Aortic valve and pacing device, method for making the same, and applications thereof

Abstract

This invention relates to an aortic valve with an embedded pacing device, a method for making the same, and application thereof. The aortic valve includes a valve frame, and a pacing device is disposed and embedded in the valve frame. The pacing device is used to deliver rapid pacing during deployment of the aortic valve into a thoracic cavity of a living object and to deliver regular pacing during a post-operative period. The aortic valve may be deployed in a transcatheter aortic valve replacement / implantation (TAVR / TAVI) procedure without a need of an additional temporary or permanent pacemaker. The pacing device may be powered by wireless power transfer or by an embedded battery.

Description

[0001] AORTIC VALVE AND PACING DEVICE, METHOD FOR MAKING THE SAME, AND APPLICATIONS THEREOF

[0002] STATEMENT AS TO RIGHTS UNDER FEDERALLY-SPONSORED RESEARCH

[0003] This invention was made with government support under grant number HL141470 awarded by the National Institutes of Health. The government has certain rights in the invention.

[0004] CROSS-REFERENCE TO RELATED APPLICATIONS

[0005] This PCT application claims priority to and the benefit of U.S. Provisional Patent Application Serial No. 63 / 528,104, which was filed July 21, 2023. The content of the aboveidentified application is incorporated herein by reference in its entirety.

[0006] FIELD OF THE INVENTION

[0007] The present invention relates generally to medical devices, and more particularly to an aortic valve with a pacing device being embedded therein, a method of making the same, and applications thereof.

[0008] BACKGROUND OF THE INVENTION

[0009] The background description provided herein is for the purpose of generally presenting the context of the invention. The subject matter discussed in the background of the invention section should not be assumed to be prior art merely as a result of its mention in the background of the invention section. Similarly, a problem mentioned in the background of the invention section or associated with the subject matter of the background of the invention section should not be assumed to have been previously recognized in the prior art. The subject matter in the background of the invention section merely represents different approaches, which in and of themselves may also be inventions. Work of the presently named inventors, to the extent it is described in the background of the invention section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the invention.

[0010] The transcatheter aortic valve replacement / implantation (TAVR / TAVI) procedure is a common procedure available for people with symptomatic severe aortic stenosis at low, intermediate or high risk for standard valve replacement surgery. Generally, aortic valve replacement requires an open-heart procedure. In comparison, the TAVR / TAVI procedure can be done through very small openings, in which a narrow flexible tube (also known as a catheter) is put into a blood vessel (generally the blood vessel in the upper leg or chest) of the patient, and is passed toward the aortic valve in the heart of the patient. The tube is used to fix a replacement valve over the top of the old valve.

[0011] Currently, every implantation of the transcatheter aortic valve requires the placement of a temporary pacemaker. Specifically, during the deployment of the aortic valve, the temporary pacemaker is placed through the central vein for in-operation rapid pacing. The temporary pacemaker is either removed right after the procedure if no conduction disturbances are observed, or left for 7 days for observation / support. After 7 days the decision is made to either implant a permanent subcutaneous pacemaker or not.

[0012] However, some patients who undergo the TAVR / TAVI procedure (e.g., to treat aortic stenosis) may encounter severe to critical conduction anomalies or disturbances, in which the aortic valve narrows and does not open fully, thus reducing or blocking the blood flow from the heart to the aorta and to the rest of the body.

[0013] Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies.

[0014] SUMMARY OF THE INVENTION

[0015] In one aspect of the present invention, an aortic valve is provided. The aortic valve includes a valve frame, and a pacing device being disposed and embedded in the valve frame. The pacing device is configured to deliver rapid pacing during deployment of the aortic valve into a thoracic cavity of a living object and to deliver regular pacing during a post-operative period. The aortic valve is deployed in a transcatheter aortic valve replacement / implantation (TAVR / TAVI) procedure without a need of an additional temporary or permanent pacemaker.

[0016] In another aspect of the present invention, a method for fabricating an aortic valve includes: providing a valve frame; and disposing a pacing device such that the pacing device is embedded in the valve frame, wherein the pacing device is configured to deliver rapid pacing during deployment of the aortic valve into a thoracic cavity of a living object and to deliver regular pacing during a post-operative period; and wherein the aortic valve is deployed in a transcatheter aortic valve replacement / implantation (TAVR / TAVI) procedure without a need of an additional temporary or permanent pacemaker. In certain embodiments, the pacing device is a leadless pacemaker having electrodes with pacing capabilities.

