Devices and methods 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 set of electrodes and a second set of electrodes, each of the first set of electrodes and the second set of electrodes including electrodes spaced apart from each other by an inter-electrode spacing and the first set of electrodes and the second set of electrodes spaced apart from each other by an inter-group spacing. In some embodiments, the inter-group spacing may be at least 50% greater than each inter-electrode spacing. In some embodiments, the first set of electrodes or the second set of electrodes may include at least one basket-shaped electrode.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 354,133, filed on June 21, 2022, entitled “APPARATUS AND METHODS FOR RENALDENERVATION,” the disclosure of which is incorporated by reference in its entirety. Background Art

[0003] Hypertension is a common condition in the modern world, and although some forms of it can be controlled by medication, resistant hypertension, as its name implies, is not easily controlled by medication. Given the association of hypertension with many disease states and the progressive nature of hypertension, it is desirable to keep hypertension under control. One form of treatment that has been used to address resistant hypertension is renal denervation, in which the renal nerves to the kidneys are ablated. This can reduce renal sympathetic nerve activity and result in a reduction in blood pressure. Although thermal modalities, such as radiofrequency (RF) ablation or ablation using ultrasound, have been employed in the present application, they generally carry the risk of collateral damage and considerable tissue necrosis in the treatment area.

[0004] Pulsed field ablation (also known as irreversible electroporation) has emerged as a potentially useful ablation modality that has been studied in some oncology applications and has recently been found to be fruitful in the context of cardiac ablation for the treatment of cardiac arrhythmias. This non-thermal ablation modality can be tissue selective and minimize collateral damage while also resulting in a natural post-ablation healing process that preserves the extracellular matrix and overall tissue integrity. While devices and waveforms suitable for cardiac ablation have been designed, new devices and tools that may be more suitable for renal denervation ablation are needed.

[0005] The present invention addresses the need for a minimally invasive device for efficiently and effectively delivering pulsed field ablation therapy, particularly renal nerve ablation for renal nerve denervation. The pulsed field ablation procedure can be rapid while minimizing the collateral tissue damage often seen in heat-based treatments. At the same time, post-operative healing can be relatively rapid with minimal side effects. Summary of the invention

[0006] The present disclosure describes tools and devices for minimally invasive access and treatment delivery (e.g., for ablation of renal nerves). The device of the present disclosure is an intravascular catheter device introduced via a standard minimal access method, and may have a distal portion having at least two groups of electrodes linearly arranged along the distal device axis. Each group of electrodes may include at least three electrodes. In an embodiment, each group of electrodes includes a plurality of solid electrodes, each solid electrode having an annular or cylindrical geometry arranged along the axis, and an inter-electrode spacing between adjacent electrodes. The two groups of electrodes are separated by an inter-group spacing, and the inter-group spacing is at least 50% greater than the inter-electrode spacing. The first group of electrodes and the second group of electrodes are individually wired with separate leads (e.g., a first lead and a second lead), respectively, for electrically connecting to a generator source of pulsed field ablation energy. Each lead 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 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, at least one of the first lead or the second lead passes through a dedicated lumen in the catheter for the lead. In an embodiment, the catheter shaft has a guidewire lumen extending along its length to the distal end of the catheter; in this case, the device is a guidewire-over-the-wire catheter introduced into at least a portion of the vasculature desired by a previously introduced guidewire, wherein the guidewire provides mechanical support for the introduction of the catheter. In an embodiment, a portion of the catheter shaft is deflectable (e.g., a pullwire is appropriately incorporated into the catheter shaft), and the deflection can be used to navigate / enter the vasculature, e.g., the renal vasculature.

[0007] In an embodiment, the distal end of the most distal electrode is spaced at least about 6mm from the distal end of the catheter. In an embodiment, the distal portion of the catheter shaft at the most distal electrode tapers in a linear or curved taper, wherein the shaft diameter gradually decreases along the distal direction. The electrode can be made of other such biocompatible materials suitable for conveying current or voltage to tissues, such as stainless steel, Nitinol, gold, platinum-iridium alloy, or known in the art. The electrode is mounted on the catheter shaft, attached to the appropriate exposed portion of the lead, and is swaged or tightly curled onto the shaft. In an embodiment, the electrode can be mounted on a short polymer tube, which is attached to the catheter shaft using a standard catheter assembly method.

[0008] In an embodiment, each electrode may include a cage structure including struts made at least in part of a highly elastic but compliant material (e.g., nitinol). The electrodes are mounted on a catheter shaft, and in an embodiment, they may be firmly crimped to the shaft at one end of the electrode, while the other end fits on the catheter shaft, but freely move or slide along the shaft when the cage structure is deformed. In an embodiment, the fixed end of the electrode has a collar portion that makes crimping or other forms of fixed attachment easier. When advancing into a vascular structure having an inner diameter less than the undeformed or unstressed outer diameter of the electrode, the cage structure may collapse (e.g., gently or with minimal force) into a configuration having a reduced diameter that fits in the vessel or vascular structure, while simultaneously extending as the free end of the cage structure slides on the catheter shaft. Therefore, the diameter of the electrode is consistent with the inner diameter of the vessel within the range of the vessel diameter. In an embodiment, the collar of the electrode may be on the proximal end of each electrode in the distal electrode group (or more distal electrode group), and on the distal end of each electrode in the proximal electrode group (or more proximal electrode group).

[0009] In embodiments, more than one lead may be connected to each electrode set. In various embodiments described herein, a first electrode set may be disposed distally relative to a second electrode set. To access the renal artery, a sheath is inserted into the femoral artery through an inguinal passage and advanced and positioned with appropriate deflection to access the left or right renal artery. The sheath may have a curved or shaped distal portion having a fixed bend, or the sheath may be a deflectable sheath. A guidewire is inserted through the sheath and advanced into the renal artery. The catheter device of the present disclosure is inserted through the sheath and over the guidewire and positioned in the appropriate renal artery.

