Patent Publication Number: US-2022226117-A1

Title: Systems and methods for delivery of chordea replacement system

Description:
PRIORITY 
     The present application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 62/859,968, filed on Jun. 11, 2019, titled “SYSTEMS AND METHODS FOR DELIVERY OF CHORDEA REPLACEMENT SYSTEM,” which is hereby incorporated by reference herein in its entirety. 
    
    
     BACKGROUND 
     The present invention relates to implantable devices. The invention is particularly useful in devices implantable by catheter for the treatment of mitral or tricuspid regurgitation. The cause of the regurgitation can be functional, degenerative, or any other reason. The invention could be used for valvular lesions as well. 
     Mitral regurgitation is a valvular dysfunction that causes blood volume to flow during systole (i.e., left ventricular contraction) from the left ventricle to the left atrium, in contrast to a healthy heart where this direction of flow is blocked by the mitral valve. The reversed flow during systole causes a rise in pressure in the left atrium. Maintaining a normal cardiac output results in increased left ventricle pressure. 
     Treating patients with mitral or tricuspid regurgitation could require valve repair or replacement in order to reduce or eliminate the regurgitation. For many years, the commonly accepted treatment was surgical repair or replacement of the native valve during open heart surgery. Valve repair is a procedure that may require complementary treatments such as utilizing annuloplasty rings with or without leaflet or chordae repair. In recent years, a trans vascular technique has been developed for introducing these devices in general and implanting an artificial chorda through a catheter in a manner that is less invasive than open heart surgery. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Aspects, features, benefits and advantages of the embodiments described herein will be apparent with regard to the following description, appended claims, and accompanying drawings where: 
         FIG. 1  depicts a short axis view of the heart in accordance with an embodiment. 
         FIG. 2  depicts mitral valve leaflets of the heart in accordance with an embodiment. 
         FIG. 3  depicts a long axis anterior to posterior view of the heart in accordance with an embodiment. 
         FIG. 4  depicts a long axis commissure to commissure view of the heart in accordance with an embodiment. 
         FIG. 5  depicts an illustrative transatrial approach in a commissure to commissure view of the heart in accordance with an embodiment. 
         FIG. 6  depicts an illustrative transatrial approach in an anterior to posterior view of the heart in accordance with an embodiment. 
         FIG. 7  depicts an illustrative transapical approach in a commissure to commissure view of the heart in accordance with an embodiment. 
         FIG. 8  depicts an illustrative transfemoral approach in an anterior to posterior view of the heart in accordance with an embodiment. 
         FIG. 9  depicts an illustrative posterior leaflet with a plurality of artificial chordae being implanted in accordance with an embodiment. 
         FIG. 10  depicts a side view of a posterior leaflet with an artificial chordae being implanted in accordance with an embodiment. 
         FIG. 11  depicts an illustrative artificial chordae with a leaflet capture mechanism in accordance with an embodiment. 
         FIG. 12  depicts an illustrative open leaflet capture configuration on an artificial chordae in accordance with an embodiment. 
         FIG. 13  depicts an illustrative closed leaflet capture configuration on an artificial chordae in accordance with an embodiment. 
         FIG. 14  depicts an illustrative pulley-based attachment and tuning mechanism in accordance with an embodiment. 
         FIG. 15  depicts an illustrative knot-based attachment and tuning mechanism in accordance with an embodiment. 
         FIG. 16  depicts an illustrative knot-based attachment and tuning mechanism in accordance with an embodiment. 
         FIG. 17  depicts another illustrative anchor-based attachment and tuning mechanism in accordance with an embodiment. 
         FIG. 18  depicts an illustrative anchor subassembly for an artificial chordae in accordance with an embodiment. 
         FIG. 19  depicts an illustrative inner member of an anchor subassembly in a deployed configuration in accordance with an embodiment. 
         FIG. 20  depicts an illustrative inner member of an anchor subassembly in a non-deployed configuration in accordance with an embodiment. 
         FIG. 21  depicts an illustrative outer member of an anchor subassembly in accordance with an embodiment. 
         FIG. 22  depicts an illustrative anchor subassembly in a non-deployed configuration in accordance with an embodiment. 
         FIG. 23  depicts an illustrative anchor subassembly in a deployed configuration in accordance with an embodiment. 
