Method and device for endovascular ablation of splanchnic nerve

Abstract

To provide safe and effective therapies improved for a heart failure patient, and a device and a system adapted and configured to perform the therapies.SOLUTION: A system, a device, and a method for transvascular ablation of target tissue are disclosed herein. The device and method may, in some examples, be used for splanchnic nerve ablation to increase splanchnic venous blood capacitance to treat at least one of heart failure and hypertension. For example, the devices disclosed herein may be advanced endovascularly to a target vessel in the region of a thoracic splanchnic nerve (TSN), such as a greater splanchnic nerve (GSN) or a TSN nerve root. Also disclosed is a method of treating heart failure, such as HFpEF, by endovascularly ablating a thoracic splanchnic nerve to increase venous capacitance and reduce pulmonary blood pressure.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Patent Application No. 62 / 622,407, filed January 26, 2018, U.S. Provisional Patent Application No. 62 / 625,183, filed February 1, 2018, and U.S. Provisional Patent Application No. 62 / 625,195, filed February 1, 2018, which are hereby incorporated by reference in their entireties for all purposes.

[0002] (Incorporated by reference) All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0003] This specification is related to the subject matter of U.S. Patent Application Publication No. 2018 / 0110561, PCT International Published Patent Application WO2018 / 023132, and PCT / US2018 / 066047 (filed December 17, 2018), which are incorporated by reference in their entireties for all purposes.

[0004] The present invention relates to methods and devices for endovascular ablation of splanchnic nerves. [Background technology]

[0005] Heart failure (HF) is a medical condition that occurs when the heart cannot pump adequately to maintain the body's organs. Heart failure is serious and affects millions of people in the United States and worldwide.

[0006] One common indicator of cardiac health is the left ventricular ejection fraction (LVEF) or ejection fraction. By definition, the volume of blood in a ventricle just before contraction is known as the end-diastolic volume (EDV). Similarly, the volume of blood remaining in the ventricle at the end of contraction is the end-systolic volume (ESV). The difference between EDV and ESV is the stroke volume (SV). SV represents the volume of blood ejected from the right and left ventricles with each heartbeat. Ejection fraction (EF) is the percentage of EDV ejected with each heartbeat, i.e., SV divided by EDV. Cardiac output (CO) is defined as the volume of blood pumped by each ventricle of the heart per minute. CO is equal to SV multiplied by the heart rate (HR).

[0007] Cardiomyopathy, in which the heart muscle weakens, stretches, or exhibits other structural problems, can be further classified into systolic dysfunction and diastolic dysfunction based on ventricular ejection fraction.

[0008] Although several pharmacologic therapies effectively target systolic dysfunction and HFrEF, no promising therapies have yet been identified for the large population of patients with diastolic dysfunction and HFpEF. The clinical course of patients with both HFrEF and HFpEF is significant due to the recurrent development of acute decompensated heart failure (ADHF), with symptoms including dyspnea, exercise intolerance, and peripheral edema. Readmissions for ADHF utilize a significant portion of current healthcare resources and are likely to continue to generate significant costs.

[0009] Although our understanding of the pathophysiology of HF is improving, modern medicine has so far been unsuccessful in developing new therapies for the chronic treatment of HF or recurrent ADHF symptoms. Over the past several decades, strategies for treating and preventing ADHF have focused on the traditional paradigm that posits salt and water retention as the cause of intravascular fluid expansion and cardiac decompensation. Summary of the Invention [Problem to be solved by the invention]

[0010] Thus, there remains a need for improved therapies for heart failure patients that are safe and effective, and for devices and systems adapted and configured to implement these therapies. [Means for solving the problem]

[0011] The first section of the following Summary of the Invention is intended to introduce the reader to various aspects of methods for endovascular ablation of one or more thoracic splanchnic nerves or nerve roots (e.g., greater splanchnic nerves or nerve roots), but is not necessarily intended to define or delimit the invention or limit the disclosure.

[0012] The present disclosure relates to methods, devices, and techniques for ablation of one or more thoracic splanchnic nerves or thoracic splanchnic nerve roots. Ablation may be performed to treat at least one of hypertension and heart failure, although the general method may also be used for other treatments. For example, the methods herein may be used to treat pain, or even to generally benefit a patient by reducing the amount of blood draining from the splanchnic bed into the central thoracic veins.

[0013] Treatment herein may be achieved by increasing splanchnic volume. Therapy generally involves ablatating one or more of a patient's preganglionic thoracic splanchnic nerves or thoracic splanchnic nerve branches to increase splanchnic volume, thereby treating at least one of hypertension and heart failure.

[0014] The methods herein describe ablation of thoracic splanchnic nerves, such as the greater splanchnic nerve or the greater splanchnic nerve root. While the methods herein may present specific examples of targeting the greater splanchnic nerve or the greater splanchnic nerve root, it may be an alternative or additional to ablating other thoracic splanchnic nerves (e.g., lesser, least) to perform one or more of the treatments herein.

[0015] One aspect of the present disclosure is a method of ablating tissue by positioning a medical device within a blood vessel near a target tissue and using the medical device to ablate the tissue to form a lesion. One aspect of the present disclosure is a method of ablating tissue by positioning a medical device within a blood vessel, within one or more target blood vessels, and using the medical device to ablate the tissue to form a lesion. The methods of the present disclosure may thus be described as methods of positioning a medical device near a target tissue to be ablated and / or methods of positioning a medical device within one or more blood vessels, wherein the target tissue is relatively close to a target region within the one or more blood vessels. Any method step herein (e.g., including, but not limited to, in the claims or description) may be incorporated into any other method herein, unless specifically indicated to the contrary herein.

[0016] One aspect of the present disclosure is a method for ablatating a greater splanchnic nerve or greater splanchnic nerve root to increase splanchnic venous blood volume, the method including advancing a medical device into a first blood vessel, advancing a medical device into a second blood vessel, and delivering ablation energy from the medical device to form a lesion in tissue surrounding the first blood vessel.

[0017] In some embodiments, the first vessel is an azygos vein and the second vessel is an intercostal vein.

[0018] In some embodiments, the intercostal vein is one of the three lowest intercostal veins.

[0019] In some embodiments, the intercostal vein is a T9, T10, or T11 intercostal vein.

[0020] The method may include positioning the distal end of the ablation element within the second blood vessel and within 30 mm (e.g., 20 mm, 15 mm, 12 mm) of the junction of the first blood vessel and the second blood vessel when delivering energy.

[0021] The method can include positioning a proximal portion of the ablation within the second blood vessel when delivering energy.

[0022] The method can include delivering a fluid from a fluid lumen of a medical device to a membrane, the membrane at least partially defining a fluid chamber. The delivered fluid can expand the membrane, changing it to an expanded configuration or state. When the membrane is expanded, it can have an outer diameter that is larger than the size of the blood vessel.

[0023] The method may include positioning the ablation element in contact with the wall of the second blood vessel, optionally along the entire length of the ablation element or at least along the effective ablation length of the ablation element.

[0024] The method can include expanding the membrane to have an outer diameter of 2 to 4 mm.

[0025] Creating the lesion can include creating a lesion having a depth of at least 5 mm around the ablation element.

[0026] Creating the lesion can include cauterizing a portion of a thoracic splanchnic nerve or thoracic splanchnic nerve root, for example, the greater splanchnic nerve or GSN root.

[0027] The lesion may be a continuous lesion. The lesion may have a length of 5 to 20 mm, for example, 10 to 20 mm, or 12 to 18 mm.

[0028] The lesion can be a circumferential lesion that extends completely around the second vessel. The lesion can extend less than completely around the second vessel, for example, 225 degrees or less, 180 degrees or less, 135 degrees or less, 90 degrees or less, or 45 degrees or less.

[0029] The method may include positioning the entire ablation element within the second blood vessel, while the method may also include positioning less than the entire length of the ablation element within the second blood vessel.

[0030] The method may include performing the ablation process in two or more target vessels, such as an intercostal vein or an azygos vein. The ablation method herein may also be performed in a second vessel.

[0031] The method may include performing an ablation confirmation test, such as any of the tests herein. If desired or necessary, the ablation element may be repositioned to a second target vessel, which may be the azygos vein or another intercostal vein.

[0032] The method may create a continuous lesion having a length of 1 to 20 mm, for example, a length of 5 to 20 mm, for example, a length of 10 to 20 mm.

[0033] The method may also include delivering stimulation energy to at least one of the first and second stimulation electrodes carried by the medical device before, during, and / or after delivery of the ablation energy. Delivering the stimulation energy may assist in determining whether the ablation element is at a target location within the intercostal vein and / or whether the ablation procedure was effective.

[0034] One aspect of the present disclosure is a method of ablating a thoracic splanchnic nerve or a thoracic splanchnic nerve root to treat at least one of hypertension and heart failure, comprising advancing an elongated medical device into an intercostal vein, the elongated medical device including an ablation member disposed at a distal region of the medical device, and further comprising expanding the ablation member within the intercostal vein and activating the ablation member to form an electromagnetic field in tissue surrounding the intercostal vein. The method may include heating the tissue surrounding the intercostal vein to a temperature of 99°C to ablate the thoracic splanchnic nerve or a thoracic splanchnic nerve root.

[0035] One aspect of the present disclosure is a method for transvascular ablation of target tissue, the method including delivering an ablation catheter through a patient's vascular system to a first blood vessel, the ablation catheter comprising at least one energy delivery element, advancing the at least one energy delivery element into a second blood vessel, the second blood vessel directly connecting to the first blood vessel, and delivering ablation energy from the at least one energy delivery element to the target tissue. The ablation catheter may include at least one RF electrode having a diameter that is within 1 mm of the diameter of the second blood vessel (e.g., 1 mm less than or 1 mm greater than the diameter of the second blood vessel).

[0036] The energy delivery element may include an RF electrode, a microwave antenna, an ultrasound transducer, a cryogenic applicator, and / or a thermal element. Advancing the at least one energy delivery element may include advancing a distal end of the energy delivery element 30 mm or less, e.g., 20 mm or less, from the first blood vessel into the second blood vessel. In one embodiment, the at least one energy delivery element has the same diameter during the advancing step and during the delivering of ablation energy step. In some embodiments, the at least one energy delivery element has a larger diameter during the delivering of ablation energy step than during the advancing step.

[0037] Any other method steps herein described in the context of another method may be performed in this example method.

[0038] Another aspect of the present disclosure is a method for transvascular ablation of a greater splanchnic nerve, comprising: delivering an ablation catheter into an intercostal vein, the ablation catheter having a distal region, an ablation element on the distal region, and two neural stimulation electrodes positioned distally and proximally relative to the ablation element; positioning the ablation element at a target region within the intercostal vein; measuring a first physiological condition without delivering energy from the ablation catheter to establish a baseline response; delivering neural stimulation signals to the two neural stimulation electrodes in a bipolar mode; measuring a second physiological condition during delivery of the neural stimulation signals; and delivering ablation energy from the ablation element if the second physiological condition indicates an increased sympathetic response relative to the first physiological condition. After or during the ablation energy delivery, delivering a second neural stimulation signal to measure a third physiological condition, and if the third physiological condition indicates a decreased sympathetic response compared to the first physiological condition, removing the catheter from the patient; adjusting the position of the ablation element within the intercostal vein or moving it to a different intercostal vein and repeating the steps of delivering the neural stimulation signal through delivering the ablation energy if the second physiological condition does not indicate an increased sympathetic response compared to the first physiological condition; moving the ablation element to an adjacent intercostal vein and repeating the steps of delivering the neural stimulation signal through delivering the ablation energy if the third physiological condition does not indicate a decreased sympathetic response compared to the first physiological condition.

[0039] The physiological condition may be, for example, venous compliance, and the measurement may be a leg raise test, a grip strength test, and / or a test that activates the SNS.

[0040] Any nerve stimulation signal herein may include, for example, 50Hz 1V.

[0041] One aspect of the present disclosure is a method that includes delivering an ablation catheter with an energy delivery element (or member) through a patient's venous system, positioning the energy delivery element at least partially (optionally completely) within a vein selected from the T9, T10, and T11 intercostal veins, and delivering ablation energy from the energy delivery element to form a contiguous lesion having a depth of at least 5 mm and a length of 10-20 mm. The contiguous lesion and its parameters can be formed by selecting or choosing specific energy delivery parameters to form the lesion. In some embodiments, the lesion can extend up to 20 mm along the intercostal vein from the ostium of the azygos vein.

[0042] Any other method steps herein described in the context of other methods may also be performed in this exemplary method.

[0043] In some other methods herein, multiple ablations (i.e., ablation energy on to energy ablation off) can be performed within a single target vessel (e.g., an intercostal vein) to form an integrated lesion from two or more lesions formed from the multiple ablations. The integrated lesion formed from the multiple lesions can have any of the characteristics of other lesions described herein. For example, the integrated lesion can be contiguous (formed by the connection of multiple lesions formed during separate ablations), up to 20 mm in length, circumferential (or non-circumferential), etc. After a first ablation, the ablation device can be moved within the same vessel to form a second lesion, which may or may not overlap the first lesion. This can be repeated as many times as desired. Even when multiple ablations are performed on a single vessel, any of the stimulation or testing steps herein can be performed before, during, or after any ablation steps.

[0044] One aspect of the present disclosure is an ablation device (e.g., an ablation catheter) adapted for endovascular ablation of a patient's greater splanchnic nerves or greater splanchnic nerve roots. The device may include a flexible shaft having a distal portion and a proximal portion, and at least one ablation element carried (directly or indirectly) by the distal portion, the at least one ablation element having an effective ablation length of 1-20 mm (optionally 5-20 mm) and an outer diameter of 2-4 mm. The effective ablation length may be 10-20 mm, e.g., 12-18 mm.

[0045] One aspect of the present disclosure is an ablation device for endovascular ablation of a patient's greater splanchnic nerves or greater splanchnic nerve roots, comprising a flexible shaft having a distal portion and a proximal portion, a fluid lumen extending through at least a portion of the flexible shaft, and at least one ablation element disposed in the distal portion, the at least one ablation element comprising a membrane having an effective ablation length of 1-20 mm (e.g., 5-20 mm) and an outer diameter of 2-4 mm, the membrane defining an internal volume of fluid in communication with the fluid lumen.

[0046] In any of the ablation devices herein, the ablation element may be adapted and configured to form a circumferential lesion around the vessel in which it is positioned.

[0047] In any of the ablation devices herein, the ablation element may be adapted and configured to form less than a circumferential lesion around the vessel in which it is placed.

[0048] In any of the ablation devices herein, the effective ablation length of at least one ablation element can be 10-20 mm, for example 12-18 mm.

[0049] In any of the ablation devices herein, the distal portion of the flexible shaft may be adapted and configured to bend at a bend angle of at least 90 degrees and a bend radius of 4 to 15 mm.

[0050] In any of the ablation devices herein, at least one ablation element may be adapted and configured to have a delivery configuration of a length of 5 to 20 mm and an outer diameter of 1.5 to 2.5 mm.

[0051] In any of the ablation devices herein, the device may further include a proximal stimulation electrode positioned proximally relative to the ablation element and a distal stimulation electrode positioned distally relative to the ablation element, optionally the proximal stimulation electrode and the distal stimulation electrode each being no more than 5 mm from the ablation element.

[0052] In any of the ablation devices herein, the device may further include a proximal stimulation electrode positioned proximally relative to the ablation element and a distal stimulation electrode positioned distally relative to the ablation element, and the proximal stimulation electrode and the distal stimulation electrode may be separated by a distance of 25 mm or less.

[0053] For any of the ablation devices herein, the effective ablation length may be 12-18 mm.

[0054] In any of the ablation devices herein, the distal portion of the flexible shaft can be configured to bend according to a bend angle of at least 90 degrees and a bend radius of 4 to 15 mm.

[0055] In any of the ablation devices herein, the device may further optionally include at least one temperature sensor disposed within the ablation element. The at least one ablation element and the at least one temperature sensor may be connectable to a source of ablation energy.

[0056] In any of the ablation devices herein, one or more of the neural stimulation electrodes may be 1.5 mm + / - 0.5 mm in length.

[0057] In any of the ablation devices herein, the device may further include a temperature sensor external to the ablation element, which may include being carried by a surface of the ablation element.

[0058] In any of the ablation devices herein, the ablation element may be configured to emit ablation energy from a segment of the circumference of the distal region. For example, the segment may be a percentage of the circumference selected from the following list: 50%, 40%, 30%, or 25% of the circumference. The segment may also be described as an angle less than 225 degrees, 180 degrees or less, 135 degrees or less, 90 degrees or less, or 45 degrees or less, etc. The remaining portion of the circumference not adapted to emit ablation energy may optionally comprise an electrically resistive material (e.g., disposed on or within a membrane layer). Optionally, the segment may be defined by perforations in the sheath. The distal region of the device may further comprise a radiopaque marker configured to indicate radial orientation. For example, the radiopaque marker may be radially aligned with the segment adapted to emit ablation energy.

[0059] In any of the ablation devices herein, the distal tip may be tapered to facilitate delivery from a first vessel to a second vessel having a smaller lumen diameter.

[0060] In any of the ablation devices herein, the device may further comprise a distal tubular extension having greater flexibility than the elongate tubular shaft, and the guidewire lumen optionally extends through the distal tubular extension.

[0061] In any ablation device herein, the effective ablation length of the ablation element is considered to be the length of the ablation element that contacts or is configured to contact tissue during the ablation step.

[0062] The following second section of the Summary of the Invention is intended to introduce the reader to various aspects of devices for intravascular venipuncture, but is not intended to define or delimit any invention.

[0063] According to a first aspect of an intravascular venipuncture device, the device includes an elongate catheter extending along a catheter longitudinal axis and having a proximal catheter portion and a distal catheter portion, and further includes a needle guide having a needle guide distal end.

[0064] In a second aspect related to the first aspect, the needle guide has a needle guide distal end that is blunt.

[0065] In a third aspect related to any one of the first and second aspects, the needle guide is deployable from the catheter from a needle guide retracted position to a needle guide activated position, wherein the needle guide distal end is radially spaced from the catheter and the needle guide retracted position is retracted toward the catheter relative to the needle guide activated position.

[0066] In a fourth aspect related to any one of the first to third aspects, the device further includes a needle having a sharp puncturing tip, the needle being deployable within the needle guide from a needle retracted position to a puncturing position, wherein the puncturing tip is inward from the distal end of the needle guide in the needle retracted position and the puncturing tip extends outward from the distal end of the needle guide in the puncturing position.

[0067] In a fifth aspect related to the third aspect in combination with the first, second and fourth aspects, the catheter has an outer catheter diameter, in other words, a cross section of the catheter may present a substantially circular outer periphery having said outer diameter.

[0068] In a sixth aspect related to the fifth aspect, in the puncture position, the puncture end is spaced from the needle guide distal end by a needle deployment distance that is less than the catheter outer diameter.

[0069] In a seventh aspect related to the sixth aspect, the needle deployment distance may be less than 2 mm, or less than 1 mm.

[0070] In an eighth aspect relating to any one of the fifth to seventh aspects, in the needle guide activated position, the needle guide distal end is radially spaced from the catheter by a needle guide deployment distance that is less than the catheter outer diameter.

[0071] In a ninth aspect related to the eighth aspect, the needle guide deployment distance may be about 0.5 to 6 mm, or about 0.5 to about 3 mm, or about 2 to about 6 mm.

[0072] In a tenth aspect relating to the third aspect in combination with any one of the first, second, fourth to ninth aspects, the catheter has a circumferential outer surface and a first side port within the circumferential outer surface, and the needle guide is deployable from the first side port.

[0073] In an eleventh aspect relating to the fourth aspect, in combination with any one of the first, second, third, fifth to tenth aspects, the device further includes a delivery device deployable from within the needle from a delivery device storage position to a delivery device processing position.

[0074] In a twelfth aspect relating to the eleventh aspect, the delivery device may be at least one of a fluid delivery device, a thermal energy delivery device, a radio frequency energy delivery device, a cryogenic energy delivery device, and an electrical energy delivery device.

[0075] In a thirteenth aspect related to either one of the eleventh and twelfth aspects, the delivery device may have a delivery device distal end that is blunt.

[0076] In a fourteenth aspect relating to any one of the eleventh, twelfth and thirteenth aspects, in the delivery device processing position, the delivery device distal end can extend beyond the puncture end by a delivery distance greater than the puncture distance.

[0077] In a fifteenth aspect related to the fourteenth aspect, the delivery distance may be up to 15 mm, or from about 3 to about 7 mm, or from about 4 to about 6 mm.

[0078] In a sixteenth aspect relating to any one of the first to fifteenth aspects, the catheter includes a guidewire lumen extending through the catheter along the catheter axis, and the catheter distal portion has a guidewire exit port.

[0079] In a seventeenth aspect relating to the sixteenth aspect, the catheter includes a distal end surface and a circumferential outer surface, and the guidewire exit port is an open notch at and between the distal end surface and the circumferential surface.

[0080] In an eighteenth aspect related to the third and seventeenth aspects, the needle guide is deployable from the catheter at a first circumferential position on the catheter, and the notch is open in the circumferential plane at a notch circumferential position that is within 30 degrees of the first circumferential position. Optionally, the notch circumferential position can be aligned with the first circumferential position.

[0081] In a 19th aspect relating to any one of the 3rd to 18th aspects, the device further includes a second needle guide deployable from the catheter and a second needle deployable from within the second needle guide.

[0082] In a twentieth aspect relating to the nineteenth aspect, the needle guide is deployable from the catheter at a first longitudinal position on the catheter, and the second needle guide is deployable from the catheter at a second longitudinal position on the catheter.

[0083] In a twenty-first aspect relating to the twentieth aspect, the second longitudinal position is spaced apart from the first longitudinal position.

[0084] In a twenty-second aspect relating to any one of the nineteenth to twenty-first aspects, the needle guide is deployable from the catheter at a first circumferential position on the catheter, and the second needle guide is deployable from the catheter at a second circumferential position on the catheter. Optionally, the second circumferential position can be aligned with the first circumferential position.

[0085] In a 23rd aspect relating to any one of the first to 22nd aspects, the device includes at least a first radiopaque marker. The first radiopaque marker can be on a catheter, a needle guide, or a needle.

[0086] In a twenty-fourth aspect relating to the twenty-third aspect, the first radiopaque marker is on the catheter and is configured to indicate a rotational orientation of the catheter.

[0087] In a 25th aspect relating to any one of the 23rd and 24th aspects, the first radiopaque marker is made of a radiopaque material.

[0088] In a 26th aspect relating to any one of the 23rd to 25th aspects, the first radiopaque marker has an asymmetrical shape, and optionally the first radiopaque marker is N-shaped.

[0089] In a 27th aspect relating to any one of the 23rd to 26th aspects, the device further includes an additional radiopaque marker on the catheter configured to visually indicate when the rotational position of the catheter is within a set tolerance.

[0090] In a 28th aspect related to the 27th aspect, the additional radiopaque marker includes two lines whose centers are circumferentially spaced approximately 180 degrees apart from the first radiopaque marker, such that the first radiopaque marker appears between the lines of the additional radiopaque marker when the orientation is within a set tolerance.

[0091] In a 29th aspect relating to any one of the 3rd to 28th aspects, in the needle guide operating position, the needle guide is either straight or curved and inclined relative to the catheter axis.

[0092] In a thirtieth aspect according to any one of the third to twenty-ninth aspects, a device includes: causing deployment of the needle guide from the needle guide retracted position to the needle guide activated position; causing deployment of the needle from the needle retraction position to the puncture position; The controller is configured to:

[0093] In a thirty-first aspect relating to the thirtieth aspect in combination with any one of the eleventh to fifteenth aspects, the controller is further configured to cause deployment of the delivery device from the delivery device storage position to the delivery device processing position.

