The present disclosure relates to prosthetic heart valves and methods for deploying a radially expandable prosthetic heart valve at a native valve with a delivery apparatus such that leaflet cusps and commissure of the radially expanded prosthetic heart valve are aligned with leaflet cusps and commissures of the native valve.
The human heart can suffer from various valvular diseases. These valvular diseases can result in significant malfunctioning of the heart and ultimately require repair of the native valve or replacement of the native valve with an artificial valve. There are a number of known repair devices (for example, stents) and artificial valves, as well as a number of known methods of implanting these devices and valves in humans. Percutaneous and minimally-invasive surgical approaches are used in various procedures to deliver prosthetic medical devices to locations inside the body that are not readily accessible by surgery or where access without surgery is desirable. In one specific example, a prosthetic heart valve can be mounted in a crimped state on the distal end of a delivery device and advanced through the patient's vasculature (for example, through a femoral artery and the aorta) until the prosthetic valve reaches the implantation site in the heart. The prosthetic valve is then expanded to its functional size, for example, by inflating a balloon on which the prosthetic valve is mounted.
When deploying the prosthetic valve at the native valve by inflating the balloon of the delivery device (or by another deployment mechanism of the delivery apparatus), the radially expanded prosthetic valve is deployed at a random radial orientation relative to the native valve. In some examples, the positioning of an implanted prosthetic heart valve relative to the native anatomy can affect the performance of the prosthetic heart valve, the function of the native anatomy, or the ability to perform future interventions.
Accordingly, a need exists for improved delivery apparatuses and methods for positioning radially expandable prosthetic heart valves relative to the native anatomy.
Described herein are examples of systems and methods for delivering a prosthetic valve to and implanting the prosthetic valve at a native valve of a heart of a patient with leaflet cusps of the prosthetic valve in alignment with leaflet cusps or with commissures of the prosthetic valve in alignment with commissures of the native valve. In some examples, the prosthetic valve can be mounted in a radially compressed state onto a delivery apparatus for delivery to a target implantation site and then deployed at the target implantation site, in the native valve, with the delivery apparatus. In some examples, the delivery apparatus can include an inflatable balloon and the prosthetic valve can be radially expanded and deployed by inflating the balloon at the target implantation site. After reaching the native valve, one or more markers configured to be visualized under fluoroscopic imaging, which are disposed on a distal end portion of the delivery apparatus and correspond to a location of one or more cusps of the prosthetic valve, can be aligned with one or more cusps of the native valve in the imaging view such that after deploying the prosthetic valve, the cusps of the prosthetic valve are aligned (for example, in a circumferential direction) with cusps of the native valve.
A method can comprise advancing a distal end portion of a delivery apparatus toward a native valve of a heart, where a prosthetic heart valve is radially compressed around a valve mounting portion of the distal end portion of the delivery apparatus.
In some examples, the method can comprise visualizing under long axis fluoroscopy, within an imaging view, a position one or more radiopaque markers relative to one or more cusps of the native valve, the one or more radiopaque markers disposed on the distal end portion of the delivery apparatus, and where at least one radiopaque marker of the one or more radiopaque markers corresponds to a location of a specified cusp of the prosthetic heart valve.
In some examples, the method can comprise rotating the distal end portion of the delivery apparatus until the one or more markers are circumferentially aligned with a middle of the one or more cusps of the native valve, and deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve such that the cusps of the prosthetic heart valve are circumferentially aligned with the cusps of the native valve.
In some examples, the method can comprise visualizing under long axis fluoroscopy, with a cusp overlap imaging view, a position of a radiopaque marker relative to a non-coronary cusp of the native valve that is disposed on a left side of the imaging view while a right coronary cusp and left coronary cusp of the native valve are superimposed with one another on a right side of the imaging view.
In some examples, the method can comprise rotating the distal end portion of the delivery apparatus until the radiopaque marker appears on a far-left side of the imaging view at a middle of the non-coronary cusp, and deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve.
In some examples, the method can comprise obtaining a 3D image of a heart and based on the obtained 3D image, selecting a long axis fluoroscopic imaging view that positions a right coronary cusp of a native valve of the heart in a center of the imaging view, anterior to a left-non commissure of the native valve.
In some examples, the method can comprise visualizing under long axis fluoroscopy, within the selected imaging view, a position of a radiopaque marker relative to the right coronary cusp of the native valve, the radiopaque marker disposed on the distal end portion of the delivery apparatus and corresponding to a location of a specified cusp of the prosthetic heart valve, rotating the distal end portion of the delivery apparatus until the radiopaque marker appears to be positioned anteriorly in the imaging view and is aligned with the middle of the right coronary cusp, and deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve.
In some examples, a method comprises advancing a distal end portion of a delivery apparatus toward a native valve of a heart, where a prosthetic heart valve is radially compressed around a valve mounting portion of the distal end portion of the delivery apparatus. The method further includes visualizing under long axis fluoroscopy, within an imaging view, a position one or more radiopaque markers relative to one or more cusps of the native valve, the one or more radiopaque markers disposed on the distal end portion of the delivery apparatus, and where at least one radiopaque marker of the one or more radiopaque markers corresponds to a location of a specified cusp of the prosthetic heart valve. The method further includes at or proximate to the native valve, rotating the distal end portion of the delivery apparatus until the one or more markers are circumferentially aligned with a middle of the one or more cusps of the native valve, and deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve such that the cusps of the prosthetic heart valve are circumferentially aligned with the cusps of the native valve.
In some examples, a method comprises advancing a distal end portion of a delivery apparatus toward a native valve of a heart, where a prosthetic heart valve is radially compressed around a valve mounting portion of the distal end portion of the delivery apparatus. The method further includes visualizing under long axis fluoroscopy, with a cusp overlap imaging view, a position of a radiopaque marker relative to a non-coronary cusp of the native valve that is disposed on a left side of the imaging view while a right coronary cusp and left coronary cusp of the native valve are superimposed with one another on a right side of the imaging view, the radiopaque marker disposed on the distal end portion of the delivery apparatus and corresponding to a location of a specified cusp of the prosthetic heart valve. The method further includes at or proximate to the native valve, rotating the distal end portion of the delivery apparatus until the radiopaque marker appears on a far left side of the imaging view at a middle of the non-coronary cusp, and deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve such that cusps of the prosthetic heart valve are circumferentially aligned with cusps of the native valve.
