Device for occlusion of a left atrial appendage

The invention provides a system for occluding a left atrial appendage of a patient. The system can include a ring occluder that can be positioned around the left atrial appendage and a ring applicator to position the ring occluder with respect to the left atrial appendage. The system can also provide a tissue-grasping tool that is separable from the ring applicator tool.

FIELD OF THE INVENTION

The invention relates to methods and devices for occlusion or ligation of an atrial appendage.

BACKGROUND OF THE INVENTION

Embolic stroke is the nation's third leading killer for adults. Embolic stroke is also a major cause of disability. The most common cause of embolic stroke is thrombus formation in the left appendage on the atrium. In almost all atrial fibrillation (AF) patients suffering from embolic stroke, a thrombus clot forms in the appendage of the left atrium.

The primary therapy for the prevention of stroke in AF patients is the administration of oral anticoagulants. Although somewhat effective, there are numerous side effects, including bleeding and lifestyle compromises. Pharmacological therapies (such as Warfarin®) are not well tolerated by patients. The introduction of biomaterials into the left atrial appendage has resulted in the biomaterials eventually breaking down resulting in clot formation. The left atrial appendage has been removed by others via open chest and thoroscopic surgical approaches. Such a procedure is described by Johnson in U.S. Pat. No. 5,306,234 entitled “Method for Closing an Atrial Appendage.” The '234 patent discloses a method for grasping the left atrial appendage and manipulating it into position in order to sever the tissue and remove the appendage. The wound on the heart is then sewn or clamped shut.

Appriva Medical, Inc. disclosed concepts for occluding the left atrial appendage from a percutaneous endocardial approach. In U.S. Pat. No. 6,152,144 entitled “Method and Device for Left Atrial Appendage Occlusion” assigned to Appriva Medical, a device and method for isolating the left atrial appendage from the inside of the heart is disclosed. A barrier or other device is anchored in the chamber of the left atrial appendage to prevent the passage of blood into and out of the chamber and thereby prevent clot formation. However, any foreign device left in the chamber of the heart is a potential thrombosis-generating site. In addition, biomaterials are known to eventually break down and result in clotting.

Some surgeons will remove or oversew the left atrial appendage as a concomitant procedure during other cardiac surgery. This is done under general anesthesia and may result in additional trauma to the patient.

While endoscopic or percutaneous approaches reduce the invasiveness of the surgical procedure, the above-described approaches have inherent limitations. Surgical removal of the left atrial appendage is very invasive and often results in loss of atrial hormones, such as atrial natriuretic peptide (ANP), and significant bleeding. In U.S. Pat. No. 6,666,861 issued to Grabek and entitled “Atrial Remodeling Device and Method,” a method is disclosed for applying a suture lasso placed endoscopically around the left atrial appendage to isolate it from the atrium. The '861 patent describes using either wet cauterization to remove the tissue or leaving the isolated appendage in place.

Endoscopic stapling devices, suture loops tied to the base of the appendage, and clips pinching the appendage from the outside surface to the base to close the appendage are used by physicians to isolate and remove the left atrial appendage. In U.S. Pat. No. 6,488,689 issued to Kaplan and entitled “Methods and Apparatus for Transpericardial Left Atrial Appendage Closure,” a method and apparatus to close the left atrial appendage is disclosed. The '689 patent describes using a grasper and a closing loop or clip applied to the outside of the left atrial appendage. The clip is applied extending toward the chamber of the atrial appendage and extending over the outside edge of the appendage. The clips of the '689 patent are a U-shaped metal clip, having a spring tendency to hold its shape, being deformed to open while positioned to extend over the tissue, before the clip is allowed to return to its resting shape, having the tissue pinched between the ends of the clip.

SUMMARY OF THE INVENTION

Some embodiments of the invention provide a system for occluding a left atrial appendage of a patient. Some embodiments of the system can include a ring occluder that can be positioned around the left atrial appendage and a ring applicator to position the ring occluder with respect to the left atrial appendage. The ring applicator can include a ring spreader with a spreader hinge coupled to an upper spreader jaw and a lower spreader jaw. The ring occluder can be coupled between the lower spreader jaw and the upper spreader jaw. The spreader hinge can move between an open position in which the ring occluder has a first diameter and a closed position in which the ring occluder has a second diameter, the first diameter being larger than the second diameter.

Other embodiments of the invention provide a clip occluder that can be positioned around the left atrial appendage. The clip occluder can include a clip hinge coupled to an upper clip jaw and a lower clip jaw. The clip occluder can include a clip lock. A clip applicator can position the clip occluder with respect to the left atrial appendage. The clip applicator can include a clip actuator coupled to the clip occluder by an actuator suture. The actuator suture can control a distance between the upper clip jaw and the lower clip jaw. The clip applicator can be removably coupled to the clip occluder with a retention suture.

In some embodiments of the invention, a ring applicator can include a shaft having a handle on a proximal end and a distal end, and a lumen or channel extending from the handle to the distal end of the shaft, an actuator coupled to the handle, and a ring spreader assembly on the distal end of the shaft. In one embodiment, the ring spreader assembly may include a plurality of ring expanding members. In an alternative embodiment, the ring spreader assembly may include a spreader drive wire. A ring occluder may be releasably attached to the plurality of ring expanding members or to the drive wire. The ring occluder can be stretched to an open position by the actuator which is coupled to the ring expanding members or the drive wire to allow the ring occluder to be manipulated over tissue to be occluded.

In some embodiments of the invention, the occluder member, e.g., a ring occluder or clip occluder, may comprise one or more pharmacological and/or biological agents, e.g., anti-inflammatory and/or anti-arrhythmic agents and/or drugs. In some embodiments, the occluder member may include a fabric covering.

DETAILED DESCRIPTION

FIG. 1illustrates an outline of the atrium10of the heart with the left atrial appendage12protruding therefrom.FIG. 1also illustrates one embodiment of an occluder14forming a ring16that is placed in a position to surround the left atrial appendage12adjacent to a left atrial appendage base18, where the left atrial appendage12is attached to the heart20. In some embodiments, the ring16can be constructed of an elastic material to allow it to be stretched into an open position, as shown inFIG. 1. The ring16can be allowed to return to a closed position, as shown inFIG. 2, to bear against the tissue of the left atrial appendage12in order to close off any interior connection between the atrium10and the left atrial appendage12.

FIG. 3illustrates the ring16attached to a patient's heart20to isolate the left atrial appendage12from the atrium10. In some embodiments, the material of the ring16can be biocompatible to allow the ring16to be left on the heart20permanently. Optionally, the ring16may have tissue engaging surfaces for enhanced positionability and/or tissue engagement. The tissue engagement surfaces may comprise bumps, detents, grooves, ridges, ribs or the like. The ring16may also include biocompatible coatings for any of the predetermined purposes disclosed herein. The biocompatible coatings may include a pharmacological agent (e.g. a controlled-release agent) for purposes of encouraging tissue ingrowth, affording local apoptosis for therapeutic reasons, local necrosis, revascularizationi, arrhythmia control, infection control, anti-bacterial, fluid balance (i.e. atrial natritic peptide replacement), etc.

FIG. 4illustrates different relative sizes of rings16that can be used to accommodate different anatomy requirements of the patient. In one embodiment, the ring16can be manufactured with radio opaque qualities, such as micro-sized glass beads26molded into the material of the ring16. Alternatively, the ring16can be made radio opaque by the addition of glass or metallic fibers28in the material of the ring16. In some embodiments, the ring16can be entirely biocompatible to allow for use for the life of the patient. The ring16can have size variations in its inner diameter30along a contact surface32. The ring16can also have different cross-sectional shapes, such as oval, rectangular, square, etc.

To apply the ring16to a patient, a ring applicator34, as shown inFIG. 5, can be used. In some embodiments, the ring applicator34can include a shaft36with a handle38on a proximal end and a ring spreader40on a distal end. The ring spreader40can include an upper spreader jaw42and a lower spreader jaw44, each connected to a spreader hinge46. A jaw actuator48on the handle38can include a knob50.

In some embodiments, the spreader hinge46can include a four-bar assembly52for use in moving the upper spreader jaw42and the lower spreader jaw44substantially in parallel. The four-bar assembly52can include a first distal link54and a second distal link56, as shown inFIG. 6. The first distal link54can include a distal end pivotally attached to the upper spreader jaw42at a top distal pivot58. The second distal link56can include a distal end pivotally attached to the lower spreader jaw44at a lower distal pivot60. The first distal link54can include a proximal end pivotally attached to the shaft36and to a proximal end of the second distal link56at a distal shaft pivot57. As a result, the first distal link54can be pivotally linked to the second distal link56.

The ring spreader40can be moved from a relaxed closed position (as shown inFIG. 9A) having the upper spreader jaw42in close proximity to the lower spreader jaw44to an open position (as shown inFIGS. 8,9B, and9C) by the jaw actuator48. In the open position, the upper spreader jaw42can be spaced from the lower spreader jaw44by a larger distance than in the closed position.

In some embodiments, as shown inFIG. 6, the ring16can be removably attached to the ring spreader40by one or more sutures tied between the handle38and the ring16. In one embodiment, the ring16can be tied on the front, back, top, and bottom to uniformly open the ring16for application to a tissue appendage. A front suture66and an upper suture68can be attached to the jaw actuator48and can loop inside the shaft36to the upper spreader jaw42and around the ring16at spaced intervals. A proximal suture70and a lower suture72can be similarly attached to the jaw actuator48and can extend inside the shaft36to the lower spreader jaw44and around the ring16at spaced intervals.

As shown inFIG. 6, the upper spreader jaw42can include a first feed slot74having a first distal aperture75extending through the upper jaw42and a first upper aperture79extending through the upper jaw42. The first upper aperture79can be disposed between the first distal aperture75and the spreader hinge46. The upper spreader jaw42can include a return slot76parallel to the first feed slot74. The return slot76can include a second distal aperture77in proximity to the first distal aperture75and a second upper aperture81in proximity to the first upper aperture79. In some embodiments, the first and second upper apertures79and81can both extend through the upper jaw42.

As shown inFIG. 7A, the lower spreader jaw44can include a similar configuration to the upper spreader jaw42. The lower spreader jaw44can include a second feed slot65with a first lower aperture67and a first proximal aperture69. The first proximal aperture69can be disposed between the first lower aperture67and the spreader hinge46. A second return slot71can be formed on the lower spreader jaw44substantially parallel to the second feed slot65. The second return slot71can include a second lower aperture73in proximity to a first lower aperture67and a second proximal aperture53in proximity to the first proximal aperture69. The second proximal aperture53can be disposed between the spreader hinge46and the second lower aperture73.

