Methods and devices for endovascular ablation of visceral nerves

Abstract

Systems, devices, and methods for transvascular ablation of target tissue are disclosed. In some examples, the devices and methods can be used for splanchnic nerve ablation to increase splanchnic venous blood volume to treat at least one of heart failure and hypertension. For example, the devices disclosed herein can be advanced intravascularly 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. Methods for treating heart failure, such as HFpEF, by intravascularly ablating thoracic splanchnic nerves to increase venous volume and reduce pulmonary blood pressure are also disclosed.

Description

[0001] Reference Addition

[0002] This application claims priority to U.S. Provisional Application No. 62 / 864,093, filed on June 20, 2019, and U.S. Provisional Application No. 62 / 881,251, filed on July 31, 2019, the contents of which are incorporated herein by reference in their entirety for all purposes.

[0003] 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.

[0004] The present disclosure is related in subject matter to the disclosures in U.S. Publication Nos. US2019 / 0175912, US2019 / 0183569, US10,376,308, US10,207,110, U.S. Application Nos. 16 / 510,503, 62 / 836,720, 62 / 837,090, 62 / 864,093, PCT / US2019 / 15400, and PCT Publication Nos. WO2018 / 023132, WO2019 / 118976, all of which are incorporated herein by reference in their entirety for all purposes. Background Art

[0005] Heart failure (HF) is a medical condition that occurs when the heart is unable to adequately pump blood to sustain the body's organs. Heart failure is a serious disease that affects millions of patients in the United States and around the world.

[0006] A common measure of heart health is the left ventricular ejection fraction (LVEF) or ejection fraction. By definition, the amount of blood in the ventricles just before they contract is called the end-diastolic volume (EDV). Similarly, the amount of blood left in the ventricles at the end of contraction is the end-systolic volume (ESV). The difference between EDV and ESV is the stroke volume (SV). SV describes the amount of blood ejected from the right and left ventricles with each heartbeat. The ejection fraction (EF) is the fraction of EDV ejected with each heartbeat; that is, it is SV divided by EDV. Cardiac output (CO) is defined as the amount of blood pumped out by each ventricle of the heart per minute. CO equals SV multiplied by heart rate (HR).

[0007] Cardiomyopathy (in which the heart muscle becomes weak, stretched, or has other structural problems) can be further divided into systolic and diastolic dysfunction based on the ventricular ejection fraction.

[0008] While many medical therapies have successfully targeted systolic dysfunction and HFrEF (heart failure with reduced ejection fraction), no promising therapies have been identified for the large number of patients with diastolic dysfunction and HFpEF (heart failure with preserved ejection fraction). The clinical course of patients with HFrEF and HFpEF is important for recurrent presentations of acute decompensated heart failure (ADHF) (symptoms include dyspnea, decreased exercise capacity, peripheral edema, etc.). Recurrent hospitalizations for ADHF use a large portion of current healthcare resources and are likely to continue to incur significant costs.

[0009] Despite an increasingly better understanding of the pathophysiology of HF, modern medicine has so far failed to develop novel therapies for the chronic management of HF or recurrent ADHF episodes. Over the past few decades, ADHF management and prevention strategies have been and continue to focus on the classic paradigm that salt and fluid retention are responsible for intravascular fluid expansion and cardiac decompensation.

[0010] Thus, there remains a need for improved safe and effective therapies for heart failure patients, and for devices and systems adapted and configured to perform such therapies. Summary of the invention

[0011] The present disclosure relates to methods, devices and methods for ablating thoracic splanchnic nerves or thoracic splanchnic nerve roots. Ablation can be performed to treat at least one of hypertension and heart failure, but the general method can also be used for other treatments. For example, the methods herein can be used to treat pain, or even generally benefit a subject to reduce the amount of blood draining from the splanchnic bed to the central thoracic veins.

[0012] The treatment herein may be accomplished by increasing visceral volume. The treatment generally includes ablating a preganglionic thoracic splanchnic nerve or a thoracic splanchnic nerve root of the patient to increase visceral volume, thereby treating at least one of hypertension and heart failure.

[0013] The methods herein describe ablating a thoracic visceral nerve, such as the greater visceral nerve or the greater visceral nerve root. Although the methods herein may provide specific examples of targeting the greater visceral nerve or the greater visceral nerve root, other thoracic visceral nerves (e.g., the lesser visceral nerve or the smallest visceral nerve) may be ablated alternatively or additionally to perform one or more treatments herein.

[0014] One aspect of the present disclosure is a method for ablating tissue by intravascularly positioning a medical device near a target tissue and using the medical device to ablate the tissue and produce damage. One aspect of the present disclosure is a method for ablating tissue by intravascularly positioning a medical device into one or more target blood vessels and using the medical device to ablate the tissue and produce damage. Therefore, the method herein can be described as a method of positioning a medical device near a target tissue to be ablated and / or a method of positioning a medical device in one or more blood vessels, wherein the target tissue is relatively close to a target area within one or more blood vessels. Unless specifically stated to the contrary herein, any method steps herein (including, for example, but not limited to, method steps in the claims or description section) can be incorporated into any other method of use herein.

[0015] One aspect of the present disclosure is a method of ablating a greater splanchnic nerve or a greater splanchnic nerve root to increase splanchnic venous blood volume and / or venous compliance, the method comprising advancing a medical device into a first blood vessel, advancing the medical device at least partially into a second blood vessel, and delivering ablative energy from the medical device to create a lesion in tissue surrounding the first blood vessel.

[0016] In some embodiments, the first blood vessel is the azygos vein and the second blood vessel is an intercostal vein. The intercostal vein may be one of the three lowest intercostal veins. The intercostal vein may be a T9, T10 or T11 intercostal vein.

[0017] The method can include positioning a distal end of the ablation element in the second vessel and no more than 30 mm (eg, 20 mm, 15 mm, 12 mm) from a junction between the first and second vessels when energy from the ablation element is delivered.

[0018] The method can include positioning a proximal portion of the ablation element in a second blood vessel while delivering the energy.

[0019] The method may include aligning or positioning the ablation element relative to a bony landmark, such as a costovertebral joint at the same vertebral level where a second blood vessel (eg, an intercostal vein) is located.

[0020] In some embodiments, aligning or positioning the ablation element relative to a bone landmark, such as a costovertebral joint, includes viewing the bone landmark with medical imaging, such as fluoroscopy.

[0021] In some embodiments, observing bone landmarks with medical imaging such as fluoroscopy includes orienting the medical imaging viewing angle at an anterior tilt angle within a range of 25° to 65° (e.g., within a range of 30° to 60°, within a range of 35° to 55°) from the AP toward the side of the patient where the target nerve is located.

[0022] In some embodiments, viewing the bone landmark with medical imaging, such as fluoroscopy, includes orienting the medical imaging viewing angle to be approximately perpendicular to a line between a first blood vessel (eg, azygos vein) of the patient and the bone landmark (eg, costovertebral joint).

[0023] In some embodiments, aligning the ablation element relative to the bone landmark includes aligning a radiopaque marker positioned on a catheter containing the ablation element with the bone landmark.

[0024] The method may include creating a lesion at a distance of 5 mm around the ablation element. Creating the lesion may include ablating a portion of a thoracic splanchnic nerve or a thoracic splanchnic nerve root, such as a greater splanchnic nerve or a GSN root. The lesion may be a continuous lesion. The lesion may have a length of 5 mm to 25 mm, such as 10 mm to 25 mm, such as 15 mm to 20 mm. The lesion may be a circumferential lesion that completely surrounds the second vessel. However, the lesion may be less than the circumference that completely surrounds the second vessel, such as 225 degrees or less, 180 degrees or less, 135 degrees or less, 90 degrees or less, 45 degrees or less.

[0025] The method may include positioning the entire ablation element in the second blood vessel, and the method may include positioning less than the entire length of the ablation element in the second blood vessel.

[0026] The method may include performing an ablation procedure from within more than one target vessel, such as an intercostal vein or an azygos vein.The ablation method herein may also be performed in a second vessel.

[0027] The method may include performing an ablation confirmation test, such as any of the tests described herein.If desired or needed, the ablation element may be repositioned into a second target vessel, which may be the azygos vein or a different intercostal vein.

[0028] The method may also include delivering stimulation energy to a first stimulation electrode and a second stimulation electrode carried by the medical device before, during, and / or after delivering the ablation energy.Delivering stimulation energy may help determine whether the ablation element is at a target location within the intercostal vein and / or whether the ablation procedure is effective.

[0029] One aspect of the present disclosure is a method comprising delivering an ablation catheter including an energy delivery element (or member) through the venous system of a patient, positioning the energy delivery element at least partially (optionally completely) within a vein selected from the T9, T10, and T11 intercostal veins, and delivering ablative energy from the energy delivery element to produce a continuous lesion having a depth of at least 5 mm and a length of 10 mm to 25 mm. The continuous lesion and its parameters can be formed by selecting or choosing certain energy delivery parameters that will produce the lesion. In some embodiments, the lesion can extend from the ostium of the azygos vein along the intercostal veins to as much as 20 mm. Any other method steps herein described in the context of other methods can be performed with this exemplary method.

[0030] In some alternative methods herein, multiple ablations (i.e., from the start of ablation energy to the shutdown of energy ablation) can be performed in a single target vessel (e.g., an intercostal vein) to produce a total lesion formed by two or more lesions formed by multiple ablations. The total lesion consisting of multiple lesions can have any characteristics of other lesions described herein. For example, the total lesion can be continuous (connected by multiple lesions produced in different ablation processes), can be up to 20 mm long, can be annular (or not), etc. After the first ablation, the ablation device can be moved in the same vessel and produce a second lesion, which may or may not overlap with the first lesion. This can be repeated as many times as needed. Even if multiple ablations are performed in a single vessel, any stimulation or testing steps herein can be performed before, during, or after any ablation step.

[0031] One aspect of the present disclosure is a method of positioning an ablation catheter in a T9, T10, or T11 intercostal vein for ablating a greater splanchnic nerve (GSN), the method comprising imaging a portion of a subject including at least one of the T9, T10, or T11 intercostal veins and a portion of the subject's spine; positioning a distal segment of the ablation catheter in the T9, T10, or T11 intercostal vein; and positioning an ablation catheter radiopaque marker at a location based on the location of the ablation catheter radiopaque marker relative to an anatomical landmark such as a portion of the spine, a rib, a costovertebral joint, an azygos vein, or one or more of the ostia between the azygos vein and the T9, T10, or T11 intercostal vein. The method may further include delivering energy from an ablation catheter ablation element to ablate tissue.

[0032] One aspect of the present disclosure is a method that includes characterizing the relative position of a patient's azygos vein to determine whether the azygos vein is centered or substantially centered, right (to the right of the patient's center), or left (to the left of the patient's center). The characterizing step can occur while viewing a particular portion of the patient's anatomy and can occur from a particular viewpoint that allows accurate characterization. The method can further include positioning an ablation catheter based on the characterizing step.

[0033] One aspect of the present disclosure is a method for characterizing the position of the azygos vein of a human patient relative to a portion of the patient's spine, comprising: imaging at least a portion of the patient's spine and the vasculature, particularly the azygos vein and / or one or more intercostal veins, by injecting a radiopaque contrast agent into the patient's vasculature using an imaging device, particularly a radiographic imaging device, or imaging at least one radiopaque device located in the azygos vein and / or one or more intercostal veins relative to a portion of the spine using an imaging device, particularly a radiographic imaging device, thereby characterizing the position of the azygos vein of the patient relative to the midline of the spine, the radiopaque device optionally including a radiopaque portion of a guidewire; and determining whether the azygos vein is centered, left or right relative to the midline of the vertebra based on one or more images generated by the imaging device. This aspect may also include a method for determining an appropriate position where a catheter should be inserted into the vasculature of a human patient, particularly to allow ablation of a greater visceral nerve or a greater visceral nerve root, the method comprising determining where to place an ablation element of a catheter for transvascular ablation, particularly any catheter described herein, based on the determination of whether the azygos vein is centered, left or right relative to the midline of the vertebra.

[0034] This aspect may also include determining where to place a radiopaque marker carried by a distal segment of the ablation catheter (optionally a proximal radiopaque marker positioned proximal to any ablation element carried by the same distal segment) based on determining whether the azygos vein is centered, left, or right relative to the midline of the vertebra.

[0035] One aspect of the present disclosure is a method for determining the correct positioning of a catheter (optionally a catheter according to any of the claims or disclosure herein) inserted into the vascular system of a human patient, wherein the catheter comprises: an elongated shaft, a distal segment of which carries one or more ablation elements; and a distal radiopaque marker, the distal segment of the elongated shaft being positioned in a T9, T10 or T11 intercostal vein; wherein the method comprises: determining whether the azygos vein is centered, deviated to the left or to the right relative to the midline of the vertebra, evaluating the position of the proximal radiopaque marker relative to the midline of the vertebra, and verifying whether the catheter is correctly positioned relative to the patient's anatomical landmarks, wherein the verification comprises deeming the catheter to be correctly positioned when one of the following occurs: if the azygos vein is deviated to the right, the proximal radiopaque marker is placed at the mouth of the intercostal vein, to the right of the midline of the vertebra, and if the azygos vein is centered or deviated to the left, the proximal radiopaque marker is aligned with the midline of the vertebra.

[0036] In any method aspect herein, a proximal radiopaque marker may be carried by the distal section and may be positioned proximal to all ablation elements. The proximal radiopaque marker may be positioned directly proximal to an ablation element or directly proximal to the proximal-most side of an ablation element carried by the distal section of the catheter.

[0037] In any of the method aspects herein, the catheter may include a distal radiopaque marker located distal to all ablation elements and wherein the verifying step further comprises: evaluating the position of the distal radiopaque marker relative to the patient's costovertebral joints and / or ribs, determining that the distal radiopaque marker is spaced at least a predetermined threshold distance from the costovertebral joints and / or ribs. The distal radiopaque marker may be positioned directly distal to the ablation element, or directly distal to the most distal of the ablation elements carried by the distal region of the catheter, and wherein determining comprises determining that the distal radiopaque marker is at least 3 mm, preferably at least 5 mm, from the costovertebral joints.

[0038] In any of the method aspects herein, verification can include deeming the catheter improperly positioned when none of the following occurs: if the azygos vein is deviated to the right, the proximal radiopaque marker is placed at the ostium of the intercostal vein, to the right of the vertebral midline, and if the azygos vein is centered or deviated to the left, the proximal radiopaque marker is aligned with the vertebral midline.

