Systems, devices, and methods for delivering pulsed electric field ablation energy to endocardial tissue

Abstract

Systems, devices, and methods for delivering pulsed electric field ablation energy to endocardial tissue include an inflatable member for positioning an ablation device within a pulmonary vein ostium. A device may include first and second shafts movable relative to each other, first and second electrodes configured to generate an electric field for ablating tissue, and an inflatable member disposed between the first and second electrodes. In some embodiments, the inflatable member is configured to transition from an undeployed configuration to a deployed configuration in response to movement of the first shaft and the second shaft. In some embodiments, the inflatable member in a deployed configuration may engage a wall of a pulmonary vein ostium and direct an electric field generated by the first electrode and the second electrode toward the wall.

Description

[0001] This application is a divisional application of the patent application with application number "201980071192.6", application date "September 19, 2019", and titled "Systems, devices and methods for delivering pulsed electric field ablation energy to endocardial tissue".

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Application No. 62 / 734,214, filed on September 20, 2018, the entire disclosure of which is incorporated herein by reference in its entirety. Background Art

[0004] In the past two decades, the generation of pulsed electric fields for tissue treatment has been transferred from the laboratory to clinical applications, and in the past four decades or more, the effects of high-voltage short pulses and large electric fields on tissues have been studied. Applying a short-lived high DC voltage to tissue may generate a local high electric field, usually within the range of hundreds of volts per centimeter, which destroys the cell membrane by creating holes in the cell membrane. Although the precise mechanism of the electric drive hole generation or electroporation continues to be studied, it is believed that applying a relatively short-lived and large electric field will produce instability in the lipid bilayer of the cell membrane, thereby causing the distribution of local gaps or holes in the cell membrane. If the electric field applied at the membrane is greater than a threshold value, the electroporation may be irreversible, so that the hole is not closed and remains open, thereby allowing biomolecular materials to exchange across the membrane, causing necrosis and / or apoptosis (cell death). Subsequently, surrounding tissues can heal naturally.

[0005] Although pulsed DC voltage can drive electroporation under appropriate circumstances, there remains an unmet need for thin, flexible, noninvasive devices that effectively deliver high DC voltage electroporation ablation therapy selectively to endocardial tissue in regions of interest while minimizing damage to healthy tissue. Summary of the invention

[0006] Systems, devices, and methods for ablating tissue by irreversible electroporation are described herein. In some embodiments, a device may include: a first shaft having a longitudinal axis and defining a lumen; a second shaft disposed within the lumen and having a distal portion extending from a distal portion of the first shaft, the second shaft being movable relative to the first shaft along the longitudinal axis; a first electrode coupled to the distal portion of the first shaft; a second electrode coupled to the distal portion of the second shaft, the first electrode and the second electrode being configured to generate an electric field for ablating tissue; and an inflatable member disposed between the first electrode and the second electrode, the inflatable member being configured to transition from an undeployed configuration to a deployed configuration in response to the second shaft moving proximally relative to the first shaft, the inflatable member in the deployed configuration being configured to engage a wall of an ostium of a pulmonary vein and direct the electric field generated by the first electrode and the second electrode toward the wall.

[0007] In some embodiments, a device may include: a shaft having a longitudinal axis and defining an inner cavity; an inflatable member disposed near a distal portion of the shaft, the inflatable member configured to transition between an undeployed configuration and a deployed configuration, the inflatable member comprising a wall having a proximal portion, a distal portion, and an intermediate portion disposed between the proximal portion and the distal portion of the wall, the intermediate portion having a minimum thickness that is less than the thickness of the proximal portion and the distal portion of the wall; and a first electrode and a second electrode disposed on opposite sides of the inflatable member along the longitudinal axis, the first electrode and the second electrode configured to generate an electric field for ablating tissue.

[0008] In some embodiments, a system may include: a signal generator configured to generate a pulse waveform; an ablation device connected to the signal generator, the ablation device including: a first electrode and a second electrode configured to receive the pulse waveform and generate an electric field for ablation; and an inflatable member formed of an insulating material and disposed between the first electrode and the second electrode, the inflatable member being configured to transition between an undeployed configuration and a deployed configuration, wherein the inflatable member is capable of advancing to a pulmonary vein orifice in the undeployed configuration, and is capable of engaging with a wall of the pulmonary vein orifice in the deployed configuration, wherein the inflatable member in the deployed configuration is configured to direct the electric field toward the wall.

[0009] In some embodiments, a method may include: retracting an inner shaft of an ablation device relative to an outer shaft of the ablation device, the inner shaft being disposed within an inner cavity of the outer shaft; in response to retracting the inner shaft relative to the outer shaft, transitioning an inflatable member of the ablation device from an undeployed configuration to a deployed configuration, in which a side of the inflatable member engages a wall of a pulmonary vein ostium; and after the transition, delivering a pulse waveform to a first electrode and a second electrode of the ablation device such that the first electrode and the second electrode generate an electric field for ablating the wall of the pulmonary vein ostium, the first electrode and the second electrode being disposed on opposite sides of the inflatable member. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 is a block diagram of an electroporation system according to an embodiment.

[0011] Figure 2A is a side view of an ablation device in an inflated state according to an embodiment.

[0012] Figure 2B is in a released state according to an embodiment Figure 2A Side view of the ablation device shown in .

[0013] Figure 3 is a cross-sectional side view of an ablation device disposed in a pulmonary vein according to an embodiment.

[0014] Figure 4A is a cross-sectional side view of an ablation device disposed in a pulmonary vein according to an embodiment. Figure 4B is according to an embodiment and when arranged in a pulmonary vein Figure 4A A perspective view of an ablation zone associated with the ablation device shown in FIG.

[0015] Figure 5A is a cross-sectional side view of an ablation device disposed in a pulmonary vein according to an embodiment. Figure 5B Located in the pulmonary vein Figure 5A Cross-sectional side view of the ablation device shown in .

[0016] Fig. 6A is a cross-sectional side view of an ablation device disposed in a pulmonary vein according to an embodiment. Figure 6B Located in the pulmonary vein Fig. 6A Cross-sectional side view of the ablation zone of the ablation device shown in .

[0017] Figure 7 is a side view of an ablation device according to an embodiment.

[0018] Figure 8 is a side view of an ablation device according to an embodiment.

[0019] Fig. 9 is a perspective view of an ablation device according to an embodiment.

[0020] Fig.10 is a schematic side view of a portion of a wall of an inflatable member of an ablation device according to an embodiment.

[0021] Fig.11 is a schematic side view of a portion of a wall of an inflatable member of an ablation device according to an embodiment.

[0022] Fig. 12A and 12B are different views of an ablation device according to an embodiment.

[0023] Fig.13 yes Fig. 12A and 12B Cross-sectional side view of the ablation device depicted in FIG.

[0024] Fig.14 yes Fig. 12A and 12B A cross-sectional side view of the ablation zone of the ablation device depicted in FIG.

[0025] Fig.15 is an exemplary waveform illustrating a train of voltage pulses with a pulse width defined for each pulse according to an embodiment.

[0026] Fig.16 A hierarchy of pulses according to an embodiment is schematically illustrated, showing pulse widths, intervals between pulses and grouping of pulses.

[0027] Fig.17 A schematic diagram of a nested hierarchy of monophasic pulses according to an embodiment is provided, showing different levels of the nested hierarchy.

[0028] Fig.18 is a schematic diagram of a nested hierarchy of biphasic pulses showing different levels of the nested hierarchy according to an embodiment.

[0029] Fig.19 The time series of electrocardiogram and cardiac pacing signals as well as atrial and ventricular refractory periods according to an embodiment are schematically shown, and the time window for irreversible electroporation ablation is indicated.

[0030] Figures 20A-20B A method for tissue ablation according to an embodiment is shown. DETAILED DESCRIPTION

[0031] Systems, devices and methods for ablating tissue by irreversible electroporation are described herein. Typically, a device for delivering a pulse waveform to tissue may include a first catheter (e.g., a shaft) defining a longitudinal axis. An expandable / inflatable member may be coupled to a distal portion of the first catheter. A first electrode may be coupled to a distal portion of the first catheter and proximal to the inflatable member. A second catheter (e.g., a shaft) or a tubular lumen may be disposed within a chamber of the lumen of the first catheter and the expandable / inflatable member, wherein the second catheter may be slidable relative to the first catheter. An expandable / inflatable member may be coupled to a distal end of the second catheter. A second electrode may be coupled to a distal portion of the second catheter and distal to the inflatable member. In some embodiments, the second catheter, particularly its distal portion, may be linearly steerable relative to the first catheter. Thus, in some embodiments, the second electrode may be steerable relative to the first electrode. The proximal portion of the expandable / inflatable member may be coupled to a distal portion of the first catheter, and the distal portion of the expandable / inflatable member may be coupled to a distal portion of the second catheter or tubular lumen. The second catheter may have a lumen diameter sufficient to allow a guidewire to pass through the lumen. The guidewire may provide mechanical support for the first catheter and the second catheter. In some embodiments, the first electrode may include a first set of electrodes, and the second electrode may include a second set of electrodes.

[0032] Typically, a system for delivering a pulse waveform to tissue may include a signal generator configured to generate the pulse waveform, and an ablation device coupled to the signal generator and configured to receive the pulse waveform. The ablation device may include an expandable / inflatable member (e.g., a balloon) coupled to a distal portion of a first catheter for delivering energy to ablate tissue by irreversible electroporation. One or more electrodes may be formed on a surface of the first catheter proximal to the expandable / inflatable member.

