Patent Document

CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of U.S. Patent Application Ser. No. 61/080,166, filed Jul. 11, 2008. The disclosure of the prior application is considered part of (and is incorporated by reference in) the disclosure of this application. 
     
    
     TECHNICAL FIELD 
       [0002]    This document relates to materials and methods for occluding left atrial appendages. 
       BACKGROUND 
       [0003]    The left atrial appendage (LAA) is derived along with the left wall of the left atrium, which forms during the fourth week of embryonic development. The tissue making up the LAA has physiological characteristics (e.g., increased distensibility) and developmental characteristics that are distinct from the tissue in the remainder of the left atrium. The LAA is positioned in close relation to the free wall of the left ventricle. The increased distensibility and location of the LAA make it suited to function as a decompression chamber during left ventricular systole and during other periods when left atrial pressure is high. During irregular heart activity (e.g., atrial fibrillation, activity caused by mitral valve disease/damage, and the like), thrombus (blood clots) can form in the LAA. These thrombi may form due to increased stagnation of blood within the interior of the LAA. As such, removal or modification of the LAA may help to reduce the risk of thromboembolism by decreasing in size, or eliminating, the space in which blood can stagnate and later be returned into circulation. 
       SUMMARY 
       [0004]    This document provides methods and materials related to minimally invasive techniques for reducing the volume of and/or occluding the left atrial appendage. Modification of a LAA in this manner can help to reduce the risk of thromboembolism in patients with cardiac disorders. 
         [0005]    In general, one aspect of this document features an implantable device for excluding the interior volume of a left atrial appendage of a heart from the circulation. The device comprises, or consists essentially of, an expandable housing having a first surface configured to contact the epicardial surface of the left atrial appendage, wherein the first surface of the expandable housing is configured to move a portion of the wall of the left atrial appendage toward the interior of a left atrium of the heart when the housing is in an unexpanded state, and wherein the first surface of the expandable housing is configured to expand to a size that extends past the perimeter of the ostium of the left atrial appendage at least one location of the perimeter, thereby excluding the interior volume of the left atrial appendage from communication with the left atrium. The expandable housing can comprise side walls. The side walls can be expandable. The side walls can be expandable to a lesser degree than the first surface. The first surface can be circular. The first surface can be square-shaped. The first surface can be convex. The implantable device can comprise an inflatable balloon attached to the expandable housing. The implantable device can comprise a connector attached to the expandable housing. The implantable device can comprise a clamping portion attached to the connector. The clamping portion and the connector can be configured such that the clamping portion is movable along the connector toward the expandable housing. The implantable device can lack a balloon. The implantable device can comprise a suture. The first surface of the expandable housing can be configured to expand to a size that extends past the entire perimeter of the ostium. The first surface of the expandable housing can be configured to expand to a size that extends past the perimeter of the ostium at at least one location of the perimeter, thereby securing the device to the heart. 
         [0006]    In another aspect, this document features a method for reducing the interior volume of a left atrial appendage of a heart. The method comprises, or consists essentially of, (a) pressing an epicardial surface of the left atrial appendage toward the interior of a left atrium of the heart, thereby reducing the volume, (b) excluding the residual of the volume from the circulation, and (c) implanting a device configured to maintain at least a portion of the reduced volume. 
         [0007]    In another aspect, this document features a method for reducing the interior volume of a left atrial appendage of a heart. The method comprises, or consists essentially of, (a) pressing an epicardial surface of the left atrial appendage toward the interior of a left atrium of the heart under conditions such that the volume is reduced and one or more portions of the left atrial appendage extends epicardially from the heart, and (b) implanting a suture around the one or more portions. 
         [0008]    In another aspect, this document features a method for reducing the interior volume of a left atrial appendage of a heart. The method comprises, or consists essentially of, implanting a device comprising at least two opposing structures configured to clamp tissue of the left atrial appendage under conditions that reduce the volume, wherein at least one of the opposing structures is located on the endocardial surface and another of the opposing structures is located on the epicardial surface. 
         [0009]    In another aspect, this document features a method for reducing the interior volume of a left atrial appendage of a heart. The method comprises, or consists essentially of, (a) pressing an epicardial surface of the left atrial appendage toward the interior of a left atrium of the heart to form an endocardial inversion of the left atrial appendage, thereby reducing the volume, and (b) implanting a suture around the endocardial inversion from the interior of the heart. 
         [0010]    In another aspect, this document features an implantable device for reducing the interior volume of a left atrial appendage of a heart. The device comprises, or consists essentially of, an expandable housing having a first surface configured to contact the epicardial surface of the left atrial appendage, wherein the first surface of the expandable housing is configured to move a portion of the wall of the left atrial appendage toward the interior of a left atrium of the heart when the housing is in an unexpanded state, and wherein the first surface of the expandable housing is configured to expand to a size that extends past the perimeter of the ostium of the left atrial appendage at least one location of the perimeter, thereby reducing the interior volume of the left atrial appendage. 
         [0011]    Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. 
         [0012]    The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. 
     
    
     
       DESCRIPTION OF DRAWINGS 
         [0013]      FIG. 1A  is a cross-sectional view of an exemplary LAA. 
           [0014]      FIG. 1B  is a cross-sectional view of the LAA of  FIG. 1A  being deflected by an invagination device, in accordance with some embodiments. 
           [0015]      FIG. 1C  is a cross sectional view of the LAA of  FIG. 1A  with an expandable-plug-type LAA occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0016]      FIG. 1D  is a top view of the LAA of  FIG. 1A  with an expandable-plug-type LAA occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0017]      FIG. 1E  is a top view of a nitinol-mesh-type LAA occlusion device, in accordance with some embodiments. 
           [0018]      FIGS. 1F-1G  are top views of alternate embodiments of the LAA occlusion device of  FIG. 1A  employing non-circular shapes. 
           [0019]      FIG. 1H  is a cross-sectional view of an exemplary LAA. 
