used. The use of a sheath  44  in conjunction with a guidewire  42  is standard in the art. Referring also to  FIG. 17 , the sheath  44  continues to be advanced along and over the guidewire  42  until the distal end of the sheath  44  passes through the PFO  2 . Alternately, the distal end of the sheath  44  may be advanced to a point where it is adjacent to the PFO  2  without passing through the PFO  2 . 
         [0048]    Next, referring to  FIG. 18 , the guidewire  42  is removed from the sheath  44 , leaving the lumen  46  of the sheath  44  clear. Alternately, the guidewire  42  may remain in place, particularly if the sheath  44  includes more than one lumen. The anchors  38  are then delivered through the lumen  46  of the sheath  44  to the side of the PFO  2  opposite to the side of the PFO  2  from which the sheath  44  approached. The anchors  38  are then expanded, simultaneously or at different times, in any suitable manner. Alternatively, a single anchor  38 , or more than two anchors  38 , can be used. As one example, at least one anchor  38  may be a tubular structure having two or more slots defined therethrough, such that compression of the anchor causes the segments  48  of the anchor  38  between the slots to deform outward. The corresponding tether  40  extends through the tubular anchor  38  and is attached to the distal end of that anchor  38 . A flexible tube (not shown) or similar structure may be connected to the proximal end of the anchor  38 , and the tether  40  may extend through that tube. To expand the anchor  38 , the tether  40  is pulled in the proximal direction, tensioning the tether  40  and imparting a force in the proximal direction on the anchor  38 . The tube connected to the proximal end of the anchor  38  prevents the anchor  38  from moving substantially in the proximal direction, and as a result the force exerted on the anchor  38  by the tether  40  exerts a compressive force on the anchor  38 . This compressive force causes the segments  48  of the anchor  38  between the slots to deform outward, expanding the anchor to its second, expanded configuration. As another example, at least one anchor  38  may be expanded in a manner substantially as disclosed in U.S. patent application Ser. No. 11/093,003. Any other suitable method or structure may be used to expand the anchors  38 , if desired. Advantageously, two anchors  38  are delivered through the sheath  44  across the PFO  2 , but more than two anchors  38  or only one anchor  38  may be used. 
         [0049]    Next, the sheath  44  is retracted back across the PFO  2 , such that the expanded anchors  38  are on one side of the PFO  2  and the sheath  44  is on the other side of the PFO  2 . Referring to  FIG. 19 , the connector applicator  12  is then delivered through the lumen  46  of the sheath  44  to the side of the PFO  2  opposite from the side on which the expanded anchors  38  are located. The tube  28  is connected to the connector applicator  12 , and extends along the lumen  46  of the sheath  44  out of the patient, or to a location where the tube  28  can be manipulated. At least one tether  40  passes through an aperture in the housing  16  of the connector applicator  12  that is different from the aperture through which at least one other tether  40  passes, as described above. Referring to  FIG. 20 , the tethers  40  are then pulled proximally, tensioning them. This motion of the tethers  40  pulls the anchors  38  and the connector applicator  12 . As the anchors  38  move toward the PFO  2 , they engage heart tissue adjacent to the PFO  2 . In the expanded state, the anchors  38  are too large to pass through the PFO  2 . Thus, when the anchors  38  engage the heart tissue adjacent to the PFO  2 , and the tethers  40  continue to be pulled proximally, the anchors  38  do not move further, and the connector applicator  12  moves toward the PFO  2 . Alternately, the connector applicator  12  may engage the heart tissue adjacent to the PFO  2  first. 
         [0050]    Referring also to  FIG. 21 , the connector applicator  12  and the anchors  38  eventually both contact the heart tissue adjacent to the PFO  2 , such that they cannot be pulled together substantially closer to one another. At that time, the length of tether  40  between the connector applicator  12  and each anchor  38  is relatively short. The apertures in the housing  16  that are spaced furthest from one another are spaced apart a distance at least as far as the expected length of the PFO  2 , and advantageously further than the expected length of the PFO  2 . Thus, as the tethers  40  are retracted and the connector applicator  12  and anchors  38  move closer together, the PFO  2  is tensioned as well. That is, the ends of the PFO  2  are stretched further apart, such that the tissue on the edges of the PFO  2  is drawn closer together. The tensioned PFO  2  thus may be more linear, and may be narrower, than in its original shape. Before the procedure, the device can be adjusted to accommodate the expected length of the PFO  2 . This can be accomplished by adjusting the positions where the anchor tethers  40  enter and/or are held by the connector applicator  12 , such that the anchor tethers  40  are spaced apart a distance slightly larger than the length of the PFO  2 . This spacing will tension the PFO  2  as described above. 