The feed slots65,74can be used to direct the sutures attached at the handle38to the jaw actuator48. The sutures66,68,70,72can be directed along the spreader jaws42,44and directed to pass through the spreader jaws42,44at the apertures67,69,75,79. The sutures can66,68,70,72then loop around the ring16at predefined locations. The sutures44,42can also pass through the apertures53,73,79,81and along the return slots71,76to return through a lumen to attach to the jaw actuator48. The front suture66can have a first end attached to the jaw actuator48. The front suture66can extend through the handle38, along the first feed slot74, through the first distal aperture75, and around the ring16in a single loop defining the front portion of the ring16. The front suture66can also extend back through the second distal aperture77, along the first return slot76, and through the handle38to a second end connected to the jaw actuator48. Likewise, the upper suture68can extend through the handle38, along the first feed slot74, through the first upper aperture79, and around the ring16in a single loop defining the upper portion of the ring16. The upper suture68can also extend back through the second upper aperture81, along the first return slot76, and through the handle38to a second end connected to the jaw actuator48.

The lower suture72can have a first end attached to the jaw actuator48. The lower suture72can extend through the handle38, along the second feed slot65, through the first lower aperture67, and around the ring16in a single loop defining the lower portion of the ring16. The lower suture72can also extend back through the second lower aperture73, along the second return slot71, and through the handle38to a second end connected to the jaw actuator48. Likewise, the proximal suture70can extend through the handle38, along the second feed slot65, through the first proximal aperture69, and around the ring16in a single loop defining the proximal portion of the ring16. The proximal suture70can also extend back through the second proximal aperture53, along the second return slot71, and through the handle38to a second end connected to the jaw actuator48.

FIG. 7illustrates a torque screw82having a hex end84channeled in the handle38and attached to the jaw actuator48, according to one embodiment of the invention. When the knob50is rotated, the torque screw82can rotatably traverse to move the hex end84in the handle38toward the ring spreader40or toward the knob50, depending on which direction the knob50is rotated. The sutures66,68,70,72can be attached to the hex end84using knots and can extend to loop around the ring16in the ring spreader40. As the knob50is turned to traverse the hex end84away from the ring spreader40, the sutures66,68,70,72can tighten to bear against the ring16and the spreader jaws42,44in order to overcome the elasticity of the ring16and move the spreader jaws42,44to the open position, as shown inFIGS. 8 and 9C. The spreader jaws42,44can be guided in a substantially parallel path by the four-bar assembly52in order to stretch the ring16to the open position. In some embodiments, the hex end and the torque screw82are replaced by a linear trigger grip. By squeezing the grip handle, the spreader jaws are spread as described above.

In some embodiments, as shown inFIGS. 9A-9C, the spreader hinge46can include a top proximal link86and a lower proximal link88. The top proximal link86can include a first end pivotally attached to the shaft36and a second end pivotally connected to the upper spreader jaw42. The lower proximal link88can include a first end pivotally connected to the shaft36and a second end pivotally connected to the lower spreader jaw44. The proximal links86,88can function with the distal links54,56to move the upper spreader jaw42in a substantially parallel relationship with respect to the lower spreader jaw44.

The sutures66,68,70,72can act as a retainer to hold the ring16in the ring spreader40. The sutures66,68,70,72can also act as a portion of the jaw actuator48by pulling the ring spreader40toward the handle38to force the spreader hinge46to pivot at the four-bar assembly52, causing the spreader jaws42,44to spread away from one other and stretching the ring16open. The sutures66,68,70,72can open the ring16into a substantially rectangular shape as shown inFIG. 9C.

As shown inFIG. 10, a left atrial appendage chamber94can be positioned within a locking clip96in an open position.FIG. 11illustrates the chamber94compressed by the locking clip96in the closed position. The locking clip96can include a lower clip jaw118made of an elastic material and an upper clip jaw124connected to the lower clip law118at a clip hinge122. In one embodiment, the locking clip96can be formed from a single piece of elastic material120and can define the clip hinge122integrally with the lower clip jaw118and upper clip jaw124. The locking clip96can also include a clip lock126(e.g., such as a clip barb128) on the upper clip jaw124, that is adapted to engage the lower clip jaw118at a lock receiver130to substantially permanently affix the upper clip jaw124to the lower clip jaw118.FIGS. 12 and 12Aillustrate an application of the locking clip96on a patient's heart.

FIG. 13illustrates one embodiment of a clip applicator98for delivering a locking clip96into a patient through an incision in a closed-chest routine. The clip applicator98can include a shaft36having a handle38on a proximal end, a clip actuator108on the handle38, and a locking clip96coupled to a distal end.

The clip actuator108can be used to move the locking clip96from an open, unlocked position to a closed, locked position. The clip actuator108can include an actuator suture110having a first end attached to the handle38and extending through a lumen112(as shown inFIG. 14) in the handle38. The actuator suture110can engage the locking clip96through a first feed aperture119in the lower jaw118and can extend through a first actuator aperture125in the upper clip jaw124of the locking clip96. The actuator suture110can loop over the upper clip jaw124and can pass through a second actuator aperture123in the upper clip jaw124. The actuator suture110can also extend through a second feed aperture117in the lower jaw118and back through the handle38to a second end attached to the clip actuator108. Alternatively, the actuator suture110can be looped outside the handle38, so that the operator can pull the actuator suture110manually to draw the upper clip jaw124to engage the lower clip jaw118when the locking clip96is in position to engage the left atrial appendage12.

The first feed aperture119can be positioned through the lower clip jaw118to allow the actuator suture110to pass through the lower clip jaw118to the upper clip jaw124. The upper clip jaw124can include the first and second actuator apertures125,123that can allow the actuator suture110to loop around the upper clip jaw124, while retaining a position near the clip lock126on the upper clip jaw124. The clip actuator108can be a movable actuator, similar to the torque screw assembly on the ring applicator shown inFIGS. 7 and 8, or alternatively, a thumb slide or lever. The clip actuator108can pull the actuator suture110to engage the locking clip96by pulling the upper clip jaw124into engagement with the lower clip jaw118at the clip lock126. The actuator suture110can include a first end coupled to the clip actuator108. The first end can extend through the lumen112passing through the lower jaw118to loop around the upper clip jaw124and back through the lower clip jaw118to terminate at the handle38. In this manner, the clip actuator108can bear against the actuator suture110to pull on the open end of the upper clip jaw124and to overcome the spring tenancy of the clip hinge122in order to draw the upper clip jaw124into a locking engagement with the lower clip jaw118.

The lower clip jaw118can include an engagement connection121to releasably connect the locking clip96to the clip applicator98with a retention suture111(as shown inFIG. 14). The retention suture111can removably attach the locking clip96to the clip applicator98. The retention suture111can include a first end coupled to the handle38. The first end can extend from the handle38to the locking clip96to releasably engage the lower clip jaw118. As shown inFIG. 14, the retention suture111can loop into an engagement portion121of the lower clip jaw118so that the retention suture111may be cut at one end. The retention suture111can be cut at the handle38to draw the retention suture111out of the patient and remove the clip applicator98, while leaving the locking clip96attached to the lower atrial appendage12. As shown inFIG. 15, the engagement connection121can include an aperture in the lower clip jaw118, adjacent the clip lock126, that can allow the retention suture111to pass into and around a portion of the lower clip jaw118and back to the handle38.

As shown inFIGS. 14-17, a clip stop114and two alignment pins116can be attached to a distal end of the handle38. The lower clip jaw118can include one or more receivers (not shown) to receive the alignment pins116in order to hold the locking clip96in alignment with the shaft36and to prevent rotation of the locking clip96with respect to the shaft36. The clip stop114can include a retractable element in the shaft36that can extend out to a position between the lower clip jaw118and the upper clip jaw124. The clip stop114can extend out to engage the locking clip96as the clip applicator98and the locking clip96are passed through a lumen, tube, or endoscope, while the operator is inserting the locking clip96into a patient, in order to prevent the locking clip96from inadvertently locking. After insertion through the lumen, the clip hinge122can bear against the clip jaws118,124to open the locking clip96for positioning around the base of the left atrial appendage12or other target tissue, and the clip stop114can be retracted into the shaft36.

FIG. 16illustrates the clip96in an insertion position in which the clip stop114is removably engaged between the upper clip jaw124and the lower clip jaw118. The insertion position can help prevent the clip lock126from engaging as clip applicator98and the locking clip96are passed into a patient's chest through an incision (possibly in a cannula or endoscope). The clip actuator108can be used to pull the actuator suture110to move the clip stop114into the shaft36away from the clip jaws118,124. The clip actuator108can bring the clip jaws118,124into a position to lock the clip lock126and to hold the locking clip96in a locking position, as shown inFIG. 16.

As shown inFIG. 17, the locking clip96can be disengaged from the clip applicator98by cutting the retention suture111at the handle38and drawing the retention suture111out of the clip applicator98. Likewise, the actuator suture110can be released from the clip actuator108, can be cut, and can be pulled out of the patient and from the clip applicator98. The locked locking clip96can releasably slide off of the alignment pins116and can remain attached to the left atrial appendage12when the clip applicator98is removed.

FIGS. 18-20illustrate one embodiment of an occluder including a clamp with a first pressure plate152and a second pressure plate154. The first and second pressure plates152,154can each have one or more end holes151. A ratcheting mechanism can include teeth155on connector rods153and a receiver157for receiving the connecting rod153and engaging the teeth155to substantially permanently hold the plates152,154in spaced relation to one other in order to isolate the chamber of the left atrial appendage12. As shown inFIG. 20, the receivers157can be positioned onto the connector rods153extending from the second pressure plate154. The receivers157can bear against the first pressure plate152to hold the plates152,154in a predefined spaced relation. As shown inFIG. 21, the ends of the connector rods153extending from the receivers157can be clipped off after the desired claming is achieved.

FIGS. 21-22illustrate one embodiment of an occluder in which the pressure plates152,154can be configured with a tie channel156passing through each plate152,154from one end to another. A tie158can be passed through the tie channels156to connect the first and second plates152,154together. The plates152,154can be positioned to clamp down on the base of the left atrial appendage12to close off the left atrial appendage chamber94.

FIGS. 23-29illustrate one embodiment of a loop clip174and a loop clip applicator172for engaging the left atrial appendage at its base in order to close the chamber of the left atrial appendage. The loop clip174can include a lower clip jaw176and a loop178. The loop178can include a fixed end187attached to the lower clip jaw176and teeth182that extend to a slidable end185. The loop178can engage the lower clip jaw176at a clip lock183to substantially permanently clamp by bearing against tissue trapped between the loop178and the lower clip jaw176.

FIG. 26illustrates an actuator attachment180that can include a retention suture111extending from the handle38to an engagement portion177on the loop clip174. The engagement portion177can include an aperture through the loop clip174to allow the retention suture111to extend from the handle38, through the shaft36around the engagement portion, and back to the handle38. The retention suture111can releasably retain the loop clip174on the loop clip applicator172, until the loop clip174is secured around the left atrial appendage. The retention suture111can be cut at one end and drawn out of the patient to leave the loop clip174engaged.

FIG. 24illustrates an actuator suture110attached to the slidable end185of the loop clip174. The actuator suture110can be removably attached to the slidable end185of the loop178by looping through an actuator aperture180. The fixed end187of the loop178can be attached to the lower clip jaw176while the remainder of the loop178having teeth182can slidably engage the clip lock183.