           [0020]      FIG. 1I  is a cross-sectional view the LAA of  FIG. 1H  being deflected by an inversion device, in accordance with some embodiments. 
           [0021]      FIG. 1J  is a cross sectional view of the LAA of  FIG. 1H  with an expandable-plug-type LAA occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0022]      FIG. 2A  is a cross-sectional view of an LAA with an expandable-disc-type occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0023]      FIG. 2B  is a cross-sectional view of an LAA with an umbrella-type occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0024]      FIG. 2C  is a cross-sectional view of an LAA with an dual-disc-balloon-type occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0025]      FIG. 2D  is a cross-sectional view of an LAA with an radially-expanding-type occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0026]      FIGS. 2E and 2F  are cross-sectional views of an LAA with a double-disc-type occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0027]      FIG. 2G  is a cross-sectional view of an LAA with an expanding-type occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0028]      FIG. 2H  is a cross-sectional view of an LAA with a nitinol-mesh-type occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0029]      FIG. 2I  is a cross-sectional view of an LAA with an patch-type occlusion device deployed against the LAA, in accordance with some embodiments. 
           [0030]      FIG. 2J  is a cross-sectional view of an LAA with an expandable-disc-type occlusion device (similar to that of  FIG. 2B  and including suture clips) deployed in the LAA, in accordance with some embodiments. 
           [0031]      FIG. 2K  is a cross-sectional view of an LAA with an endocardially deployed loop/suture around a portion of the LAA, in accordance with some embodiments. 
           [0032]      FIG. 2L  is a cross-sectional view of an LAA with endocardially and epicardially deployed anchors securing a portion of the LAA, in accordance with some embodiments. 
           [0033]      FIGS. 2M ,  2 N, and  2 O are cross-sectional views of an LAA with a nitinol-mesh-type occlusion device being deployed in the LAA, in accordance with some embodiments. 
           [0034]      FIG. 2P  is a cross-sectional view of an LAA after deflection by an invagination device, in accordance with some embodiments. 
           [0035]      FIG. 2Q  is a cross sectional view of the LAA of  FIG. 2P  with a coil-type LAA occlusion device deployed in the LAA, in accordance with some embodiments. 
           [0036]      FIGS. 3A-3B  are cross sectional views of a LAA with a dual-disc type LAA occlusion device is different stages of deployment in the LAA, in accordance with some embodiments. 
           [0037]      FIG. 3C  is a cross sectional view of a LAA with a dual-disc type LAA occlusion device including an additional securement mechanism, in accordance with some embodiments. 
           [0038]      FIG. 3D  is a cross sectional view of a LAA with a dual-disc type LAA occlusion device including an additional space-filling mechanism, in accordance with some embodiments. 
           [0039]      FIGS. 3E-3F  are cross sectional views of a LAA with dual-disc type LAA occlusion devices, in accordance with some embodiments. 
           [0040]      FIGS. 4A-4C  are cross sectional views of the LAA and occlusion device of  FIG. 3A  being deployed by a needle, in accordance with some embodiments. 
       
    
    
       [0041]    Like reference symbols in the various drawings indicate like elements. 
       DETAILED DESCRIPTION 
       [0042]    For some individuals (e.g., individuals suffering from atrial fibrillation), anatomical structures within the heart, such as a LAA, can be problematic with respect to the pooling of blood, the formation of blood clots, and subsequent damage (e.g., heart attacks, strokes, and the like) that can be caused by these clots. Reduction of the size of, or occlusion/covering of a LAA can minimize the risk of clot formation and subsequent damage caused by the formed clots. 
         [0043]    Referring now to  FIG. 1A , a left atrium  10  can include a lateral wall  12  with a LAA  20  having physiological characteristics that are distinct from the other portions of the lateral wall  12  of the left atrium  10 . Exemplary characteristics that distinguish the LAA  20  from the surrounding lateral wall  12  can include increased distensibility of the LAA, higher concentration of atrial natriuretic factor (ANF) granules, differing neuronal configuration, and the like. During normal heart function, the LAA  20  can expand and contract in synchronization with the left atrium  10 , but to a greater degree due in part to the increased distensibility of the LAA  20 . When the LAA  20  expands, an interior  22  of the LAA  20  can fill with blood, which can be emptied during subsequent contraction of the left atrium  10  and the LAA  20 . During irregular heart function (e.g., atrial fibrillation, irregular function due to mitral valve disease, or the like) blood may pool and stagnate within the interior space  22 , leading to the formation of blood clots. These clots can travel from the interior  22  of the LAA  20 , to the interior  16  of the left atrium  10 , and throughout the circulatory system, possibly resulting in heart attack or stroke. Preventing blood flow in and out of the LAA  20  by decreasing the size of, and/or occluding/covering the LAA  20  may reduce the risk of thromboembolism. 
         [0044]    In some cases, only a small amount of the LAA can be inverted ( FIGS. 1H-1J ). For example, a small portion of the LAA (as seen in  FIG. 1I ) or a large portion of the LAA (as seen in, e.g.,  FIG. 1A ) can be inverted depending upon, e.g., the type of device, the size of the device, and/or the desired treatment. In some cases, a device provided herein can be used to stiffen the lateral wall of the left atrium. 
         [0045]    Referring now to  FIG. 1B-1C , pressure can be applied to the LAA  20  through the use of an externally placed occlusion device  30 . The inversion device  30  can approach the LAA  20  from a position external to the LAA (e.g., the epicardial/pericardial space  14 ) and can apply pressure to the LAA  20  causing at least a portion of the LAA  20  to prolapse toward the interior  16  of the atrium  10  into the ostium  26 . The inversion device  30  can be designed in such a way as to minimize damage and avoid puncturing or piercing the LAA  20  when used. Once tissue  24  of the LAA  20  has been inverted into the ostium  26  (e.g., as shown in  FIG. 1B ), an occlusion device, such as a LAA occlusion plug  100 , can be placed in the LAA  20 . The occlusion plug  100  can retain the LAA  20  in an at least partially inverted position (e.g., as depicted in  FIG. 1C ), minimize or eliminate the remaining interior space  22 , and/or isolate the interior space  22  of the LAA  20  from the interior space  16  of the left atrium  10 . In the position depicted in  FIG. 1C , blood can continue to flow within the interior  16  of the atrium  10 , but may be prevented from flowing into the occluded interior space  22  of the LAA  20 . 
