WO2018165225A1

WO2018165225A1 - Systems, methods and devices for prosthetic heart valve with single valve leaflet

Info

Publication number: WO2018165225A1
Application number: PCT/US2018/021244
Authority: WO
Inventors: Jeffrey W. Chambers; Saravana B. KUMAR; Joseph P. Higgins; Robert J. Thatcher; Jason S. DIEDERING; Jeffrey R. Stone
Original assignee: 4C Medical Technologies, Inc.
Priority date: 2017-03-07
Filing date: 2018-03-07
Publication date: 2018-09-13
Also published as: CN110505854B; CA3054814C; CA3054814A1; US20180256329A1; AU2018231187A1; JP2020509835A; AU2018231187B2; EP3592296A4; CN110505854A; EP3592296A1

Abstract

Devices and methods for supplementing and/or replacing native cardiac valve functionality, e.g., the mitral valve with a single prosthetic leaflet. An exemplary device is directed to dysfunctional mitral valves. In some cases, the entire device, including the single prosthetic leaflet, will be arranged entirely above the dysfunctional mitral valves and, therefore, disposed entirely within the left atrium. In other cases, the valve support and/or single prosthetic leaflet may extend a distance into the annulus between the left atrium and left ventricle. In some cases, the device will not physically interact with the native leaflets. In other cases, the device may physically interact with the native leaflets.

Description

TITLE OF THE INVENTION

Systems, Methods and Devices for Prosthetic Heart Valve with Single Valve Leaflet

INVENTORS

Jeffrey W. Chambers, Maple Grove, MN, a citizen of the United States of America;

Saravana B. Kumar, Minnetonka, MN, a citizen of India;

Joseph P. Higgins, Minnetonka, MN, a citizen of the United States of America

Robert J. Thatcher, Blaine, MN, a citizen of the United States of America;

Jason S. Diedering, Minneapolis, MN, a citizen of the United States of America; and

Jeffrey R. Stone, Minnetonka, MN, a citizen of the United States of America.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application Serial No. 62/468112, filed March 7, 2017, and titled SYSTEMS, METHODS AND DEVICES FOR PROSTHETIC HEART VALVE WITH SINGLE VALVE LEAFLET, the entire contents of which are incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR

DEVELOPMENT

Not Applicable

INCORPORATION BY REFERENCE

All references, including but not limited to publications, patent applications and patents mentioned in this specification are hereby incorporated by reference to the same extent and with the same effect as if each reference was specifically and individually indicated to be incorporated by reference.

BACKGROUND OF THE INVENTION [0001] FIELD OF THE INVENTION

(0002] The invention relates to supplementing and/or replacing native heart valve leaflet function.

[0003] DESCRIPTION OF THE RELATED ART

[0004] The human heart comprises four chambers and four heart valves that assist in the forward (antegrade) flow of blood through the heart. The chambers include the left atrium, left ventricle, right atrium and left ventricle. The four heart valves include the mitral valve, the tricuspid valve, the aortic valve and the pulmonary valve.

[0005] The mitral valve is located between the left atrium and left ventricle and helps control the flow of blood from the left atrium to the left ventricle by acting as a one-way valve to prevent backflow into the left atrium. Similarly, the tricuspid valve is located between the right atrium and the right ventricle, while the aortic valve and the pulmonary valve are semilunar valves located in arteries flowing blood away from the heart. The valves are all one-way valves, with leaflets that open to allow forward (antegrade) blood flow. The normally functioning valve leaflets close under the pressure exerted by reverse blood to prevent backflow (retrograde) of the blood into the chamber it just flowed out of.

[0006] Native heart valves may be, or become, dysfunctional for a variety of reasons and/or conditions including but not limited to disease, trauma, congenital malformations, and aging. These types of conditions may cause the valve structure to either fail to properly open (stenotic failure) and/or fail to close properly (regurgitant).

[0007] Mitral valve regurgitation is a specific problem resulting from a dysfunctional mitral valve. Mitral regurgitation results from the mitral valve allowing at least some retrograde blood flow back into the left atrium from the left ventricle. This backflow of blood places a burden on the left ventricle with a volume load that may lead to a series of left ventricular compensatory adaptations and adjustments, including remodeling of the ventricular chamber size and shape, that vary considerably during the prolonged clinical course of mitral regurgitation.

[0008] A similar problem may occur when the tricuspid valve weakens or begins to fail. The tricuspid valve separates the right atrium and right ventricle. Tricuspid regurgitation, also known as tricuspid insufficiency, occurs when the tricuspid valve doesn't properly close, causing blood to flow back up into the right atrium when the right ventricle contracts. Various embodiments of the present invention discussed herein may apply to mitral valve and/or tricuspid valve regurgitation. [0009] Native heart valves generally, e.g., mitral valves, therefore, may require functional repair and/or assistance, including a partial or complete replacement. Such intervention may take several forms including open heart surgery or open heart implantation of a replacement heart valve. See e.g., U.S. Pat. No. 4,106,129 (Carpentier), for a procedure that is highly invasive, fraught with patient risks, and requiring not only an extended hospitalization but also a highly painful recovery period.

