Ablation catheter apparatuses and methods

Abstract

Methods and apparatuses for providing pulsed electrical treatment (including high voltage, sub-microsecond pulsed electric energy) to tissue, including cardiac tissue. The apparatus may include electrodes that conform to tissue surfaces. These apparatuses may include wire electrodes in the plane of a paddle-shaped applicator. Any of these apparatuses and methods may include a distal support portion.

Description

ABLATION CATHETER APPARATUSES AND METHODSCLAIM OF PRIORITY

[0001] This patent application claims priority to U.S. Provisional Patent Application No. 63 / 548,845, titled “ABLATION CATHETER APPARATUSES AND METHODS,” filed on February 1, 2024, which is herein incorporated by reference in its entirety.BACKGROUND

[0002] Short, high-field strength electric pulses have been described for electromanipulation of biological cells. For example, electric pulses may be used in treatment of human cells and tissue. The effect of the voltage induced across a cell membrane may depend on the pulse length and pulse amplitude. Pulses shorter than about 1 microsecond may result in a delayed cell death with intact cell membranes. Such shorter pulses may trigger programmed cell death (e.g., apoptosis) in some or all of the cells exposed to the described field strength and pulse duration. These higher electric field strengths and shorter electric pulses may be useful in manipulating intracellular structures, such as nuclei, endoplasmic reticulum and mitochondria. For example, such sub-microsecond (e.g., nanosecond) high voltage pulse generators have been proposed for biological and medical applications.

[0003] In some cases, two or more electrodes are used to deliver electric pulses, including high-field strength electric pulses to a selected treatment area. The two electrodes may be configured for bipolar operation. The electrodes are placed in contact with tissue in the area to receive treatment. In some cases, the treatment area may have a varying or irregular shape. For example, the treatment area may transition from a first diameter to a second diameter. The varying diameters and / or irregular shapes may make it difficult for the electrodes to maintain constant and uniform contact.

[0004] Thus, it may be beneficial to provide electrodes that may conform to varying and / or irregularly shaped treatment areas.SUMMARY OF THE DISCLOSURE

[0005] Described herein are methods and apparatuses (e.g., devices and systems, including applicators) for delivery of short, high-field strength electric pulses, including, but not limited to, nanosecond pulses, to treat a target tissue. These methods and apparatuses may be configured to perform ablation of target tissue, such as, but not limited to, cardiac tissue.

[0006] For example, descried herein are apparatus that may be configured to treat a target tissue having a paddle-shaped applicator that may conform to the target tissue while securingto the tissue to allow reliable and effective treatment of the target tissue, with minimal arcing, particularly when applying microsecond or sub -microsecond (e.g., nanosecond) pulsing. Also described herein are methods of using any of these apparatuses for treating tissue.

[0007] The apparatuses and methods described herein may be configured for treating the walls of an anatomical structure, such as a body passage, lumen, cavity or vessel (e.g., a heart chamber, atrial roof, atrial posterior wall, ventricular wall, heart valve, valve annulus, sinus node, Purkinje fiber, and all other cardiac outer and / or inner surface, a vein, an artery, a vessel, a trachea, a pharynx, a larynx, a bronchi, an ureter, a urethra, a fallopian tube, a cervix, a uterus, male reproductive organs, an intestine (large and / or small), a gallbladder, a bladder, a pancreas, a liver, an esophagus, a stomach, a nasal cavity, etc.) using pulsed electrical fields, including (but not limited to) nanosecond pulsed electrical fields, microsecond pulsed electrical fields, etc. For convenience of the description, all such anatomical structures, cavities, tubes, lumens, passages or vessels will be referred here as a body vessel or tissue, or portion of a tissue (e.g., target tissue). In some examples the body vessels may include pulmonary veins, antrums / ostiums, heart valve annuli and other appropriate lumina or opening. In particular, the methods and apparatuses described herein may be configured to selectively treat body vessels with varying, transitioning, and / or irregular surfaces. Electrodes that may conform to the body vessels may include a first electrode (e.g., first ablation electrode) and a second electrode (e.g., second ablation electrode) that in some implementations may be configured to deploy from an elongate body (e.g., catheter, sheath, etc.) and conform to a target tissue, for example, to a portion of a wall of a body vessel, and provide non-thermal (e.g., nanosecond or microsecond) pulsed electrical fields in a localized manner that limits or prevents damage to deeper, non-targeted regions.

[0008] The methods and apparatuses described herein are not limited to cardiac or cardiovascular treatments, such as treatments of pulmonary veins ostium, pulmonary veins lumen, atrial roof, atrial posterior wall, ventricular wall, heart valve, valve annulus, sinus node, Purkinje fiber and all other cardiac surfaces, but may be used to treat any other body regions, lumens and tissue, as appropriate. These instruments and devices may be configured for insertion into anatomical structures, for example, they may be configured as an elongate applicator tool, including catheters, tube, etc. sized and shaped to fit within and / or to treat an associated anatomical structure. For example, described herein are methods and apparatuses configured for the delivery of sub-microsecond (e.g., nanosecond) pulsed electrical fields to a portion of the gastrointestinal tract, e.g., stomach, small intestine, large intestine, duodenum,colon, etc., including, but not limited to the esophagus. Also described herein are methods and apparatuses configured for the delivery of sub -microsecond (e.g., nanosecond) pulsed electrical fields to a portion of the respiratory tract, including the trachea, pharynx, larynx, bronchi and bronchioles. The methods and apparatuses described herein are also especially useful, among other things, in cardiac applications, including but not limited to treatment of atrial fibrillation, ventricular tachycardia, etc.

[0009] The apparatuses described herein may be configured for use with and / or may include elongate applicator tools (e.g., catheters) that may be inserted into a body vessel or lumen, including but not limited to a blood vessel (an artery, a vein, etc.). These applicator tools may include an elongate, flexible body extending in a proximal-to-distal direction. One or more (e.g., a plurality) of electrodes configured for the delivery of electrical pulses (e.g., nanosecond pulses) to a target tissue may be present at an end region of the flexible body.

[0010] The applicator (“applicator tool”) may be configured to removably couple to a pulse generator configured to generate a non-thermal, for example, nanosecond or microsecond pulsed energy, such coupling may be through a handle that is proximal to the distal end region including the electrodes. The electrodes may be deployable, including (but not limited to self-deploying, manually deploying, or semi-automatically deploying) and may be on an expanding member that expands to contact the vessel wall. The handle may control the deployment. Alternatively, in some cases the apparatus (e.g., applicator tool or device) may be configured to couple to the pulse generator directly, without the need for a handle. According to one example, apparatuses described herein comprise medical devices and instruments for use in procedures inserting the applicator tools into a body lumen. These apparatuses may be introduced, for example, through an outer delivery catheter or a guiding sheath into a body lumen.

[0011] In general, any of these apparatuses and methods may be configured for use with or including an endoscope and / or laparoscope. For example, the apparatus may be configured to pass through the working channel of an endoscope. In some examples the distal end region (e.g., the paddle-shaped applicator) may be configured to have a lower profile delivery configuration that may more easily fit through a working channel and / or delivery catheter, and an expanded, deployed configuration. In some examples the elongate shaft or body may be rigid, and the device can be used laparoscopically. Alternatively, in some examples the elongate shaft may be flexible or semi-flexible.

[0012] In general, any of these apparatuses may include: an elongate body; a paddleshaped applicator at a distal end region of the elongate body, the paddle-shaped applicatorcomprising: a first electrode comprising a first wire extending across the paddle-shaped applicator; a second electrode comprising a second wire extending across the paddle-shaped applicator substantially parallel to the first electrode; and a distal support portion extending distally from the first and second electrodes; wherein the first electrode and the second electrode are configured as a bipolar pair to apply ablation energy therebetween.

[0013] In any of these apparatuses the paddle-shaped applicator may comprise an elongate body, or in some cases it may extend and / or retract from the elongate body. The elongate body may be a catheter or tube. In some examples the elongate body may be flexible. In some examples the elongate body may be rigid. The elongate body may include an internal lumen. In some examples the paddle-shaped applicator may be configured to be retracted and / or extend from the lumen of the elongate body. Any of these apparatuses may include a second elongate body including an internal lumen through which the first elongate body and paddle-shaped applicator may be passed, e.g., to deliver the paddle-shaped applicator to the target tissue region. In any of these examples the paddle-shaped applicator may extend from the distal end of the elongate body. In some examples the paddle-shaped applicator may be coupled to the distal end region of the elongate body. Alternatively, in some examples the paddle-shaped applicator may be configured to be retracted at least partially into the elongate body. Alternatively or additionally, the elongate body and paddleshaped applicator may be configured to be inserted into, and / or extended / retracted from a catheter, endoscope (e.g., working channel), bronchoscope, sheath, introducer, etc.

