Improvements for balloon-expandable and self-expandable prosthetic heart valves and valve delivery systems

Abstract

The present invention includes improvements to the design and construction of prosthetic heart valves having leaflet structures formed by polymer components, particularly expandable and collapseable structural supports. Improved manufacturing techniques are also provided to enable improved design and performance of the prosthetic valves. Similarly, improvements to delivery systems for specific valve designs described herein are also provided. The improvements include improvements to both balloon-expandable and self-expanding prosthetic valve structures, and improvements to the prosthetic valve, manufacturing process components, and delivery systems, respectively.

Description

Background Art

[0001] (Background of the Invention) Diseases of the heart valves are an important factor in cardiovascular insufficiency and death. When a patient suffers from valvular heart disease, one treatment is surgical replacement of the diseased or malfunctioning valve with a prosthetic valve. The first cases in which prosthetic heart valves were used to replace a patient's diseased or malfunctioning valve required open chest surgery to allow for external access to the heart and the ability to surgically implant the replacement prosthetic heart valve at the target site of the diseased native valve. To avoid the need for open chest surgery, physicians and engineers have developed minimally invasive techniques and devices in which the new prosthetic valve can be crushed to a very narrow diameter, confined inside the end of a catheter, and introduced at a peripheral point within the patient's vasculature, such as an artery inside the thigh. Using a minimally invasive catheter, the prosthetic valve is advanced through the patient's circulatory system until it reaches the location where prosthetic valve replacement is needed.

[0002] Prosthetic valves suitable for a minimally invasive approach must have several unique design and performance characteristics, such as the ability to be radially crushed to a small diameter inside a delivery catheter so that the prosthetic valve can be introduced into the patient's vasculature and then expanded at the target site within the patient's heart. Once proper placement of the prosthetic valve in the crushed state is achieved, some valves are designed to self-expand and other prosthetic valves are expanded using a balloon incorporated into the delivery catheter. The ability to implant a prosthetic heart valve through either a balloon-expandable delivery system or a system designed for a self-expanding valve played an important role in the early stages of this minimally invasive technique, which is known in the industry as transcatheter aortic valve replacement (TAVR).

[0003] TAVR technology thereby facilitates the placement of collapsible prosthetic heart valves in a minimally invasive manner for replacing affected natural valves. Collapsed prosthetic valves typically contain movable leaflets that form a portion of the valve that opens and closes in response to blood pressure pulses occurring across the valve. The leaflet portion of the prosthetic valve is formed inside a metal stent structure frame that is itself collapsible to a size smaller than the inner diameter of the delivery catheter and expandable to a predetermined diameter within the patient's natural heart annulus. In practice, the prosthetic valve is manufactured in an expandable configuration and then later crimped to a size smaller than the inner diameter of the delivery catheter. In balloon-based delivery systems, the prosthetic valve may be configured to surround or be placed in immediate proximity to an inflatable balloon that expands inside the heart to engage the prosthetic valve with the patient's heart at the target site. Other valve designs are designed to self-expand so that the process of releasing the valve from the delivery catheter causes the valve to expand in position. In either case, whether using self-expansion or balloon inflation of the valve, the valve and delivery system must have special design features to take advantage of minimally invasive TAVR.

[0004] The use of self-expanding and balloon-inflatable valves in the TAVR approach has rapidly expanded in the years following the original pioneering research, leading to the TAVR procedure becoming more widely adopted. As the safety of the TAVR procedure has been established in large, multicenter clinical trials confirming the safety and efficacy of TAVR using both self-expanding and balloon-inflatable valves, a series of modifications to both prosthetic valves and delivery systems have been introduced over the past two decades. However, many challenges remain in developing prosthetic valves for the TAVR procedure, as the valve design itself must provide adequate function for years to decades inside the patient's heart, without structural or mechanical failure and without chemical or biochemical degradation, over billions of opening and closing cycles inside the beating heart over decades of use following implantation in the patient. This ability to function continuously over many years and billions of cycles also requires a delivery system that places the prosthetic valve into the natural annulus with significant precision, so that the deployment of the prosthetic valve from the distal end of the delivery catheter can be controlled carefully and in a manner that allows the surgeon to verify in real time that the prosthetic valve is properly placed. For this reason, there is always a need to develop improved designs for prosthetic heart valves, their components, and delivery systems for minimally invasive heart valve replacement procedures.

[0005] Current prosthetic valve replacement options can also be limited by structural valve degeneration, requiring reoperation to replace or repair the original prosthetic valve, or creating the need for lifelong treatment with anticoagulants. In addition to simple mechanical failures, many existing designs incorporate animal tissue as part of the valve leaflets, and these animal tissue materials can react with human blood and be subject to calcification or the formation of blood clots or thrombi, threatening their long-term efficacy following implantation. To circumvent some of these drawbacks, new polymer technologies have been developed in recent years with the expectation of creating ideal polymer heart valve substitutes that overcome these limitations. Polymeric materials and prosthetic valves using these materials are described in U.S. Patents and Publications 9301837, 9539089, 10918477, 10213833, 10286657, 10723844, 11534293, 11129712, and U.S. Publications 20190060061A1, 11000369, and U.S. 20210038379A1 (specifically incorporated herein by reference). These compounds and prosthetic valve devices are in various stages of research and development and have both unique advantages and design and manufacturing challenges inherent in the use of polymers and the nature of prosthetic valves that incorporate polymers into the overall design of the valve itself and the delivery system.

[0006] Therefore, research and development of improved valve structures, delivery systems, and manufacturing methods will continue to improve the performance of prosthetic heart valves for the TAVR approach. In particular, when polymer materials are used, there is a continuing need for new inventive designs and configurations for the valve structure itself, specific manufacturing methods using polymer materials, and improved designs for delivery systems for such prosthetic devices in order to advance the clinical acceptance of such surgical techniques and devices and improve the health of patients with valvular heart disease. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] U.S. Publication No. 9,301,837 [Patent Document 2] U.S. Publication No. 9,539,089 [Overview of the project] [Means for solving the problem]

[0008] (Brief summary of the invention) The present invention includes improvements to the design and construction of prosthetic heart valves having a leaflet structure formed by polymer components, particularly expandable and collapsible structural supports. Improved manufacturing techniques are also provided to enable improved design and performance of such prosthetic valves. Similarly, improvements to delivery systems for specific valve designs described herein are also provided.

[0009] Specifically with respect to the prosthetic valve design and structure, the expandable support structure has an open frame design to provide better fluid access to the coronary arteries within the heart and to protect the polymer valve leaflet structure from collision with the frame during introduction and deployment. The support structure consists of a grid of individual cells, sized and configured to form a one-piece structure that can be compressed during a crimping step, allowing the polymer used to form the valve leaflets to be integrally molded with the grid, and the expanded valve configuration to be crimped to a smaller diameter required for introduction into the reduced diameter of the delivery catheter. The frame design may be formed from either polymer or shape memory metal, and both options provide a collapseable structure having an initial configuration that is manufactured and designed in accordance with deployment after confinement in the collapse configuration within the delivery catheter. The aspect ratio, height-to-width dimension and ratio, and other dimensional parameters are optimized to reduce the strain induced on the polymer incorporated into the polymer valve leaflet structure and the individual cells of the grid support structure.

[0010] The secondary support structure is incorporated into the primary support structure to minimize the deflection of the commissural portion, i.e., the point where adjacent polymer leaflets join to the support structure, along its length in a given configuration, for optimal performance of the expandable support structure and improved coordination with the polymer leaflet material. On one side, the geometry of the individual struts of the support structure avoids contact with the polymer leaflets during the crimping process. The secondary support struts also isolate the prosthetic polymer leaflets to prevent damage when the prosthetic valve is deployed and displaces the natural leaflets at the target annulus. In advanced valvular disease, calcified natural leaflets in the patient may collide with the new polymer leaflets in the prosthetic valve, mechanically damaging the valve and thereby reducing its long-term viability. The designs disclosed herein anticipate this potential problem and configure the prosthetic valve to avoid damage in this system.