[0033] In some embodiments, a system may include a signal generator configured to generate a pulse waveform. An ablation device may be coupled to the signal generator and configured to receive the pulse waveform. The ablation device may include a handle configured to move a second electrode relative to a first electrode. The system may include a cardiac stimulator for generating a pacing signal and for delivering a pulse waveform synchronously with the pacing signal. In some embodiments, one or more of the electrodes may have an insulated electrical lead associated therewith, the insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation, the insulated electrical lead being disposed in an inner cavity of the catheter. In some embodiments, one or more of the electrodes may be independently addressable.

[0034] In some embodiments, the pulse waveform may include a first level of a hierarchy of pulse waveforms in the form of a first group of pulses, each pulse having a pulse duration, a first time interval separating consecutive pulses. A second level of the hierarchy of pulse waveforms includes a plurality of first groups of pulses as a second group of pulses, a second time interval separating consecutive first groups of pulses, the second time interval being at least three times the duration of the first time interval. A third level of the hierarchy of pulse waveforms includes a plurality of second groups of pulses as a third group of pulses, a third time interval separating consecutive second groups of pulses, the third time interval being at least thirty times the duration of the second level time interval. In some of these embodiments, the pulse waveform includes a fourth level of the hierarchy of pulse waveforms including a plurality of third groups of pulses as a fourth group of pulses, a fourth time interval separating consecutive third groups of pulses, the fourth time interval being at least ten times the duration of the third level time interval.

[0035] In some embodiments, the distal portion of the ablation device can also include a radiopaque portion. In some embodiments, the second catheter defines a lumen therethrough.

[0036] In some embodiments, a method of ablation via irreversible electroporation includes the step of advancing an ablation device toward the pulmonary vein ostium. The ablation device may include a first catheter, a second catheter or tubular lumen, and an expandable / inflatable member connected to the distal end of the catheter shaft. The sides of the inflatable member may be electrodes mounted on the device proximally and distally of the inflatable member. A pulse waveform may be generated. The pulse waveform may be delivered to the pulmonary vein ostium via the electrodes on the ablation device.

[0037] In some embodiments, the expandable / inflatable member of the ablation device can transition from a first configuration to a second configuration. In some embodiments, transitioning the expandable / inflatable member from the first configuration to the second configuration includes injecting distilled or deionized water into the expandable / inflatable member to cause mechanical expansion. In some embodiments, the pulsed electric field ablation energy can be delivered through the first set of electrodes and the second set of electrodes of the ablation device. In some embodiments, the ablation device is configured to generate an electric field strength between about 200 V / cm and about 800 V / cm.

[0038] In some embodiments, the ablation device may include a handle. In some embodiments, a portion of the first catheter shaft proximal to or near the first set of electrodes may be deflectable, the deflection being controlled by a knob or other control mechanism on the handle. The method may also include the step of deflecting a portion of the ablation device using the handle. For example, the second electrode may be movable relative to the first electrode, and the shape of the expandable / inflatable member in the second configuration may be changed by injecting distilled or deionized water through an injection port attached to the handle, and the distal shaft may be deflected using a deflection knob on the handle.

[0039] In some embodiments, the method may include the steps of creating a transseptal opening in the left atrium, advancing a guidewire and a steerable sheath into the left atrium through the transseptal opening, and advancing an ablation device over the guidewire into a pulmonary vein. In some embodiments, the method may include the steps of creating a first access site in a patient, advancing a guidewire through the first access site and into the right atrium, advancing a dilator and a steerable sheath into the right atrium over the guidewire, advancing the dilator from the right atrium into the left atrium through the atrial septum to create a transseptal opening, and dilating the transseptal opening using the dilator. In some embodiments, a second access site may be created in the patient for advancing a cardiac pacing catheter. In some embodiments, the method may include the steps of advancing a pacing catheter into the right ventricle, generating a pacing signal for cardiac stimulation of the heart using a cardiac stimulator, and applying the pacing signal to the heart using the cardiac stimulator, and then delivering a pulsed electric field voltage pulse waveform in synchronization with the pacing signal once the ablation device having an inflatable member is properly positioned at the ostium of the pulmonary vein.

[0040] In some embodiments, the method may include the step of performing fluoroscopic imaging of a radiopaque portion of the ablation device during one or more steps. In some embodiments, the first access site is a femoral vein. In some embodiments, the atrial septum includes the fossa ovalis.

[0041] In some embodiments, the pulse waveform may include a first level of a hierarchy of pulse waveforms in the form of a first group of pulses, each pulse having a pulse duration, a first time interval separating consecutive pulses. A second level of the hierarchy of pulse waveforms includes a plurality of first groups of pulses as a second group of pulses, a second time interval separating consecutive first groups of pulses, the second time interval being at least three times the duration of the first time interval. A third level of the hierarchy of pulse waveforms includes a plurality of second groups of pulses as a third group of pulses, a third time interval separating consecutive second groups of pulses, the third time interval being at least thirty times the duration of the second level time interval. In some of these embodiments, the pulse waveform includes a fourth level of the hierarchy of pulse waveforms including a plurality of third groups of pulses as a fourth group of pulses, a fourth time interval separating consecutive third groups of pulses, the fourth time interval being at least ten times the duration of the third level time interval.

[0042] The systems, devices, and methods described herein can be used to generate a large electric field amplitude at a desired region of interest to generate irreversible electroporation. An irreversible electroporation system as described herein may include a signal generator and a processor configured to apply one or more voltage pulse waveforms to a set of electrodes to deliver energy to the region of interest. The pulse waveforms disclosed herein may contribute to therapeutic therapies of arrhythmias (e.g., atrial fibrillation). In order to deliver the pulse waveforms generated by the signal generator, one or more electrodes of the ablation device may have an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In some embodiments, at least some of the electrodes may be independently addressable so that each electrode may be controlled (e.g., delivered energy) independently of any other electrode of the device.

[0043] As used herein, the term "electroporation" refers to applying an electric field to a cell membrane to change the permeability of the cell membrane to the extracellular environment. As used herein, the term "reversible electroporation" refers to applying an electric field to a cell membrane to temporarily change the permeability of the cell membrane to the extracellular environment. For example, cells undergoing reversible electroporation can observe temporary and / or intermittent formation of one or more holes in their cell membranes, which are closed when the electric field is removed. As used herein, the term "irreversible electroporation" refers to applying an electric field to a cell membrane to permanently change the permeability of the cell membrane to the extracellular environment. For example, cells undergoing irreversible electroporation can observe the formation of one or more holes in their cell membranes, which still exist when the electric field is removed.

[0044] Pulse waveforms for electroporation energy delivery as disclosed herein can enhance the safety, efficiency, and effectiveness of energy delivery to tissue by reducing the electric field threshold associated with irreversible electroporation, thereby producing more effective ablative lesions while reducing the total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein can be graded and have a nested structure. For example, the pulse waveform can include graded groupings of pulses associated with time stamps. In some embodiments, the methods, systems, and devices disclosed herein may include one or more of the methods, systems, and devices described in one or more of International Application Serial No. PCT / US2016 / 057664, filed on October 19, 2016 and entitled “Systems, Devices, and Methods for Delivering Ablative Energy to Tissue” and U.S. Patent Application Serial No. 16 / 405,515, filed on May 7, 2019 and entitled “Systems, Devices, and Methods for Delivering Ablative Energy to Tissue,” the contents of each of which are incorporated herein by reference in their entirety.

[0045] In some embodiments, the system may further include a cardiac stimulator for synchronizing the generation of a pulse waveform with a paced heartbeat. The cardiac stimulator may be used to electrically pace the heart with a cardiac stimulator and ensure pacing capture to establish periodicity and predictability of the cardiac cycle. A time window within the refractory period of a periodic cardiac cycle may be selected for voltage pulse waveform delivery. Thus, a voltage pulse waveform may be delivered during the refractory period of the cardiac cycle, thereby avoiding disruption of the sinus rhythm of the heart. In some embodiments, the ablation device may include one or more catheters, guidewires, expandable / inflatable members, and electrodes. The ablation device may be transformed into different configurations (e.g., deflation and inflation) to position the device within the endocardial space.

[0046] Typically, to ablate tissue, one or more catheters can be advanced to a target location through the vascular system in a minimally invasive manner. The methods described herein can include introducing the device into the endocardial cavity of the heart and placing the device at the pulmonary vein orifice. A pulse waveform can be generated and delivered to the electrodes of the device to ablate tissue. In some embodiments, the pulse waveform can be generated synchronously with the pacing signal of the heart to avoid disruption of the sinus rhythm of the heart. In some embodiments, the electrodes can be configured as anode-cathode subgroups. The pulse waveform can include a graded waveform to help tissue ablation and reduce damage to healthy tissue.

[0047] I. System

[0048] Overview

[0049] Disclosed herein are systems and devices configured for tissue ablation via selective and rapid application of voltage pulse waveforms to assist tissue ablation resulting in irreversible electroporation. Typically, the system described herein for ablating tissue may include a signal generator and an ablation device having one or more electrodes and an expandable / inflatable member (e.g., a balloon) for selectively and rapidly applying a DC voltage to drive electroporation. As described herein, the system and device may be deployed endocardially to treat arrhythmias. A voltage pulse waveform may be applied to a subset of electrodes via a suitable anode / cathode electrode selection. A pacing signal for cardiac stimulation may be generated and a pulse waveform may be generated by a signal generator in synchronization with the pacing signal.