[0014] In general, a paddle-shaped applicator may have a relatively flat (e.g., planar) shape. Alternatively, in some implementations, it may have a bow / curved shape. In general, the ends may be tapered or rounded (e.g., at the proximal and / or distal ends) and may be elongated. In some cases the paddle-shaped applicator may comprise a wire frame forming an outer perimeter. The outer perimeter of the paddle-shaped applicator may be any appropriate shape, e.g., rounded, rectangular, square, oval, etc.

[0015] As mentioned, the paddle-shaped applicator may be configured to retract into the distal end region of the elongate body and / or extend from the distal end region of the elongate body. The paddle shaped applicator may be configured to expand and contract. In some cases the paddle-shaped applicator may be generally electrically insulating, except where the first and second electrodes are exposed. The outer perimeter of the paddle-shaped applicator may be formed of one or more electrically insulated wires. In some cases the paddle-shaped applicator may be formed as a wire frame that is configured to expand and collapse (e.g., when pulled into the lumen at the distal end region of the elongate body.

[0016] In any or some of these examples the paddle-shaped applicator may form a substantially flat plane. The first and second electrodes (e.g., lengths of wire) extending across the paddle shaped applicator may extend in the plane of the paddle-shaped applicator. For example, the first electrode and the second electrode may extend within the substantially flat plane of the paddle-shaped applicator. The first electrode and the second electrode may extend from one side of the paddle-shaped applicator to the other side (e.g., from opposite sides of the perimeter of the paddle-shaped applicator) or they may extend partially across the width of the paddle-shaped applicator.

[0017] In general, the first electrode and the second electrode may be parallel or substantially parallel to each other. For example, the first electrode may be separated from the second electrode by a minimum distance, d, which is substantially constant along the length of the first and second electrodes. The substantially constant distance, d, may be within about + / - 15-% of the same value (e.g., within about + / - 12%, within about + / - 10%, within about + / - 9%, within about + / - 8%, within about + / - 7%, within about + / - 6%, within about + / - 5%, within about + / - 4%, within about + / - 3%, within about + / - 2%, within about + / - 1%, etc.).

[0018] The minimum distance, d, may be between about 1-40 mm (e.g., between about 2- 40 mm, between about 3-35 mm, between about 4-30 mm, between about 2-25 mm, between about 1-20 mm, etc.).

[0019] In general, the distal support portion extends distally from the first electrode and the second electrode. In any of these examples the first electrode may be arranged distal to the second electrode, and the distal support portion may be distal to both. The first electrode and the second electrode may extend transverse to the long axis of the elongate body. Alternatively, in some examples the first electrode and the second electrode may extend at an angle (between about 1 degree and 90 degrees, between 5 degrees and 90 degrees, between about 10 degrees and 90 degrees, between about 15 and 90 degrees, between about 20 and 90 degrees, between about 30 and 90 degrees, etc.) relative to the long axis of the elongate body. In some examples the first electrode and the second electrode may extend between the outer perimeter of the paddle-shaped applicator transverse to a long axis of the elongate body.

[0020] The distal support portion may be configured to form a shelf configured to provide additional non-conductive (non-electrically conductive) support for ridge stability. In any of these apparatuses the distal support portion may comprise a wire frame formed, at least in part, from a portion of the outer perimeter of the paddle-shaped applicator. The distal support portion may be configured to form a shelf for stabilizing or securing the applicatoragainst the tissue, when in use. For example, the distal support portion may provide ridge stability. Thus, in some examples, the distal support portion may be configured as a shelf to provide stability to the paddle-shaped applicator when the paddle-shaped applicator is applied to the tissue, for example, to prevent the applicator from sliding or slipping relative to the target tissue. The distal support portion may be any appropriate size and / or shape. In general, the distal support portion may extend distally from the first electrode by a distance d. In some implementations, the distance d may be may be less than about half the distance between the first electrode and the second electrode (e.g., about 40% or less); in other implementations the distance d may be greater than about half the distance between the first electrode and the second electrodes (e.g., about 50% or more of the distance, about 60% or more, about 70% or more, about 80% or more, about 90% or more, about 100% or more, about 120% or more, about 130% or more, about 140% or more, about 150% or more, etc.).

[0021] In general, these apparatuses may be used with sensing, mapping and / or navigation, including using sensing electrodes / mapping electrodes. In some examples the paddle-shaped applicator may include one or more sensing / mapping electrodes.Alternatively, any of these apparatuses may be used with a separate mapping, including electrical mapping, apparatus. In some cases, the elongate body may include one or more sensing / mapping electrodes. In further examples, the apparatus may include one or more sensing / mapping electrodes on the outer perimeter of the paddle-shaped applicator. The apparatus may be configured to determine spacing of the paddle-shaped applicator relative to the elongate body using one or more sensing electrodes on the elongate body. For example, the apparatus may include one or more sensing / mapping electrodes on a shaft of the elongate body.

[0022] The sensing and / or mapping (e.g., navigation) electrodes may be positioned on the frame forming the paddle-shaped applicator. In some cases one or more sensing and / or mapping electrodes may be positioned on the elongate shaft proximal to the paddle-shaped applicator. As used herein, these sensing and / or mapping electrodes may be configured for use in sensing electrical properties of material (e.g., tissue) near the paddle-shaped applicator. In some examples the sensing and / or mapping electrodes may be used for navigation, e.g., confirming or determining the location of the paddle-shaped applicator based on the electrical properties of the tissue. In some examples the sensing and / or mapping electrodes may be used to confirm treatment of the tissue by the wire electrodes.

[0023] In general, any of these apparatuses may include one or more sensors (e.g., additional sensors) for detecting position, operation and / or surrounding environment of theapplicator, including, but not limited to the sensing and / or mapping electrodes. For example, any of these apparatuses may include one or more electromagnetic (“EM”) sensors. An EM sensor may be positioned, e.g., in the distal end region of the elongate body and may be used to determine the position of the applicator in space (e.g., within the body).

[0024] Any of these apparatuses may include one or more lateral extension portions in addition to (or instead of) the distal extension (e.g., distal support) portions. The lateral extension portions may be alternatively and equivalently referred to as lateral support portions. These lateral extension portions may be used to increase a number of sensing / mapping electrodes to improve mapping and navigation, as well as for additional lateral support. For example, the apparatus may include a first lateral extension portion of the paddle-shaped applicator extending laterally from a first side of the first electrode and a first side of the second electrode, and / or a second lateral extension portion of the paddle-shaped applicator extending laterally from a second side of the first electrode and a second side of the second electrode. The lateral extension portion may be formed as a solid, wire-frame or hybrid solid and wire-frame portion, similar or identical to the distal support portion. In addition to providing additional structure for placement of the sensing / mapping electrodes, the lateral extension portions may be configured to space the first and second wires of the electrodes from a region of the tissue and / or to help secure the paddle-shaped applicator against the tissue.

[0025] The first electrode and the second electrodes may generally be formed as wires of electrically conductive material that is exposed to allow contact with the tissue. The first wire of the first electrode and the second wire of the second electrode may be any appropriate material (e.g., electrically conductive material) and dimension. For example, the first and second wires may each have a thickness that is 0.38 mm or less (e.g., 0.2 mm or less, etc.). In some examples the first and / or second electrodes may be formed of a superelastic material, such as a superelastic nickel titanium alloy (e.g., Nitinol). The first and second wire electrodes may be formed of the same material or different materials. In some examples the first and second wire electrodes may have any appropriate cross-sectional diameter, including, but not limited to, rounded, rectangular, square, flattened, etc. In some cases the wire electrodes may be formed of a flattened (e.g., ribbon-shaped) wire. In general, the shape of the wire electrodes, including the cross-sectional diameter, may be configured to hold with tissue engagement.

[0026] In general, any of these apparatuses may include a pulse generator. For example, any of these apparatuses may include a microsecond or a nanosecond pulse generatorconfigured to provide electrical pulses having an amplitude of greater than 0.1 kV. In some implementations the pulse generator may be configured to provide electrical pulses having a duration of less than 1000 nanoseconds to paddle-shaped applicator.

[0027] In some examples, an apparatus may include: an elongate body; a paddle-shaped applicator extending or configured to extend from a distal end region of the elongate body, the paddle-shaped applicator having an outer perimeter and comprising: a first electrode comprising a first wire extending across the paddle-shaped applicator; a second electrode comprising a second wire extending across the paddle-shaped applicator substantially parallel to the first electrode and transverse to the elongate body; and a distal support portion of the outer perimeter of the paddle-shaped applicator extending distally from the first and second electrodes; wherein the first and second electrodes are configured to form a bipolar pair of electrodes to apply ablation energy therebetween.

