Apparatus and method for renal denervation

Abstract

The systems, devices, and methods described herein relate to catheter devices for therapeutic delivery in renal denervation applications. In some embodiments, the catheter includes a shaft having a first and a second set of electrodes, each set of electrodes including electrodes spaced from each other by an inter-electrode spacing and spaced from each other by an inter-set spacing. In some embodiments, the inter-set spacing can be at least 50% greater than each inter-electrode spacing. In some embodiments, the first or second set of electrodes can include at least one basket electrode.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the priority and benefit of U.S. Provisional Patent Application No. 63 / 354,133, filed on June 21, 2022, entitled "APPARATUS AND METHODS FOR RENAL DENERVATION", the disclosure of which is hereby incorporated by reference in its entirety.

Background Art

[0002] Hypertension is a widespread condition in the modern world. Some forms of it can be controlled by medication, but refractory hypertension, as the name suggests, is not easily controlled by drugs. Considering the association of hypertension with many disease states and its progressive nature, it is desirable to continue suppressing hypertension. One form of treatment that has been used to address refractory hypertension is renal denervation, in which the renal nerves connected to the kidneys are ablated. This can reduce renal sympathetic nerve activity and potentially lead to a decrease in blood pressure. In this application, thermal modalities such as radiofrequency (RF) ablation or ablation using ultrasound have been used, but these are often associated with collateral damage and a significant risk of tissue necrosis in the treated area.

[0003] Pulse - field ablation, also known as irreversible electroporation, has emerged as a potentially useful ablation modality that has been studied in some tumor applications and has recently been found to be beneficial in the context of cardiac ablation for the treatment of arrhythmias. This non - thermal ablation modality is tissue - selective and can minimize collateral damage while also resulting in a natural healing process after ablation that maintains the extracellular matrix and overall tissue integrity. Devices and waveforms have been devised that are appropriate in the context of cardiac ablation, but new devices and tools are needed that may be more appropriate for use in the context of renal denervation ablation.

[0004] The present invention addresses the need for minimally invasive devices for the efficient and effective delivery of pulsed field ablation therapy, particularly for the ablation of renal nerves for renal denervation. The pulsed field ablation procedure can be rapid while minimizing the collateral tissue damage often seen in heat-based therapies. At the same time, healing after the procedure can be relatively rapid with minimal side effects.

Summary of the Invention

[0005] The present disclosure describes, for example, tools and devices for minimally invasive access and treatment delivery for ablation of renal nerves. The devices of the present disclosure are intravascular catheter devices that are introduced via standard minimal access methods and can have a distal portion with at least two sets of electrodes linearly arranged along a distal device shaft. Each set can include at least three electrodes. In embodiments, each set of electrodes comprises a plurality of solid electrodes, and each electrode has a ring-shaped or cylindrical geometry arranged along the shaft with an interelectrode spacing between adjacent electrodes. The two sets of electrodes are separated by a set-to-set spacing that is at least 50% greater than the interelectrode spacing. The first set of electrodes and the second set of electrodes are separately wired, for example, with a first and a second lead wire, respectively, for electrical connection to a generator source for pulsed field ablation energy. Each lead wire is insulated with an insulator that can withstand a voltage of at least about 300 volts across its thickness without dielectric breakdown. In embodiments, each lead wire is insulated with an insulator that can withstand a voltage of at least about 700 volts across its thickness without dielectric breakdown. In embodiments, at least one of the first lead wire or the second lead wire extends through a dedicated lumen within the catheter for that lead wire. In embodiments, the catheter shaft has a guidewire lumen that extends all the way along its length to the distal tip of the catheter. In this case, the device is an over-the-wire catheter that is introduced over a pre-introduced guidewire onto at least a portion of a desired vasculature, and the guidewire provides mechanical support for the introduction of the catheter. In embodiments, a portion of the catheter shaft is deflectable (e.g., using a suitable pull wire appropriately incorporated within the catheter shaft), and this deflection can be used for navigation / access to a vasculature, e.g., a renal vasculature.

[0006] In embodiments, the most distal electrode is separated from the distal tip of the catheter by at least about 6 mm. In embodiments, the portion of the catheter shaft distal to the most distal electrode is tapered with a linear or curved taper such that the shaft diameter gradually decreases along the distal direction. The electrodes can be made of stainless steel, nitinol, gold, platinum-iridium alloy, or other such biocompatible materials known in the art that are suitable for delivering current or voltage to tissue. The electrodes are mounted on the catheter shaft and attached to appropriately exposed portions of the lead wires and are firmly swaged or crimped to the shaft. In embodiments, the electrodes can be mounted on short polymer tubes that are attached to the catheter shaft using standard catheter assembly methods.

[0007] In embodiments, each electrode can comprise a cage-like structure comprising struts that are at least partially made of a highly elastic yet flexible material such as, for example, nitinol. The electrodes are mounted on the catheter shaft and, in embodiments, the electrodes can be firmly crimped to the shaft at one end of the electrode, while the other end fits over the catheter shaft and is free to move or slide along the shaft as the cage-like structure deforms. In embodiments, the fixed end of the electrode has a collar portion that facilitates crimping or other forms of secure attachment. When advanced into a vascular structure having an inner diameter smaller than the undeformed or unstressed outer diameter of the electrode, the cage-like structure can be (e.g., gently or with minimal force) crushed into a configuration having a reduced diameter that fits within the blood vessel or vasculature, while at the same time extending as the free end of the cage-like structure slides over the catheter shaft. Accordingly, the diameter of the electrode matches the inner diameter of the blood vessel over a range of blood vessel diameters. In embodiments, the collar of the electrode can be on the proximal end of each electrode within the distal electrode set (or more distal electrode set) and on the distal end of each electrode within the proximal electrode set (or more proximal electrode set).