[0094] In a 32nd aspect relating to any one of the 30th and 31st aspects, the controller is an analog or digital circuit or a combination thereof, and the controller is connected to a suitable actuator (such as an electric motor, a pneumatic or hydraulic actuator, or other type of actuator or motor) configured to cause deployment of the above-mentioned deployable component upon command from the controller.

[0095] In a 33rd aspect relating to any one of the 11th to 15th aspects, the delivery device is a cryogenic energy delivery device including a first lumen for delivery of cryogenic fluid from a source to a distal end of the cryogenic energy delivery device and a second lumen for returning the cryogenic fluid to the source.

[0096] In a thirty-fourth aspect relating to the thirty-third aspect, the source of cryogenic fluid includes a fluid reservoir, a supply valve between the fluid reservoir and the first lumen, a pressure relief valve at the outlet of the second lumen for discharging the returned cryogenic fluid to the atmosphere, and a controller configured to control the supply valve and the pressure relief valve, or the controller.

[0097] In a thirty-fifth aspect relating to the thirty-fourth aspect, the controller is in communication with a temperature sensor at the distal end of the delivery device and is configured to control the supply of cryogenic fluid in response to a temperature sensed by the temperature sensor.

[0098] In a thirty-sixth aspect relating to any one of the first to thirty-fifth aspects, the device is used to cauterize a thoracic splanchnic nerve, a thoracic splanchnic nerve root, or a greater splanchnic nerve.

[0099] The following third section of the Abstract is intended to introduce the reader to various aspects of methods for intravascular venipuncture, but is not intended to define or delimit any invention. Optionally, the methods described in this third section of the Abstract may use a device according to any one of aspects 1 through 36.

[0100] According to some embodiments, a method of intravascular venipuncture and treatment includes: a. advancing a distal portion of a catheter through a patient's venous system to a target location within the vein; b. deploying a needle guide from the catheter in a direction transverse to the longitudinal axis of the catheter; c. contacting a wall of the vein with the blunt distal end of the needle guide and continuing to deploy the needle guide to press the blunt distal end against the wall of the vein; d. deploying a needle from the distal end of the needle guide to puncture the wall of the vein with the sharp piercing tip of the needle; and e. delivering a treatment to an area outside the vein via the sharp piercing tip.

[0101] In some examples, the catheter has a catheter outer diameter, and step b includes deploying the needle guide to a deployment distance that is less than the catheter outer diameter. The deployment distance can be 0.5 to 6 mm, or 0.5 to 3 mm, or 2 to 6 mm.

[0102] In some examples, the catheter has a catheter outer diameter, and step d includes deploying the needle to a puncture distance that is less than the catheter outer diameter. The puncture distance can be less than 2 mm, or less than 1 mm.

[0103] In some examples, the method includes, prior to step e, delivering a nerve stimulation test pulse via the distal blunt or sharp piercing tip.

[0104] In some examples, step e includes deploying the delivery device from the puncture end and delivering the treatment using the delivery device. Step e can include deploying the delivery device a delivery distance greater than the puncture distance. The delivery distance can be up to 15 mm, or 3-7 mm, or 4-6 mm.

[0105] In some instances, step e includes ablating the nerve.

[0106] In some examples, step e includes delivering at least one of a fluid, a thermal energy treatment, a cryogenic energy treatment, and a radio frequency energy treatment.

[0107] In some instances, the target location is within the azygos vein or within an intercostal vein. The target location can be within the T9, T10, or T11 intercostal vein. The target location can be within the azygos vein between the T11 and T9 intercostal veins.

[0108] In some instances, step e includes delivering the treatment to a thoracic splanchnic nerve or a thoracic splanchnic nerve root.

[0109] In some instances, step e includes delivering the treatment to the greater splanchnic nerve.

[0110] In some instances, step e includes delivering a treatment for heart failure.

[0111] In some examples, the method includes coordinating step e with the patient's breathing to avoid damaging the patient's lungs during the procedure. The method may include monitoring the proximity of the needle to the patient's lungs.

[0112] In some examples, step a includes advancing the catheter over the guidewire. The target location may be in the azygos vein, and the guidewire may extend beyond the azygos vein into an intercostal vein. Prior to step b, the method may include orienting the catheter to the target orientation by rotating the catheter until the guidewire is positioned within an orientation notch in the catheter distal portion. Step b may include deploying a needle guide from a side port in the outer circumferential surface of the catheter. The notch may be at a notch circumferential location, and the side port may be at a first circumferential location that is within 30 degrees, or within 20 degrees, or within 10 degrees of the notch circumferential location.

[0113] In some examples, the method includes, after step a, deploying a second needle guide from the catheter in a second direction transverse to the longitudinal axis of the catheter, contacting the venous wall with the second distal blunt end of the second needle guide, continuing to deploy the second needle guide to press the second distal blunt end against the venous wall, deploying a second needle from the second distal end of the second needle guide to puncture the venous wall with the second puncture end of the second needle, and delivering a second treatment through the second puncture end. The needle guide can be deployed from a first side port in the distal catheter section, and the second needle guide can be deployed from a second side port in the distal catheter section, and the first and second side ports can be longitudinally separated. The first and second side ports can be longitudinally separated by 3 to 5 cm. The first and second side ports can be circumferentially aligned.

[0114] In some instances, step c includes continuing to deploy the needle guide to urge the catheter away from the vein wall and against the opposing vein wall.

[0115] One aspect of the present disclosure is an ablation method that includes endovascularly puncturing at least one of an intercostal vein and an azygos vein with a medical ablation device, and ablating a thoracic splanchnic nerve or a thoracic splanchnic nerve root with the medical ablation device, which may be any of the medical devices described herein.

[0116] One aspect of the present disclosure is an intravascular medical device configured to be advanced intravascularly into at least one of an azygos vein and an intercostal vein, the medical device including a puncturing element adapted to be deployed from an outer shaft of the intravascular medical device to puncture at least one of the azygos vein and an intercostal vein, like any of the related medical devices herein.

[0117] The following fourth section of the Summary is intended to introduce the reader to various aspects of embodiments of transvascular nerve ablation, but is not intended to define or delimit any invention. Optionally, the methods described in this fourth section of the Summary may use devices according to any one of the preceding or following aspects.

[0118] One embodiment is an ablation catheter configured for endovascular nerve ablation, and in particular for endovascular splanchnic nerve ablation, comprising an elongate shaft and an ablation assembly carried by a portion of the elongate shaft, the ablation assembly configured to form either a circumferential ablation pattern, e.g., having a length of at least 12 mm, or a directional ablation pattern, e.g., having a length of at least 12 mm.

[0119] The ablation assembly may be configured to produce either a circumferential ablation pattern having a length of 12-30 mm, optionally 12-20 mm, or a directional ablation pattern having a length of 12-30 mm, optionally 12-20 mm.

[0120] The ablation assembly may be carried by a distal straight portion of the elongate shaft.

[0121] The ablation assembly may further include an expandable member carried by the elongate shaft and having an unexpanded state and an expanded state, the ablation assembly being mounted on the expandable member.

[0122] The catheter may be configured to be inserted into an arterial vein of a human.

[0123] The expandable member may be configured to be inserted into an intercostal vein of a human patient in an unexpanded state and configured to abut a vessel wall of said intercostal vein in an expanded state.

[0124] The expandable member may include a circumferential treatment zone extending along the longitudinal axis of the catheter, configured to contact the vessel wall in an expanded state and having a length in the range of 12 to 30 mm, optionally in the range of 12 to 20 mm.

[0125] The expandable member, in its unexpanded state, can have a diameter in the range of about 1 to 2.5 mm and a circumference in the range of about 3.14 to 7.85 mm.

[0126] The expandable member, in its expanded state, can have a diameter in the range of about 3-5 mm and a circumference in the range of about 9.4-15.7 mm.

[0127] The ablation assembly and expandable member may be configured such that when the expandable member is in an expanded state, the ablation assembly forms a circumferential ablation pattern at least 12 mm in length, preferably between 12 and 30 mm in length.

[0128] The expandable member is attached to a distal portion of the elongate shaft and may optionally comprise a deployable balloon made of a compliant material or a non-compliant material that flexibly folds and contracts.

[0129] The elongate shaft may include a flexible neck positioned within 10 mm of the expandable member or within 10 mm of the ablation assembly. The flexible neck may be capable of bending to a minimum radius of curvature of 4 mm, thereby allowing orientation of the distal portion of the elongate shaft to facilitate insertion of that portion into the intercostal vein in a natural orientation. The flexible neck may be fabricated from a polymer, optionally Pebax, that has a softer durometer than the material used for the portion of the elongate shaft adjacent to the flexible neck. A wire coil may be embedded within the material of the flexible neck.

[0130] The ablation assembly may include a plurality of electrode pad assemblies attached to the outer surface of the expandable member and configured to directly contact the vessel wall when the catheter is inserted into a patient's blood vessel. Each electrode pad assembly may include a plurality of electrodes in the form of electrode pads, electrically interconnected by electrical traces, optionally formed by a common conductive support substrate. The electrode pads and electrical traces of the same electrode pad assembly may be aligned substantially parallel to the longitudinal axis of the catheter. The electrode pad assemblies may be attached to the expandable member and define a plurality of electrode pads arranged around the expandable member to form a circumferential ablation pattern up to 20 mm in length, optionally having a length comprised between 12 and 18 mm. Each electrode pad may be circumferentially separated from an angularly adjacent electrode pad by a distance of less than 5 mm, optionally less than 2.5 mm. Each electrode pad may extend around the expandable member along an arc length in the range of 3 to 3.5 mm. Each electrode pad may have a length measured parallel to the catheter longitudinal axis of about 3-5 mm. Each electrode pad assembly may extend substantially linearly along the catheter and include a row of electrical pads separated by respective electrical traces.

[0131] The catheter may include a plurality of electrode pad assemblies, each having a plurality of electrode pads disposed thereon, the plurality of electrode pad assemblies forming rows of electrode pads, optionally at least four rows of electrode pads connected to each other by electrical traces. The rows of electrode pads may be evenly spaced around the circumference of the expandable member. The electrode pads in one row may be longitudinally offset from the electrode pads in an adjacent row. The spacing between adjacent electrode pads when the expandable member is in its unexpanded state is smaller than the spacing between adjacent electrode pads when the expandable member is in its expanded state. When the expandable member is expanded, each electrode pad may be circumferentially spaced from an adjacent electrode pad by a distance comprised between 0 and 1 mm. The electrode pads in adjacent rows may be connected to each other when the expandable member is in its unexpanded state. When the expandable member is in its expanded state, each electrode pad may be circumferentially spaced from an adjacent electrode pad by a distance comprised between approximately 2 and 5 mm.

[0132] The electrical trace connecting two consecutive electrode pads may comprise a narrowed conductive strip presenting a width measured circumferentially around the expandable member that is significantly less than the arc length of the electrode pads, and optionally, the width of each electrical trace is less than 0.5 mm.

[0133] The electrode pad assembly can be configured to place electrode pads on only one side of the expandable member, optionally covering 25-50% of the circumference of the expandable member, to generate a directional ablation pattern that is all facing the same side and the length of the target ablation zone.

[0134] The ablation assembly may include a plurality of electrodes in the form of axially spaced tubular electrodes mounted on an elongate shaft. The tubular electrodes may have an outer diameter in the range of 2-3 mm. The tubular electrodes may be mounted consecutively on the elongate shaft with a spacing between two consecutive tubular electrodes in the range of 2-4 mm. The tubular electrodes may each have a length in the range of 1-4 mm. The catheter may include a plurality of tubular electrodes arranged along a straight portion of the elongate shaft. The plurality of tubular electrodes may be arranged along the straight portion of the elongate shaft and may span a distance comprised between 12-20 mm. The elongate shaft may have a loop-shaped portion adjacent to the straight portion. The loop-shaped portion may include a plurality of tubular electrodes. The tubular electrodes or the portion of the shaft between the tubular electrodes may include an irrigation port configured to deliver a fluid and connectable to a fluid source.

[0135] The ablation assembly may include at least one straight electrode parallel to the axis of the expandable member, having a length ranging from 12 to 20 mm. The straight electrode may cover at least a 25% segment of the circumference of the expandable member. The catheter may include multiple straight electrodes arranged around the expandable member for circumferential ablation. The catheter may include only one single straight electrode covering a 25% to 50% segment of the circumference of the expandable member for directional ablation. Each straight electrode may be in the form of an electrode strip. Each straight electrode may include one or more irrigation ports configured to be connected to a source of fluid.

[0136] The catheter may include multiple ultrasound transducers disposed within the expandable member. The ultrasound transducers may be carried by a support shaft disposed at the center of the expandable member. The transducers may be disposed continuously over a length ranging from 12 to 20 mm to generate ablation of the same length. Struts or protrusions may be disposed between the transducers and the expandable member. The struts may comprise polymer strands elastically preformed to radially expand away from the transducer. The transducers are optionally at least 4 mm long and spaced apart with flexible gaps between them. The ultrasound transducers may be cylindrical to form circumferential ablations around the target vessel. The ultrasound transducers may be flat or semi-cylindrical to form ablations that are partial segments of the circumference of the target vessel.

[0137] The ablation assembly may include multiple electrodes, and the expandable member may optionally include a basket of three or more rows of elastic struts, each strut having at least one electrode attached thereto. The basket may have a contracted delivery state with a diameter of less than 2.00 mm, optionally about 1.7 mm. The basket may have an expanded ablation state with a diameter ranging from about 2.5 to 4 mm. The catheter may include a non-occlusive, radially expandable tubular membrane associated with the struts, with the electrodes on the outer surface of the tubular membrane. The tubular membrane may be an electrically insulating material. The tubular membrane may be connected to the struts and optionally disposed over the struts. The catheter may also include a coolant delivery port configured to inject coolant into a volume externally bounded by the tubular membrane to enable convective cooling of the electrodes. The coolant delivery port may be at the distal end of the basket. The struts may include a constricted portion between the attached electrodes that has greater flexibility than the remainder of the struts to facilitate bending. The basket and electrode positions may be configured to form an ablation pattern ranging from 12 to 20 mm in length, optionally 15 mm in length. The basket and electrode positions may be configured to form a circumferential ablation pattern along substantially the entire length of the basket. Electrodes may be attached to only one or two struts of the basket to ablate only a circumferential segment of the vessel for directional ablation. The catheter may also include radiopaque markers in a distal region of the catheter, optionally located on the struts, indicating the radial direction of the basket. Each strut may have a cross-section with a respective maximum width and a respective maximum thickness, and each electrode may have a respective maximum width and a respective maximum thickness, the electrode's maximum thickness being greater than the strut's maximum thickness, and the electrode's maximum width being greater than the strut's maximum width. Each strut may have a cross-section with a width of approximately 0.5 mm and a thickness of approximately 0.13 mm. Each electrode may have a cross-section with a width of approximately 1 mm and a maximum thickness of approximately 0.33 mm, tapering to approximately 0.25 mm at the edge.

[0138] The power source may be connected to the ablation assembly, and the control unit may be configured to control the power source and to instruct the power source to deliver ablation energy, particularly RF ablation energy, to the ablation assembly. The control unit may be configured to control the power source so that a greater amount of ablation power, optionally RF energy, is delivered to the proximal electrode(s) than to the remaining electrode(s) to compensate for blood flow cooling. The control unit may be configured to control the power source so that a longer duration of ablation power, optionally RF energy, is delivered to the proximal electrode(s) than to the remaining electrode(s) to compensate for blood flow cooling. The control unit may be configured to control the power source to deliver RF ablation energy in at least one of a sequential unipolar mode, a simultaneous unipolar mode, and a bipolar mode. The control unit may be configured to control the power source to deliver RF ablation energy in a pulsed waveform. The control unit may be configured to control the power source to drive bipolar energy, particularly bipolar RF ablation energy, between paired electrodes, particularly pairs of electrode pads of separate electrode pad assemblies. The coolant source may be connected or connectable to a coolant inlet port of the catheter, which may be in fluid communication with the interior of the expandable member. The control unit may further control the coolant source and may be configured to command the coolant source to inject coolant fluid into the expandable member via the coolant inlet port. The catheter may also include a coolant outlet port that is either connected to an outlet lumen extending within the catheter elongate shaft or in direct communication with the exterior of the catheter so that coolant may be deposited into the bloodstream. The coolant outlet port may be smaller than the coolant inlet port to increase pressure within the expandable member, causing it to expand.

[0139] The catheter may further include a radiopaque marker positioned on the distal region of the catheter to indicate the radial direction, and optionally the radiopaque marker is asymmetric and positioned on the same side or opposite side as the electrode.

[0140] The catheter may also include one or more temperature sensors each disposed between a pair of electrodes. The temperature sensors may be configured to directly contact the vessel wall when the catheter is inserted into the vessel and the expandable member is in its expanded state. The control unit may be configured to receive temperature signals from the temperature sensors and, based on the temperature signals, control the coolant source to infuse coolant and / or control the power emission of ablation energy based on the temperature signals.

[0141] The following fifth section of the Summary of the Invention is intended to introduce the reader to various aspects related to dual-electrode transvascular nerve ablation embodiments, but is not intended to define or delimit any invention. Optionally, the methods and devices described in this fifth section of the Summary may use devices or methods according to any one of the preceding or following aspects.

[0142] One aspect of this portion is a transvascular ablation device adapted and configured for transvascular ablation of a preganglionic TSN or TSN nerve root, comprising a proximal portion adapted to remain external to the patient and a distal portion sized for insertion through the patient's vasculature, the distal portion comprising an elongate shaft, a first ablation member carried by the elongate shaft, a second ablation member carried by the elongate shaft, and an occlusion member carried axially by the elongate shaft between the first ablation member and the second ablation member, the occlusion member adapted to have a delivery configuration and an expanded configuration.

[0143] The second ablation element may be axially spaced from the first ablation element by a distance of 3 to 6 mm.

[0144] At least one of the first ablation member and the second ablation member may have a length of 3-5 mm.

[0145] The outer diameter of the first ablation member may be 1.5 to 3 mm, and the outer diameter of the second ablation member may be 1.5 to 3 mm.

[0146] The occlusion member may have an axial length of 1 to 6 mm.

[0147] The occlusion member may have a diameter of 3-5 mm in the expanded configuration, and optionally has a diameter of 1.5-2 mm in the delivery configuration.

[0148] The device may further include a guidewire lumen extending from the proximal portion to a guidewire exit port in the distal portion.

[0149] The first ablation member may be in electrical communication with a first electrical conductor, and the second ablation member may be in electrical communication with a second electrical conductor different from the first electrical conductor.

[0150] The first and second ablation members may each include one irrigation outlet port in fluid communication with at least one irrigation lumen that extends through the elongate shaft to a proximal portion where it is connectable to an irrigation fluid supply.

[0151] The first and second ablation members may each include one irrigation outlet port in fluid communication with an independent irrigation lumen that extends through the elongate shaft to a proximal portion where an irrigation fluid supply can be connected.

[0152] Any irrigation outlet port may have a diameter of 0.020 inches + / - 0.005 inches. Any irrigation outlet port may be located on the first ablation member side or the second ablation member side, respectively.

[0153] The first ablation member may comprise an electrode having at least one irrigation outlet port disposed within at least one channel running the length of the electrode.The first ablation member may comprise an electrode having at least one irrigation outlet port disposed within at least one scallop running at least a portion of the length of the electrode to a distal or proximal end of the electrode.

[0154] At least one of the first and second ablation members may include a cavity in fluid communication with at least two irrigation lumens through the elongate shaft to a proximal portion where a first of the at least two irrigation lumens is connectable to an irrigation fluid supply and a second of the at least two irrigation lumens is connectable to a fluid return receptacle.

[0155] At least one of the first and second ablation members may include a temperature sensor.

[0156] The occlusion member may be an inflatable occlusion balloon.

[0157] The occlusion balloon may include a chamber that may be in fluid communication with an inflatable lumen that extends through the elongate shaft to a proximal portion where it is connectable to an inflation fluid supply. A temperature sensor may be disposed within the chamber, and the temperature sensor may be adapted to monitor the temperature of the fluid within the chamber.

[0158] One aspect of this portion is a transvascular ablation device adapted and configured for transvascular ablation of preganglionic greater splanchnic nerves or nerve roots, comprising a proximal portion adapted to remain external to the patient and a distal portion sized for insertion through the patient's vasculature, the distal portion comprising an elongate shaft, a first ablation member carried by the elongate shaft, a second ablation member carried by the elongate shaft and axially spaced from the first ablation member, and an occlusion member carried axially by the elongate shaft between the first and second ablation members, the occlusion member adapted to have a delivery configuration and an expanded configuration.

[0159] At least one of the first and second ablation members may have an outer diameter of 1.5 to 3 mm. The occlusion member may have a diameter of 3 to 5 mm in the expanded configuration.

[0160] At least one of the first ablation member and the second ablation member may have a length of 3-5 mm.

[0161] One aspect of this portion is a transvascular ablation device adapted and configured for transvascular ablation of preganglionic greater splanchnic nerves or nerve roots, comprising a proximal portion adapted to remain outside the patient, and a distal portion sized to be inserted through the patient's vasculature, the distal portion comprising an elongate shaft, a first ablation member carried by the elongate shaft, and a second ablation member carried by the elongate shaft and axially spaced from the first ablation member, both of which have an outer dimension, optionally a diameter, that is less than the diameter of the elongate shaft.

[0162] The outer dimensions can be 1.5 to 2.5 mm.

[0163] The diameter of the elongated shaft may be 2 to 3 mm.

[0164] The outer dimension may be 0.2 to 1 mm smaller than the diameter.

[0165] A portion of each of the first ablation member and the second ablation member may be electrically insulating, and the remaining portion of each may be conductive, with the conductive portion comprising a segment that is less than 50%, less than 40%, less than 30%, or less than 25% of the circumference.

[0166] The device may be adapted to be connected to an ablation console, the ablation console adapted to operate the ablation device in at least one of a bipolar mode, a monopolar mode, and a combination of bipolar and monopolar modes.

[0167] One embodiment of this section is a method for ablatating a TSN or TSN nerve root (e.g., a greater splanchnic nerve or a greater splanchnic nerve root) to increase splanchnic venous blood volume, comprising advancing an elongated medical device into an azygos vein, the elongated medical device including a distal region including a flexible shaft, a first ablation member carried by the shaft, and a second ablation member carried by the shaft and axially spaced from the first ablation member, and advancing the first ablation member from the azygos vein into a T9, T10, or T11 intercostal vein, delivering ablation energy from the first ablation member to form an ablation lesion, thereby ablating a portion of the greater splanchnic nerve or the greater splanchnic nerve root.

[0168] The method may further include advancing a second ablation member through the azygos vein into the T9, T10, or T11 intercostal vein and delivering ablation energy from the second ablation member.

[0169] The delivering step may include delivering energy from the first and second ablation members in a monopolar mode.

[0170] The delivering step may include delivering energy from the first and second ablation members in a bipolar mode.

[0171] The delivering step may include delivering energy from the first and second ablation members in a combination of monopolar and bipolar modes.

[0172] The method may also include advancing an occlusion member into the T9, T10, or T11 intercostal vein between the first and second ablation members. The occlusion member may be carried by the elongate shaft between the first and second ablation members. The method may further include expanding the occlusion member within the T9, T10, or T11 intercostal vein. The method may further include completely occluding the T9, T10, or T11 intercostal vein with the occlusion member.

[0173] Advancing the second ablation member may include positioning a proximal end of the second ablation member at the ostium of the azygos vein and an intercostal vein.

[0174] Advancing the first ablation member from the azygos vein into the T9, T10 or T11 intercostal vein may include advancing the first ablation member into the T9, T10 or T11 intercostal vein from the ostium of the azygos vein up to 20 mm toward the intercostal vein, and delivering ablation energy from the first ablation member may occur when the first ablation member is positioned up to 20 mm from the ostium.

