Patent Document

FIELD OF THE INVENTION 
       [0001]    The present invention relates generally to treatment of aortic dissections and treatment of type-B aortic dissections using a tubular implant to stabilize and remodel the tissues of the aorta. 
       BACKGROUND 
       [0002]    Aortic dissection most commonly occurs in patients between the age of 40 to 60 years old and is two or three times more frequent in men than women within this age group. Hypertension, a coexisting condition in 70% of the patients, is almost invariably the most important factor causing or initiating aortic dissection. Other risk factors that predispose a patient to develop aortic dissection include aortic dilation, aortic aneurysm, congenital valve abnormality, coarctation of aorta, and Marfan syndrome. These patients often present with sudden, severe, and tearing pain that may be localized in the front or back of the chest. Other symptoms include syncope, dyspnea, and weakness. These presentations are the consequence of intimal tear in the aorta, dissecting hematoma, occlusion of involved arteries, and compression of adjacent tissues. For example, patients may have neurological symptoms, such as hemiplegia, due to carotid artery obstruction, or paraplegia, due to spinal cord ischemia. Patients may also present with bowel ischemia or cardiac ischemia due to occlusion of major arteries by the dissecting aorta. 
         [0003]    Aortic dissection can be classified by the Stanford method into type A and type B depending on the location and the extent of the dissection. Type A dissection, or proximal dissection, involves the ascending aorta. Type B dissection, or distal dissection, usually begins just downstream of the left subclavian artery, extending downward into the descending and abdominal aorta. If left untreated, the risk of death from aortic dissection can reach 35% within 15 minutes after onset of symptoms and 75% by one week. 
         [0004]    Once diagnosed, aortic dissection is treated with immediate medical management aimed at reducing cardiac contractility and systemic arterial pressure, thereby reducing shear stress on the aorta. Beta-adrenergic blockers, unless contraindicated, are usually used to treat acute dissection. Surgical correction, including reconstruction of the aortic wall, is usually the preferred treatment for ascending aortic dissection (type A). Medical therapy is the preferred treatment for stable and uncomplicated distal aortic dissection (type B), unless there is clinical evidence of propagation, obstruction of major arterial branches, or impending aortic rupture in which case surgical correction is preferred. In-hospital mortality for medically treated patients with type B dissection is between 15 to 20 percent. Morbidity and mortality for surgical correction is not significantly better than medically treated patients. Currently, there is no good treatment for type B aortic dissection. A need for devices and methods therefore exists to treat patients suffering from Type B dissection. 
       SUMMARY OF THE INVENTION 
       [0005]    The present invention relates to devices and methods for treating aortic dissection and in particular type-B aortic dissection. Type-B dissections typically have an entry point immediately downstream of the takeoff of the left subclavian artery from the aorta. The device used herein is a catheter having a proximal end, a distal region, and a distal end. The catheter carries an endoluminal implant, commonly referred to as a stent, which comprises a porous mesh that is releaseably mounted on the distal region of the catheter. The implant is a generally cylindrical member having a length and the implant is expandable between a low-profile compressed state and an enlarged state. The implant may be pre-curved in the enlarged state. In the enlarged state, the implant has a proximal opening (downstream opening), a distal opening (upstream opening), and a lumen therebetween. The implant may also be equipped with a porous mesh or a textile covering a portion of the upstream region, the downstream region, or both the upstream and downstream regions of the implant. Further, the implant may be over-curved relative to the aorta in the region proximate to or upstream of the entry point of the dissection. Over-curvature ensures that the distal region of the implant adjacent the lesser curvature of the aorta achieves uniform wall contact with the lesser curvature of the aorta. 
         [0006]    The methods of the present invention make use of a catheter with endoluminal implant or stent as described above. The catheter is generally introduced into the patient&#39;s aorta through an access site in the femoral artery. The catheter is advanced into the abdominal and thoracic aorta taking care not to enter the false lumen formed by the dissection. The catheter is advanced through the native lumen and positioned adjacent the entry point on the aorta. The self-expanding endoluminal implant is held in a collapsed state by an elongate capture sheath that extends proximal from the region that carries the implant. Once in place, the endoluminal implant is released by withdrawing the capture sheath. The implant assumes its enlarged, optionally pre-curved state and engages the endoluminal surface of the aorta. 