[0050] Generally, the systems and devices described herein include one or more catheters configured to ablate tissue in a chamber of a heart. Figure 1 An ablation system (100) configured to deliver a voltage pulse waveform is shown. The system (100) may include a device (120) including a signal generator (122), a processor (124), a memory (126), and a cardiac stimulator (128). The device (120) may be coupled to an ablation device (110) and, optionally, to a pacing device (130).

[0051] The signal generator (122) can be configured to generate a pulse waveform for irreversible electroporation of tissue such as, for example, a pulmonary vein. For example, the signal generator (122) can be a voltage pulse waveform generator and is configured to deliver the pulse waveform to the ablation device (110). In some embodiments, the return electrode (140) can be connected to the patient (e.g., disposed on the back of the patient) to allow current to flow from the ablation device (110) through the patient and then to the return electrode (140). In other embodiments, the electrode of the ablation device can be used as a return so that there may not be a separate return electrode (140). The processor (124) can merge data received from the memory (126) to determine parameters of the pulse waveform to be generated by the signal generator (122), and some parameters such as voltage can be input by a user. The memory (126) can also store instructions to cause the signal generator (122) to execute modules, processes and / or functions associated with the system (100), such as pulse waveform generation and / or cardiac pacing synchronization. For example, the memory (126) may be configured to store pulse waveforms and / or cardiac pacing data for use in pulse waveform generation and / or cardiac pacing, respectively.

[0052] In some embodiments, the ablation device (110) may include a catheter having an expandable / inflatable member (e.g., a balloon) configured to deliver a pulse waveform described in more detail below. In each of the embodiments described herein, the expandable / inflatable member can be inflated using, for example, saline or, in some cases, a non-conductive or poorly conductive fluid (e.g., a gas, a liquid such as distilled water, deionized water, etc.). The fluid can be input through the lumen of the catheter coupled to the expandable / inflatable member. For example, the ablation device (110) can be introduced into the endocardial space and positioned at the ostium of a pulmonary vein and inflated so that the inflatable member is well juxtaposed or engaged at the wall of the pulmonary vein, and then the pulse waveform can be delivered to the ablated tissue. The ablation device (110) can include one or more electrodes (112), which in some embodiments can be independently addressable electrodes. Each electrode can include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In some embodiments, the insulation on each electrical lead can maintain a potential difference of between about 200V and about 3,000V across its thickness without dielectric breakdown. For example, the electrodes (112) can be grouped into one or more anode-cathode subgroups, for example, a subgroup including a proximal electrode and a distal electrode. In some embodiments, the distal electrode can include at least a portion of an expandable / inflatable member. As used herein, the proximal side is toward the handle of the ablation device, while the distal side is toward the tip of the ablation device.

[0053] When used, the pacing device (130) can be suitably coupled to a patient (not shown) and configured to receive a cardiac pacing signal generated by a cardiac stimulator (128). An indication of the pacing signal can be transmitted by the cardiac stimulator (128) to the signal generator (122). Based on the detection of the pacing signal by the generator, a voltage pulse waveform can be generated by the signal generator (122) for ablation delivery. In some embodiments, the signal generator (122) can be configured to generate the pulse waveform synchronously with the indication of the pacing signal (e.g., such that the ablation delivery occurs during a refractory window of a cardiac chamber). In some embodiments, the refractory window can be a common refractory window of two cardiac chambers (e.g., the atrium and the ventricle). For example, in some embodiments, the common refractory window can begin substantially immediately (or after a very small delay) after the ventricular pacing signal and continue thereafter for a duration of approximately 250 ms or less. In such an embodiment, the entire pulse waveform can be delivered within this duration.

[0054] The processor (124) can be any suitable processing device configured to run and / or execute a set of instructions or codes. The processor can be, for example, a general purpose processor, a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), a digital signal processor (DSP), etc. The processor can be configured to run and / or execute application processes and / or other modules, processes and / or functions associated with the system and / or a network associated therewith (not shown). The underlying device technology can be provided in various component types, for example, metal oxide semiconductor field effect transistor (MOSFET) technology such as complementary metal oxide semiconductor (CMOS), bipolar technology such as emitter coupled logic (ECL), polymer technology (e.g., silicon conjugated polymer and metal conjugated polymer-metal structure), hybrid analog and digital, etc.

[0055] The memory (126) may include a database (not shown) and may be, for example, a random access memory (RAM), a memory buffer, a hard drive, an erasable programmable read-only memory (EPROM), an electronically erasable read-only memory (EEPROM), a read-only memory (ROM), flash memory, etc. The memory (126) may store instructions to cause the processor (124) to execute modules, processes, and / or functions associated with the system (100), such as pulse waveform generation and / or cardiac pacing.

[0056] The system (100) can communicate with other devices (not shown) via, for example, one or more networks, each of which can be any type of network. A wireless network can refer to any type of digital network that is not connected by any type of cable. However, a wireless network can be connected to a wired network to interface with the Internet, other operator voice and data networks, business networks, and personal networks. Wired networks are typically carried over copper twisted pair, coaxial cable, or fiber optic cable. There are many different types of wired networks, including wide area networks (WANs), metropolitan area networks (MANs), local area networks (LANs), campus networks (CANs), global area networks (GANs), such as the Internet, and virtual private networks (VPNs). In the following, a network refers to any combination of wireless, wired, public, and private data networks that are typically interconnected through the Internet to provide a unified networking and information access solution.

[0057] Ablation Device

[0058] The systems described herein may include one or more multi-electrode ablation devices configured to ablate tissue in the pulmonary veins of the heart for treating indications such as arrhythmias. Figure 2A 1 is a side view of an ablation device (200) (e.g., similar in structure and / or function to ablation device (110)), the ablation device comprising a first catheter (203) (e.g., a catheter shaft or outer shaft) defining an inner lumen, a second catheter (210) (e.g., a tubular guidewire or inner shaft defining an inner lumen), and an inflatable member (207). The second catheter (210) can be disposed within the inner lumen of the first catheter (203) and the chamber of the inflatable member (207), wherein the second catheter (210) can be slidable relative to the first catheter (203). The inflatable member (e.g., a balloon) (207) can be coupled to the second catheter (210) so that the second catheter can pass through the inner chamber of the inflatable member (207). The first electrode (213) can be disposed on a surface of a distal portion (217) of the first catheter (203) and can be detachable from or attached to a proximal portion of the inflatable member (207). The second electrode (220) can be disposed on a distal portion (223) of the second catheter (210) and can be detachable from or attached to a distal portion of the inflatable member (207). The distal portion (223) of the second catheter (217) can be linearly movable and surround a portion distal to the first catheter (203). In some embodiments, the second electrode (223) can be movable relative to the first electrode (213). The proximal portion of the inflatable member (207) can be coupled to the distal portion of the first catheter (203).

[0059] The proximal end of the inflatable member (207) may be attached proximal to the distal end of the first catheter (203). The first electrode (213) may be disposed on the first catheter (203) just proximal to the proximal end of the inflatable member (207). Figure 2A-2B , a second catheter or tubular lumen (210) is shown extending from the distal end (217) of the first catheter (203) beyond the distal end of the inflatable member (207). A second electrode (220) is disposed on the surface of the second catheter (210) proximal to the distal end (223) of the second catheter (210). The distal end of the inflatable member (207) can be attached to the second catheter (210) just proximal to the second electrode (220).

[0060] In some embodiments, a handle (not shown) can be coupled to a proximal portion of the ablation device (200) and can include a bending mechanism (not shown) (e.g., a knob, switch, a pull) configured to deflect a portion of the second catheter (210) just proximal to the first catheter (203). For example, operation of the pull of the handle can increase or decrease the curvature in the distal portion of the first catheter. A fluid port can be attached to the handle for injecting a fluid such as distilled water or deionized water to inflate the inflatable member. In an embodiment, the handle can include a deployment mechanism configured to advance and retract the second catheter or guidewire lumen (210) so that the distance between the first electrode (213) and the second electrode (220) can be varied. For example, after the inflatable member is properly positioned in the pulmonary vein, it can be inflated and well juxtaposed in the vein. Subsequently, the first electrode (213) and the second electrode (220) can be brought closer together by retracting the second catheter (210) relative to the first catheter (203). In this way, the device can be configured for PEF ablation delivery.

[0061] The inflatable member (207) can be configured to be in a first configuration (e.g., Figure 2B a deflated inflatable member in the middle) and a second configuration (e.g., Figure 2AThe inflatable member (207) in the first configuration can be in a compact deflated state suitable for advancement through the vasculature. For example, the inflatable member (207) in the first configuration can be substantially free of fluid, such as sterile distilled or deionized water or saline. In some embodiments, the fluid can enter the inflatable member (207) via an injection port connected to the handle of the ablation device. The inflatable member (207) in the second configuration can hold a volume of saline or distilled or deionized water, which fills and inflates the inflatable member (207) to a suitable size and shape (e.g., having a diameter that contacts the diameter of the pulmonary vein) under pressure from a syringe or other infusion device. The inflatable member (207) can transition to an intermediate configuration between the first configuration and the second configuration as needed, such as to conform to an inner cavity or to advance the device through the vasculature. In some embodiments, the inflatable member can be pressurized using one or more of a manual syringe, a pump, an infusion device, a combination thereof, and the like. In some embodiments, the infusion pressure can be between about 2 psi and about 20 psi.

