Patent Publication Number: US-2022211492-A1

Title: Modified prosthetic heart valve stent

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of International Patent Application No. PCT/US2020/052496, filed Sep. 24, 2020, which claims the benefit of U.S. Patent Application No. 62/907,476, filed Sep. 27, 2019, the entire disclosures all of which are incorporated by reference for all purposes. 
    
    
     TECHNICAL FIELD 
     The present disclosure generally relates to controlled expansion of a prosthetic heart valve stent and, more particularly, to modifications and/or asymmetric expansion of a subvalvular stent to avoid compression and potential mechanical injury to the heart&#39;s electrical conduction system. 
     BACKGROUND 
     Heart valve disease continues to be a significant cause of morbidity and mortality, resulting from a number of ailments including rheumatic fever and birth defects. Currently, the primary treatment of aortic valve disease is valve replacement. Worldwide, an estimated 300,000 heart valve replacement surgeries are performed annually. Many patients receive bioprosthetic heart valve replacements, which utilize biologically derived tissues for flexible fluid occluding leaflets. The most successful bioprosthetic materials for flexible leaflets are whole porcine valves and separate leaflets made from bovine pericardium stitched together to form a tri-leaflet valve. The most common flexible leaflet valve construction includes three leaflets mounted to commissure posts around a peripheral non-expandable support structure with free edges that project toward an outflow direction and meet or coapt in the middle of the flowstream. A suture-permeable sewing ring is provided around the inflow end. 
     In recent years, advancements in minimally-invasive surgery and interventional cardiology have encouraged some investigators to pursue percutaneous repair and/or replacement of heart valves. One prosthetic valve for use in such a procedure can include a radially collapsible and expandable frame to which leaflets of the prosthetic valve can be coupled. For example, U.S. Pat. Nos. 6,730,118, 7,393,360, 7,510,575, and 7,993,394, which are incorporated herein by reference, describe exemplary collapsible transcatheter heart valves (THVs). Edwards Lifesciences of Irvine, Calif., has developed a plastically- or balloon-expandable stent integrated with a bioprosthetic valve. The stent/valve device, now called the Edwards Sapien® Heart Valve, is deployed across the native diseased valve to permanently hold the valve open, thereby alleviating a need to excise the native valve. 
     Another prior bioprosthetic valve for aortic valve replacement is provided by the Edwards Intuity Elite® valve system also available from Edwards Lifesciences. Aspects of the system are disclosed in U.S. Pat. Nos. 8,641,757 and 9,370,418 both to Pintor, et al. and 8,869,982 to Hodshon, et al. The Edwards Intuity Elite® valve is a hybrid of a generally non-expandable valve member and an expandable anchoring stent that helps secure the valve in place in a shorter amount of time. The implant process only requires three sutures which reduces the time-consuming process of tying knots. A delivery system advances the Edwards Intuity valve with the stent at the leading end until it is located within the left ventricular outflow tract (LVOT), at which point a balloon inflates to expand the stent against the left ventricular outflow tract wall. 
     With all expandable prosthetic heart valves, there is the potential that under certain conditions the expanding stent could impinge on the conduction system of the heart, therefore affecting its function. Solutions are needed. 
     SUMMARY 
     The present application provides a prosthetic heart valve comprising a plurality of flexible leaflets arranged to close together along a flow axis through the valve to prevent blood flow in one direction, and a support frame surrounding and supporting the leaflets. An expandable stent connected to the support frame defines a circumference and is convertible from a radially contracted configuration to a radially expanded configuration. The stent is defined by a plurality of interconnected struts, wherein a pattern of the interconnected struts is consistent around the circumference except in a modified region on one circumferential side so that when converted to the expanded configuration the modified region of the stent expands radially outward a smaller distance than around a remainder of the circumference. Alternatively, the modified region when converted to the expanded configuration has larger cells defined between the interconnected struts than around a remainder of the circumference 
     The support frame may be non-expandable, non-collapsible and the expandable stent connects to an inflow end of the support frame and is generally non-expandable and non-collapsible as a consequence, and wherein the expandable stent has an inflow end that converts from the radially contracted configuration to the radially expanded configuration. Preferably, the expandable stent is plastically-expandable. 
     The plurality of interconnected struts may include a series of circumferential row struts between axial column struts, the row struts defining bends between the column struts, and wherein at least one row strut in the modified region defines shallower bends than around a remainder of the at least one row strut. The final bend angles of the at least one row strut in the modified region are preferably between about 135-160°, while final bend angles around the remainder of the at least one row strut are preferably between about 45-90°. 
     The heart valve may be configured for implant at an aortic annulus and defines three commissure posts at intersections between three of the flexible leaflets, and the modified region is centered at one of the three commissure posts and will correspond to the location of the membranous interventricular septum and the conduction system zone. Desirably, the modified region extends circumferentially between about 90-120°. 
     In one embodiment, the support frame is expandable and the expandable stent forms a portion of the support frame such that the heart valve is fully expandable. The support frame in the fully expandable heart valve may be plastically-expandable or self-expandable. 