In some examples, a method comprises obtaining a 3D image of a heart and based on the obtained 3D image, selecting a long axis fluoroscopic imaging view that positions a right coronary cusp of a native valve of the heart in a center of the imaging view, anterior to a left-non commissure of the native valve. The method further includes advancing a distal end portion of a delivery apparatus toward the native valve of the heart, where a prosthetic heart valve is radially compressed around a valve mounting portion of the distal end portion of the delivery apparatus, and visualizing under long axis fluoroscopy, within the selected imaging view, a position of a radiopaque marker relative to the right coronary cusp of the native valve, the radiopaque marker disposed on the distal end portion of the delivery apparatus and corresponding to a location of a specified cusp of the prosthetic heart valve. The method further includes at or proximate to the native valve, rotating the distal end portion of the delivery apparatus until the radiopaque marker appears to be positioned anteriorly in the imaging view and is aligned with the middle of the right coronary cusp, and deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve such that cusps of the prosthetic heart valve are circumferentially aligned with cusps of the native valve.
In some examples, a method comprises one or more of the features recited in Examples 1-40 below.
The above method(s) can be performed on a living animal or on a simulation, such as on a cadaver, cadaver heart, anthropomorphic ghost, or simulator (e.g., with body parts, heart, tissue, etc. being simulated).
The foregoing and other objects, features, and advantages of the disclosed technology will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.
For purposes of this description, certain aspects, advantages, and novel features of the examples of this disclosure are described herein. The described methods, systems, and apparatus should not be construed as limiting in any way. Instead, the present disclosure is directed toward all novel and non-obvious features and aspects of the various disclosed examples, alone and in various combinations and sub-combinations with one another. The disclosed methods, systems, and apparatus are not limited to any specific aspect, feature, or combination thereof, nor do the disclosed methods, systems, and apparatus require that any one or more specific advantages be present, or problems be solved.
Features, integers, characteristics, compounds, chemical moieties, or groups described in conjunction with a particular aspect or example of the disclosure are to be understood to be applicable to any other aspect or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract, and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The disclosure is not restricted to the details of any foregoing examples. The disclosure extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract, and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.
Although the operations of some of the disclosed methods are described in a particular, sequential order for convenient presentation, it should be understood that this manner of description encompasses rearrangement, unless a particular ordering is required by specific language set forth below. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed methods, systems, and apparatus can be used in conjunction with other systems, methods, and apparatus.
As used herein, the terms “a,” “an,” and “at least one” encompass one or more of the specified element. That is, if two of a particular element are present, one of these elements is also present and thus “an” element is present. The terms “a plurality of” and “plural” mean two or more of the specified element.
As used herein, the term “and/or” used between the last two of a list of elements means any one or more of the listed elements. For example, the phrase “A, B, and/or C” means “A,” “B,” “C,” “A and B,” “A and C,” “B and C,” or “A, B, and C.”
As used herein, the term “coupled” generally means physically coupled or linked and does not exclude the presence of intermediate elements between the coupled items absent specific contrary language.
Directions and other relative references (e.g., inner, outer, upper, lower, etc.) may be used to facilitate discussion of the drawings and principles herein, but are not intended to be limiting. For example, certain terms may be used such as “inside,” “outside,”, “top,” “down,” “interior,” “exterior,” and the like. Such terms are used, where applicable, to provide some clarity of description when dealing with relative relationships, particularly with respect to the illustrated examples. Such terms are not, however, intended to imply absolute relationships, positions, and/or orientations. For example, with respect to an object, an “upper” part can become a “lower” part simply by turning the object over. Nevertheless, it is still the same part and the object remains the same. As used herein, “and/or” means “and” or “or,” as well as “and” and “or.”
As used herein, with reference to the prosthetic heart valve and the delivery apparatus, “proximal” refers to a position, direction, or portion of a component that is closer to the user and/or a handle of the delivery apparatus that is outside the patient, while “distal” refers to a position, direction, or portion of a component that is further away from the user and/or the handle of the delivery apparatus and closer to the implantation site. The terms “longitudinal” and “axial” refer to an axis extending in the proximal and distal directions, unless otherwise expressly defined. Further, the term “radial” refers to a direction that is arranged perpendicular to the axis and points along a radius from a center of an object (where the axis is positioned at the center, such as the longitudinal axis of the prosthetic valve).
As used herein, “e.g.” means “for example,” and “i.e.” means “that is.”
Described herein are examples of prosthetic valve delivery apparatuses and methods for delivering and implanting a radially expandable prosthetic valve at a native valve of a heart such that leaflet cusp of the prosthetic valve are circumferentially aligned with leaflet cusps of the native valve, thereby resulting in commissure alignment between the prosthetic valve and native valve.
In some examples, a delivery apparatus can include a handle portion, a balloon catheter extending distally from the handle portion, and an inflatable balloon mounted at a distal end portion of the balloon catheter. In some examples, the balloon catheter can include a valve mounting portion configured to receive a radially compressed prosthetic heart valve, the valve mounting portion including or disposed adjacent to a portion of the inflatable balloon. In some examples, the balloon catheter can be configured to rotate relative to the handle portion. Further, in some examples, the delivery apparatus can include one or more radiopaque markers mounted on or embedded within a distal end portion of a shaft of the balloon catheter and which correspond to a location of one or more leaflet cusps of the prosthetic heart valve.
In this way, the delivery apparatus can be configured to allow a user to visualize under standard fluoroscopy, during an implantation procedure, the one or more radiopaque markers relative to the native anatomy. For example, a user may rotate the distal end portion of the delivery apparatus including the radially compressed prosthetic heart valve until the one or more radiopaque markers appear anteriorly and appear to overlap a middle of one or more cusps of the native valve in the imaging view. As a result, the prosthetic heart valve can be implanted in the annulus of the native valve with leaflet cusps in alignment with the native valve, thereby enabling future interventional procedures that require access to coronary arteries or the valve leaflets.