         [0051]    At this point, the connector applicator  12  is substantially aligned with the PFO  2 , and is adjacent to the PFO  2 . The connector applicator  12  may be characterized as being registered to the PFO  2  in this position. At this time, the driver  14  is actuated to begin deployment of the connectors  18 . The driver  14  may be actuated in any suitable manner. As one example, referring also to  FIG. 19A , a control wire  32  is attached to the driver  14 , and the control wire  32  is pulled proximally, causing the driver  14  to slide along the lumen  22  of the housing  16 . However, the driver  14  may be actuated in any other suitable manner. 
         [0052]    Advantageously, the driver  14  sequentially deforms and deploys the connectors  18 , such that different connectors  18  may be in different stages of deformation and/or deployment at any particular moment. For clarity, the deformation and deployment of a single connector  18  is described, and this deformation and deployment may be generalized to all of the connectors  18 . Referring to  FIG. 7 , a side view of the driver  14  is shown. The driver  14  moves in the left direction, this being no limitation on the orientation of the connector applicator  12  in use or the orientation of the driver  14  in the connector applicator  12 . Connectors that have not yet been deformed are positioned at or to the left of cross-section line A-A, with the base  34  of the connector positioned within the passage  24  of the driver. Referring to  FIG. 8 , at the cross-section line A-A, the passage  24  is open laterally, to allow the straight base of the connector  18  to be held therein. The upper surface  50  of the passage  24  may be substantially flat, such that the base  34  of the connector  18  may contact that upper surface  50 . Alternately, the upper surface  50  may be shaped in any other suitable manner. The lower surface  52  of the passage  24  may be flat in proximity to each lateral edge of the passage  24 , and include a depression  54  at a location substantially in the center of the lower surface  52 . The depression  54  may be a concave, curved surface, or may be shaped in any other suitable manner. 
         [0053]    As the driver  14  is moved to the left, the connector  18  is held in substantially the same longitudinal position. Referring to  FIG. 7 , the cross-section of the driver  14 , and of the passage  24 , change between cross-section line A-A and cross-section line H-H. Thus, the connector  18  encounters the changes in the shape of the driver  14  and passage  24  as it is held in one place and the driver  14  is moved relative to it. As a result, the cross-section of the driver  14  and passage  24  can be shaped along a length of the driver  14  to produce a sequence of desired effects on the connector  18  as the driver  14  is moved relative to the connector  18 . Referring also to  FIG. 9 , as the driver  14  is moved left, the connector  18  encounters the portion of the driver  14  at cross-section line B-B. At this cross-section B-B, a projection  56  extends downward at a location substantially in the center of the upper surface  50 . The projection  56  may be a convex, curved surface, or may be shaped in any other suitable manner. The lower surface  52  of the passage  24  at cross-section line B-B may be shaped in substantially the same manner as at cross-section A-A. Referring also to  FIG. 9A , when the portion of the driver  14  at cross-section B-B encounters the connector  18 , the projection  56  from the upper surface  50  of the passage  24  begins to bend the center of the base  34  of the connector  18  downward. Consequently, the ends of the tines  36  begin to move outward, apart from one another. This deformation of the connector  18  may be referred to as “splaying”. As the connector  18  begins to splay, at least a portion of at least one tine  36  may move out of the housing  16  through the corresponding slot  20  in the housing  16 . As a result, the ends of the tines  36  may move apart from one another a distance greater than the diameter of the housing  16 . During splaying of the connector  18 , the tines  36  themselves may remain substantially undeformed; rather, the base  34  of the connector  18  deforms to cause the ends of the tines  36  to move apart from one another. Alternately, at least one tine  36  may deform at some point during splaying of the connector  18 . Where the connector  18  is made from a plastically-deformable material such as stainless steel, the connector  18  deforms plastically as it splays from its initial configuration to the splayed configuration. Plastic deformation is deformation that remains after the load that caused it is removed, or that would remain if the load were removed. Alternately, the connector  18  is elastically or superelastically deformable from its initial configuration to the splayed configuration. 