     A further understanding of the nature and advantages of the present invention are set forth in the following description and claims, particularly when considered in conjunction with the accompanying drawings in which like parts bear like reference numerals. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention will now be explained, and other advantages and features will appear with reference to the accompanying schematic drawings wherein: 
         FIG. 1  illustrates delivery to an aortic annulus of a prior art heart valve/holder combination using a valve delivery tube; 
         FIG. 2  is a partially cutaway perspective view of a prior art assembled hybrid prosthetic heart valve; 
         FIGS. 2A and 2B  are elevational views of a prior art anchoring skirt used in the hybrid prosthetic heart valve and shown in both radially contracted and expanded states, respectively; 
         FIG. 3  is a schematic diagram of the conduction system of the heart with primary features labeled; 
         FIG. 4  is a laid-flat image of the aortic valve showing the general location of the adjacent conduction system zone; 
         FIG. 5  is a schematic representation of the outline of a hybrid prosthetic heart valve; 
         FIG. 6  is a laid-flat image of the hybrid prosthetic heart valve outline of  FIG. 5  superimposed over the laid-flat image of the aortic valve of  FIG. 4 ; 
         FIG. 7  is a schematic plan view of an aortic valve indicating the location of the adjacent conduction system components; 
         FIG. 8  is a perspective view of an assembled hybrid prosthetic heart valve showing marking on the exterior thereof to indicate rotational placement when implanting the valve; 
         FIGS. 9A-9C  are elevational views of exemplary stent frames of the present application for use in an anchoring skirt of a hybrid prosthetic heart valve, the stent frames shown radially expanded with struts modified to reduce impact on an adjacent heart conduction system; 
         FIG. 10  is an elevational view of another exemplary stent frame radially expanded with struts modified to reduce impact on an adjacent heart conduction system; 
         FIGS. 11A and 11B  are elevational views of a further exemplary stent frame shown radially expanded with struts modified to reduce impact on an adjacent heart conduction system; 
         FIG. 12A  shows a still further exemplary stent frame from below prior to expansion, and  FIG. 12B  shows the stent frame after expansion showing how one side does not expand as far as the remainder; 
         FIG. 13  is a perspective view of a fully-expandable prosthetic heart valve of the prior art shown expanded; 
         FIG. 14  is a perspective view of a modified fully-expandable prosthetic heart valve of the present application; 
         FIG. 15  is an elevational view of another fully-expandable prosthetic heart valve of the prior art shown expanded; 
         FIG. 16  illustrates placement of the fully-expandable prosthetic heart valve of  FIG. 15  at an aortic annulus; 
         FIGS. 17A and 17B  are elevational views of fully-expandable prosthetic heart valves like that shown in  FIG. 15  with a portion modified to reduce impact on an adjacent heart conduction system; 
         FIG. 18  is a perspective view of a hybrid prosthetic heart valve/holder combination on a distal end of a valve delivery system showing expansion of a distal skirt using an asymmetric balloon; 
         FIG. 19  is a perspective view of a fully-expandable prosthetic heart valve on a distal end of a valve delivery tube showing expansion thereof using an asymmetric balloon; 
         FIG. 20A  is an elevational view of an asymmetric balloon used to expand heart valves as modified herein, and  FIG. 20B  is a cross-sectional view taken along line  20 B- 20 B in  FIG. 20A ; and 
         FIG. 21  is an alternative asymmetric balloon used to expand heart valves as modified herein. 
     
    
    
     DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS 
     As mentioned above, one promising prior art technique for heart valve replacement is a hybrid valve with a non-expandable valve member and an expandable stent thereon which, though still requiring cardiopulmonary bypass, can be implanted in a much shorter time frame. The hybrid valve is delivered through direct-access ports introduced through the chest. 
     Hybrid Heart Valve 
       FIG. 1  illustrates a snapshot in the process of delivering a prior art heart valve  20  to an aortic annulus AA using a valve delivery tube or handle  10 . As will be seen, the valve delivery handle  10  has a distal coupler  12  and a proximal coupler  14 . For purpose of orientation, the heart valve  20  has an inflow end down and an outflow end up, and the terms proximal and distal are defined from the perspective of the surgeon delivering the valve inflow end first. Thus, proximal is synonymous with up or outflow, and distal with down or inflow. 
     As also illustrated in  FIG. 2 , the prosthetic heart valve  20  is considered a hybrid type because it has a non-expandable, non-collapsible valve member  30  and an expandable anchoring skirt  32  attached to and projecting from a distal end of the valve member  30 . The valve member  30  can take a variety of forms, and may include a cloth-covered wireform that follows an undulating path around the periphery of the valve with alternating cusps  33  and commissure posts  34 . A plurality of flexible leaflets  36  extend across a generally circular orifice defined within the valve member  30 , each of which receives peripheral support along the wireform, in particular by two adjacent commissure posts  34 . An annular, preferably contoured, sewing or sealing ring  38  circumscribes the valve  20  at an axial location approximately between the valve member  30  and expandable anchoring skirt  32 . Three markings  39  are often evenly spaced around the cloth-covered sealing ring  38  to delineate to the surgeon the center of each of the cusps  33 . 
     The term “valve member” refers to that component of a heart valve that possesses the fluid occluding surfaces to prevent blood flow in one direction while permitting it in another. Various constructions of valve members are available. The leaflets may be bioprosthetic, synthetic, or other suitable expedients. When used for aortic valve replacement, the valve member  30  preferably has three flexible leaflets  36  which provide the fluid occluding surfaces to replace the function of the native valve leaflets. In various preferred embodiments, the valve leaflets may be taken from another human heart (cadaver), a cow (bovine), a pig (porcine valve) or a horse (equine). The three leaflets are supported by an internal generally tubular frame, which typically include a synthetic (metallic and/or polymeric) support structure of one or more components covered with cloth for ease of attachment of the leaflets. 
     Although the exemplary heart valve  20  is constructed as mentioned, the present invention is broader and encompasses any valve member  30  having an expandable anchoring skirt  32  projecting from an inflow end thereof (for example, one without a wireform). 
     For definitional purposes, the terms “skirt” or “anchoring skirt” refer to an expandable structural component of a heart valve that is capable of attaching to tissue of a heart valve annulus. The anchoring skirt  32  described herein may be tubular or conical, and have varying shapes or diameters. 
     By utilizing an expandable skirt  32  coupled to a non-expandable valve member  30 , the duration of the implant operation is greatly reduced as compared with a conventional sewing procedure utilizing an array of sutures. The expandable skirt  32  may simply be radially expanded outward into contact with the implantation site, or may be provided with additional anchoring means, such as barbs. This provides a rapid connection means as it does not require the time-consuming process of suturing the valve entirely around the annulus. The operation may be carried out using a conventional open-heart approach and cardiopulmonary bypass. In one advantageous feature, the time on bypass is greatly reduced due to the relative speed of implanting the expandable stent. 
     As a point of further definition, the term “expandable” is used herein to refer to a component of the heart valve capable of expanding from a first, delivery diameter to a second, implantation diameter. An expandable structure, therefore, does not mean one that might undergo slight expansion from a rise in temperature, or other such incidental cause such as fluid dynamics acting on leaflets or commissures. Conversely, “non-expandable” should not be interpreted to mean completely rigid or dimensionally stable, merely that the valve member is not expandable/collapsible like some proposed minimally-invasively or percutaneously-delivered valves, and some slight expansion of conventional “non-expandable” heart valves, for example, may be observed. 