[0175] As energy is delivered from the first ablation member, a second ablation member may be positioned within the azygos vein.

[0176] The method may further include expanding an obstruction member at the ostium of the azygos vein and the intercostal vein, the expanding obstruction member directing blood flow away from the ostium.

[0177] Energy may be delivered from the first ablation member in a monopolar mode.

[0178] Creating the lesion may not include delivering ablation energy from a second ablation member.

[0179] When the second ablation member is positioned within the azygos vein, the first and second ablation members may be operated in a bipolar mode.

[0180] Creating the ablation lesion can include creating an ablation region having a depth of at least 5 mm from the intercostal vein.

[0181] Forming the ablation lesion can include forming a circumferential ablation region.

[0182] The method may further include advancing the first ablation member from the azygos vein into another of the T9, T10, and T11 intercostal veins, and delivering ablation energy from the first ablation member when within the other of the T9, T10, and T11 intercostal vein.

[0183] Creating the lesion may not include delivering ablation energy from a second ablation member.

[0184] The method may further include delivering a stimulation signal from at least one of the first and second ablation members. Delivering the stimulation signal may include delivering the stimulation signal in a bipolar mode between the first and second ablation members. The method may further include measuring a response to the stimulation signal. Delivering the stimulation signal and measuring the response may occur after delivering ablation energy from the first ablation member.

[0185] The method may further include advancing an occlusion member into the T9, T10, or T11 intercostal vein proximal to the first ablation member. The occlusion member may be carried by an elongate shaft. The method may further include expanding the occlusion member within the T9, T10, or T11 intercostal vein. The method may further include completely occluding the T9, T10, or T11 intercostal vein with the occlusion member. Expanding the occlusion member may include delivering a fluid to the occlusion member.

[0186] The method may further include delivering irrigation fluid to at least one of the first and second ablation members. The method may include monitoring the irrigation fluid for exceeding a threshold temperature. The method may further include modifying energy delivery parameters when the monitoring step indicates that the irrigation fluid has exceeded a threshold temperature. The method may further include controlling an irrigation fluid flow rate. [Brief explanation of the drawings]

[0187] The drawings included herein are for the purpose of illustrating various examples of the items, methods and apparatus herein and are not intended to limit the scope of the disclosure in any way.

[0188] [Figure 1] 1 is a perspective view of an exemplary intravascular venipuncture device. FIG. [Figure 2] 2 is an enlarged perspective view of a distal portion of the catheter of the device of FIG. 1. FIG. [Figure 3] 2 is an enlarged perspective view of the distal portion of the catheter of the device of FIG. 1, showing the needle guide in an activated position. [Figure 4] 2 is an enlarged perspective view of the distal portion of the catheter of the device of FIG. 1, showing the needle in the puncture position. [Figure 5] 2 is an enlarged perspective view of the distal portion of the catheter of the device of FIG. 1, showing the delivery device in a processing position. [Figure 6] FIG. 10 is an enlarged perspective view of a distal portion of a catheter of another exemplary intravascular venipuncture device. [Figure 7] FIG. 7 is a further enlarged perspective view of the distal portion of the catheter of FIG. 6. [Figure 8] FIG. 7 is an enlarged plan view of the distal portion of the catheter of FIG. 6. [Figure 9] 2 is a schematic diagram of a portion of a patient's thorax with a guidewire positioned within the patient's T10 intercostal vein and the device of FIG. 1 advanced over the guidewire to a target location. [Figure 10]FIG. 10 is a schematic diagram of FIG. 9 with the needle guide of the device advanced toward the activated position. [Figure 11] FIG. 11 is a schematic diagram of FIG. 10 with the needle guide of the device in an activated position. [Figure 12] FIG. 12 is a schematic diagram of FIG. 11 with the needle guide of the device in the puncture position. [Figure 13] FIG. 13 is a schematic diagram of FIG. 12 with the device delivery device in a treatment position adjacent to the greater splanchnic nerve. [Figure 14] FIG. 2 is a schematic diagram of a portion of a patient's thorax with a guidewire positioned within the patient's T11 intercostal vein and the device of FIG. 1 advanced over the guidewire to a target location within the azygos vein. [Figure 15] FIG. 15 is a schematic diagram of FIG. 14 with the catheter of the device rotated to adjust its orientation until the guidewire fits into the notch in the catheter. [Figure 16] FIG. 16 is a schematic diagram of FIG. 15 with the needle guide and needle deployed. [Figure 17] FIG. 10 is an enlarged top plan view of a distal portion of a catheter of another exemplary intravascular vein puncture device. [Figure 18] FIG. 18 is a schematic diagram showing how the radiopaque markers of the device of FIG. 17 appear under fluoroscopy when the device is in a desired rotational orientation. [Figure 19] FIG. 18 is a schematic diagram showing how the radiopaque markers of the device of FIG. 17 appear under fluoroscopy when the device is in a rotational orientation opposite to the desired rotational orientation. [Figure 20] FIG. 18 is a schematic diagram showing how the radiopaque markers of the device of FIG. 17 appear under fluoroscopy when the device is in a rotational orientation transverse to the desired rotational orientation. [Figure 21] FIG. 18 is an enlarged bottom view of the distal portion of the catheter of the device of FIG. 17. [Figure 22] FIG. 18 is a schematic diagram showing how additional radiopaque markers of the device of FIG. 17 appear under fluoroscopy when the device is within a desired rotational tolerance. [Figure 23]FIG. 18 is a schematic diagram illustrating how additional radiopaque markers of the device of FIG. 17 appear under fluoroscopy when the device is not within the desired rotational tolerances. [Figure 24] FIG. 10 is a schematic diagram of a delivery device for another exemplary intravascular venipuncture device. [Figure 25] FIG. 25 is a schematic diagram of the device of FIG. 24 in use. [Figure 26A] 1 is a schematic diagram of an ablation catheter with an ablation balloon positioned in an intercostal vein for ablation of thoracic splanchnic nerves. [Figure 26B] FIG. 26B is a cross-sectional view of the device of FIG. 26A. [Figure 27] 1 is a schematic diagram of an ablation catheter positioned in an intercostal vein for ablation of thoracic splanchnic nerves. [Figure 28] 1 is a schematic diagram of an ablation catheter with an ablation balloon positioned in an intercostal vein for ablation of thoracic splanchnic nerves. [Figure 29] 1 is a schematic diagram of an ultrasound ablation catheter positioned in an intercostal vein for ablation of thoracic splanchnic nerves. [Figure 30A] 1 is a schematic diagram of an ablation catheter with an ablation balloon positioned in an intercostal vein for ablation of thoracic splanchnic nerves. [Figure 30B] 30B is a cross section of the device shown in FIG. 30A. [Figure 31] 1 is a schematic diagram of an ablation catheter positioned in an intercostal vein for ablation of thoracic splanchnic nerves. [Figure 32A] ~ [Figure 32B] 10 is a schematic diagram of another embodiment of an electrode having a fluid outflow mechanism. [Figure 33] 32 is a schematic diagram of the ablation catheter of FIG. 31 positioned at the ostium of an intercostal vein for ablation of a thoracic splanchnic nerve. [Figure 34A] 1 is a schematic diagram of an ablation catheter positioned in an intercostal vein for ablation of thoracic splanchnic nerves. [Figure 34B] FIG. 34B is a cross-sectional view of the ablation catheter shown in FIG. 34A. DETAILED DESCRIPTION OF THE INVENTION

[0189] This disclosure is related in content to the disclosures in U.S. Patent Application Publication No. 2018 / 0110561, PCT International Published Patent Application No. WO2018 / 023132, and PCT / US2018 / 066047 (filed December 17, 2018), which are incorporated herein by reference in their entireties for all purposes.

[0190] The present disclosure generally relates to methods for treating at least one of heart failure and hypertension by increasing splanchnic volume. Some techniques include systems, devices, and methods for transvascular (e.g., transvenous) ablation of target tissue to increase splanchnic volume. The devices and methods may, in some instances, be used to ablate one or more splanchnic nerves to increase splanchnic volume. For example, the devices disclosed herein may be advanced intravascularly to a target vessel within the region of a target nerve, including a thoracic splanchnic nerve ("TSN"), such as the preganglionic greater splanchnic nerve ("GSN"), the lesser splanchnic nerve, or the least splanchnic nerve, or one of their roots (the TSN nerve root). The target vessel may be, for example, an intercostal vein or azygos vein (or both), or a vein of the azygos venous system, preferably one or more of the lowest (i.e., most caudal) three intercostal veins (which may be T9, T10, and T11). The target region within the target vein may include, for example, a lumen within an intercostal vein, extending no more than 30 mm into the vein from the adjacent azygos or hemiazygos vein, and optionally no more than 20 mm into the vein from the adjacent azygos or hemiazygos vein. Thus, the target region has a distal end no more than a specified distance (or range of distances) from the ostium. Thus, the methods herein for positioning an ablation element (or ablation member generally) within a target region of a blood vessel are not limited to requiring the entire length of the ablation element to be positioned within the target blood vessel, but rather include methods in which a proximal portion, perhaps a relatively small portion thereof (e.g., less than 25% of its length), remains disposed within an adjacent blood vessel (e.g., the azygos vein). Thus, methods herein describing positioning an ablation element or member within a target blood vessel within a specified distance from the ostium generally describe positioning the distal end of the ablation element within the target region of the target blood vessel, regardless of whether the entire ablation element is disposed within the same blood vessel (e.g., the intercostal vein) or a portion is disposed within an adjacent blood vessel (e.g., the azygos vein). In any of the methods herein, less than 50% of the length of the ablation element may be positioned within an adjacent blood vessel, for example, less than 45%, or less than 40%, or less than 35%, or less than 30%, or less than 25%, or less than 20%, or less than 15%, or less than 10%.

[0191] In most humans, the TSN may be located up to 5 mm from the target intercostal vein. Intercostal veins at lower levels (e.g., T9, T10, and T11 levels) may have an internal lumen with a diameter ranging from 2 to 3.5 mm within the target area. The TSN, particularly a fully formed GSN, may cross the target intercostal vein within the target area between adjacent azygos or hemiazygos veins and at a distance of 15 mm or less from the adjacent azygos or hemiazygos veins. Sympathetic nerves may cross the intercostal vein beyond a distance of 20 mm from the adjacent azygos or hemiazygos veins.

[0192] Ablation of the TSN by thermocoagulation may involve heating the tissue with an ablation element positioned within the target intercostal vein, which prevents various technical difficulties. Thermal ablation from small veins can constrict the vessel during energy delivery, which, caused by significant changes in tissue contact or blood flow, for example, can dramatically change the thermal and electrical environment of the ablation element, making energy delivery unstable and ablation less predictable and controllable, especially if the vessel constricts around the ablation element.

[0193] With the devices and methods disclosed herein, TSNs can be ablated in a relatively safe manner with minimal or reduced adverse effects (such as damage to the lungs or other nerves). Some method-of-use embodiments herein temporarily occlude blood flow to reduce the effects of venous collapse, thereby advantageously avoiding the challenges of thermal and electrical environmental changes during the heating process. Some method-of-use embodiments herein can ablate nerves up to 5 mm from the target vessel. Some of the devices herein are sized and configured for delivery and positioning within the vasculature identified to ablate target nerves (e.g., TSN, GSN).

[0194] Some of the devices herein may have one or more features that provide for safe delivery to the target vessel.

[0195] Some of the devices and methods of use herein may deliver energy safely with temperature-monitored energy delivery.

[0196] Some of the methods of use herein may, with a single positioning and delivery of energy, create lesions capable of targeting nerves within a target area up to 5 mm from the target vessel and having uninterrupted lesion lengths up to 20 mm in length (e.g., 15 mm, 12 mm).

[0197] Some of the devices and methods herein are adapted to avoid the risk of boiling, hot spots, or erratic energy delivery that can reduce ablation efficacy. Additionally, some embodiments may include nerve stimulation to identify targeted or non-targeted nerves to confirm positioning before ablation or to confirm technical success during or after ablation.

[0198] Studies conducted to inform this disclosure suggested that the lowest three intercostal veins may be the best location for placement of a medical ablation device because the TSN, GSN, or GSN root (target nerve) is likely to cross one or more of the lowest three intercostal veins between the ostium and the azygos vein and is within a specific distance from the ostium. Accordingly, one aspect of the present disclosure is a preferred method that includes positioning a medical device (at least its ablation member portion) in one of a specific number of intercostal veins and, in addition, within a specific distance from the ostium of the azygos vein. This location and placement may provide the best likelihood that the medical device, when activated, will effectively ablate the target nerve, as described in more detail below.

[0199] Although not required, it may be preferable for the ablation method to create a contiguous ablation zone (i.e., not have separate, discrete regions of ablated tissue that are not connected to one another). This ensures that the region of tissue in which the target GSN nerve or GSN nerve root may be located is most likely to be effectively ablated by the ablation energy. The contiguous ablation zone may be circumferential or less than circumferential.

[0200] Although not required, it may also be preferred that the ablation method create an ablation zone having a depth of at least 5 mm and a length in the range of 5-20 mm, preferably in the range of 10-20 mm. Ablation regions or zones with these parameters increase the likelihood that the ablation region will include the target GSN or GSN root. While the present disclosure generally describes lesions with lengths in the range of 5-20 mm, it may also be possible to effectively ablate target nerves with lesions having lengths less than 5 mm, e.g., 1-5 mm. For example, some target nerves may be very close to the ostium between the azygos vein and the intercostal veins, allowing for the creation of an ablation region or zone less than 5 mm in length while still being able to effectively ablate the target nerve. Unlike procedures that target nerves innervating blood vessels (e.g., some renal denervation techniques), these exemplary treatment methods target one or more target nerves that are in relatively close proximity to the intercostal veins and that traverse or cross the veins rather than along them. Transverse in this context does not mean that the nerve penetrates the venous structure in any way, but rather refers to the general relative orientation of the nerve and vein.

[0201] While some methods herein form lesions having lengths within a particular range, it should be understood that the methods may inherently form these ablation lengths even if the ablation zone length is not directly input into the procedure. For example, when a console or energy generator is used to deliver energy, one or more delivery parameters may be selected as part of the procedure (e.g., time, power, etc.), and the ablation length may not necessarily be input into the procedure. This means that the ablation length may occur as a result of the procedure without being specifically selected by a user or input into an energy-generating device such as a generator. If the result of the procedure is the formation of a lesion with a length within the ranges specified herein (or if formed with a length within the ranges specified), the method is understood to be within the scope of the claims that include the ablation zone length.

[0202] Embodiments of Intravascular Vascular Puncture Disclosed herein are devices and methods for endovascular venipuncture and subsequent treatment of target structures (e.g., nerves) external to a vein. The devices and methods may, in some instances, be used for splanchnic nerve ablation for the treatment of heart failure. For example, the devices disclosed herein may be advanced intravascularly to a target vein in the region of the thoracic splanchnic nerve (TSN), such as the greater splanchnic nerve (GSN) or the TSN nerve root. The target vein may be, for example, an intercostal vein or an azygos vein or veins of the azygos venous system. The device may then be activated or deployed again to treat the TSN, for example, by temporarily blocking the TSN or permanently ablatating the TSN. Ablation of the TSN may be performed, for example, by radiofrequency (RF) ablation, cryoablation, thermal ablation, chemical ablation, or drug ablation. Ablation of the TSN can affect circulating blood volume, blood pressure, blood flow, and overall cardiac and circulatory system function, as described in patent application PCT / US2017 / 044747 to treat heart failure. Ablation of the TSN may also have therapeutic benefits, such as treating intractable abdominal pain or mobility. With the devices and methods disclosed herein, the TSN can be ablated in a relatively safe manner with minimal or reduced adverse effects (such as damage to the lungs or other nerves).

[0203] Intravascular puncture device Referring to FIG. 1, a first embodiment of an intravascular venipuncture device 100 is shown. The device 100 includes an elongate catheter 102 extending along a longitudinal axis 104 (also referred to herein as the "catheter axis") (shown in FIG. 2) and having a proximal catheter section 106 and a distal catheter section 108. The distal catheter section 108 generally serves as the working end of the device 100. The proximal catheter section 106 may generally remain external to the patient during use and may be manipulated by a surgeon or other professional. The catheter 102 has an outer catheter diameter 110 (shown in FIG. 2).

[0204] In some examples, the catheter may include a braided shaft to facilitate torque-ability (ie, transmission of torque from the catheter proximal portion 106 to the catheter distal portion 108), particularly over tortuous delivery paths.

[0205] 2, in the illustrated example, the catheter 102 includes a guidewire lumen (not shown) extending therethrough (along the catheter axis 104), and the catheter distal section 108 includes a guidewire exit port 112 so that the catheter 102 can be advanced into the venous system over a guidewire. The catheter 102 has a circumferential outer surface 114 and a distal end face 116, and in the illustrated example, the guidewire exit port 112 is at the distal end face 116.

[0206] In another example, the guidewire lumen and exit port may be omitted and the catheter may be advanced into the patient's cardiovascular system (eg, a vein or artery) without the assistance of a guidewire.

[0207] The catheter outer diameter 110 may be sized to fit into a patient's azygos vein, and optionally, may be sized to fit into a patient's intercostal veins. For example, the catheter outer diameter 110 may be about 1-5 mm, or about 1-3 mm.

[0208] 2 and 3, in the illustrated example, device 100 further includes a needle guide 101 having a blunt distal end 103 (also referred to herein as the "needle guide distal end") that is deployable from catheter 102 from a needle guide retracted position (shown in FIG. 2, where needle guide 101 is not visible) to a needle guide activated position (shown in FIG. 3).

[0209] In general, the needle guide retracted position can be any position in which the needle guide distal end 103 is retracted toward the catheter 102 relative to the needle guide activated position. Still referring to FIGS. 2 and 3 , in the illustrated example, when the needle guide 101 is in the retracted position, the needle guide distal end 103 is nested within the catheter. The needle guide 101 is deployable from the catheter 102 through a side port 109 in the outer circumferential surface 114 of the catheter. When in the deployed position, the needle guide 101 extends from the side port 109, such that the needle guide distal end 103 is radially spaced from the catheter 102 (i.e., spaced from the catheter 102 transversely relative to the catheter axis 104). In the illustrated example, when in the needle guide activated position, the needle guide 101 is generally straight and angled relative to the catheter axis 104. In another example, the needle guide may be bent or curved and / or perpendicular to the catheter axis 104.

[0210] 3 , in the illustrated example, the needle guide 101 is relatively short. That is, in the illustrated example, when the needle guide 101 is in the needle guide activated position, the needle guide distal end 103 is radially spaced from the catheter by a needle guide deployed distance 111. In some examples, the needle guide deployed distance 111 is selected so that when the needle guide 101 is in the deployed position and abuts a vein wall (e.g., an intercostal vein wall, an azygos vein wall, or a wall of a vein in the azygos venous system), the needle guide distal end 103 presses against the vein wall with some pressure (as described below). For example, when the needle guide 101 abuts a vein wall in the deployed position, the needle guide 101 pushes the catheter 102 against the opposite vein wall, which in turn presses the needle guide distal end 103 against the vein wall. To facilitate application of sufficient pressure to the vein wall by the needle guide distal end 103, the catheter diameter 110 plus the needle guide deployment distance 111 may be equal to or slightly greater than the inner diameter of the target vein when the needle guide is fully deployed. In situations where the patient's vein diameter is slightly smaller than the combined distance of the catheter diameter 110 and the needle guide deployment distance 111, the vein may stretch to accommodate full deployment of the needle guide 101. For example, for such a catheter configured for use within a human T10 or T11 intercostal vein, the catheter diameter 110 plus the needle guide deployment distance 111 may be equal to a distance in the range of 2 to 4 mm (e.g., in the range of 2.5 to 3.5 mm). In another example, for such a catheter configured for use within a human azygos or hemiazygos vein at the T10 or T11 level, the catheter diameter 110 plus the needle guide deployment distance 111 may be equal to a distance in the range of 3.5 to 6.5 mm (e.g., in the range of 4 to 5 mm). Optionally, the user may measure the size of the target blood vessel (e.g., by CT angiography or other medical imaging modality) before delivering the ablation catheter and select an appropriate ablation catheter according to the diameter of the target vein. In some examples, the needle guide deployment distance 111 is smaller than the catheter outer diameter 110. For example, the needle guide deployment distance 111 may be about 0.5 to about 6 mm, or about 0.5 to about 3 mm, or about 2 to about 6 mm.

[0211] 3 and 4, in the illustrated example, the device further includes a needle 105 having a sharp puncturing end 107. The needle 105 is deployable from within the needle guide 101 from a needle retracted position (shown in FIG. 3, where the needle 105 is not visible) to a puncturing position (shown in FIG. 4).

[0212] 3 and 4, in the illustrated example, when the needle 105 is in the needle retracted position, the needle 105 is within the needle guide 101, such that the puncturing end 107 is inboard of the needle guide distal end 103. When in the puncturing position, the needle 105 protrudes from the needle guide 101, such that the puncturing end 107 protrudes outboard of the needle guide distal end 103.

[0213] 4 , in the illustrated example, the needle 105 is relatively short. That is, in the illustrated example, when the needle 105 is in the puncture position, the puncture tip 107 is separated from the needle guide distal end 103 by a needle deployment distance 113. In some examples, the needle deployment distance 113 is selected to be long enough to puncture only the wall of a vein, such as an intercostal vein wall or an azygos vein wall, without significantly protruding beyond the vein wall. This may allow for accurate puncture of the vein while minimizing or reducing the risk of damaging nearby tissue, such as lung tissue. For example, the needle deployment distance 113 may be less than 2 mm, or less than 1 mm, or approximately 0.5 mm. In some examples, the needle deployment distance 113 is less than the catheter outer diameter 110.

[0214] 5, in the illustrated example, device 100 further includes a delivery device 115 capable of delivering a treatment to the patient. The treatment, in some examples, may be for nerve ablation, such as TSN nerve ablation. For example, delivery device 115 may be a fluid delivery device (for delivery of an ablation chemical or agent), a thermal energy delivery device (for delivery of heat), a cryoablation energy delivery device, an electrical energy delivery device, and / or an RF energy delivery device. The treatment may be delivered circumferentially from delivery device 115 or longitudinally (also referred to as "directionally") from delivery device 115.

[0215] 5, in the illustrated example, delivery device 115 is a probe having a generally rounded blunt distal tip 117 (also referred to herein as the "delivery device distal tip"). Delivery device 115 further includes a fluid port 118 disposed proximate to blunt distal tip 117 on a sidewall of delivery device 115. Fluid port 118 may be for delivering a fluid, such as a chemical or pharmaceutical cauterizing agent, an anesthetic, a cooling fluid, or other fluid.

[0216] 4 and 5, in the illustrated example, the delivery device 115 is deployable from within the needle 105 from a delivery device storage position (shown in FIG. 4, but with the delivery device 115 not visible) housed within the needle 105 and needle guide 101, to a delivery device handling position (shown in FIG. 5) in which the delivery device distal end 117 protrudes beyond the puncture end 107 of the needle. In the illustrated example, a fluid port 118 also protrudes beyond the puncture end 107 of the needle.

[0217] In the illustrated example, when in the delivery device treatment position, the delivery device 115 extends a delivery distance 99 beyond the needle puncture tip 107. The delivery distance 99 may be selected to position the delivery device 115 proximate to the treatment position. For example, if the device 100 is being used to ablate the GSN by puncturing an intercostal vein, the delivery distance 99 may be from about 3 to about 7 mm, or from about 4 to about 6 mm. Alternatively, if the device 100 is being used to ablate the GSN by puncturing an azygos vein or a vein of the azygos venous system, the delivery distance 99 may be up to 15 mm.

