Baroreflex gauges, mapping devices, and methods of use

Abstract

Provided herein are methods for measuring baroreflex response, and baroreflex gauge devices and systems. Such methods and devices position and expand an expandable structure at a target site within a patient's vasculature, preferably the aortic arch, and measure the baroreflex response in one or more transverse dimensions of the expandable structure. The baroreflex gauge device can optionally expand the structure to multiple expanded configurations while monitoring the patient's blood pressure to determine optimal dimensions for baroreflex response. These gauge devices and methods aid in assessing a patient's suitability for treatment and in selecting or customizing an implant to be placed within the vasculature for long-term treatment of hypertension. The baroreflex gauge device can also be integrated into an implant delivery system, allowing partial deployment to enable response measurement and full deployment to enable long-term treatment.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Application No. 63 / 485,849, filed February 17, 2023, and U.S. Provisional Application No. 63 / 594,919, filed October 31, 2023, the entire disclosures of which are incorporated herein by reference in their entirety for all purposes.

[0002] This application is generally related to commonly owned PCT patent applications entitled "Aortic Arch Baroreceptor Implant for Treating Hypertension," serial number PCT / US2023 / 020612, filed May 1, 2023, and entitled "Delivery Catheter and Delivery Method for Aortic Arch Baroreceptor Hypertension Implant," serial number PCT / US2023 / 020608, filed May 1, 2023, the contents of which are incorporated herein by reference in their entireties for all purposes. This application is also related to U.S. Provisional Application No. 63 / 594,915, filed October 31, 2023, entitled "Delivery Catheter and Delivery Method for an Aortic Arch Baroreceptor Hypertension Implant," and U.S. Provisional Application No. 63 / 594,903, filed October 31, 2023, entitled "Aortic Arch Baroreceptor Implant for Treating Hypertension," both of which are commonly owned, the contents of which are also incorporated herein by reference in their entireties for all purposes.

[0003] FIELD OF THE INVENTION In one aspect, the present invention relates to methods for assessing baroreceptor response and location, baroreflex gauges, mapping catheter devices, and hypertensive implant delivery methods and devices. [Background technology]

[0004] In the United States, one in two adults suffers from hypertension. However, only 24% of patients have adequate control of their blood pressure. Hypertension is the leading preventable cause of heart attack, stroke, and death. However, a 10 mmHg reduction in blood pressure reduces this cardiovascular risk by 20%.

[0005] Despite reportedly low patient compliance with antihypertensive medication regimens, pharmacotherapy has remained the mainstay of hypertension treatment for decades. In 2004, a landmark clinical trial involving a catheter-based device (i.e., Symplicity 1) first demonstrated the blood pressure-lowering effects of renal denervation with a radiofrequency ablation catheter. Findings from additional clinical trials of radiofrequency energy renal denervation and ultrasound energy renal denervation (i.e., the SPYRAL and RADIANCE clinical trials, respectively) supported these findings, although blood pressure reduction results were more modest, resulting in a reduction of approximately 5–10 mmHg in ambulatory systolic blood pressure.

[0006] An intravascular implant developed by Vascular Dynamics for hypertension relies on a stent-like device inserted into the carotid artery, which stretches the arterial wall from the inside and lowers blood pressure by enhancing the carotid baroreflex. A 2017 study showed that this carotid baroreflex modulation device significantly reduced ambulatory systolic blood pressure, more than double the reduction reported in renal denervation clinical trials. Although clinical results initially appeared promising, with several patients reporting dramatic blood pressure reductions that persisted for 2–3 years, clinical outcomes were mixed, as some patients suffered transient ischemic attacks (TIAs), which prevented further clinical trials and subsequent development.

[0007] Another challenge arose with regard to device deployment in the carotid sinus, the device's primary target. Because the carotid sinus supplies blood to the brain, any difficulties encountered at this site, such as damage to arterial tissue during deployment, subsequent device dislodgement, and / or plaque buildup in the area due to the device or trauma, could contribute to a TIA or stroke, resulting in adverse or fatal patient outcomes. For clinicians lacking experience with this sensitive area, performing a procedure at this site, such as placing a carotid stent, could pose unnecessary risks to the patient.

[0008] Thus, there remains a need for devices and methods for treating hypertension that provide the clinical benefits seen in the baroreflex response while avoiding the significant drawbacks associated with the conventional approaches described above. There is a further need for such devices that allow for improved ease and consistency of implantation to avoid the side effects described above, allowing for implantation by a wider range of clinicians, and more reliably providing positive patient outcomes for long-term relief of hypertension.

[0009] Despite the ongoing development of implants for the treatment of hypertension, uncertainty and variability remain regarding patient outcomes with such implants. Therefore, a better understanding of the baroreflex response is needed to assess the feasibility of therapeutic approaches and further improve hypertension treatment. Summary of the Invention [Means for solving the problem]

[0010] The present invention relates to a method for assessing the baroreflex response of a patient and a baroreflex gauge device for performing such an assessment.

[0011] In one aspect, the present invention relates to a method for assessing a patient's baroreflex response, which may include advancing a delivery catheter carrying an expandable structure at a distal portion thereof, the expandable structure being disposed on the delivery catheter in a collapsed configuration to facilitate advancement through the patient's vasculature and being expandable to a plurality of expanded configurations having different transverse dimensions; positioning the distal portion of the catheter carrying the implant in the collapsed configuration at a target region within the vasculature; expanding the expandable structure within the target region such that the expandable structure expands to an expanded configuration having a transverse dimension sufficient to engage an arterial wall along the treatment region to stretch at least a portion of the arterial wall along the target region, thereby eliciting a baroreflex response of aortic arch baroreceptors within the target region and lowering blood pressure; and monitoring the patient's blood pressure with the expandable structure in the expanded configuration, the expanded configuration having a transverse dimension corresponding to the implant to be deployed at the target site. In some embodiments, each of the plurality of expanded configurations having different transverse dimensions is circular in cross section. In some embodiments, the step of positioning the expandable structure involves observing one or more visualization markers positioned on the expandable structure. The different transverse dimensions can range from 20 mm to 100 mm, typically from 20 mm to 60 mm. Preferably, the different transverse dimensions correspond to the transverse dimensions of multiple implants having different sizes, facilitating the selection of each implant to optimize the baroreflex response. Typically, the target region is within the aortic arch, and in particular, the target region is the cylindrical segment between the left common carotid artery and the left subclavian artery. Utilizing an adjustable expandable structure that can be adjusted between multiple expanded configurations with different transverse dimensions is advantageous because it facilitates measuring the baroreflex response at multiple stages of stretching without requiring removal or replacement of structures with different sizes, thereby improving ease of use and reducing the time and risks involved in the procedure.This approach has the added advantage that it allows these different sizes to be adjusted at precisely the same location without requiring axial movement of the catheter between adjustments, thereby allowing for more accurate assessment of baroreceptor location and precise mapping of target sites for subsequent implant placement.

[0012] In some embodiments, the expanded configuration is a first configuration having a first lateral dimension, and the method further includes adjusting the expanded expandable structure to a second configuration having a second lateral dimension and monitoring the patient's blood pressure while the expandable structure is in the second expanded configuration. The method may further involve repeating adjusting the expandable structure to one or more additional configurations having different lateral dimensions and monitoring the blood pressure in each configuration until the monitored blood pressure indicates the desired blood pressure reduction. The clinician records the lateral dimension at which the blood pressure monitoring indicates the desired blood pressure reduction. In some embodiments, the method includes repeating adjusting the expandable structure to one or more additional positions along or near the target region and monitoring the blood pressure in each configuration to determine a maximum expanded diameter of the target region within the vasculature, above which there is little or no improvement in blood pressure. In some embodiments, the method further includes repeatedly adjusting the expandable structure to one or more additional positions along or near the target region and monitoring blood pressure at each position to determine the minimum expanded diameter of the target region within the vasculature required to produce a baroreflex response that lowers blood pressure.

[0013] In some embodiments, the expanded configuration is in a first position within the target region, and the method further includes repositioning the expandable structure to a second position within or near the target region and monitoring the patient's blood pressure with the expandable structure in the second position. The method may further involve repeating adjusting the expandable structure to one or more additional positions along or near the target region and monitoring the blood pressure in each configuration until the monitored blood pressure indicates the desired blood pressure reduction. The clinician records the location where the monitored blood pressure indicates the desired blood pressure reduction for later implanting a hypertension treatment at that location.

[0014] In another aspect, the present invention relates to a method for deploying an implant for treating hypertension within a patient's vasculature. The method may include performing a baroreflex assessment as described above, selecting or customizing an implant and / or selecting a location for the implant based on the baroreflex assessment, and deploying the implant at a target site within the vasculature to treat hypertension. In some embodiments, selecting the implant includes selecting an implant from a plurality of implants having different transverse dimensions, the selected implant having a transverse dimension corresponding to a transverse dimension at which monitored blood pressure indicates a desired reduction in blood pressure. In some embodiments, customizing the implant includes adjusting the dimensions of the implant and locking the implant at a dimension corresponding to an optimal dimension for baroreflex response. In some embodiments, the implant includes two expandable structures connected in series by a flexible connector, at least one expandable structure having a transverse dimension corresponding to a transverse dimension at which monitored blood pressure indicates a desired reduction in blood pressure. In some embodiments, the implant includes three expandable structures connected in series by a flexible connector, at least a central expandable structure having a transverse dimension corresponding to a transverse dimension at which monitored blood pressure indicates a desired reduction in blood pressure. In some embodiments, the method includes partially deploying an implant having multiple structures (e.g., three structures) to fully expand at least one structure (e.g., a central structure) in the target region and assessing the physiological response (e.g., baroreflex response) before fully deploying the entire implant. In some embodiments, the most proximal expandable structure is only partially deployed or undeployed during the measurement. Such an implant may be defined by multiple expandable structures (e.g., expandable rings) interconnected by helically oriented bridges, allowing the implant to conform to the curvature of the aortic arch. In some embodiments, at least one structure has a larger lateral dimension than the other expandable structures, stretching the target region and eliciting a baroreflex response.In some embodiments, the central expandable structure has a lateral dimension that is 1.3 to 1.5 times the lateral dimension of the proximal and distal structures.

[0015] In yet another aspect, the present invention relates to a baroreflex gauge catheter device. Such a device may include: a shaft extending between a proximal end and a distal end, the shaft having one or more lumens therethrough; an expandable structure disposed on a distal portion of the shaft in a collapsed configuration, the expandable structure being convertible between the collapsed configuration and an expanded configuration for engaging an arterial wall at a target region within the vasculature, the expandable structure being adjustable to a plurality of expanded configurations, each having a different transverse dimension; a retractable outer sheath having a proximal end and a distal end, the outer sheath disposed on the shaft, including the distal end at which the expandable structure is disposed, such that the delivery catheter is configured to facilitate deployment of the expandable structure at the target region; and a catheter handle disposed at or near the proximal end of the shaft, the outer sheath being retractable from the catheter handle to facilitate deployment of the expandable structure at the target region, the catheter handle further comprising an adjustment for adjusting the expandable structure between any of the expanded configurations. The baroreflex gauge device may further be incorporated into a system that includes a blood pressure monitor. Typically, the device is manually adjusted by a clinician, but in some embodiments, all or part of the operation may be automated based on the monitored blood pressure to optimize the baroreflex measurement procedure.

[0016] In some embodiments, the expandable structure comprises a plurality of struts configured to allow lateral blood flow therethrough to ensure accurate blood pressure monitoring and better simulate an implant. The struts may include visualization markers to facilitate positioning the expandable structure at the target area. Preferably, the expandable structure of the gauge is configured for deployment within the aortic arch, particularly within the cylindrical segment between the left common carotid artery and the left subclavian artery. In some embodiments, the expandable structure of the gauge is configured to expand to a range of lateral dimensions or diameters, such as within a range of 20 mm to 100 mm, preferably within a range of 20 mm to 60 mm. In some embodiments, the expandable structure comprises two wires having spines that articulate laterally at a central segment of the wires to facilitate bending and straightening the arterial wall. In some embodiments, the structure may be a single wire that articulates and stretches at least a portion of the arterial wall.

[0017] In some embodiments, the catheter handle control of the baroreflex gauge includes an adjustment for incrementally adjusting the lateral dimension of the expandable structure. The adjustment may include a slider, and optionally, one or more precision controls, such as a rotary wheel or dial, for adjusting the structure in smaller increments. In some embodiments, the catheter handle further includes a locking mechanism for locking the lateral dimension of the expandable structure during monitoring. In some embodiments, the guide catheter device is configured with a rack and pinion mechanism that allows the lateral dimension of the expandable structure to be adjusted without substantially moving the midpoint of the expandable structure within the vasculature. The guide catheter device is configured with a worm gear that allows the lateral dimension of the expandable structure to be adjusted without substantially moving the midpoint of the expandable structure within the vasculature.

[0018] In another aspect, the implant itself can be used as a baroreflex gauge. In some embodiments, the implant can be partially deployed so that one or more expandable structures are deployed at the target site, after which physiological responses (e.g., blood pressure) can be monitored to assess the effectiveness of the implant. Based on the response, the implant can then be fully deployed, repositioned, or removed. If the response is satisfactory, the implant can be fully deployed at the target site. In some embodiments, the remaining portion of the implant is deployed and released from the delivery catheter, otherwise leaving the already deployed portion from which the response was measured unchanged. If the response is suboptimal or not at all, the implant can be repositioned or pulled back into the delivery catheter and deployed to another site for further measurement and evaluation. If no response is obtained, the implant can be pulled back into the delivery sheath and removed. Optionally, a different size implant can be selected and deployed in a similar manner for further measurement and evaluation. In such embodiments, the implant can be releasably coupled to the delivery catheter by a locking element. In some embodiments, the locking element is releasably coupled to one or more proximal connectors on the implant. In some embodiments, the locking element is a locking collar having holes or notches that engage with multiple connectors. The connectors may be located at the proximal end of the implant or at the proximal end of a tether extending proximally from the implant. The tether allows at least a central portion of the implant to be fully deployed at the target site for measuring the baroreflex response, while the proximal portion remains connected to the delivery catheter for subsequent repositioning or removal. In some embodiments, the delivery catheter may further comprise any of the fine adjustment features described herein to precisely position the implant at the target site within the aortic arch. [Brief explanation of the drawings]