     
    
    
     DETAILED DESCRIPTION 
     This disclosure is not limited to the particular systems, devices, and methods described, as these may vary. The terminology used in the description is for the purpose of describing the particular versions or embodiments only, and is not intended to limit the scope. 
     As used in this document, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Nothing in this disclosure is to be construed as an admission that the embodiments described in this disclosure are not entitled to antedate such disclosure by virtue of prior invention. As used in this document, the term “comprising” means “including, but not limited to.” 
     When the term “valvular apparatus” is used in different variations, it may refer to the mitral valve apparatus and/or to the tricuspid valve apparatus and include the leaflets, the chordae, and/or the papillary muscles. 
     In an embodiment, an artificial chordae device is delivered to the target site, the mitral or tricuspid valve apparatus, through a catheter while the artificial chordae and their anchoring accessories are housed within a low diameter shaft which is correctly positioned and anchored to the functional configuration geometry and location. The catheter may be advanced to the target site through the vascular system. In an embodiment, the catheter may be advanced from the femoral vein or artery. In alternate embodiments, the catheter may be advanced from any blood vessel that allows access to the target site. In some embodiments the catheter may be advanced transapically, where a catheter is advanced through a small incision made in the chest wall and then through the apex. In some embodiments, the catheter may be advanced transatrially, where a catheter is advanced through a small incision made in the chest wall and then through the left or right atrium. 
     The artificial chordae device may include one or more of a variety of attachment methods for attachment to the native leaflet and myocardium. The artificial chordae device may include one or more of a variety of locking mechanisms between the leaflet capture subassembly and the native leaflet. In some embodiments, the artificial chordae device may include barbs to prevent rocking and device movement in relation to the leaflet upon insertion. The artificial chordae device may include one or more of a variety of tuning mechanisms. In addition, the artificial chordae device may include one or more of a variety of features that lock the tuning mechanism. Examples of the above-identified variations will be described further herein, although the described variations are illustrative only and are not meant to be limiting. 
     The illustrated example embodiments will be best understood by reference to the figures. The following description is intended only by way of example and illustrates certain example embodiments. 
       FIG. 1  depicts a short axis view of the heart displaying the four valves: the mitral valve  121 , the tricuspid valve  109 , the pulmonary valve  110 , and the aortic valve  107 . As shown, the mitral valve  121  includes the posterior leaflet  104  and the anterior leaflet  105 , which will be discussed further herein in relation to various embodiments. 
       FIG. 2  depicts a perspective of the mitral valve commonly known as the “surgical view” which identifies individual segments of the native leaflets of the mitral valve  221 . As depicted in  FIG. 2 , individual segments (A1, A2, A3) of the anterior leaflet  205  and individual segments (P1, P2 and P3) of the posterior leaflet  204  are identified. The lateral commissure  219  and medial commissure  220  are also noted for reference. 
       FIG. 3  depicts a left ventricular outflow tract view, anterior to posterior, of the heart which shows how the anterior  305  and posterior  304  leaflets are attached to the papillary muscles  303  by the chordae  306 .  FIG. 3  further depicts the left ventricle  302  and the right ventricle  301  separated by the intraventricular septum  312 , the apex  316 , the left atrium  308 , and the aortic valve  307 . Within the left ventricle  302 , the posterior wall  311 , mitral groove  314 , and aortic-mitral continuity  315  are specifically identified. 
       FIG. 4  depicts a perspective of the left side of the heart in commissure to commissure view showing the left atrium  408 . Similar to  FIG. 3 ,  FIG. 4  depicts the attachment of the posterior leaflet  404  to the myocardium  403  via the chordae  406  near the apex of the heart  416 . 
       FIG. 5  depicts an illustrative transatrial approach of a chordae repair device to the mitral valve apparatus in a commissure to commissure view of the heart in accordance with an embodiment. When using the transatrial approach, a catheter  545  is introduced into the left atrium  508  directly. In addition, the transatrial approach may pass by or cross-over the mitral valve and allow implantation of a chordae repair device between the posterior leaflet  504  and/or the papillary muscles  503  to repair the chordae  506 . 
       FIG. 6  depicts an illustrative transatrial approach of a chordae repair device to the mitral valve apparatus in an anterior to posterior view of the heart in accordance with an embodiment. The catheter  645  is introduced into the left atrium  608  directly at the native valve comprising the anterior  605  and posterior  604  leaflets. Using this approach, implantation of aa chordae repair device may be made to the leaflets  604 ,  605  and the papillary muscles  603  in repair of the chordae  606  within the left ventricle  602 .  FIG. 6  further depicts the right ventricle  601  and aortic valve  607  for reference. 