As shown inFIG. 27, the loop clip174can be attached to the loop clip applicator172and maintained in an insertable position. The loop clip174and the shaft36can be inserted into the patient's chest to bring the loop178to a position adjacent the left atrial appendage12. The loop clip174can be manipulated to a position where the lower jaw clip176is adjacent the base of the left atrial appendage12and the loop178extends around the left atrial appendage12. The actuator suture110can be attached to an actuator108, which can include a knob50and a torque screw82, as shown inFIG. 23. The knob50can be turned to traverse the hex head of the torque screw82to bear against the actuator suture110in order to pull the slidable end185of the loop178through the clip lock183where the teeth182can be engaged by the lower jaw clip176to substantially permanently hold the loop178in position. The knob50can be turned until the loop178is pulled as tight as desired against the tissue of the left atrial appendage12in order to isolate the chamber from the atrium. Alternatively, the actuator suture110can be looped outside the handle38to be pulled manually by the operator to lock the loop clip174in relation the lower clip jaw176. Other embodiments of the actuator108can include a linear trigger grip, a linear slider, etc.

As shown inFIG. 28, the loop clip174, which is shown in a position for encircling and occluding the left atrial appendage to close the chamber94, can be disengaged from the loop clip applicator172by cutting one end of the retention suture111and pulling the retention suture111from around the engagement portion177and out of the patient's body. As shown inFIG. 28, the loop178can be engaged by the teeth182to the lower clip jaw176to a closed position. The loop178can be disengaged from the loop clip applicator172by cutting one end of the actuator suture110and pulling the actuator suture110through the actuator aperture180and out of the patient.

Some embodiments of the invention provide a tool designed to place a ring-style left atrial appendage occlusion device. The tool can include a handle with a long neck. An upper and a lower jaw can be attached to the handle with a four-bar assembly on a distal end and a knob50and a torque screw82on a proximal end. Some embodiments of the tool can include four separate sutures (2 front and 2 rear) that can loop around a ring and then into the upper and lower jaws. The sutures can be positioned in slots on outside edges of the upper and lower jaws and down into the handle. A retaining suture can be positioned through the lower jaw of a ring into a distal end of the handle, and the loop can be completed outside a proximal end of the tool. The retaining suture can be used to pull and then hold the ring tight against the distal end of the handle. Two holes can be positioned in an end of the lower jaw of the ring. Alignment pins can be inserted into the two holes to help hold and position the ring. After routing through the handle, the retaining suture can be positioned into the hex end of the torque screw and through to the other side where the retaining suture are then tied off.

According to some embodiments of a method of the invention, a port can be placed in the patient's chest so that when the ring is placed and opened, the left atrial appendage can be pulled into the opening with a grasper, a vacuum source (e.g. a cone), an adhesive tool tip, a cryo device for temporarily sticking to tissue, etc. A neck of the tool can include articulation to aid in placement of the ring. A distal end of the tool can be guided through the port and placed near the left atrial appendage. As the torque screw is turned, the upper and lower jaws open parallel to one another. Continuing to turn the torque screw stretches the ring open. Other methods of actuation can be used to pull the sutures, such as a trigger, slider, etc. When the ring is fully opened, the left atrial appendage can be pulled between the upper and lower jaws until properly located. The torque screw can be turned in the opposite direction to release tension on the sutures and relax the ring around the left atrial appendage. The torque screw can be tightened and relaxed multiple times, if necessary to achieve proper placement. Once the ring is properly positioned, the sutures can be cut (either near the ring or on a proximal end of the tool) to release the ring, and the tool can be retracted. An inside edge of the port can be used to close the upper and lower jaws so the tool can be removed.

Other embodiments of the invention provide a tool designed to place a clip-style left atrial appendage occlusion device. The clip can be a rigid one-piece clip with a snap-in lock on one end. The clip can also include a living hinge that is spring biased open on the other end. However, other embodiments of the tool can be used with other types of rigid clips, as well as a different hinge or latching mechanism. The tool can include a handle with a long neck. Two separate suture loops can be positioned along the length of the handle inside the neck. A stop on a distal end of the tool can be actuated on a proximal end of the tool. An actuation suture can be positioned through an upper clip jaw of the left atrial appendage clip, then through a lower clip jaw, into a distal end of the handle and complete a loop outside a proximal end of the handle. A port can be created in the patient's chest such that when the clip is positioned near the left atrial appendage, the left atrial appendage can be pulled between the upper and lower clip jaws with a grasper. The neck on the tool can articulate to aid in placement of the clip. The stop can be placed in its forward position to keep the upper clip jaw from latching while pushing it through the port. The clip can spring open after it has passed through the port. The handle can be used to position the clip near the left atrial appendage and the left atrial appendage can be pulled between the upper and lower clip jaws with a grasper. Once the clip is positioned on the left atrial appendage as desired, a stop actuation knob50can be pulled back to retract the stop. The actuation suture can be pulled (or actuated with a trigger, slide, screw, etc.) until the upper clip jaw snap latches into the lower clip jaw. The left atrial appendage is then occluded. The sutures can be cut and pulled through the handle, which can release the clip. The sutures can be cut with a scalpel, scissors, or other surgical instruments, or the sutures can be cut with a mechanism that is built into the tool itself. The tool can then be removed from the port.

Some embodiments of the invention provide a tool designed to place a loop-clip style left atrial appendage occlusion device. The tool can include a handle with a long neck. The tool can include two separate suture loops that can be positioned through the length of the handle and a shaft. The tool can include a knob50and a torque screw on a proximal end of the handle and the shaft. The loop clip174can include a rigid base with a flexible loop that can include one-way teeth molded into it. The loop can wrap around one end of the rigid member and through a slot with a locking snap (like a cable tie). This allows the loop to be pulled in, but not release. The end of the loop can include a hole that a suture can be routed through. The suture can be positioned into the distal end of the placement device, can be positioned through the handle, into the hex end of the torque screw, and tied off on an opposite end. A retaining suture can be positioned through a hole in an end of the loop clip, then into a distal end of the placement device, positioned through the handle, and tied off on a proximal end of the tool. The retaining suture can be used to pull and hold the loop clip tight against a distal end of the handle. An alignment boss on an end of the handle can be inserted into a matching slot on the loop clip to ensure proper alignment. A port can be created in the patient's chest so that when the loop clip is positioned, the left atrial appendage can be pulled between the loop and the base with a grasper. The neck on the placement tool can articulate to aid in placement of the loop clip. The flexible loop can be pushed down to place the loop clip through the port, then once it is through, the loop can return to its original shape. The handle can be used to position the loop clip near the left atrial appendage and the left atrial appendage can be pulled inside the loop with a grasper. Once the loop clip is positioned on the left atrial appendage as desired, turning the torque screw can gradually tighten the loop (a trigger, slide, etc. could also be used to tighten the loop). The torque screw can be turned until the loop is tight enough to occlude flow and remain securely placed. After the loop is tight enough, the actuation suture and the retaining suture can be cut and pulled through the handle. The tool can then be removed from the port.

Some embodiments of the invention include a device and method for occlusion or ligation of an atrial appendage or other tissue. The method and applicators disclosed herein describe a minimally-invasive approach to ligation of an atrial appendage, specifically, of the left atrial appendage of patients with atrial fibrillation. Some embodiments of the invention include a method and apparatus to access the left appendage through a small incision and the use of a delivery tool to apply an occluder to the appendage. The tool can be used to grasp the appendage to help stabilize the appendage to allow for application of the ligation device. The ligation device may be applied and left behind as a permanent implant.

Some embodiments of the invention include a device and procedure that can occlude the left atrial appendage from the body of the left atrium—thereby substantially preventing the formation of a clot within the appendage and a subsequent embolism. Some embodiments of the invention include an implantable device and applicator for substantially permanently occluding the left atrial appendage. Some embodiments of the invention include a device and procedure that is minimally invasive to apply a device as a simple and quick method to deliver therapy to prevent embolic strokes. Some embodiments of the invention include a device and procedure that does not require the use of blood-contacting biomaterials. Some embodiments of the invention include a device and procedure that results in tissue necrosis at the left atrium/left atrial appendage junction that is necessary to help prevent reentry. Some embodiments of the invention include a device and procedure that places a device to occlude while preserving the tissue of the left atrial appendage for the production of atrial hormones. Some embodiments of the invention include a device and procedure with a substantially permanently-implanted clamp used for occluding the left atrial appendage. Some embodiments of the invention include a device and procedure that is applied from the exterior of the heart, which may be accessed by a sternotomy, thorocotomy, minimally invasive, endoscopic or other means. Some embodiments of the invention include a device and procedure that may be practiced by a number of different embodiments of the clamping mechanism as disclosed herein.

FIG. 30illustrates a device200for ligation of an atrial appendage. The device200can include a ring applicator or delivery tool202and an occlusion member or ring214. In one embodiment, the occlusion ring214can be made of a30A durometer silicone rubber, although other hardnesses of silicone or other materials, such as polyurethane can be used. The ring214can be covered with a material such as Dacron® polyester to promote tissue ingrowth or prevent ring slippage after placement or to spread the load bearing surfaces of the ring. The ring214can be generally expandable for placement around the atrial appendage. The delivery tool202can be used to expand the ring214. The delivery tool202can include a shaft220and a handle230coupled to shaft220. The delivery tool202can be sized for reaching an atrial appendage through an opening in the patient's chest, for example, through a sternotomy or thoracotomy. The delivery tool202can include a tissue-grasping member210. The tissue-grasping member110can be a mechanical grasping member, for example, hooks, barbs, or graspers, or it can be a suction grasping member (as shown inFIG. 30), or it can be an adhesive. The delivery tool202can include one or more suction lumens fluidly coupled to suction grasping member210. The suction lumens can pass through the shaft220and/or handle230, or portions thereof. The suction grasping member210can be coupled to a suction source. The tissue-grasping member210can be used to grasp the atrial appendage and pull it through ring214. In one embodiment, the tissue-grasping member210can be moved distally and/or proximally relative to shaft220. In one embodiment, the delivery tool202can include a mechanism for controllably moving the tissue-grasping member210. This mechanism can be located at or near the handle230.

The delivery tool202can include a ring spreader240having ring-expanding members242used to hold and expand the ring214. The ring spreader240can be coupled to a distal end of shaft220. In one embodiment, the delivery tool202can include multiple ring-expanding members242, for example, four, as shown inFIG. 30. Alternatively, the delivery tool202can include three or five expanding members242, for example. The ring214can be releasably coupled or attached to a distal end of ring-expanding members242, for example, via one or more sutures250. The sutures250can loop around the ring214. The ends of the sutures250can pass through one or more lumens within the ring expanding members242, the shaft220, and the handle230. In one embodiment, one or more portions of the sutures250can be exposed at or near distal or proximal ends of the handle230. For example, portions of sutures250can be exposed at a suture cutting location270. Exposure of the sutures250at or near the handle230can enable the release of the ring214from the delivery tool202remotely. In one embodiment, the sutures250can be cut and removed, thus releasing the ring214from the delivery tool202. Cutting the sutures250can release the ring214from the ring-expanding members242. In one embodiment, the delivery tool202can include one or more suture cutting members.