[0019] [Figure 1A] FIG. 1A illustrates an exemplary baroreflex gauge device with a distal expandable basket, according to some embodiments. [Figure 1B] FIG. 1B shows a detailed view of an expandable structure, according to some embodiments. [Figure 2] FIG. 2 shows a cross-sectional view (without the handle body and slider) further illustrating the means by which the expandable structure 10 is expanded by actuation of the shaft. [Figure 3A] FIG. 3A illustrates various incremental adjustment mechanisms for a baroreflex gauge device, according to some embodiments. [Figure 3B] FIG. 3B illustrates various incremental adjustment mechanisms for a baroreflex gauge device, according to some embodiments. [Figure 4A] FIG. 4A shows an alternative design of a baroreflex gauge device, according to some embodiments. [Figure 4B] FIG. 4B illustrates an alternative design of a baroreflex gauge device, according to some embodiments. [Figure 4C] FIG. 4C illustrates an alternative design of a baroreflex gauge device, according to some embodiments. [Figure 4C-1] FIG. 4C-1 illustrates an incremental adjustment mechanism for a baroreflex gauge device, according to some embodiments. [Figure 4C-2] FIG. 4C-2 illustrates an incremental adjustment mechanism for a baroreflex gauge device, according to some embodiments. [Figure 5A-1] FIG. 5A-1 shows various views of an alternative design of an expandable member for a baroreflex gauge device, according to some embodiments. [Figure 5A-2] 5A-2 show various views of an alternative design of an expandable member for a baroreflex gauge device, according to some embodiments. [Figure 5A-3] 5A-3 show various views of an alternative design of an expandable member for a baroreflex gauge device, according to some embodiments. [Figure 5B-1] FIG. 5B-1 shows various views of an alternative design of an expandable member for a baroreflex gauge device, according to some embodiments. [Figure 5B-2] FIG. 5B-2 shows various views of an alternative design of an expandable member for a baroreflex gauge device, according to some embodiments. [Figure 5B-3] 5B-3 show various views of an alternative design of an expandable member for a baroreflex gauge device, according to some embodiments. [Figure 5C-1] FIG. 5C-1 illustrates various aspects of how an expandable structure may stretch the arterial wall, according to some embodiments. [Figure 5C-2] 5C-2 illustrate various aspects of how an expandable structure may stretch the arterial wall, according to some embodiments. [Figure 5C-3] 5C-3 illustrate various aspects of how an expandable structure may stretch the arterial wall, according to some embodiments. [Figure 5C-4] 5C-4 illustrate various aspects of how an expandable structure may stretch the arterial wall, according to some embodiments. [Figure 5C-5] 5C-5 illustrate various aspects of how an expandable structure may stretch the arterial wall, according to some embodiments. [Figure 5C-6] 5C-6 illustrate various aspects of how an expandable structure may stretch the arterial wall, according to some embodiments. [Figure 5D-1] FIG. 5D-1 illustrates various aspects of how an expandable structure having a generally circular cross-section can stretch the arterial wall, according to some embodiments. [Figure 5D-2] FIG. 5D-2 illustrates various aspects of how an expandable structure having a generally circular cross-section can stretch the arterial wall, according to some embodiments. [Figure 5D-3] 5D-3 illustrate various aspects of how an expandable structure having a generally circular cross-section can stretch the arterial wall, according to some embodiments. [Figure 5D-4] 5D-4 illustrate various aspects of how an expandable structure having a generally circular cross-section can stretch the arterial wall, according to some embodiments. [Figure 5D-5] 5D-5 illustrate various aspects of how an expandable structure having a generally circular cross-section can stretch the arterial wall, according to some embodiments. [Figure 5D-6]5D-6 illustrate various aspects of how an expandable structure having a generally circular cross-section can stretch the arterial wall, according to some embodiments. [Figure 6] FIG. 6 illustrates an exemplary baroreflex gauge device deployed along a target region within a patient's aortic arch for assessment of the baroreflex, according to some embodiments. [Figure 7A] FIG. 7A illustrates delivery of an exemplary implant for treating hypertension, according to some embodiments. [Figure 7B] FIG. 7B illustrates an exemplary implant for treating hypertension placed in the aortic arch, according to some embodiments. [Figure 7C] FIG. 7C illustrates another exemplary implant for treating hypertension placed in the aortic arch, according to some embodiments. [Figure 8A] FIG. 8A shows a conventional diagram of the vasculature and baroreceptor anatomy and an illustration of the location of the carotid baroreceptors targeted by conventional devices. [Figure 8B] Figure 8B shows details of a typical baroreceptor called PEIZO1. [Figure 8C] FIG. 8C shows the central nervous system response to baroreflex stimulation in blood pressure regulation. [Figure 8D] Figure 8D shows the anatomy of the aortic arch vasculature. [Figure 8E] Figure 8E shows the fetal anatomy that later develops into the aortic arch. [Figure 8F] FIG. 8F illustrates the anatomy of the aortic arch showing additional details regarding the target region, according to an embodiment of the present invention. [Figure 8G] FIG. 8G shows the histology of the arterial tissue within the target area. [Figure 8H] FIG. 8H shows fluorescent staining images from animal studies showing the distribution of baroreceptors in the target area. [Figure 8I] FIG. 8I shows a fluorescent staining image showing the location of baroreceptors within the arterial wall of the aortic lumen. [Figure 9A]FIG. 9A shows the results of a previous animal study demonstrating the increased sensitivity of baroreceptors in the aorta compared to baroreceptors in the carotid artery. [Figure 9B] FIG. 9B shows the results of a previous animal study demonstrating the increased sensitivity of baroreceptors in the aorta compared to baroreceptors in the carotid artery. [Figure 10A] FIG. 10A shows an exemplary implant having two expandable structures interconnected by a flexible connector, according to some embodiments, the structure being defined by four frames and having a square cross section. [Figure 10B] FIG. 10B shows an exemplary implant having two expandable structures interconnected by a flexible connector, according to some embodiments, the structure being defined by four frames and having a square cross section. [Figure 10C] FIG. 10C shows an exemplary implant having two expandable structures interconnected by a flexible connector, according to some embodiments, the structure being defined by four frames and having a square cross section. [Figure 10D] FIG. 10D shows an exemplary implant having two expandable structures interconnected by a flexible connector, according to some embodiments, the structure being defined by four frames and having a square cross section. [Figure 10E] FIG. 10E illustrates an exemplary implant having three expandable structures, according to some embodiments, with FIG. 10E illustrating an embodiment having three structures with the same lateral dimension. [Figure 10F] FIG. 10F illustrates an exemplary implant having three expandable structures, according to some embodiments, where FIG. 10F illustrates an embodiment in which the lateral dimension of the central structure is increased. [Figure 11A] FIG. 11A shows an alternative embodiment of the implant in which the expandable structure is defined by three frames and has a triangular cross section. [Figure 11B]FIG. 11B shows an alternative embodiment of the implant in which the expandable structure is defined by three frames and has a triangular cross section. [Figure 12A] FIG. 12A shows an alternative embodiment of the implant in which the expandable structure is defined by five frames and has a hexagonal cross section. [Figure 12B] FIG. 12B shows an alternative embodiment of the implant in which the expandable structure is defined by five frames and has a hexagonal cross section. [Figure 13] Figure 13 shows various calculated dimensions (A, B, C, D, E) of the aorta that were developed in a patient study to determine the appropriate size of the implant construct for deployment within the aorta. [Figure 14] Figure 14 shows various calculated dimensions (A, B, C, D, E) of the aorta that were developed in a patient study to determine the appropriate size of the implant construct for deployment within the aorta. [Figure 15A] FIG. 15A illustrates a mechanism of action in accordance with an embodiment of the present invention in which an appropriately sized structure engages and stretches a roughly circular (e.g., 25 mm diameter) aortic wall to achieve sufficient stretch to induce a baroreflex. [Figure 15B] FIG. 15B illustrates a mechanism of action in accordance with an embodiment of the present invention in which an appropriately sized structure engages and stretches a roughly circular (e.g., 25 mm diameter) aortic wall to achieve sufficient stretch to induce a baroreflex. [Figure 15C] FIG. 15C illustrates a mechanism of action in accordance with an embodiment of the present invention in which an appropriately sized structure engages and stretches a roughly circular (e.g., 25 mm diameter) aortic wall to achieve sufficient stretch to induce a baroreflex. [Figure 15D] FIG. 15D illustrates a mechanism of action in accordance with an embodiment of the present invention in which an appropriately sized structure engages and stretches a roughly circular (e.g., 25 mm diameter) aortic wall to achieve sufficient stretch to induce a baroreflex. [Figure 16]FIG. 16 illustrates a target region of the aorta, according to some embodiments, which is the entire aortic segment between the LCCA and the LSA. [Figure 17] FIG. 17 illustrates a delivery catheter configured to deliver and deploy an implant within the aortic arch, according to some embodiments. [Figure 18] FIG. 18 illustrates delivery of an exemplary implant to the aortic arch along a target region using a delivery catheter, according to some embodiments. [Figure 19] FIG. 19 illustrates delivery of an exemplary implant to the aortic arch along a target region using a delivery catheter, according to some embodiments. [Figure 20] FIG. 20 illustrates delivery of an exemplary implant to the aortic arch along a target region using a delivery catheter, according to some embodiments. [Figure 21] FIG. 21 illustrates delivery of an exemplary implant to the aortic arch along a target region using a delivery catheter, according to some embodiments. [Figure 22] FIG. 22 illustrates delivery of an exemplary implant to the aortic arch along a target region using a delivery catheter, according to some embodiments. [Figure 23] FIG. 23 illustrates delivery of an exemplary implant to the aortic arch along a target region using a delivery catheter, according to some embodiments. [Figure 24] FIG. 24 illustrates a method of treating hypertension with an implant, according to some embodiments. [Figure 25] FIG. 25 illustrates a method of treating hypertension with an implant, according to some embodiments. [Figure 26A] FIG. 26A shows a histology image of the tissue showing baroreceptor staining in the target region within the aortic arch. [Figure 26B] FIG. 26B shows a histology image of the tissue showing baroreceptor staining in the target region within the aortic arch. [Figure 27A] FIG. 27A illustrates a tethered articulated implant and various stages of deployment, according to some embodiments. [Figure 27B] FIG. 27B illustrates a tethered articulated implant and various stages of deployment, according to some embodiments. [Figure 27C] FIG. 27C illustrates a tethered articulated implant and various stages of deployment, according to some embodiments. [Figure 27D] FIG. 27D illustrates a tethered articulated implant and various stages of deployment, according to some embodiments. [Figure 27E] FIG. 27E illustrates a tethered articulated implant and various stages of deployment, according to some embodiments. [Figure 27F] FIG. 27F illustrates a tethered articulated implant and various stages of deployment, according to some embodiments. [Figure 28A] FIG. 28A illustrates an exemplary aortic arch configuration and deployment of a tethered articulating implant therein, according to some embodiments. [Figure 28B] FIG. 28B illustrates an exemplary aortic arch configuration and deployment of a tethered articulating implant therein, according to some embodiments. [Figure 29A] FIG. 29A illustrates a two-ring implant, according to some embodiments. [Figure 29B] FIG. 29B illustrates a three-ring implant, according to some embodiments. [Figure 30A] FIG. 30A shows a multi-ring tethered implant, according to some embodiments. [Figure 30B] FIG. 30B illustrates a multi-ring tethered implant, according to some embodiments. [Figure 31A] FIG. 31A illustrates an alternative implant structure, according to some embodiments. [Figure 31B] FIG. 31B illustrates an alternative implant structure, according to some embodiments. [Figure 32A] FIG. 32A shows various views of an exemplary eight-cell implant structure, according to some embodiments. [Figure 32B]FIG. 32B illustrates various views of an exemplary eight-cell implant structure, according to some embodiments. [Figure 32C] FIG. 32C illustrates various views of an exemplary eight-cell implant structure, according to some embodiments. [Figure 32D] FIG. 32D illustrates various views of an exemplary eight-cell implant structure, according to some embodiments. [Figure 32E] FIG. 32E illustrates various views of an exemplary eight-cell implant structure, according to some embodiments. [Figure 33A] FIG. 33A shows various views of an exemplary four-cell implant structure, according to some embodiments. [Figure 33B] FIG. 33B illustrates various views of an exemplary four-cell implant structure, according to some embodiments. [Figure 33C] FIG. 33C illustrates various views of an exemplary four-cell implant structure, according to some embodiments. [Figure 33D] FIG. 33D shows various views of an exemplary four-cell implant structure, according to some embodiments. [Figure 33E] FIG. 33E illustrates various views of an exemplary four-cell implant structure, according to some embodiments. [Figure 34A] FIG. 34A illustrates various tether configurations and the interface of the tether within the collar, according to some embodiments. [Figure 34B] FIG. 34B illustrates various tether configurations and the interface of the tether within the collar, according to some embodiments. [Figure 34C] FIG. 34C illustrates various tether configurations and the interface of the tether within the collar, according to some embodiments. [Figure 35A] FIG. 35A illustrates tether configurations for an eight-cell implant structure and a four-cell implant structure, according to some embodiments. [Figure 35B] FIG. 35B illustrates tether configurations for an eight-cell implant structure and a four-cell implant structure, according to some embodiments. [Figure 36] FIG. 36 shows various views of a retention collar for retaining an implant structure prior to full deployment, according to some embodiments. [Figure 37] FIG. 37 illustrates a constraining implant releasably connected to a collar of a delivery catheter by a tether, according to some embodiments. [Figure 38A] FIG. 38A shows a cross-sectional view of an implant tether interfaced with a retention collar, according to some embodiments. [Figure 38B] FIG. 38B shows a detailed view of an implant tether interfaced with a retention collar, according to some embodiments. [Figure 39A] FIG. 39A shows a cross-sectional view of an exemplary implant that may be used for baroreflex measurement and hypertension treatment, according to some embodiments. [Figure 39B] FIG. 39B illustrates a cross-sectional view of an exemplary implant that may be used for baroreflex measurement and hypertension treatment, according to some embodiments. [Figure 39C] FIG. 39C illustrates a cross-sectional view of an exemplary implant that may be used for baroreflex measurement and hypertension treatment, according to some embodiments. [Figure 39D] FIG. 39D illustrates a cross-sectional view of an exemplary implant that may be used for baroreflex measurement and hypertension treatment, according to some embodiments. [Figure 40A] FIG. 40A shows a cross-sectional view of an exemplary implant that may be used for baroreflex measurement and hypertension treatment, according to some embodiments. [Figure 40B] FIG. 40B illustrates a cross-sectional view of an exemplary implant that may be used for baroreflex measurement and hypertension treatment, according to some embodiments. [Figure 40C] FIG. 40C illustrates a cross-sectional view of an exemplary implant that may be used for baroreflex measurement and hypertension treatment, according to some embodiments. [Figure 40D] FIG. 40D shows a cross-sectional view of an exemplary implant that may be used for baroreflex measurement and hypertension treatment, according to some embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0020] In one aspect, the present invention relates to a method for assessing a patient's baroreflex response and an associated baroreflex gauge catheter device. In some embodiments, the baroreflex gauge catheter device is adjustable between a plurality of different lateral dimensions. In some embodiments, the baroreflex gauge has a handle with incremental adjustment controls that allow a clinician to adjust the expandable structure between different sizes or lateral dimensions. In some embodiments, a method for measuring a baroreflex response includes incrementally adjusting the expandable structure and observing the blood pressure response to find the optimal, maximum, or maximum / minimum stretch of the vasculature that results in a baroreflex response. In some embodiments, the baroreflex gauge has an expandable structure with a generally circular cross-section, which facilitates vascular stretching in the target area while avoiding high stress / strain points and limiting vascular dissection during baroreflex response measurement.