       FIG. 7  depicts an illustrative transapical approach of a chordae repair device to the mitral valve apparatus in an anterior to posterior view of the heart in accordance with an embodiment. Using the transapical approach, the catheter  745  is introduced between the left atrium  708  and the ventricle  702 . The transapical approach is a direct approach where the catheter  745  is introduced into the left ventricle across the apex  716  to allow implantation of the chordae repair device to the valvular apparatus to anchor between the leaflet  704  (e.g., posterior leaflet, interior leaflet, etc.) and the papillary muscles  703  to repair the chordae  706 . 
       FIG. 8  depicts an illustrative transfemoral approach of the chordae repair device to the mitral valve apparatus in an anterior to posterior view of the heart in accordance with an embodiment. The transfemoral approach is a percutaneous approach where the catheter  845  is introduced into the femoral vein and advanced along the inferior vena cava to the right atrium, across the septum  812 , to allow implantation of a chordae repair device to the valvular apparatus including the anterior  805  and posterior  804  leaflets, papillary muscles  803 , and chordae  806 . The aortic valve  807  is also shown for reference. 
       FIG. 9  depicts an illustrative posterior leaflet with a plurality of artificial chordae being implanted in accordance with an embodiment. As shown in  FIG. 9 , an artificial chordae device  922  is implanted at a plurality of locations on the posterior leaflet  904  of the left ventricle  902 . The artificial chordae device  922  may be used to repair chordae  906  that failed due to, for example and without limitation, leaflet prolapse, flail, or other pathology. In some embodiments, the artificial chordae device  922  comprises a plurality of artificial chordae  944 , an anchor subassembly  923  configured to attach to the myocardium, and a leaflet capture subassembly  935 , with a tuning mechanism  942  and stress relief pad  938 , configured to attach to the native leaflet. The implantation of one or more artificial chordae devices  922  may be performed serially or in parallel. Each artificial chordae device  922  may be tuned separately using the corresponding tuning mechanism  942 . The one or more artificial chordae devices  922  may be visualized using, for example and without limitation, endoscopy, fluoroscopy, a CT scan, an MRI scan, and/or vital signals to assist in optimizing the result. 
       FIG. 10  depicts a side view of a posterior leaflet with an artificial chordae device being implanted in accordance with an embodiment. As shown in  FIG. 10 , one or more leaflet capture assemblies  1035  may be attached to the posterior leaflet  1004  in the left ventricle  1002  from a side view. The one or more leaflet capture assemblies  1035  may include a mechanism to ensure connectivity and proper tension. In some embodiments, the connectivity and tension may be tunable (e.g., separately or in combination) during and/or after deployment and attachment. An anchor assembly  1023  may be used to attach the artificial chordae  1044  to the myocardium. The anterior leaflet  1005  and aortic valve  1007  are shown for reference. 
       FIG. 11  depicts an illustrative artificial chordae with a leaflet capture mechanism in accordance with an embodiment. An artificial chordae device comprises an artificial chordae  1144 , a leaflet capture subassembly  1135 , and an anchor subassembly  1123 . 
       FIGS. 12 and 13  depict the leaflet capture subassembly  1235  of the artificial chordae, which is composed of an upper jaw  1239 , a lower jaw  1240 , and a lock feature  1236  to assure proper attachment to the native leaflet. The jaws  1239 ,  1240  capture the leaflet and have a depth of 2-8 mm, shown as dimension A  1241 . In an embodiment, the geometry and the attachment depth of the jaws  1239 ,  1240  may be designed to prevent damage and unintentional detachment from the native leaflet. The artificial chordae  1244  may be attached to the jaws  1239 ,  1240  at the tuning mechanism  1242 . The artificial chordae  1244  may be attached to a muscle using an anchor subassembly  1223 .  FIG. 12  depicts the artificial chordae  1244  with the leaflet capture subassembly  1235  in an open configuration. 
       FIG. 13  depicts the artificial chordae  1344  with the leaflet capture subassembly  1335  in a closed configuration. As shown in  FIG. 13 , the locking mechanism  1336  is engaged. As shown, dimension A  1341  represents the attachment depth of the leaflet capture subassembly  1335  to the native leaflet. In some embodiments, the tension of the artificial chordae  1344  may be adjusted at the tuning mechanism  1342 . In some embodiments, the artificial chordae  1344  may be attached to a muscle using an anchor subassembly  1323 . 
