Catheter for neuromodulation of the subclavian ansae

Abstract

A method of treating heart disease in a subject includes percutaneously introducing a catheter into vasculature of the subject. The catheter may include a neuromodulation element. The neuromodulation element may be positioned on an electrode platform. The electrode platform may deflect away from or toward a central axis defined by the catheter in response to an operator translating a compression shaft. The neuromodulation element of the catheter can be positioned in a subclavian artery of the subject. The catheter can be used to stimulate at least one of a dorsal subclavian ansa or a ventral subclavian ansa. The method can include confirming stimulation of the dorsal subclavian ansa and / or the ventral subclavian ansa by monitoring a cardiac parameter. After confirming stimulation of the dorsal subclavian ansa and / or the ventral subclavian ansa, ablation energy can be provided to the dorsal subclavian ansa and / or the ventral subclavian ansa.

Description

ARTHA.023WO PATENTCATHETER FOR NEUROMODULATION OF THE SUBCLAVIAN ANSAEINCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

[0001] This application claims priority benefit of U.S. Provisional Application No. 63 / 730,338 filed December 10, 2024, which is hereby incorporated by reference in its entirety herein.BACKGROUNDField

[0002] The present disclosure relates generally to systems and methods for facilitating modulation (e.g., denervation, ablation), including for example catheters having one or more electrodes or other elements for treating tissue.Description of the Related Art

[0003] Cardiac ventricular arrhythmia is responsible for over 80,000 deaths per year in the United Kingdom and over 150,000 deaths per year in the United States, the vast majority of ventricular arrhythmia is associated with coronary heart disease and / or heart failure, but the morbidity and cost burden associated with this goes far beyond these figures. Cardiovascular disease accounts for £12 billion of United Kingdom direct healthcare expenditure per year and an estimated $378 billion of direct and indirect costs in the United States per year, and heart failure and the associated arrhythmia care are major drivers of spending. Atrial Fibrillation (AF) is a common and significant medical problem that affects approximately 3% of the population. The prevalence of AF in the United States is estimated to increase from about 5.2 million in 2010 to about 12.1 million in 2030. Individuals with AF have an increased risk of death, both in males and females, the age-adjusted mortality rate attributable to AF is 6.5 per 100,000 people. AF is associated with increased risk factors for other cardiovascular conditions including heart failure, myocardial infarction, and sudden cardiac death, diabetes, gastrointestinal bleeding and stroke, among other conditions.SUMMARY

[0004] Cardiac arrhythmias are due to heterogeneity built in the cardiac muscle but made worse by dynamic changes in sympathetic (adrenergic) and parasympathetic- I -(cholinergic) signaling. In cardiac disease, there is a higher sympathetic signaling emanating from the brainstem and traverses to the heart via the thoracic sympathetic nerves. Most surgical denervation procedures (e.g., a stellectomy) deal with surgeons locating the ganglia and empirically removing the thoracic segments (T1-T4) level of the sympathetic ganglia; as they are the most accessible nerves, which may have accompanying side-effects that negatively impact the patient’s quality of life. Nerves that surround the blood vessels that feed the arms (the subclavian arteries) called subclavian ansae, connect two paravertebral sympathetic ganglia on the same side of the body, thereby forming a highly selective access pathway of sympathetic neural innervation to the heart. As a result, targeting the subclavian ansae on one or both sides for ablation is a novel mechanism to selectively modulate the sympathetic innervation to the heart according to several embodiments described herein.

[0005] The catheters described herein may be ideal for performing neuromodulation on the subclavian ansae or other vessels with similar nerve arrangements. Other examples of vessels with adjoining nerves include the renal artery and aorticorenal ganglia, the pulmonary artery, and cardiac pulmonary nerve and / or cardiac plexus, the carotid artery and the superior and / or middle and / or inferior cervical cardiac nerve, and the brachiocephalic artery and the superior and / or inferior cervical cardiac nerve, any of which may be suitable targets for the catheters described herein. In some embodiments, systems and methods for facilitating therapeutic modulation of the nerves around a subject’s left and / or right subclavian artery to treat a heart disease (e.g., atrial fibrillation) are provided.

[0006] The design structure of the disclosed catheters allows for localized contact between the neuromodulation elements and the target anatomy. For example, the neuromodulation elements may only contact one side of the vessel (e.g., the ventral subclavian ansa or the dorsal subclavian ansa) during stimulation. The design structure also provides improved stability of the device while positioned in the subclavian artery. Although several embodiments disclosed here provide neuromodulation, tissue other than nerves may also be treated. For example, the devices and techniques described herein may be used to close or shunt a vessel such as veins.

[0007] Certain techniques described herein relate to a catheter for treating heart disease in a subject. The catheter can include a catheter shaft configured to be positioned in a vessel, for example at least one of a left subclavian artery or a right subclavian artery. Thecatheter shaft can define an axis and a lumen. The catheter can include a compression shaft disposed with the lumen of the catheter shaft. The catheter can include a neuromodulation platform (e.g., an electrode platform) having a pre-formed, curvilinear shape such as a helix, a sigma, an irregular wave, a planar circle, a trough, etc. In some examples, the electrode platform may have a substantially helical shape extending at least partially around (e.g., fully) or only partially around the compression shaft. The curvilinear shape of the electrode platform may extend less than 360°, less than 300°, less than 270°, less than 235°, less than 180°, less than 150°, or less than 110° around the compression shaft. One or more neuromodulation elements may be positioned on the electrode platform and / or a distal or proximal hub. The distal hub may be coupled to a distal end of the electrode platform and a distal end of the compression shaft. The catheter may include a proximal hub coupled to a distal end of the catheter shaft, and a proximal end of the electrode platform may be coupled to the proximal hub.

[0008] The catheter may include an actuator configured to translate the compression shaft along the axis of the catheter shaft. The translation of the compression shaft causes the electrode platform to transition between an elongated configuration and a compressed configuration. In the compressed configuration, the electrode platform may be configured to contact a dorsal subclavian ansa and / or a ventral subclavian ansa. The compression shaft may be configured to contact an opposing wall of the left subclavian artery and / or the right subclavian artery. In some embodiments, translation of the compression shaft in a proximal direction may cause the electrode platform to transition from the elongated configuration to the compressed configuration, and translation of the compression shaft in a distal direction may cause the electrode platform to transition from the compressed configuration to the elongated configuration.

[0009] In some embodiments, the one or more neuromodulation elements may be positioned on a neuromodulation portion of the electrode platform. The neuromodulation portion may extend only partially along the electrode platform (e.g., along less than 100%, less than 75 %, less than 50%, less than 25%, less than 10% of the electrode platform).

[0010] In some embodiments, the electrode platform may include an inner member including a shape memory material and an outer polymer member surrounding the inner member. The inner member may be pre-shaped to the compressed configuration or pre-shapedto bias towards the compressed configuration in response to translation of the compression shaft in a proximal direction.

[0011] In some embodiments, the catheter may include one or more fluoroscopic markers disposed on the electrode platform. In some aspects, the one or more neuromodulation elements may be electrodes including one of the following shapes: round, segmented round, compressed ring, and half-moon. The one or more neuromodulation elements may include one or more of: gold, tantalum and / or platinum iridium.

[0012] In some embodiments, the one or more neuromodulation elements may span a covered angle of at least about 90 degrees and / or less than or equal to about 180 degrees when the electrode platform is in the compressed configuration, for example less than or equal to about 150 degrees, or less than or equal to about 120 degrees. The curvilinear shape of the electrode platform may have an outer diameter between of at least about 6 mm and / or less than or equal to about 10 mm when in the compressed configuration. A ratio of a compressed outer diameter of the curvilinear shape to the elongated outer diameter of the curvilinear shape may be between approximately 2: 1 and approximately 6: 1. The one or more neuromodulation elements may span a covered length between 10 mm and 15 mm when the electrode platform is in the compressed configuration.

[0013] Any of the catheters described herein may be configured to be positioned in a subclavian artery, a renal artery, a pulmonary artery, a carotid artery, a brachiocephalic artery, or an internal jugular vein. Any of the catheters described herein may be configured to deliver energy to a subclavian ansa, an aorticorenal ganglion, a cardiac pulmonary nerve, cardiac plexus, asuperior and / or middle and / or inferior cervical cardiac nerve, a superior and / or inferior cervical cardiac nerve, or a vagus nerve

[0014] Certain techniques described herein relate to a catheter for treating a condition in a subject. The catheter may include a catheter shaft configured to be positioned in a vessel, for example at least one of a left subclavian artery or a right subclavian artery. The catheter shaft defines an axis and a lumen. The catheter may include a compression shaft disposed within the lumen of the catheter shaft. The catheter may include an electrode platform having a curvilinear shape (e.g., a helix, a sigma, an irregular wave, a planar circle, a trough, etc.) extending less than 260 degrees around the compression shaft. The curvilinear shape may include at least or only a proximal turn and a distal turn. The catheter may include one or moreneuromodulation elements (e.g., electrodes) positioned on a neuromodulation portion of the electrode platform and / or a proximal or distal hub. For example, the neuromodulation portion of the electrode platform may be located on or only on the proximal turn. The neuromodulation portion may extend only partially along the electrode platform (e.g., along less than 100%, less than 75 %, less than 50%, less than 25%, less than 10% of the electrode platform) and may be configured to only contact a dorsal subclavian ansa or a ventral subclavian ansa. The catheter may include a distal hub coupled to a distal end of the electrode platform and a distal end of the compression shaft. The catheter may include an actuator configured to translate the compression shaft along the axis of the catheter shaft, wherein the translation of the compression shaft may cause the electrode platform to transition between an elongated configuration and a compressed configuration. Transition to the compressed configuration may cause the electrode platform to expand radially. In some embodiments, translation of the compression shaft in a proximal direction may cause the electrode platform to transition from the elongated configuration to the compressed configuration, and translation of the compression shaft in a distal direction may cause the electrode platform to transition from the compressed configuration to the elongated configuration.

[0015] In some embodiments, the catheter may include a proximal hub coupled to a distal end of the catheter shaft, and a proximal end of the electrode platform may be coupled to the proximal hub. The catheter may include one or more fluoroscopic orientation markers. The one or more orientation markers may be disposed on the electrode platform, for example at a location between the proximal hub and the neuromodulation portion.

[0016] In some embodiments, the one or more neuromodulation elements may be electrodes including one of the following shapes: round, segmented round, compressed ring, and half-moon. The one or more neuromodulation elements may include one or more of: gold, tantalum and / or platinum iridium.

[0017] In some embodiments, the one or more electrodes may be configured to contact a dorsal subclavian ansa and / or a ventral subclavian ansa, and the compression shaft may be configured to contact an opposing wall of the left subclavian artery and / or the right subclavian artery. In some aspects, the electrode(s) may be ring electrodes, wire electrodes, or irrigation electrodes, although suitable alternatives are also possible.

[0018] In some embodiments, the catheter may be configured to be positioned in a subclavian artery, a renal artery, a pulmonary artery, a carotid artery, a brachiocephalic artery, or an internal jugular vein. The catheter may be configured to deliver energy to a subclavian ansa, an aorticorenal ganglion, a cardiac pulmonary nerve, cardiac plexus, asuperior and / or middle and / or inferior cervical cardiac nerve, a superior and / or inferior cervical cardiac nerve, or a vagus nerve.

[0019] In some embodiments, the catheter may include or be used in conjunction with a basket structure for embolic protection. The basket structure may capture plaque segments as they are broken off during ablation of the target site.

[0020] In some embodiments, the one or more neuromodulation elements may span a covered angle of at least about 90 degrees and / or less than or equal to about 180 degrees when the electrode platform is in the compressed configuration, for example less than or equal to about 150 degrees, or less than or equal to about 120 degrees. The curvilinear shape of the electrode platform may have an outer diameter between of at least about 6 mm and / or less than or equal to about 10 mm when in the compressed configuration. A ratio of a compressed outer diameter of the curvilinear shape to the elongated outer diameter of the curvilinear shape may be between approximately 2: 1 and approximately 6: 1. The one or more neuromodulation elements may span a covered length between 10 mm and 15 mm when the electrode platform is in the compressed configuration.

[0021] In some embodiments, the electrode platform may include an inner member including a shape memory material and an outer polymer member surrounding the inner member. The inner member may be pre-shaped to the compressed configuration or pre-shaped to bias towards the compressed configuration in response to translation of the compression shaft in a proximal direction.

[0022] In some embodiments, a kit can include the catheter and instructions for placing the one or more neuromodulation elements against target anatomy.

[0023] In some embodiments, a neuromodulation system can include the catheter and a power source configured to deliver energy to the one or more neuromodulation elements.

[0024] Certain techniques described herein relate to a catheter for treating a condition in a subject. The catheter can include a catheter shaft configured to be positioned in at least one of a left subclavian artery or a right subclavian artery. The catheter shaft can definean axis and a lumen. The catheter can include a compression shaft disposed within the lumen of the catheter shaft. The catheter can include an electrode platform having a curvilinear shape (e.g., a helix, a sigma, an irregular wave, a planar circle, a trough, etc.) extending only partially around the compression shaft (e.g., less than 360°, less than 300°, less than 270°, less than 235°, less than 180°, less than 150°, or less than 110° around the compression shaft). The curvilinear shape can include a proximal turn and a distal turn. The catheter can include one or more electrodes positioned on a neuromodulation portion of the electrode platform. The neuromodulation portion may extend only partially along the electrode platform (e.g., along less than 100%, less than 75 %, less than 50%, less than 25%, less than 10% of the electrode platform). The catheter can include a distal hub coupled to a distal end of the electrode platform and a distal end of the compression shaft. The catheter can include an actuator configured to translate the compression shaft along the axis of the catheter shaft, wherein translation of the compression shaft causes the electrode platform to transition between an elongated configuration and a compressed configuration.

[0025] In some embodiments, the neuromodulation portion of the electrode platform is located on the proximal turn.

[0026] In some embodiments, the catheter includes a proximal hub coupled to a distal end of the catheter shaft, wherein a proximal end of the electrode platform is coupled to the proximal hub.

[0027] In some embodiments, the catheter may include one or more fluoroscopic orientation markers The one or more orientation markers may be disposed on the electrode platform at a location between the proximal hub and the neuromodulation portion.

[0028] In some embodiments, translation of the compression shaft in a proximal direction causes the electrode platform to transition from the elongated configuration to the compressed configuration. Translation of the compression shaft in a distal direction may cause the electrode platform to transition from the compressed configuration to the elongated configuration.

[0029] In some embodiments, the one or more electrodes may be configured to contact a dorsal subclavian ansa and / or a ventral subclavian ansa, and the compression shaft is configured to contact an opposing wall of the left subclavian artery and / or the right subclavian artery.

[0030] In some embodiments, the one or more electrodes may be ring electrodes.

[0031] In some embodiments, the catheter may further include an electrode disposed on the distal hub.

[0032] Certain techniques described herein relate to a method of treating heart disease in a subject. The method may include percutaneously introducing a catheter having a neuromodulation element into vasculature of the subject; positioning the neuromodulation element in a vessel (e.g., subclavian artery) of the subject; translating a compression shaft (e.g., in a proximal direction) to cause an electrode platform located at a distal end of the catheter to transition from an elongated configuration to a compressed configuration; stimulating (e.g., electrically stimulating) the only one of the dorsal subclavian ansa or the ventral subclavian ansa; confirming stimulation of the dorsal subclavian ansa and / or the ventral subclavian ansa by monitoring a cardiac parameter; and / or after confirming stimulation of the dorsal subclavian ansa and / or the ventral subclavian ansa, providing ablation energy to the dorsal subclavian ansa and / or the ventral subclavian ansa. In the compressed configuration, the electrode platform contacts only one of a dorsal subclavian ansa or a ventral subclavian ansa and the compression shaft contacts an opposing vessel wall of the subclavian artery of the subject, but other substantially helical designs are possible where the electrode platform contacts both the dorsal and ventral subclavian ansae.

[0033] In some embodiments, the method further includes, after providing ablation energy, restimulating the the dorsal subclavian ansa and / or the ventral subclavian ansa and, if a cardiac parameter confirms stimulation, providing further ablation energy to the s the dorsal subclavian ansa and / or the ventral subclavian ansa. In some embodiments, the method may further include repeating the restimulating and providing further ablation energy until the cardiac parameter does not confirm stimulation. The method may further include rotating the catheter and stimulating the other of the dorsal subclavian ansa or the ventral subclavian ansa.

[0034] Percutaneously introducing the catheter to the vasculature may include inserting the catheter into one of a femoral artery of the subject, a radial artery of the subject, or a carotid artery of the subject. In some embodiments, percutaneously introducing the catheter to the vasculature includes inserting the catheter into a femoral vein of the subject. At least one of positioning the neuromodulation element in a left subclavian artery or positioningthe neuromodulation element in a right subclavian artery may include crossing from venous vasculature to arterial vasculature.

[0035] Positioning the neuromodulation element in the subclavian artery of the subject may include positioning the neuromodulation element against a dorsal subclavian ansa and / or a ventral subclavian ansa and positioning the compression shaft against an opposing wall of the subclavian artery.

[0036] Translating the compression shaft proximally may cause the electrode platform to transition from an elongated helical shape to a compressed helical shape, wherein a radius of each turn in the elongated helical shape is less than a radius of each turn in the compressed helical shape. Translating the compression shaft distally may cause the electrode platform to transition from the compressed configuration to the elongated configuration.

[0037] In some embodiments, the method further includes monitoring an orientation of the neuromodulation element in the vasculature of the subject using fluoroscopic imaging.

[0038] Certain techniques described herein relate to a neuromodulation system including a catheter having any of the features described above. The catheter may include a catheter shaft defining an axis and a lumen. The catheter may include a compression shaft disposed with the lumen of the catheter shaft. The catheter can include a neuromodulation platform (e.g., an electrode platform) having a curvilinear shape such as a helix, a sigma, an irregular wave, a planar circle, a trough, etc. In some examples, the electrode platform may extend at least partially around (e.g., fully) or only partially around the compression shaft. The curvilinear shape of the electrode platform may extend less than 360°, less than 300°, less than 270°, less than 235°, less than 180°, less than 150°, or less than 110° around the compression shaft. One or more neuromodulation elements (e.g., electrodes) may be positioned on the electrode platform, and / or a distal hub. The distal hub may be coupled to a distal end of the electrode platform and a distal end of the compression shaft. The neuromodulation system may include an actuator configured to translate the compression shaft along the axis of the catheter shaft, wherein the translation of the compression shaft causes the substantially helical platform to transition between an elongated configuration and a compressed configuration. The neuromodulation system may include a power source configured to deliver energy to the one or more neuromodulation elements.

