Patent Application
20210298896
The application relates generally to replacement heart valves, e.g., for replacing diseased mitral and/or tricuspid valves. More particularly, embodiments of the subject matter relate to tissue-based, collapsible and expandable replacement heart valves.
The mitral valve (MV) has two distinct large leaflet cusps, or leaflets. As shown in
When the mitral valve is closed, the respective anterior and posterior leaflets are in close contact to form a single zone of apposition. As one skilled in the art will appreciate, normal mitral valve function involves a proper force balance, with each of its components working congruently during a cardiac cycle. Pathological alterations affecting any of the components of the mitral valve, such as chord rupture, annulus dilatation, papillary muscle displacement, leaflet calcification, and myxomatous disease, can lead to altered mitral valve function and cause mitral valve regurgitation (MR).
Mitral regurgitation is dysfunction of the mitral valve that causes an abnormal leakage of blood from the left ventricle back into the left atrium during systole (i.e., the expulsion phase of the heart cycle in which blood moves from the left ventricle into the aorta). While trivial mitral regurgitation can be present in healthy patients, moderate to severe mitral regurgitation is one of the most prevalent forms of heart valve disease. The most common causes of mitral regurgitation include ischemic heart diseases, non-ischemic heart diseases, and valve degeneration. Both ischemic (mainly due to coronary artery diseases) and non-ischemic (idiopathic dilated cardiomyopathy for example) heart diseases can cause functional, or secondary, mitral regurgitation through various mechanisms, including impaired left ventricle wall motion, left ventricle dilatation, and papillary muscle displacement and dysfunction. In functional mitral regurgitation, the mitral valve apparatus remains normal. Incomplete coaptation of the leaflets is due to enlargement of the mitral annulus secondary to left ventricle dilation and possibly left atrium enlargement. In addition, patients with functional mitral regurgitation can exhibit papillary muscle displacement due to the left ventricle enlargement, which results in excessive tethering of the leaflets. In contrast, degenerative (or organic) mitral regurgitation is caused by structural abnormalities of the mitral leaflets and/or the subvalvular apparatus, which can include stretching or rupture of tendinous chords.
The current treatments for mitral valve diseases include surgical repair and replacement of the mitral valve. Mitral valve repair, benefiting from improved understanding of mitral valve mechanics and function, may be now preferred to complete mitral valve replacement. However, the complex physiology and three-dimensional anatomy of the mitral valve and its surrounding structure present substantial challenges when performing these repair procedures.
In one early example of a transcatheter mitral valve replacement device, Endovalve-Herrmann (Micro Interventional Devices, Inc.), developed a mitral prosthesis that had a foldable Nitinol-based valve with a sealing skirt. Similarly, Tendyne Holdings, Inc. produces a prosthetic mitral valve replacement device comprising a pericardial valve with a self-expandable Nitinol stent. The device is designed for transapical delivery and has a ventricular fixing anchor. CardiAQ uses a pericardial valve with a Nitinol self-expandable stent in their mitral valve replacement device. Finally, Tiara (Neovasc, Inc.) uses a mitral valve replacement system that is deliverable trans-apically with a 30 Fr catheter that has anchor structures, and a pericardial valve on a self-expandable stent with a D-shaped atrial portion and a ventricular portion that has an outer coating. These devices and the techniques to deliver the mitral prosthesis into the operative position are still at development stages and, though promising, challenges to the efficacy of these devices continue to exist.
The noted challenges to an efficacious mitral valve replacement device generally include operative delivery challenges; positioning and fixation challenges; seal and paravalvular leakage challenges; and hemodynamic function challenges such as left ventricular outflow tract (LVOT) obstruction. With respect to the noted operative delivery challenges, since a conventional mitral prosthesis is larger than a conventional aortic prosthesis, it is more difficult to fold and compress the larger mitral prosthesis into a catheter for deployment as well as retrieval through either conventional trans-apical or trans-femoral delivery techniques.
Turning to the positioning and fixation challenges, instability and migration are the most prominent obstacles given that the mitral valve is subjected to high and repetitive loads in a cardiac cycle, with a high transvalvular pressure gradient that is near zero at diastole and can rise to 120 mmHg or more during systole and higher than 150 mmHg of systolic pressure for patients with aortic stenosis and systemic hypertension. The lack of calcium distribution at the mitral annulus also affects device stability and anchoring. Further, the transcatheter mitral valve replacement can be easily dislodged as the heart moves during each beating cycle.
With respect to sealing and paravalvular leakage, a good fit between the native annulus and the prosthesis that minimizes paravalvular leak is desirable. Since the mitral valve annulus is large, typically, a prosthetic mitral valve may have a large overhanging atrial portion or flare which can prevent leakage, but, problematically, it also requires a large valve size at the ventricular level so that the prosthesis can be tightly fitted in the native mitral valve. Conventionally, a prosthetic mitral valve is smaller than the diseased native valve and additional material is added around the prosthetic valve to compensate for the large native mitral annulus. Undesirably, adding more material to a prosthetic valve increases the size of the delivery system.
Finally, with respect to the preservation of hemodynamic function, the operative positioning of a prosthetic mitral valve, which is conventionally large as described above, should not obstruct the LVOT at the anterior portion of the mitral annulus and should not interfere with the associated structures of a native mitral valve.
Accordingly, it would be beneficial to have a heart valve leaflet replacement system that does not suffer from the shortcomings and deficiencies of conventional valve prosthetics. It is desirable to secure the prosthetic mitral valve replacement system to the native mitral annulus. It is also desirable to improve positioning of a mitral prosthesis and prevent leaking of blood between the mitral prosthesis and the native mitral valve. Similarly, it is desirable to prevent further dilation of the native mitral annulus. Furthermore, other desirable features and characteristics will become apparent from the subsequent detailed description and the appended claims, taken in conjunction with the accompanying drawings and the foregoing technical field and background.
Described herein are examples of a prosthetic hemi heart valve or prosthetic hemi-valve and a method of securing a prosthetic hemi-valve to one of the native valve annuli. It is contemplated that the method of securing a prosthetic hemi-valve to one of the native valve annuli is configured to prevent dislodgement of the prosthetic hemi-valve from the annulus and to ensure the proper coaptation between the implanted prosthetic hemi-valve leaflets with the remaining native leaflets. It is contemplated that the prosthetic hemi-valve can be implanted via an open surgical procedure or percutaneously via catheter. In one aspect, the prosthetic hemi-valve comprises a plurality of dual guiding and fixation (DGF) members, described elsewhere herein, which can be configured to secure the prosthetic hemi-valve to the native mitral annulus. In a further aspect, the associated methods can be configured to implant the replacement valve prosthesis and to help prevent further dilation of the native mitral annulus. For clarity, it will be appreciated, although the present disclosure may focus on the treatment of functional mitral regurgitation, it is contemplated that the heart valve leaflet replacement system and the associated methods can be used or otherwise configured to be used to treat other valve disease conditions such as degenerative mitral regurgitation and replace other valves (e.g., tricuspid valve) of the human heart, or could be used or otherwise configured to be used in other mammals suffering from valve deficiencies as well.
