Pre-assembled bioprosthetic valves and sealing catheters

Abstract

This application relates to pre-assembled bioprosthetic valves and sealing catheters. The valved catheter includes a bioprosthetic valve, such as a heart valve, and a tubular catheter sealed with a bioresorbable material. The bioprosthetic heart valve comprises artificial tissue that has been treated to allow for long-term dry storage without valvular functional decline. The bioprosthetic heart valve may have independent bovine pericardial leaflets or a whole porcine valve. The sealing catheter includes a tubular matrix impregnated with a bioresorbable medium such as gelatin or collagen. The valved catheter is stored dry in an encapsulation material, wherein a desiccant bag is provided with a limited capacity to absorb moisture from the encapsulation material to prevent the bioprosthetic tissue from drying beyond a point that would impair its usability as a bioprosthetic heart valve. The heart valve may be sutured within the sealing catheter or coupled to the sealing catheter via a snap-fit ​​connection.

Description

[0001] This application is a divisional application. The original application was filed on June 3, 2013, with application number 201380029301.0 (the divisional application it addresses has application number 201811431917.1), and the invention title is "Pre-assembled biological prosthetic valve and sealing catheter".

[0002] Related applications

[0003] This application claims priority to U.S. Provisional Application No. 61 / 655,405, filed June 4, 2012, pursuant to 35 U.S.SC §119. Technical Field

[0004] The present invention generally relates to artificial heart valves assembled with flow conduits, and more specifically to pre-assembled bioprosthetic heart valves and sealing conduits. Technical Background

[0005] Heart valve disease remains a leading cause of morbidity and mortality, stemming from a variety of conditions, including rheumatic fever and birth defects. Cardiovascular disease is the leading cause of death, killing more than 600,000 Americans each year. According to the American Heart Association, more than 5 million Americans are diagnosed with heart valve disease each year. Heart valve disease can occur in any one valve or a combination of all four, but disease of the aortic and mitral valves is the most common, affecting more than 5% of this population. An estimated 85,000 aortic valve replacement surgeries are performed annually in the United States. Worldwide, approximately 300,000 heart valve replacement surgeries are performed annually. About half of these patients receive bioprosthetic heart valve replacements, using biologically derived tissue to flexibly and fluidly seal the leaflets.

[0006] The most successful bioprosthetic materials for flexible leaflet valves are whole-pig valves and individual leaflets made from bovine pericardium—which are sutured together to form a tricuspid valve. The most common flexible leaflet valve construction consists of three leaflets mounted to a conjoined post around a peripheral support structure, with free edges projecting outwards and converging or joining at the midpoint of the flow path. Suture loops that can be penetrated by sutures are provided around the inflow end. Various tissue therapies prolong the life of heart valves—such as by reducing calcification, thus delaying the need for a second surgery to replace the initially implanted valve. The use of glutaraldehyde in such tissue therapies has proven effective in preventing the reabsorption of treated tissue after implantation.

[0007] For transport and storage before use in the operating room, prosthetic heart valves are often sealed in containers filled with preservative solution. The preservative solution maintains the functionality of the prosthetic tissue within the heart valve. Glutaraldehyde and formaldehyde are widely used as preservatives due to their bactericidal properties.

[0008] Artificial heart valves can be implanted independently into one of the orifices or rings of the heart, or coupled to a flow catheter extending a predetermined distance along the valve. For example, they are available from Edwards Lifesciences of Irvine, California, Carpentier- Bioprosthetic valved catheters introduce a porcine bioprosthetic heart valve coupled with inflow and outflow braided polyester extensions. Edwards valved catheters are particularly suitable for treating dysfunctional pulmonary valves. Other valved catheters are designed not only to replace the function of the valve itself but also to reconstruct portions of the flow passages above and below the ascending aorta in aortic valves. Valved catheters also have other applications, such as providing bypass pathways that allow direct connection of the apex of the heart to the descending aorta. Existing bioprosthetic valved catheters—such as those with bioprosthetic heart valves—are stored in a liquid preservation solution, and therefore the catheters are formed of braided polyester without a bioresorbable seal. While such catheters are suitable for certain conditions and tend to seal relatively quickly in vivo through tissue inward growth, excessive initial blood leakage through their walls after implantation can be harmful. Uncoated fabrics such as polyethylene terephthalate (PET) have high leakage rates, so surgeons need to pre-coagulate the graft with the patient's blood before use. However, even with these grafts, unacceptable leakage still occurs. Others have proposed using non-bioresorbable sealing layers—such as silicone, as described in Ashton et al. U.S. Patent Publication No. 2008 / 0147171, published June 19, 2008—but such layered catheters tend to have relatively thick walls and are not very flexible, and are therefore not preferred.

[0009] Therefore, some surgeons prefer catheters or grafts in which a porous tubular structure, such as woven polyester (e.g., Dacron), is impregnated with a bioresorbable material, such as gelatin, collagen, or albumin. These catheters are not initially porous, thus preventing blood loss, but the sealing medium eventually degrades through hydrolysis upon exposure to water after implantation and is replaced by natural tissue ingrowth. Gelatin in grafts can also be treated to cause cross-linking between the amino groups present in the gelatin molecules, making the gelatin more resistant to hydrolysis. For a method of forming such grafts, see U.S. Patent No. 4,747,848, issued to Maini on May 31, 1988.

[0010] Unfortunately, due to the complexity of storage, it is impossible to pre-assemble catheters or grafts sealed with bioresorbable materials with bioprosthetic heart valves. That is, the liquid sterilizing agent used to store the tissue valve will eventually wash away the bioresorbable sealing media (gelatin, collagen, albumin, etc.) from the permeable catheter material. Because of the benefits of using sealed catheters or grafts and the positive properties of bioprosthetic heart valves, some surgeons couple these two components together during surgery after storage. That is, the technician in the operating room connects the sealed catheter, which has been stored dry, to the bioprosthetic heart valve, which has been stored moist. This assembly can be seen in U.S. Patent Publication No. 2010 / 0274351 by Rolando et al. – published October 28, 2010, and U.S. Patent No. 7,575,592 by Woo et al., granted August 18, 2009. Sealing catheters can be sutured to the suture ring of a bioprosthetic heart valve, or other forms of rapid-connect coupling devices can be provided, as seen in Campbell's U.S. Patent Publication No. 2006 / 0085060, published April 20, 2006. While these assemblies are theoretically ideal, the time and effort required to connect the sealing catheter to the bioprosthetic heart valve present problems under the high-pressure environment of a cardiac operating room. This increases the complexity of the connection procedure; the bioprosthetic valve must be kept moist to prevent tissue degradation, while the graft must be kept dry to prevent hydrolysis. Furthermore, prolonged exposure of the valve and catheter in the operating room before implantation increases the risk of infection. For aortic catheters, even a small leak in such a connection can be fatal due to the high pressure. Therefore, the surgeon performing the implantation must suture these components together rapidly and without any leaks.