As shown inFIG. 30, the handle230can include a ring expansion mechanism260used to control the expansion of the ring214. The ring expansion mechanism260can be coupled to the ring-expanding members242. The ring expansion mechanism260can control movement of the ring expanding members242from a closed or collapsed configuration to an open or expanded configuration, as shown inFIG. 30. In one embodiment, the ring expansion mechanism260can include a screw mechanism. The ring expansion mechanism260can control movement of the ring-expanding members242into and out of shaft220. The pulling of the ring-expanding members242into the shaft220can collapse the ring-expanding members242into a closed configuration. The pushing of the ring-expanding members242out of the shaft220can expand the ring-expanding members242into an open configuration. The ring-expanding members242can be spring biased into an open expanded configuration. In one embodiment, the ring expansion mechanism260can be located at or near distal or proximal ends of the handle230. In one embodiment, the ring expansion mechanism260can include one or more knobs261and one or more threaded members262, as shown inFIG. 30.

As shown inFIG. 31, the delivery tool202can be placed around the left atrial appendage12of a heart20.FIG. 31schematically illustrates the structure of the left and right atria11and21, respectively, as viewed from a posterior aspect, including the bases of the pulmonary veins23and the bases of the superior vena cava and inferior vena cava25and27, respectively, which enter the right atrium21.FIG. 31also schematically illustrates the left and right atrial appendages12and22, respectively.

FIGS. 32 and 33schematically illustrate an outline of the left atrium11of the heart20with the left atrial appendage12protruding therefrom. The ring214can be placed in a position to surround the left atrial appendage12adjacent to the left atrial appendage base18where the left atrial appendage12is attached to the heart20. The ring214can be made of an elastic material to allow it to be stretched into an open or expanded position, as shown inFIG. 32. The ring214can be allowed to return to a closed or collapsed position, as shown inFIG. 33, in order to bear against the tissue of the left atrial appendage12and to substantially close off any interior connection between the left atrium11and the left atrial appendage12.

As shown inFIG. 32, the ring214can be attached to a patient's heart20to isolate the left atrial appendage12from the left atrium11. In some embodiments, multiple rings214can be placed successively more and more proximal to the base18of the left atrial appendage12. The elastic material of the ring214can be any biocompatible material, thereby allowing the ring214to be left on the heart20permanently. In one embodiment, the ring214can have different relative sizes to accommodate different anatomy requirements of the patient. The ring214can be manufactured with radio opaque qualities, such as micro-sized glass beads molded into the elastic material. Alternatively, the ring214can be made radio opaque by the addition of glass or metallic fibers in the elastic material. The ring214can be entirely biocompatible to allow for use for the life of the patient. The ring214can have size variations in its inner diameter along a contact surface.

In one embodiment, surgical access to the left atrial appendage can be through a left-sided thoracotomy or laproscopic port incision. The delivery tool and attached collapsed ring can be inserted through the left thoracotomy access. The ring can then be expanded. The left atrial appendage can be grasped and drawn or pulled through the expanded ring. The ring can be positioned toward the base of the left atrial appendage and released from the delivery tool. The delivery tool can then be removed from the patient, and the incision can be closed. Various imaging methods can be employed before, during, and after the tissue occlusion procedure. For example, contrast fluoroscopy, trans-thoracic ultrasound, and/or transesophageal echo (TEE) can be employed. Other surgical approaches are possible including sub-xyphoid.

As shown inFIG. 34, some embodiments of the invention provide an adjustable band occluder314. The adjustable band occluder314can include a band316, a loop318, and an adjustment mechanism320. The size of the loop318can be varied by moving the adjustment mechanism320along the length of the band316. The adjustable band occluder can be locked in a fixed position by any suitable means, such as, but not limited to, a crimper region, a ratchet mechanism or other mechanical engagement structure, or other suitable locking mechanism.

Some embodiments of the invention address a number of problems, such as surgical access to the endocardial surfaces of the atrial chambers of a beating heart and permanent closure of the atrial appendage volume. These problems have been addressed by others using various methods and devices, such as percutaneous catheters. The right atrium may be accessed via transvenous catheters placed through a femoral vein in the groin, as well as through superior veins such as the subclavian, brachiocephalic, or jugular veins. The left atrium is more difficult to reach transvenously, requiring first, right atrial access followed by a transseptal puncture through the fosa ovalis of the inter-atrial septum into the left atrium. With these transvenous methods, only relatively small diameter catheters can be passed through the vasculature. In addition, these devices must be navigated using fluoroscopic guidance or some form of electronic navigation.

Positioning and placement of the therapeutic elements of such catheters can be a challenge, because the movement is controlled remotely from the point of venous access. From point of entry into the body to the therapeutic end of the catheter, the distance may be 70-110 cm through a difficult path. In cases where tissue contact force is critical, this can be a significant problem. Stability of the catheter tip is an issue in a beating heart compared to firm control possible with much shorter and more rigid surgical implements. A number of commercially-available catheters may be able to be positioned in most areas of the atria, but only one catheter-based device has been developed to permanently close off the left atrial appendage following a procedure. This device, known as PLAATO (percutaneous left atrial appendage total occlusion) must be carefully sized to allow positioning within the left atrial appendage such that it is retained in position distal to the ostium with the left atrial chamber. This presents a significant risk that the device may be released into the atrium and pass into the left ventricle and become entangled in the chordae tendinae supporting the mitral valve or become lodged in the left ventricular outflow tract or aorta. The risks of such a procedure were documented in an abstract by Fischer at the 2005 meeting of the American College of Cardiology—Evelyn Fischer, et al., “Left Atrial Appendage Occlusion to Prevent Stroke in Suboptimal Warfarin Candidates: Current Results of the European Multicenter Registry Trial,” American College of Cardiology, Abstract presented at 2005 National Meeting, which is herein incorporated by reference in its entirety.

The atria may be accessed through sternotomy, thoracotomy, intercostals ports, or under the sub-xiphoid process. Access to the atria is important for treatment of atrial fibrillation (AF), atrial-septal-defects (ASD's), patent foramen ovalis (PFO), and mitral or tricuspid valve disease. Also of importance is the elimination of the left atrial appendage volume at the end of the procedure in order to reduce stroke risk. Surgical removal and closure of the left atrial appendate has been accomplished by using a surgical stapler/ligation device or by suturing the appendage closed followed by surgical excision of the distal appendage. This is not without risks as noted by Krum et al.—David Krum, David L. Olson, Daniel Bloomgarden, Jasbir Sra, “Visualization of Remnants of the Left Atrial Appendage following Epicardial Surgical Removal,”Heart Rhythm(2004) 1,249. Such surgical removal may result in an incomplete reduction of the left atrial appendage and allow a volume to remain unclosed, which is herein incorporated by reference in its entirety.

Regarding the relationship between the left atrial appendage and stroke risk, Blackshear et al. stated that left atrial appendage obliteration “is a routine part of modern ‘curative’ operations for nonrheumatic atrial fibrillation, such as the maze and corridor procedures.” Joseph L. Blackshear, MD, John A. Odell, FRCS(Ed), “Appendage Obliteration to Reduce Stroke in Cardiac Surgical Patients with Atrial Fibrillation,”Ann. Thorac. Surg.,1996; 61:755-759, which is herein incorporated by reference in its entirety. To assess the potential of left atrial appendage obliteration to prevent stroke in nonrheumatic atrial fibrillation patients, they reviewed previous reports that identified the etiology of atrial fibrillation and evaluated the presence and location of left atrial thrombus by transesophageal echocardiography, autopsy, or operation.

They reviewed the results of twenty-three separate studies and found that 446 of 3,504 (13%) rheumatic atrial fibrillation patients, and 222 of 1,288 (17%) nonrheumatic atrial fibrillation patients had a documented left atrial thrombus. Anticoagulation status was variable and not controlled for. Thrombi were localized to, or were present in the left atrial appendage and extended into the left atrial cavity in 254 of 446 (57%) of patients with rheumatic atrial fibrillation. In contrast, 201 of 222 (91%) of nonrheumatic atrial fibrillation-related left atrial thrombi were isolated to, or originated in the left atrial appendage (p<0.0001). Their data suggested that left atrial appendage obliteration is a strategy of potential value for stroke prophylaxis in nonrheumatic atrial fibrillation. A device was developed that allows percutaneous left atrial appendage transcatheter occlusion (PLAATO) via transseptal catheterization. Initial studies in dogs demonstrated the ability of the device to seal the left atrial appendage. Sievert et al. reported their initial experience with PLAATO in a human clinical trial involving 15 patients. Horst Sievert, MD et al, “Percutaneous Left Atrial Appendage Transcatheter Occlusion to Prevent Stroke in High-Risk Patients with Atrial Fibrillation,”Circulation, 2002, 105:1887, which is herein incorporated by reference in its entirety.

PLAATO was purported to be a less invasive, percutaneous approach to closing the left atrial appendage. Previous animal studies of the device with follow-up of up to 1 year have demonstrated occlusion of the left atrial appendage with complete healing, absence of erosions, new thrombus formation on the device, or interference with atrial function.

In the initial cohort of 15 patients, occlusion of the left atrial appendage was successful in all, as proven by left atrial angiography. There were no complications associated with the device, either acutely during the implantation procedure or during follow-up. The only complication during the study was hemopericardium in the first patient attempted, which was not device-related. It resulted from left atrial appendage access, and should be easily avoided with increased experience. The procedure was successful in a second attempt in that patient.

All patients did well in follow-up. One theoretical concern is the development of new thrombi on the implant. However, the use of ePTFE on the implant surface should result in relatively benign healing. Histological examination in dogs undergoing PLAATO reveal partial endothelialization at1month, which is complete by 2 to 3 months. In these 15 patients, transesophageal echo (TEE) at 1 month showed the surface to be completely smooth and free of mobile thrombi.FIG. 35illustrates a deployed PLAATO device. Fluoroscopic images of non-occluded left atrial appendage, deployment of the PLAATO device, and left atrial appendage post-deployment can be taken.

A larger cohort of patients was included in the European PLAATO Registry Trial by Fischer, et al. a study that was finished in January 2003 that examined the safety and feasibility of this procedure. This study described the experience of 92 patients. Inclusion criteria were atrial fibrillation (AF) with inability to take Warfarin®, prior cerebral ischemia and/or two clinical risk factors for stroke. After implantation of the PLAATO occluder, the patients were followed with X-ray, TEE and NIH stroke scale in regular intervals. Of the 92 patients, 67% were male with a mean age of 70±9 years. All candidates were successfully implanted. The mean procedure time was 76±36 minutes and the mean left atrial appendage orifice diameter was 20±3 mm. During follow up, one patient died of a bronchial carcinoma diagnosed 3 months before the one year follow up. One patient sustained a stroke six months post implant. Thus, the yearly incidence of stroke after implantation is 1.9%. With this small number of patients, the estimated risk reduction was 55%.