In one aspect, the prosthetic hemi-valve is configurable or otherwise sizable to be crimped down to fit within a delivery sheath and to subsequently be selectively re-expanded to an operative size and position once removed from the delivery sheath within the heart. In a further aspect, at least a portion of the prosthetic hemi-valve can have a stent shape, which can comprise an upper atrial portion and a lower ventricular portion. In one aspect, the atrial portion can be configured to facilitate anchoring of the stent, which can help prevent paravalvular leakage and dislodgement of the stent. Further, the ventricular portion can displace a diseased native leaflet out of the blood flow tract and house at least one prosthetic leaflet. In another aspect, the prosthetic hemi-valve can comprise a lining skirt that can be coupled to at least a portion of the inner and/or outer surfaces of the stent. In one exemplary aspect, at least one prosthetic leaflet can be mounted on the inner lumen of the stent and/or on at least a portion of the outer side of the stent, which can function in place of at least one native leaflet to restore normal valve function, i.e., to prevent mitral regurgitation.
In one aspect, at least one prosthetic leaflet of the prosthetic hemi-valve can be configured with at least one leg structure which prevents the valve leaflet from billowing into the atrium and prolapsing. The at least one leg structure also acts to distribute prosthetic leaflet stress and facilitate the coaptation with at least one of the native mitral valve leaflets, in order to recreate the competent closure anatomy of a native mitral valve with sufficient leaflet coaptation length and height and proper leaflet angles during systole.
In one aspect, the delivery of the prosthetic hemi-valve can be conducted using several desired delivery access approaches, such as, for example and not meant to be limiting, a surgical approach, a trans-septal approach, a trans-atrial, or a trans-apical approach, similar to the methods disclosed in the applications incorporated by reference herein. In one exemplary aspect, the trans-septal approach can comprise creating an opening in the internal jugular or femoral vein for the subsequent minimally invasive delivery of portions of the prosthetic hemi-valve through the superior vena cava, which flows into the right atrium of the heart. In this exemplary aspect, the access path of the trans-septal approach crosses the atrial septum of the heart, and once achieved, the components of the prosthetic hemi-valve can operatively be positioned in the left atrium, the native mitral valve, and the left ventricle. In one aspect, it is contemplated that a main delivery catheter can be placed along the access path to allow desired components of the prosthetic hemi-valve to be operatively positioned in the left atrium without complications.
In one aspect the prosthetic hemi-valve has a unique crescent-shape, forming a half- or hemi-valve. The prosthetic hemi-valve is configured to have a ventricular portion that lies in the left ventricle and displaces at least one diseased native mitral leaflet. An atrial portion of the hemi-valve is configured to prevent paravalvular leak and engage with DGF members to fix the entirety of the prosthetic hemi-valve on the mitral annulus. An angled neck region forms a transition between the ventricular and atrial portions of the hemi-valve.
In an additional aspect, the stent is configured to span at least a portion, or the entirety, of the circumference of the native posterior mitral valve via a network of compressible and self-expanding diamond-shaped cells occupying a non-uniform, semi-elliptical shape with varying lengths as to avoid interfering with surrounding native valve structures. In a further aspect, the stent can assume an asymmetric, semi-conical or semi-circular cross-sectional profile.
In one aspect, the atrial portion of the stent includes a plurality of cells that assume a shape designed to conform to the native mitral annulus. The atrial portion of the stent includes curved atrial stent tips so as to not interfere with the atrial wall, and a plurality of through-holes. It connects to the neck region that curves downward along the native mitral annulus and transitions to the ventricular portion of the stent.
In a further aspect, the through-holes on the atrial portion of the stent are configured to accept DGF locking members to fix the prosthetic hemi-valve in place on the mitral annulus.
In one aspect, the neck region transitions from the atrial portion to the ventricular portion of the stent. The ventricular portion of the stent is configured with at least one prosthetic leaflet coupled to the inner surface, which is configured to form a C-shape which can extend to a D-shape in systole in the operative position.
In one aspect, the ventricular portion of the stent can be configured with a plurality of through-holes to facilitate attachment of at least a portion of the prosthetic leaflet.
In one aspect, a plurality of tabs extends from the ventricular portion of the stent, e.g., making the stent a shape similar to a stingray. The tabs can be directly extended from the tips of the stent, or coupled via an extended strut. The tabs are configured to be a safety mechanism for the prosthetic valve throughout the housing, positioning, and locking process.
In one aspect, a component of the prosthetic hemi-valve is at least one dome-shaped prosthetic leaflet. At least one prosthetic leaflet can be mounted to the inner surface of the ventricular portion of the stent frame, and displace at least one diseased native posterior mitral leaflet.
In an operative aspect, the prosthetic valve includes a plurality of dome-shaped leaflets, which are configured to be flexible and mobile throughout the cardiac cycle. During the systolic phase, the at least one prosthetic leaflet extends radially to form a D-shape to coapt with healthy native anterior leaflets by extending radially outwards from the stent, thus preventing transvalvular leakage and mitral regurgitation. During diastole, the at least one prosthetic leaflet is configured to move towards the stent in a C-shape to allow for ventricular filling.
Due to the hemi-valve nature of the device, it is contemplated that thicker leaflet material can be used to enhance prosthetic valve durability. Furthermore, the half-valve can also be crimped to a smaller profile, compared to a full-valve, allowing a greater portion of the at-risk population to undergo a transcatheter mitral valve replacement operation.
In an exemplary embodiment, the at least one prosthetic leaflet can mimic the configuration of the native mitral posterior leaflets with three adjoined semilunar cusps extended from the neck portion of the stent into the ventricle, with the central cusp extending further downwards and radially inwards than the two smaller lateral cusps. In a further embodiment, each prosthetic leaflet can comprise a parabolic attachment line, two commissures, a belly region, a coaptation region and optionally, at least one leg.
