# Patent

## Title
Non-electric field renal denervation electrode

## Abstract

A renal denervation device can include an elongated catheter body extending along a longitudinal axis, and an assembly connected to the catheter body. The assembly includes a plurality of heating elements connected to the catheter body. Each heating element has a conductor and a layer of an RF dissipating material such as a polymer overlying the conductor. During operation of the device, the layer of RF dissipating material is disposed between the conductor and body tissues of a subject. The layer of RF dissipating material is substantially thicker than the Debye length within the material in order to reduce the electric field reaching the tissue and to eliminate direct contact of the electrode with the body tissue.

## Background
CROSS REFERENCE TO RELATED APPLICATION
This application claims the benefit of the filing date of U.S. Provisional Patent Application No. 61/635,512 filed Apr. 19, 2012, the disclosure of which is hereby incorporated herein by reference.


FIELD OF THE INVENTION
This invention relates generally to electrodes for RF energy application and to devices and methods incorporating such electrodes including renal denervation devices and methods.
BACKGROUND OF THE INVENTION
Hypertension is a major public health concern. An estimated 30-40% of the adult population in the developed world suffers from this condition. Diagnosis and treatment of hypertension remain suboptimal. Despite the availability of numerous safe and effective pharmacological therapies, the percentage of patients achieving adequate blood-pressure control to guide-line target values remains low. Much failure of the pharmacological strategy to attain adequate blood-pressure control is attributed to both physician inertia and patient non-compliance and non-adherence to a lifelong pharmacological therapy. Thus, the development of new approaches for the management of hypertension is a priority. These considerations are especially relevant to patients with so-called resistant hypertension (i.e., those unable to achieve target blood-pressure values despite multiple drug therapies at the highest tolerated dose). Such patients are at high risk of major cardiovascular events.
Renal sympathetic efferent and afferent nerves, which lie within and immediately adjacent to the wall of the renal artery, are crucial for initiation and maintenance of systemic hypertension. Indeed, sympathetic nerve modulation as a therapeutic strategy in hypertension had been considered in the past. Surgical methods for thoracic, abdominal, or pelvic sympathetic denervation had been successful in lowering blood pressure in patients with so-called malignant hypertension. However, these methods were associated with high perioperative morbidity and mortality and long-term complications, including bowel, bladder, and erectile dysfunction, in addition to severe postural hypotension. Renal denervation is the application of a chemical agent, or a surgical procedure, or the application of energy to partially or completely damage renal nerves to partially or completely block renal sympathetic nerve activity. Renal denervation reduces or completely blocks renal sympathetic nerve activity, increases renal blood flow, decreases renal plasma norepinephrine content, and reduces the release of renin into the systemic circulation.
The objective of renal denervation is to neutralize the effect of excess renal sympathetic nerve activity which is involved in both arterial hypertension and heart failure. Device-based renal denervation is known in the art. For example, U.S. Patent Application Publication 2011/0118726 titled “Assembly of Staggered Ablation Elements,” the contents of which are hereby incorporated by reference herein, describes a catheter based renal denervation device featuring a catheter with an expandable structure connected to the distal end of the catheter. Once the device is located at the desired position within a renal artery or vein, ablation elements connected to the expandable structure can be energized to ablate the desired renal nerves or to otherwise block nerve activity.
Current devices for renal denervation utilize metallic electrodes to apply a radiofrequency (“RF”) electrical field to resistively heat the adjacent arterial endothelium. Subsequent heat transfer across the arterial wall, from endothelium to adventitia, results in denervation of the renal nerve. Procedural damage to the renal artery endothelium during a renal denervation process can be undesirable since the subsequent healing response may result in stenosis. Direct exposure of the endothelium to the RF electric field may also result in irreversible electroporation and surface electrolysis. This is because RF fields can have concentrated effects at the tissue surface which are more concentrated than heat transfer to the tissue surface.