[0039] In any method aspect herein, if it has been verified that the catheter is not properly positioned, the method may further include adjusting the position of the catheter by aligning a proximal radiopaque marker on the ablation catheter with a corresponding anatomical landmark, and / or by further moving a distal radiopaque marker away from the costovertebral joint.

[0040] In any method aspects herein, the step of determining whether the azygos vein is centered, left-biased, or right-biased relative to the midline of the vertebrae may include: using an imaging device, particularly a radiographic imaging device, to image at least a portion of the patient's spine and vasculature, particularly the azygos vein and / or one or more intercostal veins, by injecting a radiopaque contrast agent into the patient's vasculature, or using an imaging device, particularly a radiographic imaging device, to image at least one radiopaque device located in the azygos vein and / or one or more intercostal veins relative to a portion of the spine, thereby characterizing the position of the patient's azygos vein relative to the midline of the spine, the radiopaque device optionally comprising a radiopaque portion of a guidewire.

[0041] In any of the method aspects herein, the step of assessing the position of the proximal radiopaque marker relative to the vertebral midline may include imaging at least a portion of the catheter including the proximal radiopaque marker using an imaging device, particularly a radiographic imaging device.

[0042] In any of the method aspects herein, the step of assessing the position of the distal radiopaque marker relative to the costovertebral joint may comprise imaging at least a portion of the catheter comprising the distal radiopaque marker using an imaging device, in particular a radiographic imaging device.

[0043] One aspect of the present disclosure is a method for determining the correct positioning of a catheter (optionally a catheter according to any of the claims or disclosures herein) inserted into the vasculature of a human patient, wherein the catheter comprises: an elongated shaft, a distal section of which carries one or more ablation elements; and a distal radiopaque marker, the distal section of the elongated shaft being positioned in a T9, T10, or T11 intercostal vein; wherein the method comprises: determining the position of the distal radiopaque marker relative to the patient's costovertebral joint, verifying whether the catheter is correctly positioned relative to the patient's anatomical landmarks, wherein the verification comprises: deeming the catheter to be correctly positioned when the distal radiopaque marker is spaced apart from the costovertebral joint by at least a predetermined threshold distance. The distal radiopaque marker may be positioned directly distal to the ablation element, or directly distal to the most distal of the ablation elements carried by the distal section of the catheter, and wherein the predetermined threshold distance is at least 3 mm, preferably at least 5 mm.

[0044] In this regard, if it has been verified that the catheter is not properly positioned, the method may further include adjusting the position of the catheter by further spacing the distal radiopaque marker away from the costovertebral joint.

[0045] In this regard, the step of determining the position of the distal radiopaque marker relative to the patient's costovertebral joint may include using an imaging device, in particular a radiographic imaging device, to image at least a portion of the patient's spine and vascular system, in particular the azygos vein and / or one or more intercostal veins, by injecting a radiopaque contrast agent into the patient's vascular system, or using an imaging device, in particular a radiographic imaging device, to image at least one radiopaque device located in the azygos vein and / or one or more intercostal veins relative to a portion of the spine, thereby characterizing the position of the patient's azygos vein relative to the midline of the spine, the radiopaque device optionally including a radiopaque portion of a guidewire; and using an imaging device, in particular a radiographic imaging device, to image at least a portion of a catheter including spaced-apart radiopaque markers.

[0046] One aspect of the present disclosure is an ablation catheter for transvascular ablation of thoracic splanchnic nerves, in particular for ablating the greater splanchnic nerve or the greater splanchnic nerve root, comprising: a slender shaft, the length of which allows the distal section of the slender shaft to be positioned in the T9, T10 or T11 intercostal vein; proximal and distal conductive flexible ablation elements carried by the distal section of the slender shaft, the length from the distal end of the distal ablation element to the proximal end of the proximal ablation element being 10mm-25mm.

[0047] In this aspect, the distal section of the elongated shaft can have an outer diameter of 1.5 mm to 3 mm.

[0048] In this regard, there can be an axial spacing of 0.1 mm to 5 mm, such as 0.1 mm to 3 mm, such as 0.1 mm to 2 mm, such as 5 mm to 1 mm, between the proximal and distal ablation elements.

[0049] In this aspect, the distal ablation element and the proximal ablation element can be electrodes.

[0050] In this aspect, the distal ablation element and the proximal ablation element can each have a length, wherein the lengths are the same.

[0051] In this aspect, the distal ablation element and the proximal ablation element can each have a length, wherein the lengths are different.

[0052] In this aspect, the distal and proximal ablation elements can each have a length of from 5 mm to 12 mm, such as from 6 mm to 10 mm, such as from 7 mm to 9 mm, such as any integer within any of these ranges.

[0053] In this aspect, the distal ablation element can have a helical configuration, and wherein the proximal ablation element can have a helical configuration. The helical configurations of the distal ablation element and the proximal ablation element can be the same. The helical configurations of the distal ablation element and the proximal ablation element have one or more different features, such as one or more of the coil direction (e.g., left-handed vs. right-handed), pitch, or thickness.

[0054] In this aspect, the distal ablation element and the proximal ablation element can each have a curvilinear cross-sectional configuration.

[0055] In this aspect, the distal ablation element and the proximal ablation element can each have a rectilinear cross-sectional configuration.

[0056] In this regard, the distal and proximal ablation elements can be made of a superelastic material such as Nitinol.

[0057] In this regard, the distal and proximal ablation elements can be sufficiently flexible and sized to allow advancement of the distal segment from the azygos vein to one of the T9, T10, or T11 intercostal veins.

[0058] In this regard, the distal and proximal ablation elements can each be attached to the shaft at the distal and proximal end regions, but not between the distal and proximal end regions.

[0059] In this regard, the catheter may further include a radiopaque marker. The radiopaque marker may be disposed distally of the distal end of the distal ablation element. The radiopaque marker may be 0 mm to 5 mm distally of the distal end of the distal ablation element, optionally 0 mm to 3 mm, or 0 mm to 2 mm. The radiopaque marker may be disposed proximally of the proximal end of the proximal ablation element. The radiopaque marker may be 0 mm to 5 mm proximally of the distal proximal end of the distal ablation element, optionally 0 mm to 3 mm, or 0 mm to 2 mm.

[0060] In this aspect, neither the distal ablation element nor the proximal ablation element is configured to deploy to a deployed configuration.

[0061] In this aspect, the distal ablation element and the proximal ablation element each have an operational configuration that is the same or substantially the same as the delivery configuration.

[0062] In this aspect, the distal ablation element and the proximal ablation element each have an outer diameter in the operative state that is the same or substantially the same as an outer diameter in the delivery state.

[0063] In this aspect, the distal ablation element and the proximal ablation element can each have an expanded configuration that is different than the delivery configuration.

[0064] In this aspect, the catheter may further include a temperature sensor carried by the shaft. The temperature sensor may be disposed at a distal end of the distal ablation element. The temperature sensor may be disposed at a proximal end of the proximal ablation element. The catheter may include a second temperature sensor disposed at the distal end of the distal ablation element and a second temperature sensor disposed at the proximal end of the proximal ablation element.

[0065] In this aspect, the catheter may further include one or more flushing ports in fluid communication with the flushing lumen, which may be connected to a fluid source at a proximal region of the ablation catheter. One of the one or more flushing ports may be axially located between the distal ablation element and the proximal ablation electrode. One or more flushing ports may be radially disposed below the ablation element structure. One or more flushing ports may be disposed between the helical winding of the distal ablation electrode and the proximal ablation electrode. In a side view, the flushing port may be disposed between each pair of adjacent ablation element helical segments of the distal ablation element and the proximal ablation element.

[0066] In this aspect, the distal ablation electrode and the proximal ablation element can be electrically configured to be independently energized in a monopolar mode.

[0067] In this aspect, the distal ablation electrode and the proximal ablation element can be electrically configured to be energized in a bipolar mode.

[0068] In this aspect, the distal section is no more than 7 cm from the distal tip of the ablation catheter.

[0069] In this regard, the distal ablation electrode and the proximal ablation element may be sized and adapted to produce a continuous ablation having a length in the range of 5 mm to 25 mm, such as 10 to 25 mm, such as 15 mm to 20 mm.

[0070] In this regard, the distal section can be adapted to flexibly pass through the bend from the azygos vein to the T9, T10, or T11 intercostal vein.

[0071] In this aspect, the catheter can also include a guidewire lumen within the elongated shaft and having a distal port at the distal tip of the catheter.

[0072] In this regard, the distal ablation electrode and the proximal ablation element can each include one or more of the following: an RF ablation electrode, a coiled wire electrode, a laser cut RF electrode, an RF electrode printed with conductive ink, an RF electrode on an inflatable balloon (e.g., conductive ink, flexible circuit), a conductive membrane RF electrode, an RF electrode on an expandable cage or mesh, an ultrasonic ablation transducer, an electroporation electrode, a cryoablation element, or a virtual RF electrode.

[0073] In this regard, the distal ablation element and the proximal ablation element can each be adapted and configured to deliver ablation energy circumferentially to create a circumferential lesion.

[0074] One aspect of the present disclosure is an ablation catheter for transvascular ablation of thoracic splanchnic nerves, in particular for ablation of the greater splanchnic nerve or the greater splanchnic nerve root, comprising: an elongated shaft, the length of which allows the distal section of the elongated shaft to be positioned in the T9, T10 or T11 intercostal vein; and a conductive flexible ablation element carried by the distal section of the elongated shaft, the ablation element having a length of 10 mm to 25 mm; and a radiopaque marker carried by the elongated shaft.

[0075] In this aspect, the distal section of the elongated shaft can have an outer diameter of 1.5 mm to 3 mm.

[0076] In this aspect, the radiopaque marker carried by the elongated shaft can be disposed 0 mm to 5 mm (such as 0 to 4 mm, or 0 to 3 mm, or 0 to 2 mm) from the end of the ablation element. The end can be the distal end of the ablation element. The end can be the distal end of a distal ablation electrode, and the ablation element can further include a proximal ablation electrode axially spaced apart from the distal ablation electrode.

[0077] In this regard, the end can be the proximal end of the ablation element.

[0078] In this aspect, the catheter can further include a second radiopaque marker carried by the elongated shaft and disposed 0 mm to 5 mm (eg, 0 to 4 mm, 0 to 3 mm, or 0 to 2 mm) from the second end of the ablation element.

[0079] In this aspect, the ablation element can include a distal ablation electrode and a proximal ablation electrode. The radiopaque marker can be distal to the distal ablation electrode, wherein the catheter can include a second marker proximal to the proximal ablation electrode.

[0080] In this aspect, the radiopaque marker may be positioned 0 mm to 3 mm, optionally 1 mm from the end of the ablation element.

[0081] In this aspect, the ablation element may include a distal ablation electrode axially spaced apart from a proximal ablation electrode. The distal ablation electrode and the proximal ablation electrode may each have a length, wherein the lengths are the same or wherein the lengths are different. The distal ablation electrode and the proximal ablation electrode may each have a length from 5 mm to 12 mm. The distal ablation electrode and the proximal ablation electrode may be axially spaced 0.1 mm to 5 mm, such as 0.1 mm to 3 mm, optionally 0.5 mm to 1 mm. In this aspect, the distal ablation electrode and the proximal ablation element may be any of the distal ablation electrodes and the proximal ablation elements of the present invention, such as a coiled element. In this aspect, the cross-sectional outer contour of the distal ablation electrode may be different from the cross-sectional outer contour of the proximal ablation electrode. The distal ablation electrode and the proximal ablation electrode may be made of a superelastic material, such as nitinol. The distal ablation electrode and the proximal ablation electrode may be flexible enough to allow the distal region to be advanced from the azygos vein to one of the T9, T10 or T11 intercostal veins.

[0082] In this aspect, the ablation element may not be configured to deploy to an deployed configuration.

[0083] In this aspect, the ablation element can have an operating configuration that is the same or substantially the same as the delivery configuration.

[0084] In this regard, the distal section can have a linear resting configuration.

[0085] In this regard, the outer diameter of the ablation element in the operative state can be the same or substantially the same as the outer diameter in the delivery state.

[0086] In this aspect, the catheter may also include one or more temperature sensors carried by the shaft. The temperature sensor may be disposed at the distal end of the ablation element. The temperature sensor may be disposed at the proximal end of the ablation element. The catheter may also include a second temperature sensor, the temperature sensor may be disposed at or near the distal end of the ablation element, and the second temperature sensor may be disposed at or near the proximal end of the ablation element.

[0087] In this aspect, the catheter can include one or more flushing ports (including any of the one or more flushing ports herein) in fluid communication with a flushing lumen, the flushing lumen being connectable to a source of fluid at a proximal region of the ablation catheter. One of the one or more flushing ports can be axially located between the distal ablation electrode and the proximal ablation electrode. One or more flushing ports can be non-radially disposed below the ablation element structure. One or more flushing ports can be disposed between a winding of a distal ablation electrode and a winding of a proximal ablation electrode, and wherein none of the one or more flushing ports can be radially disposed below the ablation element structure. In a side view, a flushing port can be disposed between each pair of adjacent ablation element spiral segments.

[0088] In this aspect, the ablation element can include a first ablation element and a second ablation element, each of which can be electrically configured to be independently energized in a monopolar mode.

[0089] In this aspect, the ablation element can include a first ablation element and a second ablation element electrically configured to be energized in a bipolar mode.

[0090] In this aspect, the distal section is no more than 7 cm from the distal tip of the ablation catheter.

[0091] In this regard, the ablation element may be adapted to produce ablation having a length in the range of 10 to 25 mm, such as 15 mm to 20 mm.

[0092] In this regard, the distal section can be adapted to flexibly pass through the bend from the azygos vein to the T9, T10, or T11 intercostal vein.

[0093] In this aspect, the catheter can also include a guidewire lumen within the elongated shaft and having a distal port at the distal tip of the catheter.

[0094] In this regard, the ablation element may include one or more of the following: an RF ablation electrode, a coiled wire electrode, a laser cut RF electrode, an RF electrode printed with conductive ink, an RF electrode on an inflatable balloon (e.g., conductive ink, flexible circuit), a conductive membrane RF electrode, an RF electrode on an expandable cage or mesh, an ultrasonic ablation transducer, an electroporation electrode, a cryoablation element, or a virtual RF electrode.

[0095] In this regard, the ablation element can be adapted and configured to deliver ablation energy circumferentially to create circumferential lesions. BRIEF DESCRIPTION OF THE DRAWINGS

[0096] The drawings included herein are used to illustrate various examples of the products, methods, and apparatuses of the present specification and are not intended to limit the scope of the teachings in any way. In the drawings:

[0097] Figure 1 is an isometric view of an ablation catheter positioned in an intercostal vein for ablation of thoracic splanchnic nerves.