[0010] Less invasive methods and devices for replacing a dysfunctional heart valve are also known and involve percutaneous access and catheter-facilitated delivery of the replacement valve. Most of these solutions involve a replacement heart valve attached to a structural support such as a stent, commonly known in the art, or other form of wire network designed to expand upon release from a delivery catheter. See, e.g., U.S. Pat. No. 3,657,744 (Ersek); U.S. Pat. No. 5,41 1,552 (Andersen). The self-expansion variants of the supporting stent assist in positioning the valve, and holding the expanded device in position, within the subject heart chamber or vessel. This self-expanded form also presents problems when, as is often the case, the device is not properly positioned in the first positioning attempt and, therefore, must be recaptured and positionally adjusted. This recapturing process in the case of a fully, or even partially, expanded device requires re-collapsing the device to a point that allows the operator to retract the collapsed device back into a delivery sheath or catheter, adjust the inbound position for the device and then re-expand to the proper position by redeploying the positionally adjusted device distally out of the delivery sheath or catheter. Collapsing the already expanded device is difficult because the expanded stent or wire network is generally designed to achieve the expanded state which also resists contractive or collapsing forces.

[0011] Besides the open heart surgical approach discussed above, gaining access to the valve of interest is achieved percutaneously via one of at least the following known access and delivery routes: femoral access, venous access, trans-apical, trans-aortic, trans-septal, trans-atrial, retrograde from the aorta delivery techniques.

[0012] Generally, the art is focused on systems and methods that, using one of the above- described known access routes, allow a partial delivery of the collapsed valve device, wherein one end of the device is released from a delivery sheath or catheter and expanded for an initial positioning followed by full release and expansion when proper positioning is achieved. See, e.g., U.S. Pat. Nos. 8,852,271 (Murray, III); 8,747,459 (Nguyen); 8,814,931 (Wang); 9,402,720 (Richter); 8,986,372 (Murray, III); and 9,277,991 (Salahieh); and U.S. Pat. Pub. Nos. 2015/0272731 (Racchini); and 2016/0235531 (Ciobanu).

[0013] However, known delivery systems, devices and methods still suffer from significant flaws in delivery methodology including, inter alia, positioning and recapture capability and efficiency.

[0014] In addition, known "replacement" heart valves are intended for full replacement of the native heart valve. Therefore, these replacement heart valves physically engage the annular throat and/or valve leaflets, thereby eliminating all remaining functionality of the native valve and making the patient completely reliant on the replacement valve. Generally speaking, it is a preferred solution that maintains and or retains the native function of a heart valve, thus supplementation of the valve is preferred rather than full replacement. Obviously, there will be cases when native valve has either lost virtually complete functionality before the interventional implantation procedure, or the native valve continues to lose functionality after the implantation procedure. The preferred solution is delivery and implantation of a valve device that will function both as an adjunctive and/or supplementary functional valve as well as be fully capable of replacing the native function of a valve that has lost most or all of its functionality. However, the inventive solutions described infra will apply generally to all types and forms of heart valve devices, unless otherwise specified.

[0015] Further, known solutions for, e.g., the mitral valve replacement systems, devices and methods require 2-chamber solutions, i.e., there is involvement and engagement of the implanted replacement valve device in the left atrium and the left ventricle. Generally, these solutions include a radially expanding stent in the left atrium, with anchoring or tethering (disposed downward through the native annulus or annular throat) connected from the stent device down through the annular throat, with the sub-annular surface within the left ventricle, the left ventricular chordae tendineae and even into the left ventricle wall surface(s). See, e.g., the MitraClip^® marketed by the Abbott Group and currently the only US approved repair device. With the MitraClip^® a catheter containing the MitraClip^® is inserted into the femoral vein. The device enters the heart through the inferior vena cava to the right atrium and delivered trans- septally. The MitraClip^® passes through the annulus into the left ventricle and sits below the leaflets, clipping the leaflets to decrease regurgitation.

[0016] Such 2-chamber and native annular solutions are unnecessary bulky and therefore more difficult to deliver and to position/recapture/reposition from a strictly structural perspective. Further, the 2-chamber solutions present difficulties in terms of making the ventricular anchoring and/or tethering connections required to hold position. Moreover, these solutions interfere with the native valve functionality as described above because the device portions that are disposed within the left ventricle must be routed through the native annulus and/or annular throat and native mitral valve, thereby disrupting any remaining coaptation capability of the native leaflets. In addition, the 2-chamber solutions generally require an invasive anchoring of some of the native tissue, resulting in unnecessary trauma and potential complication.

[0017] It will be further recognized that the 2-chamber mitral valve solutions require sub-annular and/or ventricular engagement with anchors, tethers and the like precisely because the atrial portion of the device fails to adequately anchor itself to the atrial chamber and/or upper portion of the annulus. Again, some of the embodiments, or portions thereof, described herein are readily applicable to single or 2-chamber solutions, unless otherwise indicated.

[0018] Finally, known prosthetic cardiac valves consist of two or three leaflets that are arranged to act as a one-way valve, permitting fluid flow therethrough in the antegrade direction while preventing retrograde flow. The mitral valve is located retrosternally at the fourth costal cartilage, consisting of an anterior and posterior leaflet, chordae tendinae, papillary muscles, ventricular wall and annulus connected to the atria. Each leaflet is supported by chordae tendinae that are attached to papillary muscles which become taut with each ventricular contraction preserving valvular competence. Both the anterior and posterior leaflets of the valve are attached via primary, secondary and tertiary chordae to both the antero-lateral and posterio-medial papillary muscles. A disruption in either papillary muscle in the setting of myocardial injury, can result in dysfunction of either the anterior or posterior leaflet of the mitral valve. Other mechanisms may result in failure of one, or both of the mitral leaflets. In the case of a single leaflet failure, the regurgitation may take the form of a non-central, eccentric jet of blood back into the left atrium. Other leaflet failures may comprise a more centralized regurgitation jet. Known prosthetic valve replacements generally comprise leaflets which are arranged to mimic the native valve structure, which may over time become susceptible to similar regurgitation outcomes.

