Self-expanding stent for placement on mitral annulus

Abstract

The invention relates to a self-expanding stent for placement on the mitral annulus, which self-expanding stent is self-expandable from an unexpanded state to an expanded state, the self-expanding stent comprising: a stent frame having at least a first portion and a second portion arranged on a longitudinal axis of the stent, wherein the stent frame is formed by a plurality of continuous arms which are connected to each other at connection points, thereby forming a mesh structure having diamond shaped pores; a dry valve made of bovine pericardium arranged at least at the second portion of the stent, wherein the dry bovine pericardium is configured to be rehydrated with a solution, a skirt surrounding the dry valve comprising at least one of bovine pericardium and polyester, and wherein in the expanded state a maximum outer diameter of the first portion is larger than a maximum outer diameter of the second portion, and wherein at least at the transition between the first portion and the second portion some of the continuous arms extend outward beyond the mesh structure forming hooks, the hooks facing towards the first portion.

Description

Technical Field

[0001] The present invention relates to a self-expanding stent for placement on the mitral valve annulus, which can expand from a non-expanded state to an expanded state. Background Technology

[0002] A healthy heart facilitates the flow of oxygenated blood to the limbs. The heart consists of two chambers: the right ventricle and the left ventricle, which handle deoxygenated and oxygenated blood, respectively. Deoxygenated blood from the upper and lower limbs flows through the two vena cava (superior and inferior vena cava) into the right atrium. It is pumped into the right ventricle via the tricuspid valve. During cardiac contraction, as the ventricle fills, the tricuspid valve closes, and blood is pumped from the right ventricle through the pulmonary valve into the pulmonary artery, where it is oxygenated in the lungs. After this oxygenation, the blood is pumped back to the left side of the heart, the left atrium, via the pulmonary veins. As the atrium contracts, oxygenated blood flows from the left atrium into the left ventricle through the mitral valve. During cardiac contraction, as the left ventricle fills, it ejects blood through the aortic valve into the aorta, reaching the rest of the body and the coronary arteries that supply the heart muscle itself.

[0003] The proper opening and closing of the atrioventricular valves depends on the function of all structures related to leaflet function, particularly the annulus, leaflets, chordae tendineae, papillary muscles, and healthy myocardial wall. During ventricular filling (diastole), the atrioventricular valves remain open, and during ventricular contraction (systole), they close due to complete leaflet alignment. If complete leaflet alignment is not achieved, valve leakage or backflow can affect cardiac function and health. Severe backflow or leakage can lead to hemodynamic deterioration and / or heart failure.

[0004] Moderate or high tricuspid regurgitation can impair cardiac function and often indicates a more extensive underlying condition, such as left ventricular dysfunction. Primary dysfunctions can include pulmonary hypertension, right ventricular volume overload, and right ventricular disease. Similarly, mitral regurgitation or leakage is primarily attributed to degenerative valvular disease. The presence of supporting structures with dysfunction can also contribute to mitral regurgitation, particularly as a result of a heart attack (ischemic mitral regurgitation) or ventricular dilation (functional mitral regurgitation). Other causes of atrioventricular regurgitation include acquired diseases (i.e., endocarditis, rheumatic heart disease) and congenital abnormalities.

[0005] Atrioventricular regurgitation can also affect the vena cava leading to the atria. During tricuspid regurgitation, changes in pressure and flow in the right atrium cause dilation of the inferior vena cava (IVC) and superior vena cava (SVC). Furthermore, the veins supplying the IVC and SVC are also affected. Specifically, tricuspid regurgitation causes dilation of the azygos vein and hepatic vein, located at the head and tail of the right atrial ostium, respectively. This leads to overall hemodynamic deterioration and liver dysfunction. Physical symptoms of tricuspid regurgitation include fatigue, loss of appetite, and abdominal distension. Similarly, mitral regurgitation affects the pulmonary veins and can lead to pulmonary effusion. Chronic mitral regurgitation often results in left ventricular remodeling or left ventricular dilation. Physical symptoms of mitral regurgitation include fatigue, decreased exercise tolerance, shortness of breath, and swollen feet. If left untreated, both severe atrioventricular regurgitation and severe atrioventricular regurgitation can lead to pulmonary hypertension, atrial fibrillation, or heart failure.

[0006] Transcatheter valves are used to treat conditions such as mitral valve disease, which alters the anatomy of the structures surrounding the mitral valve, deforms the aortic valve, or causes coronary artery or vein occlusion. These anatomical deformities lead to abnormal cardiac function, including in the aortic valve. Other complications arising from mitral valve replacement surgery include changes in the flow characteristics of blood leaving the mitral valve due to the design of the replacement valve or thrombosis in the atrium. Furthermore, if the atrioventricular valves are not properly placed, they cannot properly seal the ventricles from the atria, thus failing to properly treat the underlying condition and leading to paravalvular leaks.

[0007] One drawback of existing technology is leakage around the valve, known as paravalvular leakage (PVL). PVL is usually the result of one of the following: implant misposition, calcium ions interfering with implant expansion, incorrect implant size, and / or implant migration.