Of concern, in three patients, a thrombus on the occluder was found prior to hospital discharge (2) and one month after the procedure (1). All thrombi were resolved without sequelae. One device was chosen too small and embolized into the aorta after its release. It was snared with a catheter and was retrieved successfully. Another device was implanted successfully in the very same procedure.

To summarize this group's experience with the PLAATO device, the incidence of stroke in high-risk patients may decrease after implantation of the device. Considerable risks exist with this procedure, including errant transseptal puncture resulting in aortic dissection or atrial free wall perforation resulting in tamponade, embolization of the PLAATO device resulting in device entanglement in cardiac structures, along with thrombus formation on the occluder surface that could lead to emboli production and stroke. In addition, the chronic nature of this implant must be considered. Constant flexture of the nitinol wire structure may lead to long term fatigue and potential fracture and perforation of cardiac or adjoining tissues.

The group of Odell et al, hypothesized that if the atrial appendage could be safely obliterated, then the incidence of embolic stroke may be lessened. John A. Odell, et al., “Thoracoscopic Obliteration of the Left Atrial Appendage: Potential for Stroke Reduction,”Ann. Thorac. Surg., 1996, 61:565-569, which is herein incorporated by reference in its entirety. If the appendage can be obliterated using a thoracoscopic technique, a procedure of lesser magnitude than thoracotomy, then it may offer an alternative form of management for patients ineligible for Warfarin® therapy. To determine the feasibility of atrial appendage obliteration done using the thoracoscope, they performed the procedure in mongrel dogs and in human cadavers.

Transesophageal echocardiography with emphasis on visualization of the left atrial appendage was performed pre-, intra-, and postoperatively. In five dogs, the atrial appendage was obliterated with staples, and in five the appendage was obliterated with an endoloop of 0 Vicryl suture material. Three ports were made—one in approximately the seventh interspace approximately 5 cm from the midsternum (port 1), a second inserted anteriorly in the fourth interspace (port 2), and a third more posteriorly in the fourth interspace (port 3). Carbon dioxide was instilled to a pressure of 4 to 10 mm to collapse the lung. In all animals, the pericardium was opened anterior and parallel to the phrenic nerve. Gordon N. Olinger, MD, “Carbon dioxide displacement of left heart chambers,”J. Thorac. Cardiovasc. Surg., 1995, 109:187-188, which is herein incorporated by reference in its entirety.

Through the first port, the camera was inserted; through the second port, the pericardium was grasped with an instrument; and, using scissors inserted through the third port, the pericardium was opened. The technique then varied depending upon whether the appendage was obliterated with staples or with the endoloop. In those having the appendage stapled, the camera was withdrawn from port 1 and inserted in port 3. Through port 1, a 35 endo GIA stapler (Ethicon Endosurgery, Cincinnati, Ohio) with the knife blade removed was inserted, positioned across the base of the atrial appendage, and fired. In dogs having the appendage obliterated with the endoloop (Ethicon), the camera position was not changed. The endoloop was introduced through port 3 and the appendage was grasped through the loop of the suture. The loop was positioned across the base of the appendage and then tightened.

At 11 weeks, the dogs were again anesthetized with sodium pentobarbital (30 mg/kg intravenously) and a midline sternotomy was made. The heart was examined using epicardial echocardiography. The dogs were euthanized, the hearts were removed, and the left atrium was inspected.

The procedure also was attempted in eight human cadavers. In the cadavers, three ports were used for access. The most appropriate sites appeared to be the second interspace anteriorly in the midclavicular line (for grasping the pericardium and the atrial appendage), the sixth interspace in the midclavicular line (for the camera or stapling instrument), and the fifth interspace in the anterior axillary line (usually for the scissors to open the pericardium, but also for the camera or for the stapling instrument). The procedure as performed in the dog and human experiments is illustrated inFIGS. 36A-E.

The group of DiSesa investigated the use of an automatic surgical stapler for ligation of the atrial appendage in sheep, and then applied this technique in patients. V. J. DiSesa, S. Tam and L. H. Cohn, “Ligation of the Left Atrial Appendage using an Automatic Surgical Stapler,”The Annals of Thoracic Surgery, Vol. 46, 652-653, which is herein incorporated by reference in its entirety. Fourteen adult sheep underwent ligation of the left atrial appendage using a surgical stapler with a rotating head and either absorbable or stainless steel staples. In four sheep, killed after two hours, no hemorrhage or intra-atrial thrombus was observed acutely. Ten sheep were allowed to recover for 90 to 100 days, twice the expected absorption time of absorbable staples. There was complete obliteration of the left atrial appendage without evidence of intra-atrial thrombus or staple migration. The absorbable staples were completely reabsorbed. They subsequently used this technique in five patients undergoing mitral valve procedures. There were no complications, and adequate obliteration of the atrial appendage was achieved. Other reports indicate that staples may require the use of reinforcement strips to prevent bleeding and tissue tearing.

Considering the simple surgical ligation methods, the group of Katz, et al. studied the incidence of incomplete ligation of the left atrial appendage during mitral valve surgery. Edward S. Katz MD, FACC, Theofanis Tsiamtsiouris MD, Robert M. Applebaum MD, FACC, Arthur Schwartzbard MD, FACC, Paul A. Tunick MD, FACC and Itzhak Kronzon MD, FACC, “Surgical Left Atrial Appendage Ligation is Frequently Incomplete: A Transesophageal Echocardiographic Study,” Journal of the American College of Cardiology, Volume 36, Issue 2, 1 August 2000, Pages 468-471, which is herein incorporated by reference in its entirety. Using transesophageal Doppler echocardiography, they studied 50 patients who underwent mitral valve surgery and ligation of the left atrial appendage. Incomplete left atrial appendage ligation was detected in 18 of 50 (36%) patients. This study demonstrated that surgical left atrial appendage ligation is frequently incomplete. Residual communication between the incompletely ligated appendage and the left atrial body may produce a milieu of stagnant blood flow within the appendage and be a potential mechanism for embolic events. Ligation of the left atrial appendage is frequently performed during mitral valve surgery to eliminate a potential source of emboli. However, the success of completely excluding the left atrial appendage from the circulation had not previously been systematically addressed. Transesophageal echocardiography offers unique visualization of the appendage in the beating heart and can evaluate the integrity of the surgical ligation. Usually, when the left atrial appendage is ligated, its cavity is obliterated with clot (since no flow enters the cavity) and cannot be seen during echocardiography. This appearance was the same whether the patient was studied in the operating room or months after the surgery. When the appendage is incompletely ligated, not only can the appendage cavity be visualized but flow can be seen within the appendage, as well as through an opening in the ligation site.

The group discovered that 36% of the time the left atrial appendage was found to be incompletely ligated after attempts at excluding it from the left atrial body. Factors, such as an enlarged left atrium or significant mitral regurgitation, which may be thought to increase left atrial tension and pressure (perhaps predisposing to incomplete ligation or dehiscence of sutures), did not appear to correlate with this finding. They also did not observe a correlation between appendage size and the incidence of incomplete ligation. In addition, the surgical procedure (mitral repair or replacement) and operative approach (traditional sternotomy or minimally invasive approach) did not change the incidence of incomplete ligation. It is possible, however, that the sample size in this report may have been too small to exclude a significant effect of these variables on the development of incomplete left atrial ligation.

Incomplete left atrial appendage ligation was as commonly seen in the operating room, evaluating the patient by transesophageal echocardiography immediately after terminating cardiopulmonary bypass, as it was seen in the laboratory evaluating patients referred for transesophageal echocardiography at various times after the surgery. This suggested that incomplete left atrial appendage ligation is not a degenerative process with suture dehiscence over time, but rather is present immediately after the initial surgery. Incomplete ligation may be secondary to several surgical factors. First, the running sutures used may not start and end exactly at the most distal edges of the atrial appendage, which may not be recognized with the appendage empty and unstretched while on cardiopulmonary bypass during surgery. In addition, caution must be taken during appendage ligation to avoid deep suture bites, which may involve the left circumflex coronary artery or its branches that may course in the area. This meticulous care may lead to shallower suture bites that may dehisce when the LA is once again filled and stretched after cardiopulmonary bypass. Both of these mechanisms may play a role, as in many cases flow was detected both at the edge of the appendage orifice (apparently around the end of the suturing line) and through an area at the midpoint of the appendage orifice (through the suture line). One group reported six cases of incomplete left atrial appendage ligation when a purse string suture was used to accomplish the ligation, a technique different from that used by surgeons. The actual incidence, however, of incomplete left atrial appendage ligation using their technique was not addressed.

The clinical significance of an incompletely ligated left atrial appendage has never been studied. Theoretically, creating a small communication between the LA and left atrial appendage may produce stagnation of low velocity blood flow within the atrial appendage. The appendage would then be a model for thrombus formation and continue to serve as a potential source of embolization since a port of entry into the systemic circulation still exists. Although the numbers in this study were small, several observations support this theory. First, spontaneous echo contrast (a marker for stagnant blood flow and a precursor of thrombus formation) was seen within the appendage in half of the patients with incomplete ligation. Second, and perhaps more importantly, in two-thirds of patients with spontaneous echo contrast within the incompletely ligated appendage, the contrast was actually denser within the appendage than within the left atrial body, suggesting a more stagnant and thrombogenic milieu. In two patients, frank thrombus was seen within the incompletely ligated appendage.

The ultimate question, however, is whether patients with incompletely ligated left atrial appendages will have a higher incidence of thromboembolic events. In the Katz study, four patients with incompletely ligated appendages had such events (one patient with Starr-Edwards prosthesis, two with St. Jude prosthesis and one patient status after mitral repair). This is quite a high number considering that only eight patients with incomplete ligation had any potential for long term follow-up (the other ten patients with incomplete ligation were discovered in the operating room). However, one cannot exclude other etiologies for embolization (as mechanical prostheses or atrial fibrillation) and referral bias still clouds this issue. Certainly, conventional ligation methods must be questioned in light of the findings of this study.

A number of devices for occlusion of ASD's have been investigated. Melhem J. A. Sharafuddin, MD; Xiaoping Gu, MD; Jack L. Titus, MD, PhD; Myra Urness, BS; J. J. Cervera-Ceballos, MD; Kurt Amplatz, MD, “Preliminary Results With a New Self-Expanding Nitinol Prosthesis in a Swine Model Transvenous Closure of Secundum Atrial Septal Defects,”Circulation,1997, 95:2162-2168, which is herein incorporated by reference in its entirety. Most of these concepts involve percutaneous delivery from femoral vein access. Varying levels of success have been achieved. Device dislodgment can occur if the size of the defect greatly exceeds the waist diameter of the device or approaches the diameter of the retention buttons. On the other hand, placement of a disproportionately large device may result in mushrooming of the retention buttons and weakening of the cross-clamping forces against the septal rim, which increases the risk of blood flow behind the discs and may result in incomplete endothelialization. In addition, follow-up studies of a clamshell occlusion device reported a delayed rate of metal fatigue fractures of one or more arms of about 30%. The Amplatzer device is shown inFIGS. 37A-E.

