EP4665279A2 - Baroreflex gauge and mapping device and methods of use - Google Patents

Abstract

Methods of gauge a baroreflex response and baroreflex gauge devices and system are provided herein. Such methods and devices position and expand an expandable structure at a target location within the patient's vasculature, preferably the aortic arch, to gauge the baroreflex response for one or more lateral dimensions of the expandable structure. The baroreflex gauge device can optionally expand the structure to multiple expanded configurations while monitoring blood pressure of the patient to determine an optimal dimension for the baroreflex response. These gauge devices and methods aid in assessing suitability of patients for therapy and in selecting or customizing an implant for placement in the vasculature for long-term treatment of hypertension. The baroreflex gauge device can further be integrated within the implant delivery system such that partial deployment allows gauging of response and full deployment allows for long-term treatment.

Description

BAROREFLEX GAUGE AND MAPPING DEVICE AND METHODS OF USE

CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] The present application claims priority to U.S. Provisional Patent Application Nos. 63/485,849 filed February 17, 2023 and 63/594,919 filed October 31, 2023; the full disclosures which are incorporated herein by reference in their entirety for all purposes.

[0002] This application is generally related to commonly-owned applications: PCT Patent Appln. No. PCT/US2023/020612 filed May 1, 2023, entitled “Aortic Arch Baroreceptor Implants for Treatment of Hypertension,” and PCT Patent Appln. No. PCT/US2023/020608 filed May 1, 2023, entitled “Delivery Catheter and Methods of Delivery for Aortic Arch Baroreceptor Hypertension Implants” the contents which are incorporated herein by reference in their entirety for all purposes. This application is also related to commonly-owned applications: U.S. Provisional Appln. No. 63/594,915 filed October 31, 2023, entitled “Delivery Catheter and Methods of Delivery for Aortic Arch Baroreceptor Hypertension Implants,” and U.S. Provisional Appln. No. 63/594,903 filed October 31, 2023, entitled “Aortic Arch Baroreceptor Implants for Treatment of Hypertension,” the contents which are also incorporated herein by reference in their entirety for all purposes.

FIELD OF THE INVENTION

[0003] In one aspect, the invention pertains to methods of assessing baroreceptor response and location, baroreflex gauge and mapping catheter devices, as well as hypertension implant delivery methods and devices.

BACKGROUND OF THE INVENTION

[0004] Hypertension affects one of every two adults in the United States. Yet only 24% of patients have their blood pressure adequately controlled. Hypertension is the leading preventable cause of heart attack, stroke and death. However, a 10 mm Hg drop in blood pressure lowers this cardiovascular risk by 20%.

[0005] Pharmacologic therapy has been the mainstay of hypertension treatment for decades, despite the documented poor medical compliance of patients to their antihypertensive medical regimens. In 2004, the landmark trial for a catheter-based medical device (i.e., Symplicity 1) first demonstrated the blood pressure lowering effect of renal denervation by a radiofrequency ablation catheter. Findings from additional clinical trials of renal denervation with radiofrequency and ultrasound energy (i.e., the SPYRAL and RADIANCE trials, respectively) have confirmed these findings, albeit with more modest blood pressure lowering results on the order of 5-10 mm Hg drops in ambulatory recorded systolic blood pressure.

[0006] An endovascular implant developed by Vascular Dynamics for hypertension relied on a stent-like device inserted into the carotid artery that lowered blood pressure by stretching the artery wall from the inside and augmenting the carotid baroreflex. In a 2017 study, this carotid baroreflex modulating device lowered ambulatory recorded systolic blood pressure considerably, over twice what had been reported in the renal denervation trials. While clinical results initially appeared promising, with several patients reporting dramatic blood pressure lowerage that persisted two to three years, clinical outcomes were mixed as some patients suffered transient ischemic attacks (TIA), which hindered further trials and subsequent development.

[0007] Another challenge arose in regard to deploying the device in the carotid sinus, which was the primary target of the device. Since the carotid sinus carries blood to the brain, any difficulties encountered in this area, for example trauma to arterial tissues during deployment, subsequent dislodgement of the device and/or accumulation of plaques in the region due to the device or trauma, may contribute to TIA or strokes, resulting in adverse or fatal patient outcomes. For clinicians that lack experience with this sensitive region, for example, placing carotid stents, performing procedures in this area may present unnecessary risks to the patient.

[0008] Thus, there is a continuing need for hypertension treatment devices and methods that provide the clinical benefits seen in the baroreflex response, yet avoid the considerable drawbacks associated with conventional approaches described above. There is further need for such devices that allow for improved ease and consistency of implantation in order to avoid the noted adverse effects, allow for implantation for a wide variety of clinicians and more reliably provide positive patient outcomes to reduce hypertension long term.

[0009] Although there have been continuing developments of implants for hypertension treatment, there remains uncertainty and variability as to patient outcomes when utilizing such implants. Therefore, there is further need for further understanding of baroreflex responses to assess viability of treatment approaches and to further improve hypertension treatments.

BRIEF SUMMARY OF THE INVENTION

[0010] The invention relates to methods of assessing the baroreflex response in a patient and a baroreflex gauge device to perform such assessments.

[0011] In one aspect, the invention pertains to a method of assessing a baroreflex response in a patient. The method can include steps of: advancing a delivery catheter carrying an expandable structure in a distal portion thereof, the expandable structure being disposed in a collapsed configuration on the delivery catheter to facilitate advancement through the vasculature of the patient and being expandable to multiple expanded configurations of differing lateral dimensions; positioning the distal portion of the catheter carrying the implant in the collapsed configuration at a target region in the vasculature; expanding the expandable structure within the target region so that the expandable structure expands to an expanded configuration having a lateral dimension sufficient to engage an arterial wall along the treatment region so as to stretch at least a portion of the arterial wall along the target region, thereby triggering a baroreflex response of aortic arch baroreceptors within the target region to reduce blood pressure; and monitoring a blood pressure of the patient while the expandable structure is in the expanded configuration, wherein the expanded configuration has a lateral dimension corresponding to an implant for treating hypertension to be deployed at the target location. In some embodiments, the multiple expanded configurations of differing lateral dimensions are each round in cross-section. In some embodiments, positioning the expandable structure entails observing one or more visualization markers disposed on the expandable structure. The differing lateral dimension can range from 20-100 mm, typically between 20-60 mm. Preferably, the differing lateral dimensions correspond to lateral dimensions of multiple implants of differing sizes to aid in selection of the respective implant to optimize the baroreflex response. Typically, the target region is within the aortic arch, in particular the target region is a cylindrical segment between the left common carotid artery and the left subclavian artery. Utilizing an adjustable expandable structure that is adjustable between multiple expanded configurations of differing lateral dimensions is advantageous as facilitates gauging a baroreflex response at multiple levels of stretch without requiring removal and replacement of structures of differing sizes, which improves ease of use and reduces the length and risks of the procedure. This approach is further advantageous as it allows these differing sizes to be effected at precisely the same location, without requiring axial movement of the catheter between adjustments, which allows for more accurate assessment of the location of the baroreceptors to allow precise mapping of the target location for placement of the subsequent implant.

[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 blood pressure of the patient while the expandable structure is in the second expanded configuration. The method can further entail repeating adjusting the expandable structure to one or more additional configuration of differing lateral dimension and monitoring the blood pressure at each configuration until the monitored blood pressure indicates a desired drop in blood pressure. The clinician records the lateral dimension at which the monitoring the blood pressure exhibits the desired drop in blood pressure. In some embodiments, the methods include repeating adjusting the expandable structure to one or more additional locations along or near the target region and monitoring the blood pressure at each configuration to determine a maximum stretched diameter of the target region in the vasculature beyond which there is little or no further improvement in blood pressure. In some embodiments, the methods further include repeating adjusting the expandable structure to one or more additional locations along or near the target region and monitoring the blood pressure at each configuration to determine a minimum stretched diameter of the target region in the vasculature needed to provide the baroreflex response of reducing blood pressure.

[0013] In some embodiments, the expanded configuration is at a first position in the target region, and the method further includes repositioning the expandable structure to a second location within or near the target region; and monitoring the blood pressure of the patient while the expandable structure is in the second position. The method can further entail repeating adjusting the expandable structure to one or more additional locations along or near the target region and monitoring the blood pressure at each configuration until the monitored blood pressure indicates a desired drop in blood pressure. The clinician records the location at which the monitored blood pressure indicates a desired drop in blood pressure for subsequent implantation of the hypertension treatment at the location.

[0014] In another aspect, the invention pertains to a method of deploying a hypertension treatment implant in a vasculature of a patient. The method can include steps of: performing a baroreflex assessment as described above; selecting or customizing the implant and/or selecting the implant location based on the baroreflex assessment; and deploying the implant at the target location in the vasculature to treat hypertension. In some embodiments, selecting the implant comprises selecting an implant from a plurality of implants having differing lateral dimensions, the selected implant having a lateral dimension corresponding to the lateral dimension at which the monitored blood pressure exhibits a desired drop in blood pressure. In some embodiments, customizing the implant comprises adjusting a dimension of the implant and locking the implant at the dimension, which corresponds to an optimal dimension for the baroreflex response. In some embodiments, the implant includes two expandable structures connected serially by flexible connectors, where at least one expandable structure has a lateral dimension corresponding to the lateral dimension at which monitored blood pressure exhibits a desired drop in blood pressure. In some embodiments, the implant includes three expandable structures connected serially by a flexible connectors, where at least the middle expandable structure expandable structure has the lateral dimension corresponding to the lateral dimension at which the monitored blood pressure exhibits a desired drop in blood pressure. In some embodiments, the method includes partially deploying an implant having multiple structures (e.g., three structures) so as to fully expand at least one structure, such as the middle structure, at the target region so as to assess a physiological response (e.g., baroreflex response) before fully deploying the entire implant. In some embodiments, the proximal most expandable structure is only partly deployed or undeployed during gauging. Such an implant can be defined by multiple expandable structures (e.g., expandable ring) interconnected by helically oriented bridges to allow the implant to accommodate the curvature of the aortic arch. In some embodiments, the at least one structure has a greater lateral dimension than the other expandable structures to stretch the target region to produce the baroreflex response. In some embodiments, the middle expandable structure has a lateral dimension 1.3 to 1.5 times that of the proximal and distal structures.

[0015] In yet another aspect, the invention pertains to a baroreflex gauge catheter device. Such devices can include: a shaft extending between a proximal end and a distal end, the shaft having one or more lumens; an expandable structure disposed on a distal portion of the shaft in a collapsed configuration, where the expandable structure is convertible between the collapsed configuration and an expanded configuration for engaging the arterial walls at a target region within the vasculature, where the expandable structure is adjustable to multiple expanded configurations each having a differing lateral dimension; a retractable outer sheath having a proximal end and a distal end and being disposed over the shaft including the distal end portion having the expandable structure disposed thereon such that the delivery catheter is configured to facilitate deployment of the expandable structures at the target region; and a catheter handle disposed at or near the proximal end of the shaft, where the outer sheath is retractable from the catheter handle to facilitate deployment of the expandable structure at the target region, where the catheter handle further includes an adjuster for adjusting the expandable structure between any of the expanded configurations. The baroreflex gauge device can further be included in a system that includes blood pressure monitor. Typically, the device is manually adjusted by the clinician, however in some embodiments, all or part of the operation can be automated based on a monitored blood pressure so as to optimize the baroreflex gauging procedure.

[0016] In some embodiments, the expandable structure includes multiple struts configured so as to allow lateral blood flow therethrough to ensure accurate blood pressure monitoring and better simulate the implant. The struts can include visualization markers to facilitate positioning of the expandable structure at the target region. Preferably, the expandable structure of the gauge is configured for deployment within the aortic arch, in particular, a 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 from 20-100 mm, preferably within 20-60 mm. In some embodiments, the expandable structure includes two wires having spine portions that articulate laterally in their mid segment to facilitate bending and stretch the arterial wall in a line. In some embodiments, the structure can be a single wire that articulates in a manner to stretch at least a portion of the arterial wall.

