EP1175178A1

EP1175178A1 - Unstented heart valve bioprostheses and methods of making the same

Info

Publication number: EP1175178A1
Application number: EP00919941A
Authority: EP
Inventors: David R. Clarke; E. Christopher Orton; Steven Goldstein; Kiby Black; Stacey Bode
Original assignee: Cryolife Inc
Current assignee: Artivion Inc
Priority date: 1999-04-02
Filing date: 2000-03-31
Publication date: 2002-01-30
Also published as: AU4054800A; HK1046353A1; WO2000059379A1; JP2002540832A; CA2366767A1

Abstract

Stentless bioprosthetic heart valves (10) are formed as root valves utilizing a portion of the anterior mitral leaflet (16-1, 16-2, 16-3) attached to each of multiple (preferably three) noncoronary leaflet sections (10-1, 10-2, 10-3). In this manner, the bioprosthetic heart valves (10) may be provided with inflow (16) and/or outflow (14) conduits which allow replacement of the entirety of a patient's diseased native aortic valve or the pulmonary valve and its outflow tract.

Description

UNSTENTED HEART VALVE BIOPROSTHESES AND METHODS OF MAKING THE SAME

CROSS-REFERENCE TO RELATED APPLICATION

This application is related to, and claims domestic priority benefits under 35 USC §119(e) from, U.S. Provisional Application Serial No.

60/127,479 filed on April 2, 1999, the entire content of which is expressly incorporated hereinto by reference.

FIELD OF THE INVENTION

The present invention relates generally to bioprostheses and methods of making the same. In preferred forms, the present invention is embodied in unstented heart valve bioprostheses and methods of making the same.

BACKGROUND AND SUMMARY OF THE INVENTION

Bioprosthetic porcine xenograft valves have been employed in the past for the successful treatment of human heart valve disease. More specifically, atrioventricular valve replacements have occurred in the past using stent mounting and glutaraldehyde fixation of porcine valves. More recently, stentless porcine xenograft valves, such as the O'Brien-Angell stentless valve, have been used with considerable success. Notwithstanding the clinical successes of such stentless porcine xenograft valves, improvements are still desirable.

For example, it would especially be desirable if stentless bioprosthetic valves were provided with integral inflow and/or outflow conduits. Such an improvement would thereby allow the bioprosthetic valve to be used as a root valve to replace the entirety of a patient's native aortic valve or the pulmonary valve and its outflow tract. Alternatively, such a valve would be suitable for use as an inclusion-type valve following appropriate trimming.

Furthermore, it would also be desirable to remove all vestiges of myocardium so that only the connective tissue portions of the heart valve remain present. In this manner, a bioprosthetic valve could be provided which is potentially less immunogenic than other unfixed tissue grafts since it is capable of being decellularized to leave primarily the extracellular matrix of the leaflets, aortic wall and mitral leaflets.

It is towards fulfilling such needs that the present invention is directed. Broadly, therefore, the present invention is embodied in stentless heart valve bioprosthesis comprised of multiple noncoronary sections sutured together along lengthwise commissure lines. These sutured noncoronary sections establish a generally tubular bioprosthetic structure having an inflow conduit, an outflow conduit and a valve section intermediate to the inflow and outflow sections. Most preferably three noncoronary leaflet sections are employed to establish a trileaflet valve section intermediate to the inflow and outflow sections.

Importantly, the heart valve bioprosthesis of the present invention is a composite structure formed of the noncoronary sections of unfixed heart valve tissue. Preferably, all myocardium is omitted from the valve components and the finished bioprosthesis in order to produce a structure with low antigenicity and maximal integrity of suturable tissue. These and other aspects and advantages of the present invention will become more clear after careful consideration is given to the following detailed description of the preferred exemplary embodiments thereof.

BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS Reference will hereinafter be made to the accompanying drawings, wherein like reference numerals throughout the various FIGURES denote like structural elements, and wherein,

FIGURE 1 is a perspective view of a stentless heart valve bioprosthesis in accordance with the present invention;

FIGURES 2A-2F represent a presently preferred technique for fabricating the stentless heart valve bioprosthesis depicted in FIGURE 1 as viewed from the exterior of the tissue segments;

FIGURES 3A and 3B schematically depict a preferred suturing technique using horizontal mattress sutures for joining adjacent noncoronary tissue segments during the fabrication of the bioprosthetic heart valve of this invention;

FIGURE 4A is a photograph of one embodiment of a completed bioprosthetic heart valve according to this invention using the mattress sutures exemplified by FIGURES 3A and 3B;

FIGURE 4B is a photograph of another embodiment of a completed bioprosthetic heart valve according to this invention using conventional interrupted sutures; and

FIGURE 5 depicts a modification of the heart valve bioprosthesis depicted in FIGURE 1 which is particularly useful for aortic valve repair. DETAILED DESCRIPTION OF THE INVENTION

Accompanying FIGURE 1 shows a stentless bioprosthetic heart valve 10 in accordance with the present invention. As depicted, the heart valve 10 is fabricated from three noncoronary aortic leaflet sections 10-1 , 10-2 and 10-3, most preferably dissected from porcine heart tissue.

Adjacent noncoronary sections 10-1 , 10-2 and 10-3 are sutured together along commissure lines 12-1 , 12-2 and 12-3. That is, noncoronary section 10-1 is sutured to noncoronary sections 10-2 and 10-3 along commissure lines 12-1 and 12-3, respectively, while noncoronary sections 10-2 and 10-3 are sutured together along commissure line 12-2. The sutured noncoronary sections 10-1 , 10-2 and 10-3 thereby form a generally tubular structure having an outflow conduit 14, an inflow conduit 16 formed of mitral leaflets 16-1 , 16-2 and 16-3, and a sinus section 18, distally of the annulus 20, intermediate to the inflow and outflow conduits 14, 16, respectively. The arterial conduit 19 is thus comprised of the outflow conduit 14 and the sinus region 18.

The sinus section 18 interiorly includes three leaflet cusps (not shown in FIGURE 1 , but see the exemplary leaflet cusps 104-1 , 104-2 and 104-3 in the bioprosthetic heart valve 100 depicted in FIGURE 5) which collectively form the trileaflet valve in the complete bioprosthetic heart valve 10. The inflow section 16, on the other hand, is formed of the individual anterior mitral leaflets associated with each of the noncoronary sections 10-1 , 10-2 and 10-3. The completed trileaflet bioprosthetic heart valve 10 will thereby approximate a patient's natural, but diseased, heart valve.

To fabricate the heart valve 10, porcine heart tissue is procured and dissected fresh leaving only the aortic valve, the mitral leaflet and a lengthwise segment (preferably approximately 3 mm from the leaflet base) of myocardium. More specifically, the porcine heart tissue is first cut longitudinally between the left and right coronary arteries and placed flat on a dissection area with the lumenal surface of the valve tissue facing upwardly. The myocardium is then cut away so that only about

3mm in length and width remain as well as the aortic arterial conduit, three leaflet cusps, and the mitral leaflet. The tissue is then cut longitudinally on either side of the noncoronary leaflet along the commissures from the free edge of the outflow conduit to approximately 2-3 mm below the base of the noncoronary leaflet. Instead of separating the left, right and noncoronary leaflet sections by making a straight incision along the line of the commissure, the cut is most preferably made slightly broader (e.g., from about 1 to about 1.5 mm wider than the natural commissure line) near the outflow free edge in order to allow for histology samples to be taken. The valve conduit is cut along the commissure lines just prior to assembly. In this regard, care should be taken so that the conduit is not more narrow than the widest portion of the leaflet.

