Patent Publication Number: US-2005137691-A1

Title: Two piece heart valve and anchor

Description:
BACKGROUND OF THE INVENTION  
      The present invention relates to methods and apparatus for endovascularly replacing a heart valve. More particularly, the present invention relates to methods and apparatus for endovascularly replacing a heart valve with a replacement valve using an expandable and retrievable anchor.  
      Heart valve surgery is used to repair or replace diseased heart valves. Valve surgery is an open-heart procedure conducted under general anesthesia. An incision is made through the patient&#39;s sternum (sternotomy), and the patient&#39;s heart is stopped while blood flow is rerouted through a heart-lung bypass machine.  
      Valve replacement may be indicated when there is a narrowing of the native heart valve, commonly referred to as stenosis, or when the native valve leaks or regurgitates. When replacing the valve, the native valve is excised and replaced with either a biologic or a mechanical valve. Mechanical valves require lifelong anticoagulant medication to prevent blood clot formation, and clicking of the valve often may be heard through the chest. Biologic tissue valves typically do not require such medication. Tissue valves may be obtained from cadavers or may be porcine or bovine, and are commonly attached to synthetic rings that are secured to the patient&#39;s heart.  
      Valve replacement surgery is a highly invasive operation with significant concomitant risk. Risks include bleeding, infection, stroke, heart attack, arrhythmia, renal failure, adverse reactions to the anesthesia medications, as well as sudden death. 2-5% of patients die during surgery.  
      Post-surgery, patients temporarily may be confused due to emboli and other factors associated with the heart-lung machine. The first 2-3 days following surgery are spent in an intensive care unit where heart functions can be closely monitored. The average hospital stay is between 1 to 2 weeks, with several more weeks to months required for complete recovery.  
      In recent years, advancements in minimally invasive surgery and interventional cardiology have encouraged some investigators to pursue percutaneous replacement of the aortic heart valve. Percutaneous Valve Technologies (“PVT”) of Fort Lee, N.J., has developed a balloon-expandable stent integrated with a bioprosthetic valve. The stent/valve device is deployed across the native diseased valve to permanently hold the valve open, thereby alleviating a need to excise the native valve and to position the bioprosthetic valve in place of the native valve. PVT&#39;s device is designed for delivery in a cardiac catheterization laboratory under local anesthesia using fluoroscopic guidance, thereby avoiding general anesthesia and open-heart surgery. The device was first implanted in a patient in April of 2002.  
      PVT&#39;s device suffers from several drawbacks. Deployment of PVT&#39;s stent is not reversible, and the stent is not retrievable. This is a critical drawback because improper positioning too far up towards the aorta risks blocking the coronary ostia of the patient. Furthermore, a misplaced stent/valve in the other direction (away from the aorta, closer to the ventricle) will impinge on the mitral apparatus and eventually wear through the leaflet as the leaflet continuously rubs against the edge of the stent/valve.  
      Another drawback of the PVT device is its relatively large cross-sectional delivery profile. The PVT system&#39;s stent/valve combination is mounted onto a delivery balloon, making retrograde delivery through the aorta challenging. An antegrade transseptal approach may therefore be needed, requiring puncture of the septum and routing through the mitral valve, which significantly increases complexity and risk of the procedure. Very few cardiologists are currently trained in performing a transseptal puncture, which is a challenging procedure by itself.  
      Other prior art replacement heart valves use self-expanding stents as anchors. In the endovascular aortic valve replacement procedure, accurate placement of aortic valves relative to coronary ostia and the mitral valve is critical. Standard self-expanding systems have very poor accuracy in deployment, however. Often the proximal end of the stent is not released from the delivery system until accurate placement is verified by fluoroscopy, and the stent typically jumps once released. It is therefore often impossible to know where the ends of the stent will be with respect to the native valve, the coronary ostia and the mitral valve.  
      Also, visualization of the way the new valve is functioning prior to final deployment is very desirable. Visualization prior to final and irreversible deployment cannot be done with standard self-expanding systems, however, and the replacement valve is often not fully functional before final deployment.  
      Another drawback of prior art self-expanding replacement heart valve systems is their lack of radial strength. In order for self-expanding systems to be easily delivered through a delivery sheath, the metal needs to flex and bend inside the delivery catheter without being plastically deformed. In arterial stents, this is not a challenge, and there are many commercial arterial stent systems that apply adequate radial force against the vessel wall and yet can collapse to a small enough of a diameter to fit inside a delivery catheter without plastically deforming. However when the stent has a valve fastened inside it, as is the case in aortic valve replacement, the anchoring of the stent to vessel walls is significantly challenged during diastole. The force to hold back arterial pressure and prevent blood from going back inside the ventricle during diastole will be directly transferred to the stent/vessel wall interface. Therefore the amount of radial force required to keep the self expanding stent/valve in contact with the vessel wall and not sliding will be much higher than in stents that do not have valves inside of them. Moreover, a self-expanding stent without sufficient radial force will end up dilating and contracting with each heartbeat, thereby distorting the valve, affecting its function and dynamic repositioning of the stent during delivery. Stent foreshortening or migration during expansion may lead to improper alignment.  
      Additionally, Garrison&#39;s stent simply crushes the native valve leaflets against the heart wall and does not engage the leaflets in a manner that would provide positive registration of the device relative to the native position of the valve. This increases an immediate risk of blocking the coronary ostia, as well as a longer-term risk of migration of the device post-implantation. Further still, the stent comprises openings or gaps in which the replacement valve is seated post-delivery. Tissue may protrude through these gaps, thereby increasing a risk of improper seating of the valve within the stent.  
      In view of drawbacks associated with previously known techniques for endovascularly replacing a heart valve, it would be desirable to provide methods and apparatus that overcome those drawbacks.  
     SUMMARY OF THE INVENTION  
      One aspect of the invention provides an apparatus for endovascularly replacing a patient&#39;s heart valve, including: a custom-designed anchor; and a replacement valve, wherein the custom-designed anchor is adapted to engage native leaflets of the heart valve, and wherein the anchor and the valve are adapted for in vivo expansion and coupling to one another to form composite apparatus that endovascularly replaces the heart valve.  
      Another aspect of the invention provides a method for endovascularly replacing a patient&#39;s heart valve. In some embodiments the method includes the steps of: providing apparatus comprising an anchor piece and a replacement valve piece; endovascularly delivering the anchor piece to a vicinity of the heart valve in a collapsed delivery configuration; expanding the anchor piece to a deployed configuration; engaging at least one valve leaflet of the heart valve with the anchor piece; endovascularly delivering the replacement valve piece to the vicinity of the heart valve in a collapsed delivery configuration; expanding the replacement valve piece to a deployed configuration; and coupling the valve piece to the anchor piece in vivo to form composite two-piece apparatus that endovascularly replaces the patient&#39;s heart valve.  
      Yet another aspect of the invention provides an apparatus for endovascularly replacing a patient&#39;s heart valve, including: an anchor having a first portion of an alignment/locking mechanism; and a replacement valve having a second portion of the alignment/locking mechanism, wherein the anchor and the valve are adapted for in vivo expansion and coupling to one another to form composite apparatus that endovascularly replaces the patient&#39;s heart valve.  
      Still another aspect of the invention provides a method for endovascularly replacing a patient&#39;s heart valve. In some embodiments the method includes the steps of: endovascularly delivering an anchor piece having a first portion of an alignment/locking mechanism to a vicinity of the heart valve in a collapsed delivery configuration; expanding the anchor piece to a deployed configuration such that the anchor piece displaces the patient&#39;s heart valve; endovascularly delivering a replacement valve piece having a second portion of the alignment/locking mechanism to the vicinity of the heart valve in a collapsed delivery configuration; expanding the replacement valve piece to a deployed configuration; and coupling the valve piece to the anchor piece in vivo by securing the first and second portions of the alignment/locking mechanism to one another, thereby forming composite two-piece apparatus that endovascularly replaces the patient&#39;s heart valve.  
     INCORPORATION BY REFERENCE  
      All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:  
      FIGS.  1 A-B show an anchor for use in a two-piece replacement heart valve and anchor embodiment of the invention.  
      FIGS.  2 A-B show a replacement heart valve for use in in a two-piece replacement heart valve and anchor embodiment of the invention.  
      FIGS.  3 A-D show a method of coupling the anchor of  FIG. 1  and the replacement heart valve of  FIG. 2 .  
       FIG. 4  shows a delivery system for use with the appartus shown in  FIGS. 1-3 .  
       FIG. 5  shows an alternative embodiment of a delivery system for use with the apparatus shown in  FIGS. 1-3 .  
       FIG. 6  shows yet another alternative embodiment of a delivery system for use with the apparatus shown in  FIGS. 1-3 .  
      FIGS.  7 A-I illustrate a method of deliverying and deploying a two-piece replacement heart valve and anchor.  
      FIGS.  8 A-B shows another embodiment of a two-piece replacement heart valve and anchor according to this invention.  