[0098] Figure 2 is a schematic lateral view of an ablation catheter positioned in an intercostal vein and the central azygos vein.

[0099] Figure 3 is a schematic lateral view of the anatomy showing the right-sided azygos vein.

[0100] Figure 4 is a schematic lateral view of the anatomy showing the left-sided azygos vein.

[0101] Figure 5is a schematic diagram of the lateral view of the anatomy showing the extent of the azygos vein and the extent of the right GSN.

[0102] Figure 6 is an AP fluoroscopic image of the patient's thoracic region from T8 to T12.

[0103] Figure 7 is a RAO30 fluoroscopic image of the patient's thoracic region from T8 to T12.

[0104] Fig. 8A is a schematic diagram of an ablation catheter with two coiled RF electrodes.

[0105] Figure 8B is a schematic diagram of an ablation catheter having two coiled RF electrodes and a distal expandable element.

[0106] Fig. 9 is a schematic diagram of an ablation catheter having two coiled RF electrodes, a distal expandable element, and a proximal expandable element.

[0107] Fig.10 is a schematic diagram of an ablation catheter having two coiled RF electrodes, a distal expandable element, a proximal expandable element, and a middle expandable element.

[0108] Fig.11 is a schematic diagram of an ablation catheter having an RF electrode including an expandable wire strut.

[0109] Fig.12 is a schematic diagram of an ablation catheter with RF electrodes, the ablation catheter including an expandable balloon with RF electrodes on its surface.

[0110] Fig.13A and Fig. 13B is a schematic diagram of an ablation catheter with RF electrodes, the ablation catheter comprising an expandable balloon having RF electrodes made of conductive ink on its surface.

[0111] Fig.14 is a schematic diagram of an ablation catheter with RF electrodes, the ablation catheter including an expandable balloon having RF electrodes in a zigzag pattern on its surface.

[0112] Fig.15 is a schematic diagram of an ablation catheter having RF electrodes in a lumen defined by a membrane.

[0113] Fig.16 is a schematic diagram of an ablation catheter having multiple RF electrode sections on a tapered shaft.

[0114] Fig.17A and Fig. 17B is a schematic diagram of an ablation catheter with RF electrode pads on an expandable balloon.

[0115] Fig.18 is a schematic diagram of an ablation catheter with an ultrasound transducer. DETAILED DESCRIPTION

[0116] The disclosure herein generally relates to methods for treating at least one of heart failure and hypertension by increasing visceral capacity. Some methods include systems, devices, and methods for transvascular (e.g., transvenous) ablation of target tissue to increase visceral venous capacity or venous compliance. In some examples, the device and method can be used to ablate visceral nerves to increase visceral capacity. For example, the device disclosed herein can be advanced intravascularly to a target vessel or multiple vessels in the thoracic splanchnic nerve ("TSN") region, such as the preganglionic greater splanchnic nerve ("GSN"), the lesser splanchnic nerve, or the smallest splanchnic nerve or one of its roots (TSN nerve roots). The target vessel can be, for example, an intercostal vein or an azygos vein (or both) or a vein of the azygos vein system, preferably one or more of the lowest (i.e., most caudal) three intercostal veins (which can be T9, T10, or T11).

[0117] Figure 1 The thoracic spine of a patient is shown, including the T12 (62), T11 (63), T10 (64) and T9 (65) vertebrae, intervertebral discs, sympathetic trunk 54, azygos vein 50, right T11 intercostal vein 55, right T10 intercostal vein 56, right T9 intercostal vein 66, GSN root 53 and fully formed GSN 52. For simplicity, the visceral nerves and the smallest visceral nerves and their roots are omitted. The primary goal of the proposed procedure is to ablate the GSNs or their roots, as will be discussed in detail herein. Note that ablation of the visceral nerves or the smallest visceral nerves or their roots may also have a therapeutic effect and may be a procedural goal. A delivery sheath 80 is shown as being positioned in the azygos vein and an ablation catheter 81 is shown being delivered through the sheath and from the azygos vein into the T11 intercostal vein. The sympathetic trunks extend generally parallel to the thoracic spine, always proximal to each costovertebral joint 61 (see Figure 2 On the right side of the body, the GSN roots branch off the sympathetic trunk (usually cephalad to the T9 vertebra) and converge to form the GSN, which runs at an angle from the sympathetic trunk toward the anterior center of the thoracic spine and lies anterior to the intercostal veins between the intercostal veins and the parietal pleura 60 (see Figure 2 The azygos vein 50 runs along the front of the thoracic spine and may be slightly straight and parallel to the axis of the thoracic spine, such as Figure 1 However, the exact location of the azygos vein relative to the thoracic spine varies from patient to patient and is located at different vertebral heights. At the T9, T10, and T11 vertebral heights, the azygos vein 50 may be as shown in FIG. Figure 2 The center of the vertebrae 69 is shown as being centered. Figure 3The azygos vein 50R is shown as being to the right of the midline 69 of the vertebrae or may be as shown in FIG. Figure 4 The azygos vein 50L is shown to the left relative to the midline of the vertebra 69. Cadaveric studies performed by the authors have shown that for most individuals, the position of the azygos vein relative to the center of the thoracic spine at the levels of T9, T10, and T11 ranges within 10 mm left or right of center. Figure 5 The left lateral azygos vein 50L, the right lateral azygos vein 50R, and the central azygos vein 50C are shown, as well as the range 67 of the azygos vein relative to the center 69 of the thoracic spine. In addition, the precise location of the right GSN is somewhat variable from patient to patient, including the location of its origin from the sympathetic trunk, the angle at which it travels, and its destination relative to the thoracic spine. Therefore, the location of the GSN relative to the vertebrae at T9, T10, and T11 can vary. Cadaveric studies performed by the authors have shown that the range of the right GSN location relative to the center of the vertebrae at the heights of T9, T10, and T11 is from 0 mm to 25 mm to the right of center 69, as shown in FIG. Figure 5 As shown in the range box 68 in FIG.

[0118] An intravascular method for transvascular ablation of TSNs, particularly GSNs, can involve one or more of the following steps: accessing the venous vasculature at the jugular or femoral vein of the patient using an access introducer sheath (e.g., 12F); delivering a delivery sheath (e.g., 9F sheath) to the azygos vein (e.g., to one or two thoracic levels above the target intercostal vein); optionally, delivering contrast agent through the sheath to visualize the location of the vein under fluoroscopy; optionally, delivering a guidewire (e.g., 0.014 inch guidewire) through the delivery sheath to the target T9, T10, or T11 intercostal vein; and delivering an ablation catheter through the delivery sheath to the azygos vein, optionally positioning an ablation element on the guidewire in the intercostal vein, the azygos vein, or both; and aligning a radiopaque marker on the ablation catheter with (or positioning relative to) an anatomical landmark to position the ablation element in an area that maximizes the efficacy of ablation of the target TSN / GSN while minimizing the risk of damaging one or more non-target structures.

[0119] Some important anatomical structures near this region that should not be damaged include the sympathetic trunk 54, the vagus nerve, the thoracic duct, and the esophagus. Therefore, to ensure safety, the ablation zone should be contained within a safe zone that will not damage such structures. Due to the variability of the position of the azygos vein and the GSN relative to the T9, T10, and T11 vertebrae, the relative position of the GSN relative to the intercostal veins or the azygos vein in which the ablation element is positioned is also variable.

[0120] Bones, blood vessels (if radiopaque contrast agents are injected), and medical devices (if made of radiopaque materials) are visible in fluoroscopy, but nerves are not. An ablation device designed for transvascular (e.g., transvenous) ablation of TSNs (e.g., GSNs) from the intercostal veins, the azygos vein, or both can be provided along with procedural steps to ensure effective ablation of TSNs (e.g., GSNs) while ensuring safety. The procedural steps can include fluoroscopic imaging to locate the ablation element of the ablation catheter relative to the bone or vascular structure.

[0121] In a first embodiment of a method of ablating the right GSN, an ablation catheter having a proximal radiopaque marker 136, a distal radiopaque marker 130, an ablation element 131 or a plurality of ablation elements 132, 133, and an optional gap 135 between the ablation element and the distal radiopaque marker is advanced from the azygos vein 50 into the intercostal vein 55 at one of the lower three thoracic vertebral levels (e.g., T9, T10, T11). The C-arm is placed in an anteroposterior (AP) orientation. The proximal radiopaque marker 136 is aligned with the midline 69 of the vertebra, which is possible if the azygos vein 50 is centered or to the left. If the azygos vein 50 is to the left, the proximal radiopaque marker will need to be advanced into the intercostal vein to align it with the midline 69 of the vertebra. If the azygos vein is to the right, the proximal radiopaque marker 136 will not be placed at the midline 69 of the vertebra. In this case, the proximal radiopaque marker 136 can be placed at the ostium of the intercostal vein, which will be to the right of the midline 69. Optionally, the position of the distal radiopaque marker 130 relative to the costovertebral joints can be assessed (e.g., by a C-arm in RAO orientation) to ensure that the sympathetic trunks are not at risk of injury, such as in very small patients with azygos vein extreme to the right. The C-arm can be angled obliquely to the right (RAO orientation) to maximize the 2D projection of the intercostal vein segments between the costovertebral joints 61 and the anterior vertebral midline 69 ( Figure 7). For example, the C-arm can be positioned at a right anterior oblique (RAO) angle within a range of 20° to 70° from AP (e.g., within a range of 30° to 60°, within a range of 35° to 55°, approximately 30°, an angle that maximizes the projected distance between the proximal RO marker and the distal RO marker). With this view, the user can check to ensure that the distal radiopaque marker is not too close to the costovertebral joint 61. For example, if the distal radiopaque marker is directly distal to the ablation element, a distance of at least 3 mm (e.g., at least 5 mm) can be selected to ensure that the sympathetic trunk is not damaged. In another example, if the distal radiopaque marker is distal to the ablation element with a known space between them, the distal radiopaque marker can be aligned with or proximal to the costovertebral joint to ensure the safety of the sympathetic joint. If the distal radiopaque marker is too close to or beyond the costovertebral joint, the catheter can be pulled back until an acceptable distance between the distal radiopaque marker and the costovertebral joint is seen, which may place the proximal radiopaque marker in the azygos vein, particularly if the azygos vein is off to the right. If the ablation element consists of multiple ablation elements (e.g., two), ablation can be performed first from the more proximal ablation element before pulling back the catheter to properly position the distal radiopaque marker relative to the costovertebral joint. Subsequent ablations can then be performed from the more distal ablation element.

[0122] In a second embodiment of a method of ablating the right GSN, an ablation catheter having a proximal radiopaque marker 136, a distal radiopaque marker 130, an ablation element 131 or multiple ablation elements 132, 133, and an optional gap 135 between the ablation element and the distal radiopaque marker is advanced from the azygos vein 50 into the intercostal vein 55 at one of the lower three thoracic vertebral levels (e.g., T9, T10, T11). The C-arm is placed in an anteroposterior (AP) orientation. The proximal radiopaque marker 136 is aligned with the intercostal vein ostium 59. For example, the ostium can be found by injecting contrast and observing the vasculature under fluoroscopy, or if the guidewire was previously positioned in the target intercostal vein, a bend in the guidewire or ablation catheter can indicate the location of the ostium. If the azygos vein is to the left, the catheter is advanced distal to the ostium to align the proximal radiopaque marker 136 with the midline 69 of the vertebra. In this placement strategy, the proximal radiopaque marker 136 will be aligned with the midline 69 of the vertebra if the azygos vein is to the left or centered, and to the right of the midline of the vertebra if the azygos vein is to the right. At the same time, the proximal radiopaque marker 136 will be aligned with the ostium if the azygos vein is to the right or centered, and at the midline 69 of the vertebra if the azygos vein is to the left. Optionally, the position of the distal radiopaque marker 130 relative to the costovertebral joints can be assessed (e.g., by a C-arm in RAO orientation) to ensure that there is no risk of injury to the sympathetic trunks, such as in patients with very small body size and extremely right-sided azygos veins. The C-arm can be angled obliquely to the right (RAO orientation) to maximize the 2D projection of the intercostal vein segments between the costovertebral joints 61 and the anterior midline 69 of the vertebrae ( Figure 7 ). For example, the C-arm can be positioned at a right anterior oblique (RAO) angle within a range of 20° to 70° from AP (e.g., within a range of 30° to 60°, within a range of 35° to 55°, approximately 30°, an angle that maximizes the projected distance between the proximal RO marker and the distal RO marker). With this view, the user can check to ensure that the distal radiopaque marker is not too close to the costovertebral joint 61. For example, if the distal radiopaque marker is directly distal to the ablation element, a distance of at least 3 mm (e.g., at least 5 mm) can be selected to ensure that the sympathetic trunk is not damaged. In another example, if the distal radiopaque marker is distal to the ablation element with a known space between them, the distal radiopaque marker can be aligned with or proximal to the costovertebral joint to ensure the safety of the sympathetic joint. If the distal radiopaque marker is too close to or beyond the costovertebral joint, the catheter can be pulled back until an acceptable distance between the distal radiopaque marker and the costovertebral joint is seen, which may place the proximal radiopaque marker in the azygos vein, particularly if the azygos vein is off to the right.