Additionally, partial contact of the electrode may expose the circulating blood flow to the concentrated resistive heating zone resulting in coagulation, charring of the electrode surface, and increasing the potential for thrombus formation.
Thus, further improvement of devices and methods for renal denervation would be desirable.
SUMMARY OF THE INVENTION
In one embodiment of the invention, an RF treatment device includes a device body and an assembly connected to the device body. The assembly includes one or more heating elements connected to the device body, each heating element having a conductor and a layer of an RF dissipating material overlying the conductor so that the layer of RF dissipating material is disposed between the conductor and body tissues of a subject when the assembly is in an operative position within the body of the subject.
The RF dissipating material may include a polymeric material, for example one selected from the group consisting of solid polymer electrolytes, polymeric hydrogel electrolytes, polyelectrolytes, ionomers and combinations thereof. The RF dissipating material may alternately include one selected from the group consisting of sulfonated perfluoropolyethers, hydrogenated and fluorinated polyakylene oxides, polyphosphazenes, polyethyleneimines, polyvinyl alcohols, polyvinyl pyrolidones, polyethylene imines, hydrolyzed polyacrylonitrile, crosslinked polypeptides, carboxylate-containing polymers, sulfonic acid-containing polymers, and phosphate-containing polymers.
The polymeric material may further comprise a salt, the salt further comprising a cationic component and an anionic component. The cationic component may be selected from the group consisting of lithium, sodium, potassium and ammonium. The anionic component may be selected from the group consisting of carboxylates, carbonates, phosphates, perchlorates and triflates.
The RF dissipating material may alternately include a ceramic material. The ceramic material may be selected from the group consisting of tricalcium phosphate, hydroxyapatite, carbonates, sulfates, zirconium oxides, zirconium phosphates, lanthanum fluoride, silver sulfide, and Nasicon.
The RF dissipating layer may have a thickness between 10 μm and 100 μm. The RF dissipating layer may have a thickness and a Debye length, the thickness of the polymeric layer being greater than the Debye length. The Debye length may be approximately 1 μm. A ratio of the thickness of the layer of polymeric material to the Debye length of the RF dissipating material may be at least 3:1.
An RF power source may be operatively connected to the at least one heating element. The power source may be capable of providing 6 watts of radiofrequency power at a frequency of 485 KHz.
The device body may include a catheter extending along a longitudinal axis. The heating elements may be distributed around the longitudinal axis.
In another embodiment of the invention, a method of providing RF treatment includes the step of positioning one or more heating elements within a blood vessel of a mammalian subject, each heating element having a conductor and a layer of an RF dissipating material overlying the metallic conductor, the positioning step being performed so that the layer of RF dissipating material is disposed between the conductor and a wall of the blood vessel. The method may also include applying RF power to the conductors of the heating elements to heat tissues of the subject, the RF dissipating material of the heating elements substantially blocking transmission of RF electric fields to the tissues of the subject.
The heating elements may be mounted to an elongated catheter body and the positioning step may include inserting the catheter body into the blood vessel. The blood vessel may be a renal artery and the heating step may be performed so that heat transferred from the heating elements at least partially causes neuromodulation of one or more renal nerves of the subject. The power source may supply about 6 watts of power. The power source may operate at a frequency of about 485 KHz. The at least one heating element may be heated for about 90 seconds.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic view of one embodiment of a heating element of a treatment device.
FIG. 2 is a schematic view of an alternate embodiment of a heating element of a treatment device.
FIG. 3 is a schematic view of still another embodiment of a heating element of a treatment device.
FIG. 4A illustrates a side view of a catheter based renal denervation device according to a further embodiment of the invention.
FIG. 4B is a sectional view taken along line 4B-4B in FIG. 4A.