       FIG. 9  shows yet another embodiment of a two-piece replacement heart valve and anchor according to this invention.  
       FIG. 10  shows yet another embodiment of a two-piece replacement heart valve and anchor according to this invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION  
      While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.  
      With reference now to  FIGS. 1-4 , a first embodiment of replacement heart valve apparatus in accordance with the present invention is described, including a method of actively foreshortening and expanding the apparatus from a delivery configuration and to a deployed configuration. Apparatus  10  comprises replacement valve  20  disposed within and coupled to anchor  30 .  FIG. 1  schematically illustrate individual cells of anchor  30  of apparatus  10 , and should be viewed as if the cylindrical anchor has been cut open and laid flat.  FIG. 2  schematically illustrate a detail portion of apparatus  10  in side-section.  
      Anchor  30  has a lip region  32 , a skirt region  34  and a body region  36 . First, second and third posts  38   a ,  38   b  and  38   c , respectively, are coupled to skirt region  34  and extend within lumen  31  of anchor  30 . Posts  38  preferably are spaced 120° apart from one another about the circumference of anchor  30 .  
      Anchor  30  preferably is fabricated by using self-expanding patterns (laser cut or chemically milled), braids and materials, such as a stainless steel, nickel-titanium (“Nitinol”) or cobalt chromium but alternatively may be fabricated using balloon-expandable patterns where the anchor is designed to plastically deform to it&#39;s final shape by means of balloon expansion. Replacement valve  20  is preferably from biologic tissues, e.g. porcine valve leaflets or bovine or equine pericardium tissues, alternatively it can be made from tissue engineered materials (such as extracellular matrix material from Small Intestinal Submucosa (SIS)) but alternatively may be prosthetic from an elastomeric polymer or silicone, Nitinol or stainless steel mesh or pattern (sputtered, chemically milled or laser cut). The leaflet may also be made of a composite of the elastomeric or silicone materials and metal alloys or other fibers such Kevlar or carbon. Annular base  22  of replacement valve  20  preferably is coupled to skirt region  34  of anchor  30 , while commissures  24  of replacement valve leaflets  26  are coupled to posts  38 .  
      Anchor  30  may be actuated using external non-hydraulic or non-pneumatic force to actively foreshorten in order to increase its radial strength. As shown below, the proximal and distal end regions of anchor  30  may be actuated independently. The anchor and valve may be placed and expanded in order to visualize their location with respect to the native valve and other anatomical features and to visualize operation of the valve. The anchor and valve may thereafter be repositioned and even retrieved into the delivery sheath or catheter. The apparatus may be delivered to the vicinity of the patient&#39;s aortic valve in a retrograde approach in a catheter having a diameter no more than 23 french, preferably no more than 21 french, more preferably no more than 19 french, or more preferably no more than 17 french. Upon deployment the anchor and replacement valve capture the native valve leaflets and positively lock to maintain configuration and position.  
      A deployment tool is used to actuate, reposition, lock and/or retrieve anchor  30 . In order to avoid delivery of anchor  30  on a balloon for balloon expansion, a non-hydraulic or non-pneumatic anchor actuator is used. In this embodiment, the actuator is a deployment tool that includes distal region control wires  50 , control rods or tubes  60  and proximal region control wires  62 . Locks  40  include posts or arms  38  preferably with male interlocking elements  44  extending from skirt region  34  and mating female interlocking elements  42  in lip region  32 . Male interlocking elements  44  have eyelets  45 . Control wires  50  pass from a delivery system for apparatus  10  through female interlocking elements  42 , through eyelets  45  of male interlocking elements  44 , and back through female interlocking elements  42 , such that a double strand of wire  50  passes through each female interlocking element  42  for manipulation by a medical practitioner external to the patient to actuate and control the anchor by changing the anchor&#39;s shape. Control wires  50  may comprise, for example, strands of suture.  
      Tubes  60  are reversibly coupled to apparatus  10  and may be used in conjunction with wires  50  to actuate anchor  30 , e.g., to foreshorten and lock apparatus  10  in the fully deployed configuration. Tubes  60  also facilitate repositioning and retrieval of apparatus  10 , as described hereinafter. For example, anchor  30  may be foreshortened and radially expanded by applying a distally directed force on tubes  60  while proximally retracting wires  50 . As seen in  FIG. 3 , control wires  62  pass through interior lumens  61  of tubes  60 . This ensures that tubes  60  are aligned properly with apparatus  10  during deployment and foreshortening. Control wires  62  can also actuate anchor  60 ; proximally directed forces on control wires  62  contacts the proximal lip region  32  of anchor  30 . Wires  62  also act to couple and decouple tubes  60  from apparatus  10 . Wires  62  may comprise, for example, strands of suture.  
       FIGS. 1A and 2A  illustrate anchor  30  in a delivery configuration or in a partially deployed configuration (e.g., after dynamic self-expansion expansion from a constrained delivery configuration within a delivery sheath). Anchor  30  has a relatively long length and a relatively small width in the delivery or partially deployed configuration, as compared to the foreshortened and fully deployed configuration of  FIGS. 1B and 2B .  
      In  FIGS. 1A and 2A , replacement valve  20  is collapsed within lumen  31  of anchor  30 . Retraction of wires  50  relative to tubes  60  foreshortens anchor  30 , which increases the anchor&#39;s width while decreasing its length. Such foreshortening also properly seats replacement valve  20  within lumen  31  of anchor  30 . Imposed foreshortening will enhance radial force applied by apparatus  10  to surrounding tissue over at least a portion of anchor  30 . In some embodiments, the anchor exerts an outward force on surrounding tissue to engage the tissue in such way to prevent migration of anchor caused by force of blood against closed leaflet during diastole. This anchoring force is preferably 1 to 2 lbs, more preferably 2 to 4 lbs, or more preferably 4 to 10 lbs. In other embodiments, the anchoring force is preferably greater than 1 pound, more preferably greater than 2 pounds, or more preferably greater than 4 pounds. Enhanced radial force of the anchor is also important for enhanced crush resistance of the anchor against the surrounding tissue due to the healing response (fibrosis and contraction of annulus over a longer period of time) or to dynamic changes of pressure and flow at each heart beat In an alternative embodiment, the anchor pattern or braid is designed to have gaps or areas where the native tissue is allowed to protrude through the anchor slightly (not shown) and as the foreshortening is applied, the tissue is trapped in the anchor. This feature would provide additional means to prevent anchor migration and enhance long term stability of the device.  
      Deployment of apparatus  10  is fully reversible until lock  40  has been locked via mating of male interlocking elements  44  with female interlocking elements  42 . Deployment is then completed by decoupling tubes  60  from lip section  32  of anchor  30  by retracting one end of each wire  62  relative to the other end of the wire, and by retracting one end of each wire  50  relative to the other end of the wire until each wire has been removed from eyelet  45  of its corresponding male interlocking element  44 .  
      As best seen in  FIG. 2B , body region  36  of anchor  30  optionally may comprise barb elements  37  that protrude from anchor  30  in the fully deployed configuration, for example, for engagement of a patient&#39;s native valve leaflets and to preclude migration of the apparatus.  
      With reference now to  FIG. 3 , a delivery and deployment system for a self-expanding embodiment of apparatus  10  including a sheath  110  having a lumen  112 . Self-expanding anchor  30  is collapsible to a delivery configuration within lumen  112  of sheath  110 , such that apparatus  10  may be delivered via delivery system  100 . As seen in  FIG. 3A , apparatus  10  may be deployed from lumen  112  by retracting sheath  110  relative to apparatus  10 , control wires  50  and tubes  60 , which causes anchor  30  to dynamically self-expand to a partially deployed configuration. Control wires  50  then are retracted relative to apparatus  10  and tubes  60  to impose foreshortening upon anchor  30 , as seen in  FIG. 3B .  
      During foreshortening, tubes  60  push against lip region  32  of anchor  30 , while wires  50  pull on posts  38  of the anchor. Wires  62  may be retracted along with wires  50  to enhance the distally-directed pushing force applied by tubes  60  to lip region  32 . Continued retraction of wires  50  relative to tubes  60  would lock locks  40  and fully deploy apparatus  10  with replacement valve  20  properly seated within anchor  30 , as in  FIGS. 1B and 2B . Apparatus  10  comprises enhanced radial strength in the fully deployed configuration as compared to the partially deployed configuration of  FIG. 3A . Once apparatus  10  has been fully deployed, wires  50  and  62  may be removed from apparatus  10 , thereby separating delivery system  100  and tubes  60  from the apparatus.  
      Deployment of apparatus  10  is fully reversible until locks  40  have been actuated. For example, just prior to locking the position of the anchor and valve and the operation of the valve may be observed under fluoroscopy. If the position needs to be changed, by alternately relaxing and reapplying the proximally directed forces exerted by control wires  50  and/or control wires  62  and the distally directed forces exerted by tubes  60 , expansion and contraction of the lip and skirt regions of anchor  30  may be independently controlled so that the anchor and valve can be moved to, e.g., avoid blocking the coronary ostia or impinging on the mitral valve. Apparatus  10  may also be completely retrieved within lumen  112  of sheath  110  by simultaneously proximally retracting wires  50  and tubes  60 /wires  62  relative to sheath  110 . Apparatus  10  then may be removed from the patient or repositioned for subsequent redeployment.  