[0017] In some embodiments, the baroreflex gauge catheter handle controls include an adjuster that incrementally adjusts the lateral dimension of the expandable structure. The adjuster can include a slider and optionally one or more precision-controls, such as a rotary wheel or dial that adjusts the structure by smaller increments. In some embodiments, the catheter handle further includes a locking mechanism so as to lock the lateral dimension of the expandable structure during monitoring. In some embodiments, the guide catheter device is configured with a rack-and-pinion mechanism by which the lateral dimensions of the expandable structure can be adjusted without substantially moving a mid-point of the expandable structure in the vasculature. The guide catheter device is configured with a worm gear by which the lateral dimensions of the expandable structure can be adjusted without substantially moving a mid-point of the expandable structure in 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 location, after which the physiological response (e.g., blood pressure) can be monitored to assess the effect 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 location. In some embodiments, the rest of the implant is deployed and released from the delivery catheter without otherwise altering the portion already deployed, from which the response was gauged. If the response is sub-optimal or absent entirely, then the implant can be repositioned or retracted back into the delivery catheter and deployed at another location for further gauging and assessment. If a response is never obtained, the implant can be retracted back into the delivery sheath and removed. In some instances, another size of implant can be selected and deployed in the same manner for further gauging and assessment. In such embodiments, the implant can be releasably coupled to the delivery catheter by a lock element. In some embodiments, the lock element is releasably coupled with one or more proximal connectors on the implant. In some embodiments, the lock element is a lock collar having holes or cut outs that engage with multiple connectors. The connectors can be at proximal end of the implant or disposed at proximal ends of tethers extending proximally from the implant. The tethers allow at least a middle portion of the implant to fully deploy at the target location for gauging the baroreflex response, while the proximal portion remains coupled with the delivery catheter to allow subsequent repositioning or removal. In some embodiments, the delivery catheter can further include any of the fine-tuned adjustment features described herein to provide precise positioning of the implant at the target location in the aortic arch.

BRIEF DESCRIPTION OF THE DRAWINGS

[0019] FIG. 1 A shows an exemplary baroreflex gauge device with distal expandable basket and FIG. IB shows a detail view of the expandable structure, in accordance with some embodiments.

[0020] FIG. 2 shows a cross-sectional view (omitting the handle body and sliders) that further illustrate the means by which expandable structure 10 is expanded by actuation of the shafts.

[0021] FIGS. 3 A-3B show various incremental adjustment mechanisms for a baroreflex gauge device, in accordance with some embodiments.

[0022] FIGS. 4A-4C show alternative designs of the baroreflex gauge device, in accordance with some embodiments.

[0023] FIGS. 4C-1 and 4C-2 shows an incremental adjustment mechanism for a baroreflex gauge device, in accordance with some embodiments.

[0024] FIGS. 5A-1 through 5A-3 show various views of an alternative design of expandable member for a baroreflex gauge device, in accordance with some embodiments.

[0025] FIGS. 5B-1 through 5B-3 show various views of an alternative design of expandable member for a baroreflex gauge device, in accordance with some embodiments.

[0026] FIGS. 5C-1 and 5C-6 show various aspects illustrating the means by which an expandable structure stretches the arterial wall, in accordance with some embodiments.

[0027] FIGS. 5D-1 and 5D-6 show various aspects illustrating the means by which an expandable structure having a substantially circular cross-section stretches the arterial wall, in accordance with some embodiments.

[0028] FIG. 6 shows an exemplary baroreflex gauge device deployed along the target region in the aortic arch of a patient for assessment of baroreflex, in accordance with some embodiments.

[0029] FIG. 7A shows delivery of an exemplary implant for hypertension treatment, in accordance with some embodiments.

[0030] FIG. 7B shows an exemplary implant for hypertension treatment placed in the aortic arch, in accordance with some embodiments. [0031] FIG. 7C shows another exemplary implant for hypertension treatment placed in the aortic arch, in accordance with some embodiments.

[0032] FIG. 8A shows an illustration of a conventional view of the anatomy of the vasculature and baroreceptors and the carotid baroreceptor location targeted by conventional devices.

[0033] FIG. 8B shows details of an exemplary type of baroreceptor called PEIZO1.

[0034] FIG. 8C shows the central nervous system response to baroreflex stimulation in regulating blood pressure.

[0035] FIG. 8D shows the anatomy of the vasculature of the aortic arch.

[0036] FIG. 8E shows the embryonic anatomy that later develops into the aortic arch.

[0037] FIG. 8F shows the anatomy of the aortic arch illustrating additional details as to a target region, in accordance with aspects of the invention.

[0038] FIG. 8G shows histology of the arterial tissue within the targeted region.

[0039] FIG. 8H shows a fluorescence staining image from an animal study illustrating the distribution of baroreceptors in the target region.

[0040] FIG. 81 shows a fluorescence staining image illustrating the location of baroreceptors within the arterial wall of the aortic lumen.

[0041] FIGS. 9A-9B illustrate results from a prior animal study showing heightened sensitivity of the baroreceptors in the aorta as compared to baroreceptors in the carotid.

[0042] FIGS. 10A-10D show an exemplary implant having two expandable structures interconnected by flexible connectors, the structures defined by four frames and having a square cross section, in accordance with some embodiments,

[0043] FIGS. 10E-10F shows an exemplary implant having three expandable structures in accordance with some embodiments, FIG. 10E showing an embodiment having three structures of the same lateral dimension and FIG 10F showing an embodiment where the middle structure has an increased lateral dimension.

[0044] FIGS. 11 A-l IB shows an alternative embodiment of the implant, where the expandable structures are defined by three frames and having a triangular cross-section. [0045] FIG. 12A-12B shows an alternative embodiment of the implant, where the expandable structures are defined by five frames and having a hexagonal cross-section.

[0046] FIG. 13-14 show various calculated dimensions of the aorta (A,B,C,D,E) that were developed in a patient study to determine appropriate sizing of the implant structure for deployment in the aorta.

[0047] FIG. 15A-15D show the mechanism of action by which an appropriately sized structure engages and stretches a substantially round (e.g., 25 mm diameter) aortic arterial wall to achieve sufficient stretch to induce baroreflex, in accordance with embodiments of the invention.

[0048] FIG. 16 illustrates a target region of the aorta, which is the entire aortic segment between the LCCA and LSA, in accordance with some embodiments.

[0049] FIG. 17 illustrates a delivery catheter configured to deliver and deploy the implant in the aortic arch, in accordance with some embodiments.

[0050] FIGS. 18-23 illustrate delivery of an exemplary implant to the aortic arch along the target region with the delivery catheter, in accordance with some embodiments.

[0051] FIGS. 24-25 illustrates methods of treating hypertension with an implant, in accordance with some embodiments.

[0052] FIGS. 26A-26B show tissue histology images showing staining of the baroreceptors in the target region in the aortic arch.

[0053] FIGS. 27A-27F illustrates a tethered articulated implant and various steps of deployment, in accordance with some embodiments.

[0054] FIGS. 28A-28B illustrate an exemplary aortic arch morphology and deployment of a tetheter articulated implant therein, in accordance with some embodiments.

[0055] FIG. 29A illustrates a two-ring implant, in accordance with some embodiments.

[0056] FIG. 29B illustrates a three-ring implant, in accordance with some embodiments.

[0057] FIGS. 30A-30B illustrate a multi-ring tethered implant, in accordance with some embodiments.

[0058] FIGS. 31A-31B illustrate alternative implant structures, in accordance with some embodiments. [0059] FIGS. 32A-32E illustrate various views of an exemplary 8-cell implant structure, in accordance with some embodiments.

[0060] FIGS. 33 A-33E illustrate various views of an exemplary 4-cell implant structure, in accordance with some embodiments.

[0061] FIGS. 34A-34C depicts various tether configurations and interfacing of tethers within a retention collar, in accordance with some embodiments.

[0062] FIGS. 35A-35B depicts tether configurations for 8-cell and 4-cell implant structures, in accordance with some embodiments.

[0063] FIG. 36 depicts various views of a retention collar for retaining the implant structure before full deployment, in accordance with some embodiments.

[0064] FIG. 37 depicts a constrained implant releasably connected by tethers to a collar of the delivery catheter, in accordance with some embodiments.

[0065] FIGS. 38A-38B depict a section and detail views of implant tethers interfaced with the retention collar, in accordance with some embodiments.

[0066] FIGS. 39A-39D and 40A-40D depicts cross-sectional views of exemplary implants that can be used for baroreflex gauging and hypertension treatment, in accordance with some embodiments.

DETAILED DESCRIPTION OF THE INVENTION

[0067] In one aspect, the invention pertains to methods of assessing a baroreflex response in a patient and an associated baroreflex gauge catheter device. In some embodiments, the baroreflex gauge catheter devices are adjustable between multiple differing lateral dimensions. In some embodiments, the baroreflex gauge has a handle with incremental adjustment control that allows the clinician to adjust the expandable structure between differing sizes or lateral dimensions. In some embodiments, the methods of gauging the baroreflex response include incrementally adjusting the expandable structure and observing a blood pressure response in order to find an optimal, a maximum, or a maximum/minimum stretch of the vasculature that provides the baroreflex response. In some embodiments, the baroreflex gauge has an expandable structure having a substantially circular cross-section to facilitate stretching the vasculature in the target region while avoiding points of heightened stress/strain to inhibit dissection of the vasculature during gauging of the baroreflex response. [0068] FIG. 1 A shows an exemplary baroreflex gauge catheter device for deployment in vasculature of the patient to assess the patient's baroreflex response. The baroreflex gauge catheter device has a distal expandable structure that transitions between a collapsed configuration for advancement through the vasculature and an expanded configuration to engage and stretch an arterial wall of the vasculature sufficiently to invoke the baroreflex response. In this embodiment, the expandable structure is adjustable to varying dimensions so as to assess the extent of the baroreflex gauge, if any, for each dimension. Typically, the expandable structure is incrementally foreshortened so as to incrementally increase the lateral dimension (e.g., diameter) of the expandable structure. The blood pressure of the patient after deployment of the expandable structure can be monitored to assess the baroreflex response upon each adjustment. Within a short period of time (e.g., less than 5 minutes, less than a minute), the presence or extent of the baroreflex response can be determined. Studies have shown that the baroreflex response is almost immediate (e.g., within seconds) if the baroreceptors are stretched significantly. This device and methodology allows the clinician to identify/confirm that a patient is a candidate for hypertension implants, and/or allows the clinician to better assess the optimal placement for a hypertension implant and/or optimal dimensions of the hypertension implant to be placed in the patient. FIGS. 2-3B shows a cross sectional view and additional details of adjustment mechanisms for a baroreflex gauge device. FIGS. 4A-4C show alternative designs of a baroreflex gauge device and adjustment mechanisms. In this embodiment, the expandable structure is a braided mesh such that when expanded the cross-section is substantially circular. FIGS. 5A-5D show alternative expandable structure designs and the mechanism of action by which such structures stretch the arterial wall. In these embodiments, the expandable structure has a stent-like design having a substantially circular cross-section. FIG. 6 shows a view of a baroreflex gauge device deployed in a patient's vasculature. FIGS. 7A-7C show delivery and deployment of exemplary hypertension implants in the aortic arch of a patient, facilitated by a baroreflex gauge device. FIGS. 8A-8I and 9A-9B illustrate details of the anatomy and results of studies that demonstrate the physiological mechanisms of the baroreflex response.

I. Physiological Baroreflex Response

[0069] In order to understand the physiological responses of the baroreflex response, it is helpful to understand the interplay between the nervous system within the patient’s anatomy. Aspects of the baroreceptor locations with the vasculature, the baroreceptor cells, and the interplay of the baroreceptors with the central nervous system, as shown in FIGS. 8A-8C. [0070] Blood pressure sensation occurs at several hotspots 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 through a fine nerve branch termed the aortic depressor nerve, while glossopharyngeal neurons access the carotid sinus through the carotid sinus nerve (see FIG. 8A). The aortic depressor and carotid sinus nerves consist of co-fasciculating fibers, including both mechanosensory and chemosensory afferents. The mechanosensory nerve fibers mediate the baroreflex. The terminals of these mechanosensory nerve fibers have specialized nerve endings called baroreceptors that penetrate the artery wall. Baroreceptors are stretch receptors, which do not measure pressure directly, but rather sense stretch of the artery. Blood pressure pulses with each heart beat radially stretch the artery wall, and this arterial distention in turn activates mechanosensitive neurons. Baroreceptor neurons are long aorta-to-brain sensory neurons that transmit inputs directly to the brainstem. Activation of these baroreceptor neurons decreases sympathetic and increases parasympathetic output from the brainstem ultimately lowering blood pressure and heart rate (termed the baroreflex).

[0071] At a molecular level, baroreceptors are actually complex protein structures that form ion channels at the sensory terminals of baroreceptor nerve fibers (see FIG. 8B). Stimulation of the ion channel results in cation influx into the neuron and depolarization with signal transmission along the nerve cell. The baroreceptor nerve terminals are located in the outer wall of the artery between the media and adventitia (see FIG. 81).