[0017] In certain embodiments, the pacing device is configured to, through rotation during deployment of the aortic valve, interrogate tissues of a septal wall of the living object, sense a heart conduction system of the living object, and adjust a pacing threshold and a final position of the aortic valve.

[0018] In certain embodiments, the pacing device includes a radiopaque marker configured to scan, interrogate and sense the heart conduction system of the living object.

[0019] In certain embodiments, the radiopaque marker of the pacing device is positioned under X-ray guidance.

[0020] In certain embodiments, the pacing device is powered by wireless power transfer or by an embedded battery.

[0021] In certain embodiments, the valve frame has a diameter within a range for appropriate positioning of the pacing device therein.

[0022] In certain embodiments, the valve frame is made of a material selected from the group consisting of graphene, MXenes, platinum, zinc, molybdenum, nitinol, titanium, a combination thereof, and alloys thereof.

[0023] In certain embodiments, the aortic valve is used for resynchronization therapy.

[0024] In certain embodiments, the aortic valve is configured for mitral, pulmonic, and tricuspid valves.

[0025] A further aspect of the present invention relates to a method for performing a transcatheter aortic valve replacement / implantation (TAVR / TAVI) procedure, which includes: providing the aortic valve as described above; and deploying the aortic valve into a thoracic cavity of a living object, wherein the pacing device is configured to deliver rapid pacing during deployment of the aortic valve into the thoracic cavity and to deliver regular pacing during a post-operative period.

[0026] In certain embodiments, the TAVR / TAVI procedure is performed without a need of an additional temporary or permanent pacemaker.

[0027] These and other aspects of the present invention will become apparent from the following description of the preferred embodiment taken in conjunction with the following drawings, although variations and modifications therein may be affected without departing from the spirit and scope of the novel concepts of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The accompanying drawings illustrate one or more embodiments of the invention and together with the written description, serve to explain the principles of the invention. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like elements of an embodiment.

[0029] FIG. 1 schematically shows global variation in the uptake of the TAVI procedure.

[0030] FIG. 2 shows the pacemaker implantation rates in the TAVI procedure.

[0031] FIG. 3 schematically shows an aortic valve with an embedded pacing device being implanted in a heart of a living object according to certain embodiments of the present invention.

[0032] FIG. 4 shows a posterior view of an aortic valve with an embedded pacing device being implanted in a heart of a living object according to a different embodiment of the present invention.

[0033] FIG. 5A shows the displacement of the valve frame of an aortic valve being implanted in a heart of a living object according to a different embodiment of the present invention.

[0034] FIG. 5B shows the valve frame of FIG. 5 A in a different viewing angle.

[0035] FIG. 6 shows extraction procedure-related complication data using a temporary pacemaker.

[0036] FIG. 7A shows data related to the hazard ratio of a new device and a reused device using an existing aortic valve with a temporary pacemaker with a table of characteristics of the patients and devices at baseline.

[0037] FIG. 7B shows a chart of data related to the hazard ratio of a new device and a reused device using an existing aortic valve with a temporary pacemaker.

[0038] FIG. 7C shows data related to the hazard ratio of a new device and a reused device using an existing aortic valve with a temporary pacemaker, including factors associated with infection or device-related death.

[0039] FIG. 8 A shows additional data of ECG of the human heart connected to the Langendorff setup, with stable capture beats from the aortic valve position via stimulation from the valve frame.

[0040] FIG. 8B shows the borderline capture, with 2 artificial spikes signifying stimulation below the pacing threshold and no capture beats visible, and then stimulation being applied above the pacing threshold and 4 visible 4 capture beats. FIG. 8C shows attempted stimulation from above the aortic valve near the atrial position in the aorta, with the small downward spike being visible before each capture beat.

[0041] DETAILED DESCRIPTION OF THE INVENTION

[0042] The invention will now be described more fully hereinafter with reference to the accompanying drawings, in which exemplary embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this specification will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like reference numerals refer to like elements throughout.

[0043] The terms used in this specification generally have their ordinary meanings in the art, within the context of the invention, and in the specific context where each term is used. Certain terms that are used to describe the invention are discussed below, or elsewhere in the specification, to provide additional guidance to the practitioner regarding the description of the invention. For convenience, certain terms may be highlighted, for example using italics and / or quotation marks. The use of highlighting has no influence on the scope and meaning of a term; the scope and meaning of a term are the same, in the same context, whether or not it is highlighted. It will be appreciated that same thing can be said in more than one way. Consequently, alternative language and synonyms may be used for any one or more of the terms discussed herein, nor is any special significance to be placed upon whether or not a term is elaborated or discussed herein. Synonyms for certain terms are provided. A recital of one or more synonyms does not exclude the use of other synonyms. The use of examples anywhere in this specification including examples of any terms discussed herein is illustrative only, and in no way limits the scope and meaning of the invention or of any exemplified term. Likewise, the invention is not limited to various embodiments given in this specification.

