Catheter for subclavian loop neuromodulation

Abstract

Methods of treating a subject for heart disease include introducing a catheter transcutaneously into the vasculature of the subject. The catheter can include a neuromodulation element. The neuromodulation element can be positioned on a flexing element. The flexing element can be deflected away from or toward a central axis defined by the catheter in response to an operator pulling or releasing a pull wire. The neuromodulation element of the catheter can be positioned in the subclavian artery of the subject. The catheter can be used to selectively target and electrically stimulate at least one of a dorsal subclavian loop or a ventral subclavian loop. The method can include confirming stimulation of the dorsal subclavian loop and / or the ventral subclavian loop by monitoring a cardiac parameter. Upon confirmation of stimulation of the dorsal subclavian loop and / or the ventral subclavian loop, ablation energy can be provided to the dorsal subclavian loop and / or the ventral subclavian loop.

Description

[0001] Incorporation through citation of any priority claim This application claims priority to U.S. Provisional Application No. 63 / 615632, filed December 28, 2023; U.S. Provisional Application No. 63 / 643821, filed May 7, 2024; and U.S. Provisional Application No. 63 / 677837, filed July 31, 2024, each of which is incorporated herein by reference in its entirety. Technical Field

[0002] This disclosure generally relates to systems and methods for promoting modulation (e.g., denervation, ablation), and in some embodiments more specifically relates to systems and methods for promoting the left and / or right subclavian peripheral nerves of a therapeutically modulated subject to treat heart disease (e.g., atrial fibrillation). Background Technology

[0003] Ventricular arrhythmias cause more than 80,000 deaths annually in the UK and more than 150,000 annually in the US. The vast majority of ventricular arrhythmias are associated with coronary artery disease and / or heart failure, but the associated morbidity and cost burden far exceed these figures. Cardiovascular disease accounts for £12 billion annually in direct healthcare spending in the UK and an estimated $378 billion annually in direct and indirect costs in the US. Heart failure and associated arrhythmia care are major drivers of expenditure. Atrial fibrillation (AF) is a common and significant medical problem affecting approximately 3% of the population. In the US, the prevalence of AF is estimated to increase from approximately 5.2 million in 2010 to approximately 12.1 million in 2030. Individuals with AF have an increased risk of death (both men and women), with an age-adjusted mortality rate of 6.5 deaths per 100,000 people. AF is associated with increased risk factors for other cardiovascular conditions, including heart failure, myocardial infarction, sudden cardiac death, diabetes, gastrointestinal bleeding, and stroke. Summary of the Invention

[0004] Cardiac arrhythmias are caused by heterogeneity within the myocardium, but dynamic changes in sympathetic (adrenergic) and parasympathetic (cholinergic) signaling can exacerbate these arrhythmias. In heart disease, the brainstem sends stronger sympathetic signals that travel to the heart via the thoracic sympathetic nerves. Most surgical denervation procedures (e.g., stellate ganglionectomy) involve surgeons locating the ganglia and, based on experience, removing the thoracic (T1-T4) levels of the sympathetic ganglia, as these are the most easily accessible nerves. This can be accompanied by side effects that negatively impact the patient's quality of life.

[0005] The nerve surrounding the blood vessel supplying the arm (subclavian artery) is called the subclavian loop, which connects to two paravertebral sympathetic ganglia on the same side of the body, thus forming a highly selective sympathetic innervation pathway to the heart. Therefore, according to several embodiments described herein, targeting and ablating one or both subclavian loops is a novel mechanism for selectively modulating cardiac sympathetic innervation. In one embodiment, energy is applied to these nerves for non-therapeutic stimulation, and the effects of the energy application on the heart-feeding nerves can be confirmed or otherwise indicated by monitoring changes in cardiac condition as indicated by at least one cardiac parameter (e.g., heart rate). Energy can then be applied long-term to ablate or destroy the affected nerves (which has beneficial effects on the heart) to reduce cardiac electrical heterogeneity and decrease the further progression of pathological diseases. Both the left and right subclavian arteries are surrounded by a posterior (dorsal) and anterior (ventral) subclavian loop, and in one embodiment, the user can selectively target and ablate any of these four nerves to any desired degree to achieve different effects. In one implementation, the stimulation is not therapeutic but is used to identify the site for therapeutic ablation. The term "ablation" or "ablation energy" as described herein should be given a general meaning and may be reversible or irreversible, and may include denervation, destruction of all or part of nerves, and / or interruption of nerve signals.

[0006] The systems and methods described herein can be used to treat a variety of conditions, such as ventricular arrhythmias, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, congestive heart failure, atrial flutter, or any combination thereof.

[0007] In some embodiments, the technology described herein relates to catheters for treating a patient with a heart condition (e.g., ventricular arrhythmias, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, congestive heart failure, atrial flutter, or any combination thereof). The catheter may include a catheter shaft configured to be positioned in at least one of the left or right subclavian arteries, defining a central axis. The catheter may include a flexion element at a distal portion of the catheter, the flexion element comprising: a proximal hub coupled to the distal end of the catheter shaft; at least one elongated leg, the proximal end of which is coupled to the proximal hub; a distal hub coupled to the distal end of the at least one elongated leg; and a drawwire positioned off-axis relative to the central axis. The distal end of the drawwire may be coupled to the distal hub. At least one elongated leg is configured to deflect away from the central axis in response to a proximal pull by an operator along the proximal direction. A neuromodulation element may be present, which is positioned on a flexure element and configured to selectively target and stimulate at least one of the dorsal or ventral subclavian loops and / or configured to selectively target and ablate at least one of the dorsal or ventral subclavian loops. The neuromodulation element is a neuromodulation element of a catheter in the subclavian artery of the subject, and the neuromodulation element includes one or more electrodes.

[0008] In some embodiments, the technology described herein relates to catheters for treating a patient with a heart condition (e.g., ventricular arrhythmia, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, congestive heart failure, atrial flutter, or any combination thereof). The catheter may include a catheter shaft configured to be positioned in at least one of the left or right subclavian arteries and defining a central axis. The catheter may further include a flexure element at a distal portion of the catheter. The flexure element may include a proximal hub coupled to a distal end of the catheter shaft and at least one elongated leg, the proximal end of each of the at least one elongated leg being coupled to the proximal hub. The at least one elongated leg may be configured to deflect away from the central axis and form a bend. When deflected away from the central axis, the at least one elongated leg may extend less than 270 degrees about the central axis. The catheter may further include a distal hub coupled to the distal end of the at least one elongated leg and coupled to the distal end of a drawwire. A neuromodulation element may be present, positioned on the flexure of at least one leg, configured to selectively target and stimulate at least one of the dorsal or ventral subclavian loops and / or configured to selectively target and ablate at least one of the dorsal or ventral subclavian loops, the neuromodulation element being a neuromodulation element of a conduit in the subclavian artery of the subject, the neuromodulation element comprising one or more electrodes.

[0009] In some embodiments, methods for treating a subject's cardiac condition (such as atrial fibrillation) include transdermal or percutaneous introduction of a catheter into the subject's vascular system. The catheter includes a neuromodulation element. This neuromodulation element is capable of providing stimulation and / or treatment (e.g., ablation or denervation). For example, in some embodiments, the same electrode can provide both stimulation and treatment. However, in other embodiments, a separate electrode can provide stimulation from the electrode providing treatment. The separate electrodes providing stimulation and treatment can be on the same catheter or different catheter devices. Neuromodulation target sites (e.g., the subclavian loop) can be located percutaneously (e.g., via percutaneous ultrasound). The method may include positioning a neuromodulation element in the subject's left subclavian artery, electrically stimulating the left dorsal subclavian loop, confirming stimulation of the left dorsal subclavian loop by monitoring a first cardiac parameter, and, after confirming stimulation of the left dorsal subclavian loop, providing ablation energy to the left dorsal subclavian loop; electrically stimulating the left ventral subclavian loop, confirming stimulation of the left ventral subclavian loop by monitoring a second cardiac parameter, and, after confirming stimulation of the left ventral subclavian loop, providing ablation energy to the left ventral subclavian loop. The procedure involves: positioning a neuromodulation element in the right subclavian artery of the subject; electrically stimulating the right dorsal subclavian loop; confirming stimulation of the right dorsal subclavian loop by monitoring a third cardiac parameter; and, after confirming stimulation of the right dorsal subclavian loop, providing ablation energy to the right dorsal subclavian loop; electrically stimulating the right ventral subclavian loop; confirming stimulation of the right ventral subclavian loop by monitoring a fourth cardiac parameter; and, after confirming stimulation of the right ventral subclavian loop, providing ablation energy to the right ventral subclavian loop. In some embodiments, an ablation temperature may be delivered to heat the target tissue to 40°C to 80°C for a duration of 20 to 240 seconds. Optionally, cooling of non-target tissue may be provided; however, in several embodiments, cooling is not required. In some embodiments, ablation energy is simultaneously applied to the left ventral and left dorsal subclavian loops after stimulation. In some embodiments, ablation energy is simultaneously applied to the right ventral and right dorsal subclavian loops after stimulation. In several embodiments, one or more sensing elements (including, but not limited to, stimulating elements) are used to locate nerves (e.g., diagnostically or non-therapeutoriously) or provide mapping, while one or more ablation elements are used for therapeutic denervation. In one embodiment, these elements are the same elements that can be used for both sensing and treatment. In another embodiment, the sensing element(s) are different from the therapeutic element(s). In yet another embodiment, there is overlap between the sensing (e.g., stimulating) element and the therapeutic (e.g., ablation) element.

[0010] The first cardiac parameter may differ from at least one of the second, third, or fourth cardiac parameters. The second cardiac parameter may differ from at least one of the first, third, or fourth cardiac parameters. The third cardiac parameter may differ from at least one of the first, second, or fourth cardiac parameters. The fourth cardiac parameter may differ from at least one of the first, second, or third cardiac parameters. The first cardiac parameter may be the same as at least one of the second, third, or fourth cardiac parameters. The second cardiac parameter may be the same as at least one of the first, third, or fourth cardiac parameters. The third cardiac parameter may be the same as at least one of the first, second, or fourth cardiac parameters. The fourth cardiac parameter may be the same as at least one of the first, second, or third cardiac parameters.

[0011] At least one of the first, second, third, or fourth cardiac parameters may include changes in arterial trajectory blood pressure (e.g., changes in systolic and / or diastolic blood pressure), whether AF is induced, whether arrhythmia is induced (e.g., ectopic beats, irregular ECG activity, etc.), whether changes in cardiac cycle length are induced, repetitive recovery curve, right atrial effective refractory period (“ERP”), left atrial ERP, dERP, heart rate, interatrial conduction time (“IACT”), P wave duration and / or dispersion, mean sinus cycle length, RR interval, or at least one of the following on a monopolar electrogram of a multipolar catheter under steady-state RV pacing or short DI after steady-state RV pacing. The method may further include restimulating the subclavian loop after providing ablation energy, and providing further ablation energy to the subclavian loop if the cardiac parameters confirm the stimulation. The method may include repeated restimulation and provision of further ablation energy until the cardiac parameters do not confirm the stimulation. The catheter may include an expansion element on which a neuromodulation element is positioned. The expansion element may be expanded to dilate the vascular system. Inflatable elements include, for example, balloons or inflatable cages.

[0012] The method may include steps such as bringing the neural target closer to the neuromodulation element by dilating the wall of a blood vessel near the nerve or by focally dilating a small portion of the arterial wall. This allows the neuromodulation element to be positioned closer to the nerve, thus enabling stimulation, ablation, and / or denervation. The catheter may include an inflatable element, such as a balloon or inflatable cage, on which the neuromodulation element may be positioned. The inflatable cage may inflate mechanically or self-inflate, for example, using shape memory materials. The inflatable element may be an inflatable element that dilates a vascular system. In other embodiments, the catheter may include non-inflatable structures, such as enlarged or maneuverable portions, to bring the neural target closer to the neuromodulation element.

[0013] In some embodiments, a method of treating a subject's heart disease includes introducing a catheter transdermally or percutaneously into the subject's vascular system. The catheter includes a neuromodulation element (e.g., one or more neurostimulation elements). The method further includes positioning the neuromodulation element in the subject's subclavian artery, electrically stimulating the subclavian loop, confirming stimulation of the subclavian loop by monitoring a first cardiac parameter, and, after confirming stimulation of the subclavian loop, providing ablation energy to the subclavian loop. In some embodiments, after electrically stimulating the subclavian loop and confirming stimulation, ablation energy is provided to the subclavian loop (towards the dorsal subclavian loop, the ventral subclavian loop, or simultaneously or sequentially to both). The neuromodulation target site (e.g., the subclavian loop) can be located percutaneously (e.g., percutaneous ultrasound).

[0014] The first cardiac parameter may differ from the second cardiac parameter. The first cardiac parameter may be the same as the second cardiac parameter. At least one of the first or second cardiac parameters may include arterial trajectory blood pressure changes (e.g., changes in systolic and / or diastolic blood pressure), whether AF is induced, whether arrhythmia is induced (e.g., ectopic beats, irregular ECG activity, etc.), whether cardiac cycle length changes are induced, repetitive recovery curve, right atrial effective refractory period (“ERP”), left atrial ERP, dERP, heart rate, interatrial conduction time (“IACT”), P wave duration and / or dispersion, mean sinus cycle length, RR interval, or at least one of the following in a multipolar catheter under steady-state RV pacing or short DI after steady-state RV pacing in a unipolar electrogram.

[0015] The method may further include restimulating the subclavian loop after providing ablation energy, and providing further ablation energy to the subclavian loop if cardiac parameters confirm the stimulation. The method may include repeating restimulation and providing further ablation energy until cardiac parameters no longer confirm the stimulation. The catheter may include an expansion element on which a neuromodulation element is positioned. The method may further include inflating the expansion element by a certain amount to dilate the vascular system.

[0016] In some embodiments, a method of treating a subject's heart disease includes introducing a catheter transdermally or percutaneously into the subject's vascular system. The catheter includes a neuromodulation element (e.g., one or more neuromodulation elements). The method further includes positioning the neuromodulation element in the subject's subclavian artery, electrically stimulating at least one of the dorsal or ventral subclavian loops, confirming stimulation of the dorsal and / or ventral subclavian loops by monitoring cardiac parameters, and, after confirming stimulation of the dorsal and / or ventral subclavian loops, providing ablation energy to the dorsal and / or ventral subclavian loops. The method may include simultaneously providing ablation energy to the dorsal and ventral subclavian loops after electrically stimulating them and / or confirming stimulation by monitoring cardiac parameters. Neuromodulation targets (e.g., the subclavian loop) can be located percutaneously (e.g., percutaneous ultrasound).

[0017] The method may further include restimulating the subclavian loop after providing ablation energy, and providing further ablation energy to the subclavian loop if cardiac parameters confirm the stimulation. The method may include repeating restimulation and providing further ablation energy until cardiac parameters no longer confirm the stimulation.

[0018] In several embodiments, the system includes a catheter or other device configured for transdermal introduction into a vascular system. Transdermal introduction of a catheter into a vascular system may include inserting the catheter into the femoral artery of the subject. Transdermal introduction of a catheter into a vascular system may include inserting the catheter into the radial artery of the subject. Transdermal introduction of a catheter into a vascular system may include inserting the catheter into the carotid artery of the subject. Transdermal introduction of a catheter into a vascular system may include inserting the catheter into the femoral vein of the subject. Positioning a neuromodulation element in at least one of the left subclavian artery or the right subclavian artery may include traversing from the venous vascular system to the arterial vascular system.

[0019] In some embodiments, the method of treating a subject's heart disease includes positioning a neuromodulation element in the subject's subclavian artery, electrically stimulating at least one of the dorsal or ventral subclavian loops, confirming stimulation of the dorsal and / or ventral subclavian loops by monitoring cardiac parameters, and, after confirming stimulation of the dorsal and / or ventral subclavian loops, providing ablation energy to the dorsal and / or ventral subclavian loops. In some embodiments, ablation energy is provided to the dorsal and ventral subclavian loops simultaneously or sequentially.

[0020] Ablation energy may include radiofrequency ablation energy. Ablation energy may consist of cryoablation energy. Electrical stimulation of the subclavian loop can be achieved using a combination of electrodes with neuromodulation elements. The delivery of ablation energy may include the same combination of electrodes using neuromodulation elements.

[0021] Heart disease can include atrial fibrillation. Heart disease can include refractory arrhythmias. Methods may further include assessing whether sympathetic nerve impulses are driving the refractory arrhythmia. Heart disease can include ventricular tachycardia. Heart disease can include ventricular fibrillation. Heart disease can include congestive heart failure. Heart disease can include atrial flutter.

[0022] In some embodiments, the catheter for treating a heart condition includes, or optionally primarily comprises, the following: an elongated element configured to be positioned in at least one of the left or right subclavian artery. The distal portion of the elongated element includes a first neuromodulation element configured to stimulate at least one of the dorsal or ventral subclavian loops, a second neuromodulation element configured to ablate at least one of the dorsal or ventral subclavian loops, and a distal protection device located distal to the first and second neuromodulation elements.

[0023] The first neuromodulation element may include a first plurality of electrodes coupled to a first plurality of pillars. The first neuromodulation element may include a first plurality of electrodes coupled to a first ring. The first neuromodulation element may include a first plurality of electrodes coupled to a first stopper drill-shaped member. The second neuromodulation element may include the first plurality of electrodes or a second plurality of electrodes coupled to a second plurality of pillars. The second neuromodulation element may include the first plurality of electrodes or a second plurality of electrodes coupled to a second ring. The second neuromodulation element may include the first plurality of electrodes or a second plurality of electrodes coupled to a second stopper drill-shaped member. At least one of the electrodes may include a triangular base including a tip configured to be pressed into the vessel wall. At least one electrode may further include a plurality of electrode protrusions located on different sides of the tip of the triangular base. The catheter may further include an expansion element. The first and second neuromodulation elements may be positioned on the expansion element.

[0024] In some embodiments, the catheter for treating a heart condition includes, or optionally primarily comprises, the following: an elongated element configured to be positioned in at least one of the left or right subclavian artery. The distal portion of the elongated element includes a neuromodulation element configured to stimulate at least one of the dorsal or ventral subclavian loop and to ablate at least one of the dorsal or ventral subclavian loop, and a distal protection device located distal to the neuromodulation element.