[0011] Therefore, there is a need for valved catheters with biological prosthetic tissue valves and catheters or grafts, which are preferably sealed with bioresorbable materials and are relatively simple to prepare and place in the operating room. Summary of the Invention

[0012] This application discloses a valved catheter comprising a bioprosthetic heart valve and a tubular catheter sealed with a bioresorbable material. The bioprosthetic heart valve comprises artificial tissue that has been treated to allow for long-term dry storage without valvular functional decline. For example, the tissue may have been cross-linked with glutaraldehyde or other aldehyde-containing agents, treated with a sealing agent, and dehydrated with a glycerol solution. The bioprosthetic heart valve may have independent bovine pericardial leaflets or a whole porcine valve. The sealed catheter comprises a tubular matrix impregnated with a bioresorbable medium, such as gelatin or collagen. The valved catheter is stored dry in an encapsulation material supplied with a desiccant pouch, which has a limited capacity to absorb moisture from the encapsulation material to prevent the bioprosthetic tissue from drying beyond a point that would impair its function in the bioprosthetic heart valve. The heart valve may be sutured into the sealed catheter, either sutured to or coupled to the catheter tip via a snap-fit ​​connection to restrict the operation of the two treated components and provide a hemostatic seal with minimal assembly complexity. In one embodiment, the bioprosthetic valve is coupled in a catheter such that the catheter extends at both ends of the valve to provide inflow and outflow extensions.

[0013] Another aspect of this application is a packaged valved catheter comprising a bioprosthetic valve, such as a heart valve having bioprosthetic tissue, said valve having been treated such that the tissue can be stored dry for extended periods without loss of valve function. The bioprosthetic valve is coupled to a catheter sealed using a bioresorbable medium to provide a valved catheter. The packaging material of the valved catheter has at least one sterile container in which the valved catheter is stored without a preservation solution. The packaging material may comprise a double-layered packaging material, wherein the valved catheter is sealed within an internal gas-permeable sterile barrier and an external gas-impermeable barrier, the internal gas-permeable sterile barrier enabling gas sterilization, while the external gas-impermeable barrier prevents long-term oxidation of the bioprosthetic tissue. Desiredly, the catheter comprises a gelatin-impregnated tubular base and further comprises a desiccant bag provided within the packaging material, having a limited capacity to absorb moisture from the packaging material to prevent the bioprosthetic tissue from drying beyond a point that would impair its ability to function as a bioprosthetic valve.

[0014] A method for preparing and delivering a valved catheter is also disclosed, comprising first obtaining a pre-assembled valved catheter comprising a bioprosthetic valve having bioprosthetic tissue coupled to a catheter sealed with a bioresorbable medium, the valved catheter being stored in a dry encapsulation material. The method then requires opening the dry encapsulation material and removing the valved catheter, and delivering the valved catheter to the implantation site. The catheter is preferably secured to the bioprosthetic valve using sutures, but may optionally be secured using snap-fit ​​connections. The bioprosthetic valve may be a heart valve having bovine pericardial leaflets, and the catheter is preferably a tubular matrix impregnated with gelatin or collagen. In one embodiment, the bioprosthetic valve is coupled to the catheter such that the catheter extends at both ends of the valve to provide inflow and outflow extensions. The bioprosthetic tissue is preferably cross-linked with glutaraldehyde or other aldehyde-containing agents, treated with a sealing agent, and dehydrated by a glycerol solution.

[0015] A further understanding of the nature and advantages of the invention is shown in the following description and claims, especially when considered in conjunction with the accompanying drawings, in which the same parts have the same reference numerals. Attached Figure Description

[0016] The present invention will now be described, and other advantages and features will be presented with reference to the accompanying schematic diagrams, wherein:

[0017] Figure 1 This is an exploded view of the combination of a bioprosthetic heart valve coupled to the sealing catheter of this application;

[0018] Figure 1A It is a view of the human heart, showing a valved catheter implant replacing the aortic valve and part of the ascending aorta;

[0019] Figure 2A and 2B This is a side front view of an exemplary valved catheter of this application, wherein a bioprosthetic heart valve is coupled to two segments of the sealed catheter extending from its two ends.

[0020] Figure 3 This is a further view of a valved catheter, in which a bioprosthetic heart valve is coupled to a sealed outflow catheter;

[0021] Figure 4A and 4B This is an enlarged cross-sectional view; the example shows the outflow conduit attached to... Figure 3 Optional technologies for biological prosthetic heart valves;

[0022] Figure 5 This is an exploded perspective view, illustrating other applications of the valved catheter in this application;

[0023] Figure 6This is an exploded view of an exemplary interlocking connection between a prosthetic heart valve (shown in partial cross-section) and a sealing catheter;

[0024] Figure 7 This is a cross-sectional view of an exemplary sealing catheter connected to a biological prosthetic heart valve suture ring by sutures;

[0025] Figure 8 It is similar to Figure 5 The front view of the valved catheter shown, in which the sealed catheter is attached to the scaffold structure of the bioprosthetic heart valve;

[0026] Figure 9A This is a front view of a valved catheter, in which the sealing catheter is attached to the suture ring of the prosthetic heart valve, and... Figure 9B It is a perspective view of a valved catheter at the outflow end of the catheter;

[0027] Figure 9C Is it through Figure 9A A cross-sectional view of the leaflet region of a heart valve, showing a possible connection between the sealing catheter and the suture ring;

[0028] Figure 10 It is similar to Figure 9A The front view of the valved catheter shown shows a longer, sealed catheter with a sinus region attached to the suture ring of a bioprosthetic heart valve.

[0029] Figure 11A-11C Is it through Figure 10 A cross-sectional view of the leaflet region of a heart valve, showing the possible connection between the sealing catheter and the suture ring;

[0030] Figure 12 This is an exploded plan view of the valved conduit and retainer thus installed in the main storage container in the form of a tray; and

[0031] Figure 13 Is it like this? Figure 12 A perspective view of the valved conduit in the tray being contained within a second storage container in the form of a bag.

[0032] Figure 14 It is an exemplary main storage container installed in the form of a tray. Figure 10 Exploded plan view of a valved duct; and

[0033] Figure 15 Is it like this? Figure 14 In the tray Figure 10 A exploded plan view of a valved conduit contained within a second storage container in the form of an outer tray. Detailed Implementation

[0034] This application provides a technique for coupling implantable valves with sealing catheters, and specifically, bioprosthetic heart valves that have been dried and stored without immersion in preservative solutions. The terms "dried" or "dry" bioprosthetic heart valves generally refer to the ability to store those heart valves without immersion in solutions (e.g., preservatives such as glutaraldehyde) and specifically, to store them dry for extended periods without functional decline. Various methods for drying bioprosthetic heart valves and for drying tissue implants are generally proposed, and this application provides encapsulation materials for bioprosthetic heart valves treated by any of these methods.