[0010] For pulsed field ablation delivery, the first electrode group and the second electrode group can be activated with opposite electrical polarity so that there is a relative potential difference between the two groups. The electric field generated thereon is concentrated in an approximately cylindrical volume disposed between the two groups of electrodes, and the target tissue within the volume can be ablated. Pulsed voltage waveforms suitable for these applications are disclosed in international patent application PCT / US23 / 25064 entitled "Apparatus, Systems and Methods for Soft Tissue Ablation" filed on June 12, 2023, which is incorporated herein by reference. Before the catheter is moved to different locations along the renal artery and ablation is delivered at different locations, the pulsed field ablation application can be repeated as needed at a given site to enhance the ablation effect. Typically, multiple such sites can be targeted in each renal artery, including, for example, such sites can be targeted in each renal artery between 1 and about 9 (including all values ​​and subranges therebetween).

[0011] In embodiments where the electrode is a ring electrode, the outer diameter of the electrode can be in the range of about 1 mm to about 5 mm, including all values ​​and sub-ranges therebetween. In embodiments where the electrode comprises a cage-like structure, the outer diameter of the unstressed or undeformed configuration can be in the range of from about 2 mm to about 10 mm, including all values ​​and sub-ranges therebetween. In embodiments where the electrode comprises a ring electrode or a cage-like structure (when the electrode is unstressed or undeformed), the length of each electrode can be in the range of between about 0.7 mm and about 20 mm, including all values ​​and sub-ranges therebetween. In embodiments, the electrodes can have unequal lengths while maintaining approximately equal spacing between adjacent electrodes in each electrode group (e.g., a first electrode group or a second electrode group) in an undeformed configuration.

[0012] In an embodiment, the inter-electrode spacing may be in the range of about 1 mm to about 7 mm, including all values ​​and sub-ranges therebetween, and the inter-group spacing may 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 group of electrodes may be in the range of 1 to about 10, including all values ​​and sub-ranges therebetween, and likewise for the second group of electrodes.

[0013] In various embodiments, the diameter of the shaft of the catheter can be in the range of about 1 mm to about 5 mm, including all values ​​and sub-ranges therebetween. In embodiments, the distal portion of the catheter can have a taper such that the distal tip of the catheter has an outer diameter at least about 0.5 mm less 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 from about 700 volts to about 10,000 volts, including all values ​​and sub-ranges therebetween. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 is a schematic diagram of a subject's anatomy representing the kidney, renal artery, and associated access vasculature.

[0015] Figure 2 An illustration of a subject's anatomy including a renal artery is provided with a device access path highlighted in accordance with an embodiment.

[0016] Figure 3A is a schematic diagram of an embodiment of a device showing a first set of electrodes and a second set of electrodes with a spacing therebetween.

[0017] Figure 3B is a schematic diagram of an embodiment of a device showing a first set of electrodes and a second set of electrodes with a spacing therebetween and having a separate lumen for at least one electrical lead for connection to the first set of electrodes.

[0018] Figure 4 The catheter device of the present disclosure is shown inserted over a guidewire, wherein the catheter device and the guidewire are inserted into a sheath having a curved distal portion, according to an embodiment.

[0019] Figure 5 is a schematic diagram of an unstressed or undeformed configuration of an electrode having a cage-like structure including struts or a substantially similar structure, according to an embodiment, wherein the electrode is part of a catheter device of the present disclosure and is located on a catheter device shaft.

[0020] Figure 6 is a schematic diagram of an unstressed or undeformed configuration of an electrode having a cage-like structure including struts or a substantially similar structure and a loop portion at one end, according to an embodiment, wherein the electrode is part of a catheter device of the present disclosure and is located on a catheter device shaft.

[0021] Figure 7 is a schematic diagram of a stressed or deformed configuration of an electrode having a cage-like structure including struts or a substantially similar structure, according to an embodiment, wherein the electrode is part of a catheter device of the present disclosure and is located on a catheter device shaft.

[0022] Figure 8 is a schematic diagram of an embodiment of a device showing a first set of electrodes and a second set of electrodes with a spacing therebetween, wherein each electrode is shown in an unstressed or undeformed configuration and includes a cage structure comprising struts or a substantially similar structure and having a separate lumen for at least one electrical conductor for connection to the first set of electrodes.

[0023] Fig. 9 A schematic diagram of an embodiment of a catheter device inserted into a blood vessel is shown, showing a first set of electrodes and a second set of electrodes, with a spacing between the first set of electrodes and the second set of electrodes, wherein when the catheter is assembled into the blood vessel, each electrode is shown as being in a stressed or deformed configuration, and wherein each electrode includes a cage structure that includes struts or a substantially similar structure.

[0024] Fig.10 is a schematic diagram of an embodiment of a device showing a first group of electrodes and a second group of electrodes with a spacing between the first group of electrodes and the second group of electrodes, and having a schematic indication of an ablation zone generated when the first group of electrodes and the second group of electrodes are excited with opposite electrical polarities when delivering a pulsed field ablation waveform. DETAILED DESCRIPTION

[0025] Device embodiments of the present disclosure provide device configurations and arrangements for delivering irreversible electroporation or pulsed field ablation therapy, such as for renal denervation where renal nerves are ablated to treat resistant hypertension. In embodiments, the devices are intended for minimally invasive use and may be intended for use as over-the-wire devices where the device follows a guidewire to be placed in the renal artery, while in other embodiments they may be deflectable devices for navigation and placement.

[0026] To place the device in the left or right renal artery, the device may first be introduced into the left or right femoral artery via a standard inguinal route. For context, Figure 1 The femoral and renal arteries and the anatomy of the kidney are shown. The left and right femoral arteries (115 and 113, respectively) branch off from the lower portion of the descending aorta 111, which runs alongside the inferior vena cava 109. The left and right renal arteries 121 and 119 branch off from the descending aorta and extend to the left and right kidneys 105 and 103, respectively.