     In the description that follows, the term “body channel” is used to define a blood conduit or vessel within the body. Of course, the particular application of the prosthetic heart valve determines the body channel at issue. An aortic valve replacement, for example, would be implanted in, or adjacent to, the aortic annulus. Likewise, a mitral valve replacement will be implanted at the mitral annulus. Certain features of the present invention are particularly advantageous for one implantation site or the other, in particular the aortic annulus. However, unless the combination is structurally impossible, or excluded by claim language, any of the heart valve embodiments described herein could be implanted in any body channel. 
     In a particularly preferred embodiment, the prosthetic valve  20  comprises a commercially available, non-expandable prosthetic valve member  30 , such as the Carpentier-Edwards PERIMOUNT Magna® Aortic Heart Valve available from Edwards Lifesciences, while the anchoring skirt  32  includes an inner plastically-expandable stent frame covered with fabric. In another embodiment, the valve member  30  comprises a PERIMOUNT Magna® Aortic valve subjected to Resilia® tissue treatment, which allows for dry packaging and sterilization and eliminates the need to rinse the valves before implantation. In this sense, a “commercially available” prosthetic heart valve is an off-the-shelf (e.g., suitable for stand-alone sale and use) prosthetic heart valve defining therein a non-expandable, non-collapsible support structure and having a sealing ring capable of being implanted using sutures through the sealing ring in an open-heart, surgical procedure. 
     In the cutaway portion of  FIG. 2 , each of the three leaflets  36  includes outwardly projecting tabs  40  that pass through inverted U-shaped commissure posts  42  of an undulating wireform and wrap around cloth-covered upstanding posts  44  of an inner polymer band. Tabs  40  from adjacent leaflets converge outside of the wireform commissure posts  42  and are sewn together to provide an outer anchor for the leaflet free edges  46 . In use, fluid forces close the leaflets (coaptation) as seen in  FIG. 2  and exert substantial force on the occluded valve, which translates into inward force on the leaflet free edges  46 . The assembly of the wrapped leaflet tabs  40  and cloth-covered posts  44  sewn together provides a solid anchor that is prevented from inward movement by the metallic wireform posts  42 . Some flexing is acceptable and even desirable. 
     One feature of the valve member  30  that is often utilized is the sewing or sealing ring  38  that surrounds the inflow end thereof. The sealing ring  38  conforms to an upper end of the anchoring skirt  32  and is located at the junction of the skirt and the valve member  30 . Moreover, the sealing ring  38  presents an outward flange that contacts an outflow side of the part of annulus, while the anchoring skirt  32  expands and contacts the opposite, ventricular side of the annulus, therefore securing the heart valve  20  to the annulus from both sides. Furthermore, the presence of the sealing ring  38  provides an opportunity for the surgeon to use conventional sutures to secure the heart valve  20  to the annulus as a contingency. 
     The preferred sealing ring  38  defines an undulating upper or outflow face and an undulating lower face. Cusps  33  of the valve structure abut valleys in the sealing ring  38  upper face opposite locations where the lower face defines peaks. Conversely, the valve commissure posts  34  align with locations where the sealing ring  38  lower face defines valleys or troughs. The undulating shape of the sealing ring  38  advantageously matches the anatomical contours of the aortic side of the annulus AA, that is, the supra-annular shelf. The ring  38  preferably comprises a suture-permeable material such as rolled synthetic fabric or a silicone inner core covered by a synthetic fabric. In the latter case, the silicone may be molded to define the undulating contour and the fabric cover conforms thereover. 
     As seen in  FIG. 2 , the anchoring skirt  32  comprises an inner stent frame  52  assembled within a tubular section of fabric  54  which is then drawn taut around the stent frame, inside and out, and sewn thereto to form the cloth-covered skirt  32 . A thicker, more plush fabric flange  56  may also be attached around the fabric  54  for additional paravalvular sealing benefits. It should be noted that  FIG. 2  shows the stent frame  52  in an outwardly expanded state, which occurs during and after implant as mentioned. 
     In an assembly process, the stent frame  52  may be initially tubular and then crimped to a conical shape as see in  FIG. 2A , for example. Of course, the frame  52  may be crimped first and then covered with cloth, or vice versa.  FIG. 2B  shows the expanded stent frame  52  isolated and expanded into its implant shape, which is generally conical and slightly flared out at a lower end. 
     With reference again to the implant step of  FIG. 1 , the aortic annulus AA is shown schematically isolated and it should be understood that various anatomical structures are not shown for clarity. The annulus AA includes a fibrous ring of tissue that projects inward from surrounding heart walls. The annulus AA defines an orifice between the ascending aorta AO and the left ventricle LV. Although not shown, native leaflets project inward at the annulus AA to form a one-way valve at the orifice. The leaflets are preferably left in place and outwardly compressed by the expandable anchoring skirt  32 , or in some cases may be removed prior to the procedure. If the leaflets are removed, some of the calcified annulus may also be removed, such as with a rongeur. The ascending aorta AO commences at the annulus AA with three outward bulges or sinuses, two of which are centered at coronary ostia (openings) leading to coronary arteries CA. It is important to orient the prosthetic valve  20  so that the commissure posts  34  are not aligned with and thus not blocking the coronary ostia. 
       FIG. 1  shows a plurality of pre-installed guide sutures  50 . The surgeon attaches the guide sutures  50  at three evenly spaced locations around the aortic annulus AA. In the illustrated embodiment, the guide sutures  50  attach to locations below or corresponding to the nadirs of the native cusps or sinuses. The guide sutures  50  are passed through the annulus AA and back out of the implantation site. Of course, other suturing methods or pledgets may be used depending on surgeon preference. 
     The guide sutures  50  extend in pairs of free lengths from the annulus AA and out of the operating site. The prosthetic heart valve  20  mounts on the distal end of the delivery handle  10  and the surgeon advances the valve into position within the aortic annulus AA along the guide sutures  50 . That is, the surgeon threads the three pairs of guide sutures  50  through evenly spaced locations around the suture-permeable ring  38 . If the guide sutures  50 , as illustrated, anchor to the annulus AA below the aortic sinuses, they thread through the ring  38  mid-way between the valve commissure posts  34 , in particular at cusp regions  33  of the sealing ring that may be axially thicker than the commissure locations, or uniform all around the circumference. 