[0035] One strategy for drying tissue is to dehydrate the bioprosthetic tissue in a glycerol / ethanol mixture, sterilize it with ethylene oxide, and “dry” package the final product. This method eliminates the potential toxicity of glutaraldehyde as a sterilizing agent and storage solution. Several methods have also been proposed using sugar alcohols (i.e., glycerol), alcohols, and combinations thereof as post-glutaraldehyde treatments to leave the resulting tissue in a “dry” state, rather than a moist state caused by excessive glutaraldehyde. Glycerol-based methods can be used for such storage, as described by Parker et al. (Thorax 197833:638). A particularly preferred method for drying bioprosthetic heart valves is disclosed in U.S. Patent No. 8,007,992 to Tian et al. (the disclosure of which is expressly incorporated herein by reference), in which the fixed tissue is treated with a non-anhydrous mixture of glycerol and C1-C3 alcohols selected from methanol, ethanol, n-propanol, and 2-propanol. Similarly, U.S. Patent No. 6,534,004 (Chen et al.) describes the storage of bioprosthetic tissue in polyols such as glycerol. In methods of dehydrating tissues in ethanol / glycerol solutions, tissues can be sterilized by ethylene oxide (ETO), gamma radiation, or electron beam radiation.

[0036] Recently, Dove et al. disclosed a solution for certain harmful changes in dehydrated tissues that can occur due to oxidation in U.S. Patent No. 7,972,376, issued July 5, 2011, the contents of which are expressly incorporated herein by reference. Dove et al. proposed permanently sealing aldehyde groups in tissues (reducing ammoniation). A preferred anti-calcification tissue treatment involves applying a calcification modifier, such as a sealing agent or antioxidant, to the tissue to specifically inhibit oxidation of dehydrated tissues and reduce in vivo calcification. This treatment specifically seals aldehyde groups in cross-linked (e.g., with glutaraldehyde) bovine, porcine, or equine pericardial tissue or porcine valves. In one method, tissue leaflets in assembled bioprosthetic heart valves are pretreated with an aldehyde sealing agent, then dehydrated and sterilized. Dove et al. also described the addition of chemical agents (e.g., antioxidants) to dehydrated solutions (e.g., ethanol / glycerol) to prevent tissue oxidation during sterilization (ethylene oxide, gamma radiation, electron beam radiation, etc.) and storage. The capping process utilizes an amine, such as ethanolamine or lysine, and a reducing agent, followed by final treatment with glycerol and an alcohol. Capping agents can be selected from amines, amino acids, and aminosulfonates (esters). The reducing agent can be a borohydride, such as sodium borohydride or cyanoborohydride. Other reducing agents include sodium bisulfite + acetylacetone, and formic acid + formaldehyde.

[0037] These and other methods for drying bioprosthetic heart valves are applied before coupling the valve to a sealing catheter. A certain percentage of water is removed from the valve and replaced with glycerol and ethanol to "dry" the device for storage (i.e., glycerolization). The "dried" valve can then be sutured into a polyester catheter or graft and is ready for implantation. This method enables the preparation of valved catheters ready for implantation without clinical rinsing in saline, thus shortening implantation time. By definition, "dried" bioprosthetic tissue is bioprosthetic tissue with less than 70% water content. For practical rehydration, functional valves have at least 70% water content. However, the most important distinction of a "dried" valve (or the tissue therein) is that it can be dried and stored for extended periods (sometimes for years) without any decline in valve function.

[0038] This application shows and describes a variety of exemplary prosthetic heart valves and catheters. Each of these different types of heart valves can be processed to allow for dry storage. The reader will understand that this method is applicable to any and all dried-stored prosthetic heart valves, and is not limited to the exemplary valves shown herein. Specifically, artificial heart valves intended for implantation in any of the four natural valve annulus planes—aortic, mitral, pulmonary, and tricuspid valves—can be dried and stored according to the principles described herein. Optionally, valved catheters prepared according to the principles disclosed herein can be used in locations other than heart valve replacement, such as venous valves—by attaching a small bileaflet valve to or within a small-diameter catheter.

[0039] In addition, this document exemplifies and describes various techniques and delivery systems for encapsulating dried bioprosthetic heart valves, but these techniques may also be applicable to other encapsulation configurations. Typically, bioprosthetic heart valves must be stored under sterile conditions, requiring at least one sterile container. However, preferably, a dual-barrier encapsulation system is used to reduce the possibility of implant contamination during surgery. For example, U.S. Patent Publication No. 2011 / 0147251 to Hodson et al. discloses an exemplary encapsulation system, the contents of which are explicitly incorporated herein by reference.

[0040] This application describes a system and method for pre-assembling and storing a bioprosthetic heart valve and sealing catheter to form a valved catheter. The term "pre-assembled" or "pre-assembled" means the connection of the heart valve and sealing catheter before a technician in the operating room opens the sterile sealing material. In other words, the valved catheter is mechanically assembled from the time of sealing and is essentially ready for delivery (after any preoperative cleaning or other such preparation).

[0041] Figure 1 This is an exploded view of an exemplary assembly of a prosthetic heart valve 20 coupled to a sealing catheter 22. As schematically shown, the prosthetic heart valve 20 is disposed within one end of the sealing catheter 22. This valved catheter can be used to replace a patient's natural heart valve and associated vessels. The aortic valve and ascending aorta are one non-limiting example of such valve and associated vessels. The pulmonary valve and pulmonary artery are another such example.

[0042] The heart valve 20 may include a rigid or semi-rigid stent, or a so-called "stent-free" type. In an example embodiment, the heart valve 20 includes a plurality of flexible leaflets 24 (generally three) mounted on a peripheral stent structure 26 and forming a fluid-sealing surface within the valve orifice to form a one-way valve. The stent structure 26 includes a plurality of generally axially extending junctions 28 distributed around the circumference of the valve among the leaflets 24, and in the same number as the leaflets 24. Although not shown, additional components of the heart valve 20 generally include an internal stent and / or linear support structure that provides a structural framework around the inflow orifice and extending upward to the junctions 28. The internal components of the heart valve 20 may be made of suitable metal or plastic. It is known that adjacent flexible leaflets 24 are connected at each junction 28 and extend upward along each junction 28 to converge. In an example embodiment, the structural components of the heart valve 20 support each flexible leaflet 24 along the leaflet 30 and along the edges of the two junctions 28. Each leaflet 24 has a free edge 25 extending inward toward the central flow orifice and engaging or mating with the free edge of another leaflet, as shown. The valve orifice is oriented about an axis in the inflow-outflow direction through the valve. The valve junction 28 protrudes in the outflow direction, and convex leaflets 30 extend in the inflow direction between adjacent junctions. The bioprosthetic heart valve further includes a suture ring 32 on the inflow end, which conforms to the wavy profile of the leaflet or defines a generally circular planar ring. This application should not be considered as limiting to any particular valve construction unless expressly stated herein.