[0044] It will be understood that, as used in the description herein and throughout the claims that follow, the meaning of “a”, “an”, and “the” includes plural reference unless the context clearly dictates otherwise. Also, it will be understood that when an element is referred to as being “on” another element, it can be directly on the other element or intervening elements may be present therebetween. In contrast, when an element is referred to as being “directly on” another element, there are no intervening elements present. As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items. It will be understood that, although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers and / or sections, these elements, components, regions, layers and / or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another element, component, region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the invention.

[0045] Furthermore, relative terms, such as “lower” or “bottom” and “upper” or “top,” may be used herein to describe one element’s relationship to another element as illustrated in the figures. It will be understood that relative terms are intended to encompass different orientations of the device in addition to the orientation depicted in the figures. For example, if the device in one of the figures, is turned over, elements described as being on the “lower” side of other elements would then be oriented on “upper” sides of the other elements. The exemplary term “lower”, can, therefore, encompasses both an orientation of “lower” and “upper,” depending on the particular orientation of the figure. Similarly, if the device in one of the figures is turned over, elements described as “below” or “beneath” other elements would then be oriented “above” the other elements. The exemplary terms “below” or “beneath” can, therefore, encompass both an orientation of above and below.

[0046] It will be further understood that the terms “comprises” and / or “comprising,” or “includes” and / or “including” or “has” and / or “having”, or “carry” and / or “carrying,” or “contain” and / or “containing,” or “involve” and / or “involving, and the like are to be open-ended, i.e., to mean including but not limited to. When used in this specification, they specify the presence of stated features, regions, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and / or groups thereof.

[0047] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and this specification, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0048] As used in this specification, “around”, “about”, “approximately” or “substantially” shall generally mean within 20 percent, preferably within 10 percent, and more preferably within 5 percent of a given value or range. Numerical quantities given herein are approximate, meaning that the term “around”, “about”, “approximately” or “substantially” can be inferred if not expressly stated.

[0049] As used in this specification, the phrase “at least one of A, B, and C” should be construed to mean a logical (A or B or C), using a non-exclusive logical OR. As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items.

[0050] The description below is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. The broad teachings of the invention can be implemented in a variety of forms. Therefore, while this invention includes particular examples, the true scope of the invention should not be so limited since other modifications will become apparent upon a study of the drawings, the specification, and the following claims. For purposes of clarity, the same reference numbers will be used in the drawings to identify similar elements. It should be understood that one or more steps within a method may be executed in a different order (or concurrently) without altering the principles of the invention.

[0051] As discussed above, in the typical TAVR / TAVI procedure, some patient may encounter severe to critical conduction anomalies or disturbances. FIG. 1 schematically shows global variation in the uptake of the TAVI procedure, and FIG. 2 shows the pacemaker implantation rates in the TAVI procedure. Specifically, every implantation of the transcatheter aortic valve requires the placement of a temporary pacemaker. In 30% of cases, the decision is made to deploy a permanent pacemaker due to the development of long-term conduction system disturbances. The conduction system disturbances are common during and after the implantation of the transcatheter aortic valve due to the radial expansion of the frame of the valve and the close proximity of the conduction system in the septum of the heart, specifically the atrioventricular node, the bundle of His, and the left and right bundle branches.

[0052] In view of the deficiency, one aspect of the present invention relates to an aortic valve with an embedded pacing device therein. The unmet need for such aortic valve to have pacing capabilities is justified by the fact that every implantation of the transcatheter aortic valve requires the placement of a temporary pacemaker. For example, FIG. 3 schematically shows an aortic valve with an embedded pacing device being implanted in a heart of a living object according to certain embodiments of the present invention. As shown in FIG. 3, the aortic valve includes a valve frame 310, and a pacing device 320 being disposed and embedded in the valve frame. The valve frame 310 of the aortic valve is designed to be implanted into the aortic valve position with the pacemaker during the TAVR / TAVI procedure. In certain embodiments, the pacing device 320 is a leadless pacemaker having electrodes with pacing capabilities, and the electrodes with pacing capabilities are capable of delivering both pacing in the post-operative period and rapid pacing required during the deployment of the valve. As shown in FIG. 3, the pacing device 320 is powered by a wireless power transfer electrode 330. In certain embodiments, the pacing device is powered by wireless power transfer or by an embedded battery. The pacing device is configured to deliver rapid pacing during deployment of the aortic valve into a thoracic cavity of a living object and to deliver regular pacing during a postoperative period. The aortic valve is deployed in the TAVR / TAVI procedure without a need of an additional temporary or permanent pacemaker.