[0028] Also described herein are methods of using any of these apparatuses. For example, described herein are methods of applying non-thermal treatment to a tissue, the method comprising: positioning a paddle-shaped applicator against a tissue so that a first electrode comprising a first wire extending across the paddle-shaped applicator and a second electrode comprising a second wire extending across the paddle-shaped applicator substantially parallel to the first wire are both in contact with the tissue, and so that a distal support region of the paddle-shaped applicator that is distal to the first and second wires is supported against a second region of the tissue; and applying a pulsed non-thermal electrical treatment between the first wire and the second wire to treat the tissue, wherein the first wire has a first polarity and the second wire has a second polarity. Positioning the paddle-shaped applicator may comprise flexibly conforming the first wire and the second wire to the tissue. The paddleshaped applicator may be poisoned against any appropriate tissue. In some cases positioning the paddle-shaped applicator comprises contacting a cardiac tissue.

[0029] In general, the applicators described herein may not need to contact the tissue (e.g., the target tissue), but may be configured to be placed and / or maintained in proximity to the target tissue to be treated. In some cases, including in cardiac applications, a conductive fluid may be used to deliver the energy to the target tissue (e.g., a conductive media such as blood). For example, blood surrounding the wire electrodes, e.g., when the electrodes are inside the heart, may conduct the electric field from the wire electrodes to the tissue, thus full contact may not be necessary. Alternatively or additionally, a conductive solution (saline, blood, etc.) may be added or applied around the electrodes during use. Thus, any of theseapparatuses may include a fluid delivery port or ports configured to apply a conductive fluid to or around the wire electrodes.

[0030] In any of these apparatuses and methods, the paddle-shaped applicator may form a substantially flat plane and the first wire, and the second wire may extend in the substantially flat plane; in some implementations the plane may be held against the tissue region, including aligning the distal support portion, so as to apply treatment between the first and second electrodes. Such a flat (or relatively flat) configuration may not be perfectly flat, but may have a very gradual curve or bend (e.g., a radius of curvature of less than 1 cm, greater than about 1 cm, greater than about 2 cm, greater than about 3 cm, greater than about 4 cm, greater than about 5 cm, etc.). Relatively flat configurations may allow a user to approach a tissue from multiple different directions. In some examples it may be beneficial for the paddleshaped applicator to be configured to bend or flex, or curve. In some cases the paddle-shaped applicator may include one or more pre-curved regions, and / or may include a bias region along which the paddle-shaped applicator may bend or curve. In some examples the distal and / or lateral extension region(s) may be configured to bend and / or curve relative to the wire electrodes. As mentioned, any of the apparatuses may include mapping or sensing in combination with or as part of the method of treating the patient. For example, any of these methods may include sensing one or more signals using one or more sensing and / or mapping electrodes on the elongate body and / or an outer perimeter of the paddle-shaped applicator.

[0031] Any appropriate pulsed electrical treatment (energy) may be applied between the first and second electrodes as part of these methods. For example, any of these methods may include applying the pulsed non-thermal electrical treatment comprises applying electrical pulses having an amplitude of greater than 0.1 kV and a duration in millisecond, microsecond, nanosecond or picosecond range (e.g., a duration of less than 1000 nanoseconds).

[0032] In some examples, the pulsed electrical treatment may include an electric field between the two or more electrodes. In another example, the pulsed electrical treatment may include an electric field between at least one of the two or more electrodes and a third electrode.

[0033] The apparatuses described herein may generally be configured to safely and reliably deliver microsecond, nanosecond, picosecond, etc. pulses, and may include an electric field with a pulse width of between 0.1 nanoseconds (ns) and less than 1000 nanoseconds, or shorter, such as 1 picosecond, which may be referred to as sub-microsecond pulsed electric field. This pulsed energy may have high peak voltages, such as 1 to 5 kilovoltsper centimeter (kV / cm), 10 kV / cm, 20 kV / cm, 100 kV / cm or higher. In some applications, the pulsed energy may be less than IkV / cm. Treatment of biological cells may use a multitude of periodic pulses at a frequency ranging from 0.1 per second (Hz) to 100,000 Hz, and may trigger regulated cell death, for example, in the in-growing tissue causing restenosis. Selective treatment of vessel walls with high voltage, sub-microsecond pulsed energy can induce regulated cell death (e.g., programmed cell death, apoptosis, etc.) within the cells that are causing restenosis without substantially affecting normal cells in the surrounding tissue due to its non-thermal nature. A subject may be a patient (human or non-human, including animals). A user may operate the apparatuses described herein on a subject. The user may be a physician (doctor, surgeon, etc.), medical technician, nurse, or other care provider. In general, the applied energy may be monophasic or biphasic. In some cases the pulsed applied energy may be charge balanced.

[0034] Thus, the application of high voltage, fast (e.g., microsecond or sub -microsecond) electrical pulses may include applying a train of monophasic or biphasic electrical pulses having a pulse width, for example, of between 0.1 nanoseconds (ns) and 1000 nanoseconds. Applying high voltage, fast electrical pulses may include applying a train of electrical pulses having peak voltages of between, for example, 1 kilovolt and 500 kilovolt (and electric field between, for example, 1 kV / per centimeter (kV / cm) and 500 kV / cm). Applying high voltage, fast electrical pulses may include applying a train of electrical pulses at a frequency, for example, of between 0.1 per second (Hz) to 100,000 Hz.

[0035] Any of these apparatuses may be used with a pulse generator. For example, described herein are systems for treating tissue that may include: an elongate applicator (e.g. applicator tool) as described herein, a connector, e.g., a high voltage connector adapted to couple the elongate applicator tool to a pulse generator; and a pulse generator configured to generate a plurality of electrical pulses having amplitude of at least 0.1 kV, the pulse generator comprising a port configured to connect to the high voltage connector. In some examples the applicator tool includes an elongate body having a distal end region from which one or more electrodes are configured to extend. The distal end may be steerable (e.g., may articulate) in some examples. The apparatuses described herein include devices that may be referred to as applicator tools, and typically include an applicator (or applicator region) at or near a distal end region for applying energy.

[0036] As mentioned, any of these apparatuses may be configured so that the proximal end of the apparatus is adapted to be coupled to a robotic or movable arm, for example, for computer-controlled activation of the set of electrodes. Alternatively, or additionally theproximal end of the applicator tool may be adapted to couple to a handle of the pulse generator which may in turn be adapted for connection to a robotic arm.

[0037] This patent application may be related to U.S. patent application 18 / 353,867, titled “MULTI-STRUT ABLATION AND SENSING CATHETER DEVICES AND METHODS,” and filed on July 17, 2023, and to PCT / US2022 / 020887, filed March 18, 2022, titled “CIRCUMFERENTIAL ABLATION DEVICES AND METHODS,” now International Publication No. WO 2022 / 231726, which claims priority to U.S. Provisional Patent Applications No. 63 / 253,119, titled “CIRCUMFERENTIAL ABLATION CATHETER DEVICES AND METHODS,” filed on October 6, 2021. This patent application may also be related to U.S. Patent Application No. 18 / 046,784, titled “CIRCUMFERENTIAL ABLATION DEVICES AND METHODS,” filed on October 14, 2022, now U.S. Patent Application Publication No. US 2023 / 0068059, each of these patent applications is herein incorporated by reference in its entirety.

[0038] Also described herein are paddle-shaped apparatuses, and methods of using them, that do not include an additional support. For example, an apparatus may include: an elongate body; a paddle-shaped applicator at a distal end region of the elongate body, the paddleshaped applicator comprising: a first electrode comprising a first wire extending across the paddle-shaped applicator; a second electrode comprising a second wire extending across the paddle-shaped applicator substantially parallel to the first electrode, wherein the first electrode and the second electrode are configured as a bipolar pair to apply ablation energy therebetween; and a plurality of sensing electrodes. The sensing electrodes may be positioned on the paddle-shaped applicator. In some examples the sensing electrodes are on the perimeter of the paddle-shaped applicator. Alternatively or additionally, the sensing electrodes may be on the elongate body (e.g., on a distal end region of the elongate body). The sensing electrodes may be used to sense the tissue and / or to sense the other electrodes on the apparatus. In some examples the sensing electrodes are configured as mapping electrodes. As mentioned, the elongate body may include one or more EM sensors.

[0039] All of the methods and apparatuses described herein, in any combination, are herein contemplated and can be used to achieve the benefits as described herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0040] A better understanding of the features and advantages of the methods and apparatuses described herein will be obtained by reference to the following detailed description that sets forth illustrative embodiments, and the accompanying drawings of which:

[0041] FIG. 1 illustrates one example of a system for delivering high voltage, fast pulses of electrical energy.

[0042] FIGS. 2A-2C illustrate an example of a paddle-like applicator that includes an outer electrode (wire electrode) and an inner electrode (wire electrode). FIG. 2A shows an example of a substantially flat paddle applicator including an outer (more distal) wire electrode and an inner (more proximal) wire electrode. FIG. 2B shows another example of a paddle-shaped applicator apparatus similar to that shown in FIG. 2A. FIG. 2C shows another example of a paddle-like applicator in which a portion of the apparatus has been made transparent.