       FIG. 14  depicts an illustrative pulley-based attachment and tuning mechanism in accordance with an embodiment. As shown in  FIG. 14 , the artificial chordae device  1422  may include a pulley tuning mechanism. In some embodiments, the tuning mechanism may include a pulley  1442  that may be controlled by a torque cable  1446  resident in a delivery catheter. In some embodiments, the torque cable  1446  may be attached to the pulley  1442  via a connection feature  1447 . In some embodiments, the leaflet capture assembly  1435  may include a stress relief pad  1438  that enables forces resulting from attachment to the native leaflet  1404  to be distributed. In such embodiments, distributing the attachment forces may prevent damage to the native leaflet  1404  and encapsulate the assembly  1435  after healing. In some embodiments, the artificial chordae  1444  may be attached to the muscle using a barbed anchor subassembly  1423 . The artificial chordae  1444  may be tuned so that the artificial chordae replace the operation of the damaged chordae  1406 . 
       FIG. 15  depicts an illustrative knot-based attachment and tuning mechanism in accordance with an embodiment. As shown in  FIG. 15 , an artificial chordae device  1522  may include a tuning mechanism that includes a knot  1542 . In some embodiments, the knot  1542  may be adjustable and may be used to tune the artificial chordae device  1522  to the correct length. In some embodiments, the knot  1542  may be tuned to the correct length through the delivery catheter  1545 . In some embodiments, the knot  1542  may be locked to a final length through movement of a proximal section of a tightening suture  1543 . In some embodiments, the artificial chordae device  1522  may be attached to the posterior leaflet  1504  and anchored via a screw-based anchor  1523  to the papillary muscles  1503  to repair the damaged chordae  1506 . 
       FIG. 16  depicts an illustrative knot-based attachment and tuning mechanism in accordance with an embodiment. As shown in  FIG. 16 , a plurality of artificial chordae  1644  are implanted in the left ventricle  1602  to properly repair the damaged chordae  1606 . In some embodiments, each artificial chordae may be attached to the posterior leaflet  1604  via a suture  1643  and anchored to the myocardium via a screw-based anchor  1623 . In some embodiments, the length of each of the artificial chordae  1644  may be adjusted independently by adjusting, for example, the corresponding knot-based tuning mechanism. In some embodiments, adjustments to the tuning mechanism may be performed from the delivery catheter. 
     In some embodiments, multiple devices may be attached to the posterior leaflet or the anterior leaflet. In such embodiments, an operator may control the distance between adjacent attachments to leaflet mechanisms. In another embodiment, one or more pads may be used for stress relief of the attachment. In some embodiments, the pads may be large patches that could support a plurality of attachment mechanisms  1638 . In alternate embodiments, smaller patches may be used that only support a single mechanism  1638 . 
       FIG. 17  depicts another illustrative anchor-based attachment and tuning mechanism in accordance with an embodiment. As shown in  FIG. 17 , artificial chordae  1744  may be implanted to replace damaged chordae  1706  in the left ventricle  1702 . In some embodiments, the artificial chordae  1744  may be attached to the posterior leaflet  1704  in pairs on stress relief pads  1738 . In some embodiments, the artificial chordae  1744  may be anchored to the myocardium below the papillary muscles  1703 . In some embodiments, the tuning mechanism may include one or more torque cables  1746  controlled via the delivery catheter  1745 . In some embodiments, a barbed assembly  1723  may be used to anchor the artificial chordae  1744 . 
     The length of each of the artificial chordae may be from about 20 mm to about 120 mm. For example, the length of an artificial chordae may be tuned to 20 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 90 mm, 100 mm, 110 mm, 120 mm, or to a length within a range between any two of these endpoints. The variation in the length of the artificial chordae may be used to address variations in ventricle size in a patient population as well as to allow the operator to make a decision as to where to anchor the assembly. For example, different operators may choose to anchor the assembly near to the apex, while other operators may choose to anchor the assembly near to the papillary muscle. Such decisions may be based on the anatomy of the patient and/or operator preference. 