In one embodiment, the central leaflet attachment line is configured to be symmetrical about the axial midline, with the central prosthetic leaflet spanning one-third to two-thirds of the ventricular portion of the stent. The two lateral leaflets are configured to mirror each other on either side of the central leaflet, spanning one-sixth to one-third of the ventricular portion of the stent, and are asymmetric about their respective axial midlines.
In an exemplary aspect, the prosthetic valve includes a plurality of prosthetic leaflets, which are configured to have arm structures extending from the commissures that stabilize the commissure region of the prosthetic leaflets by restricting backwards motion of the prosthetic leaflet towards the stent frame during the diastolic phase of the cardiac cycle.
In one aspect, the arm structures can be configured to fold-over portions of the at least one prosthetic leaflet to increase the leaflet thickness at the commissure region. It is contemplated that, in exemplary embodiments, the arm structures can be triangular, rectangular, or irregularly shaped.
In a further aspect, at least one dog-bone, rectangular, cylindrical-, or conical shaped leg structure may be provided on the prosthetic leaflet, which can be configured to attach to, and extend radially away from, the stent frame. One skilled in the art can appreciate that the leg structures mimic the native chordae tendineae, in that they can prevent over-extension and prolapse of the prosthetic leaflet, which is especially necessary with larger prosthetic leaflets. The leg structures also serve to distribute force throughout the prosthetic leaflet and frame.
In one embodiment, the prosthetic hemi-valve is configured to occupy about one-half of the mitral orifice in the D-shape configuration when coapting with the native anterior mitral leaflets. The prosthetic leaflets are designed to extend radially inwards, up to the lateral edges of the stent, and not beyond.
In one aspect, a skirt is coupled to at least a portion of the inner and outer surface of the stent. The skirt serves dual purposes: acting as a means to mount the prosthetic leaflets onto the ventricular portion of the stent, and also creating a paravalvular seal along the atrial portion of the stent.
In one aspect, the skirt material can be made of polymers, fabric, biological tissue, and the like. An important characteristic of the skirt is that it is biaxially oriented, allowing it to stretch in both the axial and transverse direction during crimping and expansion of the prosthetic hemi-valve.
In one aspect, the skirt can be a single piece of material, or alternatively, the skirt can be configured from multiple separate pieces of material, coupled to the stent via one or more non-absorbable sutures or strings.
In one embodiment, a sealing ring can be coupled to the circumference of the prosthetic hemi-valve to promote tissue ingrowth, and to protect the native mitral valve surrounding structures from abrasion by the prosthetic valve.
In one aspect, a plurality of DGF members can be operatively positioned and implanted at desired locations in the native annulus prior to the delivery of the replacement prosthetic hemi-valve. In this aspect, the DGF members can improve the subsequent positioning and anchoring of the replacement prosthetic hemi-valve. In a further aspect, the plurality of DGF members can help prevent leakage of blood between the operatively positioned prosthesis and the native mitral valve.
In an exemplary aspect, the DGF members can comprise a permanent head and body portion with a removable flexible tail portion. The DGF head member can comprise a coil shape that can be operatively embedded in the annular tissue. The DGF body member can be coupled to a plurality of DGF locking members to fix the prosthetic hemi-valve device onto the native mitral annulus. The DGF tail member can be configured as a tether component that extends from the proximal portion of the DGF body, and links the DGF member to the crimped prosthetic hemi-valve within the prosthetic hemi-valve delivery and implantation system.
In one aspect, the DGF member body is coupled to a plurality of DGF locking members. In one embodiment, the DGF locking members comprise a plurality of radially compressible legs, e.g., forming a cone shape. In a further embodiment, the tip of the cone is configured to have a smaller diameter than the legs of the cone, and also a diameter smaller than the holes on the atrial portion of the stent, while the legs of the cone have a larger diameter than the holes on the atrial portion of the stent.
In one embodiment, the DGF tails can be tensioned to pull the DGF locking members through the holes on the atrial portion of the stent, thereby compressing the legs of the DGF locking members inward to allow for the passage of the DGF locking member through the hole of the atrial portion if the stent. After passing through the holes in the atrial portion of the stent, the legs of the DGF locking members re-expand to their operative position, and prevent backward motion of the DGF locking member through the holes in the atrial flare portion of the stent, effectively locking the prosthetic hemi-valve in the operative position.
Various implementations described in the present disclosure can include additional systems, methods, features, and advantages, which can not necessarily be expressly disclosed herein but will be apparent to one of ordinary skill in the art upon examination of the following detailed description and accompanying drawings. It is intended that all such systems, methods, features, and advantages be included within the present disclosure and protected by the accompanying claims.
A better understanding of the features and advantages of the present subject matter will be obtained by reference to the following detailed description that sets forth illustrative embodiments and the accompanying drawings. The features and components of the following figures are illustrated to emphasize the general principles of the present disclosure. Corresponding features and components throughout the figures can be designated by matching reference characters for the sake of consistency and clarity.
The present invention can be understood more readily by reference to the following detailed description, examples, drawings, and claims, and their previous and following description. However, before the present devices, systems, and/or methods are disclosed and described, it is to be understood that this invention is not limited to the specific devices, systems, and/or methods disclosed unless otherwise specified, and, as such, can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.
The following description is provided as an enabling teaching of the invention in its best, currently known embodiment. To this end, those skilled in the relevant art will recognize and appreciate that many changes can be made to the various aspects of the invention described herein, while still obtaining the beneficial results of the present invention. It will also be apparent that some of the desired benefits of the present invention can be obtained by selecting some of the features of embodiments described herein without utilizing other features.
Accordingly, those who work in the art will recognize that many modifications and adaptations are possible and can even be desirable in certain circumstances and are a part of the present invention. Thus, the following description is provided as illustrative of the principles of the present invention and not in limitation thereof.
For clarity, it will be appreciated that this disclosure will focus on the treatment of functional mitral regurgitation, however it is contemplated that the heart valve leaflet replacement system and the associated methods can be used or otherwise configured to be used to treat other types of mitral regurgitation or to replace other diseased valves of the human heart, such as tricuspid valve, or could be used or otherwise configured to be used in other mammals suffering from valve deficiencies as well.
As used throughout, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a leaflet” can include two or more such leaflets unless the context indicates otherwise.
Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.
As used herein, the terms “optional” or “optionally” mean that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.
The word “or” as used herein means any one member of a particular list and also includes any combination of members of that list. Further, one should note that conditional language, such as, among others, “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain aspects include, while other aspects do not include, certain features, elements and/or steps. Thus, such conditional language is not generally intended to imply that features, elements and/or steps are in any way required for one or more particular aspects or that one or more particular aspects necessarily include logic for deciding, with or without user input or prompting, whether these features, elements and/or steps are included or are to be performed in any particular embodiment.