[0025] The neuromodulation element may include multiple electrodes coupled to multiple supports. The neuromodulation element may include multiple electrodes coupled to a ring. The neuromodulation element may include multiple electrodes coupled to a stopper drill. At least one of the multiple electrodes may include a triangular base including a tip configured to be pressed into the vessel wall. At least one electrode may further include multiple electrode protrusions located on different sides of the tip of the triangular base. The catheter may further include an expansion element. The neuromodulation element may be positioned on the expansion element.

[0026] In some implementations, the method of treating a subject includes stimulating specific electrodes of a neuromodulation device, providing the results to an interface computer configured to perform real-time data analysis and overlaying anatomical images with the response to the stimulus (including marking the locations of the strongest response), and ablation at those locations.

[0027] The method may further include re-stimulating the ablation site after ablation to verify its efficacy. The method may further include performing further ablation if it is ineffective. The method may include repeated verification and further ablation until the ablation is effective.

[0028] In some implementations, the method of treating a subject with refractory arrhythmias includes stabilizing the subject, assessing the cause of the refractory arrhythmia, assessing whether sympathetic nerve transmission is driving the refractory arrhythmia, and if sympathetic nerve transmission is not driving the refractory arrhythmia, coordinating the assessment of the arrhythmogenic focus, and if sympathetic nerve transmission is driving the refractory arrhythmia, performing a subclavian loop ablation procedure.

[0029] Assessing whether sympathetic nerve conduction is driving refractory arrhythmias may include administering epidural anesthesia. Assessing whether sympathetic nerve conduction is driving refractory arrhythmias may include disabling the subject's implantable cardioverter-defibrillator.

[0030] In some implementations, the method of treating a patient's heart disease includes positioning a neuromodulation element in the patient's subclavian artery and delivering ablation energy to the dorsal and / or ventral subclavian loops.

[0031] Delivering ablation energy may include selectively delivering ablation energy. Selectively delivering ablation energy may include non-therapeutic stimulation to determine the location of the dorsal and / or ventral subclavian loops. Selectively delivering ablation energy may include imaging the subclavian artery to determine the possible location of the dorsal and / or ventral subclavian loops. Delivering ablation energy includes delivering ablation energy around the subclavian artery.

[0032] In some embodiments, the method of treating a subject includes positioning a neuromodulation element of a catheter within the subject's subclavian artery. The neuromodulation element may include an array of electrodes circumferentially spaced around the catheter and longitudinally spaced along its length. The method may include stimulating specific electrodes of the electrode array, providing the results to an interface computer configured to perform real-time data analysis; overlaying anatomical images (including marking locations of maximum response) in response to stimulation; and ablation at the marked locations.

[0033] The method may further include re-stimulating the ablation point after ablation to verify its effectiveness. The method may include further ablation if the ablation is ineffective. The method may include repeating re-stimulation and further ablation until the ablation is verified to be effective. The neuromodulation element may be positioned on an expansion element. The method may include inflating the expansion element by a certain amount to dilate the subclavian artery.

[0034] In some embodiments, the catheter for treating a patient's heart condition may include an elongated element configured to be positioned in at least one of the left or right subclavian artery. The distal portion of the elongated element may include a neuromodulation element configured to stimulate at least one of the dorsal or ventral subclavian loops and to ablate at least one of the dorsal or ventral subclavian loops. The neuromodulation element of the catheter is configured to be positioned within the patient's subclavian artery. The neuromodulation element includes an array of electrodes circumferentially around the catheter and spaced longitudinally along the length of the catheter.

[0035] The neuromodulation element may include multiple electrodes coupled to multiple pillars. The neuromodulation element may include multiple electrodes coupled to a ring. The neuromodulation element may include multiple electrodes coupled to a stopper drill. At least one of the multiple electrodes may include a triangular base including a tip configured to be pressed into the vessel wall. The catheter may include an expansion element. The expansion element may include a balloon.

[0036] In some embodiments, a method of treating a patient's heart disease includes introducing a catheter transdermally or percutaneously into the patient's vascular system, wherein the catheter includes a neuromodulation element; positioning the neuromodulation element in the patient's subclavian artery; electrically stimulating at least one of the dorsal or ventral subclavian loops, confirming stimulation of the dorsal and / or ventral subclavian loops by monitoring biomarkers, wherein the biomarkers include at least one of systolic biomarkers, chronotropic biomarkers, transconductance biomarkers, relaxation biomarkers, or inflammatory biomarkers; and, after confirming stimulation of the dorsal and / or ventral subclavian loops, delivering ablation energy to the dorsal and / or ventral subclavian loops. The neuromodulation target site (e.g., the subclavian loop) can be located percutaneously (e.g., percutaneous ultrasound).

[0037] The method may further include restimulating the subclavian loop after providing ablation energy, and providing further ablation energy to the subclavian loop if the biomarker confirms the stimulation. The method may include repeating restimulation and providing further ablation energy until the biomarker does not confirm the stimulation. Biomarkers may include at least one of the following: developmental pressure (dP / dt), arterial blood pressure (systolic, diastolic, mean), pulse pressure changes, generalized blood pressure elevation, or left ventricular developmental pressure (dP / dt). Biomarkers may include at least one of the following: heart rate changes (changes in RR or QQ intervals on a surface ECG), increased heart rate (shortened RR interval), changes in right and / or left atrial ERPs, changes in p-wave duration and / or dispersion, or changes in sinus cycle length or baseline cycle length on an intracardiac electrocardiogram. Biomarkers may include variable conductivity biomarkers (e.g., IACT). The catheter may include a balloon, and a neuromodulation element may be positioned on the balloon. The method may include inflating the balloon catheter by a certain amount to dilate the vascular system of the target.

[0038] In some embodiments, the method of treating a patient's heart disease includes positioning a neuromodulation element on an expansion element in the patient's subclavian artery; expanding the expansion element; electrically stimulating at least one of the dorsal or ventral subclavian loops; confirming stimulation of the dorsal and / or ventral subclavian loops by monitoring cardiac parameters; and, after confirming stimulation of the dorsal and / or ventral subclavian loops, providing ablation energy to the dorsal and / or ventral subclavian loops.

[0039] Ablation energy may include radiofrequency ablation energy. Ablation energy may also be cryogenic ablation energy. Methods may include electrical stimulation using a combination of electrodes employing neuromodulation elements, wherein the ablation energy is provided using the same combination of electrodes employing neuromodulation elements. Heart disease may include atrial fibrillation. Heart disease may include refractory arrhythmias.

[0040] In some embodiments, the catheter for treating a heart condition includes an elongated element configured to be positioned in at least one of the left or right subclavian artery, wherein the distal portion of the elongated element includes: an expansion element; and a neuromodulation element positioned on the expansion element and configured to stimulate at least one of the dorsal or ventral subclavian loop and to ablate at least one of the dorsal or ventral subclavian loop, the neuromodulation element being a neuromodulation element of the catheter in the subject's subclavian artery, the neuromodulation element including an array of electrodes circumferentially around the circumference of the catheter and longitudinally spaced along the length of the catheter.

[0041] The neuromodulation element may include multiple electrodes coupled to multiple pillars. The neuromodulation element may include multiple electrodes coupled to a loop. At least one of the multiple electrodes may include a triangular base comprising a tip configured to be pressed into the vessel wall.

[0042] In some embodiments, the treatment system includes, is primarily composed of, or comprises one or more of the features described herein.

[0043] In some embodiments, the tissue treatment system includes, is primarily composed of, or comprises one or more of the features described herein.

[0044] In some embodiments, the method of ablating the subclavian loop includes, consists primarily of, or comprises one or more of the features described herein.

[0045] This disclosure relates to a catheter having a flexible element at a distal portion of the catheter. The flexible element may include a proximal hub coupled to a distal end of the catheter shaft. The flexible element may include at least one elongated leg (e.g., one, two, three, four, or more). The proximal end of at least one elongated leg may be coupled to the proximal hub. The flexible element may include a distal hub coupled to the distal end of at least one elongated leg. The catheter may include a control feature (e.g., a drawstring) coupled to the distal hub. The catheter may include a neuromodulation element positioned on the flexible element and configured to stimulate and / or ablate tissue.

[0046] The distal hub may include one or more electrodes for sensing, stimulation, and / or ablation. The same or different electrodes may provide one or more of these modulatory mechanisms. Electrodes on the distal hub may be larger than electrodes at other locations on the flexure element. The distal hub electrodes provide increased arterial wall contact compared to electrodes placed at other locations on the flexure element. Bends in the flexure element stabilize the distal hub electrodes. The distal hub may dilate the vessel wall near the nerve or a small portion of the arterial wall. The distal hub may also force other electrodes on the opposite side of the bend to be pushed into the opposing arterial wall, thus bringing them closer to the opposing loop, whether ventral or anterior.

[0047] In some embodiments, the catheter can be used to treat a patient's heart condition. For example, the catheter shaft can be positioned in at least one of the left or right subclavian artery. While some embodiments described herein relate to the subclavian artery or its use in treating heart conditions, the catheter described herein can be used in other blood vessels for other treatments, such as renal denervation, hepatic denervation, or other treatments.

[0048] The catheter shaft may define a central axis. The distal portion of the catheter shaft may include a flexural element configured to flex relative to the central axis. The flexural element may include at least one elongated leg, such as one, two, three, four, or more elongated legs. At least one elongated leg may extend between a proximal hub and a distal hub. The catheter may also include a drawstring to actuate the flexural element. The proximal hub may be individually or integrally coupled to the distal end of the catheter shaft. The proximal end of at least one elongated leg may be coupled to the proximal hub, and the distal end of at least one elongated leg may be coupled to the distal hub. The distal end of the drawstring may also be coupled to the distal hub. The drawstring and the proximal end of the catheter shaft may be attached to a handle. A neuromodulation element may be positioned on the flexural element. The neuromodulation element may be configured to stimulate at least one of the dorsal or ventral subclavian loop and / or configured to ablate at least one of the dorsal or ventral subclavian loop.

[0049] The neuromodulation element of the catheter can be positioned within the subclavian artery of the subject. The neuromodulation element may include one or more electrodes (e.g., one electrode, two electrodes, three electrodes, four electrodes, etc.). The one or more electrodes may be circumferentially connected around the circumference of at least one slender leg. The one or more electrodes may be positioned at both the proximal and distal ends of the slender leg. In some embodiments, the electrodes may be circumferentially positioned around the middle portion of at least one leg. The one or more electrodes may be made of a platinum-iridium (PT / IR) alloy or other suitable conductive materials such as stainless steel, platinum, titanium, gold, silver, etc.

[0050] One or more electrodes may be placed at one or more locations along the flexural element, such as at the distal tip or distal hub, on the strut, and / or at the proximal hub. One or more electrodes may be positioned on the strut at a location (one or more) distal to the bow bend, at the bow bend, or proximal to the bow bend. The electrodes provided herein may generate more specific electric and RF fields, for example, between the tip and the external ground plane, between the tip and any ring electrodes on the strut element, or between electrodes on one or more struts.

[0051] In some implementations, the neuromodulation element may include electrodes coupled to a distal hub.

[0052] At least one leg may include one leg, two legs, three legs, four legs, five legs, six legs, seven legs, etc. The legs may extend along an arcuate interval of less than approximately 360 degrees (e.g., less than 270 degrees, less than 200 degrees, less than 180 degrees, less than 90 degrees, and so on, within such values) about the central axis. At least one leg may be configured to deflect away from the central axis defined by the catheter axis in response to a proximal pull of the cable by the operator in a proximal direction. The leg may be configured to return to a position aligned with the central axis in response to a distal release of the cable by the operator. At least one leg may be configured to deflect to a position substantially perpendicular to the central axis in response to a maximum proximal pull of the cable by the operator. The flexural element may have a bending radius up to 90 degrees, for example at least about 45 degrees and less than or equal to about 90 degrees, for example at least about 60 degrees or at least about 75 degrees. At least one leg may be completely or partially enclosed by a sheath.

[0053] In some embodiments, the pull cord may be positioned off-axis relative to the central axis and may be positioned on one side of the legless catheter. In other configurations, the pull cord may be positioned along the central axis. The pull cord may be completely or partially enclosed by a sheath.

[0054] In some implementations, the catheter shaft, proximal hub, and distal hub may include a central lumen configured to receive a guidewire to allow for over-the-wire system placement. Other delivery methods are possible, such as guided catheter tracing, direct navigation, and / or other navigation methods.

[0055] In some embodiments, the central lumen may include a plurality of perforations around its circumference, such that when the catheter is coupled to a flushing system, flushing can be radially released through the perforations to cool the catheter.

[0056] The catheter may include one or more of the following: an ultrasound crystal, a piezoelectric element or other element for ultrasound ablation, an electrode for RF ablation, a return electrode, or any electrode suitable for neuromodulation (e.g., one or more, three or more, six or more, etc.). The catheter may include one or more of the following devices for modulation: cryogenic element, radio frequency element, ultrasound element, laser element, heat delivery element, chemical delivery element, microwave element, electrical element, pressure element, acoustic element, vibration element, mechanical stretching element, and / or similar element.

[0057] The conduit may include one or more RF wires for supplying RF energy to the neuromodulation element. The conduit may also include one or more thermocouple wires for supplying thermal energy to the neuromodulation element.

[0058] In some implementations, the distal hub and / or proximal hub may include deployable umbrella-shaped elements configured to capture emboli.

[0059] In some embodiments, a method of treating a patient's heart disease includes positioning a neuromodulation element, which is positioned on a catheter, within the patient's subclavian artery. The method may include, for example, repositioning a flexure element located distal to the catheter relative to a central axis defined by the catheter's axis by pulling a traction wire in a proximal direction. The method may include electrically stimulating at least one of the dorsal or ventral subclavian loops and confirming stimulation of the dorsal and / or ventral subclavian loops by monitoring cardiac parameters. The method may include delivering ablation energy to the dorsal and / or ventral subclavian loops.

[0060] In some embodiments, the method may further include providing ablation energy. The method may include restimulating the subclavian loop and, if cardiac parameters confirm stimulation, providing further ablation energy to the subclavian loop. The method may further include repeating restimulation and providing further ablation energy until cardiac parameters no longer confirm stimulation.

[0061] In some embodiments, transdermal introduction of a catheter into a vascular system includes inserting the catheter into the subject's left or right radial artery. Transdermal introduction of a catheter into a vascular system may include inserting the catheter into the subject's carotid artery. Transdermal introduction of a catheter into a vascular system may include inserting the catheter into the subject's left or right femoral vein and positioning the neuromodulation element in the left or right subclavian artery by traversing from the venous vascular system to the arterial vascular system. Any of these access methods can be used to access the ipsilateral and / or contralateral subclavian arteries.

[0062] In some embodiments, pulling the cable proximally moves the flexure element to a position substantially perpendicular to the central axis. Pulling the cable moves the flexure element to a position up to 90 degrees relative to the central axis defined by the axis of the catheter. Releasing the cable moves the flexure element to a position aligned with the central axis.

[0063] In several embodiments, the catheter described herein has one or more of the following advantages: • In some implementations, a portion of the object's vascular system (e.g., the ventral and / or subclavian loop) is allowed to be selectively targeted to achieve nerve innervation; • In some implementations, multiple parts of the object's vascular system (e.g., opposite sides of the vascular wall) are allowed to be innervated simultaneously; • Improved maneuverability when navigating through tortuous vascular systems; • The bends in the flexure element or various features on the flexure element can promote the dilation of the blood vessel walls near the nerve or local expansion of a small portion of the arterial wall; or • Reduce the amount of energy required to stimulate and eventually denervate. Attached Figure Description

[0064] The following figures are for illustrative purposes only and show non-limiting embodiments. Features in different figures may be combined in several embodiments.

[0065] Figure 1 This is a schematic diagram illustrating an example of the sympathetic nerve bundle's innervation of the heart.

[0066] Figure 2A This is a schematic diagram illustrating an example method of regulating the nerves surrounding the left subclavian artery.

[0067] Figure 2B This is a schematic diagram illustrating an example method of regulating the nerves surrounding the right subclavian artery.

[0068] Figure 3 This is a schematic diagram of an example system for regulating nerves.

[0069] Figure 4 This is a schematic diagram of an example neural modulation element.

[0070] Figure 5 This is a schematic diagram of another example of a neural modulation element.

[0071] Figure 6 This is a schematic diagram of another example of a neural modulation element.

[0072] Figure 7 This is a schematic diagram of another example of a neural modulation element.

[0073] Figure 8 This is another example of a neural modulatory element in a blood vessel.

[0074] Figure 9 This is a schematic diagram or cross-sectional view of an example neural modulatory element in a blood vessel.

[0075] Figure 10 This is a schematic diagram of another example of a neural modulation element.

[0076] Figure 11 An example neural modulatory element is schematically shown in an end view in a blood vessel.

[0077] Figure 12 This is a flowchart of example method 1100 for the treatment object.

[0078] Figure 13 It is based on Figure 12 The method can be shown by examples provided by the computer.

[0079] Figure 14A Another example of a neural modulatory element is shown schematically in a side view of a vasomotor vessel.

[0080] Figure 14BAnother example of a neural modulatory element is shown schematically in a side view of a dilated blood vessel.

[0081] Figure 15A yes Figures 14A-14B Example of a neural modulatory element in a systolic blood vessel (cross-sectional view).

[0082] Figure 15B yes Figures 14A-14B Example of a neural modulatory element in a dilated blood vessel (cross-sectional view).

[0083] Figure 16 This is a stereoscopic view of another example of a neural modulatory element.

[0084] Figure 17 yes Figure 16 A front view of an example neural modulation element.

[0085] Figure 18A yes Figure 16 A side view of an example neural modulation element.

[0086] Figure 18B It is along Figure 18A The line AA is intercepted Figure 16 A cross-sectional view of an example neural modulation element.

[0087] Figure 19 This is a side view of another example of a neural modulation element.

[0088] Figure 20 It is a display Figure 16 A schematic diagram of the bending radius of an example neural modulation element.

[0089] Figure 21 It is the opposite side that contacts the blood vessel wall. Figure 16 Example view of a neural modulation element.

[0090] Figure 22A It is in the normal position. Figure 16 A three-dimensional diagram of the neural regulatory elements.

[0091] Figure 22B It is located in a partial deployment position. Figure 16 A three-dimensional diagram of the neural regulatory elements.