[0043] The sealing catheter 22 defines a generally tubular structure that extends from the inlet end 42 to the outlet end 44. In the illustrated embodiment, the valve 20 is associated with the catheter 22 in such a way that the valve leaflet 24 controls the flow of blood through the catheter by allowing blood to flow into the catheter (e.g., blood to flow into the aorta, when the catheter is used for aortic replacement) while preventing blood from flowing out of the catheter in the opposite direction (i.e., flowing back into the patient's left ventricle, when used for aortic replacement).

[0044] The example catheter 22 is particularly suitable for attachment within the aortic annulus and ascending aorta, thereby closely fitting the aortic root anatomy, and includes an enlarged area or expansion 46 conforming to the Valsalva sinus directly above the aortic annulus, near the inflow end 42. In a preferred embodiment, catheter 22 comprises a tubular textile structure, such as Dacron, sealed with a bioresorbable medium. Most catheters 22 include a pleated (i.e., grooved) structure, providing longitudinal flexibility and radial compressibility while ensuring that the catheter does not unduly expand radially under the pressure of flowing blood. Catheter 22 is desirablely to have a length of several centimeters to 10-12 centimeters.

[0045] Figure 1AExample human heart H, showing a heart implanted above the left ventricle (LV) to replace the aortic valve and part of the ascending aorta (AA). Figure 1 A valved catheter is inserted. The surgeon sutures the inflow end 42 to the aortic annulus and the outflow end 44 to the remainder of the ascending aorta AA. With the entire valve and the portion of the ascending aorta AA including the sinus removed, the two coronary arteries CA (one shown) are attached at the anastomosis AN to the enlarged region 46 of the ductus 22 between two of the three adjacent pairs of junctions 28 of the valve 20. The enlarged region 46 mimics the natural sinus and helps improve blood flow into the coronary artery CA.

[0046] In one embodiment, catheter 22 may be Gelweave Valsalva TM Grafts gelatin-sealed aortic root grafts, indicated for aortic root replacement using valve replacement or replacement techniques, are available from Vascutek Business of Terumo Cardiovascular Systems Corporation of AnnArbor, MI. As described below, a bioresorbable medium is preferably used to provide a temporary seal to the implanted graft, and it can be pre-assembled with the exemplary bioprosthetic heart valves disclosed herein. However, the exemplary bioprosthetic heart valves can also be pre-assembled with other sealing grafts or catheters, such as those utilizing non-bioresorbable materials. It should be understood that various sealing catheters are included unless excluded by the text of the claims.

[0047] In a preferred embodiment, the sealed graft or catheter 22 is relatively impermeable in its dry state, but begins to become permeable immediately after implantation. This reaction can be achieved by perfusing a porous tubular structure with a material such as gelatin, collagen, or albumin. Gelatin-perfused grafts are not porous, but the gelatin degrades through hydrolysis when exposed to water, with the rate of hydrolysis occurring at 37°C body temperature higher than at room temperature. If the rate at which the graft becomes porous is too rapid to keep pace with coagulation and tissue growth, the gelatin can be treated in a manner that leads to cross-linking between the amino groups present in the gelatin molecules. This cross-linking makes the gelatin more hydrolytically resistant, thus significantly reducing the rate of increase in graft permeability. One method of inducing cross-linking involves exposing the gelatin to formaldehyde. This application contemplates catheters or grafts that do not require pre-perfusion with blood, begin to degrade after implantation, and become permeable at a precisely known rate. It should be understood that, depending on the medical environment in which the graft is implanted, the porosity of the implanted graft should increase at a rate sufficient to prevent bleeding. A method for preparing vascular grafts based on these principles, which involves perfusing a flexible porous material tube with gelatin material and then treating the perfusing tube to cause cross-linking only of amino groups that are always present in the gelatin material molecules, is disclosed in U.S. Patent No. 4,747,848, granted to Maini on May 31, 1988, the contents of which are expressly incorporated herein by reference.

[0048] Figure 2A and 2B Example of an optional valved catheter 50 of this application, wherein a bioprosthetic valve 52 is coupled to two segments 54, 56 extending from both ends of a sealed catheter. The segments 54, 56 of the sealed catheter comprise braided polyester sealed by the technique described above. The valved catheter 50 extends between an inflow end at the free end of the inflow segment 54 and an outflow end at the free end of the outflow segment 56. This configuration can be applied in multiple locations within the body, including in the venous vascular system, as a bypass graft from the left ventricle to the descending aorta, or in the aforementioned aortic annulus. Thus, the diameter A of the valved catheter 50 can be as small as the smallest venous valve (2-5 mm) or as large as the largest heart valve (30 mm). A preferred diameter-to-size ratio is between about 12-36 mm. An exemplary combination is a 29 mm valve connected to or within a 34 mm sealed catheter. The catheterized bioprosthetic heart valve is also used in pulmonary and apical catheters. It should be noted that the example bioprosthetic valve 52 is a bioprosthetic heart valve with three leaflets. Alternatively, the bioprosthetic valve 52 can be bileaflet—typically a venous valve.

[0049] The inflow and outflow sections 54 and 56 are of different lengths and can be trimmed to an appropriate size. In fact, the two sections 54 and 56 are generally trimmed to approximate the size of the bioprosthetic valve 52. In embodiments used for lung valve replacement, the outflow section 56 is approximately 50% longer than the inflow section 54, e.g., 9 cm vs. 6 cm. In one embodiment, the valved catheter 50 is configured in a manner similar to that available from Edwards Lifesciences of Irvine, California. The bioprosthetic valved catheter is similar, but catheter segments 54 and 56 are preferably sealed with a bioresorbable medium such as gelatin or collagen. For aortic valve replacement, the inflow extension segment 54 is generally not used, but a very short (<1 cm) inflow segment 54 can be provided, and the outflow segment 56 is preferably expanded, rather than... Figure 2A The straight pipe in / 2B.

[0050] Figure 3 This is a further view of the valved catheter, in which a bioprosthetic heart valve 58 is coupled within a sealed outflow catheter 66. In some patients requiring aortic valve replacement, a portion of the aorta itself may be damaged or diseased, necessitating replacement, and the outflow catheter 66 serves to replace the damaged aorta. The bioprosthetic heart valve 58 is similar to the bioprosthetic heart valve described above and includes a flexible leaflet 62 supported by a corrugated stent 64 with an engagement. Unlike the aforementioned valved catheter 20, the heart valve 58 is coupled to the outflow catheter 66 with the leaflet 62 within the catheter lumen and the valve's suture ring 60 outside the catheter. This allows for conventional attachment of the suture ring 60 to the aortic annulus.