[0043] FIGS. 3 A and 3B illustrate an example of an apparatus including an elongate body and a paddle-shaped applicator having a distal support portion. The outer (distal) and inner (proximal) wire electrodes of the apparatus of FIG. 3 A are arranged so that the minimum distance, d, between the outer and inner wire electrodes is substantially the same along their lengths. In FIG. 3B the paddle applicator and elongate body include a plurality of sensing and / or mapping electrodes.

[0044] FIG. 4 illustrates another example of an apparatus including a paddle-shaped applicator. In this example the applicator includes a distal support portion as well as a right and left lateral extension portions.

[0045] FIGS. 5A-5B illustrate extension or deployment of the paddle-shaped distal end region of one example of an apparatus from a distal end region of a catheter.

[0046] FIGS. 5C-5D illustrate examples of a paddle-shaped applicator having more than 2 (two) wire electrodes.

[0047] FIG. 6A shows an example of an apparatus including an elongate body and a paddleshaped distal end region having a first electrode and a second electrode (forming the bipolar pair) in which the wires forming the first and second electrodes are substantially parallel with each other, and angled relative to the long axis of the elongate body.

[0048] FIG. 6B shows an example of an apparatus including an elongate body and a paddleshaped distal end region having a first electrode and a second electrode (forming the bipolar pair) in which the wires forming the first and second electrodes are arranged substantially parallel to the long axis of the elongate body, as well as lateral extension regions.

[0049] FIG. 7 schematically illustrates one example of a method of treating tissue using an apparatus as described herein.DETAILED DESCRIPTION

[0050] Described herein are apparatuses (systems, devices, etc.) and methods for treating a tissues, including tissues of a body lumen such as a body vessel, with pulsed electricalfields using paddle-shaped applicators including one or more pairs of wire electrodes that are configured to deliver the pulsed electrical fields to the tissue while maintaining a stable position of the electrodes on the tissue. The apparatuses and methods described herein may be positioned inside of a region of a body, including, but not limited to, a lumen of a body such as a tubular body member or vessel, against any wall of an organ, and / or in transitional areas (e.g., antrum, ostia, carina, annulus, etc.). These methods and apparatuses may be particularly useful for treating cardiac tissues.

[0051] In general, these apparatuses may include: an elongate body and a paddle-shaped applicator at a distal end region of the elongate body. In some implementations, the paddleshaped applicator may be configured to collapse into a narrower-profile delivery configuration and expand (e.g., self-expand) into the broader, flattened paddle-shape. In general, the paddle-shaped applicator may have a first electrode (e.g., a first ablation electrode, typically a wire electrode) that extends at least partially across the paddle-shaped applicator. A second electrode (e.g., second ablation electrode, also typically a wire electrode) may extend at least partially across the paddle-shaped applicator substantially parallel to the first ablation electrode. The first and second electrodes may be approximately the same length. Any of these applicators may include a distal support portion of the paddle-shaped applicator that extends distally from the first and second ablation electrodes. The first electrode and the second electrode may be configured as a bipolar pair of electrodes to apply ablation energy therebetween.

[0052] These apparatuses may be referred to as focal point applicators, as they may deliver the pulsed electrical energy to a particular region (focal region or focal point) and may be repeatedly repositioned to treat a target region or regions. The distal support region may be particularly helpful in positioning and maintaining the position of the applicator. In any of these apparatuses the applicator may be delivered through a catheter. In some examples the catheter may be included as part of the apparatus (e.g., system). The elongate body may be a catheter. In some examples these apparatuses may be used with a second, e.g., delivery catheter.

[0053] In some applications, without the distal support portion extending distally from the first and second wire electrodes (e.g., “ablation electrodes”), the applicator may not be sufficiently stable and may slide over the ridge of the tissue when placed, for example, for linear ablation. Thus, these apparatuses may include the distal support portion to provide stability of the ridge. Examples of the distal support portion are provided herein; in some cases the distal support portion may be formed as the distal end region of the paddle-shapedapplicator and may be generally flat or flattened (e.g., having a thickness that is less than the width and length of the paddle-shaped applicator, such as about 10% or less of the width (e.g., 10% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, etc.), and / or about 10% or less of the length (e.g., 10% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, etc.). The paddle-shaped applicator may be alternatively or equivalently referred to as a spatula applicator.

[0054] The distal support portion, like the rest of the paddle-shaped applicator, may be formed as a frame, or may include a frame (e.g., a wire frame). The frame may be formed of a material such as a shape memory / superelastic material or a material that is capable of being collapsed into a delivery configuration, which may fit into the lumen of the elongate body and / or of a delivery catheter, and of expanding out into a deployed configuration, e.g., having a generally flat, paddle-shaped configuration for contacting tissue. In some examples the applicator, including the distal support portion, may be configured to be more easily collapsed in the radial direction than the longitudinal direction (e.g., along the long axis corresponding to the long axis of the elongate body). This may allow the apparatus to be applied securely against the target tissue, while still being retractable / expandable and collapsing / retracting into the lumen of the elongate body and / or a delivery catheter or endoscope (or bronchoscope, laparoscope, introducer, sheath, etc.).

[0055] These apparatuses may be configured for insertion into the body and may be sized appropriately based on the target tissue. In some examples the paddle-shaped applicator may be between about 1-20 mm wide (e.g., between about 2-20 mm, between about 4-15 mm, between about 1-10 mm, between about 4-10 mm, etc.) and / or between about 1-40 mm long (e.g., between about 1-35 mm, between about 1-30 mm, between about 1-25 mm, between about 1-20 mm, between about 1-15 mm, between about 4-40 mm, between about 4-35 mm, between about 4-30 mm, between about 4-25 mm, etc.). The first and second electrodes may be any appropriate length. In some examples the first and second electrodes extend across the full width or length of the paddle-shaped applicator (e.g., from one edge of the outer perimeter to an opposite edge of the outer perimeter). Alternatively in some examples the length of the first and second electrode may extend just partially across the paddle-shaped applicator. The length of the first and second electrodes may be the same or approximately the same. The length of the first and second electrodes may refer to the active surface of the first and second electrodes, which may be uninsulated (e.g., exposed wire surfaces). The wires forming the first and / or second electrodes may be exposed over the active region butmay extend further across and / or around the paddle-shaped applicator. In some examples the wires forming the first and second electrodes may be insulated and may form all or a portion of the frame of the paddle-shaped applicator. The lengths of the first and second electrodes (e.g., the active regions of the first and second electrodes) may be any appropriate length. In some examples the lengths of the first and second electrodes may be between about 3-10 mm (e.g., between about 4-8 mm, between about 5-6 mm, between about 4-5 mm, etc.). The length, as with the overall dimensions of the paddle-shaped applicator, may be selected to produce a target size and / or depth of treatment, such as ablation.

[0056] The first and second ablation electrodes may also be used as sensing / mapping / navigation electrodes, or the apparatus may comprise separate electrodes for sensing, mapping and navigation. Although any of these apparatuses may include one or more additional electrodes for sensing and / or navigation (e.g., in some examples, mapping), these apparatuses may also or alternatively be configured for use with a separate mapping and / or navigation tool. Alternatively or additionally, the device may include one or more electrodes that may be used to sense the deployment state of the paddle-shaped applicator, e.g., relative to the elongate body. In some examples one or more sensing electrodes may be present on the elongate body and may be used in conjunction with one or more sensing electrodes, or alternatively in some examples the first and / or second (e.g., ablation or wire) electrodes on the paddle-shaped applicator, to detect when the applicator is deployed and / or the extent to which the applicator is deployed. Alternatively or additionally, the sensor(s) electrodes (including electromagnetic sensors) on the elongate body may be used by the system to define where shaft of the elongate body is within the body. Any of these apparatuses may use mapping (e.g., bipolar mapping) using sensing electrodes and / or the ablation electrodes.

[0057] Any of the apparatuses described herein may include one or more markers that allow imaging of the apparatus using, e.g., ultrasound and / or fluoroscopy, etc.

[0058] In general, the apparatuses described herein may generally provide for the safe application of even very high energy pulse (e.g., nanosecond pulses). The wire electrodes may be optimized for the non-thermal application of microsecond or sub-microsecond (e.g., nanosecond) pulses; for example, the dimensions of the wire electrodes (length, thickness, etc.) may be chosen for the delivery of high energy, sub-microsecond pulsing while minimizing arcing and / or sliding (mispositioning) of the applicator. These applicators may also result in a relatively uniform applied field. Any of these apparatuses may include a bipolar pair of electrodes formed by the first and second (wire) electrodes, that may be arranged in parallel or substantially parallel with each other along their length. For example, the spacing (minimum distance) between the first and second electrodes, d, may remain relatively constant along the lengths of the first and secondelectrodes. For example, the spacing between the first and second electrodes, d, may vary along the length by 25% or less (e.g., 22% or less, 20% or less, 18% or less, 15% or less, 12% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, etc.). As mentioned, in some examples this distance, d, is between about 1-10 mm (e.g., between about 2-8 mm, between about 2-7 mm, between about 2-6 mm, between about 3-5 mm, etc.).