[0011] Furthermore, with regard to the improved design of the prosthetic valve, the prosthetic valve has both an inlet portion into which blood first enters the prosthetic valve and a downstream or distal outlet portion of the valve structure into which blood moves away from the longitudinal dimension of the prosthetic valve. According to the present invention, a self-expanding sealing skirt is configured to surround the outlet portion of the prosthetic valve and to surround the collapsible support structure circumferentially. The self-expanding sealing skirt can be used in combination with a self-expanding support frame having polymer leaflets, or in combination with a balloon expandable support frame having polymer leaflets. The inner wall of the self-expanding sealing skirt is coated with polymer to prevent any metal-to-metal abrasion with the inner leaflet frame. The sealing skirt has a predetermined height at the inlet portion of the support structure and has two distinctly different geometric configurations. At the end closest to the inlet portion, the sealing skirt is substantially annular and conforms to the circumferential portion and shape of the expandable support stent. At the opposite end closest to the outflow portion of the prosthetic valve, the sealing skirt has a corrugated or undulating shape, and the portions of the sealing skirt spaced apart around the outer portion of the annular support structure are not attached to the outer layer of the support structure. These non-attached portions of the corrugated edge extend radially outward from the access of blood flow through the valve and can provide an additional sealing structure around the outer wall of the support structure against leakage passing in the direction of blood flow, and provide a series of additional attachment points around the outer portion of the inflow portion of the prosthetic valve.

[0012] The structural frame also includes markers incorporated into the structural frame, detectable through existing imaging modalities, to enable annular alignment and positioning of the prosthetic valve within the natural valve annulus. While several different geometric shapes are possible, the markers may be formed as part of the structural frame as open cavities between adjacent cells of the frame structure. The markers are placed in unique or multiple locations as part of the structural frame so that the images generated by the markers can be used for both annular alignment and positioning relative to the coronary artery within the natural valve annulus. More than one marker may be used, but the markers should be symmetrical, either as a single structural feature or as a structural feature that uniquely and easily communicates the location of the structural frame element using an imaging modality.

[0013] Another improved embodiment of the prosthetic valve features a two-part valve assembly including a separate sealing skirt frame that unfolds separately from the assembly comprising the prosthetic valve leaflets. In this embodiment, the sealing skirt frame is first expanded to engage with the natural valve annulus and retract the existing affected valve leaflets and valve structure. Next, the support structure containing the polymer valve leaflets unfolds to contact the sealing skirt frame and provide an integrated prosthetic valve assembly. One or both of the primary sealing skirt frame or the secondary valve leaflet frame contains structural features for the interlocking engagement of the two components of the assembly. This embodiment allows for a smaller total outer diameter in the collapse configuration of one or both components compared to a one-part assembly. As described below, this embodiment may feature a two-balloon delivery catheter employed with each of the sealing skirt frame and polymer valve leaflet frame, which are positioned around the periphery of two inflatable balloons and incorporated into a single delivery system.

[0014] Regarding the improved manufacturing process, the manufacturing method enables a closed-cell self-expandable or balloon-expandable heart valve frame that is immersion-cast in polymer without the need for an open-cell structure or lattice in the support frame. In this process, polymer leaflets are formed without integral connection to the support frame. The leaflets are independently cured, measured, and trimmed prior to attachment to the structural frame. Subsequently, the leaflet and frame masks are attached to the frame and leaflet assembly to prepare for the subsequent immersion step, and the polymer flows around the unmasked struts of the structural frame, bonding selected unmasked portions of the leaflets to the structural sidewalls using the immersed polymer. Following that step, the leaflets in the structural frame assembly are placed in an ambient humidity chamber to complete the formation of the assembly under specified conditions. Following exposure to ambient humidity chamber conditions, the masking of the leaflets and frame is removed, and the assembly is subsequently cured to produce the final prosthetic valve structure and assembly. See U.S. Publication No. 20190060061A1 (which is incorporated herein by reference).

[0015] In another improved manufacturing process embodiment, the sealing skirt is formed on the structural frame by electrospinning directly onto the frame. The skirt and structural frame are joined with a separate polymer valve leaflet structure using a valve leaflet mask, and the cured polymer valve leaflet structure is attached to the expandable frame, completing the outflow edge seal across the sealing skirt in the same process. The valve assembly is completed by sealing the inflow edge at the base of the frame to both the frame and the sealing skirt, completing the assembly of the structural frame and the cast polymer valve leaflet.

[0016] With respect to the improved delivery system, the improvements comprise both additional features that can be incorporated into the delivery system to improve the performance of valve deployment of prosthetic valves of any design and configuration, as well as specific improved designs of the delivery system that, advantageously, facilitate the deployment of specific prosthetic valve designs described herein that use polymer leaflet materials. An embodiment includes a deflectable member at the distal end of a catheter-based delivery system that locates the natural aortic sinus, allowing for easier visualization of the natural valve annulus and sinus, thereby leading to more accurate and stable deployment in either a self-expanding or balloon-expandable system. The deflectable member extends from a portion of the delivery system proximal to its distal end such that feedback delivered to the user via engagement between the deflectable member and the natural valve annulus guides the precise deployment of the prosthetic valve. The deflectable member is radiopaque so as to be visible under imaging modalities.

[0017] In another embodiment, a three-balloon delivery system consists of separate balloons having three expandable members, which are combined with a common expansion system such that these three expandable members or lobes inflate independently and selectively engage and interact with only one of the valve commissations, and not with the valve leaflets. In this approach, the polymer valve leaflets are isolated during balloon expansion. This design protects the polymer valve leaflets and prevents any balloon-leaflet contact that could cause damage to the polymer valve leaflets during the balloon-based valve deployment process. In addition to the three-balloon system, delivery systems with more than three balloons, including up to six or more balloons, are provided to facilitate round or more circular deployment into the inner diameter of the natural valve annulus. In this embodiment, three primary expansion balloons expand to bring the prosthetic valve into contact with the natural valve annulus, and one, two, or three smaller balloons, positioned tangentially on the outer surfaces of the three primary balloons, provide more circular deployment of the prosthetic valve and engage with the natural valve annulus. The three main or primary inflation balloons interact only with the valve commissure shape and not with the valve leaflets. The smaller secondary balloons interact only with the frame located beneath the valve leaflets and are sized so as not to come into contact with the polymer valve leaflet structure.

[0018] Another improvement to the delivery system involves the distal end of the delivery catheter having a tear-open sheath, allowing for easier access to smaller introducers and patient vascular anatomical structures. When a larger object is pushed through the distal tear-open sheath, the distal end opens in a zipper manner along a perforation line manufactured to a specified length of the distal end of the delivery catheter. The remaining (zip-open) sheath has an outer diameter for housing the valve and the introducer of the delivery system. Once the crimped valve assembly has passed through the sheath, the sheath collapses to a smaller outer shape resulting from a linear reduction of the outer shape along the length of the tear-open region. The tear region may have a linear set of openings, or other geometric configurations with perforations or openings at the distal end, where a progressive tear in sequential openings perforating the length of the distal end of the delivery catheter allows the prosthetic valve to be deployed by expansion. Once the tear-opening process is complete, the overall diameter of the distal end of the delivery system collapses to a smaller profile than a comparable delivery catheter, allowing for improved techniques to remove the delivery catheter through the length of the patient's blood vessel. In all cases of development in delivery catheter re-entry, some degree of inherent trauma occurs along the wall of the patient's blood vessel. A reduced-diameter delivery catheter inherently reduces the trauma that occurs in response to the removal of the delivery system, leading to the less traumatic complete removal of the length of the delivery system catheter.

[0019] An additional improvement to the minimally invasive delivery system is that a two-balloon delivery system consists of a distal balloon embedded in a delivery catheter, which is first used for pre-dilation of the natural valve annulus. Once pre-dilation is complete, the distal balloon is reduced and moved forward or distally to allow the deployment of a separate proximal balloon containing a crimped valve that engages with it in a surrounding manner. In this configuration, the surgeon may perform both separate natural valve dilation and subsequent valve deployment procedures using the same delivery device and system. In any of the balloon deployment embodiments described herein, the balloon positioned to engage with the prosthetic valve may be tapered proximal to its distal end. In such a configuration, the distal end of the balloon may have a larger distal diameter and a smaller proximal diameter, which may be formed in discrete steps from distal to proximal, and / or may have a smoothly tapered outer diameter reduction that facilitates a firm engagement of the distal end of the prosthetic valve with the natural valve annulus without applying pressure or stress to the more proximal portion containing the valve leaflet assembly. [Brief explanation of the drawing]

[0020] [Figure 1] Figures 1A and 1B show prosthetic flaps having marker bands or structures incorporated into a structural frame for annular orientation and alignment with the coronary arteries.