[0027] like Figure 2 As shown in the example of FIG. 1 , the catheter device 207 is introduced into the right femoral artery 201 via the inguinal passage, and thus introduced into the right renal artery 205 via the descending aorta 213, as indicated by the distal portion of the device 209 positioned in the right renal artery. In an embodiment, the catheter device can be passed over a guidewire within a sheath (in Figure 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 follow the guidewire and be positioned in the renal artery under fluoroscopic visualization or other appropriate type of visualization. The electrodes on the catheter can be visualized on an X-ray image. In an embodiment, the electrodes or portions of the shaft below or near the electrodes can be "doped" with additional material (e.g., such as tungsten) for enhanced visualization on an X-ray image. In an embodiment, the catheter device can be deflected via a standard mechanism (e.g., one or more pull wires), and the catheter is navigated and positioned in the renal artery without a guidewire.

[0028] Figure 3A3 is a schematic diagram of an embodiment of a device with a ring electrode, which shows a first group of electrodes and a second group of electrodes, wherein there is a spacing between the first group of electrodes and the second group of electrodes. Each group of electrodes may include at least three electrodes. Catheter 300 is shown as having a guidewire lumen 302 extending to its distal end along the length of the catheter. In the example of the figure, the first group of electrodes 314, 316, 318 and 320 are shown together with the second group of electrodes 304, 306, 308 and 310, and the first group of electrodes and the second group of electrodes are spaced apart by an intergroup spacing 327. In some embodiments, the total length of the first group of electrodes measured from the proximal end of the most proximal electrode of the first group of electrodes to the distal end of the most distal electrode of the first group of electrodes is at least about three times the diameter of the catheter shaft. Similarly, in some embodiments, the total length of the second electrode group measured from the proximal end of the most proximal electrode of the second electrode group to the distal end of the most distal electrode of the second electrode group is at least about three times the diameter of the catheter shaft. In the first group of electrodes, electrodes 314 and 316 are spaced apart by an inter-electrode spacing 330 (i.e., the spacing between the nearest edges of adjacent electrodes in a group of electrodes), electrodes 316 and 318 are spaced apart by an inter-electrode spacing 332, and electrodes 318 and 320 are spaced apart by an inter-electrode spacing 334. Similarly, there are inter-electrode spacings in the second group of electrodes. In embodiments, the inter-electrode spacings may be approximately equal, while in other embodiments, they may be different from one another. In either case, the inter-group spacing 327 is at least 50% greater than any inter-electrode spacing. In embodiments, the distal edge of the most distal electrode is spaced apart from the distal end 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 tapers in a straight or curved taper 325, wherein the shaft diameter gradually decreases in the distal direction.

[0029] In an embodiment, the first group of electrodes and the second group of electrodes are individually wired with separate leads (e.g., first leads and second leads) for being electrically connected to a generator source of pulsed field ablation energy. Each lead 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 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 in which the catheter shaft has a guidewire lumen extending along its length to the distal end of the catheter, the catheter can be an on-guidewire catheter introduced into at least a portion of the desired vascular system on a previously introduced guidewire, wherein the guidewire provides mechanical support for the introduction of the catheter. In an embodiment, a portion of the catheter shaft is deflectable (e.g., a pullwire is appropriately incorporated in the catheter shaft), and the deflection can be used for navigation and / or access to the renal vascular system.

[0030] In embodiments, the electrodes may be made of stainless steel, nitinol, gold, platinum-iridium alloys, or other such biocompatible materials known in the art as suitable for delivering current or voltage to tissue. The electrodes are mounted on the catheter shaft, attached to the appropriate exposed portions of the leads, and swaged or tightly crimped to the shaft. In embodiments, the electrodes may be mounted on a short polymer tube that is attached to the catheter shaft using standard catheter assembly methods.

[0031] In an embodiment, at least one of the first lead or the second lead passes through a dedicated lumen within the catheter for that lead. Figure 3B A device embodiment 351 is schematically shown, showing a first set of electrodes 361 and a second set of electrodes 363, with a spacing between the first set of electrodes and the second set of electrodes, with a dedicated guidewire lumen 352, and with a separate lumen 356 terminating at a location between the first set of electrodes and the second set of electrodes. The separate lumen 356 is a dedicated lumen for passing one or more electrical leads connected to the first set of electrodes 361. The lumen 356 can terminate in an open space where one or more leads with insulation partially removed 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 leads in the lumen and any exposed leads outside of the lumen 356, including, for example, leads connected to the second set of electrodes 363. In some embodiments, the polymeric material defining or forming the lumen 356 is capable of withstanding a voltage of at least about 300 volts across its thickness without dielectric breakdown.

[0032] In the case of the annular electrode embodiment as described above, the outer diameter of the electrode of the present disclosure can be in the range of from about 1 mm to about 5 mm, including all values ​​and sub-ranges therebetween. In such an embodiment, the length of each electrode can be in the range of between about 0.7 mm and about 20 mm, including all values ​​and sub-ranges therebetween. In an embodiment, the electrodes may have unequal lengths while maintaining approximately equal spacing between adjacent electrodes in each electrode group (e.g., the first electrode group or the second electrode group). The inter-electrode spacing can be in the range of from about 1 mm to about 7 mm, including all values ​​and sub-ranges therebetween, and the inter-group spacing can be in the range of from about 3 mm to about 15 mm, including all values ​​and sub-ranges therebetween. In an embodiment, the number of electrodes in the first group of electrodes can be in the range of from 1 to about 10, including all values ​​therebetween, and the same is true for the second group of electrodes.

[0033] Figure 4A catheter device 403 of the present disclosure inserted on a guide wire 405 according to an embodiment is shown, wherein the catheter device and the guide wire are inserted into a sheath 401 having a curved distal portion. The sheath 401 can be a deflectable sheath or it can be a fixed curved sheath. In use, the sheath 401 can be positioned at or near the entrance of the renal artery with appropriate deflection to enter the renal artery, for example, as visible under fluoroscopic guidance. The guide wire 405 extends into the renal artery and provides support for making the catheter 403 follow the guide wire and positioning the catheter 403 in the renal artery.