[0092] Figure 22C It is in a fully deployed position. Figure 16 A three-dimensional diagram of the neural regulatory elements.

[0093] Figure 23 This is a flowchart of another example method for treating the object. Detailed Implementation

[0094] Most arrhythmic events are caused by myocardial infarction (MI) due to coronary artery disease, but heart failure from any cause can lead to a strong tendency for arrhythmias. Treatments for myocardial infarction (such as primary angioplasty and stent implantation) can effectively restore blood flow, but may cause serious residual myocardial damage. A common finding in patients with myocardial damage is potentially elevated sympathetic nerve signaling, which can further increase stress on the cardiovascular system. This harmful cascade drives heart failure and arrhythmias. Beta-blockers can reduce the effects of elevated sympathetic tone and are a major force in preventing arrhythmias and are key to treating heart failure. However, these drugs are not entirely effective and have serious systemic side effects at the high doses required for therapeutic efficacy.

[0095] Implantable cardioverter-defibrillators (ICDs) are implanted to suppress sudden cardiac death caused by ventricular arrhythmias. These devices monitor heart rhythm and provide direct electrical cardioversion when irregular tachycardia is detected, thus providing a safety net as a reactive therapy. However, ICDs are associated with serious iatrogenic morbidity: patients will have generator and lead replacements throughout their lives, life-threatening device infections are common, and extremely painful inappropriate shocks are frequent (1 in 20 patients), even causing skin burns. The vast majority of ICDs are implanted as primary prevention devices (e.g., in the event of an arrhythmia), yet even in these patients, a moderate reduction in arrhythmia risk can reverse the risk / benefit profile of the ICD. Multiple clinical trials and meta-analyses have demonstrated the prevalence of inappropriate shocks caused by ICDs. Although most patients are implanted for primary prevention, algorithms do not predict arrhythmias well, thus patients may receive inappropriate shocks (either at inappropriate times or in the absence of a life-threatening arrhythmia). Emerging literature suggests that a cumulative increase in the number of shocks can lead to further cardiac electrical instability, driving more arrhythmias and hospitalizations due to inappropriate shocks, ranging from extreme discomfort (pain to skin burns) to death. In these patients who still experience arrhythmias despite ICD implantation, thoracic epidural anesthesia is provided to alleviate pain, and patients who may be candidates for stellate ganglionectomy are stratified. Stellate ganglionectomy, or stellate decentralization, addresses elevated sympathetic signaling (caused by cardiac disease) mediated by direct neural pathways originating from the heart, traveling to the brainstem, and then returning to the heart via extracardiac, intrathoracic nerve bundles (such as the paravertebral sympathetic chain and its associated nerves, e.g., the subclavian loop), providing a perceived biological target for reducing life-threatening arrhythmias and the progression of heart failure. The limited available treatment strategies for primary heart failure and secondary arrhythmias leave many patients with few options as the disease progresses. While catheter ablation for ventricular arrhythmias is effective in some patients, it is a highly complex procedure and does not alter the underlying pathology. Many patients considered at risk for ventricular arrhythmias, regardless of whether they have an implanted device (ICD), undergo a progressive, escalating pharmacological titration process before ICD implantation.

[0096] Atrial arrhythmias—the most common type of arrhythmia, atrial fibrillation—are caused by an imbalance in the neural supply to the different anatomical structures of the atria (composed of cardiac tissue, vascular tissue, and interspersed with fat pads), which accelerates the arrhythmia. Current treatment strategies involve electrophysiological procedures that directly map the most heterogeneous regions of the atria and then disconnect / electrically isolate these regions from the rest of the atria. All of these procedures target intracardiac structures and do not provide complete arrhythmia-free survival. A significant proportion of patients experience recurrent arrhythmias and undergo experimental procedures such as fat pad ablation or ganglion plexus ablation on the surface of the heart. These intracardiac structures receive their neural supply from extracardiac sympathetic and parasympathetic bundles, with the sympathetic bundles causing significant heterogeneity and accelerating atrial fibrillation. Operators performing ganglion plexus ablation are unaware of the success of ablation of all neural tissues at the time of the procedure.

[0097] The key nexus point of pathologically upregulated cardiac sympathetic signaling originates from the ganglia of the upper thoracic sympathetic chain. Increased sympathetic signaling is a major cause of both atrial and ventricular arrhythmias in most severe cardiac arrhythmias. Increased or decreased sympathetic signaling plays a significant role in regulating cardiac contractility, conductivism, relaxation, and chronotropy. Furthermore, the regulation of cardiac activation-recovery intervals or refractory periods is well-described in preclinical and human studies. Therefore, cardiac conditions such as long QT syndrome with underlying sympathetic overdrive are considered candidates for surgical removal of the stellate ganglion (stellate ganglionectomy / stellate ganglion decentralization). Cardiac surgeons have performed highly invasive stellate ganglionectomy / stellate ganglion decentralization (denerenement of the heart by removing the stellate ganglion) to treat life-threatening arrhythmias with good results. For example, these procedures can alleviate the arrhythmic burden in patients with long QT syndrome. In patients presenting with refractory ventricular arrhythmias, the only effective treatment is thoracic epidural anesthesia to block sympathetic traffic, followed by surgical removal of the stellate ganglion using video-assisted thoracoscopic surgery. However, these stellate ganglion resection / decentralization procedures are highly invasive, requiring general anesthesia and highly specialized surgical skills and / or robotic equipment, and are associated with increased procedural risks in patients with advanced heart disease. Despite advancements in techniques such as video-assisted thoracoscopic surgery, this procedure is performed only by select surgeons in specific centers, and is currently only considered a "last resort" treatment for refractory patients.

[0098] While stellate ganglionectomy effectively reduces cardiac arrhythmias by over 90%, postoperative complications are highly variable. Because the stellate ganglion controls the sympathetic innervation of the arm, shoulder, and upper back, surgeons must visually inspect the area to remove it, as it is a highly delicate segment. Due to the lack of clearly discernible margins during surgery, and the inability to clearly identify the axonal, thoracic, and cardiac fibers, surgeons often perform stellate ganglionectomy via open-eye surgery. As this is an empirical and highly subjective procedure, many patients exhibit symptoms of severed nerve damage, leading to increased pain perception in the affected upper limb (hyperalodysplasia) and asymmetrical sweating (hyperhidrosis / anhidrosis). Furthermore, the required robotic surgery is a highly complex endeavor, driving up medical costs and reducing accessibility.

[0099] In the pathophysiology of cardiac arrhythmias, there can be important interactions between the heart and the autonomic nervous system (ANS). ANS derangement has been shown to play a significant role in the occurrence of arrhythmias. The role of the ANS in the onset and maintenance of arrhythmias is associated with autonomic imbalance. Modulation of autonomic signaling shows great promise in reducing (e.g., preventing) and treating cardiac arrhythmias (e.g., vagus nerve stimulation clinical trials). The cardiac autonomic nervous system is a complex structure and provides many easily accessible, minimally invasive targets. Treatment of arrhythmias using autonomic modulation may include potential therapeutic targets such as autonomic ganglion plexuses, 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 (such as those using stellate ganglion block / sympathectomy) may produce off-target side effects, while others do not directly affect the reduction of sympathetic signaling. Anesthesia of the stellate ganglion is reversible, and patients experience symptoms of nerve damage for months afterward, and it is only offered as palliative care in extreme cases. In animal models, increased exogenous cardiac neural activity was observed in the left stellate ganglion prior to the occurrence of paroxysmal atrial tachycardia or atrial fibrillation (AT / AF). Stimulation of the stellate ganglion increases sinus rate and susceptes patients to atrial arrhythmias. Unilateral transient stellate ganglion block can prolong the atrial effective refractory period (ERP), reduce the AF induction rate, and / or shorten the duration of AF. Renal denervation significantly improves the absence of AF compared to standard pulmonary vein isolation alone.

[0100] Therapies that selectively target the cardiac sympathetic neuronal supply using transdermal intravascular devices could provide users (e.g., cardiologists) with the ability to offer effective, safe, and permanent neuromodulation therapy to individuals at risk of arrhythmias, and could even serve as an adjunct to primary catheterization procedures. Synergistic effects across pathophysiological mechanisms suggest this could be used as a novel treatment option for patients with heart failure, particularly those who cannot tolerate beta-blockers.

[0101] Cardiac dysfunction drives an increase in sensory signals to the brainstem, which in turn upregulates compensatory contractile mechanisms, potentially pathogenic in the early stages of the disease. In ischemic heart disease leading to reduced pump function, cardiac sympathetic signaling is enhanced in the early stages to maintain cardiac output and adequate oxygen supply to the limbs. As the disease progresses, these sympathetic responses are amplified, driving cardiac pathology. This pathology drives the following responses: myocardial alternative fibrosis and increased cardiac sympathetic sprouting. While the former is a maladaptive response to stress, the increase in sympathetic sprouting is initially an adaptive response, leading to increased heterogeneity over time. Fibrotic myocardium acts as a shunt, while sympathetic sprouting regions act as acceleration pathways. This provides an ideal substrate for the development of cardiac arrhythmias. Cardiac ANS has a significant impact on cardiac electrophysiology and the occurrence of arrhythmias. This impact is diverse: different types of arrhythmias have different autonomic triggers. As knowledge of identifying these specific triggers grows, appropriate therapeutic modalities through neuromodulation can be applied accordingly.

[0102] Figure 1This is a schematic diagram showing an example of the innervation of the sympathetic nerve bundles leading to the heart. The subclavian artery 102 is surrounded by the dorsal subclavian loop 104 and the ventral subclavian loop 106. The subclavian loops 104 and 106 are nerve cords that loop downward around the subclavian artery 102 and connect to the inferior cervical ganglion and the middle cervical ganglion (also known as the C8 and T1 layers of the paravertebral sympathetic chain). The vagus nerve 108 is also shown. Arrow 110 indicates that the indicated nerve extends toward the heart. In most subjects, the C8 / T1 layers of the sympathetic chain (stellate ganglion) are predominantly fused or slightly separated and provide nerve supply to the muscles of the shoulder, arm, and heart. The function of the subclavian loops 104 and 106 is to conduct sympathetic nerve conduction, which specifically innervates the heart, to the heart and directly connect the heart to the T1 segment. The sympathetic pathway to the heart originates via the stellate ganglion, which receives sympathetic input from the middle cervical ganglion via two discrete nerve bundles: the dorsal subclavian loop 104 and the ventral subclavian loop 106. These two nerves pass above and below the subclavian artery 102, carrying sympathetic efferent (motor) neurons that increase heart rate (chronotropic), contractility (constrictive), relaxation (relaxative), and conduction velocity (variant). Efferent fibers traveling through the subclavian loop 102 originate from the T1-T4 thoracic sympathetic chain ganglia; these fibers, originating from the ventral branches of the spinal cord, ascend through T4, T3, T2, and T1 towards T1, converging and then flowing through the subclavian loops 104 and 106 into the middle cervical ganglion (C8-T1), from where they distribute to the heart. Afferent fibers appear to bypass the subclavian loops 104 and 106 and travel directly to the C8 ganglion. Surgical denervation for the treatment of cardiac arrhythmias relies on the removal of half of the entire T4 to C8 / T1 complex (removal of the four ganglion cell bodies and their interganglionic bundles, without affecting the subclavian loops 104 and 106 due to the complexity of the procedure performed around the subclavian artery 102).

[0103] Preganglionic fibers originating from the thoracic spinal cord ascend along the paravertebral chain through the T1-T2 region. Some synapse with postganglionic neurons in the stellate ganglion, while others project through the subclavian loops 104 and 106 to more distal intrathoracic ganglia (middle cervical ganglion, mediastinal ganglion, and intrinsic ganglion) to mix with parasympathetic vagal fibers. Therefore, the subclavian loops 104 and 106 and the T1-T2 region of the paravertebral chain are key nodes for sympathetic nerve conduction to the heart. Based on structural and functional considerations, both sites are potential targets for cardiac neural modulation.

[0104] Preclinical studies in dogs and recently in pigs have shown that stimulation of the subclavian loop 104 and 106 produces reproducible increases in heart rate, contractility, and conduction velocity, as well as decreases in relaxation. Denervation of the subclavian loop 104 and 106, followed by stimulation of the proximal stellate ganglion (C8), did not induce changes in cardiac indices, confirming the nodal intervention point for cardiac sympathetic conduction. Due to their close anatomical association in size and structure, modulation of the subclavian loop 104 and 106 is possible via catheter insertion into the subclavian artery 102. Modulation of the subclavian loop 104 and 106 can produce reproducible increases in heart rate and contractility while increasing conduction velocity. Denervation of the subclavian loop 104 and 106, followed by stimulation of the stellate ganglion, did not induce changes in cardiac indices, confirming the nodal intervention point for cardiac sympathetic conduction.

[0105] A transdermal catheter can be inserted into the subclavian artery to target the subclavian loops 104 and 106 to map these nerves along the length of the subclavian artery 102, detect the presence of nerves 104 and 106 (e.g., by non-therapeutic energy stimulation), and selectively ablate nerves 104 and 106 via the subclavian artery. This is a cost-effective alternative to robotic surgery.

[0106] Optionally, the subclavian loops 104 and 106 can be targeted percutaneously. A neuromodulation element as described herein can be placed on or within the distal tip of a needle, probe, or other guide device and guided to the location of loops 104 and 106 using imaging modalities such as ultrasound or fluoroscopy. If ultrasound guidance is used, the distal tip of the needle, probe, or guide device may include an ultrasound band to aid in tracking the neuromodulation element toward loops 104 and 106. Stimulating or ablating energy can be applied when the neuromodulation element is shown to be in contact with or very close to loops 104 and 106. For example, the same needle or guide used for placing the neuromodulation element can be used to perform stimulation and / or ablation. The needle tip may have two or more exposure areas to provide bipolar ablation. In other embodiments, a catheter or probe may be advanced via a guide to provide ablation. Percutaneous approaches (e.g., percutaneous ultrasound) can also be used to locate, stimulate, and / or ablate the stellate ganglion and inferior cervical ganglion. This type of percutaneous approach can advantageously eliminate the need for and associated risks of vascular catheter insertion into the patient and reduce procedure time.

[0107] Figure 2A This is a schematic diagram of an example method for regulating the nerves 204 and 206 around the left subclavian artery 202. Figure 2A Showing Figure 1Additional anatomical structures include the aorta 222 and its branch vessels. The brachiocephalic artery branches from the aorta 222 into the right subclavian artery 203, supplying the right arm, and the right common carotid artery 225, supplying the cerebral vascular system. The left common carotid artery 224, supplying the cerebral vascular system, branches directly from the aorta 222. The left subclavian artery 202, supplying the left arm, also branches directly from the aorta 222. The aorta 222 descends to 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 loop 204 and the ventral subclavian loop 206. The right subclavian artery 203 is surrounded by the dorsal subclavian loop 205 and the ventral subclavian loop 207. The vagus nerve 208 is also shown.

[0108] Figure 2A The conduit 230, positioned to achieve neuromodulation of nerves 204 and 206, is schematically shown. Figure 2A As shown, catheter 230 has been navigated from an entry site in the lower body (such as the right femoral artery) to the left subclavian artery 202 (e.g., a location within the left subclavian artery 202 surrounded by the dorsal subclavian loop 204 and the ventral subclavian loop 206). Catheter 230 can be traced on a guidewire, traced via a guiding catheter, directly navigated, and / or other navigation methods. Other vascular entry sites are also possible. For example, entry into the right femoral artery, left or right radial access, carotid artery, etc., can be made, and catheter 230 can then be guided along a path through such vascular systems to reach the left subclavian artery 202. As another example, entry into a venous vascular system is possible, and catheter 230 can cross from the venous vascular system to the arterial vascular system (e.g., through the foramen ovale, through a dialysis fistula, etc.).

[0109] The distal portion of catheter 230 includes a neuromodulation element 232, which, as described, can provide non-therapeutic stimulation and / or therapeutic treatment through the same or different modulation mechanisms. For example, the neuromodulation element 232 may include one or more of the following modulation mechanisms: cryogenic elements, radiofrequency elements, ultrasound elements, laser elements, heat transfer elements, chemical transfer elements, microwave elements, electrical elements, pressure elements, acoustic elements, vibration elements, mechanical stretching elements, and / or similar elements. In some embodiments, as discussed above, the left subclavian artery 202 may be located percutaneously (e.g., percutaneous ultrasound) prior to transdermal delivery of the neuromodulation element 232.

[0110] Once the neuromodulation element 232 is located in the left subclavian artery 202, a signal can be applied to the neuromodulation element 232 (e.g., stimulation with an appropriate energy level, also for procedural safety) to localize the nerves of the subclavian loops 204, 206 to achieve subclavian loop stimulation (SAS), which is non-therapeutic. In some embodiments, stimulation is directed away from treatment, for example because stimulation can cause side effects such as inducing arrhythmias. Contractility, chronotropic and / or transconductive properties can be measured before, during and / or after the SAS to determine whether the subclavian loops 204, 206 have been stimulated, for example, compared to baseline (resting), vagal nerve stimulation and / or induced atrial tachycardia. SAS can be determined by cardiac hemodynamics, electrophysiological measurements and / or induced atrial irregular tachycardia.

[0111] In some embodiments, the vagus nerve 208 may or may optionally be stimulated to achieve vagus nerve stimulation (VNS). For example, an electrode catheter may be positioned in the internal jugular vein (IJV) and deliver energy to the vagus nerve 208 (e.g., an amplitude of 0.5 to 1 V / kg, a frequency of 30 Hz, and a pulse width of 50 μs for 30 s). The output threshold may be determined to achieve a 10-20% reduction in heart rate. Arterial trajectories may be recorded to determine the effect on arterial pressure waveforms.

[0112] Skin electrodes can be placed before, during, or after the procedure to monitor diaphragmatic electromyography. The procedure can be performed under general anesthesia in a sterile setting, and appropriate therapeutic agents (such as heparin) can be administered as needed. Transdermal sites, such as the femoral vein, femoral artery, or radial artery, can be accessed under ultrasound guidance. Arterial access is not routinely performed to achieve AF ablation. In some embodiments, an arterial line may be placed to monitor arterial pressure.