[0008] Therefore, biological tissues are widely used as prosthetic replacements for heart valves and blood vessels, as well as transcatheter heart valves. These are connective tissues containing collagen as a major component. Among these tissues, bovine pericardium is one of the most widely used. The pericardial tissue is a sac surrounding the heart, providing a natural barrier against infection and preventing adhesion to surrounding tissues. The pericardium also plays a mechanical role, for example, by preventing excessive cardiac distension, maintaining the correct anatomical position of the heart, and regulating the pressure-volume ratio of the left ventricle during diastole. The structure of the tissue determines its behavior under physiological conditions and under load as a prosthetic device.

[0009] However, biological tissues obtained from slaughterhouses, particularly from pig and cattle carcasses, begin to degrade immediately. Therefore, storing this material has proven difficult. For this reason, biological tissues, such as the pericardium or heart valves of cattle or pigs, are typically chemically treated to improve their mechanical properties and immunogenicity, reduce thrombosis and degradation, maintain sterility, and extend their permissible shelf life.

[0010] Therefore, known biological tissues suitable for use as artificial bioprosthetic valve devices can be dried and preserved before clinical application. Furthermore, special attention must be paid to the preparation method to avoid the formation of denatured calcified deposits. Calcification of soft biological tissues due to the deposition of calcium phosphate inorganic salts in the implanted tissue, especially pathological calcification, is undesirable, as calcified deposits can severely affect device performance. Calcification of the implant can lead to stiffness, structural instability, and ultimately device malfunction.

[0011] Despite the difficulties in using biological tissues, they have proven to perform much better in the human body. Summary of the Invention

[0012] Therefore, the object of the present invention is to provide a stent that can maximally prevent PVL and reduce surgical trauma, thereby also making the stent suitable for elderly patients. The above object can be achieved through the following methods.

[0013] This self-expanding stent for placement on the mitral valve annulus can self-expand from a non-expanded state to an expanded state, and includes a stent frame having at least a first portion and a second portion arranged along the longitudinal axis of the stent, wherein the stent frame is formed by a plurality of endless arms that connect to each other at connection points to form a mesh structure with rhomboid cells. The stent also includes a desiccated valve made of bovine pericardium, the desiccated valve being arranged in at least the second portion of the stent, and the desiccated bovine pericardium being configured to be rehydrated with a solution; and a skirt surrounding the desiccated valve and comprising at least one of bovine pericardium and polyester, preferably containing both materials. In the expanded state, the maximum outer diameter of the first portion is greater than the maximum outer diameter of the second portion. Furthermore, at least at the transition between the first and second portions, some of the endless arms extend outward beyond the mesh structure to form hooks facing the first portion.

[0014] The stents described in this article for use in implants or prostheses are particularly well-suited for treating mitral valve disease by replacing defective mitral valves via minimally invasive transcatheter implantation.

[0015] In this regard, it should be noted that throughout the application documents, the terms "Part One" and "Part Two" refer to, respectively, as follows: Figure 1 The diagram shows the upper and lower portions of the stent. Specifically, the first portion of the stent refers to the first part of the stent that deploys in the direction of blood flow; that is, the portion into which blood enters when the stent deploys at the patient's mitral valve. Therefore, the second portion refers to the second part in the direction of blood flow, including the portion through which blood exits the stent.

[0016] The stent comprises multiple continuous arms that form a stent frame consisting of two parts: a first part and a second part. The interconnected arms in this manner enable the stent to expand, adapting to the anatomical needs of the stent's location as it expands. Thus, this stent design is adapted to accommodate anatomical requirements and implantation sites. Self-expanding stent frames are also available. Furthermore, 6 to 50 arms can be provided to form the stent frame.

[0017] Multiple arms connect to each other at the connection points, forming a mesh structure composed of multiple diamond-shaped support cells.

[0018] In this regard, it should be noted that the portions forming the multiple arms on the sides of the support cell are linear, giving the resulting support cell a rhomboid shape. This shape allows for simple manufacturing and provides increased stability and flexibility to the support frame.

[0019] The increased flexibility of the stent allows for more precise placement of implants, including such stents, within the heart using appropriate design options, thus improving implant function through increased juxtaposition with the natural anatomy. The flexibility within the stent is designed to aid in the guideability and deployment of the implant within the vascular system. Furthermore, the increased flexibility, even when the stent is not deployed, enhances the ability to guide the implant from the entry site to the implantation site. This is essential for minimizing trauma to the patient during implantation and ensuring accurate implant placement. Reduced trauma to the patient also lowers the surgical risk, allowing this implant to be used for patients who were previously ineligible for surgery due to the excessive risks associated with implants designed with existing technologies.

[0020] Furthermore, in the inflated state, the maximum outer diameter of the first part is larger than that of the second part. This design, by achieving an interference fit between the stent and the patient's mitral valve, can further improve the function of the implant.

[0021] A further feature of the invention is that, at least at the transition between the first and second portions, some continuous arms extend outward beyond the mesh structure to form hooks facing the first portion. That is, some arms interrupt the mesh structure by extending outward beyond the main body of the support frame, such that the continuous arms extending beyond the main body form corresponding hooks. Because the arms forming the hooks interrupt the mesh structure, the cells below the corresponding hooks, i.e., the radially inward cells compared to the hooks, have a much larger area than the cells forming the mesh structure. However, these larger cells are also interconnected with the rest of the support frame.

[0022] The tip of the hook faces the first portion, aligning it against the direction of blood flow within the patient's heart. Therefore, the tip faces the left atrium of the patient's heart. Such a hook can act as an anchor to help better secure the stent to the patient's natural mitral valve, particularly on the valve's annulus.