[0034] Figure 5 is a schematic diagram of an unstressed or undeformed configuration of an electrode 501 having a cage-like structure, the cage-like structure comprising a plurality of struts (or substantially similar structures) such as 503 and 505, and having ends 510 and 512. In an embodiment, the electrode 501 may be or form a part of a catheter device (e.g., catheter device 207) of the present disclosure and is located on a catheter device shaft. The struts of the cage-like structure comprise a superelastic or superelastic material (e.g., such as nitinol) that is flexible and can deform under applied mechanical stress while being able to quickly return to its unstressed configuration when the mechanical stress is released. In the unstressed 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. Figure 5 When the electrode 501 is stressed, these parameters may change and transform from an unstressed configuration to a stressed configuration.

[0035] In an embodiment, Figure 6 As shown, electrode 601 includes a cage-like structure that includes a plurality of struts (or substantially similar structures), such as 603 and 605, and may include a collar portion 612 at one end, wherein collar portion 612 is a ring or annular extension. The collar portion 612 may be used to secure electrode 601 to a shaft of a catheter device, such as by crimping, swaging, or other attachment means, and to connect a lead wire to the underside of collar portion 612, and thus to electrode 601. When electrode 601 is mounted on a catheter shaft, the other end 610 of electrode 601 (e.g., the end opposite to collar portion 612 or the open end) may be free to move or slide on the catheter shaft when the electrode is compressed, thereby allowing the cage-like structure of electrode 601 to change to a stressed or deformed configuration. Figure 7 Such a stressed configuration is shown in , which is a schematic diagram of a stressed or deformed configuration of an electrode 701 having a cage-like structure including a plurality of struts (or substantially similar structures), such as 703 and 705, and ends 710 and 712. In embodiments, the electrode may comprise a portion of a catheter device of the present disclosure and be located on a catheter device shaft. Although Figure 7 No indication of Figure 6 The cage structure may include a collar on one end, but it will be appreciated that in embodiments the cage structure may include a collar on one end. Figure 7 In the stressed or deformed configuration shown, electrode 701 has a length L2 between its ends 710 and 712 and a diameter d2 at its widest portion. Figure 5 As shown, Figure 7 The length L2 and diameter d2 in the stressed configuration of d2 are different from their respective unstressed values ​​L1 and d1. Specifically, when the electrode is radially compressed, 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 are not significant in electrode embodiments without a collar (e.g., as Figure 5 and 7 ) and embodiments including a collar (e.g., Figure 6 As shown).

[0036] Figure 8 806, there is a first group of electrodes 808, 810 and 812 and a second group of electrodes 802, 804 and 806, with an intergroup spacing 841 between the first and second groups of electrodes, each electrode comprising a cage structure, as shown in an unstressed or undeformed configuration, the cage structure comprising a support (or a substantially similar structure), and having a separate lumen 852 for at least one electrical conductor, the at least one electrical conductor being used to connect to the first group of electrodes. Each group of electrodes may include at least three electrodes. In an embodiment, the catheter 800 also includes a guidewire lumen 811 extending along the length of the catheter to its distal end. The electrodes 808, 810 and 812 of the first electrode group have loop portions 830, 832 and 834, respectively, while the electrodes 802, 804 and 806 of the second electrode group have loop portions 820, 822 and 824, respectively. In some embodiments, the total length of the first group of electrodes measured from the proximal end of the most proximal electrode of the first group of electrodes to the distal end of the most proximal electrode of the first group of electrodes is at least about three times the diameter of the catheter shaft. Similarly, in some embodiments, the total length of the second electrode group measured from the proximal end of the most proximal electrode of the second electrode group to the distal end of the most proximal electrode of the second electrode group is at least about three times the diameter of the catheter shaft. Adjacent electrodes of each electrode group are separated by an inter-electrode spacing. For example, electrodes 802 and 804 are separated by an inter-electrode spacing 818, and electrodes 804 and 806 are separated by an inter-electrode spacing 819. When the collar is secured to the shaft, the other end of each electrode (e.g., the end without the collar) is free to slide along the catheter shaft. Therefore, the inter-electrode spacings such as 818 and 819 can vary according to the deformation of the corresponding electrodes 804 and 806, respectively. Figure 8In the illustrated embodiment, although the inter-electrode spacing can vary according to the deformation of the electrodes, the collars 824 and 830 are adjacent to the inter-group spacing 841, and since the collars are fixed, the inter-group spacing 841 is fixed. In an embodiment, the inter-group spacing 841 is at least 50% greater than the maximum inter-electrode spacing included in the entire variation range of the inter-electrode spacing (e.g., caused by the deformation of the electrodes). In other embodiments, Figure 8 , the collars may be relatively placed (i.e., the electrode ends adjacent to the intergroup spacing 841 may not have collars), in which case the intergroup spacing may vary. In this case, the minimum value of the intergroup spacing 841 (e.g., when electrodes 806 and 808 are deformed) is at least 50% greater than the maximum inter-electrode spacing within the entire range of variation of the inter-electrode spacing.

[0037] In embodiments, the inter-electrode spacings (e.g., in the case of a cage electrode, when the electrode is not deformed or stressed) may be approximately equal, while in other embodiments, they may be different from one another. In either case, the inter-group spacing 841 is at least 50% greater than any inter-electrode spacing. In embodiments, the distal edge of the distal-most electrode is spaced at least about 6 mm from the distal end of the catheter. In embodiments, the portion of the catheter shaft distal to the distal-most electrode tapers in a straight or curved taper 815, wherein the catheter shaft diameter gradually decreases in the distal direction.

[0038] In embodiments, the electrodes may have unequal lengths when unstressed or undeformed while maintaining substantially equal spacing between adjacent electrodes in each electrode set (eg, the first electrode set or the second electrode set).