[0053] In another aspect of the present invention, a method for fabricating an aortic valve includes: providing a valve frame; and disposing a pacing device such that the pacing device is embedded in the valve frame, wherein the pacing device is configured to deliver rapid pacing during deployment of the aortic valve into a thoracic cavity of a living object and to deliver regular pacing during a post-operative period; and wherein the aortic valve is deployed in a TAVR / TAVI procedure without a need of an additional temporary or permanent pacemaker.

[0054] As shown in FIG. 3, the pacemaker electrode and components of the pacing device 320 are located on the side of the valve frame 310. In certain embodiments, the pacing device is configured to, through rotation during deployment of the aortic valve, interrogate tissues of a septal wall of the living object, sense a heart conduction system of the living object, and adjust a pacing threshold and a final position of the aortic valve. Thus, through the rotation maneuver during the deployment of the valve, the pacing / sensing component of the aortic valve will interrogate the tissue of the septal wall, sense the heart conduction system, and interrogate it by adjusting the pacing threshold and the final position of the valve. Also, the positioning of the pacing component of the system may be pre-determined on the frame of the valve to allow for the majority of cases.

[0055] FIG. 4 shows a posterior view of an aortic valve with an embedded pacing device being implanted in a heart of a living object according to a different embodiment of the present invention. As shown in FIG. 4, the aortic valve has been deployed at the final position, which is approximately above the interventricular septum, and the valve frame has been expanded to fit in the cavity. The pacing device 320 has a pacemaker electrode with pacing capabilities, and is powered by a wireless power transfer coil.

[0056] In certain embodiments, the valve frame of the aortic valve may be made of one or more of the following materials: graphene, MXenes, platinum, zinc, molybdenum, nitinol, and titanium. In certain embodiments, the valve frame of the aortic valve may be made from alloys containing different percentages of these metals. The materials may be bioresorbable or partially bioresorbable, and may include metals such as molybdenum or compounds like lactic acid. Specifically, the current iteration of the valve frame is comprised of the titanium / titanium alloy, which has slightly lower conductivity than that of Au and Pt, but higher mechanical stress and lower price. However, Au and Pt are also promising options, especially gold serpentine electrodes. Further, the inventors have conducted tests with graphene wires without reaching a target conductivity (as the tests show that the mix of graphene and silicone had the conductivity 1 / 10 of a wire), and further tests utilizing graphene may be required.

[0057] FIGS. 5A and 5B show the displacement of the valve frame of an aortic valve being implanted in a heart of a living object according to a different embodiment of the present invention. Specifically, the human hear as shown in FIGS. 5A and 5B, which is declined for transplantation because of size-mismatch, is connected to the Langendorff perfusion system and actively contracting. Further, the valve frame as shown in FIGS. 5A and 5B is a nitinol frame 510, which is inserted in the aortic position via the delivery system to keep the coronary artery orifices intact. Moreover, the left ventricle 520, the right ventricle 530, the left coronary cannula 540 as well as the right coronary cannula 550 are also shown in FIG. 5Ato indicate the displacement of the nitinol frame 510. FIG. 5B, which has a different viewing angle, is provided with the right coronary cannula 550 being removed before reinsertion.

[0058] In certain embodiments, the pacing device includes a radiopaque marker configured to scan, interrogate and sense the heart conduction system of the living object. Specifically, the radiopaque marker may enable scanning, interrogation, positioning, and electrical engagement of the conduction system by the embedded electrodes in the valve frame. In certain embodiments, the radiopaque marker of the pacing device is positioned under X-ray guidance.

[0059] In certain embodiments, the valve frame has a diameter within a range for appropriate positioning of the pacing device therein. For example, in one embodiment, the valve frame may have diameters ranging from 12 mm for infant applications to 36 mm for various sizes of the aortic valve. In an alternative embodiment, the valve frame of the aortic valve can be crimped to a size as small as 6 Fr for low-profile delivery through any of the aforementioned delivery routes.