[0039] In some embodiments, the catheter shaft may be configured to be positioned in at least one of a left subclavian artery or a right subclavian artery. The catheter may further include one or more fluoroscopic markers disposed on the electrode platform. In some embodiments, the system may further include a mapping system configured to display the position of the one or more neuromodulation elements in a patient's anatomy. The mapping system may include a processor and a display.

[0040] Certain techniques described herein relate to a catheter for treating heart disease in a subject. The catheter may include a catheter shaft defining an axis and a lumen, a compression shaft disposed with the lumen of the catheter shaft, and a neuromodulation platform. The neuromodulation platform (e.g., an electrode platform) can have a curvilinear shape such as a helix, a sigma, an irregular wave, a planar circle, a trough, etc. In some examples, the neuromodulation platform may extend at least partially around (e.g., fully) or only partially around the compression shaft. The curvilinear shape of the neuromodulation platform may extend less than 360°, less than 300°, less than 270°, less than 235°, less than 180°, less than 150°, or less than 110° around the compression shaft. The neuromodulation platform may be configured to not touch at least a partial circumferential region of a target vessel, in use. One or more neuromodulation elements may be positioned on the neuromodulation platform. The catheter may include a distal hub coupled to a distal end of the neuromodulation platform and a distal end of the compression shaft. The catheter may include an actuator configured to translate the compression shaft along the axis of the catheter shaft, wherein the translation of the compression shaft causes the neuromodulation platform to transition between an elongated configuration and a compressed configuration.

[0041] In some embodiments, a covered angle of the one or more neuromodulation elements is less than 180 degrees, less than 150 degrees, or less than 120 degrees.

[0042] In some embodiments, a covered length of the one or more neuromodulation elements is less than 20 mm, less than 15 mm, or less than 10 mm.

[0043] In some embodiments, when viewed from a distal end of the catheter, the neuromodulation elements are positioned in no more than two adjacent quadrants.

[0044] In some embodiments, the curvilinear shape extends less than 300 degrees, less than 270 degrees, less than 225 degrees, or less than 180 degrees around the compression shaft.

[0045] In some embodiments, the one or more neuromodulation elements may be electrodes.

[0046] Certain techniques described herein relate to a method of modulating and / or ablating a subclavian ansa having one or more of the features described above.

[0047] Certain techniques described herein relate to a treatment system having one or more of the features described above

[0048] Certain techniques described herein relate to a tissue treatment system having one or more of the features described above.

[0049] Applying energy to non-therapeutically stimulate the subclavian ansae in one embodiment can confirm or otherwise indicate that the nerves feeding the heart are affected by the application of the energy by a change in a heart condition as indicated by monitoring at least one heart parameter (e.g., heart rate, etc.). Energy can then be applied to ablate or destroy the affected nerves on a longer-term basis, which has a beneficial effect on the heart to reduce cardiac electrical heterogeneity and reduce further pathological disease progression. There are posterior (dorsal) and anterior (ventral) subclavian ansae around both the left and right subclavian arteries, and a user can selectively target stimulation and ablate any of the four to any extent desired to have different effects in one embodiment. The stimulation is not therapeutic in some embodiment but is used to identify a location for therapeutic ablation. Ablation or “ablation energy”, as described herein, shall be given its ordinary meaning and may be reversible or irreversible and may include denervation, destruction of all or a portion of the nerve, and / or interruption of nerve signals. Further details regarding this method may be found in PCT. Pub. No. WO 2024 / 006466, which may be found in the attached appendix.

[0050] In several embodiments, the catheters described herein have one or more of the following advantages:• allows for localized neuromodulation of the subclavian ansae;• improves stability of the catheter in the subclavian artery, improving accuracy of the localized stimulation• improves steerability when navigating through tortuous vasculature; or• transitioning the electrode platform to the expanded configuration at the vessel site can facilitate dilation of the vessel wall near the nerve or focally expanding a small portion of the arterial wall.- I I -• deployment mechanism allows for ease of repositioning and adjustment in the target artery.• catheter shape and visibility under fluoroscopy further refines location ventral and dorsal in the artery.BRIEF DESCRIPTION OF THE DRAWINGS

[0051] The following drawings are for illustrative purposes only and show nonlimiting embodiments. Features from different figures may be combined in several embodiments.

[0052] FIG. 1 is a schematic diagram showing an example innervation of the sympathetic nerve tracts to the heart.

[0053] FIG. 2A is a schematic diagram of an example method of modulating nerves around a left subclavian artery.

[0054] FIG. 2B is a schematic diagram of an example method of modulating nerves around a right subclavian artery.

[0055] FIG. 3 is a schematic diagram of an example system for modulating nerves.

[0056] FIG. 4 is a side view of an example neuromodulation element.

[0057] FIG. 5 is a front view of the example neuromodulation element of FIG. 4.

[0058] FIG. 6A is a side view of the example neuromodulation element of FIG. 4 in a first rotational position.

[0059] FIG. 6B is a front view of the example neuromodulation element of FIG. 4 in the rotational position shown in 6A.

[0060] FIG. 7A is a side view of the example neuromodulation element of FIG. 4 in a second rotational position.

[0061] FIG. 7B is a front view of the example neuromodulation element of FIG. 4 in the rotational position shown in 7A.

[0062] FIG. 8A is a side view of the example neuromodulation element of FIG. 4 in a third rotational position.

[0063] FIG. 8B is a front view of the example neuromodulation element of FIG. 4 in the rotational position shown in 8A.

[0064] FIG. 9A is a side view of the neuromodulation element of FIG. 4 in a delivery configuration.

[0065] FIG. 9B is a side view of the neuromodulation element of FIG. 4 in a first deployment phase.

[0066] FIG. 9C is a side view of the neuromodulation element of FIG. 4 in a in a second deployment phase.

[0067] FIG. 9D is a side view of the neuromodulation element of FIG. 4 in a fully deployed configuration.

[0068] FIG. 10 is a side view of another example neuromodulation element.

[0069] FIG. 11 is a front view of the neuromodulation element of FIG. 10.

[0070] FIG. 12A is a side view of the neuromodulation element of FIG. 10 in a delivery configuration.

[0071] FIG. 12B is a side view of the neuromodulation element of FIG. 10 in a fully deployed configuration in a first rotational position.

[0072] FIG. 12C is a side view of the neuromodulation element of FIG. 10 in a fully deployed configuration in a second rotational position.

[0073] FIG. 13 is a flowchart of an example method of treating a subject.

[0074] FIG. 14A is a side view of another example neuromodulation element in a delivery configuration.

[0075] FIG. 14B is a side view of the neuromodulation element of FIG. 14A in a fully deployed configuration.

[0076] FIG. 15 is a side view of shaping member of the neuromodulation element of FIG. 14A and FIG. 14B.

[0077] FIG. 16 is a side view of an electrode platform of another example neuromodulation element.

[0078] FIG. 17 is a side view of a shape spline of the neuromodulation element of FIG. 16.

[0079] FIG. 18A is a side of the neuromodulation element of FIG. 17 in a delivery configuration.

[0080] FIG. 18B is a side view of the neuromodulation element of FIG. 17 in a deployed configuration.

[0081] FIG. 19A is a side view of the neuromodulation element of FIG. 18 in a fully deployed configuration within a vessel wall in a first rotational position.

[0082] FIG. 19B is a side view of the neuromodulation element of FIG. 18 in a fully deployed configuration within a vessel wall in a second rotational position.

[0083] FIG. 20 is a side view of a shape spline of another example neuromodulation element.

[0084] FIG. 21 A is a side view of the neuromodulation element of FIG. 20 in a delivery configuration.

[0085] FIG. 21 B is a side view of the neuromodulation element of FIG. 20 in a fully deployed configuration.

[0086] FIG. 22 is a top view of an example catheter with neuromodulation elements.

[0087] FIG. 23A is a top view of a distal portion of the catheter of FIG. 22 in an elongated configuration.

[0088] FIG. 23B is a side view of the distal portion of the catheter of FIG. 22 in an elongated configuration.

[0089] FIG. 24A is a top view of a distal portion of the catheter of FIG. 22 in a compressed configuration.

[0090] FIG. 24B is a side view of the distal portion of the catheter of FIG. 22 in a compressed configuration.

[0091] FIG. 25 is a front view of the distal portion of the catheter of FIG. 22 in a compressed configuration.

[0092] FIG. 26A is a lateral x-ray image of the catheter of FIG. 22 in a blood vessel.

[0093] FIG. 26B is an anterior-posterior x-ray image of the catheter of FIG. 22 in a blood vessel.

[0094] FIG. 27A is a longitudinal cross-section view of a distal hub of the catheter of FIG. 22.

[0095] FIG. 27B is a transverse cross-section view of an electrode platform and a compression shaft of the catheter of FIG. 22.

[0096] FIG. 28 A is a top view of a control handle of the catheter of FIG. 22.

[0097] FIG. 28B is a side view of a control handle of the catheter of FIG. 22.

[0098] FIG. 28C is an internal top view of a control handle of the catheter of FIG. l.DETAILED DESCRIPTION

[0099] The majority of arrhythmic events result from myocardial infarction (MI) due to coronary artery disease, but heart failure from any cause gives a strong predisposition towards arrhythmia. Therapies for myocardial infarction such as primary angioplasty and stenting can be effective at restoring blood flow, but significant residual myocardial damage can result. A common finding amongst patients with myocardial damage is an underlying elevated sympathetic nerve signaling that acts to increase stress of the cardiovascular system even further. This deleterious cascade drives heart failure and arrhythmia. Beta-blockers can reduce the impact of elevated sympathetic tone and are a mainstay of arrhythmia prevention and key treatment for heart failure. However, these drugs are incompletely effective and have major systemic side effects at the high doses required for therapeutic effects.

[0100] An implantable cardioverter defibrillator (ICD) can be implanted to inhibit sudden cardiac death due to ventricular arrhythmias. These devices monitor the heart rhythm and provide a direct electrical cardioversion if a tachyarrhythmia is detected, thereby offering an insurance pathway as a reactive therapy. However, ICDs are associated with major iatrogenic morbidity: patients have a life punctuated by generator and lead revisions, lifethreatening device infections are common, and very painful inappropriate shocks are frequent (1 in 20 patients), and can even cause skin burns. The overwhelming majority of ICDs are implanted as primary prevention devices (e.g., in case an arrhythmia occurs), yet in these patients even a modest reduction in arrhythmic risk would reverse the risk / benefit profile of ICDs. Multiple clinical trials and meta-analysis have shown the prevalence of inappropriate shocks from ICDs. While most patients are implanted for primary prevention, the algorithms do not predict arrhythmias well, and, as a result, patients receive inappropriate shocks (shocks delivered when it is not appropriate or when fatal arrhythmia is absent). There is also emerging literature evidence to demonstrate that cumulative increase in shocks leads to further electrical instability in the heart that drives more arrhythmias and hospitalization for inappropriate shocks for symptoms ranging from extreme discomfort (pain to skin bums) to death. In these patients who present with arrhythmias despite ICD implants, thoracic epidural anesthesia is provided for pain relief and to stratify patients who are likely candidates for stellectomy. Astellectomy or stellate decentralization procedure can address the elevated sympathetic signaling (due to cardiac disease) mediated by direct neural pathways that emanate from the heart, travel to the brain stem regions, and travel back to the heart via extracardiac, intrathoracic nerve tracts (like the paravertebral sympathetic chain and its associated nerves (e.g., subclavian ansae)) and can provide a tangible biological target to reduce life-threatening arrhythmia and progression of heart failure. The limited treatment strategies available for incipient heart failure and secondary arrhythmias leave many patients with few choices during disease progression. Although catheter ablation of ventricular arrhythmia can be effective for some patients, it is a highly complex procedure and does not alter the underlying pathology. Many patients who are considered at risk for ventricular arrhythmia progress through levels of increasing pharmacological titration, with or without a device (ICD) implant, before ICD implantation can be performed.

[0101] In the case of atrial arrhythmias, the most prevalent arrhythmia, atrial fibrillation, is caused due to imbalance of the nerve supply to the disparate anatomy of the atria (composed of cardiac tissue meeting vascular tissue, interspersed with fat pads) that precipitate arrhythmias. Current treatment strategies are electrophysiological procedures that directly map the most heterogeneous regions of the atria and then disconnecting / electrically isolating these areas from the rest of the atria. All these procedures target intracardiac structures that do not provide complete arrhythmia free survival. A significant proportion of patients have recurrence of arrhythmias, and experimental procedures like fat pad ablation or ganglionated plexi (GP) ablation are carried out on the surface of the heart. These intracardiac structures receive their neural supply from the sympathetic and parasympathetic nerve tracts that are extracardiac, with sympathetic nerves causing significant heterogeneity that precipitates atrial fibrillation. The operator performing the ganglionated plexi ablation is not aware of the success of ablation of all neural tissue at the time of the procedure.

[0102] The nexus point for pathological upregulated cardiac sympathetic signaling derives from the thoracic sympathetic chain ganglia at the upper thoracic levels. In most severe cases of cardiac arrhythmias, increased sympathetic signaling is a major cause of arrhythmia induction in both atria and ventricle. Sympathetic signaling increase or decrease plays a significant role in modulating the cardiac inotropic, dromotropic, lusitropic, and chronotropic properties. In addition, modulation of the cardiac activation recovery intervals or refractoryperiods is well depicted in the literature in both preclinical studies and human studies. As a result, cardiac disease conditions like long Q-T syndrome patients who have an underlying sympathetic overdrive have been considered as candidates for surgical removal of stellate ganglion (stellectomy / stellate decentralization). Highly invasive stellectomy / stellate decentralization (denervation of the heart by resection of stellate ganglia) has been performed by cardiac surgeons to treat life-threatening arrhythmias with good effect. For example, these procedures can reduce arrhythmia burden in long QT syndrome patients. In patients who exhibited refractory ventricular arrhythmias, the only effective treatment was thoracic epidural anesthesia to block the sympathetic traffic followed by surgical stellate removal using video assisted thoracoscopy. However, these stellectomy / stellate decentralization procedures are highly invasive, requiring general anesthesia and highly specialized surgical skills and / or robotic equipment, and are associated with elevated procedural risks in a patient population with advanced cardiac disease. Despite technical advances, such as video-assisted thoracoscopy, only select surgeons perform this procedure in specific centers, and currently this procedure is only carried out for refractory patients as a “last resort” therapy.

[0103] While stellectomy can be effective in reducing the arrhythmias by >90%, the patients suffer from post-operative complications that are highly variable. The surgeon has to remove the stellate ganglion by visual examination, and this is a highly delicate part as the stellate ganglion controls the sympathetic innervation to the arms, shoulders, and the upper back. Due to lack of clear identifiable margins during surgery that cannot be ascertained during surgery to understand axial, pectoral vs. cardiac fibers, surgeons perform stellectomy by naked eye surgery. As a result of this empirical and highly subjective procedure, many patients exhibit symptoms of spared nerve injury, which drives increased pain sensation (hyperalgesia) and asymmetrical sudomotor function (hyperhidrosis / anhidrosis) of the affected upper extremities. Furthermore, existing robotic surgical techniques are highly complex endeavor driving up healthcare costs and reducing access.

[0104] There may be an important interaction between the heart and the autonomic nervous system (ANS) in the pathophysiology of arrhythmias. Derangement of ANS has proven to play an important role in cardiac arrhythmogenesis. The role of ANS in the onset and maintenance of AF is related to autonomic imbalance. Modulation of autonomic nervous signaling holds a significant promise for the reduction (e.g., prevention) and treatment ofcardiac arrhythmias (e.g., vagal nerve stimulation clinical trials). The cardiac autonomic nervous system is a complex structure and provides many easily accessible minimally invasive targets. Use of autonomic modification for treatment of AF may include potential targets for therapy such as autonomic ganglionic plexi, renal denervation, stellate ganglion block, vagus nerve stimulation (e.g., low level vagus nerve stimulation), tragus stimulation, renal denervation, spinal cord stimulation, baroreceptor activation, and cardiac sympathetic denervation. Some targets like stellate ganglion block / sympathectomy may have off-target side-effects, while other targets do not directly impact the reduction of sympathetic signaling. Anesthetic blocks of the stellate ganglia are reversible, and patients experience symptoms of spared nerve injury after a few months and is offered only as a palliative treatment in extreme cases. Paroxysmal atrial tachycardia or atrial fibrillation (AT / AF) in animal models are preceded by increased extrinsic cardiac nerve activity demonstrated in the left stellate ganglion. Stimulation of the stellate ganglion increases sinus rate and predisposes to atrial arrhythmias. Unilateral temporary stellate ganglion block can prolong atrial effective refractory period (ERP), reduce AF inducibility, and / or decrease AF duration. Renal denervation can result in a significantly greater freedom from AF compared to standard pulmonary vein isolation alone.

[0105] A therapy that selectively targets the cardiac sympathetic neuronal supply using a percutaneous, intravascular device can provide users (e.g., cardiologists) with the ability to be able to provide effective, safe, and permanent neuromodulatory treatment for electrical disease (e.g., subjects at risk of arrhythmia), even as an adjunct to primary catheterization procedures. Synergy across pathophysiological mechanisms indicates that this could be useful as a novel treatment angle for heart failure patients, particularly those unable to tolerate beta-blockade.

[0106] Cardiac dysfunction drives increased sensory signaling to the brain stem, which in turn upregulates compensatory inotropic mechanisms, which can be pathogenic in the early stage of the disease. In the case of an ischemic heart disease leading to reduction in pump function, cardiac sympathetic signaling is enhanced in the early stages to maintain cardiac output and adequate oxygenation of the extremities. As the disease progresses, these sympathetic responses get amplified, and this drives cardiac pathology. This pathology drives the following responses: replacement fibrosis of the cardiac muscle and increased sympathetic nerve sprouting in the heart. While the first is a mal-adaptive response to stress, increase insympathetic nerve sprouting is initially an adaptive response, which over time sets up increased heterogeneity. Fibrosed cardiac muscles act as diversion and areas with sympathetic nerve sprouting act as speed paths. This is an ideal substrate for the development of cardiac arrhythmias. The cardiac ANS has a significant impact on cardiac electrophysiology and arrhythmogenesis. This impact is diverse: different types of arrhythmias have different autonomic triggers. With growing knowledge in the identification of those specific triggers, appropriate treatment modalities through neural modulation can be applied accordingly.