[0039] In an embodiment, the first group of electrodes and the second group of electrodes are individually wired with separate leads (e.g., first leads and second leads) for electrical connection to a generator source of pulsed field ablation energy. Each lead 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 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 in which the catheter shaft has a guidewire lumen extending all the way along its length to the distal end of the catheter, the device is a guidewire catheter introduced into at least a portion of the desired vascular system over a previously introduced guidewire, wherein the guidewire provides mechanical support for the introduction of the catheter. In an embodiment, a portion of the catheter shaft is deflectable (e.g., appropriately combined with (one or more) pullwires in the catheter shaft), and the deflection can be used for navigation / entry to the renal vascular system.

[0040] In an embodiment, the electrode comprising the cage-like structure may be made of a superelastic or super-stretch or shape memory conductive material, such as Nitinol, which is also known in the art to be a biocompatible material suitable for delivering current or voltage to tissue. In an embodiment, the electrode is mounted on a catheter shaft, attached to an appropriately exposed portion of the lead, and swaged or tightly crimped to the shaft at one end. In an embodiment, the electrode may 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 or the second lead passes through a dedicated lumen within the catheter for that lead. For example, in Figure 8 In the illustrated embodiment, the separate lumen 852 is a dedicated lumen for one or more electrical leads, wherein the lumen 852 terminates at a location between the first electrode set and the second electrode set. The separate lumen 852 is a dedicated lumen for passing one or more electrical leads connected to the first set of electrodes 808, 810, or 812. The lumen terminates in an open space, wherein the lead(s) with partial insulation removed can be connected to the electrodes of the first set of electrodes. The lumen 852 can be made of a polymeric material that provides an additional layer of electrical insulation between the leads in the lumen and any exposed leads outside the lumen 852 (e.g., including leads connected to the second set of electrodes 802, 804, and 806), wherein the polymeric material is capable of withstanding a voltage of at least about 300 volts across its thickness without dielectric breakdown.

[0041] Fig. 9 A schematic diagram of an embodiment of a catheter device 901 inserted into a blood vessel 900 is shown, showing a first group of electrodes 911, 913 and 915 and a second group of electrodes 905, 907 and 909, with an inter-group spacing 923 between the first electrode group and the second electrode group, and each electrode includes a cage structure that includes struts (or a substantially similar structure), and each electrode is shown as being in a stressed or deformed configuration when the catheter device 901 is disposed in the blood vessel 900. The nearest edges of adjacent electrodes in each electrode group are spaced apart by an inter-electrode spacing (such as 925). In an embodiment, the catheter device also includes a guidewire lumen 903 extending along the length of the catheter to its distal end. Although Fig. 9 Intended to show Figure 8 The same device, but in Fig. 9 In the embodiment of the present invention, the device (and in particular, the electrodes) are constrained to fit within the blood vessel 900, and thus Fig. 9 The electrode configuration and Figure 8 In particular, Fig. 9 The corresponding electrode diameters in (at their respective widest values) are Figure 8 Compared with the smaller, and the electrode spacing (such as 925) is also relatively Figure 8, their corresponding counterparts in the first electrode group are smaller because the free ends of the electrodes move to mechanically compensate for electrode compression. Since the diameter of the vessel 900 can vary along its length, it can be appreciated that the electrode diameter and inter-electrode spacing 925 can differ between adjacent electrodes in each electrode group, for example, depending on the shape or diameter of the immediately adjacent portions of the vessel 900 proximate to the adjacent electrodes and how these portions will compress or deform the electrodes. For example, as the portion of the catheter shaft distal to the most distal electrode (shown as tapering in a straight or curved taper 920 with the shaft diameter gradually decreasing in the distal direction) is further inserted into an artery or vessel having a decreasing diameter along the advancement path, the guide electrodes in the first electrode group can become more compressed or deformed in some cases compared to the second electrode group. However, the comparative relationships described herein, such as the minimum inter-group spacing being at least 50% greater than the maximum inter-electrode spacing (over the entire range of variation of the inter-electrode spacing), continue to hold.

[0042] In embodiments where the electrodes include a cage-like structure, the outer diameter of the unstressed or undeformed configuration may be in the range of from about 2 mm to about 10 mm, including all values ​​and subranges therebetween. In such embodiments, the length of each electrode may be in the range of between about 0.7 mm and about 20 mm, including all values ​​and subranges therebetween. In embodiments, the electrodes may have unequal lengths while maintaining approximately equal spacing between adjacent electrodes in each electrode group (e.g., the first electrode group or the second electrode group) in the undeformed configuration.

[0043] Within the range of configurations or variations of the cage structures of the electrodes disclosed herein, the inter-electrode spacing may be in the range of about 1 mm to about 7 mm, including all values ​​and sub-ranges therebetween, and the inter-group spacing may 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 group of electrodes may be in the range of 1 to about 10, including all values ​​and sub-ranges therebetween, and the same is true for the second group of electrodes.

[0044] For pulsed field ablation delivery, the first electrode set and the second electrode set may be energized with opposite electrical polarity, which results in an electric field suitable for achieving irreversible electroporation in a volume surrounding a portion of the catheter at the inter-set spacing. Fig.101 is a schematic diagram of a catheter device 1003 in an embodiment having an annular electrode placed in a blood vessel 1001, showing a first set of electrodes 1011, 1012, 1013, and 1014 and a second set of electrodes 1005, 1006, 1007, and 1008, with an inter-set spacing 1040 between the first electrode set and the second electrode set, and with a schematic indication of an ablation zone 1020 generated when the first and second electrodes are energized with opposite electrical polarity when a pulsed ablation field waveform is delivered. For example, when the device is placed at a location in a renal artery and pulsed field ablation is delivered, renal nerves within ablation zone 1020 are ablated. When a pulsed field ablation waveform is applied, the spatial distribution of the resulting electric field determines the area of ​​ablation or cell death.