[0008] In embodiments, there can be two or more lead wires connected to each electrode set. In the various embodiments described herein, the first electrode set can be disposed in a distal direction relative to the second electrode set. For access to the renal artery, the sheath is inserted into the femoral artery through a groin access, advanced, and positioned with a suitable deflection for accessing the left or right renal artery. The sheath may have a curved or shaped distal portion with a fixed curvature or may be a deflectable sheath. A guide wire is inserted through the sheath and advanced into the renal artery. The catheter device of the present disclosure is inserted onto the guide wire through the sheath and positioned within the appropriate renal artery.

[0009] For pulsed field ablation delivery, the first and second electrode sets can be activated with opposite electrical polarities such that a relative voltage potential difference exists between the two sets. The electric field generated thereon is concentrated within a generally cylindrical volume disposed between the two sets of electrodes and can ablate the target tissue within this volume. A pulsed voltage waveform suitable for such applications is disclosed in International Application No. PCT / US23 / 25064, entitled "Apparatus, Systems and Methods for Soft Tissue Ablation," filed on June 12, 2023, which is incorporated herein by reference. The catheter can be moved to different positions along the renal artery and the pulsed field ablation application can be repeated at a given site as needed to enhance the ablation effect before delivering ablation at different positions. Generally, multiple such sites can be targeted in each renal artery, for example, 1 to about 9 such positions in each renal artery can be targeted, including all values and subranges therebetween.

[0010] In embodiments where the electrode is a ring electrode, the electrode can have an outer diameter in the range of about 1 mm to about 5 mm, including all values and sub - ranges therebetween. In embodiments where the electrode has a cage - like structure, the outer diameter of the unstressed or undeformed configuration can be in the range of about 2 mm to about 10 mm, including all values and sub - ranges therebetween. In embodiments where the electrode has a ring electrode or a cage - like structure (when the electrode is unstressed or not deformed), the length of each electrode can be in the range of about 0.7 mm to about 20 mm, including all values and sub - ranges therebetween. In an embodiment, the electrodes can have unequal lengths while maintaining approximately equal spacing between adjacent electrodes within each electrode set (e.g., the first electrode set or the second electrode set) in the undeformed configuration.

[0011] In embodiments, the inter - electrode spacing can be in the range of about 1 mm to about 7 mm, including all values and sub - ranges therebetween, and the inter - set spacing can be in the range of about 3 mm to about 15 mm, including all values and sub - ranges therebetween. In embodiments, the number of electrodes in the first electrode set can be in the range of 1 to about 10, including all values and sub - ranges therebetween, and the same is true for the second electrode set.

[0012] The catheter shaft can be in the range of about 1 mm to about 5 mm in diameter, including all values and sub - ranges therebetween, in various embodiments. In an embodiment, the distal portion of the catheter can be tapered such that the distal tip of the catheter has an outer diameter that is at least about 0.5 mm smaller than the diameter of the more proximal portion of the shaft. In embodiments, the voltage associated with pulsed - field ablation delivery can be in the range of about 700 volts to about 10,000 volts, including all values and sub - ranges therebetween.

[0013] In some embodiments, the device includes a shaft having a distal flexible portion, a first set of electrodes disposed on the distal flexible portion, the first set of electrodes including at least three electrodes spaced apart from each other by a set of first electrode-to-electrode spacings, the first set of electrodes being wired together via a first lead wire, a second set of electrodes disposed on the distal flexible portion distal to the first set of electrodes, the second set of electrodes including at least three electrodes spaced apart from each other by a set of second electrode-to-electrode spacings, the second set of electrodes being wired together via a second lead wire, the second set of electrodes being spaced from the first set of electrodes by a set-to-set spacing that is at least 50% greater than each electrode-to-electrode spacing of the set of first and second electrode-to-electrode spacings, and the first and second sets of electrodes being configured to deliver pulsed field ablation.

[0014] In some embodiments, the device includes a shaft having a distal flexible portion, a first set of electrodes disposed on the distal flexible portion, the first set of electrodes including at least one basket electrode formed from a superelastic material and having a diameter greater than the diameter of the shaft in a stress-free configuration, the first set of electrodes being spaced apart from each other by a set of first electrode-to-electrode spacings, the first set of electrodes being wired together via a first lead wire, a second set of electrodes disposed on the distal flexible portion distal to the first set of electrodes, the second set of electrodes being spaced apart from each other by a set of second electrode-to-electrode spacings, the second set of electrodes being wired together via a second lead wire, the second set of electrodes being spaced from the first set of electrodes by a set-to-set spacing that is at least 50% greater than each electrode-to-electrode spacing of the set of first and second electrode-to-electrode spacings, and the first and second sets of electrodes being configured to deliver pulsed field ablation.