[0072] Baroreceptor neurons are long artery -to-brain sensory neurons that transmit inputs directly to the brainstem. The aortic arch baroreceptor nerve signal emanates from the artery wall, travels through the aortic depressor nerve, then via the superior laryngeal nerve to the vagus nerve, and from there, to the brainstem (see FIGS. 8A and 8B). The brainstem modulates this signal reflexively decreasing sympathetic and increasing parasympathetic nerve output to the circulation. Blood pressure and heart rate fall. This cascade of events is termed the baroreflex.

[0073] Early animal studies demonstrated that this response was associated with stretching of the arterial walls, which occurs naturally at high blood pressures. Later animal studies demonstrated that the baroreflex response could be transitory or persistent depending upon whether the arterial receptor stimulation was static or pulsatile, respectively. Static stimulus resulted in a systemic blood pressure drop but then normalized a few minutes later, whereas a non-static, pulsatile stimulus (e.g., similar to natural pulsatile blood flow) showed that the systemic blood pressure drop was sustained.

[0074] Since the 1960s, modulation of the baroreflex — specifically the carotid baroreflex — has been the primary target of device-based therapy for difficult to control hypertension. The first efforts involved pacemaker-type devices: electrodes placed around the carotid sinus nerve connected via wires to an implantable stimulator. Stimulation of this nerve — which innervates the carotid baroreceptor — circumvents the stimulus within the artery and can lower blood pressure through the carotid baroreflex arc. This technology continues in human clinical trials. A similar type device for the aortic arch baroreceptor — or more precisely, the aortic depressor nerve — has been used successfully in a goat experimental model to lower blood pressure. Still, pacemaker-type implants are unlikely to be the device-based solution for resistant hypertension due to their obvious drawbacks — for one, patients would prefer not to have a generator surgically inserted into their chest. To overcome this limitation, Vascular Dynamics developed a stent-like endovascular implant that stretches the carotid artery wall from the inside and amplifies the carotid baroreflex signal. This device has a non-articulated, monomorphic design configured for a straight segment of the proximal internal carotid artery. In early clinical trials, the device was successful at lowering blood pressure in a resistant hypertension population but at the risk of a small number of cerebral transient ischemic attacks (TIA). There are various drawbacks associated with this approach that may contribute to the increased risk of stroke and TIAs.

[0075] The present invention seeks to optimize the utility of such implants by assessing the baroreflex response of individual patients before deployment of the implant. The baroreflex gauge is advantageous as this assessment provides additional insight as to a particular patient’s baroreflex response for any of: confirming patient suitability for hypertension implant; determining an optimal position for deployment of the implant; and determining an optimum type and/or dimension of the hypertension implant for a given patient. By use of an appropriately placed and sized implant, made possible by an assessment of the baroreflex response as described herein, the implant induces an improved baroreflex response within the aortic arch long-term.

[0076] In an exemplary embodiment, the invention pertains to a baroreflex gauge to assess a baroreflex response to facilitate subsequent deployment of an implant having one or more expandable structures configured to stretch the arterial walls along a target region of the aorta, in particular the aortic arch. In some embodiments, the gauge is configured to engage a target region of the aortic arch, including an inner curvature, opposite the left subclavian artery. This target region can be defined as a cylindrical segment of the aortic arch between the LCCA and the LSA. It is theorized that this portion of the aortic arch is particularly rich in baroreflex receptors and that these receptors have increased sensitivity, as compared to baroreceptors in various other regions, such as the carotid sinus. Since this region of the aortic arch is believed to provide a heightened response, the implant can achieve more consistent, reliable reductions in blood pressure. Further, implantation in this area avoids the drawbacks associated with delivering and implanting at the sensitive area of the carotid sinus, which may increase the risk of TIAs and strokes. Thus, the implant described herein provides a more robust baroreflex response to reduce blood pressure, improves ease of delivery and implantation, and is believed to reduce the risk of adverse events.

[0077] Early animal studies of differing baroreceptor responses have identified anatomic “hotspots” of baroreceptors at various locations in the vasculature, including a narrow cylindrical strip that extends circumferentially around the aortic arch between the takeoffs of the left common carotid and left subclavian arteries (this originates from the left embryonic 4^th pharyngeal arch artery as can be seen in FIGS. 8D and 8E). This region is shown in the fluorescence staining image of FIG. 8H, which shows the baroreceptors stained in red. This area rich in baroreceptors can be defined as a cylindrical segment of the aortic arch between the LCCA and the LSA, shown as target T in FIG. 8D.

[0078] These “hotspots” of baroreceptors originate from the embryonic pharyngeal arch arteries, shown in FIG. 8E. The third pharyngeal arch arteries develop into symmetric structures, the right and left carotid arteries. By contrast, the fourth pharyngeal arch artery on the right (R4PA) becomes the proximal right subclavian artery while the left fourth pharyngeal arch artery (L4PA) develops into the relatively narrow cylindrical strip B of the aortic arch noted in FIG. 8F. This strip has distinct features as compared to other regions in the aortic arch.

[0079] This strip of the aortic arch is histologically distinct from other areas as it has fewer smooth muscle cells and increased elastic lamellae. FIG. 8G shows in the left column, histologic sections through aortic arch segment B, indicating fewer smooth muscle cells and increased elastic lamella as compared to aortic section C in FIG. 8F, shown in the right column. It is in this region B that the more commonly known aortic arch baroreceptors are located (as indicated in FIG. 8A). However, various animal and human studies have shown there is actually a unique localized distribution of baroreceptors in this region that extends along the band B that wrap the aortic arch, as shown in FIG. 8H. Additionally, the baroreceptors of the aortic lumen are located on an outer layer of the arterial wall within the aorta, as shown in the fluorescence image of FIG. 81, which shows the baroreceptors nerve fibers stained in pink.

[0080] There are very few human reports localizing the aortic arch baroreceptors. One early investigational study indicated baroreceptor nerves wrap the aorta at the original of the left subclavian artery, and the same author later indicated they may extend about the aorta from the brachiocephalic artery to the ligamentum arteriosum. Some early studies have shown that the baroreceptors are found along this region of the aortic arch extending 40% of the circumference, although some baroreceptors may extend outside of this region. Due in part to the histology of this region noted above, it is believed that the baroreceptors behave differently than baroreceptors in other regions, including the carotid artery. At least one animal study demonstrated that the pressure threshold to stimulate action potential was lower in aortic baroreceptors than carotid baroreceptors, see FIGS. 9 A. The animal study further suggested that a uniaxial stretch of 20% induced a marked increase in cytosolic calcium fluorescence in the aortic arch baroreceptor neurons but not in the carotid baroreceptor neurons, as shown in FIG. 9B. Thus, it is believed that the aortic baroreceptors in the human aorta are more sensitive than baroreceptors in the carotid arteries. Hence, utilizing an implant specifically configured for deployment within the aortic region to stretch the arterial wall in this target region allows for a more consistent pronounced baroreflex response than conventional carotid artery implants.

[0081] It is noted that the literature has described the presence of baroreceptors at various locations in the body, including the carotid artery and the aorta, and that some publications describing passive baroreflex implants have mentioned a list of various possible implantations sites in passing, including generally the aorta; however, none have taught any particular target region of the aortic arch. Moreover, none address the unique challenges of implanting in the aortic arch region, challenges which have led the conventional approaches to focus primarily on the carotid artery, which has been commonly accessed to perform certain other procedures, such as placement of carotid stents to address stenosis in this region.

[0082] Thus, the present invention seeks not only to provide an improved baroreflex response by implanting at a particular target region in the aortic arch, but also to allow for implantation at this unique site, while improving ease of implantation. Importantly, this claimed implant and approach avoids the drawbacks associated with procedures and implantation within the carotid artery, which can lead to adverse events due to deployment complications in this area.

[0083] While there are marked advantages to delivering the implant in the aortic arch, namely the ability to target the aortic arch baroreceptors in the narrow band that wrap the aorta, there are also certain challenges associated with deployment in this area. Since the aortic arch is considerably larger in diameter than the carotid, the implant diameter must be made to correspond to the diameter in the aortic arch in order to sufficiently engage tissues to achieve the requisite stretching of the arterial walls (e.g., a stretch of 20% or more, 20-50%, 30%, or even 30-100%). Accordingly, the expandable structure of the baroreflex gauge is configured to effect a same or similar stretching of the arterial walls so as to correspond to the stretching provided by the implant. To prevent flipping or rotation of the implant, the implant typically has a length substantially greater than its largest lateral dimension (e.g., diameter), for example about 40 mm or greater. In some embodiments, the length of the entire implant is 70 mm or greater (e.g., about 85 mm). However, since the baroreflex gauge seeks to invoke the baroreflex response from only the target region, the expandable structure of the baroreflex gauge can be less than the entire length of the corresponding hypertension implant.

[0084] Another challenge is that the aorta is a main artery within the body such that there is a high volume of blood flow that is carried through the aortic arch as well as into secondary arteries that branch off from the aorta (e.g., BA, LCCA, LSA). Therefore, in order to provide consistent engagement and stretching at the target region that corresponds to the implant, the expandable structure should be configured to withstand the forces from the pulsatile blood flow through the aortic arch as well as the lateral forces from blood flow directed into the secondary arteries without dislodging and to maintain the targeted stretch of the arterial wall at the target region to better simulate the effect of the corresponding implant. Additionally, the expandable structure can be configured to expose a majority of the arterial walls in the target region to pulsatile blood flow, which better mimics the implant itself which is also designed with major openings to expose the arterial walls to pulsatile blood flow in order to provide a sustained blood pressure drop noted above, rather than a transitory response if the arterial walls were isolated from blood flow. In some embodiments, the implant provides sufficient stretch to induce a baroreflex response that drops blood pressure in hypertensive patients by at least 10 mm Hg, 20 mm Hg, 30 mm Hg, 40 mm Hg, 50 mm Hg, or 60 mm Hg or greater. Further, expandable structure can be designed so that blood flows freely in a lateral direction into the secondary branch arteries to ensure blood pressure monitoring is accurate. Accordingly, the expandable structure itself can be configured with major openings that allow exposure of the arterial walls and allow lateral blood flow to feed any adjacent secondary arteries.

II. Exemplary Baroreflex Gauge Catheter Device

[0085] FIG. 1A shows an example baroreflex gauge catheter device 100, which includes an expandable structure 10 on a distal end, and a catheter handle 20 with controls on a proximal end of the catheter device. A detail view of the expandable structure 10 is shown in FIG. IB. The expandable structure 10 is configured to transition between a collapsed configuration when elongated (as shown in FIG. 2) to facilitate advancement through the vasculature to a target region, and an expanded configuration (as shown in FIG. 1 A) when axially foreshortened so as to engage and stretch an arterial wall sufficiently (e.g., 20% or more) to invoke the baroreflex response. The entire catheter can be advanced along a guidewire 1 placed in the vasculature before the procedure so as to advance the expandable structure collapsed within outer sheath 14 to the target location in the vasculature.

[0086] The expandable structure can be a splined structure, basket, stent-like structure, or any suitable structure. Preferably, the expandable structure 10 is defined by splines or struts with sufficient strength to stretch the arterial wall when expanded (similar to the implant) yet includes spaces between splines or struts to allow lateral blood flow into lateral body lumens. In this embodiment, the expandable structure can have a diameter between 20 and 100 mm, preferably by 20 and 60 mm, which is appropriate sized to stretch the arterial wall by at least 20% in a human aorta. It is appreciated that, if configured for deployment elsewhere (e.g., carotid artery), the expandable structure can be sized accordingly. In this embodiment, the expandable structure is configured with a variable expanded diameter, thus the structure can be expanded to multiple expanded configurations have differing diameters, for example, multiple diameters within a range between 20 and 60 mm. In this embodiment, the length of the expandable structure is defined so that the tissue contact length I is between 10-20 mm. It is appreciated that the length of tissue contact may change in proportion to the diameter, but preferably at least a 10 mm length engages the tissue throughout the range of expanded diameters. The expandable structure can further include radiopaque markers 11 to allow visualization of the structure at the target region.

[0087] The variable expansion and contraction of the expandable structure 10 is effected by controls on the catheter handle 20. In this embodiment, the expandable structure is attached to two shafts which effect transitioning of the structure between configurations by relative movement of the shafts. The distal end of the expandable structure is attached to a distal gage control shaft 12 and the proximal end of the expandable structure is attached to a proximal gage control shaft 13. Relative movement of the shafts 12, 13 by controls on the proximal catheter handle 20 either axially elongate the expandable structure 10 to the collapsed configuration or axially foreshorten the expandable structure 10 to the various expanded configurations.