[0062] although Figure 2A and 2BAn ablation device having one proximal electrode (213) and one distal electrode (223) is depicted, but it should be appreciated that more electrodes may be used in other embodiments. For example, the first electrode (213) may include a group of electrodes (e.g., two or more proximal electrodes formed along the length of the first catheter). Similarly, the second electrode (220) may include a group of electrodes (e.g., two or more distal electrodes formed along the length of the second catheter). In some embodiments, the diameter of the electrodes (213, 220) may be between about 1 mm and about 6 mm, including all values ​​and sub-ranges therebetween. The length of the electrodes (213, 220) (measured along the longitudinal axis of the first and second catheters) may be between about 1 mm and about 8 mm, including all values ​​and sub-ranges therebetween. In some embodiments, a group of electrodes (e.g., a group of two or more proximal electrodes (213)) disposed on the surface of the first catheter may be spaced apart between about 0.5 mm and about 9 mm, including all values ​​and sub-ranges therebetween. In some embodiments, a set of electrodes (e.g., a set of two or more distal electrodes (220)) disposed on the surface of the second catheter can be spaced apart by between about 0.5 mm and about 9 mm, including all values ​​and sub-ranges therebetween. In some embodiments, the inflatable member in the second configuration (e.g., inflated, deployed) can have an outer diameter (e.g., maximum width) between about 20 mm and about 40 mm, including all values ​​and sub-ranges therebetween. In some embodiments, when the first and second electrodes (213, 220) are maximally separated, the inflatable member in the first configuration (e.g., deflated, undeployed state) can have a length (measured along the longitudinal axis of the second catheter) between about 10 mm and about 80 mm, including all values ​​and sub-ranges therebetween.

[0063] Figure 3 An ablation device (300) (e.g., similar in structure and / or function to ablation devices (110, 200)) is shown, comprising an inflatable member (305) in a second configuration (e.g., inflated) and coaxially deployed at the ostium of a pulmonary vein (301). The ablation device (300) comprises a first electrode (311) coupled to a proximal end of the inflatable member (305) and a second electrode (313) coupled to a distal end of the inflatable member (305). For clarity, a first catheter and a second catheter (e.g., a guidewire catheter defining an inner lumen) similar to those described herein are not shown. Figure 3 In Figure 3In the embodiment of the present invention, the second catheter or guidewire lumen (not shown) has been retracted relative to the first catheter so that the first electrode (311) and the second electrode (313) are minimally separated. When the inflatable member is in the second configuration and the first and second electrodes (311, 313) are retracted toward each other, the central region (308) of the inflatable member (305) can be similarly retracted or pulled in toward each other so that the proximal and distal ends of the inflatable member (305) are pulled closer together. In this way, the first and second electrodes (311, 313) can be at least partially surrounded by a portion of the inflatable member (305) (with the balloon folded inward).

[0064] Figure 4A is a cross-sectional side view of an ablation device (400) (e.g., similar in structure and / or function to ablation devices (110, 200, 300)) disposed at a pulmonary vein ostium (402). In particular, the longitudinal axis of the ablation device (400) is disposed at an angle relative to the longitudinal axis of the pulmonary vein. Figure 4B is located in the pulmonary vein (411) Figure 4A A cross-sectional perspective view of an ablation region (408) of an ablation device is shown. The ablation device (400) can include an inflatable member (404) and a first electrode (e.g., an electrode proximal to the inflatable member (404)) and a second electrode (e.g., an electrode distal to the inflatable member (404)). The first and second electrodes can be configured as an anode-cathode pair to deliver ablation energy to tissue. When the anode-cathode pair delivers energy exceeding a threshold required to generate irreversible electroporation, the ablation region (408) can form a continuous annular shape on the pulmonary vein ostium (402).

[0065] Figure 5A is a cross-sectional side view of an ablation device (500) (e.g., similar in structure and / or function to ablation devices (110, 200, 300, 400)) disposed in a pulmonary vein ostium (502) (e.g., coaxially deployed). The ablation device (500) includes a first electrode (508) coupled to a proximal end of an inflatable member (505) and a second electrode (509) coupled to a distal end of the inflatable member (505). Alternatively or in addition, the first electrode and the second electrode can be coupled to a distal portion of a first catheter proximal to the inflatable member and a distal portion of a second catheter / guidewire lumen distal to the inflatable member, respectively. For clarity, a first catheter or outer shaft and a second catheter or inner shaft (e.g., a guidewire lumen) similar to those described herein are not shown in FIG. Figure 5A-5B In Figure 5AIn some embodiments, the inflatable member (505) may form a frustum shape when inflated (e.g., a trapezoidal shape when viewed in lateral cross-section). In some embodiments, the diameter of the inflatable member (505) at its widest portion may be between about 20 mm and about 40 mm, including all values ​​and subranges therebetween. The length of the inflatable member (505) when fully deployed (measured along the longitudinal axis of the first and second catheters) may be between about 3 mm and about 30 mm, including all values ​​and subranges therebetween. Figure 5B yes Figure 5A , wherein the longitudinal axis of the ablation device (500) is disposed at an angle relative to the longitudinal axis of the pulmonary vein (502).

[0066] Fig. 6A is a cross-sectional side view of an ablation device (600) (e.g., similar in structure and / or function to ablation devices (110, 200, 300, 400, 500)) disposed in a pulmonary vein ostium (603) (e.g., coaxially deployed). The ablation device (600) includes a first electrode (609) coupled to a proximal end of an inflatable member (606) and a second electrode (611) coupled to a distal end of the inflatable member (606). Additionally or alternatively, the first electrode and the second electrode can be coupled to a distal portion of a first catheter / outer shaft proximal to the inflatable member and a distal portion of a second catheter / guidewire lumen distal to the inflatable member, respectively. For clarity, first catheter / outer shaft and second catheter (e.g., inner shaft defining a lumen) similar to those described herein are not described herein. Figure 6A-6B As shown in Fig. 6A As shown in FIG, the inflatable member (606) in the inflated configuration may form a diamond shape in a side view. Figure 6B It is located in the pulmonary vein (603) Fig. 6A 600. The first and second electrodes (609, 611) can be configured as an anode-cathode pair to deliver ablation energy to tissue. When the energy delivered by the anode-cathode pair exceeds the threshold required to generate irreversible electroporation, the ablation zone (610) can form a ring shape on the pulmonary vein ostium (603).

[0067] Figure 7is a schematic cross-sectional side view of an ablation device (700) (e.g., similar in structure and / or function to ablation devices (110, 200, 300, 400, 500, 600)). The ablation device (700) may include a first catheter (703) (e.g., an outer catheter shaft) defining an inner lumen, a second catheter (705) (e.g., an inner shaft defining an inner lumen), and an inflatable member (710). The second catheter (705) may be disposed within the inner lumen of the first catheter (703) and within a chamber of the inflatable member (710), wherein the second catheter (705) may be slidable relative to the first catheter (703). The inflatable member (e.g., a balloon) (710) may be coupled to the second catheter (705) such that the second catheter (705) may pass through the inner chamber of the inflatable member (710). The first electrode (707) can be disposed on the surface of the distal portion of the first catheter (703) and just proximal to the inflatable member (710). The second electrode (709) can be disposed on the distal portion (712) of the second catheter (705) and just distal to the inflatable member (710). The second catheter (705) can be linearly slidable relative to the first catheter (703). Therefore, the second electrode (709) can be linearly slidable relative to the first electrode (707). The proximal portion of the inflatable member (710) can be coupled to the distal portion of the first catheter (703). Figure 7 In the embodiment of the present invention, the inflatable member (710) may be formed into a shape approximating a diamond.

[0068] In some embodiments, the ablation device (700) may include a handle (not shown) coupled to a proximal portion of the ablation device (700) and may include a mechanism (not shown) (e.g., a knob, a switch, a pullwire) configured to advance and retract the second catheter or guidewire (705) relative to the first catheter (703) such that the distance between the first electrode (707) and the second electrode (709) can be varied. For example, the first electrode (707) and the second electrode (709) can be brought closer together by retracting the second catheter (705) relative to the first catheter (703). Figure 7 , a central portion ( 713 ) of the distal end of inflatable member ( 710 ) is shown retracted toward the proximal end of inflatable member ( 710 ).

[0069] When properly inflated, the proximal main portion (715) and the distal main portion (719) of the inflatable member (710) can be angled relative to the longitudinal axis of the first catheter (703) such that the surface of the inflatable member (710) forms an angle (731) greater than about 45 degrees relative to the longitudinal axis. In some embodiments, the middle portion (721) of the inflatable member (710) can be relatively short compared to the main portions (715, 719).

[0070] although Figure 7 An ablation device having one proximal electrode (707) and one distal electrode (709) is depicted, but it should be appreciated that more electrodes may be used in other embodiments. For example, the first electrode (707) may include a group of electrodes (e.g., two or more proximal electrodes). Similarly, the second electrode (709) may include a group of electrodes (e.g., two or more distal electrodes). In some embodiments, the diameter of the electrodes (707, 709) may be between about 1 mm and about 6 mm, including all values ​​and subranges therebetween. The length of the electrodes (707, 709) (measured along the longitudinal axis of the first catheter and the second catheter) may be between about 1 mm and about 8 mm, including all values ​​and subranges therebetween. In some embodiments, a group of electrodes (e.g., a group of two or more proximal electrodes (707)) disposed on the surface of the first catheter (703) may be spaced apart between about 0.5 mm and about 9 mm, including all values ​​and subranges therebetween. In some embodiments, a set of electrodes (e.g., a set of two or more distal electrodes (709)) disposed on the surface of the second catheter (705) can be spaced apart by between about 0.5 mm and about 9 mm, including all values ​​and sub-ranges therebetween. In some embodiments, the inflatable member (710) in the second configuration (e.g., inflated) can have an outer diameter between about 20 mm and about 40 mm, including all values ​​and sub-ranges therebetween. In some embodiments, when the first and second electrodes (707, 709) are maximally separated, the inflatable member (710) in the first configuration (e.g., deflated, undeployed state) can have a length (measured along the longitudinal axis of the second catheter) between about 10 mm and about 80 mm, including all values ​​and sub-ranges therebetween. In the fully deployed state where the second catheter (705) is retracted to have minimal separation between the first and second electrodes (707, 709), the length of the inflatable member (710) (measured along the longitudinal axis of the first catheter (703)) can be between about 3 mm and about 30 mm, including all values ​​and sub-ranges therebetween.