The tissue is next cut at an angle from left to right (usually an angle between about 30° to about 50°, and more preferably an angle of about 45°, depending on the natural anatomy of the distal myocardium) starting from the end of the first vertical cuts (near the plane of the leaflet base) to the free end of the mitral leaflet, thus removing most of the myocardium as well as the right and left coronary leaflets and conduit. This trimming is performed on either side of the noncoronary section. It should be noted here that the chordae tendineae of the mitral leaflet are not removed until the valve 10 is assembled (as will be discussed in greater detail below). However, following assembly of the valve 10, the chordae tendineae are cut around the circumference of the inflow region 16 about 1.5 mm proximal to the final interrupted suture along the free edge of the mitral valve in a manner that is parallel to the presumptive annulus of the composite.

All myocardium and excess adventitia are removed from the noncoronary portion that remains. Portions of the annular region 20 are also bladed so that the tissue has no jagged areas and to assure that the tissue displays uniform thickness.

The noncoronary tissue segment may then be subjected to a conventional decellularization process. In this regard, following dissection, the tissue may be subjected to one or more of the treatments by which the tissue may be decellularized, soluble proteins removed, tissue constituent covalently or ionically modified, chemical or biochemical substituents added, or tissue crosslinked. Upon completion of these processes, the tissue is stored in a suitable medium and temperature (e.g., at about 4°C in an aqueous medium) to stabilize the tissue and/or modification until completion of the valve.

As shown in FIGURE 2A, the noncoronary sections 10-1 , 10-2 and 10-3 are selected from tissue storage due to their approximate similar size (e.g., ± 2 mm) and are measured for purposes of such matching. In this regard, the measurements include the distance and/or dimensions (i) between commissures, (ii) from the anterior of the leaflet (point of coaptation) to the posterior (base) of the leaflet, (iii) from the top of the commissure on either side of the leaflet to the center of the base of the leaflet, and (iv) from the free edge of the leaflet to the base of the coaptive margin. The noncoronary sections 10-1 , 10-2 and 10-3 are then filled with storage solution (e.g., saline) in order to observe the shape and extension of the leaflet.

Prior to production of the valve 10, however, the three noncoronary sections 10-1 , 10-2 and 10-3 are subjected to further dissection and inspection to assure optimal alignment for suturing. Straight cuts are made along each commissure line of the non-coronary segment. The cuts should be made as close to the leaflets and commissure tips as possible without causing any damage. The cuts are performed at a slight angle toward the right, which should follow the angle at the point of coaptation (approximately 10° to 15° to the right of the vertical leaflet/commissure line).

Any excess adventitia must be removed. The commissures should also not have any remaining leaflet tissue from the discarded left or right coronary sections, and the non-coronary leaflet and commissures should be inspected for damage after trimming this area. The free edges along the commissure lines 12-1 , 12-2 and 12-3 should also be smooth to avoid gaps between tissue sections following suture placement. Any variance in the thickness of the outflow free edges 10-1 a, 10-2a and 10-3a of the outflow conduit sections 14-1 , 14-2 and 14-3 (which ultimately will collectively form the outflow conduit 14 of the valve 10) should be trimmed carefully to a substantially uniform thickness without leaving any jagged areas. This trimming should, however, only be done if the variance is less than or equal to about 1mm. If the variance is greater than about 1mm, the tissues should not be matched for assembly.

Any remaining myocardium is also removed and the annulus 20 bladed to a smooth finish of substantially constant thickness. The noncoronary sections 10-1 , 10-2 and 10-3 are frequently inspected for any damage, such as tears, holes or cuts that rendered an area too thin, and are discarded if any such defects are present.

The initial pair of noncoronary sections 10-1 and 10-2 are sutured together beginning generally at the base of the sinuses 18-1 , 18-2 of each tissue segment as depicted in accompanying FIGURE 2B. In this regard, the first joining stitch 22-1 a' is a basic interrupted suture placed through the arterial conduit with entry and exit points approximately 1.5 mm from the free edges of the commissure lines 12-1 on the exterior of the noncoronary sections using suitable suture material and needle (e.g., 6-0 Prolene monofilament polypropylene sterile suture with 3/8 inch tapered needle). The depth of the suture 22-1 a' through the tissue thickness should be about 0.5 mm from the lumenal surface of each conduit, without penetrating any interior surface of the tissue, particularly the leaflet. The suture 22-1 a is completed using a triple surgeon's knot and the free ends of the suture should be cut to less than about 1 mm in length.