         [0054]    The driver  14  continues its motion to the left. Referring to  FIG. 10 , the connector  18  next encounters the portion of the driver  14  at cross-section line C-C. At this cross-section C-C, a projection  56  extends downward to a greater extent than at cross-section line B-B. The lower surface  52  of the passage  24  at cross-section line C-C may be shaped in substantially the same manner as at cross-section B-B. The shape of the projection  56  may be substantially the same as the depression  54  in the lower surface  52 , and the space between the depression  54  and the surface  53  may be substantially the same as the thickness of the base  34  of the connector  18 . The enlargement of the projection  56  in the downward direction causes the base  34  to bend to a greater degree than it did at cross-section B-B, causing the connector  18  to splay further outward. At cross-section line C-C, the connector  18  has completed splaying, such that the distal ends of the tines  36  are at their furthest point from each other. The tines  36  extend outward from the housing  16  through the corresponding slot  20 . 
         [0055]    Referring also to  FIG. 11 , as the driver  14  is moved left, the connector  18  encounters the portion of the driver  14  at cross-section line D-D. The upper surface  50  and the lower surface  52  are shaped substantially as at cross-section line C-C. However, both the upper surface  50  and the lower surface  52  are located below their positions at cross-section line C-C, because the passage  24  is sloped downward between cross-section line C-C and cross-section line D-D. The term “below” and other related terms such as “down” or “downward” are used solely for convenience, and refer to the orientation of the figures on the printed page; they do not and cannot limit the orientation or usage of the connector applicator  12 . The passage  24  may be sloped in a linear manner, in a curved manner, or in any other suitable manner. The slope of the passage  24  pushes the connector  18  downward as the driver  14  moves left past the connector  18 . Referring also to  FIG. 22 , as the connector  18  is pushed downward, the ends of the tines  36  engage heart tissue adjacent the PFO  2 . Advantageously, the PFO  2  is located between the tines  36 . The splayed configuration of the connector  18  allows capture of heart tissue across a width greater than that of the housing  16 , and maximizes the amount of tissue that can be grasped between the tines  36 . 
         [0056]    Referring also to  FIG. 12 , as the driver  14  is moved left, the connector  18  encounters the portion of the driver  14  at cross-section line E-E. The passage  24  continues to slope downward across at least part of the distance between cross-section line D-D and cross-section line E-E, pushing the connector  18  further downward and further into heart tissue in proximity to the PFO  2 . At cross-section line E-E, the driver  14  is shaped to begin to close the connector  18 . The lower surface  52  now extends across only a portion of the lateral width of the driver  14 , providing room for the tines  36  to move inward. The lower surface  52  may be substantially centered laterally. Alternately, the lower surface  52  may be configured in any other suitable manner. Referring also to  FIGS. 6-7 , at this cross-section line E-E, the lower surface  52  of the passage  24  may be characterized as the upper surface of an anvil  62  formed in the driver  14 . The upper surface  50  now is shaped to have two downward-extending projections  58 , one at or in proximity to each lateral edge of the passage  24 . Between the projections  58 , the upper surface  50  may extend upward. Advantageously, the upper surface  50  includes a center projection  60  substantially centered between the lateral edges of the passage  24 , and extending downward lower than the projections  58 . Alternately, the center projection  60  is located differently, or extends downward a different length. Alternately, the upper surface  50  is configured in any other suitable manner. As the connector  18  encounters the portion of the driver  14  at cross-section line E-E, the projections  58  begin to deform the tines  36  about the lower surface  52 . The center projection  60  holds the base  34  of the connector  18  between itself and the lower surface  52 . The lower surface  52  prevents downward motion of the connector  18  as a whole, such that the downward force exerted on the splayed tines  36  by the projections  58  causes those tines  36  to rotate about the lower surface  52  and begin to close the connector  18 . As the connector  18  closes, the tines  36  move closer to one another, compressing tissue between them.  FIG. 12A  shows the connector  18  beginning to close. 