[0060] In certain embodiments, the aortic valve may be deployed through, without being limited to, the following methods:

[0061] (1) Transaortic route: in the case where the aortic valve is a TAVI valve, the TAVI valve may be delivered transaortically until it is deployed in the supravalvular position, at the aortic valve position, or below the valve. The human heart ex vivo tests with separate cannulation of the coronary arteries has been performed on three human hearts, one of which had considerable aortic sclerosis and two of the delivery methods have been tested, including (1) direct insertion into the aorta in the position of the aortic valve; and also (2) the route from the apex of the left ventricle, through making an orifice in the left ventricle. Both delivery methods have proven to be effective and viable options, with the transapical route being slightly more traumatic one.

[0062] (2) Free wall of the left ventricle: the aortic valve may be deployed through the free wall of the left ventricle or the apex of the left ventricle.

[0063] (3) Carotid arteries: in the case where the aortic valve is a TAVI valve, the TAVI valve may be deployed through one of the carotid arteries.

[0064] (4) Subclavian artery: in the case where the aortic valve is a TAVI valve, the TAVI valve may also be deployed through the subclavian artery.

[0065] In certain embodiments, the valve frame of the aortic valve may be weaved together with wire or material that conducts electrical current. Alternatively, in certain embodiments, the valve frame may be formed out of conductive struts, and the conductive struts may encompass the entire valve frame of the TAVI valve or form clusters distributed along the valve frame in various sequences. In certain embodiments, another approach may apply to make some of the struts of the valve frame coated with isolating material. Since the whole frame is conductive, some isolation has to be put around in order to block the conduction where it is not needed. In one embodiment, some of the struts and connections of the frame may be coated with non- conductive materials, making some “islands” of the conductive struts for delivery of pacing through these uncovered stmts. In certain embodiments, the clusters of electrically conductive stmts may be positioned near the non-coronary cusp, left coronary cusp, or right coronary cusp. Alternatively, the clusters may be positioned within the tissue or on the surface of the septum, particularly under the aortic valve.

[0066] In certain embodiments, for the method of fabrication, the conductive materials or stmts may be weaved, embedded, or attached to the frame of the device. In certain embodiments, fabrication may be achieved through weaving, laser-cutting, injection molding, molding, extrusion, soldering, or other methods depending on the material of the device.

[0067] In certain embodiments, the pacing device of the aortic valve may interrogate tissue and underlying structures through dynamic impedance measurements. Specifically, the pacing device may inject current in a sequence of pulses to determine the pacing threshold, with current ranging from as low as 0.00001 mA or 0.00001 V to as high as 2 A and 20 V For example, the standard sequence may be 10 V, 9 V, . . . until 4 V, then 3.5 V, 3.0 V, . . . until 1 V, then 0.8 V, 0.7 V, . . . until 0.1 V, and then setting the delivery current twice the threshold, if the threshold is above 3 V, the location of the electrode has to be adjusted, as it will drain the wearable battery fast. In certain embodiments, the pacing device will dynamically measure pacing thresholds (as the electrode part of the aortic valve opposes the conduction system in the septal portion of the heart) for tissue. In other words, the dynamic measurement may be achieved by performing cycle fast through the sequence to determine the threshold and selecting the location with the lowest pacing threshold. The pacing device may also provide a map indicating favorable locations with the lowest pacing threshold, with the color-coding of the high threshold locations and low ones (e g., 12 on average). In certain embodiments, the pacing device may also include a decision support system to facilitate the human operator in deployment of the device.

[0068] In certain embodiments, the aortic valve itself is made visible on the X-ray (because of the titanium being used as the material thereof), but the aortic valve may include radiopaque markers, such as platinum or platinum iridium alloy, that are also visible under X-ray guidance or other markers that are visible under ultrasound guidance. This allows for double-control through X-ray and transesophageal ultrasound for correct valve deployment.

[0069] In certain embodiments, the power module of the pacing device may include a capacitor capable of storing and discharging energy to ensure uninterrupted and continuous functioning. In certain embodiments, the wearable module of the wireless power transfer system may be located on any surface of the body, including the chest, back, clavicular, axillar, and scapular locations, as long as power is transferred effectively. In certain embodiments, the power module may transmit across a variety of frequencies, including but not limited to 6.78 MHz to 13.56 MHz. In particular, the experiments being conducted show that the frequency that is closest to 13.56 MHz has worked best. However, radio wavelength to coil / antenna size ratio, coupler geometry, shape may all affect the wireless power transfer efficiency. The most important aspect is the combination of these factors, which result in the efficiency of the system and how it performs under different angular, placement misalignments and separation distances’ conditions. Therefore, a broader range of frequencies, which may depend upon the placement of the wearable module, and in turn depend on the constitution of the patient (e.g., body-mass index), may also be considered.