[0021] [Figure 2A] Figures 2A, 2B, and 2C show complete frame, corrugated frame, and open frame designs for the structural frame or stent member of a prosthetic valve. [Figure 2B] Figures 2A, 2B, and 2C show complete frame, corrugated frame, and open frame designs for the structural frame or stent member of a prosthetic valve. [Figure 2C] Figures 2A, 2B, and 2C show complete frame, corrugated frame, and open frame designs for the structural frame or stent member of a prosthetic valve.

[0022] [Figure 2D]Figure 2D shows a two-part structure having a single immersion-cast valve leaflet and a separate sealing skirt with internal and external seals, both parts configured to engage with each other in an interlocking relationship and lockable manner to form an integrated prosthetic valve assembly. The two-part structure can be mechanically joined via sutures, rivets, and / or welding of the two frames.

[0023] [Figure 3] Figure 3 shows the design for the structural frame sidewall, which is sized and molded to allow the polymer valve leaflets to collapse when the prosthetic valve is crimped into the collapse configuration within the delivery catheter, and the aspect ratio A:B of the individual cells is maximized to reduce the strain induced on the polymer. In the right panel, the prosthetic valve is shown in the collapse configuration to illustrate the advantages of the aspect ratio of the individual cells and the reduced strain induced on the polymer structure.

[0024] [Figure 4] Figure 4 shows a secondary support structure incorporated into a structural frame support member or stent to create a larger, complete frame C at the outflow end of the grid of the support structure frame.

[0025] [Figure 5] Figure 5 shows a self-expanding sealing skirt that opens alongside the balloon-expandable frame and functions as a separate sealing skirt that sits on top of the structure at the inlet end of the support structure at D.

[0026] [Figure 6] Figure 6 shows a molded sealing skirt at the inlet edge of a prosthetic valve, which may have a corrugated shape for improved sealing against the natural valve ring.

[0027] [Figure 7] Figures 7A and 7B show the positioning of the stent frame on the mold during the manufacturing process, and are molds used in the manufacturing process to produce closed-cell self-expandable or balloon-expandable prosthetic valves.

[0028] [Figure 8] Figure 8 shows valve leaflet and sidewall masks for the manufacturing embodiments of Figures 7A and 7B, including locking features, cavities for frame supports, and fin masks.

[0029] [Figure 9] Figure 9 is a schematic manufacturing process with step-by-step graphics illustrating the manufacturing process in which immersion-cast valve leaflets are initially created on a mold without any accompanying frame, and when combined with a structural frame, they form separate polymer valve leaflet components for a prosthetic valve assembly. This allows for quality rejection testing of the isolated valve leaflet structure itself, without assembly to a frame.

[0030] [Figure 10] Figure 10 is a schematic diagram with stepwise graphics of the alternative manufacturing process for the embodiment of Figure 9, in which the valve leaflets are hardened in the alternative configuration.

[0031] [Figure 11] Figure 11 is a schematic diagram with step-by-step graphics of a manufacturing method in which the valve is assembled by first electrospinning the polymer directly onto the frame and then joining the cast polymer valve leaflets to the frame.

[0032] [Figure 12] Figure 12 shows a two-part balloon catheter having a sealing skirt and a distal portion to facilitate the two-part deployment of the structural frame and polymer valve leaflets.

[0033] [Figure 13] Figure 13 shows a delivery system with a distal probe that provides feedback to the user for positioning the prosthetic valve within the natural valve annulus.

[0034] [Figure 14]Figure 14 shows a three-lobe or three-balloon design in which individual lobes or balloons are aligned with the commissural portion of the prosthetic valve to protect the polymer valve leaflets from damage during deployment.

[0035] [Figure 15] Figure 15 is a schematic diagram of a three-lobe or three-balloon embodiment having both a primary and a secondary inflation balloon, the secondary inflation balloon being positioned tangentially along the primary inflation balloon and arranged longitudinally, resulting in an alternative deployment strategy and engagement of the prosthetic valve along the length of the balloon member.

[0036] [Figure 16] Figure 16 shows a tear-open sheath that opens along the perforation line during valve deployment, resulting in a reduced diameter outer shape.

[0037] [Figure 17] Figure 17 shows a delivery system with a distal balloon embedded in a catheter, used for pre-dilation of the natural valve annulus. [Modes for carrying out the invention]

[0038] (Detailed description of the invention) Before the subject matter is described in detail, it should be understood that this disclosure is not limited to the specific embodiments described and is therefore naturally subject to change. Furthermore, it should be understood that the terminology used herein is for the purpose of describing only specific embodiments and is not intended to be limiting, as the scope of this disclosure will be limited only by the appended claims.

[0039] The exemplary embodiments described herein relate to improved implantable prosthetic valves, such as prosthetic heart valves, having a support structure, stent, or frame coupled with two or more leaflets, and techniques for the manufacture and manufacturability of implantable valves. These embodiments are particularly suited for artificial (non-biological tissue) polymer leaflets, and the resulting prosthetic valves offer advantages comparable to current approaches, with the additional benefit of a longer lifespan. Valves with polymer-based leaflets are advantageous because the polymer can provide the same structural support as biological tissue, while allowing the valve to be much thinner and more easily shrunk for delivery. This, in turn, results in less stress on the polymer when it is shrunk, which prevents long-term degradation of the leaflets. In addition, the manufacturing methods described herein allow for the fabrication of valves without suturing or molding the leaflets to a support structure or stent, thus promoting high-quality, reproducible results.

[0040] The embodiments described herein are particularly suitable for all applications relating to heart valves, but are also suitable for use in conjunction with stents and stent graft devices, or other medical devices that can be implanted in the human body.

[0041] Referring to Figures 1A and 1B, the prosthetic heart valve 1 incorporates a visible marker band 12 (indicated by an arrow in Figure 1A) as part of the heart valve frame 10 to assist in both annular and coronary alignment. In combination with the imaging modality, the marker band 12 facilitates the precise placement of the prosthetic valve and gives the user or surgeon improved control over coronary alignment, which in the long term allows for better circulatory access to the coronary arteries and increased blood flow into the coronary arteries. The marker 12 may be a separate structure positioned within the grid 11 of the valve frame 10, or it may be incorporated into the structure of the stent frame 10 and integral with the stent frame at any point along the frame 10 or grid 11. The stent frame 10 or grid 11 may consist of cells having multiple sizes, such as smaller 13 and larger cells 14, with the marker band 12 operably positioned between cells of different sizes to assist in the visualization and orientation of the valve 1 or stent frame 10.

[0042] Multiple markers 12a, 12b may be positioned at circumferential points around the outer portion of the valve 10 and may be distinguished from one another by size, design structure, or location for orientation around a radius or horizontal axis traversing the internal flow path of the valve 1. In one embodiment, the multiple markers 12a, 12b have distinct appearances under imaging modality and are displaced both vertically and horizontally from one another, allowing for distinct visualization and alignment under imaging modality. The markers will typically be fully encapsulated in a polymer. An imaging modality capable of enabling the user to visualize the presence and orientation of the markers is coupled with the valve delivery system. Together, this combination of the stent frame 10, valve leaflets (see below), and other structural features described herein forms an integrated unit for transvascular delivery of the valve 1, along with the ability to orient the valve 1 using an imaging modality for real-time detection and visualization of the presence and orientation of the markers. The incorporation of visually detectable markers 12 into the stent frame 10 also allows a surgeon to visualize the marker band using an imaging modality and rotate the stent frame 10 of the valve 1 for alignment with the natural annulus and coronary arteries of the heart. This method involves using a minimally invasive technique to advance the valve 1 through the patient's blood vessels, using the markers to position and orient the valve 1 with respect to one or both of the natural annulus and coronary arteries, and then deploying the valve to act as a prosthetic valve in place of the affected natural valve.

[0043] The structure of individual visible markers 12 may be circular, oval, or have open cavities in other configurations for structurally creating visually detectable frame markers 12. When having open cavities, the markers 12 may be formed directly and integrally as part of the stent frame 10 for both annular alignment with the natural valve annulus and / or coronary alignment with the coronary arteries. As described above, the stent frame 10 is made of a shape memory material such as metal or polymer, and the integral incorporation of the marker bands 12 can be easily fabricated using either material. The markers 12 may be preferentially placed on one side of the stent frame 10 to provide improved visibility, and the method of oriented the markers may include oriented one side of the stent frame 10 to a specific position with respect to the natural valve annulus or coronary arteries, and visibility may occur when the valve 1 and the stent frame 10 are in either a collapsed or expanded configuration.