[0071] Figure 8is a schematic cross-sectional side view of an ablation device (800) (e.g., similar in structure and / or function to ablation devices (110, 200, 300, 400, 500, 600, 700)). The ablation device (800) may include a first catheter (803) (e.g., an outer catheter shaft) defining an inner cavity, a second catheter (805) (e.g., an inner shaft defining a guidewire inner cavity), and an inflatable member (810). The second catheter (805) may be disposed within the inner cavity of the first catheter (803) and the chamber of the inflatable member (810), wherein the second catheter (805) may be slidable relative to the first catheter (803). The inflatable member (e.g., a balloon) (810) may be coupled to the second catheter (805) such that the second catheter (805) may pass through the inner cavity of the inflatable member (810). The first electrode (807) can be disposed on the surface of the distal portion of the first catheter (803) and just proximal to the inflatable member (810). The second electrode (809) can be disposed on the distal portion (812) of the second catheter (805) and just distal to the inflatable member (810). The second catheter (805) can be linearly slidable relative to the first catheter (803). Therefore, the second electrode (809) can be slidable relative to the first electrode (807). The proximal portion of the inflatable member (810) can be coupled to the first catheter (803), and the distal portion of the inflatable member (810) can be coupled to the second catheter (805) so that the second catheter (805) can pass through the inner chamber of the inflatable member (810).

[0072] In some embodiments, the ablation device (800) can include a handle (not shown) coupled to a proximal portion of the ablation device (800) and can include a mechanism (not shown) (e.g., a knob, a switch, a pullwire) configured to advance and retract the second catheter (805) such that the distance between the first electrode (807) and the second electrode (809) can be varied. For example, by retracting the second catheter or guidewire (805) relative to the first catheter (803), the first electrode (807) and the second electrode (809) can be brought closer together. Figure 8 , a central portion ( 813 ) of the distal end of inflatable member ( 810 ) is shown being retracted toward the proximal end of inflatable member ( 810 ) using the handle and bending mechanism described herein.

[0073] When properly inflated, the proximal main portion (815) and the distal main portion (819) of the inflatable member (810) can be gradually curved, with the surfaces locally angled relative to the longitudinal axis of the first catheter (803), such that the surface of the inflatable member (810) locally forms an angle (831) relative to the longitudinal axis. In some embodiments, the length of the middle portion (821) of the inflatable member (810) can be relatively short compared to the main portions (815, 819). In some embodiments, the main portions (815, 819) can be gradually curved at a steep slope relative to the longitudinal axis (825) of the first catheter (803). In Figure 8 In the embodiment of the present invention, a local tangent (829) relative to the surface of the inflatable member (ie, the component of the local tangent in a plane defined by the radial and axial directions) can form an angle (831) greater than about 45 degrees with the longitudinal axis (825).

[0074] In some embodiments, the length of the middle portion (821) of the inflatable member (810) can be relatively short compared to the main portions (815, 819). When the inflatable member 810 is inflated (e.g., suitably pressurized), the middle portion (821) can be as Figure 8 In some embodiments, the middle portion (821) of the inflatable member (810) can be made of thinner material than the main portion (815, 819). For example, the thickness of the wall of the inflatable member (810) of the main portion (815, 819) can be at least 20% greater than the thickness of the wall at the middle portion (821). In some embodiments, the thickness of the wall of the inflatable member (810) of the main portion (815, 819) can be at least 50% greater than the thickness of the wall at the middle portion (821). In some embodiments, the thickness of the wall of the inflatable member (810) of the main portion (815, 819) can be at least 100% greater than the thickness of the wall at the middle portion (821).

[0075] Fig.10 is a schematic side view of a portion of a wall (1000) of an uninflated inflatable member including a proximal portion (1003), a middle portion (1005), and a distal portion (1007). Fig.10 It is schematically shown that the thickness of the proximal portion (1011) and the thickness of the distal portion (1013) may be significantly greater than the thickness of the middle portion (1012).

[0076] Fig.111 is a schematic side view of a portion of an inflatable member wall (1700) of an ablation device including a proximal portion (1703), a middle portion (1705), and a distal portion (1707) arranged along a longitudinal or central axis (1710) of the inflatable member. Any inflatable member described herein (e.g., inflatable members 207, 305, 404, 505, 606, etc.) may have structural and / or functional differences with the inflatable member. Fig.11 1700. A proximal portion (1703) of wall (1700) may have a length L1 extending along the longitudinal axis (1710), a mid-portion (1705) of wall (1700) may have a length L2 extending along the longitudinal axis (1710), and a distal portion (1707) of wall (1700) may have a length L3 extending along the longitudinal axis (1710). The lengths L1 and L3 may be greater than L2, and the ratios L1 / L2 and L3 / L2 may be greater than three.

[0077] like Fig.11 As shown in , the proximal portion (1703) of the wall (1700) of the inflatable member can have a maximum thickness D1, the middle portion (1705) of the wall (1700) can have a minimum thickness D2, and the distal portion (1707) of the wall (1700) can have a maximum thickness D3. In some embodiments, the thicknesses D1 and D3 of the proximal and distal portions (1703, 1707), respectively, can be equal to (or approximately equal to) each other, and the thickness D2 of the middle portion (1705) can be equal to or less than about one-third of the thicknesses D1 and D3.

[0078] although Figure 8An ablation device having one proximal electrode (807) and one distal electrode (809) is depicted, but it should be appreciated that more electrodes may be used in other embodiments. For example, the first electrode (807) may include a group of electrodes (e.g., two or more proximal electrodes). Similarly, the second electrode (809) may include a group of electrodes (e.g., two or more distal electrodes). In some embodiments, the diameter of the electrodes (807, 809) may be between about 1 mm and about 6 mm, including all values ​​and subranges therebetween. The length of the electrodes (807, 809) (measured along the longitudinal axis of the first catheter and the second catheter) may be between about 1 mm and about 8 mm, including all values ​​and subranges therebetween. In some embodiments, a group of electrodes (e.g., a group of two or more proximal electrodes (807)) disposed on the surface of the first catheter (803) may be spaced apart between about 0.5 mm and about 9 mm, including all values ​​and subranges therebetween. In some embodiments, a set of electrodes (e.g., a set of two or more distal electrodes (809)) disposed on the surface of the second catheter (805) can be spaced apart by between about 0.5 mm and about 9 mm, including all values ​​and sub-ranges therebetween. In some embodiments, the inflatable member (810) in the second configuration (e.g., inflated) can have an outer diameter between about 20 mm and about 40 mm, including all values ​​and sub-ranges therebetween. In some embodiments, when the first and second electrodes (807, 809) are maximally separated, the inflatable member (810) in the first configuration (e.g., deflated, undeployed state) can have a length (measured along the longitudinal axis of the second catheter) between about 10 mm and about 80 mm, including all values ​​and sub-ranges therebetween. In the fully deployed state where the second catheter (805) is retracted to have minimal separation between the first and second electrodes (807, 809), the length of the inflatable member (810) (measured along the longitudinal axis of the first catheter (803)) can be between about 3 mm and about 30 mm, including all values ​​and sub-ranges therebetween.

[0079] Fig. 9 is a perspective view of an ablation device (900) (e.g., similar in structure and / or function to ablation devices (110, (801))). In particular, ablation device (900) corresponds to Figure 8. The ablation device (800) shown in FIG. 9 may include a first catheter (903) (e.g., an outer catheter shaft) defining an inner cavity, a second catheter (e.g., an inner shaft or guidewire inner cavity) (its tip (912) is shown), and an inflatable member (910). The second catheter may be disposed within the inner cavity of the first catheter (903) and the chamber of the inflatable member (910), wherein the second catheter may be slidable relative to the first catheter (903). The inflatable member (e.g., a balloon) (910) may be coupled to the second catheter so that the second catheter may pass through the inner chamber of the inflatable member (910). The first electrode (907) may be disposed on the surface of the distal portion of the first catheter (903) and separated from the inflatable member (910). The second electrode (909) may be disposed on the distal portion (912) of the second catheter and separated from the inflatable member (910). The second catheter may be linearly slidable relative to the first catheter (903). Thus, the second electrode (909) can be slidable relative to the first electrode (907). The proximal portion of the inflatable member (910) can be coupled to the distal portion of the first catheter (903). The proximal main portion (915) and the distal main portion (919) of the inflatable member (910) can be gradually curved, with the surfaces locally angled relative to the longitudinal axis of the first catheter (903). In some embodiments, the length of the middle portion (921) of the inflatable member (910) can be relatively short compared to the main portions (915, 919). In some embodiments, the main portions (915, 919) can be gradually curved at a steep slope relative to the longitudinal axis of the first catheter (903).