       FIG. 1  illustrates the dual nature of the valve delivery handle  10  in that it provides both a portion of the handle of the delivery system, as well as a through lumen that leads directly through the holder  22  and a leaflet parting member (described below) to the space within the anchoring skirt  32 . Although not shown, other elements of the delivery system mate with the proximal coupler  14  to provide an elongated access channel for delivery of an expander such as a balloon to a space within the anchoring skirt  32 . 
     The surgeon advances the heart valve  20  until it rests in a desired implant position at the aortic annulus AA. The undulating suture-permeable ring  38  desirably contacts the ascending aorta AO side of the annulus AA, and is thus said to be in a supra-annular position. Such a position enables selection of a larger orifice prosthetic valve  20  as opposed to placing the ring  38 , which by definition surrounds the valve orifice, within the annulus AA, or infra-annularly. Further details of the delivery procedure are shown and described in U.S. Pat. No. 8,641,757, filed Jun. 23, 2011, the contents of which are expressly incorporated herein. 
     After seating the prosthetic heart valve  20  at the aortic annulus AA, the anchoring skirt  32  is expanded into contact with a subvalvular aspect of the aortic valve annulus, such as with a balloon, to anchor the valve  20  to the annulus AA and seal a concentric space between aortic annulus/LVOT and bio-prosthesis so as to prevent paravalvular leaks. The operator then severs any retention sutures (not shown) between the holder  22  and valve  20 , deflates the balloon and withdraws it along with the entire assembly of the leaflet parting member, holder  22  and valve delivery handle  10 . Finally, the guide sutures  50  will be tied off to further secure the valve in place. 
     The inner stent frame  52  seen in detail in  FIGS. 2A and 2B  may be similar to an expandable stainless-steel stent used in the Edwards SAPIEN® Transcatheter Heart Valve. However, the material is not limited to stainless steel, and other materials such as Co—Cr alloys, nitinol, etc., may be used. In one embodiment, the radial thickness of the plurality of struts is around 0.4-0.6 mm. In a preferred embodiment, the material used should have an elongation at break greater than 33%, and an ultimate tensile strength of greater than about 490 MPa. The stent frame  52  may be initially formed in several ways. For instance, a tubular portion of suitable metal such as stainless steel may be laser cut to length and to form the latticework of chevron-shaped interconnected struts. After laser cutting, the stent frame  52  is desirably electro-polished. Other methods including wire bending and the like are also possible. Following manufacture, and crimping, the inner stent frame  52  assumes a crimped, tapered configuration that facilitates insertion through the calcified native aortic valve (see  FIG. 1 ). 
     It should be noted that the stent frame  52  in  FIG. 2A  commences at its upper end  62  in a generally tubular shape and then angles inwardly to be tapered toward its lower end  64 . That is, the generally tubular portion has a height h which is only a portion of the total height H. As shown, the tubular portion has a height h which generally corresponds to the height between troughs  60   a  and the peaks  60   b  of an upper end  62  of the stent frame. The upper end  62  is preferably defined by a thicker wire for reinforcement. The upper end  62  follows an undulating path with alternating arcuate troughs  60   a  and pointed peaks  60   b  that generally corresponds to the undulating contour of the underside of the sewing ring  38  (see  FIG. 3A ). Desirably, the height h of the peaks  60   b  above the troughs  60   a  is between about 25-36% of the total stent frame height H, with the ratio gradually increasing for larger valve sizes. 
     With reference still to  FIG. 2A , the constricted stent frame  52  of the anchoring skirt  32  has an initial shape following manufacture in a tapered configuration with a lower (inflow/leading) end  64  defining a smaller first diameter D 1  orifice than that described by the upper (outflow/trailing) end  62 . As mentioned, the anchoring skirt  32  attaches to an inflow end of the valve member  30 , typically via sutures through the upper end  62  of the stent frame  52  connected to fabric on the valve member  30  or sewing ring  38 . The particular sewing ring  38  as shown in  FIG. 3A  includes an undulating inflow contour that dips down, or in the inflow direction, in the regions of the valve cusps  33 , and arcs up, in the outflow direction, in the regions of the valve commissures  34 . This undulating shape generally follows the inflow end of the heart valve member wireform  50  (see  FIG. 2 ) which seats down within the sewing ring  38 . The scalloped upper end  62  of the stent frame  52  also conforms to this undulating shape, with peaks  60   b  aligned with the valve commissures  34  and valleys  60   a  aligned with the valve cusps  33 . 
     The mid-section of the frame  52  has three rows of expandable struts  66  in a sawtooth pattern between axially-extending struts  68 . The axially-extending struts  68  are in-phase with the peaks  60   b  and troughs  60   a  of the upper end  62  of the stent frame. The reinforcing ring defined by the thicker wire upper end  62  is continuous around its periphery and has a substantially constant thickness or wire diameter interrupted by eyelets  70 , which may be used for attaching sutures between the valve member  30  and skirt  32 . Note that the attachment sutures ensure that the peaks of the upper end  62  of the skirt  32  fit closely to the troughs of the sewing ring  38 , which are located under the commissures of the valve. 
     As seen in  FIG. 2B , the minimum diameter d of the upper end  62  of the covered skirt  32  will always be bigger than the ID (which defines the valve orifice and corresponding labeled valve size) defined by the prosthetic valve member  30  to which it attaches. For instance, if the upper end  62  secures to the underside of the sewing ring  38 , which surrounds the support structure of the valve, it will by definition be equal to or larger than the ID or flow orifice of the support structure. Typically, however, the upper end  62  attaches via sutures to fabric covering an inner stent structure (not shown), one part of which is the inner polymer band  44 . 
       FIG. 2B  illustrates the stent frame  52  isolated and in its expanded configuration. Balloon inflation is designed to expand only the inflow or lower end  64  of the frame, and no expansion loads are exerted on the outflow or upper end  62  to prevent damage to the supra-annular elements of the valve, and therefore the supra-annular valve remains dimensionally unchanged. The inflow end  64  of the prior art stent frame  52  is designed to expand symmetrically and radially as the balloon inflates. The lower end  64  has a diameter D 2  which is larger than the diameter of the upper end  62 . The expanded shape of the stent  52  is also preferably slightly flared outward toward its lower end  64 , as shown, by virtue of expanding with a spherical balloon. This shape helps the stent conform to the subvalvular contours of the left ventricle, below the aortic valve, and thus helps anchor the valve in place. 