[0023] The stent comprises a dried valve made from bovine pericardium, which can be rehydrated with a solution such as a saline solution before final placement on the aorta. Therefore, pericardium is used as an animal biological tissue material, particularly pericardium obtained from bovine hearts that may have been treated with a cross-linking agent. The invention is intended to fix a natural human heart valve, specifically the mitral valve. Thus, pericardium is used to replace damaged or diseased naturally occurring heart valves. Similarly, such a valve allows for preloading of the stent within the delivery system.

[0024] The valves are made from bovine pericardium. ECM (extracellular matrix) tissue is typically obtained from the pericardial sac of a bovine animal and then used to create the leaflets. Pericardial sac tissue is particularly well-suited for valve leaflets due to its durable physical properties. These tissues are glutaraldehyde-fixed, non-viable, chemically treated (decellularized), and sterilized, thus removing biomarkers and making them more compatible with the patient's immune system.

[0025] The potential benefits of bovine pericardium include excellent biocompatibility, minimal suture bleeding, and readily verifiable permeability via ultrasound (e.g., TEE ultrasound). They also offer advantages such as the absence of calcification, supportive cell inward growth, and reduced restenosis and infection rates. Pericardium is durable, robust, and available in a variety of sizes.

[0026] To ensure a seal once the stent is in place, the stent also includes a skirt that at least surrounds the dry valve. Thus, the skirt provides a seal between the stent and the left ventricle of the heart. The skirt comprises at least one of calf pericardium and polyester, preferably both of these materials.

[0027] To help secure the valve to the heart, the valve can further have a PET fabric skirt that attaches tissue to the support frame. PET material is highly inert and does not produce any adverse reactions in the human body. PET material also allows cells to grow inwards into the fabric, thus helping to secure the valve in place and minimizing the risk of blood clots.

[0028] Generally, PTFE sutures can be used to secure stents to the heart.

[0029] The support frame can be further made of nitinol. Nitinol is a foldable and flexible metal that is also self-expanding and has shape memory properties.

[0030] Similarly, as mentioned above, the stent can be divided into at least two parts, namely, a first part and a second part, which are arranged adjacent to each other along the longitudinal axis. It is believed that the length, size, and scale of each part are particularly suitable for minimally invasive treatment of mitral valve disease. Appropriate selection of length allows for an interference fit between the stent and the mitral valve sufficient to prevent stent displacement in a timely manner.

[0031] According to an embodiment of the invention, the hook is formed by two adjacent arms that are connected to each other, and in particular, the tip of the hook is formed by the vertex of the corresponding rhomboid cell. In this respect, it should be noted that the term "vertex" refers to the corner region of each cell, i.e., the region where the cell forms a corner, where the two corresponding portions of the arms intersect. Preferably, the vertex at least substantially forms an origin of the corner, where the two corresponding portions of the arms intersect at the origin of the corner. Moreover, the shape of the hook may follow the outline of the first part of the support, although it is radially further outward than the outline of the support. Therefore, it can be claimed that the hook is arranged parallel to the outline of the first part.

[0032] The stent frame may further include additional struts arranged at least in the transition between at least the second portion and / or the first and second portions, respectively, the additional struts extending outward beyond the mesh structure and facing the first portion to form additional anchors. The additional struts can function as barbs, which helps to secure the stent at the location of the natural mitral valve. Such barbs can help to properly secure the stent even under difficult conditions, such as when someone is affected by a collision (e.g., an accident).

[0033] The number of additional supports placed in the second part and / or in the transition between the first and second parts can vary, i.e., can be freely chosen.

[0034] In some embodiments, the additional support may be selected to be straight, while in other embodiments, the additional support may follow the shape of the second part and / or the shape of the transition between the first and second parts.

[0035] The length of the support column can also be freely chosen. In this regard, it should be noted that the exact shape of the support column can be chosen according to its length; that is, longer support columns can follow the shape of the second part and / or transition section, while shorter support columns can be straight.

[0036] The additional support can be further secured at the connection points of the arms. That is, the support can be secured at the apex, and the apex can therefore include eyelets. Secure the support to these eyelets at at least some apexes between the arms, making the support more flexible. This is because eyelets are generally not as rigid as connection points designed in the prior art.

[0037] According to another embodiment of the invention, at the transition between the first part and the second part, all the arms of the first part extend outward relative to the second part because the maximum outer diameter of the first part is greater than the maximum outer diameter of the second part.

[0038] The first part may further include a generally sac-like external shape, and the second part may include a generally cylindrical shape. It can be shown that such a shape can help improve the interference fit between the stent and the natural mitral valve, so that once the stent is deployed, it can be properly held in place.

[0039] According to another embodiment, the end of the first arm may be radially inward, and / or the end of the second arm may be arranged coaxially with the longitudinal axis, i.e., parallel to the longitudinal axis. Such an arrangement prevents the end of the arm from puncturing the heart wall during deployment and / or after the stent expands.

[0040] According to another implementation, at least some cells in the first part are larger than the cells in the second part. This may be because the maximum outer diameter of the first part is greater than the maximum outer diameter of the second part. Therefore, since the mesh structure is stretched more in the first part than in the second part, the cells can simply be larger.