[0080] Fig. 12A and 12B Depicted are different views of an ablation device (1800), which may include components that are structurally and / or functionally similar to components of other ablation devices described herein. The ablation device (1800) may include a first electrode (1809) coupled to the proximal end of an inflatable member (1806) and a second electrode (1811) coupled to the distal end of the inflatable member (1806). In some embodiments, the second electrode (1811) may be coupled to an inner catheter or inner shaft or guidewire lumen, which in turn may be attached to a proximal handle (not shown) for deployment of the ablation device (1800). For example, the ablation device (1800) may be deployed by moving (e.g., pulling) the inner shaft proximally, such that the second electrode (1811) is pulled toward the first electrode (1809) and the inflatable member (1806) is inflated. Once deployed, ablation device (1800) may be locked in place via an appropriate locking mechanism (eg, a locking mechanism disposed in the handle).

[0081] The inflatable member (1806) in the inflated and deployed configuration may form a conical shape, e.g. Fig. 12A and 12B The shape shown in Fig.13 , the inflatable member (1806) can have a maximum width W, a height H, and rounded sides (e.g., sides) having a radius of curvature R. In some embodiments, for example, when the inflatable member (1806) is designed for use within a pulmonary vein of a heart, the width W can be less than about 40 mm, the height H can be less than about 25 mm, and the radius R can be less than about 15 mm.

[0082] In some embodiments, the first and second electrodes (1809, 1811) can be similar in structure. For example, each of the first and second electrodes (1809, 1811) can have an outer diameter of about 1 mm to about 7 mm and a length of about 1 mm to about 15 mm. In some embodiments, the second electrode (1811) can have a round or non-invasive shape, such as Fig.14 The inner shaft or guidewire lumen can be used to pass a guidewire therethrough to facilitate engagement with the pulmonary veins so that the catheter can be delivered over the guidewire to the target anatomy.

[0083] In some embodiments, the proximal portion of the inflatable member (1806) in the deployed configuration can be angled at angle A1 relative to the longitudinal axis of the ablation device (1800), and the distal portion of the inflatable member (1806) can be angled at angle A2 relative to the longitudinal axis of the ablation device (1800). In some embodiments, angle A2 can be greater than angle A1, so that the inflatable member (1806) has an asymmetric shape when deployed. For example, in some embodiments, angle A1 can be in a range between about 50 degrees to about 75 degrees, while angle A2 can be between about 80 degrees to about 90 degrees.

[0084] Fig.14 A cross-sectional side view of an ablation device (1900) is depicted, for example, including components that are structurally and / or functionally similar to components of other ablation devices described herein, while being disposed in a pulmonary vein ostium (1901) of the heart. In particular, similar to ablation device (1800), ablation device (1900) includes two electrodes (1909, 1911) disposed on opposite sides of an inflatable member (1906). The electrode (1911) disposed at the distal end of the inflatable member (1906) can have a rounded or atraumatic tip (1911a). When deployed, the inflatable member (1906) of the ablation device (1900) can have a side that engages with a wall (1902) of the pulmonary vein ostium (1901) and can hold the ablation device (1900) relative to the pulmonary vein ostium (1901). In Fig.14In the arrangement shown, the ablation device (1900) can be held so that its longitudinal axis is generally aligned with the longitudinal axis of the pulmonary vein ostium (1901), and the proximal side of the inflatable member (1906) faces the blood pool (1903) of the heart chamber. Alternatively, the ablation device (1900) can be held in other orientations relative to the pulmonary vein ostium (1901) and different ablation zones can be generated within the surrounding tissue.

[0085] When Fig.14 When oriented as shown in , when the electrodes (1909, 1911) are configured as an anode-cathode pair they can generate an ablation zone (1920) for delivering ablation energy, for example, via irreversible electroporation, as further described herein. The inflatable member (1906) can be formed of an insulating material and, as oriented and shaped, can direct the electric field generated by the electrodes (1909, 1911) toward the wall (1902) of the pulmonary vein ostium (1901).

[0086] Each ablation device (110, 200, 300, 400, 500, 600, 700, 800, 900, 1800, 1900, etc.) described herein may include a handle (not shown) that may be coupled to a proximal portion of the ablation device in some embodiments and may include a mechanism (not shown) (e.g., a knob, a switch, a pullwire) configured to change the position of the second electrode relative to the first electrode. For example, the first electrode and the second electrode may be brought closer together by retracting the second catheter or the guidewire lumen relative to the first catheter. In some embodiments, the first catheter may have a deflectable portion proximal to the proximal electrode, the shape of which is controlled by a steering knob or other control on the catheter handle. In an embodiment, the device is tracked on a guidewire located in a pulmonary vein by a steerable sheath, and the deflection of the sheath may provide steering control for positioning the guidewire and inflatable member of the ablation catheter in the pulmonary vein. The inflatable member may be inflated through a fluid port attached to the catheter handle, into which distilled or deionized water may be injected under pressure. In this manner, apposition of the ablation device to the tissue may be provided at a desired location and orientation (eg, at the ostium of a pulmonary vein).

[0087] The ablation devices described herein can be useful for forming lesions on an endocardial surface (e.g., the inner surface of a pulmonary vein), as described herein. The distal portion of the inflatable member can include and / or be formed into an atraumatic shape that reduces trauma to the tissue (e.g., prevents and / or reduces the possibility of tissue puncture). The inflatable member can be sized to advance into the endocardial space. A set of electrical leads and / or a fluid (e.g., saline) can be disposed within the lumen of the first catheter.

[0088] In some embodiments, the electrodes can be shaped to conform to the shape of the catheter on which they are placed. For example, the electrodes can be press-fit (e.g., crimped) to the first catheter or outer shaft, or attached using an adhesive with electrical leads attached to the electrodes. The first catheter can include a flexible portion (e.g., can be deflectable) to enhance flexibility and allow the device to deflect.

[0089] Each electrode of any ablation device discussed herein can be connected to an insulated electrical lead (not shown) that leads to a handle (not shown) that is coupled to the proximal portion of the first catheter. The insulation on each electrical lead can maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulator on each electrical lead can maintain a potential difference of about 200V to about 3,000V (including all values ​​and subranges therebetween) across its thickness without dielectric breakdown. This allows the electrode and the inflatable member coupled thereto to effectively deliver electrical energy and ablate tissue by irreversible electroporation. The electrode can, for example, receive a charge supplied by a device as described above with respect to the inflatable member. Figure 1 The pulse waveform generated by the signal generator (122) in question.

[0090] For each ablation device discussed herein, the electrode may include a biocompatible metal, such as titanium, palladium, gold, silver, platinum, or a platinum alloy. For example, the electrode may preferably include platinum or a platinum alloy. In some embodiments, the proximal electrode may have a biocompatible coating that allows capacitive voltage delivery with a biphasic waveform. Each electrode may include an electrical lead with sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulator on each electrical lead can maintain a potential difference of about 200V to about 3,000V (including all values ​​and subranges therebetween) across its thickness without dielectric breakdown. The insulated electrical leads can extend to the proximal handle portion of the ablation device, from where they can be connected to a suitable electrical connector. The first catheter can be made of a flexible polymeric material such as Teflon, Nylon, Pebax, etc.

[0091] In some embodiments, the inflatable member as described herein can have an expandable structure and can be composed of any of a variety of insulating or dielectric materials, including but not limited to polyvinyl chloride (PVC), polyethylene (PE), cross-linked polyethylene, polyolefins, polyolefin copolymers (POC), polyethylene terephthalate (PET), polyester, nylon, polymer blends, polyester, polyimide, polyamide, polyurethane, silicone, polydimethylsiloxane (PDMS), PEBAX, etc. Preferred embodiments can be composed of polyurethane or silicone. Together with the use of distilled or deionized water to inflate the inflatable member, the inflatable member acts as an effective insulator during the delivery of the pulsed electric field waveform and drives the electric field to the area outside the inflatable member or balloon and surrounding the balloon.

[0092] II. Methods

[0093] Also described herein are methods of ablating tissue in a pulmonary vein (e.g., a pulmonary vein in the left atrium) using the above-described systems and devices. Typically, the methods described herein include guiding and positioning the device in the ostium of a pulmonary vein. A pulse waveform can be delivered by one or more electrodes and an inflatable member (e.g., a balloon) of the device to ablate tissue. In some embodiments, a cardiac pacing signal can synchronize the delivered pulse waveform with the cardiac cycle. Additionally or alternatively, the pulse waveform can include multiple levels of hierarchy to reduce total energy delivery. Tissue ablation so performed can be delivered synchronously with a rhythmic heartbeat and with less energy delivery to reduce damage to healthy tissue. It should be appreciated that any ablation device described herein can ablate tissue using the methods discussed below as appropriate.

[0094] Usually, and if Figures 20A-20B As shown in , method (1600) includes introducing a device (e.g., an ablation device, such as ablation device (110, 200, 300, 400, 500, 600, 700, 800, 900)) into the endocardial space of a pulmonary vein. The ablation device can be introduced into the ostium of the pulmonary vein in a first or deflated configuration and transitioned to a second or inflated configuration. Once positioned, a voltage pulse waveform can be applied to the tissue during a refractory period of the cardiac cycle. Electrophysiological data of the cardiac chamber can be recorded to determine the efficacy of the ablation.

[0095] The method (1600) may begin by creating an access site (1602) in a patient. For example, the first access site may be via the femoral vein of the patient. A guidewire may be advanced to the access site via the femoral vein and into the right atrium of the patient (1604). A dilator and a deflectable sheath may be advanced over the guidewire and into the right atrium (1606). The sheath may, for example, be configured to deflect up to about 180 degrees or more. The dilator may be advanced from the right atrium to the left atrium (1608) through the septum to create a transseptal opening. For example, the dilator may be advanced from the right atrium to the left atrium through the atrial septum to create a transseptal opening. The atrial septum may include the fossa ovalis of the patient. A dilator may be used to dilate the transseptal opening (1610). For example, a dilator may be pushed out of the sheath and used to puncture the fossa ovalis to form a transseptal opening (assuming the patient is heparinized). Alternatively, a transseptal opening may be created using a transseptal needle (e.g., a Brockenbrough needle). The sheath may be advanced from the right atrium to the left atrium through the transseptal opening (1612).The ablation device may be advanced over the guidewire into the left atrium (1614) with a second catheter or guidewire lumen of the ablation device tracked over the guidewire.