[0015] In some embodiments, the method comprises positioning a distal flexible portion of a catheter within a first section of a vascular anatomy, the distal flexible portion having a first and a second set of electrodes disposed thereon, each of the first and second sets of electrodes comprising: (1) at least three electrodes having an inter-electrode spacing between adjacent electrodes, and (2) being separated from each other by an inter-set spacing that is at least 50% greater than each inter-electrode spacing; delivering high voltage pulses to the first and second sets of electrodes to ablate the first section of the vascular anatomy; moving the distal flexible portion of the catheter to a second section of the vascular anatomy; and delivering high voltage pulses to the first and second sets of electrodes to ablate the second section of the vascular anatomy. BRIEF DESCRIPTION OF THE DRAWINGS

[0016]

Figure 1

Figure 2

Figure 3A

Figure 3B

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Mode for Carrying Out the Invention

[0017] Device embodiments of the present disclosure provide, for example, device structures and configurations for delivering irreversible electroporation or pulsed field ablation therapies for renal denervation, where renal nerves are ablated for the treatment of refractory hypertension. In embodiments, the devices are intended for minimally invasive use and may be intended for use as an over-the-wire device where the device is tracked over a guide wire for placement within the renal artery. In other embodiments, however, they may be deflectable devices for navigation and placement.

[0018] For placement of the device into the left or right renal artery, the device may first be introduced into the left or right femoral artery via a standard groin access. Contextually, FIG. 1 shows the anatomical structure of the femoral artery and renal artery as well as the kidney. The left and right femoral arteries (115 and 113 respectively) branch from the lower portion of the descending aorta 111 that runs along the inferior vena cava 109. The left renal artery 121 and right renal artery 119 branch from the descending aorta and extend to the left kidney 105 and right kidney 103 respectively.

[0019] As shown in the example of FIG. 2, the catheter device 207 is introduced into the right femoral artery 201 via a femoral access, and from there, through the descending aorta 213, it is introduced into the right renal artery 205 as shown by the distal portion of the device 209 positioned within the right renal artery. In an embodiment, the catheter device may be passed over a guidewire within a sheath (a separate device is not shown in the schematic of FIG. 2). With the distal portion of the sheath appropriately deflected and positioned to gain access to the renal artery, the guidewire is extended into the renal artery, and the catheter can be tracked over the guidewire and positioned within the renal artery under fluoroscopic visualization or other suitable type of visualization. The electrodes on the catheter can be visualized on an X-ray image. In an embodiment, the electrodes, or the portion of the shaft under or near the electrodes, can be "doped" with additional material (e.g., tungsten, etc.) to improve visualization on an X-ray image. In an embodiment, the catheter device can be made deflectable via standard mechanisms such as, for example, one or more pull wires, and the catheter can be navigated and positioned within the renal artery without a guidewire.

[0020] FIG. 3A is a schematic diagram of a device embodiment having a ring-shaped electrode, showing that a first set of electrodes and a second set of electrodes have a spacing between the first and second sets of electrodes. Each set of electrodes can include at least three electrodes. The catheter 300 is shown having a guidewire lumen 302 that extends along the length of the catheter to its distal tip. In the example of this figure, a first set of electrodes 314, 316, 318, and 320 is shown having a set-to-set spacing 327 that separates the first and second sets of electrodes together with a second set of electrodes 304, 306, 308, and 310. In some embodiments, the overall length of the first set of electrodes, measured from the proximal end of the most proximal electrode of the first set of electrodes to the distal end of the most distal electrode of the first set of electrodes, is at least about three times greater than the catheter shaft diameter. Similarly, in some embodiments, the overall length of the second set of electrodes, measured from the proximal end of the most proximal electrode of the second set of electrodes to the distal end of the most distal electrode of the second set of electrodes, is at least about three times greater than the catheter shaft diameter. In the first set of electrodes, an interelectrode spacing 330 (i.e., the spacing between the closest edges of adjacent electrodes within the set of electrodes) separates electrodes 314 and 316, an interelectrode spacing 332 separates electrodes 316 and 318, and an interelectrode spacing 334 separates electrodes 318 and 320. Similarly, the second set of electrodes has interelectrode spacings. In embodiments, the interelectrode spacings can be approximately equal, but in other embodiments, they can be different from each other. In either case, the set-to-set spacing 327 is at least 50% greater than any of the interelectrode spacings. In embodiments, the distal edge of the most distal electrode is separated from the distal tip of the catheter 300 by at least about 6 mm. In embodiments, the portion of the catheter shaft distal to the most distal electrode 320 is tapered with a linear taper or a curved taper 325 in which the shaft diameter gradually decreases along the distal direction.

[0021] In an embodiment, the first set of electrodes and the second set of electrodes are separately wired, e.g., as separate first and second lead wires, for electrical connection to a generator source for pulsed field ablation energy. Each lead wire is insulated with an insulator that can withstand a voltage of at least about 300 volts across its thickness without dielectric breakdown. In an embodiment, each lead wire is insulated with an insulator that can withstand a voltage of at least about 700 volts across its thickness without dielectric breakdown. In an embodiment where the catheter shaft has a guide wire lumen that extends all the way along its length to the distal tip of the catheter, the catheter can be an over-the-wire catheter that is introduced over a pre-introduced guide wire to at least a portion of a desired vasculature structure using the guide wire to provide mechanical support for introduction of the catheter. In an embodiment, a portion of the catheter shaft is deflectable (e.g., using a suitable pull wire properly incorporated within the catheter shaft), and this deflection can be used for navigation and / or access to the renal vasculature structure.