Disclosed are components that can be used to perform the disclosed methods and systems. These and other components are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these components are disclosed that while specific reference of each various individual and collective combinations and permutation of these cannot be explicitly disclosed, each is specifically contemplated and described herein, for all methods and systems. This applies to all aspects of this application including, but not limited to, steps in disclosed methods. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods.
The present methods and systems can be understood more readily by reference to the following detailed description of the exemplary embodiments.
Throughout the description, the terms “prosthetic valve” and “prosthesis” and “valve stent” and “heart valve leaflet replacement device” and “valve device” are used interchangeably and is contemplated as a heart valve replacement device described herein.
Referring to
Turning to the drawings, an exemplary embodiment of a prosthetic hemi-valve device 1 is shown that is designed to treat mitral regurgitation in patients with regurgitation and normal anterior mitral leaflet 6 motion by replacing the posterior mitral leaflet 10, e.g., as shown in
In one exemplary aspect, the prosthetic hemi-valve device 1 can include a crescent-shaped stent 100, at least one dome-shaped prosthetic leaflet 200, and at least one sealing skirt 300 to facilitate sealing and mounting of the prosthetic leaflet 200 onto the stent 100. The prosthetic hemi-valve device 1 is configured such that at least one prosthetic leaflet 200 will coapt with at least one native anterior leaflet 6 during the systolic phase of the cardiac cycle in operation, e.g., as shown in
In one aspect, it is contemplated that, in the expanded configuration, the stent 100 can define a substantially semi-circular cross-sectional profile. It is further contemplated that the stent 100 can be configured such that the surface of the stent 100 defines a non-circular cross-sectional profile, including but not limited to, a semi-elliptical cross-sectional profile or an asymmetric cross-sectional profile, e.g., to at least partially conform to the shape of the natural valve annulus. As used herein, the term “asymmetric cross-sectional profile” includes any non-circular cross-sectional shape.
In one aspect, referring to
Referring again to
In one aspect, the atrial portion 104 of the stent can be configured to be positioned on or above the native mitral annulus to facilitate anchoring and sealing of the prosthetic hemi-valve 1.
In addition or alternatively, the atrial portion 104 of the stent may be configured to span at least some or all of the native mitral annulus.
In one aspect, the atrial portion 104 of the stent is configured to flare out radially over some or all of the posterior annulus of the native mitral annulus. In this aspect, the upper atrial portion 104 can be configured with at least one row of cells. In the example shown, the cells include struts that are oriented in a collapsible diamond-shaped structure that extend outward radially from the neck portion 109 of the stent. In this aspect, the diameter of the upper atrial portion 104 is smallest near the neck portion 109 and increases moving outward towards the atrial crowns 117 and the left atrial wall.
Referring to
In an exemplary aspect, some of the junctions 103 of the atrial portion of the stent can be configured with a through-hole or hole 108. In this aspect, the through-holes 108 are used for anchoring and fixing the stent 100 onto the mitral annulus. The holes 108 can be configured with an inner diameter of approximately 0.5 to three millimeters (0.5-3 mm), and approximately five to fifteen (5-15) holes can be configured along the atrial portion 104 of the stent. The holes 108 in the atrial portion 104 of the stent are configured to allow for passage of the locking members 131 in one direction only.
In another aspect, the fixation of the stent 100 to the mitral annulus can be also achieved by other methods such as one or more of using adhesives, tissue grabbing, capturing, and suturing methods.
In an optional aspect, the holes 108 can have circular, rectangular, square or oval shapes.
In one aspect, because of the hemi aspect of the prosthetic valve 1, lateral edge 107 of the lateral cells 106 of the atrial portion 104 of the stent do not share a junction 103 with adjacent cells.
In this aspect, the junction 103 of the lateral cells 106 can be configured with binding sites on the lateral edges 107. In this aspect, the binding sites of the lateral edges 107 of the stent can be configured with matching corresponding shapes such that they fit together snugly and keep the stent in a cylindrical configuration throughout crimping. In this aspect, the shape of one junction 103 on one side can be configured to match and fit to the shape of the other junction on the opposite side.
In one exemplary aspect, the binding sites can be straight, zigzagged, wavy, semi-circular, semi-oval, rectangular or irregular shaped struts.
In one aspect, the atrial portion 104 of the stent is configured to conform to the annulus in operation. The upper struts of the cells on the atrial portion 104 of the stent, also referred to as crowns or free stent tips, can be configured with curved tips 117, e.g., as shown in
In an optional aspect, the stent tips 117 on the atrial portion 104 of the stent can be configured with a curvature such that they lie substantially parallel to the mitral annulus in operation.
In one exemplary aspect, the atrial portion 104 of the stent can be configured with two rows of cells. In this aspect, the row of cells near the neck region 109 have smaller dimensions than the other row of cells towards the stent tip 117. In this aspect, the further row of cells can be configured with bend struts with angle between 90°-145°.
In another aspect, the cells in two rows of the atrial portion 104 of the stent can be of the same dimensions.
In one aspect, a neck region 109 joins the atrial 104 and ventricular 110 portions of the stent. In this aspect, the neck region 109 is continuous with the upper atrial 104 and lower ventricular 110 portions of the stent. The neck region 109 can be configured with at least one row of cells, e.g., with a height of approximately one to seven millimeters (1.0-7.0 mm). The top portion of the neck 109 can be curved or angled to ease the transition between the atrial 104 and neck 109 portions of the stent. Likewise, the bottom portion of the neck 109 can be curved or angled to ease the transition between the neck 109 and ventricular 110 portions of the stent.
In one exemplary aspect, referring to
In one aspect, shown in
In one exemplary aspect, the ventricular portion 110 of the stent is configured to span at least some or all of the posterior leaflet 10 of the native mitral valve 4. Optionally, the lateral edges 112 of the stent can extend circumferentially to the native mitral commissures 14 (not shown, see, e.g.,
In one aspect, in the expanded configuration, the stent 100 is configured to have an anterior-posterior (AP) dimension. In exemplary embodiments, the AP dimension at the ventricular level ranges from about ten to forty millimeters (10-40 mm) and/or the AP dimension at the atrial level ranges from about twenty to sixty millimeters (20-60 mm). In further examples, the anterior commissure to posterior commissure length, namely the commissure-to-commissure (CC) length can range from about twenty to sixty millimeters (20-60 mm) and/or the CC length can range from about thirty to ninety millimeters (30-90 mm) at the atrial level. The ventricular portion 110 of the stent is configured to form a “C-shape” in the operative position, thereby displacing the native posterior mitral leaflets 10 and allowing for at least one prosthetic leaflet 200 to extend radially up to the lateral edges of the stent 100 to coapt with the native anterior leaflet 6.