         [0007]    The implant or stent is composed of a woven metal structure or strutted configuration, e.g., as produced by laser etching of a metal tube (e.g., stainless steel or nitinol) or weaving/braiding of a metal wire. In cases where the stent is pre-curved, the stent conforms substantially to the curvature of the aorta without distorting native anatomy. In cases where the stent is over-curved relative to the aorta in the region proximate to the entry point of the dissection, the upstream edge of the stent achieves uniform wall contact and does not lift away from the endoluminal surface of the lesser curvature. The upstream edge may also include an extension to assist in maintaining contact at the endoluminal surface of the lesser curvature. The woven or strutted configuration is sufficiently porous to allow perfusion of arteries that branch from the aorta, e.g., the intercostal arteries, celiac trunk, superior mesenteric artery, renal arteries, left subclavian artery, left common carotid, and inferior mesenteric artery. 
         [0008]    In cases where the stent is covered at its upstream, downstream, or upstream and downstream ends with a textile, a porous textile is used. The textile is selected from various biocompatible textiles that promote tissue in-growth to promote healing. The textile extends only over limited parts of the stent, e.g., over the portion of the stent that engages the entry point of the dissection and/or re-entry point of the dissection. The remainder of the stent is free of covering to allow perfusion of arteries that branch from the aorta. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0009]      FIG. 1A  depicts the anatomy of the aorta. 
           [0010]      FIGS. 1B and 1C  depict the various tissue layers of the aorta in cross-section. 
           [0011]      FIG. 1D  depicts the aorta in cross-section with dissection. 
           [0012]      FIG. 2  depicts an aorta with the beginning stages of a dissection. 
           [0013]      FIG. 3  depicts the aorta of  FIG. 2  having a dissection that has progressed downstream along a length of the aorta. 
           [0014]      FIG. 4A  depicts the aorta of  FIG. 3  having a dissection that has progressed to a re-entry point downstream in the aorta. 
           [0015]      FIG. 4B  is a cross-section view of the aorta in  FIG. 4A  through section line A-A. 
           [0016]      FIG. 5  depicts a catheter for use in repair of aortic dissection as described herein. 
           [0017]      FIG. 6  depicts the catheter of  FIG. 5  with the implant partially deployed. 
           [0018]      FIG. 7  depicts the catheter of  FIG. 5  advanced into the thoracic aorta. 
           [0019]      FIG. 8  depicts the deployment of the implant to close the entry point of the aortic dissection. 
           [0020]      FIG. 9  depicts the implant of  FIG. 8  deployed to close an aortic dissection. 
           [0021]      FIG. 10  depicts a pre-curved or over-curved implant for use herein to treat aortic dissection. 
           [0022]      FIG. 11  depicts an implant having portions of textile covering for use herein to treat aortic dissection. 
       
    
    
     DETAILED DESCRIPTION 
       [0023]    The aorta of a normal individual is depicted in  FIG. 1A . Aorta  2  is anatomically designated as having ascending aorta  3 , aortic arch  4 , and descending aorta  5 . Aortic arch  4  includes greater curvature  12  and lesser curvature  13 . A number of arteries branch from aorta  2  and supply blood to many of the body&#39;s vital organs. For example, innominate artery  6 , left common carotid artery  7 , and left subclavian artery  8  supply blood to various regions of the brain. If blood flow to any of these arteries is interrupted, stroke may result. Intercostal arteries  9  branch from descending aorta  5  and supply blood to various regions of the spine and spinal cord. Interruption of blood flow in the intercostal arteries can result in paraplegia. The superior and inferior mesenteric arteries supply blood to the intestines, the celiac artery supplies blood to the liver, and the renal arteries supply blood to the kidneys. Interruption of blood flow in any of these arteries can have devastating results. 
         [0024]      FIG. 2  illustrates the initiation of an aortic dissection. The most common aortic dissections occur near the ostium of left subclavian artery  8 , just downstream where blood passing along the greater curvature of the arch impacts the intimal lining of the aorta at the takeoff of the left subclavian artery. Intimal lining  15  begins to tear away from outer layers  16  of the aorta, which layers include the media and adventitia (see  FIGS. 1B ,  1 C, and  1 D). Entry point  17  opens as a result of tearing, which creates a chamber between torn intima  15  and outer layers  16 . The chamber receives and traps blood, and as the pressure builds within the chamber, blood flow causes the tear to progress downstream as depicted in  FIG. 3 . As intima  15  pulls away from outer layers  16 , a false lumen  19  is formed that progresses downstream in descending aorta  5  as depicted in  FIG. 4A . Re-entry point  18  forms where the intima tears from itself to allow blood to re-enter the natural lumen. 