[0059] As mentioned, these apparatuses may be used in any appropriate body region. In some cases, the apparatus may be used within a body vessel; the vessel may have an irregular or varying shape. For example, the antrum of a pulmonary vein may transition from a relatively large area or diameter to a relatively small area or diameter. These body vessel surfaces may be difficult for existing systems including electrodes to establish an effective contact with which to provide treatment. The various applicators, including electrodes, described herein may more easily adapt and conform to irregular and / or varying shapes and provide positive contact with the body vessel.

[0060] Any of these apparatuses may include and / or may be configured for use with a pulse generator. The pulsed electrical treatment may be microsecond pulsed treatment, or submicrosecond pulsed treatment, including nanosecond pulses. For example, nanosecond pulsed electric fields treatment may refer to the application of relatively high voltages (in some cases IkV or greater, and in some cases 5kV or greater) for a relatively short amount of time (in some cases between about 1 nanosecond and 999 ns). These high voltages and short duration times create a pulsed electric field in the region where the voltages are applied. In some cases, nanosecond pulsing may induce regulated cell death within cellular structures which may reduce a cells’ inflammatory response.

[0061] Any of the methods described herein may be ablation methods. For example, the methods described herein may be particularly useful for the treatment of cardiac regions, vessels, etc., such as, but not limited to, an antrum. In some examples, these methods and apparatuses may be used for the treatment of atrial fibrillation and other cardiac conditions, including for ablation of cardiac tissue. As will be described in greater detail below, any of these methods and apparatuses may be used for treating body regions, such as the antrum of the pulmonary vein, that has a tapered or narrowing profile. Thus, in some examples the apparatuses and methods described here are adapted for use where the shape of the body lumen in which they are to be used has a diameter that changes abruptly.

[0062] Alternatively or additionally, these apparatuses and methods may be used to treat the walls of vessels or other lumen that are not necessarily tapered or are only slightly tapered. In some examples these methods and apparatuses may be used to treat the walls of a vascular orrespiratory lumen. For example, these methods and apparatuses may be used to treat arterial stenosis, including in combination with a stent or angioplasty procedure. Thus, in some cases, these methods may be performed within the first 2-4 days following angioplasty and / or stenting. Untreated, smooth muscle cells (SMCs) at the luminal surface in deendothelialized areas may continue to proliferate at a low rate. The methods and apparatuses described herein may prevent or reduce this effect.

[0063] FIG. 1 illustrates one example of a system 100 (also referred to herein by way of example as a sub-microsecond generation system) for delivering fast pulses of electrical energy. Such system may include an elongate applicator 102, a pulse generator 107, footswitch 103, and user interface 104. Footswitch 103 is connected to housing 105 (which may enclose the electronic components) through a cable and connector 106. The elongate applicator tool 102 may include any of the apparatuses and / or applicators described herein, e.g., the paddle-shaped applicators, and may be connected to housing 105 and the electronic components therein through a cable 137 and high voltage connector 112. The system 100 may also include a handle 110 and storage drawer 108. The system 100 may also include a holder (e.g., holster, carrier, etc.) (not shown) which may be configured to hold the elongate applicator tool 102. The applicator tool may include the elongate body and paddle-shaped applicator. In some examples the system may be configured for monopolar treatment and may optionally include a dispersive electrode 133 (e.g., a return electrode pad).

[0064] The applicator tool may be any of the apparatuses for delivery pulsed electrical fields within a body vessel, as described in detail herein. These apparatuses may generally include an elongate, flexible body (generically referred to herein as an elongate body, a catheter or elongate catheter body) at the end of which are one or more electrodes, which may apply pulsed electrical fields to the body. In some cases, the elongate applicator tool 102 includes one or more imaging sensors, such as one or more cameras and / or fiber optics at or near the distal end of the elongate applicator tool 102. The camera(s) (not shown for simplicity) may be forward-facing and / or side facing. The system 100 may be configured to display images (in real time, and / or recorded) taken by the elongate applicator tool 102, in order to identify the target treatment area(s) and / or region(s).

[0065] A human operator may select a number of pulses, amplitude, pulse duration, and frequency information, for example by inputting such parameters into a numeric keypad or a touch screen of user interface 104. In some examples, the pulse width can be varied. A controller (e.g., microcontroller) may send signals to pulse control elements within the system 100. In some examples, fiber optic cables are used which allow control signaling while also electrically isolating the contents of the metal cabinet (e.g., the housing 105) with a sub-microsecond pulsegeneration system 100, e.g., the high voltage circuit, from the outside. The system 100 may be battery powered and / or powered from a wall outlet.

[0066] The elongate applicator tool 102 portion of the apparatus may be hand-held (e.g., by a user) or it can be affixed to a movable arm of a robotic system, and its operation may be at least partially automated or fully automated, including computer-controlled operation.

[0067] FIG. 2 illustrates an example of an applicator tool apparatus 200. This example includes an elongate body 205, configured as an elongate shaft. This elongate body may be flexible or rigid along all or some of its length. For example, the elongate body may be configured as a cannula, having a lumen therethrough, in which the distal end is more flexible than the proximal end. The apparatus may also include an applicator region 221 that includes a paddle-shaped applicator having a first ablation electrode 201 and a second ablation electrode 203. In this example the second ablation electrode 203 is at the distal -most end of the applicator. In some examples the apparatus includes a distal support portion or lateral extensions / supports (not present in the example applicator shown in FIGS. 2A-2C).

[0068] In FIGS. 2A-2C the applicator includes a plurality of shaft sensors (e.g., sensing electrodes 209, 209’, 209”) arranged along the distal end region of the elongate body 205 that may be used to determine how far the applicator is extended from a sheath (e.g., delivery catheter) and / or if the paddle-shaped applicator is deployed. In FIG. 2Athe shaft sensing electrodes are configured as ring electrodes; other electrode configurations may be used, including spot electrodes, etc. Any of the apparatuses described herein may be used with a delivery catheter (e.g., sheath) not shown.

[0069] In the apparatus 200 in FIGS. 2A-2C, the paddle-shaped applicator 221 also includes four sensing (or mapping) electrodes 219, 219’, 219”, 219’”. The sensing electrodes may be positioned on the perimeter (e.g., the outer perimeter 230) of the paddle-shaped applicator, as shown. The paddle-shaped applicator may be formed of the wires (e.g., the insulated portions of the wires) forming the first and second electrodes. In any of the apparatuses described herein, the wires forming the first and second electrodes may be formed of a superelastic material, e.g., nickel -titanium (Nitinol) wires with platinum / iridium coils wrapped around for radiopacity. In any of these examples the cross-sectional diameter of the wires forming the wire electrodes may be rounded, oval, flattened (e.g., ribbonshaped), etc.

[0070] In FIGS. 2B-2C, the flat paddle-shaped applicators are substantially flat. In this example, each electrode is formed by an un-insulated portion of a wire that is otherwise insulated. Similarly, the wire paddle-shaped apparatus in FIG. 2B also includes an outeractive region of a first electrode 201 and a second electrode 203. FIG. 2C schematically illustrates another example of a wire paddle-shaped apparatus 200 that also includes a first 201 active region electrode and a second 203 active region electrode. In FIG. 2C the applicator is also coupled to an electromagnetic sensor 235 (referred herein as “EM”, such as a six degree of freedom EM) that may also be used to help sensing the position of the apparatus in use, in addition to or instead of the sensing electrodes (e.g., sensing electrodes 209, 209’, 209” on the elongate body or sensing electrodes 219, 219’, 219”, 219’” on the paddle-shaped applicator). Any number of EM sensors may be used. For example, in some cases two or more EM sensors may be used. The EM sensors may be on the elongate body and / or on the paddle-shaped applicator.

