Patent Publication Number: US-RE46126-E

Title: Cardiac valve installation with enhanced anchoring to the annulus based on tissue healing

Description:
NOTICE: More than one reissue application has been filed for the reissue of U.S. Pat. No. 8,430,926. The reissue applications are the present application and application Ser. No. 14/699,447, both of which are reissues of U.S. Pat. No. 8,430,926. 
     CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. provisional application No. 60/822,113, filed Aug. 11, 2006, which is incorporated herein by reference. 
     BACKGROUND 
     In the recent past, many advances have been made to reduce the invasiveness of cardiac surgery. In an attempt to avoid open, stopped-heart procedures, which may be accompanied by high patient morbidity and mortality, many devices and methods have been developed for performing surgery on a heart through smaller incisions, operating on a beating heart, and finally, in the past years, performing cardiac procedures via transvascular access. Significant technological advances have been made in various types of cardiac procedures, such as cardiac ablation techniques for treating atrial fibrillation, stenting procedures for atherosclerosis, and valve repair procedures. More specifically, much progress has been made on treating conditions such as mitral valve regurgitation. In implementing many minimally invasive cardiac surgery techniques, especially beating-heart techniques, one of the most significant challenges is positioning a treatment device and once positioned, to effectively deploy and fix a given device or treatment into or on the surface of the target cardiac tissue. 
     Traditional treatment of heart valve stenosis or regurgitation, such as mitral or tricuspid regurgitation, typically involves an open-heart surgical procedure to replace or repair the valve. Valve repair procedures typically involve annuloplasty, a set of techniques designed to restore the valve annulus shape and strengthen the annulus. Conventional annuloplasty surgery generally requires a thoracotomy, and sometimes a median sternotomy. These open heart procedures involve placing the patient on a cardiopulmonary bypass machine for sustained periods so that the patient&#39;s heart and lungs can be artificially stopped during the procedure. Finally, valve repair and replacement procedures are technically challenging and require a relatively large incision through the wall of the heart to access the valve. 
     Due to the highly invasive nature of open heart valve repair or replacement, high risk patients are usually not candidates for these procedures and thus are destined to functional deterioration and cardiac enlargement. Often, such patients have no feasible alternative treatments for their heart valve conditions. 
     In order to try and solve this problem, a number of devices and methods for repairing cardiac valves in a less invasive manner have been described. Some devices offer heart valve repair through minimally invasive incisions or intravascularly, while others attempt to improve open heart surgical procedures on beating hearts, stopped hearts or both. Difficulties in performing minimally invasive intra-cardiac surgery include positioning a minimally invasive treatment device in a desired location for performing a procedure and effectively placing and fixing a device into or on the surface of the target cardiac tissue. In heart valve repair procedures, for example, it is often essential for a physician to fix a device to valve annulus tissue. Annular tissue tends to be more fibrous than surrounding muscular or valve leaflet tissue, thus providing a more suitable location for securing such a device. In the past, various types of anchors and anchoring techniques have been developed in order to fix treatment devices to the annular tissue. This is an important stage in all annuloplasty procedures and especially in procedures for treating mitral or tricuspid valve regurgitation. 
     Devices and methods that address these difficulties are described in U.S. patent application Ser. Nos. 60/445,890, 60/459,735, 60/462,502, 60/524,622, 10/461,043, 10/656,797 and Ser. No. 10/741,130. For example, these references describe devices and methods for exposing, stabilizing and/or performing procedure on a heart valve annulus, such as a mitral valve annulus. Many of these methods and devices have shown preliminary promise, however a highly safe and effective method and engaging apparatus for performing cardiac valve annuloplasty has, until now, been lacking. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows the location of the mitral annulus in a cross-section of the heart. 
         FIG. 2  shows a first approach for positioning a first embodiment of an engaging apparatus at the annulus. 
         FIG. 3  shows a cross section of the embodiment shown in  FIG. 2 . 
         FIG. 4  shows an embodiment of a delivery system in which a multi-pronged device is used to place the engaging apparatus at the annulus. 
         FIG. 5  shows a close up of the end of the  FIG. 4  embodiment. 
         FIG. 6  is a detailed view of the first embodiment of the engaging apparatus. 
         FIG. 7  shows a detailed view of another embodiment of the engaging apparatus. 
         FIG. 8  shows the engaging apparatus of  FIG. 7  in location at the mitral annulus immediately after being positioned and anchored to the tissue. 
         FIG. 9  shows the engaging apparatus of  FIG. 7  after being left in place for sufficient time for tissue healing and remodeling to occur. 
         FIG. 10  shows another embodiment of an engaging apparatus that contains an integral anchoring delivery system. 