         [0057]    Referring also to  FIG. 13 , as the driver  14  is moved left, the connector  18  encounters the portion of the driver  14  at cross-section line F-F. The lower surface  52  of the passage  24  at cross-section line F-F may be substantially the same as at cross-section line E-E. At cross-section line F-F, the connector  18  is closed completely, and the lower surface  52  may be configured substantially as at cross-section line E-E to facilitate its use in closing the connector  18 . Alternately, the lower surface  52  may be configured in any other suitable manner. The projections  58  extend downward further than at cross-section line E-E, and may extend to a location below the lower surface  52 . The projections  58  increase their downward length from cross-section line E-E to cross-section line F-F, thereby continuing to exert a downward force on the connector  18 . The connector  18  continues to deform about the lower surface  52  as a result, to a configuration such as shown in  FIG. 13A . The tines  36  may stop their motion about the lower surface  52  before encountering each other when the connector  18  has reached the closed position, such as shown in  FIG. 13A . Alternately, the tines  36  may pass one another before the connector  18  reaches the closed position. The center projection  60  continues to provide stability to the connector  18  as it deforms to the closed position. 
         [0058]    Referring also to  FIG. 14 , as the driver  14  is moved left, the connector  18  encounters the portion of the driver  14  at cross-section line G-G. At cross-section line G-G, the passage  24  opens up, such that the lower surface  52  is no longer present. That is, the anvil  62  has ended before the cross-section line G-G of the driver  14 . Thus, the connector  18  is no longer restrained from moving completely out of the housing  16  through the corresponding slot  20 . That is, the connector  18  has been released. The upper surface  50  may include projections  58  at its lateral edges to push the closed connector  18  out of the slot  20 . Alternately, the force holding the closed connector  18  to tissue is greater than any frictional force holding the connector  18  to the connector applicator  12 , such that the connector  18  is released from the connector applicator  12  at a later time when the connector applicator  12  is moved away from the PFO  2 . Finally, as the driver  14  is moved left, referring also to  FIG. 15 , the passage  24  is no longer present in the driver  14  at cross-section line H-H. This transition in the shape of the driver  14  can act to eject the connector if it has not already moved out of the slot  20 . Between cross-section line G-G and cross-section line H-H, the passage  24  extends downward, whether linearly, in a curved manner, or any other suitable manner. This downward extension of the passage  24  before the passage  24  disappears completely ejects the closed connector  18  from the housing  16  through the corresponding slot  20 , because no space remains in the lumen  22  of the housing  16  to receive the base  34  of the connector  18 . 
         [0059]    Referring also to  FIGS. 19A and 22 , as the driver  14  is moved relative to the housing  16  by actuation of the control wire  32 , the connectors  18  are deployed sequentially. As a result, different connectors  18  may be in different states of deployment simultaneously. For example, one or more connectors  18  may be moving toward or in the splayed configuration at the same time that one or more connectors  18  may be moving toward the closed configuration. The sequential splaying and closing of the connectors  18  results from the configuration of the driver  14  and the motion of the driver  14  relative to the connectors  18 . Alternately, the driver  14  is configured and moved such that the connectors  18  are deployed substantially simultaneously, rather than sequentially. 
         [0060]    Referring also to  FIG. 23 , after the driver  14  has completed its travel, the connectors  18  have all been deployed. The connectors  18  are in the closed position, straddling the PFO  2 . The PFO  2  is now closed. Advantageously, each connector  18  is spaced substantially 1 mm apart from the neighboring connector  18  or connectors  18 . Optionally, at least two connectors  18  are interconnected by a backbone  19 , as described above. Alternatively, groups of connectors  18  can be joined together with multiple backbones  19 . As an example, twelve connectors  18  can be joined together with four backbones  19 , forming four groups of three connectors  18  each. The backbone  19  acts to hold the connectors  18  together, and may provide added stability and support for a connector  18  that may engage heart tissue with less force than other connectors  18 . The connectors  18  are sized to minimize the amount of metal that is in contact with the bloodstream. Of course, the connectors  18  may be fabricated from a nonmetallic material. Similarly, where the backbone  19  is metallic, it is fabricated to be thin, in order to minimize the amount of metal in contact with the bloodstream. Alternately, the backbone  19  may be fabricated from a nonmetallic material. For example, the backbone  19  may be one or more strands of polyethylene. 