In one aspect, the ventricular portion 110 of the stent is configured with different heights along its circumference such that it does not interfere with the papillary muscles 14.
In a currently preferred embodiment of the ventricular portion 110 of the stent, the stent height in the center of the valve can range between about ten and forty millimeters) 10-40 mm) and the stent height at the lateral sides of the stent 112 can range between about five and fifteen millimeters (5-15 mm).
In one aspect, the ventricular portion 110 of the stent can comprise at least one row of cells. A row of cells can span all or a portion of the circumference of the ventricular portion 110 of the stent.
In one exemplary aspect, the ventricular portion 110 of the stent is configured to have three rows of cells. Rows I, II, and III 134,135,136 are configured to be at the top, middle, and bottom of the ventricular portion 110 of the stent, respectively. Each row is configured to have a plurality of conjoined struts that assume a collapsible diamond-shaped cell with a height of 7-8 mm and a width of 4-6 mm. Each row can include the same number of cells, or differ in their number of cells.
In one aspect, Row I cells 134 are attached to the neck region 109 at the top of the cell, and share Row II cells 135 at the lower struts 101. Optionally, one or more of the Row I cells 134 can be configured to be covered with the sealing skirt 300 to facilitate prosthetic leaflet 200 coupling and prevent leakage.
In an additional aspect, Row II cells 155 share Row I cells 154 to the top and Row III cells 156 to the bottom. In one regard, a plurality of Row II cells 155 positioned behind the at least one prosthetic leaflet 200 can optionally be configured to be open cells, without being covered by the skirt 300. This configuration promotes radial extension of the at least one prosthetic leaflet 200 and prevents blood stagnation behind the leaflet(s) 200. The cells which are covered by the skirt 300 include a leaflet attachment line, e.g., to couple a plurality of prosthetic leaflets 200 to the stent 100.
In another aspect, Row III cells 136 are shared with Row II cells 135 to the top and are free standing on the bottom. The two lateral edges 112 are configured to be covered with at least one layer of fabric 300. Portions of the Row III cells 136 corresponding to prosthetic leaflet 200 attachment regions can be configured to be covered with the sealing skirt 300, while other regions can optionally be left open without a skirt 300.
In one aspect, the height and width of the cells in each row can be the same. In another aspect, the height and width of the cells in each row can be different.
In one aspect, the ventricular portion 110 of the stent can be configured with a hemi-conical shape where the diameter is smallest near the neck portion 109 and increases moving downward towards the ventricle 3 in operation.
In one optional aspect, referring to
In one aspect, the binding junction 103 can be configured as a non-straight section on the lateral edges 112 wherein opposing lateral edges 112 are configured to engage each other during stent crimping 18.
In one aspect, one or more cell struts can be configured with through-holes 113 that provide a mechanism for attachment of at least a portion of the prosthetic leaflet 200 to the frame without the need for skirt 300 material on that cell.
In an exemplary embodiment of the prosthetic hemi-valve device 1, one or more struts in Row III 136 of the ventricular portion 110 of the stent can be configured with through-holes 113 for attachment of at least one prosthetic leaflet legs 205 directly to the strut. In this aspect, the plurality of through-holes 113 can range from about 0.1 mm-1 mm in diameter. Optionally, the struts containing the through-holes 113 can be configured to be approximately 1.1 to 2.5 times wider than other struts to accommodate for the presence of the through-holes 113.
In an exemplary embodiment, the ventricular portion 110 of the stent can be configured such that the at least one prosthetic leaflet commissures 201 attach to the frame 100 at one or more of the ventricular stent tips 118, such that the stent tips 118 can radially deflect when the leaflet 200 is loaded.
Referring to
Referring to
In another aspect, the extended member 114 with the central tab 116 can extend from different cells along the circumference of the ventricular portion 110 of the stent. In this aspect, the length of the extended member 114 can be about 1.0 to 5.0 mm so that it will not interfere with the native surrounding structures.
In another aspect, referring to
In another aspect, at least a portion of the ventricular portion 110 is configured such that the lowest tips 118 bend inwards radially. In an example, the bend angle can be configured to be between 10°-50° with respect to the axial direction of the stent 100.
In one exemplary aspect, the tabs 115, 116 can comprise at least one hole. The tabs 115,116 can be configured with various shapes for various delivery system engagement mechanisms, including but not limited to magnetic engagement mechanisms, male-female coupling engagement mechanisms, turning locks, etc., which can selectively engage at least a portion of the delivery system throughout the valve deployment process, thereby stabilizing the deployment process.
In one aspect, the tabs 115, 116 can be made of the same as or different materials to the stent 100, and can be permanently connected to the stent 110 via a variety of attachment means such as adhesives, magnetic engagement, etc. The tabs 115,116 and their extension structures 114 can be connected to the delivery system in different directions. In a further aspect, the tabs 115,116 can be detached from the stent 100 after the stent deployment.
In one aspect, at least one prosthetic leaflet 200 is mounted to a skirt 300 that is coupled to the ventricular portion of the stent 110 via non-absorbable sutures. The stent 100 can be configured to permit the natural dynamic motion of any remaining native leaflet(s) to coapt with the prosthetic leaflet(s) 200.
In one aspect, the ventricular portion 110 of the stent is configured to displace the native posterior mitral leaflet 10 in the left ventricular chamber 3 of the heart and position at least one prosthetic leaflet 200 in its place.
A sealing skirt 300 is coupled to at least a portion of the inner and outer surfaces of the stent 100 to prevent leakage between the prosthetic hemi valve frame 100 and at least one prosthetic leaflet 200, and to also provide a base for attachment of the at least one prosthetic leaflet 200.
The skirt 300 can be made of a synthetic or natural biocompatible non-permeable material including, but not limited to, polymers, fabric, biological materials, and the like. The skirt 300 may be cut from a similar or different material as the leaflets 200 to ensure compatibility within the body. The skirt 300 can be laser cut, die cut, or manually cut to optimize uniformity and accuracy of the desired dimensions. In an exemplary embodiment, the skirt 300 thickness can range between about 0.1 mm and 0.15 mm.
In one aspect, the skirt 300 can be configured to exhibit a biaxial orientation, with the fibers aligned circumferentially, thus allowing the skirt 300 to stretch axially during the crimping and release process such that the skirt 300 can conform to the elongated stent shape without tearing or damaging the prosthetic leaflets 200.