Prosthetic valves disclosed herein can be radially compressible and expandable between a radially compressed configuration and a radially expanded configuration. Thus, the prosthetic valves can be crimped on a delivery apparatus in the radially compressed configuration during delivery, and then expanded to the radially expanded configuration once the prosthetic valve reaches the implantation site. In some examples, the prosthetic valve can be deployed from the delivery apparatus at the implantation site (for example, a native valve of a heart) via inflating an inflatable balloon of the delivery apparatus.
The valvular structure 14 can comprise three leaflets 40, collectively forming a leaflet structure, which can be arranged to collapse in a tricuspid arrangement, although in other examples there can be greater or fewer number of leaflets. The leaflets 40 can be secured to one another at their adjacent sides to form commissures 22 of the valvular structure 14. The lower edge of valvular structure 14 can have an undulating, curved scalloped shape and can be secured to the inner skirt 16 by sutures (not shown). In some examples, the leaflets 40 can be formed of pericardial tissue (for example, bovine pericardial tissue), biocompatible synthetic materials, or various other suitable natural or synthetic materials as known in the art and described in U.S. Pat. No. 6,730,118, which is incorporated by reference herein.
The frame 12 can be formed with a plurality of circumferentially spaced slots, or commissure windows 20 that are adapted to mount the commissures 22 of the valvular structure 14 to the frame. The frame 12 can be made of any of various suitable plastically-expandable materials (for example, stainless steel, etc.) or self-expanding materials (for example, Nitinol), as known in the art. When constructed of a plastically-expandable material, the frame 12 (and thus the prosthetic valve 10) can be crimped to a radially collapsed configuration on a delivery catheter and then expanded inside a patient by an inflatable balloon or equivalent expansion mechanism. When constructed of a self-expandable material, the frame 12 (and thus the prosthetic valve 10) can be crimped to a radially collapsed configuration and restrained in the collapsed configuration by insertion into a sheath or equivalent mechanism of a delivery catheter. Once inside the body, the prosthetic valve can be advanced from the delivery sheath, which allows the prosthetic valve to expand to its functional size.
Suitable plastically-expandable materials that can be used to form the frame 12 include, metal alloys, polymers, or combinations thereof. Example metal alloys can comprise one or more of the following: nickel, cobalt, chromium, molybdenum, titanium, or other biocompatible metal. In some examples, the frame 12 can comprise stainless steel. In some examples, the frame 12 can comprise cobalt-chromium. In some examples, the frame 12 can comprise nickel-cobalt-chromium. In some examples, the frame 12 comprises a nickel-cobalt-chromium-molybdenum alloy, such as MP35N™ (tradename of SPS Technologies), which is equivalent to UNS R30035 (covered by ASTM F562-02). MP35N™/UNS R30035 comprises 35% nickel, 35% cobalt, 20% chromium, and 10% molybdenum, by weight.
Like the valvular structure 14 of
A reinforcing element (not shown), such as a fabric strip, can be connected directly to the cusp edges of the leaflets and to the struts of the frame to couple the cusp edges of the leaflets to the frame.
Similar to the frame 12 of
The frame 52, at each of the inflow end 66 and the outflow end 68, may comprise a plurality of apices 80 spaced apart from one another around a circumference of the frame 52.
The sealing member 56 in the illustrated example is mounted on the outside of the frame 52 and functions to create a seal against the surrounding tissue (for example, the native leaflets and/or native annulus) to prevent or at least minimize paravalvular leakage. The sealing member 56 can comprise an inner layer 76 (which can be in contact with the outer surface of the frame 52) and an outer layer 78. The sealing member 56 can be connected to the frame 52 using suitable techniques or mechanisms. For example, the sealing member 56 can be sutured to the frame 52 via sutures that can extend around the struts 72 and through the inner layer 76. In alternative examples, the inner layer 76 can be mounted on the inner surface of the frame 52, while the outer layer 78 is on the outside of the frame 52.
The outer layer 78 can be configured or shaped to extend radially outward from the inner layer 76 and the frame 52 when the prosthetic valve 50 is deployed. When the prosthetic valve is fully expanded outside of a patient's body, the outer layer 78 can expand away from the inner layer 76 to create a space between the two layers. Thus, when implanted inside the body, this allows the outer layer 78 to expand into contact with the surrounding tissue.
Additional details regarding the prosthetic valve 50 and its various components are described in U.S. Patent Publication No. 2018/0028310, which is incorporated herein by reference.
The guide catheter 114 and the balloon catheter 116 in the illustrated example are adapted to slide longitudinally relative to each other to facilitate delivery and positioning of the prosthetic valve 10 (or another prosthetic valve or expandable prosthetic medical device) at an implantation site in a patient's body, as described further below.
The guide catheter 114 includes a handle portion 120 (handle) and an elongated guide tube, or shaft, 122 extending from handle portion 120 (
An inflatable balloon 128 is mounted at the distal end portion of balloon catheter 116 (
In alternate examples, the delivery apparatus 100 can be configured to mount the prosthetic valve directly on and around the balloon 128 (for example, in the position shown in
A nose cone 132 (
As can be seen in
The proximal portion 124 can also define an inner lumen that is in communication with a lumen 138 of the inner shaft 134 (
The inner shaft 134 and outer balloon catheter shaft 126 of the balloon catheter 116 can be formed from any of various suitable materials, such as nylon, braided stainless steel wires, or a polyether block amide (commercially available as Pebax®). In some examples, the inner and outer shafts 126, 134 can have longitudinal sections formed from different materials in order to vary the flexibility of the shafts along their lengths. In some examples, the inner shaft 134 can have an inner liner or layer formed of Teflon® to minimize sliding friction with a guide wire.
The distal end portion of the guide catheter shaft 122 comprises a steerable section 168 (
The distal handle portion 146 can be operatively connected to the steerable section 168 and can function as an adjustment mechanism to permit operator adjustment of the curvature of the steerable section via manual adjustment of the handle portion. Explaining further, the distal handle portion 146 can comprise a flex activating member 150, an indicator pin, and a cylindrical main body, or housing (
In particular examples, the steerable section 168 in its non-deflected shape is slightly curved and in its fully curved position, the steerable section generally conforms to the shape of the aortic arch. In other examples, the steerable section 168 can be substantially straight in its non-deflected position.