DETAILED DESCRIPTION
A heating element 100 can be used to apply energy during a tissue treatment procedure. In one embodiment of the invention, as shown in FIG. 1, a heating element 100 is brought into proximity with a body tissue 140. The heating element 100 is coupled to a structure 160. Structure 160 may be an ablation catheter as shown in FIGS. 4A-B, configured to introduce the heating element into the body and to the desired treatment area, for example. The heating element 100 is powered with RF alternating current from a source 110. Alternating current is passed to a conductor, for example an electrode 120. The electrode 120 includes a layer of an RF-dissipating material 130. The RF alternating current 110 passing through the electrode 120 heats the layer of RF dissipating material 130 which then transfers heat to tissue 140. The circuit is completed with a dispersive electrode 150, which may, for example, a large grounding pad positioned on the patient's skin, or alternately an adjacent counter-electrode.
The RF dissipating material has properties, such as a high dielectric constant, such that the material is capable of being heated by the RF field. Preferably, the RF dissipating material does not have substantial electronic conductivity arising from free electrons in a conduction band, but may have appreciable ionic conductivity, i.e., electrical conductivity arising from mobile ions in the material. For example, the RF dissipating material may include a polymeric material or a ceramic.
Examples of such polymeric materials include solid polymer electrolyte solutions, polymers having permanent mobile dipole segments, hydrogels and polyelectrolytes.
Solid polymer electrolytes include polymer materials capable of dissolving polar components so as to enable RF heating. These polymers may include, for example, hydrogenated and fluorinated polyalkylene oxides such as polyethylene glycol, polypropylene glycol, and polytetramethylene oxide. Other polymers that can be used as solid polymer electrolytes include, for example, polyphosphazenes and polyethyleneimines.
Hydrogels include hydrophilic polymer networks that absorb significant quantities of water. Hydrogel polymer coatings may, for example, include polyvinyl alcohols, polyvinyl pyrolidones, polyethylene imines, hydrolyzed polyacrylonitrile, water soluble carbohydrates such as hyaluronic acid, and crosslinked polypeptide compounds such as albumin.
Polyelectrolytes include polymers possessing a polar functionality pendant to the polymer chain. Examples of polyelectrolytes can include, for example, carboxylate containing polymers such as polyacrylic acid and sodium salts of polymethacrylic acid, sulfonic acid containing polymers such as perfluorinated polyether sulfonic acids, and phosphate containing compounds such as DNA. Polyelectrolytes can also include polymers having pendant groups possessing large polar moments such as polyphosphorylcholines.
Additional components may be used in combination with a polymer coating, including ionic compositions known to partially or fully dissociate within the polymer matrix. These can include, for example, lithium, potassium, sodium, magnesium and NR4+ salts of stable anions known to yield high degrees of dissociation. These anions may be, for example, Cl4−, CF3SO3−, AsF6−, PF6−, I−, Br−, SCN−, B10Cl10−, CF3CO2−, and Cl−.
The polymeric material may be chemically crosslinked to enhance mechanical properties. Alternately the polymeric material may comprise a phase separated block copolymer as a means to impart physical properties similar to a thermoplastic elastomer.
Examples of ceramic dissipating materials include ionically conducting ceramics, including phosphate compositions such as tricalcium phosphate and hydroxyapatite, carbonates, sulfates, and other solid state ceramics known to ionically conduct such as zirconium oxides, zirconium phosphates, lanthanum fluoride, silver sulfide, and Nasicon.
Other additional components can include those with relatively large polar moments and known to dissolve within the polymer matrix. Examples of these may include, for example, high dielectric solvents such as ethylene carbonate, propylene carbonate, butylene carbonate, and cyclic and linear alkyloxylene oligomers.
Combinations of the aforementioned materials also can be used. For example, the combinations can include multiple sub-layers of different RF-dissipating materials cooperatively constituting the layer or can include alloys or mixtures of plural RF-dissipating materials.
In order to reduce or prevent exposure of the tissue 140 to an electric field, the thickness of the layer of polymeric material 130 is preferably significantly larger than the RF field penetration depth (Debye length) within the polymeric material 130. The Debye length refers to the distance from the electrode 120 at which the magnitude of the electric field decreases to 1/e the magnitude of the electric field at the location at which the electrode 120 contacts the layer of polymeric material 130. After a few Debye lengths, the magnitude of the electric field approaches zero asymptotically. The Debye length is dependent, in part, on both the radiofrequency employed and the properties of the polymeric material. The term Debye length, as used herein, refers to the Debye length at the operating frequency of the device. Where the device is connected to an RF power source adapted to supply power at a particular frequency, or accompanied by instructions to connect the device to such a source, the frequency of the source should be taken as the operating frequency of the device. Where the device is associated with instructions to apply a particular frequency, that frequency should be taken as the operating frequency of the device. Absent the aforementioned conditions, the operating frequency of the device should be taken as 1 MHz, which is the highest frequency that would generally be used. In some embodiments of the invention, the Debye length for the frequencies used is on the order of 0.01 μm to 1 μm. The layer of polymeric material 130 is preferably substantially larger than the Debye length, and in some embodiments of the invention can be on the order of 5 μm to 50 μm, more typically 15 μm to 25 μm, for example 20 μm. In one embodiment, the ratio of the length of the polymeric material 130 to the Debye length is 20:1 or more. Other ratios, such as 10:1 or more, 5:1 or more, or 3:1 or more, are also contemplated.