[0096] In some embodiments, the ablation device may include a catheter lumen and a set of insulated electrical leads extending through the lumen. In embodiments, a fine catheter having a circular distal shape and having electrodes mounted on the circular shape may be guided into the pulmonary veins through a second catheter or guidewire lumen and used to record intracardiac ECG data to confirm successful ablation.

[0097] Still refer to Figures 20A-20B , a second access site can be created in the patient to advance a lead or catheter for cardiac stimulation into the patient's heart. For example, the second access site can be via the patient's jugular vein. The device for cardiac stimulation can be advanced into the right ventricle (1620) (e.g., near the apex of the right ventricle) through the second access site. A pacing signal can be generated by a cardiac stimulator and applied to the heart to perform cardiac stimulation on the heart. An indication of the pacing signal can be transmitted from the cardiac stimulator to the signal generator. In some embodiments, the operator can confirm pacing capture and determine that the ventricle is responding to the pacing signal as expected. For example, pacing capture can be confirmed on an ECG display on the signal generator. Confirmation of pacing capture is a safety feature because the mandatory periodicity of the Q wave brought about by pacing is synchronized with the pacing for ablation. Similarly, in some embodiments, in addition to the right ventricle, the right atrium can be paced using, for example, an additional pacing catheter, and ablation can be delivered during the common refractory window of the two heart chambers.

[0098] The ablation device can be advanced toward a target pulmonary vein (1622) for delivery of a pulse waveform configured for tissue ablation. In particular, the ablation device in a second configuration can be advanced toward the pulmonary vein of the heart to engage the tissue surface. The sheath can be deflected as needed to guide the ablation device toward the target vein. The inflatable member can transition to a second configuration, wherein the inflatable member is inflated to contact the inflatable member against the pulmonary vein. Once the ablation device is in place within the heart to deliver one or more pulse waveforms, an extension cable can be used to electrically connect a signal generator to the proximal end of the handle of the ablation device. After pacing the right ventricle using a pacing device (1624), the pulse waveform can be delivered to the target site using the ablation device to ablate tissue. The pulse waveform can be delivered synchronously with the pacing signal.

[0099] Although examples of ablation devices configured for delivering irreversible electroporation pulsed electric field therapy have been described herein, the examples described herein are provided for exemplary purposes only, and other variations may be devised by those skilled in the art without departing from the scope of the invention. For example, a wide variety of materials, polyhedral sides, electrode diameters, device sizes, voltage levels, proximal electrodes, and other such details are possible and may be implemented as convenient for the application at hand without departing from the scope of the invention. In embodiments where the distal shaft of the catheter is deflectable, the catheter shaft may undergo a range of deflections by controlling the deflection from the catheter handle.

[0100] As discussed herein, a pulse waveform may be generated by a signal generator coupled to an ablation device. The signal generator may be electrically coupled to the proximal end of the handle of the ablation device. For example, an extension cable may electrically couple the signal generator to the proximal end of the handle. In some embodiments, the pulse waveform may include a time offset relative to a pacing signal. In some embodiments, the pulse waveform may include a first level of a hierarchy of pulse waveforms comprising a first group of pulses. Each pulse has a pulse duration and a first time interval separating consecutive pulses. A second level of the hierarchy of pulse waveforms may include a plurality of first groups of pulses as a second group of pulses. A second time interval may separate consecutive first groups of pulses. The second time interval may be at least three times the duration of the first time interval. A third level of the hierarchy of pulse waveforms may include a plurality of second groups of pulses as a third group of pulses. A third time interval may separate consecutive second groups of pulses. The third time interval may be at least thirty times the duration of the second level time interval. A fourth level of the hierarchy of pulse waveforms may include a plurality of third groups of pulses as a fourth group of pulses. A fourth time interval may separate consecutive third groups of pulses. The fourth time interval may be at least ten times the duration of the third level time interval.

[0101] In other embodiments, the ablation device can be withdrawn from the heart over the guidewire and the mapping catheter can be advanced over the guidewire to record post-ablation electrophysiological data of the target site. If the ablation is determined to be unsuccessful based on the electrophysiological data and predetermined criteria (1630-No), the process can return to step 1626 to deliver additional pulse waveforms. For subsequent ablation cycles, the pulse waveform parameters can be the same or changed.

[0102] If the analysis of the electrophysiological data indicates that the ablation was successful (e.g., the tissue portion is electrically silent) (1630—yes), then other target portions to be ablated can be determined (1632) (e.g., other pulmonary veins). Another target portion can be selected when other portions are to be ablated (1624) and the process can return to step 1622. When switching between target tissues, the inflatable member can be at least partially deflated and the ablation device can be advanced toward another portion of the tissue. If there are no other portions to be ablated (1632—no), the ablation device, pacing catheter, sheath, guidewire, etc. can be removed from the patient (1636).

[0103] It should be noted that for any of the steps described herein, the radiopaque portion of the ablation device can be imaged fluoroscopically to assist the operator. For example, a radiopaque marker band placed on the distal portion of the device can be used to visually confirm that the inflatable member in the second configuration is in contact with the vein and is approximately centered in the vein by fluoroscopic imaging.

[0104] It should be understood that the examples and illustrations in the present disclosure are for illustrative purposes and that changes and variations, such as the nature of the inflatable member, the number of electrodes, etc., may be constructed and deployed in accordance with the teachings herein without departing from the scope of the present invention.

[0105] Pulse waveform

[0106] Disclosed herein are methods, systems, and devices for selectively and rapidly applying pulsed electric fields / waveforms to achieve tissue ablation using irreversible electroporation. The (one or more) pulse waveforms disclosed herein can be used with any system (100), device (e.g., 200, 300, 400, 500, 600, 700, 800, 900), and method (e.g., 1600) described herein. Some embodiments relate to pulsed high voltage waveforms and sequence delivery schemes for delivering energy to tissue via multiple groups of electrodes. In some embodiments, peak electric field values ​​can be reduced and / or minimized while maintaining sufficiently large electric field amplitudes in areas where tissue ablation is desired. In some embodiments, a system that can be used for irreversible electroporation includes a signal generator and a processor that can be configured to apply a pulsed voltage waveform to a selected plurality of electrodes or electrode subgroups of an ablation device. In some embodiments, the processor is configured to control an input, whereby anode-cathode subgroups of a selected pair of electrodes can be triggered simultaneously or sequentially based on a predetermined sequence, and in one embodiment, sequence delivery can be triggered from a cardiac stimulator and / or pacing device. In some embodiments, the ablation pulse waveform is applied during the refractory period of the cardiac cycle, thereby avoiding disruption of the heart's sinus rhythm. An example method of performing this is to electrically pace the heart with a cardiac stimulator and ensure pacing capture to establish periodicity and predictability of the cardiac cycle, and then define a time window that is completely within the refractory period of the periodic cycle, within which the ablation waveform is delivered.

[0107] In some embodiments, the pulse voltage waveforms disclosed herein are hierarchical in organization and have a nested structure. In some embodiments, the pulse waveforms include hierarchical groupings of pulses with various associated time scales. In addition, the associated time scales and pulse widths, as well as the number and hierarchical groupings of pulses, can be selected so as to satisfy one or more of a set of Diophantine inequalities related to cardiac pacing frequency.

[0108] Pulse waveforms for electroporation energy delivery as disclosed herein can enhance the safety, efficiency, and effectiveness of energy delivery by reducing the electric field threshold associated with irreversible electroporation, thereby producing more effective ablative lesions with reduced total energy delivery.

[0109] Fig.15 A pulse voltage waveform in the form of a rectangular double pulse train is shown, wherein each pulse (e.g., pulse (1100)) is associated with a pulse width or duration. The pulse width / duration may be about 0.5 microseconds, about 1 microsecond, about 5 microseconds, about 10 microseconds, about 25 microseconds, about 50 microseconds, about 100 microseconds, about 125 microseconds, about 140 microseconds, about 150 microseconds, including all values ​​and subranges therebetween. Fig.15The pulse waveform shows a set of monophasic pulses where all pulses are of the same polarity (measured from a zero baseline, Fig.15 In some embodiments, such as for irreversible electroporation applications, the height of each pulse (1100) or the voltage amplitude of the pulse (1100) can be in the range of about 400 volts, about 1,000 volts, about 5,000 volts, about 10,000 volts, about 15,000 volts, including all values ​​and subranges therebetween. Fig.15 As shown in , pulses (1100) are separated from adjacent pulses by a time interval (1102), which is sometimes referred to as a first time interval. As an example, the first time interval can be about 1 microsecond, about 50 microseconds, about 100 microseconds, about 200 microseconds, about 500 microseconds, about 800 microseconds, about 1 millisecond, including all values ​​and subranges therebetween, to generate irreversible electroporation.