[0045] In an embodiment, multiple pulsed field ablation deliveries may be performed at a given location to enhance the ablation effect. Subsequently, as the device is moved to a different location along the renal artery and pulsed field ablation is delivered, the renal nerves within a similar new approximately cylindrical ablation zone are ablated. Typically, multiple such locations may be targeted in each renal artery, including, for example, from 1 to about 9 such locations may be targeted in each renal artery.

[0046] According to an embodiment, the diameter of the shaft of the catheter can be in the range of from about 1 mm to about 5 mm. In an embodiment, the distal portion of the catheter can have a taper so 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 from about 700 volts to about 10,000 volts, including all values ​​and subranges therebetween. A variant embodiment as disclosed herein can be in the form of a deflectable catheter, wherein the deflection of the device is controlled by a control mechanism in, for example, a handle, and using a mechanism such as a pull wire familiar to those skilled in the art of using interventional catheters.

[0047] In operation, a catheter or device such as those described herein (e.g., catheters 300, 351, 800, 901, 1003) may be advanced within a sheath (e.g., sheath 401) disposed within a vascular anatomical structure. In some embodiments, the catheter may be advanced with a guidewire, wherein the guidewire extends out of the catheter lumen. The catheter may be advanced until the distal end of the catheter extends distally from the distal end of the sheath. In some embodiments, the guidewire may be further extended, and the catheter may be further advanced on the guidewire. The catheter may be advanced until it is positioned at a target location to deliver pulsed field ablation. In some embodiments, in the case where the catheter includes one or more basket electrodes, the basket electrode may automatically expand when the catheter extends to the outside of the sheath. As described above, the basket electrode may have a predetermined diameter in an unstressed configuration. When the basket electrode is within the sheath, the basket electrode may have a diameter that is less than or substantially equal to the inner diameter of the sheath. Then, when the basket electrode extends outside the sheath, the basket electrode can automatically expand to the diameter of its unstressed configuration, and if the basket electrode is set in a blood vessel having an inner diameter smaller than the diameter of the unstressed basket electrode, the basket electrode can automatically expand to the inner diameter of the blood vessel. In other words, when the basket electrode is set in a blood vessel having a size smaller than the unstressed configuration of the basket electrode, the basket electrode can only partially expand within the blood vessel. In many cases, the diameter of the blood vessel can decrease or narrow in the distal direction, so that as the catheter advances, any basket electrode set on the catheter can be compressed based on the changing inner diameter of the blood vessel. In some cases, the catheter can start from the distal side in the blood vessel and ablate at multiple locations along the blood vessel after the catheter is gradually retracted. In this case, the basket electrode can start in a more compressed configuration in the blood vessel and then gradually expand as the catheter is retracted or withdrawn, such as expanding to the diameter of its unstressed configuration or expanding to a partially expanded diameter based on the anatomy of the blood vessel.

[0048] The systems, devices, and methods described herein may be embodied in one or more embodiments, as set forth below.

[0049] Embodiment 1: A catheter device for delivering pulsed field ablation, wherein two groups of electrodes in a distal flexible portion include a first proximal electrode group and a second distal electrode group, each group of electrodes has at least three electrodes, adjacent electrodes in the first group of electrodes have a first series of inter-electrode spacings, adjacent electrodes in the second group of electrodes have a second series of inter-electrode spacings, and the first electrode group and the second electrode group are separated by an inter-group spacing, the inter-group spacing is at least 50% larger than any inter-electrode spacing in the first electrode group or the second electrode group, the first group of electrodes are electrically connected together with a first electrical conductor, and the second group of electrodes are electrically connected together with a second electrical conductor.

[0050] Embodiment 2: The catheter of Embodiment 1, wherein each lead is electrically insulated with at least one insulating layer capable of withstanding a voltage of at least about 300 volts across its insulation thickness without dielectric breakdown.

[0051] Embodiment 3: The catheter of Embodiment 1, wherein the at least one lead wire passes through a lumen in the catheter, wherein a wall of the lumen is capable of withstanding a voltage of at least about 300 volts across its thickness without dielectric breakdown.

[0052] Embodiment 4: The catheter according to Embodiment 1, wherein the inter-group spacing between the first electrode group and the second electrode group is greater than about 3 mm.

[0053] Embodiment 5: The catheter according to embodiment 1, wherein the first group of electrodes and the second group of electrodes each include at least 3 electrodes.

[0054] Example 6: The catheter of Example 1, wherein a portion of the catheter shaft distal to a distal-most electrode of the second set of electrodes is tapered such that the catheter shaft diameter gradually decreases in the distal direction.

[0055] Example 7: The catheter of Example 1, wherein the catheter comprises a guidewire lumen such that the catheter can be inserted over a guidewire inserted into a vascular structure of the subject's anatomy.

[0056] Example 8: A catheter according to Example 1, wherein the catheter shaft is deflectable.

[0057] Embodiment 9: The catheter of Embodiment 1, wherein a length of the first electrode group from a proximal end of a most proximal electrode of the first electrode group to a distal end of a most distal electrode of the first electrode group is at least 3 times a diameter of the catheter.

[0058] Embodiment 10: The catheter of Embodiment 1, wherein the length of the second set of electrodes from the proximal end of the most proximal electrode of the second set to the distal end of the most distal electrode of the second set is at least 3 times the diameter of the catheter.

[0059] Embodiment 11: The catheter of Embodiment 1, wherein the first set of electrodes and the second set of electrodes have opposite electrical polarities for high voltage pulse delivery during ablation delivery.