The layer of polymeric material 130 is preferably less electrically conductive than metals. In a preferred embodiment of the invention, the layer of polymeric material 130 is chosen from the group of solid polymer electrolytes, synthetic hydrogels, polyelectrolytes and ionomers. In polymer electrolytes, which are polymers having ionic moieties, conductivity is ionic, not electronic. One example of a polymer electrolyte is sulfonated tetrafluoroethylene, which is also referred to by the trademark NAFION® and is commercially available from the DuPont company of Wilmington, Del.
Other configurations of heating elements 100 are also contemplated. For example, in a bipolar electrode configuration, a pair or heating elements 100 can be configured to simultaneously contact a tissue 140 when applying energy to the tissue 140, as seen in FIG. 2. In this embodiment, an alternating current power source 110 provides power to two electrodes 120 that flank a tissue 140 that is to be treated in a procedure, such as a renal denervation procedure. Each electrode 120 includes a layer of polymeric material 130 sandwiched between the respective electrodes 120 and the tissue 140 to be treated, and is carried by a structure 160.
In yet another embodiment of the invention, an alternating current power source 110 provides power to two electrodes 120 encapsulated in a single layer of polymeric material 130, as shown in FIG. 3. The electrodes 120 are carried on a structure (not shown), such as that described below.
Although it is preferable for the polymeric material to fully cover the surface of the electrode that is targeting the tissue, this is not an absolute requirement. For example, minor breaks, holes, openings or other imperfections in the polymeric material will not dramatically affect the dissipation of the electric field between the electrode and the tissue, and also will not dramatically affect the ability of heat to transfer through the polymeric material to the tissue.
An example of a structure 160 that can be used to carry one or more heating elements 100 is illustrated in FIGS. 4A-B. A catheter 10 includes an elongated catheter body 12 extending longitudinally between a proximal end 13 and a distal end 14 along a longitudinal axis 16. An expandable assembly 20, including four struts 30a-d, is connected to the distal end 14 of the catheter body 12. The struts 30a-d are spaced circumferentially about the longitudinal axis 16 of the catheter, as best seen in FIG. 4B, which represents a sectional view of the expandable assembly 20 as viewed along the longitudinal axis 16.
Each strut 30a-d includes a corresponding energy emitter 40a-d, such as an RF electrode 120. The electrodes may include one or more of a number of materials, the materials generally being radiopaque.
The expandable assembly 20 is movable between a collapsed arrangement (not shown) and the expanded arrangement shown in FIG. 4A. A distal end of pull wire 25 is connected to the distal end of the expandable assembly 20 and runs proximally through the catheter body 12 to a location where it can be actuated. Actuating the pull wire 25, for example by the operator grasping and pulling the pull wire 25, causes the expandable assembly 20 to move from a collapsed arrangement (not shown) to the expanded arrangement shown in FIG. 2A. The pull wire 25 is just one of various options that can be used to effectuate movement of an electrode-carrying assembly from a collapsed arrangement to an expanded arrangement. Other mechanisms might include, for example, springs, memory metals, or balloons. A more complete description of suitable structures for the expandable assembly 20, along with various features of struts 30a-d, can be found in U.S. Patent Application Publication 2011/0118726, which is hereby fully incorporated by reference herein.
In use, the catheter 10 with the expandable assembly 20 is inserted into a blood vessel or the like in a collapsed arrangement (inside a guiding sheath or the like) and deployed into the expanded arrangement shown in FIG. 4A. Preferably, the struts 30a-d are designed to allow blood flow in the blood vessel across the expandable assembly 20 and reduce or avoid obstruction. The expandable assembly 20 preferably has no sharp corners or edges but has rounded corners and edges to facilitate easier and smoother movement within the blood vessel. The heating elements in the expanded arrangement contact surfaces to be treated to ablate tissue and/or denervate nerves. The heating elements are positioned on structure 160 so that when the structure is in the operative condition depicted, a portion of the layer 130 of conductive polymer in each heating element (FIG. 1) faces outwardly away from the longitudinal axis. In use, a portion of the polymer layer 130 of each heating element faces the interior wall of the renal artery. The metal electrode 120 (FIG. 1) desirably does not contact the artery wall.
Other structures 160 can be used to carry electrodes to a tissue site for treatment. For example, although FIGS. 4A-B illustrate an assembly with four electrodes, alternate embodiments of a structure could include a single electrode, two electrodes, or any other number of electrodes desired.
Structures other than an expandable basket configuration can also be used in other embodiments of the invention. For example, the electrodes could be connected to an expandable balloon. Another support structure that could be used, by means of example and not limitation, is an assembly with an expandable tree configuration. In such a configuration, one or more resilient biasing members with corresponding electrodes attached thereto are connected to a distal end of a catheter body. During treatment, the biasing members bring the electrodes into proximity with the area of tissue to be treated. Although the devices and methods are described above with reference to renal denervation, they can also be applied in other procedures where tissues must be heated as, for example, thermal ablation procedures.
These and other embodiments of the invention may result in multiple advantages over renal denervation devices in the prior art. For example, embodiments of the invention may (i) eliminate exposure or delivery of the electric field to endothelium; (ii) eliminate direct contact of endothelium with conductive metal and thus preclude Faradaic electrolysis and metal leaching; and (iii) allow for lower operating temperatures for a renal denervation process, minimizing thermal damage to the endothelium, and reducing the possibility of coagulum formation, electrode charring, and thrombotic events, and improve apposition of the electrode to the vessel wall.
Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims.