A small introduction system, simple and reliable placement technique, and favorable initial experimental success may provide promising potential of such a device for the percutaneous closure of secundum ASDs in all age groups. Heparinization is advocated in clinical use to lower the risk of catastrophic systemic embolization.

ASD device thrombosis is likely to be similar to thrombosis to be expected on left atrial appendage closure devices. This makes the study by Krumsdorf et al, on the incidence, morphology, and clinical course of thrombus formation after catheter closure of ASD closure devices of interest regarding devices such as PLAATO. Krumsdorf U, Ostermayer S, Billinger K, Trepels T, Zadan E, Horvath K, Sievert H, “Incidence and Clinical Course of Thrombus Formation on Atrial Septal Defect and Patient Foramen Ovale Closure Devices in 1,000 Consecutive Patients,”J. Am. Coll. Cardio., Jan. 21, 2004. 43(2):302-9, which is herein incorporated by reference in its entirety.

A total of 1,000 consecutive patients were investigated after patent foramen ovale (PFO) (n=593) or atrial septal defect (ASD) (n=407) closure. Transesophageal echocardiography (TEE) was scheduled after four weeks and six months. Additional TEEs were performed as clinically indicated. Thrombus formation in the left atrium (n=11), right atrium (n=6), or both (n=3) was found in 5 of the 407 (1.2%) ASD patients and in 15 of the 593 (2.5%) PFO patients (p=NS). The thrombus was diagnosed in 14 of 20 patients after four weeks and in 6 of 20 patients later on. The incidence was: 7.1% in the CardioSEAL device (NMT Medical, Boston, Mass.); 5.7% in the StarFLEX device (NMT Medical); 6.6% in the PFO-Star device (Applied Biometrics Inc., Burnsville, Minn.); 3.6% in the ASDOS device (Dr. Ing, Osypka Corp., Grenzach-Wyhlen, Germany); 0.8% in the Helex device (W.L. Gore and Associates, Flagstaff, Ariz.); and 0% in the Amplatzer device (AGA Medical Corp., Golden Valley, Minn.). The difference between the Amplatzer device on one hand and the CardioSEAL device, the StarFLEX device, and the PFO-Star device on the other hand was significant (p<0.05). For a device such as PLAATO, specifically designed to reduce or eliminate thromboembolic events coming from the region of the implant, occurrence of thrombus on ASD devices is a concern.

A method and apparatus for thoracoscopic intracardiac procedures was described U.S. Pat. No. 6,401,720, entitled “Method and Apparatus for Thoracoscopic Intracardiac Procedures,” Stevens, John H.; Palo Alto, Calif. 94303, Reitz, Bruce A.; Stanford, Calif. 94305, Roth, Alex T.; Redwood City, Calif. 94061, Peters, William S.; Woodside, Calif. 94062, Gifford, Hanson S.; Woodside, Calif. 94062, which is herein incorporated by reference in its entirety. They described devices, systems, and methods provided for accessing the interior of the heart and performing procedures therein while the heart is beating. In one embodiment, a tubular access device having an inner lumen is provided for positioning through a penetration in a muscular wall of the heart, the access device having a means for sealing within the penetration to inhibit leakage of blood through the penetration. The sealing means may comprise a balloon or flange on the access device, or a suture placed in the heart wall to gather the heart tissue against the access device. An obturator is removably positionable in the inner lumen of the access device, the obturator having a cutting means at its distal end for penetrating the muscular wall of the heart. The access device is preferably positioned through an intercostal space and through the muscular wall of the heart. Elongated instruments may be introduced through the tubular access device into an interior chamber of the heart to perform procedures, such as septal defect repair and electrophysiological mapping and ablation. A method of septal defect repair includes positioning a tubular access device percutaneously through an intercostal space and through a penetration in a muscular wall of the heart, passing one or more instruments through an inner lumen of the tubular access device into an interior chamber of the heart, and using the instruments to close the septal defect. Devices and methods for closing the septal defect with either sutures or with patch-type devices are disclosed. While this concept allows access to the heart chambers similar to the present invention, it does not provide for a simple means of incisional closure as do some embodiments of the invention.

Some embodiments of the invention may provide any one or more of the following advantages: a single point of access for surgical treatment of atrial fibrillation; fewer intercostal access ports may be needed for treating atrial fibrillation, as opposed to existing minimally-invasive methods; blunt dissection of cardiac tissue is generally not required; pericardium is left substantially intact, except for a small incision; access to the heart for delivery of therapies for various disease states; a single device can provide surgical access to the heart chambers, as well as providing a means of closing the point of access at the end of the procedure; and the left atrial appendage can be ligated and/or eliminated at the close of the procedure with little or no risk of tearing. The left atrial appendage can be eliminated at the close of the procedure such that a residual remaining volume which could lead to strokes is avoided.

Some embodiments of the invention provide a device that can provide access to the interior of the heart chambers. The device can allow for single point access to treat atrial fibrillation, atrial-septal defects, patent foramen ovalis, and valvular disease, as well as other arrhythmias. Some embodiments of the device can be used to access the ventricles from the access achieved through either appendage. Ventricular septal defects can be addressed. The device can be applied to other body structures, such as the stomach where a portion of the stomach wall could be ligated by the elastic band and excluded. This may be suitable as a treatment for obesity.

Some embodiments of the invention provide methods and devices to allow entry into the atria of a beating heart to perform delivery of therapy to the structures within the heart and endocardial surfaces and valves associated with the heart chambers. Upon removal of the device from the appendage, a permanent closure and elimination of the appendage volume can be affected. More specifically, the entry points can be located in the left and right atrial appendages. Of these, the left atrial appendage may be most appropriate, because closure and elimination of this appendage following a procedure has become a standard surgical practice performed by many surgeons.

According to embodiments of the method of the invention, pre-procedure includes placement of one or two chest wall access ports for visualization and placement of the invention. The lung can be deflated and a small opening in the pericardium can be made adjacent to the left atrial appendage.FIG. 38schematically illustrates the relative locations of structures of the heart and chest of interest regarding the invention. More specifically, the left atrial appendage is shown in a stretched state without the pericardium in place. The heart structures noted onFIG. 38include the following: SVC—superior vena cava, IVC—inferior vena cava, TV—tricuspid valve, FO—fossa ovalis, MV—mitral valve, PV—pulmonary vein, and left atrial appendage—left atrial appendage.FIGS. 39-68illustrate devices and methods of using the devices according to various embodiments of the invention. In some embodiments, a device400can include an elastic cinch ring410, ring expansion arms412, and a portal tube assembly414. The ring expansion or cinch ring support arms412can include three or four arms. The device400can be positioned through a chest port416in a portion of the chest wall418. The device400can be passed through a chest port416placed between the ribs. The anatomical drawings ofFIGS. 39-57have been simplified to show only the left atrial appendage and the chest wall.

FIG. 39illustrates the elastic cinch ring410in a contracted state.FIG. 40illustrates the device400being advanced toward the left atrial appendage.FIG. 41illustrates a suction cup or Babcock grasper probe420being advanced through the portal tube assembly414.

FIG. 42illustrates the suction cup or Babcock grasper probe420being attached to an end of the left atrial appendage. In other embodiments, any suitable type of grasper, vacuum device, adhesive, cyrogenic device, or nanotechnology device can be used to grasp and pull the left atrial appendage.FIG. 43illustrates the support arms412being expanded and the left atrial appendage being pulled toward the portal tube assembly414.FIG. 44illustrates the cinch ring410being advanced over the left atrial appendage.FIG. 45illustrates the cinch ring410being positioned over the mid to proximal left atrial appendage.

FIG. 46illustrates the cinch ring410being allowed to contract over left atrial appendage and occlude a lumen422of the left atrial appendage.FIG. 47illustrates the suction cup or Babcock grasper probe420removed from portal tube assembly414.FIG. 48illustrates a dilator/sheath assembly424including a dilator426and a sheath428being advanced through the portal tube assembly414. In some embodiments, prior to puncturing into the atrial appendage, the thoracic cavity can be inflated with carbon dioxide gas. Carbon dioxide inflation of the pericardial space can be used to lessen the prevalence and consequences of air embolism, can help limit the chances of air introduction, and can help limit bleeding.FIG. 49illustrates a needle or sharp wire430being advanced through a lumen of the dilator426to puncture into the left atrial appendage lumen422.

FIG. 50illustrates the dilator426being advanced into the lumen422of the left atrial appendage and the needle430retracted.FIG. 50illustrates the sheath428being advanced over the dilator426into the left atrial appendage lumen422.FIG. 51illustrates the left atrial appendage being filled with heparinized saline, as blood and air are removed. As shown inFIG. 52, the left atrial appendage lumen422can be aspirated of blood432and flushed with heparinized saline using a syringe434to prevent thrombus formation. As shown inFIG. 53, the left atrial appendage lumen422can be filled with heparinized saline as blood and air are removed. However, in some embodiments, it may be desirable to allow blood to form a thrombus in the remaining left atrial appendage volume to promote healing and absorption of the closed-off portion of the left atrial appendage by surrounding tissue.

As shown inFIG. 54, the dilator426can be advanced past the cinch ring410and into the left atrium. As shown inFIG. 55, the sheath428can be advanced over the dilator426past the cinch ring410and into the left atrium. As shown inFIG. 56, the dilator426can be removed. A hemostasis valve (not shown) can be positioned on a proximal end of the sheath. As shown inFIG. 57, therapeutic implements can be advanced into the left atrium for the treatment of various conditions.

FIG. 58illustrates one embodiment of a balloon ablation device436positioned at the right inferior pulmonary vein ostium. The use of a cryogenic or high-intensity focused ultrasound balloon ablation device can be used in some embodiments of the invention.FIG. 59illustrates one embodiment of a balloon ablation device436positioned at the left superior pulmonary vein ostium.

FIG. 60illustrates one embodiment of an encircling ablation device438approaching the left superior pulmonary vein ostium. The ablation device438can use radiofrequency (RF) energy, cryothermy, high-intensity focused ultrasound, microwaves, or any other suitable ablation energy.FIG. 61illustrates one embodiment of an encircling ablation device438placed around the left superior pulmonary vein ostium.

FIG. 62illustrates one embodiment of a left atrial de-bulking spiral ablation device440placed against the posterior left atrium.FIG. 63illustrates one embodiment of a high intensity focused ultrasound ablation device442that can create a lesion over the left atrial isthmus.FIG. 64illustrates one embodiment of a PFO or ASD closure device444being deployed in the fossa ovalis of the inter-atrial septum.FIG. 65illustrates one embodiment of a linear ablation device446forming connecting lesions between the pulmonary veins.