[0107] FIG. 1 is a schematic diagram showing an example innervation of the sympathetic nerve tracts to the heart. The subclavian artery 102 is surrounded by dorsal subclavian ansa 104 and ventral subclavian ansa 106. Each of the subclavian ansa 104, 106 is a nerve cord that forms a loop inferiorly around the subclavian artery and connects the inferior cervical ganglion and middle cervical ganglia (also referred to as the C8 and T1 levels of the paravertebral sympathetic chain). The vagus nerve 108 is also illustrated. The arrows 110 indicate that the illustrated nerves extend towards the heart. C8 / T1 levels of the sympathetic chain (stellate ganglia) are predominantly fused or mildly separated in most human subjects and provide nerve supply to the muscles of the shoulders, arms, and the heart. The subclavian ansae 104, 106 serve to route the sympathetic traffic exclusively innervating to and from the heart and connect the heart to the T1 segment directly. The route of sympathetic traffic to the heart occurs via the stellate ganglia that receives sympathetic input from the middle cervical ganglia via two discrete nerve tracts, the dorsal subclavian ansa 104 and the ventral subclavian ansa 106. These two nerves pass over and under the subclavian artery 102, carrying in them the sympathetic efferent (motor) neurons that increase cardiac rate (chronotropy), contractility (inotropy), relaxation (lusitropy), and conduction velocity (dromotropy). The origins of the efferent fibers that pass via the subclavian ansae are the T1-T4 thoracic sympathetic chain ganglia, which converge up toward T1 as they travel from ventral rami of the spinal cord to T4, to T3, to T2, to Tl, before converging at the middle cervical ganglia (C8-T1) through the subclavian ansae 104, 106, and then proceeding to the heart. The afferent fibers seem to bypass the subclavian ansae 104, 106 and pass directly to C8 ganglia. Surgical denervation for cardiac arrhythmia treatment relies on removing entire T4 to half of C8 / T1 complex (removal of four ganglionic cell bodies and their inter-ganglionic tracts, without impacting subclavian ansae 104, 106 due to the procedural complexity of operating around the subclavian artery 102).

[0108] Cardiac-related preganglionic fibers arising from the thoracic cord traverse up the paravertebral chain through the T1-T2 region, some making synaptic contact with postganglionic neurons in the stellate with others projecting through the subclavian ansae 104, 106 to more distal intrathoracic ganglia (middle cervical, mediastinal, and intrinsic) to mix with parasympathetic vagal fibers. As such, the subclavian ansae 104, 106 and the T1-T2 region of the paravertebral chain are nexus points for sympathetic nerve traffic to afferent projections of the heart. Based on structure and function consideration, both sites are potential targets for cardiac neuromodulation.

[0109] Preclinical studies in dogs and more recently pigs showed that stimulation of the subclavian ansae 104, 106 produces reproducible increases in cardiac rate, contractility, and conduction velocity and a decrease in relaxation. Denervation of the subclavian ansae 104, 106 followed by stellate ganglion stimulation at the proximal end (C8) results in no change in cardiac indices confirming the nodal intervention point for cardiac sympathetic traffic. Due to close anatomical correlation in size and anatomy, modulation of subclavian ansae 104, 106 is possible via subclavian artery 102 catheterization. Modulation of the subclavian ansae 104, 106 can produce reproducible increases in cardiac rate and contractility while speeding up conduction velocity. Denervation of the subclavian ansae 104, 106 followed by stellate ganglion stimulation results in no change in cardiac indices, confirming the nodal intervention point for cardiac sympathetic traffic.

[0110] The subclavian ansae 104, 106 can be targeted using percutaneous catheterization of the subclavian artery as described herein to map the nerves along the length of the subclavian artery 102, detect the presence of the nerve(s) 104, 106 (e.g., by non- therapeutic stimulation energy), and selectively ablate the nerve(s) 104, 106 through the subclavian artery. This is a cost-effective alternative to robotic surgery.

[0111] FIG. 2A is a schematic diagram of an example method of modulating nerves 204, 206 around a left subclavian artery 202. FIG. 2A shows additional anatomy to FIG. 1, including the aorta 222 and its branch vessels. The innominate artery branches off the aorta 222 into the right subclavian artery 203, which supplies blood to the right arm, and the right common carotid artery 225, which supplies blood to the cerebral vasculature. The left common carotid artery 224, which supplies blood to the cerebral vasculature, branches directly off the aorta 222. The left subclavian artery 202, which supplies blood to the left arm, also branchesdirectly off the aorta 222. The aorta 222 descends towards the lower body, branching into the left renal artery 226 and the right renal artery 227, and then into the left iliac artery 228 and the right iliac artery 229. The left subclavian artery 202 is surrounded by the dorsal subclavian ansa 204 and the ventral subclavian ansa 206. The right subclavian artery 203 is surrounded by the dorsal subclavian ansa 205 and the ventral subclavian ansa 207. The vagus nerve 208 is also illustrated.

[0112] FIG. 2A schematically illustrates a catheter 230 positioned to effect neuromodulation of the nerves 204, 206. The catheter 230 may be the same catheter or a different catheter than shown and described with respect to FIGS. 2A, 4-12C, or 14A-21B. As illustrated in FIG. 2A, the catheter 230 has been navigated from an access site in the lower body, such as the right femoral artery, to the left subclavian artery 202 (e.g., a position in the left subclavian artery 202 surrounded by the dorsal subclavian ansa 204 and the ventral subclavian ansa 206). The catheter 230 can be tracked over a guidewire, tracked through a guide catheter, directly navigated, and / or other methods of navigation. Other vascular access sites are also possible. For example, the right femoral artery, left or right radial access, a carotid artery, etc. can be accessed and then the catheter 230 can be routed through such vasculature to the left subclavian artery 202. For additional examples, venous vasculature may be accessed, and the catheter 230 may cross from the venous vasculature to the arterial vasculature (e.g., through a foramen ovale, through a dialysis fistula, etc.).

[0113] A distal portion of the catheter 230 comprises a neuromodulation element 232, which may be the same or have similar properties as the neuromodulation elements 406, 406A, 406B described herein. As described, the neuromodulation element 232 may provide non-therapeutic stimulation and / or therapeutic treatment either by the same or different means for modulation. For example, the neuromodulation element 232 may comprise one or more of the following means for modulation: a cryogenic element, a radiofrequency element, an ultrasound element, a laser element, a thermal delivery element, a chemical delivery element, a microwave element, an electrical element, pressure element, an acoustic element, a vibratory element, a mechanical stretching element, and / or the like.

[0114] Once the neuromodulation element 232 is positioned in the left subclavian artery 202, a signal can be applied to the neuromodulation (e.g., using appropriate energy levels for stimulation and safety of the procedure) to locate the nerves of the subclavian ansae 204,206 for subclavian ansae stimulation (SAS), which is non-therapeutic. In some embodiments, the stimulation teaches away from therapy, for example because the stimulation causes a side effect such as inducing arrhythmias. Before, during, and / or after SAS, inotropy, chronotropy, and / or dromotropy can be measured to determine whether the subclavian ansae 204, 206 have been stimulated, for example in comparison to baseline (resting), vagal nerve stimulation, and / or induction of AF. SAS can be determined by cardiac hemodynamic, electrophysiological measurements, and or inducible atrial tachyarrhythmia.

[0115] In some embodiments, the vagus nerve 108 may also or alternatively be stimulated for vagus nerve stimulation (VNS). For example, an electrode catheter can be positioned in the internal jugular vein (IJV) and deliver energy to the vagus nerve 108 (e.g., at an amplitude of 0.5 to 1 V / kg, a frequency of 30 Hz, and a pulse width of 50 ps for 30 s). The output threshold can be determined to achieve a 10-20% reduction in heart rate. An arterial trace can be recorded to determine effects on arterial pressure wave form.

[0116] Skin electrodes may be placed for monitoring diaphragmatic electromyography before, during, and / or after the procedure. The procedure may be performed under general anesthesia in a sterile field, and appropriate therapeutics such as heparin can be administered as needed. The percutaneous site, such as a femoral vein, femoral artery, or radial artery, can be accessed under ultrasound guidance. Arterial access is not routinely performed for AF ablation. In some embodiments, an arterial line may be placed for monitoring arterial pressure.

[0117] Baseline measurements prior to SAS / VNS can include, for example, baseline arterial trace, electrocardiogram, hearth rate, right atrial and / or left atrial ERP, difference in ERP between the left and right atria (dERP), heart rate, interatrial conduction time (IACT), and / or unipolar electrograms at baseline, during steady state right ventricular (RV) pacing at 20-30% above basal heart rate, and / or restitution curve with RV steady state pacing and short diastolic interval (S1-S2).

[0118] Measurements during and / or after SAS / VNS can include, for example, arterial trace blood pressure change, whether AF is induced, whether arrhythmia is induced, whether a change in cardiac cycle length is induced, repeat restitution curve, right atrial and / or left atrial ERP, dERP, heart rate, IACT, and / or unipolar electrogram from multipolar catheter under steady state RV pacing and / or with short DI after steady state RV pacing. Parametersmonitored can vary based on the nerve. For example, the cardiac parameter(s) monitored when stimulating the dorsal subclavian ansa 204 can be different than the cardiac parameter(s) monitored when stimulating the ventral subclavian ansa 206 because modulation of those nerves may be expected to have different effects on the heart. Parameters monitored can also or alternatively vary based on the side. For example, the cardiac parameter(s) monitored when stimulating the left dorsal subclavian ansa 204 can be different than the cardiac parameter(s) monitored when stimulating the right dorsal subclavian ansa 206 (FIG. 2B) because modulation of those nerves may be expected to have different effects on the heart. The cardiac parameter(s) monitored when stimulating each subclavian ansa can be tailored. In some embodiments, the cardiac parameter(s) monitored when stimulating all of the subclavian ansae are the same. In some embodiments, the cardiac parameter(s) monitored when stimulating some of the subclavian ansae are the same and the cardiac parameter(s) monitored when stimulating others of the subclavian ansae are different. For example, the cardiac parameter(s) monitored when stimulating the left and right dorsal subclavian ansae may be the same the cardiac parameter(s) monitored when stimulating the left and right ventral subclavian ansae may be the same, but the cardiac parameter(s) monitored when stimulating the right dorsal subclavian ansa may be different than the cardiac parameter(s) monitored when stimulating the left ventral subclavian ansa. For another example, the cardiac parameter(s) monitored when stimulating the left ventral subclavian ansa may be the same the cardiac parameter(s) monitored when stimulating the right dorsal subclavian ansa may be the same, but the cardiac parameter(s) monitored when stimulating the left ventral subclavian ansa may be different than the cardiac parameter(s) monitored when stimulating the right dorsal subclavian ansa.

[0119] Referring again to FIG. 2A, once the neuromodulation element 232 is positioned in the left subclavian artery 202, non-therapeutic stimulation can be applied to locate the dorsal subclavian ansa 204 and / or the ventral subclavian ansa 206 by achieving a target increase in cardiac function. For example, an increase in heart rate (e.g., an increase of about 5% to about 30% (e.g., about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, ranges between such values, and the like)) can indicate that the sympathetic nervous system is being stimulated. For another example, an increase in a cardiac parameter (e.g., increase in heart rate (R-R interval shortening), increase in systemic blood pressure, increase in left ventricular contractility, increase in ventricular developed pressure (dP / dt), shorteningof P-R interval and Q-T interval, shortening of effective refractory period / activation recovery intervals of the atria and / or ventricle, induction of atrial tachyarrhythmias or ventricular tachyarrhythmias that can be stopped by cardioversion or electric shock, combinations thereof, and the like) can indicate that the sympathetic nervous system is being stimulated. Once the subclavian ansae 204, 206 have been located by the non-therapeutic stimulation, the neuromodulation element 232 can be used to therapeutically ablate or denervate the subclavian ansae 204, 206. In some embodiments, the neuromodulation element 232 includes multiple modalities (e.g., a first modality for stimulating the subclavian ansae 204, 206 and a second modality for ablating the subclavian ansae 204, 206). For example, the neuromodulation element 232 can include an array of electrodes configured to provide electrical stimulation and a different array of electrodes configured to provide radiofrequency ablation. For example, the neuromodulation element 232 can include an array of electrodes configured to provide electrical stimulation and a cryogenic ablation device. Additionally, the array of electrodes configured to provide electrical stimulation may have a different surface area or size than the array of electrodes configured to provide radiofrequency ablation. In some embodiments, the neuromodulation element 232 includes a single modality (e.g., configured to stimulate the subclavian ansae 204, 206 based on a first set of stimulation parameters and configured to ablate the subclavian ansae 204, 206 based on a second set of ablation parameters). For example, the neuromodulation element 232 can include an array of electrodes configured to provide electrical stimulation (e.g., in a bipolar mode in which one or more electrodes act as a cathode and one or more electrodes act as an anode) and configured to provide radiofrequency ablation (e.g., using one or more electrodes in a monopolar mode). When in bipolar mode, two adjacent or non-adjacent electrodes of the neuromodulation element 232 can provide electrical stimulation and / or ablation. When in monopolar mode, only one electrode of the neuromodulation element 232 may provide electrical stimulation and / or ablation. In another embodiment, electrical stimulation and / or ablation can be provided in a bipolar mode in which one electrode of the neuromodulation element is activated in combination with an external neuromodulation element attached to the body of the patient (e.g., a neural stimulation patch applied to the skin of the patient). The ablation, and not mere stimulation, of the subclavian ansae 204, 206, can provide long term effects. For clarity, the ablation signals are destructive signals that are not reversible in the short run (e.g., it is possible that the nerves may grow backafter many years). The ablation is selective by use of a percutaneous catheter 230 and is not surgical stellectomy. The ablation described herein preferably does not target the stellate ganglia in some embodiments. The ablation is preferably from within the subclavian artery, and not, for example due to accessing the paravertebral gutter.

[0120] The dorsal subclavian ansa 204 and the ventral subclavian ansa 206 may be separately stimulated and / or ablated. A possible advantage of this approach is to enable mapping and discrete localization of the nerves, visualized with biomarker change superimposed over the anatomical mapping, like CARTO mapping. In some embodiments, less than 360° of tissue around the left subclavian artery is ablated. This is in contrast, for example, to renal denervation that aims to fully ablate all of the tissue around the renal arteries and stellectomy that removes all of the nerves around the subclavian artery. More specific ablation of only the dorsal subclavian ansa 204 and / or the ventral subclavian ansa 206 can reduce side effects (e.g., sensory deficits (like hyperalgesia) and / or sudomotor abnormalities can be avoided) compared to more complete ablation by targeting the heart-feeding nerves and avoiding nerves and other tissue related to the head, neck, and other body parts.

[0121] The dorsal subclavian ansae 204 and the ventral subclavian ansae 206 may be stimulated at the same time (at least partially) and / or ablated at the same time (at least partially), but in other configurations, may be sequentially stimulated and / or sequentially ablated. In certain embodiments, the dorsal subclavian ansae 204 and the ventral subclavian ansae 206 may be stimulated at least partially at the same time or simultaneously and / or ablated at least partially the same time or simultaneously. For example, in certain embodiments, the dorsal subclavian ansae 204 and the ventral subclavian ansae 206 are stimulated separately but ablated at the same time (or a portion of the same time) or simultaneously. A possible advantage of this approach is to enable mapping and discrete localization of the nerves but using simultaneous ablation of the dorsal subclavian ansae 204 and the ventral subclavian ansae 206 so as to reduce treatment time.

[0122] FIG. 2B is a schematic diagram of an example method of modulating nerves205, 207 around a right subclavian artery 203. The method may be similar to or the same as the method of modulating the nerves 204, 206, except that the catheter 230, which can be the same catheter or a different catheter than shown and described with respect to FIGS. 2 A, 4- 12C, or 14A- 2 IB, has been positioned in the right subclavian artery 203 (e.g., a position inthe right subclavian artery 203 surrounded by the dorsal subclavian ansa 204 and the ventral subclavian ansa 206). As illustrated in FIG. 2B, catheter 230 has been navigated from an access site in the lower body, such as the right femoral artery, to the right subclavian artery 203. The catheter 230 can be tracked over a guidewire, tracked through a guide catheter, directly navigated, and / or other methods of navigation. In some embodiments in which the same catheter 230 is used for treatment around both the left subclavian artery 202 and the right subclavian artery 203, the catheter 230 can be repositioned without withdrawing the catheter 230 from the body. For example, a first guidewire can be navigated to the left subclavian artery202 and the catheter 230 can be tracked over the first guidewire. The first guidewire can remain in place during treatment around the left subclavian artery 202, partially retracted, or fully retracted. Once the treatment around the left subclavian artery 202 is complete, the first guidewire can be advanced and navigated to the right subclavian artery 203. If the first guidewire was fully retracted, the first guidewire or a second guidewire can be advanced through the catheter 230. The catheter 230 can be advanced over the repositioned first guidewire or the second guidewire in the right subclavian artery 203. The right subclavian artery 203 may be treated before the left subclavian artery 202 or vice versa.

[0123] If two catheters 230 are used, the treatment of the right subclavian artery203 and the left subclavian artery 202 may be at least partially simultaneous. For example, a first catheter 230 can extend from a right radial access point to the right subclavian artery 203 and a second catheter 230 can extend from a left radial access point to the left subclavian artery 202. The first and second catheters can be the similar or different (e.g., comprising a different size, a different neuromodulation element 232, etc.).