         [0046]    Referring now to  FIG. 1C , the occlusion plug  100  can include a “mushroom” shape with a smaller proximal portion  110  and a larger distal portion  120 . The occlusion plug  100  can be delivered to the ostium  26  and abut the at least partially inverted tissue  24  of the LAA  20  in an unexpanded state (not shown) that is smaller than the expanded state shown in  FIG. 1C . Once delivered in the unexpanded state to the ostium  26  of the LAA  20 , the occlusion plug  100  can be expanded to the state shown in  FIG. 1C . In some embodiments, when the plug  100  is transitioned to the expanded state, the LAA can be further pushed inward into the interior  16  of the atrium  10 , increasing the amount of the tissue  24  prolapsed into the interior  16  of the atrium  10  and decreasing one or more portions  28  of the LAA  20  remaining in the epicardial/pericardial space  14 . As the occlusion plug  100  expands, the cross-sectional area of the distal portion  120  can become larger than the cross-sectional area of the ostium  26 , such that portions of the inverted tissue  24  (e.g., the portions  25   a  and  25   b ) can contact the lateral wall  12  of the atrium  10 . In the case of a plug  100  that has a cross-sectional area that is circular in shape (shown in  FIG. 1D ), a ring of tissue  24  from the LAA  20  can contact a ring shaped portion of the lateral wall  12 , effectively sealing off the remaining interior space  22  of the LAA from the interior space  16  of the atrium  10 . In some embodiments, the plug  100  can include cross-sectional shapes other than circular (e.g., square, rectangular, triangular, and the like) that, when expanded, can fluidly disconnect the interior space  22  from the interior space  16 . With the interior space  22  fluidly disconnected from the interior space  16 , blood may no longer flow from the interior space  16  to the interior space  22 . If clots form within the interior space  22 , these clots may not enter the interior space of the atrium  16  to be moved throughout the circulatory system, thus minimizing the risk of heart attack, stroke, and the like, caused by embolisms formed in the interior space  22  of the LAA  20 . 
         [0047]    In some embodiments, the occlusion plug  100  is a balloon-type plug, made of an expandable, biocompatible material, that can be deployed in the area of the LAA  20  in a non-expanded state. After deployment to the LAA  20 , the occlusion plug  100  can be expanded by filling the interior under pressure. Exemplary materials that can be used to fill the interior of the plug  100  can include saline, silicone, expanding foam, a liquid polymer than can solidify when cured, and the like. In some embodiments, the plug  100  can include an expanding mechanism that biases the plug  100  to the expanded state shown in  FIG. 1C . As explained in more detail in connection with  FIG. 1D , the plug  100  can include expansion arms that bias the plug to the expanded state. Prior to deployment, the plug  100  can be stressed from the expanded state to the non-expanded state. After deployment, the force applied to transition the plug  100  to the non-expanded state can be removed, thus allowing the bias of the expansion mechanism to return the plug  100  to the expanded state. 
         [0048]    Referring now to  FIG. 1C-1D , in some embodiments, the occlusion plug  100  can have a generally cylindrical shape, with the distal end  120  having a larger diameter than the proximal end  110 . When deployed, the distal end  120  of the plug  100  can invaginate a portion of the tissue  24  such that it can completely cover the ostium  26  without encroaching on blood flow within the interior  16  of atrium or from the pulmonary veins. The plug  100  can include one or more expansion arms  140  that can bias the expansion device toward the expanded state shown in  FIGS. 1C-1D . In some embodiments, the expansion arms include a material that exhibits superelasticity when used in the patient&#39;s body. As such, the expansion arms can flexibly shift from a non-expanded state to an expanded state when deployed in the body. For example, the arms  140  may be formed from a length of nitinol wire or from a sheet of nitinol material, which has been processed to exhibit superelasticity below or at about a normal human body temperature, such as below or at about 37 degrees C. The nitinol material may comprise, for example, Nickel Titanium (NiTi), Niobium Titanium (NbTi), or the like. In some cases, the expansion arms  140  may include a metal material such as stainless steel, spring steel, titanium, MP35N and other cobalt alloys, or the like. In these embodiments, the expansion arms  140  can be formed from a material or materials that allow them to be reversibly adjustable from a non-deployed position to a deployed position. 
         [0049]    Referring now to  FIG. 1E , some embodiments of the occlusion device can include a woven nitinol disc  145 . The woven structure could be circular (as shown in  FIG. 1E ), or any other shape, examples of which are shown in  FIGS. 1F &amp; 1G . The weave pattern  147  and nitinol gauge may be selected such that the device can remain flexible and deployable (through a catheter) while being rigid enough to resist forces (e.g., the pressures exerted by the left atrium) and remain in position. As with other embodiments, the nitinol disc  145  can have an atraumatic covering (fabric, polymer, etc.). 
         [0050]    In some embodiments, the exterior surfaces of the occlusion device can include a porous, biocompatible material that can allow for tissue ingrowth. For example, the outer skin of the expandable plug can include porous polyethylene terephthalate, porous polytetrafluoroethylene, and the like. After implantation, the body can produce tissue ingrowth into the surface of the occlusion device, therefore adding additional securement to the device. 