         [0025]    A catheter for aortic dissection repair is depicted in  FIG. 5 . Catheter  21  is an elongate tubular member and has proximal end  22 , distal end  23 , and is adapted and sized for advancement into the aorta through a femoral artery access site. Catheter  21  may include a lumen that extends proximally from one or more ports at a distal region for administering pharmaceutical agents. A self-expanding stent  25  is loaded on the distal region or distal end of catheter  21 . Stent  25  is held in a low profile configuration by sheath  24 , which is an elongate tubular member operable from the proximal end of catheter  21 . Sheath  24  is withdrawn proximally to uncover and thereby release stent  25  as illustrated in  FIG. 6 . As stent  25  is released, it expands to an enlarged state adapted to engage the endoluminal surface of the aorta. 
         [0026]    In use, stent delivery catheter  21  is advanced through a femoral access site into the descending aorta as illustrated in  FIG. 7 . Catheter  21  is advanced retrograde past the downstream edge of torn intima  15  so that catheter  21  remains within the native lumen (not within the false lumen). Distal end  23  of catheter  21  is positioned adjacent entry point  17  of the aortic dissection. The procedure may be conducted using standard fluoroscopic visualization techniques to align catheter  21  with anatomical landmarks visible by angiography. One or more fluoroscopic markers may be included on catheter  21 , on the distal region or distal end  23  of catheter  21 , on covering  41  (see  FIG. 11 ), on covering  42  (see  FIG. 11 ), and/or on stent  25  for purposes of alignment. The takeoff of left subclavian artery  8  or entry point  17  are among anatomical landmarks useful for alignment. 
         [0027]    After distal end  23  of catheter  21  is aligned with entry point  17  at the most upstream edge of the intimal tear, sheath  24  is withdrawn proximally to release stent  25  as shown in  FIG. 8 . Stent  25  expands to engage intima  15  and then displace intima  15  until it makes contact again with outer layers  16  of aorta  2 . Intima  15  is thereby pressed into contact with the outer layers of the aorta. Stent  25  contacts the intimal tear to close entry point  17  at a first position  33  on the circumference of the upstream region (distal region) or upstream end of stent  25 . A second position  31  on the circumference of the upstream region (distal region) or upstream end of stent  25 , approximately 180° relative to first position  33 , engages the endoluminal surface of the aorta at the lesser curvature. As will be explained in greater detail below, stent  25  may be pre-curved, and in certain cases over-curved relative to the curvature of the aorta so that second position  31  on stent  25  achieves uniform wall contact along the endoluminal surface at the lesser curvature. 
         [0028]    As stent  25  displaces intima  15  toward outer layers  16  of the aorta, blood is purged from the false lumen and the false lumen is gradually closed. This process continues as shown in  FIG. 8  as sheath  24  is withdrawn proximally until proximal end  32  (the downstream end) of stent  25  is released in the downstream region of the descending aorta as shown in  FIG. 9 . Proximal end  32  of stent  25  expands to close re-entry point  18 . Substantially all blood is forced out of the false lumen created by the aortic dissection. Catheter  21  and sheath  24  may then be withdrawn from the aorta and removed from the patient. With time, any remaining blood trapped between layers of the vessel will be removed by the healing process as the aorta is remodeled by re-attachment of intimal layer  15  to outer layers  16 . The woven or strut pattern of stent  25  moreover is sufficiently porous to allow perfusion of intercostal arteries  9  and other arteries that branch from the aorta in the region now covered by the stent. 
         [0029]    The subject matter herein may be implemented so that stent  25  achieves uniform wall contact, especially where the stent contacts the lesser curvature of the aorta arch, and conforms to the curvature of the aorta without distorting native anatomy. These objectives may be accomplished using a pre-curved stent as depicted in  FIG. 10 . The upstream or distal end  31  of stent  25  has longitudinal axis  35 . The downstream or proximal end  32  of stent  25  has longitudinal axis  36 . Axis  35  and axis  36  meet at angle theta. As described herein, it is understood that stent  25  may desirably be implemented with pre-curved angle theta of 145° or less, 140° or less, 130° or less, 120° or less, 110° or less, 100° or less, 90° or less, 80° or less, 70° or less, 60° or less, or 50° or less. By using a stent that is over-curved relative to the aorta in the region proximate to the entry point of the dissection  17  (see  FIGS. 7 ,  8  and  9 ), the leading edge  31  of stent  25  achieves uniform wall contact with the endoluminal surface of the lesser curvature of the aorta. Without uniform wall contact at leading edge  31 , blood flow along the lesser curvature will impact leading edge  31 , pulling the leading edge away from the lesser curvature and causing blood flow turbulence. 