[0021] FIG. 1A illustrates an exemplary baroreflex gauge catheter device deployed within a patient's vasculature to assess the patient's baroreflex response. The baroreflex gauge catheter device has a distal expandable structure that transitions between a contracted configuration for advancement through the vasculature and an expanded configuration for engaging the arterial walls of the vasculature and stretching sufficiently to elicit a baroreflex response. In this embodiment, the expandable structure is adjustable to various dimensions, allowing the extent of baroreflex measurement (if present) to be assessed at each dimension. Typically, the expandable structure is shortened in stages, such that the lateral dimension (e.g., diameter) of the expandable structure is increased in stages. The patient's blood pressure after deployment of the expandable structure can be monitored to assess the baroreflex response at each adjustment. The presence or extent of a baroreflex response can be determined within a short period of time (e.g., less than 5 minutes, less than 1 minute). Studies have shown that when baroreceptors are significantly stretched, a baroreflex response occurs almost immediately (e.g., within a few seconds). This device and method allows a clinician to identify / confirm a patient as a candidate for a hypertensive implant and / or to better assess the optimal placement for a hypertensive implant and / or the optimal size of a hypertensive implant to be placed in a patient. Figures 2-3B show cross-sectional views and additional details of the adjustment mechanism of a baroreflex gauge device. Figures 4A-4C show alternative designs for the baroreflex gauge device and adjustment mechanism. In this embodiment, the expandable structure is a braided mesh that, when expanded, has a generally circular cross-section. Figures 5A-5D show alternative expandable structure designs and how such structures stretch the arterial wall. In these embodiments, the expandable structure has a stent-like design with a generally circular cross-section. Figure 6 shows a diagram of a baroreflex gauge device deployed within a patient's vasculature. Figures 7A-7C show the delivery and deployment of an exemplary hypertensive implant in a patient's aortic arch, facilitated by the baroreflex gauge device. 8A-8I and 9A-9B show anatomical details and the results of studies illustrating the physiological mechanism of the baroreflex response.

[0022] I. Physiological baroreflex response To understand the physiological response of the baroreflex, it is useful to understand the interactions between the nervous system and the patient's anatomy. Figures 8A-8C show the location of baroreceptors and their interactions with the vasculature, baroreceptor cells, and the central nervous system.

[0023] Blood pressure sensing occurs at several hot spots within the vascular system. Afferents of the vagus nerve (i.e., cranial nerve 10) and glossopharyngeal nerve (i.e., cranial nerve 9) target the aortic arch and carotid sinus, respectively. Vagal sensory neurons access the aorta via a thin nerve branch called the aortic depressor nerve, and glossopharyngeal neurons access the carotid sinus via the carotid sinus nerve (see Figure 8A). The aortic depressor nerve and carotid sinus nerve consist of co-fasciculating fibers containing both mechanosensory and chemosensory afferents. Mechanosensory nerve fibers mediate the baroreflex. These mechanosensory nerve fibers terminate in specialized nerve endings called baroreceptors, which penetrate the arterial wall. Baroreceptors are stretch receptors that sense arterial stretch rather than directly measuring pressure. The blood pressure pulse associated with each heartbeat stretches the arterial walls radially, and this arterial distension in turn activates mechanoreceptor neurons. Baroreceptor neurons are long sensory neurons that connect the aorta to the brain and transmit input directly to the brainstem. Activation of these baroreceptor neurons decreases sympathetic output and increases parasympathetic output from the brainstem, ultimately decreasing blood pressure and heart rate (called the baroreflex).

[0024] At the molecular level, baroreceptors are actually complex protein structures that form ion channels at the sensory endings of baroreceptor nerve fibers (see Figure 8B). Stimulation of the ion channels causes an influx of cations into the neuron, depolarization, and signal transmission along the nerve cell. Baroreceptor nerve endings are located in the outer wall of the artery, between the tunica media and adventitia (see Figure 8I).

[0025] Baroreceptor neurons are long sensory neurons that extend from the arteries to the brain and transmit input directly to the brainstem. Aortic arch baroreceptor nerve signals originate from the arterial wall, travel through the aortic depressor nerve, and then through the superior laryngeal nerve to the vagus nerve, which then travels to the brainstem (see Figures 8A and 8B). The brainstem reflexly modulates these signals, decreasing sympathetic output and increasing parasympathetic output to the circulatory system. Blood pressure and heart rate decrease. This series of responses is called the baroreflex.

[0026] Early animal studies demonstrated that this response is associated with the stretching of the arterial wall that occurs naturally during hypertension. Subsequent animal studies demonstrated that the baroreflex response can be transient or sustained, depending on whether the stimulation of arterial receptors is static or pulsatile, respectively. Static stimulation caused a decrease in systemic blood pressure that normalized after several minutes, whereas nonstatic, pulsatile stimulation (e.g., similar to natural pulsatile blood flow) showed a sustained decrease in systemic blood pressure.

[0027] Since the 1960s, modulation of the baroreflex, particularly the carotid baroreflex, has been a primary target of device-based treatment for difficult-to-control hypertension. Initial approaches employed pacemaker-type devices, in which electrodes placed around the carotid sinus nerve were connected via wires to an implanted stimulator. Stimulating this nerve, which innervates the carotid baroreceptor, can avoid stimulation within the artery and lower blood pressure through the carotid baroreflex arc. This technology continues in human clinical trials. A similar type of device targeting the aortic arch baroreceptor, or more precisely, the aortic depressor nerve, has been successfully used to lower blood pressure in a goat experimental model. However, pacemaker-type implants are unlikely to be a viable device-based solution for refractory hypertension due to their obvious drawbacks (for one, patients are reluctant to have a generator surgically inserted into their chest). To overcome this limitation, Vascular Dynamics developed a stent-like intravascular implant that stretches the carotid artery wall from the inside, amplifying the carotid baroreflex signal. This device has a non-articulating, monomorphic design configured for the straight segment of the proximal internal carotid artery. In previous clinical trials, this device was successful in lowering blood pressure in a population with refractory hypertension, but at the risk of a small number of transient ischemic attacks (TIAs). This approach has several drawbacks that may contribute to an increased risk of stroke and TIAs.

[0028] The present invention aims to optimize the utility of an individual patient's baroreflex response by assessing the baroreflex response of such an implant prior to implant deployment. A baroreflex gauge is advantageous because this assessment provides additional insight into a particular patient's baroreflex response to either confirm the patient's suitability for a hypertensive implant, determine the optimal location for implant deployment, or determine the optimal type and / or size of hypertensive implant for a particular patient. The use of a properly positioned and appropriately sized implant, enabled by the baroreflex response assessment described herein, allows the implant to induce an improved baroreflex response in the aortic arch over the long term.

[0029] In one embodiment, the present invention relates to a baroreflex gauge that assesses the baroreflex response and facilitates subsequent deployment of an implant having one or more expandable structures configured to stretch the arterial wall along a target region of the aorta, particularly the aortic arch. In some embodiments, the gauge is configured to engage a target region of the aortic arch, including the medial curvature opposite the left subclavian artery. This target region may be defined as the cylindrical segment of the aortic arch between the LCCA and LSA. This portion of the aortic arch is particularly rich in baroreflex receptors, which are believed to be more sensitive than baroreceptors in various other regions, such as the carotid sinus. Because this region of the aortic arch is believed to be more responsive, the implant may achieve more consistent and reliable blood pressure reduction. Furthermore, implantation in this region avoids the drawbacks associated with delivery and implantation in the sensitive region of the carotid sinus, which may increase the risk of TIA and stroke. Thus, the implants described herein are believed to provide a stronger baroreflex response to lower blood pressure, improve ease of delivery and implantation, and reduce the risk of adverse events.

[0030] Early animal studies of various baroreceptor responses identified anatomical "hot spots" of baroreceptors at various locations within the vasculature, including a narrow, cylindrical strip extending circumferentially around the aortic arch between the origins of the left common carotid artery and the left subclavian artery (which originates from the left embryonic fourth pharyngeal arch artery, as seen in Figures 8D and 8E). This region is depicted in the fluorescent staining image in Figure 8H, which shows red-stained baroreceptors. This baroreceptor-rich region can be defined as the cylindrical segment of the aortic arch between the LCCA and LSA, shown as target T in Figure 8D.

[0031] These baroreceptor "hot spots" originate from the embryonic pharyngeal arch arteries, shown in Figure 8E. The third pharyngeal arch artery develops into the left and right carotid arteries, which are symmetrical structures. In contrast, the right fourth pharyngeal arch artery (R4PA) becomes the proximal right subclavian artery, while the left fourth pharyngeal arch artery (L4PA) develops into a relatively narrow, cylindrical strip B of the aortic arch, shown in Figure 8F. This strip has distinct characteristics compared to other regions of the aortic arch.

[0032] This strip of the aortic arch is histologically distinct from other regions due to fewer smooth muscle cells and increased elastic lamellae. Figure 8G shows a histological cross-section through aortic arch segment B (left column), which shows fewer smooth muscle cells and increased elastic lamellae compared to aortic section C (right column) in Figure 8F. The more commonly known aortic arch baroreceptors are located in this region B (as shown in Figure 8A). However, various animal and human studies have shown that a unique regional distribution of baroreceptors actually exists in this region extending along band B enveloping the aortic arch, as shown in Figure 8H. Furthermore, baroreceptors in the aortic lumen are located in the outer layer of the arterial wall within the aorta, as shown in the fluorescent image in Figure 8I, which shows the baroreceptor nerve fibers stained pink.

[0033] There are very few human reports identifying the location of aortic arch baroreceptors. One early research study showed that the baroreceptor nerve wraps around the aorta at the origin of the left subclavian artery, and the same authors later showed that this baroreceptor nerve may extend around the aorta from the brachiocephalic trunk to the ligamentum arteriosum. Some earlier studies have shown that baroreceptors are found along this region of the aortic arch, which extends over 40% of the circumference, but some baroreceptors may extend outside this region. Due in part to the histological characteristics of this region described above, baroreceptors are thought to behave differently from baroreceptors in other regions, including the carotid artery. At least one animal study has demonstrated that the pressure threshold for stimulating an action potential is lower in aortic baroreceptors than in carotid baroreceptors (see Figure 9A). The animal study further suggested that uniaxial stretching of 20% induced a significant increase in cytoplasmic calcium fluorescence in aortic arch baroreceptor neurons, but not in carotid baroreceptor neurons, as shown in Figure 9B. Therefore, aortic baroreceptors in the human aorta are believed to be more sensitive than those in the carotid arteries, and therefore, by using an implant specifically configured for deployment in the aortic region to stretch the arterial wall in this targeted region, a more consistent and pronounced baroreflex response can be achieved than with conventional carotid implants.

[0034] It should be noted that while the literature notes the presence of baroreceptors in various locations within the body, including the carotid arteries and aorta, and some publications describing passive baroreflex implants mention in passing a list of various possible implantation sites, generally including the aorta, none of the literature teaches any specific target region of the aortic arch. Furthermore, none of the literature addresses the challenges inherent in implantation in the aortic arch region, which has led to prior approaches focusing primarily on the carotid arteries, which have typically been accessed for certain other procedures, such as carotid stenting to treat stenosis in this region.

[0035] Thus, the present invention aims not only to improve baroreflex response by implantation in a specific target region within the aortic arch, but also to improve ease of implantation while enabling implantation in this unique location. Importantly, the claimed implant and approach avoids the drawbacks associated with treatment and implantation within the carotid artery that can lead to adverse events due to the complexity of deployment in this region.

[0036] While delivering an implant into the aortic arch offers significant advantages, such as targeting the aortic arch baroreceptors in the narrow band surrounding the aorta, deployment in this region presents several challenges. Because the diameter of the aortic arch is significantly larger than that of the carotid artery, the diameter of the implant must correspond to the diameter within the aortic arch to adequately engage the tissue and achieve the required stretch of the arterial wall (e.g., 20% or more, 20-50%, 30%, or even 30-100% stretch). Therefore, the expandable structure of the baroreflex gauge is configured to provide the same or similar stretch of the arterial wall to accommodate the stretch provided by the implant. To prevent implant inversion or rotation, the implant typically has a length substantially greater than its largest lateral dimension (e.g., diameter), e.g., about 40 mm or greater. In some embodiments, the overall implant length is 70 mm or greater (e.g., about 85 mm). However, because the baroreflex gauge is intended to elicit a baroreflex response only from the target site, the expandable structure of the baroreflex gauge may be shorter than the overall length of the corresponding hypertension implant.

[0037] Another challenge is that because the aorta is the body's primary artery, a significant amount of blood flow is carried through the aortic arch and into secondary arteries (e.g., the aorta, LCCA, and LSA) branching off from the aorta. Therefore, to provide consistent engagement and stretching in the target area corresponding to the implant, the expandable structure must be configured to withstand not only the lateral forces from blood flow toward the secondary arteries, but also the forces from pulsatile blood flow through the aortic arch without shedding, maintaining a targeted stretch of the arterial wall in the target area and better simulating the effect of the corresponding implant. Furthermore, the expandable structure may be configured to expose a large portion of the arterial wall in the target area to pulsatile blood flow, thereby better mimicking the implant itself, which is also designed with major openings for exposing the arterial wall to pulsatile blood flow to provide the sustained blood pressure reduction described above, rather than the temporary response that occurs when the arterial wall is isolated from blood flow. In some embodiments, the implant provides sufficient stretch to elicit a baroreflex response that reduces blood pressure in a hypertensive patient by at least 10 mmHg, 20 mmHg, 30 mmHg, 40 mmHg, 50 mmHg, or 60 mmHg or more. Additionally, the expandable structure can be designed to allow blood to flow freely laterally into secondary branch arteries to ensure accurate blood pressure monitoring. Thus, the expandable structure itself can be configured with a primary opening that exposes the arterial wall and allows lateral blood flow to supply any adjacent secondary arteries.

[0038] II. Exemplary Baroreflex Gauge Catheter Device FIG. 1A shows an example of a baroreflex gauge catheter device 100, which includes an expandable structure 10 at its distal end and a catheter handle 20 with a control section at its proximal end. A detailed view of the expandable structure 10 is shown in FIG. 1B. The expandable structure 10 is configured to transition between a contracted configuration (shown in FIG. 2) when stretched to facilitate advancement through the vasculature to a target area, and an expanded configuration (shown in FIG. 1A) when axially shortened to engage the arterial wall and stretch sufficiently (e.g., 20% or more) to elicit a baroreflex response. The entire catheter can be advanced over a guidewire 1 placed within the vasculature prior to the procedure, with the contracted expandable structure within the outer sheath 14 advanced to the target site within the vasculature.

[0039] The expandable structure may be a spline structure, a basket, a stent-like structure, or any suitable structure. Preferably, the expandable structure 10 is defined by splines or struts that are strong enough to stretch the arterial wall when expanded (similar to an implant), but have spaces between the splines or struts to allow lateral blood flow into the lateral body lumen. In this embodiment, the expandable structure may have a diameter of 20 mm to 100 mm, preferably 20 mm to 60 mm, which is a size suitable for stretching the arterial wall by at least 20% in the human aorta. It will be understood that when configured for deployment in other locations (e.g., the carotid artery), the expandable structure may be sized accordingly. In this embodiment, the expandable structure is configured to have a variable expanded diameter, allowing the structure to be expanded into multiple expanded configurations with different diameters, for example, multiple diameters within the range of 20 mm to 60 mm. In this embodiment, the length of the expandable structure is defined so that the tissue contact length I is 10 mm to 20 mm. It is understood that the tissue contact length may vary proportionally with diameter, but preferably a length of at least 10 mm engages tissue over the range of expanded diameters. The expandable structure may further comprise radiopaque markers 11 to allow visualization of the structure in the target area.

[0040] Variable expansion and contraction of the expandable structure 10 is achieved by manipulation of the catheter handle 20. In this embodiment, the expandable structure is attached to two shafts, such that relative movement of these shafts causes the structure to transition between configurations. The distal end of the expandable structure is attached to the distal gauge manipulation shaft 12, and the proximal end of the expandable structure is attached to the proximal gauge manipulation shaft 13. Relative movement of the shafts 12, 13, by manipulation with respect to the proximal catheter handle 20, either axially extends the expandable structure 10 to a contracted configuration, or axially shortens the expandable structure 10 to various expanded configurations.