[0113] Baseline measurements prior to SAS / VNS may include, for example, baseline arterial trajectory, electrocardiogram, heart rate, right and / or left atrial ERP, ERP difference between the left and right atria (dERP), heart rate, interatrial conduction time (IACT), and / or unipolar electrograms during steady-state right ventricular (RV) pacing at baseline at 20-30% above baseline heart rate, and / or recovery curves of steady-state RV pacing and short diastolic intervals (S1-S2).

[0114] Measurements during and / or after SAS / VNS may include, for example, changes in arterial trajectory blood pressure, induction of AF, induction of arrhythmias, induction of changes in cardiac cycle length, repetitive recovery curves, right and / or left atrial ERPs, dERPs, heart rate, IACT, and / or monopolar electrograms of multipolar catheters during steady-state RV pacing and / or short DI following steady-state RV pacing. Monitored parameters may vary based on neural pathways. For example, cardiac parameters (one or more) monitored when stimulating the dorsal subclavian loop 204 may differ from those monitored when stimulating the ventral subclavian loop 206, as the modulation of these neural pathways is expected to have different effects on the heart. Monitored parameters may also, or optionally, vary based on which side is being monitored. For example, cardiac parameters (one or more) monitored when stimulating the left dorsal subclavian loop 204 may differ from those monitored when stimulating the right dorsal subclavian loop 206. Figure 2B This is because the modulation of these nerves is expected to have different effects on the heart. The cardiac parameters(s) monitored when stimulating each subclavian loop can be customized. In some implementations, the cardiac parameters(s) monitored when stimulating all subclavian loops (e.g., both the dorsal and ventral subclavian loops) are the same. In some implementations, the cardiac parameters(s) monitored when stimulating some subclavian loops are the same, while the cardiac parameters(s) monitored when stimulating other subclavian loops are different. For example, the cardiac parameters(s) monitored when stimulating the left and right dorsal subclavian loops may be the same, the cardiac parameters(s) monitored when stimulating the left and right ventral subclavian loops may be the same, but the cardiac parameters(s) monitored when stimulating the right dorsal subclavian loop may be different from those monitored when stimulating the left ventral subclavian loop. To give another example, the cardiac parameters (one or more) monitored when stimulating the left ventral subclavian loop may be the same as those monitored when stimulating the right dorsal subclavian loop, but the cardiac parameters (one or more) monitored when stimulating the left ventral subclavian loop may be different from those monitored when stimulating the right dorsal subclavian loop.

[0115] Refer again Figure 2AOnce the neural modulatory element 232 is positioned in the left subclavian artery 202, non-therapeutic stimulation can be applied to the dorsal subclavian loop 204 and / or the ventral subclavian loop 206 by achieving a targeted 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%, in such a range, etc.)) can indicate stimulation of the sympathetic nervous system. As another example, an increase in cardiac parameters (e.g., an increase in heart rate (shortened RR interval), an increase in systemic blood pressure, an increase in left ventricular contractility, an increase in ventricular developmental pressure (dP / dt), a shortening of the PR and QT intervals, a shortening of the effective refractory period / activation recovery period of the atria and / or ventricles, induction of atrial or ventricular irregular tachycardia (which can be stopped by cardioversion or electric shock), combinations thereof, etc.) can indicate stimulation of the sympathetic nervous system. Once the subclavian loops 204 and 206 have been located via non-therapeutic stimulation, the neuromodulation element 232 can be used to therapeutically ablate or denervate the subclavian loops 204 and 206. In some embodiments, the neuromodulation element 232 includes multiple modes (e.g., a first mode for stimulating the subclavian loops 204 and 206 and a second mode for ablating the subclavian loops 204 and 206). For example, the neuromodulation element 232 may include an electrode array configured to provide electrical stimulation and different electrode arrays configured to provide radiofrequency ablation. For example, the neuromodulation element 232 may include an electrode array configured to provide electrical stimulation and a cryoablation device. In some embodiments, the neuromodulation element 232 includes a single mode (e.g., configured to stimulate the subclavian loops 204 and 206 based on a first set of stimulation parameters and configured to ablate the subclavian loops 204 and 206 based on a second set of ablation parameters). For example, the neuromodulation element 232 may include an electrode array configured to provide electrical stimulation (e.g., in bipolar mode, where one or more electrodes act as cathodes and one or more electrodes act as anodes) and configured to provide radiofrequency ablation (e.g., in unipolar mode using one or more electrodes). Ablation of the subclavian loops 204, 206, rather than just stimulation, can produce long-term effects. For clarity, the ablation signal is an irreversible destructive signal in the short term (e.g., the nerve may regrow years later). Ablation is performed selectively via a transdermal catheter 230 or an image-guided percutaneous approach, rather than surgical stellate ganglion resection. In some embodiments, the ablation described herein is preferably not targeted at the stellate ganglion. Ablation is preferably performed within the subclavian artery, rather than, for example, due to access to the paravertebral gutter.

[0116] The dorsal subclavian loop 204 and ventral subclavian loop 206 can be stimulated and / or ablated individually. A potential advantage of this approach is the ability to map and discretize nerves, visualized through changes in biomarkers superimposed on anatomical maps (such as CARTO maps). In some implementations, less than 360° of tissue around the left subclavian artery is ablated. This differs from, for example, renal denervation aimed at completely ablating all tissue around the renal artery and stellate ganglion resection removing all nerves around the subclavian artery. More specific ablation of only the dorsal subclavian loop 204 and / or ventral subclavian loop 206, compared to more comprehensive ablation, can reduce side effects (e.g., avoiding sensory deficits such as hyperalgesia) and / or abnormal sweating by targeting nerves supplying the heart and avoiding nerves and other tissues associated with the head, neck, and other body parts.

[0117] The dorsal subclavian loop 204 and the ventral subclavian loop 206 can be (at least partially) simultaneously stimulated and / or (at least partially) simultaneously ablated, but in other configurations, they can be stimulated and / or ablated sequentially. In some embodiments, the dorsal subclavian loop 204 and the ventral subclavian loop 206 can be at least partially simultaneously or synchronously stimulated and / or at least partially simultaneously or synchronously ablated. For example, in some embodiments, the dorsal subclavian loop 204 and the ventral subclavian loop 206 are stimulated individually but simultaneously (or partially simultaneously) or synchronously ablated. A possible advantage of this approach is the ability to map and discretize the nerves, but simultaneous ablation of the dorsal subclavian loop 204 and the ventral subclavian loop 206 can shorten treatment time.

[0118] Figure 2B This is a schematic diagram illustrating an example method of modulating nerves 205 and 207 around the right subclavian artery 203. The method may be similar to or identical to that used for modulating nerves 204 and 206, the difference being the catheter 230 (which may be related to…) Figure 2A The same or different catheters shown and described have been positioned in the right subclavian artery 203 (e.g., in the right subclavian artery 203 surrounded by the dorsal subclavian loop 204 and the ventral subclavian loop 206). Figure 2BAs shown, catheter 230 has been navigated from an entry point in the lower body (such as the right femoral artery) to the right subclavian artery 203. Catheter 230 can be tracked on a guidewire, tracked via a guiding catheter, directly navigated, and / or other navigation methods. In some embodiments where the same catheter 230 is used for treatment around both the left and right subclavian arteries 202 and 203, catheter 230 can be repositioned without withdrawing it from the body. For example, a first guidewire can be navigated to the left subclavian artery 202 and catheter 230 can be tracked on the first guidewire. During treatment around the left subclavian artery 202, the first guidewire may remain in place, be partially retracted, or be fully retracted. Once 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 is fully retracted, either the first or second guidewire can be advanced through catheter 230. The catheter 230 can be advanced over a first or second guidewire that has been repositioned in the right subclavian artery 203. The right subclavian artery 203 can be treated before the left subclavian artery 202, and vice versa.

[0119] If two catheters 230 are used, treatment of the right subclavian artery 203 and the left subclavian artery 202 can be at least partially synchronized. For example, a first catheter 230 may extend from the right radial (artery) entry point to the right subclavian artery 203, while a second catheter 230 may extend from the left radial (artery) entry point to the left subclavian artery 202. The first and second catheters may be similar or different (e.g., including different sizes, different neuromodulation elements 232, etc.). In some embodiments, as discussed above, the right subclavian artery 203 may be located percutaneously (e.g., percutaneous ultrasound) before transdermal delivery of the neuromodulation element 232.

[0120] In some embodiments, subclavian loop ablation is unilateral (only the left dorsal subclavian loop 204 and / or the left ventral subclavian loop 206, or only the right dorsal subclavian loop 205 and / or the right ventral subclavian loop 207). In some embodiments, subclavian loop ablation is bilateral (the left dorsal subclavian loop 204 and / or the left ventral subclavian loop 206, and the right dorsal subclavian loop 205 and / or the right ventral subclavian loop 207). This provides at least four degrees of freedom for treatment customization for specific outcomes and / or subjects. The right dorsal subclavian loop 205 and the right ventral subclavian loop 207 may be stimulated and / or treated simultaneously (at least partially), but in other configurations, they may be stimulated and / or treated sequentially. Similar to the left subclavian artery 202, in some embodiments, the right dorsal subclavian loop 205 and the right ventral subclavian loop 207 can be simultaneously or synchronously stimulated and / or simultaneously or synchronously ablated. For example, in some embodiments, the right dorsal subclavian loop 205 and the right ventral subclavian loop 207 are stimulated individually but simultaneously (or partially simultaneously) or synchronously ablated. A possible advantage of this approach is the ability to map and discretize the nerves, while simultaneously ablating the right dorsal subclavian loop 205 and the right ventral subclavian loop 207 to shorten treatment time.

[0121] Figure 3 This is a schematic diagram of an example system 300 for modulating nerves. System 300 includes a catheter 230 (which includes a neuromodulation element 232) and a signal generator 302. The signal generator can be an external signal generator, an internal signal generator (e.g., the signal generator 302 can be powered externally via inductive coupling), or a signal generator with components separated between the internal and external parts. The signal generator 302 can include 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 mobile phone or tablet computer)). System 300 may also include a control system / controller 301, which may include a processor for controlling one or more operations of system 300 as described herein, a display 303 for displaying information as described herein, and a computer interface 305 for inputting information to the control system / controller 301. System 300 may also include a pressure sensor on the distal tip of catheter 230 to aid in anatomical mapping and / or marking of sites where stimulation and / or ablation have been applied. For example, when the pressure sensor contacts the arterial wall, the reading from the pressure sensor can be transmitted by the signal generator 302 to generate a real-time reconstruction of the patient's artery on the display 303.

[0122] If the neuromodulation element 232 includes electrodes, the signal generator 302 can generate an electrical signal configured for non-therapeutic SAS. For example, non-therapeutic SAS may include monopolar, bipolar, or multipolar stimulation with pulse widths between about 0.05 milliseconds (ms) and about 4 ms, such as between 2 ms and 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, and ranges between such values, etc.), frequencies between at least about 0.1 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, and ranges between such values, etc.), and amplitudes between about 0.1 mA and about 30 mA. The voltage range is between 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, etc.), and the duration is between about 15 seconds and about 30 seconds (e.g., about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, 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 10 Hz, or less than or equal to about 5 Hz. The output voltage required for SAS may depend on the type of conduit used and / or the distance of the neural modulation element 232 to the left or right subclavian loop. When the neural modulation element 232 is in contact with or very close to the loop, SAS can be performed at a lower output voltage compared to when the neural modulation element 232 is farther from the loop. Signals configured for non-therapeutic SAS may have an output voltage between about 5 volts (V) and / or less than or equal to about 70 volts (e.g., about 5 volts, about 10 volts, about 20 volts, about 30 volts, about 40 volts, about 50 volts, about 60 volts, about 70 volts, and so on). For example, a signal may have an output voltage of at least about 5 V and / or less than or equal to about 25 V, such as less than or equal to about 20 V, less than or equal to about 10 V, 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 a 2:1 recharge pulse width or an active first phase with a passive recharge phase), wherein the duration is based on the capacitance connected to ground. The duty cycle may depend on hysteresis or the cardiac system (e.g., stimulation-induced RR shortening). The duration of stimulation may be less than 1 second or greater than 30 seconds, or any intermediate value. The recovery time may be several seconds or several minutes, after which stimulation may be repeated as desired.

[0123] Signal generator 302 can also, or optionally, generate signals configured for ablation. Tissue denervation occurs above 50°C. Various modes can be used for ablation of the subclavian loop, including, for example, radiofrequency (RF), high-power short-term RF (HPSD RF), cryoablation (CB), microwave, high-intensity focused ultrasound (HIFU), electroporation, and combinations thereof. The RF energy used to produce RF ablation can be between approximately 50 kHz and approximately 1,500 kHz (e.g., approximately 500 kHz, approximately 100 kHz, approximately 250 kHz, approximately 350 kHz, approximately 400 kHz, approximately 450 kHz, approximately 500 kHz, approximately 600 kHz, approximately 750 kHz, approximately 1,000 kHz, approximately 1,500 kHz, and so on), and within a specific time window, such as between approximately 15 s and approximately 90 s (e.g., approximately 15 s, approximately 20 s, approximately 30 s, approximately 40 s, approximately 50 s, approximately 60 s, approximately 75 s, approximately 90 s, and so on), using approximately 10 watts (W) to approximately 60 W (e.g., approximately 10 W, approximately 20 W, approximately 30 W, approximately 40 W, approximately 50 W, approximately 60 W, and so on). Power generation is typically in the range of W, etc. Most damage is caused by conductive heat, which is inversely proportional to the distance from the electrode tip. HPSD RF employs higher power and shorter durations. For example, HPSD RF can use power between approximately 50 W and approximately 90 W (e.g., approximately 50 W, approximately 90 W, etc.) and durations between approximately 4 s and approximately 15 s (e.g., approximately 4 s, approximately 15 s, etc.). The principle of high-power, short-duration ablation aims to alter the balance between resistive and conductive energy transfer and improve the persistence of tissue damage. Prior to RF ablation, DC or DC ablation primarily causes cell damage through electroporation or thermal injury. Electroporation can be applied with energy greater than approximately 200 joules (J) for several milliseconds. CB involves three phases of tissue damage. The first phase occurs during CB delivery and is known as the cryo-thaw phase. As the temperature drops below -15°C, micro-extracellular ice formation occurs, followed by intracellular ice formation when the temperature drops below -40°C, leading to local tissue damage. With thawing, ice crystals fuse with microthrombi, and platelets aggregate. Subsequently, a hemorrhage-inflammatory phase occurs, accompanied by local tissue inflammation and edema, and finally, a replacement-fibrosis phase occurs, developing into fibrotic scarring. The signal generator can accommodate all these settings and timings as needed to achieve complete ablation and denervation of the subclavian loop.Cryoprobes can be used to ablate the subclavian loop by utilizing tissue cooling and the Joule Thompson effect, as well as by circulating rare inert gases such as argon or helium. The cryogenic probe can be used with circulating cryoprobes.

[0124] Figure 4 This is a schematic diagram of an example neuromodulation element 400. The neuromodulation element 400 is positioned at the distal portion of a conduit 402, which may also be referred to as an elongated element. The neuromodulation element 400 includes a plurality of supports 404 and a plurality of electrodes 406 connected to the supports 404. The term "support" should not be limited to material left after cutting from a tube, but may also include filaments woven together, strips of material joined together (e.g., at the proximal and distal ends), tubular elements, combinations thereof, etc. Electrodes 406 may be directly connected to the supports 404 (e.g., as shown in the diagram). Figure 4 (Illustrated in the diagram) or as part of an electrode assembly connected to the support 404. The assembly of electrodes 406 can be used to provide electrical stimulation to the subclavian loop. Multiple electrodes (such as...) Figure 4 (As shown) can be referred to as an array of electrodes 406. For example, one or more of electrodes 406 can be used as an anode, and one or more of electrodes 406 can be used as a cathode. If electrical stimulation shows nerve capture, the same combination of electrodes 406 can be used with different parameters to ablate the nerve.

[0125] Figure 5 This is a schematic diagram of another example of a neuromodulation element 500. The neuromodulation element 500 is positioned at the distal portion of the conduit 502. The neuromodulation element 500 includes a ring 504 and a plurality of electrodes 506 coupled to the ring 504. The term ring should not be limited to circular or arcuate members and may include helical, partially arcuate members, combinations thereof, etc. Electrodes 506 may be directly coupled to the ring 504 (e.g., as shown in the diagram). Figure 5 (Illustrated in the diagram) or as part of an electrode assembly coupled to ring 504. A separate neuromodulation element may be used for SAS prior to ablation, such as any of the neuromodulation elements described herein. In some embodiments, stimulation with cryoenergy can be applied after initial cooling; this stimulation can be very localized and short-lived. Once the location of the target tissue is identified, cryoenergy can be applied to electrode 506 to ablate the tissue surrounding ring 504.

[0126] Figure 6This is a schematic diagram of another example of a neuromodulation element 600. The neuromodulation element 600 is positioned at the distal portion of the conduit 602. Similar to neuromodulation element 500, neuromodulation element 600 includes a ring 504 and a plurality of electrodes 506 coupled to the ring 504, these electrodes being configured to apply cryoenergy to ablate tissue surrounding the ring 504. Neuromodulation element 600 further includes a second ring 604 and a second plurality of electrodes 606. The electrodes 606 may be directly coupled to the ring 604 (e.g., as shown in the diagram). Figure 6 (Illustrated schematically) or as part of an electrode assembly coupled to ring 604. The combination of electrodes 606 can be used to provide electrical stimulation to the subclavian loop. For example, one or more of electrodes 606 can be used as an anode, and one or more of electrodes 606 can be used as a cathode. If electrical stimulation shows nerve capture, the corresponding combination of electrodes 506 can be used to ablate the nerve with cryo-energy. Rings 504 and 604 are positioned close enough that this short distance does not negatively affect the ablation location, even if it slightly deviates from the location of the captured nerve. In some embodiments, the distance between rings 504 and 604 is between about 0 mm (e.g., contact) and about 3 mm (e.g., about 0 mm, about 0.5 mm, about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 3 mm, and so on). In some embodiments, after identifying the location of the target tissue with ring 604, the catheter 602 is advanced distally a known distance between rings 504 and 604 so that the ablation electrode 506 is in the same position as the stimulating electrode 606. For example, the handle of catheter 602 may include a slider in the channel that, when advanced distally, advances catheter 602 and / or neuromodulation element 600 distally between the known distances of rings 504, 604.