     Conduction System of the Heart 
     As mentioned above, it is important to ensure that the expanding stent frame  52  seals well the space between the implant and the LVOT and it does not impinge on the conduction system of the heart, therefore affecting its function. Indeed, such a concern is not limited to the hybrid prosthetic heart valve  20  illustrated herein, but applies to any expandable valves, in particular those with balloon-expandable stents. 
     As seen in  FIG. 3 , the conduction system of the heart is not uniformly distributed around the native heart valves, but instead is concentrated in several regions. The cardiac conduction system or impulse conduction system of the heart generally consists of four structures: 1. The sinoatrial node (SA node) 2. The atrioventricular node (AV node) 3. The atrioventricular bundle (AV bundle) bifurcated into left and right branches, and 4. The Purkinje fibers in the wall of the heart muscle (not illustrated). The cardiac muscle fibers that compose these structures are specialized for impulse conduction rather than the normal specialization of muscle fibers for contraction. The impulses commence at the SA node which is sometime described as the heart&#39;s pacemaker and is located at the upper portion of the right atrium. From there, signals transmit through internodal tracts to the AV node located in the lower part of the right atrium, through the AV bundle in the central fibrous tissue between the chambers, and to the fibers in the left and right ventricular myocardial tissue. 
       FIG. 3  shows the AV node adjacent the aortic valve. A conduction bundle (Bundle of His) traverses a membranous septum to an interventricular septum. During its course, a Left bundle branch is closer to the Right Coronary annulus and innervates the left ventricle through fascicles and Purkinje fibers. The Right bundle branch exits from membranous septum, penetrates the upper part of the septum and on to the right side of the interventricular septum, leading to the right ventricle and its fascicles and Purkinje fibers. Numerous anatomical studies have attempted to map the course of these conductive fibers in and around the heart&#39;s chambers. 
     With reference to laid-flat depiction of the aortic valve in  FIG. 4 , the conductive pathway adjacent the aortic valve is typically understood to be located in a subvalvular region between the right coronary sinus and the non-coronary sinus. This conduction system zone is depicted schematically as a triangular area extending up between the two sinuses and expanding downward into the left ventricle. The precise location, depth and lateral span of the conduction system zone varies between patients, though the zone commences at a depth below the annulus where the Bundle of His emerges, and that depth is believed to decrease in those with aortic stenosis. Some clinical results demonstrate that the shorter the depth below which the Bundle of His emerges, the higher the risk of conduction abnormalities. A longer depth, on the other hand, indicates a longer distance from the annulus to the Bundle of His, which may allow longer and wider heart valve implants without necessarily causing conduction abnormalities. 
       FIG. 5  illustrates the outlines of a typical hybrid prosthetic heart valve, such as the valve  20  shown in  FIG. 2 . A dashed line  100  indicates the undulating shape of the support structure for the three flexible leaflets. The lower circle  102  is an imaginary line connecting the lower arcuate cusps of the support structure, which is intended to be located at the lower ends of the coronary sinuses when implanted. The two lines  100 ,  102  generally describe the outline of a conventional surgical valve. The lower conical shape indicated at  104  corresponds to the footprint of an expanded subvalvular stent or skirt, such as the skirt  32  shown for the valve  20  in  FIG. 2 . 
     Now with reference to  FIG. 6 , the same general outlines of the hybrid prosthetic valve from  FIG. 5  are superimposed on the laid-flat aortic annulus as if implanted. The three upstanding posts of the valve defined by dashed line  100  extend up between the three sinuses—right, non-coronary, and left. The lower circle  102  extends just below the sinuses, and the subvalvular skirt shape  104  lies against the inside of the left ventricle. This superposition illustrates where possible sources of interference with the conduction system zone are located. That is, expansion of the skirt  32  into the triangular conduction system zone (hatched area) between the right coronary sinus and the non-coronary sinus may impact the heart&#39;s conduction system. 
       FIG. 7  is a schematic plan view of an aortic valve indicating the approximate location of the adjacent conduction system components. Namely, the Left bundle branch and Bundle of His are embedded in the cardiac tissue just outside of the membranous interventricular septum on the posterior side of the aortic valve. As stated above, the normal position of the conduction system components is adjacent the valve commissure between the right coronary sinus or cusp (RCS) and the non-coronary sinus or cusp (NCS). This location helps inform modifications to prosthetic valves, as set forth below. 
     Hybrid Heart Valve Modifications 
       FIG. 8  is a perspective view of an assembled hybrid prosthetic aortic heart valve  20 ′ modified to avoid interference with the heart&#39;s conduction system. In particular, the expandable skirt  32 ′ will be modified as explained below. A preferred modification involves modification of an inner stent frame of the skirt  32 ′ around only a portion of the circumference thereof. The portion modified corresponds to a portion that will be implanted adjacent the conduction system, or generally adjacent the valve commissure between the right coronary sinus or cusp (RCS) and the non-coronary sinus or cusp (NCS), as seen in  FIG. 7 . To guide the surgeon during implant of the valve  20 ′, markings on the exterior thereof are provided to indicate rotational placement. That is, the surgeon can discern the anatomical features around the aortic valve visually, but the portion of the stent frame that is modified will not be apparent due to the outer cloth coverings  54 ′,  56 ′. 
     Conventional aortic heart valves typically have three distinct markings around their periphery that indicates to the surgeon the cusp regions  33 , as seen at  39  in  FIG. 2 . In particular, thick black marker thread is used to form the markings  39 . The modified valve  20 ′ also has the three cusp markings  39 ′, as well as a distinct elongated marking  72  extending between two of the cusp markings  39 ′. The elongated marking  72  thus extends around ⅓ of the way (120°) around the modified valve  20 ′ and is aligned with a modified arcuate span of the stent frame of the skirt  32 ′. When the surgeon implants the valve  20 ′, he or she rotates the linear marking  72  to align with that portion of the anatomy in which is located the conduction system. As explained above with reference to  FIG. 7 , the conduction system is expected to be located adjacent the valve commissure between the right coronary sinus or cusp (RCS) and the non-coronary sinus or cusp (NCS). Thus, the arcuate marking  72  is centered on the valve commissure post  42 ′. The elongated marking  72  may be formed by a printed indicator, or by sewing one or more lengths of suture along the appropriate area. The elongated marking  72  is colored so as to contrast highly with the sealing ring  38 ′, such as a black marker suture against a white cloth covering. Bright or fluorescent colors may also be used to be more visible in dim lighting. 