[0041] As shown in FIG. 1A, the catheter handle 20 includes an ergonomic handle body 21. In this embodiment, the handle has a variable diameter ranging from 40 mm to 76 mm and a length ranging from 150 mm to 305 mm. The catheter handle includes a sheath retraction actuator, which is a slider 24 coupled to the proximal end of the outer sheath 14, allowing the user to retract the sheath and expose the expandable structure 10 after positioning it at the target. The catheter handle may include a strain relief 29 at the handle interface that supports the outer sheath 14. The handle further includes a gauge adjustment 23 configured to control the expansion of the expandable structure 10 between various expansion configurations. The gauge adjustment 23 may include one or more controls, such as a main control and one or more fine controls for fine adjustment. In this embodiment, the gauge adjustment 23 includes a slider 22 that slides along a slot having incremental markings 25 corresponding to different diameters or lateral dimensions of the expandable structure 10. In this embodiment, the adjustment unit 22 allows for incremental adjustment of the transverse dimension or diameter of the expandable structure between 20 mm and 60 mm. Preferably, these different diameters / dimensions correspond to the diameters / dimensions of different sizes of hypertension implants provided to clinicians. Alternatively, the implant may be adjustable to accommodate optimal dimensions determined by a baroreflex gauge. The catheter handle may optionally include one or more additional precision controls for finer adjustments. For example, in this embodiment, the adjustment unit controls further include a micro-rotary adjustment unit 26 that moves the slider in smaller increments (e.g., 1 mm) and a rotary ergonomic adjustment unit 27 with additional markings to further quantify fine adjustments. The handle may further include a luer lock connection 28 for accommodating a guidewire or fluid (e.g., contrast medium, flushing, etc.).

[0042] While a spline structure is shown here, it is understood that the baroreflex gauge catheter may utilize a variety of other expansion structures, including the stent-like structures shown in Figures 5A-5B, and may include a variety of other handle designs, including the handle designs shown in Figures 4A-4C and 6. It is also understood that the handle may include a variety of other features or functions, such as a lock for fixing the configuration of the expansion structure during blood pressure monitoring, and that these other features or functions may be integrated with or separate from the operating portion of the adjustment portion.

[0043] FIG. 2 shows a cross-sectional view (without the handle body and slider) further illustrating the means for expanding the expandable structure 10 by actuation of the shaft. In this cross-sectional view of the catheter device 100, the expandable structure 10 is in a contracted configuration and is covered by an outer sheath 14. The catheter handle 20 can include an adjustment mechanism 15 operably coupled to an adjustment section 22, which facilitates relative movement of the shafts 12, 13 to incrementally expand the expandable structure. Preferably, the adjustment mechanism is configured to move each shaft relative to one another so that the midpoint of the expandable structure does not substantially move from its position at the target site. Advantageously, this allows the lateral dimension of the expandable structure to be varied while maintaining the expandable structure in a target position, thereby eliminating the need to reposition the structure before each adjustment. In contrast, conventional expansion structure designs that rely on axial shortening typically move only one shaft, resulting in misalignment of the expansion structure as the diameter increases. Such a design can be problematic for a wide diameter range, potentially shifting the gauge position outside the target area. As shown in FIG. 2 , the adjustment mechanism 15 can be defined, for example, as a rack-and-pinion structure, where the proximal portions of the proximal and distal shafts 12 and 13 each include a rack portion 15-1, 15-2 with a notch that engages a corresponding pair of pinion gears 15-3. The pinion gears 15-3 interact with the rack such that proximal translation of the proximal shaft rotates one pinion gear, which in turn rotates the other pinion gear, causing the distal shaft to translate in the opposite direction. Thus, this mechanism moves the shafts apart while substantially maintaining the position of the expansion structure. In some embodiments, the expandable sheath can be made of metal (e.g., nitinol) or any suitable material. The sheath actuator can be made of a polymer, metal, or any suitable material. Another example of a rack-and-pinion mechanism for moving multiple shafts in opposite directions is shown in FIG. 3A . In other embodiments, the adjustment mechanism may include a worm gear 16, which may provide a similar function, as shown in Figure 3B. It will be appreciated that a variety of other mechanisms may be used in a similar manner.For example, alternative baroreflex gauge catheter designs 101, 102, 103 are shown in Figures 4A-4C.

[0044] 4A-4C illustrate an alternative design for a baroreflex gauge device, in which the adjustable expansion structure is a braided mesh that, when expanded, has a generally circular cross-section. This design is advantageous because it avoids deforming the circular vasculature of the aorta into irregular shapes, thereby avoiding high stress / strain points that could lead to vasculature dissection. This is beneficial because it allows the clinician to stretch the vasculature beyond the range required for the implant to determine the optimal stretch, determining maximum and minimum stretches while minimizing the risk of dissection. It is understood that the subsequently placed implant need not be circular, as it is sized according to the optimal stretch determined by the measurement procedure. FIG. 4C-1 illustrates features of an alternative baroreflex gauge catheter 103, in which a handle 20′ includes an adjustment portion 23′ defined by a slider 24a and an unlocking detent 24b, allowing the user to incrementally adjust the expandable member 10′ to expand or contract to different gauge diameters. The slider is attached to a shaft 12 (i.e., inner hypotube) attached to the distal end of the expandable member 10′, while a shaft 13 (i.e., outer hypotube) is attached / anchored to the proximal end of the handle. Notably, in this design, the midpoint shifts position as the expandable member expands. Figure 4C-2 shows an alternative design for the expandable member 10′ defined by a braided stent-like structure or basket. In Region A, the proximal end of the expandable gauge structure is attached to the distal end of the outer hypotube, providing axial control for expansion and contraction of the gauge. In Region B, the distal end of the expandable gauge structure is attached to the distal end of the inner hypotube.

[0045] 5A-1 through 5B-3 illustrate yet other alternative designs for the expansion structure of a baroreflex gauge catheter device. These designs provide a stent-like structure with interconnected struts that provide sufficient strength to laterally stretch the arterial wall while allowing blood to flow freely laterally through the struts to ensure accurate blood pressure measurements. While specific dimensions are shown, it is understood that embodiments are not limited to these dimensions and may have a variety of other dimensions as desired.

[0046] In the embodiment shown in Figures 5A-1-5A-3, the design includes a strut arrangement with a proximal transition region, a distal transition region, and a relatively flat central region that ensures sufficient engagement with the arterial wall at a given diameter of the expandable structure. The design is configured to have a central length of approximately 15 mm. Advantageously, this design provides a consistent length of central region that engages the arterial wall across a range of diameters. As shown in cross section AA, the cross section of the expansion structure that contacts the vasculature is generally circular to provide a more uniform stretch of the vasculature and avoid high stress / strain points, thereby reducing dissection.

[0047] In the embodiment shown in Figures 5B-1-5B-3, the design includes a strut arrangement with a proximal transition region, a distal transition region, and a relatively flat central region that ensures sufficient engagement with the arterial wall at a given diameter of the expandable structure. This design is configured with a central section length of approximately 10 mm. This design may be more suitable for patients with reduced vasculature size. Furthermore, this design is suitable for animal testing using animals with very small aortas. As shown in cross section B-B, the cross section of the expandable structure that contacts the vasculature is generally circular to allow for more uniform stretching of the vasculature and avoid high stress / strain points, thereby reducing dissection.

[0048] 5C-1 through 5C-6 are cross-sectional views illustrating the interaction of the expandable structure 10 with the arterial vessel wall before and after expansion. FIG. 5C-1 shows arterial vessel A before intervention, where the vessel diameter is D0. FIG. 5C-2 shows the constraining device 10 positioned within vessel A, where the vessel diameter remains D0 and the constraining device diameter is Φ0. FIGS. 5C-3 through 5C-6 show vessel A after the device 10 has been expanded within vessel A. FIG. 5C-3 shows the device 10 expanded to a diameter Φ1, which is equal to the original vessel diameter D0. Because vessel diameter D1 is equal to the original vessel diameter D0, no change has occurred to the vessel. FIG. 5C-4 shows the device 10 expanded 11% to a diameter Φ2, where the vessel shape has changed from circular to square. Because the vessel is no longer circular, vessel diameter D2 and device diameter Φ2 are "apparent diameters." Because little or no stretching has occurred yet, the circumference of the vessel is approximately the original circumference. FIG. 5C-5 shows the device 10 expanded 30% to a diameter Φ3, expanding the square vessel size to a diameter D3. Because of the approximately 17% stretch, the vessel circumference is larger than the original circumference. FIG. 5C-6 shows the device 10 expanded 50% to a diameter Φ4, expanding the square vessel size further to a diameter D4. Because of the approximately 35% stretch, the vessel circumference is even larger than the original circumference. These figures illustrate the relationship between the size, shape, and diameter of the expandable member in stretching the arterial wall. It is understood that this relationship can also be extended to the size, shape, and diameter of hypertension implants. In this embodiment, the expandable structure is formed by four struts and has a square cross-section, similar to the design in FIG. 1A. This allows the vasculature to stretch, but creates high stress / strain points at the corners, complicating calculations of vasculature stretch during expansion.

[0049] FIGS. 5D-1 through 5D-6 show cross-sectional views of the expandable structure 10 interacting with the arterial vessel wall before and after expansion in a blood vessel A. FIG. 5D-1 shows blood vessel A before intervention, with a vessel diameter of D0. FIG. 5D-2 shows the constraining device 10 deployed within the blood vessel. The vessel diameter remains D0, and the diameter of the constraining device is Φ0. FIGS. 5D-3 through 5D-6 show blood vessel A after the device 10 has been expanded within the blood vessel A. FIG. 5D-3 shows the device 10 expanded to a diameter of Φ1, with no change to the blood vessel, as the vessel diameter D1 remains equal to the original vessel diameter D0. FIG. 5D-4 shows the device 10 expanded by 11% to a diameter of Φ2, with the vessel diameter D2 also expanding by 11% while maintaining its original circular shape. FIG. 5D-5 shows the device 10 expanded by 30% to a diameter of Φ3, with the vessel diameter D3 also expanding by 30%, while maintaining its original circular shape. 5D-6 show the device 10 expanded 50% to a diameter Φ4, where the vessel diameter D4 is also expanded 50%, but the vessel maintains its original circular shape, thereby avoiding high stress / strain points and preventing vessel dissection. These figures illustrate the relationship between the size, shape, and diameter of the expandable member in stretching the arterial wall. It is understood that this relationship can be extended to the size, shape, and diameter of hypertensive implants, or that implants of different configurations and shapes may provide corresponding stretching. In this embodiment, the expandable structure is designed to have a generally circular cross-section upon expansion, thereby stretching the vasculature more uniformly and avoiding high stress / strain points that could lead to dissection. This allows the vasculature to be stretched to determine optimal, maximum, or maximum and minimum stretches that result in a baroreflex response, while reducing the risk of dissection. Thus, before stretching, the vasculature is generally circular with a constant radius, and after being stretched by the expandable structure, the vasculature, while still generally circular, has a larger, constant radius, rather than the reduced radius region created by an expandable structure with a non-circular cross section.This approach is further advantageous because the size of the implant corresponds directly to the size of the vasculature, thereby simplifying the determination of stretch during the measurement procedure. It is understood that subsequently placed implants need not be the same shape, but may be sized to achieve the optimal stretch determined by the measurement procedure.

[0050] FIG. 6 shows an example of a baroreflex gauge catheter device 110 with the expandable structure 10 deployed at a target region T within the aortic arch. As described above, the catheter device 110 is advanced along a guidewire 1 positioned within the aortic arch until the marker 11 indicates that the expandable member 10 is located at the target region T. The outer sheath 14 is then pulled back using the control of the catheter handle 20, and the adjustment unit 22 is actuated to expand the expandable structure 10 to one or more diameters and engage the arterial wall. The level of expansion is indicated by markings 25 on the catheter handle. After each adjustment, the patient's blood pressure is monitored by the sphygmomanometer 400 for a short period until the blood pressure stabilizes. The adjustment unit 22 is used to incrementally increase expansion until the desired blood pressure reduction is observed. Once the desired blood pressure is reached, or the lowest achievable blood pressure is reached, the diameter is recorded and can be used to inform subsequent long-term placement of an implant in the patient. Typically, this involves selecting an implant of the same corresponding diameter and delivering and deploying the selected implant using an implant delivery catheter, such as the implant delivery catheters shown in Figures 7A-7C, to achieve the same desired long-term blood pressure reduction. In some embodiments, this may involve adjusting the implant. In some embodiments, a gauge catheter device may be incorporated into the implant delivery catheter. In some embodiments, the expandable member itself may be locked and released from the catheter device and may also function as a long-term implant.

[0051] III. Exemplary Delivery Catheters and Implants FIG. 7A illustrates an exemplary implant device 300 for treating drug-resistant hypertension, delivered by an exemplary delivery catheter 200 and implanted within the aortic arch AA, facilitated by the baroreflex gauge device described above. The delivery catheter system includes an elongate catheter shaft 201 extending between a distal end and a proximal end, the shaft having one or more lumens. One lumen may receive a guidewire GW therethrough to facilitate advancement of the catheter over a guidewire GW previously placed within the aortic arch. The delivery catheter may further include a tapered distal tip 203 for guiding advancement of the catheter over the guidewire GW. After positioning the distal end at a target region within the aortic arch, the implant 300 is deployed by retracting an outer sheath 202, which constrains the implant in a collapsed configuration during delivery through the vasculature. Retraction of the outer sheath is effected through a catheter handle 210 at the proximal end. The catheter handle may include a hub 220 attached to the proximal end of the outer sheath so that retracting the proximal hub retracts the outer sheath. The outer sheath may include markings thereon to allow the clinician to confirm that the sheath is sufficiently retracted to deploy part or all of the implant (e.g., in the case of a self-expanding implant). In other embodiments including a balloon-expandable implant, the delivery catheter may include one or more balloons at its distal portion that can be expanded via the handle. The catheter handle may further include a flush port 211 fluidly connected to a lumen extending to the distal end (e.g., the distal opening of the catheter shaft or outer sheath) to allow the clinician to flush the aortic arch before, during, or after implant deployment. The catheter is sized and configured for advancing the implant to the target region T of the aortic arch. The delivery catheter and / or implant may include one or more markers to facilitate accurate placement at the target site using visualization techniques.For example, the implant may include one or more markers on one or both of the expandable structures 310, 320, or on the flexible connector 330 between the expandable structures. The catheter may also include one or more markers at various locations, such as the distal end of the shaft, the location of the implant on the shaft, and the distal end of the sheath 204. Optionally, in some embodiments, the catheter system further includes a second guidewire GW2 for placement in a secondary branch, such as the left subclavian artery, which can facilitate placement of the implant at the target site relative to the LSA. In other embodiments, the implant is positioned relative to the anatomy without the need for an additional guidewire.

[0052] 7B shows an exemplary implant device 300 for treating drug-resistant hypertension implanted within the aortic arch AA. The implant is an expandable device inserted into the aortic arch and lowers blood pressure by medially stretching the aortic arch arterial wall and enhancing the aortic arch baroreflex. Branching from the upper portion of the AA are secondary branch vessels: the brachiocephalic artery (BA), left common carotid artery (LCCA), and left subclavian artery (LSA). While the first expandable structure 310 is shown deployed off-center, it is understood that the structure can also be centered in the target region T.