[0088] As shown in FIG. 1 A, the catheter handle 20 includes an ergonomic handle body 21. In this embodiment, the handle has a varying diameter between 40-76 mm and a length between 150-305 mm. The catheter handle includes a sheath retraction actuator, which is a slider 24 that is coupled to the proximal end of outer sheath 14 to allow the user to retract the sheath and expose the expandable structure 10 once positioned at the target. The catheter handle can include a strain relief portion 29 that supports the outer sheath 14 at the junction of the handle. The handle further includes a gauge adjuster 23 configured to control the expansion of the expandable structure 10 between the various expanded configurations. Gauge adjuster 23 can include one or more controls, for example, a primary control and one or more precision controls for fine-tuned adjustment. In this embodiment, the gauge adjuster 23 includes a slider 22 that slides along a slot having incremental markings 25 that correspond to the differing diameters or lateral dimensions of the expandable structure 10. In this embodiment, the adjuster 22 allows the lateral dimension or diameter of the expandable structure to be incrementally adjusted between 20 and 60 mm. Preferably, these differing diameters/dimensions correspond to the diameters/ dimensions of differing sizes of hypertension implants provided to the clinician. Alternatively, the implant can be adjustable so as to correspond to an optimal dimension determined by the baroreflex gauge. The catheter handle can optionally include additional one or more precision controls for effecting smaller adjustments. For example, in this embodiment, the adjuster control further includes a micro rotary adjuster 26 that moves the slider in smaller increments (e.g., 1 mm), and a rotary ergo adjuster 27, which includes additional markings to further quantify the microadjustments. The handle can further include a Luer-lock connection 28 to accommodate a guide-wire or fluids (e.g., contrast dye, flushing, etc.).

[0089] While a splined structure is shown here, it is appreciated that the baroreflex gauge catheter could utilize various other expandable structure, include the stent-like structures shown in FIGS. 5A-5B and can include various other handle designs, including that shown in FIGS. 4A-4C and 6. It is further appreciated that the handle could include various other features or functionality, such as a lock to secure the expandable structure configuration during blood pressure monitoring, which can be integrated with the adjuster control or separate.

[0090] FIG. 2 shows cross-sectional view (omitting the handle body and sliders) that further illustrate the means by which expandable structure 10 is expanded by actuation of the shafts. In this cross-sectional view of the catheter device 100, the expandable structure 10 is in the crimped configuration and covered by outer sheath 14. The catheter handle 20 can include an adjustment mechanism 15 operably coupled to adjuster 22 that facilitates relative movement of the shafts 12, 13 to incrementally expand the expandable structure. Preferably, the adjustment mechanism is configured so that the shafts each move relative each other so that the mid-point of the expandable structure does not substantially move from its position at the target location. Advantageously, this allows the expandable structure to be varied in its lateral dimension while being maintained at the target location, which avoids the need to reposition the structure before each adjustment. In contrast, conventional designs of expandable structures that rely on axial foreshortening, typically move only one shaft, which results in a shift of the location of the expandable structure as the diameter increases. Such designs may be problematic over a large range of diameters as this could potentially alter the position of the gauge outside the target region. As shown in FIG. 2, the adjustment mechanism 15 can be defined as a rack-and-pinion structure, for example, the proximal portion of each of the proximal and distal shafts 12, 13 can each include a rack portion 15-1, 15-2 with notches that engage with a corresponding pair of pinion gears 15-3, which interact with the racks so that translation of the proximal shaft in the proximal direction rotates one pinion gear, which in turn rotates the other pinion gear so as to translate the distal shaft in the opposite direction. Accordingly, this mechanism moves the shafts apart form each other while substantially maintaining the location of the expandable structure. In some embodiments, the expandable sheath can be made from metal (e.g., Nitinol) or any suitable material. The sheath actuators can be made from polymer, metal or any suitable material. Another example of a rack-and-pinion mechanism to move shafts in opposing directions is shown in FIG. 3 A. In other embodiments, the adjuster mechanism can include a worm gear 16, as shown in FIG. 3B, which can provide a similar function. It is appreciated that various other mechanisms could be used in a similar manner. For example, alternative baroreflex gauge catheter designs 101, 102, 103 are shown in FIGS. 4A-4C.

[0091] FIGS. 4A-4C show an alternative designs of the baroreflex gauge device in which the adjustable expandable structure is a braided mesh such that when expanded the crosssection is substantially circular. This design is advantageous as it avoids reshaping the round vasculature of the aorta into an irregular shape, which avoids points with heightened stress/strain that could contribute to dissection of the vasculature. This is beneficial as it allows the clinician to stretch the vasculature beyond that required for the implant in order to determine the optimal stretch or to determine the maximum and minimum stretch while minimizing risk of dissection. It is understood that the subsequently placed implant need not be round since it is sized according to the optimal stretch determined by the gauging procedure. FIGS. 4C-1 shows features of the alternative baroreflex gauge catheter 103 the handle 20' has an adjuster 23' defined by a slider 24a with lock-release detents 24b that allow the user to incrementally adjust expandable member 10' for expansion or contraction to different gage diameters. The slider is attached to an shaft 12 (i.e., inner hypo-tube) attached to the distal end of the expandable member 10', while shaft 13 (i.e., outer hypo-tube) is attached/fixed to the proximal end of the handle. Notably, this design does shift the location of the midpoint as the expandable member expands. FIG. 4C-2 shows an alternative design of the expandable member 10' defined by a woven stent-like structure or basket. At region A, the proximal end of the expandable gauge structure is attached to the distal end of an outer hypo-tube, which provides axial control for gauge expansion and retraction. At region B, the distal end of the expandable gauge structure is attached to a distal end of an inner hypo-tube.

[0092] FIGS. 5A-1-5B-3 show still other alternative designs for an expandable structure of a baroreflex gauge catheter device. These designs provide a stent-like structure having multiple interconnected struts that provide sufficient strength to laterally stretch the arterial walls, yet still allow free flow of blood laterally therethrough to ensure accurate blood pressure measurements. It is appreciated that while certain dimensions are shown, that the embodiment is not limited to these dimension and can be of various other dimensions as desired.

[0093] In the embodiment shown in FIGS. 5A-1 through 5A-3, the design has an arrangement of struts having proximal and distal transition regions and a central region that is relatively flat to ensure sufficient engagement with the arterial wall at a given diameter of the expandable structure. This design is configured so that the center portion is about 15 mm in length. Advantageously, this design provides a consistent length of the center portion in engagement with the arterial wall throughout the range of diameters. As shown in the crosssection A-A, the cross-section of the expanded structure that contacts the vasculature is substantially circular so as to stretch the vasculature more uniformly and avoid higher stress/strain points to inhibit dissection. [0094] In the embodiment shown in FIGS. 5B-1 through 5B-3, the design has an arrangement of struts having proximal and distal transition regions and a central region that is relatively flat to ensure sufficient engagement with the arterial wall at a given diameter of the expandable structure. This design is configured so that the center portion is about 10 mm in length. This design may be better suited for patient's having vasculature of reduced size. Further, this design is well suited for animal studies, in which animals have aortas of considerably smaller size. As shown in the cross-section B-B, the cross-section of the expanded structure that contacts the vasculature is substantially circular so as to stretch the vasculature more uniformly and avoid higher stress/strain points to inhibit dissection.

[0095] FIGS. 5C-1 through FIGS. 5C-6 show cross-sectional views that illustrate the interaction of the expandable structure 10 with the arterial vessel wall before and after expansion. FIG. 5C-1 shows the arterial vessel A prior to intervention in which the vessel diameter is Do. FIG. 5C-2 shows the constrained device 10 positioned in vessel A, where the vessel diameter remains Do and the constrained device diameter is < o. FIGS. 5C-3 to 5C-6 shows the vessel A after device 10 is expanded therein. FIG. 5C-3 shows device 10 expanded to diameter <fn, which is equal to the original vessel diameter Do , the vessel diameter Di remains equal to the original vessel diameter Do such that there is no change to the vessel yet. FIG. 5C-4 shows device 10 expanded 11% to diameter < >2, where the vessel shape changes from a circle to a square. Vessel diameter D2 and device diameter < >2 are “apparent diameters” because the vessel is no longer circular. The vessel perimeter is about the original circumference such that little to no stretch is imparted yet. FIG. 5C-5 shows device 10 expanded 30% to diameter < >3 where the square shaped vessel expands in size to diameter D3 . The vessel perimeter is greater than the original circumference such that stretch is about 17%. FIG. 5C-6 shows device 10 expanded 50% to diameter <f>4 where the square shaped vessel expands further in size to diameter D4 . The vessel perimeter is even greater than the original circumference such that stretch is about 35%. These figures demonstrate the relationship between the size, shape and diameter of the expandable member in stretching the arterial wall. It is appreciated that this relationship can also be extended to the size, shape and diameter of the hypertension implant. In this embodiment, the expandable structure is formed by four struts, similar to the design in FIG. 1 A, such that the cross-section is square, which stretches the vasculature but creates heighted stress/strain points at the corners and complicates calculation of the stretch of the vasculature during expansion.

[0096] FIGS. 5D-1 through FIGS. 5D-6 show cross-sectional views that illustrate the interaction of the expandable structure 10 with the arterial vessel wall before and after expansion in vessel A. FIG. 5D-1 shows the vessel A prior to intervention where the vessel diameter is Do. FIG. 5D-2 shows the constrained device 10 positioned in the vessel. The vessel diameter remains Do and the constrained device diameter is < o. FIGS. 5D-3 to 5D-6 shows the vessel A after device 10 is expanded therein. FIG. 5D-3 shows device 10 expanded to diameter <fn, where the vessel diameter Di remains equal to the original vessel diameter Do such that there is no change to the vessel yet. FIG. 5D-4 shows device 10 expanded 11% to diameter < >2 where the vessel diameter D2 also expands by 11% while the vessel retains its original round shape. FIG. 5D-5 shows device 10 expanded 30% to diameter < >3 where the vessel diameter D3 also expands 30%, while the vessel retains its original round shape. FIG. 5D-6 shows device 10 expanded to 50% to diameter <f>4 where the vessel diameter D4 also expands to 50%, while the vessel retains its original round shape, thereby avoiding heightened stress/strain points to avoid dissection of the vessel. These figures demonstrate the relationship between the size, shape and diameter of the expandable member in stretching the arterial wall. It is appreciated that this relationship can also be extended to the size, shape and diameter of the hypertension implant, or that the implant could differ in construction and shape yet still provide a corresponding stretch. In this embodiment, the expandable structure is designed so that, when expanded, the cross-section is substantially circular to stretch the vasculature more uniformly to avoid points with heightened stress/strain points that may contribute to dissection. This allows the vasculature to be stretched with a reduced risk of dissection in order to determine an optimal stretch, a maximum stretch, or a maximum and minimum stretch that provides the baroreflex response. Accordingly, before stretching the vasculature is substantially round having a constant radius and after stretching with the expandable structure, the vasculature is still substantially round but with a larger constant radius, rather than regions of reduced radius that would be produced by expandable structures with non-circular cross sections. This approach is further advantageous as the size of the implant corresponds directly to the size of the vasculature, thereby simplifying the determination of stretch during the gauging procedure. It is understood that the subsequently placed implant need not be of the same shape, but can be sized to achieve the optimal stretch determined by the gauging procedure.

[0097] FIG. 6 shows an example baroreflex gauge catheter device 110 with the expandable structure 10 deployed at the target region T within the aortic arch. As described above, the catheter device 110 is advanced along guidewire 1 placed in the aortic arch until the markers 11 indicate the expandable member 10 is positioned at the target region T. Then, the outer sheath 14 is withdrawn using the catheter handle 20 controls, and the adjuster 22 is actuated to expand the expandable structure 10 to one or more diameters to engage the arterial walls. The level of expansion is indicated by markings 25 on the catheter handle. Upon each adjustment, the blood pressure of the patient is monitored by blood pressure monitor 400 for a short time until the blood pressure is stabilized. The adjuster 22 is used to incrementally increase the expansion until a desired drop in blood pressure is observed. Upon reaching the desired blood pressure, or upon reaching the lowest attainable blood pressure, the diameter is recorded and can be used to inform subsequent placement of an implant in the patient longterm. Typically, this entails selecting an implant of the same corresponding diameter and delivering and deploying the selected implant with an implant delivery catheter, such as that shown in FIGS. 7A-7C, to achieve the same desired drop in blood pressure long-term. In some embodiments, this may entail adjusting an implant. In some embodiments, the 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 also serve as the long-term implant.