## Claims

1. An RF treatment device comprising:
a device body; and
an assembly connected to the device body comprising one or more heating elements connected to the device body, each heating element having a conductor and a layer of an RF dissipating material overlying the conductor so that the layer of RF dissipating material is disposed between the conductor and body tissues of a subject when the assembly is in an operative position within the body of the subject, wherein the RF dissipating layer has a thickness and a Debye length, the thickness of the dissipating layer being greater than the Debye length.

2. The device of claim 1, wherein the RF dissipating material includes a polymeric material.

3. The device is selected wherein the polymeric from the group consisting of solid polymeric hydrogel electrolytes, polyelectrolytes, ionomers and combinations thereof.

4. The device of claim 2, wherein the polymeric material is selected from the group consisting of sulfonated perfluoropolyethers, hydrogenated and fluorinated polyakylene oxides, polyphosphazenes, polyethyleneimines, polyvinyl alcohols, polyvinyl pyrolidones, hydrolyzed polyacrylonitrile, crosslinked polypeptides, carboxylate-containing polymers, sulfonic acid-containing polymers, and phosphate-containing polymers.

5. The device of claim 4 wherein the polymeric material further comprises a salt, the salt further comprising a cationic component and an anionic component.

6. The device of claim 5 wherein the cationic component is selected from the group consisting of lithium, sodium, potassium and ammonium.

7. The device of claim 5 wherein the anionic component is selected from the group consisting of carboxylates, carbonates, phosphates, perchlorates and triflates.

8. The device of claim 1, wherein the RF dissipating material includes a ceramic material.

9. The device of claim 8, wherein the ceramic material is selected from the group consisting of tricalcium phosphate, hydroxyapatite, carbonates, sulfates, zirconium oxides, zirconium phosphates, lanthanum fluoride, silver sulfide, and Nasicon.

10. The device of claim 1, wherein the RF dissipating layer has a thickness between 10 μm and 100 μm.

11. The device of claim 1, wherein the Debye length is approximately 1 μm.

12. The device of claim 1, wherein a ratio of the thickness of the layer of polymeric material to the Debye length of the RF dissipating material is at least 3:1.

13. The device of claim 1, further comprising an RF power source operatively connected to the at least one heating element.

14. The device of claim 13, wherein the power source is capable of providing 6 watts of radiofrequency power at a frequency of 485 KHz.

15. The device of claim 1, wherein the device body includes a catheter extending along a longitudinal axis.

16. The device of claim 15, wherein the heating elements are distributed around the longitudinal axis.

17. A method of providing RF treatment comprising the steps of:
positioning one or more heating elements within a blood vessel of a mammalian subject, each heating element having a conductor and a layer of an RF dissipating material overlying the metallic conductor, the positioning step being performed so that the layer of RF dissipating material is disposed between the conductor and a wall of the blood vessel; and
applying RF power to the conductors of the heating elements to heat tissues of the subject, the RF dissipating material of the heating elements substantially blocking transmission of RF electric fields to the tissues of the subject.

18. A method as claimed in claim 17 wherein the heating elements are mounted to an elongated catheter body and the positioning step includes inserting the catheter body into the blood vessel.

19. A method as claimed in claim 18 wherein the blood vessel is a renal artery and the heating step is performed so that heat transferred from the heating elements at least partially causes neuromodulation of one or more renal nerves of the subject.

20. The method of claim 19, wherein the power source supplies about 6 watts of power.

21. The method of claim 20, wherein the power source operates at a frequency of about 485 KHz.

22. The method of claim 21, wherein the at least one heating element is heated for about 90 seconds.