[0070] In certain embodiments, rapid pacing functionality may be embedded into the frame to rapidly pace the heart above 160 bpm during deployment, countering device parachuting and allowing precise delivery. This rapid pacing may be achieved through the struts of the pacing device, conductive wires weaved into the valve frame, or an extension of the device in the form of a guidewire structure engaging the tissue of the left ventricle or septum.

[0071] In certain embodiments, it is especially worth mentioning that the resynchronization capability of the device as the timing, thresholds and the location of the pacing may be adjusted to facilitate a more physiological conduction of the excitation wave.

[0072] In certain embodiments, the aortic valve as described above may be configured for mitral, pulmonic, and tricuspid valves. For example, for the pulmonic valve, in the Langendorff setup, the pacing thresholds have been tested with the implantation of the frame resembling the pulmonary valve. Specifically, the pacing thresholds gathered were primarily in the position of the Right Ventricle Outflow Tract (RVOT), and were as low as 0.8V with 1 ms pulse width, which is promising for the pacing of the conduction from the pulmonary valve area adjacent to the RVOT. Further, the location adjacent to the His-bundle allows physiologic pacing and resynchronisation by pacing selectively the His Bundle (His-Bundle Pacing). For the mitral valve, the device can be deployed in the mitral position, which is able to pace the heart by engaging the free wall of the left ventricle. This has also been tested, however the pacing thresholds were rather large for this position (3.5 V and 3-5 ms pulse width). For the tricuspid valve, the positioning on the tricuspid valve is also promising due to the proximity to the Atrioventricular node (AVnode) which allows AVnode pacing. Further, the His-bundle is nearby, which allows selective His-Bundle pacing (S-HBP). In this way, the frame with the tricuspid valve can effectively engage both the AVnode and the His-Bundle.

[0073] The primary advantage of the aortic valve according to certain embodiments of the present invention exists in that it is a fully implantable pacemaker capable of sensing and thus determining the need for pacing and subsequent on-demand / prolonged pacing of the conduction system. This will eliminate the need for implantation of the additional either temporary or permanent pacemaker. A further aspect of the present invention relates to a method for performing a TAVR / TAVI procedure, which includes: providing the aortic valve as described above; and deploying the aortic valve into a thoracic cavity of a living object, wherein the pacing device is configured to deliver rapid pacing during deployment of the aortic valve into the thoracic cavity and to deliver regular pacing during a post-operative period. In certain embodiments, the TAVR / TAVI procedure is performed without a need of an additional temporary or permanent pacemaker.

[0074] Compared to the existing aortic valve that requires an additional temporary pacemaker, the aortic valve according to certain embodiments of the present invention is a medical device capable of helping patients with aortic stenosis and addressing conduction disturbances frequently observed during and after transcatheter aortic valve implantation, which may resol ve / support the electrical conduction for patients with severe to critical aortic stenosis who undergo TAVR / TAVI procedure.

[0075] In comparison, as discussed above, the current clinical practice involves placement of the temporary pacemaker through the central vein for in-operation rapid pacing. The temporary pacemaker is either removed right after the procedure if no conduction disturbances are observed, or left for 7 days for observation / support. After 7 days the decision is made to either implant a permanent subcutaneous pacemaker or not. The existing used valves cannot pace the heart or sense the conduction system. The existing pacemakers feature configuration either with or without lead, with an extemal / or subcutaneously implanted control box / battery. It should be noted that none of the existing aortic valve has any sensing / pacing capability to date, most likely due to the energy transfer problem, as it is required to deliver power from a power source to the pacing electrodes.

[0076] The inventors have conducted the experiments on 6 human hearts which were declined for transplantation. In particular, the hearts were perfused in the Langendorff perfusion setup which kept them functional, and the inventors implanted the device in the three positions: supraaortic, aortic, and subaortic. The frame of the devices was made out of nitinol, hence the struts were conductive, and the pacing thresholds for each of the locations as well as the locations were determined with regards to the coronary cusps. The device was deployed utilizing the delivery system and expansion of the device was achieved. The pacing thresholds were in the range of 1.3 V to 3 V, which corresponds to the usual clinical threshold values. The location under the aortic valve next to the septum had the lowest pacing threshold of 1.3 V and is considered the aiming point for deployment of the conductive part of the frame / electrodes.