Optionally, the non-permeable sealing skirt 300 further comprises atrial 302 and ventricular 301 portions. In this option, the atrial 302 and ventricular 301 portions can be configured as one piece. In another option, the atrial 302 and ventricular 301 portions can be configured as two separate pieces.
In one aspect, the skirt 300 is coupled to the stent 100 via one or more of sutures, adhesive, and/or other biocompatible materials.
In one aspect, a ventricular skirt 301 is used as a structure to attach the prosthetic leaflets 200 to the stent 100. In this aspect, the ventricular skirt 301 can be configured to cover at least a portion of the ventricular portion 110 of the stent to facilitate attachment of the prosthetic leaflet 200.
In one aspect, the ventricular portion of the skirt 301 is configured with a plurality of tabs configured to wrap around stent struts at the commissural regions to prevent skirt translation during crimping.
In one aspect, the ventricular skirt 301 can be configured to conform to the inner surface of the ventricular portion 110 of the stent. The upper edge of the ventricular skirt covers the neck region 109 of the stent and also provides a path for a connection line 303 to attach the ventricular skirt 301 to the atrial skirt 302. The ventricular skirt 301 is configured to cover select cells on the ventricular portion 110 of the stent.
In one aspect, prosthetic leaflets 200 are configured to attach to the ventricular skirt 301 along an engineering-designed parabolic leaflet attachment line. The ventricular skirt 301 is configured to cover the stent portions 110 where the leaflet attachment line should align to facilitate attachment of the at least one prosthetic leaflet 200 to the stent 100.
In one embodiment, as seen in
In one aspect, an atrial skirt 302 is used to encourage paravalvular sealing in the atrium 2, and further anchoring the valve 1 to the annulus. The atrial skirt 302 is configured to conform to the unique curvature of the atrial portion 104 of the stent.
In one aspect, the atrial skirt 302 can be configured with a material that can be penetrated by the DGF member head such that after the valve 1 is deployed and locked into place, additional DGF members can be implanted through the atrial skirt 302 to further fasten the valve 1.
In the example shown in
Optionally, as seen in
In one embodiment, a sealing ring 316 can be affixed to at least a portion of the atrial portion 104 of the frame to create a paravalvular seal along the annulus.
The sealing ring 316 can be made of a flexible synthetic or natural biocompatible material including, but not limited to, polymers, fabric, biological material, and the like. The sealing ring 316 can surround the lateral and top edges of the valve 1 that can come into contact with the native tissue, avoiding the bottom edge of the valve 1 as to not interfere with leaflet motion in operation. The sealing ring 316 may be permanently fixed to the valve 1, e.g., with one or more sutures, adhesives, and/or other biocompatible materials.
In one aspect of the prosthetic hemi-valve device 1, at least one dome-shaped prosthetic leaflet 200 can be mounted on the inner surface of the frame. In one aspect, at least one prosthetic leaflet 200 can be mounted to the inner surface of the lower ventricular portion 110 of the frame. It is contemplated that at least one prosthetic leaflet 200 can comprise a plurality of leaflets wherein all of the prosthetic leaflets 200 can have the same shape and size or wherein one or more of the plurality of leaflets 200 have different shapes and/or sizes.
In an exemplary embodiment shown in
In one aspect, the dome-shaped prosthetic leaflet(s) 207 can be configured to be mobile throughout the cardiac cycle such that the belly and coaptation regions extend radially inward from the frame 100 at systole to prevent transvalvular central or commissural leakage, and to move towards the frame 100 during diastole to allow ventricular filling. The prosthetic leaflet commissures 201, attachment edge 202, and feet 214 of the legs 205 that are attached to the stent 100 are immobile with respect to the stent 100.
In one aspect, the at least one prosthetic leaflet 207 can be configured with at least one arm 215 extending from the leaflet commissure 201.
In one aspect, the dome-shaped leaflet(s) 207 can be configured such that they exhibit limited collapsibility and radial extension such that they do not hit the frame 100 during valve opening, and cannot extend beyond the frame 100 radius during valve closing, in operation.
In one aspect, the dome-shaped prosthetic leaflet(s) 207 can be configured to coapt with the native anterior mitral leaflet 6 during systole in operation. Referring to
The prosthetic hemi-valve device 1 anchoring mechanism can be configured to resist separation from the posterior mitral annulus during systole and device migration in operation. In one aspect, the prosthetic hemi-valve device 1 can be configured to cover about half or ⅔ of the mitral orifice during systole. In this aspect, given the half valve nature of the prosthetic hemi-valve 1, only about half of the total force induced by the blood flow during systole will act on the prosthetic hemi-valve device 1, thus only half of the total force will act on the anchoring mechanism. The rest of the force induced by the blood flow will act on the native anterior mitral leaflet 6 and annulus. As such, it is contemplated that a prosthetic hemi-valve 1 may be easier to secure to the mitral annulus compared to a full circumference prosthetic valve. One skilled in the art can appreciate that anchoring of full circumference prosthetic valve devices in the mitral position continues to be a challenge.
In one aspect of the prosthetic hemi-valve device 1, with continued reference to
In one aspect, the plurality of prosthetic leaflets 200 can comprise pericardial tissue, or other biological or tissue engineered materials, polymeric, fabric, or flexible metallic material, and the like. In this aspect, it is contemplated that a moveable, flexible prosthetic leaflet 200 would exhibit give when interacting with a native anterior leaflet 6, and thus would induce minimal damage to a native valve leaflet 6 due to repeated contact.
It is contemplated that due to the hemi-valve 1 nature of the device, the prosthetic leaflet 200 can be configured with a thicker leaflet material than other prosthetic mitral valves intended to be implanted via catheter, and still have a small crimped device profile which is desirable for procedure feasibility and patient safety. One skilled in the art can appreciate that a thicker prosthetic leaflet 200 is desirable for prosthetic valve 1 durability.
Referring to
Referring to
In the exemplary embodiments shown in
In one embodiment of the prosthetic hemi-valve device 1, the prosthetic leaflets 200 can be configured to attach to the frame 100 starting just below the neck region 109 of the frame 100 and extending axially to the tips of the ventricular portion 118 of the frame and cover the circumference of the ventricular portion 110 of the frame. In other optional aspects, the prosthetic leaflets 200 can be configured to wrap around the lateral edges of the frame 112 or only cover a portion of the frame 100 circumference. Further, the prosthetic leaflets 200 can be configured to extend axially from the upper flared 104 or neck portions 109 of the frame to the ventricular portion 110 of the frame. Optionally, the prosthetic leaflet 200 can be configured to cover only a portion of the ventricular portion 110 of the frame.