         [0061]    Referring also to  FIG. 24 , after the connectors  18  have all been deployed, the connector applicator  12  is allowed to move away from the closed PFO  2 . This may be accomplished by releasing tension on the tethers  40  and retracting the tube  28  attached to the connector applicator  12 . By releasing tension on the tethers  40 , the connector applicator  12  can be moved away from the anchors  38 . Alternately, the connector applicator  12  may be moved away from the closed PFO  2  in any other suitable manner. Referring also to  FIG. 25 , the connector applicator  12  is then pulled substantially into the lumen  46  of the sheath  44 , such as by continuing to retract the tube  28  attached to the connector applicator  12 . The connector applicator  12  may remain substantially at the distal end of the lumen  46  of the sheath  44 , may be removed completely from the sheath  44 , or may be moved to any other suitable location within the lumen  46  of the sheath  44 . 
         [0062]    Referring also to  FIG. 26 , the anchors  38  are collapsed from the second, expanded configuration back to the first, narrower configuration. The anchors  38  may be collapsed simultaneously, or at different times. This collapse may be performed in a manner opposite to which the anchors  38  were previously expanded. For example, the tension applied to at least one tether  40  may be released, allowing the corresponding anchors  38  to collapse back to the first, narrower configuration. Alternately, at least one tether  40  may be configured to allow transmission of compressive force. If so, each such tether  40  may be advanced distally, while a flexible tube or other structure connected to the proximal end of the corresponding anchor  38  holds the proximal end of the corresponding anchor  38  in place. As a result, the force exerted on the anchor  38  by the tether  40  exerts a tensile force on the anchor  38 . This tensile force causes the segments  48  of the anchor  38  between the slots to deform inward, collapsing the anchor  38  to its second, expanded configuration. This method of collapsing the anchor  38  may be advantageous where the anchor  38  is plastically deformable, rather than elastically deformable. 
         [0063]    Referring also to  FIG. 27 , the anchors  38  are then pulled through the closed PFO  2 , such as by retracting the tethers  40 . In the collapsed configuration, each anchor  38  is small enough to pass through the space between an end of the PFO  2  and the closest connector  18  and/or through the space between adjacent connectors  18 . The anchors  38  are then pulled into the lumen  46  of the sheath  44 , such as by continuing to retract the tethers  40 . The anchors  38  may remain substantially at the distal end of the lumen  46  of the sheath  44 , may be removed completely from the sheath  44 , or may be moved to any other suitable location within the lumen  46  of the sheath  44 . The sheath  44  is then removed from the patient, and the procedure is complete. Alternatively, one or more of the anchors  38  can be left in the PFO  2  as an implant. In such a case, the anchors  38  would assist in the closure of the PFO  2 . The connectors  18  would engage the anchors  38  when they are formed. The anchors  38  would then be released from the connector applicator  12 , leaving the connectors  18  and the anchors  38  in the PFO  2 . This method may be advantageous where the anchors  38  include material that would help close the PFO  2 . The vascular access incision made in the patient for insertion of the sheath  44  is closed in any suitable manner, such as by utilizing a device and method substantially as disclosed in U.S. patent application Ser. No. 11/093,003. 
         [0064]    While the invention has been described in detail, it will be apparent to one skilled in the art that various changes and modifications can be made and equivalents employed, without departing from the present invention. It is to be understood that the invention is not limited to the details of construction, the arrangements of components, the process of closing the PFO  2 , and/or the sequence of operations for closing the PFO  2  set forth in the above description or illustrated in the drawings. Exemplary steps set forth in the method for closing the PFO  2  may be omitted as the practitioner sees fit. Further, the invention is not limited to the closure of a PFO  2 . Other heart or tissue defects, such as atrial septal defects, may be closed utilizing the present invention. Statements in the abstract of this document, and any summary statements in this document, are merely exemplary; they are not, and cannot be interpreted as, limiting the scope of the claims. Further, the figures are merely exemplary and not limiting. Topical headings and subheadings are for the convenience of the reader only. They should not and cannot be construed to have any substantive significance, meaning or interpretation, and should not and cannot be deemed to indicate that all of the information relating to any particular topic is to be found under or limited to any particular heading or subheading. Therefore, the invention is not to be restricted or limited except in accordance with the following claims and their legal equivalents.