[0071] Any of the apparatuses described herein may include a distal support portion of the paddle-shaped applicator that extends distally from the first and second ablation electrodes, as illustrated in FIGS. 3A and 3B. in This example, the apparatus 300 also includes an elongate body 305 from which a paddle-shaped applicator 321 extends. The paddle-shaped applicator has an outer perimeter 330 and is formed as non-electrically conductive frame. The frame forming the paddle shape may include the wires forming the first electrode 301 and the second electrode 303 that extend across the width of the paddleshaped applicator. The first and second electrodes (ablation electrodes) are also arranged so that the minimum distance, d, between the first and the second electrodes is substantially the same along their lengths. The paddle-shaped applicator in this example is otherwise expanded. In some examples the paddle-shaped applicator may be formed of a material (e.g., a polymeric material) that covers all or a portion of the flat body of the paddle-shaped applicator. The distal support portion 332 extends distally beyond the second electrode 303, forming the non-electrically conductive distal end of the paddle-shaped applicator, as shown. In some examples the distance from the distal portion of the second electrode 303 and the distal end / tip of the distal support portion of the paddle-shaped applicator, ds, may be less than about half the distance between the first electrode and the second electrode (e.g., about 40% or less); in other implementations the distance may be greater than about half the distance between the first electrode and the second electrodes (e.g., about 50% or more of the distance, about 60% or more, about 70% or more, about 80% or more, about 90% or more, about 100% or more, about 120% or more, about 130% or more, about 140% or more, about 150% or more, 160% or more, 170% or more, 180% or more, 190% or more, 200% or more, etc.). The distal support portion may form a shelf for providing stability when contacting the tissue. The material forming the distal support portion may be nonconductive(e.g., electrically insulative), and may be configured to be atraumatic, e.g., rounded, curved, etc. to prevent damage to the tissue.

[0072] FIG. 3B shows another example of an apparatus similar to the one shown in FIG. 3 A, but with additional sensing electrodes, as shown and described in FIGS. 2A-2C. For example, the apparatus shown in FIG. 3B includes a plurality of shaft sensing electrodes 309, 309’, 309” on the elongate body 305. In this example, three shaft sensing electrodes are included, one sensing electrode 309” on a distal end region of the shaft of the elongate body 305, a second sensing electrode 309’ offset proximally on the shaft from the first sensing electrode, and a third sensing electrode 309 that is offset proximally on the shaft from the second (and first) sensing electrodes.

[0073] The paddle-shaped applicator shown in FIG. 3B also includes sensing (e.g., mapping) electrodes 319, 319’, 319” arranged on the outer perimeter of the paddle-shaped applicator. The sensing electrodes may be raised (e.g., proud) of the paddle-shaped applicator, as shown in FIGS. 3B, or they may be flush with (or in some cases recessed relative to) the paddle-shaped applicator. These sensing electrodes may be referred to and may operate as frame sensing electrodes. In some examples the apparatus includes only the shaft electrodes or only the sensing electrodes on the paddle-shaped applicator (frame sensing electrodes).

[0074] Any of the apparatuses described herein may also or alternatively include one or more lateral extension portions, as illustrated in FIG. 4. A lateral extension portion may extend laterally (e.g., enlarging the width of the paddle-shaped applicator) and form a buffer region between the ends of the first 401 and second 403 electrodes (ablation electrodes) of the paddle-shaped applicator 421. In FIG. 4, as in FIGS. 3A-3B, the apparatus 400 includes an elongate body 405 (e.g., shaft) that may also include one or more sensing electrodes. In FIG. 4, three shaft sensing electrodes 409, 409’, 409” are shown progressively more proximally from the distal end region of the elongate body. A paddle-shaped applicator 421 extends from the distal end of the elongate body 405, forming a substantially planar paddle shape (spatula shape). In this example, the first 401 and second 403 wire electrodes extend across the middle region of the paddle-shaped applicator, also separated by a predetermined distance, c which is substantially constant across the length of the wire electrodes. The distal end of the applicator forms a distal support portion 432 that extends distally from the first 401 and second 403 wire electrodes. In addition the paddle-shaped applicator also includes a left 436 and right 436’ lateral extension portions extending laterally of the wire electrodes. The lateral extension portion may be continuous with the distal support portion and may also be formed as a wire frame and / or a solid structure. The paddle-shaped applicator may alsoinclude one or more (e.g., a plurality of) sensing electrodes 419 (e.g., frame sensing electrodes). In this example, the sensing electrodes on the paddle-shaped applicator may be positioned both on the perimeter of the lateral extension portions and on the inner region (on either ends of the first and second wire electrodes) of the frame forming the paddle-shaped applicator. As mentioned, the sensing electrodes, particularly those on the paddle-shaped applicator, may be used as mapping or navigation electrodes.

[0075] In general, the apparatuses described herein, and in particular the paddle-shaped applicator portion of the apparatuses described herein, may be configured to be inserted and / or withdrawn from a delivery catheter. Thus, the paddle-shaped applicator may be configured to be collapsed into a compressed configuration, within which it may be stored or held within a lumen of either or both the elongate body (e.g., shaft) or of a separate delivery catheter. In some examples the paddle-shaped applicator is configured to be withdrawn into the distal end region of the elongate body in a collapsed configuration and to expand into a deployed configuration when extending distally out of the distal end region. In some examples the paddle-shaped applicator is affixed to the distal end region of the elongate body (e.g., shaft) but may be withdrawn into the lumen (at the distal end) of a delivery catheter in a collapsed configuration and may expand into a deployed configuration when extending distally out of the catheter. FIGS. 5A and 5B illustrate an example of an apparatus having a paddle-shaped applicator 521 being held within (FIG. 5 A) and advanced distally out 528 of (FIG. 5B) a catheter 549. In FIG. 5A the distal end (e.g., the distal support portion 532) of the paddle-shaped applicator is shown in a compressed / collapsed configuration beginning to extend distally out of the catheter 549. The apparatus may be driven distally out of the catheter by, e.g., pushing the proximal end of the elongate body / shaft 505, not visible in FIG. 5 A, to extend the applicator out of the catheter 549 and into the body near the region to be treated (as shown in FIG. 5B). The paddle-shaped applicator may be configured to selfexpand (e.g., self-deploy). For example, the wire frame of the paddle-shaped applicator may be formed of a shape memory material such as nitinol (e.g., nickel titanium).

[0076] In general, these apparatuses may be used with a catheter, endoscope, laparoscope, etc. For example, as described above, the apparatus may include a paddleshaped applicator extending from an elongate body that may be inserted into / through a lumen of a second device, such as a delivery catheter (as shown in FIGS. 5A-5B), endoscope, laparoscope, etc. For example, the apparatus may be inserted through a working channel of an endoscope. As mentioned, the elongate body may be flexible. In some cases the elongate body may be rigid and may be configured to be used laparoscopically.

[0077] In FIG. 5B the paddle-shaped applicator 521 includes a first 501 and second 503 wire electrodes arranged similar to those shown in FIGS. 2A-2C, 3 A-3B and 4, in which the wires forming the first and second electrodes, e.g., ablation electrodes, are configured to be substantially parallel to each other, with a relatively constant distance, c between each other, and arranged substantially transverse to the long axis of the elongate body 505 extending in the distal -to-proximal direction. The paddle-shaped applicator 521 may be collapsed back to fit into the lumen of the catheter / delivery sheath by pulling it back (proximally) into the catheter, so that it may be withdrawn from the body and / or repositioned.

[0078] FIGS. 5C and 5D illustrate examples of apparatuses including paddle-shaped applicators 521’, 521” similar to that shown in FIGS. 3 A and 5B, but having a three or more wire electrodes. For example, in FIG. 5C, the apparatus includes a paddle-shaped applicator 521’ having three wire electrodes 501’, 503’ and 507, which are shown arranged perpendicular to the long axis of the elongate body 505’. In this example, the distal-most wire electrode 503’ is configured to act as a negative electrode,, the middle wire electrodes 507 and the proximal-most wire electrode 501’ are configured as positive electrodes. Alternatively, the polarity of the electrodes may be changed, or may be arranged differently so that energy may be applied therebetween. The paddle-shaped applicator 521’ extends distally from the elongate body 505’ and both the elongate body and the paddle-shaped applicator may be used with a catheter 549’, such as a delivery catheter.

[0079] In FIG. 5D the paddle-shaped applicator 521” is attached at distal end of an elongate body 505” and can be positioned axially relative to a catheter 549” (e.g., delivery catheter). The paddle-shaped applicator 521” includes four wire electrodes 501”, 503”, 507” and 509. The applicator may be configured so that the polarity of the wire electrodes has any appropriate order. In some examples the wire electrodes are arranged so that their polarity alternates along the length from positive 501”, negative 507”, positive 509 and back to negative 503”, as shown in FIG. 5D. As mentioned, in some cases the polarity of the electrodes may be different, e.g., only one of the wire electrodes may be positive (or negative) and the other wire electrodes may be configured to have the opposite polarity. In any of these apparatuses the polarity of the wire electrodes may be selectable.