     In some embodiments, the design of a chordae replacement device may allow loading the device into a low profile shaft having an outer diameter that is, for example, less than or equal to 13 mm. In some embodiments, the chordae replacement device and the associated delivery system may enable delivery of a plurality of devices, such as the leaflet capture assembly, anchor assembly, and artificial chordae. In some embodiments, the plurality of devices may be delivered consecutively or simultaneously. In some embodiments, the plurality of devices may be housed in parallel inside the catheter prior to delivery. In some embodiments, the plurality of devices may be housed consecutively within the catheter prior to delivery. In some embodiments, only one of the plurality of devices may be loaded into the catheter at a time. In some embodiments, the control mechanism (e.g., the torque cable  1746 ) may be retained within the catheter. 
     The leaflet capture assembly may be configured to attach to the native leaflets of the tricuspid valve or the mitral valve. When used in the mitral position, the leaflet capture assembly may lean in against the edges of the mitral leaflets, anterior or posterior, according to the area that requires treatment. In some embodiments, the attachment mechanism may enable tuning of the tension on the artificial chordae that attaches leaflets to the myocardium. In some embodiments, the attachment mechanism may enable precise positioning with respect to the leaflet. In some embodiments, the attachment mechanism may include a padded surface to distribute the forces and/or to encourage encapsulation of the assembly into the leaflet. 
     One of ordinary skill in the art will be aware that any combination of the various components described herein and equivalents may be used for the construction of a particular device based on this disclosure. In other words, the devices depicted herein are merely illustrative of the types of devices that may be constructed according to the teachings of this disclosure and are not meant to be limited to these illustrative embodiments. 
       FIG. 18  depicts an illustrative anchor subassembly for an artificial chordae in accordance with an embodiment. The anchor assembly  1823  may be configured to attach to the myocardium. In some embodiments, the anchor assembly  1823  may include a self-expanding stent comprising a shape memory material (e.g., Nitinol). In some embodiments, the anchor assembly  1823  may be cut from a tube or sheet and/or use a pattern that allows crimping and expanding. In one embodiment, the anchoring assembly  1823  may be constructed from a wire formed into a coiled geometry configured to be screwed into the tissue. The coiled portion  1824  of the anchor assembly  1823  may be configured to penetrate into tissue and maintain an anchoring force during implantation and in vivo life expectancy. 
     In some embodiments, the anchor assembly  1823  may feature an interface portion  1825  that is configured to enable an attachment with a catheter during implantation. The interface portion  1825  may include an attachment  1826  to the delivery catheter that allows transmission of torque forces. The torque forces may be applied to the attachment  1826  to rotate the anchor assembly  1823  and enable the coiled portion  1824  to penetrate into tissue. In some embodiments, axial forces may also be applied to advance the anchor assembly  1823  into or retract the anchor assembly from tissue. In some embodiments, the interface portion  1825  may include one or more holes  1827  configured to attach artificial chordae to the anchor assembly  1823 . Illustrative coil-based anchor assemblies are further depicted in  FIGS. 10-13, 15, and 16 . 
       FIG. 19  depicts an illustrative inner member of an anchor subassembly in a deployed configuration in accordance with an embodiment. In some embodiments, an anchor subassembly may include an outer member (depicted in  FIG. 21 ) and an inner member  1928 . The inner member may include a tube having a specific pattern that allows two different configurations as depicted in  FIGS. 19 and 20 . As shown in  FIG. 19 , a plurality of anchors  1929  may be positioned on a first end of the anchor subassembly  1928 . The plurality of anchors  1929  may expand radially to anchor into tissue. In some embodiments, the opposite end  1930  of the anchor subassembly  1928  may provide an interface for attachment to the artificial chordae. 
       FIG. 20  depicts the illustrative inner member of the anchor subassembly of  FIG. 19  in a non-deployed configuration. As shown in  FIG. 20 , the anchors  2029  of the anchor subassembly  2028  may be aligned parallel with the interface  2030  of the anchor subassembly. The anchor  2029  may be in the non-deployed configuration when housed within the outer member of the anchor subassembly as discussed further in reference to  FIGS. 21 and 22 . 
     In some embodiments, the inner member of the anchor subassembly may be constructed from one or more metals and/or an alloy. In one embodiment, the inner member is constructed from one or more metals that are biocompatible and are configured to permit the device to transform between the two configurations. For example, the inner member may comprise one or more of cobalt, chrome, stainless steel, or Nitinol. 