         FIG. 11  shows the  FIG. 10  embodiment with an artificial valve anchored to the engaging apparatus. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       FIG. 1  shows the location of the mitral annulus  2  in a cross-section of the heart. The method and engaging apparatus of the current delivery system are used to facilitate transvascular, minimally invasive and other “less invasive” surgical procedures, by facilitating the placing and fixing of a treatment engaging apparatus  6  at a treatment site. As used herein, “less invasive” means any procedure that is less invasive than traditional, large-incision, open surgical procedures. Generally, any procedure in which a goal is to minimize or reduce invasiveness to the patient may be considered less invasive. Although the methods described herein are developed for use in minimally invasive procedures, they may be applied to performing or enhancing any suitable procedure, including traditional open heart surgery. The present application describes methods and apparatuses for performing heart valve repair or replacement procedures, and more specifically heart valve annuloplasty procedures such as mitral valve annuloplasty to treat mitral regurgitation and mitral valve replacement to treat mitral stenosis. In other embodiments, the devices and methods may be used to enhance a laparoscopic or other endoscopic procedure on any part of the body, such as the bladder, stomach, gastroesophageal junction, vasculature, gall bladder, or the like. Therefore, although the following description typically focuses on mitral valve  8  and other heart valve  9  repair, such description should not be interpreted to limit the scope of the invention. 
       FIG. 2  shows a cross-section of the heart, with a full view of one embodiment of a balloon delivery system  4  and a full view of an engaging apparatus  6 . The balloon delivery system  4  can be used for placement of the engaging apparatus  6  at the annulus  2 . Initially, the balloon is routed to the proper position in its deflated state (not shown) using any suitable route or method (e.g., an endoscopic technique), and then inflated. At this point, the system will resemble  FIG. 2 , in which the balloon  4  is shown in its inflated state, positioned at the mitral valve  8 . The engaging apparatus  6  is located around the balloon  4 , and the inflation brings the engaging apparatus  6  into proximity of the annular tissue  2  and presses them towards each other. The engaging apparatus  6  initially surrounds the balloon  4  and anchors to the annular tissue  2  upon inflation of the balloon  4 . 
       FIG. 3  depicts the same items as  FIG. 2  except that the delivery system is shown in cross section. The balloon is shown with a central channel  10  and flexible leaflets  12  seen within its lumen. These leaflets  12  act as a temporary replacement valve in order to allow normal heart function during the insertion procedure. In some embodiments, valve repair or replacement may be implemented using a hollow, inflatable balloon  4  with integral flexible valve leaflets  12  within its lumen which act as a temporary replacement for the natural valve upon inflation, while maintaining adequate flow through from the atrium  1  to the ventricle  3  throughout the procedure via channel  10 . Because of the channel  10 , blood can flow through the system even when the balloon  6  is inflated, which facilitates installation of the device into a beating heart. 
     Upon deflation of the balloon, the engaging apparatus  6  will detach from the balloon  4  and remain attached to the annulus  2  with enough anchoring force to withstand normal cardiac contraction, flow and valve movement. Attachment to the annulus can be aided by using appropriate anchors, hooks, barbs, etc. Alternatively, the engaging apparatus  6  can hold itself in place by exerting a centripetal pressure on the annulus, generated by the springiness of the engaging apparatus. 
     In some embodiments (not shown), the engaging apparatus  6  may be contained within a hidden circumferential pocket surrounding the balloon  4  and will engage the annular tissue  2  only upon release from this pocket. The release of the engaging apparatus  6  from the balloon  4  may be performed by releasing a slip-knot like suture from the balloon  4  or any other suitable alternative approach. In these embodiments, conventional balloon and balloon inflation technology may be used, similar to those used in other annuloplasty procedures (e.g., conventional balloon procedures for widening a stenotic valve). 
       FIG. 4  shows a cross-section of the heart, a full view of the first embodiment of an engaging apparatus  6 , and a full view of the second embodiment of a delivery system. This delivery system uses a multi-pronged device  14  that is preferably collapsible (similar to an umbrella frame, a truncated wire whisk, etc). to place the engaging apparatus  6  at the annulus  2 . The methods and engaging apparatus of the delivery system, however, may be used in any suitable procedure, both cardiac and non-cardiac. For example, they may be used in procedures to repair any heart valve  9 , to replace any heart valve  9 , to repair an atrial-septal  11  defect, to access and possibly perform a valve repair from (or through) the coronary sinus. 
       FIG. 5  shows a detail view of the multi-pronged delivery system  14  shown in  FIG. 4 . In some embodiments, valve repair may be implemented using a delivery device  14  which can be extended from the tip of a catheter  16  to allow for the correct positioning of the engaging apparatus  6  at the annulus. The multi-pronged placement device  14  can be introduced into the left atrium  1  (shown in  FIG. 4 ) during on-pump or off-pump procedures through the wall of the atrium or through the intra-atrial septum, with the catheter  16  introduced by intravascular or minimal invasive approach. Placement and tightening may be performed on a beating heart because blood can flow through the spaces between the prongs. Access to the beating heart may be accomplished by any available technique, including intravascular, trans-thoracic, and the like. Intravascular access to a heart valve may be achieved using any suitable route or method. 