The distal handle portion 146 can have other configurations that are adapted to adjust the curvature of the steerable section 168. One such alternative handle configuration is shown in co-pending U.S. Pat. No. 7,780,723, which is incorporated herein by reference in its entirety. Additional details relating to the steerable section and handle configuration discussed above can be found in U.S. Pat. Nos. 8,568,472 and 9,339,384, both of which are incorporated herein by reference in their entireties.
As described above, when the delivery apparatus 100 is introduced into the vasculature of the patient, a crimped prosthetic valve 10 can be positioned proximal to the balloon 128 (
In some examples, the proximal handle portion 148 can comprise an adjustment mechanism which is configured to adjust the axial position of the outer balloon catheter shaft 126 relative to the guide catheter shaft 122, the adjustment mechanism comprising an adjustment knob 184 (
In some examples, the proximal handle portion 148 can further comprise a securement mechanism 198 (
One exemplary method for implanting the prosthetic valve 10 in the native aortic valve is as follows. The prosthetic valve 10 initially can be crimped on a mounting portion (or region) 125 (
After the prosthetic valve 10 is advanced through the narrowest portions of the patient's vasculature (for example, the iliac artery), the prosthetic valve 10 can be moved onto the balloon 128. For example, a convenient location for moving the prosthetic valve onto the balloon is the descending aorta. The prosthetic valve can be moved onto the balloon 128, for example, by holding the handle portion 120 steady (which retains the guide catheter shaft 122 in place) and moving the outer balloon catheter shaft 126 in the proximal direction relative to the guide catheter shaft 122. As the outer balloon catheter shaft 126 is moved in the proximal direction, the distal end 140 of the guide catheter shaft 122 pushes against the prosthetic valve 10, allowing the balloon 128 to be moved proximally through the prosthetic valve 10 in order to center the prosthetic valve 10 on the balloon 128, as depicted in
In some examples, the outer balloon catheter shaft 126 can include one or more radiopaque markers to assist the user in positioning the prosthetic valve at the desired location on the balloon 128. The outer balloon catheter shaft 126 can be moved in the proximal direction by simply sliding/pulling the outer balloon catheter shaft 126 in the proximal direction if the securement mechanism 198 is not engaged to retain the outer balloon catheter shaft 126. For more precise control of the outer balloon catheter shaft 126, the securement mechanism 198 can be engaged to retain the outer balloon catheter shaft 126, in which case the adjustment knob 184 is rotated to effect movement of the outer balloon catheter shaft 126 and the balloon 128.
In some examples, as shown in
In some examples, as shown in
As shown in
As the prosthetic valve 10 is guided through the aortic arch and into the ascending aorta, the curvature of the steerable section 168 can be adjusted (as explained in detail above) to help guide or steer the prosthetic valve through that portion of the vasculature. As the prosthetic valve is moved closer toward the deployment location within the aortic annulus, it becomes increasingly more difficult to control the precise location of the prosthetic valve by pushing or pulling the handle portion 120 due to the curved section of the delivery apparatus. When pushing or pulling the handle portion 120, slack can be removed from the curved section of the delivery apparatus before the pushing/pulling force is transferred to the distal end of the delivery apparatus. Consequently, the prosthetic valve tends to “jump” or move abruptly, making precise positioning of the prosthetic valve difficult.
For more accurate positioning of the prosthetic valve within the aortic annulus, the prosthetic valve 10 can be placed as close as possible to its final deployment location (for example, within the aortic annulus such that an inflow end portion of the prosthetic valve is in the left ventricle and an outflow end portion of the prosthetic valve is in the aorta) by pushing/pulling the handle portion 120, and final positioning of the prosthetic valve can be accomplished using the adjustment knob 184 (
When the prosthetic valve 10 is at the deployment location, the balloon 128 is inflated to expand the prosthetic valve 10 so as to contact the native annulus. The expanded prosthetic valve (for example, as shown in
In some examples, the delivery apparatus 100 (or another, similar delivery apparatus) can be configured to deploy and implant a prosthetic heart valve (for example, prosthetic valve 10 of
As shown in
Thus, instead of deploying the prosthetic heart valve with the delivery apparatus in a random rotational orientation relative to the aorta 205, which may result in commissures 210 of the prosthetic heart valve 206 being arranged in front of the coronary arteries 204 (as shown in
As explained further below, the delivery apparatus can be configured such that the user can visualize, under fluoroscopic imaging (or fluoroscopy), the rotational positioning of the prosthetic heart valve 206 relative to the native valve. This may enable a user to rotate the prosthetic heart valve 206 into a desired rotational position to achieve the cusp and commissure alignment shown in the example of
For example, as shown in
As shown in
Thus, it is desirable for a user operating the delivery apparatus to be able to determine during an implantation procedure where the cusps (and/or commissures) of the prosthetic heart valve are located relative to the native anatomy (for example, the native leaflet cusps of the native valve). During an implantation procedure, fluoroscopy (for example, long axis fluoroscopy) can be used to visualize the distal end portion of the delivery apparatus, including the radially compressed prosthetic valve, relative to the surrounding native anatomy (for example, the native aortic valve). An exemplary fluoroscopic image 300 of a native (for example, aortic) valve 302 viewed with long axis fluoroscopy in a standard, three-cusp imaging view is shown in
In contrast, computed tomography (CT) imaging (or another type of 3D imaging) can be used to visualize the circumferential orientation of the commissures 310 and cusps of the native aortic valve 302, around a circumference of the native aortic valve 302.
However, during a prosthetic heart valve implantation procedure, short axis CT imaging is not available and an image such as that shown in
Further, even if (for the sake of argument) a short axis CT image were available during the valve implantation procedure, it would not be possible to visualize the circumferential position of the commissures of the prosthetic heart valve 404, as shown in the exemplary CT image 450 of
To address these issues with commissure and cusp alignment between the native valve and the prosthetic heart valve, one or more radiopaque markers that are visible under medical imaging can be incorporated into the distal end portion of the delivery apparatus. At least one radiopaque marker can correspond to a specified location on the prosthetic heart valve, such as a selected cusp of the prosthetic heart valve. Thus, the delivery apparatus can include at least one and up to three radiopaque markers, at least one marker (and in some examples, all three markers) corresponding to a circumferential location of a middle of a corresponding cusp of the prosthetic heart valve. As a result, when the prosthetic heart valve is radially expanded by the delivery apparatus, a middle of the selected cusp of the prosthetic heart valve can be located at the same circumferential position as the corresponding radiopaque marker on the delivery apparatus. As described further below, the delivery apparatus can include one, two, or three radiopaque markers, where one or more of the markers correspond to the location of a middle of one or more corresponding cusps of the prosthetic heart valve. As such, in the case of multiple markers, the markers can be spaced 180 degrees (for two markers) or 120 degrees (for three markers) apart from one another around the delivery apparatus. The markers can have various shapes and sizes that are distinguishable in the fluoroscopic image, as described further below.