III. Exemplary Delivery Catheter and Implant

[0098] FIG. 7A shows an exemplary implant device 300 for treatment of drug-resistant hypertension that is implanted within the aortic arch AA as delivered by an exemplary delivery catheter 200, which is facilitated by the baroreflex gauge device as described above. The delivery catheter system includes an elongated catheter shaft 201 extending between a distal end and proximal end, the shaft having one or more lumens. One lumen can receive a guidewire GW therethrough to facilitate advancement of the catheter over the guidewire GW, previously positioned in the aortic arch. The delivery catheter can further include a tapered distal tip 203 to guide advancement of the catheter over the guidewire GW. The implant 300 is deployed after positioning the distal end portion at the target region within the aortic arch by retraction of an outer sheath 202 constraining the implant in the collapsed configuration during delivery through the vasculature. Retraction of the outer sheath is effected from the catheter handle 210 at the proximal end. The catheter handle can include a hub 220 attached to the proximal end of the outer sheath such that retracting the proximal hub retracts the outer sheath. The outer sheath can include markings thereon to allow the clinician to ensure the sheath is sufficiently retracted to deploy part or all of the implant (e.g., for a self-expandable implant). In other embodiments with a balloon-expandable implant, the delivery catheter can include one or more balloons on the distal portion that can be expanded via the handle. The catheter handle can further include a flush port 211 that is fluidically connected to a lumen extending to the distal end (e.g., a distal opening of the catheter shaft or outer sheath) so that the clinician can flush the aortic arch before, during or after deployment of the implant. The catheter is dimensioned and configured for advancing the implant to the target region T of the aortic arch. The delivery catheter and/or implant can include one or more markers to facilitate precise positioning at the target via visualization techniques. For example, the implant can include one or more markers on one or both of the expandable structures 310, 320 or the flexible connectors 330 between the expandable structures. The catheter can also include one or more markers at various locations, for example, at any of: the distal end of the shaft, the implant location on the shaft, and the distal end of the sheath 204. Optionally, in some embodiments, the catheter system can further include a second guidewire GW2 for placement in a secondary branch, such as the left subclavian artery, to facilitate placement of the implant at the target region relative the LSA. In other embodiments, the implant is positioned relative the anatomy without requiring any additional guidewire.

[0099] FIG. 7B shows an exemplary implant device 300 for treatment of drug-resistant hypertension that is implanted within the aortic arch AA. The implant is an expandable device inserted into the aortic arch and lowers blood pressure by stretching the aortic arch artery wall from the inside and augmenting the aortic arch baroreflex. Branching from the top of the AA are the secondary branch vessel, the brachiocephalic artery (BA), the left common carotid artery (LCCA) and the left subclavian artery (LSA). While shown deployed with the first expandable structure 310 deployed off-center, it is appreciated that the structure could be centered on the target area T.

[0100] As shown, the implant 300 includes two expandable structures 310, 320 interconnected serially by axially expandable connectors 330. The expandable structures are arranged longitudinally along the aorta, which helps anchor and stabilize placement of the implant within the curved aortic arch. Given the relatively large size of the aorta, the high blood flow rate, as well as the curved morphology, anchoring of a single expandable structure in this region can prove challenging. By utilizing two or more structures disposed along differing portions of the aorta, the implant accommodates the curvature and complex geometry of the aorta to help anchor the implant at the target location. Moreover, by relying on engagement of two or more structures along the aorta, the anchoring forces of the implant are distributed over a larger area, thereby minimizing trauma to the arterial walls, which can reduce inflammation and formation of thrombus that can contribute to formation of atherosclerotic plaques. [0101] As shown in FIG. 7B, the expandable structures are formed by multiple open wire frames formed by spaced apart struts defining each lateral side. The lateral sides of adjacent frames are interconnected along lateral struts so that the frames form a regular polygonal shape, which is axi symmetrical along a longitudinal axis of the expandable structure. The expandable structures have 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 arterial walls of the aorta, thereby stretching the arterial walls between each pair of struts in a frame sufficiently to induce the baroreflex response. The flexible connectors 30 are axially expandable (e.g., zig zag connectors) to allow the two expandable structures to extend along differing longitudinal axes so as to accommodate varying degrees of curvature and the complex three-dimensional geometry of the aortic arch. By this configuration, distortion of the aorta or the adjacent great vessels is minimized, and compressive injury to surrounding anatomic structures such as the left recurrent laryngeal nerve is avoided. FIG. 7C shows another embodiment having three expandable structures 310, 320 and 340 connected by flexible connectors 330. In this embodiment, the middle expandable structure is placed at the target region T. Further, the middle structure can be sized larger (e.g., 1.3 - 1.5 times larger) than the outer expandable structures, thereby providing greater stretch at the target while the outer expandable structures provide a transition to reduce risk of dissection of the arterial wall. Additional details regarding the expandable structures can be understood by referring to FIGS. 10A-12B.

[0102] FIG. 10A-10 shows the exemplary implant device 300 having two laterally expandable structures 310, 320 that are interconnected serially by multiple flexible connectors 330. FIG. 10A shows the cross-sectional view, while FIG. 10B shows a lateral side view. FIGS. 10C -10D show the same views but with the device rotated by 45 degrees along a longitudinal axis. The implant device can further include one or more visualization markers 331 thereon, for example a coating on the flexible connectors 330, to aid in positioning during implantation. In this embodiment, the flexible connectors are axially expandable (e.g., zig-zag connectors) and there are four connectors in total extending between the apex of adjacent crown portions of the first and second expandable structures. FIG. 10E shows exemplary implant device 300”’ having three laterally expandable structures 310, 320, 340 that are interconnected by flexible connectors 330. It is appreciated that some embodiments can further include additional such structures (e.g., 4, 5, 6, etc.) connected in the same or different manner. [0103] In this embodiment, each expandable structure 310, 320 includes four elongated frames (310a/310b/310c/3 lOd) joined along adjacent lateral sides to form a square cross section, as shown in FIG. 10 A. Each frame includes at least two linear strut sections 311, 312 defining opposing lateral sides and curved atraumatic crowns 313,314 connecting the proximal and distal ends, respectively. Accordingly, the overall shape of the frame is oblong or pill-shaped. As shown, the atraumatic crowns 313, 314 are gently curved forming an arc of a half-circle or less so that engagement of the proximal or distal ends against tissues does not cause trauma to the arterial wall. The struts and crowns define the overall frame, which leaves a major opening 315 through which the arterial wall is exposed to pulsatile blood flow and which allows lateral blood flow into secondary branch arteries. In some embodiments, the struts of adjacent frames are defined as a single strut, such that a square-cross sectional implant would have only four total struts, one strut on each comer. It is further noted that the entire frame can be formed as a single continuous wire such that the crowns and struts are differing portions of the same wire. In some embodiments, the frames are designed to avoid any sharp comers or angled features of less than 100 degrees, which ensure the proximal and distal ends of the frame remain atraumatic and helps avoid formation of thrombus or plaques within the frame along the major openings through which lateral blood flow is maintained. This design is advantageous as the square cross-section provides sufficient stretch of the arterial walls between the opposite side stmts of each frame without overstretching any one portion of the arterial wall, yet still retains normal function and blood flow of the aorta.

Although this embodiment includes two expandable structures interconnected by four flexible connectors, the implant could include additional expandable structures connected serially in the same fashion and could include more or fewer flexible connectors.

[0104] It is understood that these concepts can be utilized in various other shapes/designs, for example triangular or any regular polygonal cross-section, such as those shown in FIGS. 11 A-12B. FIGS. 11 A-l IB show an implant 300’ with first and second expandable structures 3107320’, each having similar frames as those in FIG. 10A, except each component is formed by three frames such that the cross-section is triangular (e.g., an equilateral triangle). In this embodiment, the largest lateral dimension of the component would be the length of each side of the triangle, which stretches three portions of the arterial wall. FIGS. 12A-12B show yet another implant 300” having first and second expandable structures 310’7320”, each formed by similar frames as those in FIG. 10A expect each component is formed by five frames to form a hexagon, which stretches five portions of the arterial wall. In this embodiment, the largest lateral dimension would be a distance between an apex and a midpoint of an opposite side.

[0105] In another aspect, the implant is sized specifically for the dimensions of the human aortic arch so as to engage the arterial walls with the lateral struts of the expandable structure so as to anchor the implant within the aortic arch and sufficiently stretch the arterial walls within the target region. In the embodiment shown in FIG. 7A, the implant is positioned so that the first expandable structure 310 is positioned opposite the LSA along the target region of the cylindrical band wrapping the aorta, as noted previously. In FIG. 7C, the implant is positioned so that the larger, middle expandable structure is disposed at the target region T. Thus, engagement of a pair of lateral struts in this region stretches the arterial wall and stimulates the highly sensitive baroreceptors in this region. In some embodiments, the implant is sized to achieve a 2: 1 implant-to-aorta diameter ratio at the baroreceptor target zone.

IV. Sizing of Implant for Aortic Arch

[0106] The baroreceptor amplification device is an endovascular implant designed to amplify the baroreflex response by stimulation of highly sensitive baroreceptors in a precise location within the aorta. This is accomplished by appropriately sizing the implant as described herein to achieve sufficient stretch (e.g., 20% or more, 30% or more) of the arterial wall within the target region. The implant is dimensioned based on the unique morphology of the aortic arch in humans. In some embodiments, the applicable dimension suitable for such an implant have been determined by a computed tomography angiographic (CTA) study of human aortas. Measurements of the aortic arch CTA were obtained from 50 patients, including both men and women between the ages of 53 and 88. The measurements were tabulated and the means and range were determined per Tables 1 and 2 below. It is appreciated that any of the sizing and dimensional aspects described with respect to the implant can also pertain to the expandable member of the baroreflex gauge.

[0107] Table 1 shows the mean of various aortic arch measurements, including the aortic arch diameters along regions A, B, C, D (see FIG. 13) and length E extending between sections A and section D (see FIG. 14). Table 1. Mean Aortic Arch Measurements

[0108] Table 2 shows the range of various aortic arch measurements, including the aortic arch diameters along regions A, B, C, D and length E noted above.

Table 2. Ranges of Aortic Arch Measurements

[0109] In one aspect, the diameter and length dimensions could be considered to display relatively little variation as demonstrated by the small standard deviations and narrow ranges. Thus, it is considered that an appropriately sized implant could be made to fit most patients within the above noted ranges. It is noted that arterial walls may be safely stretched up to 50%, potentially up to 100% in healthy patients, such that variability of stretch due to differences in aortic dimensions may be acceptable, so long as the target region is sufficiently stretched (e.g., by at least 20%). In the alternative, it could be considered that these means and ranges of dimension warrant differing sizes of implants. In some embodiments, a set of differently sized implants (e.g., 3-10 different sizes) could be provided and a size could be readily selected based on the particular measurements of the aortic arch of a given patient (see Table 3 below). In another alternative, an implant could be custom-made according to the unique measurement of a patient. The latter two options may be well suited for patients with highly variable morphology or particularly complex geometry of the aortic arch.

[0110] In accordance with the above noted means and ranges of the human aorta, the two or more expandable structures can be suitably dimensioned for placement in the aorta. In an exemplary embodiment, each of the expandable structures are between 30 and 60 mm in length, typically about 40 mm in length, and the greatest lateral dimension (e.g., diameter) is between 30 and 55 mm, typically between 30 and 46 mm. These dimensions accommodate a majority of aortas in the average adult human while providing the requisite stretching along the target region to induce the baroreflex response. The expandable structures can be of the same length or of differing lengths and can be the same or differing diameters. [0111] Table 3 below shows a set of differing sizes of implants and associated diameters based on a tabulation of the relevant dimensions of aortic arches of over 50 patients per the CTA study. Component A refers to the more distal expandable structure (20 in FIG. 1 A), and component B refers to the more proximal expandable structure (10 in FIG. 1 A) disposed at the target region. As described above, the size of implant can be selected for the unique morphology of a patient based on a CT scan of the patient’s aortic arch. It is appreciated that a set of sizes could include any of the sizes noted, or any combination thereof, as well as various additional combinations not listed.

Table 3, Size of Implant Configurations ( Diameters)

[0112] While the above tables provide a general guidelines for sizing the implant, the use of the baroreflex gauge device as described herein, allows the implant to be sized more precisely to better optimize the baroreflex response to improve the hypertension treatment.

[0113] In another aspect, the two or more expandable structures are connected serially by multiple flexible connectors. Preferably, the connectors are axially expandable (e.g., zig-zag design) to optimize conformity to the outer and inner curvatures of the aortic arch. In some embodiments, the connectors are axially expandable by 5-20 mm, typically about 5-10 mm. In some embodiments, the connectors are between 5 mm unexpanded and up to about 10 mm or more fully expanded so 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 can remain unexpanded, as shown in FIG. 7A.