The next interrupted suture 22-1 a in the suture line 22-1 is placed about 1.5 mm from the initial suture 22-1 a' in the direction of the mitral leaflets 16-1 , 16-2. Four or five of these interrupted sutures 22-1 a in the suture line 22-1 should be completed for the purpose of easing the later placement of the horizontal mattress sutures (a few of which are identified in FIGURE 1 , for example, by reference numeral 24-1 a and collectively form the suture line 24-1) by having a joined section to grasp and anchor the tissue. The remainder of the interrupted sutures 22-1 a of the suture line 22-1 are placed once the entire line of mattress sutures 24-1 a forming suture line 24-1 are completed, as will now be described. Specifically, as shown in FIGURE 2C, the first horizontal mattress suture 24-1 a' is positioned approximately 0.5 mm distal to the initial interrupted suture 22-1 a' (i.e., toward the outflow) using the same Prolene material and needle as for the interrupted sutures forming the suture line 22-1 discussed previously.

As is perhaps more clearly depicted in FIGURES 3A and 3B, the needle is inserted approximately 1 mm from the free edge of the conduit exterior. The depth of the suture is the same as for the interrupted sutures (that is, less than or equal to about 0.5 mm from the lumenal surface). The first exit point of the suture is approximately 1 mm from the free edge of the adjacent tissue's conduit exterior. The suture is pulled through the tissue, leaving about a 2 cm tail of suture extending out of the entry point to allow the suture to be tied off. The needle is then inserted between about 1 mm to about 1.5 mm from the first exit point in a direction parallel to the commissure line and towards the outflow tissue, leaving the tissue about 0.5 mm from the lumenal surface and a distance of between about 1 mm to about 1.5 mm from the first half-loop of the suture. Next, the suture is placed through the thickness of the opposing tissue and exits the tissue no more than about 1 mm from the free edge 12-1 of the conduit exterior. The final exit point should be 1 to 1.5 mm from the initial entry point (where the tail of the suture is protruding). The suture should be tied off using a triple surgeons knot and the free ends should be trimmed to less than about 1 mm in length. The angle of the mattress sutures 24-1 a causes a minor eversion (depicted by tissue mounds 30-1 and 30-2 in FIGURE 3B) between the connected tissues.

This eversion creates a seal between the sections that substantially reduces leakage along the suture line. However, the tissue mounds 30-1 , 30-2 should not protrude more than 1 mm outwardly from the external surface of the conduit to avoid causing an obstructive surface.

The next mattress suture 24-1 a in the suture line 24-1 should be initiated on the opposite tissue from that which had the knot for the initial suture 24-1 a'. Each mattress suture 24-1 a is begun on the opposite tissue from the suture 24-1 a before it. This alternating method reduces the puckering on the lumenal side of the tissue. Each mattress suture should be positioned approximately 0.5 mm to 1 mm from the external loop of the previous suture. The alternating mattress sutures in the suture line 24-1 should be completed from the base of the sinus region to the free edge of the outflow conduit (see FIGURE 2D). The width of the eversion mounds 30-1 and 30-2 between tissues for the entire suture line should be no more than 3 mm for size 19 to 23 mm InOD and no more than 4 mm for size 25 to 29 mm InOD valves.

Once the mattress suture line 24-1 is complete, the interrupted sutures forming the suture line 22-1 along the mitral leaflets should be finished as depicted in FIGURE 2E. In this regard, the interrupted sutures of suture line 22-1 should extend as far along the mitral leaflets 16-1 , 16-2 as possible until the chordae tendineae begin to proliferate. However, the length of the inflow must extend at least 4 mm beyond the base of each leaflet. One final interrupted suture 22-1 b (see FIGURE 2E) is placed 1 to 1.5 mm from the free edge of the outflow proximal to the final mattress suture in suture line 24-1. This procedure aids the cylindrical shaping of the outflow region.