In some examples, the delivery apparatus can include two radiopaque markers 500 that are disposed 180 degrees apart from one another around a circumference of the delivery apparatus. For example, as shown in the schematic of the exemplary fluoroscopic image 502 of
As an example, during an implantation procedure, the fluoroscopic image 502 of
For example,
The two markers 500 can be configured with a different shape, size, or longitudinal alignment such that are distinguishable in the imaging view and a user can identify which of the two markers 500 is anterior and posterior within the imaging view. The user can then rotate the delivery apparatus until the two markers 500 are overlapping in the imaging view and the anterior marker is aligned with the right coronary cusp (or alternate specified cusp of the native valve). In this way, a pair of radiopaque markers 500 on the delivery apparatus can enable a user to orient the delivery apparatus using a standard long axis fluoroscopic imaging view such that the prosthetic heart valve is implanted in the native valve annulus with cusps aligned with cusps of the native valve.
The markers 500 and additional marker examples described herein can be configured to be visible under medical imaging. For example, the markers 500 can comprise a radiopaque material that is configured to be visible under medical imaging, such as fluoroscopy and/or other types of X-ray imaging. In some examples, the markers 500 can comprise a radiopaque or other material that is configured to be visible under MRI, ultrasound, and/or echocardiogram
Exemplary configurations for the pair of markers 500 are shown in
As explained further below with reference to
The first marker 702 is V-shaped (or shaped as a “V”) and the second marker 704 is a linear marker (for example, shaped as a line). As shown in
In alternate examples, instead of being V-shaped, the first marker 702 can have an asymmetric shape with a discernable axis or connecting point that is configured to align with and overlap the linear second marker 704 in the imaging view, such as an E-shape, half Y-shape (for example, only one arm of the top of the Y), a P-shape, a greater or less than sign (“>”) that is meant to connect on one side with the linear second marker 704, or the like. For example, the first marker 702 can have a portion that is configured to extend outward to one side of a longitudinal axis 716 of the first marker 702 that is configured to align with the linear second marker 704.
The shaft (for example, shaft 600) of the delivery apparatus on which the radiopaque markers (for example, markers 500, 602 and 604, 702 and 704, 800, or 900, as described herein) can be mounted on or embedded within can be one of the shafts of the balloon catheter 116 of the delivery apparatus 100 (
For example, in one instance, the radiopaque markers 500 (or any of the other radiopaque markers described herein) can be mounted on or embedded within the outer balloon catheter shaft 126 of the balloon catheter 116 (
In another example, the radiopaque markers 500 can be mounted on or embedded within the inner shaft 134 of the balloon catheter 116. For example, as shown in
In other examples, the radiopaque markers 500 can be disposed on a distal end portion of the inner shaft 134 which is arranged proximate to the distal end of the outer balloon catheter shaft 126 (in some examples, at the valve mounting portion 125).
It should be noted that each of the dashed lines representing the radiopaque markers 500 in
As disclosed above with reference to
Alternatively, by unlocking the balloon catheter 116 and the guide catheter 114 (for example, via the securement mechanism 198) such that the balloon catheter 116 can move independent of the guide catheter 114, the distal end portion of the balloon catheter 116, including the prosthetic valve mounted thereon, can be rotated by rotating the proximal end portion of the balloon catheter 116 (disposed proximal to the handle portion 120). For example, the shaft of the balloon catheter on which the pair of radiopaque markers 500 are disposed can be rotated relative to the handle portion 120. In this way, upon reaching the implantation site, the distal end portion of the balloon catheter 116 can be rotated, thereby rotating the outer balloon catheter shaft 126, the inner shaft 134, the balloon 128, and the prosthetic valve (for example, valve 10 shown in
In some examples, instead of two radiopaque markers, the delivery apparatus can include a single radiopaque marker 800 that is reflection asymmetric about its longitudinal axis. For example,
In still other examples, instead of one or two radiopaque markers, the delivery apparatus can include three radiopaque markers 900 that are spaced 120 degrees apart around a circumference of the delivery apparatus, as shown in the exemplary schematic image 902 of
By incorporating a one or more radiopaque markers on the delivery apparatus 402, at least one of the markers corresponding to a location of a middle of cusp of the prosthetic heart valve 404, a user can more easily position the prosthetic heart valve 404 in a target rotational (or circumferential) position at the implantation site relative to the native anatomy. For example, a user utilizing fluoroscopy during an implantation procedure can more easily visualize the distal end portion of the delivery apparatus 402 within the imaging view and rotationally position the distal end portion of the delivery apparatus 402 and the prosthetic heart valve 404 such that at least one of the markers aligns with a middle of one of the native cusps (of the native heart valve). As a result, when the prosthetic heart valve 404 is radially expanded, as shown in the exemplary schematic 950 of
In some examples, a different fluoroscopic imaging view can be selected and used for alignment of the one or more radiopaque markers of the delivery apparatus with the native cusps of the native heart valve. For example,
As another example, when the marker(s) are a pair of markers, such as the pair of markers 500 shown in
A method for implanting a prosthetic heart valve with cusps circumferentially aligned with the native cusps of the native heart valve using any combination of the one or more markers and imaging views disclosed herein is shown at
At 1004, the method can include visualizing under long axis fluoroscopy, within an imaging view, a position of the one or more radiopaque markers of the delivery apparatus relative to one or more cusps of the native valve. At least one of the one or more radiopaque markers can correspond to a location of a specified cusp of the prosthetic heart valve. For example, in the case of a single radiopaque marker (for example, marker 800), the marker can correspond (or relate to) a location of a middle of a first cusp of the cusps of the prosthetic heart valve. In the case of two radiopaque markers (for example, markers 500), a first marker of the two markers can correspond to a location of a middle of a first cusp of the cusps of the prosthetic heart valve while the second marker corresponds to a commissure of the prosthetic heart valve. In the case of three radiopaque markers (for example, markers 900), the first, second, and third markers can correspond to a location of a middle of a first, second, and third cusp, respectively, of the cusps of the prosthetic heart valve. As described above, the imaging view can be a three-cusp view, a cusp overlap view, or another selected fluoroscopic imaging view.