         [0051]    Referring now to  FIGS. 1H-1J , some embodiments of the occlusion device can invert only a small amount of the LAA  20  into the interior  16  of the left atrium  10 . As depicted in previous embodiments, a large amount of the tissue of the LAA  20  can be inverted and/or manipulated such that the remaining interior volume  22  of the LAA  20  can be only a small fraction (e.g., 10%, 14%, 21%, 27%, less than half, or the like) of the original volume. In other examples, such as those shown in  FIGS. 1H-1J  can invert only a small amount of the tissue associated with the LAA  20 , such that the remaining volume  22  is greater than half of the original volume. The amount of tissue that is inverted can depend on factors such as the diameter of the ostium  26 , the size of the occlusion device, the method used to secure the occlusion device in place, the size of the involution tool  30 , and the like. 
         [0052]    In use, the occlusion device can be deployed via a catheter with a lumen capable of delivering a stabilizing catheter/sheath, performing measurements (e.g., electrograms, impedance, ultrasound, pressure, and the like) and having suction capabilities to remove and potentially recirculate blood. In some embodiments, where an intercostal approach is used, it is preferable to not puncture, pierce, or in other way damage the lung, which generally lies between the chest wall and the LAA  20 . Once the pleural space is entered, the lung can be mechanically displaced, for example, by using a deflectable paddle/sweeper-type catheter, inflating a balloon, injecting an inert gas such as helium to temporarily deflate the lung, wet gauze/cloth, and the like. In some cases, the pleural space need not be entered. For example, both the pleura and lung can be deflected away using the techniques described herein. In such cases, the need to leave a chest tube in place can be avoided. In some cases, the pleural space can be entered when there might be pleural or pericardial adhesions making it difficult to deflect the pleural space with the lung. 
         [0053]    With the lung partially out of the way, direct access to the LAA can be possible. In one example, the pleural space can be entered using a dual lumen needle, through which two flexible wires can pass. One wire can be used to place an asymmetrically expanding balloon in the pleural space. The asymmetrically expanding balloon may be biased to expand to a greater degree toward the exterior and posterior of the patient. In other words, when the balloon is expanded, it can encourage the lung to move out of the pleural space, thus leaving a working space. The second wire can be used to advance, for example, a sheath, a needle, an occlusion device, and the like into the vicinity of the LAA  20 . In another example, a balloon in front of and around an access sheath can be used to move the lung out of the way while the same sheath, having a lumen to be used with appropriate deflection, can be used to target the LAA and deploy a LAA occlusion device. In some embodiments, selective intubation of the right main bronchus can be used to deflate (wholly or partially) the left lung to allow placement of an access sheath. It would be apparent to one skilled in the art that there exist many methods of delivering an occluding device to a LAA, using a catheter, and not puncture or pierce the lung. In some embodiments, an access sheath can be coated with lung repellent substances (e.g. a wet sponge coating) and/or a tissue compatible/atraumatic coating. 
         [0054]    In some embodiments, techniques for imaging for the lung, pleural space, pericardial space, LAA, LAA ostium, and the like, can be incorporated to assist in placement of the occluding device. Exemplary forms of imaging may include direct imaging (e.g., ultrasound, CT, or the like), or indirect/inferred imaging (e.g., measuring oxygen saturation, impedance, electrical signals, and the like). For example, ultrasound may be used directly to guide the catheter. This may be two-dimensional imaging and/or Doppler (e.g., as is used to check pulses) which could be implemented in a hollow tube/sheath. In examples using Doppler, an operator can identify heart sounds blood flow when in close proximity to the LAA, and/or sounds typical of pulmonary auscultation when the lungs are in the way. When respiratory interference is audible, the patient can be instructed to exhale allowing a needle that is measuring impedance and an electrocardiographic signal to be passed through the hollow Doppler sheath or guide. This can be incorporated into a timed respiratory training for the patient who will be awake (e.g., when local anesthesia is used) to control breathing and facilitate deployment. In some examples, a side arm of the sheath can have capabilities for lung deflation, lung deflection, suction, and the like, as noted above. 
         [0055]    Referring now to  FIGS. 1F-1G , embodiments of the occlusion device can include expandable plugs, such as expandable plugs  150  ( FIG. 1F) and 160  ( FIG. 1G ) that are not generally cylindrical in shape. Expandable plug  150  can have a generally triangular shape, while plug  160  has a generally square shape. Many other shapes can be designed and utilized to cover, occlude, and/or prolapse a LAA for the purpose of preventing blood flow in and out of the LAA. 
         [0056]    Referring now to  FIGS. 2A-2L , some embodiments of the occlusion device can be used to maintain, and/or further invert, at least a portion of the LAA  20  in the interior space  16  of the atrium  10  and isolate the remaining interior space  22  of the LAA  20  from the interior space  16  of the left atrium. For example,  FIG. 2A  depicts an expandable disc  200  which can be delivered to the LAA  20 . After use of the inversion device  30 , the expandable disc  200  can be delivered to the LAA  20  in a non-expanded state (not shown), where the cross-sectional area of the expandable disc  200  in the non-expanded state is smaller than the cross-sectional area of the ostium  26 . Once in place, the disc  200  can expanded (e.g., in a way that is similar to the way in which the plug  100  is expanded), to further invert a portion of the tissue  24  of the LAA  20  and cause portions of the tissue  24  (e.g., the portions  25   a  and  25   b ) to contact the lateral wall  12 , thus effectively isolating the remaining interior space  22  of the LAA  20  from the interior space  16  of the left atrium. 
         [0057]    Referring now to  FIG. 2J , in some embodiments, the expandable disc  200  can be further secured to the atrium  10  through the use of securement devices such as sutures or clips (e.g., clips  201   a  and  202   b ). 