[0127] Figure 7 This is a schematic diagram of another example of a neuromodulation element 700. The neuromodulation element 700 is positioned at the distal portion of a conduit 702. Similar to neuromodulation element 400, neuromodulation element 700 includes a plurality of struts 404 and a plurality of electrodes 406 coupled to the struts, these electrodes being configured to apply SAS (subclavian articulation). Similar to neuromodulation element 500, neuromodulation element 700 includes a ring 504 and a plurality of electrodes 506 coupled to the ring 504, these electrodes being configured to apply cryoenergy to ablate tissue surrounding the ring 504. The combination of electrodes 406 can be used to provide electrical stimulation to the subclavian loop. If electrical stimulation shows nerve capture, the ring 504 can be moved longitudinally and / or rotatably to the appropriate position such that the cryoenergy applied to the selected electrode 506 ablates tissue. The conduit 702 may include, for example, a tether 708 attached to the ring 504 and configured to move the ring 504 longitudinally and / or rotatably orient the ring 504, thereby orienting the electrodes 506.

[0128] Figure 8 This is another example of a neuromodulation element 800 in a blood vessel 808 (e.g., an artery such as the subclavian artery). The neuromodulation element 800 is positioned at the distal portion of a conduit 802. The neuromodulation element 800 includes a bottle-stop drill or helical member 804 and a plurality of electrodes 806 coupled to the bottle-stop drill 804. The electrodes 806 may be directly coupled to the bottle-stop drill 804 (e.g., as shown in the diagram). Figure 8 (Illustrated in the diagram) or as part of an electrode assembly coupled to a bottle stopper drill 804. The bottle stopper drill 804 may be configured to dilate the wall of the artery 808 (e.g., as shown in the diagram). Figure 8 (As shown in the diagram), for example, to reduce the distance between electrode 806 in artery 808 and the nerve of interest, thereby providing additional targeting and / or providing isolation. A separate neuromodulation element may be used for SAS prior to ablation, such as any of the neuromodulation elements described herein. Once the location of the target tissue is identified, energy can be applied to electrode 806 to ablate the tissue surrounding the stopper drill 804.

[0129] Figure 9 This is an example schematic diagram or cross-sectional view of the end of a neural modulation element 900 in a blood vessel 902 (e.g., an artery such as the subclavian artery). The neural modulation element 900 can be used as described herein. Figures 4-8 The described stimulation and / or ablation element or any other stimulation and / or ablation element is compatible. The features of the neuromodulation element 900 are compatible with or can be used with any of the catheters described herein (e.g., catheters 230, 402, 502, 602, 702, 802, 1002, 1401, and 1500 (described below)). The neuromodulation element 900 includes a trunk 904 and a plurality of electrodes 906 connected to the trunk 904. The trunk 904 may include, for example, a strut, a ring, a stopper-shaped element, etc. The electrodes 906 include a tip 908 having a triangular shape. The base 908 is shaped to push the tip of the electrode 906 into the vessel wall. The electrode 906 optionally further includes one or more electrode protrusions 910 (e.g., located on each side of the tip 908), for example, to disperse energy and / or push the electrode 906 into tissue contact.

[0130] Figure 10 This is a schematic diagram of another example of a neuromodulation element 1000. The neuromodulation element 1000 is positioned at the distal portion of a conduit 1002, which may also be referred to as an elongated element. The neuromodulation element 1000 may include a stimulation and / or ablation element 1004 (e.g., as described herein). Figures 4-9The neuromodulation element 1000 may include, for example, multiple spokes comprising electrode pads covering specific radial locations (e.g., relative to a clock face, 2:00 to 3:00, 3:00 to 4:00, etc.) to enable selective stimulation of the subclavian loop. The neuromodulation element 1000 further includes a distal protection device 1006. The distal protection device 1006 may include, for example, a filter having a distally facing opening configured to capture blood clots, thrombi, emboli, and / or any other substances that may form during SAS and / or ablation, preferably preventing them from flowing into the subject's arm or other areas. Similar to other neuromodulation elements described herein, the neuromodulation element 1000, in several embodiments, preferably does not obstruct blood flow.

[0131] Figure 11 An end view of an example neural modulation element 1100 in a blood vessel (e.g., subclavian artery 1102) is schematically shown. The neural modulation element 1100 can be, for example, neural modulation elements 232, 400, 500, 600, 700, 800, 900, 1000, and 1500 (discussed below). The central spline of the neural modulation element 1100 opens in the subclavian artery 1102 in response to operator adjustments to catheter control to expose electrode contacts 1104, which flare out radially and remain in close proximity to the wall of the subclavian artery 1102. This close proximity determines the ability to stimulate the lumen 1103 of the subclavian artery 1102 at the selected electrode contacts 1104 to determine the location of the dorsal subclavian loop 1106 and the ventral subclavian loop 1108. This information is then sent to a computer, which integrates the location information, stimulated channels / electrodes, and biomarker analysis, and overlays the measured biomarker changes onto the anatomical structure of the subclavian artery 1102, as illustrated and divided into regions. This overlay informs the operator of the location of the strongest SAS response, thus indicating where to direct the ablation energy, and allows for re-verification of ablation success through repeated SAS stimulation. This process can be repeated multiple times until successful ablation of all subclavian loop 1106 and 1108 nerves is achieved and the operator is satisfied.

[0132] Figure 12This is a flowchart of an example method 1200 for treating a subject. Method 1200 can be performed using any of the neuromodulation elements described herein (e.g., neuromodulation elements 232, 400, 500, 600, 800, 900, 1000, 1100, 1400) or other neuromodulation elements such as catheter 1500 (discussed below). At box 1202, a specific electrode is stimulated to provide non-therapeutic stimulation. At box 1204, the results are fed to a computer interface (e.g., automatically, manually, or semi-automatically). At box 1206, real-time data analysis is performed on the results. At box 1208, the computer overlays anatomical images (e.g., schematic depictions, real ultrasound images, combinations thereof, or similar images) with the response to the neurostimulation. At box 1210, the point of maximum response marked with an asterisk or other indicator is ablated. At box 1212, the specific electrode is restimulated to examine efficacy. For example, if the stimulation continues to produce changes in cardiac parameters, it indicates that the stimulated nerve has not been adequately ablated.

[0133] Figure 13 It is possible to base Figure 12 Method 1200 is illustrated by an example provided by a computer. The depiction of the subclavian artery 1302 is divided into eight radial segments 1304. For example, based on the expected, known, and / or detected location of the subclavian loop, segments 1304 may be asymmetrical (e.g., as shown in the image). Figure 13 (As shown). Although Figure 13 Eight segments 1304 are shown, but more or fewer segments 1304 are possible (e.g., depending on the number of electrodes). The computer places a first asterisk 1306 at a location believed to include the dorsal subclavian loop and a second asterisk 1308 at a location believed to include the ventral subclavian loop. The percentage shown in segments 1304 indicates the likelihood that segment 1304 including the subclavian loop will be ablated. Segments 1304 may also, or optionally, be color-coded.

[0134] Figure 11 , Figure 12 and Figure 13 Embodiments of a method and system for allowing identification of the subclavian loop along the circumference of the subclavian artery are shown. In addition to identifying the anterior and posterior loops along the circumference, the neural modulation element 1100 (which may be, for example, neural modulation elements 232, 400, 500, 600, 700, 800, 900, 1000, 1400 (discussed below)) may also have electrodes simultaneously along the circumference and along the length of the conduit. For example, 5 to 20 electrodes are used in one embodiment. In such a configuration, Figure 11 , Figure 12 and Figure 13The methods and systems can be configured to allow identification of the subclavian loop along the length of the subclavian artery. For example, when the central spline of the neural modulation element 1100 opens in the subclavian artery 1102 in response to an operator's adjustment of catheter control to expose electrode contacts 1104, the electrode contacts 1104 are radially flared outward and longitudinally distributed along the length of the subclavian artery 1102. In addition to circumference, the above superposition may also include superposition of the length of the subclavian artery 1102, such that the subclavian artery 1302 is divided into radial segments 1304 (e.g., eight) and longitudinal segments (e.g., two to eight longitudinal segments). Such longitudinal segments can be labeled, shown, and incorporated into the algorithm as described above. For example, in one embodiment, the neural modulation element 1100 may be, for example, neural modulation elements 232, 400, 500, 600, 700, 800, 900, 1000, 1400 (discussed below). The central spline of the neuromodulation element 1100 opens in the subclavian artery 1102 in response to operator adjustments to catheter control to expose electrode contacts 1104, which flare out radially and also extend along the length of the subclavian artery 1302 (e.g., as shown in the image). Figure 14A The catheter (shown as 1400) is kept in close proximity to the wall of the subclavian artery 1102. This close proximity determines the ability to stimulate the lumen 1103 of the subclavian artery 1102 at the selected electrode contact 1104 to determine the location of the dorsal subclavian loop 1106 and the ventral subclavian loop 1108. This information is then fed to a computer, which integrates the location information, the stimulated channel / electrode, and biomarker analysis, and overlays the measured biomarker changes onto the anatomy of the subclavian artery 1102, as shown and divided into radially extending regions along the artery length. The overlay informs the operator of the location of the greatest SAS response, thus indicating where to direct the ablation energy, and allows for rechecking the success of the ablation by repeating SAS stimulation. This process can be repeated multiple times until successful ablation of all nerves in the subclavian loops 1106 and 1108 is achieved and the operator is satisfied.

[0135] Figure 12This is a flowchart of an example method 1200 for treating a patient. At box 1202, a specific electrode is stimulated to provide non-therapeutic stimulation. At box 1204, the results are fed to a computer interface (e.g., automatically, manually, or semi-automatically). At box 1206, real-time data analysis is performed on the results. At box 1208, the computer overlays an anatomical image (e.g., a schematic depiction, a real ultrasound image, a combination thereof, or similar) with the response to nerve stimulation. This anatomical image may include radial locations / segments along more than one location along the length of the artery. At box 1210, the point of maximum response, marked with an asterisk or some other indicator, is ablated. At box 1212, the specific electrode is restimulated to check efficacy. For example, if stimulation continues to produce changes in cardiac parameters, it indicates that the stimulated nerve has not been adequately ablated. In one embodiment, catheters 230, 402, 500, 600, 700, 800, 900, 1000, and 1400 may also be moved to different locations along the length of the artery, and one or more of the above actions may be repeated to collect additional information at different locations along the length of the artery. This process may be repeated at one or more different locations.

[0136] Figure 13 It is possible to base Figure 12 Method 1200 is illustrated by an example provided by a computer. In embodiments where the radial positions / segments are located at more than one location along the length of the artery, the depiction of the subclavian artery 1302 is divided into eight radial segments 1304, and can provide a similar arrangement to... Figure 13 Additional images are provided to represent radial segments at different locations along the length of the artery. In some embodiments, the artery length for which the detection is made may extend from the orifice or opening of the subclavian artery to the portion where the artery begins to bend toward the arm. In some embodiments, this length of the artery may be divided into equal or unequal longitudinal segments, while in some embodiments it may be divided into 5, 6, 7, 8, 9, or 10 equal or unequal longitudinal segments. In some embodiments, fewer or additional segments may also be used. In some embodiments, the artery length for which the detection is made may be between approximately 1 cm and 5 cm. For example, segment 1304 may be asymmetrical (e.g., as shown in the image) based on the expected, known, and / or detected location of the subclavian loop. Figure 13 (As shown in the diagram). Segment 1304 can be asymmetric. Although Figure 13 Eight segments 1304 are shown, but more or fewer segments 1304 are also possible (e.g., depending on the number of electrodes). As mentioned above, in addition to showing the radial segments, more than one image may be provided (such as...). Figure 13Images (of the artery) are used to illustrate data collected at different locations along the length of the artery. Each image may be provided with a visual indicator indicating the location along the length of the artery. Furthermore, in one embodiment, a three-dimensional representation of radial segments along more than one location along the length of the artery may be provided on the display. In one embodiment, tables or charts may also be provided to display the information. Additionally, in some embodiments, ultrasound may be used to visualize the location of the stellate ganglion and subclavian artery. For example, in some embodiments, markers may be positioned on the patient, such as skin markers visible under fluorescence examination. These markers can be used to identify the peripheral boundaries of the artery.

[0137] In the embodiments described herein, the damage or ablation pattern formed by the electrodes can have a variety of shapes, such as, for example, circular, annular, cigar-shaped, linear, donut-shaped, elliptical, and / or spherical. In some embodiments, the damage width can be between 5 mm and 15 mm (e.g., 5 mm, 7 mm, 9 mm, 11 mm, 13 mm, 15 mm, etc.), and the depth can be between 2 mm and 10 mm (e.g., 2 mm, 4 mm, 6 mm, 8 mm, 10 mm, etc.).

[0138] Various modes can be used to ablate the subclavian loop, including radiofrequency (RF), high-power short-time RF (HPSDRF), cryoablation (CB), microwave, ultrasound, high-intensity focused ultrasound (HIFU), electroporation, steam, laser, heat, alcohol or other alcohols or other chemicals, cryoablation or combinations thereof, and the ablation can be reversible or irreversible. The RF energy that produces RF ablation can be at frequencies between approximately 50 kHz and approximately 1,500 kHz (e.g., approximately 500 kHz, approximately 100 kHz, approximately 250 kHz, approximately 350 kHz, approximately 400 kHz, approximately 450 kHz, approximately 500 kHz, approximately 600 kHz, approximately 750 kHz, approximately 1,000 kHz, approximately 1,500 kHz, and so on), and within specific time windows, such as between approximately 15 seconds (s) and approximately 90 seconds (e.g., approximately 15 s, approximately 20 s, approximately 30 s, approximately 40 s, approximately 50 s, approximately 60 s, approximately 75 s, approximately 90 s, and so on), using approximately 10 watts (W) to approximately 60 W (e.g., approximately 10 W, approximately 20 W, approximately 30 W, approximately 40 W, approximately 50 W). Power generation is typically between approximately 50 W and approximately 60 W, or within such ranges, etc. Most damage occurs due to conductive heat, which is inversely proportional to the distance from the electrode tip. HPSD RF employs higher power and shorter durations. For example, HPSD RF can use power between approximately 50 W and approximately 90 W (e.g., approximately 50 W, approximately 90 W, or within such ranges, etc.) and durations between approximately 4 s and approximately 15 s (e.g., approximately 4 s, approximately 15 s, or within such ranges, etc.). The principle of high-power, short-duration ablation aims to alter the balance between resistive and conductive energy transfer and improve the persistence of tissue damage. Prior to RF ablation, DC or DC ablation primarily causes cell damage through electroporation or thermal injury. Electroporation can be applied using energy greater than approximately 200 joules (J) for several milliseconds. CB involves three phases of tissue damage. The first phase occurs during CB delivery and is referred to as the freeze-thaw phase. As the temperature drops below -15°C, micro-extracellular ice formation occurs, followed by intracellular ice formation when the temperature drops below -40°C, leading to local tissue damage. With thawing, ice crystals fuse with microthrombi, and platelets aggregate. Subsequently, a hemorrhage-inflammatory phase occurs, accompanied by local tissue inflammation and edema, and finally, a replacement-fibrosis phase occurs, developing into fibrotic scarring. The signal generator can be adapted to all these settings and timings as needed to achieve complete ablation and denervation of the subclavian loop.Cryoprobes can be used to ablate the subclavian loop by utilizing tissue cooling and the Joule Thompson effect, as well as by circulating rare inert gases such as argon or helium. The cryogenic probe can be used with circulating cryoprobes.

[0139] Figures 14A-14B and Figures 15A-15B Embodiments of methods and systems for measuring the expansion or dilation of the subclavian artery are illustrated. A neuromodulation element 1400 (which may be, for example, neuromodulation elements 232, 400, 500, 600, 700, 800, 900, 1000, 1100) may include a catheter 1401, also referred to as an elongated element, and may include an expansion element 1404, which may expand or contract by operator adjustment of the catheter 1401 (e.g., by adding or removing water or gas, or other mechanical means). In the illustrated embodiments, the expansion element 1404 may be formed in a variety of ways to provide radial expansion of the surface of the expansion element 1404. In some embodiments, the expansion element 1404 may include a balloon, which may be inflated with an inflating medium. In some embodiments, the expansion element 1404 may be mechanically inflated using a self-expanding stent or a linkage mechanism. In embodiments utilizing a balloon, the inflating element 1404 pushes against the inner wall of artery 1402, causing artery 1402 to dilate. The deflation of the inflating element 1404 allows artery 1402 to contract back to its original size. The neuromodulation element 1400 may be in the form of electrodes 1406 extending both along the length of catheter 1401 and / or around its circumference (including along the length of the outer surface of the inflating element 1404 and around its circumference), these electrodes may be arranged in an array and may be referred to as an array of electrodes 1406. The operator can determine whether to inflate or deflate the inflating element 1404, and to what extent, based on various parameters measured by the electrodes 1406. Such parameters include, but are not limited to, vessel diameter, proximity of catheter 1401 to the nerve of interest, and tissue compliance. These dilation measurements can be used for radial and longitudinal segmentation of the arterial wall.

[0140] Figure 14A A schematic side view of the catheter / elongated element 1401 is shown, wherein the expansion element 1404 includes a neuromodulation element 1400 positioned on the expansion element 1404 and wherein the expansion element 1404 is in a partially expanded configuration within the artery 1402. The expansion element 1404 may be designed such that, in its partially expanded configuration, the electrode 1406 of the neuromodulation element 1400 contacts the inner wall of the artery 1402. Figure 14BA schematic side view of catheter 1401 is shown, in which expansion element 1404 is in a second, more fully expanded configuration within artery 1402, causing artery 1402 to dilate. The inner diameter and / or amount of dilation of artery 1402 may be determined by catheter 1401 (e.g., via electrodes and / or sensors located on the radially opposite side of expansion element 1404).

[0141] As the expansion element 1404 expands and the artery 1402 dilates, the distance between the electrode 1406 and the nerve of interest 1410 can be reduced, resulting in a decrease in the stimulation threshold measured by the electrode. This allows the distance between the electrode 1406 and the nerve of interest 1410 to be determined using the stimulation threshold measured by the electrode 1406. A smaller distance between the electrode 1406 and the nerve of interest 1410 advantageously minimizes the amount of ablation energy required and allows for more targeted application of the ablation energy. In addition to utilizing the stimulation threshold, biomarker measurements, as described herein, can also be used to identify movement of the electrode 1406 closer to the nerve of interest 1410. As described above, these measurements can also be made along radial and longitudinal segments of the arterial wall.