[0053] As shown, implant 300 comprises two expandable structures 310, 320 interconnected in series by an axially expandable connector 330. The expandable structures are positioned longitudinally along the aorta, which helps secure and stabilize the placement of the implant within the curved aortic arch. Given the aorta's relatively large size, high blood flow velocity, and curved shape, anchoring a single expandable structure in this region can be challenging. By utilizing two or more structures positioned along different portions of the aorta, the implant conforms to the aortic curvature and complex shape, which helps secure the implant at the target site. Furthermore, by relying on the engagement of two or more structures along the aorta, the implant's fixation force is distributed over a wider area, thereby minimizing trauma to the arterial wall and thereby reducing inflammation and thrombus formation, which can lead to atherosclerotic plaque formation.

[0054] As shown in FIG. 7B, the expandable structure is formed by multiple open wire frames, each formed by a plurality of spaced struts defining each side. Adjacent frame sides are interconnected along lateral struts so that the frame forms an axisymmetric regular polygon along the longitudinal axis of the expandable structure. The expandable structure has a collapsed configuration for advancement through the vasculature (e.g., within a delivery catheter) and an expanded configuration (as shown) in which the lateral struts engage the aortic arterial wall, thereby sufficiently stretching the arterial wall between each pair of struts in the frame to elicit a baroreflex response. The flexible connector 30 is axially expandable (e.g., a zigzag connector), allowing the two expandable structures to extend along different longitudinal axes and conform to the various curvatures and complex three-dimensional shape of the aortic arch. This configuration minimizes distortion of the aorta or adjacent large vessels and avoids compression injury to surrounding anatomical structures, such as the left recurrent laryngeal nerve. FIG. 7C shows another embodiment having three expandable structures 310, 320, and 340 connected by flexible connectors 330. In this embodiment, a central expandable structure is positioned at target region T. Additionally, the central structure may be larger (e.g., 1.3-1.5 times larger) in size than the outer expandable structures, thereby providing greater stretch at the target site while the outer expandable structures provide transition and reduce the risk of arterial wall dissection. Additional details regarding the expandable structures can be understood by reference to FIGS. 10A-12B.

[0055] 10A-10D show an exemplary implant device 300 having two laterally expandable structures 310, 320 interconnected in series by multiple flexible connectors 330. FIG. 10A shows a cross-sectional view, and FIG. 10B shows a side view. FIGS. 10C-10D show the same views, except the device is rotated 45° along its longitudinal axis. The implant device may further include one or more visualization markers 331, e.g., a coating on the flexible connectors 330, to aid in placement during implantation. In this embodiment, the flexible connectors are axially expandable (e.g., zigzag connectors), with a total of four connectors extending between the apexes of adjacent crowns of the first and second expandable structures. FIG. 10E shows an exemplary implant device 300′″ having three laterally expandable structures 310, 320, 340 interconnected by flexible connectors 330. It will be appreciated that some embodiments may further comprise additional such structures (eg, four, five, six, etc.) connected in the same or different ways.

[0056] In this embodiment, each expansion structure 310, 320 comprises four elongated frames (310a / 310b / 310c / 310d) connected along adjacent sides to form a square cross-section, as shown in FIG. 10A. Each frame comprises at least two straight struts 311, 312 defining opposing sides and curved atraumatic crowns 313, 314 connecting the proximal and distal ends, respectively. The overall shape of the frame is therefore oval or pill-shaped. As shown, the atraumatic crowns 313, 314 are gently curved, forming arcs of less than half a circle, so that engagement of the proximal or distal ends with tissue does not cause trauma to the arterial wall. The struts and crowns define the entire frame, thereby defining a primary opening 315 through which the arterial wall is exposed to pulsatile blood flow and allows lateral blood flow to secondary branch arteries. In some embodiments, adjacent frame struts are defined as a single strut, resulting in a square-section implant with only four struts, one at each corner. Alternatively, the entire frame can be formed as a single continuous wire, with the crowns and struts being different portions of the same wire. In some embodiments, the frame is designed to have no sharp corners or elements that form angles less than 100°; this design ensures that the proximal and distal ends of the frame remain atraumatic and helps prevent thrombus or plaque from forming within the frame along the primary openings through which lateral blood flow is maintained. This design is advantageous because the square cross-section provides sufficient stretch of the arterial wall between the opposing lateral struts of each frame without overstretching any portion of the arterial wall, while still maintaining normal aortic function and blood flow. Although this embodiment includes two expandable structures interconnected by four flexible connectors, the implant may include additional expandable structures connected in series in a similar manner, and may include more or fewer flexible connectors.

[0057] It is understood that these concepts can be utilized in a variety of other shapes / designs, such as triangular or any regular polygonal cross section as shown in Figures 11A-12B. Figures 11A-11B show an implant 300' with first and second expandable structures 310' / 320', each having a frame similar to that shown in Figure 10A, but with each component formed from three frames, resulting in a triangular (e.g., equilateral) cross section. In this embodiment, the largest lateral dimension of the component is the length of each side of the triangle that stretches three portions of the arterial wall. 12A-12B show yet another implant 300'' with first and second expandable structures 310'' / 320'', each formed by a frame similar to that shown in FIG. 10A, but with each component formed by five frames forming a hexagon that stretches five portions of the arterial wall. In this embodiment, the largest lateral dimension is the distance between the vertex and the midpoint of the opposing side.

[0058] In another aspect, the implant is specifically sized for the dimensions of the human aortic arch, engaging the lateral struts of the expandable structure with the arterial wall, anchoring the implant within the aortic arch and fully stretching the arterial wall in the target region. In the embodiment shown in Figure 7A, the implant is positioned such that the first expandable structure 310 is positioned opposite the LSA along the target region of the cylindrical band encircling the aorta, as described above. In Figure 7C, the implant is positioned such that the larger central expandable structure is positioned at the target region T. Engagement of the pair of lateral struts in this region thus stretches the arterial wall and stimulates sensitive baroreceptors in this region. In some embodiments, the implant is sized to provide a 2:1 ratio of implant diameter to aortic diameter in the baroreceptor target region.

[0059] IV. Sizing of Aortic Arch Implants The baroreceptor amplification device is an intravascular implant designed to amplify the baroreflex response by stimulating sensitive baroreceptors at precise locations within the aorta. This is achieved by appropriately sizing the implant as described herein to achieve sufficient stretching of the arterial wall in the target area (e.g., 20% or more, 30% or more). The implant is sized based on the unique morphology of the human aortic arch. In some embodiments, suitable applicable dimensions for such an implant are determined by computed tomography angiography (CTA) examination of the human aorta. Aortic arch CTA measurements were obtained from 50 patients, including both men and women, aged 53 to 88 years. The measurements were tabulated, and means and ranges were determined according to Tables 1 and 2 below. It is understood that all sizing and dimension aspects discussed with respect to the implant also apply to the expandable member of the baroreflex gauge.

[0060] Table 1 shows the average of various aortic arch measurements, including the diameter of the aortic arch along regions A, B, C, and D (see Figure 13 ) and the length E extending between sections A and D (see Figure 14 ).

[0061] [Table 1]

[0062] Table 2 shows the range of various aortic arch measurements, including the aortic arch diameter along regions A, B, C, and D, and the length E mentioned above.

[0063] [Table 2]

[0064] In one aspect, the diameter and length dimensions are expected to have relatively small variations, as evidenced by small standard deviations and narrow ranges. Therefore, it is expected that appropriately sized implants can be created to fit most patients within the aforementioned ranges. It should be noted that because the arterial wall can be safely stretched up to 50%, and in some cases up to 100%, in healthy patients, variations in stretch due to differences in aortic dimensions may be tolerated as long as the target area is sufficiently stretched (e.g., at least 20%). Alternatively, the averages and ranges of these dimensions may be considered to require different sized implants. In some embodiments, a set of different sized implants (e.g., 3-10 different sizes) may be provided, and sizes may be easily selected based on the specific measurements of a particular patient's aortic arch (see Table 3 below). Alternatively, implants may be custom-made according to patient-specific measurements. These latter two options may be well-suited for patients with highly variable aortic arch morphology or particularly complex aortic arch shapes.

[0065] According to the aforementioned average and range of human aortas, two or more expandable structures may be appropriately sized for placement within the aorta. In one embodiment, each expandable structure has a length of 30 mm to 60 mm, typically about 40 mm, and a maximum transverse dimension (e.g., diameter) of 30 mm to 55 mm, typically 30 mm to 46 mm. These dimensions accommodate most of the aorta of an average adult while providing the necessary stretch along the target region to elicit a baroreflex response. The multiple expandable structures may be the same or different lengths and may have the same or different diameters.

[0066] Table 3 below shows a set of different sized implants and corresponding diameters based on a compilation of relevant dimensions of the aortic arches of over 50 patients based on CTA examinations. Part A refers to the more distal expandable structure (20 in FIG. 1A ) and part B refers to the more proximal expandable structure (10 in FIG. 1A ) positioned at the target area. As noted above, the size of the implant can be selected to suit the patient's unique morphology based on a CT scan of the patient's aortic arch. It is understood that the set of sizes can include any of the listed sizes or any combination thereof, as well as various additional combinations not listed.

[0067] [Table 3]

[0068] While the above table provides general guidelines for implant sizing, the baroreflex gauge device described herein can be used to more accurately size implants to better optimize the baroreflex response and improve hypertension treatment.

[0069] In another aspect, two or more expandable structures are connected in series by multiple flexible connectors. Preferably, the connectors are axially expandable (e.g., zigzag design) to optimize conformance to the outer and inner curvatures of the aortic arch. In some embodiments, the connectors are axially expandable by 5 mm to 20 mm, typically about 5 mm to 10 mm. In some embodiments, the connectors are 5 mm in an unexpanded state and up to about 10 mm or more in a fully expanded state, such that the connectors on the outer curvature of the aortic arch can be expanded while the connectors on the inner curvature of the aortic arch remain unexpanded, as shown in FIG. 7A.

[0070] In another embodiment, the length of each expansion structure is typically 30 mm to 50 mm, preferably about 40 mm, resulting in a total implant length, including the flexible connectors, of 65 mm to 110 mm, typically 70 to 90 mm, depending on the axial extension of the connectors. These lengths allow the implant to extend a minimum of 10 mm beyond the lateral surface of both the brachiocephalic artery and the left subclavian artery, ensuring a safe and stable loading area for the device. CTA studies have shown that the implant extends approximately 85 mm when the connectors are unexpanded and approximately 10 mm or more (e.g., 10 mm to 20 mm) when the connectors are fully expanded.

[0071] Previous animal studies suggest that human aortic arch baroreceptors need to be stretched by at least about 20% to achieve a significant increase in baroreceptor neural signaling. Therefore, the implant is sized so that its maximum transverse dimension or diameter is at least 20% larger than the natural diameter of the target area (e.g., measurement C on CT angiography). The diameter of the implant is preferably large enough to ensure adequate adhesion to the aortic arch wall at the terminal landing area just beyond the transverse origins of the brachiocephalic artery and the left subclavian artery (e.g., locations A and D in Figure 13 ). For sizing purposes, the diameter of the implant is measured as the maximum transverse dimension (e.g., the diagonal line shown in Figure 10A for a square cross-section). Based on CTA studies, the implant can be sized to a variety of different diameters, e.g., 30 mm, 34 mm, 38 mm, 42 mm, 46 mm, and 50 mm. The implant can be configured with parts A and B having different diameters, e.g., as shown in Table 3.

[0072] V. Mechanism of Action To further understand the effects of implant size and diameter, it is desirable to understand how the implant works to lower blood pressure. It is convenient to consider the cross section of the aortic arch as a circle and the arterial walls as individual arc lengths, as defined by the diagram and arc length equation shown in FIG. 15A. For an implant with a square cross section (as shown in FIG. 10A), the diameter of the aorta is considered to be the circle divided into equal parts (e.g., four equal parts). If the aortic arch diameter is 25 mm, the radius will be 12.5 mm and each arc length will be 19.6 mm, as shown in FIG. 15B. In this same example, after insertion of a 30 mm diameter implant, the aortic arch radius will be 15 mm and each arc length will be 23.6 mm, but only if the aortic arch remains circular, as shown in FIG. 15C.

[0073] Thus, the change in arc length from baseline ( FIG. 15B ) to post-implant ( FIG. 15D ) is a 20% increase because the radius increases by 20% while other variables are constant. In other words, each aortic arch is stretched by 20%. However, after implant insertion, the aortic arch does not remain circular. While the radius of curvature of each arc length increases, the central angle corresponding to that arc length simultaneously decreases (see FIG. 23C ). While the opposing changes in these two variables make it difficult to accurately estimate the resulting arc length and the degree of aortic arch stretch, this approach provides a sufficiently reasonable estimate of the resulting stretch to appropriately size the implant to achieve at least 20% stretch. Note that while the above analysis assumes the square implant cross-section of FIG. 10A , this analysis can be modified to account for the implant of FIG. 11A , which divides the cross-section into three equal parts, or the implant of FIG. 12A , which divides the cross-section into five equal parts.

[0074] Thus, with the above approach, the implant can be sized to provide at least 20% stretch of the target arterial wall. In some embodiments, the implant may be slightly oversized to ensure at least 20% stretch, or to accommodate variations in aortic size while still ensuring at least 20% stretch in all cases. In some embodiments, the implant can be configured to provide additional stretch, e.g., 20-30%, 50% stretch, or even 100% stretch, which can be safely achieved in many patients.

[0075] As previously mentioned, this design allows the device to be deployed and stabilized at key anatomical targets within the vasculature. Preferably, this target site is within the aortic arch to stretch aortic arch baroreceptors located along the cylindrical segment of the aortic arch that encases the aorta between the origin of the left common carotid artery and the origin of the left subclavian artery (including along the inner curve), as seen in CT angiograms of the human aortic arch. Although aortic arch baroreceptors extend along the inner curve of the aortic arch and circumferentially around the aortic arch to the outer curve or saddle region of the aortic arch, the highest concentration of these baroreceptors is in the segment of the aortic arch that encases the aorta along diameter C, adjacent to the left subclavian artery, shown as target T in FIG. 16 . The implant configurations described herein are specifically configured to target this site, as well as to safely and as fully stretch the adjacent baroreceptors as possible.

[0076] VI. Delivery and placement at the target site In yet another embodiment, the implant device is particularly suited for intravascular delivery and deployment, as the implant has a collapsed configuration for advancement through the vasculature and an expanded configuration for engaging the arterial wall, as shown in Figures 7A-7C. In the collapsed configuration, the implant is positioned within a delivery catheter to facilitate intravascular delivery and subsequent deployment to a target site in the aortic arch.

[0077] In one example, the implant is a self-expanding structure preloaded within a sheathed delivery catheter, as shown in FIG. 17 . As shown, the intravascular delivery catheter is designed to deliver the implant in a collapsed configuration and position and deploy the implant at a target site, such as that shown in FIG. 16 . The delivery catheter includes an internal guidewire lumen so that the implant can be advanced along a guidewire GW positioned within the aortic arch. In the illustrated embodiment, the delivery catheter 200 includes a catheter shaft 201 and a retractable sheath 202, over which the implant 100 is collapsed and over which the sheath 202 is positioned, which constrains the implant in the collapsed configuration until the implant is positioned at the desired target site, for example, by visualization of a marker (e.g., a radiopaque marker or an ultrasound marker). The marker can be a coating or marker attached to the connector and / or the expandable structure. In some embodiments, the connector can be constructed from a different material than the frame so that the connector itself is clearly visible using visualization techniques. The delivery catheter may further include a tapered distal tip 203 for guiding advancement over the GW and a flush port 211 for flushing before, during, or after delivery. The delivery catheter includes a handle 210, which allows a clinician to retract the sheath to deploy the self-expanding implant, and the handle 210 may include a hub 220 for manually retracting the sheath 202 to deploy the implant. The sheath and / or shaft may include markings on the sheath and / or shaft to measure the distance the sheath is retracted during deployment, facilitating partial, incremental deployment, or complete deployment of the entire implant. Typically, the overall length (l) of the delivery catheter is 100 cm to 150 cm (e.g., approximately 135 cm) to allow easy access to the aortic arch by inserting the catheter through the femoral artery.