[0041] The dry valve may further comprise 2 to 6 leaflets, preferably 3 or 4 leaflets, wherein the leaflets are fixed to the stent frame at the fixation point of the second part. It has been shown that a valve comprising 3 leaflets is optimal for a circular stent in the valve attachment area to ensure a uniform distribution of the forces of blood flow present in the heart during valve opening and closing. However, the exact number of leaflets can be selected based on the application, medical condition, patient anatomy, etc. The fixation point of the second part may be an eyelet to which the leaflets can be sutured.

[0042] Dried bovine pericardium can have a maximum tensile stress selected in the range of 20 to 25 MPa, and / or rehydrated bovine pericardium can have a tensile stress selected in the range of 12 to 15 MPa. Therefore, dried bovine pericardium can have a tensile strength up to 15 times higher than that of the lobules of the human heart. This is primarily for safety reasons, to minimize the risk of pericardial tearing or rupture.

[0043] The mechanical properties of materials, especially tensile strength, can be tested under strain-stress assessment using a Universal Testing Machine (Oswaldo Filizzola, model AME-2kN).

[0044] Additionally, the calcium content of dried bovine pericardium can be selected within the range of 0.01 to 0.1 g / kg. Bovine leaflets are generally as flexible and durable as the patient's natural tissue, so individuals with this type of replacement valve may not require continuous use of blood thinners. Given its similarity to natural flexible leaflet valves, bovine pericardial tissue has better hemodynamic properties; however, the durability of some bovine pericardial valves may be somewhat limited due to calcification and degeneration processes. The valves undergo specialized anti-calcification treatment, enhancing their resistance to calcification. Therefore, valves with this calcium content are more resistant to calcification and more durable.

[0045] According to another embodiment of the present invention, a method for preparing dried bovine pericardium includes the following steps: (1) Soaking the veal heart treated with a cross-linking agent in a salt solution; (2) Contact the soaked veal heart with an aqueous solution containing hydrogen peroxide; (3) Contact the bovine pericardium with an aqueous solution containing PBS and EDTA; (4) Contact the bovine pericardium with a solution containing glycerol, ethanol, and EDTA; and (5) Make the bovine pericardium come into contact with the glycerol solution.

[0046] One embodiment of the present invention involves soaking bovine pericardium treated with a cross-linking agent in a salt solution.

[0047] As used herein, the cross-linking agent is glutaraldehyde, which is preferably used in biochemical and medical applications as an amine-reactive, bifunctional cross-linking agent. Glutaraldehyde treatment produces stable cross-links in cellular and extracellular matrix proteins, thereby significantly reducing the immunogenicity of the graft. However, such tissues exhibit altered mechanical properties, early mechanical failure, cytotoxicity, and incomplete inhibition of immunological recognition. Furthermore, severe calcification has been observed in glutaraldehyde-treated bovine pericardium. An emerging alternative to glutaraldehyde treatment is a further treatment according to the steps described herein, namely, a method to reduce bovine pericardial calcification.

[0048] Preferably, the amount of crosslinking agent used is 0.1 vol% to 5.0 vol%, more preferably 0.2 vol% to 3.0 vol%, even more preferably 0.3 vol% to 2.0 vol%, and particularly preferably 0.5 vol% to 1.0 vol%.

[0049] In this regard, as a first step, the calf pericardium is immersed in a saline solution containing 0.9% sodium chloride (9.0 g / L). This solution is commonly referred to as physiological saline, physiological saline, or isotonic saline solution.

[0050] In the second step, the soaked veal heart is brought into contact with an aqueous solution containing hydrogen peroxide. The concentration of hydrogen peroxide is preferably from 0.05 vol% to 5.0 vol%, more preferably from 0.1 vol% to 3.0 vol%, and even more preferably from 0.2 vol% to 2.0 vol%.

[0051] In the third step of this invention, the bovine pericardium is contacted with an aqueous solution containing PBS and EDTA.

[0052] As used herein, the term “contact” refers to the treatment, soaking, exposure, or rinsing of biological tissues used in the methods of this invention.

[0053] As used herein, the term "PBS" refers to a phosphate-buffered saline solution with a pH of 7.4, which is an aqueous salt solution containing disodium hydrogen phosphate and sodium chloride, and in some formulations contains potassium chloride and potassium dihydrogen phosphate. PBS is used in biological and medical applications such as washing cells, transporting tissues, and diluting because PBS closely mimics the pH, molar osmotic pressure, and ion concentration of the human body.

[0054] The term "aqueous solution" refers to a solution containing a substance or compound and water, which has been purified to remove contaminants that could affect the final product. Preferably, distilled water, double-distilled water, or deionized water is used in the method of the present invention.

[0055] The term "EDTA" used in this article refers to ethylenediaminetetraacetic acid, a chelating agent capable of chelating metal ions, especially Fe. 2+ / Fe 3+ Al 3+ Mg 2+ Ca 2+ Mn 2+ Zn 2+ And so on, and remove them from the solution to form the so-called EDTA complex.

[0056] According to the implementation method, it is particularly important to remove calcium ions from the solution by forming a calcium chelating agent, which has been shown to inhibit the mineralization of biological tissues, especially bovine pericardial tissue. It is suggested that EDTA binds to calcium ions on the outer shell of hydroxyapatite crystals formed from calcium phosphate crystals, thereby chelating and removing calcium ions from the crystals, causing the tissue material to shrink and thus demineralize the material.