In some examples, the method at 1004 can include, first obtaining a 3D image of the patient's heart (for example, via CT or another 3D imaging modality) and selecting a long axis fluoroscopic imaging view, based on the 3D image, that positions a specified cusp of a native valve of the heart in a known location in the selected imaging view. In some instances, the specified cusp can be a right coronary cusp and the known location in the selected imaging view can be a center (and front) of the imaging view. For example, the obtained CT image can allow a user to find a fluoroscopic imaging view that positions the right coronary cusp directly in front of the left non-commissure of the native valve. Further, the selected imaging view can position the middle of the right coronary cusp front and center in the selected imaging view (anterior).
The method continues to 1006 and includes, at or proximate to the native valve, rotating the distal end portion of the delivery apparatus until the one or more markers are circumferentially aligned with a middle of the one or more cusps of the native valve. For example, the rotating at 1006 can include rotating the distal end portion of the delivery apparatus until one marker of the one or more radiopaque markers is aligned with a middle of the specified cusp of the native valve in the known location in the selected imaging view.
In some instances, the imaging view is a three-cusp imaging view where a right coronary cusp of the native valve disposed in a center of the imaging view, and the rotating at 1006 includes rotating the distal end portion of the delivery apparatus until one marker of the one or more markers appears to be positioned anteriorly in the imaging view and is aligned with the middle of the right coronary cusp.
In some instances, the imaging view is a cusp overlap view where a non-coronary cusp of the native valve is disposed on a left side of the imaging view while a right coronary cusp and left coronary cusp of the native valve are superimposed with one another on a right side of the imaging view, and the rotating at 1006 includes rotating the distal end portion of the delivery apparatus until one marker of the one or more markers appears on a far left side of the imaging view at a middle of the non-coronary cusp.
At 1008, the method includes deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve such that the cusps of the prosthetic heart valve are circumferentially aligned with the cusps of the native valve. Consequently, the commissures of the prosthetic heart valve are also aligned with the commissures of the native valve.
For implanting a prosthetic valve within the native aortic valve via a transfemoral delivery approach, the prosthetic valve is mounted in a radially compressed state along the distal end portion of a delivery apparatus. The prosthetic valve and the distal end portion of the delivery apparatus are inserted into a femoral artery and are advanced into and through the descending aorta, around the aortic arch, and through the ascending aorta. The prosthetic valve is positioned within the native aortic valve and radially expanded (for example, by inflating a balloon, actuating one or more actuators of the delivery apparatus, or deploying the prosthetic valve from a sheath to allow the prosthetic valve to self-expand). Alternatively, a prosthetic valve can be implanted within the native aortic valve in a transapical procedure, whereby the prosthetic valve (on the distal end portion of the delivery apparatus) is introduced into the left ventricle through a surgical opening in the chest and the apex of the heart and the prosthetic valve is positioned within the native aortic valve. Alternatively, in a transaortic procedure, a prosthetic valve (on the distal end portion of the delivery apparatus) is introduced into the aorta through a surgical incision in the ascending aorta, such as through a partial J-sternotomy or right parasternal mini-thoracotomy, and then advanced through the ascending aorta toward the native aortic valve. A prosthetic valve may also be introduced via carotid, subclavian, and axiallary arteries.
For implanting a prosthetic valve within the native mitral valve via a transseptal delivery approach, the prosthetic valve is mounted in a radially compressed state along the distal end portion of a delivery apparatus. The prosthetic valve and the distal end portion of the delivery apparatus are inserted into a femoral vein and are advanced into and through the inferior vena cava, into the right atrium, across the atrial septum (through a puncture made in the atrial septum), into the left atrium, and toward the native mitral valve. Alternatively, a prosthetic valve can be implanted within the native mitral valve in a transapical procedure, whereby the prosthetic valve (on the distal end portion of the delivery apparatus) is introduced into the left ventricle through a surgical opening in the chest and the apex of the heart and the prosthetic valve is positioned within the native mitral valve.
For implanting a prosthetic valve within the native tricuspid valve, the prosthetic valve is mounted in a radially compressed state along the distal end portion of a delivery apparatus. The prosthetic valve and the distal end portion of the delivery apparatus are inserted into a femoral vein and are advanced into and through the inferior vena cava, and into the right atrium, and the prosthetic valve is positioned within the native tricuspid valve. A similar approach can be used for implanting the prosthetic valve within the native pulmonary valve or the pulmonary artery, except that the prosthetic valve is advanced through the native tricuspid valve into the right ventricle and toward the pulmonary valve/pulmonary artery.
Another delivery approach is a transatrial approach whereby a prosthetic valve (on the distal end portion of the delivery apparatus) is inserted through an incision in the chest and an incision made through an atrial wall (of the right or left atrium) for accessing any of the native heart valves. Atrial delivery can also be made intravascularly, such as from a pulmonary vein. Still another delivery approach is a transventricular approach whereby a prosthetic valve (on the distal end portion of the delivery apparatus) is inserted through an incision in the chest and an incision made through the wall of the right ventricle (typically at or near the base of the heart) for implanting the prosthetic valve within the native tricuspid valve, the native pulmonary valve, or the pulmonary artery.
In all delivery approaches, the delivery apparatus can be advanced over a guidewire previously inserted into a patient's vasculature. Moreover, the disclosed delivery approaches are not intended to be limited. Any of the prosthetic valves disclosed herein can be implanted using any of various delivery procedures and delivery devices known in the art.