[0044] Referring to Figures 2A-2C, the improvement to the heart valve structure is the use of an open frame design to allow for better coronary artery access. These open frame designs, accompanied by a single strut support structure 17, also prevent leaflet collisions with the heart valve framework during function, which can lead to premature failure of the valve implant. The frame design is shaped to provide structural support along the outer shape of the leaflet. The struts are designed in a manner that follows the curved shape of the leaflet. The frame remains open where there is no leaflet. This provides an open volume for both blood flow to the coronary sinus during valve function and easy catheter access after any coronary artery procedure. The open area is reinforced by an additional frame structure, which may consist of either a single V-shaped strut running across each leaflet body or rhomboid struts covering the open area circumferentially. The rhomboid cells may be larger than the cells located on the leaflet sidewalls to allow for a larger access site for coronary catheters. The frame structure within the open area will not be coated with polymer to eliminate the possibility of embolism caused by thin polymer detachment during valve compression and expansion.

[0045] Referring to Figure 2D, the multi-component prosthetic heart valve assembly 20 comprises a separate heart valve structure-supporting stent frame, with the inner frame 21 having the size and dimensions as further described below. The inner frame component 21 contains the valve leaflets and a separate sealing skirt 23a. The second component is a separate outer frame 22 containing the sealing skirt 23b. Both structures have a stent frame 24 formed from polymer or shape memory metal to traverse from a collapsed configuration to an expanded configuration and to the separate sealing skirt as described herein. The single-component frame 21 includes a full frame docking portion with a subframe containing the valve leaflets 25. This improvement would enable a dual-frame structure and allow for an overall reduced diameter during the placement of the prosthetic heart valve. This allows the inner frame 21 to be crimped onto the delivery system independently of the outer frame 22 holding the sealing skirt. This independent crimping of both valve structures would reduce the catheter outline by distributing the valve structures axially along the length of the catheter. The independent deployment of the valve structures 21 and 22 reduces the outer diameter of the delivery system, thus leading to a smaller delivery profile through the inlet sheath. The structure has a single immersion-cast valve leaflet 25, and separate sealing skirts 23a and 23b allow for both internal and external sealing, and the components of both assemblies 21 and 22 are capable of interlocking relationships such that the two elements of assemblies 21 and 22 are structurally locked together to form an integrated prosthetic valve assembly. The internal frame 21 may include a tridentate projection that aligns with a slot located within the external frame 22, which self-aligns during valve expansion. The mechanical locking mechanism may also incorporate a peg and hole design, allowing a standoff on the internal frame 21 to align with a similarly shaped cavity within the external frame 22, which is mounted on the external frame 22 using the mechanical expansion of the internal frame 21.

[0046] The deployment method for the two-part valve assembly includes the deployment of a separate outer sealing skirt frame 22, which is first deployed over the natural valve leaflets. Next, the inner frame 21 containing the valve leaflets is deployed within the separate sealing skirt frame 22. The meshing engagement is created by the inner frame 21, which includes a trident projection that aligns with a slot located within the outer frame 22, which self-aligns during valve expansion. The mechanical locking mechanism may also incorporate a peg and hole design, which allows standoffs on the inner frame 21 to mesh with similarly shaped cavities within the outer frame 22, which are aligned and mounted on the outer frame 22 using the mechanical expansion of the inner frame 21.

[0047] To facilitate this two-part deployment, the delivery catheter may include two balloons (see Figure 12), with the distal balloon deploying the outer frame 22 first and the proximal balloon deploying the inner frame 21. This allows a single device to operably deploy both structural features of both sealing skirts 23a, 23b into a single, integrated structure that provides sealing engagement between both outer skirts and orients the leaflets 25 as part of the overall assembly 20 in the natural valve annulus. The design of the inner frame design 21 includes features that allow the outer leaflet frame 22 to position and dock with the inner leaflet frame 21. The inner frame 21 may include a tridentate that aligns with a slot located within the outer frame 22, which self-aligns during valve expansion. The mechanical locking mechanism may also incorporate a peg and hole design that allows a standoff on the inner frame 21 to engage with a similarly shaped cavity within the outer frame 22, which aligns and mounts on the outer frame 22 using the mechanical expansion of the inner frame 21. Referring to Figure 3, the support frame 10 of the prosthetic valve 1 has cells 13, 14 of various dimensions, and the varying cell sizes in the frame valve structure increase circulation and retention potential at the valve annulus. As shown in Figure 3 (see arrow), smaller cells 13 at the bottom (inflow portion) of the heart valve also promote even contact with the natural valve annulus, resulting in better PVL results. The frame sidewall cells 18 are sized to allow the polymer to compress during valve compression. The optimal linear dimensions of the larger cells 14 in the distal or outflow portion have a height-to-width ratio (1.5:2) defined by dimensions A, B.

[0048] Referring to Figure 4, the aspect ratio (height to width 1.5:2) between the larger cell 14 and the outflow portion of valve 1 is maximized to reduce the strain induced on the polymer incorporated into the stent frame 10 during crimping. The larger cell 14 with dimension D induces high strain on the polymer, which causes the polymer to tear away from the stent frame 10. The aspect ratio is 1.5:2 between cell height and cell width in the larger cell 14 in the outflow portion and should be greater than 1 to reduce polymer strain during crimping.

[0049] The secondary support structure minimizes commissure deflection. Less commissure deflection is required to reduce valve leaflet distortion and thereby improve valve durability. The strut geometry allows the stent frame 10 to fold when the valve 1 is crimped onto the delivery system (as described below). The geometry of the valve 1 and the secondary support structure is designed not to be crushed over the polymer valve leaflet 25 during crimping. The frame struts that traverse the polymer valve leaflet are designed to bend at the center and remain radially outward during the crimping process. The struts 26 provide a secondary purpose of protecting the polymer valve leaflet 25 from any mechanical damage caused by natural calcification of the valve leaflet. While natural calcification of the valve leaflet helps to anchor the TAVR valve, if the total height of the valve leaflet 25 is too large relative to the linear length of the stent frame 10, the valve leaflet 25 may collide with the stent frame 10, mechanically damaging the valve and potentially leading to premature valve failure.

[0050] Referring to Figures 5 and 6, an improvement to the balloon-expandable heart valve structure is the addition of a self-expanding skirt 23' to the open valve stent frame 10. As shown in Figure 5, the self-expanding skirt 23' can be molded as a tent-like structure, tapering from a larger diameter proximally at the inlet to a smaller diameter distally, closer to but not reaching the midpoint of the entire length of the prosthetic valve 1. The self-expanding sealing skirt is sized to protect the polymer valve leaflets 25 by providing a barrier between the valve structure and the natural calcified valve leaflets. A constant outward radial force on the annulus will push out the calcified natural valve leaflets, preventing them from colliding with the polymer valve leaflets of the prosthetic valve. In this configuration, the self-expanding skirt 23' acts as a leaflet protector, improving the functionality of the prosthetic heart valve implant 1. The self-expanding skirt 23' is machined and oriented to be tightly crimped together with the expandable stent frame 10 for placement at the distal end of a minimally invasive delivery catheter.

[0051] The self-expanding skirt 23' can be formed by electrospinning and opens alongside the balloon-expandable stent frame 10, functioning as a separate sealing skirt 23' and polymer valve leaflet protector 25. The inner wall of the self-expanding structure of the sealing skirt 23' is coated with polymer to prevent intermetallic interactions between the different metals of the self-expanding skirt 23' and the balloon-expandable structure of the stent frame 10.