[0057] Therefore, treating biological tissues with EDTA can slow down the calcification process by binding calcium before the calcium reaction forms hydroxyapatite. Since calcification of biological tissues used (e.g., for use as bioartificial heart valves) is a clinically significant problem leading to implant failure, reducing the calcium level in biological tissues used as implants is of great importance. Therefore, in this invention, EDTA treatment can reduce the calcium level in biological tissues, particularly in bovine or porcine pericardium or heart valves, by 20%, more preferably 30%, further preferably 40%, and particularly preferably 50%. Furthermore, to increase demineralization and biocompatibility, it is preferable to use EDTA in combination with PBS.

[0058] Furthermore, EDTA is preferably used, particularly in steps (3) and (4), with a concentration greater than 0.01 wt%, preferably greater than 0.05 wt%, more preferably greater than 0.10 wt%, more preferably greater than 0.15 wt%, and less than 10.0 wt%, preferably less than 8.0 wt%, more preferably less than 6.0 wt%, also preferably less than 5.0 wt%, and even more preferably less than 3.0 wt%. Additionally, disodium EDTA is preferably used in this invention.

[0059] In the fourth step of this invention, the bovine pericardium is contacted with a solution containing glycerol, ethanol, and EDTA, and in the fifth step, the bovine pericardium is contacted with a glycerol solution to further reduce calcification of the biological tissue and dehydrate the bovine pericardium. The following steps describe the implementation of these processes in the method.

[0060] After the bovine pericardium is treated by steps (1) to (3) of this method, it is treated in a solution containing glycerol, ethanol and EDTA.

[0061] Phospholipids within and around biological tissue cells have been identified as the most prominent nucleation sites for calcification. Therefore, the removal of these tissue components has been proposed to reduce mineralization, particularly calcification. Various studies have shown that these are effective strategies for preventing calcification. Organic solvents, such as ethanol or glycerol, or mixtures of ethanol and glycerol, can be used similarly for this purpose. For example, treatment with at least 70% ethanol, preferably at least 80% ethanol, more preferably at least 90% ethanol, extracts phospholipids from the tissue while also inducing a change in collagen conformation, thereby increasing the resistance of the bioprosthetic to collagenases. Thus, ethanol treatment allows for the extraction of almost all phospholipids and cholesterol from the bioprosthetic, thereby eliminating calcification of biological tissue cells. Additionally, ethanol treatment prevents the adsorption of phospholipids and cholesterol in solution. Methods for fixing biological tissues with glycerol are not fully understood, but a concentration of 98% (preferably 99%) is sufficient to treat biological tissues to make them more biocompatible and resistant to calcification.

[0062] In this regard, biological tissues are treated at room temperature, particularly between 10°C and 25°C, preferably between 15°C and 25°C, more preferably between 18°C ​​and 22°C, in a solution containing glycerol, ethanol, and EDTA, under stirring conditions of no more than 500 rpm, preferably no more than 300 rpm, more preferably no more than 50 rpm, for at least 60 minutes, preferably at least 75 minutes, and more preferably at least 90 minutes. During this time, most of the water molecules present in the biological tissues, especially the pericardial tissue, are replaced by glycerol.

[0063] Furthermore, a mixture of glycerol and ethanol is preferred, wherein the volume ratio of glycerol to ethanol is preferably 1:5 to 5:1, more preferably 1:4 to 4:1, even more preferably 1:3 to 3:1, and even more preferably 1:2 to 2:1.

[0064] The veal heart is then removed from the solution and placed in glycerol for further dehydration at room temperature, particularly at 10°C to 25°C, preferably at 15°C to 25°C, more preferably at 18°C ​​to 22°C, for at least 60 minutes, preferably at least 75 minutes, more preferably at least 90 minutes, wherein the stirring speed is not greater than 500 rpm, preferably not greater than 300 rpm, more preferably not greater than 50 rpm.

[0065] An additional step may also be preferred, involving contacting or rinsing the bovine pericardium with ethanol at a concentration of at least 70% by volume, preferably at least 80% by volume, and more preferably at least 90% by volume. This additional step, particularly step (3a), is preferably performed before contacting the biological tissue with a solution containing glycerol, ethanol, and EDTA. Another additional step (5a), contacting the biological tissue with ethanol, may also be preferably performed after the step of contacting the biological tissue with glycerol and before the step of drying the biological tissue. It is still further preferred to use a mixture of ethanol and EDTA at the same concentration as in step (3) or (4) for the additional steps (3a) and / or (5a).

[0066] The pericardium is removed from the solution and exposed to ambient air or an inert environment such as nitrogen at room temperature and humidity to avoid adverse effects on tissue properties. Preferably, it is dried in a cleanroom under ambient conditions for at least 12 hours, more preferably at least 16 hours, and more preferably at least 20 hours. More preferably, the drying is carried out in a high-efficiency particulate air (HEPA) filter, particularly under HEPA conditions in a cleanroom. As used herein, the term "ambient conditions" refers to an ambient temperature greater than 10°C, preferably greater than 12°C, more preferably greater than 14°C, particularly preferably greater than 18°C, and preferably less than 25°C, more preferably less than 23°C, and more preferably less than 22°C. Furthermore, in this invention, each of steps (1) to (7) is preferably carried out under the above-described ambient conditions.

[0067] The processed and dried veal heart capsules are then packaged in essentially liquid-free containers or packs for subsequent surgical implantation. As used herein, the term “essentially liquid-free” refers to a non-fluid environment in which the presence of water or other substances is limited to levels approximating those found in ambient air.