         [0058]    Referring now to  FIG. 2B , an embodiment of the occlusion device includes an umbrella device  210  that can include a mechanical device that can be used to transition the umbrella device  210  from a non-expanded state (not shown), where the cross-sectional area of the device  210  is smaller than the cross-section area of the ostium  26 , to the expanded state shown in  FIG. 2B , where portions of the LAA  20  can contact the lateral wall  12 , thus effectively fluidly disconnecting the remaining interior space  22  of the LAA  20  from the interior space  16  of the left atrium  10 . In this embodiment, the mechanical device can include arms  212  that are biased to the orientation shown in  FIG. 2B . During storage and/or prior to insertion, the arms  212  can be stressed into a position that increases the longitudinal length  213  of the umbrella device  210  while decreasing the cross-sectional area of the device  210  to a size that is smaller than the cross-sectional area of the ostium  26 . When deployed, the force applied to maintain the arms  212  in the stressed positions can be removed, thus allowing the bias of the arms  212  to reversibly transition the umbrella device  210  to the expanded state shown in  FIG. 2B . 
         [0059]    Referring now to  FIG. 2C , an embodiment of the occlusion device can include an occlusion device  220  that includes a combination of a mechanically expandable disc  221 , which is biased to a expanded state shown in  FIG. 2C  and a conforming/spacing filling balloon  222 . For example, after use of the inversion device  30 , the expandable disc  221  can be stressed to a non-expanded state (not shown), where the cross-sectional areas of the expandable disc  221  and the balloon  222  are smaller than the cross-sectional area of the ostium  26 , and delivered to the LAA  20 . Once in place, the disc  221  can be allowed to expand to further invert the tissue  24  of the LAA  20 . After allowing the expandable disc  221  to transition to the expanded state shown, the balloon can be inflated/expanded until portions (e.g., the portions  25   a  and  25   b ) contact the lateral wall  12 , thus effectively isolating the remaining interior space  22  of the LAA  20  from the interior space  16  of the left atrium. The conforming/space filling balloon can be expanded, for example, by filling it with saline, which will be retained within the balloon  222 . Referring now to  FIG. 2D , an embodiment of the occlusion device can include a radial expander  230  which can be retained in place through radial force applied at or within the ostium  26  of the LAA  20 . For example, the radial expander  230 , prior to placement in an LAA  20 , can be transitioned to a non-expanded state where the radial expander  230  is smaller than the space created through the use of the inversion device  30  (not shown). Once positioned, the radial expander  230  can be expanded in the radial direction (e.g., in the directions represented by arrow  231 ) to the partially expanded state shown. Continued expansion of the radial expander  230  can exert force on portions of the LAA  20  (e.g., portions  25   a  and  25   b ). The expansion of the radial expander  230  can cause portions of the LAA  20  (e.g., the portions  233   a  and  233   b ) to contact the lateral wall  12  of the atrium, thus fluidly disconnecting the interior  16  of the atrium  10  from the remaining interior  22  of the LAA  20 . In some embodiments, the radial expansion of the radial expander  230  can occur due to actuation of a mechanical expansion system, such as the turning of a screw, advancement of a ratchet system, and the like. The actuation of the mechanical system can cause the radius of the radial expander  230  to increase, thus displacing portions of the LAA  20 . In other embodiments, the radial expander  230  may include a balloon that can be expanded by filling the balloon with, for example, saline, silicone, or the like. In still other embodiments, the expander  230  can be biased by one or more mechanical devices toward the fully expanded state (not shown). In some embodiments, the radial expander  230  can be nitinol based (e.g., constructed of a nitinol mesh) such that the expander  230  is normally biased toward the expanded state. Prior to insertion, the radial expander  230  can be stressed from the expanded state to a non-expanded state where the diameter of the expander  230  is smaller than the diameter of the ostium  26 . After being positioned, the stress maintaining the device  230  in the non-expanded state can be removed, allowing the bias of the device  230  to transition it to the expanded state. 
         [0060]    Referring now to  FIG. 2E-2F , another embodiment of the occlusion device can include a double-disc system  240  delivered to the LAA  20 . After use of the inversion device  30 , the expandable discs  241  and  242  can be delivered to the LAA  20  in non-expanded states (not shown), where the cross-sectional areas of the expandable discs  241  and  242  are smaller than the cross-sectional area of the ostium  26 . Once in place, the discs  241  and  242  can expanded. The disc  241  can further invert the LAA  20 , for example, causing the inverted tissue  24  to have a diameter that is greater than that of the ostium  26 . As with the embodiment described in connection with  FIG. 2A , the expansion of the disc  241  can cause portions of the LAA  20  (e.g., the portions  25   a  and  25   b ) to contact the lateral wall  12  of the left atrium  20 , thereby fluidly disconnecting the interior  16  of the atrium  10  from the remaining interior  22  of the LAA  20 . To further secure the system  240  in place and/or increase the force sealing the LAA  20  against the lateral wall  12 , the second disc  242  can be secured against the LAA  20  and/or the lateral wall  12  through the use of an adjustment mechanism  244 . For example, the adjustment mechanism  244  may include teeth that can interact with a ratchet mechanism included in the second disc  242 . When the discs  241  and  242  are deployed to the positions shown in  FIG. 2E , force can be applied to the second disc  242  causing it to move toward the disc  241  with the direction indicated by arrow  243 , while a balancing force is applied to the adjustment mechanism  244 , maintaining the disc  241  against the lateral wall  12  of the left atrium  20 , minimizing it&#39;s impinging of the left atrial interior space. The disc  242  can be moved until reaching the position shown in  FIG. 2F . Through the combination of the adjustment mechanism  244  and the discs  241  and  242 , the discs  241  and  242  can be held in the positions shown in  FIG. 2F , thus securing the system  240  in place, minimizing the remaining interior space  22  of the LAA  20 , and fluidly disconnecting the interior space  22  from the interior space  16  of the atrium  10 . In this embodiment, the discs  241  and  242  are positioned on opposing sides of the lateral wall  12 , while still remaining epicardially in that neither disc  241  nor disc  242  contact the blood. In alternate embodiments, the system  240  can be deployed from the endocardial side. In some cases, the margins at the circumference of the disc that is more external (away from the heart; e.g., disc  242 ) can tilt towards the disc that is relatively more internal (e.g., disc  241 ). 