[0052] Referring to Figure 6, the self-expanding sealing skirt 23' has a corrugated outflow edge 24 of the sealing skirt 23' that provides specific mounting points for improved engagement with the natural valve ring and to actively seal the periphery of the valve 1 and reduce periphery leakage, and allows the unmounted portion of the skirt material to bulge outward by expanding radially outward. The woven PET sealing skirt 23' is attached to an underlying solid polymer inner sealing skirt (not shown) using polymer. Another advantage provided by the sealing skirt 23' is its ability to feature mounting points 28 of the sealing skirt to the valve assembly without sutures, for example, using polymer. The corrugated outflow edge 24 of the sealing skirt 23' will provide specific mounting points 28 that are circumferentially oriented and spaced apart with respect to the periphery of the outer portion of the valve 1. As shown in Figure 6, this will allow the unmounted skirt material at the corrugated outflow edge 24 to bulge outward for emergency valve sealing against periphery leakage (PVL), which will improve function.

[0053] Referring to Figures 7A and 7B, and Figures 8 and 9, the method described herein allows a closed-cell self-expandable or balloon-expandable heart valve frame 10 to be immersion-cast in polymer without the need for an open-cell structure. The frame, which is the closed-cell structure of the heart valve 1, remains rounded during valve compression and deployment.

[0054] Referring to Figure 7, the elements of the initial structure are a mold 30, which has no mechanical mounting or support structure incorporated into the valve 1 prior to the formation of the polymer valve leaflet 25. The mold 30 may be operably meshed with a mask 31 which may be upper (Figure 7A) or lower (Figure 7B) to the stent structure, and the orientation of the mask and molding machine may have either structure at the uppermost part of the assembly prior to the introduction of the polymer for forming the valve leaflet 25.

[0055] Referring to Figure 8, embodiments of the leaflet masks 50, 51 consist of a locking feature 41, a leaflet mask profile fin leaflet 43, and a cavity for receiving a support from the stent frame (from the leaflet side) to reside below for protection during polymer immersion. In this embodiment, the masks 50, 51 interlock with the profile 30 according to the manufacturing embodiments of Figures 7A and 7B, including the locking feature, the cavity 41 for the frame support, and the fin mask, and may be used in the following techniques for selectively applying polymer to the bare profile 30, the frame assembly, and the pre-cured leaflet 25, in particular for immersion of the stent frame 10 and profile 30 assembly prior to being placed in a humidity chamber for polymer curing. Specially designed leaflet masks 51, 52 are preferably applied to the stent frame 10 and polymer leaflet 25 assembly. The use of masks 51, 52 prevents or inhibits polymer intrusion onto the cured valve leaflets 25 or polymer coating over cells of the stent 10 that are intended to remain open for coronary artery access after valve implantation. Masks 51, 52 may include silicone gaskets (not shown) that are circumferentially aligned around the outer edge diameter of the masks to seal against polymer intrusion during the polymer immersion processes 114, 123.

[0056] Referring to Figure 9, the manufacturing process steps include the following, and the structure and assembly are produced as follows:

[0057] 1. The immersion-cast valve leaflet 25 is formed on a new, bare mold 30, in which no stent frame 10 is present. In method step 101, the polymer valve leaflet is formed, measured, and verified to be within critical tolerances and dimensions for assembly into the final prosthetic valve. Once the quality control measurements are deemed to be met, the frame is placed on the polymer valve leaflet, which is still integrated with the bare mold 30, in the next method step. Subsequently, in valve leaflet fabrication method step 103, the valve leaflet 25 is masked with a protective cover 50 prior to the curing of the valve leaflet 25. A frame mask 51 is added to the assembly as shown in Figure 9 as part of the frame masking step 104 to fabricate a complete assembly prior to the application of the liquid polymer. The specially designed valve leaflet 50 and frame mask (see Figure 8) are placed on the frame and valve leaflet assembly. This prevents polymer intrusion onto any cured valve leaflet, or polymer coating over frame cells that are intended to be left open for coronary artery access after valve implantation. Once masked, the assembly is immersed in the polymer with the valve leaflets 25 facing downwards. The polymer is allowed to flow around the unmasked supports of the frame 10, bonding the valve leaflets 25 to the frame assembly 10. The valve leaflet / frame 50, 51 masks may include silicone gaskets (not shown) at their edges to seal against polymer ingress.

[0058] Next, the polymer immersion step 105 integrates the previously formed valve leaflets 25 and stent frame 10 into the integrated assembly, protecting the selective frame 10 and valve leaflet 25 portions of the entire valve 1 from exposure to the liquid polymer. The mold material 30 is immersed with the valve leaflets 25 facing downwards. Following the immersion step 105, the assembly is placed in a humidity chamber for a specified time under specified humidity conditions for polymer thickening, and then the valve leaflets 25 are placed in an oven for a specified time to fully cure (see U.S. Publication No. 20190060061A1 for curing of the immersed polymer). Following curing in the humidity chamber, the frame mask 51 is removed, and the prosthetic valve 1 is placed in an oven to fully cure the assembly. The polymer valve leaflets may be trimmed using either an ultrasonic knife, die cutting, or a laser cutting system.

[0059] A self-expanding or balloon-expandable stent frame 10 is fixed over the cured valve leaflets 25. Once curing is complete, the valve leaflets and frame masking 50, 51 are removed, and the valve 1 is inspected for dimensions, tolerances, and any necessary quality control parameters.

[0060] In another embodiment of the manufacturing process, referring to Figure 10, several steps similar to the methodology in Figure 9 are performed. Once the assembly of the stent frame within the polymer valve leaflets is immersed in the polymer, the frame mask is removed from the humidification chamber and cured in an oven with the valve leaflets facing upward. This embodiment of the valve assembly process allows the prefabricated valve leaflets 25 to cure with the valve leaflet tips (not shown) facing upward, which prevents polymer intrusion across the valve leaflet commissure. The methodology in Figure 10 allows for less polymer use, i.e., when the valve is immersed with the valve leaflets facing upward, polymer use is reduced because, in this orientation, the valve leaflet mask 51 is not immersed in the polymer. Generally, the smaller the surface area of ​​the assembly parts of the mold material 30, stent frame 10, and masks 51, 52 that are immersed in the polymer, the less polymer is extracted from the polymer wells during immersion. The mold 30 includes threads at its base to allow for the attachment of a retainer, which enables the assembly to be placed in an oven with the valve leaflets facing downward for final leaflet curing. This also allows the mold 30 to be held and immersed in two orientations. Thus, the assembly of the mold 30, stent 10, and masks 51, 52 may be immersed in polymer and then cured with the valve leaflets facing either downward (Figure 9) or upward (Figure 10), or a combination of both. In particular, the methodology of Figure 10 is implemented to reduce the total amount of polymer used in methodologies 110-115 with respect to a sufficient portion of the curing process to ensure the benefits of reduced polymer use, and the orientation may then be modified with respect to any preferred further curing process to complete the assembly process. As described above, any process may involve a step of trimming the polymer valve leaflets 25 using either an ultrasonic knife, die cutting, or a laser cutting system.

[0061] With respect to the structural and method steps described above, the formation of the final assembly comprising polymer valve leaflets 25 and a stent frame 20 is designed for either self-expansion upon placement on the natural heart valve annulus, or deployment by a conventional or improved balloon deployment system as described below.

[0062] Referring to Figure 11, another embodiment is a method of assembling the valve by electrospinning a sealing skirt 60 directly onto a frame and joining a cast polymer valve leaflet 25 to a stent frame 10. In the first step 120, the sealing skirt 60 is electrospinned directly onto the stent frame 10. In the next step 121, the valve leaflet 25 is formed by immersing a bare mold material 30 in polymer. Once the polymer valve leaflet 25 is formed, step 121 includes trimming and performing a quality analysis of several parameters of the polymer valve leaflet, including dimensions (height, thickness), overall quality, and qualification of the downstream end of the valve leaflet portion of the overall polymer valve leaflet structure. In the next step, the valve leaflet mask 51, the polymer valve leaflet 25, and the stent frame 10 form an assembly and the outflow edge seal is formed. When the sealing skirt 60 is electrospinned, the inner layer of polymer is first cured on the valve 1 prior to spinning. This provides a cured polymer substrate for which micron-sized polymer fibers, electrospun during the electrospinning process, are attached. Prosthetic valve 1 production is completed by sealing the inlet edge at the base of the stent frame 10, which is attached to an inner cast polymer layer (not shown) that is assembled with both the stent frame 10 and the sealing skirt 60. In this embodiment, the valve leaflets 25 are formed using a bare mold material 30, as described in the method shown in Figures 9 and 10. The valve leaflet and sidewall masks 51, 52 are assembled over the pre-cured valve leaflets 25, and the frame sidewalls are immersed in polymer to integrally form the connection between the stent frame 10 and the sidewalls of the valve leaflet structure and to form the outlet edge seal.