     For example, to perform a procedure on a mitral valve  8  a catheter  16  may be advanced through a femoral artery, to the aorta, and into the left ventricle of the heart, to contact a length of the mitral valve. After it is so positioned, the device  14  is expanded so as to press the engaging apparatus  6  against the annulus. The expansion of the delivery system  14  may be implemented using any suitable technique such as withdrawal of a sheath that permits the prongs to to spring out to their natural state. Alternatively, access may be gained through the venous delivery system, to a central vein, into the right atrium of the heart, and across the inter-atrial septum to the left side of the heart to contact a length of the mitral valve. In alternative embodiments, the catheter device  16  may access the coronary sinus and a valve procedure may be performed directly from the sinus. Furthermore, in addition to beating heart access, methods of the present delivery system may be used for intravascular stopped heart access as well as stopped heart open chest procedures. Any suitable intravascular or other access method may be substituted. 
       FIG. 6  shows a detailed view of the first embodiment of the engaging apparatus. This embodiment uses a helical spring  18  that has been formed to be substantially arc-shaped preferably subtending an arc of at least 180°, and more preferably at least 270°, with a wire  20  within it for subsequent tightening. The spring geometry allows for changes in ring diameter, and creates a channel for the tightening wire. It also allows for tissue healing into the spaces in the spring  22 , thereby bonding the engaging apparatus to the annulus wall by embedding the engaging apparatus within the annulus wall. Some time after the initial placement, a second procedure for tightening the engaging apparatus  6  is preferably implemented. 
     Tightening of the engaging apparatus may be accomplished, for example, by retracting a wire  20  left within the engaging apparatus  6  during its placement at the annulus using a minimally invasive approach. However, any alternative method or device for the tightening of a structure at the annulus may be used. This includes, but is not limited to, different types of steerable catheter tips  16  (as shown in  FIG. 4 ) catheters allowing for direct manipulation of objects at the tip, catheters allowing for visualization of the annulus, and catheters which deliver energy at the area of interest (ultrasound, heat, radiofrequency fields, etc.). Non-invasive techniques for tightening the engaging apparatus  6  may also be used, including but not limited to magnetic manipulation through the chest wall, radiofrequency energy delivery through the chest wall and ultrasound energy transmitted through the chest wall. 
     The engaging apparatus  6  may be made of Stainless Steel, Nitinol, Elgiloy or Titanium; however any material with the necessary strength, flexibility and biocompatibility to withstand cardiac pressures may be used. A suitable diameter for the arc is between about 25 and about 60 mm. A suitable diameter for the helix is between about 1 and about 3 mm, and a suitable pitch for the helix is between about 1 and about 3 mm. 
     In some embodiments, the engaging apparatus  6  may be constructed of a spring like ring  18  with or without a central cavity for a tightening wire  20 . This spring like ring  18  may be configured to facilitate the growth of annular tissue into the engaging apparatus  6  strengthening the adhesion between the annulus and the engaging apparatus  6 . However, other surface geometries which facilitate tissue anchoring into the engaging apparatus may also be used, including but not limited to serrated, hooked, porous or folded surfaces. A tube with holes or serrations cut therein (not shown) may also be used. 
     In some embodiments, the tightening wire  20  may be made of silk or plastic, however, any material with sufficient strength, elasticity and biocompatibility may be used for this purpose. As used herein, the term “wire” includes all such materials and constructions. The wire  20  may be used for subsequent tightening of the engaging apparatus  6  (e.g., by pulling on both ends of the wire) leading to a tightening of the annulus of the patient&#39;s heart. 
       FIG. 7  shows a detailed view of a second embodiment of an engaging apparatus. This embodiment is similar to the  FIG. 6  embodiment discussed above, but anchors  24  are added to the spring like ring  18  for initial anchoring of the engaging apparatus  56  to the annulus to better withstand cardiac contraction, valve motion and blood flow. One type of anchoring element—a two pronged, open ended miniature spring  26 —is shown in the insert A, but alternative anchors may be used instead. Any of the delivery systems described above may be used to position the engaging apparatus  56  at the annulus and fix it in place by gentle centripetal pressure  4  alone or in conjunction with any existing placing and anchoring technique or by the use of existing placing and anchoring techniques alone. Alternatively, the engaging apparatus  56  may be placed using any other minimally invasive or invasive placement delivery systems. 