[0218] In another example, the delivery device 115 may be omitted. In such an example, the treatment may be delivered directly from the needle 105. For example, a drug may be delivered directly from the needle.

[0219] 1-5 may include one or more radiopaque markers to aid in the advancement, positioning, or orientation of the device. The radiopaque marker(s) may be on, for example, the catheter, needle guide, needle, or delivery device. For example, the catheter distal portion 108 may be advanced to a target location within a blood vessel, and before deploying the needle guide 101, a user may visually assess the rotational orientation of the catheter distal portion 108 by imaging the catheter 102, the radiopaque markers, and / or portions of the patient's anatomy using fluoroscopy. This may indicate the direction in which to deploy the needle guide 101.

[0220] Referring to FIG. 17 , a device 1700 is shown that includes a radiopaque marker 1746 configured to facilitate placement of a catheter 1702 in a desired orientation. Device 1700 is similar to device 100, and for the sake of brevity, similar features of device 100 will not be described in detail. In device 1700, radiopaque marker 1746 is configured to distinguish when radiopaque marker 1746 is aimed at the C-arm head. Because the position of radiopaque marker 1746 is circumferentially aligned with the direction of deployment of the needle guide (not shown), radiopaque marker 1746 can be used to indicate when the needle guide is aimed at the C-arm head. In the illustrated example, radiopaque marker 1746 is made of a radiopaque material and has an asymmetric shape. Specifically, radiopaque marker 1746 is N-shaped. When the radiopaque marker 1746 is facing towards the C-arm head, the radiopaque marker 1746 will appear as the letter N, as shown in Figure 18. When the radiopaque marker 1746 is facing away from the C-arm head (e.g., towards the vertebrae), the radiopaque marker 1746 will appear as the back of the letter N, as shown in Figure 19. When the radiopaque marker 1746 is facing sideways, the radiopaque marker 1746 will appear as a line, as shown in Figure 20.

[0221] 21 , in the depicted example, device 1700 further includes an additional radiopaque marker 1748 configured to visually indicate when the rotational position of catheter 1702 is within a set tolerance. In particular, additional radiopaque marker 1748 includes two lines, the centers of both lines being circumferentially spaced approximately 180 degrees from radiopaque marker 1746, such that when the orientation is within the set tolerance, radiopaque marker 1746 appears between the lines of additional radiopaque marker 1748, as shown in FIG. 22. When the orientation is outside the set tolerance, radiopaque marker 1746 either overlaps one of the lines of additional radiopaque marker 1748 or is outside the lines of additional radiopaque marker 1748, as shown in FIG. 23. For example, the set tolerance can be up to 45 degrees on either side of perfect alignment (eg, up to 35 degrees, or 25 degrees, or 15 degrees, or 5 degrees).

[0222] 6-8, another exemplary device 600 for intravascular venipuncture is shown. Device 600 is similar to device 100 of FIGS. 1-5, and for the sake of brevity, features similar to those of device 100 will not be described in detail. Furthermore, in describing device 600, features similar to those of device 100 will be designated with the same reference numerals as those of device 100, but increased by 500.

[0223] 6, similar to device 100, device 600 includes a catheter 602, a needle guide 620a (also referred to herein as the "first needle guide") deployable from catheter 602 in a direction transverse to catheter axis 104, and a relatively short needle 628a (also referred to herein as the "first needle") deployable from needle guide 620. However, device 600 also includes a second needle guide 620b deployable from catheter 602 in a direction transverse to catheter axis 104 (this direction may also be referred to herein as the "second direction," which is transverse to the catheter axis), and a second needle 628b deployable from second needle guide 620b. Second needle guide 620b and second needle 628b are identical in construction and operation to first needle guide 620a and first needle 628a and will not be described in detail.

[0224] 6, in the illustrated example, first needle guide 620a and first needle 628a are longitudinally spaced apart from notch 642 in distal end 608 by a distance 609 of 1.5 to about 2.5 cm, or about 2 cm, to correspond to the distance between the tethering vein and the first target location (e.g., the tethering vein may be the T11 intercostal vein through which the guidewire is delivered, and the first target location may be the azygos vein between the T10 and T11 intercostal veins). Additionally, first needle guide 620a and first needle 628a are longitudinally spaced apart from second needle guide 620b and second needle 628b. That is, the first needle guide 620a is deployable from the catheter 602 at a first longitudinal position of the catheter 602, and the second needle guide 620b is deployable from the catheter 602 at a second longitudinal position of the catheter 602, the second longitudinal position being spaced apart from the first longitudinal position. The second longitudinal position may be spaced apart from the first longitudinal position by a distance 644 of about 3 to about 5 cm, or about 4 cm, to correspond to the distance between the target locations (e.g., the first target location may be the azygos vein between the T10 and T11 intercostal veins, and the second target location may be the azygos vein between the T9 and T10 intercostal veins).

[0225] 6, in the illustrated example, the first needle guide 620a and first needle 628a are circumferentially aligned from the second needle guide 620b and second needle 628b, i.e., the first needle guide 620a is deployable from the catheter 602 at a first circumferential position on the catheter, and the second needle guide 620b is deployable from the catheter 602 at a second circumferential position on the catheter 602, the second circumferential position being aligned with the first circumferential position.

[0226] 6 may allow treatment of relatively large anatomical areas in a simple and / or relatively short time frame, i.e., treatments (e.g., ablation treatments) may be delivered simultaneously from first needle 628a and second needle 628b to ablate large areas.

[0227] Similar to device 100, first needle 628a and second needle 628b may each optionally house a respective delivery device for delivering a treatment.

[0228] 7 and 8, similar to device 100, the device includes a guidewire lumen and a guidewire exit port 612 at catheter distal end 608. However, guidewire exit port 612 is a notch 642 (also referred to herein as an "orientation notch") that is open on both distal end face 616 and circumferential outer surface 614 and spans these two surfaces.

[0229] In the illustrated example, the notch 642 is open at a notch circumferential location on the catheter. The notch circumferential location may be within 30 degrees of the first circumferential location and / or the second circumferential location in some examples. In the illustrated example, the notch circumferential location is aligned with the first circumferential location and the second circumferential location.

[0230] The circumferential positioning of the notch 642 relative to the first and second needle guides 620a, 620b can be used to facilitate positioning the first and second needle guides 620a, 620b in a desired orientation during use. For example, as described in more detail below, during use, a guidewire can be directed in a particular direction, such as laterally from a first blood vessel (e.g., a vein or artery) to a second blood vessel. The catheter 602 can then be advanced over the guidewire and stopped within the first vein. The catheter 602 can then be rotated about the catheter axis 604 until the guidewire is seated within the notch 642. Once the guidewire is seated within the notch 642, the first and second needle guides 620a, 620b will be facing laterally and in the same direction as the second vein.

[0231] 6-8 may include one or more radiopaque markers to aid in the advancement, positioning, and / or orientation of the device. The radiopaque marker(s) may be on, for example, the catheter, needle guide(s), needle(s), or delivery device(s). In the illustrated example, the distal tip of the catheter (including the distal end face 616 and the portion of the circumferential outer surface 614 adjacent the notch 642) is radiopaque.

[0232] As mentioned above, the devices described herein may include a delivery device for delivering the treatment, which may deliver cryogenic energy (also referred to as cryoablation energy). Using cryogenic energy for ablation is advantageous in some instances because it may allow for a controllable and predictable ablation zone (e.g., a zone extending circumferentially about 3-5 mm around the delivery device), may eliminate the need for fluid to be freely delivered to the target zone, may allow for better visualization of the treatment (because ice is visible in medical imaging), may be less painful than other ablation modes, and may be used for temporary nerve blockade. Referring now to FIG. 24, one exemplary cryogenic energy delivery device 2334 is shown. For simplicity, other features of the device, such as the needle guide and needle, are not shown in FIG. 24.

[0233] In the illustrated example, the cryogenic energy delivery device 2334 includes a first lumen 2350 (also referred to as a supply lumen) for delivery of cryogenic fluid (e.g., liquid nitrogen such as supercritical liquid nitrogen as described in U.S. Pat. No. 7,921,657) from a source 2358 to a distal end 2336 of the cryogenic energy delivery device 2334, and a second lumen 2352 (also referred to as a return lumen) for return of the cryogenic fluid to the source 2358 (e.g., for regeneration or for ultimate disposal or exhaust). In the illustrated example, the first lumen 2350 is formed by a central tube 2354 within the cryogenic energy delivery device 2334, and the second lumen is formed between the central tube 2354 and an outer wall 2356 of the cryogenic energy delivery device 2334, such that the first lumen 2350 and the second lumen 2352 are coaxial. In another example, first lumen 2350 and second lumen 2352 may be formed in other ways, for example, by two adjacent tubes within cryogenic energy delivery device 2334.

[0234] In some examples, the central tube 2354 and outer wall 2356 may be formed from stainless steel hypotubing. The distal end 2336 of the delivery device 2334 may have a dome welded end.

[0235] In some examples, the distal end 2336 of the delivery device 2334 may include one or more temperature sensors (not shown). In some examples, the delivery device 2334 may include one or more stimulation electrodes (not shown). For example, the delivery device 2334 may include two spaced apart band electrodes, which may be used in a bipolar mode.

[0236] In some examples (not shown), the catheter and / or needle and / or needle guide may be thermally insulated so that cryoablation is delivered only from the delivery device 2334 and not from other parts of the device.

[0237] In examples where a device includes two needles, two needle guides, and two cryogenic energy delivery devices (such as device 600), a single supply lumen may feed both cryogenic energy delivery devices.

[0238] 24 , in the illustrated example, the source of cryogenic fluid 2358 includes a fluid reservoir 2360, a supply valve 2362 between the fluid reservoir 2360 and the first lumen 2350, a pressure relief valve 2364 at the outlet of the second lumen 2352 for venting the returning cryogenic fluid to atmosphere, and a controller 2366 for controlling the supply valve 2362 and the pressure relief valve 2364. The controller 2366 may be in communication with a temperature sensor at the distal end 2336 of the delivery device 2334, and the supply of the cryogenic fluid may be automatically controlled in response to the sensed temperature. Alternatively, the supply of the cryogenic fluid may be manually controlled.

[0239] In some examples, the delivery device 2334 may cyclically deliver cryogenic energy and thermal energy (e.g., using RF). This may be used for reversible blocking of myelinated nerves by delivering thermal energy to reversibly block the nerve (i.e., delivering thermal energy at a relatively low temperature for a relatively short time, e.g., 1-4 minutes, less than 2-50 Watts to the 60th power, or less than 20 Watts), and then delivering cryogenic energy to reversibly block the nerve (i.e., delivering cryogenic energy for a relatively short time and at a relatively high temperature, e.g., above 15 degrees Celsius). RF energy may be delivered through an outer wall 2356 of the delivery device 2334. Alternatively, the delivery device may include one or more electrodes (e.g., two band electrodes) on the outer wall 2356, which may be electrically insulating.

[0240] In some examples (not shown), a delivery device similar to delivery device 2334 may be used in a device that does not include a needle guide or needle to deliver cryogenic energy without puncturing a vein. In such a device, RF energy may be used to warm the vein and cause it to contract around the cryogenic energy delivery device before cooling so that blood flow is reduced (thus inhibiting cooling). Alternatively, occlusion balloons may be deployed distally and proximally to the cryogenic energy delivery device to stop blood flow inhibiting cooling.

[0241] The above-described devices may optionally include various sensors and electrodes. For example, device 100 and / or 600 may include one or more temperature sensors and / or bioimpedance sensors. As a further example, device 100 and / or 600 may include one or more electrical stimulation electrodes. Such sensors and electrodes may be positioned on the catheter, needle guide(s), needle(s), and / or delivery device(s). Such sensors and electrodes are described in detail in patent application PCT / US2017 / 044747.

[0242] In any of the above examples, the delivery device (e.g., delivery device 115) can be configured to be flexible so that if contact with the lung occurs, the delivery device can bend to accommodate lung movement, minimizing or reducing lung damage. For example, even if a flexible delivery device contacts or punctures the lung, lung movement can cause the delivery device to bend instead of puncturing the lung. For example, the flexible delivery device can include a flexible shaft of sufficient axial compressive strength to allow advancement through soft tissue, such as fat, as it advances toward the target, and the flexible shaft can be a coil spring.

[0243] Method of using an intravascular vascular puncture device Reference is made below to certain anatomical structures of the thorax, which are described and illustrated in detail in U.S. Patent Application Publication No. 2018 / 0110561, PCT International Published Patent Application No. WO2018 / 023132, and PCT / US2018 / 066047 (filed December 17, 2018), which are incorporated herein by reference in their entirety for all purposes.

[0244] In the context of this specification, TSN may refer to the right or left thoracic splanchnic nerves and their contributing nerves, and endovascular puncture and procedures (e.g., ablation) may be performed from the azygos vein or one or more intercostal veins to access the right thoracic splanchnic nerve, or from the hemiazygos vein or intercostal veins or their respective branches to access the left thoracic splanchnic nerve, or bilateral procedures may be performed from both the azygos and hemiazygos veins and their branches to access both the right and left thoracic splanchnic nerves.

[0245] A first exemplary method for intravascular puncture and processing will be described with reference to Figures 9-13. The method will be described with reference to device 100 of Figures 1-5. However, the method is not limited to device 100, and device 100 is not limited to use with this method.

[0246] In the illustrated example, the method is for intravascular intercostal vein puncture and treatment of GSNs by ablation. The method is shown in the T10 intercostal vein. In another example, the method may be performed in other intercostal veins, such as the T9 or T11 intercostal veins, examples of which are described herein. Ablation of GSNs may be for treating heart failure or other related conditions, as described in U.S. Patent Application Publication No. 2018 / 0110561, PCT International Published Patent Application Nos. WO2018 / 023132, and PCT / US2018 / 066047 (filed December 17, 2018). In another example, the same method may be used for intravascular puncture of other blood vessels for other therapeutic purposes.

[0247] Intercostal veins may be accessed intravascularly by several techniques, including through the subclavian, jugular, or femoral veins. Various techniques are described in U.S. Patent Application Publication No. 2018 / 0110561, PCT International Published Patent Application Nos. WO2018 / 023132, and PCT / US2018 / 066047 (filed December 17, 2018), and are not necessarily detailed herein.

[0248] 9 , as a first step, a guidewire 900 may be advanced through a patient's venous system into a T10 intercostal vein 902. The catheter distal portion 108 is then advanced over the guidewire 900 through the venous system into the T10 intercostal vein 902 and to a target location within the T10 intercostal vein 902. In some instances, the target location is approximately 3 cm into the T10 intercostal vein 902. In some instances where the procedure is ablation of a GSN 904 and damage to the sympathetic chain is to be avoided, the target location may be approximately 1.5 cm from the azygos vein 906 into the T10 intercostal vein 902, or approximately 1 cm into the T10 intercostal vein 902. In some instances, the catheter 102 may be advanced approximately 3 cm or more into the T10 intercostal vein, and then a stimulation pulse is applied from the catheter 102. Once the pulse stimulates the sympathetic chain, the catheter may be slightly retracted. Stimulation and retraction can be repeated until the stimulation pulse stimulates the GSN without stimulating the sympathetic chain.

[0249] In some instances (not shown), radiopaque markers on the catheter 102 (such as the radiopaque markers 1746 and 1748 described above) may be used to facilitate placement of the catheter 102 in a desired rotational orientation. The desired orientation may be one in which the needle guide 101 is deployed radially away from the vertebra (e.g., opposite the vertebra) and toward the TSN. For example, if the target vessel is the right T11 intercostal vein, the C-arm fluoroscope may be centered on the T11 vertebra and optionally rotated from an anterior-posterior center position (AP position) to the patient's right side to achieve an angle approximately perpendicular to the tangent to the vertebra. In this position, it may be desirable to deploy the needle guide 101 radially toward the C-arm head, where the GSN often crosses the intercostal vein. The catheter 102 may be torqued to rotate the catheter distal portion 108 within the intercostal vein until the radiopaque marker indicates that the needle guide 101 is deployed toward the C-arm and therefore toward the target nerve.

[0250] Because the GSN is between the intercostal veins and the parietal pleura, and the pleura at this location often has roughly the same contour as the spine, deploying the needle guide 101 perpendicular to the vertebral tangent may orient the needle guide perpendicular to the pleura. Even though the needle 105 may penetrate only a small amount beyond the venous wall and the delivery device 115 may have a blunt tip, there may still be some risk of penetrating through the parietal pleura, in which case fluid or energy may not be effectively delivered to the GSN. Delivering the needle 105 or delivery device 115 at an oblique angle (e.g., about 45 degrees) instead of a right angle may reduce the risk of puncturing the pleura. Thus, in another example, the catheter may include a radiopaque marker circumferentially spaced from the needle guide, such that when the radiopaque marker is aimed at the C-arm head, the needle guide is deployed in a direction that does not aim at the C-arm head (e.g., 45 degrees away from the C-arm head).

[0251] 10 and 11 , the needle guide 101 may then be deployed from the catheter 102. As discussed above in the "Device" section, the needle guide 101 may be deployed transversely to the catheter axis 104 such that the needle guide distal end 103 is radially spaced from the outer circumferential surface 114 of the catheter 102 (as shown in FIG. 1 ). The needle guide 101 may be deployed until the needle guide distal end 103 contacts the venous wall 908, as shown in FIG. 10 . Continued deployment presses the needle guide distal end 103 against the venous wall 908 (in preparation for deployment of the needle 105). For example, continued deployment may push the catheter 102 away from the venous wall 908, such that the catheter 102 abuts the opposite wall 910 of the vein 902 (also referred to herein as the "opposite venous wall"), as shown in FIG. 11 , or contacts another anatomical structure. Alternatively, continued deployment may cause other movement of the catheter 102, resulting in the distal end 103 applying pressure to the vein wall 908 in preparation for deployment of the needle 105.

[0252] 12 , when the needle guide distal end 103 is pressed against the vein wall 908 (e.g., as a result of the catheter 102 abutting the opposing vein wall 910 or other anatomical structure), the needle 105 is deployed from the needle guide distal end 103, puncturing the vein wall 908 with the sharp puncture tip 107 of the needle 105. The relatively short puncture distance of the needle 105 allows the vein wall 908 to be accurately punctured while minimizing or reducing the risk of puncturing the lung or other nearby tissue. For example, as described above, the needle 105 can be deployed to a deployment distance of less than the catheter outer diameter 110 (shown in FIG. 2 ) and / or less than 2 mm, or less than 1 mm, or about 0.5 mm.

[0253] Once the vein 902 has been punctured, various optional steps may be performed. For example, a nerve stimulation test may be performed by delivering an electrical stimulation pulse through the sharp puncture tip 107 to confirm the position of the sharp puncture tip 107 relative to the GSN 904 or other nerves or anatomical structures. As a further example, contrast may be delivered to confirm that the lung or parietal pleura has not been punctured.

[0254] A treatment may then be delivered to an area outside of the vein 902 via the sharp puncture tip 107 of the needle 105. In the illustrated example, a delivery device 115 is deployed from the puncture tip 107 and used to deliver the treatment. In another example, the needle 105 itself delivers the treatment. For example, a fluid (such as a cauterizing fluid) may be delivered through the needle.

[0255] 13, as described above, delivery device 115 can be deployed a delivery distance 99 from puncture tip 107 (shown in FIG. 5). Depending on the mode of operation, delivery distance 99 can be, for example, up to 15 mm, or 3-7 mm, or 4-6 mm. Often, to ablate GSN 904 from an intercostal vein using RF energy, delivery device 115 can be deployed 4-6 mm. Optionally, neurostimulation testing can be performed by delivering pulses through delivery device 115 to confirm the position of delivery device 115 relative to GSN 904 or other neuroanatomical structures.

[0256] A treatment can then be delivered from the delivery device 115. For example, as described above, a treatment fluid can be delivered, or a thermal energy treatment can be delivered, or a cryogenic energy treatment can be delivered, or an RF energy treatment can be delivered.

[0257] Once the procedure is complete, the device 100 may be withdrawn from the patient by retracting the delivery device 115 towards the needle 105, retracting the needle 105 towards the needle guide 101, retracting the needle guide 101 towards the catheter 102, and then withdrawing the catheter distal portion 108 through the patient's venous system.

[0258] 14-16, another method for intravascular puncture and processing will be described. The method will be described with reference to device 600 of Figures 6-8. However, the method is not limited to device 600, and device 600 is not limited to use in accordance with this method.

[0259] In the illustrated example, the method is for treatment of a GSN 904 by endovascular cannulation and ablation of the azygos vein 906 at the right T9-T11 level. The azygos vein 906 may be accessed intravascularly by several techniques, including from the subclavian, jugular, or femoral veins. Various techniques are described in International Patent Application No. PCT / US2017 / 044747 and will not be described in detail herein.

[0260] 14 , in the illustrated example, as a first step, a guidewire 900 may be advanced through a patient's venous system. The azygos vein 906 is the target for puncture, and the guidewire 900 may be advanced through the azygos vein 906 and into the T11 intercostal vein 912. The catheter distal portion 608 may then be advanced over the guidewire 900 through the venous system into the azygos vein 906 to a target location within the azygos vein 960. In some examples, the target location may be between the T9 and T11 levels. For example, the catheter distal portion 608 may be positioned such that the first needle guide 620a (shown in FIG. 16 ) is between the T10 intercostal vein 902 and the T11 intercostal vein 912 when deployed, and the second needle guide 620b is between the T9 intercostal vein (not shown) and the T10 intercostal vein 902 when deployed.

[0261] Referring to FIG. 15, when the catheter distal section 608 is at the target location, its orientation is: When deployed, first needle guide 620a and second needle guide 620b (shown in FIG. 16 ) may be adjusted to point toward GSN 904. On the right side of the body, the intercostal veins are generally on the same side as GSN 904 and azygos vein 906 and are generally coplanar with GSN 904, and positioning guidewire 900 within T11 intercostal vein 912 can facilitate adjusting the catheter rotational orientation 602. That is, with guidewire 900 within T11 intercostal vein 912 and catheter distal portion 608 at a target location within azygos vein 906, catheter 602 can be rotated about catheter axis 604. When the notch 642 in the catheter distal section 608 faces in the same direction as the T11 intercostal vein 912, i.e., toward the GSN 904, the guidewire 900 fits within the notch 642 and nests within the portion of the notch 642 that opens on the outer circumferential surface 614. This positioning of the guidewire 900 (i.e., nesting within the portion of the notch 642 that opens on the outer circumferential surface 614) can be confirmed under fluoroscopy.

[0262] In another example, a device may be used in which the notch and first and second needle guides are circumferentially spaced about 30 degrees apart, which points the first and second needle guides slightly away from the lungs and toward the vertebrae, thereby reducing or minimizing the risk of lung puncture.

[0263] 16 , once the orientation of the catheter 602 has been confirmed, the first needle guide 620a and the second needle guide 620b may be deployed sequentially or simultaneously from the catheter 602. As described above, the first needle guide 620a and the second needle guide 620b may be deployed until the needle guide distal blunt ends 622a and 622b, respectively, contact the azygos vein wall 916 and until the catheter 602 is pushed against the opposite azygos vein wall 918. The first needle 628a and the second needle 628b may then be deployed to puncture the azygos vein wall 916.

[0264] Optionally, the first and second delivery devices can then be deployed from the first needle 628a and the second needle 628b and used to deliver the treatment. For example, with reference to FIG. 25, the cryogenic energy delivery device 2334 (described above with respect to FIG. 24) can be used to deliver the cryogenic energy. In some examples, the cryogenic energy delivery device 2334 can be deployed a delivery distance of up to 15 mm to treat the GSN 904 from the azygos vein 906.

[0265] Alternatively, the first needle 628a and the second needle 628b themselves can be used to deliver the treatment.