[0063] Referring to Figure 12, for example, to facilitate the two-part deployment of the two-part valve in Figure 2D, the delivery catheter 70 has two balloons 71a, 71b located at the distal end of the catheter. The most distal balloon 71a first deploys a separate sealing skirt frame 74 having a first frame element, and the more proximal balloon 71b deploys a separate leaflet frame 75 having a second frame element integrated with the polymer leaflet. In this configuration, a single delivery device assembly 72 deploys both the sealing skirt element 74 and the separate combination of the stent frame 10 and polymer leaflet 25 elements. One or both of the sealing skirt element 74 and the polymer leaflet elements 75 include features that allow the polymer leaflet components 75 to engage with each other and lock together integrally, and once integrated, form a single integrated assembly 72 that functions as a prosthetic valve 1.

[0064] Referring to Figure 13, an improvement to the delivery system 80 for heart valve replacement procedures is the use of a deployable sensor 82 or “tactile device” that provides the surgeon mechanical feedback regarding the position and orientation of the distal end of the delivery system 80. In a preferred embodiment, the tactile device is positioned longitudinally parallel to the length of the distal end of the catheter 70. The tactile device 81 may be maintained at the distal end by the outer body of the catheter 70, or it may be enclosed in an annular capsule 82 that surrounds the distal end portion of the catheter 70 containing the tactile device 81. The tactile device 81 is deployed by either advancing the distal end of the catheter 70 relative to the capsule 82, or by proximal withdrawal of the capsule 82, allowing the tactile device 81 to deploy outward, preferably circumferentially, at a point around the prosthetic valve 1. Manual feedback from the tactile sensor 81 to the surgeon is provided by a mechanical connection, such as a guidewire or other mechanically rigid member, which extends along the axial length of the catheter to connect a mechanical sensor for sensing its position and orientation at the proximal end of the catheter. The manual feedback received by the user / surgeon at the proximal end allows for more sensitive and stable deployment of the prosthetic flap 1 in either a self-expanding or balloon-inflatable system.

[0065] As reflected in the deployment of the sensor 81 in Figure 13, the method of the present invention includes the use of a delivery system 80 having a mechanical or structural addition of the sensor 81 to the distal end of the system, and using the mechanical feedback provided to the proximal end of the delivery system through the axial length of the catheter in a method for deploying the prosthetic valve 1, so as to inform the surgeon when it is time to deploy the prosthetic valve, either by mechanical feedback of the sensor 81, through conventional imaging techniques, or a combination of both. Thus, the addition of the sensor to the distal end of the delivery system would allow for selective positioning of the delivery system 80 prior to and during deployment of the prosthetic valve 1 as a preliminary step toward the final positioning of the prosthetic valve 1.

[0066] Referring to Figures 14 and 15, the modified design for the deployment strategy of the prosthetic valve 1 uses a combination of balloons to enable more complete and predictable deployment and expansion of the prosthetic valve 1. The modified balloon configuration consists of three main inflation balloons 90a, 90b, 90c, or lobes that interact only with the shape of the commissure 90 of the prosthetic valve 1. In this configuration, the valve leaflets 25 are separated from the main inflation balloons 90a-c so that no contact occurs between the balloons 90a-c and the valve leaflets 25 during expansion. This design protects the polymer valve leaflets 25 and prevents any balloon-leaflet interaction that could cause leaflet damage during the valve deployment process. Preferably, the triple-shaped balloon design and orientation conform to the shape of the cardiac valve commissure 90.

[0067] Referring to Figure 15, a schematic cross-sectional view shows the orientation of the main inflation balloons 90a-c for orientation along the valve connection 90. In one embodiment, secondary inflation balloons 91a-c are positioned between each of the main inflation balloons 90a-c and are positioned to engage longitudinally and tangentially along the length of the main balloons. The main and secondary balloons can be inflated separately, individually, or sequentially, such that all the main inflation balloons are inflated first, and the secondary inflation balloons are inflated second. Thus, each of the six balloons can have its own lumen, or separate lumens can be provided to selectively inflate any of the six balloons in three groups, or collectively in a stepwise manner. Preferably, once a certain pressure is reached, a selective pressure valve is incorporated into the delivery system so that the pressure valve alternates between inflating the main balloons 90a-c and the secondary balloons 91a-c. In this methodology, more consistent circular deployment is caused by outward pressure on the prosthetic flap, first by the deployment of the primary expansion balloons 90a-c, which contact the commissure, and second by the deployment of the secondary expansion balloons 91a-c. In the fully deployed configuration, the inner secondary balloons 91a-c fill the gap between the larger primary expansion balloons 90a-c.

[0068] As described, the three main balloons 90a-c interact only with the valve commissure 90 and not with the valve leaflets 25. The smaller balloons 91a-c are sized to interact only with the frame located below the valve leaflets 25 and do not come into contact with the valve leaflets 25. The smaller secondary balloons 91a-c will facilitate the even deployment of the stent frame 10 during the deployment of the prosthetic valve 1.

[0069] The method of use includes separate steps for inflating primary and secondary inflation balloons, along with a discrete set of pressurization times and pressure values ​​selectively applied to different balloon types. The method steps also include a separate discrete inflation stage in which the valve leaflets do not come into contact with the primary inflation balloon.

[0070] Referring to Figure 16, the tear-open sheath 95 allows for a smaller inlet diameter at the distal end of the catheter 70, and the smaller inlet diameter provides easier access to the patient's anatomical structures. Once the surgeon advances a structure larger than the inner diameter of the tear-open sheath 95, including the prosthetic valve 1, the larger diameter of the prosthetic valve 1 zips open the distal end of the tear-open sheath 95 along a linear set of perforations 96. The zip-open sheath, having the opening 96 along axis A, increases in outer diameter B to accommodate the introduction of the prosthetic valve 1 and the delivery system 70. Once crimped, the valve assembly passes through the tear-open sheath 95, and the sheath collapses to a smaller diameter outer shape, allowing for easier withdrawal through the patient's blood vessels. Therefore, the present invention includes both a structure and a methodology for deploying a zip-open sheath 95, which has an initial diameter smaller than the diameter of the integrated valve leaflet / stent frame assembly, expands to an outer diameter that separates the zip-open sheath 95 along the linear axis of the perforation 96, and once the prosthetic valve 1 is deployed in the natural valve annulus, the zip-open sheath 95 is further compressed to a much smaller diameter. The zip-open sheath 95 allows for the manufacture of smaller diameter introducers and easier access during the advance of the heart valve delivery system to the natural valve annulus for deploying the prosthetic valve 1, followed by the removal of the structure having a much smaller outer diameter.

[0071] Referring to Figure 17, the distal balloon 101a is incorporated into the catheter 100, which has laterally expandable features 106a, 106b at its distal tip, which are specifically designed to accommodate the passage of the distal balloon 101a and are used for balloon pre-expansion of the natural valve annulus prior to the deployment of the prosthetic valve 1. The laterally expandable regions 106a, 106b may be inflatable or expandable through mechanical action, or they may be static with respect to the axial structure of the catheter but may be constructed to be easily pushed in a substantially annular manner relative to the natural valve annulus by the expansion of the distal balloon 101a, for example, by a lateral opening that facilitates more easily aligning these regions 106a, 106b perpendicular to the linear path of the catheter. The distal balloon 101a is preferably positioned immediately proximal to the distal tip 102 of the catheter and immediately proximal to the distal portion 105 of the prosthetic valve, and the proximal portion 103 of the prosthetic valve is also positioned around the body of the catheter 100. Any number of features, generally described in 104, that are inside the catheter 100 and extend proximal to the proximal portion 103 of the valve pass through the inside of the catheter 101 and facilitate the outward expansion of the distal balloon 101a. Once pre-expansion is completed by the expansion of the distal balloon 101a, the distal balloon is reduced to a reduced diameter 109 and moved distally, allowing the proximal valve deployment balloon 103 to advance. Thus, the methodology of the present invention allows surgeons to perform both pre-expansion and valve deployment functions using the same catheter device, reducing procedure time and complexity. As a procedure, the catheter 100 carrying the distal balloon 101a is advanced to the natural valve annulus with the balloon in its deflated position. Once securely positioned within the natural valve annulus, the distal balloon 101a expands, applying an outward force to regions 106a and 106b that is approximately annular with respect to the natural valve annulus and approximately perpendicular to the longitudinal axis of the catheter 100, thereby producing an expanded natural valve annulus in preparation for the deployment of the prosthetic valve. The distal balloon 101a then deflates, and the catheter 100 advances distally until the prosthetic valve is in a fixed position for deployment within the natural valve annulus.In this configuration, the proximal portion 107 of the valve and the distal portion 108 of the valve are positioned across a pre-enlarged native valve annulus. Following deployment of the prosthetic valve, both the distal balloon 101a and the proximal valve deployment balloon 103 are deflated, and the entire device is withdrawn through the vasculature.