[0022] In an embodiment, the electrodes can be made of stainless steel, nitinol, gold, a platinum-iridium alloy, or other such biocompatible materials known in the art that are suitable for delivering current or voltage to tissue. The electrodes are mounted on the catheter shaft, attached to appropriately exposed portions of the lead wires, and swaged or crimped firmly to the shaft. In an embodiment, the electrodes can be mounted on a short polymer tube that is attached to the catheter shaft using standard catheter assembly methods.

[0023] In an embodiment, at least one of the first lead wire or the second lead wire extends through a dedicated lumen inside a catheter for that lead wire. FIG. 3B schematically shows an embodiment 351 of a device showing a first set of electrodes 361 and a second set of electrodes 363, having a spacing between the first and second sets of electrodes, having a dedicated guide wire lumen 352, and having a separate lumen 356 that terminates at a position between the first and second sets of electrodes. The separate lumen 356 is a dedicated lumen for the passage of one or more electrical lead wires that connect to the first set of electrodes 361. The lumen 356 can terminate in an open space, and one or more lead wires with partially removed insulation can be connected to the electrodes of the first set of electrodes 361. The lumen 356 can be made of a polymeric material that provides an additional layer of electrical insulation between the lead wire within the lumen and any exposed lead wire outside the lumen 356, including, for example, a lead wire that connects to the second set of electrodes 363. In some embodiments, the polymeric material that defines or forms the lumen 356 can be capable of withstanding a voltage of at least about 300 volts over its thickness without dielectric breakdown.

[0024] For embodiments of the ring electrodes as described above, the electrodes of the present disclosure can have an outer diameter in the range of about 1 mm to about 5 mm, including all values and sub-ranges therebetween. In such embodiments, the length of each electrode can be in the range of about 0.7 mm to about 20 mm, including all values and sub-ranges therebetween. In an embodiment, the electrodes can have unequal lengths while maintaining substantially equal spacing between adjacent electrodes within each set of electrodes (e.g., the first set of electrodes or the second set of electrodes). The inter-electrode spacing can be in the range of about 1 mm to about 7 mm, including all values and sub-ranges therebetween, and the inter-set spacing can be in the range of about 3 mm to about 15 mm, including all values and sub-ranges therebetween. In an embodiment, the number of electrodes in the first set of electrodes can be in the range of 1 to about 10, including all values and sub-ranges therebetween, and the same is true for the second set of electrodes.

[0025] FIG. 4 shows a catheter device 403 of the present disclosure inserted over a guide wire 405 and with the catheter device and guide wire inserted into a sheath 401 having a curved distal portion. The sheath 401 may be a deflectable sheath or a fixed-curve sheath. In use, the sheath 401 can be positioned at or near the entrance of the renal artery with a suitable deflection for access to the renal artery, for example, to be visualized under fluoroscopic guidance. The guide wire 405 extends into the renal artery and provides support for tracking the catheter 403 over the guide wire and positioning the catheter 403 within the renal artery.

[0026] FIG. 5 is a schematic view of a configuration of an electrode 501 having a cage-like structure with a plurality of struts (or substantially similar structures) such as 503 and 505 and having ends 510 and 512, in a non-stressed or undeformed configuration. In an embodiment, the electrode 501 can be or form part of a catheter device of the present disclosure (e.g., catheter device 207) and can be positioned on the catheter device shaft. The struts of the cage-like structure are flexible and can deform under the application of mechanical stress, while being able to quickly return to their non-stressed configuration when the mechanical stress is released, and include a superelastic or hyperelastic material (e.g., nitinol, etc.). In the non-stressed configuration, the electrode 501 has a length L1 between its ends 510 and 512 and a diameter d1 at its widest portion, as shown in FIG. 5. These parameters can change when the electrode 501 is stressed and transitions from its non-stressed configuration to a stressed configuration.

[0027] In an embodiment, as shown in FIG. 6, the electrode 601 has a cage-like structure with a plurality of struts (or substantially similar structures) such as 603 and 605, and can include a collar portion 612 at one end, and the collar portion 612 is a ring or a ring-shaped extension. The collar portion 612 can be used to fix the electrode 601 to the shaft of the catheter device, for example, by crimping, swaging or other attachment means, and to connect the lead wire under the collar portion 612 and thus to the electrode 601. When the electrode 601 is mounted on the catheter shaft, the other end 610 of the electrode 601 (for example, the end or the open end opposite to the collar portion 612) can move or slide freely on the catheter shaft as the electrode is compressed, thus enabling the cage-like structure of the electrode 601 to change to a stressed or deformed configuration. Such a stressed configuration is shown in FIG. 7, which is a schematic view of a stressed or deformed configuration of an electrode 701 having a cage-like structure with a plurality of struts (or substantially similar structures) such as 703 and 705 and having ends 710 and 712. In an embodiment, the electrode can be part of the catheter device of the present disclosure and can be located on the catheter device shaft. FIG. 7 does not show a collar at one end as in FIG. 6, but it can be understood that in an embodiment, the cage-like structure can include a collar at one end. In the stressed or deformed configuration shown in FIG. 7, the electrode 701 has a length L2 between its ends 710 and 712 and a diameter d2 at its widest part. For example, compared to the unstressed configuration as shown in FIG. 5, the length L2 and the diameter d2 in the stressed configuration of FIG. 7 are different from their respective unstressed values L1 and d1. Specifically, when the electrode is compressed radially, the stressed length and diameter have values such that L2 > L1 and d2 < d1, respectively. These comparative relationships between the stressed and unstressed electrode configurations apply also in electrode embodiments without a collar (such as shown in FIGS. 5 and 7), as well as in embodiments with a collar (such as shown in FIG. 6).