Any of the systems, devices, apparatuses, etc. herein can be sterilized (for example, with heat/thermal, pressure, steam, radiation, and/or chemicals, etc.) to ensure they are safe for use with patients, and any of the methods herein can include sterilization of the associated system, device, apparatus, etc. as one of the steps of the method. Examples of heat/thermal sterilization include steam sterilization and autoclaving. Examples of radiation for use in sterilization include, without limitation, gamma radiation, ultra-violet radiation, and electron beam. Examples of chemicals for use in sterilization include, without limitation, ethylene oxide, hydrogen peroxide, peracetic acid, formaldehyde, and glutaraldehyde. Sterilization with hydrogen peroxide may be accomplished using hydrogen peroxide plasma, for example.
The treatment techniques, methods, steps, etc. described or suggested herein or in references incorporated herein can be performed on a living animal or on a non-living simulation, such as on a cadaver, cadaver heart, anthropomorphic ghost, simulator (e.g., with the body parts, tissue, etc. being simulated), etc.
In view of the above described implementations of the disclosed subject matter, this application discloses the additional examples enumerated below. It should be noted that one feature of an example in isolation or more than one feature of the example taken in combination and, optionally, in combination with one or more features of one or more further examples are further examples also falling within the disclosure of this application.
Example 1. A method comprising: advancing a distal end portion of a delivery apparatus toward a native valve of a heart, wherein a prosthetic heart valve is radially compressed around a valve mounting portion of the distal end portion of the delivery apparatus; visualizing under long axis fluoroscopy, within an imaging view, a position of one or more radiopaque markers relative to one or more cusps of the native valve, the one or more radiopaque markers disposed on the distal end portion of the delivery apparatus, and wherein at least one radiopaque marker of the one or more radiopaque markers corresponds to a location of a specified cusp of the prosthetic heart valve; at or proximate to the native valve, rotating the distal end portion of the delivery apparatus until the one or more radiopaque markers are circumferentially aligned with a middle of the one or more cusps of the native valve; and deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve such that the cusps of the prosthetic heart valve are circumferentially aligned with the cusps of the native valve.
Example 2. The method of any example herein, particularly example 1, further comprising, prior to the visualizing, obtaining a 3D image of the heart and selecting the imaging view based on the 3D image such that a specified cusp of the native valve is positioned in a known location in the selected imaging view, and wherein the rotating includes rotating the distal end portion of the delivery apparatus until one marker of the one or more radiopaque markers is aligned with a middle of the specified cusp of the native valve in the known location in the selected imaging view.
Example 3. The method of any example herein, particularly either example 1 or example 2, wherein the imaging view is a three-cusp imaging view where a right coronary cusp of the native valve disposed in a center of the imaging view, and wherein the rotating includes rotating the distal end portion of the delivery apparatus until one marker of the one or more radiopaque markers appears to be positioned anteriorly in the imaging view and is aligned with the middle of the right coronary cusp.
Example 4. The method of any example herein, particularly either example 1 or example 2, wherein the imaging view is a cusp overlap view where a non-coronary cusp of the native valve is disposed on a left side of the imaging view while a right coronary cusp and left coronary cusp of the native valve are superimposed with one another on a right side of the imaging view, and wherein the rotating includes rotating the distal end portion of the delivery apparatus until one marker of the one or more radiopaque markers appears on a far left side of the imaging view at a middle of the non-coronary cusp.
Example 5. The method of any example herein, particularly any one of examples 1-4, wherein the one or more radiopaque markers include three radiopaque markers that are spaced 120 degrees apart from each other around a circumference of the distal end portion of the delivery apparatus.
Example 6. The method of any example herein, particularly any one of examples 1-4, wherein the one or more radiopaque markers include a pair of radiopaque markers that are spaced 180 degrees apart from each other around a circumference of the distal end portion of the delivery apparatus.
Example 7. The method of any example herein, particularly example 6, wherein the pair of radiopaque markers are linear markers configured as lines having one or more of a different width, length, or longitudinal position on the delivery apparatus.
Example 8. The method of any example herein, particularly example 6, wherein the pair of radiopaque markers include first marker configured as a linear marker and a second marker configured as a V-shaped marker.
Example 9. The method of any example herein, particularly any one of examples 1-4, wherein the one or more radiopaque markers include a single asymmetric radiopaque marker disposed on the distal end portion of the delivery apparatus.
Example 10. The method of any example herein, particularly example 9, wherein the single asymmetric radiopaque marker has a C shape.
Example 11. The method of any example herein, particularly any one of examples 1 -10, wherein the one or more radiopaque markers are mounted on or embedded within a distal end portion of a shaft of a balloon catheter of the delivery apparatus, the balloon catheter extending distally from a handle portion of the delivery apparatus.
Example 12. The method of any example herein, particularly example 11, wherein the shaft of the balloon catheter is an outer shaft to which a proximal end portion of an inflatable balloon of the delivery apparatus is mounted.
Example 13. The method of any example herein, particularly example 12, wherein the balloon catheter further comprises an inner shaft including a distal end portion that extends distally from a distal end of the outer shaft, the inner shaft extending coaxially through the outer shaft and through the inflatable balloon.
Example 14. The method of any example herein, particularly example 11, wherein the shaft of the balloon catheter is an inner shaft that extends coaxially through and distally to an outer shaft of the balloon catheter.
Example 15. The method of any example herein, particularly any one of examples 11-14, wherein rotating the distal end portion of the delivery apparatus includes rotating the balloon catheter relative to the handle portion.
Example 16. The method of any example herein, particularly any one of examples 11-15, wherein deploying the radially compressed prosthetic heart valve includes inflating an inflatable balloon mounted on a distal end portion of the balloon catheter.
Example 17. A method comprising: advancing a distal end portion of a delivery apparatus toward a native valve of a heart, wherein a prosthetic heart valve is radially compressed around a valve mounting portion of the distal end portion of the delivery apparatus; visualizing under long axis fluoroscopy, with a cusp overlap imaging view, a position of a radiopaque marker relative to a non-coronary cusp of the native valve that is disposed on a left side of the imaging view while a right coronary cusp and left coronary cusp of the native valve are superimposed with one another on a right side of the imaging view, the radiopaque marker disposed on the distal end portion of the delivery apparatus and corresponding to a location of a specified cusp of the prosthetic heart valve; at or proximate to the native valve, rotating the distal end portion of the delivery apparatus until the radiopaque marker appears on a far left side of the imaging view at a middle of the non-coronary cusp; and deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve such that cusps of the prosthetic heart valve are circumferentially aligned with cusps of the native valve.