[0080] In the examples of the paddle-shaped applicators shown in the apparatuses of FIGS. 2A-2C, 3A-3B, 4 and 5A-5D, the first and second wire electrodes are shown to extend transverse to the long axis of the apparatus. However, any appropriate orientation may be used. In general the first and second wire electrodes may be substantially parallel, and may extend completely or partially across the paddle-shaped applicator. In some cases, shown inFIGS. 6A-6B, the first 601 and second 603 electrodes may remain parallel, e.g., separated by a relatively constant distance, c and may extend at an angle (e.g., a non-transverse angle) relative to the long axis. For example, FIG. 6A shows an example of an apparatus 600 having an elongate body (shaft) 605 from which a paddle-shape applicator 621 extends, including a distal support portion 632. The first 601 and second 603 wire electrodes extend across the paddle-shaped applicator 621 at an angle (0) relative to the long axis of the elongate body 605. In this case 0 may be between 90 and 0 degrees (e.g., between 1-89 degrees, between 20-60 degrees, etc.). The distal support portion 632 in this example may therefore be larger on one side of the paddle-shaped applicator than on the other side.

[0081] FIGS. 6B shows an example of an apparatus 600’ in which the first 601’ and second 603’ wire electrodes extend across the paddle-shaped applicator 621 in parallel (or substantially parallel) with the long axis of the elongate body 605. In this example the wires forming the electrodes, e.g., the active uninsulated regions, are bracketed on either side by insulated regions. Thus, the distal end region of the paddle-shaped applicator forms a distal support portion 632, as described above.

[0082] Any of the apparatuses described herein may include one or more lumen. For example, any of these apparatuses may include one or more lumen for a guidewire or guide catheter. In some cases the lumen may extend down the entire length of the apparatus (e.g., the elongate body portion of the apparatus; in some examples the lumen may be at the distal end region, e.g., configured as a rapid exchange device.

[0083] In some examples the apparatus may include one or more irrigation lumen extending from a proximal end of the apparatus. Alternatively or additionally, the apparatus may include a suction lumen extending therethrough. The lumen may extend into (and be continuous with) the paddle-shaped applicator or, in some examples, may terminate at the distal end region of the elongate body, proximal to the end of the paddle-shaped applicator.

[0084] In operation, the apparatuses described above may be used to treat a target tissue. For example, FIG. 7 schematically illustrates one example of a method of treating a target tissue using an apparatus as described herein. In any of these methods, the apparatus may be prepared prior to inserting into the body, e.g., by inserting into or through a delivery catheter. This may include collapsing the paddle-shaped applicator within a lumen of a delivery catheter and / or the elongate body of the apparatus. The apparatus may then be delivered near to the target region to be treated, e.g., by advancing the delivery catheter and / or the apparatus (e.g., within the delivery catheter) distally near to the target region. Once in position, the paddle-shaped applicator may be deployed out and allowed to expand / extend so that thepaddle-shaped applicator is deployed from a distal end of the elongate body and / or catheter (step 701).

[0085] Any of the methods may then place the applicator against the tissue using the distal support portion. For example, the method may include positioning the paddle-shaped applicator against a first tissue region (such as a target tissue region) so that a first ablation electrode (e.g., a first wire) extending across the paddle-shaped applicator and a second ablation electrode (e.g., a second wire) extending across the paddle-shaped applicator (e.g., substantially parallel to the first wire) are both in contact with the first (target) tissue region, while a distal support region of the paddle-shaped applicator (e.g., shelf region) is supported against a second tissue region (step 703).

[0086] Once in position, energy may be applied to the first and second wire electrodes to treat the tissue (e.g., the target tissue region). The energy may be applied from a pulse generator as described above. For example, the method may include applying non-thermal, pulsed, electrical treatment (e.g., pulses having a duration of <1000 ns, in some cases >0.1 kV amplitude) between the first and second wire electrodes to treat the tissue (step 705). This process may be repeated as necessary to achieve a desired treatment. In some examples the paddle-shaped applicator may be repositioned to one or more additional regions of the tissue to effect treatment (step 707).Use with Cardiac Mapping

[0087] As described above, any of these apparatuses and methods may be used with cardiac mapping and navigation systems. For example, any of these apparatuses and methods may be part of an ablation method for treatment of cardiac regions, including but not limited to the pulmonary veins (or the antrum / ostium / carina associated with a pulmonary vein or other opening), etc., and may include coordinating position of the energy applying (e.g., the sub-microsecond pulsing energy applying) electrodes of the applicator with mapping, such as 3D electro-anatomical mapping / maps of the relevant tissue.

[0088] As mentioned, the apparatus may include one or more sensors, including electrical sensors (e.g., sensing electrodes), electromagnetic sensors, and / or imaging sensors, etc. The apparatus may integrate data from these one or more sensors with one or more maps of the tissue to be treated. These electro-anatomical maps may be generated by a separate mapping system, including commercially available mapping systems, or apparatuses described herein may include an integrated mapping system or sub-system into the apparatus. In some examples the sensors are configured as electrodes that may be used as sensors for a mapping (e.g., 3D electro-anatomical mapping) system or sub-system and in combination with one or more patches that may be applied to the patient and connected to the mapping system / sub-system.

[0089] In addition to the sensing and / or mapping electrodes shown on the paddle-shaped applicator and / or elongate body (see, e.g., FIGS. 2A-2C, 3B and 4), in any of these apparatuses, one or more of the wire electrodes may be configured for use as a sensing and / or mapping electrode.

[0090] Any of the applicators described herein may include additional electrodes and sensors (e.g., electromagnetic sensor) to allow visualization and navigation of the apparatus in combination with a mapping system.

[0091] All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. Furthermore, it should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the inventive subject matter disclosed herein and may be used to achieve the benefits described herein.

[0092] Any of the methods (including user interfaces) described herein may be implemented as software, hardware or firmware, and may be described as a non-transitory computer-readable storage medium storing a set of instructions capable of being executed by a processor (e.g., computer, tablet, smartphone, etc.), that when executed by the processor causes the processor to control perform any of the steps, including but not limited to: displaying, communicating with the user, analyzing, modifying parameters (including timing, frequency, intensity, etc.), determining, alerting, or the like. For example, any of the methods described herein may be performed, at least in part, by an apparatus including one or more processors having a memory storing a non-transitory computer-readable storage medium storing a set of instructions for the processes(s) of the method.

[0093] While various embodiments have been described and / or illustrated herein in the context of fully functional computing systems, one or more of these example embodiments may be distributed as a program product in a variety of forms, regardless of the particular type of computer-readable media used to actually carry out the distribution. The embodiments disclosed herein may also be implemented using software modules that perform certain tasks. These software modules may include script, batch, or other executable files that may be stored on a computer-readable storage medium or in a computing system. In some embodiments, these software modules may configure a computing system to perform one or more of the example embodiments disclosed herein.

[0094] As described herein, the computing devices and systems described and / or illustrated herein broadly represent any type or form of computing device or system capable of executing computer-readable instructions, such as those contained within the modules described herein. In their most basic configuration, these computing device(s) may each comprise at least one memory device and at least one physical processor.

[0095] The term “memory” or “memory device,” as used herein, generally represents any type or form of volatile or non-volatile storage device or medium capable of storing data and / or computer-readable instructions. In one example, a memory device may store, load, and / or maintain one or more of the modules described herein. Examples of memory devices comprise, without limitation, Random Access Memory (RAM), Read Only Memory (ROM), flash memory, Hard Disk Drives (HDDs), Solid-State Drives (SSDs), optical disk drives, caches, variations or combinations of one or more of the same, or any other suitable storage memory.

[0096] In addition, the term “processor” or “physical processor,” as used herein, generally refers to any type or form of hardware-implemented processing unit capable of interpreting and / or executing computer-readable instructions. In one example, a physical processor may access and / or modify one or more modules stored in the above-described memory device. Examples of physical processors comprise, without limitation, microprocessors, microcontrollers, Central Processing Units (CPUs), Field-Programmable Gate Arrays (FPGAs) that implement softcore processors, Application-Specific Integrated Circuits (ASICs), portions of one or more of the same, variations or combinations of one or more of the same, or any other suitable physical processor.

[0097] Although illustrated as separate elements, the method steps described and / or illustrated herein may represent portions of a single application. In addition, in some embodiments one or more of these steps may represent or correspond to one or more software applications or programs that, when executed by a computing device, may cause the computing device to perform one or more tasks, such as the method step.

[0098] In addition, one or more of the devices described herein may transform data, physical devices, and / or representations of physical devices from one form to another. Additionally or alternatively, one or more of the modules recited herein may transform a processor, volatile memory, non-volatile memory, and / or any other portion of a physical computing device from one form of computing device to another form of computing device by executing on the computing device, storing data on the computing device, and / or otherwise interacting with the computing device.

[0099] The term “computer-readable medium,” as used herein, generally refers to any form of device, carrier, or medium capable of storing or carrying computer-readable instructions. Examples of computer-readable media comprise, without limitation, transmission-type media, such as carrier waves, and non-transitory-type media, such as magnetic-storage media (e.g., hard disk drives, tape drives, and floppy disks), optical-storage media (e.g., Compact Disks (CDs), Digital Video Disks (DVDs), and BLU-RAY disks), electronic-storage media (e.g., solid-state drives and flash media), and other distribution systems.