[0266] In any of the above examples, various techniques may be used to avoid puncture or other damage to the lungs by the needle or delivery device. For example, the patient may be instructed to hold their breath for a short period during the procedure to keep the lungs away from the device. Alternatively or additionally, various sensors (e.g., flow sensors, bioimpedance sensors, pressure sensors) may be used to detect lung movement. Such techniques are described in U.S. Patent Application Publication No. 2018 / 0110561, PCT International Published Patent Application Nos. WO2018 / 023132, and PCT / US2018 / 066047 (filed December 17, 2018), and will not be described in detail herein.

[0267] In any of the above examples, when heat is used to ablate the GSN (e.g., by direct heat treatment or by RF energy treatment), blood flow in the region of the GSN (e.g., blood flow in the azygos vein) can interfere with the treatment by cooling the region. In some such examples, blood flow to the region of the GSN can be blocked or redirected away from the region of the GSN. For example, a balloon can be inflated in the azygos vein near the mouth of an intercostal vein. Such techniques are described in U.S. Patent Application Publication No. 2018 / 0110561, PCT International Published Patent Application Nos. WO2018 / 023132, and PCT / US2018 / 066047 (filed December 17, 2018), and will not be described in detail herein.

[0268] In any of the above examples in which a treatment fluid is delivered, the fluid may optionally have a relatively high, or potentially relatively high, viscosity so that the fluid remains in the region of the GSN. For example, the fluid may initially have a relatively low viscosity (e.g., at or below room temperature) but increase in viscosity at body temperature. Alternatively, the fluid may be provided as two separate components via two separate lumens within the device. Both fluid components may have a relatively low viscosity but may increase in viscosity when combined.

[0269] In either of the above examples, stimulation is performed after the ablation process is completed to confirm that the GSN has been ablated. Such stimulation is described in U.S. Patent Application Publication No. 2018 / 0110561, PCT International Published Patent Application Nos. WO2018 / 023132 and PCT / US2018 / 066047 (filed December 17, 2018), and will not be described in detail herein.

[0270] In either of the above examples, the catheter is advanced into the venous system through a delivery sheath.

[0271] In either of the above examples, once the device is retracted from the patient, a substance may be infused through the device to promote healing of the puncture in the vein.

[0272] Although the above description provides one or more examples of processes or apparatus, other processes or apparatus may be within the scope of the following claims.

[0273] Transvascular Nerve Ablation Embodiments Several devices specifically configured for transvascular nerve ablation for renal denervation to treat hypertension are commercially available, in development, and disclosed in patent applications. These devices are designed for use within the renal artery and are designed to target the nerves innervating the renal artery. Some of the energy modalities used in these devices could theoretically be used for GSN ablation from within the intercostal veins. However, these devices are not suitable for placement within, and for, GSN ablation from within, the intercostal veins. This disclosure recognizes this and addresses what modifications may be needed to one or more aspects of these devices and methods of use to implement the therapies described herein.

[0274] For example, renal arteries have a diameter of approximately 5 mm, while intercostal veins have a diameter of approximately 3 mm. This difference in diameter may require miniaturization of device components such as electrodes, catheter shafts, or deployable structures such as balloons. Furthermore, intercostal veins contain significantly less blood flow than renal arteries. Some renal nerve ablation devices rely on blood flow to cool the ablation energy delivery elements for proper function. Therefore, some devices may need to be modified to account for the lower blood flow. For example, GSN ablation devices may require active cooling by irrigating the ablation element, pumping coolant into the vessel, or by different energy delivery parameters, e.g., at lower power for a longer period of time. Renal nerve ablation devices aim to ablate nerves within the adventitia of the renal artery in an unpredictable pattern around the artery, and a target ablation zone less than 3 mm deep may be sufficient. Conversely, GSN ablation from intercostal veins aims to ablate larger nerves further from the vessel, and a target ablation zone up to 5 mm deep may be required. Furthermore, renal denervation ablation patterns typically include several ablations spaced apart in a spiral pattern, both longitudinally and circumferentially. Circumferential ablations are generally avoided in renal denervation. On the other hand, such a pattern deployed in an intercostal vein may miss the target GSN. In transvascular renal denervation, a catheter may be advanced from the femoral artery through the aorta and into the renal artery. The size of the aorta and renal artery allows for a larger bending radius than the size of the azygos vein and intercostal veins. Therefore, devices intended for GSN ablation may need to be more flexible and capable of traversing a smaller bending radius compared to renal denervation devices. Several specific modifications to existing renal denervation devices to make them more suitable for GSN ablation are further described herein.

[0275] Vessix Vascular has previously disclosed balloon ablation catheters that contain many features beneficial for transvascular ablation of tissue, as described, for example, in U.S. Patent Nos. 9,028,472, 9,037,259, 9,174,050, 9,566,114, 9,592,386, and 9,072,902, which are incorporated herein by reference. Modifications to these devices and methods are necessary to make them suitable for GSN ablation from within the intercostal veins.

[0276] One embodiment of a transvascular ablation catheter 241 for ablating the TSN or GSN from within an intercostal nerve is shown in FIG. 26A. The device 241 may include a catheter extending along a longitudinal axis. An expandable member, e.g., in the form of a balloon 242, having an unexpanded state and an expanded state, may be coupled to a distal region 243 of the catheter. The expandable member or balloon may have a circumferential treatment zone 248 (e.g., having a length in the range of 12-20 mm) extending along the longitudinal axis and surrounding the blood vessel 55 in the expanded state. An electrode assembly 252 including a plurality of electrode pads 244 may be attached to the balloon 242. Each electrode pad assembly may include a substrate supporting first and second electrode pads, each having a pair of elongated bipolar electrodes connected to electrical traces 249. The electrode pads of each electrode pad assembly are longitudinally and circumferentially offset from one another. The method may further include inflating the balloon within the intercostal vein, thereby electrically coupling the electrodes to the wall of the intercostal vein, and driving bipolar energy between the electrodes of each bipolar pair to therapeutically alter the TSN or GSN within 5 mm of the intercostal vein so that the patient's blood volume is redistributed for the treatment of conditions such as pulmonary hypertension or heart failure.

[0277] Each electrode pad may include a temperature sensor disposed between the pair of electrodes. Inflating the balloon may couple the temperature sensor to a wall of the intercostal vein. In some embodiments, the method may further include directing energy to the bipolar pair in response to a temperature signal from the temperature sensor to heat the wall substantially uniformly.

[0278] To create ablation depths of 5 mm to target GSNs from intercostal veins, the electrode pads may be cooled to allow greater power to be delivered without causing the tissue in the vein wall to dry out, which would prevent ablation depth. The electrodes may be cooled, for example, by circulating a coolant within the balloon 242. In one embodiment, coolant may be injected into the balloon 242 through a coolant injection port 246 at one end of the balloon chamber, allowing the coolant to exit the chamber through an exit port 247 at the opposite end of the chamber and return through the catheter via the exit lumen.

[0279] In another embodiment, the coolant may be deposited into the bloodstream instead of returning through a lumen in the catheter. This embodiment may allow for a thinner, more flexible catheter shaft or a larger coolant delivery lumen, increasing the coolant flow rate. The coolant outlet port may be smaller than the coolant inlet port to allow pressure to build up within the balloon, causing it to expand. The coolant outlet port may be in communication with a lumen that does not pass entirely through the catheter shaft to the proximal end, but instead passes to the distal end of the catheter to deposit coolant (e.g., saline) into an intercostal vein. Optionally, the coolant outlet lumen may be the same lumen as the guidewire delivery lumen.

[0280] The electrode pads may be positioned around the balloon to form a circumferential ablation pattern up to a length (e.g., up to 20 mm, about 15 mm, 12-18 mm) to the target ablation zone 58. For example, as shown in FIG. 26B, a balloon with electrode pads attached to an elongate shaft 253 can have an undeployed state with a diameter of about 1-2.5 mm and a circumference of about 3.14-7.85 mm, and is expandable to a deployed state with a diameter in the range of about 3-5 mm and a circumference in the range of about 9.4-15.7 mm. The electrode pads 244 may be spaced apart by a distance 250 of less than 5 mm (e.g., less than 2.5 mm) and a width or arc length 251 in the range of 3-3.5 mm. The electrode pads 244 may each have a length of about 3-5 mm. As shown in FIG. 26A, the electrode pad assembly 252 may include a plurality of electrode pads 244 arranged in four separate rows connected to each other by electrical traces 249, the rows evenly spaced around the circumference of the balloon 242 (e.g., four rows in each 90-degree quadrant). The pads 244 in one row may be offset longitudinally from the pads in an adjacent row. When the balloon is in its unexpanded state, the spacing between the electrode pads is reduced (e.g., to about 0-1 mm), and adjacent rows are interconnected. In its expanded state, the spacing 250 between the pads is expanded by the expandable balloon 242 to about 2-5 mm. The balloon 242 may be a compliant material, such as latex, or a non-compliant material that flexibly folds and contracts.

[0281] Alternatively, electrode pads may be placed on only one side (e.g., 50%, 40%, 30%, 25% of the balloon's circumference) to create a directional ablation pattern that faces the same side as the target ablation zone 58 and is the length of the target ablation zone 58. For directional ablation catheters, radiopaque markers may be placed on the distal region of the catheter to indicate the radial direction. For example, the radiopaque marker may be asymmetric and placed on the same or opposite side as the directional electrode pad to provide guidance, and in use, the physician torques the catheter to target the radiopaque marker, thus deflecting the electrode pad away from the vertebrae, which always face toward the GSN. Figure 26A shows several small electrode pads. Alternatively, a device may have more or fewer electrode pads, for example, two or three directional electrode pads (e.g., 3-5 mm long) on ​​the same side of the balloon that span the target ablation zone 58. A gap between the electrode pads (e.g., 1-3 mm) may facilitate bending of the device as it traverses from the azygos vein to the intercostal veins.

[0282] Immediately adjacent to the balloon, the catheter shaft may include a flexible neck 245 that allows the ablation balloon to conform to the natural orientation of the intercostal vein. Having a small bend radius at this location prevents a rigid shaft from exerting force on the ablation balloon, causing it to deform the intercostal vein and reducing the predictability of the ablation zone. The flexible neck may be made of a softer durometer polymer (e.g., Pebax) and may have a wire coil embedded in the material, which may allow for flexible bending while still providing pushability.

[0283] The most proximal electrode(s) are intended to be placed just within the intercostal veins near the ostium. Blood flow through the azygos vein metabolically cools the nearby tissue, preventing ablation formation. To compensate for blood flow cooling, a greater amount of ablation power (e.g., RF) or a longer duration may be delivered to this proximal electrode(s) than the rest of the electrode(s).

[0284] Medtronic / Ardian Inc., the disclosures of which are incorporated herein by reference, disclose catheters for renal denervation that have several electrodes attached along the length of the catheter's distal shaft, which form a helical shape when deployed in the renal artery. For example, U.S. Patent No. 9,125,661 and U.S. Patent Application Publication No. 2012 / 0143293, the distal section of the catheter, contain many features beneficial for transvascular tissue ablation. Modifications to these devices and methods are necessary to make them suitable for GSN ablation from within the intercostal veins. These devices have extremely small, low-profile electrodes, which result in ablation depths no greater than 3 mm, rely on blood flow similar to that of the renal artery to avoid tissue charring, and the electrode spacing and helical shape of the shaft create an ablation pattern that is not suitable for GSN ablation because it may miss the target nerve.

[0285] FIG. 27 shows a catheter 200 having an elongate shaft 205 with proximal and distal regions and an ablation assembly 211 attached to the distal region. To modify the catheter 200 for GSN ablation, the electrodes 201 may be increased in size (e.g., 2-3 mm diameter 202) and the interelectrode spacing 203 may be decreased (e.g., 2-4 mm apart). The electrode length 204 may remain in the 1-2 mm range or may be increased to the 3-4 mm range. A helical shaft configuration is not necessary in intercostal spaces, where a straight shaft is preferred if the electrodes have a diameter 202 that approximates the diameter of the blood vessel lumen. Electrodes positioned along a straight portion 209 cover the target ablation zone 58 over a distance of up to 20 mm (e.g., 18 mm, 15 mm). The electrodes 201 are attached to a tubular shaft 205. The shaft material in the distal region need not be rigid, with elastic properties forming a helical preform shape, but instead can be highly flexible to facilitate delivery through a small bending radius from the azygos vein to the intercostal veins. Optionally, the shaft can have a section 210 that elastically forms a loop shape adjacent to the straight section 209, intended for placement within the intercostal vein 55. The loop shape can include an electrode 206 and can be intended for placement against the ostium 59, which can ablate tissue around the ostium where the target nerve may be located, and can also act as a depth stop to position the straight section 209 at the correct depth (e.g., 10-20 mm) within the intercostal vein 55. RF ablation energy can be delivered sequentially or simultaneously in a unipolar mode, or, optionally, in a bipolar mode, to achieve both deep (e.g., 5 mm) and sequential ablation. Optionally, RF may be delivered in a pulsed waveform that allows for slight cooling of superficial tissue during pauses while deeper tissue cools more slowly, facilitating the targeted 5 mm ablation depth. Optionally, the electrodes may also be irrigated. For example, the electrodes or the portion of the shaft between the electrodes may have irrigation ports 207 for delivery of fluids such as saline. Optionally, catheter 200 may have a guidewire lumen 208 for delivery over a guidewire 79.

[0286] Covidien has disclosed renal denervation catheters and methods of use having a deployable balloon with flexible RF electrodes attached in a helical configuration to the balloon, which further includes an opening for dripping a liquid, such as cooled saline or an anesthetic, as disclosed in U.S. Patent Application Publication No. 2015 / 0105659, which is incorporated by reference and contains many features beneficial for transvascular tissue ablation. Modifications to these devices and methods are necessary to make them suitable for GSN ablation from within intercostal veins. An in situ deployed ablation catheter 180 is shown in FIG. 28. The distal region 181 of the catheter contains an ablation assembly 190 with an inflatable balloon 182 attached to an elongated tubular shaft 183. The balloon dimensions accommodate the intercostal vein (e.g., 2.5-4 mm diameter when inflated) and can be varied to span a length ranging from 12-30 mm. The helical shape of the electrodes in the Covidien device may result in missing the target GSN. The electrodes 184 may be linear and parallel to the balloon axis and may be varied to cover a segment of the balloon's circumference (e.g., 50%, 40%, 30%, 25%) for directional ablation. The electrodes 184 may have a length 189 ranging from 12 to 20 mm (e.g., up to 20 mm) that can create ablation of the length of the target ablation zone 58. The distal region 181 may have a radially identifiable radiopaque marker 186 to confirm that the electrodes 184 are oriented toward the anterior portion of the body where the target GSN 52 passes over the intercostal veins 55. Alternatively, one or more electrodes may be positioned around the balloon for circumferential ablation, such as one or more electrodes carried by the balloon and positioned perpendicular to the balloon's long axis. The electrode strip 184 may include irrigation ports 185 on its surface for fluid weeping. The fluid openings may be increased in size to allow for greater flow rates. Optionally, shaft 183 may have a flexible neck 187 within 10 mm of balloon 182 to allow distal region 181 to fit comfortably within an intercostal vein. Optionally, catheter 180 may have a guidewire lumen 188.

[0287] Recor Medical has disclosed renal denervation devices and methods for using ultrasound to ablate tissue around the renal artery, e.g., U.S. Patent Application Publication Nos. 2015 / 0290427 and 2014 / 0031727, which are incorporated by reference and contain many features beneficial for transvascular tissue ablation. The ultrasound transducer is housed within a balloon that centers the transducer within the vessel. The transducer is cylindrical and creates a circumferential ablation around the vessel. A cooling fluid is injected into the balloon to cool the transducer. The ablation created by this device is approximately 5 mm in length.

[0288] Ultrasound ablation has the potential to direct energy and is primarily limited by the size of the ultrasound transducer relative to ablation energy delivery parameters, which dictate the energy dose expressed in terms of frequency, power, and time. To ablate a nerve up to 5 mm from an intercostal vein, a frequency of 10-30 MHz and a power of approximately 1-10 watts may be required to effectively ablate the nerve in approximately 2-20 seconds from a small transducer (e.g., a 5 mm long, 1.5 mm diameter cylindrical transducer) placed within the intercostal vein. At these settings, significant heating of the ultrasound transducer can be mitigated, for example, by circulating a liquid in a sealed chamber around the ultrasound transducer, or alternatively, by allowing blood flow to contact an open-surface biocompatible transducer, or by allowing blood flow to contact a cooling membrane that can be used to control the local heat generated by the oscillating ultrasound transducer as part of a controlled ablation cycle. Heat generated by the ultrasound transducer can be dissipated inside the vein, altering the temperature field around the ultrasound transducer. The resulting effect of such a combination of inductive heating and active ultrasound ablation may provide an effective method for the formation of necrotic regions near any small blood vessel. Heat dissipation is a requirement for the proper functioning of the ultrasound transducer, and care must be taken to avoid increased risk of vessel wall damage. Careful titration of ultrasound energy, taking into account local heat dissipation, constitutes an innovative and more stringent intravascular ablation technique, especially when efficient, parallel, and injury-free nerve ablation is the procedural goal.

[0289] In another embodiment, diagnostic and therapeutic ultrasound can be delivered from an external transducer to the target ablation zone. The proximity of the patient's external intercostal veins allows for the possibility of external ablation delivery through the intercostal space. The ultrasound transducer may fit within the palm of the hand and operate in a frequency window of 3-10 MHz by directing energy to the vasculature using a set of anatomical reference points. Specifically, the approximately 90-degree angle from the azygos vein to the intercostal vein ostium provides Doppler signal visualization of blood flow perpendicular to the direction of the ultrasound pulse emitted from the externally placed transducer, which focuses the ablative ultrasound energy to the target ablation zone. Thus, the location of the ostium allows for anatomical reference for further targeting of the greater splanchnic nerve between the T11 and T10 vertebrae or between the T9 and T10 vertebrae. External ultrasound may also be used to detect the lungs adjacent to the target ablation zone and titrate energy delivery to avoid damaging the lungs. In one example, ablation energy can be delivered when the lungs move away from the target ablation zone during exhalation (e.g., greater than a threshold distance of 10 mm) and reduced or discontinued when the lungs are approaching the target ablation zone (e.g., within a threshold distance of 10 mm).

[0290] 29 shows a catheter 220 having an elongate shaft 231 with proximal and distal regions and an ablation assembly 232 attached to the distal region. To modify the device for GSN ablation from within an intercostal vein, the ultrasound ablation catheter 220 has an inflatable balloon 221 that may have a geometry suitable for expansion within the intercostal vein (e.g., an outer diameter 222 in its inflated state ranging from 3 to 4 mm) and a length 223 ranging from 12 to 30 mm. Within the balloon 221, multiple ultrasound transducers 224 are positioned on the shaft 233 centered within the balloon 221. The transducers 224 may be arranged consecutively over a length 226 ranging from 12 to 20 mm to generate an ablation of the same length that can form an ablation of the length of the target ablation zone 58. Due to the small diameter of the intercostal veins, a reduced balloon size risks contact with or overheating by the transducer, which could rupture the balloon or reduce the effectiveness of the ablation. To rectify this risk, struts or protrusions 227 can be placed between the transducer and the balloon. The struts 227 can be, for example, elastically preformed polymer strands that radially expand away from the transducer 224. To allow longer ablation lengths across the target ablation zone, multiple transducers can be incorporated (e.g., three 4 mm long transducers), spaced apart with flexible gaps 228 between them to facilitate traversing the tight bend radius from the azygos vein to the intercostal veins. For example, the shaft 225 can be a braided polyimide tube carrying electrical conductors that energize the transducer 224, with an optional guidewire lumen 229 for delivery over a guidewire 79. The ultrasound transducer 224 may be cylindrical to create a circumferential ablation around the target vein.Alternatively, the ultrasound transducer may be flat or semi-cylindrical to create an ablation that is a partial segment of the vein's circumference, and a radially identifiable radiopaque marker 230 may be positioned on the distal region to allow the user to orient the ablation toward the front of the patient, where the GSN passes over the vein 55. Optionally, the ultrasound transducer may be configured for imaging as well as ablation, and the imaging function may be used to evaluate nearby structures such as the lungs, vertebrae, ribs, etc. The imaging ultrasound may be used to confirm that the transducer is aimed toward the lungs, in the direction of the target GSN. Optionally, the shaft may have a flexible neck 231 within 10 mm of the balloon 221 so that the distal region fits snugly within the intercostal vein.

[0291] In another embodiment of an ultrasound ablation catheter, the catheter may consist of an active ultrasound transducer and an inflatable reflector balloon, which may be on the same catheter or, alternatively, on a separate catheter. The reflector balloon may have an inflated diameter ranging from 2.5 to 4 mm and have a shape, such as a concave bay, on its proximal surface that focuses reflected waves onto the target ablation zone. The reflector balloon is positioned distal to the transducer and inserted into the narrower intercostal vein, while the ultrasound transducer resides in the larger azygos vein. The ultrasound transducer may be exposed to the blood flow in the azygos vein, or alternatively, may be housed in a chamber within the inflatable balloon filled with a circulating coolant (e.g., sterile water or saline). Ultrasound energy is directed toward the distal reflector balloon and is reflected and focused by the tissue surrounding the splanchnic nerves. The advantages of this approach are that the active ultrasound transducer can be large and does not need to undergo a sharp turn from the azygos vein to the intercostal vein. A second advantage is that several intercostal veins can be used to target ablation with the same catheter.

[0292] Renal Dynamics has disclosed renal denervation devices and methods of use, such as those in EP2934357 and WO2016132340, which are incorporated by reference and contain many features beneficial for transvascular tissue ablation. These devices deploy RF electrodes (e.g., eight RF electrodes spaced in quadrants) attached to radially expandable struts to form a basket for ablating tissue surrounding the renal artery, and also include a non-occlusive membrane intended to isolate blood, minimize heat loss, and enable deeper tissue ablation. The device relies on blood flow within the renal artery to provide thermal characteristics such as electrode cooling for ablation. Potentially, in some patients, there may be sufficient blood flow within the intercostal space to cool the electrode, but this may be significantly less than in the renal artery, and alternative energy delivery parameters may compensate for the lower blood flow. For example, a pulsed RF waveform that allows superficial tissue to cool during amplitude pauses produces an effective 5 mm deep ablation. 30A and 30B show an RF ablation catheter 260 having an elongate shaft 275 with proximal and distal regions and an ablation assembly 276 attached to the distal region. The ablation assembly 276 is formed of a basket of elastic struts 261 (e.g., three or four rows of struts), each with at least one electrode 262 attached in a configuration that allows the basket to have a contracted delivery state having a diameter of approximately 1.7 mm and an expanded ablation state having a diameter ranging from approximately 2.5 to 4 mm. A non-occlusive, radially expandable tubular membrane 263 is electrically insulating and is connected to (e.g., positioned on) the struts 261, with the electrodes 262 on the outer surface of the membrane. The membrane 263 prevents electrical RF energy from being shunted through the blood, allowing the electrical RF energy to be focused by the vessel wall at the target ablation zone. Optionally, additional electrode cooling may be achieved by injecting a coolant 264, such as saline, through the lumen of the non-occlusive membrane to convectively cool the electrode. Because blood flow within the intercostal space is from the distal end of the device to the azygos vein, coolant may be injected through a coolant delivery port 265 at the distal end of the basket to flow in the same direction as the blood flow.The dimensions of the struts forming the basket can be modified to accommodate smaller vessels, e.g., having a maximum diameter in the range of 3-4 mm. The struts may have a narrowed section 266 between attached electrodes (e.g., at the same longitudinal distance) that is more flexible than the rest of the struts to facilitate bending during delivery across the tight bending radii from the azygos vein to the intercostal veins. The basket length 267 and electrode location can be shortened to generate ablation along a target ablation zone 58 in the range of 12-20 mm in length (e.g., 15 mm in length). Electrodes can be positioned to create circumferential ablation along the entire length of the target ablation zone. Alternatively, electrodes can be attached to only one or two struts of the basket to ablate only a segment of the vessel circumference (e.g., 50%, 40%, 30%, 25%) for directional ablation. Radiopaque markers 268 identifying the radial orientation of the basket are positioned on the distal region of the catheter (e.g., on the struts, using the struts as the location of electrodes, which may be radiopaque, on the catheter shaft near the basket). As shown in the cross-sectional views of Figures 30B and 30A, the struts 261 may have a width 269 of approximately 0.5 mm and a thickness 270 of approximately 0.13 mm. The electrode 262 may have a width 271 of approximately 1 mm and a maximum thickness 272 of approximately 0.33 mm, tapering to a thickness 273 of approximately 0.25 mm at the edge. The electrode length may be approximately 3-5 mm. Optionally, the shaft may have a flexible neck 274 within 10 mm of the balloon basket to allow the distal region to fit comfortably within an intercostal vein.