      Referring now to  FIG. 4 , step-by-step deployment of apparatus  10  via delivery system  100  is described. In  FIG. 4A , sheath  110  is retracted relative to apparatus  10 , wires  50  and tubes  60 , thereby causing self-expandable anchor  30  to dynamically self-expand apparatus  10  from the collapsed delivery configuration within lumen  112  of sheath  110  to the partially deployed configuration. Apparatus  10  may then be dynamically repositioned via tubes  60  to properly orient the apparatus, e.g. relative to a patient&#39;s native valve leaflets.  
      In  FIG. 4B , control wires  50  are retracted while tubes  60  are advanced, thereby urging lip region  32  of anchor  30  in a distal direction while urging posts  38  of the anchor in a proximal direction. This foreshortens apparatus  10 , as seen in  FIG. 4C . Deployment of apparatus  10  is fully reversible even after foreshortening has been initiated and has advanced to the point illustrated in  FIG. 4C .  
      In  FIG. 4D , continued foreshortening causes male interlocking elements  44  of locks  40  to engage female interlocking elements  42 . The male elements mate with the female elements, thereby locking apparatus  10  in the foreshortened configuration, as seen in  FIG. 4E . Wires  50  are then pulled through eyelets  45  of male elements  44  to remove the wires from apparatus  10 , and wires  62  are pulled through the proximal end of anchor  30  to uncouple tubes  60  from the apparatus, thereby separating delivery system  100  from apparatus  10 . Fully deployed apparatus  10  is shown in  FIG. 4F .  
      Referring to  FIG. 5 , a method of endovascularly replacing a patient&#39;s diseased aortic valve with apparatus  10  and delivery system  100  is described. As seen in  FIG. 5A , sheath  110  of delivery system  100 , having apparatus  10  disposed therein, is endovascularly advanced over guide wire G, preferably in a retrograde fashion (although an antegrade or hybrid approach alternatively may be used), through a patient&#39;s aorta A to the patient&#39;s diseased aortic valve AV. A nosecone  102  precedes sheath  110  in a known manner. In  FIG. 5B , sheath  110  is positioned such that its distal region is disposed within left ventricle LV of the patient&#39;s heart H.  
      Apparatus  10  is deployed from lumen  112  of sheath  110 , for example, under fluoroscopic guidance, such that anchor  30  of apparatus  10  dynamically self-expands to a partially deployed configuration, as in  FIG. 5C . Advantageously, apparatus  10  may be retracted within lumen  112  of sheath  110  via wires  50 —even after anchor  30  has dynamically expanded to the partially deployed configuration, for example, to abort the procedure or to reposition apparatus  10  or delivery system  100 . As yet another advantage, apparatus  10  may be dynamically repositioned, e.g. via sheath  110  and/or tubes  60 , in order to properly align the apparatus relative to anatomical landmarks, such as the patient&#39;s coronary ostia or the patient&#39;s native valve leaflets L. When properly aligned, skirt region  34  of anchor  30  preferably is disposed distal of the leaflets, while body region  36  is disposed across the leaflets and lip region  32  is disposed proximal of the leaflets.  
      Once properly aligned, wires  50  are retracted relative to tubes  60  to impose foreshortening upon anchor  30  and expand apparatus  10  to the fully deployed configuration, as in  FIG. 5D . Foreshortening increases the radial strength of anchor  30  to ensure prolonged patency of valve annulus An, as well as to provide a better seal for apparatus  10  that reduces paravalvular regurgitation. As seen in  FIG. 5E , locks  40  maintain imposed foreshortening. Replacement valve  20  is properly seated within anchor  30 , and normal blood flow between left ventricle LV and aorta A is thereafter regulated by apparatus  10 . Deployment of apparatus  10  advantageously is fully reversible until locks  40  have been actuated.  
      As seen in  FIG. 5F , wires  50  are pulled from eyelets  45  of male elements  44  of locks  40 , tubes  60  are decoupled from anchor  30 , e.g. via wires  62 , and delivery system  100  is removed from the patient, thereby completing deployment of apparatus  10 . Optional barb elements  37  engage the patient&#39;s native valve leaflets, e.g. to preclude migration of the apparatus and/or reduce paravalvular regurgitation.  
      With reference now to  FIG. 6 , a method of endovascularly replacing a patient&#39;s diseased aortic valve with apparatus  10  is provided, wherein proper positioning of the apparatus is ensured via positive registration of a modified delivery system to the patient&#39;s native valve leaflets. In  FIG. 6A , modified delivery system  100 ′ delivers apparatus  10  to diseased aortic valve AV within sheath  110 . As seen in  FIGS. 6B and 6C , apparatus  10  is deployed from lumen  112  of sheath  110 , for example, under fluoroscopic guidance, such that anchor  30  of apparatus  10  dynamically self-expands to a partially deployed configuration. As when deployed via delivery system  100 , deployment of apparatus  10  via delivery system  100 ′ is fully reversible until locks  40  have been actuated.  
      Delivery system  100 ′ comprises leaflet engagement element  120 , which preferably self-expands along with anchor  30 . Engagement element  120  is disposed between tubes  60  of delivery system  100 ′ and lip region  32  of anchor  30 . Element  120  releasably engages the anchor. As seen in  FIG. 6C , the element is initially deployed proximal of the patient&#39;s native valve leaflets L. Apparatus  10  and element  120  then may be advanced/dynamically repositioned until engagement element positively registers against the leaflets, thereby ensuring proper positioning of apparatus  10 . Also delivery system  100 ′ includes filter structure  61 A (e.g., filter membrane or braid) as part of push tubes  60  to act as an embolic protection element. Emboli can be generated during manipulation and placement of anchor from either diseased native leaflet or surrounding aortic tissue and can cause blockage. Arrows  61 B in  FIG. 6E  show blood flow through filter structure  61 A where blood is allowed to flow but emboli is trapped in the delivery system and removed with it at the end of the procedure.  
      Alternatively, foreshortening may be imposed upon anchor  30  while element  120  is disposed proximal of the leaflets, as in  FIG. 6D . Upon positive registration of element  120  against leaflets L, element  120  precludes further distal migration of apparatus  10  during additional foreshortening, thereby reducing a risk of improperly positioning the apparatus.  FIG. 6E  details engagement of element  120  against the native leaflets. As seen in  FIG. 6F , once apparatus  10  is fully deployed, element  120 , wires  50  and tubes  60  are decoupled from the apparatus, and delivery system  100 ′ is removed from the patient, thereby completing the procedure.  
      With reference to  FIG. 7 , an alternative embodiment of the apparatus of  FIG. 6  is described, wherein leaflet engagement element  120  is coupled to anchor  30  of apparatus  10 ′, rather than to delivery system  100 . Engagement element  120  remains implanted in the patient post-deployment of apparatus  10 ′. Leaflets L are sandwiched between lip region  32  of anchor  30  and element  120  in the fully deployed configuration. In this manner, element  120  positively registers apparatus  10 ′ relative to the leaflets and precludes distal migration of the apparatus over time.  
      Referring now to  FIG. 8 , an alternative delivery system adapted for use with a balloon expandable embodiment of the present invention is described. In  FIG. 8A , apparatus  10 ″ comprises anchor  30 ′ that may be fabricated from balloon-expandable materials. Delivery system  100 ″ comprises inflatable member  130  disposed in a deflated configuration within lumen  31  of anchor  30 ′. In  FIG. 8B , optional outer sheath  110  is retracted, and inflatable member  130  is inflated to expand anchor  30 ′ to the fully deployed configuration. As inflatable member  130  is being deflated as in earlier embodiments, wires  50  and  62  and tubes  60  may be used to assist deployment of anchor  30 ′ and actuation of locks  40 , as well as to provide reversibility and retrievability of apparatus  10 ″ prior to actuation of locks  40 . Next, wires  50  and  62  and tubes  60  are removed from apparatus  10 ″, and delivery system  100 ″ is removed, as seen in  FIG. 8C .  
      As an alternative delivery method, anchor  30 ′ may be partially deployed via partial expansion of inflatable member  130 . The inflatable member would then be advanced within replacement valve  20  prior to inflation of inflatable member  130  and full deployment of apparatus  10 ″. Inflation pressures used will range from about 3 to 6 atm, or more preferably from about 4 to 5 atm, though higher and lower atm pressures may also be used (e.g., greater than 3 atm, more preferably greater than 4 atm, more preferably greater than 5 atm, or more preferably greater than 6 atm). Advantageously, separation of inflatable member  130  from replacement valve  20 , until partial deployment of apparatus  10 ″ at a treatment site, is expected to reduce a delivery profile of the apparatus, as compared to previously known apparatus. This profile reduction may facilitate retrograde delivery and deployment of apparatus  10 ″, even when anchor  30 ′ is balloon-expandable.  