[0114] In another aspect, the length of each expandable structure is typically between 30 and 50 mm, preferably about 40 mm, such that the overall length of the entire implant including the flexible connectors is between 65 and 110 mm, typically between 70-90 mm depending on the axial extension of the connectors. These lengths allow the implant to extend a minimum of 10 mm beyond both the lateral aspects of the brachiocephalic artery and the lateral aspect of the left subclavian artery to ensure a safe and stable loading zone for the device. Based upon the CTA study, implant is about 85 mm when the connectors are unexpanded and approximately 10 mm or greater (e.g., 10-20 mm) when the connectors are fully expanded.

[0115] Based on previous animal studies, it is believed that human aortic arch baroreceptors need to be stretched a minimum of about 20% to achieve a significant increase in baroreceptor nerve signaling. Consequently, the implant is dimensioned with a greatest lateral dimension or diameter that is a minimum of 20% greater than the natural diameter of the target region (e.g., measurement C from the CT angiographic study). The diameter of the implant should be sufficient to ensure adequate aortic arch wall apposition at the terminal landing zones just beyond the lateral take-offs of the brachiocephalic and left subclavian arteries (e.g., locations A and D in FIG. 13). For sizing purposes, the diameter of the implant is measured as the largest lateral dimension (e.g., for a square cross-section, the diagonal shown in FIG. 10A). Based upon the CTA study, the implant can be sized in various differing diameters, for example, 30, 34, 38, 42, 46, and 50 mm. The implant can be constructed with components A and B of different diameters, for example, as shown in Table 3.

V. Mechanism of Action

[0116] To further understand the effect of the size and diameter of the implant, the mechanism of action by which the implant reduces blood pressure should be understood. It is helpful to consider the aortic arch as a circle in cross-section and to consider the arterial wall in discrete arc lengths, as determined by the figure and the arc length formula shown in FIG. 15 A. In the case of an implant having a square cross-section (as in FIG. 10 A), the aorta diameter is considered to be a circle divided into equal parts (e.g., four equal parts). If the aortic arch diameter is 25 mm then the radius would be 12.5 mm and each arc length would be 19.6 mm, as shown in FIG. 15B. Following insertion of a 30 mm diameter implant with this same example, the aortic arch radius would be 15 mm and each arc length would be 23.6 mm, but only if the aortic arch remained circular, as show in FIG. 15C.

[0117] Accordingly, the change in arc length from baseline (FIG. 15B) to post-implant (FIG. 15D) would be an increase of 20% since the radius increases 20% while the other variable stays the same. In other words, each arc of the aorta would be stretched by 20%. However following insertion of the implant, the aortic arch does not remain circular. The radius of curvature of each arc increases, while at the same time the central angle corresponding to that arc decreases (see FIG. 23 C). The change of these two variables in opposite directions confounds an exact estimate of the resultant arc length and the extent of the aortic arch stretch, however, this approach provides a reasonable enough estimate of the stretch obtained to appropriately size the implant to achieve at least 20% stretch. It is noted that the analysis above assumes the square cross-section of the implant in FIG. 10A, but this analysis could be modified to account for the implant in FIG. 11 A that would divide the cross-section into three equal parts or the implant in FIG. 12A which divides the crosssection into five equal parts.

[0118] Thus, by the above approach, the implant can be dimensioned to provide at least a 20% stretch of the target arterial wall. In some embodiments, the implant may be slightly oversized to ensure at least a 20% stretch or to accommodate variations in aorta sizes while still ensuring at least a 20% stretch in all cases. In some embodiments, the implant can be configured to provide additional stretch, for example, 20-30%, 50% stretch, even a 100% stretch may be safely performed in many patients.

[0119] As noted previously, this design allows the device to be deployed and stabilized at a prime anatomic target within the vasculature. Preferably, this target location is within the aortic arch to stretch the aortic arch baroreceptors located along a cylindrical segment of the aortic arch that wraps the aorta between the take-offs of the left common carotid and the left subclavian arteries (including along the inner curvature) from the human aortic arch CT angiographic study. The aortic arch baroreceptors extend along the inner curvature of the aortic arch and extend circumferentially around the arch to the outer curvature or saddle region of the arch, but the greatest concentration of these baroreceptors is located on a segment adjacent the left subclavian artery on the aortic arch that wraps the aorta along diameter C, which is shown as target T in FIG. 16. The implant configuration described herein is specifically configured to target this location but also to stretch adjacent baroreceptors as much as is safe and possible. VI. Delivery and Placement at Target Region

[0120] In yet another aspect, the implant device is especially suited for intravascular delivery and deployment since the implant has a collapsed configuration for advancement through the vasculature and an expanded configuration for engaging the arterial walls, as shown in FIGS. 7A-7C. In the collapsed configuration, the implant is disposed in a delivery catheter to facilitate intravascular delivery to the target site at the aortic arch and subsequent deployment.

[0121] In an exemplary embodiment, the implant is a self-expandable structure that is preloaded into a sheathed delivery catheter, as shown in FIG. 17. As shown, the intravascular delivery catheter is designed to deliver the implant in the collapsed configuration, and to position and deploy the implant at the target location, such as that shown in FIG. 16. The delivery catheter includes an internal guidewire lumen so that it can be advanced along an guidewire GW positioned in the aortic arch. In the embodiment shown, the delivery catheter 200 includes a catheter shaft 201 on which the implant 100 is collapsed, and over which is disposed a retractable sheath 202 that constrains the implant in the collapsed configuration until the implant is positioned at the desired target location, for example by visualization of a marker (e.g., radiopaque or ultrasound marker). The marker can be a coating or marker attached to the connectors, and/or either or both of the expandable structures. In some embodiments, the connectors may be made from a differing material than the frames so that the connectors themselves are distinctly visible through visualization techniques. The delivery catheter can further include a tapered distal tip 203 to guide advancement over the GW and a flush port 211 for flushing before, during, or after delivery. The delivery catheter includes a handle 210 by which the clinician can retract the sheath to deploy the selfexpanding implant, which can include a hub 220 for manually retracting sheath 202 to deploy the implant. The sheath and/or shaft can include markings thereon to gauge the distance the sheath is retracted during deployment to facilitate partial incremental deployment or full deployment of the entire implant. Typically, the overall length (/) of the delivery catheter is between 100-150 cm (e.g., about 135 cm) so as to readily access the aortic arch by insertion of the catheter through the femoral artery.

[0122] In some embodiments, the delivery catheter can be configured to deliver the entire implant upon retraction of the sheath, deploying both the first and second expandable structures in rapid succession. The length of the expandable structure is sufficient such that the expandable structure 310 is deployed at the target location despite any minor axial movement upon deployment. Although structure 320 is deployed first, the positioning and deployment is targeting the deployment of structure 310 at the target location. In other embodiments, the delivery catheter can be configured to allow incremental retraction of the sheath by specified distance so as to deliver the expandable structures sequentially, first placing the second, more distal structure, then positioning the first expandable structure precisely at the target location, the axially expandable connectors provides some leeway as to the positioning of the last deployed expandable structure. In still other embodiments, the implant may be balloon expandable and disposed in a collapsed configuration on a balloon of the delivery catheter, the balloon suitably dimensioned for expansion in the aorta to expand and deploy the implant in the target region.

[0123] Upon deployment, the implant forms an open lattice with the struts of the frames designed to stretch the aortic arch and stimulate the aortic arch baroreceptors, thereby lowering blood pressure, while the arterial wall is exposed to each aortic pulsation through the major openings of the frames, as shown in the example embodiments in FIGS. 10A-12B.

[0124] FIGS. 18-23 illustrate sequential steps of an exemplary method of assessing a baroreflex response and deploying the implant device described herein. It is appreciated that this method is exemplary and there may be additional intervening steps or alternative steps in other embodiments.

[0125] As shown in FIG. 18, a guidewire is placed in the aortic arch and baroreflex gauge catheter device 100 is advanced along the guidewire GW. A baseline of the patient's hypertensive blood pressure is obtained by blood pressure monitor 400 and the patient's blood pressure is monitored during the baroreflex gauging procedure.

[0126] As shown in FIG. 19, after the expandable structure 10 is positioned at the target region T, the expandable structure 10 is exposed and expanded to engage and stretch the arterial wall sufficiently to induce the baroreflex response. After expansion, the clinician measures the patient's blood pressure with blood pressure monitor 400. If the monitored blood pressure drops to a desired blood pressure (e.g., normal range, or significantly reduced), the diameter of the expandable structure is recorded and a correspondingly sized implant can be selected for implantation. If there is insufficient drop in blood pressure, the expandable member can be incrementally increased in diameter until the observed blood pressure drops to a desired blood pressure. Once the baroreflex response of the patient is confirmed and the optimal implant size determined, the clinician proceeds with implantation of the selected implant, as shown in FIGS. 18C-18F. [0127] As shown in FIG. 20, a guidewire GW is advanced through an entry point (e.g., the femoral artery) and advanced through the vasculature and into the aortic arch. Visualization techniques fluoroscopy can verify placement of the GW in the target region.

[0128] As shown in FIG. 21, the delivery catheter 200 is advanced along the GW, the catheter having an implant 300 disposed in a collapsed configuration on a catheter shaft 201 and constrained within a retractable outer sheath 202.

[0129] As shown in FIG. 22, once the implant is positioned at the desired target location within the aortic arch, the outer sheath 202 is retracted, thereby allowing the self-expandable implant 300 to resilient deploy into its expanded configuration with the two expandable structures 310, 320 engaging the arterial walls.

[0130] As shown in FIG. 23, the guidewire GW and delivery catheter 201 are then withdrawn, leaving the implant anchored at the target location in the aortic arch with at least one expandable structure 300 engaged against and stretching the arterial walls at the target region for long-term reduction in blood pressure.

[0131] FIG. 24 shows an exemplary method of assessing a baroreflex response with a baroreflex gauge catheter, in accordance with some embodiments. The method includes steps of: advancing a baroreflex gauge catheter carrying an expandable structure for gauging the baroreflex response in a distal portion thereof, the expandable structure being in a collapsed configuration to facilitate advancement through the vasculature; deploying the expandable structure in the target region to stretch the arterial wall in the target region by at least 20% and subsequently monitoring the blood pressure of the patient to observe any reduction in blood pressure; and confirming the baroreflex response based on observing a reduction in blood pressure while the expandable structure is expanded and determining a course of treatment based on the confirmed baroreflex response.

[0132] FIG. 25 shows an exemplary method of assessing a baroreflex response with a baroreflex gauge catheter for determination of an optimal dimension for a subsequent implant, in accordance with some embodiments. The method includes steps of: advancing a baroreflex gauge catheter carrying an expandable structure for gauging the baroreflex response in a distal portion thereof, the expandable structure being in a collapsed configuration to facilitate advancement through the vasculature; deploying the expandable structure in the target region and monitoring the blood pressure of the patient, and incrementally adjusting the lateral dimension of the expandable structure while monitoring blood pressure to determine an optimal dimension of the baroreflex response; and selecting an implant and/or customizing the implant according to the optimal dimension for the baroreflex response and delivering and deploying the implant at the target location to maintain the baroreflex response long-term for treatment of hypertension.

[0133] Accordingly, the implant devices and associated methods described herein address the unmet clinical need to treat patients with severe hypertension unresponsive to multiple pharmacologic agents. Existing conventional treatment 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 effect or risk of adverse events, respectively. The presently described implant is designed to fulfill this unmet clinical need based on historical and animal studies and identifying the unique anatomy and physiology of the aortic arch baroreceptors and the CT angiographic study outlined above. The implants described allow for sufficient stretching of a particular target region of the aortic arch triggering highly sensitive baroreceptors, so as to consistently and reliably lower blood pressure in the patient, while avoiding adverse risks and drawbacks associated with other approaches targeting other vasculature (e.g., carotid artery).

[0134] FIG. 26A shows tissue histology images with tissue believed to be the baroreceptors stained brown. Tissue histology images indicated that the baroreceptors were present in the target region of the aortic arch noted previously and that such baroreceptors can extend along the aorta toward the left subclavian take off and slightly beyond. FIG. 26B shows a closer view of the baroreceptors surrounded by elastic tissue. While it is believed that the location of the baroreceptors in this region are fairly consistent between patients, the shape and morphology of the aortic arch can vary between patients, thus, it is possible that the location of the baroreceptors can also vary. Accordingly, the device and methods herein allow the clinician to investigate and gauge the location of the baroreflex response in a given patient and to map or confirm the location of the baroreceptors before deployment of the permanent implant.