[0123] In a third embodiment of a method of ablating the right GSN, an ablation catheter having a distal radiopaque marker 130, an ablation element 131 or a plurality of ablation elements 132, 133, and a gap 135 between the ablation element and the distal radiopaque marker is advanced from the azygos vein 50 into the intercostal vein 55 at one of the lower three thoracic vertebral levels (e.g., T9, T10, T11). The C-arm is angled obliquely to the right to maximize the 2D projection of the intercostal vein segment between the costovertebral joint 61 and the anterior midline 69 of the vertebrae ( Figure 2 For example, the C-arm can be positioned at a right anterior oblique (RAO) angle within a range of 20° to 70° (e.g., within a range of 30° to 60°, within a range of 35° to 55°, approximately 30°, an angle that maximizes the projected distance between the proximal RO marker and the distal RO marker) to AP. Figure 6 A fluoroscopic image in the anteroposterior (AP) view is shown. In contrast, Figure 7Fluoroscopic images at RAO 30° are shown. The catheter is advanced to align the distal radiopaque marker 130 with the costovertebral joint 61. Since the sympathetic trunk 54 is next to the costovertebral joint 61, the gap between the distal radiopaque marker and the ablation element can ensure that the sympathetic trunk is not damaged. The gap can be, for example, a length in the range of 0 mm to 25 mm (e.g., a range of 3 mm to 25 mm, a range of 5 mm to 25 mm, a range of 5 mm to 20 mm). Optionally, an inflatable balloon 134 can be positioned on the catheter shaft within the gap, which can help anchor the catheter or contain ablative energy close to the balloon. Optionally, the catheter shaft 138 distal to the ablation element can be narrower or more flexible than the rest of the shaft to facilitate delivery through the narrower distal portion of the intercostal vein. Optionally, when the distal radiopaque marker is aligned with the costovertebral joint, the ablation element has a length that can be ablated to the anterior midline 69 of the vertebra. For example, the total length of the ablation element can be in the range of 5 to 25 mm (e.g., in the range of 10 to 25 mm, in the range of 15 to 20 mm). The ablation catheter can have a proximal radiopaque marker positioned proximal to the ablation element. Optionally, before delivering ablation energy, the user can image the proximal radiopaque marker to ensure that it is located at the anterior midline 69 of the vertebra. If the proximal radiopaque marker is located to the left of the midline 69, for example if the patient is very small, there may be a risk of damaging non-target tissue (such as the thoracic duct or esophagus). To mitigate this risk, a catheter with a smaller sized ablation element can be used, or if the ablation element is made of multiple ablation elements, only the elements between the midline 69 and the distal radiopaque marker can be activated for ablation. Conversely, if the proximal radiopaque marker is located to the right of the midline 69, for example if the patient is very large, there may be a risk of missing the GSN. To mitigate this risk, another ablation may be performed at another intercostal level or within the same intercostal vein, with the position of the ablation element retracted until the proximal radiopaque marker is aligned with the midline 69 .

[0124] In a fourth embodiment of a method of ablating the right GSN, an ablation catheter having an ablation element 131 that may include multiple ablation elements, a distal radiopaque marker at the distal end of the ablation element, and a proximal radiopaque marker at the proximal end of the ablation element is advanced from the azygos vein to an intercostal vein at one of the lower three thoracic vertebral levels (e.g., T9, T10, T11). The C-arm is angled obliquely to the right to maximize the 2D projection of the intercostal vein segment between the costovertebral joint 61 and the anterior midline 69 of the vertebrae ( Figure 5). For example, the C-arm can be positioned at a right anterior oblique (RAO) angle in the range of 25° to 65° from AP (e.g., in the range of 30° to 60°, in the range of 35° to 55°, approximately 30°). The catheter is advanced to align the distal radiopaque marker with the position relative to the relative edges of the costovertebral joint and the vertebral body in the oblique view. For example, the distal radiopaque marker can be aligned with a midpoint midway between the relative edges of the costovertebral joint and the vertebral body in the oblique view. In most patients, the ablation element can have a total length that is expected to cover the range of GSN positions 68. Similar to the previously described methods, the proximal end of the ablation element can be located at the anterior midline 69 of the vertebra in the case of a centered or partial azygos bone, or on the left side, and can be located in the azygos vein in the case of a partial right azygos vein. Ablative energy from the ablation element can be delivered to ablate the range without moving the catheter. Optionally, the catheter can be moved to another intercostal height and a second ablation can be performed using the same method steps.

[0125] When performing any of the exemplary embodiments of the placement strategies disclosed above, when the total length of the ablation element 131 is less than 30 mm (e.g., less than 25 mm, less than 20 mm, approximately 15 mm), it is expected that in most patients, the sympathetic trunk will not be damaged even if the azygos vein is deviated to the right. In addition, when performing the methods herein, when the total length of the ablation element 131 is greater than or equal to 15 mm, it is expected that in most patients, the GSN will be ablated. Therefore, the total length of the ablation element 131 can be in the range of 15 mm to 30 mm to be effective and safe for most patients using these placement strategies. However, a smaller total length of the ablation element may be appropriate for special patients. For example, the total length of the ablation element can be in the range of 5 to 25 mm (e.g., in the range of 10 to 20 mm, or in the range of 10 to 15 mm).

[0126] As used herein, an ablation element may refer to a single structure or a plurality of structures. For example, as used herein, an ablation element may include a plurality of axially spaced ablation electrodes, and each ablation electrode may be adapted to facilitate delivery of ablation energy.

[0127] Once acceptable ablation element placement is achieved, such as using one of the exemplary embodiments of the placement strategies herein, ablative energy from the ablation element or elements can be delivered without having to move the catheter. Ablative energy from the ablation element can be delivered to ablate tissue circumferentially surrounding the intercostal vein to a depth in the range of 2 mm to 10 mm (e.g., a range of 2 mm to 8 mm, a range of 3 mm to 8 mm, approximately 5 mm). Optionally, the procedure can be repeated at another thoracic vertebral height (e.g., a height closer to the head, a height closer to the tail, another T9, T10, T11 intercostal vein on the same side of the patient), particularly if the azygos vein is to the right. Alternatively or in addition to having distal radiopaque markers and proximal radiopaque markers at both ends of the ablation element or elements, the ablation element itself can be radiopaque, and the same method herein can be used to position the distal end or proximal end of the ablation element relative to anatomical landmarks (e.g., thoracic midline, costovertebral joints, etc.). If the ablation element is radiopaque, the phrase "radiopaque marker" as used herein may therefore describe the ablation element. In some alternative embodiments, the radiopaque marker may include a relatively long radiopaque marker located below or beside one or more ablation elements, wherein the proximal end of the long radiopaque marker is at least aligned with the proximal end of the ablation element or extends up to 3 mm proximal to the ablation element, and the distal end of the long radiopaque marker is at least aligned with the distal end of the ablation element or extends up to 3 mm distal to the ablation element.

[0128] For any of the exemplary embodiments of the placement strategies disclosed above, there may be situations where a portion of the ablation element is in the azygos vein and the remainder is in the intercostal veins, particularly when the ablation catheter has one or more ablation elements with a total length in the range of 10 to 25 mm. The azygos vein is larger than the intercostal veins and has a greater blood flow, which may affect the ability to produce effective ablations around or even in the intercostal veins and may require different energy delivery parameters than ablations performed entirely in the intercostal veins. To address this issue, the ablation catheter may have multiple ablation elements, at least one of which is positioned entirely in the intercostal veins and the remainder may be in the intercostal veins or the azygos veins or both. Different ablation energy delivery parameters may be used for different scenarios, such as higher power or energy may be delivered to ablation elements in the azygos vein, or ablation energy may be delivered only to elements that are located entirely or partially in the intercostal veins. The locations of the multiple ablation elements may be determined by fluorescence imaging or by monitoring the electrical impedance between each ablation element (e.g., an RF electrode) and a dispersive electrode.

[0129] Optionally, two or even three levels may be ablated, particularly if the azygos vein is to the right, but even if the azygos vein is median or left, this may further improve efficacy.

[0130] Alternative devices and methods of use may include a shorter ablation element that is used to create relatively shorter ablations and is repositioned multiple times to create multiple ablations within the GSN location range 68. If the azygos vein is centered or left-lateralized, all ablations can be performed in the intercostal veins 55 and cover the range 68. If the azygos vein is right-lateralized, ablations can be performed in the intercostal veins to cover a portion of the range 68, and then ablations can be performed at another intercostal height to increase the likelihood of ablating the GSN. Alternatively, ablations can be performed from the azygos vein, which can use different energy delivery parameters, such as higher energy or power.

[0131] An ablation catheter suitable for ablating TSNs (e.g., GSNs) from the intercostal veins and / or the azygos vein, for example, using one or more embodiments of the placement strategies disclosed herein, can have features that allow it to be delivered transvascularly to a desired location in the T9, T10, or T11 intercostal veins, features that allow positioning relative to anatomical features to effectively ablate the target TSN while safely avoiding important non-target structures in most patients, and features that allow delivery of ablative energy capable of ablating the target TSN. The ablation catheter and system features can allow a user to ablate TSNs relatively easily and efficiently without sacrificing efficacy or safety. For example, once the ablation element of the catheter is positioned (e.g., using the methods disclosed herein), the ablation energy can be delivered from a computerized ablation console with the push of a button or at least with minimal adjustment, repositioning, dragging, twisting of the catheter, or minimal user decision-making regarding energy delivery. Even given the variability in the location of the GSN 68 and the location of the azygos vein 67 (see FIG. 2 ), the ablation energy can be delivered from a computerized ablation console with minimal adjustment, repositioning, dragging, twisting of the catheter, or minimal user decision-making regarding energy delivery. Figure 5 ), features of the ablation catheters and systems disclosed herein may also allow TSN / GSN to be ablated with a high likelihood of success in most patients from a single placement and energy delivery procedure, or in some cases from an additional placement (e.g., in another of the T9, T10, or T11 intercostal veins) and energy delivery.

[0132] An ablation catheter for transvascular ablation of GSN can have a proximal end, a distal end, and an elongated shaft between the proximal and distal ends, a distal segment (e.g., including the most distal 7 cm) and an ablation element on or at the distal segment. The ablation element can be suitable for producing ablation with a length in the range of 5 mm to 25 mm, preferably 10 to 25 mm (such as 15 mm to 20 mm) and a radial depth of at least 5 mm from the surface of the blood vessel. A handle can be located at the proximal end of the catheter to include an electrical connection or a fluid connection or to facilitate manipulation of the catheter. The elongated shaft can have a length of 100 cm to 140 cm (such as 110 cm to 130 cm, such as about 120 cm) from the strain relief region to the distal head end to allow the distal segment to be delivered from the femoral venous access to the T11 intercostal vein in most human patients, or can have a length of 50 cm to 140 cm to allow the distal segment to be delivered from the jugular venous access to the T11 intercostal vein in most patients. To be deliverable through a 9F delivery sheath, the catheter, at least in its delivery state, can have a maximum outer diameter of 3 mm (e.g., 2.5 mm, 2 mm, 1.5 mm). In some embodiments, the catheter can optionally have an expandable structure that expands beyond this size once advanced from the delivery sheath and positioned in the target vessel. The proximal region of the elongated shaft can be adapted for pushability, kink resistance, torque transmission, and flexibility. For example, the elongated shaft can have wires woven into the outer layer of the shaft from the proximal end to about 7 cm from the distal end. Example materials for the elongated shaft can be extruded The distal section can be adapted to flexibly pass through the bend from the azygos vein to the intercostal vein (e.g., with a radius of curvature of >=5 mm and an angle of up to 120 degrees). For example, by using a material of lower hardness or a more flexible braided outer layer or without a braided outer layer, the distal section (e.g., the most distal 7 cm) can be more flexible than the section of the catheter near the distal section (such as the rest of the elongated shaft). At least in the delivery state, the maximum outer diameter of the distal section can be in the range of 1.5 to 3 mm. The guidewire lumen can pass through the elongated shaft through the outlet port of the distal head end of the shaft. The guidewire lumen can be made of a 0.014 inch ID polyimide tube, for example, located in the lumen of the shaft.

[0133] The ablation catheter can have an ablation element suitable for delivering ablation energy to a target nerve up to 5 mm from the surface of the vessel over a total length in the range of 10 mm to 25 mm (such as 10 mm to 20 mm, such as 15 mm to 20 mm). The ablation element can be made of multiple ablation elements (e.g., two) located in an area of ​​the shaft having a total length in the range of 10 mm to 25 mm (such as 10 mm to 20 mm, such as 15 mm to 20 mm), even if the ablation elements are axially spaced apart. The ablation element can include one or more of an RF ablation electrode, a coiled wire electrode, a laser cut RF electrode, an RF electrode printed with conductive ink, an RF electrode on an expandable balloon (e.g., made of conductive ink or a flexible circuit), a conductive film RF electrode, an RF electrode on an expandable cage or mesh, an ultrasonic ablation transducer, an electroporation electrode, a cryoablation element, or a virtual RF electrode.

[0134] The ablation element can be adapted to deliver ablative energy circumferentially (i.e., radially symmetrically around the ablation element and around the vessel in which the ablation element is positioned). Although the GSN always passes in front of the intercostal veins and the azygos vein, ablating tissue around the intercostal veins or the azygos vein is safe and acceptable, and circumferential ablation can allow for a simpler, faster procedure that is also less prone to user error because there is no need to aim the energy delivery. Features that can allow for circumferential ablation can include, but are not limited to, ablation electrodes that expand to contact the vessel wall uniformly around the circumference of the vessel, ablation electrodes used with a conductive fluid, an electrically insulating balloon, or an expandable structure that contains the ablative energy in a section of the target vessel to allow it to be radially directed, and an ablation element (such as a cylindrical ultrasonic transducer) that directs the ablation energy circumferentially.

[0135] In some embodiments, the ablation element is an RF electrode and saline can be delivered to a blood vessel in fluid communication with the RF electrode. In some embodiments, an irrigation lumen in communication with the irrigation port can be located distal to the ablation element, below the ablation element (in some designs, the irrigation saline can pass through the ablation element), or in the deployable structure. The irrigation lumen can be, for example, a lumen in the elongated shaft that is in fluid communication with a tube on the proximal end of the catheter that can be connected to a fluid source and a pump.

[0136] Optionally, at least one expandable occlusive structure (e.g., a balloon, bellows, wire mesh, wire braid, coated wire mesh, or coated wire braid) can be positioned on the shaft distal to the ablation element. The expandable structure can be used to anchor the catheter in place during energy delivery, and safety may be improved by providing an electrical insulator or including saline proximal to the expandable structure to avoid ablation of the sympathetic trunk. Optionally, the expandable occlusive structure can be located just proximal to the proximal end of the ablation element, which can be used to divert blood flowing in the azygos vein away from the ablation area. For example, the expandable occlusive structure can be a balloon, such as a urethane balloon having a length of about 2.5 mm (along the axis of the shaft) and an expanded diameter of about 2.5 mm to 7 mm (e.g., 3 mm to 6 mm, 4 mm to 5 mm). The balloon can be in fluid communication with an expansion port that connects the balloon to an expansion lumen that can be connected to an expansion source on the proximal end of the catheter. Optionally, the inflation lumen may be in fluid communication with an irrigation lumen connectable to an irrigation source and pump. Optionally, such a catheter may have a balloon with holes that allow irrigation fluid to exit the inflated balloon and flow toward the ablation element.