[0293] Dual Electrode Embodiment The following disclosure generally relates to systems, devices, and methods for transvascular ablation of target tissue. The devices and methods may, in some instances, be used for splanchnic nerve ablation for the treatment of heart failure. For example, the devices disclosed herein may be advanced intravascularly to a target vein in a region within the thoracic splanchnic nerve (TSN), such as the greater splanchnic nerve (GSN) or TSN nerve root. Any disclosure herein related to nerve ablation applies to and is incorporated by reference into the following disclosure.

[0294] Dual-electrode catheter FIG. 31 shows one exemplary embodiment of an ablation device in an exemplary position of use. In FIG. 31, device 120 is shown positioned in an exemplary position for transvascular ablation of target nerves (e.g., GSN 52, GSN root 53, TSN) from small veins (e.g., T11 intercostal vein 55, T10 intercostal vein 56, T9 intercostal vein, lower three intercostal veins). Device 120 includes an elongate shaft 121, a proximal catheter section (not shown) intended to remain external to the patient during use and capable of being manipulated by a physician, and a distal catheter section 122 including at least two ablation elements (also referred to herein as ablation members) including a proximal electrode 123, a distal electrode 124, and an occlusion element 128 therebetween. Any occlusion element herein may also be referred to as an occlusion member.

[0295] In the illustrated example, the catheter 120 includes a guidewire lumen (not shown) therethrough, and the catheter distal section 122 includes a guidewire exit port 126 located at or near the distal end of the distal section 122 so that the catheter 120 can be advanced into the venous system along a guidewire 79. The catheter can be delivered through a delivery sheath 80. In some examples, the elongate shaft 121 can include a braided shaft to facilitate torque-ability (i.e., transmission of torque from the catheter proximal section to the catheter distal section 122), particularly over tortuous delivery paths. In other examples, the guidewire lumen and exit port 126 can be omitted, and the catheter can be advanced into a patient's cardiovascular system (e.g., a vein or artery) without the assistance of a guidewire. For example, the catheter may have a deflectable distal tip that is controllable by an actuator on a handle on the proximal portion that controls the tension of a pull wire connected to the deflectable distal tip, which can be bent (e.g., a 90 degree deflectable bend with a bend radius in the range of 6 to 15 mm) to facilitate advancement from a first vein to a second vein, or the ablation catheter may be advanced through a delivery sheath that can be advanced over a guidewire into the target vessel, and the guidewire may be removed before advancing the ablation catheter.

[0296] The ablation elements 123 and 124 shown in FIG. 31 comprise electrodes each connected to their own independent conductors that run through the catheter shaft 121 to the proximal region of the catheter where they can be connected to an energy delivery console, which can operate the two electrodes in bipolar RF mode. Each electrode can have dimensions suitable for fitting into and delivering RF ablation energy to small blood vessels (e.g., the T10 intercostal vein 56, the T11 intercostal vein 55, the T9 intercostal vein, or the lower three intercostal veins in humans). Each electrode 123 and 124 can be cooled by irrigation and optionally includes an irrigation outlet port 129 at its side or end that is in fluid communication with at least one irrigation lumen (not shown) that runs through the catheter shaft 121 to the proximal region of the catheter where it can be connected to an irrigation fluid supply. Optionally, a separate irrigation lumen can be present to provide irrigation to each electrode separately. Separate irrigation lumens may facilitate tighter control of irrigation flow rate to each electrode. The irrigation outlet port 129 may have a diameter of approximately 0.020 inches + / - 0.005 inches. Alternatively, electrode irrigation may be closed-loop and contained within the catheter, instead of delivering irrigation fluid to the bloodstream via an outlet port. An embodiment with closed-loop irrigation may include at least one irrigation fluid delivery lumen that delivers fluid to a chamber within each electrode and at least one return lumen that returns fluid to the proximal region of the catheter. Each electrode 123 and 124 may have a length in the range of 3-5 mm (e.g., 4 mm) and an outer diameter in the range of 1.5-3 mm (e.g., 2 mm). The distance 127 between the electrodes may be in the range of 3-6 mm (e.g., 4.5 mm). This combination of electrode length and inter-electrode distance, along with the appropriate ablation energy profile disclosed herein, occlusion balloon 128, and electrode irrigation may be appropriate to create a desired ablation size capable of covering a target region 58 including lengths up to 20 mm and depths up to 5 mm.Each electrode 123 and 124 may have an associated temperature sensor 131 within or on the electrode that can be used to control energy delivery (e.g., a thermocouple or thermistor electrically connected to a conductor that passes through the catheter shaft 121 to the proximal region of the catheter and is connectable to an ablation energy console. Optionally, the electrodes may be made of a radiopaque material such as platinum-iridium.

[0297] The device 120 may further include an inflatable occlusion member 128, which in this embodiment is an ablation balloon 128 positioned on the catheter shaft between the proximal electrode 123 and the distal electrode 124. The balloon may be fabricated from a membrane (e.g., a compliant, semi-compliant, or non-compliant balloon) and may be manufactured using techniques known in the medical device industry for manufacturing catheter balloons. The membrane may be sealed to the shaft at the proximal and distal ends of the balloon to define a chamber within the membrane. A balloon inflation port 130 may be positioned within the chamber and in fluid communication with an inflation lumen (not shown) that extends through the catheter shaft 121 to a proximal region of the catheter where an inflation fluid supply (e.g., gas or liquid delivered by a pressurized device such as a syringe or pump) can be connected. A temperature sensor 132 may be located within the chamber within the balloon 128, which may be used to monitor inflation fluid temperature. The balloon may have a diameter in the range of 1.5-2 mm in an uninflated state, and may have a diameter in the range of 3-5 mm or approximately the same size as the target vessel lumen in an inflated state. Optionally, in use, a first amount of inflation fluid may be injected into the balloon when placed in a first vessel (e.g., an intercostal vein) to increase the balloon's diameter and occlude the first vessel, and a second amount of inflation fluid may be injected into a second vessel (e.g., an azygos vein) to increase the balloon's diameter and occlude the second vessel. The balloon may function to occlude the vessel, providing a more stable ablation environment (e.g., thermal and electrical properties) around the electrode to prevent the target vessel from constricting when heated, which may provide a more stable ablation environment, maintain vessel patency, or direct ablation energy into tissue.

[0298] Irrigation ports 129 may be positioned on the sides of electrodes 123 and 124. Optionally, the irrigation ports may have features that allow irrigation fluid to continue flowing even if the blood vessels constrict around the electrodes. FIGS. 32A and 32B are schematic illustrations of a single electrode not connected to a catheter, which may optionally replace either the proximal electrode 123 or the distal electrode 124 of FIG. 31 or any other embodiment herein. As shown in FIG. 32A, another embodiment of electrode 140 may include irrigation ports 141 positioned within a channel 142 that spans the length of electrode 140. Multiple ports and channels, e.g., three as shown, may be positioned around the catheter. Electrode 140 includes a central lumen 143 for attachment to shaft 121 over the irrigation lumen, electrical conductors for ablation energy, or a temperature sensor (not shown). As shown in FIGURE 32B, another embodiment of electrode 146 (which may be used as any ablation element or member herein) may include irrigation ports 147 disposed within scallops 148 that span only a portion of the length of electrode 146. Multiple ports and scallops may be disposed around the catheter, e.g., six ports and channels as shown, although more or fewer ports and channels may be used. Electrode 146 includes a central lumen 149 for attachment to shaft 121 over the irrigation lumen, electrical conductors for ablation energy, or a temperature sensor (not shown).

[0299] An ablation energy delivery console (not shown) may be connected to the catheter 120 to deliver radio frequency (RF) current to one or more of the electrodes 123, 124 to form individual ablations simultaneously or individually to form a larger overall ablation across the target zone 58. Alternatively, smaller ablations may be formed by energizing only one of the electrodes, in which case it may be desirable to deliver a neural stimulation signal from the electrode to confirm that the target nerve is within the ablation zone of the single electrode. When both electrodes 123 and 124 are energized simultaneously, they may be energized with an in-phase voltage or current, and the two RF sources energizing each electrode may float relative to each other. Energy delivery parameters, such as the temperature setpoint for temperature-controlled energy delivery or the power setpoint for constant-power energy delivery, may be set to the same value and automatically modified based on response due to different blood flow or impedance, particularly since the proximal electrode 123 may experience more blood flow from the nearby azygos vein. For example, if the temperature increase during energy delivery is slower for the proximal electrode, it may indicate increased convective cooling provided by blood flow. The power delivery algorithm may recognize the slower temperature increase for the proximal electrode and increase the power setpoint, or a higher temperature setpoint or duration of energy delivery may be used to compensate. Example energy delivery parameters for constant power mode may include a power setpoint in the range of 5-10 W (e.g., 7-8 W), a maximum perfused electrode temperature to avoid tissue charring in the range of 60-95°C (e.g., approximately 85°C), a maximum temperature in the balloon chamber less than 100°C, and a duration in the range of 60-240 seconds.

[0300] Another energy delivery protocol may include a two-channel combined monopolar-bipolar RF ablation configuration. This configuration involves delivering RF energy at different voltages to each of the electrodes 123 and 124 in monopolar mode, which communicate with a dispersive electrode. The difference in applied RF voltage results in a partial bipolar mode effect, where energy is transferred from the higher-voltage electrode to the electrode with a lower voltage relative to the higher-voltage electrode. This results in an intentional monopolar-bipolar combo mode. Therefore, it may be preferable for the two sources driving the electrodes to have a common ground. This energy delivery configuration, combined with the electrode size, spacing, and balloon of the catheter 120, may be effective in producing an ablation across the target ablation zone 58 and up to 5 mm deep to ablate the target nerve within the ablation zone. As mentioned above, energy delivery parameters, such as temperature or power setpoint, may be automatically adjusted to compensate for the different thermal and electrical environments of the proximal and distal electrodes.

[0301] Optionally, the energy delivery algorithm may monitor the pooled saline for the onset of boiling (e.g., via sudden fluctuations in impedance and / or temperature). If boiling is detected (e.g., by a temperature sensor), the algorithm reduces power and / or temporarily shuts off power, waits a predetermined time or until the temperature drops below a certain threshold (e.g., 95°C), and then increases power again. The algorithm may identify the maximum power at which boiling was previously detected and use that value to limit the maximum power during the resumed power period. Alternatively, the algorithm may select a temperature setpoint lower than the target temperature that previously resulted in boiling.

[0302] The console may also control electrode irrigation by switching the irrigation fluid pump on and off so that irrigation occurs while RF is delivered. The irrigation flow rate may be set at a constant rate (e.g., approximately 2 mL / min). Alternatively, a higher flow rate may be delivered to the distal electrodes, which experience less cooling from blood flow than the proximal electrodes when used as shown in FIG. 31. Alternatively, the flow rate may be higher for electrodes with a higher temperature-to-power ratio.

[0303] Methods of use of device 121 include versatile positioning and energy delivery profiles that may be beneficial for use with a wide range of anatomical variability. In particular, when using the device for GSN ablation from within an intercostal vein, methods of use may include ablating a first target area from within the lowest intercostal vein (e.g., the T11 intercostal vein) and subsequently ablating a second target area from within a second lowest intercostal vein (e.g., the T10 intercostal vein). A first method of use involves delivering both electrodes 123 and 124 completely within the lowest intercostal vein 55 such that the proximal end 129 of the proximal electrode 123 is aligned with the ostium 59 where the intercostal vein connects to the azygos vein 50; This may include performing an ablation procedure, repositioning the distal region 122 to the second most inferior intercostal vein 56, and performing a second ablation procedure.

[0304] In some patients, one or more target intercostal veins may be too narrow or tortuous to fully deliver both electrodes 123 and 124 into the target vein. In this scenario, a second method of use may involve inserting only the distal electrode 124 into the target vein to create a shorter ablation compared to the first method of use. It may or may not be possible to deliver both electrodes to the second or third lowest intercostal vein to ablate the entire target area. Optionally, when ablating only the distal electrode 124 within an intercostal vein, ablation energy may be delivered only to the distal electrode 124, in which case the electrical circuit is optionally completed by a dispersive electrode elsewhere in the catheter or on the patient's skin. Alternatively, the proximal electrode 123 may complete the circuit in bipolar mode, in which case the proximal electrode is expected to be positioned in the azygos vein, where greater blood flow cools the proximal electrode and the vessel. The occlusion balloon 128 may be inflated to divert blood flow away from the ostium.

[0305] 33, where the distal electrode 124 is within the intercostal vein 55 (or other intercostal vein) and the balloon 128 is inflated to divert azygos vein blood flow away from the ablation zone, and to create an additional ablation around the intercostal vein and within 10 mm (e.g., 6 mm) of the ostium 59. Blood flow within the azygos vein 50 may cool tissue near the ostium that is within the targeted ablation region 58, potentially limiting effective ablation size.

[0306] Any of the methods of use described herein may further include a visualization step to determine the location of the device within the target nerve. Medical imaging techniques such as fluoroscopy may be used to image the device, particularly radiopaque aspects of the device, such as the proximal and distal electrodes 123, 124, in relation to the patient's vasculature. A radiopaque contrast agent may be injected into the patient's bloodstream (e.g., via the delivery sheath 80, the guidewire lumen and exit port 126, or the electrode irrigation port 129) to facilitate fluoroscopic imaging.

[0307] Dual electrode catheter with concave electrode In another embodiment, a catheter 155 for transvascular ablation (e.g., from an intercostal vein to the TSN or GSN) is shown in FIGS. 34A and 34B. This catheter 155 has at least one electrode for delivering ablation energy or neural stimulation signals. As shown, the catheter 155 has two electrodes, a proximal electrode 156 and a distal electrode 157 separated by a distance 158. The electrodes 156 and 157 are attached to a shaft 159 at a distal region 160 of the catheter and have a diameter 161 that is smaller than a diameter 162 of the shaft 159 at the distal region. For example, for transvascular ablation from within an intercostal vein, the electrode diameter 161 may be in the range of 1.5-2.5 mm, the shaft diameter 162 may be in the range of 2-3 mm, and the electrode diameter 161 may be smaller than the shaft diameter 162 by 0.2-1 mm. Delivering ablation energy from within small blood vessels (e.g., less than 4 mm) can heat the vessel wall, causing it to contract. By recessing the electrode surface from the shaft surface, the shaft 159 in the distal region 160 can hold the vessel wall away from the electrode surface, maintaining a gap, which in turn can provide a more consistent thermal and electrical environment during energy delivery, which in turn can improve the safety and efficacy of energy delivery. Each electrode 156 and 157 can be cooled with irrigation and optionally includes irrigation outlets 163 on their sides that fluidly communicate with at least one irrigation lumen (not shown) through the catheter shaft 159 to the proximal region of the catheter, where it can be connected to an irrigation fluid supply. Electrode irrigation cools the electrode during energy delivery, allowing for the delivery of greater ablation power, which may be necessary to ablate vessel walls up to 5 mm deep (e.g., for GSN ablation). Optionally, separate irrigation lumens may be present to provide irrigation separately to each electrode. Separate irrigation lumens may facilitate tighter control of irrigation flow rate to each electrode. Irrigation outlet port 163 may have a diameter of approximately 0.020 inches + / - 0.005 inches. Alternatively, electrode irrigation may be closed-loop and contained within the catheter instead of delivering irrigation fluid to the bloodstream through an outlet port.Embodiments with closed-loop irrigation may include at least one irrigation fluid delivery lumen that delivers fluid to the chamber and at least one return lumen that returns fluid to the proximal region of the catheter. In embodiments with open-loop irrigation, such as those shown in FIGS. 34A and 34B, the shaft 159 in the distal region 160 may have a channel or groove 164 extending along at least a portion of its length that allows fluid to flow along the channel 164 even if the blood vessels constrict around the shaft 159. This may avoid undesirable stagnation or stagnant irrigation fluid around the electrodes 156 and 157, which could cause the fluid to overheat and result in ineffective and unsafe ablation energy delivery. FIG. 34B shows a cross-section of the shaft 159 at the cross-sectional location shown in FIG. 34A, where the shaft 159 has a diameter 162 that is larger than the diameter 161 of the electrode 157, and the shaft 159 has a channel 164 for fluid flow along its length. Also shown is a guidewire lumen 326 for delivery over a guidewire 79 (shown in Figure 34A).

[0308] The irrigation fluid may optionally be hypertonic saline, which can conduct ablation energy from electrodes 156 and 157 to the vessel wall even when the electrodes are not in contact with the wall.

[0309] Each electrode 156 and 157 may have a length in the range of 3-5 mm (e.g., 4 mm). The distance 158 between the electrodes may be in the range of 3-6 mm (e.g., 4.5 mm). This configuration may enable ablation of tissue within a targeted ablation zone 58 suitable for GSN ablation.

[0310] The electrodes (123 and 124 in the device of FIG. 31 or 156 and 157 in the device of FIG. 34A) may alternatively be coil wire electrodes made of a resilient and conductive material such as spring stainless steel. The coil electrodes may improve the flexibility of the distal region of the catheter, allowing it to traverse sharp curves such as the bend from the azygos vein to the intercostal veins. The coil electrodes may be irrigated by passing fluid from an irrigation lumen through small gaps in the coil pitch.

[0311] In some embodiments, such as the device shown in FIG. 31 , ablation elements 123 and 124 are conductive around the circumference of the electrode, enabling ablation energy to be delivered circumferentially, or in other words, in a radially symmetric pattern, to a target region 58 of a target vessel 55. An advantage of this feature may be that the user does not need to consider radial orientation or adjust the catheter's radial orientation by applying torque, thereby reducing procedure time or user error. However, in other embodiments, the ablation elements may direct ablation energy toward a segment of the circumference, for example, the segment may be 50% or less of the circumference (e.g., less than 40%, less than 30%, less than 25%). A directional ablation catheter may direct ablation energy toward the target nerve, which requires less ablation energy, reduces the risk of damaging non-target tissue, reduces pain, or reduces target vessel damage or constriction. When used to ablate a TSN or GSN from an intercostal vein, the TSN or GSN is always in the same direction relative to the vein, which is directed away from the vertebrae and toward the lungs. In some instances (not shown), radiopaque markers on the catheter may be used to facilitate radial orientation of the catheter. The desired orientation may be a radially aimed orientation in which the directed ablation energy is directed away from the vertebrae (e.g., opposite the vertebrae) and toward the lungs. For example, if the target vessel is the right T11 intercostal vein, the C-arm fluoroscope may be centered on the T11 vertebra and optionally rotated to the patient's right side from an anterior-posterior center position (AP position) to obtain an angle approximately perpendicular to the tangent to the vertebra. In this position, it may be desirable to aim the desired ablation energy radially toward the C-arm head, where the TSN often crosses the intercostal vein. The catheter may be torqued to rotate the catheter distal portion 122 within the intercostal vein until the radiopaque marker indicates that the ablation energy is aimed toward the C-arm and, therefore, toward the target nerve.The radiopaque marker can be configured to distinguish when the radiopaque marker is rotationally aimed at the C-arm head. Because the position of the radiopaque marker is circumferentially aligned with the ablation direction, the radiopaque marker can be used to indicate when the ablation direction is aimed at the C-arm head. The radiopaque marker is made of a radiopaque material and has an asymmetric shape. For example, the radiopaque marker can be N-shaped. If the radiopaque marker is facing toward the C-arm head, the radiopaque marker will appear as the letter N. If the radiopaque marker is facing away from the C-arm head (e.g., toward the vertebrae), the radiopaque marker will appear as the back side of the letter N. If the radiopaque marker is oriented transverse to the C-arm, the radiopaque marker will appear as a line. Optionally, the device may further include additional radiopaque markers configured to visually indicate when the rotational position of the catheter distal portion 84 is within a set tolerance. In particular, the additional radiopaque marker may include two lines, the center of which is circumferentially spaced approximately 180 degrees from the first radiopaque marker, such that the first radiopaque marker appears between the lines of the additional radiopaque marker when the orientation is within the set tolerance. When the orientation is outside the set tolerance, the radiopaque marker overlaps one of the lines of the additional radiopaque markers or is outside the lines of the additional radiopaque markers. For example, the set tolerance may be up to 45 degrees on either side of perfect alignment (e.g., up to 35 degrees, or 25 degrees, or 15 degrees, or 5 degrees).

[0312] The electrodes can be configured for directed energy delivery by electrically isolating the portions of the electrodes that point away from the ablation direction.

[0313] Method of processing In some embodiments of the GSN ablation procedure herein, the lowest intercostal vein is targeted first because in the majority of patients, a fully formed GSN traverses the lowest intercostal vein within the target region, between the adjacent azygos veins and up to 20 mm from its ostium into the intercostal vein. However, in some patients in whom the first ablation is insufficient, a trial may be performed to assess clinical efficacy and whether subsequent ablation of the target region at one or two additional levels may be performed to achieve a clinically significant effect. For example, the following is an exemplary method of treating heart failure in a human patient by ablating the thoracic splanchnic nerve. A distal region of an ablation catheter equipped with an ablation element may be delivered to the patient's first intercostal vein (e.g., the lowest intercostal vein, T11 intercostal vein). Ablation energy may then be delivered from the ablation catheter to form a first lesion (e.g., a lesion having a length in the range of 10-20 mm, e.g., 12-15 mm) in tissue up to 5 mm from the first intercostal vein. The distal region of the ablation catheter may be moved to a second intercostal vein above the first intercostal vein (e.g., above and adjacent to the first intercostal vein). An ablation confirmation test may then be performed. Monitoring may be performed for a physiological response to the ablation confirmation test (e.g., splanchnic vasoconstriction, increased heart rate, increased blood pressure). If the physiological response indicates that the first lesion did not provide a clinically significant amount of GSN blockage (e.g., a lack of physiological response is observed), ablation energy may be delivered from the ablation catheter to form a second lesion in tissue up to 5 mm from the second intercostal vein. The distal region of the ablation catheter may be moved to a third intercostal vein above the second intercostal vein (e.g., above and adjacent to the second intercostal vein). The same or a different ablation confirmation test may be performed, followed by another monitoring test.If the physiological response indicates that the first and second lesions did not provide a clinically significant amount of GSN blockage (e.g., if a lack of physiological response is observed), ablation energy is delivered from the ablation catheter to create a third lesion in tissue up to 5 mm from the third intercostal vein. Any ablation confirmation test may include delivering a nerve stimulation signal from a stimulation electrode positioned on a distal region of the ablation catheter configured to generate action potentials in the thoracic splanchnic nerve. Alternatively or additionally, the ablation confirmation test may include a leg raise test. Alternatively or additionally, the ablation confirmation test may include adding a volume of fluid to the venous system. Alternatively or additionally, the ablation confirmation test may include a grip strength test.