      Although anchor  30 ′ has illustratively been described as fabricated from balloon-expandable materials, it should be understood that anchor  30 ′ alternatively may be fabricated from self-expanding materials whose expansion optionally may be balloon-assisted. In such a configuration, anchor  30 ′ would expand to a partially deployed configuration upon removal of outer sheath  110 . If required, inflatable member  130  then would be advanced within replacement valve  20  prior to inflation. Inflatable member  130  would assist full deployment of apparatus  10 ″, for example, when the radial force required to overcome resistance from impinging tissue were too great to be overcome simply by manipulation of wires  50  and tubes  60 . Advantageously, optional placement of inflatable member  130  within replacement valve  20 , only after dynamic self-expansion of apparatus  10 ″ to the partially deployed configuration at a treatment site, is expected to reduce a delivery profile of the apparatus, as compared to previously known apparatus. This reduction may facilitate retrograde delivery and deployment of apparatus  10 ″.  
      With reference to  FIGS. 9 and 10 , methods and apparatus for a balloon-assisted embodiment of the present invention are described in greater detail.  FIGS. 9 and 10  illustratively show apparatus  10 ′ of  FIG. 7  used in combination with delivery system  100 ″ of  FIG. 8 .  FIG. 10  illustrates a sectional view of delivery system  100 ″. Inner shaft  132  of inflatable member  130  preferably is about 4 Fr in diameter, and comprises lumen  133  configured for passage of guidewire G, having a diameter of about 0.035″, therethrough. Push tubes  60  and pull wires  50  pass through guide tube  140 , which preferably has a diameter of about 15 Fr or smaller. Guide tube  140  is disposed within lumen  112  of outer sheath  110 , which preferably has a diameter of about 17 Fr or smaller.  
      In  FIG. 9A , apparatus  10 ′ is delivered to diseased aortic valve AV within lumen  112  of sheath  110 . In  FIG. 9B , sheath  110  is retracted relative to apparatus  10 ′ to dynamically self-expand the apparatus to the partially deployed configuration. Also retracted and removed is nosecone  102  which is attached to a pre-slit lumen (not shown) that facilitates its removal prior to loading and advancing of a regular angioplasty balloon catheter over guidewire and inside delivery system  110 .  
      In  FIG. 9C , pull wires  50  and push tubes  60  are manipulated from external to the patient to foreshorten anchor  30  and sufficiently expand lumen  31  of the anchor to facilitate advancement of inflatable member  130  within replacement valve  20 . Also shown is the tip of an angioplasty catheter  130  being advanced through delivery system  110 .  
      The angioplasty balloon catheter or inflatable member  130  then is advanced within the replacement valve, as in  FIG. 9D , and additional foreshortening is imposed upon anchor  30  to actuate locks  40 , as in  FIG. 9E . The inflatable member is inflated to further displace the patient&#39;s native valve leaflets L and ensure adequate blood flow through, and long-term patency of, replacement valve  20 , as in  FIG. 9F . Inflatable member  130  then is deflated and removed from the patient, as in  FIG. 9G . A different size angioplasty balloon catheter could be used repeat the same step if deemed necessary by the user. Push tubes  60  optionally may be used to further set leaflet engagement element  120 , or optional barbs B along posts  38 , more deeply within leaflets L, as in  FIG. 9H . Then, delivery system  100 ″ is removed from the patient, thereby completing percutaneous heart valve replacement.  
      As will be apparent to those of skill in the art, the order of imposed foreshortening and balloon expansion described in  FIGS. 9 and 10  is only provided for the sake of illustration. The actual order may vary according to the needs of a given patient and/or the preferences of a given medical practitioner. Furthermore, balloon-assist may not be required in all instances, and the inflatable member may act merely as a safety precaution employed selectively in challenging clinical cases.  
      Referring now to  FIG. 11 , alternative locks for use with apparatus of the present invention are described. In  FIG. 11A , lock  40 ′ comprises male interlocking element  44  as described previously. However, female interlocking element  42 ′ illustratively comprises a triangular shape, as compared to the round shape of interlocking element  42  described previously. The triangular shape of female interlocking element  42 ′ may facilitate mating of male interlocking element  44  with the female interlocking element without necessitating deformation of the male interlocking element.  
      In  FIG. 11B , lock  40 ″ comprises alternative male interlocking element  44 ′ having multiple in-line arrowheads  46  along posts  38 . Each arrowhead comprises resiliently deformable appendages  48  to facilitate passage through female interlocking element  42 . Appendages  48  optionally comprise eyelets  49 , such that control wire  50  or a secondary wire may pass therethrough to constrain the appendages in the deformed configuration. To actuate lock  40 ″, one or more arrowheads  46  of male interlocking element  44 ′ are drawn through female interlocking element  42 , and the wire is removed from eyelets  49 , thereby causing appendages  48  to resiliently expand and actuate lock  40 ″.  
      Advantageously, providing multiple arrowheads  46  along posts  38  yields a ratchet that facilitates in-vivo determination of a degree of foreshortening imposed upon apparatus of the present invention. Furthermore, optionally constraining appendages  48  of arrowheads  46  via eyelets  49  prevents actuation of lock  40 ″ (and thus deployment of apparatus of the present invention) even after male element  44 ′ has been advanced through female element  42 . Only after a medical practitioner has removed the wire constraining appendages  48  is lock  40 ″ fully engaged and deployment no longer reversible.  
      Lock  40 ′″ of  FIG. 11C  is similar to lock  40 ″ of  FIG. 11B , except that optional eyelets  49  on appendages  48  have been replaced by optional overtube  47 . Overtube  47  serves a similar function to eyelets  49  by constraining appendages  48  to prevent locking until a medical practitioner has determined that apparatus of the present invention has been foreshortened and positioned adequately at a treatment site. Overtube  47  is then removed, which causes the appendages to resiliently expand, thereby fully actuating lock  40 ′″.  
      With reference to  FIG. 12 , an alternative locking mechanism is described that is configured to engage the patient&#39;s aorta. Male interlocking elements  44 ″ of locks  40 ′″ comprise arrowheads  46 ′ having sharpened appendages  48 ′. Upon expansion from the delivery configuration of  FIG. 12A  to the foreshortened configuration of  FIG. 12B , apparatus  10  positions sharpened appendages  48 ′ adjacent the patient&#39;s aorta A. Appendages  48 ′ engage the aortic wall and reduce a risk of device migration over time.  
      With reference now to  FIG. 13 , a risk of paravalvular leakage or regurgitation around apparatus of the present invention is described. In  FIG. 13 , apparatus  10  has been implanted at the site of diseased aortic valve AV, for example, using techniques described hereinabove. The surface of native valve leaflets L is irregular, and interface I between leaflets L and anchor  30  may comprise gaps where blood B may seep through. Such leakage poses a risk of blood clot formation or insufficient blood flow.  
      Referring to  FIG. 14 , optional elements for reducing regurgitation or leakage are described. Compliant sacs  200  may be disposed about the exterior of anchor  30  to provide a more efficient seal along irregular interface I; Sacs  200  may be filled with an appropriate material, for example, water, blood, foam or a hydrogel. Alternative fill materials will be apparent.  
      With reference to  FIG. 15 , illustrative arrangements for sacs  200  are provided. In  FIG. 15A , sacs  200  are provided as discrete sacs at different positions along the height of anchor  30 . In  FIG. 15B , the sacs are provided as continuous cylinders at various heights. In  FIG. 15C , a single sac is provided with a cylindrical shape that spans multiple heights. The sacs of  FIG. 15D  are discrete, smaller and provided in larger quantities.  FIG. 15E  provides a spiral sac. Alternative sac configurations will be apparent to those of skill in the art.  
      With reference to  FIG. 16 , exemplary techniques for fabricating sacs  200  are provided. In  FIG. 16A , sacs  20  comprise ‘fish-scale’ slots  202  that may be back-filled, for example, with ambient blood passing through replacement valve  20 . In  FIG. 16B , the sacs comprise pores  204  that may be used to fill the sacs. In  FIG. 16C , the sacs open to lumen  31  of anchor  30  and are filled by blood washing past the sacs as the blood moves through apparatus  10 .  