[0135] In another aspect, the implant itself can be used as a baroreflex gauge. In some embodiments, the implant can be partially deployed so that an expandable structure is deployed at the target location, after which the physiological response (e.g., blood pressure) can be monitored to assess the effect of the implant. Based on the 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 tethers extend proximally and releasably couple the implant to a delivery shaft to allow subsequent repositioning or removal after gauging a physiological response of a partially deployed implant. Such an all-in-one baroreflex gauge and implant delivery system is advantageous for several reasons. First, the baroreflex response is gauged from the implant itself, which avoids the potential for any differences in stretch by a separate gauge device that is different in design from the implant or differences in placement. Secondly, by integrating the gauge function within the implant delivery catheter system, the procedure can be simplified and shortened, which is ideal for higher risk patients. Third, this integration may reduce the overall device costs and complexity of the procedure. Examples of a tethered implant that allows for this all-in-one gauge and implant delivery system are provided below.

[0136] FIGS. 27A-27F illustrates a tethered articulated implant 130 and various steps of deployment, in accordance with some embodiments. FIG. 27A shows an implant structure 130 defined as three expandable rings 10, 20, 40 joined by helically oriented bridges 31 in a reduced diameter Di for delivery to the target location, as described previously. Each ring can have a sinusoidal or zig-zag shape having 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 tube). The design further can further include tethers 50 that extend proximally to engage a tool or delivery catheter. In this embodiment, each tether is attached to a proximal apex of a peak of the proximal-most structure 10 and terminates in a proximal connector that is configured to releasably couple with the delivery catheter or tool. FIG. 27B shows the implant structure having been deployed to an expanded diameter D2. In some embodiments, the implant structure can be configured for uniform expansion to a diameter that is 2-4 mm greater than the nominal diameter of the aortic arch. As shown in FIG. 27C, the bridges are configured such that the outer rings (i.e., proximal and distal expandable structures 10, 20) are twisted relative to the center ring, increasing the circumferential orientation of the bridges. This configuration improves flexion hinge properties, and also reduces the total length of the implant. It is appreciated that various other bridge orientations could be used as well, and that the implant structure could be configured for greater diameters or variable diameters as well. FIG. 27D shows an embodiment in which the center expandable structure 40 (i.e., center ring) has a greater deployed diameter than the proximal and distal expandable structures (i.e., outer rings). In this embodiment, the center ring is expanded to a greater diameter D3, increasing the outward force delivered to the arch at the baroreceptor target location. FIG. 27E illustrates the tethered articulated implant 130 deployed in the curved aortic arch AA from the delivery catheter 200, the proximal connectors of the tethers still being coupled with a distal portion of the delivery catheter, which can allow 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 to conform to the curvature of the aortic arch. In this embodiment, the tether includes sinusoidal portions that stretch to allow angular transition between the catheter tip and proximal ring of the implant. As shown in FIG. 27F, the sinusoidal tethers can extend to differing lengths, LI, L2, L3, thereby accommodating the curve of the arch. It is appreciated that in other embodiments, shorter tethers can be used without any sinusoidal or stretching portions such that the proximal-most structure remains only partly deployed.

[0137] FIGS. 28A-28B illustrate an exemplary aortic arch AA and deployment of a tethered articulated implant 130 therein, in accordance with some embodiments. FIG. 28A shows an exemplary curvature of the aortic arch which has a relatively tight curvature. FIG. 28B shows the implant 130 having helically oriented bridges and proximally extending tethers 50, which allow for controlled positioning, retrieval, repositioning, and removal of the implant by a tool or the delivery catheter 200 if necessary. Although shorter, straight tethers could be used, in this embodiment, the tethers are axially flexible (e.g., sinusoidal, zig-zag portions), which allows the rings to fully expand, appose the arch, and conform to arch curvature. In this example, the outer tether is extended to a length of about 27 mm, while the inner is extended to a length of about 17 mm. In this embodiment, each tether can be of a sinusoidal design that can stretch from about 20-30 mm when fully extended.

[0138] FIG. 29A illustrates a two-ring implant, in accordance with some embodiments. The prototype design includes two expandable structures 10, 20 (i.e., 2 rings) that are joined by helically oriented bridges 31. The active helical bridges provide hinging and stretching movement between the expandable structures. This design can be used to form an implant of any suitable material, including an expandable structure that is laser cut from a metal tube (e.g., Nitinol tube).

[0139] FIG. 29B illustrates a three-ring implant, in accordance with some embodiments. The prototype design includes three expandable structures 10, 20, 40 (i.e., 3 rings) that are joined by helically oriented bridge structures 31. The active helical bridges provide hinging and stretching movement between the expandable structures, thereby accommodating the curvature of the aortic arch. This design can be used to form an implant of any suitable material, including an expandable structure that is laser cut from a metal tube (e.g., Nitinol tube). [0140] FIG. 30A-30B illustrate a multi-ring tethered articulated implant, in accordance with some embodiments. The prototype design include three expandable structures 10, 20, 40 (i.e., 3 rings) that are joined by helically oriented bridge structures 31 and extendable tethers 50 extending from the proximal most ring. The active helical bridges provide hinging and stretching movement between the expandable structures, accommodating the curvature of the aortic arch and are of sufficient length such that the center ring can be fully expanded while the tethers are still attached to the delivery catheter, as demonstrated by FIG. 30B, thereby allowing the center ring to be used as a gauge of blood pressure response. This design can be used to form an implant of any suitable material, including an expandable structure that is laser cut from a metal tube (e.g., Nitinol tube). As in previous embodiments, the center ring 40 can be defined so as to have a greater diameter than the outer rings. Varying the diameter of the center active ring varies the amount of “oversizing” applied by the implant to the arch. In some embodiments, it is recommended to shape the implant to have a center active ring at a diameter between 25 mm and 40 mm, typically between 25 mm and 30 mm.

[0141] FIGS. 31A-31B illustrate alternative implant structures 131, 131’, in accordance with some embodiments. While particular diamond-shaped patterns are used, it is appreciated that the expandable structures could utilize various other expandable shapes and patterns as well.

[0142] FIGS. 32A-32E illustrate various views of an exemplary implant 132 having three expandable structures 10, 20, 40 (i.e., 3 rings) joined by helically oriented bridges 31 and having short tethers 50 extending proximally, as shown in FIG. 32A, thereby defining an 8- cell structure. The implant can be laser cut from a Nitinol tube (e.g., 5.0 mm diameter tube), or formed by any suitable means. FIG. 32B shows the implant 132 in a constrained configuration. FIG. 32C shows uniform partial expansion of the implant 132 (when fully expanded the center ring can have a greater diameter than the outer rings). FIG. 32D shows various cross-sectional views of the implant. FIG. 32E shows an unrolled view of the implant 132, illustrating the three expandable rings and the 8 helically oriented bridges that define the 8-cell structure noted above. It is appreciated that differing widths of the struts and ring portions of the design can be used to provide differing strengths to provide a desired force on the vessel wall. The expanded diameter corresponds to an equivalent stretch and outward pressure exerted by the implant. For example, in a high strength 8-cell design, the expanded diameters 20 mm, 25, mm and 30 mm may correspond to a stretch of 4, 13 and 23% respectively, and an outward pressure of 100, 356 and 628 mm Hg, respectively. In a moderate strength 8-cell design, the expanded diameters 20 mm, 25, mm and 30 mm may correspond to a stretch of 2, 7 and 12% respectively, and an outward pressure of 39, 140 and 247 mm Hg, respectively.

[0143] FIGS. 33A-33E illustrate various views of another exemplary implant 133 having three expandable structures 10, 20, 40 (i.e., 3 rings) joined by helically oriented bridges 30 and having short tethers 50 extending proximally, as shown in FIG. 33 A, thereby defining a 4-cell structure. The implant 133 can be laser cut from a Nitinol tube (e.g., 5.0 mm diameter tube), or formed by any suitable means. FIG. 33B shows the implant 133 in a constrained configuration (e.g., constrained to 4 mm). FIG. 33C shows uniform partial expansion of the implant 133 (when fully expanded the center ring can have a greater diameter than the outer rings). FIG. 33D shows various cross-sectional views of the implant. FIG. 33E shows an unrolled view of the implant 133, illustrating the three expandable rings and the 4 helically oriented bridges that define the 4-cell structure noted above. As shown, the pattern is a flat laser cut pattern of a circumference corresponding to a 5.0 mm diameter of tubing. It is appreciated that differing widths of the struts and rings of the design can be used to provide differing strengths to provide a desired force on the vessel wall. The expanded diameter of a higher strength corresponds to an equivalent stretch and outward pressure exerted by the implant. For example, in a high strength 4-cell design, the expanded diameters 20 mm, 25, mm and 30 mm may correspond to a stretch of 1, 5 and 9%, respectively, and an outward pressure of 25, 105 and 190 mm Hg, respectively. In a moderate strength 4-cell design, the expanded diameters 20 mm, 25, mm and 30 mm may correspond to a stretch of 1, 2 and 4%, respectively, and an outward pressure of 11, 41 and 74 mm Hg, respectively.

[0144] FIGS. 34A-C depict various configurations of tethers 50 and interfacing of tethers within a retention collar 500, in accordance with some embodiments. FIG. 34A shows straight axially extending tethers 50a extending to a proximal connector 51. In this embodiment, the connector is a circular or rounded portion. FIG. 34B shows a tether 50b in which the proximal connector is a portion that curves inward to engage within a recess of a locking collar 500 of the delivery catheter, from which the tether can spring outward upon deployment to release the implant from the delivery catheter. FIG. 34C shows another tether 50c having sinusoidal portions that allow for axial stretch, as described previously, and that extend to a proximal connector 51 having a mushroom shape. It is appreciated that various other dimensions, shapes, and sizes could be used for the tether and proximal connectors. [0145] FIGS. 35A-35B depicts shorter tethers 50 that can be used for the 8-cell and 4-cell implant structures noted previously. In these embodiments, the tethers extend linearly and are relatively short (e.g., 1-10 mm, 2-6 mm, 2-4 mm) and extend to a proximal connector, which can also be referred to as a lock. In these embodiments, the proximal connector 51 can have a mushroom shape, although any suitable shape could be used. The proximal connector can be captured by a corresponding cut out within a retention collar disposed on a distal portion of the delivery catheter (as shown in FIG. 38).

[0146] FIG. 36 depicts various views of a retention collar 500 for retaining the implant structure before full deployment, in accordance with some embodiments. The retention collar 500, which can also be referred to as a collar lock, can be laser cut, machined or formed by any suitable means. In this embodiment, the retention collar is formed from a metal tube (e.g., 4 ID Nitinol tube). The distal end include cut outs 501d correspond in shape to the proximal connector so as to secure the tether to the collar to facilitate control axial longitudinal movement of the implant when constrained within an outer sheath of the delivery catheter. The collar can further include an array of small holes (e.g., 1 mm holes) to facilitate adhesive bonding with the delivery shaft of the delivery catheter 200.

[0147] FIG. 37 depicts the implant 133 in the constrained configured extending from the outer shaft of the delivery catheter 200, where the retention tethers 50 are proximally engaged with the retention collar 500 attached to an advanceable delivery shaft of the delivery catheter. In some embodiments, this assembly can be fed through a 14 Fr 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 to allow the proximal connectors to spring outward from the corresponding cut outs. This configuration allows the implant to be partially deployed, assessing of a baroreflex response, and then the implant can be repositioned or removed based on the response. FIG. 38A depicts a cross-section view and FIG. 38B depicts a detail view of the proximal connectors of the tethers interfaced with the retention collar 500 where the implant is constrained within an outer sheath 210 of the delivery catheter, in accordance with some embodiments.

[0148] FIGS. 39A-39D and FIGS. 40A-40D illustrate cross-sections of the 4-cell and 8-cell expandable structures noted above for the all-in-one implant and baroreflex gauge. As shown in FIGS. 39A-39D, the expandable structure 133 is defined as a 4-cell structure with a regular polygonal cross-section. As shown in FIGS. 40A-40D, the expandable structure 132 is defined as a 8-cell structure with a substantially circular cross-section. Either design can be used to stretch the arterial wall by a suitable amount (e.g., 20% or more) for gauging of the baroreflex response and inducing the baroreflex response long-term after full deployment and implantation. In some embodiments, the implant may further include features to promote implantation, such as barbs, or features such as coatings, holes or slots to promote tissueingrowth. In some embodiments, these features may be disposed on a portion not yet deployed during gauging.