       FIGS. 9A-9C  are elevational views of exemplary stent frames  52   a ,  52   b ,  52   c  of the present application for use in an anchoring skirt of a hybrid prosthetic heart valve, the stent frames are shown radially expanded with struts modified to reduce impact on an adjacent heart conduction system. It should be noted that the stent frames are constructed generally the same as with the stent frame  52  of  FIG. 2A , described above, aside from the modifications below, and thus like elements will have like numbers with the addition of a prime (e.g.,  62 ′). 
     In  FIG. 9A , the stent frame  52   a  is shown with a thicker wire upper end  62 ′ having an undulating periphery with alternating troughs  60   a ′ and the peaks  60   b ′. The stent frame  52   a  when constricted has a generally tubular shape at its upper end  62 ′ and then angles inwardly to be tapered toward its lower end  64 ′. When expanded, the lower end  64 ′ expands radially outward as shown, with a flared configuration. As before, a mid-section of the frame  52   a  has three circumferential rows of expandable struts  66 ′ in a sawtooth pattern with V-shaped bends between axially-extending struts  68 ′. The axially-extending struts  68 ′ are in-phase with the peaks  60   b ′ and troughs  60   a ′ of the upper end  62 ′ of the stent frame. 
     In a region  120   a  (bracketed) of the stent frame  52   a  centered on one of the peaks  60   b ′, the three rows of expandable struts  66 ′ exhibit shallower (greater) included angles θ in the bends of the sawtooth pattern in the expanded state of the stent frame  52   a  than in the rest of the frame. More precisely, the bends are shallower in the region  120   a  that extends about 120° between two of the troughs  60   a ′. Generally, the region  120   a  may extend circumferentially between about 90-120°. In an exemplary embodiment, the included angles of the bends in the region  120   a  are between about 135-160°, while the bends in the rows of expandable struts  66 ′ around the rest of the stent frame are between about 45-90°. The result is that the rows of expandable struts  66 ′ in the region  120   a  expand less than around the rest of the stent frame  52   a  when caused to straighten out and lengthen. In other words, they straighten out faster, as shown by the final angle θ of the bends in the expanded frame versus the rest of the bends. This produces an asymmetric expansion of the stent frame  52   a , with about ⅔ of the frame expanding normally and about ⅓ expanding less. The region  120   a  forms something of an arcuate chordal shape when expanded, extending between circular adjacent regions, as seen best in  FIG. 12B . 
     It should be noted that the final angle θ of the bends in the expanded frame  52   a  is typically the same bend angle of the stent frame in region  120   a  when initially formed. That is, the frame  52   a  is fabricated in a tubular shape, then crimped down to a smaller diameter prior to packaging and shipping, as the stent frame is delivered in the contracted state. Consequently, the final bend angles θ of the frame  52   a  are set at the time of frame formation. One method of frame construction is laser-cutting the various struts from a tubular blank of plastically-expandable material such as stainless steel or an elastic material such as nitinol. 
     In one embodiment, the majority of the stent frame  52   a  is configured to normally flare outward to a maximum diameter that is several millimeters greater than the nominal heart valve size. The “nominal heart valve size” means the labeled heart valve size selected for that particular annulus, and generally corresponds in odd mm increments to the measured diameter of the naïve heart valve orifice. The “nominal heart valve size” is also slightly less than the diameter d of the upper end  62 ′ of the stent frame  52   a . For example, the “nominal heart valve size” may be 21 mm, and the lower end  64 ′ of the stent frame  52   a  flares outward to a maximum diameter of about 23.5 mm. However, the region  120   a  of the stent frame  52   a  centered on one of the peaks  60   b ′ is configured to expand outward by between 1-2 mm less, or to a diameter of between about 21.5-22.5 mm. This helps reduce the force applied to the surrounding subvalvular region where the conduction system is assumed to be. 
     In another solution to potential impaction on the conduction system,  FIG. 9B  shows a stent frame  52   b  with a lower circumferential row of expandable struts  66 ′ removed in the region  120   b  (bracketed) of the stent frame  52   b  centered on one of the peaks  60   b ′. In the illustrated embodiment, as with the stent frame  52   a , the region  120   b  extends around ⅓ of the periphery of the stent frame between cusps, or about 120°. More generally, the region  120   b  may extend circumferentially between 90-120°. The included angles of the bends in the region  120   b  remain as in the rest of the frame, between about 45-90°, and thus that portion of the region  120   b  with circumferential struts  66 ′ expands normally. As mentioned above, in some patients the electrical conduction system adjacent the aortic valve does not commence until some ways down into the left ventricle, in which case expansion of the stent frame  52   b  may avoid even contacting that zone. 
     Finally,  FIG. 9C  shows a third alternative stent frame  52   c  which also has the lower circumferential row of expandable struts  66 ′ removed in the region  120   c  (bracketed). In addition, the next adjacent circumferential row of expandable struts  66 ′ in the region  120   c  has shallow included bend angles in the expanded state of the stent frame  52   c , such as in the range stated above for the included angles of the bends for the stent frame  52   a  of  FIG. 9A . Thus, when the stent frame  52   c  expands, the conduction system zone may be avoided altogether because of the missing lower row, and the next adjacent row of struts  66 ′ expands less than the rest of the stent frame (e.g., asymmetric radial expansion) which reduces outward pressure on that zone. As before, the region  120   c  preferably extends circumferentially between about 90-120° between two of the troughs  60   a ′ and is centered on one of the peaks  60   b′.    