[0028] FIG. 8 is a schematic view of a device embodiment in the form of a catheter 800, showing a first set of electrodes 808, 810, and 812 and a second set of electrodes 802, 804, and 806, having an inter-set spacing 841 between the first and second electrode sets, and each electrode including a cage-like structure including struts (or substantially similar structures) as shown in a configuration not under stress or deformation, and having a separate lumen 852 for at least one electrical lead for connecting to the first set of electrodes. Each set of electrodes can include at least three electrodes. In an embodiment, the catheter 800 also includes a guidewire lumen 811 that extends along the length of the catheter to its distal tip. The electrodes 808, 810, and 812 of the first set of electrodes each have a collar portion 830, 832, and 834, respectively, and the electrodes 802, 804, and 806 of the second set of electrodes each have a collar portion 820, 822, and 824, respectively. In some embodiments, the overall length of the first set of electrodes, measured from the proximal end of the most proximal electrode of the first set of electrodes to the distal end of the most distal electrode of the first set of electrodes, is at least about three times greater than the catheter shaft diameter. Similarly, in some embodiments, the overall length of the second set of electrodes, measured from the proximal end of the most proximal electrode of the second set of electrodes to the distal end of the most distal electrode of the second set of electrodes, is at least about three times greater than the catheter shaft diameter. Adjacent electrodes of each electrode set are separated by an inter-electrode spacing. For example, the inter-electrode spacing 818 separates the electrodes 802 and 804, and the inter-electrode spacing 819 separates the electrodes 804 and 806. The collars are fixed to the shaft, but the other end of each electrode (e.g., the end without a collar) is free to slide along the catheter shaft. Thus, the inter-electrode spacings, such as 818 and 819, can vary depending on the deformation of the corresponding electrodes 804 and 806, respectively. In the embodiment shown in FIG. 8, the collars 824 and 830 abut the inter-set spacing 841, and since the collars are fixed, the inter-set spacing 841 is fixed, but the inter-electrode spacing can vary depending on the deformation of the electrodes.In an embodiment, the inter-set spacing 841 is at least 50% greater than the maximum electrode-to-electrode spacing, including over the entire range of variations of the maximum electrode-to-electrode spacing (such as may be caused by deformation of the electrodes). In other embodiments, the colors can be arranged oppositely compared to the illustration of FIG. 8 (i.e., the electrode ends abutting the inter-set spacing 841 can be colorless), in which case the inter-set spacing can vary. In this case, the minimum value of the inter-set spacing 841 (e.g., when electrodes 806 and 808 are deformed) is at least 50% greater than the maximum electrode-to-electrode spacing over the entire range of variations of the maximum electrode-to-electrode spacing.

[0029] In an embodiment, the electrode-to-electrode spacing (e.g., in the case of a cage-shaped electrode, when the electrodes are not deformed or under stress) can be approximately equal, but in other embodiments, they can be different from each other. In either case, the inter-set spacing 841 is at least 50% greater than any of the electrode-to-electrode spacings. In an embodiment, the distal edge of the most distal electrode is separated from the distal tip of the catheter by at least about 6 mm. In an embodiment, the portion of the catheter shaft distal to the most distal electrode is tapered with a linear taper or a curved taper 815 in which the catheter shaft diameter gradually decreases along the distal direction.

[0030] In an embodiment, the electrodes when not under stress or deformed can have unequal lengths while maintaining approximately equal spacing between adjacent electrodes within each electrode set (e.g., the first electrode set or the second electrode set).

[0031] In an embodiment, the first set of electrodes and the second set of electrodes are wired separately, e.g., as first and second lead wires respectively, for electrical connection to a generator source for pulsed field ablation energy. Each lead wire is insulated with an insulator that can withstand a voltage of at least about 300 volts across its thickness without dielectric breakdown. In an embodiment, each lead wire is insulated with an insulator that can withstand a voltage of at least about 700 volts across its thickness without dielectric breakdown. In embodiments where the catheter shaft has a guidewire lumen that extends all the way along its length to the distal tip of the catheter, the device is an over-the-wire catheter that is introduced over a pre-introduced guidewire to at least some portion of the desired vasculature for mechanical support for introduction of the catheter. In an embodiment, a portion of the catheter shaft is deflectable (e.g., using appropriate pull wire(s) suitably incorporated within the catheter shaft), and this deflection can be used for navigation / access to the renal vasculature.

[0032] In an embodiment, an electrode having a cage-like structure can be made of a superelastic or hyperelastic or shape memory conductive material such as nitinol, and the material is also a biocompatible material known in the art that is suitable for delivering current or voltage to tissue. In an embodiment, the electrode is mounted on a catheter shaft, attached to a properly exposed portion of a lead wire, and swaged or crimped firmly to the shaft at one end. In an embodiment, the electrode can be mounted on a short polymer tube that is attached to the catheter shaft using standard catheter assembly methods. In an embodiment, at least one of the first lead wire or the second lead wire extends through a dedicated lumen inside the catheter for that lead wire. For example, in the embodiment shown in FIG. 8, a separate lumen 852 is a dedicated lumen for one or more electrical lead wires, and the lumen 852 terminates at a position between the first and second electrode sets. The separate lumen 852 is a dedicated lumen for the passage of one or more electrical lead wires that connect to the first set of electrodes 808, 810, or 812. The lumen terminates in an open space, and a lead wire (s) with insulation partially removed can be connected to the electrodes of the first set of electrodes. The lumen 852 can be made of a polymer material that provides an additional electrical insulation layer between the lead wire inside the lumen and any exposed lead wire outside the lumen 852 (including, for example, the lead wire connecting to the second set of electrodes 802, 804, and 806), and the polymer material can withstand a voltage of at least about 300 volts over its thickness without dielectric breakdown.