[0149] In the foregoing specification, the invention is described with reference to specific embodiments thereof, but those skilled in the art will recognize that the invention is not limited thereto. Various features, embodiments and aspects of the above-described invention can be used individually or jointly. Further, the invention can be utilized in any number of environments and applications beyond those described herein without departing from the broader spirit and scope of the specification. The specification and drawings are, accordingly, to be regarded as illustrative rather than restrictive. It will be recognized that the terms “comprising,” “including,” and “having,” as used herein, are specifically intended to be read as open-ended terms of art. Unless stated otherwise, the term “about” is considered to mean within +/- 10%. Unless stated otherwise, the term “about” is considered to mean within +/- 10%. It is appreciated that various dimensions of embodiments described herein and that, in some embodiments, a respective dimension could encompass variations, such as within +/- 25%, within +/- 10% of the recited value. It is appreciated that while certain dimensions are shown in various figures, that the embodiment depicted is not limited to these dimensions and can be of various other dimensions as desired. Any references to publication, patents, or patent applications are incorporated herein by reference in their entirety for all purposes.

Claims

WHAT IS CLAIMED IS:

1. A method of assessing a baroreflex response and/or location in a patient, the method comprising: advancing a delivery catheter carrying an expandable structure in a distal portion thereof, the expandable structure being disposed in a collapsed configuration on the delivery catheter to facilitate advancement through the vasculature of the patient, wherein the expandable structure is expandable to a plurality of expanded configurations having differing lateral dimensions; positioning the distal portion of the catheter carrying the implant in the collapsed configuration at a target region in the vasculature; expanding the expandable structure within the target region so that the expandable structure expands to an expanded configuration having a lateral dimension sufficient to engage an arterial wall along the treatment region so as to stretch at least a portion of the arterial wall along the target region, thereby triggering a baroreflex response of aortic arch baroreceptors within the target region to reduce blood pressure; and monitoring a blood pressure of the patient while the expandable structure is in the expanded configuration, wherein the expanded configuration has a lateral dimension corresponding to an implant for treating hypertension to be deployed at the target location.

2. The method of claim 1, wherein the plurality of expanded configurations are each round.

3. The method of any preceding claim, wherein the differing lateral dimension range from 20 mm to 60 mm.

4. The method of any preceding claim, wherein the differing lateral dimensions correspond to a plurality of implants for treating hypertensions such that each lateral dimension corresponds to a different implant of the plurality.

5. The method of any preceding claim, wherein the expanded configuration is a first configuration having a first lateral dimension, the method further comprising: adjusting the expanded expandable structure to a second configuration having a second lateral dimension; and monitoring the blood pressure of the patient while the expandable structure is in the second expanded configuration.

6. The method of claim 5, further comprising: repeating adjusting the expandable structure to one or more additional configurations of differing lateral dimensions and monitoring the blood pressure at each configuration until the monitored blood pressure indicates a desired drop in blood pressure.

7. The method of any preceding claim, further comprising: recording the lateral dimension at which the monitoring the blood pressure exhibits the desired drop in blood pressure.

8. The method of claim 5, further comprising: repeating adjusting the expandable structure to one or more additional locations along or near the target region and monitoring the blood pressure at each configuration to determine a maximum stretched diameter of the target region in the vasculature beyond which there is little or no further improvement in blood pressure.

9. The method of claim 8, further comprising: repeating adjusting the expandable structure to one or more additional locations along or near the target region and monitoring the blood pressure at each configuration to determine a minimum stretched diameter of the target region in the vasculature that provides the baroreflex response to reduce blood pressure.

10. The method of any preceding claim, wherein the expanded configuration is at a first position in the target region, the method further comprising: repositioning the expandable structure to a second location within or near the target region; and monitoring the blood pressure of the patient while the expandable structure is in the second position.

11. The method of claim 10, further comprising: repeating adjusting the expandable structure to one or more additional locations along or near the target region and monitoring the blood pressure at each configuration until the monitored blood pressure indicates a desired drop in blood pressure.

12. The method of claim 11, further comprising: recording the location at which the monitored blood pressure indicates a desired drop in blood pressure for subsequent implantation of the hypertension treatment at the target location.

13. The method of any preceding claim, wherein positioning the expandable structure comprises observing one or more visualization markers disposed on the expandable structure.

14. The method of any preceding claim, wherein the target region is within the aortic arch.

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

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

17. The method of claim 16, wherein selecting the implant comprises selecting an implant from a plurality of implants having differing lateral dimensions, the selected implant having a lateral dimension corresponding to the lateral dimension at which the monitored blood pressure exhibits a desired drop in blood pressure.

18. The method of claim 16 or 17, wherein selecting the implant location comprises selecting the location within the vasculature at which the monitored blood pressure exhibits a desired drop in blood pressure.

19. The method of any of claims 16-18, wherein positioning the distal portion of the catheter within the aortic arch comprises advancing the delivery catheter along a guidewire positioned within the aortic arch.

20. The method of any of claims 16-19, wherein the implant comprises two expandable structures connected serially by a plurality of flexible connectors, wherein at least one expandable structure has the lateral dimension corresponding to the lateral dimension at which the monitored blood pressure exhibits a desired drop in blood pressure.

21. The method of any of claims 16-20, wherein the implant comprises three expandable structures connected serially by a plurality of flexible connectors, wherein at least the middle expandable structure expandable structure has the lateral dimension corresponding to the lateral dimension at which the monitored blood pressure exhibits a desired drop in blood pressure.

22. The method of any of claims 16-21, wherein the target region is within the aortic arch.

23. A baroreflex gauge and/or mapping device comprising: 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, wherein the expandable structure is convertible between the collapsed configuration and an expanded configuration for engaging the arterial walls at a target region within the vasculature, wherein the expandable structure is adjustable to a plurality of expanded configurations each having a differing lateral dimension; a retractable outer sheath having a proximal end and a distal end and being disposed over the shaft including the distal end portion having the expandable structure disposed thereon such that the delivery catheter is configured to facilitate deployment of the expandable structures at the target region; and a catheter handle disposed at or near the proximal end of the shaft, wherein the outer sheath is retractable from the catheter handle to facilitate deployment of the expandable structure at the target region, wherein the catheter handle further includes an adjuster control for adjusting the expandable structure between any of the plurality of expanded configurations.

24. The baroreflex gauge device of claim 23 wherein the expandable structure comprises a stent-like structure having a plurality of struts so as to allow lateral blood flow therethrough.

25. The baroreflex gauge device of claim 24 wherein the plurality of struts comprise visualization markers to facilitate positioning of the expandable structure at the target region.

26. The baroreflex gauge device of claim 24 or 25, wherein the plurality of struts are configured so that the expanded configurations include a flattened central region for engaging the arterial wall, wherein the flattened central region is at least 10 mm in length.

27. The baroreflex gauge device of any of claims 23-26, wherein the expandable structure is configured for deployment within the aortic arch.

28. The baroreflex gauge device of any of claims 23-27, wherein lateral dimensions of the plurality of expanded configurations range between 20 mm and 60 mm.

29. The baroreflex gauge device of any of claims 23-28, wherein the adjuster comprises a slider mechanism.

30. The baroreflex gauge device of claim 29 wherein the guide catheter device is configured so that movement of the slider in one direction incrementally increases the lateral dimension of the expandable structure.

31. The baroreflex gauge device of claim 29 or 30 wherein the catheter handle further comprises one or more fine-tune controls by which the lateral dimension of the expandable structure can be further adjusted in smaller increments.

32. The baroreflex gauge device of any of claim 29-31 wherein the catheter handle further comprises a locking mechanism so as to lock the lateral dimension of the expandable structure during monitoring.

33. The baroreflex gauge device of any of claims 23-32, wherein the guide catheter device is configured with a rack-and-pinion mechanism by which the lateral dimensions of the expandable structure can be adjusted without substantially moving a midpoint of the expandable structure in the vasculature.

34. The baroreflex gauge device of any of claims 23-33, wherein the guide catheter device is configured with a worm gear by which the lateral dimensions of the expandable structure can be adjusted without substantially moving a mid-point of the expandable structure in the vasculature.

35. A baroreflex assessment system comprising: a baroreflex gauge catheter device as in claim 23; and a blood pressure monitor by which a blood pressure of the patient can be monitored while the expandable structure is in the expanded configuration in the target region.

36. A method of assessing a baroreflex response and/or location in a patient, the method comprising: advancing a delivery catheter carrying an implant in a distal portion thereof, the implant having a plurality of expandable structures interconnected by a plurality of bridges, the implant being disposed in a collapsed configuration on the delivery catheter to facilitate advancement through the vasculature of the patient, wherein the implant is expandable to an expanded configuration for engaging and stretching an arterial wall; positioning the distal portion of the catheter carrying the implant in the collapsed configuration at a target region in the vasculature; partially deploying the implant such that at least one expandable structure is expanded within the target region to engage an arterial wall along the treatment region so as to stretch at least a portion of the arterial wall along the target region, thereby triggering a baroreflex response of aortic arch baroreceptors within the target region to reduce blood pressure; and monitoring a blood pressure of the patient while the expandable structure is in the expanded configuration, wherein the expanded configuration has a lateral dimension corresponding to an implant for treating hypertension to be deployed at the target location.

37. The method of claim 36, wherein the expanded configuration of the at least one expandable structure is polygonal or round.

38. The method of claim 36 or 37, wherein a lateral dimension of the expanded configuration is within a range from 20 mm to 60 mm.

39. The method of claim 36, further comprising: upon observation of a suitable drop in blood pressure, fully deploying the implant at the target location while the at least one expandable structure remains expanded at the target location.

40. The method of claim 39, wherein fully deploying the implant comprises releasing one or more proximal connectors of the implant from a lock element of the delivery catheter.

41. The method of claim 40, wherein fully deploying the implant comprises advancing the lock element distally of an outer delivery sheath so that the one or more proximal connectors expand outwardly, thereby releasing the one or more proximal connectors of the implant from the lock element of the delivery catheter.

42. The method of any of claims 36-41, further comprising: upon observation of a sub-optimal response, moving the implant to another location and re-assessing the baroreflex response.

43. The method of claim 42, wherein moving the implant to another location comprises retracting a lock element of the catheter attached to the implant proximally into the delivery sheath, thereby drawing the implant into the delivery sheath to allow repositioning and subsequent deployment of the implant at the other location.

44. The method of any of claims 36-43, further comprising: upon observation of a sub-optimal or lack of response, removing the implant by withdrawing the implant through the sheath and selecting another implant of differing dimensions for deployment at the target location and reassessment of the response.

45. A baroreflex gauge and implant delivery system comprising: a shaft extending between a proximal end and a distal end, the shaft having one or more lumens therethrough; an implant comprising a plurality of expandable structures disposed on a distal portion of the shaft in a collapsed configuration, wherein each expandable structure is convertible between the collapsed configuration and an expanded configuration for engaging the arterial walls at a target region within the vasculature, wherein the implant is releasably coupled at or near a proximal end to a lock element disposed at or near the distal end of the shaft; an outer sheath having a proximal end and a distal end and being disposed over the shaft including the distal end portion having the expandable structure disposed thereon such that the delivery catheter is configured to facilitate deployment of the expandable structures at the target region; and a catheter handle disposed at or near the proximal end of the shaft, wherein the outer sheath and/or shaft is retractable from the catheter handle to facilitate both partial deployment of the implant at the target region to allow gauging of the baroreflex response and to allow full deployment of the implant at the target region implant for long-term treatment.

46. The system of claim 45, wherein the expanded configurations of the at least one expandable structure has a polygonal or round cross section.

47. The system of claim 45 or 46, wherein a lateral dimension of the expanded configuration is within a range from 20 mm to 60 mm.

48. The baroreflex gauge device of any of claims 45-47 wherein the catheter is configured to allow partial deployment of the implant while the lock element remains coupled with the implant.

49. The baroreflex gauge device of any of claims 45-48 wherein the lock element comprises a lock collar having holes or cutouts that interface with a plurality of proximal connectors of the implant.

50. The baroreflex gauge device of claim 49 wherein the plurality of proximal connectors are disposed at proximal ends of a plurality of tethers extending proximally from the implant.

51. The baroreflex gauge device of claim 49 wherein the plurality of proximal connectors each comprise an enlarged portion having a rounded or mushroom shape.

52. The baroreflex gauge device of any of claims 45-51 wherein the implant comprises at least three expandable structures interconnected serially by helically oriented bridges.

53. The baroreflex gauge device of claim 52 wherein a middle expandable structure has a greater lateral dimension than a proximal and distal expandable structure.

54. The baroreflex gauge device of any of claims 45-53 wherein the handle includes an adjuster comprising a slider mechanism for precise controlled deployment or partial deployment of the implant at the target location within the aortic arch.