The procedures discussed above are repeated so as to join the noncoronary sections 10-2 and 10-3 along commissure line 12-2 as depicted in accompanying FIGURE 2F. Thereafter, the noncoronary sections 10-1 and 10-3 are joined to one another along the commissure line 12-3 in a similar manner so as to form the tubular valve 10 depicted in FIGURE 1. In this regard, when initiating the final suture lines 22-1 and 24-1 along commissure 12-3, it is sometimes necessary to insert a sizing dilator (e.g., a suitably sized steel rod) into the inflow and sinus region 16,

18, respectively, when tying the knot of the suture. This procedure will thereby hold the noncoronary sections 10-1 , 10-2 and 10-3 in a generally cylindrical shape, easing the knotting process. The sizing dilator may be removed after completing each stitch.

Once the entire valve 10 has been sutured, the outflow conduit section 14 is trimmed along the circumference of its free edges 10-1 a, 10- 2a and 10-3a so as to present a substantially level border around the circumference of the outflow conduit section 14. The inflow region fashioned with the mitral leaflets 16-1 , 16-2 and 16-3 is also trimmed approximately 1.5 mm beyond the final interrupted mitral suture.

Specifically, the mitral leaflets 16-1 , 16-2 and 16-3 should be trimmed substantially parallel to the annulus 20 and all chordae tendineae must be removed.

The thus assembled valve may then be placed in a specimen cup containing a sufficient quantity of storage solution to fully cover the entire valve 10 and held at about 4°C in aqueous medium for further processing. In this regard, further processing may include one or more of the treatments by which the tissue may be decellularized, soluble proteins removed, tissue constituents covalently or ionically modified, chemical or biochemical substituents added, or tissue crosslinked. Furthermore, the tissue may be treated with suitable mammalian cells in a manner such as to produce a recellularized tissue. Accompanying FIGURE 4A is a photograph of an exemplary bioprosthetic heart valve in accordance with the present invention. In this regard, a suture line comprised of horizontal mattress sutures is clearly visible in FIGURE 4A between the bases of the leaflet sections to the distal outflow free edges of the joined tissue segments. Moreover,

FIGURE 4A visibly reveals a line of everted tissue which protrudes outwardly from the noncoronary sections formed by the mattress sutures.

Although the discussion previously focused on forming the suture line 22-1 from interrupted sutures 22-1 a, and forming the suture line 24-1 from horizontal mattress sutures 24-1 a, it should be evident that the suture lines 22-1 and/or 24-1 can be formed from any type and/or combination of sutures suitable for the tissue involved and/or the ultimate placement of the bioprosthetic valve 10. In this regard, the sutures used for the suture lines should not tear the tissue and should accommodate relatively compliant tissue. The sutures should also form a substantially leak-free juncture between the tissue segments. Suitable sutures that may be employed in the practice of this invention include continuous sutures, lock-stitch sutures, interrupted sutures, mattress and the like. By way of example, another embodiment of a bioprosthetic heart valve in accordance with the present invention is depicted in FIGURE 4B as having noncoronary tissue sections joined together by interrupted sutures.

In use, the valve 10 may be surgically implanted as a total replacement for a patient's native aortic valve or the pulmonary valve and its outflow tract.

The attending surgeon may modify the bioprosthetic heart valve 10 to suit the particular anatomy of the patient. Thus, the inflow and/or outflow conduits 16, 14, respectively, may be trimmed in their lengthwise direction between adjacent sutures prior to surgical implantation so as to provide an overall lengthwise size suitable for the patient only if a continuous suture line has not been used to from the valve.