[0314] In an exemplary method in which the ablation confirmation test includes a leg-raising test, the method may include any of the following steps: Prior to ablation in the lowest intercostal vein, a baseline measurement may be obtained by elevating the leg and measuring the change in central venous pressure and waiting for equilibrium, which is a measure of total venous compliance including the central veins and the splanchnic bed. The leg is then lowered and allowed to equilibrate, allowing blood to redistribute to the leg. Ablation in the lowest intercostal vein (e.g., T11) may then be performed as described herein. The leg may then be elevated, followed by a remeasurement of central venous pressure while waiting for equilibrium. A measurement may then be taken to determine whether there has been an appropriate decrease in total venous compliance. If there has been a decrease, the GSN has been successfully ablated. If there has not been a decrease, then an ablation in the next highest intercostal vein (e.g., T10) may be performed as described herein. The measurement may then be repeated. A measurement may then be taken to determine whether there has been an appropriate decrease in total venous compliance. If there has been a decrease, the GSN has been successfully ablated. If there is no reduction, then ablation in the next highest intercostal vein (eg, T9) may be performed.

[0315] An exemplary method in which the ablation confirmation test includes a grip strength test or other action to increase sympathetic nervous system (SNS) outflow to the splanchnic bed may include the following steps: An ablation may be performed in the lowest intercostal vein (e.g., T11). Venous compliance may then be measured. A grip strength test may then be performed for a predetermined period (e.g., 60 seconds). Venous compliance may then be remeasured. If there is no change in venous compliance, the initial ablation was sufficient to achieve a clinically significant outcome. If compliance still decreases, some of the SNS activity caused by the grip strength test is transmitted. Therefore, the ablation in the lowest intercostal vein was insufficient to achieve a clinically significant effect. Next, an ablation may be performed in the next highest intercostal vein (e.g., T10). A grip strength test may then be performed for a predetermined period (e.g., 60 seconds). Venous compliance may then be remeasured. If there is no change in venous compliance, a second ablation is sufficient. If compliance is reduced, some of the SNS activity elicited by the grip strength test is transmitted, and ablation in the next highest intercostal vein nerve is thus insufficient to achieve a clinically significant effect. Next, ablation in the next highest intercostal vein (T9) can be performed. At this point, procedures performed at a level higher than the third lowest intercostal vein are not envisioned.

[0316] The ablation confirmation test may include delivering neural stimulation signals and monitoring and evaluating physiological responses. Any of the methods of use described herein may further include a neural stimulation step. For example, electrodes used for ablation or other electrodes may be used to deliver one or more neural stimulation signals. For example, proximal and distal electrodes (123 and 124 in FIGS. 31 and 33, or 156 and 157 in FIG. 34A) may be used to deliver one or more neural stimulation signals. Each electrode is electrically connected through a catheter via a movable independent conductor (not shown) to the proximal end of the catheter, where it can be connected to a stimulation signal supply, which may be a computer-controlled RF ablation energy console. The console may be switched between delivering stimulation signals and ablation signals so that the electrodes can be used for either stimulation or ablation. In use, electrodes (e.g., 123 and 124 in FIG. 31 ) may be placed at the proximal and distal ends of a target region 58 of a target vessel 55, which may be visualized under fluoroscopy by placing the proximal electrode (e.g., 123 in FIG. 31 ) at the ostium 59 of the target vessel 55, as shown in FIGS. 31 and 34A . The neural stimulation electrodes may deliver neural stimulation signals in a bipolar mode, focusing the signal between the two electrodes to generate action potentials in nerves located between the two electrodes and within a predetermined ablation zone. A distance of 25 mm or less (e.g., 4-6 mm) between the two neural stimulation electrodes ensures vector pacing with a neural stimulation signal strength sufficient to stimulate nerves within the vector. Neural stimulation (i.e., pacing) parameters may include 50 Hz 1 V used to generate TSN or GSN action potentials. Stimulation of the TSN or GSN may also result in a measurable physiological response, such as an epigastric response, such as a contraction of the rectus abdominis muscle, an increase in heart rate, or an increase in blood pressure. Positive stimulation of the TSN or GSN can confirm that the ablation element is in the proper position to ablate the target TSN or GSN, whereas a lack of response can suggest that the ablation element needs to be moved.Neurostimulation parameters may include 2Hz 2V used to stimulate the intercostal or sympathetic nerves to confirm intercostal nerve clearance when a lack of intercostal muscle response is measured, or to confirm sympathetic nerve clearance when a lack of sympathetic nerve response is measured. Electrodes may optionally or alternatively be used to measure bioimpedance and tissue phase within the pacing range, which may be used to detect the presence of neural tissue, to detect tissue changes caused by ablation, and to detect sudden impedance changes that may predict subsequent safety concerns (e.g., blood clotting, overheating, bubble formation). Optionally, the neurostimulation signal may have characteristics that stimulate the target TSN or GSN while reducing or eliminating stimulation of pain-sensing nerve fibers.

[0317] Not all steps in any of the methods herein, including the ablation confirmation tests herein, need be performed. Some of the steps may occur in a different order. Note that the procedures herein are intended to target specific nerves or nerve roots, do so through specific target veins, and place ablation elements or members in specific regions within those veins. The anatomical regions evaluated and targeted necessitate specific design requirements. For other procedures targeting different anatomical locations for placement and different target nerves, the devices that can be used in these procedures may be very different, as the device design constraints for these procedures are very different. Thus, the disclosure herein provides specific reasons for designing specific devices, including the ability to effectively perform the procedures specifically described herein.

[0318] While the above description presents one or more example processes or apparatus, it will be understood that other processes or apparatus are within the scope of the appended claims.

[0319] Although not specifically indicated, one or more techniques described in this disclosure may be implemented, at least in part, in hardware, software, firmware, or any combination thereof. For example, many of the techniques of various aspects or components may be implemented in one or more processors, including one or more microprocessors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), programmable logic circuits, etc., alone or in any suitable combination. The term "processor" or "processing circuitry" may generally refer to any of the above circuitry, alone or in combination with other circuitry, or in combination with any other equivalent circuitry.

[0320] Such hardware, software, or firmware may be implemented within the same device or within separate devices to support various associated operations or functions described in this disclosure. Furthermore, any of the described units, modules, or components may be implemented together or as separate but interoperable logic devices. The description of different features as modules or units is for the purpose of highlighting different functional aspects and does not necessarily imply that such modules or units must be realized by separate hardware or software components. Rather, functionality associated with one or more modules or units may be performed by separate hardware or software components or may be integrated within common or separate hardware or software components.

[0321] When implemented in software, the functionality attributed to the systems, devices, and techniques described in this disclosure may be embodied as instructions on a computer-readable medium, such as random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, etc. The instructions may be executed by a processor to support one or more aspects of the functionality described in this disclosure.

[0322] Any modifications, characterizations, or assertions previously made regarding prior art or other art (in this application or any other patent application or patent, including any parent, sibling, or child application) may be construed as a disclaimer of any subject matter supported by the present disclosure of this application, and Applicant hereby invalidates and rejects such disclaimers. Applicant further respectfully submits that it may be necessary to reconsider any prior art previously considered in any related patent application or patent, including any parent, sibling, or child application.

[0323] The specific embodiments described herein are not intended to be limited by any claim, and any claim may cover a process or apparatus different from that described below, unless expressly stated otherwise. A claim is not limited to an apparatus or process having all of the features of any one apparatus or process described below, or to features common to more than one or all of the apparatuses described below, unless expressly stated otherwise. An apparatus or process described below may not be an embodiment of any exclusive rights granted by the issuance of this patent application. Any subject matter described below, or to which exclusive rights are not granted by the issuance of this patent application, may be the subject of a separate protective instrument, e.g., a pending patent application, and the applicant, inventor, or owner does not intend to waive, discharge, or obviate such subject matter by its disclosure herein. [Explanation of symbols]

[0324] 58 Targeted Ablation Zone 100 devices 101 Needle guide 102 Catheter 103 Needle guide distal end 104 Long axis 105 needles 106 Catheter proximal end 107 Puncture end 108 Catheter distal end 109 Side Port 110 outer diameter 121,159,183,205,225,253,275 Long shaft 134,165,190,211,232,252,276 Ablation Assembly 182,221,242,261 Expandable members 184 Straight Electrode 185,207 Irrigation port 189,204 length 201 Tubular electrode 203 Interval 207 Irrigation Port 209 Straight section 210 Loop section 224 Ultrasonic Transducer 227 Post 233 Support shaft 244 Electrode Pads 245,187,231,274 Flexible neck 248 Circumferential Treatment Zone 249 Electrode Traces 250 distance 251 Arc Length 252 Electrode Assembly 262 Electrode 263 Tubular membrane 269, 271 maximum width 270, 272 Maximum thickness

Claims

1. 1. A device for intravascular venipuncture, comprising: a. an elongate catheter extending along a catheter longitudinal axis and having a proximal catheter section and a distal catheter section; b. a needle guide having a blunt needle guide distal end, the needle guide being deployable from the catheter from a needle guide retracted position to a needle guide activated position, wherein the needle guide distal end is radially spaced from the catheter and wherein the needle guide distal end is retracted toward the catheter relative to the needle guide activated position; c. a needle having a sharp piercing tip, the needle being deployable from within the needle guide from a needle retracted position to a piercing position, wherein in the needle retracted position the piercing tip is inboard of the needle guide distal end and in the piercing position the piercing tip protrudes from the needle guide distal end; 1. A device for intravascular venipuncture comprising:

2. - the catheter has an outer catheter diameter; - in the puncture position, the puncture tip is spaced from the needle guide distal end by a needle deployment distance that is less than the catheter outer diameter; The device of claim 1 .

3. 3. The device of claim 2, wherein the needle deployment distance is less than 2 mm.

4. 4. The device of claim 2 or 3, wherein the needle deployment distance is less than 1 mm.

5. - the catheter has an outer catheter diameter; 10. The device of claim 1, wherein in the needle guide activated position, the needle guide distal end is radially spaced from the catheter by a needle guide deployed distance that is less than the catheter outer diameter. Alternatively, in the needle guide activated position, the needle guide distal end is radially spaced from the catheter by a needle guide deployed distance that is less than an outer diameter of the catheter.

6. The device of claim 5, wherein the needle guide deployment distance is about 0.5 to 6 mm.

7. 7. The device of claim 5 or 6, wherein the needle guide deployment distance is about 0.5 to about 3 mm.

8. 7. The device of claim 5 or 6, wherein the needle guide deployment distance is about 2 to about 6 mm.

9. 9. The device of claim 1, wherein the catheter has a circumferential outer surface and a first side port within the circumferential outer surface, and the needle guide is deployable from the first side port.

10. 10. The device of any one of claims 1 to 9, further comprising a delivery device deployable from within the needle from a delivery device storage position to a delivery device processing position.

11. The device of claim 10 , wherein the delivery device is at least one of a fluid delivery device, a thermal energy delivery device, a radio frequency energy delivery device, a cryogenic energy delivery device, and an electrical energy delivery device.

12. 12. The device of claim 10 or 11, wherein the delivery device has a delivery device distal end that is blunt.

13. 13. The device of claim 10, wherein in the delivery device handling position, the delivery device distal end projects beyond the puncture end by a delivery distance that is greater than a needle puncture distance.

14. 14. The device of claim 13, wherein the delivery distance is from about 3 to about 15 mm.

15. 15. The device of claim 13 or 14, wherein the delivery distance is about 4 to about 6 mm.

16. 16. The device of any one of claims 1 to 15, wherein the catheter has a guidewire lumen extending therethrough along the catheter axis, the distal catheter portion having a guidewire exit port.

17. 17. The device of claim 16, wherein the catheter has a distal end face and a circumferential outer surface, and the guidewire exit port comprises a notch that opens across the distal end face and the circumferential surface.

18. - the needle guide is deployable from the catheter at a first circumferential position on the catheter; The device of claim 17, wherein the notch is open in the circumferential surface at a notch circumferential position within 30 degrees of the first circumferential position.

19. 20. The device of claim 18, wherein the notch circumferential location is aligned with the first circumferential location.

20. a. a second needle guide deployable from said catheter; b. a second needle deployable from within said second needle guide; 20. The device of any one of claims 1 to 19, further comprising:

21. 21. The device of claim 20, wherein the needle guide is deployable from the catheter at a first longitudinal position on the catheter and the second needle guide is deployable from the catheter at a second longitudinal position on the catheter, the second longitudinal position being spaced apart from the first longitudinal position.

22. 22. The device of claim 20 or 21, wherein the needle guide is deployable from the catheter at a first circumferential position on the catheter and the second needle guide is deployable from the catheter at a second circumferential position on the catheter, the second circumferential position being aligned with the first circumferential position.

23. 23. The device of any one of claims 1 to 22, further comprising at least one first radiopaque marker, said first radiopaque marker being on said catheter, said needle guide or said needle.

24. 24. The device of claim 23, wherein the radiopaque marker is on the catheter and configured to indicate the rotational orientation of the catheter.

25. 25. A device according to any one of claims 1 to 24 for cauterizing the greater splanchnic nerve.

26. 1. A method of intravascular puncture and processing, said method comprising: a. advancing the catheter distal portion through the patient's venous system to a target location within a vein; b. deploying a needle guide from said catheter in a direction transverse to a longitudinal axis of said catheter; c. contacting the venous wall with the blunt distal end of the needle guide and continuing to deploy the needle guide to press the blunt distal end against the venous wall; d. deploying a needle from the distal end of the needle guide to puncture the vein wall with the sharp puncture tip of the needle; e. Delivering treatment to an area outside the vein via the sharp puncture tip; The method includes:

27. 27. The method of claim 26, wherein the catheter has an outer catheter diameter, and step b comprises deploying the needle guide to a deployed distance that is less than the outer catheter diameter.

28. 28. The method of claim 27, wherein the deployment distance is between 0.5 and 6 mm.

29. The method according to claim 27 or 28, wherein the deployment distance is between 0.5 and 3 mm.

30. The method according to claim 27 or 28, wherein the deployment distance is between 2 and 6 mm.

31. 27. The method of claim 26, wherein the catheter has an outer catheter diameter, and step d comprises deploying the needle to a puncture distance that is less than the outer catheter diameter.

32. 32. The method of claim 31, wherein the puncture distance is less than 2 mm.

33. 33. The method of claim 31 or 32, wherein the puncture distance is less than 1 mm.

34. 34. The method of any one of claims 26 to 33, further comprising, prior to step e., delivering a nerve stimulation test pulse via the distal blunt tip or the sharp piercing tip.

35. 35. The method of any one of claims 26 to 34, wherein step e) comprises deploying a delivery device from the puncture end and delivering the treatment using the delivery device.

36. 36. The method of claim 35, wherein step e comprises deploying the delivery device a delivery distance that is greater than a puncture distance.

37. 37. The method of claim 36, wherein the delivery distance is up to 15 mm.

38. 38. The method of claim 36 or 37, wherein the delivery distance is between 3 and 7 mm.

39. 39. The method of any one of claims 36 to 38, wherein the delivery distance is between 4 and 6 mm.

40. 40. The method of any one of claims 26 to 39, wherein step e. comprises ablating the nerve.

41. 36. The method of any one of claims 23 to 35, wherein step e. comprises delivering at least one of a fluid, a thermal energy treatment, a cryogenic energy treatment, and a radio frequency energy treatment.

42. 42. The method of any one of claims 26 to 41, wherein the target location is in an azygos vein or an intercostal vein.

43. 43. The method of claim 42, wherein the target location is within the T9, T10, or T11 intercostal vein.

44. 43. The method of claim 42, wherein the target location is in the azygos vein between the T11 and T9 intercostal veins.

45. 45. The method of any one of claims 26 to 44, wherein step e comprises delivering the treatment to a thoracic splanchnic nerve or a thoracic splanchnic nerve root.

46. 46. ​​The method of any one of claims 26 to 45, wherein step e comprises delivering the treatment to the greater splanchnic nerve.

47. 47. The method of any one of claims 26 to 46, wherein step e comprises delivering a treatment for heart failure.

48. 48. The method of any one of claims 26 to 47, further comprising: coordinating step e) with the patient's breathing to avoid damaging the patient's lungs during said process.

49. 49. The method of claim 48, further comprising monitoring the proximity of the needle to the patient's lungs.

50. 50. The method of any one of claims 26 to 49, wherein step a comprises advancing the catheter over a guidewire.

51. - the target location is within the azygos vein and the guidewire extends beyond the azygos vein into an intercostal vein; - the method further comprises, prior to step b, orienting the catheter to a target orientation by rotating the catheter until the guidewire is positioned within an orientation notch in the catheter distal section; 51. The method of claim 50.

52. - step b includes deploying the needle guide from a side port in the outer circumferential surface of the catheter; - said notch is at a notch circumferential position; the side port is at a first circumferential position that is within 30 degrees of the notch circumferential position; 52. The method of claim 51.

53. After step a, - deploying a second needle guide from the catheter in a second direction transverse to the longitudinal axis of the catheter; - contacting the vein wall with the second distal blunt end of the second needle guide and continuing to deploy the second needle guide to press the second distal blunt end against the vein wall; - deploying a second needle from the second distal end of the second needle guide to puncture the vein wall with a second puncture end of the second needle; - delivering a second treatment via said second piercing end; 53. The method of any one of claims 26 to 52, comprising:

54. 54. The method of claim 53, wherein the needle guide is deployed from a first side port in the catheter distal portion and the second needle guide is deployed from a second side port in the catheter distal portion, the first side port and the second side port being longitudinally spaced apart from one another.

55. 55. The method of claim 54, wherein the first side port and the second side port are longitudinally spaced apart from each other by 3 to 5 cm.

56. 56. The method of claim 55, wherein the first side port and the second side port are circumferentially aligned.

57. 57. The method of any one of claims 26 to 56, wherein step c comprises continuing to deploy the needle guide to urge the catheter away from the venous wall and against an opposing venous wall.

58. 25. A device according to any one of claims 1 to 24, wherein in the needle guide active position the needle guide is either straight or curved and angled relative to the catheter axis.

59. 25. The device of claim 23 or 24, wherein the first radiopaque marker is made of a radiopaque material and is asymmetrically shaped, optionally the radiopaque marker is N-shaped.

60. 60. The device of claim 23, 24 or 59, further comprising an additional radiopaque marker on the catheter configured to visually indicate when the rotational position of the catheter is within a set tolerance.

61. 61. The device of claim 60, wherein the additional radiopaque marker includes two lines, the centers of which are circumferentially spaced approximately 180 degrees from the first radiopaque marker such that the first radiopaque marker appears between the lines of the additional radiopaque marker when orientation is within the set tolerance.

62. causing deployment of the needle guide from the needle guide retracted position to the needle guide activated position; causing the needle to deploy from the needle retracted position to a puncture position; 62. A device according to any one of claims 1 to 24 or claims 58 to 61, comprising a controller configured to:

63. 63. The device of claim 62 in combination with any one of claims 10 to 15, wherein the controller is further configured to cause deployment of the delivery device from the delivery device storage position to the delivery device processing position.

64. 63. The device of any one of claims 10 to 15 in combination with any one of claims 1 to 9, claims 16 to 24 and claims 58 to 63, wherein the delivery device is a cryogenic energy delivery device including a first lumen for delivery of cryogenic fluid from a source to a distal end of the cryogenic energy delivery device and a second lumen for returning the cryogenic fluid to the source.

65. 65. The device of claim 64, wherein the source of cryogenic fluid includes a fluid reservoir, a supply valve between the fluid reservoir and the first lumen, a pressure relief valve at the outlet of the second lumen for discharging returning cryogenic fluid to the atmosphere, and a controller or the controller configured to control the supply valve and the pressure relief valve.

66. 66. The device of claim 65, wherein the controller is in communication with a temperature sensor at a distal end of the delivery device and is configured to control the supply of the cryogenic fluid in response to a temperature sensed by the temperature sensor.

67. an elongated shaft (121, 159, 183, 205, 225, 253, 275); an ablation assembly (134, 165, 190, 211, 232, 252, 276) carried by a portion of the elongate shaft, the ablation assembly configured to create either a circumferential ablation pattern having a length of at least 12 mm or a directional ablation pattern having a length of at least 12 mm; An ablation catheter configured for endovascular nerve ablation, particularly for endovascular splanchnic nerve ablation.

68. 68. The catheter of claim 67, wherein the ablation assembly (134, 165, 190, 211, 232, 252, 276) is configured to create either a circumferential ablation pattern having a length of 12-30 mm, optionally 12-20 mm, or a directional ablation pattern having a length of 12-30 mm, optionally 12-20 mm.

69. 69. The catheter of claim 67 or 68, wherein the ablation assembly (134, 165, 190, 211, 232, 252, 276) is carried by a distal straight portion of the elongate shaft.

70. 70. The catheter of claim 67, 68 or 69, comprising an expandable member (182, 221, 242, 261) carried by the elongate shaft and having an unexpanded state and an expanded state, and the ablation assembly (134, 165, 190, 211, 232, 252, 276) is attached to the expandable member (182, 221, 242, 261).

71. an elongated shaft (121, 159, 183, 205, 225, 253, 275); an expandable member (182, 221, 242, 261) carried by the elongate shaft and having an unexpanded state and an expanded state; an ablation assembly (134, 165, 190, 211, 232, 252, 276) attached to the expandable member (242); An ablation catheter configured for endovascular nerve ablation, particularly for endovascular splanchnic nerve ablation, comprising:

72. 72. A catheter according to any one of claims 67 to 71 configured for insertion into an arterial vein of a human.

73. 73. A catheter according to any one of claims 70 to 72, wherein the expandable member (182, 221, 242, 261) is configured to be inserted into an intercostal vein of a human patient in the unexpanded state and configured to abut a vascular wall of the intercostal vein in the expanded state.

74. 74. A catheter according to any one of claims 70 to 73, wherein the expandable member (182, 221, 242, 261) comprises a circumferential treatment zone (248) configured to contact a vessel wall in the expanded state, the circumferential treatment zone (248) having a length along the longitudinal axis of the catheter in the range of 12 to 30 mm, optionally 12 to 20 mm.

75. 75. A catheter according to any one of claims 70 to 74, wherein the expandable member (182, 221, 242, 261) has a diameter in the range of about 1 to 2.5 mm and a circumference in the range of about 3.14 to 7.85 mm in the unexpanded state.

76. 76. A catheter according to any one of claims 70 to 75, wherein the expandable member (182, 221, 242, 261) has a diameter in the range of about 3 to 5 mm and a circumference in the range of about 9.4 to 15.7 mm in the expanded state.

77. 77. The catheter of any one of claims 70 to 76, wherein the ablation assembly and the expandable member are configured such that when the expandable member is in the expanded state, the ablation assembly forms a circumferential ablation pattern at least 12 mm in length, preferably 12 to 30 mm in length.

78. 78. A catheter according to any one of claims 70 to 77, wherein the expandable member (182, 221, 242, 261) comprises a deployable balloon attached to a distal portion of the elongate shaft and optionally made of a compliant material or a non-compliant material that is flexibly folded and contracted.

79. 79. A catheter according to any one of claims 67 to 78, wherein the elongate shaft comprises a flexible neck (245; 187; 231; 274) positioned within 10 mm of the expandable member or within 10 mm of the ablation assembly.

80. 80. The catheter of claim 79, wherein the flexible neck is bendable according to a minimum radius of curvature of 4 mm to allow orientation of the distal portion of the elongate shaft and facilitate insertion of the distal portion of the elongate shaft in its natural orientation in an intercostal vein.

81. 80. The catheter of claim 78 or 79, wherein the flexible neck is made of a softer durometer polymer, optionally Pebax, compared to the material used in the portion of the elongate shaft adjacent the flexible neck.

82. 81. A catheter as described in claim 78, 79 or 80, wherein the flexible neck material has a wire coil embedded therein.