[0051] For example, Figure 4A and 4B This example illustrates a technique for attaching an outflow catheter 66 to a bioprosthetic heart valve 58. In both techniques, the outflow catheter 66 is attached to a fabric covering a wireform 63 that forms part of a scaffold 64, once the tissue leaflet 62 is fixed. (See reference) Figure 4A The duct 66 can be fixed to the side of the linear structure 54 opposite to the tissue leaflet 62 by, for example, suture. Alternatively, as... Figure 4B As shown, the duct 66 can be sutured and fixed to the linear structure 54 on the same side as the tissue leaflet 62, or sandwiched therebetween. A third option is to simply fix the duct 66 to the periphery of the completed valve (not shown) as a subsequent suturing step. The valve 58 can be attached to an outflow duct, with or without a sinus, as shown. It should be noted that the short portion of the outflow duct 66 that directly contacts the leaflet 62 may not contain a bioresorbable sealing medium to prevent any long-term reaction between the medium and the bioprosthetic leaflet during storage. Although Figure 4A and 4BThis is associated with valved catheters 50 used for aortic implantation, but the construction method is not preferred for pericardial valve aortic catheters because the fabric of the catheter abutting the pericardial leaflet can cause leaflet abrasion and eventual failure. However, this construction is suitable for porcine valve lung catheters. Aortic catheters with pericardial leaflet valves require alternative construction techniques for attaching the catheter to the valve suture ring.

[0052] Figure 5 This is an exploded perspective view, illustrating further applications including the valved catheter of a modified prosthetic heart valve 58. Specifically, in applications such as artificial hearts or left ventricular assist devices (LVADs), the suture ring 60 is not necessary; therefore, the lower end of the stent 64 can be attached to the flange 68 for mounting the valve in the artificial heart or LVAD. Further alternative applications include those requiring an inflow catheter 70. In such applications, the inflow catheter 70 can be directly attached to the stent 64 of the valve 58. More specifically, the inflow catheter 70 can be configured to have a stepped periphery 72 that fits snugly to and can be sutured to the outer periphery (or optionally, the inner periphery) of the stent 64. In this configuration, for example in artificial heart or LVAD applications, the suture ring 60 can be attached to the inflow catheter 70, rather than to the valve 58.

[0053] The pre-assembled valved catheters disclosed herein all include a bioprosthetic valve attached to a sealing catheter. The connection can be sutured into or to the end of the sealing catheter using sutures as described above or by less time-consuming techniques to limit the manipulation of the two components and provide a hemostatic seal with minimal assembly complexity. For example, the bioprosthetic valve and catheter can be snapped together to minimize manipulation. Various possible snapping mechanisms are disclosed in the art, including Campbell's U.S. Patent Publication No. 2006 / 0085060, the contents of which are expressly incorporated herein by reference. The snapping mechanism can employ a suture, metal, or plastic ring sutured to the proximal end of the catheter to capture the tissueed valve around a metal or plastic ring. Alternatively, the catheter can be positioned between the outer ring and the bioprosthetic valve, or it can be snapped around the outside of the ring, provided that the catheter does not obstruct the suture needle passing through the valve suture ring.

[0054] Figure 6This is an exploded view of an exemplary engagement connection between a prosthetic heart valve 80 and a sealing catheter 82. Specifically, a coupling ring 84 of a suture ring 86 attached to the valve 80 is connected to the inlet end 90 of the sealing catheter 82. The inner circumference of the coupling ring 84 may be sutured or attached to the suture ring 86 by barbs or the like, and includes an open end that surrounds the junction 92 of the valve 80 by an inwardly projecting edge 94. The edge 94 engages with an outwardly projecting edge 96 on the inlet end 90 of the sealing catheter 82. It should be understood that the engagement between the exemplary coupling ring 84 and the inlet end of the catheter 82 is merely an example and representative of many different such structures.

[0055] In an exemplary embodiment, the sealing catheter 82 has a tubular structure, wherein the body portion 100 has pleated or ruched sidewalls extending between an inlet end 90 and an outlet end (not shown). The catheter 82 is preferably formed of a biocompatible fabric infused with a bioresorbable sealing medium such as gelatin or collagen. The pleated or ruched sidewalls provide longitudinal flexibility and radial compressibility while ensuring that the graft does not unduly expand radially under the pressure of flowing blood. The catheter 82 further includes an expandable portion 102 located between the body portion 100 and the inlet end 90. The expandable portion 102 may be formed of a material with a stronger radial expansion capacity than the pleated body portion 100 to allow expansion to the Valsalva sinus at that location.

[0056] Figure 7 An exemplary sealing catheter 110 is connected to a suture ring 114 of a bioprosthetic heart valve 116 via suture 112. Partially, the sealing catheter 110 is wrapped around and captured by an elastic biocompatible band 118. Specifically, the suture 112 causes the elastic band 118 to be sealed within the sac of the sealing catheter 110. The band 118 strengthens the structural connection between the catheter 110 and the valve 116 to prevent separation and can therefore be made of a variety of biocompatible materials, including Elgiloy, titanium, or other such metals, or suitable polymers such as polypropylene.

[0057] Figure 8 Display similar to Figure 5 The valved catheter 130 is shown, with a sealed catheter 132 attached to the stent structure 134 of the prosthetic heart valve 136. Specifically, the inlet end of the catheter 132 is sutured along a wavy path following the leaflets and junction of the stent structure 134. Axis marking lines 138 are provided on the catheter 132 to indicate the location of the three junction posts. This connection offers the advantage that the surgeon can easily see the junction location, but because the catheter is located within the junction, the anastomosis attachment of the coronary arteries is slightly more difficult. Furthermore, as described above regarding the aortic pericardial catheter, there is a greater possibility of leaflet abrasion.

[0058] on the other hand, Figure 9A and9B The valved catheter 140 is shown, wherein a sealing catheter 142 is attached to a suture ring 144 of a bioprosthetic heart valve 146. The valve 146 is located within the catheter 142, and an axis marking line 147 is provided on the catheter 142 to indicate the positions of three engagement posts. Figure 9C This is a cross-sectional view through the leaflet region of the heart valve 146, schematically showing a suture loop 148 passing through a suture ring 144 to attach a sealing catheter 142 to the suture ring. The valve 146 has a fabric-covered linear structure 150 situated above a fabric-covered metal or polymer support 152, with leaflets 154 sandwiched therebetween. A portion of the leaflet edges 156 and flaps 158 of the fabric surrounding the linear structure 150 extend outwards onto a protrusion 160 formed by a fabric-covered silicone waffle ring 162 constituting the suture ring. The suture loop 148 passes through the entire waffle ring 162 and secures the inlet end of the sealing catheter 142 (for clarity). Figure 9C (Not shown in the image). This leaves the outer edge of the suture ring 144 outside the catheter 142, as... Figure 9A As shown, the anchoring suture can be pre-passed through the outer edge to allow the valved conduit 140 to descend to the target annular surface.

[0059] Figure 10 Display similar to Figure 9A The valved catheter 170 shown has a longer, sealed catheter 172 with a sinus region 174 that is attached to a suture ring 176 of a bioprosthetic heart valve (not visible). Figure 11A-11C Is it through Figure 10 A cross-sectional view of the leaflet region of a heart valve, showing the possible connection between the sealing catheter 172 (not shown for clarity) and the suture ring 176. Figure 11A The stitch loop 178 is shown, which has just passed the upper fabric layer 180 of the stitch ring 176, or has just passed the supplementary upper ring gasket 182 formed of a polymer such as Nylon, which is sometimes used for the stitch ring. Figure 11B Showing the entire axial height of the suture loop 184 extending the suture loop 176, with Figure 9C Very similar. Finally, Figure 11C Two loops 186 and 188 are shown, which pass through the entire stitching loop 176 and just through the upper fabric layer 180 to increase fixation.