[0078] In some embodiments, the delivery catheter can be configured to deliver the entire implant when the sheath is retracted, allowing for rapid succession of deployment of both the first and second expandable structures. The length of the expandable structure is long enough to allow for slight axial movement during deployment while still allowing for deployment of expandable structure 310 at the target site. Although structure 320 is deployed first, the deployment and deployment are targeted to deploy structure 310 at the target site. In other embodiments, the delivery catheter can be configured to allow for sequential delivery of multiple expandable structures by incrementally retracting the sheath a specified distance, with the more distal second structure being placed first, followed by the first expandable structure to precisely position it at the target site, with the axially expandable connector providing some leeway for positioning the last-deployed expandable structure. In yet other embodiments, the implant can be balloon-expandable and disposed in a collapsed configuration on a balloon on the delivery catheter, the balloon suitably sized to expand within the aorta and deploy the implant at the target site.

[0079] When deployed, the implant forms an open lattice with struts in the frame that are designed to stretch the aortic arch and stimulate the aortic arch baroreceptors, thereby reducing blood pressure, with the arterial wall exposed to each aortic pulsation through the main opening in the frame, as shown in the example in Figures 10A-12B.

[0080] 18-23 illustrate sequential steps of an exemplary method for assessing baroreflex response and deploying an implant device described herein. It is understood that this method is exemplary and that in other embodiments, additional intervening or alternative steps may be present.

[0081] 18, a guidewire is placed in the aortic arch and the baroreflex gauge catheter device 100 is advanced along the guidewire GW. A baseline of the patient's hypertensive blood pressure is obtained by the sphygmomanometer 400, and the patient's blood pressure is monitored during the baroreflex measurement procedure.

[0082] As shown in FIG. 19, after the expandable structure 10 is positioned in the target region T, it is exposed and expanded to engage and sufficiently stretch the arterial wall to elicit a baroreflex response. After expansion, the clinician measures the patient's blood pressure using a sphygmomanometer 400. If the measured blood pressure drops to a desired level (e.g., within the normal range or significantly lowered), the diameter of the expandable structure is recorded and a correspondingly sized implant can be selected for implantation. If the blood pressure drop is insufficient, the diameter of the expandable member can be increased incrementally until the observed blood pressure drops to the desired level. Once the patient's baroreflex response has been confirmed and the optimal implant size determined, the clinician proceeds with implanting the selected implant, as shown in FIGS. 18C-18F.

[0083] A guidewire GW is advanced through the entry point (e.g., femoral artery) and advanced through the vasculature to the aortic arch, as shown in Figure 20. Fluoroscopy, a visualization technique, can confirm that the GW has been placed in the target area.

[0084] As shown in FIG. 21, a delivery catheter 200 is advanced along the GW, the catheter carrying an implant 300, which is disposed in a collapsed configuration on the catheter shaft 201 and constrained within a retractable outer sheath 202.

[0085] As shown in FIG. 22, once the implant is positioned at the desired target site within the aortic arch, the outer sheath 202 is retracted, thereby allowing the self-expanding implant 300 to elastically deploy into an expanded configuration, with the two expandable structures 310, 320 engaging the arterial wall.

[0086] As shown in FIG. 23, the guidewire GW and delivery catheter 201 are then withdrawn, leaving the implant anchored in the target site in the aortic arch, with at least one expandable structure 300 engaging and stretching the arterial wall in the target area to provide long-term blood pressure reduction.

[0087] 24 illustrates an exemplary method for assessing a baroreflex response using a baroreflex gauge catheter, according to some embodiments, comprising advancing a baroreflex gauge catheter carrying an expandable structure at its distal end for measuring the baroreflex response, the expandable structure being in a collapsed configuration for facilitating advancement through the vasculature, deploying the expandable structure at a target area to stretch an arterial wall in the target area by at least 20%, thereafter monitoring the patient's blood pressure to observe a decrease in blood pressure, confirming a baroreflex response based on observing a decrease in blood pressure while the expandable structure is expanded, and determining a course of treatment based on the confirmed baroreflex response.

[0088] 25 illustrates an exemplary method for assessing a baroreflex response using a baroreflex gauge catheter to determine optimal dimensions for a subsequent implant, according to some embodiments. The method includes advancing a baroreflex gauge catheter carrying an expandable structure at its distal end for measuring the baroreflex response, the expandable structure being in a contracted state to facilitate advancement through the vasculature; deploying the expandable structure at a target area, monitoring the patient's blood pressure, and incrementally adjusting the lateral dimensions of the expandable structure while monitoring the blood pressure to determine optimal dimensions for the baroreflex response; selecting and / or customizing an implant according to the optimal dimensions for the baroreflex response; and delivering and deploying the implant at the target site to maintain the baroreflex response over time for the treatment of hypertension.

[0089] Thus, the implant devices and related methods described herein address an unmet clinical need for the treatment of patients with severe hypertension unresponsive to multiple medications. Existing conventional treatments and therapies (e.g., renal denervation, carotid artery devices) have had minimal or limited impact on this population due to their limited blood pressure lowering efficacy or the risk of adverse events, respectively. The implants described herein are designed to meet this unmet clinical need based on previous animal studies identifying the unique anatomical and physiological characteristics of the aortic arch baroreceptors and the CT angiography studies outlined above. By enabling sufficient stretching of specific target regions of the aortic arch that stimulate sensitive baroreceptors, the described implants consistently and reliably lower a patient's blood pressure while avoiding the adverse risks and drawbacks associated with other approaches that target other vasculature (e.g., the carotid arteries).

[0090] FIG. 26A shows a histology image of the tissue, with potential baroreceptors stained brown. The histology image of the tissue indicates that baroreceptors are present in the target region of the aortic arch, potentially extending along the aorta toward and slightly beyond the origin of the left subclavian artery. FIG. 26B shows a close-up of the baroreceptors surrounded by elastic tissue. While the location of baroreceptors in this region is believed to be fairly consistent between patients, the shape and morphology of the aortic arch can vary between patients, and therefore the location of baroreceptors can also vary. Thus, the devices and methods described herein enable clinicians to investigate and measure the location of baroreflex responses in a particular patient and map or confirm the location of baroreceptors prior to deploying a permanent implant.

[0091] Alternatively, the implant itself can be used as a baroreflex gauge. In some embodiments, the implant can be partially deployed so that the expandable structure is deployed at the target site, after which a physiological response (e.g., blood pressure) can be monitored to assess the implant's effectiveness. Based on this response, the implant can then be fully deployed, repositioned, or removed. The use of a tethered implant is particularly useful for this purpose, as the tether extends proximally, releasably connecting the implant to a delivery shaft and allowing the partially deployed implant to be repositioned or removed after measuring the physiological response. Such an integrated baroreflex gauge and implant delivery system is advantageous for several reasons. First, because the baroreflex response is measured from the implant itself, it avoids the potential for differential stretching or placement caused by a separate gauge device designed differently from the implant. Second, integrating the measurement functionality into the implant delivery catheter system can simplify and shorten the procedure, which is ideal for higher-risk patients. Third, this integration can reduce the overall device cost and procedural complexity. An example of a tethered implant that enables this integrated gauge and implant delivery system is shown below.

[0092] 27A-27F illustrate a tethered articulating implant 130 and various deployment steps, according to some embodiments. FIG. 27A shows the implant structure 130 defined as three expandable rings 10, 20, 40 connected by helically oriented bridges 31 and, as previously described, at a reduced diameter D1 for delivery to the target site. Each ring may have a sinusoidal or zigzag shape with peaks and valleys. In some embodiments, the design is formed from one or more wires. In some embodiments, the design is laser cut from a tube (e.g., Nitinol tubing). The design may further include a tether 50 extending proximally and engaging a tool or delivery catheter. In this embodiment, each tether is attached to the proximal apex of the crest of the proximal-most structure 10 and terminates in a proximal connector configured to releasably couple with a delivery catheter or tool. Figure 27B shows the implant structure deployed to an expanded diameter D2. In some embodiments, the implant structure can be configured to uniformly expand to a diameter 2-4 mm larger than the nominal diameter of the aortic arch. As shown in Figure 27C, the bridges are configured so that the outer rings (i.e., the proximal and distal expandable structures 10, 20) twist relative to the central ring, thereby increasing the circumferential orientation of the bridges. This configuration improves flexural hinge characteristics and reduces the overall length of the implant. It is understood that various other bridge orientations can also be used, and the implant structure can be configured to have larger or variable diameters. Figure 27D shows an embodiment in which the central expansion structure 40 (i.e., the central ring) has a larger deployed diameter than the proximal and distal expansion structures (i.e., the outer rings). In this embodiment, the central ring is expanded to a larger diameter D3, thereby increasing the outward force transmitted to the arch at the baroreceptor target site.FIG. 27E illustrates a tethered articulating implant 130 deployed from a delivery catheter 200 into the curved aortic arch AA, with the tether's proximal connector still connected to the distal portion of the delivery catheter, allowing for retrieval and repositioning of the implant. The circumferentially oriented hinges separate at the outer radius and compress at the inner radius, allowing the entire implant 20 to conform to the curvature of the aortic arch. In this embodiment, the tether includes sinusoidal sections that stretch to allow for angular transitions between the catheter tip and the proximal rings of the implant. As shown in FIG. 27F, the sinusoidal tether can extend to different lengths L1, L2, and L3 to conform to the curvature of the arch. It is understood that in other embodiments, shorter tethers without sinusoidal sections or stretched sections can be used, such that the most proximal structures remain only partially deployed.

[0093] 28A-28B illustrate an exemplary aortic arch AA and the deployment of a tethered articulating implant 130 within the aortic arch AA, according to some embodiments. FIG. 28A illustrates an exemplary aortic arch curvature having a relatively steep curvature. FIG. 28B illustrates an implant 130 having a helically oriented bridge and a proximally extending tether 50 that allows for controlled placement, retrieval, repositioning, and removal of the implant, as needed, via a tool or delivery catheter 200. While shorter, straight tethers could also be used, in this embodiment the tethers are axially flexible (e.g., sinusoidal, zigzag), allowing the rings to fully expand, contact the arch, and conform to the arch curvature. In this example, the outer tether is elongated to a length of approximately 27 mm, while the inner tether is elongated to a length of approximately 17 mm. In this embodiment, each tether may be a sinusoidal design tether that stretches approximately 20-30 mm when fully extended.

[0094] 29A shows a two-ring implant, according to some embodiments. This prototype design comprises two expandable structures 10, 20 (i.e., two rings) connected by a helically oriented bridge 31. The active helical bridge allows for hinging and extension action between the expandable structures. This design can be used to form implants of any suitable material, including expandable structures laser cut from metal tubing (e.g., Nitinol tubing).

[0095] 29B shows a three-ring implant, according to some embodiments. This prototype design comprises three expandable structures 10, 20, 40 (i.e., three rings) connected by a helically oriented bridge structure 31. The active helical bridge allows for hinging and extension action between the expandable structures, thereby conforming to the curvature of the aortic arch. This design can be used to form implants of any suitable material, including expandable structures laser-cut from metal tubing (e.g., Nitinol tubing).

[0096] 30A-30B show a multi-ring tethered articulating implant according to some embodiments. This prototype design includes three expandable structures 10, 20, 40 (i.e., three rings) connected by a helically oriented bridge structure 31, with an extensible tether 50 extending from the most proximal ring. The active helical bridge allows for hinge and extension between the expandable structures to conform to the curvature of the aortic arch and is long enough to allow the central ring to be fully expanded while the tether is still connected to the delivery catheter, as shown in FIG. 30B, allowing it to be used as a gauge of blood pressure response. This design can be used to form implants of any suitable material, including expandable structures laser-cut from metal tubing (e.g., Nitinol tubing). As with the previous embodiment, the central ring 40 can be defined to have a larger diameter than the outer rings. Varying the diameter of the central active ring changes the amount of "oversizing" the implant exerts on the arch. In some embodiments, it is recommended to shape the implant so that the diameter of the central active ring is 25-40 mm, typically 25-30 mm.

[0097] 31A-31B illustrate alternative implant structures 131, 131', according to some embodiments. While a particular diamond-shaped pattern is used, it is understood that the expandable structure can utilize a variety of other expandable shapes and patterns.

[0098] FIGS. 32A-32E show various views of an exemplary implant 132 having three expandable structures 10, 20, 40 (i.e., three rings) connected by helical bridges 31, as shown in FIG. 32A, and a short proximally extending tether 50, thereby defining an eight-cell structure. The implant may be laser cut from a nitinol tube (e.g., a 5.0 mm diameter tube) or formed by any suitable means. FIG. 32B shows the implant 132 in a constrained configuration. FIG. 32C shows the uniform partial expansion of the implant 132 (in a fully expanded state, the middle ring may have a larger diameter than the outer rings). FIG. 32D shows various cross-sectional views of the implant. FIG. 32E shows an exploded view of the implant 132, showing the three expandable rings and eight helically oriented bridges that define the aforementioned eight-cell structure. It is understood that varying the width of the struts and rings in this design can be used to provide different strengths and apply desired forces to the vessel wall. The expanded diameters correspond to equivalent stretching and outward pressure exerted by the implant. For example, in a high-strength 8-cell design, expanded diameters of 20 mm, 25 mm, and 30 mm can accommodate 4%, 13%, and 23% stretching, respectively, and outward pressures of 100 mmHg, 365 mmHg, and 628 mmHg, respectively. In a medium-strength 8-cell design, expanded diameters of 20 mm, 25 mm, and 30 mm can accommodate 2%, 7%, and 12% stretching, respectively, and outward pressures of 39 mmHg, 140 mmHg, and 247 mmHg, respectively.

[0099] FIGS. 33A-33E show various views of another exemplary implant 133, as shown in FIG. 33A, having three expandable structures 10, 20, 40 (i.e., three rings) connected by helically oriented bridges 30 and having a short proximally extending tether 50, thereby defining a four-cell structure. The implant 133 may be laser cut from a nitinol tube (e.g., a 5.0 mm diameter tube) or formed by any suitable means. FIG. 33B shows the implant 133 in a constrained configuration (e.g., a 4 mm constrained configuration). FIG. 33C shows uniform partial expansion of the implant 133 (in a fully expanded state, the middle ring may have a larger diameter than the outer rings). FIG. 33D shows various cross-sectional views of the implant. FIG. 33E shows an exploded view of the implant 133, showing the three expandable rings and four helically oriented bridges that define the four-cell structure described above. As shown, the pattern is a flat, laser-cut pattern with a circumference corresponding to a 5.0 mm diameter tube. It is understood that varying the width of the struts and rings in this design can be used to provide different strengths and apply desired forces to the vessel wall. Higher strength expanded diameters correspond to equivalent stretching and outward pressure exerted by the implant. For example, in a high-strength four-cell design, expanded diameters of 20 mm, 25 mm, and 30 mm may correspond to 1%, 5%, and 9% stretch, respectively, and outward pressures of 25 mmHg, 105 mmHg, and 190 mmHg, respectively. In a medium-strength four-cell design, expanded diameters of 20 mm, 25 mm, and 30 mm may correspond to 1%, 2%, and 4% stretch, respectively, and outward pressures of 11 mmHg, 41 mmHg, and 74 mmHg, respectively.