As shown inFIG. 66, at the completion of all the endocardial therapeutic procedures, the elastic cinch ring410can be allowed to constrict down around the base of the left atrial appendage. The sutures or other devices holding the cinch ring410can be released such that the support arms412and the portal tube assembly414can be pulled away from the heart, while leaving the cinch ring410substantially permanently in place at the base of the appendage. As shown inFIG. 67, immediately following the procedure, the left atrial appendage will generally include a volume that is contained by the cinch ring410. Healing will then occur and the vestige of the left atrial appendage will be absorbed into the atrial wall. As shown inFIG. 68, after approximately 12 weeks, the left atrial appendage is expected to have been absorbed and assimilated by the atrial wall. The ring410can remain embedded in the remaining scar448.

FIGS. 69-71illustrate a device500for ligation of an atrial appendage. The device500can include a ring applicator or delivery tool502and an occlusion member or ring514. In one embodiment, the occlusion ring514can be made of a30A durometer silicone rubber, although other hardnesses of silicone or other materials, such as polyurethane can be used. The ring514can be covered with a material such as Dacron® polyester to promote tissue ingrowth or prevent ring slippage after placement or to spread the load bearing surfaces of the ring. The ring514can be generally expandable for placement around the atrial appendage. The delivery tool502can be used to expand the ring514. The delivery tool502can include a shaft520and a handle530coupled to shaft520. The delivery tool502can be sized for reaching an atrial appendage through an opening in the patient's chest, for example, through a sternotomy or thoracotomy. The delivery tool502can include a tissue-grasping tool channel570extending from the handle530to the distal end of the shaft520. A tissue-grasping tool580may be movably positioned within tissue-grasping tool channel570. For example, shaft584of tissue-grasping tool580fits within tool channel570. In one embodiment, tissue-grasping tool580may include one or more hooks, barbs, suction ports and/or graspers. For example, as shown inFIGS. 72 and 73, tissue grasping tool580may include tissue graspers582. The tissue-grasping tool580can be used to grasp the atrial appendage and pull it through ring514. In one embodiment, the tissue-grasping tool580can be moved distally and/or proximally relative to shaft520.

In one embodiment, the delivery tool502can include a ring spreader540having a pair of ring-expanding members542used to hold and expand the ring514. The ring spreader540can be coupled to a distal end of shaft520. The ring514can be releasably coupled or attached to the distal ends of ring-expanding members542and the distal end of shaft520, for example, via one or more sutures550. The sutures550can loop around the ring514. The ends of the sutures550can pass through one or more lumens within the ring expanding members542, the shaft520, and the handle530. In one embodiment, the two ring-expanding members542open ring514into a triangular shape. The proximal ends of the ring-expanding members542are pivotally coupled to the distal end of shaft520, thereby allowing the ring-expanding members542to pivot from a closed or collapsed position, as shown inFIG. 69, to an open or extended position, as shown inFIG. 70. In the collapsed position, ring-expanding members542run parallel to shaft520and the distal ends of the ring-expanding members542point in a direction towards handle530. In the extended position, ring-members542are aligned perpendicular to each other and to shaft520. In the extended position, ring514has an open triangular configuration, as shown inFIG. 70. In one embodiment, sutures550are used to control the opening and closing of ring-expanding members542. Sutures550run through suture lumens525of shaft520. The proximal ends of sutures550are attached or coupled to suture tension knob or ring expansion mechanism532located at handle530. Suture tension knob532is rotatable and may include a ratcheting mechanism. The ratcheting mechanism may be used to keep tension on the sutures without having to continuously hold onto knob532. As knob532is rotated, sutures550stretch ring514toward the distal ends of ring-expanding members542and actuate ring-expanding members542to move from a collapsed configuration to an extended configuration wherein ring514is opened into a triangular configuration. Ring514may be released when desired, for example, around tissue via actuation of suture cutting mechanism562. Suture cutting mechanism562is used to cut sutures550, thereby releasing ring514from delivery tool502remotely. Suture cutting mechanism562includes cutting blade564, which is used to cut sutures550.

In one embodiment, shaft520is approximately 12 mm in diameter and tool channel570is approximately 5.5 mm in diameter. In one embodiment, tool channel570provides guidance for positioning and manipulating tissue-grasping tool580. In addition, tool channel570allows deliver tool502and tissue-grasping tool580to be positioned together through a single port, for example, a 12 mm port placed between the patient's ribs and it allows the two tools to be held by one hand.

In one embodiment of the present invention, the distal end of delivery tool502may be passed through a port or small incision, for example, in the chest of a patient and positioned adjacent the left atrial appendage of a heart. Next, knob532may be rotated, thereby opening ring514. A tissue-grasping tool580may then be slid distally along tissue-grasping tool channel570so that graspers582protrude through ring514. Graspers582may then be manipulated by handle586to grasp tissue of the left atrial appendage. Tissue-grasping tool580and delivery tool502are then manipulated so as to position a desired portion of the left atrial appendage within the triangular opening of ring514. Ring514is then released from delivery tool502and allowed to constrict tissue of the left atrium.

The ring or band occluders and the clip occluders disclosed herein can be constructed of any one or more of the following materials: silicone rubber, polyurethane, super-elastic material, shape-memory polymer or metal, latex, nitrile, butyl, styrene-butadiene, polyacrylate, acrylic, polyisoprene, chloroprene, fluoroelastomers, or other suitable biocompatible elastomeric materials. The ring or band occluders and the clip occluders disclosed herein can incorporate any one or more of the following features: texturing to aid in mechanical stability (i.e., ridges, bumps, grooves, etc.); fabric such as Polyethyleneterapthalate (i.e., Dacron®), polyester, ePTFE, etc. to promote tissue ingrowth; other types of coatings to promote tissue ingrowth; and pharmacological agents (e.g. a controlled release agent) to aid in tissue ingrowth, local therapeutic apoptosis, local necrosis, revascularization, arrhythmia control, infection control, anti-bacterial, fluid balance (i.e., atrial natritic peptide replacement).

One or more drugs or agents may be incorporated into the ring, band or clip, e.g., within a polymeric material of the ring, band or clip. One or more drugs or agents may be incorporated into one or more coatings of the ring, band or clip, e.g., within a polymeric coating covering at least a portion of the ring, band or clip. One or more drugs or agents may be incorporated into one or more fabrics of the ring, band or clip, e.g., within or on a fabric coating covering at least a portion of the ring, band or clip. In some embodiments of the invention, one or more drugs or agents may be loaded uniformly throughout one or more materials of the ring, band or clip. In some embodiments of the invention, one or more drugs or agents may be loaded non-uniformly in one or more materials of the ring, band or clip. In some embodiments of the invention, one or more drugs or agents may be loaded within an inner circumference of the ring, band or clip. In some embodiments of the invention, one or more drugs or agents may be loaded within an outer circumference of the ring, band or clip.

In some embodiments of the invention, one or more materials incorporated into the ring, band or clip may be “smart materials” which may alter their structure in response to one or more external factors, e.g., temperature. For example, the application of heat may cause a material, e.g., a polymer, to change shape or conformation, thereby resulting in the release of a drug or agent. In one embodiment, ultrasound, e.g., focused ultrasound, may be used to create heat needed to cause the material change shape or conformation.

In some embodiments of the invention, the ring, band or clip may comprise one or more radiopaque materials, e.g., barium sulfate, thereby making the ring, band or clip observable during fluoroscopic procedures. In some embodiments of the invention, the ring, band or clip may comprise one or more echogenic materials, e.g., perfluorocarbon, thereby making the ring, band or clip observable during ultrasound procedures.

In some embodiments of the invention, the ring, band or clip may release one or more drugs or agents via a diffusion-controlled mechanism. For example, a drug or agent may be uniformly or non-uniformly dispersed or dissolved in a material, e.g., a polymeric material, of the ring, band or clip and/or a coating of the ring, band or clip and/or a fabric covering of the ring, band or clip. The drug or agent may diffuse from an area of high concentration (e.g., from the material(s) of the band or clip) to an area of low concentration (e.g., an area of tissue such as the LAA).

In some embodiments of the invention, the ring, band or clip may release one or more drugs or agents via a biodegradable mechanism. For example, a drug or agent may be uniformly or non-uniformly dispersed or dissolved in a material, e.g., a polymeric material, of the ring, band or clip and/or a coating of the ring, band or clip and/or a fabric covering of the ring, band or clip. The drug or agent may be released during degradation of the material. The material may be designed to either degrade completely or to degrade partially, e.g., leaving the core structure of the material intact.

In some embodiments of the invention, the ring, band or clip may comprise a cross-sectional shape that may be round, square, rectangular, oval, triangular, star-shaped, etc. In some embodiments of the invention, the ring, band or clip may be reversibly placed, and its position may be adjusted if necessary. In some embodiments of the invention, multiple ring, band or clip may be placed more and more proximal to the base of the left atrial appendage.

In some embodiments of the invention, the ring, band or clip may include one or more sensors, for example to monitor changes in one or more tissue properties. One or more properties of surrounding tissue may change over time and/or in response to drug delivery, as described above, for example. In one embodiment, the band or clip may include a sensing electrode. Sensors may be monitored and/or controlled via wireless telemetry, for example, thereby providing wireless monitoring of one or more tissue properties over time.

In one embodiment, one or more sensors may comprise a biosensor, for example, comprising an immobilized biocatalyst, enzyme, immunoglobulin, bacterial, mammalian or plant tissue, cell and/or subcellular fraction of a cell. For example, the tip of a biosensor may comprise a mitochondrial fraction of a cell, thereby providing the sensor with a specific biocatalytic activity. In one embodiment, one or more sensors may be based on potentiometric technology or fiber optic technology. For example, a sensor may comprise a potentiometric or fiber optic transducer. An optical sensor may be based on either an absorbance or fluorescence measurement and may include an UV, a visible or an IR light source. In one embodiment, one or more sensors may be used to detect naturally detectable properties representative of one or more characteristics, e.g., chemical, physical or physiological, of a patient's bodily tissues or fluids. For example, naturally detectable properties of patient's bodily tissues or fluids may include pH, fluid flow, electrical current, impedance, temperature, pressure, components of metabolic processes, chemical concentrations, for example, the absence or presence of specific peptides, proteins, enzymes, gases, ions, etc. In one embodiment, one or more sensors may include one or more imaging systems, camera systems operating in UV, visible, or IR range; electrical sensors; voltage sensors; current sensors; piezoelectric sensors; electromagnetic interference (EMI) sensors; photographic plates, polymer-metal sensors; charge-coupled devices (CCDs); photo diode arrays; chemical sensors, electrochemical sensors; pressure sensors, vibration sensors, sound wave sensors; magnetic sensors; UV light sensors; visible light sensors; IR light sensors; radiation sensors; flow sensors; temperature sensors; or any other appropriate or suitable sensor. In one embodiment, one or more sensors may be powered by a suitable power source. In addition, one or more sensors may be coupled to any appropriate output device, for example, a LCD or CRT monitor which receives and displays information regarding one or more sensors.