       FIG. 21  depicts an illustrative outer member of an anchor subassembly in accordance with an embodiment. As shown in  FIG. 21 , an outer member  2133  of an anchor assembly may comprise a tube with a plurality of windows  2132 . In some embodiments, each of the plurality of windows may be located radially. Different window locations are contemplated within the scope of this disclosure. In some embodiments, the outer member  2133  may include a distal portion  2134  having a sharp edge. The sharp edge of the distal portion  2134  may be configured to enable the outer member to penetrate into tissue. In some embodiments, the outer member  2133  may further include a proximal section  2131 . In some embodiments, the proximal section  2131  of the outer member  2133  may be used for attachment to the delivery system and/or to the artificial chordae. 
     In some embodiments, the outer member  2133  of the anchor subassembly may be constructed from one or more metals and/or an alloy. In one embodiment, the outer member  2133  is constructed from one or more metals that are biocompatible. For example, the outer member  2133  may comprise one or more of cobalt, chrome, stainless steel, or Nitinol. In some embodiments, the outer member  2133  may comprise a plastic, such as polyetheretherketone, other materials, or other combinations of materials that are biocompatible. 
       FIGS. 22 and 23  depict an illustrative anchor subassembly in a non-deployed configuration  2223  and a deployed configuration  2323 , respectively, in accordance with an embodiment. In some embodiments, the inner member  2228 / 2328  may include a plurality of anchors  2229 / 2329  and the artificial chordae interface  2230 / 2330 . In some embodiments, the inner member may be inserted into the outer member  2233 / 2333 . In some embodiments, the outer member  2233 / 2333  may include a plurality of anchor windows  2232 / 2332 , a control interface  2231  to the delivery system, and a distal end  2234 / 2334 . 
     In some embodiments, transitioning between the non-deployed configuration and the deployed configuration may be controlled via the delivery catheter by advancing, retracting, and/or rotating the catheter. In some embodiments, transitioning between the two configurations may further be performed with the outer member. For example, linear movement of the inner member  2228 / 2328  with respect to the outer member  2233 / 2333  may cause the plurality of anchors  2229 / 2329  to transition between the two configurations. In some embodiments, movement of the inner member  2228 / 2328  may cause the outer member  2233 / 2333  to deflect the anchors through the windows  2232 / 2332  mechanically. In some embodiments, the inner member  2228 / 2328  may be manufactured from a shape memory material, such as Nitinol, and movement of the inner member with respect to the outer member  2233 / 2333  may cause the anchors to transition to the deployed configuration. In some embodiments, the control interface  2231  may be designed to allow an easy and safe release after the device is anchored to the tissue. 
     In some embodiments, the inner member may be manufactured by machining, grinding, and/or laser cutting. In some embodiments, the distal ends  2234 / 2334  of the anchors  2229 / 2329  may be sharpened or grinded to enable tissue penetration. In some embodiments, the anchors  2229 / 2329  may be aligned in a specific direction. In some embodiments, the anchors  2229 / 2329  may be aligned in two opposing directions. In some embodiments, the anchors  2229 / 2329  may be aligned in a plurality of directions. 
     Any number of anchors  2229 / 2329  may be used within the scope of this disclosure. In some embodiments, the distal ends  2234  may be inside the corresponding windows  2232  to assure deployment through the windows when the inner member  2228  is within the outer member  2233  in the non-deployed configuration. In some embodiments, the inner member  2228  may be stored within the catheter and advanced into the outer member  2233  separately. In some embodiments, the inner diameter of the outer member  2233  may be in a range of about 0.8 mm to about 4 mm. In some embodiments, the outer diameter of the inner member  2228  may be in a range of about 0.8 mm to about 4 mm, but in any event is less than the inner diameter of the outer member  2233  to allow movement of the inner member therein. 
     For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (for example, “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. 
     In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (for example, the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example, “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, et cetera). In those instances where a convention analogous to “at least one of A, B, or C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example, “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, et cetera). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.” 
     As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, et cetera. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, et cetera. As will also be understood by one skilled in the art all language such as “up to,” “at least,” and the like include the number recited and refer to ranges that can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 cells refers to groups having 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth. 
     Various of the above-disclosed and other features and functions, or alternatives thereof, may be combined into many other different systems or applications. Various presently unforeseen or unanticipated alternatives, modifications, variations or improvements therein may be subsequently made by those skilled in the art, each of which is also intended to be encompassed by the disclosed embodiments.