[0142] In some embodiments, impedance spectroscopy measurements taken by electrode 1406 can be used to estimate tissue compliance. This advantageously allows ensuring that the vasculature is not over-expanded and / or damaged as the balloon assembly (also referred to as the balloon) 1404 is inflated to attempt to increase the proximity of electrode 1406 to nerve 1410 of interest. For example, in some embodiments, a signal and / or alarm can be provided to the user to stop the expansion of the inflator element 1406 if the impedance exceeds a threshold for a given frequency (exceeds the threshold for a given frequency and / or falls below the threshold for a given frequency) so as not to over-expand or damage the vasculature. In one embodiment, if the impedance exceeds a threshold for a given frequency (exceeds the threshold for a given frequency and / or falls below the threshold for a given frequency), the system can automatically stop the expansion of the inflator element 1406 or reduce the expansion of the inflator element 1406 so as not to over-expand or damage the vasculature. Impedance spectroscopy measurements can be used to estimate the impedance of fluid and / or tissue surrounding electrode 1406. As the fluid / tissue in contact with electrode 1406 changes with the expansion of inflator element 1404, the impedance also changes. Furthermore, as the tissue thickness changes with the expansion element 1404, the impedance also changes. Impedance spectroscopy can provide feedback to the system at one or more different frequencies. In some embodiments, the feedback may indicate the uniformity of the circumferential contact between the electrode 1406 and the blood vessel 1402. In other embodiments, the feedback may provide information about how much blood is in contact with the electrode 1406. In yet another embodiment, feedback from impedance spectroscopy may provide the approximate location of the nerve target 1410 because the impedance on the electrodes 1406 closest to the nerve 1410 changes compared to those electrodes 1406 that have only slight contact with the smooth muscle, especially when the expansion element 1404 is expanded.

[0143] Figure 15A A cross-sectional view of the expansion element 1404 in a partially expanded configuration within the artery 1402 is shown. Figure 15B A cross-sectional view is shown showing the expansion element 1404 in a second, more expanded configuration within the artery 1402, resulting in the expansion of the artery 1402.

[0144] In some embodiments, a custom system for treating the subclavian loop includes one or more of the following features. It is assumed that the lumen of the subclavian artery is circular and can be divided like a clock face. The dorsal subclavian loop may be between approximately 7:00 and approximately 11:00, while the ventral subclavian loop may be between approximately 2:00 and approximately 5:00, and electrodes can be concentrated at these locations. Furthermore, as described above, the electrodes may also be distributed along the length of the catheter, such that the lumen of the subclavian artery is divided not only along its circumference but also along its length. In some embodiments, the catheter may be moved longitudinally along the length of the subclavian artery lumen to generate longitudinal partitions and / or create additional longitudinal partitions, and / or the catheter may be rotated to generate radial partitions and / or create additional radial partitions. In some arrangements, a combination of radial and longitudinal partitions can form a grid. Non-therapeutic stimulation along the length and / or circumference of the artery provides precise localization of the loop, thereby providing ablation sites along its length and / or circumference. After ablation, the loop may be re-stimulated to verify the success of the ablation. Sympathetic nerve stimulation biomarkers may include, for example, (i) systolic biomarkers, such as, for example, developmental pressure (dP / dt), arterial blood pressure (systolic, diastolic, mean), pulse pressure changes, generalized blood pressure elevation, and left ventricular developmental pressure (dP / dt) elevation; (ii) chronotropic biomarkers, such as, for example, changes in heart rate or sinus cycle length (RR or QQ interval changes on surface ECG), increased heart rate (RR interval shortening), and changes in basal cycle length on intracardiac electrocardiogram; (iii) transconductance biomarkers, such as, for example, PR interval changes (indicators of changes in heart rate and AV conduction time), QT interval changes (indicators of changes in ventricular excitation and denervation). / Indicators of increased ablation activation recovery interval (measured by electrocardiography in an EP laboratory), changes in QT variability, changes in T peak-T end interval, increased atrial and ventricular refractory periods due to denervation / nerve signal blockade, decreased arrhythmogenic induction demonstrated by S1-S2 stimulation pulse train testing, increased left ventricular contractility, shortened PR and / or QT intervals, shortened effective refractory / activation recovery intervals of the atria and / or ventricles, induction of atrial irregular tachycardia, changes in atrial conduction time and / or ventricular irregular tachycardia, which can be stopped by cardioversion or electric shock); (iv)Relaxation biomarkers, such as, for example, the negative derivative of developmental pressure. (v) differentiated function), and changes in the basic slope of the pressure-volume loop; (v) inflammatory biomarkers, such as, for example, decreases in inflammatory markers—changes in CRP (blood and tissue), local tissue TNFα levels, decreased inflammasome levels, changes in leukotrienes and prostaglandin levels or their precursors, and decreased 3-nitrotyrosine levels in myocardial or tissue biopsies.For some biomarkers, ablation may produce adverse effects below baseline, such as a slight decrease in baseline heart rate, a mild decrease in arterial pressure, little change in left ventricular contractility, and / or a prolonged effective refractory period. If repeated stimulation does not produce the same changes in sympathetic stimulation biomarkers, the ablation is considered successful. Therefore, in some applications, the location of the neural modulator 1110 within the subclavian artery is first confirmed, followed by stimulation to identify the loop, identification of cardiac biomarkers, and then a denervation procedure (e.g., ablation) is performed on the loop. Once the denervation procedure is complete, the result can be confirmed by applying stimulation again and showing that the biomarkers no longer change with stimulation. Denervation (such as ablation) can be partial or complete, and can be reversible or permanent.

[0145] In some embodiments, the controller 301 may employ a machine learning algorithm that can be used to set and / or automatically adjust the stimulation applied by the catheter and / or analyze monitored cardiac parameters and / or biomarkers. In some embodiments, the machine learning algorithm may adjust stimulation parameters (e.g., power, duration, amplitude, etc.) based on monitored cardiac parameters and / or biomarkers and / or in conjunction with monitored cardiac parameters and / or biomarkers after ablation of the targeted nerve. In some embodiments, training of the machine learning algorithm yields determinations of typical locations, stimulation parameters, ablation parameters, cardiac parameters, and / or biomarkers.

[0146] Figure 16 Figure 22 illustrates an embodiment of a method and system that allows simultaneous innervation of contralateral blood vessels and navigation of vascular anatomy. A catheter 1500 (which may include, for example, any features of catheters 230, 402, 502, 602, 702, 802, 1002, 1401), also referred to as an elongated element, can be used in conjunction with any of the aforementioned methodologies to stimulate or ablate any of the aforementioned nerves for any of the aforementioned indications. The catheter 1500 may include a flexure element 1502 at a distal location for neuromodulation. The flexure element 1502 may change configuration (e.g., position) relative to the central axis XX defined by the catheter shaft 1520 in response to operator adjustments to control features (e.g., via a drawstring or shaping needle). The catheter 1500 may include a neuromodulation element positioned on the flexure element 1502. The neuromodulation element may be configured to provide sensing, stimulation, and / or therapy. The neuromodulation element may include one or more electrodes as described below.

[0147] Figure 16 A perspective view of the flexural element 1502 is shown. Figure 17 The front view of the flexural element 1502 is shown. Figure 18A A side view of the flexural element 1502 is shown, and Figure 18BThe flexural element 1502 is shown along... Figure 18A The cross-section is taken by line AA in the diagram. The flexural element 1502 may include a proximal hub 1504 fixed to the distal end of the conduit shaft 1520. The proximal hub 1504 may be made of, for example, metal, polymer, a metal-polymer composite, or other similar materials. In some embodiments, the proximal hub 1504 may include one or more electrodes 1516, or the proximal hub 1504 itself may function as an electrode.

[0148] The flexural element 1502 may further include at least one elongated leg 1508. In the illustrated embodiment, the flexural element 1502 has three legs 1508, but more legs (e.g., four, five, six, seven, etc.) or as few as one leg 1508 are also possible. In embodiments containing more than one elongated leg 1508, when viewed from the front (e.g., Figure 17 When viewed, the elongated leg 1508 extends along an arcuate interval around the central axis XX, wherein the arc extends less than 360 degrees around the central axis XX, for example, less than approximately 300 degrees, less than approximately 270 degrees, less than 180 degrees, or less than 90 degrees around the central axis XX. This achieves selective stimulation of only one side of the blood vessel. In some cases, the arc may extend between 225 degrees and 315 degrees (e.g., approximately 270 degrees). At least one leg 1508 may be flexible and made of, for example, nitinol, spring-tempered stainless steel, or other materials with similar properties. The proximal end of at least one leg 1508 may be secured to a proximal hub 1504. The leg 1508 may include one or more electrodes or electrode rings 1516. The leg 1508 and the electrodes 1516 are shaped and positioned to drive one or more electrodes 1516 into contact with the blood vessel wall. For example, when axially compressed, a portion of leg 1508 (e.g., the middle portion) bends, flexes, or deflects away from the central axis XX of the assembly, rather than toward the central axis XX (as described below). Figure 20 and Figures 22A-22C(Shown and described). During actuation, the proximal end of at least one leg 1508 remains in place. In some embodiments, at least one leg 1508 may be completely or partially surrounded by a sheath 1510 to isolate the leg 1508 during neural modulation. The flexure element 1502 may further include a distal hub 1506 fixed to the distal end of at least one leg 1508, such that at least one leg 1508 extends between the proximal hub 1504 and the distal hub 1506. In some embodiments, the distal hub 1506 may include one or more electrodes 1516, or the distal hub 1506 itself may serve as an electrode. The distal hub 1506 may be made of, for example, metal, polymer, a metal-polymer composite, or other similar materials. The axial and / or circumferential positions of the electrodes 1516 or hubs 1504, 1506 on the leg 1508 may be positioned such that bending of the flexure element positions the electrodes in contact with the vessel wall.

[0149] The flexure element 1502 may further include a control feature, shown as a drawstring 1514 fixed to the distal hub 1506, capable of axial translation to control the configuration of the flexure element 1502. The drawstring 1514 may extend proximally along the entire length of the conduit 1500 and may slide freely within the conduit shaft 1520 and the proximal hub 1504. The drawstring 1514 may be made of, for example, nitinol, stainless steel, or other similar materials. In some embodiments, the drawstring 1514 may be completely or partially surrounded by a drawstring sheath 1524 to isolate the drawstring 1514 during neural modulation. As shown, the drawstring 1514 is positioned off-axis relative to the central axis XX and may be positioned on the side of the conduit 1500 without legs(one or more) 1508. In other configurations, the drawstring 1514 may be positioned along the central axis XX. As an alternative to the drawstring, the conduit 1500 may include a shaped needle to navigate the flexure element off-axis relative to the central axis XX. For example, the catheter can be pre-shaped to position the flexure element 1502 off-axis relative to the central axis XX. When a core needle is advanced through the catheter, the core needle forces the catheter 1500 into a different configuration for delivery, for example, a straight configuration along the central axis XX. Once the catheter 1500 is positioned at the target location in the vascular system, when the core needle is removed from the catheter 1500, at least a portion of the catheter 1500 can return to the pre-shaped configuration, causing the flexure element 1502 to bend off-axis relative to the central axis XX.

[0150] The proximal ends of the catheter shaft 1520 and the pull cord 1514 can be attached to a handle (not shown), which provides the operator with a means to hold the catheter shaft 1520 stationary and pull the pull cord 1514. At least one leg 1508 can bend, flex, or deflect away from the central axis XX in response to the operator pulling the pull cord 1514 proximally, and return to a position aligned with the central axis XX when the operator releases the pull cord 1514 distally, as described below. Figure 20 and Figures 22A-22C Further description.

[0151] At least one leg 1508 may include one or more electrodes 1516 (e.g., one electrode, two electrodes, three electrodes, four electrodes, etc.), such as an electrode ring 1516, for one or more of sensing, stimulation, or ablation (i.e., denervation) as described herein. While these examples may be described with respect to an electrode ring, any electrode structure (including points or arrays) is possible. The entire leg 1508 and / or hubs 1504, 1508 may also include conductive material, allowing the leg 1508 and / or hubs 1504, 1508 to serve as neuromodulation elements providing sensing, stimulation, and / or therapy. The same electrodes(one or more) 1516 may provide non-therapeutic sensing or stimulation as well as therapeutic denervation—for example, by causing a signal generator to generate different signals. However, in other configurations, different electrodes or modulation devices may provide non-therapeutic sensing or stimulation compared to the electrodes providing therapeutic denervation. Due to the arrangement of one or more legs 1508, one or more electrodes 1516 may be located on one side of a blood vessel. The electrode may be arranged along an arc less than 360 degrees around the central axis XX, for example, an arc less than approximately 300 degrees around the central axis XX, less than approximately 270 degrees around the central axis XX, less than 180 degrees around the central axis XX, or less than 90 degrees around the central axis XX. One or more electrodes 1516 may be displaced from hubs 1504, 1506. One or more electrodes 1516 may be located around a curved region of a corresponding leg, wherein the curved region is configured to contact the vessel wall, for example, being positioned at the apex of the curved region.

[0152] One or more electrode rings 1516 may be arranged circumferentially around one or more portions of the leg 1508, or, in an embodiment where the leg 1508 is surrounded by a sheath 1510, circumferentially around one or more portions of the sheath 1510. One or more electrode rings 1516 may be disposed on both the proximal and distal ends of at least one leg 1508 such that when at least one leg 1508 is pulled into an approximately 90° bend by the draw wire 1514 (e.g., ...), Figure 20 and Figure 22CAs shown in the fully deployed position 2006, the electrode ring 1516 is located at either end of the bending radius. This advantageously allows multiple portions of the subject's vascular system to be simultaneously targeted with non-therapeutic stimulation and / or therapeutic treatment, but also allows for sequential application of non-therapeutic stimulation and / or therapeutic treatment to different targets. In some embodiments, one or more electrode rings 1516 may be circumferentially disposed around the middle portion of at least one leg 1508. The one or more electrode rings 1516 may be made of a platinum-iridium (PT / IR) alloy or other suitable conductive materials such as stainless steel, platinum, titanium, gold, silver, etc. A sheath 1510 may cover and isolate the portion of the leg 1508 not surrounded by the electrode rings 1516 to allow selective application of neuromodulation at the location of the electrode rings 1516.

[0153] The flexural element 1502 may include one or more RF and / or thermocouple wires 1526 that extend along at least one leg 1508 to one or more electrode rings 1516 to deliver RF and / or thermal energy to one or more electrode rings 1516.

[0154] As shown in the figure, each of the catheter 1500, proximal hub 1504, and distal hub 1506 may also include a central lumen 1518 for use with the guidewire 1522 to allow placement of the on-wire system. However, in other configurations, the catheter 1500 can be tracked or directly navigated via a guide catheter.

[0155] In some embodiments, the central cavity 1518 may include an ultrasonic crystal for ultrasonic ablation. However, the catheter 1500 may include any of the ablation modes described above. For example, the central cavity 1518 may include one or more electrodes and / or return electrodes, or similar electrodes, for RF ablation.

[0156] In some embodiments, the catheter 1500 may be configured to be coupled to a flushing system, for example, for cooling. The central lumen 1518 may include a small hole or perforation around its circumference to allow flushing to be radially released to allow cooling of the tip of the catheter 1500 during use, whether ultrasound, RF, or other denervation modes. Cooling the catheter 1500 in this way advantageously allows for deeper ablation, resulting in greater lesions, and reduces condensation on the surfaces of one or more electrodes 1516.

[0157] One or more electrodes 1516 may be included at multiple locations along the flexure element 1502 to provide one or more of ablation, stimulation, or sensing. As shown in the previous figure, one or more electrodes may be positioned along the leg(s) 1508, for example, at a flexed location of the leg(s) 1508. Each of at least one leg 1508 may carry one, two, three, or more electrodes. Figure 19The shaded areas indicate one or more additional or optional locations for the electrodes. In some implementations, such as Figure 19 As shown, at least part or all of the distal hub 1506 and / or proximal hub 1504 can also be made into electrodes for one or more of ablation, stimulation, or sensing. For example, the distal hub 1506 and / or proximal hub 1504 may carry electrode rings 1516. As another example, the distal hub 1506 and proximal hub 1504 may be larger electrodes, which may be larger than one or more electrode rings 1516 on the leg 1508. There may be electrode rings 1516 disposed distal to the radius of curvature of the leg 1508 and electrode rings 1516 disposed proximal to the radius of curvature of the leg 1508. In some embodiments, one or more electrode rings 1516 may be unidirectional to allow energy to be confined to the arterial wall side. Due to the radius of curvature of the leg 1508 (as described below regarding...), Figure 20 and Figures 22A-22C (Further described) When fully deployed, the distal hub 1506 and proximal hub 1504 are able to make very close contact with the arterial wall. In such an embodiment, the flexure element 1502 may include RF and / or thermocouple wires 1526 extending along the length of the draw wire 1514 to the distal hub 1506 and / or proximal hub 1504 to provide RF and / or thermal energy to the distal hub 1506 and / or proximal hub 1504. In some embodiments, the electrode sheath 1510 may cover and isolate at least one leg 1508 to allow selective application of neuromodulation at the location of the distal hub 1506 and / or proximal hub 1504. Furthermore, or as an alternative to any of the above examples, the catheter shaft carrying the flexure element may include one or more electrodes 1516.

[0158] In some embodiments, the proximal hub 1504 and / or the distal hub 1506 may also include a deployable umbrella or basket (not shown) for capturing any potential embolisms that may form during use. The location, size, and other parameters of the deployable umbrella or basket may be configured to protect the patient’s arteries (e.g., common carotid artery, vertebral artery, distal subclavian artery, etc.).