       FIGS. 17 and 18  show yet another alternative embodiment of the anchor lock. Anchor  300  has a plurality of male interlocking elements  302  having eyelets  304  formed therein. Male interlocking elements are connected to braided structure  300  by inter-weaving elements  302  (and  308 ) or alternatively suturing, soldering, welding, or connecting with adhesive. Valve commissures  24  are connected to male interlocking elements  302  along their length. Replacement valve  20  annular base  22  is connected to the distal end  34  of anchor  300  (or  30 ) as is illustrated in  FIGS. 1A and 1B . Male interlocking elements  302  also include holes  306  that mate with tabs  310  extending into holes  312  in female interlocking elements  308 . To lock, control wires  314  passing through eyelets  304  and holes  312  are pulled proximally with respect to the proximal end of braided anchor  300  to draw the male interlocking elements through holes  312  so that tabs  310  engage holes  306  in male interlocking elements  302 . Also shown is release wires  314 B that passes through eylet  304 B in female interlocking element  308 . If needed, during the procedure, the user may pull on release wires  314 B reversing orientation of tabs  310  releasing the anchor and allowing for repositioning of the device or it&#39;s removal from the patient. Only when final positioning as desired by the operating physician, would release wire  314 B and control wire  314  are cut and removed from the patient with the delivery system.  
       FIGS. 19-21  show an alternative way of releasing the connection between the anchor and its actuating tubes and control wires. Control wires  62  extend through tubes  60  from outside the patient, loop through the proximal region of anchor  30  and extend partially back into tube  60 . The doubled up portion of control wire  62  creates a force fit within tube  60  that maintains the control wire&#39;s position with respect to tube  60  when all control wires  62  are pulled proximally to place a proximally directed force on anchor  30 . When a single control wire  62  is pulled proximally, however, the frictional fit between that control wire and the tube in which it is disposed is overcome, enabling the end  63  of control wire  62  to pull free of the tube, as shown in  FIG. 21 , thereby releasing anchor  30 .  
       FIGS. 22-24  show an alternative embodiment of the anchor. Anchor  350  is made of a metal braid, such as Nitinol or stainless steel. A replacement valve  354  is disposed within anchor  350 . Anchor  350  is actuated in substantially the same way as anchor  30  of  FIGS. 1-4  through the application of proximally and distally directed forces from control wires (not shown) and tubes  352 .  
       FIGS. 25 and 26  show yet another embodiment of the delivery and deployment apparatus of the invention. As an alternative to the balloon expansion method described with respect to  FIG. 8 , in this embodiment the nosecone (e.g., element  102  of  FIG. 5 ) is replaced by an angioplasty balloon catheter  360 . Thus, angioplasty balloon catheter  360  precedes sheath  110  on guidewire G. When anchor  30  and valve  20  are expanded through the operation of tubes  60  and the control wires (not shown) as described above, balloon catheter  360  is retracted proximally within the expanded anchor and valve and expanded further as described above with respect to  FIG. 8 .  
       FIGS. 27-31  show seals  370  that expand over time to seal the interface between the anchor and valve and the patient&#39;s tissue. Seals  370  are preferably formed from Nitinol wire surrounded by an expandable foam. As shown in cross-section in  FIGS. 28 and 29 , at the time of deployment, the foam  372  is compressed about the wire  374  and held in the compressed form by a time-released coating  376 . After deployment, coating  376  dissolves in vivo to allow foam  372  to expand, as shown in  FIGS. 30 and 31 .  
       FIGS. 32-34  show another way to seal the replacement valve against leakage. A fabric seal  380  extends from the distal end of valve  20  and back proximally over anchor  30  during delivery. When deployed, as shown in  FIGS. 33 and 34 , fabric seal  380  bunches up to create fabric flaps and pockets that extend into spaces formed by the native valve leaflets  382 , particularly when the pockets are filled with blood in response to backflow blood pressure. This arrangement creates a seal around the replacement valve.  
      FIGS.  35 A-H show another embodiment of a replacement heart valve apparatus in accordance with the present invention. Apparatus  450  comprises replacement valve  460  (see  FIGS. 37B and 38C ) disposed within and coupled to anchor  470 . Replacement valve  460  is preferably biologic, e.g. porcine, but alternatively may be synthetic. Anchor  470  preferably is fabricated from self-expanding materials, such as a stainless steel wire mesh or a nickel-titanium alloy (“Nitinol”), and comprises lip region  472 , skirt region  474 , and body regions  476   a ,  476   b  and  476   c . Replacement valve  460  preferably is coupled to skirt region  474 , but alternatively may be coupled to other regions of the anchor. As described hereinbelow, lip region  472  and skirt region  474  are configured to expand and engage/capture a patient&#39;s native valve leaflets, thereby providing positive registration, reducing paravalvular regurgitation, reducing device migration, etc.  
      As seen in  FIG. 35A , apparatus  450  is collapsible to a delivery configuration, wherein the apparatus may be delivered via delivery system  410 . Delivery system  410  comprises sheath  420  having lumen  422 , as well as wires  424   a  and  424   b  seen in  FIGS. 35D-35G . Wires  424   a  are configured to expand skirt region  474  of anchor  470 , as well as replacement valve  460  coupled thereto, while wires  424   b  are configured to expand lip region  472 .  
      As seen in  FIG. 35B , apparatus  450  may be delivered and deployed from lumen  422  of catheter  420  while the apparatus is disposed in the collapsed delivery configuration. As seen in  FIGS. 35B-35D , catheter  420  is retracted relative to apparatus  450 , which causes anchor  470  to dynamically self-expand to a partially deployed configuration. Wires  424   a  are then retracted to expand skirt region  474 , as seen in  FIGS. 35E and 35F . Preferably, such expansion may be maintained via locking features described hereinafter.  
      In  FIG. 35G , wires  424   b  are retracted to expand lip region  472  and fully deploy apparatus  450 . As with skirt region  474 , expansion of lip region  472  preferably may be maintained via locking features. After both lip region  472  and skirt region  474  have been expanded, wires  424  may be removed from apparatus  450 , thereby separating delivery system  410  from the apparatus. Delivery system  410  then may be removed, as seen in  FIG. 35H .  
      As will be apparent to those of skill in the art, lip region  472  optionally may be expanded prior to expansion of skirt region  474 . As yet another alternative, lip region  472  and skirt region  474  optionally may be expanded simultaneously, in parallel, in a step-wise fashion or sequentially. Advantageously, delivery of apparatus  450  is fully reversible until lip region  472  or skirt region  474  has been locked in the expanded configuration.  
      With reference now to FIGS.  36 A-E, individual cells of anchor  470  of apparatus  450  are described to detail deployment and expansion of the apparatus. In  FIG. 36A , individual cells of lip region  472 , skirt region  474  and body regions  476   a ,  476   b  and  476   c  are shown in the collapsed delivery configuration, as they would appear while disposed within lumen  422  of sheath  420  of delivery system  410  of  FIG. 35 . A portion of the cells forming body regions  476 , for example, every ‘nth’ row of cells, comprises locking features.  
      Body region  476   a  comprises male interlocking element  482  of lip lock  480 , while body region  476   b  comprises female interlocking element  484  of lip lock  480 . Male element  482  comprises eyelet  483 . Wire  424   b  passes from female interlocking element  484  through eyelet  483  and back through female interlocking element  484 , such that there is a double strand of wire  424   b  that passes through lumen  422  of catheter  420  for manipulation by a medical practitioner external to the patient. Body region  476   b  further comprises male interlocking element  492  of skirt lock  490 , while body region  476   c  comprises female interlocking element  494  of the skirt lock. Wire  424   a  passes from female interlocking element  494  through eyelet  493  of male interlocking element  492 , and back through female interlocking element  494 . Lip lock  480  is configured to maintain expansion of lip region  472 , while skirt lock  490  is configured to maintain expansion of skirt region  474 .  
      In  FIG. 36B , anchor  470  is shown in the partially deployed configuration, e.g., after deployment from lumen  422  of sheath  420 . Body regions  476 , as well as lip region  472  and skirt region  474 , self-expand to the partially deployed configuration. Full deployment is then achieved by retracting wires  424  relative to anchor  470 , and expanding lip region  472  and skirt region  474  outward, as seen in  FIGS. 36C and 36D . As seen in  FIG. 36E , expansion continues until the male elements engage the female interlocking elements of lip lock  480  and skirt lock  490 , thereby maintaining such expansion (lip lock  480  shown in  FIG. 36E ). Advantageously, deployment of apparatus  450  is fully reversible until lip lock  480  and/or skirt lock  490  has been actuated.  
      With reference to FIGS.  37 A-B, isometric views, partially in section, further illustrate apparatus  450  in the fully deployed and expanded configuration.  FIG. 37A  illustrates the wireframe structure of anchor  470 , while  FIG. 37B  illustrates an embodiment of anchor  470  covered in a biocompatible material B. Placement of replacement valve  460  within apparatus  450  may be seen in  FIG. 37B . The patient&#39;s native valve is captured between lip region  472  and skirt region  474  of anchor  470  in the fully deployed configuration (see  FIG. 38B ).  