[0068] According to another embodiment, the skirt is arranged to cover at least the second portion from the inside, and preferably also the first portion, particularly the entire stent. The skirt may at least cover the area occupied by the valve. Typically, to provide a better seal, the length of the skirt is longer than the length of the valve. In some embodiments, the skirt may even cover the entire stent from the inside.

[0069] Once in place, the skirt will press against the stent frame as blood flows through the valves from the first section to the second section. Depending on the patient's precise anatomy, the stent can come in different sizes, and therefore can also include different skirt sizes. In some cases, a longer skirt that covers most of the stent is preferable, while in others, a shorter skirt that covers only a smaller portion of the first and second sections may suffice.

[0070] All ends of the arm at the first and second ends can be located on the same plane to avoid having a single arm that could puncture the ventricle and / or atrium.

[0071] According to another embodiment, the stent further includes an eyelet disposed at a first end of the first portion for attaching the stent to a delivery device, which preferably protrudes beyond the common plane of the end of the arm, wherein the eyelet is located in a further common plane. A common plane is again provided for safety reasons. The eyelet for attaching the stent to the delivery device enables stent placement at the mitral valve without the need for open-heart surgery.

[0072] The orifice of the first part protrudes inward relative to the longitudinal axis, wherein the orifice specifically follows the same profile as the end of the first part of the stent away from the transition portion. Since the aforementioned orifice is used to attach the stent to the delivery device during deployment, it is advantageous to make the orifice follow the same profile as the end of the stent so that it protrudes inward to prevent the attachment from puncturing the artery and / or vein while moving the stent through the body to the heart.

[0073] The stent may also include additional means for attaching the stent frame to a point of interest, particularly the mitral valve, at a first and / or second portion of the stent frame, thereby ensuring that the stent is held in its intended position. Such means may, for example, be additional eyelets disposed at the end of the arm. These eyelets may be located in a common plane spanned by the end of the arm, or may extend beyond said plane. In the second case, the eyelets may also be located in a common plane that overlaps with the common plane of the eyelets used to secure the stent frame to the delivery device.

[0074] The stent may further include additional perforations at the second part, particularly at the end of the arm at the second part, to attach the dry valve to the stent frame.

[0075] According to a second aspect of the invention, a conveying device is provided for conveying a self-expanding stent according to the invention. The conveying device includes a flushing port, a main body portion for holding, expanding, and / or releasing the stent, and an actuation mechanism for moving the stent to a conveying section.

[0076] The device can be pre-loaded with a stent for storage and preparation for use on shelves in medical facilities, significantly reducing treatment time for acute aortic syndrome and thus lowering its mortality rate. The actuation mechanism can have torque control and be able to rotate the stent about the axis of the body. In this way, the stent can be positioned as well as possible relative to the limbs at the mitral valve to deploy the valve and stent at the desired delivery site. The device can be further improved by controlling the steering to enhance the precision and accuracy of deployment.

[0077] Furthermore, the device may have a knob or similar component at the actuation mechanism, wherein the knob is particularly capable of rotating about the rotation axis of the actuation mechanism. By rotating the knob, the lumen can be deflected, allowing for better positioning of the tip and the body of the delivery device, and resulting in less pressure on the system during deployment. This improves the accuracy of deployment of the delivery device and thus the support used to deliver the device to the delivery location. Attached Figure Description

[0078] The invention will be described in detail by way of embodiments and with reference to the accompanying drawings. These drawings illustrate preferred embodiments. The described features can be configured in various combinations, which are also included herein. The drawings are shown below: Figure 1 It is a support frame according to the first embodiment; Figure 2 The support frame according to the second embodiment also includes a drying valve and a skirt; Figure 3 yes Figure 2Different views of the bracket; Figure 4 These are CT reconstruction images of deployed stents; Figure 5 Looking at it from different angles Figure 4 CT reconstruction images of stents already deployed in the center. Detailed Implementation

[0079] Figures 1 to 3 Different views of a self-expanding stent 10 configured for placement at a patient's mitral valve are shown, wherein the stent 10 has a stent frame 12 composed of multiple different arms 14. The stent frame 12 is made of nitinol, a flexible material with shape memory, and therefore, it is capable of self-expanding once the stent 10 is deployed. Thus, the stent 10 can be delivered to the mitral valve in a compressed state before it self-expands at the delivery site.

[0080] The frame 12 also includes at least two parts, namely, a first part 16A and a second part 16B, which are arranged at the longitudinal axis A. The terms "first" and "second" refer to the direction of blood flow through the stent once it is deployed at the desired location on the stent. Thus, once placed in place, blood first flows through the first part 16A of the stent 10 and then through the second part 16B. Additionally, the stent 10 includes a transition section T between the first part 16A and the second part 16B. All parts 16A, 16B, and T are interconnected with each other.

[0081] The frame 12 is further characterized in that the arms 14 are connected to each other at multiple connection points 18, forming a mesh structure of diamond-shaped cells 20. For example... Figures 1 to 3 As shown, the support 10 can be composed of rows of cells 20 arranged on the longitudinal axis A. The number of rows of cells 20 can be selected according to the patient's anatomical condition, etc.

[0082] Each support cell 20 in this embodiment is formed by four sides and four vertices. The four sides of the support cell 20 are each formed by a portion of the arm 14, and the vertices are formed by the ends or connection points 18 of the arm 14.