[0159] Figure 20 This is a schematic diagram showing the bending radius of the flexural element 1502. During actuation of the flexural element 1502, the operator can bend, flex, or deflect at least one leg 1508 away from the central axis XX and move the distal hub 1506 laterally and proximally. Figure 20As shown, the flexure element allows the proximal hub 1504 and distal hub 1506 to selectively target multiple portions of the patient's anatomy (e.g., the ventral or dorsal subclavian loop). For example, the operator can keep the catheter axis 1520 stationary and pull the drawstring 1514 proximally to induce bending, flexion, or deflection. This feature advantageously aids in the efficiency of the neuromodulation process. When no tension is applied to the drawstring 1514, the flexure element 1502 is aligned with the central axis XX in its normal position 2002 (i.e., at a 0° angle relative to the central axis XX). As the operator pulls the drawstring 1514 proximally, the flexure element 1502 will begin to flex or deflect away from the central axis XX to a partially deployed position 2004. When the operator has pulled the drawstring to its maximum distance, the flexure element 1502 will be in the fully deployed position 2006. In the illustrated embodiment, the flexure element 1502 is positioned at a 90° angle or approximately 90° angle relative to the central axis XX in the fully deployed position 2006 (e.g., approximately perpendicular). The maximum flexure angle may be less than 180 degrees, for example, less than or equal to 135 degrees or less than or equal to approximately 90 degrees. As the operator releases the drawstring 1514, the flexure element 1502 changes from the fully deployed position 2006 to the partially deployed position 2004, and eventually returns to the normal position 2002. The partially deployed position 2004 can be any position of the flexure element 1502 relative to the central axis XX between 0° and 90°. The bending radius of the flexure element 1502 is advantageous for simultaneous neuromodulation of opposite sides of the vascular wall, but sequential neuromodulation of opposite sides of the vascular wall is also possible. The bending radius of the flexure element 1502 also aids in navigating vascular anatomy.

[0160] Figures 22A-22C A three-dimensional view of the flexural element 1502 at each actuation stage is shown. Figure 22A The flexural element 1502 is shown in its normal position 2002 (i.e., aligned with the central axis XX, or at a 0° angle relative to the central axis XX). Figure 22B The flexural element 1502 is shown in a partially deployed position 2004 (i.e., at an angle of 0° to 90° relative to the central axis XX). Figure 22C The diagram shows the flexural element 1502 in its fully deployed position 2006 (i.e., substantially perpendicular to the central axis XX, or at an angle of approximately 90° relative to the central axis XX). While the illustrated embodiment shows the flexural element 1502 at a 90° angle relative to the central axis XX in its fully deployed position 2006, in other embodiments, the flexural element 1502 may be at an angle greater than 90° relative to the central axis XX in its fully deployed position 2006 (e.g., 91°, 93°, 95°, 100°, 110°, and ranges between such values, etc.).

[0161] In some embodiments, the catheters, such as catheters 230, 402, 502, 602, 702, 802, 1002, 1401, and 1500, may be actuated by a robot control system and / or have automatic or semi-automatic control capabilities. For example, in some embodiments, longitudinal movement and / or rotation of the catheter may be controlled by a robot with linear and / or rotary actuators. Bending and expansion at the distal end of the catheter may also be controlled by the robot system. In one example embodiment, the movement and motion of the catheter may be automatically controlled by the robot system to collect data as described above along radial and longitudinal partitions of the artery. Once the information is collected, the robot system may automatically or semi-automatically move the neuromodulation element to a designated or target area to perform ablation as described herein.

[0162] Figure 23 This is a flowchart of another example method 2300 for treating a subject. At box 2302, the subject presents with a refractory arrhythmia. At box 2304, the subject is stabilized, and the cause of the refractory arrhythmia is assessed. At box 2306, any ICDs are closed, and epidural anesthesia is infused to assess whether sympathetic nerve transmission is driving the arrhythmia. If sympathetic nerve transmission is not driving the arrhythmia, the arrhythmogenic lesion is assessed by an electrophysiology laboratory (EP laboratory) at box 2308. If sympathetic nerve transmission is driving the arrhythmia, a subclavian loop ablation procedure (e.g., as described herein) is performed at box 2310.

[0163] This disclosure relates to the neuromodulation (such as stimulation) and ablation of the subclavian loop of a subject according to several embodiments for the treatment of heart disease. Heart disease can refer to ventricular arrhythmias, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, congestive heart failure, and atrial flutter. Furthermore, methods and systems for neuromodulation (such as stimulation and ablation) of the subclavian loop of a subject can also be used to treat other conditions or diseases. For example, one aspect of this disclosure recognizes that stellate ganglion block or denervation, or subclavian loop ablation, can also affect hemodynamic function. In some applications, the use of pharmacological agonists or neural stimulation to activate the sympathetic nervous system can alter heart rate, contractility, conduction, and relaxation. In one embodiment, targeted sympathetic denervation / decentralization or blockade can lead to improved cardiac diastolic function. Specifically, in some embodiments, any effect that increases left ventricular compliance thereby accelerating the reduction of afterload is achieved. This increase in compliance can have a positive effect on stroke volume and resulting in an increase in cardiac output. Therefore, blocking the stellate ganglion using neural modulation (such as the ablation method proposed in this paper) can lead to improvements in diastolic function parameters, measured by changes in end-systolic meridional wall stress, peripheral vascular resistance, end-diastolic volume, and cardiac output and / or cardiac output. This can occur with or without measurable changes in heart rate, due to direct sympathetic effects on the myocardium, and is independent of conduction variations.

[0164] Ablation can also be performed without stimulation before and / or after ablation. For example, ablation can be performed entirely around the subclavian artery, including the dorsal and ventral subclavian loop locations. As another example, ablation can be performed at the intended location within the subclavian loop. For example, the longitudinal and / or radial location of the neuromodulation element can be visualized (e.g., using fluorescence examination, ultrasound, etc.), and electrodes can be selected based on the ablation energy. For example, the longitudinal and / or radial location of the neuromodulation element, with electrodes selectively positioned to correspond to the intended subclavian loop location, can be visualized (e.g., using fluorescence examination, ultrasound, etc.), and some or all electrodes can be selected based on the ablation energy. In one implementation, stimulation can be applied only after ablation to verify the ablation effect.

[0165] Combined neuromodulation therapy targeting sympathetic and parasympathetic nerves As described herein, ablation of sympathetic targets (e.g., the subclavian loop, stellate ganglion, etc.) can be used to suppress certain cardiac arrhythmias, such as atrial fibrillation or ventricular tachycardia. The efficacy of this therapy can be enhanced when the suppression of sympathetic activity is combined with the enhancement of parasympathetic activity, thereby further altering the patient's autonomic balance. Long-term stimulation therapy following sympathetic ablation advantageously provides the opportunity to sense patient-specific arrhythmia conditions (e.g., via leadless ECG, via cardiac leads, etc.) to allow for case-by-case adjustment of stimulation parameters in response to arrhythmia detection. Therefore, immediate ablation of sympathetic targets (e.g., the subclavian loop, stellate ganglion, etc.) can be combined with the implantation of a second immediate or long-term therapy to parasympathetic targets (e.g., a stimulation device).

[0166] For example, a system for combined neuromodulation of sympathetic and parasympathetic targets may include any of the systems described herein in conjunction with long-term therapies, the long-term therapy having an implantable stimulator with a lead configured to stimulate peripheral nerves (e.g., the vagus nerve, visceral nerves, their branches, etc.). The lead may be a nerve cuff lead, a self-sizing helix lead, 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. Renal denervation or ablation of the sympathetic ganglia on the epicardial surface of the heart may be performed before and / or after stimulation.

[0167] Available neural targets While this disclosure relates to selective targeting and stimulation and / or ablation of the subclavian loop, it should be understood that the systems and methods described herein can be used to selectively target other parts of the anatomical structures used for neuromodulation in order to treat other diseases or conditions. For example, the systems and methods described herein can be used to selectively target and denervate the renal nerve to treat hypertension. In another example, the systems and methods described herein can be used to target one or more of the liver, pancreas, duodenum, and kidney to perform multi-organ denervation to treat hypertension and / or diabetes.

[0168] Pharmacological therapy In several embodiments, the neuromodulation therapies described herein can be used as alternatives to pharmacological (pharmaceutical) therapies. However, in other embodiments, pharmaceutical therapy can be used in combination with the neuromodulation therapies described herein, but at a reduced frequency or dosage, thereby reducing undesirable side effects. For example, when a drug (or combination of drugs) is combined with the neuromodulation therapies described herein, the total duration of administration can be shorter, the number of daily / weekly / monthly administrations less, and / or the dosage lower. In addition to reducing undesirable pharmacological side effects, this can also reduce addiction or dependence. The neuromodulation therapies described herein can also be used to reduce or otherwise discontinue the use of analgesics and other medications.

[0169] Some experiments are described in relation to the application of drugs before, during, and / or after stimulation and / or ablation, for example, to induce certain physiological conditions. The apparatus and methods described herein can be used without the application of drugs (e.g., without the use of drugs to induce certain physiological conditions). Anesthetics and other drugs that enable electrode contact placement may be used, for example. Substances released by the subject in response to stimulation (e.g., calcitonin gene-related peptide (CGRP)) will not be considered as administered drugs.

[0170] The above description and examples are provided for illustrative purposes only and are not intended to be limiting. Each disclosed aspect and example may be considered individually or in combination with other aspects, examples, and variations of this disclosure. Furthermore, unless otherwise specified, no step of the method of this disclosure is limited to any specific order of execution. Reasonable modifications to the disclosed examples that are incorporated into the spirit and substance of this disclosure fall within the scope of this disclosure. In addition, all references cited herein are incorporated herein by reference in their entirety. The headings used herein are for organizational purposes only and should not be used to unduly limit the scope of the claims or the implementation.

[0171] While the methods and apparatus described herein may readily yield various modifications and alternatives, specific examples have been shown in the accompanying drawings and described in detail herein. However, it should be understood that these embodiments are not limited to the specific apparatus or method disclosed, but rather encompass all reasonable modifications, equivalents, and alternatives falling within the spirit and scope of the various examples described and the appended claims. Furthermore, the disclosure herein, in conjunction with examples, of any specific feature, aspect, method, property, characteristic, quality, attribute, element, or like thereof is applicable to all other examples set forth herein. No method disclosed herein need to be performed in the order described. Depending on the example, one or more actions, events, or functions of any algorithm, method, or process described herein may be performed in a different order, may be added, combined, or omitted entirely (e.g., not all described actions or events are necessary for the practice of the algorithm). Algorithms, modules, chains, steps, blocks, elements, features, etc., may be stored in machine-readable storage. In some examples, actions or events may be performed concurrently, for example, through multithreaded processing, interrupt handling, or multiple processors or processor cores or other parallel architectures, rather than sequentially. Furthermore, no element, feature, chain, box, or step, or group of elements, features, chains, boxes, or steps, is necessary or indispensable for each example. Moreover, all possible combinations, sub-combinations, and rearrangements of systems, methods, features, elements, modules, chains, boxes, etc., are within the scope of this disclosure. Unless specifically stated otherwise, or understood differently according to the context, the use of sequential or temporal terms such as “then,” “next,” “after,” “following,” etc., is generally for the purpose of facilitating the writing and is not intended to limit the order of operations performed. Therefore, some examples may be performed using the order of operations described herein, while other examples may be performed in a different order.

[0172] The various illustrative logic chains, blocks, modules, processes, methods, and algorithms described in conjunction with the examples disclosed herein can be implemented as electronic hardware, computer software, or a combination of both. To clearly illustrate this interchangeability between hardware and software, the various illustrative components, chains, modules, operations, and steps have been generally described above in terms of their functionality. Whether such functionality is implemented as hardware or software depends on the specific application and the design constraints imposed on the overall system. For each specific application, the described functionality can be implemented in different ways, but such implementation decisions should not be construed as causing a departure from the scope of this disclosure.

[0173] The various illustrative logic chains and modules described in conjunction with the examples disclosed herein can be implemented or executed by a machine, such as a general-purpose processor, digital signal processor (DSP), application-specific integrated circuit (ASIC), 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. The general-purpose processor may be a microprocessor, but alternatively, the processor may be a controller, microcontroller, or state machine, a combination thereof, or similar devices. The processor may also be implemented as a combination of computing devices, such as a combination of a DSP and a microprocessor, multiple microprocessors, one or more microprocessors combined with a DSP core, or any other such configuration.

[0174] The chains, operations, or steps of the methods, processes, or algorithms described in conjunction with the examples disclosed herein may be embodied directly in hardware, in a software module executed by a processor, or in a combination of both. The software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, removable disk, optical disk (e.g., CD-ROM or DVD), or any other form of volatile or non-volatile computer-readable storage medium known in the art. The storage medium may be coupled to the processor so that the processor can read information from and write information to the storage medium. Alternatively, the storage medium may be integrated with the processor. The processor and storage medium may reside in an ASIC. The ASIC may reside in a user terminal. Alternatively, the processor and storage medium may reside as discrete components in the user terminal.

[0175] Conditional terms used in this document, such as “can,” “may,” “may,” “for example,” etc., unless specifically stated otherwise or understood otherwise in the context in which they are used, are generally intended to express that some examples include certain features, elements, and / or states, while other examples do not. Therefore, such conditional terms are generally not intended to imply that features, elements, chains, and / or states are required in any one or more examples, or that one or more examples necessarily include logic for determining whether such features, elements, and / or states are included in any particular example or whether they should be performed in any particular example, with or without author input or prompting.

[0176] The methods disclosed herein may include certain actions taken by a practitioner; however, these methods may also include any third-party instructions for such actions, whether explicit or implicit. For example, an action such as “stimulating a nerve” includes “instructing to stimulate a nerve.”

[0177] The scope of this document also encompasses any and all overlapping, sub-scopes, and combinations thereof. Terms such as “up to,” “at least,” “greater than,” “less than,” and “between” include the numbers stated. Numbers preceded by terms such as “about” or “approximately” include the numbers stated and should be interpreted according to the specific circumstances (e.g., as accurately as reasonably possible in the specific circumstances, such as ±5%, ±10%, ±15%, etc.). For example, “about 1 mm” includes “1 mm.” Phrases preceded by terms such as “substantially” include the phrase stated and should be interpreted according to the specific circumstances (e.g., as reasonably possible in the specific circumstances). For example, “substantially parallel” includes “parallel.” Unless otherwise stated, all measurements are performed under standard conditions, including temperature and pressure. The phrase “at least one of…” is intended to require at least one of the following lists, not a single category for each item listed below. For example, “at least one of A, B, and C” may include A, B, C; A and B; A and C; B and C; or A, B, and C.

[0178] 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 this disclosure pertains. As used herein, the singular forms “a,” “an,” and “the” also include the plural forms unless the context clearly indicates otherwise. As used herein, the terms “comprising” and / or “including” may indicate the presence of the stated features, steps, operations, elements, components, and / or groups, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups. As used herein, the term “and / or” may include any and all combinations of one or more associated listed items. As used herein, the terms “first,” “second,” etc., should not limit the elements described by these terms. These terms are merely used to distinguish one element from another. Therefore, a “first” element discussed below may also be referred to as a “second” element without departing from the teachings of this disclosure. Unless specifically indicated otherwise, the order of operations (or actions / steps) is not limited to the order presented in the claims or drawings.

[0179] As used herein, the term "neuromodulation" can refer to electrical signals delivered to nerve tissue as a therapy. In some cases, nerve tissue may include at least a portion of the sympathetic chain. For example, the sympathetic chain may refer to the lumbar sympathetic chain (LSC). As used herein, the term "sympathetic nervous system" can refer to the portion of the autonomic nervous system that activates a "fight or flight" response (generally increasing heart rate, dilating pupils, dilating bronchi, inhibiting digestion, constricting blood vessels, increasing cardiac output, and raising blood pressure) to prepare the body for strenuous physical activity. As used herein, the term "electrical signal" can refer to voltage or current that varies over time. As an example, an electrical signal can be represented by a waveform (a graphical representation of current or voltage changing over time). As used herein, the term "electrode contact" can refer to a material that acts as a conductor through which current enters or leaves. At least a portion of the material may be biocompatible. As used herein, the terms “object” and “patient” are used interchangeably and refer to any warm-blooded organism, including but not limited to humans, pigs, rats, mice, dogs, cats, goats, sheep, horses, monkeys, apes, rabbits, cattle, etc.

Claims

1. A catheter for treating a patient with heart disease, said catheter comprising: The catheter axis is configured to be located in at least one of the left or right subclavian artery and to define a central axis. A flexural element at the distal portion of the catheter, the flexural element comprising: The proximal hub is connected to the distal end of the duct shaft. At least one elongated leg, the proximal end of which is connected to the proximal hub. The distal hub is coupled to the distal end of the at least one elongated leg, and A cable, the distal end of which is connected to the distal hub; and A neuromodulation element, positioned on the flexure element and configured to selectively target and stimulate at least one of the dorsal or ventral subclavian loops and / or configured to selectively target and ablate at least one of the dorsal or ventral subclavian loops, the neuromodulation element being a neuromodulation element of a duct in the subclavian artery of the subject, the neuromodulation element comprising one or more electrodes.

2. A catheter for treating a patient with heart disease, said catheter comprising: The catheter axis is configured to be located in at least one of the left or right subclavian artery and to define a central axis. A flexural element at the distal portion of the catheter, the flexural element comprising: The proximal hub is connected to the distal end of the duct shaft. At least one elongated leg, the proximal end of each of the at least one elongated leg being connected to the proximal hub. The distal hub is coupled to the distal end of the at least one elongated leg, and The pull cable is positioned off-axis relative to the central axis, and the distal end of the pull cable is connected to the distal hub, wherein at least one elongated leg is configured to deflect away from the central axis in response to an operator pulling the proximal end of the pull cable in a proximal direction; and A neuromodulation element, positioned on the flexure element and configured to selectively target and stimulate at least one of the dorsal or ventral subclavian loops and / or configured to selectively target and ablate at least one of the dorsal or ventral subclavian loops, the neuromodulation element being a neuromodulation element of a duct in the subclavian artery of the subject, the neuromodulation element comprising one or more electrodes.

3. A catheter for treating a patient with heart disease, said catheter comprising: The catheter axis is configured to be located in at least one of the left or right subclavian artery and to define a central axis. A flexural element at the distal portion of the catheter, the flexural element comprising: The proximal hub is connected to the distal end of the duct shaft. At least one elongated leg, the proximal end of each of the at least one elongated leg being connected to the proximal hub, the at least one elongated leg being configured to deflect away from the central axis and form a bend, wherein when deflected away from the central axis, the at least one elongated leg extends less than 270 degrees about the central axis. The distal hub is coupled to the distal end of the at least one elongated leg, and A cable, the distal end of which is connected to the distal hub; and A neuromodulation element, positioned on the flexure of at least one leg and configured to selectively target and stimulate at least one of the dorsal or ventral subclavian loops and / or configured to selectively target and ablate at least one of the dorsal or ventral subclavian loops, the neuromodulation element being a neuromodulation element of a duct in the subclavian artery of the subject, the neuromodulation element comprising one or more electrodes.