[0137] The ablation catheter may have a proximal radiopaque marker positioned proximally on the shaft at the proximal end of the ablation element or proximally. Optionally, the ablation catheter may include a distal radiopaque marker positioned distally on the shaft at the distal end of the ablation element or distally. Optionally, there may be a space between the distal radiopaque marker and the distal end of the ablation element, the length of the space being in the range of 0.1 mm to 25 mm (such as 0.1 mm to 5 mm, such as 0.1 mm to 3 mm, such as 0.5 mm, 1 mm or 1.5 mm). For example, Figure 2 As shown, the distal radiopaque marker 130 can be aligned with or positioned relative to an anatomical landmark (such as a costovertebral joint 61), and a space 135 (e.g., 0.1 mm to 25 mm) is located between the distal radiopaque marker 130 and the distal end of the ablation element 132 to ensure that the ablation element is safely away from the sympathetic nerve trunk 54. Optionally, the expandable structure 134 can be positioned in the space, can be converted between a contracted state (OD similar to the shaft OD, for example, in the range of 1.5 mm to 3 mm) and an expanded state (OD increased to a range of 3 mm to 7 mm). The expandable structure can be a balloon, a bellows, a wire mesh, a wire braid, a coated wire mesh, or a coated wire braid.

[0138] Figure 2An example of an ablation catheter sized and suitable for GSN ablation is shown. The ablation catheter 81 has an elongated shaft sized and suitable for reaching the T11 intercostal vein from an introduction site at the femoral vein or jugular vein. The distal section of the catheter 81 (shown as being located in the intercostal vein 55) includes: a distal radiopaque marker 130 aligned with or positioned relative to the costovertebral joint 61; an ablation element 131 including or consisting of a distal conductive coiled RF electrode 132 and a proximal conductive coiled RF electrode 133; an optional inflatable balloon 134 disposed between the ablation element 131 and the distal radiopaque electrode 130. The distal radiopaque marker 130 is optionally spaced apart a distance 135 distally from the distal end of the ablation element 132, the distance 135 being, for example, in the range of 0 to 25 mm (e.g., such as a range of 0.1 mm to 20 mm, such as a range of 0.1 mm to 15 mm, a range of 0.1 mm to 3 mm, such as 0.5 mm, 1 mm, or 1.5 mm). The catheter 81 also includes a proximal radiopaque marker 136 located at or near the proximal edge of the ablation element 131. In some embodiments, the proximal radiopaque marker 136 is axially spaced between 0 mm and 25 mm from the proximal end of the ablation element 31 (which may be from the proximal end of the ablation element 133).

[0139] The exemplary axial distances between markers and electrodes described herein (eg, 0 mm to 25 mm, or 0 mm to 15 mm) may be incorporated into any other ablation catheter described herein unless otherwise indicated herein.

[0140] Ablation electrodes 132 and 133 (or any other ablation electrode herein) can be made of, for example, nitinol wire coiled around a catheter shaft, which can allow the electrodes to be flexible so they can pass through tight bends from the azygos vein to the intercostal veins and also produce long ablations (e.g., 5 to 25 mm). Nitinol is an example of a superelastic material that allows the ablation element to bend when passing through anatomical bends and then elastically return to a linear or straight configuration once the electrode has passed the bend.

[0141] Thus, any distal segment herein may be described as having a static (when manufactured) linear or straight configuration. This would be in contrast to a distal segment that can recover or assume a nonlinear static configuration (e.g., a distal segment having an electrode thereon that returns to a coiled configuration).

[0142] Optionally, the ablation catheter 81 includes at least one flushing port 137 (eg, Figure 2), the irrigation port is in fluid communication with an irrigation lumen near the coil electrode for delivering a fluid such as saline. For example, saline delivery can facilitate delivery or removal of the device, or can be used during energy delivery to improve ablation formation and prevent overheating. Optionally, the catheter 81 can include a guidewire lumen 82 for delivery over the guidewire 79.

[0143] Fig. 8A A portion of an exemplary ablation catheter is shown, including at least a portion of a distal section thereof. Fig. 8A The ablation catheter in the present invention comprises an ablation element, wherein the ablation element comprises a distal ablation element and a proximal ablation element. Fig. 8A As shown, the ablation element (and other ablation elements herein) includes or consists of a distal conductive coiled RF electrode 132 and a proximal conductive coiled RF electrode 133. Both the distal coiled electrode and the proximal coiled electrode can be a spiral coil that surrounds the outer surface of the shaft and is at least partially located on the outer surface of the shaft, optionally located in a groove of the shaft. The coiled electrodes can be spiral and can have varying directions, pitches or wire thicknesses, and can be made of round wire or ribbon wire of a conductive material (such as stainless steel or superelastic nitinol), optionally electropolished, and optionally including a radiopaque material such as platinum iridium. Alternatively, one or more coiled electrodes can be made of a laser cut tube, such as a nitinol tube formed into a coiled pattern or other flexible pattern. Alternatively, the ablation element (e.g., ablation element 131) can be made of a distal flexible electrode and a proximal flexible electrode in the form of a wire mesh or braid. Alternatively, the flexible ablation element can include a plurality of ring electrodes, each ring electrode having a length not exceeding 5 mm, such as 3 mm. Optionally, the flexible ablation element can have an expandable diameter (eg, having an outer diameter of up to about 5 mm) that can be transitioned from a contracted delivery state to an expanded deployed state whereby it can expand to contact a vessel wall.

[0144] The length of the electrodes herein, such as the proximal electrodes and distal electrodes (e.g., the distal electrodes 132 and the proximal electrodes 133) herein, can be in the range of 4 mm to 12 mm (such as 5 mm to 11 mm), and in some embodiments, they are or about 5 mm, 5.5 mm, 6 mm, 6.5 mm, 7 mm, 7.5 mm, 8 mm, 8.5 mm, 9 mm, 9.5 mm, 10 mm, 10.5 mm or 11 mm. The proximal electrodes and the distal electrodes can have the same or substantially the same length, including the length within the range (e.g., 5 mm to 11 mm) provided herein. In some embodiments, the electrodes can have different lengths. For example, in some examples, the distal electrode 132 can be longer than the proximal electrode 133, but the electrode can have any length herein individually. In some examples, the distal electrode 132 can be shorter than the proximal electrode 133, but the electrode can have any length herein individually.

[0145] For catheters with multiple electrodes, each electrode can be connected to a separate conductor that passes through the elongated shaft to the proximal region of the catheter, where it can be connected to an extension cable or a source of ablative energy. This can allow each electrode to be independently powered in either a monopolar mode or a bipolar mode.

[0146] For some catheters with distal electrodes and proximal electrodes, the catheter may include a gap between the distal end of the proximal electrode and the proximal end of the distal electrode. In some embodiments, the gap may be in the range of 0 mm to 5 mm, such as 0 mm to 4 mm, such as 0.1 mm to 1.25 mm, such as 0.25 mm, 0.5 mm, 0.75 mm, 1 mm or 1.25 mm. Preferably, the proximal electrode and the distal electrode do not communicate electrically with each other. Alternatively, the proximal electrode and the distal electrode may overlap each other at least partially along their lengths, as long as they do not communicate electrically with each other.

[0147] The gap between the proximal electrode and the distal electrode can be such that it is not so large as to prevent the formation of continuous ablation lesions. The gap described herein (e.g., 0mm to 5mm, such as 0.1mm to 1.25mm, such as 0.25mm, 0.5mm, 0.75mm, 1mm or 1.25mm) can provide an exemplary benefit of providing continuous lesion formation.

[0148] The ablation catheters herein may include one or more temperature sensors. Fig. 8A An exemplary ablation catheter including at least one temperature sensor is shown. The ablation catheter shown includes, for example, a proximal temperature sensor 139, which can be positioned to contact the proximal electrode 133 and optionally located at the proximal end of the proximal electrode 133. The ablation catheter shown also includes a distal temperature sensor 140, which can be positioned to contact the distal electrode 132 and optionally located on the distal end of the distal electrode. Any ablation catheter herein may optionally include another temperature sensor, which can be positioned between the proximal electrode and the distal electrode or between multiple electrodes. For catheters including one or more temperature sensors, the temperature sensor can be a thermocouple (e.g., T-type) or a thermistor. Optionally, at least one temperature sensor can extend radially from the catheter shaft or can be radially extended to contact tissue up to 3mm from the catheter surface. The temperature sensor can be connected to a computerized energy delivery console at the proximal region of the catheter, where the signal from the sensor can be input and used in the energy delivery control algorithm.

[0149] Any ablation catheter herein may include one or more flushing ports (which may be referred to herein as holes or orifices) in fluid communication with a flushing lumen, which may be connected to a fluid source at a proximal region of the catheter for delivering a fluid such as saline (e.g., saline or hypertonic saline) to a blood vessel. The port may be formed in one or more layers of the elongated shaft to form a fluid connection between the port and the flushing lumen. The fluid may be used to cool the electrode and / or the vessel wall or remove heat from the electrode and / or the vessel wall, flush blood from the vessel to reduce the risk of clot formation or improve ablation consistency, conduct electrical energy from the ablation electrode, control pressure in the vessel, facilitate delivery of the distal segment of the ablation catheter to the target vessel (e.g., an intercostal vein), or facilitate removal of the distal segment of the ablation catheter from the target vessel. Optionally, one or more flushing ports may be distal to the ablation element, or distal to each of a plurality of flexible ablation elements. In some embodiments, any flushing port may be positioned radially below the flexible ablation element. In some embodiments, one or all flushing ports may be disposed between the windings of the coiled ablation element so that the port is not radially located below the windings of the ablation element. Optionally, the irrigation port can be positioned in the axial gap or space between adjacent ablation electrodes. Optionally, one or more irrigation ports can be in the lumen of an expandable occlusive structure (e.g., a balloon) and can be used to inflate the balloon, wherein the balloon can have perforations on its proximal side that allow fluid to escape from the balloon into a target area of ​​the blood vessel.

[0150] FIG. 8A to FIG. 10 The distal section of the ablation catheter is shown, including irrigation ports between the windings of the coiled ablation element (although only one port 137 is labeled, the others can be seen in the figure). FIG. 8A to FIG. 10 In the side view shown, the exemplary ports are aligned linearly, parallel to the long axis of the distal segment. FIG. 8A to FIG. 10 , there are irrigation ports between each pair of adjacent winding materials (even though the coiled elements 132 and 133 are each formed from a continuous winding along their length). A central port 137 between ablation elements may or may not be included. In any embodiment, each port in the distal section may be between windings (in the side view). Alternatively, in any embodiment, no port may be located radially below the winding structure.

[0151] Optionally, the ablation catheter can have an expandable element that can be transformed from a contracted delivery state (e.g., having an OD in the range of 1.5 mm to 3 mm) to an expanded deployed state (e.g., having an OD in the range of 2.5 mm to 6 mm) for one or more of the following: anchoring the distal segment of the catheter in a target area of ​​the vessel, occluding blood flow, containing a delivery fluid such as saline, maintaining vessel patency, or serving as an electrical insulator. For example, Figure 8B As shown, any catheter herein may also include a distal expandable element 134 coupled to an optimized irrigation flow, the expandable element may create a virtual electrode that provides effective ablation without requiring wall contact. The distal expandable element 134 may be such as Figure 8B The balloon shown (eg, a compliant balloon), or alternatively, a bellows or coated stent or mesh. The distal expandable element 134 is distal to the ablation element, and the ablation element may include, for example, Figure 8B The proximal and distal electrodes are shown.

[0152]

[00136] Optionally, any ablation catheter herein may have a proximal expandable element. Fig. 9 An exemplary ablation catheter is shown that includes a proximal expandable element 141 that can be collapsed in a delivery state to have an OD in the range of 1.5 to 3 mm and can be expanded in a deployed state to have an OD in the range of 4 to 10 mm, as shown in FIG. Fig. 9 As shown. The proximal expandable element 141 can be used for one or more of the following: anchoring the distal segment of the catheter in a target area of ​​the vessel, occluding blood flow, containing a delivery fluid such as saline, acting as an electrical insulator, maintaining vessel patency, acting as a depth stopper (e.g., the expanded OD is greater than the target intercostal vein) to prevent the distal segment from being advanced too far into the intercostal vein, or directing blood flow in the azygos vein away from the ostium to facilitate ablation near the ostium. The proximal expandable element and the distal expandable element coupled with an optimized irrigation flow can create a virtual electrode that provides effective ablation without the need for wall contact. The proximal expandable element can be as Fig. 9 The balloon shown (eg, a compliant balloon), or alternatively a bellows or coated stent or mesh. Any catheter herein may include a proximal expandable element and a distal expandable element.

[0153]

[00136] Optionally, any ablation catheter herein may include an intermediate or central expandable element. Fig.10 An exemplary ablation catheter is shown that includes an intermediate expandable element 142 that can be collapsed in a delivery state to have an OD in the range of 1.5 mm to 3 mm and expanded to an expanded state (e.g., having an OD in the range of 2.5 mm to 6 mm), as shown in FIG. Fig.10 The intermediate expandable element can be used for one or more of the following: anchoring the distal segment in a target area of ​​the vessel, occluding blood flow, containing a delivery fluid such as saline, maintaining vessel patency, or acting as an electrical insulator. The intermediate expandable element can be used to isolate the vessel between the distal expandable element and the intermediate expandable element and around the distal ablation element to create a virtual electrode that provides effective ablation without the need for wall contact. Likewise, the vessel segment between the intermediate expandable element and the proximal expandable element can be isolated. The intermediate expandable element can be as shown. Fig.10 The balloon shown (e.g., a compliant balloon), or alternatively a bellows or coated stent or mesh. In embodiments where the ablation energy is electroporation, the middle expandable element can serve as an electrical insulator to direct the current out of the vessel, through the tissue surrounding the vessel to more effectively ablate the target nerve. In alternative embodiments, the ablation catheter can have a middle expandable element and only a distal expandable element (i.e., no proximal expandable element) or only a proximal expandable element (i.e., no distal expandable element).

[0154] The above disclosure describes an exemplary method for positioning an ablation catheter within an intercostal vein to ablate a GSN while minimizing or avoiding damage to non-target structures. Fig. 8A , Figure 8B , Fig. 9 and Fig.10 ) include one or more radiopaque markers (e.g., distal marker 130 and proximal marker 136) that can be used as part of those localization methods. Fig. 8A , Figure 8B , Fig. 9 and Fig.10 The ablation catheter in is an example of an ablation catheter that can be used when performing the method of the present invention, but it should be understood that a variety of ablation catheters can be used to perform the method. Therefore, it should be understood that the method of the present invention is not limited to the specific ablation catheter of the present invention. It should also be understood that the ablation catheter of the present invention does not need to be used with the positioning method of the present invention.

[0155] Alternative embodiments of the TSN / GSN ablation catheter may have one or more of the features described herein, such as proximal and distal radiopaque markers spaced apart, flushing lumens, temperature sensors, guidewire lumens, flexible shaft segments, and may also include alternative ablation elements. For example, the ablation element may be an ablation element having RF electrodes of different configurations or delivering different types of ablation energy (such as ultrasound, electroporation, cryoablation, laser, chemical or other ablation modes). Unless otherwise specified in the present disclosure, the ablation catheter features described with respect to one embodiment or example herein may be incorporated into other suitable embodiments. Features with the same or similar reference numerals are understood to be optionally included and may be the same component.