[0100] 34A-34C illustrate various configurations of tethers 50 and their interfaces within a retention collar 500, according to some embodiments. FIG. 34A illustrates a straight, axially extending tether 50a, which terminates at a proximal connector 51. In this embodiment, the connector is a rounded or radiused section. FIG. 34B illustrates a tether 50b, in which the proximal connector curves inward to engage a recess in the locking collar 500 of the delivery catheter, allowing the tether to spring outward upon deployment, thereby releasing the implant from the delivery catheter. FIG. 34C illustrates another tether 50C, which has a sinusoidal section that allows axial extension as described above and terminates at a mushroom-shaped proximal connector 51. It is understood that various other dimensions, shapes, and sizes may be used for the tether and proximal connector.

[0101] 35A-35B show a shorter tether 50 that can be used for the eight-cell and four-cell implant structures described above. In this embodiment, the tether is straight and relatively short (e.g., 1-10 mm, 2-6 mm, 2-4 mm), and extends to a proximal connector, which may also be referred to as a lock. In this embodiment, the proximal connector 51 may have a mushroom shape, although any suitable shape may be used. The proximal connector may be captured by a corresponding notch in a retention collar located at the distal portion of the delivery catheter (as shown in FIG. 38).

[0102] FIG. 36 shows various views of a retention collar 500 for retaining an implant structure before it is fully deployed, according to some embodiments. The retention collar 500, which may also be referred to as a collar lock, may be laser cut, machined, or formed by any suitable means. In this embodiment, the retention collar is formed from a metal tube (e.g., 4ID nitinol tubing). The distal end includes a notch 501d shaped to correspond to the proximal connector, allowing a tether to be secured to the collar to facilitate control of axial longitudinal movement of the implant while constrained within the outer sheath of the delivery catheter. The collar may further include an array of small holes (e.g., 1 mm holes) to facilitate attachment to the delivery shaft of the delivery catheter 200.

[0103] FIG. 37 shows the implant 133 in a constrained configuration extending from the outer shaft of a delivery catheter 200, with the retention tether 50 proximally engaged with a retention collar 500 attached to the delivery catheter's advanceable delivery shaft. In some embodiments, this assembly can be delivered through a 14 French outer shaft (i.e., introducer). Thus, by advancing the delivery shaft, the implant can be partially deployed (e.g., by maintaining the retention collar within the outer shaft) or fully deployed by advancing the collar beyond the distal end of the outer shaft and allowing the proximal connector to pop out of the corresponding notch. This configuration allows the implant to be partially deployed, the baroreflex response assessed, and then repositioned or removed based on the response. FIG. 38A shows a cross-sectional view of the tether's proximal connector interfaced with the retention collar 500, according to some embodiments, and FIG. 38B shows a detailed view of the proximal connector, in which the implant is constrained within the delivery catheter's outer sheath 210.

[0104] FIGS. 39A-39D and 40A-40D show cross sections of the four-cell and eight-cell expandable structures described above for an integrated implant and baroreflex gauge. As shown in FIGS. 39A-39D, expandable structure 133 is defined as a four-cell structure with a regular polygonal cross-section. As shown in FIGS. 40A-40D, expandable structure 132 is defined as an eight-cell structure with a generally circular cross-section. Either design can be used to stretch the arterial wall an appropriate amount (e.g., 20% or more) to measure the baroreflex response and to elicit a long-term baroreflex response after full deployment and implantation. In some embodiments, the implant can further include features to facilitate implantation, such as barbs, or features to promote tissue ingrowth, such as coatings, holes, or slots. In some embodiments, these features can be placed in the undeployed portion during measurements.

[0105] While the present invention has been described in the foregoing specification with reference to specific embodiments thereof, those skilled in the art will recognize that the present invention is not limited to these embodiments. The various configurations, embodiments, and aspects of the present invention described above may be used individually or in combination. Moreover, the present invention may be utilized in any number of environments and applications other than those described herein without departing from the broader spirit and scope of the present specification. Accordingly, the specification and drawings are to be regarded as illustrative and not restrictive. It will be understood that the terms "comprising," "including," and "having," as used herein, are specifically intended to be read as open-ended terms. Unless otherwise stated, the term "about" is intended to mean within ±10%. Unless otherwise stated, the term "about" is intended to mean within ±10%. It is understood that the various dimensions of the embodiments described herein, and in some embodiments, each dimension, may encompass variations, such as variations of ±25% of the stated value, variations of ±10%, etc. While specific dimensions are shown in the various figures, it is understood that the illustrated embodiments are not limited to these dimensions and may have various other dimensions as desired. Any reference to a publication, patent, or patent application is incorporated herein by reference in its entirety for all purposes.

[0106] (Addendum) (Appendix 1) 1. A method for assessing a baroreflex response and / or location of a baroreflex in a patient, comprising: advancing a delivery catheter carrying an expandable structure at a distal portion thereof, the expandable structure being disposed on the delivery catheter in a collapsed configuration to facilitate advancement through the patient's vasculature, the expandable structure being expandable to a plurality of expanded configurations having different transverse dimensions; placing the distal portion of the catheter carrying the implant in the collapsed configuration at a target region within the vasculature; expanding the expandable structure within the target region such that the expandable structure expands to an expanded configuration having a lateral dimension sufficient to engage an arterial wall along the treatment region to stretch at least a portion of the arterial wall along the target region, thereby eliciting a baroreflex response of aortic arch baroreceptors within the target region to reduce blood pressure; monitoring the patient's blood pressure with the expandable structure in the expanded configuration, the expanded configuration having a lateral dimension corresponding to a hypertension treatment implant deployed at the target site; Including, method.

[0107] (Appendix 2) each of the plurality of expanded configurations is circular; The method described in Appendix 1.

[0108] (Appendix 3) The different lateral dimensions are in the range of 20 mm to 60 mm. 3. The method according to claim 1 or 2.

[0109] (Appendix 4) the different lateral dimensions correspond to a plurality of implants for treating hypertension, such that each lateral dimension corresponds to a different implant of the plurality of implants; A method according to any one of appendices 1 to 3.

[0110] (Appendix 5) the expanded configuration is a first configuration having a first lateral dimension; The method comprises: adjusting the expanded expandable structure to a second configuration having a second lateral dimension; monitoring the patient's blood pressure with the expandable structure in the second expanded configuration; further comprising: A method according to any one of appendices 1 to 4.

[0111] (Appendix 6) further comprising repeating the steps of adjusting the expandable structure to one or more additional configurations having different lateral dimensions and monitoring blood pressure in each configuration until the monitored blood pressure indicates a desired reduction in blood pressure. The method described in Appendix 5.

[0112] (Appendix 7) and wherein monitoring the blood pressure further comprises recording a lateral dimension indicative of a desired reduction in blood pressure. A method according to any one of appendices 1 to 6.

[0113] (Appendix 8) and further comprising the step of repeatedly adjusting the expandable structure to one or more additional positions along or near the target area and monitoring blood pressure at each configuration to determine a maximum expanded diameter of the target area within the vasculature, above which there is little or no improvement in blood pressure. The method described in Appendix 5.

[0114] (Appendix 9) and further comprising the step of repeatedly adjusting the expandable structure to one or more additional positions along or near the target area and monitoring blood pressure at each position to determine a minimum expanded diameter of the target area within the vasculature that produces a baroreflex response and reduces blood pressure. The method described in Appendix 8.

[0115] (Appendix 10) the expanded configuration is at a first position within the target area; The method comprises: repositioning the expandable structure to a second location within or near the target area; monitoring the patient's blood pressure with the expandable structure in the second position; further comprising: A method according to any one of appendices 1 to 9.

[0116] (Appendix 11) repeating adjusting the expandable structure to one or more additional positions along or near the target area and monitoring blood pressure at each configuration until the monitored blood pressure indicates a desired reduction in blood pressure. 11. The method described in Appendix 10.

[0117] (Appendix 12) and recording the location where the monitored blood pressure indicated the desired reduction in blood pressure for subsequent implantation of a hypertension treatment at the target site. The method described in Appendix 11.

[0118] (Appendix 13) wherein the step of positioning the expandable structure includes observing one or more visualization markers positioned on the expandable structure. A method according to any one of appendices 1 to 12.

[0119] (Appendix 14) the target area is within the aortic arch; A method according to any one of appendices 1 to 13.

[0120] (Appendix 15) the target region is a cylindrical segment within the aortic arch between the left common carotid artery and the left subclavian artery; The method described in Appendix 14.

[0121] (Appendix 16) 1. A method for deploying a hypertension treatment implant in a patient's vasculature, comprising: Performing a baroreflex assessment according to the method described in Appendix 1; selecting or customizing an implant and / or implant location based on said baroreflex assessment; deploying the implant at the target site within the vasculature to treat hypertension; Including, method.

[0122] (Appendix 17) the step of selecting the implant includes selecting an implant from a plurality of implants having different lateral dimensions, the selected implant having a lateral dimension corresponding to a lateral dimension along which the monitored blood pressure indicates a desired blood pressure reduction. The method described in Appendix 16.

[0123] (Appendix 18) selecting a location for the implant includes selecting a location within the vasculature where monitored blood pressure indicates a desired reduction in blood pressure. 18. The method according to claim 16 or 17.

[0124] (Appendix 19) placing the distal portion of the catheter within the aortic arch includes advancing the delivery catheter over a guidewire positioned within the aortic arch. 19. The method according to any one of appendices 16 to 18.

[0125] (Appendix 20) the implant comprises two expandable structures connected in series by a plurality of flexible connectors, at least one expandable structure having a lateral dimension corresponding to a lateral dimension along which monitored blood pressure indicates a desired reduction in blood pressure; 20. The method according to any one of appendices 16 to 19.

[0126] (Appendix 21) the implant comprises three expandable structures connected in series by a plurality of flexible connectors, at least a central expandable structure having a lateral dimension corresponding to a lateral dimension along which monitored blood pressure indicates a desired reduction in blood pressure; A method according to any one of appendices 16 to 20.

[0127] (Appendix 22) the target area is within the aortic arch; A method according to any one of appendices 16 to 21.

[0128] (Appendix 23) a shaft extending between a proximal end and a distal end, the shaft having one or more lumens extending therethrough; an expandable structure disposed on the distal portion of the shaft in a collapsed configuration, the expandable structure being convertible between the collapsed configuration and an expanded configuration for engaging the arterial wall at the target region within the vasculature, the expandable structure being adjustable to a plurality of expanded configurations each having a different transverse dimension; a retractable outer sheath having a proximal end and a distal end, the outer sheath disposed over the shaft, including the distal end at which the expandable structure is disposed, such that the delivery catheter is configured to facilitate deployment of the expandable structure at the target area; and a catheter handle disposed at or near the proximal end of the shaft, the outer sheath being retractable from the catheter handle to facilitate deployment of the expandable structure at the target area, the catheter handle further comprising an adjustment control for adjusting the expandable structure between any of the plurality of expanded configurations; Equipped with Baroreflex gauge and / or mapping device.

[0129] (Appendix 24) the expandable structure comprises a stent-like structure having a plurality of struts to allow lateral blood flow through the stent-like structure; 24. The baroreflex gauge device of claim 23.

[0130] (Appendix 25) the plurality of struts comprising visualization markers to facilitate placement of the expandable structure at the target area. 25. The baroreflex gauge device of claim 24.

[0131] (Appendix 26) the plurality of struts are configured to have a flattened central region in the expanded configuration for engaging the arterial wall, the flattened central region having a length of at least 10 mm; 26. The baroreflex gauge device of claim 24 or 25.

[0132] (Appendix 27) the expandable structure is configured for deployment within the aortic arch. 27. A baroreflex gauge device according to any one of appendices 23 to 26.

[0133] (Appendix 28) The lateral dimensions of the plurality of expanded configurations are in the range of 20 to 60 mm; 28. A baroreflex gauge device according to any one of appendices 23 to 27.

[0134] (Appendix 29) The adjustment unit includes a slider mechanism. 29. A baroreflex gauge device according to any one of appendices 23 to 28.

[0135] (Appendix 30) the guide catheter device is configured such that moving the slider in one direction increases the transverse dimension of the expandable structure in a stepwise manner; 30. The baroreflex gauge device of claim 29.

[0136] (Appendix 31) the catheter handle further comprising one or more fine adjustment controls by which the transverse dimensions of the expandable structure can be further adjusted in smaller increments; 31. The baroreflex gauge device of claim 29 or 30.

[0137] (Appendix 32) the catheter handle further comprising a locking mechanism for locking the lateral dimension of the expandable structure during monitoring. A baroreflex gauge device according to any one of appendices 29 to 31.

[0138] (Appendix 33) the guide catheter device is configured to include a rack and pinion mechanism that allows for adjustment of a lateral dimension of the expandable structure without substantially moving a midpoint of the expandable structure within the vasculature; 33. A baroreflex gauge device according to any one of appendices 23 to 32.

[0139] (Appendix 34) the guide catheter device is configured to include a worm gear that allows for adjustment of a lateral dimension of the expandable structure without substantially moving a midpoint of the expandable structure within the vasculature; 34. A baroreflex gauge device according to any one of appendices 23 to 33.

[0140] (Appendix 35) 24. A baroreflex gauge catheter device according to claim 23; a sphygmomanometer capable of monitoring the patient's blood pressure with the expandable structure in the expanded configuration at the target area; and Equipped with Baroreflex assessment system.

[0141] (Appendix 36) 1. A method for assessing a baroreflex response and / or location of a baroreflex in a patient, comprising: advancing a delivery catheter carrying an implant at a distal portion thereof, the implant having a plurality of expandable structures interconnected by a plurality of bridges, the implant disposed on the delivery catheter in a compressed configuration to facilitate advancement through the patient's vasculature, the implant being expandable to an expanded configuration for engaging and stretching an arterial wall; placing the distal portion of the catheter carrying the implant in the collapsed configuration at a target region within the vasculature; partially deploying the implant such that the at least one expandable structure expands within the target area to engage the arterial wall along the treatment area such that the at least one expandable structure stretches at least a portion of the arterial wall along the target area, thereby eliciting a baroreflex response of aortic arch baroreceptors in the target area to reduce blood pressure; monitoring the patient's blood pressure with the expandable structure in the expanded configuration, the expanded configuration having lateral dimensions corresponding to a hypertension treatment implant deployed at the target site; Including, method.

[0142] (Appendix 37) the expanded configuration of the at least one expandable structure is polygonal or circular; The method described in Appendix 36.

[0143] (Appendix 38) The lateral dimension of the expanded form is within the range of 20 to 60 mm. 38. The method according to claim 36 or 37.

[0144] (Appendix 39) and when an adequate reduction in blood pressure is observed, fully deploying the implant at the target site while the at least one expandable structure remains expanded at the target site. The method described in Appendix 36.

[0145] (Appendix 40) fully deploying the implant includes releasing one or more proximal connectors of the implant from a locking element of the delivery catheter. 39. The method described in Appendix 39.

[0146] (Appendix 41) fully deploying the implant includes advancing the locking element distally of the outer delivery sheath such that the one or more proximal connectors expand outward, thereby releasing the one or more proximal connectors of the implant from the locking element of the delivery catheter. 41. The method described in Appendix 40.