[0077] FIG. 6 shows extraction procedure-related complication data using a temporary pacemaker. As discussed above, the temporary pacemakers require removal or extraction, which makes the patients prone to complications as shown in FIG. 6.

[0078] FIGS. 7Ato 7C shows data related to the hazard ratio of a new device and a reused device using an existing aortic valve with a temporary pacemaker. Specifically, FIG. 6A shows a table of characteristics of the patients and devices at baseline, FIG. 6B shows a chart of data related to the hazard ratio of a new device and a reused device using an existing aortic valve with a temporary pacemaker, and FIG. 6C shows data related to the hazard ratio of a new device and a reused device using an existing aortic valve with a temporary pacemaker, including factors associated with infection or device-related death. As shown in FIG. 6, the hazard ratios for both the new device and the reused device are super high, as the numbers of patients at risk at the time of the implantation of the existing aortic valve is close to 100%, and after 2 years of the implantation, the patients being implanted with a new device still has an over 99% risk, while the patients being implanted with a reused device is at the 98% risk. This clearly shows the need of the aortic valve according to certain embodiments of the present invention.

[0079] FIGS. 8Ato 8C show additional data of the capture beats. Specifically, the data as shown in FIGS. 8 A to 8C are the ECG of the human heart connected to the Langendorff setup, with three patterns. In particular, FIG. 8A shows stable capture beats from the aortic valve position via stimulation from the valve frame. FIG. 8B shows the borderline capture, with 2 artificial spikes signifying stimulation below the pacing threshold and no capture beats visible, and then stimulation being applied above the pacing threshold and 4 visible capture beats. FIG. 8C shows attempted stimulation from above the aortic valve near the atrial position in the aorta, with the small downward spike being visible before each capture beat, which is indicative of the location of the stimulation and the capabilities for the resynchronization therapy.

[0080] In sum, the aortic valve according to certain embodiments of the present invention is a heart valve or an aortic valve for minimally-invasive implantation into the aortic position to treat such a condition as aortic stenosis. The aortic valve can pace the heart, both rapidly and to sustain the normal rate of the heart. The aortic valve may be able to mitigate the conduction system disturbances observed frequently among these patients, as the less number of devices involved -the less access sites for infections, the better the outcomes. Further, the aortic valve allows on-demand pacing with no cables, skin pockets and associated scars. Moreover, since there is no need to implant additional pacemakers, the overall procedure becomes less invasive.

[0081] The foregoing description of the exemplary embodiments of the invention has been presented only for the purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations are possible in light of the above teaching.

[0082] The embodiments were chosen and described in order to explain the principles of the invention and their practical application so as to enable others skilled in the art to utilize the invention and various embodiments and with various modifications as are suited to the particular use contemplated. Alternative embodiments will become apparent to those skilled in the art to which the invention pertains without departing from its spirit and scope. Accordingly, the scope of the invention is defined by the appended claims rather than the foregoing description and the exemplary embodiments described therein.

[0083] Some references, which may include patents, patent applications, and various publications, are cited and discussed in the description of this invention. The citation and / or discussion of such references is provided merely to clarify the description of the invention and is not an admission that any such reference is “prior art” to the invention described herein. All references cited and discussed in this specification are incorporated herein by reference in their entireties and to the same extent as if each reference was individually incorporated by reference.

[0084] REFERENCE LIST:

[0085] 1. Coffey, S., Brown, A., Carapetis, J., Chen, M., Ztihlke, L., & Prendergast, B. D. (2021).

[0086] Global epidemiology of valvular heart disease. Nature Reviews Cardiology, 75(12), 853 - 864. https: / / d oi org / 10.1038 Zs41569-021 -00570-z

[0087] 2. Cheol Hyun Lee et al. JACC: Asia 2021; 1 :279-293.

[0088] 3. Kusumoto FM, Schoenfeld MH, Wilkoff BL, et al. 2017 HRS expert consensus statement on cardiovascular implantable electronic device lead management and extraction [published correction appears in Heart Rhythm. 2021 Oct; 18(10): 1814], Heart Rhythm.

[0089] 2017;14(12):e503-e551. doi: 10.1016 / j.hrthm.2017.09.001

[0090] 4. TF Khairy et al. N Engl J Med 2020;382: 1823-1831

Claims

CLAIMSWhat is claimed is:

1. An aortic valve, comprising: a valve frame; and a pacing device, being disposed and embedded in the valve frame, wherein the pacing device is configured to deliver rapid pacing during deployment of the aortic valve into a thoracic cavity of a living object and to deliver regular pacing during a post-operative period; wherein the aortic valve is deployed in a transcatheter aortic valve replacement / implantation (TAVR / TAVI) procedure without a need of an additional temporary or permanent pacemaker.