[0060] Figure 12An exemplary main storage container for the valved conduit 200 of this application is provided. The main storage container includes a molded storage tray 210 and a sheet-like, breathable cap 212. Specifically, the valved conduit 200 is assembled and disposed within the cavity of the storage tray 210, and then the cap 212 is bonded to the upper edge 214 of the tray. The upper edge 214 defines the upper surface of the tray, and the process of bonding the cap 212 to the edge 214 can be easily performed using automated equipment. The adhesive may be provided on the upper edge 214 or on the underside of the cap 212.

[0061] In a preferred embodiment, components provided within the cavity of tray 210 ensure that the valved catheter 200 therein does not move and prevent the sealing catheter 218 from contacting any inner surface of the tray. If contact with the interior of the tray were permitted during operation, the bioresorbable sealing medium in the sealing catheter 218 could be abraded, potentially reducing its sealing capability. For example, a valve retainer 220 may be attached to the engagement post of a heart valve 222, and an elongated delivery handle 224 extends from the retainer to the outflow end 226 of the sealing catheter 218. A series of assist brackets 226 securely hold the handle 224 in place within tray 210, while the valved catheter 200, specifically the sealing catheter 218, is suspended within the enlarged cavity (not shown) of the tray. Because the tray 210 secures the components in this manner, the valved catheter 200 is securely suspended within the cavity without contacting the sides of tray 210.

[0062] Preferably, the lid 212 is sized close to the outer periphery of the upper edge 214, and the adhesive tape is a pressure-sealing or heat-sealing adhesive to promote a seal under pressure and / or temperature. The material of the lid 212 is breathable or permeable to allow the contents sealed within the tray 210—specifically, a dried tissue heart valve with valved catheter 200—to be gas-sterilized. A suitable permeable material is a high-density polyethylene fiber sheet, which is difficult to tear but can be easily cut with scissors. This material is highly breathable, and water vapor and gas can pass through the fibers, but liquid water cannot. For example, different Tyvek materials from DuPont can be used. Moreover, exemplary hot melt adhesives used to secure the lid 212 to the tray 210 can be, for example, obtained from Perfecseal or Oliver-Tolas. This material allows the tray contents to be sterilized with ethylene oxide (ETO) in stages, passing through the lid 212 to the inner tray. The lid 212 provides a sterile barrier and prevents microbial entry. Tray 210 is made of an impermeable molding material, such as polyethylene terephthalate copolymer (PETG). Various medical storage and encapsulation materials suitable for assembling the components of this application are available from companies including DuPont, Perfecseal, Oliver-Tolas, and Mangar. Other sterilization methods include gamma radiation or electron beam radiation.

[0063] Ethylene oxide (ETO), also known as ethylene oxide, is an organic compound with the formula C2H4O. It is commonly handled and shipped as a refrigerated liquid. ETO is frequently used as a disinfectant because it kills bacteria (and their endospores), molds, and fungi. It is used to sterilize substances that would otherwise be destroyed by high-temperature techniques such as pasteurization or autoclaving. Ethylene oxide is widely used in traditional sterilization methods to sterilize most medical supplies such as bandages, sutures, and surgical instruments, where most of the oxygen in the chamber is removed (to prevent explosions) and then the chamber is filled with a mixture of ethylene oxide and subsequently other gases.

[0064] Certain components in tray 210 facilitate gas sterilization, such as gas sterilization via ETO, but other methods, such as gamma radiation or electron beam radiation, can be applied. Specifically, tray 210 securely holds the valved conduit 200 within it, but provides sufficient passage within and around the assembly to eliminate any enclosed spaces. Therefore, sterilizing gas can flow evenly throughout the entire package.

[0065] One advantage of the encapsulation solution described herein is its dual sterility barrier, where both the inner and outer sterile containers allow for gas sterilization, such as by ETO, and, with a second seal, the outer sterile container also provides an oxygen barrier to the product after sterilization. The inner sterile container has been referenced above. Figure 12 The storage tray 210 is described in the form of a sealed cap 212. The sealed storage tray 210 is received within a second or external container, and the dual-barrier assembly is then sterilized, thus creating an additional sterile barrier. The dual-barrier assembly is subsequently sealed to prevent oxygen from reaching the valved catheter 200, thereby preventing oxidation and potentially reducing post-implantation calcification. In an exemplary encapsulation sequence, the first and second containers are first assembled together and encapsulated with permeable barriers, respectively, to form a gas-sterilized dual-barrier assembly. An oxygen barrier is then added—e.g., by converting the second container from permeable to impermeable. However, if the entire process is performed under aseptic conditions, such as in a clean indoor environment, the first container can be sealed and sterilized, then placed inside the second container, which is then sealed and sterilized. In other words, there may be one or two sterilization steps, followed by sealing the entire assembly to prevent oxygen ingress.

[0066] Desiccants are intended to be used within the inner and / or outer encapsulation layers. For example, a desiccant bag may be inserted into the inner encapsulation material using a flap conduit 200 to absorb any residual water vapor trapped therein when the breathable tray cover 212 is closed. A second desiccant bag may be inserted between the inner and outer barriers to absorb any residual water vapor therein, or it may be the sole desiccant bag used.

[0067] This application describes two distinct second barriers—one is a storage tray described below, and the other is a flexible bag. The second barriers protect and maintain the first sterile barrier encapsulation material in a sterile environment and prevent oxygen from reaching the heart valve within the valved catheter 200. Further external shelf boxes can be used to facilitate temperature monitoring during dispensing and storage, and to protect vulnerable implants from dispensing hazards such as vibration, impact, and extreme temperatures.

[0068] Figure 13 Is it like this? Figure 12 A perspective view of a valved conduit 200 located in a first storage tray 210 to which a lid 212 (not shown) is attached, and then contained within a second storage container in the form of a bag 230. Desiredly, the storage bag 230 includes a double-sealing system at its open end, providing a permeable portion and an impermeable portion—depending on the closure seal.

[0069] Figure 14 An example of a valved conduit 220 is mounted in an exemplary main storage container in the form of a tray 240 and a sheet-like, breathable cover 242. The tray 240 has a cavity for the valved conduit 220, which holds and stabilizes the components therein. The cover 242 is adhered to the upper edge 244 of the tray 240.

[0070] Figure 15 For example Figure 14 The flap conduit 220 is placed in a tray (whose cover 242 is visible), which is then placed in a second storage container in the form of an outer tray or a second tray 250 of the double-barrier packaging system. The second storage tray 250 is intended to mimic the shape of the first storage tray 240 so that the latter can be easily inserted into the cavity formed therein. The second storage tray 250 includes an upper surface that includes an outer peripheral flange 252.