[0156] For example, Fig.11A distal section of an ablation catheter is shown. The ablation catheter includes an ablation element, which can be an RF electrode, which includes a plurality of wire struts 143 extending along the length of the ablation element and arranged around the circumference of the shaft. The wire struts are conductive, such as made of stainless steel, nitinol, etc., and can be transformed from a contracted delivery state (e.g., having an OD in the range of 1.5mm to 3mm) to an expanded deployed state (e.g., having an OD in the range of 2.5mm to 6mm) to contact the vessel wall, particularly the intercostal veins. The wire struts can be deployed by applying tension to the pullwire (which moves a loop that holds or otherwise affixed to one end of the wire strut), shortening the distance between the two ends (which causes the wire strut to bend outward). The struts can be in an offset configuration (such as Fig.11 Alternatively, the RF electrode may have multiple (e.g., two) RF electrodes made of wire struts, wherein the multiple electrodes are placed adjacent to each other, similar to FIGS. 8 to 9. Fig.10 Alternatively, the wire struts may be made from laser cut tubes. Optionally, the distal end, the proximal end, or both ends of the expandable wire electrode may have a membrane that, when expanded, acts to occlude a blood vessel and is similar to FIG. 8A to FIG. 10 The expandable structure (eg, balloon) shown in FIG.

[0157] Fig.12 An exemplary ablation catheter having an ablation element carried by an expandable balloon is shown. Fig.12 A distal section of an ablation catheter with an RF ablation element is shown, wherein the ablation element includes one or more conductive elements located on an expandable balloon 144. The conductive element can be a film or conductive ink or a flexible circuit. A sensor (e.g., a temperature sensor) can also be positioned on the balloon. Optionally, the balloon can be inflated by delivering a fluid such as saline or air into the balloon. Optionally, the conductive element or balloon can have perforations that allow fluid to pass through to cool the electrode or conduct energy. The pattern of the conductive element can be cylindrical 148 ( Fig.12 ), spiral 149( Fig.13A ), both have a helical configuration 150 ( Fig. 13B ) having a plurality of electrodes, a wavy (eg, sinusoidal) or zigzag pattern 151 ( Fig.14 ) electrodes or other patterns suitable for circumferential ablation around a blood vessel. Figure 12 to Figure 14 The example shown in includes optional distal and proximal radiopaque markers that can be used with any of the localization methods described above.

[0158] Fig.15 Additional exemplary distal sections of ablation catheters are shown, the distal sections including conductive elements within the membrane. Fig.15The catheter in includes an RF ablation element, which is a conductive wire 145 (e.g., a wire coil) located on or around the catheter shaft within a cavity defined by a membrane 185. The membrane can be an ionomer, a conductive membrane, or a liquid-permeable membrane. Optional distal and proximal markers are shown on the distal and proximal sides of the balloon, respectively.

[0159] Fig.16 An example of a distal section of an ablation catheter is shown, which can be used with the positioning method herein. Another embodiment of an RF ablation element is shown in Fig.16 , where the ablation element is a plurality of shorter RF electrodes 146 on a tapered shaft 147. This embodiment differs in that the total length of the shaft carrying the ablation element can be longer than the 5 mm to 25 mm (preferably 10 mm to 15 mm) previously described. Instead, the catheter includes multiple segments (e.g., two or three), each of which has a length within this range but is selectively selected to deliver ablation energy based on how they fit in the intercostal veins. The tapered shaft can be used to fit a range of intercostal veins (e.g., in the range of 2.5 mm to 5 mm). The distal end is narrower than the proximal end, and the electrodes can be independently and selectively energized. If the distal segment of the catheter is delivered to a relatively narrow intercostal vein (e.g., having an inner diameter of approximately 2.5 mm), the distal narrow portion can be advanced into the vein and selected for energy delivery, while the proximal larger portion can remain in the azygos vein and not used to deliver ablation energy. If the intercostal vein is large, for example, with an inner diameter of 5 mm, the distal segment can be further advanced into the intercostal vein until the larger electrode wedges into the vessel and contacts the wall. A larger proximal electrode can be selected for energy delivery, while the distal electrode is inactive to avoid damaging the sympathetic trunk. Optionally, the size of the middle segment of the electrode can be designed to fit the intercostal vein with an inner diameter of about 3.5 mm. The multiple electrodes can be coiled wires, laser cut tubes, or solid electrodes. The electrodes can be radiopaque or have radiopaque markers associated therewith, so the user can image the location of the electrode in the intercostal vein and select the electrode segment to be activated.

[0160] Another embodiment of a transvascular ablation catheter 241 for ablating TSN or GSN from within an intercostal nerve is described in Fig.17A. The catheter 241 can extend along the longitudinal axis. An expandable member (e.g., in the form of a balloon 242 having an unexpanded state and an expanded state) can be connected to the distal section 243 of the catheter. The expandable member (e.g., a balloon) can have a circumferential treatment area 248 (e.g., a length in the range of 5mm to 25mm, in the range of 10mm to 15mm) extending along the longitudinal axis and surrounding the blood vessel 55 in the expanded state. The catheter includes an electrode assembly 252, which includes a plurality of electrode pads 244 and can be mounted or otherwise fixed to the balloon 242. Each electrode pad assembly may include a substrate supporting a first electrode pad and a second electrode pad, each electrode pad having a pair of elongated bipolar electrodes and connected to an electrical trace 249. The electrode pads of each electrode pad assembly can be offset longitudinally and circumferentially from each other. The method may also include inflating a balloon in the intercostal vein to electrically couple the electrode 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 to redistribute the patient's blood volume to treat a condition such as pulmonary hypertension or heart failure (e.g., HFpEF).

[0161] Each electrode pad may include a temperature sensor disposed between the pair of electrodes. The expansion of the balloon may couple the temperature sensor to the 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 so as to substantially uniformly heat the wall.

[0162] To produce ablation to a depth of 5 mm to target GSNs from the intercostal veins, the electrode pads may be cooled to allow for greater power to be delivered without drying out the tissue of the vein wall, which would impede ablation depth. For example, the electrodes may be cooled by circulating a coolant in the balloon 242. In one embodiment, coolant may be injected into the balloon 242 from a coolant injection port 246 at one end of the balloon chamber, and the coolant may exit the chamber through an outlet port 247 at the opposite end of the chamber and allowed to return through the catheter through the outlet lumen.

[0163] In another embodiment, the coolant can be deposited into the blood stream rather than returning through a lumen in the catheter. This embodiment can allow for a thinner, more flexible catheter shaft or a larger coolant delivery lumen to increase the flow of the coolant. The coolant outlet port can be smaller than the coolant injection port to allow for increased pressure in the balloon to inflate it. The coolant outlet port can be in communication with a lumen that does not pass through the entire catheter shaft to the proximal end but passes through to the distal end of the catheter to deposit coolant (e.g., saline) into the intercostal veins. Optionally, the coolant outlet lumen can be the same lumen as the guidewire delivery lumen.

[0164] The electrode pads can be positioned around the balloon to form a circumferential ablation pattern as long as the target ablation area 58 (e.g., up to 20 mm, about 15 mm, between 12 and 18 mm). Fig. 17B As shown, a balloon having electrode pads mounted to an elongated shaft 253 can have an undeployed state having a diameter of about 1 mm to 2.5 mm and a circumference of about 3.14 mm to 7.85 mm, and can be expanded to a deployed state having a diameter in the range of about 3 mm to 5 mm and a circumference in the range of about 9.4 mm to 15.7 mm. The electrode pads 244 can be separated or 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 mm to 3.5 mm. The electrode pads 244 can each have a length of about 3 to 5 mm. As shown Fig.17A As shown, the electrode pad assembly 252 may include a plurality of electrode pads 244 connected together by electrical traces 249 and arranged in four separate rows, which are evenly spaced around the periphery of the balloon 242 (e.g., four rows per 90 degree quadrant). Longitudinally, the pads 244 on one row may be offset from the pads of an adjacent row. When the balloon is in an unexpanded state, the space between the electrode pads is reduced (e.g., reduced to about 0 to 1 mm) and adjacent rows are interlocked with each other. In its expanded state, the space 250 between the pads is expanded to about 2 mm to 5 mm due to the expandable balloon 242. The balloon 242 may be a compliant material, such as latex or a non-compliant material that is flexibly folded to shrink.

[0165] Alternatively, the electrode pads may be positioned on only one side (e.g., 50%, 40%, 30%, 25% of the balloon circumference) to produce a directional ablation pattern that is all toward the same side and has the length of the target ablation area 58. For a directional ablation catheter, a radiopaque marker may be positioned on the distal section of the catheter to indicate the radial direction. For example, the radiopaque marker may be asymmetric and may be positioned on the same side or on the opposite side as the directional electrode pads to indicate and in use, the physician may twist the catheter to aim the radiopaque marker, thereby moving the electrode pads away from the vertebrae, which are always toward the GSN. Fig.17A Several small electrode pads are shown. Alternatively, the device can have more or fewer electrode pads, such as two or three directional electrode pads (e.g., 3 to 5 mm long) on ​​the same side of the balloon that span the target ablation area 58. The gaps between the electrode pads (e.g., 1 to 3 mm) can facilitate bending of the device to cross from the azygos vein to the intercostal veins. Fig.17A and Fig. 17B The ablation catheter in may include proximal and / or distal radiopaque markers and may be used with the positioning methods described herein.

[0166] Just proximal to the balloon, the catheter shaft may include a flexible neck 245 that allows the ablation balloon to be positioned in a natural orientation in the intercostal veins. Given the small bend radius at this location, a rigid shaft may exert forces on the ablation balloon, causing it to distort the intercostal veins and reduce the predictability of the ablation zone. The flexible neck may be made of a softer durometer polymer (e.g., ) and can embed a wire coil in the material, which can allow flexible bending while providing pushability. This type of flexible neck can be incorporated into other ablation catheters herein.

[0167] The most proximal electrode can be placed just in the intercostal vein near the mouth. Blood flow through the azygos vein may metabolically cool tissue near it, thereby hindering the production of ablation. A greater amount of ablation power (e.g., RF) or a longer duration can be delivered to this proximal electrode compared to the rest of the electrode to compensate for blood flow cooling.

[0168] The catheter 241 can have a distal radiopaque marker 255 positioned distal to the ablation element, for example, distal to the balloon 242, and / or a proximal radiopaque marker 254 positioned proximal to the ablation element 244, for example, proximal to the balloon 242. The distal radiopaque marker 255 and the proximal radiopaque marker 254 can be separated by a distance in the range of 5 mm to 25 mm (e.g., 10 mm to 15 mm) along the longitudinal axis of the shaft. Any other features or descriptions of radiopaque markers herein can be applied to markers 255 and / or 254.

[0169] Fig.18An exemplary ultrasonic ablation catheter is shown. The catheter 220 includes an elongated shaft 225 having a proximal region and a distal section and an ablation assembly 232 mounted to or at the distal section. The ultrasonic ablation catheter 220 has an expandable balloon 221, which can have a geometry suitable for expansion in an intercostal vein (e.g., an outer diameter 222 in its expanded state in the range of 2.5 to 5 mm) and a length 223 in the range of 8 to 30 mm. Within the balloon 221, a plurality of ultrasonic transducers 224 are positioned on a shaft 233 in the center of the balloon 221. The transducers 224 can be placed in series across a length 226 in the range of 5 to 25 mm to produce ablation of similar lengths capable of producing ablation of the length of the target ablation zone 58. Due to the small diameter of the intercostal veins, a reduced balloon size may risk contacting the transducer or being overheated by the transducer, which may rupture the balloon or reduce the efficiency of the ablation. To eliminate this risk, a support or protrusion 227 can be positioned between the transducer and the balloon. Support 227 can be, for example, a preformed polymer strand of elasticity to radially expand away from transducer 224. In order to perform a longer ablation to span the target ablation area, multiple transducers (e.g., three 4 mm long transducers) can be incorporated and spaced apart with flexible gaps 228 between them to facilitate passing through a small bending radius from the azygos vein to the intercostal vein. For example, shaft 225 can be a braided reinforced polyimide tube with an optional guidewire lumen 229 to deliver on guidewire 79, and carries an electrical conductor that powers transducer 224. Ultrasonic transducer 224 can be cylindrical for producing circumferential ablation around the target vein. Alternatively, the ultrasound transducer can be flat or semi-cylindrical to produce ablation as a partial segment of the periphery of the vein, and a radially identifiable radiopaque marker 230 can be positioned on the distal segment to allow the user to orient the ablation direction toward the front of the patient (where the GSN passes over the vein 55). Optionally, the ultrasound transducer can be configured for imaging as well as ablation, and the imaging function can be used to assess nearby structures such as the lungs, vertebrae, and ribs. Imaging ultrasound can be used to confirm that the transducer is aimed at the lungs, which is the direction of the target GSN. Optionally, the shaft can have a flexible neck 231 within 10 mm proximal to the balloon 221 to allow the distal segment to be well positioned in the intercostal veins.

[0170] In an alternative embodiment of an ultrasonic ablation catheter, the catheter can be composed of an active ultrasonic transducer and an inflatable reflective balloon, which can be on the same catheter or alternatively on a separate catheter. The reflective balloon can have an inflated diameter in the range of 2.5 to 4 mm and have a shape such as a concave curvature on its proximal surface that focuses the reflected waves to the target ablation area. The reflective balloon is located distal to the transducer and inserted into the narrower intercostal vein, while the ultrasonic transducer remains in the larger azygos vein. The ultrasonic transducer can be exposed to the blood flow in the azygos vein, or alternatively can be contained in a chamber filled with a coolant (e.g., a circulating coolant, such as sterile water or saline) in an inflatable balloon. Ultrasonic energy is directed to the distal reflective balloon and reflected and focused into the tissue surrounding the visceral nerves. The advantage of this approach is that the active ultrasonic transducer can be made larger and does not need to pass through a sharp bend from the azygos vein to the intercostal vein. The second advantage is that several intercostal veins can be used for targeted ablation using the same catheter.

[0171] The catheter 220 can have a distal radiopaque marker 230 located distally of the ablation element, e.g., distally of the balloon 221, and a proximal radiopaque marker located proximally of the ablation element, e.g., proximally of the balloon. The distal and proximal radiopaque markers can be separated by a distance in the range of 5 mm to 25 mm (e.g., 10 mm to 15 mm) along the longitudinal axis of the shaft.