[0124] In some embodiments, the subclavian ansae ablation is unilateral (only the left dorsal subclavian ansa 204 and / or the left ventral subclavian ansa 206, or only the right dorsal subclavian ansa 205 and / or the right ventral subclavian ansa 207). In some embodiments, the subclavian ansae ablation is bilateral (the left dorsal subclavian ansa 204 and / or the left ventral subclavian ansa 206, and the right dorsal subclavian ansa 205 and / or the right ventral subclavian ansa 207). This provides at least four degrees of freedom to tailor a treatment for a particular result and / or subject. The right dorsal subclavian ansa 205 and the right ventral subclavian ansa 207 may be stimulated at the same time (at least partially) and / or treated at the same time (at least partially), but in other configurations, may be sequentiallystimulated and / or sequentially treated. As with the left subclavian artery 202, in some embodiments, the right dorsal subclavian ansa 205 and the right ventral subclavian ansa 207 can be stimulated at the same time or simultaneously and / or ablated at the same time or simultaneously. For example, in certain embodiments, the right dorsal subclavian ansa 205 and the right ventral subclavian ansa 207 can be stimulated separately but ablated at the same time (or a portion of the same time) or simultaneously. A possible advantage of this approach is to enable mapping and discrete localization of the nerves while using simultaneous ablation of the right dorsal subclavian ansa 205 and the right ventral subclavian ansa 207 so as to reduce treatment time.

[0125] FIG. 3 is a schematic diagram of an example system 300 for modulating nerves. The system 300 comprises the catheter 230, which comprises the neuromodulation element 232, and a signal generator 302. Alternatively, any of the catheters shown and described with respect to FIGS. 2A, 4-12C, or 14A-21B may be used. The signal generator can be an external signal generator, an internal signal generator (e.g., the signal generator 302 can be externally powered via inductive coupling), or a signal generator with components split between both internal and external. The signal generator 302 can comprise wired or wireless communication (e.g., configured to communicate with the neuromodulation element 232, a hospital system, a computer, a handheld device such as a phone or tablet, etc.). The system 300 can also include a control system / controller 301 that can include a processor for controlling one or more operations of the system 300 as described herein, a display 303 for displaying information as described herein and a computer interface 305 which can be used to input information to the control system / controller 301. The system 300 can also include a pressure sensor on a distal tip of the catheter to aid in anatomical mapping, and / or to mark locations where stimulation and / or ablation have been applied. Alternatively, the guidewire itself may serve as a pressure sensor. Readings from the sensor as it contacts the arterial walls may be transmitted by the signal generator 302 to produce a real-time reconstruction of a patient’s artery on the display 303.

[0126] If the neuromodulation element 232 comprises electrodes, the signal generator 302 can generate an electrical signal configured for non-therapeutic SAS. For example, non-therapeutic SAS can include monopolar, bipolar, or multipolar stimulation using a pulse width between about 0.05 milliseconds (ms) and about 4 ms, such as between 2 ms and- 1-4 ms, (e.g., about 0.05 ms, about 0.1 ms, about 0.25 ms, about 0.5 ms, about 0.75 ms, about 1 ms, about 1.5 ms, about 2 ms, about 2.5 ms, about 3 ms, about 4 ms, ranges between such values, etc.), a frequency between at least about 0.1 hertz (Hz) and / or less than or equal to about 150 Hz (e.g., about 0.1 Hz, about 1 Hz, about 5 Hz, about 10 Hz, about 25 Hz, about 50 Hz, about 75 Hz, about 100 Hz, about 125 Hz, about 150 Hz, ranges between such values, and the like), an amplitude between about 0.1 milliamperes (mA) and about 30 mA (e.g., about 0.1 mA, about 1 mA, about 2.5 mA, about 5 mA, about 10 mA, about 15 mA, about 20 mA, about 25 mA, about 30 mA, ranges between such values, etc.), and for a time period of about 15 to about 30 seconds (e.g., about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, ranges between such values, etc.). The frequency may be less than or equal to about 20 Hz, less than or equal to 15 Hz, less than or equal to about 10Hz, or less than or equal to about 5 Hz. The output voltage required for SAS may depend on the type of catheter or used and / or the distance of the neuromodulation element 232 to the left subclavian ansa or right subclavian ansa. SAS may be performed at a lower output voltage when the neuromodulation element 232 is in contact or close proximity with the ansa as compared to when the neuromodulation element 232 is further away from the ansa. The signal configured for non- therapeutic SAS may have an output voltage between about 5 volts (V) and / or less than or equal to about 70 V, (e.g., about 5 V, about 10 V about 20 V, about 30 V, about 40 V, about 50 V, about 60 V, about 70 V, ranges between such values, etc.). For example, the signal may have an output voltage of at least about 5 V and / or less than or equal to about 25 V, for example than or equal to about 20 V, less than or equal to about 10V, or less than or equal to about 5 V. The signal may include a charge balanced wave, a symmetrical wave, and / or an asymmetrical wave (e.g., using 2: 1 recharge pulse width or active first phase with a passive recharge phase), with a duration based on capacitance coupled to ground. Duty cycle may be dependent on hysteresis or the cardiac system (e.g., stimulation induced R-R shortening). The duration of stimulation may be less than 1 second or greater than 30 seconds. Recovery time can be seconds or minutes, after which the stimulation can be repeated if desired.

[0127] The signal generator 302 can also or alternatively generate signals configured for ablation. Tissue denervation occurs above 50 °C. A variety of modalities can be employed for ablation of the subclavian ansae including, for example, chemical, radiofrequency (RF), high-power short duration RF (HPSD RF), cryoablation (CB),microwave, high-intensity focused ultrasound (HIFU), electroporation, combinations thereof, and others. RF energy to produce RF ablation may be generated at frequencies between about 50 (kilohertz) kHz and about 1,500 kHz (e.g., about 500 kHz, about 100 kHz, about 250 kHz, about 350 kHz, about 400 kHz, about 450 kHz, about 500 kHz, about 600 kHz, about 750 kHz, about 1,000 kHz, about 1,500 kHz, ranges between such values, and the like) and using about 10 watts (W) to about 60 W (e.g., about 10 W, about 20 W, about 30 W, about 40 W, about 50 W, about 60 W, ranges between such values, and the like) of power over a specific time window, such as between about 15 s and about 90 s (e.g., about 15 s, about 20 s, about 30 s, about 40 s, about 50 s, about 60 s, about 75 s, about 90 s, ranges between such values, and the like). A majority of the lesions occur as a result of conductive heat, which is inversely proportional to the distance from the tip of the electrode. HPSD RF uses higher power and shorter durations. For example, HPSD RF may use power between about 50 W and about 90 W (e.g., about 50 W, about 90 W, ranges between such values, and the like) and a duration between about 4 s and about 15 s (e.g., about 4 s, about 15 s, ranges between such values, and the like). The principle of high-power short duration ablation seeks to change the balance between resistive and conductive energy transfer and improve the durability of the tissue damage. Before the creation of RF ablation, direct current or DC ablation created cell injury primarily by electroporation or thermal injury. Electroporation can be applied using energies greater than about 200 joules (J) applied for milliseconds. CB involves three phases of tissue damage. The first occurs during delivery of the CB and is known as the freezing-thawing phase. As the temperature drops below -15 °C, microscopic extracellular ice formation occurs, followed by intracellular ice formation when the temperature drops below -40 °C and results in localized tissue damage. As thawing occurs, there is fusion of the ice crystals with microthrombi and platelet aggregation. Subsequently, the hemorrhagic-inflammatory phase occurs with localized tissue inflammation and oedema, and, finally, the replacement-fibrosis phase takes place and a fibrotic scar develops. The signal generator can accommodate all of these settings and timing as needed for complete ablation and denervation of the subclavian ansae. CB can used in the subclavian artery to ablate the subclavian ansae using tissue cooling and the Joule Thompson effect and circulating rare noble gases like argon, helium, etc. Cryoprobes can be used with circulating cryogen.

[0128] A variety of modalities may be employed for ablation of the subclavian ansae including, for example, chemical ablation, radiofrequency (RF) ablation, high power short duration RF (HPSD RF) ablation, cryoablation (CB), microwave ablation, ultrasound ablation, high-intensity focused ultrasound (HIFU) ablation, electroporation ablation, steam ablation, laser ablation, thermal ablation, alcohol ablation or other chemical, cryo, or combinations thereof, and others and the ablation can be reversible or irreversible. RF energy to produce RF ablation may be generated at frequencies between about 50 kilohertz (kHz) and about 1,500 kHz (e.g., about 500 kHz, about 100 kHz, about 250 kHz, about 350 kHz, about 400 kHz, about 450 kHz, about 500 kHz, about 600 kHz, about 750 kHz, about 1,000 kHz, about 1,500 kHz, ranges between such values, and the like) and using about 10 watts (W) to about 60 W (e.g., about 10 W, about 20 W, about 30 W, about 40 W, about 50 W, about 60 W, ranges between such values, and the like) of power over a specific time window, such as between about 15 seconds (s) and about 90 s (e.g., about 15 s, about 20 s, about 30 s, about 40 s, about 50 s, about 60 s, about 75 s, about 90 s, ranges between such values, and the like). A majority of the lesions occur as a result of conductive heat, which is inversely proportional to the distance from the tip of the electrode. HPSD RF uses higher power and shorter durations. For example, HPSD RF may use power between about 50 W and about 90 W (e.g., about 50 W, about 90 W, ranges between such values, and the like) and a duration between about 4 s and about 15 s (e.g., about 4 s, about 15 s, ranges between such values, and the like). The principle of high-power short duration ablation seeks to change the balance between resistive and conductive energy transfer and improve the durability of the tissue damage. Before the creation of RF ablation, direct current or DC ablation created cell injury primarily by electroporation or thermal injury. Electroporation can be applied using energies greater than about 200 joules (J) applied for milliseconds. CB involves three phases of tissue damage. The first occurs during delivery of the CB and is known as the freezing-thawing phase. As the temperature drops below -15 °C, microscopic extracellular ice formation occurs, followed by intracellular ice formation when the temperature drops below -40 °C and results in localized tissue damage. As thawing occurs, there is fusion of the ice crystals with microthrombi and platelet aggregation. Subsequently, the hemorrhagic-inflammatory phase occurs with localized tissue inflammation and oedema, and, finally, the replacement-fibrosis phase takes place, and a fibrotic scar develops. The signal generator can accommodate all of these settings and timingas needed for complete ablation and denervation of the subclavian ansae. CB can used in the subclavian artery to ablate the subclavian ansae using tissue cooling and the Joule Thompson effect and circulating rare noble gases like argon, helium, etc. Cryoprobes can be used with circulating cryogen.

[0129] Figures 4-9D illustrate a catheter 400, which can be used in connection with any of the above-described methodologies to stimulate or ablate any of the above-described nerves for any of the above-described indications. Although several embodiments disclosed here provide neuromodulation, tissue other than nerves may also be treated. For example, the devices and techniques described herein may be used to close or shunt a vessel such as veins. The catheter 400 may include a neuromodulation platform (e.g., an electrode platform 402) at a distal end containing one or more neuromodulation elements 406 (e.g., one, two, three, four, five, or more) for neuromodulation of a blood vessel and / or nerve target. The neuromodulation element(s) 406 may be round, segmented round, compressed ring, half-moon, or any other suitable shape. The neuromodulation element(s) 406 may comprise one or more gold, tantalum, platinum iridium, or any other suitable materials with similar conductive properties. In some embodiments, the neuromodulation elements are electrodes, such as, for example, ring electrodes, stamped electrodes, formed foil electrodes, gold-deposit on polyimide (e.g., flex circuit) electrodes, or wire electrodes, although suitable alternatives are also possible. Any of these configurations may also have accommodation for irrigation through the electrodes into the ablation area. The neuromodulation element(s) 406 may be configured to provide one or more sensing, stimulation, ablation and / or therapeutic treatment. In embodiments containing more than one neuromodulation element, each of the neuromodulation elements 406 may be selectively or simultaneously powered. The electrode platform 402 may also have a unique shape to control where in the anatomy the one or more neuromodulation elements 406 contact the vasculature. The electrode platform 402 may transition between an elongated or delivery configuration and a compressed or deployed configuration in response to an operator translating a compression shaft 404 proximally or distally along an axis 408 defined by the compression shaft 404. The axis 408 of the compression shaft 404 may be off-centered relative to a central axis of the catheter shaft 410 to aid in positioning the one or more neuromodulation elements 406 in contact with the target anatomy (e.g., the subclavian ansa).

[0130] Figure 4 shows a side view of catheter 400. In some embodiments, the catheter shaft 410 defines a lumen 412 housing proximal ends of the compression shaft 404 and the electrode platform 402. In other embodiments, only the proximal end of the compression shaft 404 may be housed within the lumen 412 of the catheter shaft 410.

[0131] The catheter shaft 410 may have variable flexibility such that it is pushable and / or torquable to aid in maneuvering the catheter 400 through vasculature to the target anatomy (e.g., the subclavian artery). The distal end of the catheter shaft 410 may contain a proximal hub 414. The proximal hub 414 may be a separate component that is attached to the catheter shaft 410 by means of gluing, welding, a screw connection, a press-fit connection, or any other suitable attachment mechanisms. Alternatively, the proximal hub 414 may be molded on to, or integrally formed with, the distal end of the catheter shaft 410. In embodiments where the proximal ends of both the compression shaft 404 and electrode platform 402 are housed in the lumen 412 of the catheter shaft 410, the compression shaft 404 and the electrode platform 402 may extend through the proximal hub 414 (e.g., via and aperture), and the distal ends of the compression shaft 404 and the electrode platform 402 may be coupled together via a distal hub 416. In embodiments where only the proximal end of the compression shaft 404 is housed within the lumen 412 of the catheter shaft 410, the proximal end of the electrode platform 402 may be coupled to the proximal hub 414 and the distal end of the electrode platform 402 may be coupled to the distal hub 416. In some embodiments, the distal hub 416 may also comprise a neuromodulation element at its distal end.

[0132] The compression shaft 404 may be made of a flexible material and define a guidewire lumen to aid in delivery of the catheter 400 to the target anatomy. In use cases where ultrasound ablation is being performed, the guidewire may be removed from the lumen of the compression shaft 404 after the catheter 400 is delivered to the site of the target anatomy and replaced with an ultrasound transducer to perform ablation. For example, where the target anatomy is the subclavian ansa, the catheter 400 may be delivered to the subclavian artery via a guidewire in the lumen of the compression shaft 404 and positioned such that the compression shaft 404 contacts a portion of the vessel wall opposing the subclavian ansa and the one or more neuromodulation elements 406 on the electrode platform 402 are aligned with the target site. Once the catheter 400 is positioned, the guidewire may be removed from the lumen of the compression shaft 404 and replaced with an ultrasound transducer to provideablation energy to the one or more neuromodulation elements 406. In other embodiments, the catheter system may be delivered without a guidewire.

[0133] In use cases where chemical ablation is being performed, the guidewire may be removed from the lumen of the compression shaft 404 after the catheter 400 is delivered to the site of the target anatomy and chemicals (e.g., ethanol) or a medicament may be delivered through the lumen of the compression shaft 404 to perform ablation.

[0134] The compression shaft 404 may be used to extend or compress the shape of electrode platform 402, causing the electrode platform 402 to transition between an elongated and a compressed configuration. For example, proximal translation of the compression shaft 404 along the axis 408 may cause the distal hub 416 to move towards the proximal hub 414 to transition the electrode platform 402 from an elongated configuration to a compressed configuration (e.g., radially expand). The electrode platform 402 may extend in the elongated configuration even when exposed from a guide sheath. When the electrode platform 402 is in a compressed configuration, distal translation of the compression shaft 404 along the axis 408 may cause the distal hub 416 to move away from the proximal hub 414 to transition the electrode platform 402 back to an elongated configuration (e.g., radially compress). In some implementations, robotic arm(s) and / or robotic control may be used to control the catheter system, including translation of the compression shaft 404. The catheters described herein can transition between the elongated configuration and the compressed configuration based on linear translation of the compression shaft without active rotation of the compression shaft or the electrode platform. The catheter may be configured to transition only between the elongated configuration and the compressed configuration without being able to transform to any third configuration with a different shape. The electrode platform may be biased to the elongated or the compressed configuration.

[0135] There may be a stopper mechanism (not shown) within the catheter shaft 410 that limits the proximal translation of the compression shaft 404 and therefore limits the diameter of the electrode platform 402 in the compressed configuration. Smaller vessels may require the electrode platform 402 to have a smaller diameter when in the compressed configuration to avoid damaging the vessel walls. Accordingly, the stopper may limit the range over which the compression shaft 404 can translate proximally along the axis 408. In contrast, larger diameter vessels may require the electrode platform 402 to have a larger diameter whenin the compressed configuration so the one or more neuromodulation elements 406 are able to contact the target site. The stopper may be adjusted via a switch or a dial to adjust the final diameter of the electrode platform 402 in the compressed configuration based on the size of the target vessel.

[0136] There may be a basket structure (not shown) included with the catheter or separate from and capable of being used with the catheter to aid in embolic protection. The basket structure may capture plaque segments as they are broken off during ablation of the target site. The electrode platform 402 may include an inner member (e.g., inner member 43 OB shown in Figures 27A and 27B) made from a shape memory material (e.g., nitinol) surrounded by an outer cover (e.g., outer cover 43 IB shown in Figures 27A and 27B) made from a polymer. Suitable polymers may include, for example, polyether block amide, nylon, polyurethane and siloxane-based polymers. The inner shape memory member can be shapeset to bias the electrode platform 402 to a desired shape when in the compressed configuration in response to proximal translation of the compression shaft 404. In such embodiments, no force (e.g., from distal translation of the compression shaft 404) may be required to transition the electrode platform 402 to the elongated configuration during delivery of the catheter 400 to the target site.

[0137] While the electrode platform 402 is shown to have a loop or substantially helical shape in Figures 4-9D, the shape of the platform 402 may alternatively take the form of other curvilinear shapes. For example, the platform 402 may take the form of an irregular wave including a central plateaued portion when deployed as shown and described below with respect to Figures 14A and 14B, a trough shape as shown and described further below with respect to Figures 21 A and 21B or a planar circle as shown and described further below with respect to Figure 17. The electrode platform 402 may additionally comprise any combination of the foregoing shapes. For example, the electrode platform 402 may comprise a central plateaued section sandwiched between proximal and distal helical sections. The electrode platform 402 may be limited to a single member or strut carrying the neuromodulation elements. The single member or strut may be non-linear or noncollinear as shown in several examples herein. In the elongated and / or compressed configuration, the electrode platform extends or turns away from the longitudinal axis of the catheter.