[0071] The outer storage tray 250 provides a rigid second sterile barrier that protects and maintains the internal sterile barrier formed by the inner storage tray 240 and its lid 242. The outer storage tray 250 may be made of an impermeable molded material, such as polyethylene terephthalate copolymer (PETG). Once the sealed inner tray 240 is placed within the outer storage tray 250, the permeable lid 254 abuts against the flange 252 for sealing, and allows sterilizing gases (e.g., ETO) to reach the space within both trays.

[0072] Subsequently, an impermeable label 262, sized to cover the second storage tray 250, is displayed. Label 262 is applied to the sterilized tray 250 and sealed to the top of the cap 254. After pressure bonding or heat sealing of the cap, label 262 provides a complete barrier against gas migration. Label 262 preferably comprises a metal foil layer laminated to a breathable material layer such as DuPont 1073BTyvek, or more preferably a single foil layer. Information about the packaged contents, such as implant type, model, manufacturer, serial number, packaging date, etc., may be printed on label 262. A pressure-sensitive adhesive layer is provided to seal the previously attached cap 254.

[0073] Optionally, the second storage tray 250 has a double flange (not shown) around its upper edge. After the inner sterile barrier encapsulation material is arranged, the inner flange can be sealed with a permeable cap (e.g., Tyvek) such as cap 254 coated with a die-cut and heat-sealing adhesive, which allows for subsequent ETO sterilization of the entire encapsulation material—specifically, the space between the two sterile barriers. An impermeable label, such as foil label 262, is then sealed to the outer flange.

[0074] The encapsulation solution disclosed herein facilitates insertion into the valved catheter during implantation. The process of removing the valved catheter 220 from its encapsulation material will be described, but similar steps can be used to remove other valved catheters. The first step is to remove the external or second sterile barrier (bag or tray). This description will assume a second storage tray 250. First, one or both sealing labels on the outer tray 250 are removed, and the inner tray 240, sealed by the sterile cap 242, is removed (optionally, a technician tears open the sterile bag). At this stage, the inner sterile encapsulation material can be moved to the immediate vicinity of the operating site, as the relatively rigid inner tray 240 and sterile seal 242 do not require excessive concern regarding the integrity of the encapsulation material.

[0075] Subsequently, technicians removed the cap 242, exposing the valved catheter 220. The valved catheter 220 was then removed from the encapsulation material and implanted according to different procedures.

[0076] The preferred dual-barrier encapsulation system offers several advantages to valved catheter manufacturers of this application. Due to the presence of a breathable sterile barrier such as the Tyvek Header (breathable opening), the product can be easily ETO sterilized and inflated to achieve acceptable residue levels. After an appropriate inflatation time, the outer container, or a second barrier, can be sealed (e.g., foil to foil) to prevent long-term oxidation of the dried tissue valve. ETO sterilization avoids conventional oven sterilization, thus reducing the amount of energy consumed by heating the encapsulated product in an oven for several days. Similarly, eliminating autoclaving before encapsulation reduces the energy consumption required for the sterilization process.

[0077] As described, the dual sterility barrier allows for gas sterilization, such as gas sterilization via ETO, and provides an oxygen barrier for the product after sterilization. Therefore, the entire assembly can be reliably stored under anaerobic conditions for extended periods, even years, while the outer sterile container can be removed before use without exposing the contents of the inner sterile container to contaminants. The dual packaging enables aseptic transfer of the inner packaging material to the aseptic operating area, and the inner packaging material can even be temporarily stored for extended periods before product use. The new packaging design is lighter due to the material selection (PETG / Tyvek and air-to-polypropylene with glutaraldehyde), which will reduce shipping costs per unit shipment.

[0078] In fact, the biggest advantage over existing "wet" heart valve encapsulation designs is the elimination of the storage and handling of liquid glutaraldehyde during encapsulation and storage, and the absence of glutaraldehyde during use. This reduces health hazards to employees, customers, patients, and the environment. Furthermore, glutaraldehyde disposal is biohazardous, therefore OSHA requires the neutralization of chemicals or appropriate control of the disposal setup prior to disposal. The reduced handling and stringent storage requirements described herein result in a less complex encapsulation process. The removal of glutaraldehyde will not require increased levels of high-temperature isolation, as dried tissue valves are already capable of withstanding temperatures as high as 55°C. Replacing water with glycerol also provides protection against freezing to -18°C. Therefore, this could potentially reduce design effort due to smaller dimensions and the need for isolation during valve shipping in summer and winter.

[0079] Desiredly, the encapsulation provided for different valved catheters includes devices to maintain a predetermined low level of humidity. Valved catheters comprising bioresorbable materials—specifically, gelatin—can hydrolyze relatively quickly in vivo if stored under excessively humid conditions. Generally, sealed catheters with bioresorbable sealing media are stored with desiccant bags to maintain very dry conditions. However, the bioprosthetic valves disclosed herein, while stored dry, must maintain a certain level of humidity to maintain functionality. In one embodiment, a desiccant bag is provided within the encapsulation material, having a limited capacity to absorb moisture from the encapsulation material to prevent the bioprosthetic tissue from drying beyond a point that would impair its ability to be used as a bioprosthetic heart valve. In short, the two components of the valved catheters described herein have slightly different requirements when faced with the moisture content of the shipping encapsulation.

[0080] While the invention has been described with respect to its preferred embodiments, it should be understood that the language used is descriptive rather than limiting. Therefore, changes may be made within the scope of the appended claims without departing from the actual scope of the invention.

Claims

1. A preassembled valved catheter comprising: a bioprosthetic valve comprising bioprosthetic tissue, said valve having been treated so that said tissue can be stored dry for extended periods without a decrease in valve functionality; a catheter sealed with a bioresorbable medium, said bioprosthetic valve coupled thereto, thereby providing said preassembled valved catheter, wherein said catheter is secured to said bioprosthetic valve with a snap-fit connection; and a desiccant pouch having a limited capacity to absorb moisture when packaged with said preassembled valved catheter to avoid drying of said bioprosthetic tissue beyond a point that impairs its ability to function as said bioprosthetic valve.

2. The preassembled valved catheter of claim 1 wherein said bioprosthetic valve is a heart valve having flexible leaflets supported by commissures and having a sewing ring, and a coupling ring attached to said sewing ring and surrounding said commissures and having an open end that extends to provide a snap-fit connection with an inflow end of said catheter.

3. The preassembled valved catheter of claim 1 wherein said bioprosthetic valve is a heart valve and comprises bovine pericardial leaflets and said catheter comprises a tubular substrate impregnated with gelatin.

4. The preassembled valved catheter of claim 1 wherein said bioprosthetic valve is a heart valve and comprises bovine pericardial leaflets and said catheter comprises a tubular substrate impregnated with collagen.

5. The preassembled valved catheter of claim 1 wherein said bioprosthetic valve is coupled within said catheter so that said catheter extends beyond both ends of said valve to provide inflow and outflow extensions.