[0033] FIG. 9 shows a schematic view of an embodiment of a catheter device 901 inserted into a blood vessel 900, showing a first set of electrodes 911, 913, and 915 having an inter-set spacing 923 between the first and second electrode sets, and a second set of electrodes 905, 907, and 909, each electrode comprising a cage-like structure with struts (or substantially similar structures), and each electrode shown in a stressed or deformed configuration when the catheter device 901 is disposed within the blood vessel 900. Electrode-to-electrode spacings, such as 925, separate the closest edges of adjacent electrodes within each electrode set. In an embodiment, the catheter device also includes a guidewire lumen 903 that extends along the length of the catheter to its distal tip. FIG. 9 is intended to show the same device as FIG. 8, but in FIG. 9, the device (and specifically the electrodes) are constrained to fit within the blood vessel 900, and thus the electrode configuration of FIG. 9 is under stress or deformed as compared to their respective counterparts in FIG. 8. In particular, since the free ends of the electrodes move to mechanically compensate for electrode compression, each electrode diameter (at its widest value) is smaller in FIG. 9 as compared to FIG. 8, and electrode-to-electrode spacings, such as 925, are also smaller relative to their respective counterparts in FIG. 8. Since the blood vessel 900 can vary in diameter along its length, it can be appreciated that the electrode diameters and electrode-to-electrode spacings 925 can vary across adjacent electrodes within each electrode set, e.g., depending on the shape or diameter of the most proximal portion of the blood vessel 900 near the adjacent electrodes, and how those portions compress or deform the electrodes. For example, the portion of the catheter shaft distal to the most distal electrode (shown tapered with a linear or curved taper 920 where the shaft diameter gradually decreases along the distal direction) is further inserted into an artery or blood vessel while decreasing in diameter along the forward path, the leading electrode within the first electrode set can, in some cases, be more compressed or deformed as compared to the second electrode set. Nevertheless, the comparative relationships described herein, e.g., that the minimum value of the inter-set spacing is at least 50% greater than the maximum electrode-to-electrode spacing (across the entire range of variation of the maximum electrode-to-electrode spacing), continue to hold.

[0034] In embodiments where the electrode has a cage-like structure, the outer diameter of the configuration that is not under stress or deformed can be in the range of about 2 mm to about 10 mm, including all values and sub-ranges therebetween. In such embodiments, the length of each electrode can be in the range of about 0.7 mm to about 20 mm, including all values and sub-ranges therebetween. In embodiments, the electrodes can have unequal lengths while maintaining a substantially equal spacing between adjacent electrodes within each electrode set (e.g., the first electrode set or the second electrode set) in the undeformed configuration.

[0035] Over the range of the configuration or deformation of the cage-like structure of the electrodes disclosed herein, the inter-electrode spacing can be in the range of about 1 mm to about 7 mm, including all values and sub-ranges therebetween, while the inter-set spacing can be in the range of about 3 mm to about 15 mm, including all values and sub-ranges therebetween. In embodiments, the number of electrodes within the set of the first electrodes can be in the range of 1 to about 10, including all values and sub-ranges therebetween, and the same is true for the set of the second electrodes.

[0036] For pulsed field ablation delivery, a first electrode set and a second electrode set can be energized with opposite electrical polarities, which results in the generation of an electric field suitable for achieving irreversible electroporation within a volume surrounding a portion of the catheter at the set - to - set spacing. FIG. 10 is a schematic diagram of a catheter device 1003 in one embodiment having ring electrodes disposed within a blood vessel 1001, showing that a first set of electrodes 1011, 1012, 1013, and 1014 and a second set of electrodes 1005, 1006, 1007, and 1008 have a set - to - set spacing 1040 between the first and second electrode sets, and a schematic indication of an ablation zone 1020 generated when the first and second sets of electrodes are energized with opposite electrical polarities during delivery of a pulsed field ablation waveform. For example, when the device is placed at a location within a renal artery and pulsed field ablation is delivered, renal nerves within the ablation zone 1020 are ablated. When a pulsed field ablation waveform is applied, the resulting spatial distribution of the electric field determines the zone of ablation or cell death.

[0037] In embodiments, to enhance the ablation effect, multiple pulsed field ablation deliveries can be performed at a given location. Thereafter, when the device is moved to different locations along the renal artery and pulsed field ablation is delivered, renal nerves within a similar new, generally cylindrical ablation zone are ablated. Generally, multiple such sites can be targeted in each renal artery, for example, 1 to about 9 such locations can be targeted in each renal artery.