83. 83. A catheter as described in any one of claims 70 to 82, wherein the ablation assembly (252) comprises a plurality of electrode pad assemblies (244) attached to an outer surface of the expandable member (242) and configured to make direct contact with a blood vessel wall when the catheter is inserted into a patient's blood vessel.

84. 84. A catheter as described in claim 83, wherein each electrode pad assembly (252) includes a plurality of electrodes in the form of electrode pads (244), the electrode pads being electrically interconnected by electrical traces (249), and optionally the electrode pads (244) and the traces (249) of the same electrode pad assembly being formed by a common conductive support substrate.

85. 85. The catheter of claim 84, wherein the electrode pad (244) and the trace (249) of the same electrode pad assembly are aligned substantially parallel to the longitudinal axis of the catheter.

86. 86. A catheter according to any one of claims 83 to 85, wherein the electrode pad assembly (252) is attached to the expandable member (242) and defines a plurality of electrode pads (244) arranged around the expandable member to form a circumferential ablation pattern up to 20 mm in length, optionally with the circumferential ablation pattern having a length comprised within the range of 12 to 18 mm.

87. 87. A catheter according to any one of claims 84 to 86, wherein each electrode pad (244) is circumferentially spaced apart from an angularly adjacent electrode pad (244) by a distance (250) of less than 5 mm, optionally less than 2.5 mm.

88. 88. The catheter of any one of claims 84 to 87, wherein each electrode pad (244) extends around the expandable member along an arc length (251) in the range of 3 to 3.5 mm.

89. 89. A catheter according to any one of claims 84 to 88, wherein each electrode pad (244) has a length measured parallel to the catheter longitudinal axis in the range of about 3 to 5 mm.

90. 90. A catheter as described in any one of claims 84 to 89, wherein each electrode pad assembly (..). comprises a row of electrical pads (244) extending substantially linearly along the catheter and separated by respective electrical traces (249).

91. 91. The catheter of claim 90, comprising a plurality of electrode pad assemblies (....), each having a plurality of electrode pads (244) arranged thereon, the plurality of electrode pad assemblies forming rows of electrode pads, optionally at least four rows of electrode pads (244) connected to each other by electrical traces (249).

92. 92. The catheter of claim 91, wherein the rows of electrode pads are evenly spaced around the circumference of the expandable member (242).

93. 93. A catheter according to claim 91 or 92, wherein the electrode pads on one row are longitudinally offset from the electrode pads on an adjacent row.

94. 94. The catheter of claim 91, 92, or 93, wherein the spacing between adjacent electrode pads when the expandable member is in its unexpanded state is smaller than the spacing between adjacent electrode pads when the expandable member is in its expanded state.

95. 95. The catheter of claim 94, wherein when the expandable member is in its unexpanded state, each electrode pad (244) is circumferentially spaced from an adjacent electrode pad by a distance (250) comprised between 0 and 1 mm.

96. 96. A catheter according to claim 94 or 95, wherein adjacent rows of the electrode pads interlock with one another when the expandable member is in its unexpanded state.

97. 97. A catheter according to any one of claims 94 to 96, wherein when the expandable member is in its expanded state, each electrode pad (244) is circumferentially spaced from an adjacent electrode pad by a distance (250) comprised within about 2 to 5 mm.

98. 98. A catheter as described in any one of claims 88 to 97, wherein each electrical trace (249) connecting two consecutive electrode pads comprises a narrowed conductive strip presenting a width measured circumferentially around the expandable member that is significantly less than the arc length of the electrode pad, and optionally the width of each electrical trace is less than 0.5 mm.

99. A catheter as described in any one of claims 83 to 85 and claims 87 to 98, wherein the electrode pad assembly is configured to position electrode pads on only one side of the expandable member, optionally covering 25-50% of the circumference of the expandable member, all facing the same side as the target ablation zone (58) to generate a directional ablation pattern the length of the target ablation zone (58).

100. 83. A catheter as described in any one of claims 67 to 69 and 79 to 82, wherein the ablation assembly (211) comprises a plurality of electrodes in the form of axially spaced tubular electrodes (201) mounted on the elongate shaft (205).

101. The catheter of claim 100, wherein the tubular electrode (201) has an outer diameter (202) in the range of 2 to 3 mm.

102. A catheter according to claim 100 or 101, wherein the tubular electrodes (201) are mounted consecutively on the elongate shaft, with a spacing (203) between two consecutive tubular electrodes in the range of 2 to 4 mm.

103. A catheter according to claim 100, 101 or 102, wherein the tubular electrodes (201) each have a length (204) in the range of 1 to 4 mm.

104. 104. A catheter according to any one of claims 100 to 103, comprising a plurality of said tubular electrodes (201) arranged along a straight portion (204) of said elongate shaft.

105. 105. The catheter of claim 104, wherein the plurality of tubular electrodes (201) arranged along the straight portion (204) of the elongate shaft spans a distance comprised within 12 to 20 mm.

106. 106. A catheter according to claim 104 or 105, wherein the elongate shaft has a looped portion (210) adjacent the straight portion (209).

107. 107. The catheter of claim 106, wherein the loop-shaped portion includes several of the tubular electrodes (201).

108. 108. A catheter according to any one of claims 100 to 107, wherein the tubular electrode (201) or the portion of the shaft between the tubular electrodes includes an irrigation port (207) configured to deliver a liquid and connectable to a fluid source.

109. 83. A catheter according to any one of claims 70 to 82, wherein the ablation assembly comprises at least one straight electrode (184) parallel to the axis (182) of the expandable member, the straight electrode (184) having a length (189) in the range of 12 to 20 mm.

110. 110. The catheter of claim 109, wherein the straight electrode covers at least a 25% segment of the circumference of the expandable member.

111. 111. The catheter of claim 109 or 110, comprising a plurality of straight electrodes arranged around the expandable member for circumferential ablation.

112. 111. The catheter of claim 109 or 110, comprising only one single straight electrode covering a segment of the circumference of the expandable member ranging from 25 to 50% for directional ablation.

113. 113. A catheter according to any one of claims 109 to 112, wherein each straight electrode is in the form of an electrode strip.

114. 114. A catheter according to any one of claims 109 to 113, wherein each straight electrode includes an irrigation port (185) configured to be connected to a source of fluid.

115. 83. The catheter of any one of claims 67 to 82, comprising a plurality of ultrasound transducers (224) disposed within the expandable member.

116. 116. The catheter of claim 115, wherein the ultrasonic transducer (224) is carried by a support shaft (233) centered within the expandable member.

117. 17. A catheter according to any one of claims 115 or 116, wherein the transducers (224) are arranged continuously over a length (226) ranging from 12 to 20 mm to produce ablation of the same length.

118. 118. A catheter according to any one of claims 115 to 117, wherein a strut or protrusion (227) is disposed between the transducer (224) and the expandable member (221).

119. 119. The catheter of claim 118, wherein the struts (227) comprise polymer strands elastically preformed to radially expand away from the transducer (224).

120. 120. A catheter according to any one of claims 115 to 119, wherein the transducers, optionally at least 4 mm in length, are spaced apart with a flexible gap (228) between them.

121. 121. The catheter of any one of claims 115 to 120, wherein the ultrasonic transducer (224) is cylindrical for forming a circumferential ablation around a target vessel.

122. 121. A catheter according to any one of claims 115 to 120, wherein the ultrasound transducer is flat or semi-cylindrical and produces an ablation that is a partial segment of the circumference of a target vessel.

123. 83. A catheter according to any one of claims 67 to 82, wherein the ablation assembly comprises a plurality of electrodes (262), and the expandable member comprises a basket of elastic struts (261), optionally including a row of three or more struts, each strut having at least one electrode (262) attached thereto.

124. 124. The catheter of claim 123, wherein the basket has a contracted delivery state diameter of less than 2.00 mm, optionally about 1.7 mm.

125. 125. The catheter of any one of claims 123 to 124, wherein the basket has an expanded ablation state with a diameter in the range of about 2.5 to 4 mm.

126. 126. A catheter as described in any one of claims 123 to 125, comprising a non-occlusive, radially expandable tubular membrane (263) associated with the strut, the electrodes (262) being on the outer surface of the tubular membrane (263).

127. 127. The catheter of claim 126, wherein the tubular membrane (263) is an electrically insulating material.

128. 128. A catheter according to any one of claims 126 to 127, wherein the tubular membrane (263) is connected to the strut (261) and optionally disposed on the strut (261).

129. a coolant delivery port (265) configured to inject a coolant (264) into a volume outer bounded by the tubular membrane to allow cooling of the electrode by convection; 129. A catheter according to any one of claims 126 to 128.

130. 130. The catheter of claim 129, wherein the coolant delivery port (265) is at a distal end of the basket.

131. 131. A catheter according to any one of claims 123 to 130, wherein the struts (261) have narrowed portions (266) between the attached electrodes that are more flexible than the remainder of the struts to facilitate bending.

132. 132. A catheter according to any one of claims 123 to 131, wherein the basket and electrode positions are configured to create an ablation pattern in the range of 12-20mm in length, optionally 15mm in length.

133. 133. The catheter of any one of claims 123 to 132, wherein the basket and electrode positions are configured to generate a circumferential ablation pattern along substantially the entire length of the basket.

134. 133. The catheter of any one of claims 123 to 132, wherein the electrodes are attached to only one or two struts of the basket for directional ablation to ablate only a circumferential segment of a blood vessel.

135. A catheter as described in any one of claims 123 to 134, comprising radiopaque markers (....) in the distal region of the catheter, optionally arranged on the struts, that identify the radial direction of the basket.

136. A catheter as described in any one of claims 123 to 135, wherein each of the struts (261) has a cross section with a respective maximum width (269) and maximum thickness (270), and each of the electrodes (262) has a cross section with a respective maximum width (271) and maximum thickness (272), the maximum thickness (272) of the electrode being greater than the maximum thickness of the strut, and the maximum width of the electrode being greater than the maximum width of the strut.

137. 137. A catheter according to any one of claims 123 to 136, wherein each of the struts (261) has a cross section with a width (269) of about 0.5 mm and a thickness (270) of about 0.13 mm.

138. 138. A catheter according to any one of claims 123 to 137, wherein each of the electrodes (262) has a cross-section with a width (271) of about 1 mm and a maximum thickness (272) of about 0.33 mm, the thickness tapering to a thickness (273) of about 0.25 mm at the edge.

139. 139. A catheter as described in any one of claims 1 to 138, further comprising a power source connected to the ablation assembly and a control unit configured to control the power source and command the power source to deliver ablation energy, in particular RF ablation energy, to the ablation assembly.

140. 140. The catheter of claim 139, wherein the control unit is configured to control the power source such that more ablation power, and optionally RF energy, is delivered to the proximal electrode(s) than to the remainder of the electrode(s) to compensate for blood flow cooling.

141. 141. The catheter of any one of claims 137 or 140, wherein the control unit is configured to control the power source such that ablation power, and optionally RF energy, for a longer period of time is delivered to a proximal electrode(s) than to the remainder of the electrode(s) to compensate for the blood flow cooling.

142. The control unit controls the RF ablation energy to: sequentially in unipolar mode, or simultaneously in unipolar mode, or In bipolar mode, 142. A catheter according to any one of claims 139 to 141, configured to control the power source to deliver.

143. 143. The catheter of any one of claims 139 to 142, wherein the control unit is configured to control the power source to deliver RF ablation energy in a pulsed waveform.

144. A catheter described in any one of claims 139 to 143, wherein the control unit is configured to control the power source to drive bipolar energy, particularly bipolar RF ablation energy, between a pair of electrodes, particularly between pairs of electrode pads of different electrode pad assemblies.

145. 145. A catheter according to any one of claims 70 to 144, comprising a source of coolant connected or connectable to a coolant injection port (246) in fluid communication with the interior of the expandable member.

146. The catheter of claim 145 in combination with any one of claims 139 to 144, wherein the control unit is further configured to control the coolant source and instruct the coolant source to inject coolant fluid into the expandable member through the coolant injection port.

147. 147. A catheter according to any one of claims 145 or 146, comprising a coolant outlet port (247) that is either connected to an outlet lumen extending within the catheter elongate shaft or that is in direct communication with the exterior of the catheter so that coolant is deposited in the bloodstream.

148. 148. The catheter of claim 147, wherein the coolant outlet port is smaller than the coolant inlet port to allow pressure within the expandable member to be increased to inflate the expandable member.

149. A catheter as described in any one of claims 1 to 148, comprising a radiopaque marker positioned on the distal region of the catheter to indicate the radial direction, and optionally the radiopaque marker is asymmetric and positioned on the same side or opposite side of the electrode.

150. A catheter as described in any one of claims 83 to 114 and claims 123 to 149, comprising a temperature sensor positioned between the pair of electrodes.

151. 151. The catheter of claim 150, wherein the temperature sensor is configured to directly contact a vessel wall when the catheter is inserted into a blood vessel and the expandable member is in its expanded state.

152. 152. A catheter as described in claim 150 or 151 in combination with any one of claims 139 to 144, wherein the control unit is configured to receive a temperature signal from the temperature sensor and to control the coolant source to inject coolant fluid based on the temperature signal, and / or to control the emission of ablation energy from the power source based on the temperature signal.

153. 1. A transvascular ablation device adapted and configured for transvascular ablation of a preganglionic great splanchnic nerve or nerve root, comprising: a proximal portion adapted to remain external to a patient and a distal portion sized to be inserted through the patient's vascular system; the distal portion A long shaft; a first ablation member carried by the elongate shaft; a second ablation member carried by the elongate shaft and axially spaced from the first ablation member by a distance of 3-6 mm; a transvascular ablation device comprising an occlusion member carried axially by the elongate shaft between the first ablation member and the second ablation member, the occlusion member adapted to have a delivery configuration and an expanded configuration.

154. 154. The ablation device of claim 153, wherein the first ablation member has a length of 3 to 5 mm.

155. The ablation device of claim 154, wherein the second ablation member has a length of 3-5 mm.

156. The ablation device of claim 153, wherein the outer diameter of the first ablation member is 1.5 to 3 mm and the outer diameter of the second ablation member is 1.5 to 3 mm.

157. The ablation device of claim 153, wherein the occlusion member has an axial length of 1 to 6 mm.

158. 154. The ablation device of claim 153, wherein the occlusion member has a diameter of 3-5 mm in the expanded configuration, and optionally has a diameter of 1.5-2 mm in the delivery configuration.

159. 154. The ablation device of claim 153, further comprising a guidewire lumen extending from the proximal portion to a guidewire exit port in the distal portion.

160. 154. The ablation device of claim 153, wherein the first ablation member is in electrical communication with a first electrical conductor and the second ablation member is in electrical communication with a second electrical conductor different from the first electrical conductor.

161. 154. The ablation device of claim 153, wherein the first and second ablation members each include an irrigation outlet port in fluid communication with at least one irrigation lumen that extends through the elongate shaft to the proximal portion where it can be connected to an irrigation fluid supply.

162. 154. The ablation device of claim 153, wherein the first and second ablation members each have an irrigation outlet port in fluid communication with an independent irrigation lumen that passes through the elongate shaft to the proximal portion where it can be connected to an irrigation fluid supply.

163. 163. The ablation device of claim 161 or 162, wherein any of said irrigation outlet ports can have a diameter of 0.020 inches + / - 0.005 inches.

164. 163. The ablation device of claim 161 or 162, wherein either of the irrigation outlet ports is located on the side of the first ablation member or the side of the second ablation member, respectively.

165. 154. The ablation device of claim 153, wherein the first ablation member comprises an electrode, the electrode comprising at least one irrigation outlet port disposed within at least one channel spanning the length of the electrode.

166. 154. The ablation device of claim 153, wherein the first ablation member comprises an electrode having at least one irrigation outlet port disposed within at least one scallop spanning at least a portion of the length of the electrode to at least the distal or proximal end of the electrode.

167. 154. The ablation device of claim 153, wherein the first and second ablation members each comprise a cavity in fluid communication with at least two irrigation lumens from the elongate shaft to the proximal portion, where a first of the at least two irrigation lumens is connectable to an irrigation fluid supply and a second of the at least two irrigation lumens is connectable to a fluid return receptacle.

168. 154. The ablation device of claim 153, wherein at least one of the first and second ablation members comprises a temperature sensor.

169. 154. The ablation device of claim 153, wherein the occlusion member is an inflatable occlusion balloon.

170. 170. The ablation device of claim 169, wherein the occlusion balloon comprises a chamber that is in fluid communication with an inflatable lumen that passes through the elongate shaft to a proximal portion where it can be connected to an inflation fluid supply, and optionally, a temperature sensor is disposed within the chamber, the temperature sensor being adapted to monitor the temperature of the fluid within the chamber.

171. 1. A transvascular ablation device adapted and configured for transvascular ablation of a preganglionic great splanchnic nerve or nerve root, comprising: a proximal portion adapted to remain external to a patient and a distal portion sized to be inserted through the patient's vascular system; the distal portion A long shaft; a first ablation member carried by the elongate shaft, the first ablation member having an outer diameter of 1.5 to 3 mm; a second ablation member carried by the elongate shaft, axially spaced from the first ablation member, the second ablation member having an outer diameter of 1.5 to 3 mm; an occlusion member carried axially by the elongate shaft between the first ablation member and the second ablation member, the occlusion member adapted to have a delivery configuration and an expanded configuration, the occlusion member having a diameter of 3 to 5 mm in the expanded configuration.

172. The ablation device of claim 171, wherein the first ablation member has a length of 3 to 5 mm.

173. 173. The ablation device of claim 171 or 172, wherein the second ablation member has a length of 3 to 5 mm.

174. 1. A transvascular ablation device adapted and configured for transvascular ablation of a preganglionic great splanchnic nerve or nerve root, comprising: a proximal portion adapted to remain external to a patient and a distal portion sized to be inserted through the patient's vascular system; the distal portion A long shaft; a first ablation member carried by the elongate shaft; a second ablation member carried by the elongate shaft and axially spaced from the first ablation member; A device wherein both the first and second ablation members optionally have outer diameter dimensions that are smaller than the diameter of the elongate shaft.

175. The device of claim 174, wherein the outer dimensions are between 1.5 and 2.5 mm.

176. The device of claim 175, wherein the elongate shaft has a diameter of 2 to 3 mm.

177. 176. The device of claim 175, wherein the outer dimension is 0.2 to 1 mm smaller than the diameter.

178. 175. The device of claim 174, further comprising the constraint of any of claims 153 to 173.

179. 175. The device of claim 174, wherein a portion of each of the first ablation member and the second ablation member is electrically insulating and a remaining portion of each is conductive, the conductive portion comprising a segment that is less than 50%, less than 40%, less than 30%, or less than 25% of the circumference.

180. 180. The device of any one of claims 153 to 179, adapted to be connected to an ablation console, the ablation console adapted to operate the ablation device in at least one of a bipolar mode, a monopolar mode, and a combination of bipolar and monopolar modes.

181. 1. A method of cauterizing the greater splanchnic nerve or greater splanchnic nerve root to increase splanchnic venous blood volume, comprising: advancing an elongate medical device into the azygos vein, said elongate medical device including a distal region, said distal region including a flexible shaft, a first ablation member carried by said shaft, and a second ablation member carried by said shaft axially spaced from said first ablation member; advancing the first ablation member from the azygos vein into a T9, T10, or T11 intercostal vein; delivering the ablation energy from the first ablation member; creating an ablation lesion, thereby cauterizing a portion of the greater splanchnic nerve or greater splanchnic nerve root; The method includes:

182. 182. The method of claim 181, further comprising advancing the second ablation member through the azygos vein into a T9, T10 or T11 intercostal vein and delivering ablation energy from the second ablation member.

183. 183. The method of claim 182, wherein the delivering step comprises delivering energy from the first and second ablation members in a monopolar mode.

184. 183. The method of claim 182, wherein the delivering step comprises delivering energy from the first and second ablation members in a bipolar mode.

185. 183. The method of claim 182, wherein the delivering step comprises delivering energy from the first and second ablation members in a combined monopolar and bipolar mode.

186. 183. The method of claim 182, further comprising advancing an occlusion member into a T9, T10, or T11 intercostal vein between the first ablation member and the second ablation member.

187. 187. The method of claim 186, wherein the occlusion member is carried by an elongate shaft between the first ablation member and the second ablation member.

188. 187. The method of claim 186, further comprising expanding the occlusion member within a T9, T10, or T11 intercostal vein.

189. 187. The method of claim 186, further comprising completely occluding the T9, T10 or T11 intercostal vein with the occlusion element.

190. 183. The method of claim 182, wherein advancing the second ablation member comprises positioning a proximal end of the second ablation member at the ostia of the azygos vein and the intercostal vein.

191. 182. The method of claim 181, wherein advancing the first ablation member from the azygos vein into a T9, T10, or T11 intercostal vein comprises advancing the first ablation member into the T9, T10, or T11 intercostal vein up to 20 mm from an ostium of the azygos vein into the intercostal vein, and wherein delivering ablation energy from the first ablation member occurs when the first ablation member is positioned within 20 mm of the ostium.

192. 182. The method of claim 181, wherein the second ablation member is positioned within the azygos vein when energy is delivered from the first ablation member.

193. 193. The method of claim 192, further comprising expanding an obstruction member at the mouths of the azygos vein and intercostal veins, wherein expanding the obstruction member directs blood flow away from the mouths.

194. 193. The method of claim 192, wherein the energy is delivered from the first ablation member in a monopolar mode.

195. 195. The method of claim 194, wherein forming the lesion does not include delivering ablation energy from the second ablation member.

196. 193. The method of claim 192, wherein the first and second ablation members operate in a bipolar mode when the second ablation member is positioned within the azygos vein.

197. 182. The method of claim 181, wherein forming the ablation lesion comprises forming an ablation region having a depth of at least 5 mm from an intercostal vein.

198. 182. The method of claim 181, wherein forming the ablation lesion comprises forming a circumferential ablation region.

199. 182. The method of claim 181, further comprising advancing the first ablation member from the azygos vein into another one of the T9, T10 and T11 intercostal veins and delivering ablation energy from the first ablation member when in the other one of the T9, T10 and T11 intercostal veins.

200. 182. The method of claim 181, wherein forming the lesion does not include delivering ablation energy from the second ablation member.

201. 182. The method of claim 181, further comprising delivering a stimulation signal from at least one of the first and second ablation members.

202. 182. The method of claim 181, wherein delivering the stimulation signal comprises delivering a stimulation signal in a bipolar mode between the first ablation member and the second ablation member.

203. 203. The method of claim 202, further comprising measuring a response to the stimulation signal.

204. 204. The method of claim 203, wherein delivering the stimulation signal and measuring the response occurs prior to delivering ablation energy from the first ablation member.

205. 204. The method of claim 203, wherein delivering the stimulation signal and measuring the response occurs after delivering ablation energy from the first ablation member.

206. 182. The method of claim 181, further comprising advancing an occlusion member into the T9, T10 or T11 intercostal vein adjacent to the first ablation member.

207. 207. The method of claim 206, wherein the occlusion member is carried by an elongate shaft.

208. 207. The method of claim 206, further comprising expanding the occlusion member within the T9, T10 or T11 intercostal vein.

209. 209. The method of claim 208, further comprising completely occluding the T9, T10 or T11 intercostal vein with the occlusion member.

210. 209. The method of claim 208, wherein expanding the occlusion member comprises delivering a fluid into the occlusion member.

211. 182. The method of claim 181, further comprising delivering irrigation fluid to at least one of the first and second ablation members.

212. 212. The method of claim 211, further comprising monitoring the irrigation fluid for being above a threshold temperature.

213. 213. The method of claim 212, further comprising altering energy delivery parameters if the monitoring step indicates that the irrigation fluid is above the threshold temperature.

214. 212. The method of claim 211, further comprising controlling the irrigation fluid flow rate.

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