      Referring to FIGS.  38 A-C, in conjunction with  FIGS. 35 and 36 , a method for endovascularly replacing a patient&#39;s diseased aortic valve with apparatus  450  is described. Delivery system  410 , having apparatus  450  disposed therein, is endovascularly advanced, preferably in a retrograde fashion, through a patient&#39;s aorta A to the patient&#39;s diseased aortic valve AV. Sheath  420  is positioned such that its distal end is disposed within left ventricle LV of the patient&#39;s heart H. As described with respect to  FIG. 35 , apparatus  450  is deployed from lumen  422  of sheath  420 , for example, under fluoroscopic guidance, such that skirt section  474  is disposed within left ventricle LV, body section  476   b  is disposed across the patient&#39;s native valve leaflets L, and lip section  472  is disposed within the patient&#39;s aorta A. Advantageously, apparatus  450  may be dynamically repositioned to obtain proper alignment with the anatomical landmarks. Furthermore, apparatus  450  may be retracted within lumen  422  of sheath  420  via wires  424 , even after anchor  470  has dynamically expanded to the partially deployed configuration, for example, to abort the procedure or to reposition sheath  420 .  
      Once properly positioned, wires  424   a  are retracted to expand skirt region  474  of anchor  470  within left ventricle LV. Skirt region  474  is locked in the expanded configuration via skirt lock  490 , as previously described with respect to  FIG. 36 . In  FIG. 38A , skirt region  474  is maneuvered such that it engages the patient&#39;s valve annulus An and/or native valve leaflets L, thereby providing positive registration of apparatus  450  relative to the anatomical landmarks.  
      Wires  424   b  are then actuated external to the patient in order to expand lip region  472 , as previously described in  FIG. 35 . Lip region  472  is locked in the expanded configuration via lip lock  480 . Advantageously, deployment of apparatus  450  is fully reversible until lip lock  480  and/or skirt lock  490  has been actuated. Wires  424  are pulled from eyelets  483  and  493 , and delivery system  410  is removed from the patient. As will be apparent, the order of expansion of lip region  472  and skirt region  474  may be reversed, concurrent, etc.  
      As seen in  FIG. 38B , lip region  472  engages the patient&#39;s native valve leaflets L, thereby providing additional positive registration and reducing a risk of lip region  472  blocking the patient&#39;s coronary ostia O.  FIG. 38C  illustrates the same in cross-sectional view, while also showing the position of replacement valve  460 . The patient&#39;s native leaflets are engaged and/or captured between lip region  472  and skirt region  474 . Advantageously, lip region  472  precludes distal migration of apparatus  450 , while skirt region  474  precludes proximal migration. It is expected that lip region  472  and skirt region  474  also will reduce paravalvular regurgitation.  
      With reference to  FIGS. 39-41 , a first embodiment of two-piece apparatus of the present invention adapted for percutaneous replacement of a patient&#39;s heart valve is described. As seen in  FIG. 41 , apparatus  510  comprises a two-piece device having custom-designed expandable anchor piece  550  of  FIG. 39  and expandable replacement valve piece  600  of  FIG. 40 . Both anchor piece  550  and valve piece  600  have reduced delivery configurations and expanded deployed configurations. Both may be either balloon expandable (e.g. fabricated from a stainless steel) or self-expanding (e.g. fabricated from a nickel-titanium alloy (“Nitinol”) or from a wire mesh) from the delivery to the deployed configurations.  
      When replacing a patient&#39;s aortic valve, apparatus  510  preferably may be delivered through the patient&#39;s aorta without requiring a transseptal approach, thereby reducing patient trauma, complications and recovery time. Furthermore, apparatus  510  enables dynamic repositioning of anchor piece  550  during delivery and facilitates positive registration of apparatus  510  relative to the native position of the patient&#39;s valve, thereby reducing a risk of device migration and reducing a risk of blocking or impeding flow to the patient&#39;s coronary ostia. Furthermore, the expanded deployed configuration of apparatus  510 , as seen in  FIG. 41D , is adapted to reduce paravalvular regurgitation, as well as to facilitate proper seating of valve piece  600  within anchor piece  550 .  
      As seen in  FIG. 39 , anchor piece  550  preferably comprises three sections. Lip section  560  is adapted to engage the patient&#39;s native valve leaflets to provide positive registration and ensure accurate placement of the anchor relative to the patient&#39;s valve annulus during deployment, while allowing for dynamic repositioning of the anchor during deployment. Lip section  560  also maintains proper positioning of composite anchor/valve apparatus  510  post-deployment to preclude distal migration. Lip section  560  optionally may be covered or coated with biocompatible film B (see  FIG. 41 ) to ensure engagement of the native valve leaflets. It is expected that covering lip section  560  with film B especially would be indicated when the native leaflets are stenosed and/or fused together.  
      Groove section  570  of anchor piece  550  is adapted to engage an expandable frame portion, described hereinbelow, of valve piece  600  to couple anchor piece  550  to valve piece  600 . As compared to previously known apparatus, groove section  570  comprises additional material and reduced openings or gaps G, which is expected to reduce tissue protrusion through the gaps upon deployment, thereby facilitating proper seating of the valve within the anchor. Groove section  570  optionally may be covered or coated with biocompatible film B (see  FIG. 41 ) to further reduce native valve tissue protrusion through gaps G.  
      Finally, skirt section  580  of anchor piece  550  maintains proper positioning of composite anchor/valve apparatus  510  post-deployment by precluding proximal migration. When replacing a patient&#39;s aortic valve, skirt section  580  is deployed within the patient&#39;s left ventricle. As with lip section  560  and groove section  570 , skirt section  580  optionally may be covered or coated with biocompatible film B (see  FIG. 41 ) to reduce paravalvular regurgitation. As will be apparent to those of skill in the art, all, a portion of, or none of anchor piece  50  may be covered or coated with biocompatible film B.  
      In  FIG. 39A , a portion of anchor piece  550  has been flattened out to illustrate the basic anchor cell structure, as well as to illustrate techniques for manufacturing anchor piece  550 . In order to form the entire anchor, anchor  550  would be bent at the locations indicated in  FIG. 39A , and the basic anchor cell structure would be revolved to form a joined 360° structure. Lip section  560  would be bent back into the page to form a lip that doubles over the groove section, groove section  570  would be bent out of the page into a ‘C’- or ‘U’-shaped groove, while skirt section  580  would be bent back into the page.  FIG. 39B  shows the anchor portion after bending and in an expanded deployed configuration.  
      The basic anchor cell structure seen in  FIG. 39A  is preferably formed through laser cutting of a flat sheet or of a hollow tube placed on a mandrel. When formed from a flat sheet, the sheet would be cut to the required number of anchor cells, bent to the proper shape, and revolved to form a cylinder. The ends of the cylinder would then be joined together, for example, by heat welding.  
      If balloon expandable, anchor piece  550  would be formed from an appropriate material, such as stainless steel, and then crimped onto a balloon delivery catheter in a collapsed delivery configuration. If self-expanding and formed from a shape-memory material, such as a nickel-titanium alloy (“Nitinol”), the anchor piece would be heat-set such that it could be constrained within a sheath in the collapsed delivery configuration, and then would dynamically self-expand to the expanded deployed configuration upon removal of the sheath. Likewise, if anchor piece  550  were formed from a wire mesh or braid, such as a spring steel braid, the anchor would be constrained within a sheath in the delivery configuration and dynamically expanded to the deployed configuration upon removal of the sheath.  
      In  FIG. 40 , valve piece  600  is described in greater detail.  FIG. 40A  illustrates valve piece  600  in a collapsed delivery configuration, while  FIG. 40B  illustrates the valve piece in an expanded deployed configuration. Valve piece  600  comprises replacement valve  610  coupled to expandable frame  620 . Replacement valve  610  is preferably biologic, although synthetic valves may also be used. Replacement valve  610  preferably comprises three leaflets  611  coupled to three posts  621  of expandable frame  620 . Expandable frame  620  is preferably formed from a continuous piece of material and may comprise tips  622  in the collapsed delivery configuration, which expand to form hoop  624  in the deployed configuration. Hoop  624  is adapted to engage groove section  570  of anchor piece  550  for coupling anchor-piece  550  to valve piece  600 . As with anchor piece  550 , valve piece  600  may be balloon expandable and coupled to a balloon delivery catheter in the delivery configuration. Alternatively, anchor piece  550  may be self-expanding, e.g. Nitinol or wire mesh, and constrained within a sheath in the delivery configuration.  
      Referring again to  FIG. 41 , a method for deploying valve piece  600  and coupling it to deployed anchor piece  550  to form two-piece apparatus  510  is described. In  FIG. 41A , valve piece  600  is advanced within anchor piece  550  in an at least partially compressed delivery configuration. In  FIG. 41B , tips  622  of frame  620  are expanded such that they engage groove section  570  of anchor piece  550 . In  FIG. 41C , frame  620  continues to expand and form hoop  624 . Hoop  624  flares out from the remainder of valve piece  600  and acts to properly locate the hoop within groove section  570 .  FIG. 41D  shows valve piece  600  in a fully deployed configuration, properly seated and friction locked within groove section  570  to form composite anchor/valve apparatus  510 .  