[0083] like Figures 1 to 3 As shown, some arms 14 of the stent 10 extend outward beyond the mesh structure of the stent frame 12 body to form hooks 40 facing the first portion 16A. Cells 21 arranged below the hooks 40 have a larger, particularly significantly larger, area than the remaining cells 20 of the stent frame. The hooks 40 can serve as anchors to more tightly attach the stent to the location of the natural mitral valve, which should be treated and / or replaced.

[0084] It can also be seen that the hook 40 begins at the transition T between the first part 16A and the second part 16B. They are formed by two adjacent arms 14 connected to each other. In particular, the tip 41 of the hook 40 is formed by the vertices of the corresponding rhomboid cell 20. Furthermore, the shape of the hook 40 generally follows the sac-like shape of the first part 16A, although its diameter is larger than that of the first part 16A.

[0085] exist Figure 1 In one embodiment, the stent 10 further includes additional struts 42 formed at the second portion 16B and the transition portion T. These struts 42 also extend outwards, acting like barbs to more precisely and securely attach the stent to the heart. The struts 42 in the illustrated embodiment have a straight shape and a relatively short length.

[0086] The length of the support can be selected from 25% to 75% of the length of the corresponding cell 20 included between the two vertices of the cell 20 parallel to the vertical axis A, particularly from 40% to 60%.

[0087] exist Figure 1 It can also be seen that the support column 42 is fixed at the connection point 18 of the arm 14. For this reason, the connection point may include an eyelet (not shown), to which the support column 42 can be fixed.

[0088] Part 16B also includes a valve 22 made of dried bovine pericardium and a skirt 24 made of dried bovine pericardium and polyester. The valve 24 typically includes two to six leaflets 26, which can be attached to the support frame 12, for example, at an opening 28 at an arm 14 located at the second end 17B of the support frame 12 (see...). Figure 1 and Figure 2 Therefore, the stent 10 also includes a first end portion 17A at the first portion 16A. In the depicted embodiment, the valve 22 includes three leaflets 26 attached to three arms 14 at the second end portion 17B of the stent 10. Figure 1 As shown, two eyelets 28 can be provided at each arm 14. It can also be seen that the eyelets 28 are located where two adjacent leaflets 26 meet, so that both leaflets 26 can be sewn onto one arm 14. Therefore, with two eyelets provided on one arm 14, the support 10 includes one eyelet 28 for each leaflet 26 at each arm 14.

[0089] The orifices 28 are arranged such that they are positioned at the apex between two directly adjacent leaflets 26, and the regions of each leaflet 26 at the apex are fixed to the orifices 28 so that the drying valve 22 is stabilized in the region to ensure that the leaflets 26 can function properly (i.e., open and close) even in the region of the apex.

[0090] Generally, each arm 14 may also be provided with an eyelet 28. The exact number of arms 14 to be provided with an eyelet 28 can be selected according to the application. For example, if a valve 22 with only two leaflets 26 is selected to be placed within the support 10, then only two arms 14 may be provided with an eyelet 28. On the other hand, in some embodiments, the eyelets 28 may always be provided in two adjacent arms 14 in order to secure two adjacent leaflets 26 to the support frame 12 (see Figure 2 ).

[0091] Due to the anatomical reasons of the left ventricle and left atrium of the heart, the skirt 24 not only surrounds the valve 22 at the second part 16B, but can also cover up to 100% of the stent 10 to prevent leakage between the stent 10 and the patient's heart. Figure 2 and Figure 3 In this implementation, most cells 20 are covered by the skirt 24. Only some cells 20 in the second part 16B are covered by the skirt 24, while the other cells, namely those between the leaflets 26, are ignored.

[0092] The external contour of the support 10 according to the invention can be described as being bladder-shaped at the first portion 16A and cylindrical at the second portion 16B. Starting from the first end 17A, the first portion 16A then transitions to the transition portion T, and then to the second portion 16B. It can be seen that the maximum outer diameter of the first portion 16A is significantly larger than the maximum outer diameter of the second portion 16B.

[0093] Generally, the external profile is selected to fit the shape of the valve to which it is installed, so as to create a tight interference fit with the mitral valve and ensure that the position of the stent 10 does not change over time. Once positioned, this interference fit can add a small but additional stability to the valve 22.

[0094] To attach the stent 10 to its respective point of interest, namely the mitral valve, the stent 10 may include additional eyelets (not shown) at its respective first end 17A and second end 17B. That is, after expansion, the stent 10 is not only secured in place by being installed in the mitral valve, but also by being sutured to the wall of the heart. The exact attachment point and technique can be selected according to the different conditions inside the different hearts being treated with the present invention.

[0095] The ends 30 of the arms 14 at both ends of the stent 10 may lie in the same plane. The orifice for attaching the stent to the mitral valve (not shown) may include a rectangular outer shape with a rectangular opening for suturing the stent 10 to the aorta. Typically, the orifice may also include different shapes, such as circular, both externally and internally. The orifice 28, as well as the orifice for suturing the stent 10 to the artery, may extend beyond the common plane of the ends 30 of the arms 14 and cross another common plane.

[0096] Additionally, the support 10 includes a means for attaching the support 10 to the conveying device (see...). Figure 1 The conveying device also protrudes beyond the common plane of the end 30 of the arm 14 through the eyelet 32.