[0138] In embodiments where the electrode platform 402 has a substantially helical shape, the electrode platform 402 may extend from or through the proximal hub 414 around the distal end of compression shaft 404 and terminate at the distal hub 416. The electrode platform 402 may at least partially or only extend partially around the compression shaft 404 (e.g., less than 360 degrees, less than 320 degrees, less than 310 degrees, less than 300 degrees, less than 280 degrees, less than 270 degrees, less than 260 degrees, less than 180 degrees, less than 150 degrees, less than 120 degrees, ranges between such values, and the like) such that, when in the elongated configuration, the electrode platform 402 resembles an elongated helix having only two turns or at least two turns (i.e. a proximal turn 418 and a distal turn 420, shown in FIGS. 6A-8B). Because the electrode platform 402 extends only partially around the compression shaft, at least a circumferential portion of the vessel will not be contacted by the electrode platform 402. For example, at least a 60 degree, 90 degree, or greater section of the vessel will not be contacted by the electrode platform 402. While certain embodiments described herein with an electrode platform extending only partially around the compression shaft, in other embodiments, the electrode platform may fully encircle the compression shaft or extend at least 360 degrees around the compression shaft. When in the elongated configuration, the proximal turn 418 may have a length between approximately 3 mm and approximately 10 mm (e.g., approximately 3 mm, approximately 4 mm, approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, ranges between such values, and the like) and the distal turn 20 may have a length between approximately 3 mm to approximately 10 mm (e.g., approximately 3 mm, approximately 4 mm, approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, ranges between such values, and the like) and with the electrode section included an overall elongated length between approximately 5 mm and approximately 20 mm (e.g., approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, approximately 11 mm, approximately 12 mm, approximately 13 mm, approximately 14 mm, approximately 15 mm, approximately 16 mm, approximately 17 mm, approximately 18 mm, approximately 19 mm, approximately 20 mm, ranges between such values, and the like). When the electrode platform 402 is compressed by the compression shaft 404 to the compressed configuration, the proximal turn 418 may have a covered angle betweenapproximately 30 degrees and approximately 180 degrees (e.g., approximately 30 degrees, approximately 40 degrees, approximately 50 degrees, approximately 60 degrees, approximately 70 degrees, approximately 80 degrees, approximately 90 degrees, approximately 100 degrees, approximately 110 degrees, approximately 120 degrees, approximately 130 degrees, approximately 140 degrees, approximately 150 degrees, approximately 160 degrees, approximately 170 degrees, approximately 180 degrees, ranges between such values, and the like) and the distal turn 420 may have a covered angle between approximately 30 degrees and approximately 180 degrees (e.g., approximately 30 degrees, approximately 40 degrees, approximately 50 degrees, approximately 60 degrees, approximately 70 degrees, approximately 80 degrees, approximately 90 degrees, approximately 100 degrees, approximately 110 degrees, approximately 120 degrees, approximately 130 degrees, approximately 140 degrees, approximately 150 degrees, approximately 160 degrees, approximately 170 degrees, approximately 180 degrees, ranges between such values, and the like). Overall the electrode shaped segment may cover a range of approximately 45-degrees and approximately 720 degrees circumferentially (e.g., (e.g., approximately 45 degrees, approximately 90 degrees, approximately 145 degrees, approximately 190 degrees, approximately 245 degrees, approximately 290 degrees, approximately 345 degrees, approximately 390 degrees, approximately 445 degrees, approximately 490 degrees, approximately 545 degrees, approximately 590 degrees, approximately 645 degrees, approximately 690 degrees, approximately 720 degrees, ranges between such values, and the like) and between approximately 5 mm and approximately 20 mm axially (e.g., approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, approximately 11 mm, approximately 12 mm, approximately 13 mm, approximately 14 mm, approximately 15 mm, approximately 16 mm, approximately 17 mm, approximately 18 mm, approximately 19 mm, approximately 20 mm, ranges between such values, and the like)^

[0139] As discussed above, the inner shape memory member of electrode platform 402 may be surrounded by an outer cover made from a polymer material. The surface of the outer cover of electrode platform 402 may include one or more neuromodulation elements 406 designed to deliver one or both of stimulation or ablation energy to the target site. As discussed above, in some embodiments, the one or more neuromodulation elements 406 are electrodes,although other suitable alternatives are also possible. While three neuromodulation elements 406 are shown in Figures 4-8B, the electrode platform 402 may include one, two, four, five, or more neuromodulation elements 406. All of the neuromodulation elements may be activated at the same time, or each of the neuromodulation elements 406 may be selectively activated, to control the location where neuromodulation is being applied to the anatomy.

[0140] The one or more neuromodulation elements 406 may only be positioned along a portion of the electrode platform 402 such that they are localized to a particular area (e.g., turn of the helix). The portion of the electrode platform 402 along which the one or more neuromodulation elements 406 are positioned may be referred to as the neuromodulation portion of the electrode platform 402. The neuromodulation portion may extend only partially along the electrode platform (e.g., along less than 100%, less than 75 %, less than 50%, less than 25%, less than 10% of the electrode platform). The neuromodulation elements 406 may be positioned such that they only contact one of either the ventral or dorsal side of the vessel (e.g., subclavian artery) wall to aid in targeting a particular nerves site (e.g., subclavian ansa) without contacting the other one of the ventral or dorsal side of the vessel.

[0141] The neuromodulation elements 406 may be positioned on the electrode platform such that the neuromodulation elements 406 contact an opposing side of a vessel wall than the compression shaft 404 when the electrode platform 402 is deployed to the compressed configuration. For example, when the compression shaft 404 is positioned in contact with the dorsal side of the subclavian artery, the position of the neuromodulation elements 406 may be selected such that they contact the ventral side of the subclavian artery in order to target the ventral subclavian ansa. Similarly, when the compression shaft 404 is positioned in contact with the ventral side of the subclavian artery, the position of the neuromodulation elements 406 may be selected such that they contact the dorsal side of the subclavian artery in order to target the dorsal subclavian ansa.

[0142] In embodiments where the electrode platform 402 comprises a substantially helical shape, the neuromodulation elements may be limited to a single turn of the electrode platform 402. For example, as shown in Figures 4-8B, the neuromodulation elements 406 may be positioned only along a proximal portion of the electrode platform 402, such as the proximal turn 418. As seen in Figure 5, the positions of the one or more neuromodulation elements 406 may not extend beyond a 90-degree arc relative to the compression shaft 404 when the distalend of the catheter 400 is viewed from the front. When viewed from the front, each of the one or more neuromodulation elements 406 may be located in no more than three quadrants, no more than two quadrants, or in a single quadrant, for example in the superior posterior (SP) quadrant.

[0143] In embodiments where the electrode platform 402 comprises other (e.g., non-helical) shapes in the compressed or fully deployed configuration, the one or more neuromodulation elements 406 maya similarly be positioned at locations along the electrode platform 402 that increase contact between the neuromodulation elements 406 and the target anatomy. For example, if the electrode platform 402 has a trough-shape, the neuromodulation elements 406 may be located only along the trough portion of the through and not along the crest portion, or at transition portions between the crest and trough portions, such that, when the compression shaft 404 is positioned in contact with a vessel wall opposite of the target site, and the electrode platform 402 is deployed, the one or more neuromodulation elements 406 contact the target site. If the electrode platform 402 has an irregular wave-shape, the neuromodulation elements 406 may be positioned only at or along the peaks of the irregular wave, such that, when the compression shaft 404 is positioned in contact with a vessel wall opposite of the target site, and the electrode platform 402 is deployed, the one or more neuromodulation elements 406 contact the target site. If the electrode platform 402 has a planar circle shape, the one or more neuromodulation elements 406 may be positioned at a region on the circumference of the circle generally opposes the compression shaft 404 when the electrode platform 402 is in the deployed or expanded configuration, such that, when the compression shaft 404 is positioned in contact with a vessel wall opposite of the target site, and the electrode platform 402 is deployed, the one or more neuromodulation elements 406 contact the target site.

[0144] A plurality of electrodes are positioned along the pre-formed curvilinear shape to allow for a range of coverage on the artery interior. The most distal electrode may be positioned between approximately 5 mm and approximately 15 mm from the distal tip of the catheter. Additional electrodes may be spaced proximally from the first electrode at an edge to edge spacing between approximately 1 mm and approximately 5 mm. The plurality of electrodes may be evenly distributed or may have staggered spacing where different electrode pairs would have different spacing between them. The plurality of electrodes may be spacedin a central portion of the curvilinear shape. Electrodes may have a length between approximately 0.5 mm and approximately 2 mm (e.g., approximately 0.5 mm, approximately 1 mm, approximately 1.5 mm, approximately 2 mm, ranges between such values, and the like) and multiple size electrodes may be used on the catheter.

[0145] The electrode platform 402 may include one or more orientation markers 422, which can be used to determine which quadrant (i.e., superior, inferior, anterior, or posterior) the one or more neuromodulation elements 406 are positioned inside the vessel compared to human anatomy. While Figures 4-8 show two orientation markings 422 more or fewer orientation markings 422 may be possible. The orientation markings 422 may be fluoroscopic such that they can be tracked via a fluoroscopic imaging modalities. Additionally, or alternatively, the orientation markings 422 may be compatible with a mapping system. For example, mapping systems using impedance-based navigation (e.g., Ensite Velocity, St Paul, MN) or electromagnetic-based (e.g., Rhythmia HDx, St Paul, MN) can be used for visualization of the catheter’s movement and location.

[0146] The orientation markers 422 may be positioned anywhere on the catheter, including the proximal hub 414, electrode platform 402, and / or distal hub 416. The neuromodulations elements 406 may be positioned adjacent to or distally of orientation markings 422 such that the rotational position of the neuromodulation elements 406 within the vessel can be determined based on the position of the orientation markings 422. For example, the orientation markings 422 may be positioned between the proximal hub 414 and the most proximal neuromodulation element 406. In examples where the electrode platform 402 is substantially helical, the orientation markings 422 may be disposed on the proximal turn 418 of the electrode platform 402 between the proximal hub 414 and the most proximal neuromodulation element 406. Orientation markers 422 may be placed in both the distal and proximal hubs. Alternately the orientation markers can be placed spaced between approximately 1 mm to approximately 10 mm (e.g., approximately 1 mm, approximately 2 mm, 3 mm, approximately 4 mm, approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, ranges between such values, and the like) from the proximal and distal hubs 414, 416.

[0147] As seen in Figure 5, the positions of the one or more orientation markers 422 may not extend beyond a 90-degree arc relative to the compression shaft 404 when thedistal end of the catheter 400 is viewed from the front. When viewed from the front, each of the one or more orientation markers 422 may be located in a single quadrant, for example in the superior anterior (SA) quadrant. The single quadrant may be a different from the quadrant having the neuromodulation elements 406. The one or more orientation markers 422 and the one or more neuromodulation elements 406 may be positioned in adjacent quadrants, leaving the other two quadrants without any orientation markers 422 and / or neuromodulation elements 406.

[0148] As shown in Figures 6-8B, the position of the orientation markings 422 and the one or more neuromodulation elements 406 change as the catheter is rotated. An operator may be able to determine the position of the one or more neuromodulation elements 406 within the vessel by viewing the position of the orientation markers 422 under fluoroscopy, a mapping system, or otherwise. Knowing the rotational position of the one or more neuromodulation elements 406 relative to the vessel wall allows the operator to target specific anatomical target sites (e.g., the subclavian ansae) for neuromodulation.

[0149] Figures 9A-D shows actuation of the catheter 400. As discussed above, the electrode platform 402 may be pre-formed to bias the electrode platform 402 into the desired substantially helical shape while in the compressed configuration in response to proximal translation of the compression shaft 404. But in other configurations, the shape may be mechanically controlled. Figure 9A shows the electrode platform 402 in an elongated or delivery configuration, where no force is being applied to the electrode platform 402 by way of proximal translation of the compression shaft 404. Figure 9B shows the electrode platform 402 beginning to transition from the elongated configuration to the compressed configuration as the compression shaft 404 begins translating proximally. Figure 9C shows the electrode platform 402 transitioning further towards the compressed configuration as the compression shaft 404 is translated further proximally. Figure 9D shows the electrode platform 402 in the fully compressed or deployed configuration. As discussed above, further proximal translation of the compression shaft 404 may be limited by a stopper disposed in the catheter shaft 410 when the electrode platform 402 is in the fully compressed configuration to control the diameter of the electrode platform 402. Although these method steps are described with respect to translation of the compression shaft 404, in other configurations, the catheter shaft 410 may be translated relative to the compression shaft 404.

[0150] Figures 10 to 12 show an example of another example catheter 400 A. Catheter 400A can include any of the features of the catheter 400 in Figures. 4-9D except as described below. Thus, reference numerals used to designate the various features or components of the catheter 400A are identical to those used for identifying the corresponding features of components of the catheter 400 in FIGS. 4-9D, except that that an “A” has been added to the numerical identifier. Therefore, the structure and description for the various features of the catheter 400 and how it’s operated in FIGS. 4-9D are understood to also apply to the corresponding features of the catheter 400A in FIGS. 10-12, except as described below.

[0151] The electrode platform 402A is preformed to a desired shape of the fully deployed configuration, while the electrode platform 402 is preformed to a desired shape of the delivery configuration. Accordingly, during delivery of the catheter 400A to the target site, the electrode platform 402A must be biased or stretched to the elongated configuration by distal translation of the compression shaft 404A.

[0152] For example, the catheter 400 A, the electrode platform 402 A may be preformed to a desired substantially helical shape of the electrode platform 402 when in the compressed or fully deployed configuration. The electrode platform 402A may be compressed within catheter shaft 410A before and / or during delivery to the target site. An operator may translate the compression shaft 404A distally during delivery such, that the electrode platform 402A is extended distally out of an opening at a distal end catheter shaft 410A and into the elongated configuration. Once the catheter 400A is positioned at the target site, subsequent proximal translation of the compression shaft 404A causes the electrode platform 402A to return to the compressed or fully deployed configuration. Figures 10 and 11 show side and front views, respectively, of the catheter 400A, where the electrode platform 402A is a relaxed or neutral state where no force is being imparted on the electrode platform 402 via proximal translation of the compression shaft 404A.

[0153] Figures 12A-12C show the example embodiment of the catheter 400A in various stages of actuation. Figure 12A shows the catheter 400A where the compression shaft 404A has been translated distally, causing the electrode platform 402 to deform from a preformed loop or substantially helical shape into an elongated helical shape suitable for delivery to the target site. Figure 12B shows the catheter 400A after the compression shaft 404A has been translated proximally, allowing the electrode platform 402A to release back to its pre-formed substantially helical shape. In the rotational position shown in Figure 12B, the one or more neuromodulation elements 406A of the electrode platform face anteriorly. Rotating the catheter 400A to the position shown in Figure 12C, results in the one or more neuromodulation elements 406A facing posteriorly changing the angle of the electrode platform electrode platform 402A. As discussed above, the rotational position of the one or more neuromodulation elements 406A may be determined by monitoring one or more orientation markings 422A, allowing for neuromodulation to be selectively performed at a specific anatomical target site.

[0154] Figure 13 is a flowchart of an example method 1300 of performing subclavian ansae ablation procedure using either of the catheters 400 or 400 A. At box 1301, a distal end of a catheter 400 or 400 A may be navigated to the target anatomy (e.g., the subclavian ansae). The catheter 400 or 400 A may be percutaneously introduced into a subject’s vasculature, for example, into one of the femoral artery, radial artery, or a carotid artery. The catheter 400 or 400A may then be navigated to the target anatomy (e.g., the subclavian artery), for example using a guidewire and over-the-wire system. Other delivery means are also possible, for example tracked through a guide catheter, directly navigated, and / or other methods of navigation.

[0155] In methods using catheter 400 where the electrode platform 402 assumes the elongated configuration when no forces are imparted onto it by the compression shaft 404, no force needs to be imparted on the electrode platform 402 by distal translation of the compression shaft 404 during delivery.

[0156] In methods using catheter 400A where the electrode platform assumes the deployed or compressed configuration when no forces are imparted onto it by the compression shaft 404A, distal translation of the compression shaft 404A is required to cause electrode platform 402A to deform to the elongated configuration during delivery to the target site.

[0157] In some embodiments, positioning the catheter 400 or 400A at the target site may involve positioning the compression shaft 404 or 404A at a location of the vessel wall that opposes the target site. For example, where the target site is the ventral subclavian ansa, the compression shaft 404 or 404A may be positioned against the dorsal wall of the subclavian artery. Where the target site is the dorsal subclavian ansa, the compression shaft 404 or 404A may be positioned against the ventral wall of the subclavian artery.

[0158] At box 1302, an operator actuates the compression shaft 404 or 404A causing it to translate proximally. As discussed, proximal translation of the compression shaft causes the electrode platform 402 or 402A to transition from an elongated configuration to a compressed configuration, bringing the one or more neuromodulation elements 406 or 406A on the electrode platform 402 or 402A in contact with the target site. At box 1303, stimulation energy may be applied to the target site via the one or more neuromodulation elements 406 or 406A. At box 1304 one or physiological changes may be monitored and / or observed to confirm correct placement of the one or more neuromodulation elements 406 or 406A relative to the target site. In some embodiments, where no or only low-level changes in physiological biomarkers are observed, the method may further comprise re-positioning the catheter 400 or 400A and re-stimulating the target site until sufficient physiological changes are observed, indicating more optimal positioning. At box 1305, ablation energy may be applied to the target site.

[0159] Figures 14A and 14B show an example of another catheter 1400, which can be used in connection with any of the above-described methodologies to stimulate or ablate any of the above-described nerves for any of the above-described indications. The catheter 1400 may comprise a catheter shaft 1402 having variable flexibility such that it is pushable and / or torquable to aid in maneuvering the catheter 1400 through vasculature to the target anatomy (e.g., the subclavian artery). The catheter 1400 may include an electrode platform at a distal end containing one or more neuromodulation elements (e.g., one, two, three, four, five, or more) for neuromodulation of a blood vessel and / or nerve target. The neuromodulation element(s) (not shown) may be round, segmented round, compressed ring, half-moon, or any other suitable shape. The neuromodulation element(s) may comprise one or more gold, tantalum, platinum iridium, or any other suitable materials with similar conductive properties. In some embodiments, the neuromodulation elements are electrodes, such as, for example, ring electrodes, wire electrodes, or irrigation electrodes, although suitable alternatives are also possible. The one or more neuromodulation elements and / or orientation markers may be localized in similar configurations to the catheters described above with respect to catheters 400, 400A, 400B.