         [0061]    Referring now to  FIGS. 2M-2O , some embodiments of the occlusion device can include a woven nitinol device  245  that can function in a similar manner to the occlusion device described in connection with  FIGS. 2E-2F . In one example, the device  245  can be constructed of a nitinol mesh that is biased toward the deployed shape depicted in  FIG. 2O . Prior to insertion, the device can be reversibly transitioned toward the non-deployed shape depicted in  FIG. 2M , thus allowing it to be passed through, for example, a catheter lumen. Once located in the vicinity of a left atrial appendage, the catheter can be withdrawn, allowing the device  245  to begin transitioning to the deployed state.  FIG. 2N  depicts the device  245  where the distal portion  246  has been allowed to return to the deployed state, while the proximal portion  247  still remains in the non-deployed state (e.g., still within a catheter lumen). Further withdrawal of the catheter can allow the entire device  245  to transition to the deployed state shown in  FIG. 2N . 
         [0062]    Referring now to  FIG. 2G , an embodiment of the occlusion device can include an LAA invaginated segment enlarging device  250  that can be employed to increase the size (e.g., diameter) of the inverted portion of the LAA  20  to a size (e.g., diameter) that is greater that that of the ostium  26 . After use of the inversion device  30  (as described in connection with  FIG. 1B ), the enlarging device  250  can be delivered to the LAA  20  such that it abuts the inverted tissue  24  of the LAA  20  (not shown). Once in position, the enlarging device  250  can be expanded to increase the amount of inverted tissue  24  of the LAA  20  to the size shown in  FIG. 2G . As the amount of inverted tissue  24  increases, portions  25   a  and  25   b  of the inverted tissue  24  can contact the lateral wall  12 , thus fluidly disconnecting the interior  16  of the atrium  10  from the remaining interior  22  of the LAA  20 . In some embodiments, the enlarging device  250  can be expanded by introducing a fluid, such as a liquid polymer, foam, or resin into the interior  251  of the enlarging device. For example, a liquid polymer can be introduced into the interior  251  to enlarge the device  250 . Once the device  250  is enlarged to a point where the portions  25   a  and  25   b  contact the lateral wall  12 , thus fluidly disconnecting the interior  16  of the atrium  10  from the remaining interior  22  of the LAA  20 , the polymer can be allowed to cure, thus maintaining the inverted tissue  24  in substantially the position shown in  FIG. 2G  and effectively isolating the interior  22  of the LAA  20  from the blood located in the interior  16  of the atrium  10   
         [0063]    In some embodiments (depicted in  FIGS. 2P-2Q ), metal coils (e.g., platinum coils, and the like) can be injected into the LAA  20  to maintain or increase the size (e.g., diameter) of the inverted portion of the LAA  20  to a size (e.g., diameter) that is greater that that of the ostium  26 . For, the inversion device  30  can be used to invert a portion of the LAA  20  (as described in connection with  FIG. 1B ) to a size similar to that shown in  FIG. 2P . Metal coils  255  can then be delivered to the LAA  20  such that they fill up space and maintain the LAA in the inverted position. Coils can be injected until the portions  25   a  and  25   b  contact the lateral wall  12 , thus fluidly disconnecting the interior  16  of the atrium  10  from the remaining interior  22  of the LAA  20 , and effectively isolating the interior  22  of the LAA  20  from the blood located in the interior  16  of the atrium  10   
         [0064]    Referring now to  FIG. 2H , an embodiment of the occlusion device can include a nitinol expanding device  260  that can be employed to secure a portion of the LAA  20  tissue in the ostium  26  and/or fluidly disconnect the interior  22  of the LAA  20  from the interior  16  of the atrium  10 . After use of the inversion device  30  (as described in connection with  FIG. 1B ), the nitinol expanding device  260  can be delivered to the LAA  20  in an elongated, non-expanded state (similar to the elongated state depicted in  FIG. 2M ), where the cross-sectional area of the expanding device  260  in the non-expanded state is smaller than the cross-sectional area of the ostium  26 . Once in place, the expanding device  260  can be allowed to expand (e.g., by removing a surrounding catheter), from the non-expanded state, to the normally-biased, expanded state shown in  FIG. 2H . The distal portion  262  can expand to further invert a portion of the tissue  24  of the LAA  20  and cause portions of the tissue  24  (e.g., the portions  25   a  and  25   b ) to contact the lateral wall  12 , thus effectively isolating the remaining interior space  22  of the LAA  20  from the interior space  16  of the left atrium, while the proximal portion  264  can expand to fill space and help maintain the device  260  in the position shown in  FIG. 2H . 
         [0065]    Referring now to  FIG. 2I , an embodiment of the occlusion device can include a patch device  270  used to further collapse the LAA  20  into the interior  16  of the atrium  10 , thus minimizing or eliminating the interior  22  of the LAA  20 . For example, after use of the inversion device  30  (as described in connection with  FIG. 1B ), the patch device  270  can be applied to the LAA  20  such that a disc or patch  271  is abutted against at least a portion of the LAA  20  in the epicardial/pericardial space  14 . In some embodiments, one more anchors (e.g., anchors  272   a  and  272   b ) can be secured around the perimeter of the patch  271  via securing sutures (e.g., sutures  273   a  and  273   b ). After placement of the patch  271 , the anchors  272   a  and  272   b  can be inserted through the cardiac tissue of the lateral wall  12  and into the interior  16  of the atrium  10 . Once inside the atrium  10 , the anchors can abut the interior of the lateral wall  12  and, via the sutures  273   a  and  273   b , hold the patch  271  in place (e.g., in the position shown in  FIG. 2I . In some embodiments, the LAA  20  can be further inverted by tightening the sutures  273   a  and  273   b , thus further minimizing or eliminating the interior  22 . 