[0147] (Appendix 42) and when a suboptimal response is observed, further comprising the step of moving the implant to another location and reassessing the baroreflex response. A method according to any one of appendices 36 to 41.

[0148] (Appendix 43) the step of moving the implant to another location includes retracting a locking element of the catheter attached to the implant proximally into the delivery sheath, thereby retracting the implant into the delivery sheath and allowing the implant to be repositioned and subsequently deployed to another location. 42. The method described in Appendix 42.

[0149] (Appendix 44) and when a suboptimal response or lack of response is observed, removing the implant by withdrawing it through the sheath and selecting another implant having different dimensions to deploy at the target site and reassess the response. A method according to any one of appendices 36 to 43.

[0150] (Appendix 45) a shaft extending between a proximal end and a distal end, the shaft having one or more lumens extending therethrough; an implant comprising a plurality of expandable structures disposed on a distal portion of the shaft in a collapsed configuration, each expandable structure being convertible between the collapsed configuration and an expanded configuration for engaging the arterial wall at a target region within the vasculature, the implant being releasably coupled at or near a proximal end to a locking element disposed at or near the distal end of the shaft; an outer sheath having a proximal end and a distal end, the outer sheath disposed over the shaft, including the distal end at which the expandable structure is disposed, such that the delivery catheter is configured to facilitate deployment of the expandable structure at the target area; a catheter handle disposed at or near the proximal end of the shaft, wherein the outer sheath and / or the shaft are retractable from the catheter handle to facilitate both partially deploying the implant at the target area to allow measurement of a baroreflex response and fully deploying the implant at the target area for long-term treatment; and Equipped with Baroreflex gauge and implant delivery system.

[0151] (Appendix 46) the expanded configuration of the at least one expandable structure has a polygonal or circular cross-section; 46. ​​The system of claim 45.

[0152] (Appendix 47) The lateral dimension of the expanded form is within the range of 20 mm to 60 mm. 47. The system of claim 45 or 46.

[0153] (Appendix 48) The catheter is configured to allow the implant to be partially deployed while the locking element remains coupled to the implant. 48. A baroreflex gauge device according to any one of appendices 45 to 47.

[0154] (Appendix 49) the locking element comprises a locking collar having holes or notches that interface with a plurality of proximal connectors of the implant; 49. A baroreflex gauge device according to any one of appendices 45 to 48.

[0155] (Appendix 50) the plurality of proximal connectors are disposed at proximal ends of a plurality of tethers extending proximally from the implant; 49. The baroreflex gauge device of claim 49.

[0156] (Appendix 51) each of the plurality of proximal connectors includes a widened portion having a round or mushroom shape; 49. The baroreflex gauge device of claim 49.

[0157] (Appendix 52) The implant comprises at least three expandable structures interconnected in series by helically oriented bridges. 52. A baroreflex gauge device according to any one of appendices 45 to 51.

[0158] (Appendix 53) the central expandable structure has a larger lateral dimension than the proximal and distal expandable structures; 53. The baroreflex gauge device of claim 52.

[0159] (Appendix 54) the handle includes an adjustment portion with a slider mechanism for precise and controlled deployment or partial deployment of the implant at the target site within the aortic arch. 54. A baroreflex gauge device according to any one of appendices 45 to 53.

Claims

1. 1. A method for assessing a baroreflex response and / or location of a baroreflex in a patient, comprising: advancing a delivery catheter carrying an expandable structure at a distal portion thereof, the expandable structure being disposed on the delivery catheter in a collapsed configuration to facilitate advancement through the patient's vasculature, the expandable structure being expandable to a plurality of expanded configurations having different transverse dimensions; placing the distal portion of the catheter carrying the implant in the collapsed configuration at a target region within the vasculature; expanding the expandable structure within the target region such that the expandable structure expands to an expanded configuration having a lateral dimension sufficient to engage an arterial wall along the treatment region to stretch at least a portion of the arterial wall along the target region, thereby eliciting a baroreflex response of aortic arch baroreceptors within the target region to reduce blood pressure; monitoring the patient's blood pressure with the expandable structure in the expanded configuration, the expanded configuration having a lateral dimension corresponding to a hypertension treatment implant deployed at the target site; Including, method.

2. each of the plurality of expanded configurations is circular; The method of claim 1.

3. The different lateral dimensions range from 20 mm to 60 mm.

3. The method according to claim 1 or 2.

4. the different lateral dimensions correspond to a plurality of implants for treating hypertension, such that each lateral dimension corresponds to a different implant of the plurality of implants; The method according to any one of claims 1 to 3.

5. the expanded configuration is a first configuration having a first lateral dimension; The method comprises: adjusting the expanded expandable structure to a second configuration having a second lateral dimension; monitoring the patient's blood pressure with the expandable structure in the second expanded configuration; further comprising: The method according to any one of claims 1 to 4.

6. further comprising repeating the steps of adjusting the expandable structure to one or more additional configurations having different lateral dimensions and monitoring blood pressure in each configuration until the monitored blood pressure indicates a desired reduction in blood pressure. The method of claim 5.

7. and wherein monitoring the blood pressure further comprises recording a lateral dimension indicative of a desired reduction in blood pressure. The method according to any one of claims 1 to 6.

8. and further comprising the step of repeatedly adjusting the expandable structure to one or more additional positions along or near the target area and monitoring blood pressure at each configuration to determine a maximum expanded diameter of the target area within the vasculature, above which there is little or no improvement in blood pressure. The method of claim 5.

9. and further comprising the step of repeatedly adjusting the expandable structure to one or more additional positions along or near the target area and monitoring blood pressure at each position to determine a minimum expanded diameter of the target area within the vasculature that will produce a baroreflex response and reduce blood pressure. The method of claim 8.

10. the expanded configuration is at a first position within the target area; The method comprises: repositioning the expandable structure to a second location within or near the target area; monitoring the patient's blood pressure with the expandable structure in the second position; further comprising: The method according to any one of claims 1 to 9.

11. repeating adjusting the expandable structure to one or more additional positions along or near the target area and monitoring blood pressure at each position until the monitored blood pressure indicates a desired reduction in blood pressure. The method of claim 10.

12. and recording the location where the monitored blood pressure indicated the desired reduction in blood pressure for subsequent implantation of a hypertension treatment at the target site. The method of claim 11.

13. wherein the step of positioning the expandable structure includes observing one or more visualization markers positioned on the expandable structure. The method according to any one of claims 1 to 12.

14. the target area is within the aortic arch; The method according to any one of claims 1 to 13.

15. the target region is a cylindrical segment within the aortic arch between the left common carotid artery and the left subclavian artery; 15. The method of claim 14.

16. 1. A method for deploying a hypertension treatment implant in a patient's vasculature, comprising: performing a baroreflex assessment according to the method of claim 1; selecting or customizing an implant and / or a location of the implant based on said baroreflex assessment; deploying the implant at the target site within the vasculature to treat hypertension; Including, method.

17. the step of selecting the implant includes selecting an implant from a plurality of implants having different lateral dimensions, the selected implant having a lateral dimension corresponding to a lateral dimension along which the monitored blood pressure indicates a desired blood pressure reduction.

17. The method of claim 16.

18. selecting a location for the implant includes selecting a location within the vasculature where monitored blood pressure indicates a desired reduction in blood pressure.

18. The method of claim 16 or 17.

19. placing the distal portion of the catheter within the aortic arch includes advancing the delivery catheter over a guidewire positioned within the aortic arch. The method according to any one of claims 16 to 18.

20. the implant comprises two expandable structures connected in series by a plurality of flexible connectors, at least one expandable structure having a lateral dimension corresponding to a lateral dimension along which monitored blood pressure indicates a desired reduction in blood pressure; The method according to any one of claims 16 to 19.

21. the implant comprises three expandable structures connected in series by a plurality of flexible connectors, at least a central expandable structure having a lateral dimension corresponding to a lateral dimension along which monitored blood pressure indicates a desired reduction in blood pressure; The method according to any one of claims 16 to 20.

22. the target area is within the aortic arch; The method according to any one of claims 16 to 21.

23. a shaft extending between a proximal end and a distal end, the shaft having one or more lumens extending therethrough; an expandable structure disposed on the distal portion of the shaft in a collapsed configuration, the expandable structure being convertible between the collapsed configuration and an expanded configuration for engaging the arterial wall at the target region within the vasculature, the expandable structure being adjustable to a plurality of expanded configurations each having a different transverse dimension; a retractable outer sheath having a proximal end and a distal end, the outer sheath disposed over the shaft, including the distal end at which the expandable structure is disposed, such that the delivery catheter is configured to facilitate deployment of the expandable structure at the target area; and a catheter handle disposed at or near the proximal end of the shaft, the outer sheath being retractable from the catheter handle to facilitate deployment of the expandable structure at the target area, the catheter handle further comprising an adjustment control for adjusting the expandable structure between any of the plurality of expanded configurations; Equipped with Baroreflex gauge and / or mapping devices.

24. the expandable structure comprises a stent-like structure having a plurality of struts to allow lateral blood flow through the stent-like structure; 24. A baroreflex gauge device according to claim 23.

25. the plurality of struts comprising visualization markers to facilitate placement of the expandable structure at the target area.

25. A baroreflex gauge device according to claim 24.

26. the plurality of struts are configured to have a flattened central region in the expanded configuration for engaging the arterial wall, the flattened central region having a length of at least 10 mm; 26. A baroreflex gauge device according to claim 24 or 25.

27. the expandable structure is configured for deployment within the aortic arch. A baroreflex gauge device according to any one of claims 23 to 26.

28. The lateral dimensions of the plurality of expanded configurations range from 20 to 60 mm. A baroreflex gauge device according to any one of claims 23 to 27.

29. The adjustment unit includes a slider mechanism. A baroreflex gauge device according to any one of claims 23 to 28.

30. the guide catheter device is configured such that moving the slider in one direction increases the transverse dimension of the expandable structure in a stepwise manner; 30. A baroreflex gauge device according to claim 29.

31. the catheter handle further comprising one or more fine adjustment controls by which the transverse dimensions of the expandable structure can be further adjusted in smaller increments; 31. A baroreflex gauge device according to claim 29 or 30.

32. the catheter handle further comprising a locking mechanism for locking the lateral dimension of the expandable structure during monitoring. A baroreflex gauge device according to any one of claims 29 to 31.

33. the guide catheter device is configured to include a rack and pinion mechanism that allows for adjustment of a lateral dimension of the expandable structure without substantially moving a midpoint of the expandable structure within the vasculature; A baroreflex gauge device according to any one of claims 23 to 32.

34. the guide catheter device is configured to include a worm gear that allows for adjustment of a lateral dimension of the expandable structure without substantially moving a midpoint of the expandable structure within the vasculature; A baroreflex gauge device according to any one of claims 23 to 33.

35. 24. A baroreflex gauge catheter device according to claim 23; a sphygmomanometer capable of monitoring the patient's blood pressure with the expandable structure in the expanded configuration at the target area; and Equipped with Baroreflex assessment system.

36. 1. A method for assessing a baroreflex response and / or location of a baroreflex in a patient, comprising: advancing a delivery catheter carrying an implant at a distal portion thereof, the implant having a plurality of expandable structures interconnected by a plurality of bridges, the implant disposed on the delivery catheter in a compressed configuration to facilitate advancement through the patient's vasculature, the implant being expandable to an expanded configuration for engaging and stretching an arterial wall; placing the distal portion of the catheter carrying the implant in the collapsed configuration at a target region within the vasculature; partially deploying the implant such that the at least one expandable structure expands within the target area to engage the arterial wall along the treatment area such that the at least one expandable structure stretches at least a portion of the arterial wall along the target area, thereby eliciting a baroreflex response of aortic arch baroreceptors in the target area to reduce blood pressure; monitoring the patient's blood pressure with the expandable structure in the expanded configuration, the expanded configuration having lateral dimensions corresponding to a hypertension treatment implant deployed at the target site; Including, method.

37. the expanded configuration of the at least one expandable structure is polygonal or circular; 37. The method of claim 36.

38. The lateral dimension of the expanded configuration is in the range of 20 to 60 mm.

38. The method of claim 36 or 37.

39. and when an adequate reduction in blood pressure is observed, fully deploying the implant at the target site while the at least one expandable structure remains expanded at the target site.

37. The method of claim 36.

40. the step of fully deploying the implant includes releasing one or more proximal connectors of the implant from a locking element of the delivery catheter.

40. The method of claim 39.

41. the step of fully deploying the implant includes advancing the locking element distally of the outer delivery sheath such that the one or more proximal connectors expand outward, thereby releasing the one or more proximal connectors of the implant from the locking element of the delivery catheter.

41. The method of claim 40.

42. and when a suboptimal response is observed, further comprising the step of moving the implant to another location and reassessing the baroreflex response. The method according to any one of claims 36 to 41.

43. the step of moving the implant to another location includes retracting a locking element of the catheter attached to the implant proximally into the delivery sheath, thereby retracting the implant into the delivery sheath and allowing the implant to be repositioned and subsequently deployed to another location.

43. The method of claim 42.

44. and when a suboptimal response or lack of response is observed, removing the implant by withdrawing it through the sheath and selecting another implant having different dimensions to deploy at the target site and reassess the response. The method according to any one of claims 36 to 43.

45. a shaft extending between a proximal end and a distal end, the shaft having one or more lumens extending therethrough; an implant comprising a plurality of expandable structures disposed on a distal portion of the shaft in a collapsed configuration, each expandable structure being convertible between the collapsed configuration and an expanded configuration for engaging the arterial wall at a target region within the vasculature, the implant being releasably coupled at or near a proximal end to a locking element disposed at or near the distal end of the shaft; an outer sheath having a proximal end and a distal end, the outer sheath disposed over the shaft, including the distal end at which the expandable structure is disposed, such that the delivery catheter is configured to facilitate deployment of the expandable structure at the target area; a catheter handle disposed at or near the proximal end of the shaft, wherein the outer sheath and / or the shaft are retractable from the catheter handle to facilitate both partially deploying the implant at the target area to allow measurement of a baroreflex response and fully deploying the implant at the target area for long-term treatment; and Equipped with Baroreflex gauge and implant delivery system.

46. the expanded configuration of the at least one expandable structure has a polygonal or circular cross-section; 46. ​​The system of claim 45.

47. The lateral dimension of the expanded configuration is in the range of 20 mm to 60 mm.

47. A system according to claim 45 or 46.

48. The catheter is configured to allow the implant to be partially deployed while the locking element remains coupled to the implant. A baroreflex gauge device according to any one of claims 45 to 47.

49. the locking element comprises a locking collar having holes or notches that interface with a plurality of proximal connectors of the implant; A baroreflex gauge device according to any one of claims 45 to 48.

50. the plurality of proximal connectors are disposed at proximal ends of a plurality of tethers extending proximally from the implant; 50. A baroreflex gauge device as described in claim 49.

51. each of the plurality of proximal connectors includes a widened portion having a round or mushroom shape; 50. A baroreflex gauge device as described in claim 49.

52. The implant comprises at least three expandable structures interconnected in series by helically oriented bridges. A baroreflex gauge device according to any one of claims 45 to 51.

53. the central expandable structure has a larger lateral dimension than the proximal and distal expandable structures; 53. A baroreflex gauge device as described in claim 52.

54. the handle includes an adjustment portion with a slider mechanism for precise and controlled deployment or partial deployment of the implant at the target site within the aortic arch. A baroreflex gauge device according to any one of claims 45 to 53.

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