[0019] Various embodiments of the present invention address these, inter alia, issues.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS [0020] Figure 1 A illustrates a side view of one embodiment of the present invention.

[0021] Figure I B illustrates a bottom cutaway view of one embodiment of the present invention.

[0022] Figure 2 A illustrates a cutaway bottom view of one embodiment of the present invention.

[0023] Figure 2B illustrates a cutaway bottom view of one embodiment of the present invention.

[0024] Figure 2C illustrates a cutaway bottom view of one embodiment of the present invention.

[0025] Figure 3 illustrates a side view of one embodiment of the present invention.

[0026] Figure 4 illustrates a side view of one embodiment of the present invention.

[0027] Figure 5 illustrates a side view of one embodiment of the present invention.

[0028] Figure 6 illustrates a side view of one embodiment of the present invention.

[0029] Figure 7 illustrates a side view of one embodiment of the present invention.

[0030] Figure 8 illustrates a bottom perspective view of one embodiment of the present invention.

[0031] Figure 9 illustrates a bottom view of one embodiment of the present invention.

[0032] Figure 10 illustrates a side view of one embodiment of the present invention.

[0033] DETAILED DESCRIPTION OF THE INVENTION

[0034] Figures 1 A and 1 B provides an exemplary expanded prosthetic valve device 100 adapted for implantation within a heart chamber, e.g., the left atrium. An anchoring portion 102 is shown with a wire, e.g., a stent, construction that may be open, or at least partially open, when expanded within an exemplary left atrium. Anchoring portion 102 may be hollow and may provide a flow channel, shown in dashed lines at 103 in Fig 1A, therethrough for blood flowing into the open wire construction of the anchoring portion 102 from the left pulmonary veins L into the left atrium where the device 100 is expanded and positioned for implantation. A lower section of anchoring portion 102, that is the section of the anchoring portion 102 that is located below the incoming blood flow points at the left pulmonary veins L, may be covered by fabric and/or tissue, either on the luminal side, the abluminal side, or on both the luminal and abluminal sides of the anchoring portion 102 to help channel the incoming blood flow into the flow channel 103 and to prevent paravalvular leakage.

[0035] The flow channel in Figs 1 A and IB terminates at a lower edge 104 of the anchoring portion with an exemplary prosthetic leaflet 106 hingedly attached thereto. As seen in Figure IB, the lower edge 104 may comprise a generally circular profile, though other shapes are within the scope of the present invention. Particularly, the undeformed expanded profile of the anchoring portion 102 and, in some cases, of the lower edge 104, may differ from a deformed expanded profile of anchoring portion 102 and lower edge 104 when the device 100 expands against atrial walls and the upper surface of the annulus. The embodiment illustrated in Fig 1 B comprises a single support wire, though a thicker configuration, e.g., a sewing ring, may also be provided. As the skilled artisan will readily recognize, lower edge 104 comprises a structure that allows a hinged or flexing connection with the single prosthetic leaflet 106.

[0036] As shown in Figs 2 A and 2B, a single prosthetic leaflet 106 may comprise a perimeter 108 and a leaflet attachment zone 1 10 located along a portion of the perimeter 108. Thus, leaflet 106 may be connected with the lower edge 104 of the anchoring structure 102 or may be a separate structure that is attached or connected with the lower edge 104 of anchoring portion 102. Perimeter 108 in these leaflets 106 comprise a width, and in some cases a thickness, that may be formed of a material that differs from the material of the inner region 105 to facilitate attachment to the lower edge 104 of anchoring portion 102. In some embodiments, leaflet 106 may comprise a single material throughout as in Fig. 2C, wherein the perimeter 108 (shown in dashed lines) may comprise the same material as the inner region 105, though perimeter 108 may comprise a reinforced, e.g., double layer or folded layer of material.

[0037] In addition, the leaflet 106 may comprise a circular or a geometric, e.g., hexagonal, outer profile, see e.g. Figs 2A and 2B. These are simply exemplary shapes, all other shapes are within the scope of the present invention, so long as the leaflet 106 covers the opening defined by the lower edge 104 of the anchoring portion 102. Accordingly, lower edge 104 may be shaped with a variety of shapes, e.g., circular, semi-circular, when either expanded and deformed or expanded and undeformed. Any shape for lower edge 104 of the anchoring portion 102 is within the scope of the present invention, so long as the leaflet 106 is sized and shaped to cover the opening defined by lower edge 104.

[0038] The attachment mechanism between the valve leaflet 106 and support structure's leaflet attachment zone 1 10 may be seen with exemplary connection methods, and leaflet 106 structures, in Figures 2A-2C. Figure 2 illustrates a series of connecting points which may be sutures or some other equivalent connective structure and that covers part of the outer surface of an exemplary circular valve leaflet such that the valve leaflet may swing open and closed using the connecting points as a hinge point. Figure 3 illustrates an exemplary hexagonal valve leaflet with a series of connecting points within a leaflet attachment zone along one side of the hexagonal valve leaflet. Other shapes besides the circular and hexagonal valve leaflets shown here, e.g., oval, square, rectangle, pentagon, octagon, polygon, etc., are now readily recognized by the skilled artisan and within the scope of the present invention. Moreover, the connecting points within the leaflet attachment zone 1 10 may comprise a structure that consists of one or more unbroken connectors, including but not limited to adhesive or gluing, continuous stitching, integrally forming the valve leaflet 106 with the anchoring structure 102, preferably with the lower edge 104 thereof, and/or clamping the valve along the leaflet attachment zone 110 to the anchoring structure, again preferably with the lower edge 104 thereof.