[0060] Embodiment 12: A catheter device for delivering pulsed field ablation, wherein two groups of electrodes in a distal flexible portion include a first proximal electrode group and a second distal electrode group, each group of electrodes having at least three electrodes, at least one electrode being in the form of a basket electrode comprising a superelastic material in a compressible configuration, wherein an unstressed diameter of the basket electrode is greater than a diameter of the catheter shaft, adjacent electrodes in the first group of electrodes have a first series of inter-electrode spacings, adjacent electrodes in the second group of electrodes have a second series of inter-electrode spacings, and the first electrode group and the second electrode group are separated by an inter-group spacing that is at least 50% greater than any inter-electrode spacing in the first or second electrode groups, the first group of electrodes are electrically connected together with a first electrical conductor, and the second group of electrodes are electrically connected together with a second electrical conductor.

[0061] Example 13: The catheter of Example 12, wherein each basket electrode includes a loop portion for attachment to the catheter shaft and electrical wire.

[0062] Embodiment 14: The catheter of Embodiment 12, wherein each basket electrode is compressible to accommodate passage through a vascular anatomy having an inner diameter that is smaller than the diameter of the basket electrode in its unstressed configuration.

[0063] Embodiment 15: The catheter of Embodiment 12, wherein each lead is electrically insulated with at least one insulating layer capable of withstanding a voltage of at least about 300 volts across its insulation thickness without dielectric breakdown.

[0064] Embodiment 16: The catheter of Embodiment 12, wherein at least one lead wire passes through a lumen in the catheter, wherein a wall of the lumen is capable of withstanding a voltage of at least about 300 volts across its thickness without dielectric breakdown.

[0065] Embodiment 17: The catheter of Embodiment 12, wherein the inter-group spacing between the first electrode group and the second electrode group is greater than about 3 mm.

[0066] Embodiment 18: The catheter of Embodiment 12, wherein the first set of electrodes and the second set of electrodes each comprise at least 3 electrodes.

[0067] Example 19: The catheter of Example 12, wherein a portion of the catheter shaft distal to a distal-most electrode of the second set of electrodes is tapered such that the catheter shaft diameter gradually decreases in the distal direction.

[0068] Example 20: The catheter of Example 12, wherein the catheter comprises a guidewire lumen such that the catheter can be inserted over a guidewire inserted into a vascular structure of the subject's anatomy.

[0069] Example 21: A catheter according to Example 12, wherein the catheter shaft is deflectable.

[0070] Embodiment 22: The catheter of Embodiment 12, wherein, in an unstressed configuration of the electrodes, the length of the first electrode group from the proximal end of the most proximal electrode of the first electrode group to the distal end of the most distal electrode of the first electrode group is at least 3 times the diameter of the catheter.

[0071] Embodiment 23: The catheter of Embodiment 12, wherein, in an unstressed configuration of the electrodes, the length of the second electrode group from the proximal end of the most proximal electrode of the second electrode group to the distal end of the most proximal electrode of the second electrode group is at least 3 times the diameter of the catheter.

[0072] Example 24: The catheter of Example 12, wherein the first set of electrodes and the second set of electrodes have opposite electrical polarity for high voltage pulse delivery during ablation delivery.

[0073] Embodiment 25: A method for renal denervation, comprising passing a catheter along a distal flexible portion thereof, the catheter having two groups of electrodes, the two groups of electrodes comprising a first proximal electrode group and a second distal electrode group, each group of electrodes having at least three electrodes, adjacent electrodes in the first group of electrodes having a first series of inter-electrode spacings, adjacent electrodes in the second group of electrodes having a second series of inter-electrode spacings, and the first electrode group and the second electrode group being separated by an inter-group spacing that is at least 50% greater than any inter-electrode spacing in the first group of electrodes or the second group of electrodes, positioning the distal portion of the catheter in a first blood vessel segment, delivering high voltage pulses to the first electrode group and the second electrode group for ablation in the first blood vessel segment, moving the catheter to position the distal portion of the catheter in a second blood vessel segment, and delivering high voltage pulses to the first electrode group and the second electrode group for ablation in the second blood vessel segment.

[0074] Although specific embodiments are provided in the drawings for purposes of example and description, it should be clear that variations may be constructed without limitation and based on the teachings herein, such as different numbers of lumens, different numbers of electrodes, electrode diameters, inter-electrode spacing, inter-group spacing, etc. Likewise, although the drawings showing cage electrodes show specific examples of cage electrode configurations, it should be noted that a variety of strut geometries may be employed in the configuration of such a configuration.

[0075] As used herein, the terms "about" and / or "approximately" when used in conjunction with numerical values ​​and / or ranges, generally refer to those numerical values ​​and / or ranges that are close to the cited numerical values ​​and / or ranges. In some cases, the terms "about" and "approximately" can refer to within ±10% of the quoted value. For example, in some cases, "about 100 [units]" can mean within ±10% of 100 (e.g., from 90 to 110). The terms "about" and "approximately" can be used interchangeably.

Claims

1. A device comprising: a shaft including a distal flexible portion; a first set of electrodes disposed on the distal flexible portion, the first set of electrodes comprising at least three electrodes spaced apart from one another by a first set of inter-electrode spacings, the first set of electrodes being commonly wired to one another via a first lead; as well as a second set of electrodes, the second set of electrodes being disposed on the distal flexible portion distal to the first set of electrodes, the second set of electrodes comprising at least three electrodes spaced apart from each other by a second set of inter-electrode spacing, the second set of electrodes being commonly wired to each other via a second lead, The second set of electrodes is spaced apart from the first set of electrodes by an inter-set spacing that is at least 50% greater than each of the inter-electrode spacings of the first set of inter-electrode spacings and the second set of inter-electrode spacings, The first set of electrodes and the second set of electrodes are configured to deliver pulsed field ablation.

2. The device according to claim 1, wherein: Each of the first lead and the second lead is electrically insulated with at least one insulating layer configured to withstand a voltage of at least about 300 volts across a thickness of the at least one insulating layer without dielectric breakdown.

3. The device according to any one of claims 1 or 2, further comprising a lumen wall defining the lumen, A first lead and a second lead are disposed in the lumen, and The lumen wall is configured to withstand a voltage of at least about 300 volts across the thickness of the lumen wall without dielectric breakdown.