[0038] The catheter shaft can be in the range of about 1 mm to about 5 mm in diameter, depending on the embodiment. In an embodiment, the distal portion of the catheter can have a taper such that the distal tip of the catheter has an outer diameter that is at least about 0.5 mm smaller than the shaft diameter of the more proximal portion of the catheter. In an embodiment, the voltage associated with pulsed field ablation delivery can be in the range of about 700 volts to about 10,000 volts, including all values and sub - ranges therebetween. The alternative embodiments disclosed herein can be in the form of a deflectable catheter having a deflection of a device that is controlled, for example, from a control mechanism within a handle and that uses mechanisms such as the use of pull wires well known to those of ordinary skill in the art of interventional catheters.

[0039] During operation, a catheter or device as described herein (e.g., catheters 300, 351, 800, 901, 1003) can be advanced within a sheath (e.g., sheath 401) disposed within a vascular anatomical structure. In some embodiments, the catheter can be advanced with a guidewire that extends from a catheter lumen. The catheter can be advanced until the distal end of the catheter extends distally from the distal end of the sheath. In some embodiments, the guidewire can be further extended and the catheter can be further advanced over the guidewire. The catheter can be advanced until positioned at a target site for delivering pulsed field ablation. In some embodiments where the catheter includes one or more basket electrodes, the basket electrodes can automatically expand as the catheter is extended outside of the sheath. As described above, the basket electrodes can have a predetermined diameter in a non-stressed configuration. When the basket electrodes are within the sheath, the basket electrodes can have a diameter that is less than or substantially equal to the inner diameter of the sheath. Then, when the basket electrodes are extended outside of the sheath, the basket electrodes can automatically expand to the diameter of the non-stressed configuration or the inner diameter of the blood vessel if the basket electrodes are disposed within a blood vessel having an inner diameter that is less than the diameter of the non-stressed basket electrodes. In other words, when the basket electrodes are disposed within a blood vessel having a size that is smaller than the non-stressed configuration of the basket electrodes, the basket electrodes can expand only partially within the blood vessel. Often, the diameter of the blood vessel can decrease or narrow distally such that any basket electrodes disposed on the catheter can be compressed based on the changing inner diameter of the blood vessel as the catheter is advanced. In some examples, the catheter can start distally within the blood vessel and ablation can be performed at multiple locations along the blood vessel after the catheter is gradually retracted.In such a case, the basket electrode starts in a more compressed configuration within the blood vessel and then gradually expands as the catheter is withdrawn or pulled out, for example, to the diameter of its stress-free configuration or to a partially expanded diameter based on the vascular anatomy.

[0040] The systems, devices, and methods described herein can be embodied in one or more embodiments as described below.

[0041] Embodiment 1: A catheter device for delivering pulsed field ablation using a set of two electrodes within a distal flexible portion, the set of a first proximal electrodes and a set of second distal electrodes, each set having at least three electrodes, having a first series of inter-electrode spacings between adjacent electrodes in the first set and a second series of inter-electrode spacings between adjacent electrodes in the second set, the set of a first proximal electrodes and a set of second distal electrodes, and an inter-set spacing separating the first and second electrode sets, the inter-set spacing being at least 50% greater than either of the inter-electrode spacings of the first or second electrode sets, the first set of electrodes being electrically wired together with a first electrical lead, and the second set of electrodes being electrically wired together with a second electrical lead, the inter-set spacing.

[0042] Embodiment 2: The catheter according to Embodiment 1, wherein each lead is electrically insulated by at least one insulating layer capable of withstanding a voltage of at least about 300 volts across its insulation thickness without dielectric breakdown.

[0043] Embodiment 3: The catheter according to Embodiment 1, wherein at least one lead passes through a lumen within the catheter, and the lumen wall is capable of withstanding a voltage of at least about 300 volts across its thickness without dielectric breakdown.

[0044] Embodiment 4: The catheter according to Embodiment 1, wherein the inter-set spacing between the first and second electrode sets is greater than about 3 mm.

[0045] Embodiment 5: The catheter according to Embodiment 1, wherein the first set of electrodes and the second set of electrodes each include at least three electrodes.

[0046] Embodiment 6: The catheter according to Embodiment 1, wherein the portion of the catheter shaft distal to the most distal electrode of the second set of electrodes is tapered such that the catheter shaft diameter gradually decreases along the distal direction.

[0047] Embodiment 7: The catheter according to Embodiment 1, comprising a guide wire lumen such that the catheter can be inserted over a guide wire inserted into the vasculature of the target anatomical structure.

[0048] Embodiment 8: The catheter according to Embodiment 1, wherein the catheter shaft is deflectable.

[0049] Embodiment 9: The catheter according to Embodiment 1, wherein the length of the first set of electrodes from the proximal end of the most proximal electrode of the first set of electrodes to the distal end of the most distal electrode of the first set of electrodes is at least three times greater than the diameter of the catheter.

[0050] Embodiment 10: The catheter according to Embodiment 1, wherein the length of the second set of electrodes from the proximal end of the most proximal electrode of the second set of electrodes to the distal end of the most distal electrode of the second set of electrodes is at least three times greater than the diameter of the catheter.

[0051] Embodiment 11: The catheter according to Embodiment 1, wherein during ablation delivery, the first set of electrodes and the second set of electrodes have opposite electrical polarities for high voltage pulse delivery.