[0039] The prosthetic valve leaflet 106 thus acts like a hinged door in that it may rotate or swing between a closed position and an open position relative to the lower edge 104 of anchoring portion 102 with a portion of the leaflet 106 secured to a portion of the lower edge 104 of the anchoring portion 102 along the leaflet attachment zone 110 by, e.g., a plurality of sutures or the equivalent.

[0040] The closed position results in a temporary engagement and sealing of an outer portion of the upper surface of the valve leaflet against the bottom surface of the lower edge 104 of the structure 102, the prosthetic valve leaflet 106 being of a size and shape to cover the opening defined by lower edge 104 of anchoring portion 102, thereby preventing retrograde blood flow therethrough. The open position disengages the upper surface of the valve leaflet 106 from the bottom surface of the lower edge 104 to allow blood to flow therethrough.

[0041] A preferred positioning within the left atrium may comprise positioning at least a portion of the bottom surface of the anchoring structure 102 on at least a portion of the upper annular surface of the left atrium as in Fig. 1A. However, in other embodiments, the prosthetic leaflet 106 may be positioned above, or spaced away from, the native valve leaflets so that physical interference does not occur between the prosthetic valve leaflet 106 and the native leaflets and to maintain the remaining functionality of the native leaflets. In this case, device 100 will function to supplement the native leaflet functionality and, if and when needed, will begin to take over progressively more functionality as the native leaflets deteriorate. Eventually, the device 100 will function to replace all, or virtually all of the native leaflet functionality. The result is a device 100 that adapts to progressively assume the functionality of the native leaflets as they deteriorate, from supplementation through full replacement.

[0042] Thus, in certain embodiments, the valve leaflet 106 may be elevated or spaced above the native annular surface so that at least a portion of the valve leaflet 106 in the opened position is also elevated or spaced above at least the upper annular surface. In other cases at least a portion of the valve leaflet 106 in the open position may be disposed above the native valve leaflets so as to not physically interfere with them, or minimize physical interaction therewith. In these embodiments, the prosthetic leaflet may serve at least a supplementary function to the native leaflet function.

[0043] In other cases, a support for the prosthetic leaflet may be disposed within the native annulus or annular throat, effectively pinning the native leaflets and requiring the inventive valve leaflet to completely replace the native leaflet function.

[0044] In the embodiments with the support structure and valve leaflets are elevated or spaced above at least the native leaflets and/or the upper annular surface, the prosthetic leaflet will open in response to increased fluid pressure in the left atrium and allow blood to flow down to the spaced away native leaflets which also open, enabling blood flow to the left ventricle. The native leaflets will then close to the extent possible in response to increased fluid pressure in the left ventricle and, in response to the regurgitation pressure in the space between the native leaflets and the prosthetic leaflet, the prosthetic leaflet will then close, preventing retrograde blood flow into the left atrium.

[0045] In the event of eventual complete native leaflet failure, the prosthetic leaflet will completely handle and manage the blood flow between the left atrium and ventricle.

[0046] It is part of the present invention to orient the prosthetic leaflet 106 opening and leaflet attachment zone 1 10 to optimize the supplemental and/or replacement function, for example and without limitation in the case where a single native leaflet is dysfunctional and a result is an eccentric, non-central regurgitation jet. The new valve leaflet 106 may be oriented, e.g., so that the eccentric regurgitation jet is focused at the bottom surface of a distal end (away from the leaflet attachment zone 1 10) of the valve leaflet 106, in the middle of the valve leaflet (as measured relative to the distal end and the leaflet attachment zone 1 10), or closer to the leaflet attachment zone 1 10, or at points between the distal end and midpoint, or between the midpoint and the leaflet attachment zone 1 10 in order to maximize closure efficiency of the prosthetic leaflet 106.

[0047] In addition, the exit flow direction and/or position may be affected by the

positioning/orientation of the leaflet attachment zone 1 10 as well as the degree to which the valve leaflet 106 is allowed to open, so as to direct the blood flow to an optimal location on the native valve leaflets. A fully opened prosthetic valve leaflet 106 may comprise opening to a position that is approximately 90 degrees from its closed position. Opening positions for the prosthetic valve leaflet 106 of less than 90 degrees from the closed position will channel the blood flow in a direction along the length of the opened leaflet 106 toward a target on the native leaflets. Thus, as seen in Figure 1A, leaflet 106 may be fully opened to approximately a 45 degree angle relative to its closed position against lower edge 104 of the anchoring structure 102. This configuration will direct the incoming blood flow 103 generally along the same direction as the open position of the leaflet 106. Therefore, not only is the opening angle of the leaflet 106 important, but so is the orientation of the anchoring structure 102 on expansion which will dictate the location of the leaflet attachment zone 1 10 which, in turn, dictates the location of the opening leaflet 106 and resultant blood flow therealong. Another variable relative to locating the blood flow along the opened leaflet 106 is the distance of the distal end of the opened leaflet 106 from the target region in the native leaflets. It will be obvious now that, in order to optimize delivery location targeting of the blood flow moving across the opened leaflet 106, that the following parameters will require systemic optimization: the maximum opened angle at the open position for the prosthetic valve leaflet 106; the orientation of the distal end of the prosthetic valve leaflet 106 when the device 100 is expanded; and the distance, height or spacing of the distal end of the prosthetic valve leaflet 106 from the targeted location on the native valve leaflets. Optimization of this system allows consistent targeting of an area of the native valve leaflets for the blood flow moving through the prosthetic valve device 100.

[0048] Figure 3 illustrates an alternate embodiment for a prosthetic valve device 200 that is similar to the prosthetic valve device 100 discussed above in certain respects. Accordingly, the anchoring structure 202 has the same or similar features and characteristics as the anchoring structure 102 of device 100, e.g., a collapsible and expandable structure that may comprise a stent-like structure with open cells.