[0072] In some embodiments, both the electrospun polymer and the polymeric valve membrane body are siloxane polyurethane ureas. In some embodiments, the polymer of the valve membrane body can be a siloxane polyurethane urea. In all of the foregoing embodiments related to siloxane polyurethane ureas, the siloxane polyurethane urea can include first, second, third, and fourth segments. The first segment can have the structure of -A 1 -L 1 -A 1 -, where L 1 is the residue of a first diisocyanate. A 1 is the residue of a poly(C1-C 12 alkanediol). The second segment can have the residue of a first siloxane-containing diol. The third segment can have the residue of a second siloxane-containing diol, and the fourth segment can have the residue of a C1-C 12 alkanediamine, and the segments are covalently bonded to each other through the residue of the diisocyanate.

[0073] In all of the foregoing embodiments related to siloxane polyurethane ureas, the siloxane polyurethane urea can have the structure of A 4 -L 4 -A 3 -L 3 -A 2 -L 2 -A 1 -L 1 -A 1 -L 2 -A 2 -L 3 -A 3 -L 4 -A 4 -, where L 1This could be a residue of the first diisocyanic acid. 1 is poly(C1-C 12 It may be a residue of an alkanediol. 2 This could be a residue of the second diisocyanic acid molecule. 2 is, -A 1 -L 1 -A 1 -, residue of the first siloxane-containing diol, residue of the second siloxane-containing diol, and C1-C 12 It can be selected from the residues of an alkanediamine. 3 This could be a third diisocyanic acid residue. 3 This consists of a residue from the first siloxane-containing diol, a residue from the second siloxane-containing diol, and C1-C 12 It can be selected from the residues of an alkanediamine. 4 This could be the fourth diisocyanic acid residue. 4 is, -A 1 -L 1 -A 1 -, residue of the first siloxane-containing diol, residue of the second siloxane-containing diol, and C1-C 12 It can be selected from the residues of an alkanediamine. 4 -L 4 -A 3 -L 3 -A 2 -L 2 -A 1 -L 1 -A 1 -L 2 -A 2 -L 3 -A 3 -L 4 -A 4 In the structure, A 2 , A 3 , or A 4 At least one example of this could be a residue of the second siloxane-containing diol, A 2 , A 3 , or A 4 At least one instance of this is C1-C 12 It could be a residue of an alkanediamine.

[0074] In all of the foregoing embodiments related to siloxane polyurethane ureas, the siloxane polyurethane urea is AA 2 -L 3 -A 3 -L 4 -A 4 (the first structure of formula II) and / or A 4 -L 4 -A 2 -L 3 -A 3 -L 2 -A 1 -L 1 -A 1 -L 2 -A 3 -L 3 -A 2 -L 4 -A 4 (the second structure of formula III). With respect to the first and second structures,

[0075] L 1 can be a residue of MDI,

[0076] A 1 can be a residue of PHMO,

[0077] L 2 can be a residue of MDI,

[0078] A 2 can be a residue of PDMS,

[0079] L 3 can be a residue of MDI,

[0080] A 3 can be a residue of BHTD,

[0081] L 4 can be a residue of MDI,

[0082] A 4 can be a residue of EDA.

[0083] In many exemplary embodiments, an implantable valve is provided, comprising a frame including a plurality of deflectable supports, and a polymer valve body coupled to the frame, wherein the polymer valve body includes a plurality of artificial valve leaflets, and the implantable valve has a radial dimension and is capable of transitioning between a contracted state and an expanded state, the radial dimension being relatively smaller in the contracted state than in the expanded state.

[0084] In these valve embodiments, the frame and valve membrane body can be bonded together with a cured polymer. The frame can be encapsulated within the cured polymer. The polymer valve membrane body can consist of a cured polymer.

[0085] In these valve embodiments, the embeddable valve may have a longitudinal axis, and when the embeddable valve is in the expanded state, the multiple deflectable struts are transverse to the longitudinal axis. When in the fully retracted state, the multiple deflectable struts may be parallel or substantially parallel to the longitudinal axis. The valve further includes multiple longitudinal struts, each of which may be positioned at the intersection between adjacent valve leaflets. Each of the multiple longitudinal struts may be parallel to the longitudinal axis of the embeddable valve when the embeddable valve is in the expanded and retracted configurations. The multiple deflectable struts may intersect and form multiple cells. The frame may include a first row of cells located adjacent to the downstream end of the frame, and the multiple longitudinal struts are in the first row of cells. The frame may include a second row of cells located upstream of the first row of cells, and no longitudinal struts are in the second row of cells.

[0086] In many exemplary embodiments, a method is provided for implanting a prosthetic valve, which includes moving the prosthetic valve through the recipient's body using an extension delivery device while the prosthetic valve is in a retracted state, and implanting the prosthetic valve into the recipient's body by at least unfolding the prosthetic valve from the delivery device, wherein the prosthetic valve is implanted in an extended configuration, and the prosthetic valve is according to one of the valve embodiments described above.

[0087] The present invention includes a prosthetic heart valve, and the prosthetic heart valve is

[0088] A polymer valve leaflet structure formed integrally with the stent frame,

[0089] Visually detectable markers are formed from a cellular grid and integrated into the stent frame. It is equipped with.

[0090] A visually detectable marker consists of features containing openings, which are incorporated into the stent frame at the junctions between the cells of the lattice, in a prosthetic heart valve.

[0091] Multiple visually detectable markers are aligned along the horizontal axis of the prosthetic valve.

[0092] The assembly is

[0093] The stent comprises a bare mold and a set of polymer valve leaflets, the set of polymer valve leaflets being cured on it in the absence of a stent frame.

[0094] The assembly is

[0095] The system comprises a mold, a set of polymer valve leaflets, a valve leaflet mask, and a frame mask, with the valve leaflet mask positioned close to the three commissures of the prosthetic heart valve.

[0096] Prosthetic heart valves are

[0097] It is a two-part structure,

[0098] A first frame and an integrated immersion-cast polymer valve leaflet,

[0099] A prosthetic heart valve comprising a two-part structure with a separate sealing skirt integrated with a second frame, having internal and external seals, wherein both polymer valve leaflets and the sealing skirt are configured to engage in an interlocking and locking relationship to form an integrated prosthetic valve assembly.

[0100] A prosthetic valve in which the first and second frames of a two-part structure are mechanically joined by sutures, rivets, and welding, and combinations thereof.

[0101] The method for manufacturing a prosthetic heart valve is,

[0102] Forming polymer valve leaflets on a bare mold,

[0103] The stent frame is placed on top of a combination of polymer valve leaflets and bare mold material,

[0104] Masking the valve leaflets and frame, forming an integrated assembly of the mask, mold material, and polymer valve leaflets,

[0105] Immersing the integrated assembly in the polymer,

[0106] Curing the polymer that encapsulates the integrated assembly Methods that include...

[0107] The method further includes measuring the dimensions of the polymer valve leaflets on the bare profile prior to the installation of the stent frame.

[0108] The method further includes electrospinning a sealing skirt onto a stent frame.

[0109] The method further includes aligning the cavity within the mask with the support columns of the stent frame.

[0110] The method further includes arranging a gasket circumferentially around the outer edge diameter of the mask to seal against polymer intrusion during the immersion step.

[0111] The prosthetic valve delivery system is

[0112] A two-part balloon catheter having a proximal balloon and a distal balloon, A sealing skirt comprising a first stent frame element surrounding the distal balloon, and a second stent frame element integral with the polymer valve leaflet and surrounding the proximal balloon, It is equipped with.