4. The catheter of claim 1, wherein the neuromodulation element comprises one or more electrodes coupled to the at least one slender leg.

5. The catheter of claim 1, wherein the neuromodulation element comprises an electrode coupled to the distal hub.

6. The catheter according to any one of claims 1 or 4-5, wherein the at least one elongated leg is configured to deflect away from the central axis in response to an operator pulling the proximal end of the cable in a proximal direction.

7. The catheter according to any one of claims 1 or 4-5, wherein the at least one elongated leg is configured to deflect to a position substantially perpendicular to the central axis in response to the operator pulling the proximal end of the cable to the maximum extent proximally.

8. The catheter according to any one of claims 1 or 4-5, wherein the at least one elongated leg is surrounded by a sheath.

9. The catheter according to any one of claims 1 or 4-5, wherein the pull wire is surrounded by a sheath.

10. The catheter according to any one of claims 1 or 4-5, wherein the distal hub and / or the proximal hub comprises a deployable umbrella-shaped element configured to capture emboli.

11. The catheter according to any one of claims 1 or 4-5, wherein the pull wire is positioned off-axis relative to the central axis.

12. The catheter according to any one of claims 1 or 4-5, wherein the heart disease includes ventricular arrhythmia, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, congestive heart failure, atrial flutter, or any combination thereof.

13. A catheter for treating a patient's condition, said catheter comprising: The catheter axis is configured to be located in at least one of the left or right subclavian artery; A flexural element at the distal portion of the catheter, the flexural element comprising: The proximal hub is connected to the distal end of the duct shaft. At least one elongated leg, the proximal end of which is connected to the proximal hub. The distal hub is coupled to the distal end of the at least one elongated leg, and A cable, the distal end of which is connected to the distal hub; and A neuromodulation element is positioned on the flexure element and configured to selectively target and stimulate tissue and / or to selectively target and ablate tissue.

14. The catheter of claim 13, wherein the neuromodulation element comprises one or more electrodes coupled to the at least one slender leg.

15. The catheter of claim 13, wherein the neuromodulation element comprises an electrode coupled to the distal hub.

16. The catheter according to any one of claims 13-15, wherein the at least one elongated leg is configured to deflect away from the central axis defined by the catheter shaft in response to an operator pulling the proximal end of the pull wire in a proximal direction.

17. The catheter according to any one of claims 13-15, wherein in the catheter shaft, the proximal hub and the distal hub include a central lumen configured to receive a guidewire.

18. The catheter of claim 17, wherein the central cavity comprises an ultrasonic crystal.

19. The catheter of claim 17, wherein the central lumen includes an electrode for RF ablation.

20. The catheter of claim 17, wherein the central lumen includes a return electrode.

21. The catheter according to any one of claims 13-15, further comprising one or more RF wires for providing RF energy to the neuromodulation element.

22. The catheter according to any one of claims 13-15, further comprising one or more thermocouple wires for providing thermal energy to the neuromodulation element.

23. The catheter according to any one of claims 13-15, wherein the distal hub and / or the proximal hub comprises a deployable umbrella-shaped element configured to capture emboli.

24. The catheter according to any one of claims 13-15, wherein the condition includes ventricular arrhythmia, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, congestive heart failure, atrial flutter, or any combination thereof.

25. A method of treating a patient's heart disease using a catheter as described in any one of claims 1 or 4-5.

26. A method of treating the condition of a subject using a catheter as described in any one of claims 1 or 4-15.

27. A method for treating a patient's heart disease, the method comprising: A catheter is transdermally introduced into the vascular system of the subject, wherein the catheter includes a neuromodulation element; The neural modulation element is positioned in the subclavian artery of the subject; Pulling the suture along the proximal direction, wherein the pull causes a flexure element located at the distal end of the catheter to change position relative to the central axis defined by the axis of the catheter and to contact the neuromodulation element with one of the dorsal and / or ventral subclavian loops. Electrical stimulation of at least one of the dorsal subclavian loop or the ventral subclavian loop; Stimulation of the dorsal subclavian loop and / or the ventral subclavian loop is confirmed by monitoring cardiac parameters; and After confirming stimulation of the dorsal subclavian loop and / or the ventral subclavian loop, ablation energy is applied to the dorsal subclavian loop and / or the ventral subclavian loop.

28. The method of claim 27, further comprising, after providing ablation energy, restimulating the subclavian loop, and if cardiac parameters confirm the stimulation, providing further ablation energy to the subclavian loop.

29. The method of claim 28, further comprising repeating the restimulation and providing further ablation energy until the cardiac parameters are no longer confirmed by the stimulation.

30. The method according to any one of claims 27-29, wherein transdermal introduction of the catheter into the vascular system comprises inserting the catheter into the femoral artery of the subject.

31. The method according to any one of claims 27-29, wherein transdermal introduction of the catheter into the vascular system comprises inserting the catheter into the radial artery of the subject.

32. The method according to any one of claims 27-29, wherein transdermal introduction of the catheter into the vascular system comprises inserting the catheter into the carotid artery of the subject.

33. The method according to any one of claims 27-29, wherein transdermal introduction of the catheter into the vascular system comprises inserting the catheter into the femoral vein of the subject, and wherein positioning the neuromodulation element in at least one of the left subclavian artery or the right subclavian artery comprises crossing from the venous vascular system to the arterial vascular system.

34. The method according to any one of claims 27-29, wherein the electrical stimulation of at least one of the dorsal or ventral subclavian loops is performed using a pulse width of 2 milliseconds to 4 milliseconds.

35. The method according to any one of claims 27-29, wherein the electrical stimulation of at least one of the dorsal or ventral subclavian loops is performed at a frequency of 10 Hz.

36. The method according to any one of claims 27-29, wherein the electrical stimulation of at least one of the dorsal or ventral subclavian loops is performed for a period of 20 to 30 seconds.

37. The method according to any one of claims 27-29, wherein the heart disease includes ventricular arrhythmia, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, congestive heart failure, atrial flutter, or any combination thereof.

38. A method for treating a patient's heart disease, the method comprising: A catheter is introduced into the vascular system of the object, wherein the catheter includes a neuromodulation element; The neural modulation element is positioned in the subclavian artery of the subject; Electrical stimulation of at least one of the dorsal or ventral subclavian loops; Stimulation of the dorsal subclavian loop and / or the ventral subclavian loop is confirmed by monitoring cardiac parameters; After confirming stimulation of the dorsal subclavian loop and / or the ventral subclavian loop, ablation energy is applied to the dorsal subclavian loop and / or the ventral subclavian loop. and The implanted wire is configured to stimulate parasympathetic or sympathetic nerve targets.

39. The method of claim 38, wherein the parasympathetic target is a baroreceptor.

40. The method of claim 38, wherein the parasympathetic target is the vagus nerve.

41. The method of claim 38, wherein the sympathetic target and / or the parasympathetic target are located on the spinal cord of the subject.

42. The method of claim 38, wherein the parasympathetic target is an visceral nerve.

43. The method of claim 38, wherein the parasympathetic target is the tragus.

44. The method of claim 38, wherein the sympathetic nerve target is the dorsal subclavian loop and / or the ventral subclavian loop.

45. The method according to any one of claims 38-44, wherein the catheter is transdermally introduced into the vascular system of the subject.

46. ​​The method according to any one of claims 38-44, wherein at least one of the dorsal subclavian loop or the ventral subclavian loop is percutaneously located before the catheter is introduced into the vascular system of the subject.

47. The method according to any one of claims 38-44, wherein the heart disease includes ventricular arrhythmia, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, congestive heart failure, atrial flutter, or any combination thereof.

48. A signal generator for generating ablation energy according to any one of the preceding claims, the signal generator having one or more of the features described in the foregoing description.

49. A method for adjusting and / or ablating the subclavian loop, said method having one or more of the features described above.

50. A treatment system having one or more of the features described above.

51. A tissue therapy system having one or more of the features described above.

52. A catheter for treating a heart condition, said catheter comprising: The catheter axis is configured to be located in at least one of the left or right subclavian artery and to define a central axis. A flexural element at the distal portion of the catheter, the flexural element comprising: The proximal hub is connected to the distal end of the duct shaft. At least two slender legs, the proximal end of each of the at least two slender legs being connected to the proximal hub. The distal hub is coupled to the distal end of each of the at least two elongated legs, and A cable, the distal end of which is connected to the distal hub; and A neuromodulation element, positioned on the flexure element and configured to stimulate at least one of the dorsal or ventral subclavian loops and / or configured to ablate at least one of the dorsal or ventral subclavian loops, the neuromodulation element being a neuromodulation element of a duct in the subclavian artery of the subject, the neuromodulation element comprising one or more electrodes.

53. The conduit of claim 52, wherein the neuromodulation element comprises one or more electrodes circumferentially connected around the circumference of each of the at least two elongated legs.

54. The catheter of claim 52, wherein the neuromodulation element comprises an electrode coupled to the distal hub.

55. The conduit of claim 52, wherein the at least two elongated legs extend along an arcuate interval of less than 270 degrees around the central axis.

56. The catheter of claim 52, wherein the at least two elongated legs comprise three elongated legs.

57. The catheter of claim 52, wherein the at least two elongated legs are configured to deflect away from the central axis in response to an operator pulling the proximal end of the cable in a proximal direction.

58. The catheter of claim 52, wherein the at least two elongated legs are configured to return to a position aligned with the central axis in response to an operator releasing the pull wire distally.

59. The catheter of claim 52, wherein the at least two elongated legs are configured to deflect to a position substantially perpendicular to the central axis in response to the operator pulling the proximal end of the cable to the maximum extent proximally.

60. The conduit of claim 52, wherein the flexural element has a bending radius of up to 90 degrees.

61. The catheter according to any one of claims 52-60, wherein each of the at least two elongated legs is surrounded by a sheath.

62. The catheter according to any one of claims 52-60, wherein the pull wire is surrounded by a sheath.

63. The catheter according to any one of claims 52-60, wherein in the catheter shaft, the proximal hub and the distal hub include a central lumen configured to receive a guidewire.

64. The catheter of claim 63, wherein the central cavity comprises an ultrasonic crystal.

65. The catheter of claim 63, wherein the central lumen includes an electrode for RF ablation.

66. The catheter of claim 63, wherein the central lumen includes a return electrode.

67. The catheter of claim 63, wherein the central lumen includes a plurality of perforations around the circumference of the central lumen, wherein the plurality of perforations are configured to allow radial release flushing to cool the catheter.

68. The catheter according to any one of claims 52-60, further comprising one or more RF wires for providing RF energy to the neuromodulation element.

69. The catheter according to any one of claims 52-60, further comprising one or more thermocouple wires for providing thermal energy to the neuromodulation element.

70. The catheter according to any one of claims 52-60, wherein the distal hub includes a deployable umbrella-shaped element configured to capture emboli.

71. The catheter according to any one of claims 52-60, wherein the proximal hub includes a deployable umbrella-shaped element configured to capture emboli.

72. A method for treating a patient's heart disease, the method comprising: A catheter is transdermally introduced into the vascular system of the subject, wherein the catheter includes a neuromodulation element; The neural modulation element is positioned in the subclavian artery of the subject; Pulling the traction wire proximally, wherein the pull causes a flexural element located at the distal end of the catheter to change position relative to a central axis defined by the axis of the catheter. Electrical stimulation of at least one of the dorsal or ventral subclavian loops; Stimulation of the dorsal subclavian loop and / or the ventral subclavian loop is confirmed by monitoring cardiac parameters; and After confirming stimulation of the dorsal subclavian loop and / or the ventral subclavian loop, ablation energy is applied to the dorsal subclavian loop and / or the ventral subclavian loop.

73. The method of claim 72, further comprising, after providing ablation energy, restimulating the subclavian loop, and if cardiac parameters confirm the stimulation, providing further ablation energy to the subclavian loop.

74. The method of claim 72, further comprising repeating the restimulation and providing further ablation energy until the cardiac parameters are no longer confirmed by the stimulation.

75. The method of claim 72, wherein transdermal introduction of the catheter into the vascular system comprises inserting the catheter into the femoral artery of the subject.

76. The method of claim 72, wherein transdermal introduction of the catheter into the vascular system comprises inserting the catheter into the radial artery of the subject.

77. The method of claim 72, wherein transdermal introduction of the catheter into the vascular system comprises inserting the catheter into the carotid artery of the subject.

78. The method of claim 72, wherein transdermal introduction of the catheter into the vascular system comprises inserting the catheter into the femoral vein of the subject, and wherein positioning the neuromodulation element in at least one of the left subclavian artery or the right subclavian artery comprises crossing from the venous vascular system to the arterial vascular system.

79. The method according to any one of claims 72-78, wherein pulling the wire proximally causes the flexural element to move to a position substantially perpendicular to the central axis.

80. The method according to any one of claims 72-78, wherein pulling the wire causes the flexural element to move to a position up to 90 degrees relative to the central axis.

81. The method according to any one of claims 72-78, further comprising releasing the pull wire to move the flexural element to a position aligned with the central axis.

82. A signal generator for generating ablation energy according to any one of the preceding claims, the signal generator having one or more of the features described in the foregoing description.

83. A method for adjusting and / or ablating the subclavian loop, said method having one or more of the features described above.

84. A treatment system having one or more of the features described above.

85. A tissue therapy system having one or more of the features described above.

86. A catheter for treating a condition of a patient, said catheter comprising: A flexural element at the distal portion of the catheter, the flexural element comprising: The proximal hub is connected to the distal end of the shaft of the conduit. At least two slender legs, the proximal end of each of the at least two slender legs being connected to the proximal hub. The distal hub is coupled to the distal end of each of the at least two elongated legs, and A pull wire, the distal end of which is connected to the distal hub; and A neuromodulation element is positioned on the flexure element and configured to stimulate tissue and / or ablate tissue.

87. The conduit of claim 86, wherein the neuromodulation element comprises one or more electrodes circumferentially connected around the circumference of each of the at least two elongated legs.

88. The catheter of claim 86, wherein the neuromodulation element comprises an electrode coupled to the distal hub.

89. The catheter of claim 86, wherein the at least two elongated legs extend along an arcuate interval of less than 270 degrees about a central axis defined by the axis of the catheter.

90. The conduit of claim 86, wherein the at least two elongated legs comprise three elongated legs.

91. The catheter of claim 86, wherein the at least two elongated legs are configured to deflect away from the central axis defined by the axis of the catheter in response to an operator pulling the proximal end of the pull wire in a proximal direction.

92. The catheter of claim 86, wherein the at least two elongated legs are configured to return to a position aligned with the central axis defined by the axis of the catheter in response to an operator releasing the pull wire distally.

93. The catheter of claim 86, wherein the at least two elongated legs are configured to deflect to a position substantially perpendicular to the central axis defined by the axis of the catheter in response to the operator pulling the proximal end of the cable to the maximum extent proximally.

94. The conduit of claim 86, wherein the flexural element has a bending radius of up to 90 degrees.

95. The conduit of claim 86, wherein each of the at least two elongated legs is surrounded by a sheath.

96. The catheter according to any one of claims 86-95, wherein the pull wire is surrounded by a sheath.

97. The catheter according to any one of claims 86-94, wherein in the catheter shaft, the proximal hub and the distal hub include a central lumen configured to receive a guidewire.

98. The catheter of claim 97, wherein the central cavity comprises an ultrasonic crystal.

99. The catheter of claim 97, wherein the central lumen includes an electrode for RF ablation.

100. The catheter of claim 97, wherein the central lumen includes a return electrode.

101. The catheter of claim 97, wherein the central lumen includes a plurality of perforations around the circumference of the central lumen, wherein the plurality of perforations are configured to allow flushing radial release to cool the catheter.

102. The catheter according to any one of claims 86-95, further comprising one or more RF wires for providing RF energy to the neuromodulation element.

103. The catheter according to any one of claims 86-95, further comprising one or more thermocouple wires for providing thermal energy to the neuromodulation element.

104. The catheter according to any one of claims 86-95, wherein the distal hub includes a deployable umbrella-shaped element configured to capture emboli.

105. The catheter according to any one of claims 86-95, wherein the proximal hub includes a deployable umbrella-shaped element configured to capture emboli.

106. The method according to any one of claims 72-78, wherein the electrical stimulation of at least one of the dorsal or ventral subclavian loops is performed using a pulse width of 2 milliseconds to 4 milliseconds.

107. The method according to any one of claims 72-78, wherein the electrical stimulation of at least one of the dorsal or ventral subclavian loops is performed at a frequency of 10 Hz.

108. The method according to any one of claims 72-78, wherein the electrical stimulation of at least one of the dorsal subclavian loop or the ventral subclavian artery is performed for a period of 20 to 30 seconds.

109. A method for treating a patient's heart disease, the method comprising: A catheter is transdermally introduced into the vascular system of the subject, wherein the catheter includes a neuromodulation element; The neural modulation element is positioned in the subclavian artery of the subject; Electrical stimulation of at least one of the dorsal or ventral subclavian loops; Stimulation of the dorsal subclavian loop and / or the ventral subclavian loop is confirmed by monitoring cardiac parameters; After confirming stimulation of the dorsal subclavian loop and / or the ventral subclavian loop, ablation energy is applied to the dorsal subclavian loop and / or the ventral subclavian loop. and The implanted wire is configured to stimulate parasympathetic or sympathetic nerve targets.

110. The method of claim 109, wherein the parasympathetic target is a baroreceptor.

111. The method of claim 109, wherein the parasympathetic target is the vagus nerve.

112. The method of claim 109, wherein the sympathetic target and / or the parasympathetic target are located on the spinal cord of the subject.

113. The method of claim 109, wherein the parasympathetic target is an visceral nerve.

114. The method of claim 109, wherein the parasympathetic target is the tragus.

115. The method of claim 109, wherein the sympathetic nerve target is the dorsal subclavian loop and / or the ventral subclavian loop.

Images