[0049] The valve support structure 204, as illustrated in Fig. 3 comprises two basic elements arranged on opposing sides of a lower opening 201 defined by the anchoring structure 202. A first fixed base side 212 that may be more stiff than, or of similar stiffness to, the structure comprising the dome and extends a distance D away from the lower opening 201 and may comprise an expanded and collapsed configurations. Positioned across the lower opening 201 from the first fixed base side 212 of valve support 204 is a moveable, rotatable valve member 214 that is connected to, or operatively engaged with, or attached to, or integrally formed with, a second fixed base side 216 that may be of similar stiffness, or different stiffness, as the first fixed base side 212 and may also comprise expanded and collapsed configurations. The rotatable valve member 214 may be formed of a tissue or fabric that is less stiff than the second fixed base side 216 and may comprise sizes and shapes as describe above regarding the prosthetic valve of Fig. 1A.

[0050] In either case, there may be a region or point of flexion 218 comprising a decreased stiffness and/or increased flexibility that allows the rotatable valve 214 to move upward to engage the first fixed base side 212 when the valve 214 is in a closed position and to move downward away from the first fixed base side 212 when the valve member 214 is in an open position. Fluid flow force generated by blood flow from the left atrium will be sufficient to push the rotatable valve member 214 to an open position as shown in Fig. 4, thereby enabling fluid communication of the atrial blood with the left ventricle. When the atrial to ventricular blood flow is complete and regurgitation forces are present, those forces cause the valve member 214 to rotate up and close against the first fixed base side 212, preventing regurgitant blood from flowing into the interior of the anchoring structure 202.

[0051] In a preferred embodiment, the rotatable valve member 214 may be biased in the closed position, pressed with a predetermined amount of biasing force against the first fixed base side 212, so that the closed position for valve member 214 is the biased position. This requires that the blood flow from the atrium exert sufficient force to overcome the biasing force of the valve member 214 against first fixed base side 212 to cause the valve member 214 to rotate into an open position. The valve member 214 may, when closed and as shown, overlap with the inner edge of the first fixed base side 212, so that the upper (upstream) side U of valve member 214 engages the inner edge I of the first fixed base side 212 in the closed position. Alternatively, the distal end 220 of valve member 214 may fit against the distal end 220 of the first base fixed side 212 to provide a generally sealed closure.

[0052] The device of Figure 3 may be positioned within the left atrium so that the first and second sides of the base 212, 216 rest upon the upper annular surface with the prosthetic rotatable leaflet 214 positioned over the annulus as in Figure 4 so that the distal end 220 of leaflet 214 may extend into the annulus when in an open position. Alternatively, the distance D of extension of the first and second sides of the base 212, 216 may be used to locate and/or position the device 200 slightly within the annulus, with the first and second sides 212, 216 of the base extending downward (downstream) into the annulus as in Figure 5.

[0053] As described in connection with device 100 above, the location of blood flow through device 200 and across rotatable leaflet 214 may be optimized as a system by configuring the degree of angle of maximum opening for leaflet 214, the rotational location of the leaflet 214, specifically the end of the leaflet located away from the point of flexion 218, and the distance or spacing of the end of the leaflet located furthermost from the point of flexion 218 when opened in the open position, i.e., maximum degree of opening. In addition, system elements that may be optimized for locating the blood flow onto native leaflets comprise the distance of extension of the first base side 212 over the annulus. In some cases, the first base side 212 may not extend over the annulus, instead the distal end 222 of the first base side 212 may be coextensive with an edge of the annulus, see e.g., Fig. 4. In other cases, the distal end 222 of the first base side 212 may extend a distance beyond the annular edge and, therefore, over the annulus the same distance.

[0054] Further, a modified embodiment of the device 200 of Fig. 3 may locate the prosthetic rotatable leaflet 214 at a position that is located above the native annular surface, i.e., in a super annular position, that does not result in any physical touching of the native valve leaflets. Thus, as shown in Fig. 6, device 300 comprises an anchoring support 302 and a valve support 330. The valve support comprises an inflow end 332 and an outflow end 334 and defines a flow channel therebetween. A first base side 336 may be attached along the flow channel of the valve support 330 and a prosthetic leaflet 338 attached at a position along the flow channel of the valve support 330 that enables engagement of the first base side 336 by the prosthetic leaflet 338 when in a closed position. Thus, the prosthetic leaflet 338 and first base side 336 may be positioned and spaced above the upper annular surface at exemplary position A, though it is understood that the prosthetic leaflet 338 and first base side 336 may be positioned at any point along the flow channel of the valve support 330. Stated differently, the prosthetic leaflet 338 and first base side 336 may be positioned at any point between the inflow and outflow ends 332, 334 of the valve support 330 including, but not limited to, a location that is coplanar with the upper annular surface.

[0055] It is understood that first base side 336 may comprise a very small lip structure to stop the upward rotation of the valve 338 and achieve the closed position to prevent regurgitation. The lip structure may surround valve support 338 to form a temporary seal between lip structure / first base side 336 and the closed prosthetic leaflet 338.

[0056] Valve support 330 may be a cylindrical structure as illustrated or may comprise a section of a cone, with increasing distance between the cone sides moving from the inflow end to the outflow end of the valve support 330. Alternatively, the valve support 330 may comprise a conical section with decreasing distance between the cone sides moving from the inflow end 332 to the outflow end 334 of the valve support 330. Other configurations for the valve support 330 may present themselves to the skilled artisan, each being within the scope of the present invention.