[0097] Finally, Figure 4 and Figure 5 The images show different CT images of stent 10, which has been placed at the patient's mitral valve, preferably using the delivery device as described above. This delivery device is prior art and therefore will not be described in detail. Figure 4 and 5 The same stent 10 is shown from different angles. As can be seen in those CT images, the stent 10 is in an inflated state and has been placed in the patient's natural mitral valve to replace it.

[0098] Figure Labels 10 supports 12 frames 14 arms 16A Part 1 16B Part 2 17A First End 17B Second End 18 connection points 20 cells 21 Larger cells 22 valves 24 skirts 26 small leaves 28-hole eye The end of the 30-arm 32-hole eye 40 hooks 41 tip 42 pillars A (vertical axis) T-transition section

Claims

1. A self-expanding stent for placement on the mitral valve annulus, capable of self-expanding from a non-expanded state to an expanded state, said self-expanding stent comprising: A support frame (12) having at least a first part (16A) and a second part (16B) arranged on the longitudinal axis (A) of the support, wherein the support frame (12) is composed of a plurality of continuous arms (14) which are connected to each other at connection points (18) to form a mesh structure with rhomboid cells (20); A dry valve (22) is disposed at least at the second portion (16B) of the stent. The skirt (24), which surrounds the drying valve (22) and comprises at least one material selected from pericardium and polyester, and In the expanded state, the maximum outer diameter of the first part (16A) is greater than the maximum outer diameter of the second part (16B), and At least at the transition (T) between the first part (16A) and the second part (16B), some continuous arms (14) extend outward beyond the mesh structure to form hooks (40), which face the first part (16A). The hook (40) is formed by two adjacent arms (14) that are connected to each other. Its features are, The dried valve (22) is a dried valve made from bovine pericardium, which is used for rehydration with a solution. The support frame (12) also includes an additional support column (42) arranged at the second part (16B), the additional support column (42) extending outward beyond the mesh structure and facing the first part (16A) to form an additional anchor.

2. The self-expanding stent according to claim 1, characterized in that, The tip (41) of the hook (40) is formed by the vertices of each rhomboid cell (20).

3. The self-expanding stent according to claim 1, characterized in that, The support frame (12) also includes an additional support column (42) arranged at the transition (T) between the first part and the second part (16A, 16B), the additional support column (42) extending outward beyond the mesh structure and facing the first part (16A) to form an additional anchor.

4. The self-expanding stent according to claim 1, characterized in that, The additional support (42) is fixed at the connection point (18) of the arm (14).

5. The self-expanding stent according to claim 1, characterized in that, At the transition (T) between the first part and the second part (16A, 16B), all the arms (14) of the first part (16A) extend outward relative to the second part (16B).

6. The self-expanding stent according to claim 1, characterized in that, The first part (16A) includes a portion of a generally sac-like shape, and / or the second part (16B) includes a generally cylindrical shape.

7. The self-expanding stent according to claim 1, characterized in that, The end (30) of the arm (14) of the first part (16A) is radially inward, and / or the end (30) of the arm (14) of the second part (16B) is arranged parallel to the longitudinal axis (A).

8. The self-expanding stent according to claim 1, characterized in that, At least some cells (20) of the first part (16A) are greater than cells (20) of the second part (16B).

9. The self-expanding stent according to claim 1, characterized in that, The dry valve (22) includes 2 to 6 leaflets (26), wherein the leaflets (26) are fixed to the support frame (12) at the fixation point of the second part (16B).

10. The self-expanding stent according to claim 9, characterized in that, The drying valve (22) comprises 3 or 4 leaflets (26).

11. The self-expanding stent according to claim 1, characterized in that, The dried veal pericardium has a maximum tensile stress selected in the range of 20 to 25 MPa, and / or the rehydrated veal pericardium has a tensile stress selected in the range of 12 to 15 MPa.

12. The self-expanding stent according to claim 1, characterized in that, The calcium content of dried veal pericardium is selected in the range of 0.01 to 0.1 g / kg.

13. The self-expanding stent according to claim 1, characterized in that, The skirt (24) is arranged to cover at least the second part (16B) from the inside.

14. The self-expanding stent according to claim 13, characterized in that, The skirt (24) is arranged to cover the first part (16A) from the inside.

15. The self-expanding stent according to claim 14, characterized in that, The skirt (24) is arranged to cover the entire support frame (12) from the inside.

16. The self-expanding stent according to claim 1, characterized in that, All ends (30) of the arm at the first end (17A) and the second end (17B) are located in the same common plane.

17. The self-expanding stent according to any one of claims 1 to 16, characterized in that, The bracket (10) further includes an eyelet (32) disposed at a first end (17A) of the first portion (16A) for attaching the bracket (10) to the conveying device.

18. The self-expanding stent according to claim 16, characterized in that, The bracket (10) further includes an eyelet (32) disposed at a first end (17A) of the first portion (16A) for attaching the bracket (10) to a conveying device that extends beyond the common plane of the end (30) of the arm (14), wherein the eyelet (32) is located in another common plane.

19. The self-expanding stent according to claim 17, characterized in that, The eyelet (32) of the first part (16A) protrudes inward relative to the longitudinal axis (A).

20. The self-expanding stent according to claim 19, characterized in that, The eyelet (32) follows the same profile as the end (30) of the arm (14) of the first part (16A) away from the transition (T).

Images