Example 18. The method of any example herein, particularly example 17, wherein the radiopaque marker is one of three radiopaque markers that are spaced 120 degrees apart from each other around a circumference of the distal end portion of the delivery apparatus, each of the three radiopaque markers corresponding to a location of a different cusp of three cusps of the prosthetic heart valve.
Example 19. The method of any example herein, particularly example 17, wherein the radiopaque marker is one of a pair of radiopaque markers that are spaced 180 degrees apart from each other around a circumference of the distal end portion of the delivery apparatus.
Example 20. The method of any example herein, particularly example 19, wherein the pair of radiopaque markers are linear markers configured as lines having a different width or length, and wherein the rotating includes rotating the distal end portion of the delivery apparatus until the pair of radiopaque markers are spaced 180 degrees apart from one another on opposite sides of the imaging view.
Example 21. The method of any example herein, particularly example 17, wherein the radiopaque marker is a single asymmetric marker disposed on the distal end portion of the delivery apparatus.
Example 22. The method of any example herein, particularly example 21, wherein the single asymmetric marker has a C shape, and wherein the rotating includes rotating the distal end portion of the delivery apparatus until the radiopaque marker appears as a line on the far left side of the imaging view at the middle of the non-coronary cusp.
Example 23. The method of any example herein, particularly any one of examples 17-22, wherein the radiopaque marker is mounted on or embedded within a distal end portion of a shaft of a balloon catheter of the delivery apparatus, the balloon catheter extending distally from a handle portion of the delivery apparatus.
Example 24. The method of any example herein, particularly example 23, wherein the shaft of the balloon catheter is an outer shaft to which a proximal end portion of an inflatable balloon of the delivery apparatus is mounted.
Example 25. The method of any example herein, particularly example 24, wherein the balloon catheter further comprises an inner shaft including a distal end portion that extends distally from a distal end of the outer shaft, the inner shaft extending coaxially through the outer shaft and through the inflatable balloon.
Example 26. The method of any example herein, particularly example 23, wherein the shaft of the balloon catheter is an inner shaft that extends coaxially through and distally to an outer shaft of the balloon catheter.
Example 27. The method of any example herein, particularly any one of examples 23-26, wherein rotating the distal end portion of the delivery apparatus includes rotating the balloon catheter relative to the handle portion.
Example 28. The method of any examples herein, particularly any one of examples 23-27, wherein deploying the radially compressed prosthetic heart valve includes inflating an inflatable balloon mounted on a distal end portion of the balloon catheter.
Example 29. A method comprising: obtaining a 3D image of a heart and based on the obtained 3D image, selecting a long axis fluoroscopic imaging view that positions a right coronary cusp of a native valve of the heart in a center of the imaging view, anterior to a left-non commissure of the native valve; advancing a distal end portion of a delivery apparatus toward the native valve of the heart, wherein a prosthetic heart valve is radially compressed around a valve mounting portion of the distal end portion of the delivery apparatus; visualizing under long axis fluoroscopy, within the selected imaging view, a position of a radiopaque marker relative to the right coronary cusp of the native valve, the radiopaque marker disposed on the distal end portion of the delivery apparatus and corresponding to a location of a specified cusp of the prosthetic heart valve; at or proximate to the native valve, rotating the distal end portion of the delivery apparatus until the radiopaque marker appears to be positioned anteriorly in the imaging view and is aligned with the middle of the right coronary cusp; and deploying the radially compressed prosthetic heart valve with the delivery apparatus to radially expand and implant the prosthetic heart valve in an annulus of the native valve such that cusps of the prosthetic heart valve are circumferentially aligned with cusps of the native valve.
Example 30. The method of any example herein, particularly example 29, wherein the radiopaque marker is asymmetric about a longitudinal axis of the marker.
Example 31. The method of any example herein, particularly example 30, wherein the radiopaque marker is shaped as a C.
Example 32. The method of any example herein, particularly example 30, wherein the radiopaque marker is shaped as a greater than or less than sign.
Example 33. The method of any example herein, particularly any one of examples 30-32, wherein the rotating includes rotating the delivery apparatus until the radiopaque marker is centered in the imaging view and is in a predetermined orientation of two possible readable orientations that indicates the radiopaque marker is positioned anteriorly.
Example 34. The method of any example herein, particularly any one of examples 29-33, wherein the radiopaque marker is one of a pair of radiopaque markers that are spaced 180 degrees apart from one another around a circumference of the distal end portion of the delivery apparatus.
Example 35. The method of any example herein, particularly any one of examples 29-33, wherein the radiopaque marker is one of three radiopaque markers that are spaced 120 degrees apart from one another around a circumference of the distal end portion of the delivery apparatus, and wherein each marker of the three radiopaque markers corresponds to a location of a different cusp of three cusps of the prosthetic heart valve.
Example 36. The method of any example herein, particularly example 35, wherein all three of the three radiopaque markers have a same shape.
Example 37. The method of any example herein, particularly example 35, wherein the three radiopaque markers have different shapes.
Example 38. The method of any example herein, wherein the method is performed on a living animal or on a non-living simulation.
Example 39. A method of treating a heart on a simulation, wherein the method includes the method of any example herein, particularly any one of examples 1-37.
Example 40. A method comprising sterilizing the prosthetic heart valve, apparatus, and/or assembly of any example.
The features described herein with regard to any example can be combined with other features described in any one or more of the other examples, unless otherwise stated. For example, any one or more of the features of one method can be combined with any one or more features of another method.
In view of the many possible examples to which the principles of the disclosed technology may be applied, it should be recognized that the illustrated examples are only preferred examples of the disclosed technology and should not be taken as limiting the scope of the claimed subject matter. Rather, the scope of the claimed subject matter is defined by the following claims and their equivalents.
This application is a continuation of PCT Application No. PCT/US2023/027179, filed Jul. 8, 2023, which claims the benefit of U.S. Provisional Patent Application No. 63/388,210, filed Jul. 11, 2022, the entire contents of each of which are incorporated by reference herein.
Number | Date | Country | |
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63388210 | Jul 2022 | US |
Number | Date | Country | |
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Parent | PCT/US2023/027179 | Jul 2023 | WO |
Child | 19007832 | US |