[0057] Alternatively, as in Fig. 7, the valve support 330, prosthetic leaflet 338 and fixed first side 336 may be positioned as extended downstream into the native annulus as indicated by position B. The length of extension of the valve support 330 relative to the lower opening of the anchoring structure 302 into the native annulus, dictates the position of the prosthetic valve leaflet 338 relative to the native leaflets. In some embodiments, the valve support 330 terminates at a point above the native leaflets, while in other cases the valve support 330 may extend to and perhaps beyond the native leaflets within the annulus, thereby pinning the native leaflets against the annulus. In all cases, the location of the prosthetic leaflet 338 and fixed first side 336 may be positioned at any point within the valve support 330 between the inflow end 332 and the outflow end 334.

[0058] Valve support 330 in Figs. 6 and 7 may comprise a separate structure that is mechanically connected with the lower opening of the anchoring structure 302.

[0059] Alternatively, and preferably, the anchoring structure 302 comprises an expandable and collapsible transition section 340 whereby the anchoring structure turns radially inwardly to form the valve support 330. In this latter case, the valve support 330, transition section 340, and anchoring structure 302 comprise a unitary structure that may comprise different characteristics in each of the valve support 330, transition section 340 and anchoring structure 302. For example, stent cell sizes and/or arrangements may differ between the afore-mentioned device elements 330, 340 and/or 302. But, in this embodiment, the unitary construction allows the device of Fig. 6, in some cases, to be turned inside out, by pulling the valve support 330 outwardly and radially away from the anchoring structure. For illustrative purposes, such a turned-out device when expanded would resemble that shown in Fig. 7. This capability is highly advantageous during transition of the collapsed device through a delivery catheter to the heart chamber as the collapsed turned-out device of, e.g., Fig. 7, comprises only two layers as opposed to the non-turned-out device of Fig. 6 which, in the region of the valve support 330 comprises four layers and is, therefore, two layers thicker.

[0060] In some cases, the device of Fig. 7 is desired in the expanded configuration to position the valve support 330 within the annulus. In other cases, the device of Fig. 6 is desired for positioning the valve support 330 radially within the anchoring support 302 and for allowing location of the prosthetic valve 338 at, or above, the annular surface.

[0061] If the device of Fig 6 is turned-out as shown in Fig. 7 for example, to facilitate delivery, the device 300 will be reconfigured after release from the distal end of the delivery catheter by pulling the valve support 330 radially back into the anchoring support 302 interior space to achieve the structure of the exemplary device of Fig. 6.

[0062] Thus, in the unitary structure case, the embodiment of Figure 6 comprises the inflow end 332 of the valve support 330 is located at a position that is radially within the interior of anchoring structure 302 and the transition section 340 forms the outflow end 334 of the valve support 302, wherein the inflow end 332 of valve support 330 is spaced radially inward and away from the transition section 340. In Figure 7, the inflow end 332 of the valve support 330 is defined by and substantially coextensive with the transition section 340, with the outflow end 334 of the valve support 330 extending radially outwardly away from the transition section 340.

[0063] Turning now to Figures 8-10, a two-door valved device 400 is illustrated and comprising an anchoring section 402 similar to the device 100, 200, 300 described above. Valve support section 404 comprises a first valve flap 406 and a second valve flap 408 that open and close against a lower opening 410 defined by anchoring section 402 and adapted to hingedly engage first and second valve flaps 406, 408.

[0064] Each of the first and second valve flaps 406, 408 may comprise a relatively stiff or rigid outer frame 412 in the general shape of a half circle, or other curvilinear form, and comprise a material on the inner portion 414 of the outer frame, e.g., tissue or fabric or other material with a central straight or linear section 41 1 connecting the two ends of the half-circle-shaped outer frame 412. At least one flexion, or hinging, region 416 is provided to bias the first and second valve flaps 406, 408 in the closed position (as shown) and to allow opening of the first and second valve flaps 406, 408 when the biasing force is overcome by blood flow pressure force as described above.

[0065] In this embodiment, the first and second valve flaps 406, 408 may comprise a sealing engagement together at the central straight or linear section 411 of the outer frame 412. This may be a total or partial seal and may be supplemented by a biocompatible and flexible gasket or liner 420 on one or both of the central straight or linear section 41 1 of the outer frame 412 to ensure sealing when the flaps close together.

[0066] An alternate embodiment shown in Fig. 10 may comprise the first and second valve flaps 406, 408 comprising a sail feature 422 attached at one end to the first and second valve flaps 406, 408 and free to move at the opposing end and comprising material having a generally

downwardly curving profile, when engaged by blood flow from below, may catch upwardly flowing fluid, similar to the way sails catching wind, to flex and aid in generating upward force to close the flaps 406, 408 more efficiently and quickly to prevent regurgitation.

[0067] Moreover, it is contemplated that any prosthetic valve devices described herein, including for example the anchoring portions as described herein, as well as the prosthetic valve leaflets or prosthetic valve flaps and/or valve support structures as described herein may comprise a releasable amount of a therapeutic agent thereon for localized application to the heart chamber tissue and/or to the native valves, annulus or other structure. Further, the therapeutic agent disposed in or on the prosthetic device may target blood vessels, bodily conduits, or specific organs contacted by the circulatory system to treat, and/or prevent, a bodily disorder and/or accelerate a desired bodily response, e.g., and without limitation endotheliazation.

[0068] For the purposes of the present invention, the following terms and definitions apply:

[0069] "Bodily disorder" refers to any condition that adversely affects the function of the body.

[0070] The term "treatment" includes prevention, reduction, delay, stabilization, and/or elimination of a bodily disorder, e.g., a failing cardiac valve or a vascular disorder. In certain embodiments, treatment comprises repairing damage cause by the bodily, e.g., valvular or vascular, disorder and/or intervention of same, including but not limited to mechanical intervention.