[0160] The distal end of the catheter 1400 may additionally include an elongate, tubular shaping member 1408, which may be formed, for example, of a polymer, stainlesssteel, nitinol, or other suitable materials. The tubular shaping member 1408 may define a lumen within which the electrode platform is housed. As shown in Figure 15, the shaping member 1408 may comprise one or more cut-outs 1410 disposed at various radial and / or longitudinal positions along its length.

[0161] Figure 14A shows catheter 1400 disposed within a blood vessel BV, with the shaping member 1408 surrounding the electrode platform. The catheter 1400 may be actuated by a pull- wire coupled to a distal end of the shaping member 1408. The pull-wire may be housed concentrically within the lumen of the shaping member 1408 or run parallel to the shaping member 1408 inside the catheter shaft 1402. Proximal translation of the pull-wire may cause the shaping member 1408 to axially compress. The one or more cuts 1410 disposed along and / or around the body of the shaping member 1408 may cause the shaping member 1408 and electrode platform to deform into a unique, pre-determined shape upon compression, as shown, for example in Figure 14B. The curvilinear shape may be, for example, an irregular wave, a helix, or other suitable shapes described herein with respect to other embodiments. The particular shape taken upon actuation may be determined by the pattern in which the one or more cuts 1410 are disposed along the shaping member 1408. For example, the diameter and shape of the shaping member 1408 and electrode platform when in the compressed configuration may be optimized for contacting the vessel in the target location and supply stabilization away from the target contact in both distal and proximal directions. In the example shown in Figure 14B, the shaping member 1408 and electrode platform have been deformed to an irregular wave-like shape upon actuation to increase contact between the one or more neuromodulation elements 1406 and the vessel walls.

[0162] Figure 15 shows an example of the shaping member 1408 of the catheter 1400. The shaping member 1408 includes cuts 1510 positioned at various longitudinal and radial positions along the length of the shaping member 1408 cause the shaping member 1408 and electrode platform to assume the shape shown in Figure 14B upon actuation. The cuts 1510 may preferentially be partially through the shaping member 1408 and spaced between approximately 0.25 mm and approximately 1 mm apart (e.g., approximately 0.25 mm apart, approximately 0.5 mm apart, approximately 0.75 mm apart, approximately 1 mm apart, ranges between such values, and the like) allowing for increased flexibility and a preferential shape when deployed.

[0163] Figures 16-18 illustrate various components of another example catheter 1600, which can be used in connection with any of the above-described methodologies to stimulate or ablate any of the above-described nerves for any of the above-described indications. The catheter 1600 may comprise an elongate shaft 1610 forming a lumen and having variable flexibility such that it is flexible and torquable to aid in maneuvering the catheter through vasculature to the target anatomy (e.g., the subclavian artery). As shown in Figure 16, the distal end of the catheter shaft 1610 may include an electrode platform 1602 containing one or more neuromodulation elements (e.g., one, two, three, four, five, or more) for neuromodulation of a blood vessel and / or nerve target. The neuromodulation element(s) (not shown) may be round, segmented round, compressed ring, half-moon, or any other suitable shape. The neuromodulation element(s) may comprise one or more gold, tantalum, platinum iridium, or any other suitable materials with similar conductive properties. In some embodiments, the neuromodulation elements are electrodes, such as, for example, ring electrodes, wire electrodes, or irrigation electrodes, although suitable alternatives are also possible.

[0164] The proximal end of the electrode platform 1602 may extend along the length of the catheter shaft 1610 within the lumen, and a distal end of the electrode platform 1602 may extend distally from a distal end of the catheter shaft 1610. The distal end of the catheter shaft 1610 may additionally include a proximal hub (not shown) securing the catheter shaft 1610 to the electrode platform 1602. The proximal hub may be a separate component that is attached to the catheter shaft 1610 by means of gluing, welding, a screw connection, a press- fit connection, or any other suitable attachment mechanisms. Alternatively, the proximal hub may be molded on to or integrally formed with the distal end of the catheter shaft 1610. Alternatively, a proximal end of the electrode platform 1602 may be coupled to and extend distally from the proximal hub.

[0165] The catheter 1600 may additionally include a distal hub (not shown) disposed at the distal end of the electrode platform 1602. The distal hub may be a stand-alone part, or an over molded end. The distal hub may additionally be used as an exit port for a guidewire lumen. In some embodiments, the distal hub may comprise a neuromodulation element.

[0166] The electrode platform 1602 may define one or more lumens which may be lined with polyimide, or other suitable alternatives, to enhance lubricity. In some embodiments, the electrode platform 1602 defined two separate lumens - a first lumen configured to receive a shaping member 1608, and a second lumen configured to receive an actuation wire 1612. In alternate embodiments, the electrode platform 1602 may only form a single lumen capable of receiving both the shaping member 1608 and the actuation wire 1612.

[0167] The shaping member 1608 may be formed of a shape-memory material (e.g., nitinol, shape memory polymer, etc.), and formed into a desired shape (e.g., helix, irregular wave, etc.), as shown in Figure 17. The shaping member 1608 may be concentrically housed within the first lumen of electrode platform 1602 and force the electrode platform into a pre-determined shape. An actuation wire 1612 may be housed concentrically within the second lumen of the electrode platform 1602 and have sufficient axial force to overcome the pre-formed shape of the shaping member 1608 in order to extend the shaping member 1608 and the electrode platform 1602 to an elongated, delivery configuration during navigation to the target site, as shown in Figure 18A. Once the distal end of catheter 1600 is positioned in the target anatomy, the actuation wire 1612 may be removed from the electrode platform 1602, allowing the shaping member 1608 and the electrode platform 1602 to resume the pre-formed shape, as shown in Figure 18B.

[0168] Figures 19A and 19B show examples of the catheter 1600 where the electrode platform 1602 has been fully deployed (e.g., where the actuation wire 1612 has been removed from the electrode platform 1602) within a vessel wall of a blood vessel BV. As shown, the substantially helical shape of the electrode platform 1602 allows for improved contact between the neuromodulation elements and the vessel wall. One or more neuromodulation elements and / or orientation markers on the electrode platform 1602 may be localized in similar configurations to the catheters described above with respect to catheters 400, 400 A, 400B. The catheter 1600 can be rotated (e.g., between the rotational position shown in Figure 19A to the rotational position shown in Figure 19B, or another rotational position) to position the one or more neuromodulation elements of the electrode platform 1602 in contact with a particular target site on the vessel wall.

[0169] Figures 20-21B show an example of catheter 1600 where the electrode platform 1602 is designed to have a trough shape when actuated. Figure 20 shows the crestportion 1607 and trough portions 1609 of the shaping member 1608. Figure 21 A shows catheter 1600 in a delivery configuration, where the axial forces of the shaping member have been overcome by the actuation wire 1612, causing the electrode platform 1602 to assume an elongated form. Figure 21B shows the catheter 1600 after the actuation wire 1612 has been removed, allowing the shaping member 1608 and electrode platform 1602 to return to the preformed trough shape.

[0170] Figures 22 to 27C show another catheter 400B. Catheter 400B can include any of the features of the catheter 400 in Figures. 4-9D and / or catheter 400A in Figures 10-12 except as described below. Thus, reference numerals used to designate the various features or components of the catheter 400B are identical to those used for identifying the corresponding features of components of the catheter 400 in FIGS. 4-9D and catheter 400 A in Figures 10-12, except that that a “B” has been added to the numerical identifier. Therefore, the structure and description for the various features of the catheter 400 and catheter 400A and how they are operated in FIGS. 4-12 are understood to also apply to the corresponding features of the catheter 400B in FIGS. 22 to 27C, except as described below. Accordingly, the catheter 400B can include one or more features and / or components of and can be utilized in the same or similar manner as the catheters 400, 400A, in addition and / or alternatively to any features, components, and. or methods described below. The catheter 400B can be used in connection with any of the above-described methodologies to stimulate or ablate any of the abovedescribed nerves for any of the above-described indications.

[0171] Figure 22 depicts a top view of the catheter 400B. As shown in Figure 22, the catheter 400B can include a catheter shaft 410 and / or a control handle 450B. The catheter shaft 410B can be coupled to and extend distally from the control handle 450B. The catheter shaft 410B may have variable flexibility such that it is pushable and / or torque-able to aid in maneuvering the catheter 400 through vasculature to the target anatomy (e.g., the subclavian artery). The stiffness of the catheter shaft 410B can increase in a distal to proximal direction. The catheter shaft 410B can include one or more layers (e.g., outer jackets, braided shafts, liners) that contribute to the varied flexibility. As described in more detail below, the catheter 400B can include a distal portion 40 IB with or more neuromodulation elements 406B. The catheter 400B can additionally include a cable 452B and / or an electrical connector 454B coupled to the cable 452B. The cable 452B and / or electrical connector 454B can couple (e.g.,electrically couple) the catheter 400B to a power source, a signal generator (e.g., signal generator 302), a monitoring system, a robotic control system, and / or any other device. The catheter 400B can additionally include a proximal port 456B for providing proximal access to a guidewire lumen 415B of the catheter 400B.

[0172] Figures 23A to 24B depict enlarged views of the distal portion 401B of the catheter 400B. As shown in Figures 23A to 24B, the distal portion 401B of the catheter 400B can include a proximal hub 414B, an electrode platform 402B, a compression shaft 404B, and / or a distal hub 416B. The catheter shaft 410B can have an outer diameter OD1 between approximately 1 mm and approximately 10 mm (e.g., approximately 1 mm, approximately 2 mm, approximately 2.57 mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, ranges between such values, and the like). The electrode platform 402B can have an outer diameter OD2 between approximately 0.1 mm and approximately 3 mm (e.g., approximately 0.1 mm, approximately 0.25 mm, approximately 0.5 mm, approximately 0.75 mm, approximately 1 mm, approximately 1.5 mm, approximately 2 mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, ranges between such values, and the like). The compression shaft 404B can have an outer diameter OD4 between approximately 0.1 mm and approximately 5 mm (e.g., approximately 0.1 mm, approximately 0.25 mm, approximately 0.5 mm, approximately 0.75 mm, approximately 0.76 mm, approximately 1 mm, approximately 1.5 mm, approximately 2 mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, ranges between such values, and the like).

[0173] With continue reference to Figures 23 A to 24B, the electrode platform 402B can include one or more neuromodulation elements 406 for neuromodulation of a blood vessel and / or nerve target. The one or more neuromodulation elements 406B can be electrodes, although other suitable alternatives are also possible. While four neuromodulation elements 406B are shown in Figures 23A to 24B, the electrode platform 402B may include one, two, three, five, or more neuromodulation elements 406B. Each neuromodulation element 406B can have a length between approximately 0.5 mm and approximately 5 mm (e.g., approximately 0.5 mm, approximately 1 mm, approximately 1.5 mm, approximately 2 mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, ranges between such values, and the like), and multiple size electrodes may be used on the catheter 400B. Each neuromodulation element406B can have an outer diameter between approximately 0.5 mm and approximately 5 mm (e.g., approximately 0.5 mm, approximately 1 mm, approximately 1.22 mm, approximately 2 mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, ranges between such values, and the like). All of the neuromodulation elements may be activated at the same time, or each of the neuromodulation elements 406B may be selectively activated, to control the location where neuromodulation is being applied to the anatomy. The one or more neuromodulation elements 406B can be spaced along the electrode platform 402B. With reference to Figure 23 A, adjacent neuromodulation elements 406B can be spaced from each other by a distance L2 between approximately 1 mm and approximately 10 mm (e.g., approximately 2 mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, ranges between such values, and the like).

[0174] With continued reference to FIGS. 23A to 24B, the distal end of the compression shaft 404 and the distal end of the electrode platform 402 may be coupled together (e.g., fixedly coupled together) via the distal hub 416. The distal hub 416B can have a length L3. The length L3 can have a value between 1 mm and 15 mm (e.g., approximately 2 mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, approximately 11 mm, approximately 12 mm, approximately 13 mm, approximately 14 mm, approximately 15 mm, ranges between such values, and the like). The distal hub 416B can have a maximum outer diameter OD3, which can be between 1 mm and 5 mm (e.g., approximately 1 mm, approximately 2 mm, approximately 2.67 mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, ranges between such values, and the like). As shown in FIG. 23 A, the distal hub 416B can have a tapered distal tip. Accordingly, the distal hub 416B can function as a dilator to facilitate advancement of the catheter 400B through a blood vessel. In a similar respect, the maximum outer diameter OD3 of the distal hub 416B can be slightly larger than the outer diameter OD1 of the catheter shaft 410B to create clearance for more proximal portions of the catheter 400B and facilitate advancement of the catheter 400B through a blood vessel. In some embodiments, the ratio of the maximum outer diameter OD3 of the distal hub 416B to the outer diameter OD1 of the catheter shaft 410B can be between 1.01: 1 and 1.2: 1 (e.g., approximately 1.02:1, approximately 1.03:1, approximately1.04: 1, approximately 1.05:1, approximately 1.075: 1, approximately 1.1: 1, approximately 1.25: 1, approximately 1.5: 1, approximately 1.75:1, approximately 1.2:1, ranges between such values, and the like).

[0175] With continued reference to FIGS. 23 A to 24B, the proximal end of the electrode platform 402B can be fixedly coupled to the distal end of the catheter shaft 410B (e.g., at or within the proximal hub 414B). The catheter shaft 410B can define a lumen 412B for receiving the compression shaft 404B. The compression shaft 404B can axially translate within the lumen 412B of the catheter shaft 410B to transition the electrode platform 402B between an elongated configuration (e.g., a delivery configuration) and a compressed configuration (e.g., a deployed configuration). Proximal translation of the compression shaft 404B can cause the distal hub 416B to move towards the proximal hub 414B to transition the electrode platform 402B from the elongated configuration to the compressed configuration. When the electrode platform 402B is in the compressed configuration, distal translation of the compression shaft 404B can cause the distal hub 416B to move away from the proximal hub 414B to transition the electrode platform 402B back to the elongated configuration. In some implementations, robotic arm(s) and / or robotic control may be used to control the catheter system, including translation of the compression shaft 404B.

[0176] Figures 23A and 23B depict top and side views, respectively, of the catheter 400B when the electrode platform 402B is in the elongated configuration. When in the elongated configuration, the electrode platform can have a length LI between 10 mm and 100 mm (e.g., approximately 20 mm, approximately 30 mm, approximately 43 mm approximately 40 mm, approximately 50 mm, approximately 60 mm, approximately 70 mm, approximately 80 mm, approximately 90 mm, approximately 100 mm, ranges between such values, and the like). When in the elongated configuration, the electrode platform 402B and the compression shaft can collectively have an outer diameter OD5 between approximately 0.5 mm and 5 mm (e.g., approximately 0.5 mm, approximately 0.75 mm, approximately 1 mm, approximately 1.5 mm, approximately 2 mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, ranges between such values, and the like). In some embodiments, the outer diameter OD5 can be less than approximately 3 mm such that the electrode platform 402B and the compression shaft 404B can fit through an 8 Fr sheath.

[0177] Figures 24A and 24B depict top and side views, respectively, of the catheter 400B when the electrode platform 402B is in the compressed configuration. When in the compressed configuration, the electrode platform 402B can have a length L4 between 10 mm and 100 mm (e.g., approximately 10 mm, approximately 20 mm, approximately 30 mm, approximately 34 mm approximately 40 mm, approximately 50 mm, approximately 60 mm, approximately 70 mm, approximately 80 mm, approximately 90 mm, approximately 100 mm, ranges between such values, and the like). The ratio of the elongated length LI to the compressed length L4 can be between approximately 1.05: 1 and approximately 2: 1 (e.g., approximately 1.05:1, approximately 1.075:1, approximately 1.1: 1, approximately 1.25: 1, approximately 1.265:1, approximately 1.5: 1, approximately 1.75:1, approximately 2: 1, ranges between such values, and the like). When in the compressed configuration, the compressed curvilinear shape of the electrode platform 402B can have an outer diameter OD6 between 1 mm and 20 mm (e.g., approximately 1 mm, approximately 2, approximately 3 mm, approximately 4 mm, approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, approximately 11 mm, approximately 12 mm, approximately 13 mm, approximately 14 mm, approximately 15 mm, approximately 16 mm, approximately 17 mm, approximately 18 mm, approximately 19 mm, approximately 20 mm, ranges between such values, and the like). Depending on the size of the blood vessel containing the target treatment site, the outer diameter OD6 of the curvilinear shape of the electrode platform 402B can be controlled by varying the distance the compression shaft 404B is proximally retracted. Accordingly, the outer diameter OD6 of the curvilinear shape of the electrode platform 402B can be continuously variable within the diameter ranges provided above. The compression shaft 404B can be locked at a specific axial position to maintain the electrode platform 402B at a desired outer diameter OD6. In some embodiments, outer diameter OD6 of the electrode platform 402B can be constrained (e.g., via the locking mechanism or structural constraints) to a maximum value (e.g., between approximately 6 mm and approximately 10 mm) corresponding to the expected size of the blood vessel containing the treatment site (e.g., an expected inner diameter between approximately 6 mm and approximately 10 mm of a subclavian artery). The ratio of the compressed outer diameter OD6 to the elongated outer diameter OD5 can be between approximately 2: 1 and approximately 6: 1(e.g., approximately 2: 1, approximately 3: 1, approximately 4: 1, approximately 5: 1, approximately 6: 1, ranges between such values, and the like).