[0100] A person of ordinary skill in the art will recognize that any process or method disclosed herein can be modified in many ways. The process parameters and sequence of the steps described and / or illustrated herein are given by way of example only and can be varied as desired. For example, while the steps illustrated and / or described herein may be shown or discussed in a particular order, these steps do not necessarily need to be performed in the order illustrated or discussed.

[0101] The various exemplary methods described and / or illustrated herein may also omit one or more of the steps described or illustrated herein or comprise additional steps in addition to those disclosed. Further, a step of any method as disclosed herein can be combined with any one or more steps of any other method as disclosed herein.

[0102] The processor as described herein can be configured to perform one or more steps of any method disclosed herein. Alternatively or in combination, the processor can be configured to combine one or more steps of one or more methods as disclosed herein.

[0103] When a feature or element is herein referred to as being "on" another feature or element, it can be directly on the other feature or element or intervening features and / or elements may also be present. In contrast, when a feature or element is referred to as being "directly on" another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being "connected", "attached" or "coupled" to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being "directly connected", "directly attached" or "directly coupled" to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed "adjacent" another feature may have portions that overlap or underlie the adjacent feature.

[0104] Terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising," when used in this specification, specify the presence of stated features, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ".

[0105] Spatially relative terms, such as "under", "below", "lower", "over", "upper" and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as "under”, or "beneath" other elements or features would then be oriented "over" the other elements or features. Thus, the exemplary term "under" can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms "upwardly", "downwardly", "vertical", "horizontal" and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.

[0106] Although the terms “first” and “second” may be used herein to describe various features / elements (including steps), these features / elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature / element from another feature / element. Thus, a first feature / element discussed below could be termed a second feature / element, and similarly, a second feature / element discussed below could be termed a first feature / element without departing from the teachings of the present invention.

[0107] In general, any of the apparatuses and methods described herein should be understood to be inclusive, but all or a sub-set of the components and / or steps may alternatively be exclusive and may be expressed as “consisting of’ or alternatively “consisting essentially of’ the various components, steps, sub-components or sub-steps.

[0108] As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word"about" or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” or “substantially” may be used when describing magnitude and / or position to indicate that the value and / or position described is within a reasonable expected range of values and / or positions. For example, a numeric value may have a value that is + / - 0.1% of the stated value (or range of values), + / - 1% of the stated value (or range of values), + / - 2% of the stated value (or range of values), + / - 5% of the stated value (or range of values), + / - 10% of the stated value (or range of values), etc. Any numerical values given herein should also be understood to include about or approximately that value, unless the context indicates otherwise. For example, if the value "10" is disclosed, then "about 10" is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed that "less than or equal to" the value, "greater than or equal to the value" and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value "X" is disclosed the "less than or equal to X" as well as "greater than or equal to X" (e.g., where X is a numerical value) is also disclosed. It is also understood that throughout the application, data is provided in a number of different formats, and that this data represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point “15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0109] Although various illustrative embodiments are described above, any of a number of changes may be made to various embodiments without departing from the scope of the invention as described by the claims. Optional features of various device and system embodiments may be included in some embodiments and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the invention as it is set forth in the claims.

[0110] The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and withoutintending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.

Claims

CLAIMSWhat is claimed is:

1. An apparatus comprising: an elongate body; a paddle-shaped applicator at a distal end region of the elongate body, the paddle-shaped applicator comprising: a first electrode comprising a first wire extending across the paddleshaped applicator; a second electrode comprising a second wire extending across the paddle-shaped applicator substantially parallel to the first electrode; and a distal support portion of the paddle-shaped applicator extending distally from the first and second electrodes; wherein the first electrode and the second electrode are configured as a bipolar pair to apply ablation energy therebetween.

2. The apparatus of claim 1, wherein the paddle-shaped applicator is configured to retract into the distal end region of the elongate body.

3. The apparatus of claim 1, wherein the paddle-shaped applicator comprises an outer perimeter formed as an electrically insulated frame.

4. The apparatus of claim 1, wherein the paddle-shaped applicator forms a substantially flat plane.

5. The apparatus of claim 4, wherein the first electrode and the second electrode extend within the substantially flat plane of the paddle-shaped applicator.

6. The apparatus of any of claims 1-5, wherein the first electrode is separated from the second electrode by a minimum distance, d, that is substantially constant along a length of the first and second electrodes.

7. The apparatus of claim 6, wherein the minimum distance, c is between 1-40 mm.

8. The apparatus of any of claims 1-6, wherein the distal support portion comprises a non-electrically conductive frame formed, at least in part, from a portion of an outer perimeter of the paddle-shaped applicator.

9. The apparatus of any of claims 1-6, wherein the distal support portion extends distally from the first electrode by a distance that is different than a distance between the first electrode and the second electrode.

10. The apparatus of any of claims 1-6, wherein the distal support portion is configured as a shelf to provide stability to the paddle-shaped applicator when the paddle-shaped applicator is applied to a tissue.

11. The apparatus of any of claims 1-6, further comprising one or more sensing and / or mapping electrodes on a shaft of the elongate body.

12. The apparatus of any of claims 1-6, further comprising one or more sensing and / or mapping electrodes on the paddle-shaped applicator.

13. The apparatus of any of claims 1-6, further comprising one or more sensing and / or mapping electrodes on an outer perimeter of the paddle-shaped applicator.

14. The apparatus of any of claims 1-6, wherein the first electrode and the second electrode extend between an outer perimeter of the paddle-shaped applicator transverse to a long axis of the elongate body.

15. The apparatus of any of claims 1-6, further comprising a first lateral extension portion of the paddle-shaped applicator extending laterally from a first side of the first electrode and a first side of the second electrode.

16. The apparatus of any of claims 1-6, further comprising a second lateral extension portion of the paddle-shaped applicator extending laterally from a second side of the first electrode and a second side of the second electrode.

17. The apparatus of any of claims 1-6, wherein at least one or both of the first wire of the first electrode and the second wire of the second electrode have a thickness that is 0.38 mm or less.

18. The apparatus of any of claims 1-6, wherein the first electrode functions as both an ablation electrode and a sensing or mapping electrode.

19. The apparatus of any of claims 1-6, further comprising a pulse generator configured to provide electrical pulses having an amplitude of greater than 0.1 kV and a duration in microsecond or nanosecond range to the paddle-shaped applicator.

20. The apparatus of any of claims 1-6, further comprising one or more electromagnetic sensors.

21. The apparatus of claim 20, wherein the one or more electromagnetic sensors are on a shaft.

22. An apparatus comprising: an elongate body; a paddle-shaped applicator extending or configured to extend from a distal end region of the elongate body, the paddle-shaped applicator having an outer perimeter and comprising: a first electrode comprising a first wire extending across the paddleshaped applicator; a second electrode comprising a second wire extending across the paddle-shaped applicator parallel to the first electrode and transverse to the elongate body; and a distal support portion of the outer perimeter of the paddle-shaped applicator extending distally from the first and second electrodes; wherein the first and second electrodes are configured to form a bipolar pair of electrodes to apply ablation energy therebetween.

23. A method of applying non-thermal treatment to a tissue, the method comprising: positioning a paddle-shaped applicator against a first tissue region so that a first electrode comprising a first wire extending across the paddleshaped applicator and a second electrode comprising a second wire extending across the paddle-shaped applicator substantially parallel to the first wire are both in contact with the first tissue region, and so that a distal support region of the paddle-shaped applicator that is distal tothe first and second wires is supported against a second tissue region; and applying a pulsed non-thermal electrical treatment between the first wire and the second wire to treat the tissue, wherein the first wire has a first polarity, and the second wire has a second polarity.

24. The method of claim 23, wherein positioning the paddle-shaped applicator comprises flexibly conforming the first wire and the second wire to the first tissue region.

25. The method of claim 23, wherein positioning the paddle-shaped applicator comprises contacting a cardiac tissue.

26. The method of claim 23, wherein the first wire and the second wire extend in the substantially flat plane.

27. The method of any of claims 23-26, further comprising sensing one or more signals using one or more sensing and / or mapping electrodes on the elongate body and / or an outer perimeter of the paddle-shaped applicator.

28. The method of claim 23, wherein the first wire and the second wire have a thickness that is 0.38 mm or less.

29. The method of claim 23, wherein the first wire and the second wire have a thickness that is 0.2 mm or less.

30. The method of any of claims 23-26, wherein applying the pulsed non-thermal electrical treatment comprises applying electrical pulses having an amplitude of greater than 0.1 kV and a duration of less than 1000 nanoseconds.

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