2. The aortic valve according to claim 1, wherein the pacing device is a leadless pacemaker having electrodes with pacing capabilities.

3. The aortic valve according to claim 1, wherein the pacing device is configured to, through rotation during deployment of the aortic valve, interrogate tissues of a septal wall of the living object, sense a heart conduction system of the living object, and adjust a pacing threshold and a final position of the aortic valve.

4. The aortic valve according to claim 3, wherein the pacing device includes a radiopaque marker configured to scan, interrogate and sense the heart conduction system of the living object.

5. The aortic valve according to claim 4, wherein the radiopaque marker of the pacing device is positioned under X-ray guidance.

6. The aortic valve according to claim 1, wherein the pacing device is powered by wireless power transfer or by an embedded battery.

7. The aortic valve according to claim 1, wherein the valve frame has a diameter within a range for appropriate positioning of the pacing device therein.

8. The aortic valve according to claim 1, wherein the valve frame is made of a material selected from the group consisting of graphene, MXenes, platinum, zinc, molybdenum, nitinol, titanium, a combination thereof, and alloys thereof.

9. The aortic valve according to claim 1, being used for resynchronization therapy.

10. The aortic valve according to claim 1, being configured for mitral, pulmonic, and tricuspid valves.

11. A method for performing a transcatheter aortic valve replacement / implantation (TAVR / TAVI) procedure, comprising: providing the aortic valve according to claim 1; and deploying the aortic valve into a thoracic cavity of a living object, wherein the pacing device is configured to deliver rapid pacing during deployment of the aortic valve into the thoracic cavity and to deliver regular pacing during a post-operative period.

12. The method according to claim 11, wherein the TAVR / TAVI procedure is performed without a need of an additional temporary or permanent pacemaker.

13. The method according to claim 11, wherein the pacing device is configured to, through rotation during deployment of the aortic valve, interrogate tissues of a septal wall of the living object, sense a heart conduction system of the living object, and adjust a pacing threshold and a final position of the aortic valve.

14. A method for fabricating an aortic valve, comprising: providing a valve frame; and disposing a pacing device such that the pacing device is embedded in the valve frame,wherein the pacing device is configured to deliver rapid pacing during deployment of the aortic valve into a thoracic cavity of a living object and to deliver regular pacing during a post-operative period; and wherein the aortic valve is deployed in a transcatheter aortic valve replacement / implantation (TAVR / TAVI) procedure without a need of an additional temporary or permanent pacemaker.

15. The method according to claim 14, wherein the pacing device is a leadless pacemaker having electrodes with pacing capabilities.

16. The method according to claim 14, wherein the pacing device is configured to, through rotation during deployment of the aortic valve, interrogate tissues of a septal wall of the living object, sense a heart conduction system of the living object, and adjust a pacing threshold and a final position of the aortic valve.

17. The method according to claim 16, wherein the pacing device includes a radiopaque marker configured to scan, interrogate and sense the heart conduction system of the living object.

18. The method according to claim 17, wherein the radiopaque marker of the pacing device is positioned under X-ray guidance.

19. The method according to claim 14, wherein the pacing device is powered by wireless power transfer or by an embedded battery.

20. The method according to claim 14, wherein the valve frame has a diameter within a range for appropriate positioning of the pacing device therein.

21. The method according to claim 14, wherein the valve frame is made of a material selected from the group consisting of graphene, MXenes, platinum, zinc, molybdenum, nitinol, titanium, a combination thereof, and alloys thereof.

22. An aortic valve fabricated by the method of claim 14.

23. The aortic valve according to claim 22, being used for resynchronization therapy.

24. The aortic valve according to claim 22, being configured for mitral, pulmonic, and tricuspid valves.

25. A method for performing a transcatheter aortic valve repl acement / im plantation (TAVR / TAVI) procedure, comprising: providing the aortic valve according to claim 22; and deploying the aortic valve into a thoracic cavity of a living object, wherein the pacing device is configured to deliver rapid pacing during deployment of the aortic valve into the thoracic cavity and to deliver regular pacing during a post-operative period.

26. The method according to claim 25, wherein the TAVR / TAVI procedure is performed without a need of an additional temporary or permanent pacemaker.

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