     Optionally, any of the engaging apparatuses described herein may be coated with an adhesive substance to facilitate integration between the engaging apparatus and the annulus. Optionally, the engaging apparatus may contain hooks, serrations, spokes or sutures for preliminary attachment to the annulus. Examples of suitable structures include, but are not limited to, a closed circular spring with a flexible diameter, open ended semi-circular structures, non circular structures capable of approximation between two or more free tips, and non-continuous structures such as individual tubes connected to the annular rim. Optionally, the engaging apparatus may be made of or elute materials which stimulate or accelerate tissue growth. These materials may include but are not limited to growth factors, pro-inflammatory agents, foreign substances which are immunogenic and lead to an enhanced tissue reaction to the engaging apparatus. Optionally, the engaging apparatus may contain an active electromechanical element, such as a motor or actuator, capable of tightening the engaging apparatus. This active component may be self powered by a battery or by mechanical energy generated by the cardiac muscle or blood flow. The active element may be activated using minimally invasive techniques or non-invasive techniques. In the case of non-invasive activation of the active element, any form of transmitted energy may be used, including but not limited to ultrasound and radiofrequency transmission. 
     The delivery systems and engaging apparatuses described herein may be used for repair of a cardiac valve annulus such as a mitral valve annulus using a two step procedure: placing and tightening. The method preferably involves bringing an engaging apparatus into position to the annulus of interest as shown in  FIG. 2  or  FIG. 4  through a minimally invasive procedure. 
       FIG. 8  shows the engaging apparatus  56  from  FIG. 7  in location at the mitral annulus  2  immediately after being left in place and anchored to the tissue using the delivery system described above or any other minimally invasive or invasive placement delivery system. No tissue healing or remodeling has occurred at this stage and the engaging apparatus  6  is attached to the annulus  2  with the minimal necessary force. 
       FIG. 9  shows the same engaging apparatus  56  after being left in place for sufficient time for tissue healing and remodeling to occur  28 . At this point the engaging apparatus  56  is integrated into the annulus  2  due to tissue healing which has embedded the engaging apparatus within the annular wall. This tissue healing  28  embeds the engaging apparatus  56  within the wall of the annulus  2  with sufficient integration to allow for subsequent tightening of the engaging apparatus  56  (e.g., by pulling on both ends of the wire  20 , shown in  FIG. 7 ) to circumferentially tighten the annulus  2 . The anchoring strength of the engaging apparatus to the annulus at this stage is preferably sufficient to withstand tightening of the engaging apparatus  56  and the entire annulus  2  in a subsequent procedure. 
     By using this procedure (i.e., install, wait for incorporation, then tighten), the initial placement of the engaging apparatus  56  at the annulus  2  requires anchoring strength much lower than that used for existing minimally invasive annuloplasty techniques. The initial anchoring strength is sufficient to withstand the normal shear-forces, flow and contraction of the beating heart but, may be less than that necessary for tightening the annulus  2 . The tightening procedure is subsequently performed during a second procedure after allowing a sufficiently long period of time for tissue remodeling  28  into and around the engaging apparatus. It is expected that one week should be sufficient, but it may be possible to use a shorter waiting time in some circumstances. 
     Alternatively, in embodiments that rely on adhesion the second step of tightening the engaging apparatus  56  may be performed during the same procedure after allowing sufficient time for adhesion to occur between the engaging apparatus  56  and the annular tissue  2 . The tightening procedure may also be performed in any number of subsequent procedures or non-invasively through the chest wall. Optionally, the engaging apparatus  56  may deliver energy or focus externally transmitted energy to the annular surface  2  in order to accelerate tissue growth into or around the engaging apparatus  28 . 
       FIG. 10  shows yet another embodiment in which the engaging apparatus  66  contains an integral anchoring delivery system  30  which allows for an artificial valve  32  to be connected to the engaging apparatus  66 , during a subsequent procedure, instead of or in addition to tightening of the annulus. The illustrated delivery system may be used for replacement of a cardiac valve, such as the mitral valve using a three step procedure: widening of the annulus, placing the engaging apparatus  66 , and anchoring an artificial valve  32  to the engaging apparatus  66 . Introduction of the artificial valve  32  to the engaging apparatus may be performed through an intravascular or minimally invasive approach. 
       FIG. 11  shows the  FIG. 10  embodiment where the artificial valve  32  is anchored to the engaging apparatus  66  during a subsequent, minimally invasive procedure. Optionally, the engaging apparatus  66  may be placed at the annulus  2  as a second step procedure following widening of the annulus  2  and valve  8  using a minimally invasive balloon inflation technique or any other method for widening a stenotic valve. Subsequently, the artificial valve  32  may be attached to the engaging apparatus  66  during a third procedure, instead of or in addition to tightening of the annulus  2 . 
     All of the above-described embodiments advantageously permit blood flow during insertion of the delivery system and the engaging apparatus.