      Anchor piece  550  and valve piece  600  of apparatus  510  preferably are spaced apart and releasably coupled to a single delivery catheter while disposed in their reduced delivery configurations. Spacing the anchor and valve apart reduces a delivery profile of the device, thereby enabling delivery through a patient&#39;s aorta without requiring a transseptal approach. With reference to  FIG. 42 , a first embodiment of single catheter delivery system  700  for use with apparatus  510  is described. Delivery system  700  is adapted for use with a preferred self-expanding embodiment of apparatus  510 .  
      Delivery system  700  comprises delivery catheter  710  having inner tube  720 , middle distal tube  730 , and outer tube  740 . Inner tube  720  comprises lumen  722  adapted for advancement over a standard guide wire, per se known. Middle distal tube  730  is coaxially disposed about a distal region of inner tube  720  and is coupled to a distal end  724  of the inner tube, thereby forming proximally-oriented annular bore  732  between inner tube  720  and middle tube  730  at a distal region of delivery catheter  710 . Outer tube  740  is coaxially disposed about inner tube  720  and extends from a proximal region of the inner tube to a position at least partially coaxially overlapping middle distal tube  730 . Outer tube  740  preferably comprises distal step  742 , wherein lumen  743  of outer tube  740  is of increased diameter. Distal step  742  may overlap middle distal tube  730  and may also facilitate deployment of valve piece  600 , as described hereinbelow with respect to  FIG. 45 .  
      Proximally-oriented annular bore  732  between inner tube  720  and middle distal tube  730  is adapted to receive skirt section  580  and groove section  570  of anchor piece  550  in the reduced delivery configuration. Annular space  744  formed at the overlap between middle distal tube  730  and outer tube  740  is adapted to receive lip section  560  of anchor piece  550  in the reduced delivery configuration. More proximal annular space  746  between inner tube  720  and outer tube  740  may be adapted to receive replacement valve  610  and expandable frame  620  of valve piece  600  in the reduced delivery configuration.  
      Inner tube  720  optionally may comprise retainer elements  726   a  and  726   b  to reduce migration of valve piece  600 . Retainer elements  726  preferably are fabricated from a radiopaque material, such as platinum-iridium or gold, to facilitate deployment of valve piece  600 , as well as coupling of the valve piece to anchor piece  550 . Additional or alternative radiopaque elements may be disposed at other locations about delivery system  700  or apparatus  510 , for example, in the vicinity of anchor piece  550 .  
      With reference now to  FIG. 43 , an alternative delivery system for use with apparatus of the present invention is described. Delivery system  750  comprises two distinct catheters adapted to deliver the anchor and valve pieces, respectively: anchor delivery catheter  710 ′ and valve delivery catheter  760 . In use, catheters  710 ′ and  760  may be advanced sequentially to a patient&#39;s diseased heart valve for sequential deployment and coupling of anchor piece  550  to valve piece  600  to form composite two-piece apparatus  510 .  
      Delivery catheter  710 ′ is substantially equivalent to catheter  710  described hereinabove, except that catheter  710 ′ does not comprise retainer elements  726 , and annular space  746  does not receive valve piece  600 . Rather, valve piece  600  is received within catheter  760  in the collapsed delivery configuration. Catheter  760  comprises inner tube  770  and outer tube  780 . Inner tube  770  comprises lumen  772  for advancement of catheter  760  over a guide wire. The inner tube optionally may also comprise retainer elements  774   a  and  774   b , e.g. radiopaque retainer elements  774 , to reduce migration of valve piece  600 . Outer tube  780  is coaxially disposed about inner tuber  770  and preferably comprises distal step  782  to facilitate deployment and coupling of valve piece  600  to anchor piece  550 , as described hereinbelow. Valve piece  600  may be received in annular space  776  between inner tube  770  and outer tube  780 , and more preferably may be received within annular space  776  between retainer elements  774 .  
      Referring now to  FIG. 44 , another alternative delivery system is described. As discussed previously, either anchor piece  550  or valve piece  600  (or portions thereof or both) may be balloon expandable from the delivery configuration to the deployed configuration. Delivery system  800  is adapted for delivery of an embodiment of apparatus  510  wherein the valve piece is balloon expandable. Additional delivery systems—both single and multi-catheter—for deployment of alternative combinations of balloon and self-expandable elements of apparatus of the present invention will be apparent to those of skill in the art in view of the illustrative delivery systems provided in  FIGS. 42-44 .  
      In  FIG. 44 , delivery system  800  comprises delivery catheter  710 ″. Delivery catheter  710 ″ is substantially equivalent to delivery catheter  710  of delivery system  700 , except that catheter  710 ″ does not comprise retainer elements  726 , and annular space  746  does not receive the valve piece. Additionally, catheter  710 ″ comprises inflatable balloon  802  coupled to the exterior of outer tube  740 ″, as well as an inflation lumen (not shown) for reversibly delivering an inflation medium from a proximal region of catheter  710 ″ into the interior of inflatable balloon  802  for expanding the balloon from a delivery configuration to a deployed configuration. Valve piece  600  may be crimped to the exterior of balloon  802  in the delivery configuration, then deployed and coupled to anchor piece  550  in vivo. Delivery catheter  710 ″ preferably comprises radiopaque marker bands  804   a  and  804   b  disposed on either side of balloon  802  to facilitate proper positioning of valve piece  600  during deployment of the valve piece, for example, under fluoroscopic guidance.  
      With reference now to  FIG. 45 , in conjunction with  FIGS. 39-42 , an illustrative method of endovascularly replacing a patient&#39;s diseased heart valve using apparatus of the present invention is described. In  FIG. 45A , a distal region of delivery system  700  of  FIG. 42  has been delivered through a patient&#39;s aorta A, e.g., over a guide wire and under fluoroscopic guidance using well-known percutaneous techniques, to a vicinity of diseased aortic valve AV of heart H. Apparatus  510  of  FIGS. 39-41  is disposed in the collapsed delivery configuration within delivery catheter  710  with groove section  570  and skirt section  580  of anchor piece  550  collapsed within annular bore  732 , and lip section  560  of anchor piece  550  collapsed within annular space  744 . Valve piece  600  is disposed in the collapsed delivery configuration between retainer elements  726  within more proximal annular space  746 . Separation of anchor piece  550  and valve piece  600  of apparatus  510  along the longitudinal axis of delivery catheter  710  enables percutaneous aortic delivery of apparatus  510  without requiring a transseptal approach.  
      Aortic valve AV comprises native valve leaflets L attached to valve annulus An. Coronary ostia O are disposed just proximal of diseased aortic valve AV. Coronary ostia O connect the patient&#39;s coronary arteries to aorta A and are the conduits through which the patient&#39;s heart muscle receives oxygenated blood. As such, it is critical that the ostia remain unobstructed post-deployment of apparatus  510 .  
      In  FIG. 45A , a distal end of delivery catheter  710  has been delivered across diseased aortic valve AV into the patient&#39;s left ventricle LV. As seen in  FIG. 45B , outer tube  740  is then retracted proximally relative to inner tube  720  and middle distal tube  730 . Outer tube  740  no longer coaxially overlaps middle distal tube  730 , and lip section  560  of anchor piece  550  is removed from annular space  744 . Lip section  560  self-expands to the deployed configuration. As seen in  FIG. 45C , inner tube  720  and middle tube  730  (or all of delivery catheter  710 ) are then distally advanced until lip section  560  engages the patient&#39;s native valve leaflets L, thereby providing positive registration of anchor piece  550  to leaflets L. Registration may be confirmed, for example, via fluoroscopic imaging of radiopaque features coupled to apparatus  510  or delivery system  700  and/or via resistance encountered by the medical practitioner distally advancing anchor piece  550 .  
      Lip section  560  may be dynamically repositioned until it properly engages the valve leaflets, thereby ensuring proper positioning of anchor piece  550  relative to the native coronary ostia O, as well as the valve annulus An, prior to deployment of groove section  570  and skirt section  580 . Such multi-step deployment of anchor piece  550  enables positive registration and dynamic repositioning of the anchor piece. This is in contrast to previously known percutaneous valve replacement apparatus.  
      As seen in  FIG. 45D , once leaflets L have been engaged by lip section  560  of anchor piece  550 , inner tube  720  and middle distal tube  730  are further distally advanced within left ventricle LV, while outer tube  740  remains substantially stationary. Lip section  560 , engaged by leaflets L, precludes further distal advancement/migration of anchor piece  550 . As such, groove section  570  and skirt section  580  are pulled out of proximally-oriented annular bore  732  between inner tube  720  and middle distal tube  730  when the tubes are distally advanced. The groove and skirt sections self-expand to the deployed configuration, as seen in  FIG. 45E . Groove section  570  pushes native valve leaflets L and lip section  560  against valve annulus An, while skirt section  580  seals against an interior wall of left ventricle LV, thereby reducing paravalvular regurgitation across aortic valve AV and precluding proximal migration of anchor piece  550 .  