[0071] A "therapeutic agent" comprises any substance capable of exerting an effect including, but not limited to therapeutic, prophylactic or diagnostic. Thus, therapeutic agents may comprise anti-inflammatories, anti-infectives, analgesics, anti-proliferatives, and the like including but not limited to antirestenosis drugs and therapeutic agents that accelerate endothelial coverage and endotheliazation, including but certainly not limited to a therapy stent marketed by

OrbusNeich™ that is designed to repair vessel injury and regenerate the endothelium, to foster vessel healing achieved by accelerating endothelial coverage and controlling neo-intimal proliferation with a combination of endothelial progenitor cell capture and a sirolimus drug elution.

[0072] Therapeutic agent as used and defined herein further comprises mammalian stem cells. Therapeutic agent as used herein further includes other drugs, genetic materials and biological materials. The genetic materials mean DNA or RNA, including, without limitation, of

DNA/RNA encoding a useful protein, intended to be inserted into a human body including viral vectors and non-viral vectors. Viral vectors include adenoviruses, gutted adenoviruses, adeno- associated virus, retroviruses, alpha virus, lentiviruses, herpes simplex virus, ex vivo modified cells (e.g., stem cells, fibroblasts, myoblasts, satellite cells, pericytes, cardiomyocytes, skeletal myocytes, macrophage), replication competent viruses, and hybrid vectors. Non-viral vectors include artificial chromosomes and mini-chromosomes, plasmid DNA vectors, cationic polymers, graft copolymers, neutral polymers PVP, SP1017, lipids or lipoplexes, nanoparticles and microparticles with and without targeting sequences such as the protein transduction domain (PTD). The biological materials include cells, yeasts, bacteria, proteins, peptides, cytokines and hormones. Examples for peptides and proteins include growth factors (FGF, FGF-1, FGF-2, VEGF, Endotherial Mitogenic Growth Factors, and epidermal growth factors, transforming growth factor .alpha, and .beta., platelet derived endothelial growth factor, platelet derived growth factor, tumor necrosis factor .alpha., hepatocyte growth factor and insulin like growth factor), transcription factors, proteinkinases, CD inhibitors, thymidine kinase, and bone morphogenic proteins. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules.

[0073] Therapeutic agents further include cells that may be of human origin (autologous or allogeneic) or from an animal source (xenogeneic), genetically engineered, if desired, to deliver proteins of interest at the transplant site. Cells within the definition of therapeutic agents herein further include whole bone marrow, bone marrow derived mono-nuclear cells, progenitor cells (e.g., endothelial progentitor cells) stem cells (e.g., mesenchymal, hematopoietic, neuronal), pluripotent stem cells, fibroblasts, macrophage, and satellite cells. [0074] Therapeutic agent also includes non-genetic substances, such as: anti-thrombogenic agents such as heparin, heparin derivatives, and urokinase; anti-proliferative agents such as enoxaprin, angiopeptin, or monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, and acetylsalicylic acid, amlodipine and doxazosin; anti-inflammatory agents such as glucocorticoids, betamethasone, dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, and mesalamine; antineoplastic/antiproliferative/anti-miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, methotrexate, azathioprine, adriamycin and mutamycin; endostatin, angiostatin and thymidine kinase inhibitors, taxol and its analogs or derivatives; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; anti-coagulants such as heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin anticodies, anti-platelet receptor antibodies, aspirin, dipyridamole, protamine, hirudin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet peptides; vascular cell growth promotors such as growth factors, Vascular Endothelial Growth Factors, growth factor receptors, transcriptional activators, and translational promotors; vascular cell growth inhibitors such as antiproliferative agents, growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; cholesterol-lowering agents; vasodilating agents; and agents which interfere with endogenous vasoactive mechanisms; anti-oxidants, such as probucol; antibiotic agents, such as penicillin, cefoxitin, oxacillin, tobranycin angiogenic substances, such as acidic and basic fibrobrast growth factors, estrogen including estradiol (E2), estriol (E3) and 17-Beta Estradiol; and drugs for heart failure, such as digoxin, beta-blockers, angiotensin-converting enzyme, inhibitors including captopril and enalopril. The biologically active material can be used with (a) biologically non-active material(s) including a solvent, a carrier or an excipient, such as sucrose acetate isobutyrate, ethanol, n-methyl pymolidone, dimethyl sulfoxide, benzyl benxoate and benzyl acetate.

[0075] Further, "therapeutic agent" includes, in particular in a preferred therapeutic method of the present invention comprising the administration of at least one therapeutic agent to a procedurally traumatized, e.g., by an angioplasty or atherectomy procedure, mammalian vessel to inhibit restenosis. Preferably, the therapeutic agent is a cytoskeletal inhibitor or a smooth muscle inhibitor, including, for example, taxol and functional analogs, equivalents or derivatives thereof such as taxotere, paclitaxel, abraxane.TM., coroxane.TM. or a cytochalasin, such as cytochalasin B, cytochalasin C, cytochalasin A, cytochalasin D, or analogs or derivatives thereof.