[0113] The delivery system for prosthetic heart valves is

[0114] The device comprises a catheter having a distal end containing a prosthetic valve in a collapse configuration, a deployable mechanical sensor, and a mechanical connection extending along the entire axial length of the catheter and providing mechanical feedback to the user regarding the positioning and orientation of the prosthetic valve at the distal end of the catheter.

[0115] The delivery system further comprises a capsule containing a mechanical sensor.

[0116] A delivery system for a balloon-inflatable prosthetic heart valve, comprising a primary and secondary inflation balloon, wherein the primary inflation balloon engages with the commissure of the prosthetic valve along its length.

[0117] The delivery system is arranged longitudinally, with the secondary inflation balloon positioned tangentially along the length of the primary inflation balloon.

[0118] The delivery system further includes check valves for the gradual inflation of the primary and secondary balloons.

[0119] The prosthetic valve delivery system comprises a catheter, the catheter having a tear-open sheath at its distal end and a set of perforations along the tear-open portion.

[0120] The perforation is aligned along the linear axis at the distal end of the catheter, and the outer diameter of the prosthetic flap is larger than the inner diameter of the tear opening.

[0121] The prosthetic valve delivery system comprises a catheter for accommodating the passage of a distal balloon, the catheter having a laterally expandable region at its distal tip, the laterally expandable region being inflatable or expandable through a mechanical action provided by the distal balloon, the expansion of the distal balloon pushing the expandable region toward the natural valve annulus, and a proximal valve deployment balloon having a prosthetic valve that engages with the catheter.

[0122] As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural nouns unless the context clearly determines otherwise.

[0123] Where a range of values ​​is provided, unless the context clearly determines otherwise, each intervening value up to one-tenth of the lower limit between the upper and lower limits of that range, and any other stated or intervening values ​​within that stated range, are included in this disclosure and may be claimed as a single value or as a smaller range. If a stated range includes one or both of the limits, the range excluding one or both of the limits that they include is also included in this disclosure.

[0124] Where discrete values ​​or ranges of values ​​are provided, those values ​​or ranges of values ​​may be claimed more broadly than they are, unless otherwise indicated, as discrete numbers or ranges of numbers. For example, each value or range of values ​​provided herein may be claimed as an approximation, and this paragraph serves as an antecedent and descriptive aid for the introduction of a claim, listing each such value or range of values ​​at any given time as “approximately” its value, “approximately” its range of values, “about” its value, and / or “about” its range of values. Conversely, where a value or range of values ​​is described as an approximation or generalization, e.g., approximately X or about X, that value or range of values ​​may be claimed discretely without using such broader terminology.

[0125] However, this specification should not be construed in any way as to imply that the subject matter disclosed herein is limited to specific values ​​or ranges of values ​​in the absence of an explicit enumeration of those values ​​or ranges of values ​​in the claims. The values ​​and ranges of values ​​are provided herein simply as examples.

[0126] All features, elements, components, functions, and steps described in relation to any embodiment provided herein are intended to be freely combined and substituted with those from any other embodiment. Where a feature, element, component, function, or step is described in relation to only one embodiment, it should be understood that, unless expressly otherwise stated, that feature, element, component, function, or step may be used in conjunction with all other features described herein. This paragraph therefore serves as an antecedent and descriptive aid for introducing claims, even if the following description does not expressly state that such combinations or substitutions are possible in particular cases, at any point in time, features, elements, components, functions, and steps from different embodiments may be combined, or features, elements, components, functions, and steps from one embodiment may be substituted with those from another embodiment. It is explicitly acknowledged that a clear enumeration of all possible combinations and substitutions would be undue burdensome, given that the permissibility of all such combinations and substitutions would be readily apparent to those skilled in the art.

[0127] While embodiments are susceptible to various modifications and alternative forms, specific examples are shown in the drawings and described in detail herein. However, it should be understood that these embodiments are not limited to any particular form disclosed, but rather encompass all modifications, equivalents, and alternatives that fall within the spirit of this disclosure. Furthermore, any features, functions, steps, or elements of the embodiments, as well as any features, functions, steps, or elements that fall outside their scope, can be enumerated or added to the claims to define the scope of the invention as claimed.

Claims

1. It is a prosthetic heart valve, A polymer valve leaflet structure formed integrally with the stent frame, A visually detectable marker, formed from a cellular grid and integrated into the stent frame, A prosthetic heart valve equipped with [a specific feature].

2. The prosthetic heart valve according to claim 1, wherein the visually detectable marker comprises a feature containing an opening and is incorporated into the stent frame at the junction between the cells of the grid.

3. The prosthetic heart valve according to claim 1, wherein the plurality of visually detectable markers are aligned along the horizontal axis of the prosthetic valve.

4. It is an assembly, An assembly comprising a bare mold and a set of polymer valve leaflets, wherein the set of polymer valve leaflets is cured thereon in the absence of the stent frame.

5. It is an assembly, An assembly comprising a mold, a set of polymer valve leaflets, a valve leaflet mask, and a frame mask, wherein the valve leaflet mask is positioned in close proximity to the three commissures of a prosthetic heart valve.

6. It is a prosthetic heart valve, It is a two-part structure, (a) A dipping-cast polymer valve leaflet integral with the first frame, (b) A separate sealing skirt integral with a second frame, having inner and outer seals, wherein both the polymer valve leaflets and the sealing skirt are configured to engage in an interlocking and locking relationship to form an integrated prosthetic valve assembly. A prosthetic heart valve consisting of a two-part structure.

7. The prosthetic valve according to claim 6, wherein the first frame and the second frame of the two-part structure are mechanically joined by sutures, rivets, welding, and combinations thereof.

8. A method for manufacturing a prosthetic heart valve, (1) Forming polymer valve leaflets on a bare mold material, (2) Installing a stent frame on the combination of the polymer valve leaflet and the bare molded material, (3) Masking the valve leaflets and frame to form an integrated assembly of the mask, the mold material, and the polymer valve leaflets, (4) Immersing the integrated assembly in a polymer, (5) Curing the polymer that encapsulates the integrated assembly Methods that include...

9. The method according to claim 8, further comprising measuring the dimensions of the polymer valve leaflets on the bare mold prior to the installation of the stent frame.

10. The method according to claim 8, further comprising electrospinning a sealing skirt onto the stent frame.

11. The method according to claim 8, further comprising aligning the cavity within the mask with the support column of the stent frame.

12. The method according to claim 8, further comprising arranging a gasket circumferentially around the outer edge diameter of the mask to seal against polymer intrusion during the immersion step.

13. A prosthetic valve delivery system, A two-part balloon catheter having a proximal balloon and a distal balloon, A sealing skirt comprising a first stent frame element surrounding the distal balloon, and a second stent frame element integral with the polymer valve leaflet and surrounding the proximal balloon, A prosthetic valve delivery system equipped with the following features.

14. A delivery system for prosthetic heart valves, A catheter having a distal end, containing a prosthetic flap in a collapse configuration, Deployable mechanical sensor, A mechanical connection extends along the entire axial length of the catheter and provides mechanical feedback to the user regarding the positioning and orientation of the prosthetic valve at the distal end of the catheter. A delivery system equipped with the following features.

15. The delivery system according to claim 14, further comprising a capsule containing the mechanical sensor.

16. A delivery system for a balloon-inflatable prosthetic heart valve, comprising a primary and secondary inflation balloon, wherein the primary inflation balloon engages with the commissure of the prosthetic valve along its length.

17. The delivery system according to claim 16, wherein the secondary inflation balloon is positioned tangentially along the length of the main inflation balloon and arranged longitudinally.

18. The delivery system according to claim 16, further comprising check valves for the stepwise inflation of the primary and secondary balloons.

19. A prosthetic valve delivery system comprising a catheter, wherein the catheter has a tear-open sheath at its distal end and a set of perforations along the tear-open portion.

20. The catheter according to claim 19, wherein the perforation is aligned along a linear axis at the distal end of the catheter, and the outer diameter of the prosthetic flap is larger than the inner diameter of the tear-open portion.

21. A prosthetic valve delivery system comprising a catheter for accommodating the passage of a distal balloon, the catheter having a laterally expandable region at its distal tip, the laterally expandable region being inflatable or expandable through a mechanical action provided by the distal balloon, the expansion of the distal balloon pushing the expandable region toward the natural valve annulus, and a proximal valve deployment balloon having a prosthetic valve that engages with the catheter.

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