6. The preassembled valved catheter of claim 1 wherein said tissue has been crosslinked with glutaraldehyde or other aldehyde-containing reagent, treated with a capping agent, and dehydrated with a glycerol solution.

7. The preassembled valved catheter of claim 1 wherein said bioprosthetic valve is coupled to said catheter so that leaflets of said bioprosthetic valve are within a lumen of said catheter and a sewing ring of said bioprosthetic valve is outside said catheter.

8. A system comprising: a bioprosthetic valve comprising bioprosthetic tissue, said bioprosthetic valve having been treated so that said bioprosthetic tissue can be stored dry without a decrease in valve functionality; and a catheter sealed with a bioresorbable medium and coupled to said bioprosthetic valve, thereby providing a preassembled valved catheter, a desiccant pouch having a limited capacity to absorb moisture when packaged with said preassembled valved catheter to avoid drying of said bioprosthetic tissue beyond a point that impairs its ability to function as said bioprosthetic valve.

9. The system of claim 8 wherein said catheter is secured to said bioprosthetic valve with sutures.

10. The system of claim 8 wherein said catheter is secured to said bioprosthetic valve with a snap-fit connection.

11. The system of claim 8 wherein said bioprosthetic valve is a heart valve and comprises bovine pericardial leaflets and said catheter comprises a tubular substrate impregnated with gelatin.

12. The system of claim 8, wherein the bioprosthetic valve is a heart valve and comprises bovine pericardial leaflets, and the catheter comprises a tubular matrix impregnated with collagen.

13. The system of claim 8, wherein the bioprosthetic valve is coupled within the catheter such that the catheter extends on both sides of the valve to provide inflow and outflow extensions.

14. The system of claim 8, wherein the tissue has been cross-linked with glutaraldehyde or other aldehyde-containing reagent, treated with a capping agent, and dehydrated with a glycerol solution.

15. A preassembled valved catheter comprising: a bioprosthetic valve, the bioprosthetic heart valve comprising bioprosthetic tissue leaflets, the valve having been treated such that the tissue can be stored dry for long periods without a decrease in valve functionality, the bioprosthetic valve having a suture ring around an inflow end, wherein the tissue leaflets are supported by three commissure posts projecting in an outflow direction equidistantly positioned around the valve, with three convex valve leaflets extending between them in an inflow direction; a catheter sealed with a bioresorbable medium, the catheter being coupled to the suture ring with sutures, thereby forming the valved catheter comprising three axial marker lines provided on the outside of the catheter in alignment with and indicative of the position of the three commissure posts; a valve holder attached to the bioprosthetic valve on the outflow side of the valve leaflets; an elongated delivery handle connected to the valve holder and extending through the catheter, thereby projecting from an outflow end thereof; and a desiccant pouch having limited capacity to absorb moisture when packaged with the preassembled valved catheter, to avoid drying of the bioprosthetic tissue beyond a point at which it loses its ability to function as the bioprosthetic valve.

16. The valved catheter of claim 15, wherein the heart valve is positioned at an inflow end of the catheter that wraps around the suture ring.

17. The valved catheter of claim 16, wherein the sutures coupling the catheter inflow end to the suture ring pass through the entire suture ring.

18. The valved catheter of claim 15, wherein the heart valve comprises bovine pericardial leaflets, and the catheter comprises a tubular matrix impregnated with gelatin or collagen.

19. The valved catheter of claim 15, wherein the bioprosthetic valve is coupled within the catheter such that the catheter extends on both sides of the valve to provide inflow and outflow extensions.

20. The valved catheter of claim 15, wherein the bioprosthetic tissue leaflets have been cross-linked with glutaraldehyde or other aldehyde-containing reagent, treated with a capping agent, and dehydrated with a glycerol solution.

21. A method for preparing a preassembled valved catheter, comprising: obtaining the preassembled valved catheter, the preassembled valved catheter comprising a bioprosthetic valve having bioprosthetic tissue leaflets, the bioprosthetic valve being coupled to a catheter sealed with a bioresorbable medium, the valved catheter along with the connected delivery handle being stored in a dry packaging material; ​ providing a desiccant pouch having limited capacity to absorb moisture when packaged with the preassembled valved conduit to avoid drying of the bioprosthetic tissue beyond a point that impairs its ability to function as the bioprosthetic valve; and opening the dry packaging material and removing the valved conduit using the delivery handle.

22. The method of claim 21, wherein the bioprosthetic valve is a heart valve and the inflow end of the conduit is secured to the bioprosthetic valve using sutures.

23. The method of claim 22, wherein the bioprosthetic valve has a valve holder attached to its outflow side and the delivery handle is connected to the valve holder and extends through the conduit so as to protrude from its outflow end.

24. The method of claim 21, wherein the bioprosthetic valve is a heart valve having bioprosthetic tissue leaflets supported by three commissure posts protruding in an outflow direction with three convex cusplets extending between them in an inflow direction.

25. The method of claim 21, wherein the bioprosthetic valve is a heart valve and comprises bovine pericardial leaflets and the conduit comprises a tubular matrix impregnated with gelatin or collagen.

26. The method of claim 21, wherein the bioprosthetic valve is coupled within the conduit so that the conduit extends on both sides of the valve to provide inflow and outflow extensions.

27. The method of claim 21, wherein the bioprosthetic tissue leaflets have been crosslinked using glutaraldehyde or other aldehyde-containing reagent, treated with a blocking agent, and dehydrated with a glycerol solution.

28. A method for preparing a preassembled valved conduit comprising: obtaining the preassembled valved conduit comprising a bioprosthetic valve having bioprosthetic tissue coupled to a conduit sealed with a bioresorbable medium, the valved conduit being stored in dry packaging material, and wherein the conduit is secured to the bioprosthetic valve using a snap-fit connection; providing a desiccant pouch having limited capacity to absorb moisture when packaged with the preassembled valved conduit to avoid drying of the bioprosthetic tissue beyond a point that impairs its ability to function as the bioprosthetic valve; and opening the dry packaging material and removing the valved conduit.

29. The method of claim 28, wherein the bioprosthetic valve is a heart valve having bioprosthetic tissue leaflets supported by commissures and having a suture ring and a coupling ring attached to the suture ring and surrounding the commissures and having an open end that extends to provide the snap-fit connection with the inflow end of the conduit.

30. The method of claim 28, wherein the bioprosthetic valve is a heart valve and comprises bovine pericardial leaflets and the conduit comprises a tubular matrix impregnated with gelatin.

31. The method of claim 28, wherein the bioprosthetic valve is a heart valve and comprises bovine pericardial leaflets, and the catheter comprises a tubular matrix impregnated with collagen.

32. The method of claim 28, wherein the bioprosthetic valve is coupled within the catheter such that the catheter extends on both sides of the valve to provide inflow and outflow extensions.

33. The method of claim 28, wherein the tissue has been cross-linked with glutaraldehyde or other aldehyde-containing reagent, treated with a capping agent, and dehydrated with a glycerol solution.

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