[0076] Additional specific examples of "therapeutic agents" that may be applied to a bodily lumen using various embodiments of the present invention comprise, without limitation: L- Arginine; Adipose Cells; Genetically altered cells, e.g., seeding of autologous endothelial cells transfected with the beta-galactosidase gene upon an injured arterial surface; Erythromycin; Penicillin: Heparin; Aspirin; Hydrocortisone; Dexamethasone; Forskolin; GP Ilb-IIIa inhibitors; Cyclohexane; Rho Kinsase Inhibitors; Rapamycin; Histamine; Nitroglycerin; Vitamin E;

Vitamin C; Stem Cells; Growth Hormones; Hirudin; Hirulog; Argatroban; Vapirprost;

Prostacyclin; Dextran; Erythropoietin; Endothelial Growth Factor; Epidermal Growth Factor; Core Binding Factor A; Vascular Endothelial Growth Factor; Fibroblast Growth Factors;

Thrombin; Thrombin inhibitor; and Glucosamine, among many other therapeutic substances.

[0077] The therapeutic agent delivery system of the present invention, i.e., the prosthetic valve device, may be used to apply the therapeutic agent to any surface of cardiac chambers, e.g., the left atrium, as well as cardiac chambers in fluid or operative communication with the left atrium, e.g., the left ventricle and/or annulus located therebetween. In addition, the delivery system may be used to deliver an effective amount of therapeutic agent(s) to a body lumen in fluid and/or operative communication with the left atrium and related circulatory system. Such body lumens include, inter alia, blood vessels, urinary tract, coronary vasculature, esophagus, trachea, colon, and biliary tract. The therapeutic agent(s) may be coated to some, or all, of the prosthetic valve device as in known in the art to enable a time-release of the therapeutic agent(s) to the target(s) within the patient's body and may be provided so as to enable administration and delivery of an effective dose of the therapeutic agent(s) to the target(s).

[0078] Delivery of the agent(s) may be achieved through pressured contact of the therapeutic agent(s) on or in the prosthetic valve device as it expands against the cardiac chamber when positioned, similar to a coated expandable intravascular balloon or stent. The therapeutic agent(s) will then diffuse into the tissue. Alternatively, the therapeutic agent(s) may be swept into the blood flow with delivery to other non-cardiac chamber targets, e.g., tissues, organs, lumens, etc., including but not limited to the dysfunctioning native valve structure including leaflets. [0079] The description of the invention and its applications as set forth herein is illustrative and is not intended to limit the scope of the invention. Features of various embodiments may be combined with other embodiments within the contemplation of this invention. Variations and modifications of the embodiments disclosed herein are possible, and practical alternatives to and equivalents of the various elements of the embodiments would be understood to those of ordinary skill in the art upon study of this patent document. These and other variations and modifications of the embodiments disclosed herein may be made without departing from the scope and spirit of the invention.

Claims

WHAT IS CLAIMED IS:

1. A prosthetic cardiac valve device for supplementing and/or replacing function of

dysfunctional native mitral valve leaflets disposed within the annulus between the left atrium and left ventricle, comprising:

an expandable anchoring section adapted to engage tissue within the left atrium;

a valve support structure comprising an inflow end and an outflow end and a single prosthetic leaflet attached to the valve support structure between the inflow end and the outflow end;

a transition section disposed between the expandable anchoring section and the expandable valve support structure, wherein the expandable anchoring section, valve support section and transition section comprise a unitary structure, and wherein the single prosthetic leaflet is adapted to move between an open and a closed position in response to fluid flow pressure.

2. The device of claim 1 , further comprising a first base side attached to the valve support structure and adapted to provide a temporary seal for the single prosthetic leaflet at the closed position.

3. The device of claim 1, wherein the inflow end of the valve support structure is located radially within the expandable anchoring structure.

4. The device of claim 1 , wherein the anchoring structure, prosthetic leaflet and valve support do not physically interact with the native leaflets.

5. The device of claim 3, wherein the outflow end of the valve support structure is defined by the transition section.

6. The device of claim 1 , wherein the outflow end of the valve support structure is located outside the expandable anchoring structure and wherein the inflow end of the valve support structure is defined by the transition section.

7. The device of claim 1 , wherein the outflow end of the valve support structure is adapted to be positioned within the annulus.

8. The device of claim 7, wherein the outflow end of the valve support structure is adapted to be positioned within the annulus and above the native leaflets.

9. The device of claim 8, wherein the single prosthetic leaflet is positioned within the valve support structure such that the single prosthetic leaflet does not physically interact with the native leaflets.

10. The device of claim 7, wherein the valve support structure is adapted to be disposed within the annulus and pins the native leaflets against the annulus.

1 1. The device of claim 1 , wherein the single prosthetic leaflet is adapted to supplement the function of the dysfunctional native leaflets.

12. The device of claim 1, wherein the single prosthetic leaflet is adapted to replace the function of the dysfunctional native leaflets.

13. The device of claim 11 , wherein the single prosthetic leaflet is further adapted to

progressively take over functionality from dysfunctional native leaflets that deteriorate over time.

14. The device of claim 13, wherein the single prosthetic leaflet is adapted to replace the functionality of the dysfunctional native leaflets when fully deteriorated.

15. The device of claim 1, wherein the expandable anchoring structure, the expandable transition structure and the expandable valve support comprise open cell stent construction.

16. A prosthetic mitral valve device adapted to anchor within the left atrium, comprising: an expandable anchoring structure defining a lower opening;

a first base side operatively engaged with expandable anchoring structure at the lower opening;

a second base side operatively engaged with the expandable anchoring structure at the lower opening and comprising a single prosthetic leaflet adapted to engage the first base side in a closed position and rotate away from the first base side in an open position.

17. The device of claim 16, wherein the first base side and the second base side are adapted to an expanded position on an upper annular surface within the left atrium and wherein the single prosthetic leaflet is positioned over the annulus.

18. The device of claim 16, wherein the first base side and the second base side extend a distance away from the lower opening of the anchoring structure.

19. The device of claim 18, wherein the first base side and the second base side are adapted to fit within the annulus.