[0172] FIG. 8A to FIG. 10 Exemplary ablation catheters are shown. The ablation catheters in these examples include an ablation element that includes a first flexible coiled ablation electrode and a second flexible coiled ablation electrode that are axially spaced apart. It may be beneficial to have first and second electrodes rather than a single longer electrode to avoid the tendency of a single longer electrode to heat tissue primarily toward one end of the electrode. Thus, having more than one electrode can help produce long and consistent ablations in tissue. FIG. 8A to FIG. 10 It is therefore an example of an ablation catheter that can more consistently produce continuous ablations of a desired length, such as 10 mm to 25 mm, such as 15 mm to 25 mm, such as 15 mm to 20 mm.

[0173] An additional exemplary benefit of having first and second electrodes is that only a single relatively short electrode can be energized instead of a single longer electrode, as compared to a single longer electrode. This may be advantageous when the patient's anatomy requires or may benefit from a shorter ablation (e.g., the azygos vein is centered). In these cases, a longer single electrode may make it difficult or dangerous to safely ablate tissue while avoiding non-target structures. This is described in more detail elsewhere herein.

[0174] in addition, FIG. 8A to FIG. 10An ablation catheter is shown having first and second ablation elements axially separated by a gap or spacing. The gap is small enough (ie, not too large) to allow a continuous lesion to form when the first and second ablation elements are energized, but large enough to avoid shorting.

[0175] The ablation catheters herein (eg, FIG. 8A to FIG. 10 )'s design features thus provide an exemplary benefit by allowing the distal segment to be advanced into position within an intercostal vein and reliably produce continuous ablation of at least 10 mm to 25 mm in length, while allowing shorter ablation segments when desired depending on the patient's anatomy.

[0176] In some methods of use, the ablation energy is RF, and the energy delivery controller is adapted to deliver RF power in the range of 15 W to 50 W. In some embodiments, the controller is adapted to deliver RF power in the range of 15 W to 40 W, in the range of 15 W to 35 W, or in the range of 20 W to 35 W, such as about 25 W, about 30 W, or about 35 W.

[0177] In some methods of use, energy is delivered over a period of time between 25 seconds and 120 seconds. For example, energy can be delivered for 90 seconds, 100 seconds, 110 seconds, or 120 seconds, wherein for a portion (e.g., half) of the period, energy can be delivered to the first electrode, and for the remainder (e.g., half) of the period, energy can be delivered to the second electrode.

[0178] In some methods of use, the flushing flow rate is 10mL / min to 20mL / min, such as 10mL / min, 15mL / min or 20mL / min. Using 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 of the method of use embodiments herein can temporarily block blood flow and reduce the effects of venous collapse, thereby advantageously avoiding the challenges of changing thermal and electrical environments during the heating process. Some of the method of use embodiments herein can ablate nerves up to 5mm from the target vessel. Some of the devices herein are sized and configured for delivery and positioning in the vasculature designated for ablation of target nerves (e.g., TSNs, GSNs).

[0179] Some devices herein may have one or more features that provide for safe delivery to a target vessel.

[0180] Some devices and methods of use herein can safely deliver energy through temperature monitored energy delivery.

[0181] Some of the methods of use herein can produce damage to nerves that are targeted up to 5 mm from a target vessel and within a target area having continuous damage lengths from 5 mm to 25 mm, such as 10 mm to 25 mm, such as 15 mm to 20 mm (e.g., 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm) through a single positioning and energy delivery.

[0182] Some devices and methods herein are adapted to avoid the risk of boiling, hot spots, or erratic energy delivery that may reduce ablation efficacy. In addition, some embodiments may include nerve stimulation to identify target or non-target nerves to confirm localization prior to ablation, or to confirm technical success during or after ablation.

[0183] It may be preferred, but not required, for the ablation method to produce a continuous ablation zone (i.e., not having separate, discrete ablation tissue regions that are not connected to each other). This ensures that the tissue region where the target GSN nerve or GSN nerve root may be located is most likely to be effectively ablated by the ablation energy. The continuous ablation zone can be circumferential, or less circumferential.

[0184] Optionally, an ablation confirmation test may then be performed, for example, by delivering a neural stimulation signal. The physiological responses to the ablation confirmation test (e.g., splanchnic vasoconstriction, increased heart rate, increased blood pressure) may be monitored. If the physiological response indicates that the first lesion does not provide a clinically significant amount of GSN blockade (e.g., by observing a lack of physiological response), ablation energy from the ablation catheter may be delivered to produce a second lesion in tissue up to 5 mm from the second intercostal vein. The distal segment of the ablation catheter may be moved to a third intercostal vein that is superior to (e.g., superior to and adjacent to) the second intercostal vein. The same or different ablation confirmation test may be performed, followed by another monitoring test. If the physiological response indicates that the first lesion and the second lesion do not provide a clinically significant amount of GSN blockade (e.g., by observing a lack of physiological response), ablation energy from the ablation catheter may be delivered to produce a third lesion in tissue up to 5 mm from the third intercostal vein. Any ablation confirmation test may include delivering a neural stimulation signal from a stimulation electrode positioned on the distal segment of the ablation catheter, the stimulation electrode being configured to produce an action potential in a 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 fluid volume to the venous system.Alternatively or additionally, the ablation confirmation test may include a hand grip test.Alternatively or additionally, the ablation confirmation test may include measuring venous compliance or capacity.

[0185] In an exemplary method in which the ablation confirmation test includes a leg raise 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 raising the leg and measuring the change in central venous pressure and waiting for equilibrium (i.e., a measure of the total venous compliance including the central vein and the visceral bed). The leg may then be lowered to allow equilibrium so that blood is redistributed back to the leg. Ablation in the lowest intercostal vein (e.g., T11) may then be performed as described herein. The leg may then be raised, then wait for equilibrium and remeasure the central venous pressure. Measurements may then be taken to determine if there is an appropriate reduction in total venous compliance. If yes, the GSN has been successfully ablated. If no, ablation may be performed in the next higher intercostal vein (e.g., T10) as described herein. The measurements may be repeated. It may then be determined if there is an appropriate reduction in total venous compliance. If yes, the GSN has been successfully ablated. If no, ablation may be performed in the next higher intercostal vein (e.g., T9).

[0186] In an exemplary method in which the ablation confirmation test includes a hand grip or other activity that increases sympathetic nervous system (SNS) outflow to the visceral bed, the following steps may be included. An ablation may be performed in the lowest intercostal vein (e.g., T11). The vein compliance may then be measured. The hand grip may then be performed for a predetermined amount of time (e.g., 60 seconds). The vein compliance may then be remeasured. If the vein compliance does not change, the initial ablation was sufficient to achieve a clinically significant result. If the compliance still decreases, some SNS activity induced by the hand grip is ongoing. Therefore, the ablation in the lowest intercostal vein was insufficient to achieve a clinically significant effect. An ablation may then be performed in the next higher intercostal vein (e.g., T10). A hand grip test may be performed for a predetermined amount of time (e.g., 60 seconds). The vein compliance may then be remeasured. If the compliance does not change, the second ablation is sufficient. If the compliance decreases, some SNS activity induced by the hand grip is ongoing, and therefore the ablation in the next higher intercostal vein is insufficient to achieve a clinically significant effect. An ablation may then be performed in the next higher intercostal vein (T9). Since ablation was not expected to be performed at a level higher than the 3rd lowest intercostal vein, the procedure was completed at this time.

[0187] In any of the methods herein (including the ablation confirmation tests herein), not all steps need to be performed. And certain steps may occur in a different order. Note that the procedures herein are intended to target specific nerves or nerve roots, and to do so from specific target veins, and to place ablation elements or members in certain areas even within these veins. The anatomical regions being reached and targeted require certain design requirements. In other treatments that are placed at different anatomical locations and target different target nerves, the device design constraints for these methods are very different, and therefore the devices that can be used for these treatments may be very different. Therefore, the disclosure herein provides specific reasons for designing specific devices, and these reasons include being able to effectively perform the treatments specifically described herein.

[0188] Although the above description provides examples of one or more processes or apparatuses, it should be understood that other processes or apparatuses may be within the scope of the appended claims.

[0189] To the extent that any modification, characterization, or other statement made previously (in this patent application or any related patent application or patent, including any parent case, family, or divisional case) regarding any prior or other art can be construed as a disclaimer of any subject matter supported by the present disclosure of this application, applicant hereby revokes and withdraws such disclaimer. Applicant also respectfully submits that any prior art previously considered in any related patent application or patent (including any parent case, family, or divisional case) may need to be revisited.

[0190] The specific embodiments described herein are not intended to limit any claims and any claims may cover processes or devices different from those described below, unless otherwise expressly noted. Unless otherwise specifically noted, claims are not limited to devices or processes having all the features of any device or process described below, or are not limited to features common to multiple or all devices described below. The devices or processes described below may not be embodiments of any exclusive rights granted by the publication of this patent application. Any subject matter described below and the subject matter of which the patent application does not publish the exclusive rights granted may be the subject matter of another protective instrument (e.g., a continuing patent application), and the applicant, inventor, or owner does not intend to abandon, deny, or donate any such subject matter to the public through the disclosure in this document.

[0191] Additional Examples

[0192] A first additional example is a method of characterizing a position of a patient's azygos vein relative to a portion of the patient's spine, comprising: simultaneously imaging at least a portion of the patient's spine; delivering a device intravascularly into the patient's azygos vein; performing at least one of the following: injecting a radiopaque contrast agent (e.g., a dye) from the device into the patient's vasculature (e.g., into the azygos vein and / or one or more intercostal veins) to visualize the vasculature relative to the position of the spine, or identifying the position of at least a portion of the device relative to a portion of the spine, thereby characterizing (e.g., defining and / or quantifying) the position of the patient's azygos vein relative to a portion of the spine (e.g., relative to the midline of the spine).

[0193] In this first additional example, imaging may include imaging in anterior-posterior views.

[0194] This first additional example can further include determining a lateral position of the patient's azygos vein relative to the patient's spine at which the azygos vein intersects the intercostal veins. The lateral position of the patient's azygos vein can be determined while imaging the patient's azygos vein. Imaging can include radiographic imaging (e.g., fluoroscopy) after injecting a radiopaque contrast agent (e.g., dye) from the device into the patient's vasculature. Determining the lateral position can be used to determine where to place an ablation catheter relative to the intercostal veins as part of an ablation procedure (optionally ablating the GSN).

[0195] A second additional example is a method that includes assessing the position of a patient's azygos vein to determine whether it is centered, dextrorectal (to the right of the patient's center), or levorectal (to the left of the patient's center). The position of the patient's azygos vein can be assessed while imaging the patient's azygos vein. Imaging can include radiographic imaging (e.g., fluoroscopy). Imaging can include imaging in anterior-posterior views. Assessing the position can be used to determine where to place an ablation catheter as part of an ablation procedure (optionally intended to ablate the GSN).

[0196] In this second additional example, the evaluating step may be used to determine where to place a radiopaque marker (optionally a proximal radiopaque marker) of an ablation catheter, wherein the ablation catheter includes an ablation element distal to the radiopaque marker.

[0197] In this second additional example, the evaluating step is used to determine whether to place the radiopaque marker at the ostium where the azygos vein intersects the intercostal veins or at (including substantially at) the midline of the spine.

[0198] In this second additional example, if the evaluating step indicates that the azygos vein is right-sided or centered (including substantially centered), the method may include positioning a radiopaque marker at the ostium where the azygos vein intersects the intercostal veins.

[0199] In this second additional example, if the evaluating step indicates that the azygos vein is deviated to the left, the method may include positioning the radiopaque marker at or substantially at the midline of the spine (eg, as determined in an anteroposterior imaging view).

[0200] In this second additional example, the evaluating step can be used to determine where to place an ablation element (eg, one or more electrodes) that is part of an ablation catheter.

[0201] In this second additional example, the method can further include evaluating the position of the distal radiopaque marker relative to at least one or more of a portion of the spine, a rib, or a costovertebral joint. The method can further include retracting the ablation catheter proximally if the evaluation indicates that the distal radiopaque marker is positioned too far distally (thereby indicating that the ablation element is positioned too far distally). The method can further ensure that the distal radiopaque marker is not further distally than the costovertebral joint.

[0202] A third additional example is a method for intravascularly positioning an ablation catheter for GSN ablation, comprising: positioning the ablation catheter in one or more of an intercostal vein (e.g., T9, T10, or T11) and an azygos vein, wherein the position of the ablation catheter is selected based on a characterized relative position of a portion of the spine and a location where the azygos vein intersects the intercostal vein.

[0203] A fourth additional example is a method for characterizing the position of a distal segment of an ablation catheter to facilitate placement of at least a portion of the ablation catheter in an intercostal vein, comprising: positioning the ablation catheter in an intercostal vein of a patient (e.g., a T9, T10, or T11 intercostal vein); simultaneously imaging a portion of the patient including the intercostal vein and a portion of the spine to determine the position of one or more components of the ablation catheter relative to a portion of the spine, a rib, or one or more of the costovertebral joints.

[0204] A fifth additional example is the method of any claim herein comprising accessing the venous vasculature at the jugular or femoral vein of the patient using an access introducer sheath (eg, 12F).

[0205] A sixth additional example is the method of any of the claims herein, comprising delivering a delivery sheath (eg, a 9F sheath) to the azygos vein (eg, to one or two thoracic vertebral levels above the target intercostal space).

[0206] A seventh additional example is the method of any of the claims herein, comprising delivering a contrast agent to show the location of the azygos vein and one or more intercostal veins, while imaging the azygos vein and one or more intercostal veins.

[0207] Any additional examples may include an imaging step that includes imaging in an anterior-posterior direction (eg, when the C-arm is in the AP position).

[0208] Any additional examples may include positioning the C-arm in a right anterior tilt angle.

[0209] Any additional examples may include positioning the C-arm within a range of 20 degrees to 70 degrees, such as 30 degrees to 60 degrees.

[0210] Any additional examples may include positioning the C-arm at an angle that maximizes a projected distance between first and second axially spaced locations on the ablation catheter (eg, locations of proximal and distal radiopaque markers).

[0211] Any additional examples may include evaluating whether a RO marker (eg, a distal RO marker) is located at or near a particular anatomical location (eg, a costovertebral joint).

[0212] Any additional examples may include, if the marker is at or near a particular anatomical location, continuing the ablation procedure (e.g., ablating tissue). If the marker is not at or near a particular anatomical location, the method may include moving the ablation catheter within an intercostal vein. If the marker is not at or near a particular anatomical location, the method may include generating ablation energy within a proximal ablation element (e.g., a coil electrode) rather than within a distal ablation element (e.g., a coil electrode).