4. The device according to any one of claims 1 to 3, wherein: The inter-group spacing between the first group of electrodes and the second group of electrodes is greater than about 3 mm.

5. The device according to any one of claims 1 to 4, wherein: The shaft includes a tapered portion distal to a distal-most electrode of the second set of electrodes, the tapered portion tapering in a distal direction.

6. The device according to any one of claims 1 to 5, wherein: The shaft defines a guidewire lumen such that the shaft can be inserted over the guidewire into a vascular structure of the subject's anatomy.

7. The device according to any one of claims 1 to 6, wherein: The shaft is deflectable.

8. The device according to any one of claims 1 to 7, wherein: The length of the first set of electrodes is defined as the distance 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, the length of the first set of electrodes being at least about three times the diameter of the shaft.

9. The device according to any one of claims 1 to 8, wherein: The length of the second set of electrodes is defined as the distance 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, the length of the second set of electrodes being at least about three times the diameter of the shaft.

10. The device according to any one of claims 1 to 9, wherein: The first set of electrodes and the second set of electrodes are configured to be energized with opposite electrical polarity to deliver pulsed field ablation.

11. A device comprising: a shaft including a distal flexible portion; a first set of electrodes disposed on the distal flexible portion, the first set of electrodes comprising at least one basket electrode formed of a superelastic material and having a diameter in an unstressed configuration that is larger than a diameter of the shaft, the first set of electrodes being spaced apart from one another by a first set of inter-electrode spacings, the first set of electrodes being commonly wired to one another via a first lead; as well as 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 second set of inter-electrode spacings, the second set of electrodes being commonly wired to each other via second leads, The second set of electrodes is spaced apart from the first set of electrodes by an inter-set spacing that is at least 50% greater than each of the inter-electrode spacings of the first set of inter-electrode spacings and the second set of inter-electrode spacings, The first set of electrodes and the second set of electrodes are configured to deliver pulsed field ablation.

12. The device according to claim 11, wherein Each of the first set of electrodes and the second set of electrodes includes at least three electrodes.

13. The device according to claim 11, wherein: Each of the first set of electrodes and the second set of electrodes includes at least three basket electrodes.

14. The device according to any one of claims 11 to 13, wherein: Each basket electrode includes a collar portion attached to the shaft and to a respective one of the first lead and the second lead.

15. The device according to any one of claims 11 to 14, wherein: Each basket electrode is compressible such that the basket electrode can conform to an inner diameter of a vascular anatomy or sheath that is smaller than a diameter of the basket electrode in an unstressed configuration to be advanced through the vascular anatomy.

16. The device according to any one of claims 11 to 15, wherein: Each basket electrode includes an open end opposite the collar portion, the open end being configured to move or slide on the shaft when the basket electrode is compressed.

17. The device according to any one of claims 11 to 16, wherein: Each of the first lead and the second lead is electrically insulated with at least one insulating layer configured to withstand a voltage of at least about 300 volts across a thickness of the at least one insulating layer without dielectric breakdown.

18. The apparatus according to any one of claims 11 to 17, further comprising a lumen wall defining the lumen, A first lead and a second lead are disposed in the lumen, and The lumen wall is configured to withstand a voltage of at least about 300 volts across the thickness of the lumen wall without dielectric breakdown.

19. The device according to any one of claims 11 to 18, wherein: The inter-group spacing between the first group of electrodes and the second group of electrodes is greater than about 3 mm.

20. The apparatus according to any one of claims 11 to 19, wherein: The shaft includes a tapered portion distal to a distal-most electrode of the second set of electrodes, the tapered portion tapering in a distal direction.

21. The apparatus according to any one of claims 11 to 20, wherein: The shaft defines a guidewire lumen such that the shaft can be inserted over the guidewire into a vascular structure of the subject's anatomy.

22. The apparatus according to any one of claims 11 to 21, wherein: The shaft is deflectable.

23. The apparatus according to any one of claims 11 to 22, wherein: The length of the first set of electrodes is defined as the distance from the proximal end of the most proximal electrode in the first set of electrodes to the distal end of the most distal electrode in the first set of electrodes, the length of the first set of electrodes being at least about three times the diameter of the shaft.

24. The apparatus according to any one of claims 11 to 23, wherein: The length of the second set of electrodes is defined as the distance from the proximal end of the most proximal electrode in the second set of electrodes to the distal end of the most distal electrode in the second set of electrodes, the length of the second set of electrodes being at least about three times the diameter of the shaft.

25. The apparatus according to any one of claims 11 to 24, wherein: The first set of electrodes and the second set of electrodes are configured to be energized with opposite electrical polarity to deliver pulsed field ablation.

26. A method comprising: Positioning a distal flexible portion of the catheter in a first segment of the vascular anatomy, the distal flexible portion having a first set of electrodes and a second set of electrodes disposed thereon, each set of electrodes in the first set of electrodes and the second set of electrodes (1) comprising at least three electrodes having an inter-electrode spacing between adjacent electrodes and (2) being spaced apart from one another by an inter-set spacing that is at least 50% greater than each inter-electrode spacing; delivering high voltage pulses to the first set of electrodes and the second set of electrodes to ablate a first segment of the vascular anatomy; moving the distal flexible portion of the catheter to a second segment of the vascular anatomy; as well as High voltage pulses are delivered to the first set of electrodes and the second set of electrodes to ablate a second segment of the vascular anatomy.

27. The method according to claim 26, wherein: At least one electrode of the first and second sets of electrodes includes a basket electrode, the method further comprising compressing or expanding the basket electrode based on a size of the vascular anatomy in response to moving the distal flexible portion of the catheter.

28. The method according to claim 27, wherein: Moving the distal flexible portion of the catheter to the second section of the vascular anatomy includes retracting the distal flexible portion of the catheter, and In response to retracting the distal flexible portion of the catheter, the basket electrode is automatically expanded.

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