Accompanying FIGURE 5 depicts a modified bioprosthetic heart valve (designated by reference numeral 100) in accordance with the present invention. In general, the heart valve 100 depicted in FIGURE 5 is a surgically modified version of the valve 10 discussed previously in that noncoronary tissue segments 100-1 , 100-2 and 100-3 have been sutured together to form a trileaflet valve structure. The valve 100, however, includes scallop regions 102-1 and 102-2 defined by excised tissue from the outflow conduit region of joined tissue segments 100-1 and 100-2. These scallop regions 102-1 and 102-2 thereby allow fluid communication between the outflow side of the trileaflet valve structure 104 (formed by the juncture of leaflet cusps 104-1 , 104-2 and 104-3) and the patient's native coronary arteries. Thus, the valve 100 shown in

FIGURE 5 is especially useful as an inclusion valve for aortic valve repair. It will be understood that, although two such scallop regions 102-1 and 102-2 are depicted in FIGURE 5, more or less scallop regions could be provided in the surgeon's discretion to suit particular aortic valve repairs. Thus, a single scallop region, or three scallop regions in each of the tissue segments 100-1 , 100-2 and 100-3 could be provided in the valve 100.

Therefore, while the invention has been described in connection with what is presently considered to be the most practical and preferred embodiment, it is to be understood that the invention is not to be limited to the disclosed embodiment, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A heart valve bioprosthesis comprised of multiple noncoronary sections sutured together along lengthwise commissure lines to establish a generally tubular bioprosthetic structure having an inflow section, an outflow section and a valve section intermediate to said inflow and outflow sections.

2. The heart valve bioprosthesis of claim 1 , which comprises three noncoronary sections to establish a trileaflet valve section intermediate to said inflow and outflow sections.

3. The heart valve bioprosthesis of claim 1 , wherein said noncoronary sections are substantially free of myocardium.

4. The heart valve bioprosthesis of claim 1 , wherein said inflow conduit is fashioned from mitral leaflet sections.

5. The heart valve bioprosthesis of claim 1 , further comprising a scallop section removed from at least one of said noncoronary sections forming said outflow conduit to provide fluid access to a native coronary artery.

6. The heart valve bioprosthesis of claim 5, wherein multiple scallop sections are removed from respective noncoronary sections forming said outflow conduit.

7. The heart valve bioprosthesis of claim 1 , wherein said noncoronary sections are sutured together by a suture line.

8. The heart valve bioprosthesis of claim 7, wherein said suture line extends between inflow free edges of said noncoronary sections to distal outflow free edges thereof.

9. The heart valve bioprosthesis of claim 7 or 8, wherein the outflow section of said noncoronary sections are sutured together by horizontal mattress sutures altematingly disposed on either side of said suture line.

10. The heart valve bioprosthesis of claim 1 , having an arterial conduit comprised of said outflow section and said valve section, and wherein said noncoronary sections are sutured together along a suture line so as to form a line of everted tissue which protrudes outwardly from the arterial conduit.

11. The heart valve bioprosthesis of claim 1 , wherein the noncoronary sections are porcine tissue.

12. A heart valve bioprosthesis comprised of three porcine noncoronary tissue segments and including an outflow conduit established by adjacent aortic wall sections of said tissue segments sutured together along generally lengthwise extending commissures lines, an inflow conduit established by sutured adjacent mitral leaflet sections of said tissue segments, and a trileaflet valve section intermediate to said inflow and outflow conduits.

13. The heart valve bioprosthesis of claim 12, further comprising a scallop section removed from at least one of said noncoronary tissue segments forming said outflow conduit to provide fluid access to a native coronary artery.

14. The heart valve bioprosthesis of claim 13, wherein multiple scallop sections are removed from respective noncoronary tissue segments forming said outflow conduit.

15. The heart valve bioprosthesis of claim 12, wherein said noncoronary tissue segments are substantially free of myocardium.

16. The heart valve bioprosthesis of claim 12, wherein said noncoronary tissue segments are sutured together by a suture line.

17. The heart valve bioprosthesis of claim 16, having an arterial conduit comprised of said outflow conduit and said valve section, and wherein said suture line extends between inflow free edges of said noncoronary tissue segments to distal outflow free edges thereof.