In one aspect, the prosthetic leaflets 200 are attached to the frame 100 along a leaflet attachment line 320 that comprises a plurality of parabolic shapes where each parabolic shape delineates a prosthetic leaflet 200.
In one aspect, the leaflet attachment line 320 can be configured to be symmetric about the center of the skirt 300. In an optional aspect, the leaflet attachment line 320 can be configured to be asymmetric.
In an exemplary embodiment, as shown in
Optionally, the PP2 leaflet attachment line 320 is configured to span about one third to two thirds of the stent 100 circumference and be symmetric about its axial midline.
In addition or alternatively, the PP1 and PP3 leaflet attachment lines 320 can be configured as mirror images of each other, and to span about one sixth to one third of the stent circumference. The PP1 and PP3 leaflet attachment lines 320 can be configured to be shorter on the lateral edges such that they are asymmetric about their respective axial midlines.
In one aspect, the plurality of leaflets 200 can be configured as separate individual pieces of flexible material that are affixed to the frame 100 along each of the parabolic leaflet attachment lines 320. Each leaflet 206, 207, 208 can be made of the same or different material. In another optional aspect, the plurality of leaflets 200 can be formed from one single piece of flexible material by affixing the material to the frame 100 along each of the parabolic leaflet attachment lines 320.
In one aspect, the parabolic shape of the leaflet attachment lines 320 can be configured to distribute blood flow induced forces throughout the prosthetic leaflets 200 and frame 100. One skilled in the art can appreciate that by distributing forces throughout the device 1, localized high stress regions which can negatively impact device 1 durability, can be prevented.
In one aspect, the leaflet attachment line 320 can be configured to align with the stent struts, particularly at high stress regions such that blood flow forces acting on the leaflet 200 will be, in part, distributed directly to the stent 100. In a further aspect, the leaflet attachment line 320 can be configured such that the prosthetic leaflet commissures 201 align with the ventricular stent tips 118 such that the ventricular stent tips 118 can deflect radially inwards, e.g., about 5° to 15° when a pressure load is applied to the prosthetic leaflets 200. In this aspect, the stent-tip 118 deflection can cushion the prosthetic leaflets 200 from forces acting on them which has been shown to be important for bioprosthetic valve 1 durability.
In another optional aspect, the leaflet attachment line 320 can be configured such that the prosthetic leaflet commissures 201 align with tabs 116 extending from the lower ventricular portion 110 of the frame, as seen in
In one aspect, the prosthetic leaflets 200 can be mounted on the frame 100 such that the stent cells behind the belly region 203 of the prosthetic leaflets 200 are open with no skirt 300 material. It is contemplated that by leaving these cells open, blood flow can reach the belly region 203 of the prosthetic leaflet 200 more quickly such that the prosthetic leaflets 200 can extend quickly to cover the mitral valve orifice in systole and prevent regurgitation. Further in this aspect, it is contemplated that by increasing blood washout between the prosthetic leaflets 200 and the frame 100, the incidence of thrombosis formation due to flow stagnation can be reduced.
Referring to
It can be appreciated by one skilled in the art that the proper dome shape proportions must be maintained for proper prosthetic leaflet 200 function, i.e., radial extension. For simplicity, consider a two-dimensional dome height-to-width ratio, if the height-to-width ratio is small, the prosthetic leaflet 200 can extend a lot radially, but can also potentially prolapse in operation, and if the height-to-width ratio is large, the prosthetic leaflet 200 radial extension is limited and potentially cannot extend far enough to cover the regurgitant orifice area.
Referring to the example shown in
Referring to the examples shown in
The height-to-width ratio determining leaflet prolapse will also depend on the angle of the ventricular portion 110 of the stent with respect to the atrial portion 104 of the stent, where an angle less than 90° will help prevent prolapse in leaflets with a low height-to-width ratio. Further, the height-to-width ratio will depend on the leaflet 200 opening angle, i.e., the angle made between the two commissures 201 and the center point of the frame 100, where a larger angle will help prevent prolapse in leaflets 200 with a low height-to-width ratio. Therefore, the leaflet 200 height-to-width ratios presented here are meant to be illustrative to demonstrate the effect of the leg structures 205, and are not meant to be limiting.
One skilled in the art can appreciate that as mitral regurgitation progresses in patients, often the mitral annulus becomes increasingly dilated, thus larger degrees of prosthetic leaflet 200 radial extension may be desirable, without necessarily proportional increases in prosthetic leaflet 200 height. Thus, in some aspects, the prosthetic leaflets 200 may require one or more additional leg structures 205, including on the smaller lateral prosthetic leaflets 206,208. In some other aspects, the prosthetic leaflets 200 may require one or more additional leaflets to make it a four- or five-leaflet valve.
One skilled in the art can also appreciate that it is beneficial for the prosthetic hemi-valve device 1 to have prosthetic leaflets 200 with limited radial extension by design, without the need for additional ventricular anchoring and independent of patient characteristics.
In one aspect, the prosthetic leaflet feet 214 at the end of the leaflet legs 205 can be directly attached to the stent 100 at the through-holes 113 for foot attachment 214 such that there is no need for additional skirt material 300 in this region.
Referring to example shown in
Referring again to
One skilled in the art can appreciate that typically, the native anterior mitral leaflet 6 covers nearly two thirds of the mitral orifice area during systole. Thus, the prosthetic leaflets 200 in
Referring to
One skilled in the art can appreciate that the leg structures 205 also act similarly to the native chordae tendineae 15, in that they can prevent over-extension and prolapse of the prosthetic leaflet 200.
In one aspect, the PP1 and PP3 leaflets 206, 208 can also be configured with leg structures 205, particularly for large size prostheses where the PP1 and PP3 leaflets 206,208 are large.
Alternatively, the PP1 and PP3 leaflets 206, 208 can be configured without leg structures 205, particularly for small size prostheses where the PP1 and PP3 leaflets 206,208 are small.
In one aspect, the foot 214 of the leg structure 205 can be configured at an angle to facilitate attachment to an angled strut of the stent with the through-holes 113.
In one aspect, the plurality of leg structures 205 can be configured with a dog-bone shape that is wider at the foot 214 where it attaches to the frame 113, and the base where it extends from the bottom of the dome-shape and relatively narrower in an intermediate region. In this aspect, the added width reduces stress in the leg structure 205 at the regions experiencing the highest forces. One skilled in the art, can appreciate that the dog-bone shape design distributes mechanical stress throughout the leg 205 which is important for durability.