[0178] With continued reference to Figures 24A and 24B, when in the compressed configuration, the neuromodulation elements 406B on the electrode platform 402B can span a covered length L5 (measured from the proximal most neuromodulation element 406B to the distal most neuromodulation element 406) between 5 mm and 25 mm (e.g., approximately 5 mm, approximately 6 mm, approximately 7 mm, approximately 8 mm, approximately 9 mm, approximately 10 mm, approximately 11 mm, approximately 12 mm, approximately 13 mm, approximately 14 mm, approximately 15 mm, approximately 16 mm, approximately 17 mm, approximately 18 mm, approximately 19 mm, approximately 20 mm, approximately 21 mm, approximately 22 mm, approximately 23 mm, approximately 24 mm, approximately 25 mm, ranges between such values, and the like). The covered length L5 of the neuromodulation elements 406B can vary depending on the outer diameter OD6 of the electrode platform 402B. The value of the covered length L5 according to the ranges provided above can be sufficiently large to ensure sufficient coverage along a blood vessel to facilitate treatment at a target site. For example, based on the mapped nerve response described above, one or more of the neuromodulation elements 406B along the covered length L5 can be activated to apply stimulation or ablation energy at a specific location along the covered length L5. Accordingly, having a longer covered length L5 can advantageously increase the possible treatment area without repositioning the catheter 400B. When in the compressed configuration, the proximal most neuromodulation element 406B can be spaced from the proximal hub 414B by a length L6 between 1 mm and 50 mm (e.g., approximately 1 mm, approximately 5 mm, approximately 10 mm, approximately 20 mm, approximately 30 mm, approximately 40 mm, approximately 50 mm, approximately 80 mm, ranges between such values, and the like).

[0179] Figure 25 depicts an enlarged front view of the catheter 400B showing the electrode platform 402B in the compressed configuration. When in the compressed configuration, the neuromodulation elements 406B on the electrode platform 402B can span a covered angle 0 between approximately 30 degrees and approximately 180 degrees (e.g., approximately 30 degrees, approximately 40 degrees, approximately 50 degrees, approximately 60 degrees, approximately 70 degrees, approximately 80 degrees, approximately 90 degrees, approximately 100 degrees, approximately 110 degrees,approximately 120 degrees, approximately 130 degrees, approximately 140 degrees, approximately 150 degrees, approximately 160 degrees, approximately 170 degrees, approximately 180 degrees, ranges between such values, and the like) without spanning a region of 360 degrees minus 0. The neuromodulation elements 406B may be positioned such that they only contact one of either the ventral or dorsal side of the vessel (e.g., subclavian artery) wall to aid in targeting a particular nerves site (e.g., subclavian ansa). Accordingly, the neuromodulation elements 406B may be positioned such that the covered angle 0 is less than approximately 180 degrees to advantageously target only one half / side (e.g., one of either the ventral or dorsal side) of the blood vessel.

[0180] Figures 26A and 26B depict X-ray images of the distal portion 40 IB of the catheter 400B positioned at a target treatment site within a blood vessel BV. Figure 26A shows a lateral view and Figure 26 A shows an anterior-posterior view. As shown in Figure 26A, when the electrode platform 402B is in the compressed configuration, the neuromodulation elements 406B contact only one side of the blood vessel BV along the clocking angle 0 without contacting the other side of the blood vessel over region of (360 degrees minus 0). As shown in Figure 26B, when the electrode platform 402B is in the compressed configuration, the neuromodulation elements 406B contact one side of the blood vessel BV along the covered length L5.

[0181] Figure 27A depicts a longitudinal cross-section view of the distal hub 416B. Figure 27B depicts a transverse cross-section view of the electrode platform 402B and compression shaft 404B. As shown in Figures 27A and 27B, the electrode platform 402B can include an outer cover 43 IB, an inner member 430B, and / or a plurality of wires. The outer cover 43 IB can be a tubular body made from a polymer (e.g., polyether block amide, nylon, polyurethane and siloxane-based polymers) or other suitable materials. The outer cover 43 IB can surround the inner member 430B. The one or more neuromodulation elements 406B can be coupled to an exterior of the outer cover 43 IB via adhesive or other suitable attachment methods. The inner member 430B can be made from a shape memory material (e.g., nitinol). The shape memory material can include a single strand or multiple strands of nitinol wire. The inner member 430B can be shape-set to bias the electrode platform 402B to a desired shape (e.g., the curvilinear shape) when in the compressed configuration in response to proximal translation of the compression shaft 404B. In such embodiments, no force (e.g., from distaltranslation of the compression shaft 404B) may be required to transition the electrode platform 402B to the elongated configuration during delivery of the catheter 400B to the target site. The plurality of wires can be coupled to the one or more neuromodulation elements 406B and can couple the neuromodulation elements 406B to a power source or signal generator (e.g., the signal generator 302). The plurality of wires can be housed within the outer cover 43 IB. As shown in Figure 27B, the plurality of wires can form a plurality of separate wire pairs 432B. Each wire pair 432B can correspond and connect to one of the neuromodulation elements 406 (e.g., each of the four wire pairs 432B corresponds to one of the four neuromodulation elements 406B). In other embodiments, any number of wire pairs 432B (e.g., one, two, three, five) can be included depending on the number of neuromodulation elements 406B. The wire pairs 432B can be thermocouple wires. For example, each wire pair 432B can a type-T thermocouple formed by a copper-constantan wire pair, In other embodiments, other types of thermocouples or wires can be used. The distal end of each pair of thermocouple wires can be welded together at a corresponding neuromodulation element 406B, and the proximal end of each pair of thermocouple wires can be welded together at the circuit board 468B (see FIG. 28C). The wire pairs 432B can be used to measure temperature at each of the neuromodulation elements 406B and deliver rF energy at the neuromodulation elements 406B.

[0182] As shown in Figure 27 A, the distal ends of the electrode platform 402B and the compression shaft 404B can extend within and be coupled to (e.g., fixedly coupled to) the distal hub 416B. The compression shaft 404b can include a guidewire lumen 415B for receiving a guidewire. As shown in Figure 27 A, at least a distal portion of the guidewire lumen 415B can be defined the distal hub 416B such that the distal hub 416B defines a distal opening of the guidewire lumen 415B. As described in more detail below, the guidewire lumen 415B can extend from the distal opening at the distal hub 416B, through the compression shaft 404B, through the control handle 45 OB, and to a proximal opening at the proximal port 456B. A guidewire can be advanced through the guidewire lumen 415B to facilitate delivery of the catheter 400B to the target anatomy within a blood vessel. In some cases, the guidewire may be removed from the guidewire lumen 415B after the catheter 400B is delivered to the site of the target anatomy and replaced with another device, tool, or catheter (e.g., an ultrasound transducer to perform ablation). The guidewire lumen 415B can have an inner diameter ID1 between approximately 0.1 mm and approximately 1 mm (e.g., approximately 0.1 mm,approximately 0.2 mm, approximately 0.3 mm, approximately 0.35 mm, approximately 0.4 mm, approximately 0.5 mm, approximately 0.6 mm, approximately 0.7 mm, approximately 0.8 mm, approximately 0.9 mm, approximately 1 mm, ranges between such values, and the like).

[0183] Figure 28A depicts a top view of the control handle 450B. Figure 28B depicts a side view of the control handle 450B. Figure 28C depicts an internal top view of the control handle 450B. As shown in Figures 28A to 28C, the control handle 450B can include a housing 464B, an actuator 462B, a sealing member 466B, and / or a circuit board.468B. As shown in Figure 28 A and 28B, the housing 464B can include an elongate, narrow shape that is dimensioned to be grasped by the single hand of an operator. The housing 464B can be ergonomically shaped to enable an operator to grasp the control handle and move the actuator 462B with one hand. The housing 464B can include a generally planar or flat top surface 465B and a generally curved bottom surface 467B. The actuator 462B can extend through an opening of the top surface 465B of the housing 464B. The housing 464B can house at least portions of internal components (e.g., the sealing member 466B, the actuator 462B, and / or the circuit board 468B) of the control handle 450B.

[0184] With reference to Figure 28C, the compression shaft 404B can be coupled (e.g., fixedly coupled) to the actuator 462B. The compression shaft 404B may be directly coupled to the actuator 462B or indirectly coupled via an intermediate shaft or component. The actuator 462B can be used to control movement (e.g., axial translation) of the compression shaft 404B to move the electrode platform 402B between the elongated and compressed configurations. Specifically, the actuator 462B can be moved distally to cause distal advancement of the compression shaft 404B and elongation of the electrode platform 402B, and the actuator 462B can be moved proximally to cause proximal retraction of the compression shaft 404B and compression of the electrode platform 402B. As shown in Figures 28A to 28C, the actuator 462B can be a thumb slider that can be actuated with a thumb or other finger of an operator to cause the actuator 462B to slide or translate axially. In other embodiments, the actuator 462B can be any other mechanism or device for controlling movement of the compression shaft 404B (e.g., a switch, a button, a lever, a dial, a pin, a touch screen, an electronic control or interface, or the like). In other embodiments, the actuator 462Bcan convert other types of inputs (e.g., rotational motion, lateral translation, or electrical inputs) into movement (e.g., proximal and distal translation) of the compression shaft 404B.

[0185] With continued reference Figure 28C, the sealing member 466B can be coupled to proximal end of the catheter shaft 41 OB. The sealing member 466B can function to create a seal between the lumen 412B of the catheter shaft 41 OB and the interior cavity of the housing 464B of the control handle 45 OB. The sealing member 466B can advantageously inhibit (e.g., prevent) fluids (e.g., blood) from flowing into the interior of the control handle 450B. For instance, without a sealing member, blood driven by arterial pressure could flow through the lumen 412B of the catheter shaft 410b and into the interior of the control handle 45 OB, potentially causing short circuiting of the circuit board, impairment of the actuator, biological hazards, and / or harm to the patient due to increased blood loss. The sealing functionality of the sealing member 466B advantageously prevents these negative outcomes. The sealing member 466B can be any suitable sealing device for preventing fluid flow, including but not limited to a Tuohy Borst valve, a hemostasis valve, other types of valves, an elastic member, a compression device, or the like. As shown in Figure 28C, the compression shaft 404B may extend through the sealing member 466B and into the catheter shaft 410b.

[0186] With continued reference to Figure 28C, the circuit board 468B can create an electrical connection between the plurality of wires (e.g., the wire pairs 432B) and the cable 452B. As shown in Figure 28C, the wire pairs 432B can extend from the neuromodulation elements 406B, through the catheter shaft 41 OB, into the interior of the housing 464B, and attach to the circuit board 468B. The cable 452B can be attached to the circuit board to couple (e.g., electrically couple) the wire pairs 432B to a power source, a signal generator (e.g., signal generator 302), a monitoring system, a robotic control system, and / or any other device. The circuit board 468B can be a printed circuit board or any other device for facilitating an electrical connection between two more electrical components. In some embodiments, the wire pairs 432B, circuit board 468B, and / or cable 452B may be provided separately from the control handle 450B.

[0187] With continued reference to Figure 28C, the guidewire lumen 415B can extend from within the catheter shaft 410B (e.g., within the compression shaft 404B) into the interior of the control handle 450B, and extend to the proximal port 456B. With reference back to FIG. 22, the proximal port 456B can extend externally from the housing 464B of the controlhandle 450B to provide access to the guidewire lumen 415B. A guidewire can be inserted into the guidewire lumen 415B via a proximal opening at the proximal port 456B. From the proximal port 456B, the guidewire can be advanced through the guidewire lumen 415B and out of the distal opening at the distal hub 416B. In some embodiments, the proximal port 456B can include a connector (e.g., a luer connector or the like) for coupling to another device or catheter. In some embodiments, the guidewire lumen 45B and / or proximal port 456B may be provided separately from the control handle 45 OB.

[0188] The present disclosure relates to neuromodulation (such as stimulation) and ablation of a subject’s subclavian ansae to treat heart disease according to several embodiments. Heart disease can refer to ventricular arrythmias, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, congestive heart failure, and atrial flutter. In addition, the method and system described for neuromodulation (such as stimulation and ablation) of a subject’s subclavian ansae can also be used to treat other conditions or diseases. For example, an aspect of the present disclosure is the recognition that stellate ganglion block or denervation, or subclavian ansae ablation can also impact hemodynamic function. In some applications, sympathetic activation with pharmacological agonists or nerve stimulation can change heart rate, contractility, conduction and relaxation. In one embodiment, targeted sympathetic denervation / decentralization or block can lead to improvement in diastolic properties of the heart. Specifically, any impact in improving compliance of the left ventricle that precipitates in reduction of afterload is achieved in some embodiments. This increased compliance can positively impact stroke volume and increased cardiac output as a result. Accordingly, stellate block using neuromodulation such as ablative methods as proposed herein in some embodiments can lead to improvements in indices of diastolic function as measured by end- systolic meridional wall stress, change in peripheral vascular resistance, an increase in end diastolic volume and increased stroke volume and / or cardiac output. This can happen with or without measurable change in heart rate due to direct sympathetic effect on cardiac muscle, independent of the dromotropic effect.

[0189] Ablation may also be performed without stimulation before and / or after the ablation. For example, the ablation can be all around the subclavian artery, which includes the locations of the dorsal and ventral subclavian ansae. For another example, the ablation can be at an expected location of the subclavian ansae. For example, the longitudinal and / or radialposition of the neuromodulation element may be visualized (e.g., using fluoroscopy, ultrasound, etc.) and electrodes may be selected for the ablation energy. For example, the longitudinal and / or radial position of the neuromodulation element that has electrodes selectively positioned to correspond to expected subclavian ansae positions may be visualized (e.g., using fluoroscopy, ultrasound, etc.) and some or all of the electrodes may be selected for the ablation energy. Stimulation may be only applied after ablation to verify the effect of the ablation in one embodiment.

[0190] While certain methods described herein relate to therapeutic methods, any of the methods may be modified to only non-therapeutically stimulate the subclavian ansae using the catheter systems described herein. The applied energy may can map, confirm or otherwise indicate that the nerves feeding the heart are affected by the application of the energy by a change in a heart condition as indicated by monitoring at least one heart parameter without providing a therapeutic effect.Kits

[0191] The disclosure describes kits comprising the devices and components described elsewhere herein. In some cases, the kit may comprise one or more of the catheters described herein. The kit may include one or more of a shipping mandrel, a valve insertion tool, a saline flushing connector, a guidewire, a guide catheter, an electrical connector cable and / or other components elsewhere described herein. The kit may include instructions for positioning the catheter at the target anatomy. The instructions may comprise instructions in an insert, and / or on a website (e.g., navigated to through a QR code). The instructions may include directions for deploying the electrode platform.Therapies for Combined Neuromodulation of Sympathetic and Parasympathetic Targets

[0192] As described herein, ablation of a sympathetic target (e.g., subclavian ansa, stellate ganglion, etc.) may be used to suppress certain cardiac arrhythmias such as atrial fibrillation or ventricular tachycardia. The efficacy of this therapy may be enhanced when suppression of sympathetic activity is combined with enhancement of parasympathetic activity, further shifting the patient’s autonomic balance. Chronic stimulation therapies following sympathetic ablation advantageously provide an opportunity to sense patientspecific arrhythmia conditions (e.g., via leadless ECG, via a cardiac lead, etc.) to allow stimulation parameters to be adjusted on a case-by-case basis in response to arrhythmiadetection. Accordingly, acute ablation of a sympathetic target (e.g., subclavian ansa, stellate ganglion, etc.) combined with implantation of a second acute or chronic therapy (e.g., a stimulation device) with a parasympathetic target may be desired.

[0134] For example, a system for combined neuromodulation of both sympathetic and parasympathetic nerve targets may comprise any of the systems described herein coupled with a chronic therapy having an implantable stimulator with a lead configured to stimulate a peripheral nerve (e.g., vagal nerves, splanchnic nerves, branches thereof, etc.). The lead may be a nerve cuff or self-sizing helix, or a transvascular stimulation lead. Additionally, or alternatively, stimulation may be delivered to the Lumbar Sympathetic Chain (LSC) or baroreceptors, and / or stimulation may be delivered to parasympathetic ganglia on the epicardial surface of the heart. Prior to and / or following stimulation, renal denervation or ablation of sympathetic ganglia on the epicardial surface of the heart may be performed. Pharmacological Therapies

[0193] In several embodiments, the neuromodulation therapies described herein can be used to replace pharmacological (drug) therapies. In other embodiments, however, drug therapies may be used in combination with the neuromodulation therapies described herein, but with reduced frequency or dose, thus reducing undesired side effects. For example, a certain drug (or drug combination) may be administered for a shorter overall duration, fewer times per day / week / month, and / or at a lower dose when combined with the neuromodulation described herein. In addition to reducing undesired pharmacological side effects, this may also reduce addiction or dependence. The neuromodulation described herein may also be used to taper or otherwise wean subjects off of pain and other medications.

[0194] Certain experiments are described with respect to application of medicaments, for example to induce certain physiological conditions before, during, and / or after stimulation and / or ablation. The devices and methods described herein can be used without administered medicaments (e.g., without medicaments inducing certain physiological conditions). Anesthetics and other medicaments that enable electrode contact placement, for example, may be used. Substances released by the subject in response to stimulation (e.g., calcitonin gene-related peptide (CGRP)) would not be considered an administered medicament.Terminology

[0195] The foregoing description and examples are set forth merely to illustrate the inventive concepts and are not intended as being limiting. Each of the disclosed aspects and examples of the present disclosure may be considered individually or in combination with other aspects, examples, and variations of the disclosure. In addition, unless otherwise specified, none of the steps of the methods of the present disclosure are confined to any particular order of performance. Reasonable modifications of the disclosed examples incorporating the spirit and substance of the disclosure are within the scope of the present disclosure. Furthermore, all references cited herein are incorporated by reference in their entirety. Headings used herein are for organizational purposes only and should not be used to unduly limit claim scope or embodiments.