[0052] Embodiment 12: A catheter device for delivering pulsed field ablation using a set of two electrodes within a distal flexible portion, comprising a first proximal set of electrodes and a second distal set of electrodes, each set having at least three electrodes, having a first series of inter-electrode spacings between adjacent electrodes in the first set and a second series of inter-electrode spacings between adjacent electrodes in the second set, at least one of the electrodes being in the form of a basket electrode comprising a superelastic material in a compressible configuration, the unstressed diameter of the basket electrode being greater than the shaft diameter of the catheter, the first proximal set of electrodes and the second distal set of electrodes, and a set-to-set spacing separating the first and second electrode sets, the set-to-set spacing being at least 50% greater than either of the inter-electrode spacings of the first or second electrode sets, the first set of electrodes being electrically wired together with a first electrical lead, the second set of electrodes being electrically wired together with a second electrical lead, the set-to-set spacing, and a catheter device comprising the same.

[0053] Embodiment 13: The catheter according to embodiment 12, wherein each basket electrode comprises a collar portion for attachment to the catheter shaft and the electrical lead.

[0054] Embodiment 14: The catheter according to embodiment 12, wherein each basket electrode is compressible to conform to passage through a vascular anatomical structure having an inner diameter smaller than the diameter of the unstressed basket electrode.

[0055] Embodiment 15: The catheter according to embodiment 12, wherein each lead is electrically insulated by at least one insulating layer capable of withstanding a voltage of at least about 300 volts across its insulation thickness without dielectric breakdown.

[0056] Embodiment 16: The catheter according to embodiment 12, wherein at least one lead passes through a lumen within the catheter, and the lumen wall is capable of withstanding a voltage of at least about 300 volts across its thickness without dielectric breakdown.

[0057] Embodiment 17: The catheter according to embodiment 12, wherein the inter-set spacing between the first and second electrode sets is greater than about 3 mm.

[0058] Embodiment 18: The catheter according to embodiment 12, wherein the first set of electrodes and the second set of electrodes each comprise at least three electrodes.

[0059] Embodiment 19: The catheter according to embodiment 12, wherein the portion of the catheter shaft distal to the most distal electrode of the second set of electrodes is tapered such that the catheter shaft diameter gradually decreases along the distal direction.

[0060] Embodiment 20: The catheter according to embodiment 12, comprising a guide wire lumen such that the catheter can be inserted over a guide wire inserted into the vasculature of the target anatomical structure.

[0061] Embodiment 21: The catheter according to embodiment 12, wherein the catheter shaft is deflectable.

[0062] Embodiment 22: The length of the first set of electrodes from the proximal end of the most proximal electrode of the first set of electrodes to the distal end of the most distal electrode of the first set of electrodes in a configuration not receiving electrode stress is at least three times greater than the diameter of the catheter. The catheter according to embodiment 12.

[0063] Embodiment 23: The length of the second set of electrodes from the proximal end of the most proximal electrode of the second set of electrodes to the distal end of the most distal electrode of the second set of electrodes in a configuration not receiving electrode stress is at least three times greater than the diameter of the catheter. The catheter according to embodiment 12.

[0064] Embodiment 24: During ablation delivery, the first set of electrodes and the second set of electrodes have opposite electrical polarities for high voltage pulse delivery. The catheter according to embodiment 12.

[0065] Embodiment 25: A method for renal denervation comprising passage of a catheter having two sets of electrodes along its distal flexible portion, the first proximal set of electrodes and the second distal set of electrodes, each set having at least three electrodes, having a first series of inter - electrode spacings between adjacent electrodes in the first set and a second series of inter - electrode spacings between adjacent electrodes in the second set, a set - to - set spacing separating the first and second sets of electrodes, the set - to - set spacing being at least 50% greater than either of the inter - electrode spacings within the first or second set of electrodes, positioning the distal portion of the catheter within a first vascular section, delivering high - voltage pulses to the first and second sets of electrodes for ablation within the first vascular section, moving the catheter to position the distal portion of the catheter within a second vascular section, and delivering high - voltage pulses to the first and second sets of electrodes for ablation within the second vascular section.

[0066] Specific examples are provided in the figures for illustrative and exemplary purposes, but it will be apparent that variations in the number of lumens, the number of electrodes, electrode diameters, inter - electrode spacings, set - to - set spacings, etc., can be constructed based on the teachings herein without limitation. Similarly, the figures showing cage - like electrodes illustrate specific examples of cage - like electrode configurations, but note that various strut geometries can be employed in the construction of such configurations.

[0067] As used herein, the terms "about" and / or "approximately", when used in conjunction with numerical values and / or ranges, generally refer to numerical values and / or ranges close to the recited numerical values and / or ranges. In some cases, the terms "about" and "approximately" may mean within ± 10% of the stated value. For example, in some cases, "about 100 [units]" may mean within ± 10% of 100 (e.g., 90 - 110). The terms "about" and "approximately" may be used interchangeably.

Claims

[Claim 1] A shaft including a distal flexible portion, A set of first electrodes positioned on the distal flexible portion, The system comprises a second set of electrodes positioned on the distal flexible portion distal to the first set of electrodes, The first set of electrodes includes at least three electrodes separated from each other by a first set of inter-electrode spacings, and the first set of electrodes is wired together with each other via a first lead wire. The second set of electrodes includes at least three electrodes separated from each other by a second set of inter-electrode spacings, and the second set of electrodes is wired together with each other via a second lead wire. The second set of electrodes is separated from the first set of electrodes by a set spacing, and the set spacing is at least 50% larger than the set spacing between each electrode in the first and second electrode spacing sets. The apparatus comprising the first and second electrode sets configured to deliver pulsed-field ablation.

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