         [0066]    Referring now to  FIG. 2K , an embodiment of the occlusion device can include an endocardially deployed suture loop. For example, pressure can be applied to the LAA  20  through the use of the inversion device  30 , as described in  FIG. 1B .  FIG. 1B  depicts an embodiment where pressure is applied until at least a portion of the LAA  20  prolapses toward the interior  16  of the atrium  10  into the ostium  26 . However, in the embodiment described here, pressure can be applied with the inversion device  30  until the majority of the LAA  20  prolapses into the interior  16  of the atrium  10 , as shown in  FIG. 2K . An endocardial catheter  280  can deploy a loop/suture  281  around the inverted tissue  24  of the LAA  20 , as shown. As the loop/suture  281  is tightened, portions  25   a  and  25   b  of the LAA  20  are drawn toward each other in the directions indicated by arrows  282  until the portions  25   a  and  25   b  contact each other, thus substantially eliminating the interior  22  of the LAA  20  and securing the majority of the tissue  24  in the interior  16  of the atrium  10 . 
         [0067]    Referring now to  FIG. 2L , another embodiment of the occlusion device can include a set of epicardially deployed anchors  290   a  and  291   a  and a set of endocardially deployed anchors  290   b  and  291   b . For example, after use of the inversion device  30  (as described in connection with  FIG. 1B ), anchor  290   a  can be deployed from an epicardial catheter  292   a  and anchor  290   b  can be deployed by from an epicardial catheter  292   b . When tightened, as depicted by anchors  291   a  and  291   b , the anchors can secure a portion of the inverted tissue  24  of the LAA  20 , minimize or eliminate the interior  22  of the LAA  20 , and/or fluidly disconnect the interior  22  of the LAA  20  from the interior  16  of the atrium  10 . 
         [0068]    Now referring to  FIG. 3A-3D , some embodiments of an occlusion device include “clam-shell” type occluding devices which can be deployed into the epicardial and/or endocardial regions (described in greater detail in connection with  FIGS. 4A-4D ). The occluding devices can then be used to exclude the flow of blood into the interior  22  of the LAA  20  and/or to minimize or eliminate the interior  22 . 
         [0069]    Referring now to  FIG. 3A , one embodiment of a “clam-shell” occluding device  300  can include expandable discs  301   a  and  301   b  connected by adjustment member  302 . For example, the expandable disc  301   a  can be deployed in the interior  16  of atrium  10 , the expandable disc  301   b  can be deployed in the epicardial/pericardial space  14 , with the adjustment member passing through the tissue of the LAA  20 . One exemplary method of deploying the occluding device  300  will be described in more detail in connection with  FIGS. 4A-4D . Once deployed as shown in  FIG. 3A , discs  301   a  and  301   b  can be brought closer together using, at least in part, the adjustment member  302 . As the discs  301   a  and  301   b  are brought together, at least the perimeter of disc  301   a  can contact the lateral wall  12  of the left atrium  10  (e.g., at portions  13   a  and  13   b ) and the disc  301   b  can contact the tissue of the LAA  20 . Due in part to the increased distensibility of the LAA  20 , as the distance between the discs  301   a  and  301   b  is decreased, the disc  301   a  can remain substantially stationary as the disc  301   b  moves toward the disc  301   a  (in the direction indicated by the arrow  303 ), thus collapsing the LAA  20 . In some embodiments, the distance between the discs  301   a  and  301   b  can be decreased until reaching the positions shown in  FIG. 3B . In other embodiments, the discs  301   a  and  301   b  can be brought closer together and can even be brought together until the LAA  20  is fully collapsed. 
         [0070]    Still referring to  FIG. 3A , in some embodiments, surfaces  305   a  and  306   a  of the disc  301   a  and surfaces  305   b  and  306   b  of the disc  301   b  can be substantially flat. In some embodiments, however, the surfaces  305   a ,  305   b ,  306   a , and  306   b  can be curved, making them convex or concave. For example, the disc  301   a  can be curved such that the surface  305   a  facing the interior  22  of the LAA  20  is concave, while the surface  306   a  facing the interior  16  of the atrium  10  is convex. In some embodiments, the disc  302   b  can also be curved such that the surface  305   b  facing the interior  22  of the LAA  20  is concave, while the surface  306   b  facing the epicardial/pericardial space  14  is convex. 
         [0071]    Referring now to  FIG. 3C , one embodiment of a “clam-shell” occluding device can employ expandable discs that are both deployed in the epicardial/pericardial space and can be used to minimize or eliminate the interior of a left LAA, and/or fluidly disconnect the interior of the LAA  20  from the interior of the left atrium. For example, an occluding device  310  can include expandable discs  311   a  and  311   b  connected by adjustment member  312 . The expandable discs  301   a  and  301   b  can both be deployed in the epicardial/pericardial space  14  on two sides of the LAA  20 , substantially parallel to each other, but substantially perpendicular to the lateral wall  12  of the left atrium  10 . In some embodiments, the adjustment member can be a pair of sutures that connect the two discs  311   a  and  311   b  and surround, but don&#39;t penetrate the LAA  20 . In other examples, one or more sutures can connect the discs  311   a  and  311   b  and pass through the LAA  20 . Once deployed as shown in  FIG. 3C , discs  311   a  and  311   b  can be brought closer together using, at least in part, the adjustment member  312 . As the discs  311   a  and  311   b  are brought together, they can remain substantially parallel to the lateral wall  12  and contacting the LAA  20 . In some embodiments, the distance between the discs  311   a  and  311   b  can be decreased until reaching the positions shown in  FIG. 3D . In other embodiments, the discs  311   a  and  311   b  can be brought closer together, further shrinking the interior  22 , isolating the interior  22  from the interior  16  of the left atrium  10 , and/or fully collapsing the LAA  20 , thus eliminating the interior  22 . 