      With anchor piece  550  deployed and native aortic valve AV displaced, valve piece  600  may be deployed and coupled to the anchor piece to achieve percutaneous aortic valve replacement. Outer tube  740  is further proximally retracted relative to inner tube  720  such that valve piece  600  is partially deployed from annular space  746  between inner tube  720  and outer tube  740 , as seen in  FIG. 45F . Expandable frame  620  coupled to replacement valve  610  partially self-expands such that tips  622  partially form hoop  624  for engagement of groove section  570  of anchor piece  550  (see  FIG. 41B ). A proximal end of expandable frame  620  is engaged by distal step  742  of outer tube  740 .  
      Subsequent re-advancement of outer tube  740  relative to inner tube  720  causes distal step  742  to distally advance valve piece  600  within anchor piece  550  until tips  622  of expandable frame  620  engage groove section  570  of anchor piece  550 , as seen in  FIG. 45G . As discussed previously, groove section  570  comprises additional material and reduced openings or gaps G, as compared to previously known apparatus, which is expected to reduce native valve tissue protrusion through the gaps and facilitate engagement of tips  622  with the groove section. Outer tube  740  then is proximally retracted again relative to inner tube  720 , and valve piece  600  is completely freed from annular space  746 . Frame  620  of valve piece  600  fully expands to form hoop  624 , as seen in  FIG. 45H .  
      Hoop  624  friction locks within groove section  570  of anchor piece  550 , thereby coupling the anchor piece to the valve piece and forming composite two-piece apparatus  510 , which provides a percutaneous valve replacement. As seen in  FIG. 451 , delivery catheter  710  may then be removed from the patient, completing the procedure. Blood may freely flow from left ventricle LV through replacement valve  610  into aorta A. Coronary ostia O are unobstructed, and paravalvular regurgitation is reduced by skirt section  580  of anchor piece  550 .  
      Referring now to  FIG. 46 , an alternative embodiment of two-piece apparatus  510  is described comprising an alignment/locking mechanism. Such a mechanism may be provided in order to ensure proper radial alignment of the expandable frame of the valve piece with the groove section of the anchor piece, as well as to ensure proper longitudinal positioning of the frame within the hoop. Additionally, the alignment/locking mechanism may provide a secondary lock to further reduce a risk of the anchor piece and the valve piece becoming separated post-deployment and coupling of the two pieces to achieve percutaneous valve replacement.  
      In  FIG. 46 , apparatus  510 ′ comprises valve piece  600 ′ of  FIG. 46A  and anchor piece  550 ′ of  FIG. 46B . Anchor piece  550 ′ and valve piece  600 ′ are substantially the same as anchor piece  550  and valve piece  600  described hereinabove, except that anchor piece  550 ′ comprises first portion  652  of illustrative alignment/locking mechanism  650 , while valve piece  600 ′ comprises second portion  654  of the alignment/locking mechanism for coupling to the first portion. First portion  652  illustratively comprises three guideposts  653  coupled to skirt section  580 ′ of anchor piece  550 ′ (only one guidepost shown in the partial view of  FIG. 46B ), while second portion  654  comprises three sleeves  655  coupled to posts  621 ′ of expandable frame  620 ′ of valve piece  600 ′.  
      When anchor piece  550 ′ is self-expanding and collapsed in the delivery configuration, guideposts  653  may be deployed with skirt section  580 ′, in which case guideposts  653  would rotate upward with respect to anchor piece  550 ′ into the deployed configuration of  FIG. 46B . Alternatively, when anchor piece  550 ′ is either balloon or self-expanding and is collapsed in the delivery configuration, guideposts  653  may be collapsed against groove section  570 ′ of the anchor piece and may be deployed with the groove section. Deploying guideposts  653  with skirt section  580 ′ has the advantages of reduced delivery profile and ease of manufacturing, but has the disadvantage of significant dynamic motion during deployment. Conversely, deploying guideposts  653  with groove section  570 ′ has the advantage of minimal dynamic motion during deployment, but has the disadvantage of increased delivery profile. Additional deployment configurations will be apparent to those of skill in the art. As will also be apparent, first portion  652  of alignment/locking mechanism  650  may be coupled to alternative sections of anchor piece  550 ′ other than skirt section  580 ′.  
      Sleeves  655  of second portion  654  of alignment/locking mechanism  650  comprise lumens  656  sized for coaxial disposal of sleeves  655  about guideposts  653  of first portion  652 . Upon deployment, sleeves  655  may friction lock to guideposts  653  to ensure proper radial and longitudinal alignment of anchor piece  550 ′ with valve piece  600 ′, as well as to provide a secondary lock of the anchor piece to the valve piece. The secondary lock enhances the primary friction lock formed by groove section  570 ′ of the anchor piece with hoop  624 ′ of expandable frame  620 ′ of the valve piece.  
      To facilitate coupling of the anchor piece to the valve piece, suture or thread may pass from optional eyelets  651   a  of guideposts  653  through lumens  656  of sleeves  655  to a proximal end of the delivery catheter (see  FIG. 47 ). In this manner, second portion  654  of mechanism  650  may be urged into alignment with first portion  652 , and optional suture knots (not shown), e.g. pre-tied suture knots, may be advanced on top of the mechanism post-coupling of the two portions to lock the two portions together. Alternatively, guideposts  653  may comprise optional one-way valves  651   b  to facilitate coupling of the first portion to the second portion. Specifically, sleeves  655  may be adapted for coaxial advancement over one-way valves  651   b  in a first direction that couples the sleeves to guideposts  653 , but not in a reverse direction that would uncouple the sleeves from the guideposts.  
      Referring now to  FIG. 47 , an alternative embodiment of apparatus  510 ′ comprising an alternative alignment/locking mechanism is described. Apparatus  510 ″ is illustratively shown in conjunction with delivery system  700  described hereinabove with respect to  FIG. 42 . Valve piece  600 ″ is shown partially deployed from outer tube  740  of catheter  710 . For the sake of illustration, replacement valve  610 ″ of valve piece  600 ″, as well as inner tube  720  and middle distal tube  730  of delivery catheter  710 , are not shown in  FIG. 47 .  
      In  FIG. 47 , anchor piece  550 ″ of apparatus  510 ″ comprises first portion  652 ′ of alignment/locking mechanism  650 ′, while valve piece  600 ″ comprises second portion  654 ′ of the alternative alignment/locking mechanism. First portion  652 ′ comprises eyelets  660  coupled to groove section  570 ″ of anchor piece  550 ″. Second portion  654 ′ comprises knotted loops of suture  662  coupled to tips  622 ″ of expandable frame  620 ″ of valve piece  600 ″. Suture  661  extends from knotted loops of suture  662  through eyelets  660  and out through annular space  746  between outer tube  740  and inner tube  720  (see  FIG. 42 ) of catheter  710  to a proximal end of delivery system  700 . In this manner, a medical practitioner may radially and longitudinally align valve piece  600 ″ with anchor piece  550 ″ by proximally retracting sutures  661  (as shown by arrows in  FIG. 47 ) while distally advancing distal step  742  of outer tube  740  against valve piece  600 ″ until tips  622 ″ of the valve piece engage groove section  570 ″ of anchor piece  550 ″. Proximal retraction of outer tube  740  then causes expandable frame  620 ″ to further expand and form hoop  624 ″ that friction locks with groove section  570 ″ of anchor piece  550 ″, thereby forming apparatus  510 ″ as described hereinabove with respect to apparatus  510 . A secondary lock may be achieved by advancing optional suture knots (not shown) to the overlap of eyelets  660  and knotted loops of suture  662 . Such optional suture knots preferably are pre-tied.  
      With reference now to  FIG. 48 , yet another alternative embodiment of apparatus  510 ′, comprising yet another alternative alignment/locking mechanism  650 , is described. First portion  652 ″ of alignment/locking mechanism  650 ″ is coupled to anchor piece  550 ′″ of apparatus  510 ′″, while second portion  654 ″ is coupled to valve piece  600 ′″. The first portion comprises male posts  670  having flared ends  671 , while the second portion comprises female guides  672  coupled to tips  622 ′″ of expandable frame  620 ′″ of valve piece  600 ′″.  
      Female guides  672  are translatable about male posts  670 , but are constrained by flared ends  671  of the male posts. In this manner, anchor piece  550 ′″ and valve piece  600 ′″ remain coupled and in radial alignment with one another at all times—including delivery—but may be longitudinally separated from one another during delivery. This facilitates percutaneous delivery without requiring a transseptal approach, while mitigating a risk of inadvertent deployment of the anchor and valve pieces in an uncoupled configuration. Additional alignment/locking mechanisms will be apparent in view of the mechanisms described with respect to  FIGS. 46-48 .  
      Prior to implantation of one of the replacement valves described above, it may be desirable to perform a valvoplasty on the diseased valve by inserting a balloon into the valve and expanding it using saline mixed with a contrast agent. In addition to preparing the valve site for implant, fluoroscopic viewing of the valvoplasty will help determine the appropriate size of replacement valve implant to use.