[0196] While the methods and devices described herein may be susceptible to various modifications and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the embodiments are not to be limited to the particular devices or methods disclosed, but, to the contrary, cover all reasonable modifications, equivalents, and alternatives falling within the spirit and scope of the various examples described and the appended claims. Further, the disclosure herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with an example can be used in all other examples set forth herein. Any methods disclosed herein need not be performed in the order recited. Depending on the example, one or more acts, events, or functions of any of the algorithms, methods, or processes described herein can be performed in a different sequence, can be added, merged, or left out altogether (e.g., not all described acts or events are necessary for the practice of the algorithm). Algorithms, modules, blocks, steps, boxes, elements, features, etc. may be stored in machine-readable memory. In some examples, acts or events can be performed concurrently, e.g., through multi -threaded processing, interrupt processing, or multiple processors or processor cores or on other parallel architectures, rather than sequentially. Further, no element, feature, block, box, or step, or group of elements, features, blocks, boxes, or steps, are necessary or indispensable to each example. Additionally, all possible combinations, subcombinations, and rearrangements of systems, methods, features, elements, modules, blocks, boxes, and so forth are within the scope of this disclosure. The use ofsequential, or time-ordered language, such as “then,” “next,” “after,” “subsequently,” and the like, unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to facilitate the flow of the text and is not intended to limit the sequence of operations performed. Thus, some examples may be performed using the sequence of operations described herein, while other examples may be performed following a different sequence of operations.

[0197] The various illustrative logical blocks, boxes, modules, processes, methods, and algorithms described in connection with the examples disclosed herein can be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, operations, and steps have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system. The described functionality can be implemented in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the disclosure.

[0198] The various illustrative logical blocks and modules described in connection with the examples disclosed herein can be implemented or performed by a machine, such as a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general-purpose processor can be a microprocessor, but in the alternative, the processor can be a controller, microcontroller, or state machine, combinations of the same, or the like. A processor can also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[0199] The blocks, operations, or steps of a method, process, or algorithm described in connection with the examples disclosed herein can be embodied directly in hardware, in a software module executed by a processor, or in a combination of the two. A software module can reside in RAM memory, flash memory, ROM memory, EPROMmemory, EEPROM memory, registers, hard disk, a removable disk, an optical disc (e.g., CD- ROM or DVD), or any other form of volatile or non-volatile computer-readable storage medium known in the art. A storage medium can be coupled to the processor such that the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium can be integral to the processor. The processor and the storage medium can reside in an ASIC. The ASIC can reside in a user terminal. In the alternative, the processor and the storage medium can reside as discrete components in a user terminal.

[0200] Conditional language used herein, such as, among others, “can,” “might,” “may,” “e.g.,” and the like, unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that some examples include, while other examples do not include, certain features, elements, and / or states. Thus, such conditional language is not generally intended to imply that features, elements, blocks, and / or states are in any way required for one or more examples or that one or more examples necessarily include logic for deciding, with or without author input or prompting, whether these features, elements and / or states are included or are to be performed in any particular example.

[0201] The methods disclosed herein may include certain actions taken by a practitioner; however, the methods can also include any third-party instruction of those actions, either expressly or by implication. For example, actions such as “stimulating a nerve” include “instructing stimulation of a nerve.”

[0202] The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “about” or “approximately” include the recited numbers and should be interpreted as ±15%. For example, “about 1 mm” includes “1 mm.” Phrases preceded by a term such as “substantially” include the recited phrase and should be interpreted based on the circumstances (e.g., as much as reasonably possible under the circumstances). For example, “substantially parallel” includes “parallel.” Unless stated otherwise, all measurements are at standard conditions including temperature and pressure. The phrase “at least one of’ is intended to require at least one item from the subsequent listing, not one type of each item in the subsequent listing. For example, “at least one of A, B, and C” can include A, B, C, A and B, A and C, B and C, or A, B, and C.

[0203] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure pertains. As used herein, the singular forms “a,” “an,” and “the” can also include the plural forms, unless the context clearly indicates otherwise. As used herein, the terms “comprises” and / or “comprising,” can specify the presence of stated features, steps, operations, elements, components, and / or groups, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups. As used herein, the term “and / or” can include any and all combinations of one or more of the associated listed items. As used herein, the terms “first,” “second,” etc. should not limit the elements being described by these terms. These terms are only used to distinguish one element from another. Thus, a “first” element discussed below could also be termed a “second” element without departing from the teachings of the present disclosure. The sequence of operations (or acts / steps) is not limited to the order presented in the claims or figures unless specifically indicated otherwise.

[0204] As used herein, the term “neuromodulation” can refer to an electrical signal delivered as a therapy to neural tissue. In some instances, the neural tissue can include at least a portion of the sympathetic chain. For example, the sympathetic chain can refer to the lumbar sympathetic chain (LSC). As used herein, the term “sympathetic nervous system” can refer to a portion of the autonomic nervous system that activates the “Fight or Flight” response (generally accelerating heart rate, dilating pupils, dilating bronchioles, inhibiting digestion, constricting blood vessels, increasing cardiac output, and raising blood pressure, etc.), which prepares the body for intense physical activity. As used herein, the term “electrical signal” can refer to a time-varying voltage or current. As an example, the electrical signal can be represented by a waveform (a graphical representation of changes in current or voltage over time). As used herein, the term “electrode contact” can refer to a material acting as a conductor through which electricity enters or leaves. At least a portion of the material can be a biocompatible material. As used herein, the terms “subject” and “patient” can be used interchangeably and refer to any warm-blooded organism including, but not limited to, a human being, a pig, a rat, a mouse, a dog, a cat, a goat, a sheep, a horse, a monkey, an ape, a rabbit, a cow, etc.

Claims

WHAT IS CLAIMED IS:

1. A catheter, the catheter comprising: a catheter shaft defining an axis and a lumen; a compression shaft disposed with the lumen of the catheter shaft; an electrode platform having a curvilinear shape extending only partially around the compression shaft for localized contact with target anatomy, the curvilinear shape comprising a proximal turn and a distal turn; one or more neuromodulation elements positioned on the electrode platform, a distal hub, the distal hub being coupled to a distal end of the electrode platform and a distal end of the compression shaft; and an actuator configured to translate the compression shaft along the axis of the catheter shaft, wherein the translation of the compression shaft causes the electrode platform to transition between an elongated configuration and a compressed configuration.

2. The catheter of claim 1 , wherein the curvilinear shape extends less than 300° around the compression shaft.

3. The catheter of claim 1 or 2, wherein, in the compressed configuration, the neuromodulation elements are positioned on the electrode platform to only contact a dorsal subclavian ansa or a ventral subclavian ansa, in use.

4. The catheter of any one of claims 1 to 3, wherein translation of the compression shaft in a proximal direction causes the electrode platform to transition from the elongated configuration to the compressed configuration.

5. The catheter of any one of claims 1 to 4, wherein translation of the compression shaft in a distal direction causes the electrode platform to transition from the compressed configuration to the elongated configuration.

6. The catheter of any one of claims 1 to 5, wherein: the electrode platform has a curvilinear shape extending less than 260 degrees around the compression shaft, the curvilinear shape comprising a proximal turn and a distal turn;the one or more neuromodulation elements are positioned on a neuromodulation portion of the electrode platform, the neuromodulation portion extending only partially along the electrode platform; translation of the compression shaft in a proximal direction causes the electrode platform to transition from an elongated configuration to a compressed configuration; and translation of the compression shaft in a distal direction causes the electrode platform to transition from the compressed configuration to the elongated configuration.

7. A catheter comprising: a catheter shaft configured to be positioned in at least one of a left subclavian artery or a right subclavian artery and defining an axis and a lumen; a compression shaft disposed within the lumen of the catheter shaft; an electrode platform having a curvilinear shape extending less than 260 degrees around the compression shaft, the curvilinear shape comprising a proximal turn and a distal turn; one or more neuromodulation elements positioned on a neuromodulation portion of the electrode platform, the neuromodulation portion extending only partially along the electrode platform and configured to only contact a dorsal subclavian ansa or a ventral subclavian ansa; and a distal hub, the distal hub being coupled to a distal end of the electrode platform and a distal end of the compression shaft; wherein translation of the compression shaft in a proximal direction causes the electrode platform to transition from an elongated configuration to a compressed configuration; and wherein translation of the compression shaft in a distal direction causes the electrode platform to transition from the compressed configuration to the elongated configuration.

8. The catheter of any one of claims 1 to 7, wherein, in the compressed configuration, the compression shaft is configured to contact an opposing wall of the left subclavian artery and / or the right subclavian artery.

9. The catheter of any one of claims 1 to 8, wherein the one or more neuromodulation elements span a covered angle between 90 degrees and 180 degrees when the electrode platform is in the compressed configuration.

10. The catheter of any one of claims 1 to 9, wherein the curvilinear shape of the electrode platform has an outer diameter between 6 mm and 10 mm when in the compressed configuration.

11. The catheter of any one of claims 1 to 10, wherein a ratio of a compressed outer diameter of the curvilinear shape to an elongated outer diameter of the curvilinear shape is between 2: 1 and 6:1.

12. The catheter of any one of claims 1 to 11 , wherein the one or more neuromodulation elements span a covered length between 10 mm and 15 mm when the electrode platform is in the compressed configuration.

13. The catheter of any one of claim 1 to 12, wherein the curvilinear shape is helical.

14. The catheter of any one of claims 1 to 13, wherein the electrode platform further comprises an inner member comprising a shape memory material and an outer polymer member surrounding the inner member.

15. The catheter of claim 14, wherein the inner member is pre-shaped to the compressed configuration.

16. The catheter of claim 14, wherein the inner member is pre-shaped to bias towards the compressed configuration in response to translation of the compression shaft in a proximal direction.

17. The catheter of any one of claims 1 to 16, further comprising a proximal hub coupled to a distal end of the catheter shaft, wherein a proximal end of the electrode platform is coupled to the proximal hub.

18. The catheter of any one of claims 1 to 17, further comprising one or more fluoroscopic markers disposed on the electrode platform.

19. The catheter of any one of claims 1 to 18, wherein the one or more neuromodulation elements are electrodes comprising one of the following shapes: round, segmented round, compressed ring, and half-moon.

20. The catheter of any one of claims 1 to 19, wherein the one or more neuromodulation elements comprise one or more of: gold, tantalum and / or platinum iridium.

21. The catheter of any one of claims 1 to 20, wherein the catheter is configured to be positioned in a subclavian artery, a renal artery, a pulmonary artery, a carotid artery, a brachiocephalic artery, or an internal jugular vein.

22. The catheter of any one of claims 1 to 21, wherein the catheter is configured to deliver energy to a subclavian ansa, an aorticorenal ganglion, a cardiac pulmonary nerve, cardiac plexus, asuperior and / or middle and / or inferior cervical cardiac nerve, a superior and / or inferior cervical cardiac nerve, or a vagus nerve.

23. A kit comprising: a catheter of any one of claims 1 to 22; and instructions for placing the one or more neuromodulation elements against target anatomy.

24. A neuromodulation system comprising: a catheter of any one of claims 1 to 22; and a power source configured to deliver energy to the one or more neuromodulation elements.

25. A catheter for treating a condition in a subject, the catheter comprising: a catheter shaft configured to be positioned in at least one of a left subclavian artery or a right subclavian artery and defining an axis and a lumen; a compression shaft disposed within the lumen of the catheter shaft; an electrode platform having a curvilinear shape extending only partially around the compression shaft, the curvilinear shape comprising a proximal turn and a distal turn; one or more electrodes positioned on a neuromodulation portion of the electrode platform, the neuromodulation portion extending only partially along the electrode platform; a distal hub, the distal hub being coupled to a distal end of the electrode platform and a distal end of the compression shaft; and an actuator configured to translate the compression shaft along the axis of the catheter shaft, wherein the translation of the compression shaft causes the electrode platform to transition between an elongated configuration and a compressed configuration.

26. The catheter of claim 25, wherein the curvilinear shape is helical.

27. The catheter of claim 25 or 26, wherein the neuromodulation portion of the electrode platform is located on the proximal turn.

28. The catheter of any one of claims 25 to 27, further comprising a proximal hub coupled to a distal end of the catheter shaft, wherein a proximal end of the electrode platform is coupled to the proximal hub.

29. The catheter of any of claims 25 to 28, further comprising one or more fluoroscopic orientation markers.

30. The catheter of claim 29, wherein the one or more orientation markers are disposed on the electrode platform at a location between the proximal hub and the neuromodulation portion.

31. The catheter of any one of claims 25 to 30, wherein translation of the compression shaft in a proximal direction causes the electrode platform to transition from the elongated configuration to the compressed configuration.

32. The catheter of any one of claims 25 to 31, wherein translation of the compression shaft in a distal direction causes the electrode platform to transition from the compressed configuration to the elongated configuration.

33. The catheter of any one of claims 25 to 32, wherein the one or more electrodes are configured to contact a dorsal subclavian ansa and / or a ventral subclavian ansa, and the compression shaft is configured to contact an opposing wall of the left subclavian artery and / or the right subclavian artery.

34. The catheter of any one of claims 25 to 33, wherein the one or more electrodes are ring electrodes.

35. The catheter of any one of claims 25 to 34, further comprising an electrode disposed on the distal hub.

36. A method of treating heart disease in a subject, the method comprising: percutaneously introducing a catheter into vasculature of the subject, wherein the catheter comprises a neuromodulation element; positioning the neuromodulation element in a subclavian artery of the subject; translating a compression shaft in a proximal direction, wherein the translating causes an electrode platform located at a distal end of the catheter to transition from anelongated configuration to a compressed configuration and wherein, in the compressed configuration, the electrode platform contacts only one of a dorsal subclavian ansa or a ventral subclavian ansa and the compression shaft contacts an opposing vessel wall of the subclavian artery of the subject; stimulating the only one of the dorsal subclavian ansa or the ventral subclavian ansa; confirming stimulation of the dorsal subclavian ansa and / or the ventral subclavian ansa by monitoring a cardiac parameter; and after confirming stimulation of the dorsal subclavian ansa and / or the ventral subclavian ansa, providing ablation energy to the dorsal subclavian ansa and / or the ventral subclavian ansa.

37. The method of claim 36, further comprising, after providing ablation energy, restimulating the the dorsal subclavian ansa and / or the ventral subclavian ansa and, if a cardiac parameter confirms stimulation, providing further ablation energy to the the dorsal subclavian ansa and / or the ventral subclavian ansa.

38. The method of claim 37, further comprising repeating the restimulating and providing further ablation energy until the cardiac parameter does not confirm stimulation.

39. The method of any one of claims 36 to 38, further comprising rotating the catheter and stimulating the other of the dorsal subclavian ansa or the ventral subclavian ansa.

40. The method of any one of claims 36 to 39, wherein percutaneously introducing the catheter to the vasculature comprises inserting the catheter into one of a femoral artery of the subject, a radial artery of the subject, or a carotid artery of the subject.

41. The method of any one of claims 36 to 40, wherein percutaneously introducing the catheter to the vasculature comprises inserting the catheter into a femoral vein of the subject, and wherein at least one of positioning the neuromodulation element in a left subclavian artery or positioning the neuromodulation element in a right subclavian artery comprises crossing from venous vasculature to arterial vasculature.

42. The method of any one of claims 36 to 41 , wherein positioning the neuromodulation element in the subclavian artery of the subject comprises positioning the neuromodulation element against a dorsal subclavian ansa and / or a ventral subclavian ansa and positioning the compression shaft against an opposing wall of the subclavian artery.

43. The method of any one of claims 36 to 42, wherein translating the compression shaft proximally causes the electrode platform to transition from an elongated curvilinear shape to a compressed curvilinear shape, wherein a radius of each turn in the elongated curvilinear shape is less than a radius of each turn in the compressed curvilinear shape.

44. The method of any one of claims 36 to 43, further comprising translating the compression shaft distally to cause the electrode platform to transition from the compressed configuration to the elongated configuration.

45. The method of any one of claims 36 to 44, further comprising monitoring an orientation of the neuromodulation element in the vasculature of the subject using fluoroscopic imaging.

46. A neuromodulation system comprising: a catheter comprising: a catheter shaft and defining an axis and a lumen; a compression shaft disposed with the lumen of the catheter shaft; an electrode platform having a curvilinear shape extending only partially around the compression shaft; one or more neuromodulation elements positioned on the electrode platform, a distal hub, the distal hub being coupled to a distal end of the electrode platform and a distal end of the compression shaft; and an actuator configured to translate the compression shaft along the axis of the catheter shaft, wherein the translation of the compression shaft causes the electrode platform to transition between an elongated configuration and a compressed configuration; and a power source configured to deliver energy to the one or more neuromodulation elements.

47. The neuromodulation system of claim 46, wherein the curvilinear shape is helical.

48. The neuromodulation system of claim 46 or 47, wherein the catheter shaft is configured to be positioned in at least one of a left subclavian artery or a right subclavian artery.

49. The neuromodulation system of any one of claims 46 to 48, wherein the catheter further comprises one or more fluoroscopic markers disposed on the electrode platform.

50. The neuromodulation system of any one of claims 46 to 49, further comprising a mapping system configured to display the position of the one or more neuromodulation elements in a patient’s anatomy.

51. The neuromodulation system of claim 50, wherein the mapping system comprises a processor and a display.

52. A catheter for treating heart disease in a subject, the catheter comprising: a catheter shaft defining an axis and a lumen; a compression shaft disposed with the lumen of the catheter shaft; a neuromodulation platform having a curvilinear shape extending only partially around the compression shaft and configured to not touch at least a partial circumferential region of a target vessel, in use; one or more neuromodulation elements positioned on the neuromodulation platform, a distal hub, the distal hub being coupled to a distal end of the neuromodulation platform and a distal end of the compression shaft; and an actuator configured to translate the compression shaft along the axis of the catheter shaft, wherein the translation of the compression shaft causes the neuromodulation platform to transition between an elongated configuration and a compressed configuration.

53. The catheter of claim 52, wherein a covered angle of the one or more neuromodulation elements is less than 180 degrees, less than 150 degrees, or less than 120 degrees.

54. The catheter of claim 52 or 53, wherein a covered length of the one or more neuromodulation elements is less than 20 mm, less than 15 mm, or less than 10 mm.

55. The catheter of any one of claims 52 to 54, wherein when viewed from a distal end of the catheter, the one or more neuromodulation elements are positioned in no more than two adjacent quadrants.

56. The catheter of any one of claims 52 to 55, wherein the curvilinear shape extends less than 300 degrees, less than 270 degrees, less than 225 degrees, or less than 180 degrees around the compression shaft.

57. The catheter of any one of claims 52 to 56, wherein the one or more neuromodulation elements are electrodes.

58. A method of modulating and / or ablating a subclavian ansa having one or more of the features described in the foregoing description.

59. A treatment system having one or more of the features described in the foregoing description.

60. A tissue treatment system having one or more of the features described in the foregoing description.

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