In a further aspect, it is desirable for the plurality of leg structures 205 to be made of a single piece of the same material as the rest of the prosthetic leaflet 200.
In an exemplary embodiment, the PP2 leaflet 207 can be configured with a tallest height in the center (belly 203 and coaptation regions 204) of the leaflet and a shorter height at each of the commissures 201, corresponding to the native posterior mitral leaflet 12 structure, e.g., as shown in
In an example of the prosthetic hemi-valve 1, the plurality of dome-shaped prosthetic leaflets 200 are configured as individual flat pieces of flexible material.
In an exemplary aspect, the prosthetic hemi-valve includes a stent 100 which is coupled to a skirt 300 on the inner surface of a stent 100 and a portion of the outer surface of the stent 100. Furthermore, a plurality of prosthetic leaflets 200 are coupled to the inner surface of the skirt 300. In a further aspect, one or more sutures are used to couple the skirt 300 to the stent 100, and the prosthetic leaflets 200 to the skirt 300.
One skilled in the art can appreciate the benefits of a hemi-valve versus a fully-circumferential valve in terms of crimp profile. The reduced stent 100, leaflet 200, and skirt 300 material allows the prosthetic hemi-valve to be crimped into lower profile catheters, enabling a greater at-risk patient population to undergo a heart valve replacement operation.
In one aspect, the prosthetic hemi-valve device 1 is fixed to the posterior mitral annulus by a plurality of DGF members which can be operatively positioned and implanted at desired locations in the native annulus prior to the delivery of the prosthesis 1, e.g., similar to the systems and methods described in the applications incorporated by reference elsewhere herein. In this aspect, the DGF members can guide the subsequent precise positioning and fixation of the prosthesis 1. In a further aspect, the plurality of DGF members can help prevent leakage of blood between the operatively positioned prosthesis 1 and the native mitral annulus.
In one aspect, each DGF member can be configured with removable and permanent components, where removable components can aid in guiding the prosthetic hemi-valve device 1 to the operable position, and then be removed from the patient's body after fixing the prosthesis 1, and permanent components remain in the patient's body to keep the prosthetic hemi-valve device 1 secured to the native annulus.
In an exemplary aspect, each DGF member can comprise head, body, and tail components. In one aspect, each DGF head member can be configured with a coil shape such that it can be operatively inserted and embedded in the annular tissue. In one aspect, each DGF body member can be configured with a DGF locking member 131 to fix the prosthetic hemi-valve device 1 to the native mitral annulus, such as that shown in
In one aspect, the prosthetic hemi-valve can be configured to engage the DGF locking members 131 via a plurality of holes 108 in the atrial flared portion 104 of the stent. In this aspect, each DGF tail member can be a tether that is configured so that one end of the tether is attached to the DGF body member and the other end of the tether can exit the body. Subsequently, the tether can be inserted through the hole 108 on the atrial flared portion 104 of the stent, such that the prosthetic hemi-valve device 1 can be delivered over the DGF tail members and the atrial flared portion 104 of the stent can be precisely delivered to the DGF body members embedded in the annulus.
In one aspect, the DGF locking member 131 can be configured to pass through the hole 108 on the atrial flared portion 104 of the stent in one direction only.
In one aspect, the DGF locking member 131 can be configured such that it can selectively be compressed to a diameter smaller than the diameter of the hole 108 on the atrial flared portion 104 of the stent, such that it can pass through the hole 108, and subsequently be selectively re-expanded to its original size, larger than the diameter of the hole 108 on the flared portion 104 of the stent to prevent backward motion of the DGF locking member 131 through the hole 108.
In one exemplary aspect, as shown in
In one aspect, referring to
In an alternative aspect, the locking members 131 are configured to be selectively expandable from a cross-sectional profile smaller than the diameter of the holes 108 to a cross-sectional profile larger than the diameter of the holes 108 such that they can pass through the holes 108 in the atrial portion 104 of the stent and then can be selectively expanded such that they cannot pass through the holes 108 in the opposite direction. In this aspect, the locking member 131 can be formed, for instance, with a shape memory material and a mechanism to selectively hold the locking member 131 in a crimped state which can be selectively released to re-expand the locking member 131.
In one embodiment, also referring to
It should be emphasized that the above-described aspects are merely possible examples of implementation, merely set forth a clear understanding of the principles of the present disclosure. Many variations and modifications can be made to the above-described embodiment(s) without departing substantially from the spirit and principles of the present disclosure. All such modifications and variations are intended to be included herein within the scope of the present disclosure, and all possible claims to individual aspects or combinations of elements or steps are intended to be supported by the present disclosure. Moreover, although specific terms are employed herein, as well as in the claims which follow, they are used only in a generic and descriptive sense, and not for the purposes of limiting the described invention, nor the claims which follow.
The present application claims benefit of co-pending U.S. provisional application Ser. No. 63/007, 418, filed Apr. 9, 2020, and is a continuation-in-part of co-pending application Ser. No. 15/453,518, filed Mar. 8, 2017, which claims the benefit of U.S. provisional applications Ser. No. 62/305,204, filed Mar. 8, 2016, 62/413,693, filed Oct. 27, 2016, and 62/427,551, filed Nov. 29, 2016, and is a continuation-in-part of co-pending application Ser. No. 17/121,615, filed Dec. 14, 2020, which is a continuation of International application No. PCT/US2019/037476, filed Jun. 17, 2019, which claims benefit of U.S. provisional application Ser. No. 62/685,378, filed Jun. 15, 2018, and is a continuation-in-part of co-pending application Ser. No. 17/198,097, filed Mar. 10, 2021, which claims benefit of U.S. provisional application Ser. No. 62/988,253, filed Mar. 11, 2020; the disclosures of which, including specification and drawings, are all expressly incorporated herein in their entirety by reference.
| Number | Date | Country | |
|---|---|---|---|
| 63007418 | Apr 2020 | US | |
| 62305204 | Mar 2016 | US | |
| 62413693 | Oct 2016 | US | |
| 62427551 | Nov 2016 | US | |
| 62685378 | Jun 2018 | US | |
| 62988253 | Mar 2020 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US2019/037476 | Jun 2019 | US |
| Child | 17121615 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 15453518 | Mar 2017 | US |
| Child | 17227196 | US | |
| Parent | 17121615 | Dec 2020 | US |
| Child | 15453518 | US | |
| Parent | 17198097 | Mar 2021 | US |
| Child | PCT/US2019/037476 | US |