         [0072]    Referring now to  FIG. 3E , one embodiment of a “clam-shell” occluding device  320  can include expandable discs  321   a  and  321   b  connected by adjustment member  322 . For example, the expandable disc  321   a  can be deployed in the interior  16  of atrium  10  and the expandable disc  321   b  can be deployed in the epicardial/pericardial space  14 , with the adjustment member passing through the tissue of the LAA  20 . One exemplary method of deploying the occluding device  300  will be described in more detail in connection with  FIGS. 4A-4D . Expandable disc  321   a  can include a protrusion  323  on one side that, when deployed, can be positioned in an ostium  324  of a pulmonary vein  325 , such the upper pulmonary vein. When positioned, the protrusion  323  can help in anchoring the disc  321   a  relative to the pulmonary vein  325 . Once deployed as shown in  FIG. 3E , discs  321   a  and  321   b  can be brought closer together using, at least in part, the adjustment member  322 . As the discs  321   a  and  321   b  are brought together, at least the perimeter of disc  321   a  can contact the lateral wall  12  of the left atrium  10 , for example, at portions  13   a  and  13   b  as shown in  FIG. 3E , isolating the interior  22  of the LAA  20  from the interior  16  of the left atrium  10 . Due in part to the increased distensibility of the LAA  20 , as the distance between the discs  321   a  and  321   b  is decreased, the disc  321   a  will remain substantially stationary, with respect to the left atrium  10 , as the disc  321   b  moves toward the disc  321   a  (in the direction indicated by the arrow  326 ), thus collapsing the LAA  20 . In some embodiments, the distance between the discs  321   a  and  321   b  can be decreased to or fluidly disconnect the interior of the LAA  20  from the interior  16  of the left atrium  10  and/or minimize or eliminate the interior  22  of the LAA  20 . 
         [0073]    Referring now to  FIG. 3F , an embodiment of a “clam-shell” occluding device  300  can include a space filling device  304  that can assist in disconnecting the interior  22  of the LAA  20  from the interior  16  of the left atrium  10  and/or filling the interior  22  of the LAA  20 . After deployment of the occluding device  300 , the adjustment mechanism  302  can be used to compress the LAA  20  by decreasing the distance between the discs  301   a  and  301   b . When desired, the space filling device can be expanded to seal off the interior  22  from the interior  16  of the atrium  10  and/or minimize or eliminate the interior  22 . In some embodiments, the space filling device  304  can be biased to the expanded state depicted in  FIG. 3F . In these embodiments, prior to expanding the space filling device  304 , the space filling device  304  can be stressed into a non-expanded state for delivery. When desired, the stress maintaining the space filling device  304  in the non-expanded state can be removed, thus causing the device  304  to return to the expanded state shown. In some embodiments, the space filling device can be a structure (e.g., a balloon) that can normally be in a non-expanded state (not shown). When desired, the space filling device  304  can be filled (e.g., with saline, silicone, or the like) causing it to expand to the state shown in  FIG. 3F . 
         [0074]    In some cases, the margins at the circumference of one or more discs for a “clam-shell” device provided herein can be configured to tilt towards the other disc. For example, both discs of a “clam-shell” device provided herein can be configured such that a portion at the circumference of each disc can tilt toward a portion of the other disc. 
         [0075]    In one exemplary use, depicted in  FIGS. 4A-4C , a fine needle  400  can be used to deploy an LAA occlusion device, such as the “clam-shell” occluding device  300  around the LAA  20 . In this example, the heart can be accessed from an epicardial position using the needle  400 , which can be advanced from the intercostal space (e.g., third, fourth, or fifth between the mid-clavicular and posterior axillary lines) through the tissue  24  of the LAA  20  and into the interior  16  of the left atrium  10 . Referring to  FIG. 4A , when the tip  405  of the catheter  400  is located in the left atrium  10 , the expandable disc  301   a  can be deployed from the tip  405  until fully deployed as shown in  FIG. 4B . As the needle  400  is withdrawn from the interior  16  of the atrium  10  into the interior  22  of the LAA  20  (e.g., as depicted in  FIG. 4B ), the adjustment mechanism  302  can be deployed from the needle  400 . The disc  301   a  can be pulled back until flow into the interior  22  of the LAA  20  is excluded. As the needle  400  is withdrawn, the adjustment mechanism  302  will continue to deploy from the tip  405 . Referring now to  FIG. 4C , at a point after the needle  400  is withdrawn from the LAA  20  into the epicardial/pericardial space  14 , the expandable disc  301   b  of the occlusion device  300  can begin to be deployed from the needle  400  into the epicardial/pericardial space  14 . The two disc  301   a  and  302   b  of the occlusion device  200  can be brought closer together with a ratchet, screw, or sliding mechanism to completely exclude flow into the interior  22  LAA  20  and/or to collapse the LAA  20  until the interior  22  is minimized or eliminated. 
         [0076]    In some cases, the expandable devices provided herein can contain expandable portions that are not only radially expandable. For example, the entire device can go from being a cylinder to a cone shape with the larger diameter portion of the cone shape being internal to the ostium (but either internal or external to the atrium itself) and the point or smaller diameter portion of the cone shape being external to the ostium. Such devices can be deployed in a manner such that when the device is ratcheted or effectuated using a mechanism to expand the internal portion, the external portion can become smaller. In some cases, an unexpanded device can resemble a cylinder that, when effectuated, the device expands internally but externally as well either radially or in a fairly gradual expansion so it resembles, for example, a dumbbell. 
         [0077]    While the previous embodiments describe the application of external pressure to invert and/or obliterate a left atrial appendage, followed by securing of the appendage, similar techniques can be applied to other appendage like structures to prevent fluid communication of an interior of a structure with a main lumen or visceral cavity. Exemplary applications can include the gallbladder, appendage, diverticula, pseudoaneurysms of the ventricle, pharyngal pouches and peripheral veins, diverticulae or aneurysmally enlarged veins/varices, and the like. 
         [0078]    It is noted that a LAA occlusion device can include any of the features, improvements, and alterations disclosed herein, in any combination. 
       OTHER EMBODIMENTS 
       [0079]    It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Technology Category: a