18. The heart valve bioprosthesis of claim 17, wherein said arterial conduit is sutured together by horizontal mattress sutures disposed alternatingly on either side of said suture line.

19. The heart valve bioprosthesis of claim 12, wherein said outflow conduit is sutured together along a suture line so as to form a line of everted tissue which protrudes outwardly from the tissue segments.

20. A bioprosthetic heart valve which comprises at least one acellular non-human, non-coronary cusp having lengthwise extending aortic wall and mitral leaflet sections, and a valve section intermediate to said aortic wall and mitral leaflet section.

21. The bioprosthetic heart valve of claim 20, wherein said non- human noncoronary cusp is a noncoronary porcine tissue segment.

22. The bioprosthetic heart valve of claim 21 , which comprises three said noncoronary porcine tissue segments to establish an outflow conduit formed by adjacently sutured ones of said aortic wall sections, an inflow conduit formed by adjacently sutured ones of said mitral leaflet sections and a trileaflet valve section intermediate to said inflow and outflow conduits.

23. The bioprosthetic heart valve of claim 22, wherein said noncoronary tissue segments are sutured together by at least one of continuous sutures, lock-stitch sutures, mattress sutures, and basic interrupted sutures.

24. A tissue section adapted for use in a bioprosthetic heart valve comprising an acellular non-human noncoronary cusp having lengthwise extending aortic wall and mitral leaflet sections, and a valve section intermediate to said aortic wall and mitral leaflet section.

25. The tissue section of claim 24, wherein said non-human noncoronary cusp is a noncoronary porcine tissue segment.

26. A method of making a heart valve bioprosthesis comprising the steps of:

(i) size-matching multiple noncoronary tissue segments, and

(ii) suturing adjacent size-matched noncoronary tissue segments to one another to form a generally tubular heart valve bioprosthesis having an outflow conduit established by adjacent aortic wall sections of said tissue segments sutured together along generally lengthwise extending commissure lines, an inflow conduit established by sutured adjacent mitral leaflet sections of said tissue segments, and a trileaflet valve section intermediate to said inflow and outflow conduits.

27. The method of claim 26, wherein step (ii) includes suturing the noncoronary tissue segments together by a suture line.

28. The method of claim 27, wherein step (ii) includes suturing the noncoronary tissue segments together by horizontal mattress sutures disposed alternafingly on either side of the suture line along the outflow conduit.

29. The method of claim 27, wherein step (ii) includes suturing the noncoronary tissue segments together to form a line of everted tissue along the suture line of the outflow conduit.

30. The method of claim 29, wherein step (ii) includes suturing the outflow conduit noncoronary tissue segments together by horizontal mattress sutures disposed alternafingly on either side of the suture line.

31. The method of claim 26, wherein prior to step (i) there includes the step of removing substantially all myocardium from said noncoronary tissue segments.

32. The method of claim 26, wherein prior to step (i), there is practiced the steps of (a) dissecting fresh porcine heart tissue to obtain the aortic valve, the mitral valve and a lengthwise segment of myocardium, (b) lengthwise cutting the porcine heart tissue obtained according to step (a) to separate the noncoronary leaflet section from the coronary leaflet sections.

33. The method of claim 32, which further comprises the step of (c) removing substantially all myocardium and adventitia.

34. The method of claim 32, wherein the inflow mitral sections are cut at an angle of between about 30° to about 50°.

35. The method of claim 26, which comprises, prior to step (i), measuring at least one of the distance (1) between commissures, (2) from the anterior of the leaflet to the posterior of the leaflet, (3) from the top of the commissure on either side of the leaflet to the central leaflet base, and (4) the free edge of the leaflet to the base of the coaptive margin.

36. The method of claim 26, which includes trimming the outflow conduit about its free edge circumference to present substantially level border therearound.

37. The method of claim 26, which includes trimming the inflow conduit about its circumference substantially parallel to the annulus of the heart valve.