       FIG. 10  is an elevational view of another exemplary stent frame  52   d  radially expanded with struts modified to produce asymmetric expansion around the skirt. In this embodiment, the lower circumferential row of expandable struts  66 ′ in a region  120   d  (bracketed) has variable included bend angles, with shallower angles toward the center of the region  120   d . In particular, there may be eighteen axially-extending struts  68 ′ in-phase with the peaks  60   b ′ and troughs  60   a ′ of the upper end  62 ′ of the stent frame, which means there are six in each ⅓ dividing the region  120   d  into six spans across which there are the bends in the expandable struts  66 ′. The inner two spans have shallow (large) bend angles, while the next two outward spans have smaller bend angles, and the outermost two spans have even smaller bend angles. The inner two spans straighten the fastest, as shown by the final angle bend angles θ, the next two outward spans straighten less as seen by final bend angles α, and the outermost two spans have more room for expansion, as seen by their final bend angles β. This alters the asymmetric expansion such that the reduction in final diameter in the region  120   d  is gradual from the adjacent unaltered regions. More particularly, in comparison with a more chordal shape between the adjacent regions, as with the embodiment of  FIG. 9A , the expanded shape of the region  120   d  is more rounded, closer to the circular shape of the rest of the stent frame  52   d . This focuses the expansion reduction in the center of the region  120   d , which again may extend circumferentially between 90-120°. Of course, the particular pattern of variance of the included bend angles may differ, and the illustrated embodiment is only exemplary. 
       FIGS. 11A and 11B  are elevational views of a further exemplary stent frame  52   e  shown radially expanded with a middle circumferential row of expandable struts  66 ′ removed in a region  120   e  (bracketed) to reduce impaction on an adjacent native conduction system zone.  FIG. 11A  shows all of the axially-extending struts  68 ′ retained to create a plurality of enlarged spaces or cells  122  between struts, while in  FIG. 11B  some of them are removed to create a plurality of even larger cells  124 . In both stent frames  52   e , the region  120   e  is desirably centered on one of the peaks  60   b ′ and preferably extends circumferentially about 120°, more generally between 90-120°. These embodiments thus create larger cells or voids within the region  120   e  which, though expanded normally, reduces direct stent contact with the surrounding native conduction system zone. Of course, the included bend angles in the remaining rows of expandable struts  66 ′ in the region  120   e  may also be shallow, as described above, to produce asymmetric radial expansion and further reduce the impact on the conduction system. 
       FIG. 12A  shows the stent frame  52   a  from below prior to expansion, and  FIG. 12B  shows the stent frame  52   a  after expansion showing how one side does not expand as far as the remainder (e.g., asymmetric radial expansion). In particular, the region  120   a  includes the shallower included bend angles θ than in the rest of the stent frame  52   a , and thus balloon expansion causes that region  120   a  to expand more in an arcuate chordal shape than circular, as with the remainder of the stent frame periphery. The distance ΔD from an imaginary circle drawn around the maximum diameter expansion is the preferred reduction in expansion diameter in the region  120   a . As mentioned above, distance ΔD is preferably between 1-2 mm, and more preferably about 1.5 mm. Such a small reduction of expanded diameter in the asymmetric region  120   a  is believed sufficient to reduce negative impacts on the conduction system. 
     Fully-Expandable Heart Valve Modifications 
       FIG. 13  is a perspective view of a fully-expandable prosthetic heart valve  140  of the prior art shown expanded. The heart valve  140  is representative of a number of such valves, in particular the Sapien® line of valves sold by Edwards Lifesciences of Irvine, Calif. The heart valve  140  includes a structural frame  142  defining a flow passage therein and a plurality of flexible leaflets  144  secured within the frame, typically via suturing to an intermediate fabric skirt  146 . In the illustrated embodiment, there are three of the leaflets  144  that meet at commissure posts  148  defined by the frame  142 . The leaflets  144  extend axially within the frame  142  at the commissure posts  148  and adjacent leaflets abut each other and are sewn together along the posts. Cusp edges (not shown) of the leaflets  144  are also sewn to the frame  142 . Free edges  150  of the leaflets  144  come together or coapt in the flow passage to form the one-way valve. 
     The structural frame  142  is fully expandable from a contracted configuration to the expanded shape shown. In this way, the contracted valve  140  may be advanced through a narrow passage into position at the target annulus, such as through a catheter or other delivery, without needing to stop the heart and put the patient on cardiopulmonary bypass. The contracted valve  140  is then expelled from the catheter or other delivery tube and expanded into contact with the annulus. The frame  142  may be self-expanding, or as in the case of the Sapien® line of valves, is balloon-expandable, such as being made of stainless steel. The frame  142  typically has a plurality of circumferential struts  152  with bends  154  that straighten out when the valve  140  expands. Prior art valves of this type have a tubular frame in both the contracted and expanded configurations stemming from a symmetrical distribution and shape of the circumferential struts  152 . 
       FIG. 14  is a perspective view of a modified fully-expandable prosthetic heart valve  160  of the present application. The valve  160  is in most respects the same construction as the representative heart valve  140  of  FIG. 13 , and so like elements are given like numbers with the addition of a prime (e.g.,  142 ′). As before, the valve  160  comprises an expandable frame  142 ′ supporting a plurality (e.g., three) flexible leaflets  144 ′. Once again, adjacent leaflets  144 ′ are secured against each other at commissure posts  148 ′ of the frame  142 ′. 
     The frame  142 ′ has a circumferentially-extending region  162  (bracketed) in which the bends  156 ′ in circumferential struts  152 ′ have a much greater included angle then the bends  154 ′ around the remainder of the frame. This modification reduces the amount of circumferential and thus radial expansion of the frame  152 ′ in the region  162 . This reduced or asymmetric expansion helps reduce contact with and thus impact on the adjacent conduction system of the heart when the valve  160  expands. If the heart valve  160  is intended for implant at the aortic annulus, the region  162  is centered at one of the commissure posts  148 ′ as the conduction system is believed to be concentrated near one of the native commissures. To assist the surgeon in rotationally orienting the heart valve  160  during implant, a marker may be placed on either the appropriate commissure post  148 ′ or on the fabric skirt  146 ′ at that location. Although not shown, the marker may be as described above with respect to  FIG. 8  (e.g., dark suture marker spanning 120°). 
       FIG. 15  is an elevational view of another fully-expandable prosthetic heart valve  170  of the prior art shown expanded. The heart valve  170  generally comprises a self-expanding structural frame  172  having a tissue valve  174  sewn thereto. In one such embodiment, the Evolut™ TAVR System available from Medtronic Cardiovascular of Minneapolis, Minn. includes a supra-annular, self-expanding nitinol frame, with a porcine pericardial tissue valve. The structural frame  172  is somewhat hourglass-shaped and defines an enlarged upper region  180 , a narrow middle region  182 , and an enlarged lower region  184 . 