A temperature sensor may incorporate one or more temperature-sensing elements such as, for example, thermocouples, thermisters, temperature-sensing liquid crystals, or temperature-sensing chemicals. A temperature sensor could be used, for example, to monitor tissue temperature.

The signals from one or more sensor may be amplified by a suitable amplifier before reaching an output device. The amplifier also may be incorporated into an output device. Alternatively, the amplifier may be a separate device. The output device may incorporate one or more processors. In one embodiment, sensors may be positioned around a perimeter of the band or clip. When sensed tissue reaches a perimeter, a corresponding sensor may send a signal. In one embodiment, a sensor may send constant signals. For example, a sensor may send a constant signal based on its voltage. As a tissue perimeter changes, the voltage of the sensor may change proportionately and the signal sent by the sensor may change proportionately.

FIGS. 74 and 75illustrate one embodiment of device200for ligation of an atrial appendage. In this embodiment, device200includes a ring applicator or delivery tool202and an occlusion member or ring214. The delivery tool202can include a ring spreader240having ring-expanding members242used to hold and expand the ring214. The ring spreader240can be coupled to a distal end of shaft220. In one embodiment, the delivery tool202can include three ring-expanding members242. As shown inFIG. 76, the ring214can be releasably coupled or attached to the distal end of ring-expanding members242, for example, via wire hooks272made of stainless steel or nitinol, for example. The wire hooks272may be passed through one or more lumens278within ring-expanding members242. The wire hooks272may be retracted partially (as shown inFIGS. 77 and 78) or completely into ring-expanding members242via a ring release mechanism273located at the proximal end of device20, thereby releasing ring214from delivery tool202. The handle230may also include a ring expansion mechanism260used to control the expansion of the ring214. In one embodiment, ring expansion mechanism260is coupled to a wedge member274via a shaft275. As the wedge member274is moved via ring expansion mechanism260from a distal position to a more proximal position the ring expanding members242are forced to move from a closed or collapsed configuration to an open or expanded configuration, as shown inFIGS. 74 and 75.

FIG. 79illustrates one embodiment of device200for ligation of an atrial appendage. In this embodiment, device200includes a ring applicator or delivery tool202and an occlusion member or ring214. The delivery tool202can include a ring spreader240having ring-expanding members242used to hold and expand the ring214. The ring spreader240can be coupled to a distal end of shaft220. In one embodiment, the delivery tool202can include three ring-expanding members242pivotally coupled to distal end of shaft220, as shown inFIG. 80. As shown inFIG. 81, the ring214can be releasably coupled to the distal end of ring-expanding members242, for example, via ring attachment members252pivotally coupled to ring expanding members242. In one embodiment, ring attachment members252may be remotely controlled to pivot thereby releasing ring214from delivery tool202. A ring release mechanism273, coupled to ring attachment members252, may be located at or near handle230. Ring release mechanism273may be used to control the pivoting of ring attachment members252thereby releasing ring214from delivery tool202. The handle230may also include a ring expansion mechanism260used to control the expansion of the ring214. The ring expansion mechanism260may be coupled to the ring-expanding members242. The ring expansion mechanism260can control movement of the ring expanding members242from a closed or collapsed configuration to an open or expanded configuration, as shown inFIGS. 79 and 80.

FIG. 82illustrates one embodiment of device34for ligation of an atrial appendage, wherein ring applicator34includes a shaft36with a handle38on a proximal end and a ring spreader40on a distal end. In one embodiment, the ring spreader40includes a pair of spreader jaws42and44. In one embodiment, a spring member may bias the jaws into an open or expanded configuration and/or a closed or collapsed configuration. In an alternative embodiment, the jaw arms42and44may ride on a cylinder51which forces the arms apart when they are pushed forward out the distal end of shaft36.FIG. 83shows one embodiment of ring spreader40in a closed or collapsed configuration.FIG. 84shows one embodiment of ring spreader40in an open or expanded configuration. In one embodiment, a jaw actuator48is moveably coupled to handle38. The jaw actuator48includes a shaft49connected to jaws42and44. When the shaft49is pushed forward within the shaft36, jaws42and44are forced out the distal end of shaft36and into an open or expanded configuration. In some embodiments, as shown inFIG. 9B, the ring16can be removably attached to the ring spreader40by one or more sutures, which may act as a retainer to hold the ring16in the ring spreader40.

In some embodiments, the shaft of the ring, band or clip delivery tool may comprise one or more flexible, bendable and/or articulation section and/or sections. One or more flexible, bendable and/or articulation section and/or sections of the shaft of the delivery tool allows the device to accommodate a variety of patient anatomies via flexing, bending and/or articulation of the delivery tool's shaft. Preferably, any flexing, bending and/or articulation of the shaft will not inhibit the opening and closing mechanism of the delivery tool for opening and closing the ring, band or clip.

In one embodiment, as shown inFIG. 85, a portion of the shaft of the delivery tool may comprise an outer tube member110made of a memory alloy and/or plastic which may be pre-bent to a desired angle, for example 90°. The shaft may then comprise an inner stiffening rod member111placed within a lumen112of the outer tube member110. The inner stiffening rod member111may be used to straighten the outer tube if advanced within the lumen112of the outer tube member110and allow the outer tube member110to return to its pre-bent shape if retracted. In one embodiment, the stiffening rod member111may be controlled by a rotating collar axially located with the outer tube member110and stiffening rod member111. In one embodiment, the shaft or outer tube member110may include one or more lumens for control lines that facilitate the opening and closing mechanism or ring spreader of the delivery tool for opening and closing the ring, band or clip.

In one embodiment, as shown inFIGS. 86 and 87, a portion of the shaft of the delivery tool may comprise on or more hinge mechanisms310, e.g., a hinge mechanism comprising multiple living hinges along a shaft section to create a gradual bend or curve for articulation. In one embodiment, one or more lumens311for control lines that facilitate the opening and closing mechanism or ring spreader of the delivery tool may be located as close to or through the pivots312of the hinges, thereby insuring that the control lines would not substantially lengthen or shorten throughout the range of hinge articulation. A cable or rod may be used, for example, to operate the hinge mechanism310, thereby articulating the shaft portion comprising the living hinges, for example. One or more lumens313may be used for the cable or rod. The articulation of the hinge mechanism310, e.g., the pushing and pulling of the cable or rod, may be controlled by a rotating collar axially located with the shaft. A gradual bend curve formed from the multiple living hinges prevents sharp bends or kinking in the opening and closing mechanism control lines, thereby insuring good working conditions for the opening and closing mechanism.

FIG. 88illustrates one embodiment of device300for ligation of an atrial appendage, wherein ring applicator300includes a shaft36with a handle or hand piece38on a proximal end and a ring spreader40on a distal end. Shaft36may include an articulation section320, for example, located at the distal portion of shaft36, seeFIG. 89. In one embodiment, articulation section320of shaft36may include one or more hinge mechanisms as shown inFIG. 90. In one embodiment, hinge mechanism325includes multiple living hinges controlled via a hinge articulation control wire330. Moving control wire330in a proximal direction causes articulation section320to form a bend or curve. Moving control wire330in a distal direction causes articulation section320to straighten. In one embodiment, articulation control wire330is coupled to an articulation actuator or drive mechanism335positioned at the distal end of handle or hand piece38. In one embodiment, as shown inFIGS. 91,92and93, articulation drive mechanism335comprises an articulation drive screw340and an articulation drive screw knob345used to manually control the movement of control wire330in both a distal direction and a proximal direction. Rotation of drive screw knob345causes drive screw340to rotate, which, in turn, causes control wire330to move distally or proximally, thereby causing the hinged section320to bend or straighten.

In one embodiment, as shown inFIG. 90, ring spreader40includes a ring spreader drive wire350used to expand at least one embodiment of ring14. For example, ring14may include a textile or fabric mesh covering355as shown inFIGS. 94 and 95. The fabric mesh covering355may cover the entire ring14. Spreader drive wire350may run through a mesh covering lumen357as shown inFIG. 95. In one embodiment, the distal end of spreader drive wire350is fixed in place within mesh covering lumen357so that as drive wire350is pushed distally into mesh covering lumen357the mesh covering expands. Expansion of the mesh covering355forces ring14to expand. When drive wire350is pulled back proximally, the mesh and band contract back to a pre-expanded configuration. In one embodiment, the ring and mesh covering are expanded via drive wire350and they are positioned on the left atrial appendage as desired. Drive wire350may then be pulled proximally out of the mesh, thereby causing the ring and mesh covering to contract around the atrial appendage. In an alternative embodiment, the ring and mesh covering are expanded via drive wire350and they are positioned on the left atrial appendage as desired. Drive wire350may then be pulled proximally, thereby causing the ring and mesh covering to contract around the atrial appendage. The drive wire and mesh covering may then be removed completely from the ring, for example, via a suture or running stitch356. The running stitch may be pulled out of the mesh covering thereby allowing the mesh covering to be removed from the ring. In one embodiment, as shown inFIG. 95, the running stitch may be located along the mesh covering and along the inside lumen of ring14. In some embodiments, drive wire350may be releasably coupled to ring14via a mesh covering, one or more sutures, and/or one or more wires, for example.

In one embodiment, as shown inFIGS. 96 and 97, ring spreader drive wire350is coupled to a ring spreader actuator or drive mechanism360positioned at the proximal end of handle or hand piece38. In one embodiment, ring spreader drive mechanism360comprises a hand trigger mechanism365used to manually control the movement of ring spreader drive wire350in both a distal direction and a proximal direction, thereby controlling the expansion and contraction of ring14. As shown inFIG. 97, ring spreader drive mechanism360may also comprise a drive wire release assembly370. Drive wire release assembly370allows the ring spreader drive wire350to be released from ring spreader drive mechanism360. Drive wire release assembly370may comprise a spring372. Spring372may be used to provide a desired amount of force or tension on drive wire350. Drive wire release assembly370may comprise a drive wire release member374. In one embodiment, drive wire release member374includes a release mechanism that is designed to release drive wire350when it is squeezed. In one embodiment, drive wire release assembly370includes locking pins375, drive shaft members376and377and plunger378and plunger shaft379. In one embodiment, as shown inFIGS. 98A,98B and98C, the drive wire release mechanism of drive wire release member374may comprise a coupler380coupled to drive wire350that when squeezed, opens a pair of jaws, which allows the user to pull the coupler free from the rest of the device.

Furthermore, other substitutions, modifications, changes, and omissions may be made in the design, operating conditions, and arrangements of the exemplary embodiments without departing from the scope of the invention as expressed in the appended claims. In addition, it will be appreciated by those skilled in the art that while the invention has been described above in connection with particular embodiments and examples, the invention is not necessarily so limited, and that numerous other embodiments, examples, uses, modifications and departures from the embodiments, examples and uses are intended to be encompassed by the claims attached hereto. The entire disclosure of each patent and publication cited herein is incorporated by reference, as if each such patent or publication were individually incorporated by reference herein.