[0213] An eighth additional example is an ablation catheter sized and configured such that a distal segment of the ablation catheter can be advanced from the azygos vein into a T9, T10, or T11 intercostal vein and suitable for delivering ablation energy, comprising: an elongated shaft having a length such that the distal segment of the catheter can be positioned in a T9, T10, or T11 intercostal vein; and a distal segment comprising a conductive, flexible ablation element carried by the elongated shaft, the conductive, flexible ablation element (which may include more than one ablation element) having a length of 5 mm to 20 mm, and the distal segment having an OD of 1.5 mm to 3 mm (at least in the delivery configuration).

[0214] A ninth additional example is an ablation catheter, the dimensions of which are designed and configured such that a distal section of the ablation catheter can be advanced from the azygos vein into a T9, T10 or T11 intercostal vein and is suitable for delivering ablation energy, comprising: an elongated shaft having a length such that the distal section of the catheter can be positioned in a T9, T10 or T11 intercostal vein; and a distal section comprising a conductive flexible ablation element carried by the elongated shaft.

[0215] In this ninth additional example, the ablation element can include a first ablation element axially spaced apart from a second ablation element, the first ablation element and the second ablation element being carried by an axis. The first ablation element can have a coiled configuration, and wherein the second ablation element can have a coiled configuration. The coiled configuration of the first ablation element can be identical in all respects to the coiled configuration of the second ablation element. The coiled configuration of the first ablation element can differ from the coiled configuration of the second ablation element in at least one aspect.

[0216] In this ninth additional example, the first ablation element can have a different length than the second ablation element.

[0217] In this ninth additional example, the first ablation element can have a different coil orientation (eg, left-handed versus right-handed) than the second ablation element.

[0218] In this ninth additional example, the first ablation element can have a different pitch than the second ablation element.

[0219] In this ninth additional example, the first ablation element can have a different filament thickness than the second ablation element.

[0220] In this ninth additional example, the OD of the distal segment at the location of the first ablation element can be different than the OD of the distal segment at the location of the second ablation element.

[0221] In this ninth additional example, the first ablation element and the second ablation element can each have a curved (eg, circular) or a rectilinear (eg, rectangular) cross-sectional outer profile.

[0222] In this ninth additional example, the first ablation element and the second ablation element can be a superelastic material, such as Nitinol.

[0223] In this ninth additional example, the first and second ablation elements can be sufficiently flexible to allow the distal segments to be advanced from the azygos vein to one of the T9, T10, or T11 intercostal veins.

[0224] In this ninth additional example, at least one of the first ablation element and the second ablation element can be made from a laser cut tubular element, such as a nitinol tube.

[0225] In this ninth additional example, at least one of the first ablation element and the second ablation element can include a mesh or a braid.

[0226] In this ninth additional example, at least one of the first ablation element and the second ablation element can be a ring electrode having a length of no more than 5 mm, optionally approximately 3 mm.

[0227] In this ninth additional example, each of the first and second ablation elements can have a length of 1 mm to 12 mm, optionally 2 mm to 12 mm, optionally 5 mm to 12 mm, optionally 6 mm to 11 mm, optionally 7 mm to 10 mm, such as approximately 8 mm.

[0228] In this ninth additional example, the axial spacing between the first ablation element and the second ablation element can be 0 mm to 8 mm, such as 0 mm to 5 mm, such as 0.5 mm to 5 mm, such as 1 mm to 4 mm.

[0229] In this ninth additional example, the total axial length of the ablation element can be 1 mm to 25 mm, optionally 2 mm to 22 mm, optionally 5 mm to 20 mm, optionally 8 mm to 20 mm, optionally 10 mm to 20 mm, optionally 10 mm to 18 mm, optionally, preferably 10 mm to 15 mm.

[0230] In this ninth additional example, the ablation element and optionally both the first ablation element and the second ablation element can have an expandable diameter.

[0231] In this ninth additional example, the ablation element can include a plurality of ablation elements, wherein the first ablation element and the second ablation element can be part of and can define an entirety of the plurality of ablation elements.

[0232] In this ninth additional example, multiple ablation elements can be configured to be independently energized in a monopolar mode (with a ground pad).

[0233] In this ninth additional example, any two of the plurality of ablation elements may be configured to be energized in a bipolar mode.

[0234] In this ninth additional example, the catheter can include a temperature sensor disposed between the first ablation element and the second ablation element and carried by the shaft.

[0235] In this ninth additional example, the catheter can further include one or more of a temperature sensor distal to the distal ablation element or a temperature sensor proximal to the proximal ablation element.

[0236] In this ninth additional example, the catheter can include at least one irrigation port in fluid communication with an irrigation lumen connectable to a fluid source at a proximal region of the ablation catheter.The ablation catheter can further include a second irrigation port distal to the proximal ablation element.

[0237] In this ninth additional example, the catheter can include one or more irrigation ports located between the distal and proximal ends of the distal ablation member, optionally between windings of the coiled distal ablation member.

[0238] In this ninth additional example, the catheter can include one or more irrigation ports located between the distal and proximal ends of the proximal ablation member, optionally between windings of the coiled proximal ablation member.

[0239] In this ninth additional example, the catheter can include one or more flushing ports beneath any flexible ablation elements, such as the distal ablation element and / or the proximal ablation member.

[0240] In this ninth additional example, the catheter may further include an expandable element (optionally expandable) carried by the shaft. The expandable element may be distal to the ablation element, optionally distal to the distal ablation element. The expandable element may be expandable, and wherein the shaft may include an expansion port within the expandable expandable element. The expandable element may have a delivery configuration and an expanded configuration having an OD greater than the delivery configuration. The expandable element may have an outer diameter of 3-6 mm in the expanded configuration, such as 4 mm to 6 mm. The OD of the expandable element may be equal to the OD of the shaft in the distal section or no more than 0.2 mm larger than it. The expandable element may include at least one of the following: a balloon, a bellows member, or a coated stent or a coated stent-like device (e.g., a reinforcing member coated with one or more layers of material).

[0241] In this ninth example, the ablation catheter may further include a proximal expandable element located proximal to the ablation element and carried by the shaft, and the proximal expandable element may be located proximal to the proximal ablation element. The proximal expandable element may be expandable, and wherein the shaft may include an expansion port within the proximal expandable element. The proximal expandable element may have a delivery configuration and an expanded configuration with an OD greater than the delivery configuration. The expandable element may have an OD of 4-10 mm in the expanded configuration, and optionally greater than the OD of the distal expandable member. The OD of the proximal expandable element may be equal to the OD of the shaft in the distal section or no more than 0.2 mm greater than it. The proximal expandable element may include at least one of the following: a balloon, a bellows member, or a coated stent or a coated stent-like device (e.g., a reinforcing member coated with one or more layers of material).

[0242] In this ninth additional example, the catheter can include a central expandable element.The central expandable element can include any of the features of the distal or proximal expandable members herein, including any combination thereof.

[0243] In this ninth additional example, the catheter is configured for transvascular ablation of GSN.The ablation catheter may include a distal section including the distal-most 7 cm of the ablation catheter.The ablation element may be adapted to produce an ablation having a length ranging from 5 mm to 25 mm.

[0244] In this ninth additional example, the distal section can be adapted to flexibly pass through the bend from the azygos vein to the T9-T11 intercostal veins (eg, radius of curvature >= 5 mm, angle up to 120 degrees).

[0245] In this ninth additional example, the outer diameter of the distal section (at least in the delivery state) is in the range of 1.5 to 3 mm.

[0246] In this ninth additional example, the ablation catheter can further include a guidewire lumen within the elongated shaft.

[0247] In this ninth additional example, the total length of the ablation element (which may include a plurality of individual ablation elements) may be from 5 mm to 20 mm, such as 10 to 15 mm.

[0248] In this ninth additional example, any ablation element may include one or more of: an RF ablation electrode, a coiled wire electrode, a laser cut RF electrode, an RF electrode printed with conductive ink, an RF electrode on an inflatable balloon (e.g., conductive ink, flexible circuit), a conductive membrane RF electrode, an RF electrode on an expandable cage or mesh, an ultrasonic ablation transducer, an electroporation electrode, a cryoablation element, or a virtual RF electrode.

[0249] In this ninth additional example, the ablation element can be adapted to deliver ablation energy circumferentially (radially symmetrically around the ablation element / around the vessel).

[0250] In this ninth additional example, the catheter can further include a proximal radiopaque marker positioned on the shaft at the proximal end of the ablation element or proximally.

[0251] In this ninth additional example, the catheter can further include a distal radiopaque marker positioned on the shaft distal to the distal end of the ablation element.

[0252] In this ninth additional example, the catheter can include an axial space between the distal radiopaque marker and the distal end of the ablation element.

[0253] Any of the additional methods can be used with any of the catheters in the additional examples. Any of the catheters in the additional examples can be used with the methods herein or in a manner not described herein.

Claims

1. An ablation catheter for transvascular ablation of thoracic visceral nerves, comprising: an elongated shaft (225) having a length such that a distal section (243) of the elongated shaft (225) can be positioned in a T9, T10, or T11 intercostal vein; and an electrically conductive, flexible ablation element (131) carried by the distal section (243) of the elongated shaft, wherein the electrically conductive, flexible ablation element (131) is connectable to a source of ablation energy; and The conductive flexible ablation element (131) comprises a plurality of ablation elements (132, 133) spaced apart axially. Features: Wherein, the axial length of the conductive flexible ablation element (131) is 10 mm to 25 mm; Each of the plurality of axially continuous ablation elements (132, 133) forming the electrically conductive flexible ablation element (131) has a length ranging from 5 mm to 12 mm; The distal section (243) is more flexible than the remainder of the elongated shaft (225) and is configured to adopt a radius of curvature as small as 5 mm and an angle as large as 120 degrees to flexibly pass through the bend from the azygos vein to the T9, T10 or T11 intercostal vein; The electrically conductive flexible ablation element (131) is configured to deliver ablation energy circumferentially and / or to deliver ablation energy radially symmetrically around the ablation element (131), and Each ablation element (132, 133) of the electrically conductive flexible ablation element (131) has a coiled configuration.

2. The ablation catheter according to claim 1, wherein: Each of the ablation elements (132, 133) has an expandable diameter.

3. The ablation catheter according to claim 1, wherein: Each of the multiple axially continuous ablation elements (132, 133) forming the conductive flexible ablation element (131) has a length greater than the maximum outer diameter adopted by the distal segment (243) of the slender shaft in the delivery state of the catheter; and, wherein the distal segment (243) of the slender shaft has a maximum outer diameter in the range of 1.5-3 mm at least in the delivery state of the catheter.

4. The ablation catheter according to claim 3, wherein: Each of the plurality of axially continuous ablation elements (132, 133) forming the electrically conductive flexible ablation element (131) has a length at least twice the maximum outer diameter adopted by the distal section (243) of the elongated shaft in the delivery state of the catheter.

5. The ablation catheter according to any one of claims 1 to 4, wherein: The electrically conductive flexible ablation element (131) includes or is formed by a first ablation element axially spaced from a second ablation element, the first ablation element and the second ablation element being carried by a shaft (225).

6. The ablation catheter according to any one of claims 1 to 4, wherein: There is an axial spacing between every two consecutive ablation elements of the plurality of axially consecutive ablation elements (132, 133), wherein there is an axial spacing between a first ablation element and a second ablation element; and Wherein, the axial spacing is less than or equal to 8 mm or 5 mm.

7. The ablation catheter according to claim 6, wherein: The axial spacing is 0.5 mm to 5 mm or 1 mm to 4 mm.

8. The ablation catheter according to claim 1, wherein: The coiled configuration of each ablation element (132, 133) is identical in all respects to the coiled configuration of the other ones of the conductive flexible ablation element (131), wherein the coiled configuration of the first ablation element is identical in all respects to the coiled configuration of the second ablation element.

9. The ablation catheter according to claim 2, wherein: The coiled configuration of the first ablation element differs from the coiled configuration of the second ablation element in at least one manner selected from: The first ablation element has a different length than the second ablation element, The first ablation element has a different coil direction than the second ablation element, the coil direction including left-handed and right-handed, The first ablation element has a different pitch than the second ablation element, the first ablation element having a different filament thickness than the second ablation element, The outer diameter OD of the distal section at the location of the first ablation element is different from the outer diameter OD of the distal section at the location of the second ablation element, or The cross-sectional outer profile of the first ablation element is different from the cross-sectional outer profile of the second ablation element.

10. The ablation catheter according to any one of claims 1 to 4, wherein: When the catheter (81) is positioned in an intercostal vein with the distal section (243), the conductive flexible ablation element (131) is configured to circumferentially ablate tissue surrounding the intercostal vein to a depth within a range of 2 mm to 10 mm, within a range of 2 mm to 8 mm, or within a range of 3 mm to 8 mm.

11. The ablation catheter according to any one of claims 1 to 4, wherein: The ablation catheter (81) comprises a proximal end, a distal end, and wherein the distal section (243) comprises the most distal 7 cm of the ablation catheter.

12. The ablation catheter according to any of the preceding claims 1-4, comprising a plurality of irrigation ports connectable to a fluid source and distributed along the distal section of the elongated shaft.

13. The ablation catheter of claim 12, comprising at least 10 irrigation ports evenly distributed along the distal section of the elongated shaft.

14. The ablation catheter of any of the preceding claims 1-4, comprising an irrigation lumen extending within the elongated shaft (225), connected to one or more irrigation ports and connectable to a fluid source at a proximal region of the elongated shaft.

15. The ablation catheter according to claim 12, wherein: The one or more irrigation ports are located on a surface of the distal end region not covered by any ablation element; and / or The one or more irrigation ports are located at the space in the distal region between consecutive ablation elements (132, 133) or ablation element portions.

16. The ablation catheter according to claim 12, wherein: One or more irrigation ports (137) are located between the distal and proximal ends of each ablation element (132, 133), the irrigation ports (137) being located between the windings of each ablation element (132, 133).

17. The ablation catheter of claim 12, comprising at least one radiopaque marker (130, 136), wherein: The at least one radiopaque marker (130, 136) includes: a proximal radiopaque marker (136) carried by the distal segment (243) and positioned proximal to all ablation elements (132, 133), and / or a distal radiopaque marker (130) positioned distal to all ablation elements (132, 133).

18. The ablation catheter according to claim 17, wherein: At least one radiopaque marker (130, 136) is within 1 mm to 15 mm, or 0.1 mm to 3 mm, of the distal ablation element.

19. The ablation catheter according to claim 17, wherein: At least one radiopaque marker (130, 136) is within 0.5 mm, 1 mm, or 1.5 mm of the distal ablation element.

Images