     The self-expanding nitinol frame  172  may be crimped down to a small diameter just prior to delivery. As shown in  FIG. 16 , after implantation of the fully-expandable prosthetic heart valve  170  at an aortic annulus, the upper region  180  enlarges into the ascending aorta, the narrow middle region  182  registers with the aortic annulus AA, and the lower region  184  enlarges into the left ventricle LV, or in a subvalvular area. Although the frame  172  is self-expandable and thus exerts less outward force on the surrounding tissue, issues may arise from contact with the adjacent conduction system of the heart, especially in the subvalvular area. Moreover, many surgeons perform a post-implant balloon expansion of the middle region  182  to help fully expand the frame  172 , which may also negatively impact the conduction system. 
     Consequently,  FIGS. 17A and 17B  show self-expandable stent frames for fully-expandable prosthetic heart valves like that shown in  FIG. 15  with a portion modified to reduce impact on an adjacent heart conduction system. In particular, the stent frame  200  in  FIG. 17A  features a region  202  (bracketed) with modified struts which cause asymmetric expansion of the frame; namely, less expansion within the region  202  as compared to the rest of the circumference. There are a number of ways to modify the struts to accomplish this, one of which includes smaller cells  204  between struts connected by short V-shaped segments  206 . The struts  206  that form the smaller cells  204  expand somewhat, but not as much as the surrounding struts. If the valve in which the stent frame  200  is used is for aortic valve replacement, the region  202  is preferably centered on one of the valve commissures, and may extend circumferentially around the valve by between 90-120°. Additionally, the modified region  202  is preferably located in the subvalvular area, preferably in the lower region  184  as see in  FIG. 15 , but also possibly extending up into the middle region  182 . 
       FIG. 17B , on the other hand, illustrates a self-expandable stent frame  210  with a region  212  (bracketed) modified to reduce the impact on an adjacent conduction system by removing a number of struts to form enlarged cells  214 . In the illustrated embodiment, two enlarged diamond-shaped cells  214  are formed by removing four intersecting struts in two places, though other patterns are also contemplated. Removal of the struts lessens the chance that the expanding frame  210  will contact and negatively impact the adjacent conduction system. Again, for aortic valve replacement, the region  212  is preferably centered on one of the valve commissures, and may extend circumferentially around the valve by between 90-120°, and is preferably located in the subvalvular area. A combination of enlarged cells as at  214  and asymmetric expansion as with stent  200  of  FIG. 17A  is also a possibility. 
     Modified Expansion Balloons 
       FIG. 18  is a perspective view of a valve delivery system  220  similar to that described above with respect to  FIG. 1  having a hybrid prosthetic heart valve  222  on a distal end thereof. As before, expansion of a distal skirt of the heart valve  222  is accomplished using a balloon  224  that extends through the middle of the valve  222 . In contrast with the prior system, the balloon  224  is modified to expand asymmetrically, with a majority of the circumference at  226  being conventional and an altered region  228 . Specifically, the region  228  is altered so as to expand less than the larger region  226 . Consequently, the portion of the skirt of the heart valve  222  adjacent the modified region  228  expands less as well. 
     The region  228  may be modified in a number of ways to undergo a smaller radial expansion. One way is to construct the balloon  224  to have the larger region formed of compliant (e.g., stretchy) balloon material with the region  228  formed of non-compliant (e.g., non-stretchy) material. Various balloons of both types of material are known, typically formed out of nylon, e.g., polyether block-amide (e.g., PEBAX®, Arkema) blend or nylon/polyether-block-amide blend materials. In one embodiment, a mesh of interconnected fibers (not shown) may be embedded within the region  228  of an otherwise homogenous balloon to create the non-compliant section. Alternatively, rigid stiffeners (also not shown) such as nylon cords may be attached to the balloon  224  in the region  228 . In any event, the region  228  is modified to create an asymmetric expansion of the balloon  224 , which in turn expands the valve skirt asymmetrically. 
     Moreover, the balloon  224  may be combined with a modified hybrid valve as discussed above, and the region  228  aligned to expand within the region of the stent frame that is modified. For instance, the region  228  may extend circumferentially between 90-120°, and be aligned within the region  120   a  of the stent frame  52   a  in  FIG. 9A  (or within any of the other modified stent frames). Although the various modified stent frames are intended to expand asymmetrically, the modified regions may simply pull the remainder of the frames toward that region, resulting in less asymmetry as desired. Consequently, using a modified expansion balloon  224  may be needed to result in the desired asymmetry. 
       FIG. 19  is a perspective view of the distal end of a valve delivery system  230  including a catheter  232  and an asymmetric balloon  234  within a fully-expandable prosthetic heart valve  236 . The balloon  234  preferably has a majority region  238  that expands normally and a modified region  240  that expands asymmetrically. The modified region  240  may be formed as described above for balloon  224 , such as being formed of a non-compliant material. When expanded within the heart valve  236 , the asymmetric expansion causes similar asymmetric expansion of the valve. Further, the asymmetric balloon  234  may be used within a fully-expandable prosthetic heart valve  160  modified as described above with respect to  FIG. 14 . In such a combination, the modified region  240  is rotationally aligned within the region  162  on the valve  160  modified for reduced expansion. 
       FIG. 20A  is an elevational view of the valve delivery system  230  having the asymmetric balloon  234 , and  FIG. 20B  is a cross-sectional view taken along line  20 B- 20 B in  FIG. 20A . As mentioned, the modified region  240  is non-compliant or stiffened so as to expand asymmetrically, as seen in  FIG. 20B . 
       FIG. 21  shows the asymmetric balloon  234  within the self-expandable prosthetic heart valve  170  of the prior art during a procedure of post-implant expansion thereof. Preferably, the modified region  240  is rotationally aligned with the area adjacent the valve annulus containing the electrical conduction system of the heart. The asymmetric balloon  234  thus avoids maximum expansion of the frame of the valve  170  in this area. Further, the valve  170  may be modified to reduce the impacts on the conduction system, as with valves  200  and  210  of  FIGS. 17A and 17B . In that case, the modified region  240  is rotationally aligned with the modified regions  202 ,  212 , respectively. 
     While this disclosure describes preferred embodiments, it is to be understood that the words which have been used are words of description and not of limitation. Therefore, changes may be made within the appended claims without departing from the true scope of the disclosure.