         [0030]    The devices may also include a portion of a textile material on the distal region (upstream region), the proximal region (downstream region), or both the proximal and distal regions. A stent having textile  41  and  42  on distal and proximal regions is illustrated in  FIG. 11 . Textile  41  at the upstream end of stent  25  may be disposed on the outer circumference of metal stent  25 . Alternatively, textile  41  at the upstream end of stent  25  may be disposed on the inner circumference of metal stent  25 . Textile  41  may extend downstream for a length of 1 cm, 2 cm, 3 cm, 4 cm or more. Textile  41  may be composed of Dacron, nylon, Teflon (PTFE), expanded PTFE (ePTFE), urethanes (Lycra Spandex), polypropylene, silicone, biodegradable synthetics, such as polyglycolide (PGA), polylactide (PLA), biologics, and composites, or any other biocompatible material suitable for intravascular use. Coatings may be added to affect physiologic response, e.g., blood clotting and healing. For instance, prothrombin, which induces clotting, may be coated on the textile positioned near or adjacent the entry tear. Coatings may be added to resist thrombogenesis, e.g., heparin coating. For instance, heparin might be used on the un-covered portion of the stent that is distal to the entry tear to prevent clotting around the intercostals. Textile  41  is advantageously composed of a porous mesh material having a pore size of greater than 50 microns, greater than 60 microns, greater than 70 microns, greater than 80 microns, greater than 90 microns, greater than 100 microns, greater than 110 microns, or greater than 120 microns. At the same time, pore size will advantageously be less than 2000 microns, less than 1500 microns, less than 1000 microns, less than 750 microns, less than 500 microns, or less than 250 microns. The porosity of the textile may also be described with reference to flow rate. Porosity will be chosen to allow a flow rate of greater than 800 mL/cm2·min at 120 mmHg, greater than 850 mL/cm2·min at 120 mmHg, greater than 900 mL/cm2·min at 120 mmHg, or greater than 1000 mL/cm2·min at 120 mmHg. Porosity will be chosen to allow a flow rate of less than 20,000 mL/cm2·min at 120 mmHg, less than 18,000 mL/cm2·min at 120 mmHg, less than 15,000 mL/cm2·min at 120 mmHg, or less than 10,000 mL/cm2·min at 120 mmHg. The textile may have the ability to promote in-growth of vascular cells to remodel the intimal lining for long-term healing. 
         [0031]    Textile  42 , when present, at the downstream end of stent  25  may be disposed on the outer circumference of metal stent  25 . Alternatively, textile  42  at the downstream end of stent  25  may be disposed on the inner circumference of metal stent  25 . Textile  42  may extend upstream for a length of 1 cm, 2 cm, 3 cm, 4 cm, or more. Textile  42  may be composed of Dacron, nylon, Teflon (PTFE), expanded PTFE (ePTFE), urethanes (Lycra Spandex), polypropylene, silicone, biodegradable synthetics, such as polyglycolide (PGA), polylactide (PLA), biologics, and composites, or any other biocompatible material suitable for intravascular use. Coatings may be added to affect physiologic response, e.g., blood clotting and healing. For instance, prothrombin, which induces clotting, may be coated on the textile positioned near or adjacent the entry tear. Coatings may be added to resist thrombogenesis, e.g., heparin coating. For instance, heparin might be used on the un-covered portion of the stent that is distal to the entry tear to prevent clotting around the intercostals. Textile  42  is likewise advantageously composed of a porous mesh material having pore sizes and flow characteristics in the ranges listed above for textile  41 . Textile  42  may also have the ability to promote in-growth of vascular cells to remodel the intimal lining for long-term healing at the reentry point. 
         [0032]    The working length of catheter  21  will generally be between 30 and 100 centimeters, preferably approximately between 50 and 80 centimeters. The outer diameter of the catheter  21  shaft will generally be between 1 French and 8 French, preferably approximately between 1.5 French and 4 French. The outer diameter of sheath  24  will generally be between 10 and 22 French, preferably approximately between 12 and 16 French. Stent  25  may vary in length but is generally approximately 5 cm to 30 cm, preferably approximately 10 cm to 20 cm. The foregoing ranges are set forth solely for the purpose of illustrating typical device dimensions. The actual dimensions of a device constructed according to the principles of the present invention may obviously vary outside of the listed ranges without departing from those basic principles. 
         [0033]    Although the foregoing invention has, for the purposes of clarity and understanding, been described in some detail by way of illustration and example, it will be obvious that certain changes and modifications may be practiced that will still fall within the scope of the appended claims. For example, the devices and features depicted in any figure or embodiment can be used in any of the other depicted embodiments.

Technology Category: 1