[0110] Fig.16 A pulse waveform with a hierarchical structure of nested pulses is introduced. Fig.16 A series of monophasic pulses are shown, such as pulses (1200) having a pulse width / pulse duration w, separated by time intervals (sometimes also referred to as first time intervals) such as time intervals (1202) of duration t1 between consecutive pulses, a number m1 of pulses arranged to form a pulse group (1210) (sometimes also referred to as a first group of pulses). In addition, the waveform has a number m2 of such pulse groups (sometimes also referred to as a second group of pulses), separated by time intervals (1212) of duration t2 between consecutive groups (sometimes also referred to as a second time interval). The set of m2 such pulse groups is represented by Fig.16 The (1220) mark in the figure constitutes the next level of the hierarchy, which can be called a group and / or a third group of pulses. Both the pulse width and the time interval t1 between pulses can be in the range of microseconds to hundreds of microseconds, including all values ​​and subranges therebetween. In some embodiments, the time interval t2 can be at least three times greater than the time interval t1. In some embodiments, the ratio t2 / t1 can be in the range of about 3 to about 300, including all values ​​and subranges therebetween.

[0111] Fig.17The structure of the nested pulse hierarchical waveform is further described. In the figure, a series of m1 pulses (individual pulses not shown) form a pulse group (1300) (e.g., a first group of pulses). A series of m2 such groups separated by an inter-group time interval (1310) of duration t2 between one group and the next (e.g., a second time interval) form a cluster (e.g., a second group of pulses). A series of m3 such groups separated by a time interval (1312) of duration t3 between one group and the next (e.g., a third time interval) form the next level in the hierarchy, a supergroup (e.g., a third group of pulses) labeled (1320) in the figure. In some embodiments, the time interval t3 can be at least about thirty times greater than the time interval t2. In some embodiments, the time interval t3 can be at least fifty times greater than the time interval t2. In some embodiments, the ratio t3 / t2 can be in the range of about 30 to about 800, including all values ​​and sub-ranges therebetween. The amplitude of a single voltage pulse in the pulse hierarchy can be any value in the range of 500 volts to 7,000 volts or more, including all values ​​and sub-ranges therebetween.

[0112] Fig.18 An example of a biphasic waveform sequence having a hierarchical structure is provided. In the example shown in the figure, a biphasic pulse such as (1400) has a positive voltage portion as well as a negative voltage portion to complete one cycle of the pulse. There is a time delay (1402) (e.g., a first time interval) between adjacent cycles of duration t1, and n1 such cycles form a pulse group (1410) (e.g., a first group of pulses). A series of n2 such groups separated by an inter-group time interval (1412) (e.g., a second time interval) of duration t2 between one group and the next group forms a group (1420) (e.g., a second group of pulses). The figure also shows a second group (1430) with a time delay (1432) (e.g., a third time interval) of duration t3 between the groups. Just like the monophasic pulses, higher levels of the hierarchical structure can also be formed. The amplitude of each pulse or the voltage amplitude of the biphasic pulse can be any value in the range of 500 volts to 7,000 volts or more, including all values ​​and sub-ranges therebetween. The pulse width / pulse duration may be in the range of nanoseconds or even sub-nanoseconds to tens of microseconds, while the delay t1 may be in the range of zero to a few microseconds. The inter-group time interval t2 may be at least ten times greater than the pulse width. In some embodiments, the time interval t3 may be at least about twenty times greater than the time interval t2. In some embodiments, the time interval t3 may be at least fifty times greater than the time interval t2.

[0113] Embodiments disclosed herein include waveforms constructed as hierarchical waveforms that include waveform elements / pulses at various levels of the hierarchy. Fig.16A single pulse of (1200) in comprises a first level of the hierarchy and has an associated pulse duration and a first time interval between consecutive pulses. A group of pulses or elements of the first level structure forms a second level of the hierarchy, e.g. Fig.16 Associated with the waveform are, among other parameters, parameters such as a total duration of the second group of pulses (not shown), a total number of first level elements / first group of pulses, and a second time interval between consecutive first level elements of the second level structure / second group of pulses. In some embodiments, the total duration of the second group of pulses may be between about 20 microseconds and about 10 milliseconds, including all values ​​and subranges therebetween. A group of pulses, a second group of pulses, or an element of a second level structure forms a third level of the hierarchy, e.g. Fig.16 The third group of pulses (1220) in the waveform is described in detail. Among other parameters, there is a total duration of the third group of pulses (not shown), a total number of second level elements / second group of pulses, and a third time interval between consecutive second level elements that describe the third level structure / third group of pulses. The general iterative or nested structure of the waveform can continue to multiple levels higher, such as ten levels or more of structure.

[0114] For example, the pulse waveform may include a fourth level of the hierarchy of pulse waveforms, may include multiple third groups of pulses as fourth groups of pulses, a fourth time interval separating consecutive third groups of pulses, the fourth time interval being at least ten times the duration of the third level time interval.

[0115] In some embodiments, the hierarchical waveforms and time intervals with nested structures described herein are useful for irreversible electroporation ablation energy delivery, thereby providing good control and selectivity for application in different tissue types. Various hierarchical waveforms can be generated using a suitable pulse generator. It should be understood that although the examples herein identify independent monophasic and biphasic waveforms for clarity, it should be noted that combined waveforms can also be generated / implemented in which some portions of the waveform hierarchy are monophasic and other portions are biphasic.

[0116] In some embodiments, the ablation pulse waveforms described herein are applied during the refractory period of the cardiac cycle, thereby avoiding disruption of the heart's sinus rhythm. In some embodiments, a treatment method includes electrically pacing the heart with a cardiac stimulator to ensure pacing capture to establish periodicity and predictability of the cardiac cycle, and then defining a time window within the refractory period of the periodic cycle within which one or more pulse ablation waveforms can be delivered. Fig.19 An example of applying both atrial pacing and ventricular pacing is shown (e.g., pacing leads or catheters are located in the right atrium and right ventricle, respectively). With time represented on the horizontal axis, Fig.19A series of ventricular pacing signals, such as (1500) and (1510), and a series of atrial pacing signals (1520, 1530), and a series of ECG waveforms (1540, 1542) driven by the pacing signals are shown. Fig.19 As shown by the thick arrows in FIG. , there is an atrial refractory time window (1522) and a ventricular refractory time window (1502) that follow the atrial pacing signal (1522) and the ventricular pacing signal (1500), respectively. Fig.19 As shown in , a common refractory time window (1550) of duration Tr can be defined, which is located within the atrial and ventricular refractory time windows (1522, 1502). In some embodiments, an electroporation ablation waveform can be applied in the common refractory time window (1550). Fig.19 As shown in , the starting point of the refractory time window (1522) is offset from the pacing signal (1500) by a time offset (1504). In some embodiments, the time offset (1504) can be less than about 25 milliseconds. At the next heartbeat, a similarly defined common refractory time window (1552) is the next time window available for applying (one or more) ablation waveforms. In this way, (one or more) ablation waveforms can be applied over a series of heartbeats, at each heartbeat that remains within the common refractory time window. In one embodiment, for a given electrode group, each pulse group defined above in the pulse waveform hierarchy can be applied over a heartbeat, so that a series of groups are applied over a series of heartbeats.

[0117] As used herein, when used in conjunction with a numerical value and / or range, the terms "about" and / or "approximately" generally refer to those numerical values ​​and / or ranges that are close to the numerical value and / or range. In some cases, the terms "about" and "approximately" can mean within ±10% of the value. For example, in some cases, "about 100 [units]" can mean within ±10% of 100 (e.g., from 90 to 110). The terms "about" and "approximately" can be used interchangeably.

[0118] Some embodiments described herein relate to a computer storage product having a non-transitory computer-readable medium (also referred to as a non-transitory processor-readable medium) having instructions or computer code thereon for performing various computer-implemented operations. A computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not itself include a transient propagating signal (e.g., a propagating electromagnetic wave that carries information on a transmission medium such as space or a cable). The medium and computer code (also referred to as code or algorithm) may be designed and constructed for one or more specific purposes. Examples of non-transitory computer-readable media include, but are not limited to, magnetic storage media such as hard disks, floppy disks, and magnetic tapes; optical storage media such as compact disks / digital video disks (CD / DVD), compact disk read-only memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical disks; carrier signal processing modules; and hardware devices specifically configured to store and execute program code, such as application specific integrated circuits (ASICs), programmable logic devices (PLDs), read-only memories (ROMs), and random access memory (RAM) devices. Other embodiments described herein relate to a computer program product that may include, for example, instructions and / or computer code disclosed herein.

[0119] The systems, devices and / or methods described herein may be implemented by software (implemented on hardware), hardware or a combination thereof. Hardware modules may include, for example, a general purpose processor (or microprocessor or microcontroller), a field programmable gate array (FPGA), and / or an application specific integrated circuit (ASIC). Software modules (implemented on hardware) may be expressed in a variety of software languages ​​(e.g., computer code), including C, C++, Ruby, and / or other object-oriented, procedural or other programming languages ​​and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, machine instructions (such as those produced by a compiler), code for generating web services, and files containing higher-level instructions executed by a computer using an interpreter. Additional examples of computer code include, but are not limited to, control signals, encrypted code, and compressed code.

[0120] The specific examples and descriptions herein are exemplary in nature and one skilled in the art may develop various embodiments based on the teachings herein without departing from the scope of the present invention, which is limited only by the appended claims.

Claims

1. A device comprising: a first shaft having a longitudinal axis and defining an inner lumen; a second shaft disposed within the lumen and having a distal portion extending from the distal portion of the first shaft, the second shaft being movable relative to the first shaft along the longitudinal axis; a first electrode coupled to a distal portion of the first shaft; a second electrode coupled to a distal portion of the second shaft, the first electrode and the second electrode configured to generate an electric field for ablating tissue; as well as An inflatable member is disposed between the first electrode and the second electrode, the inflatable member being configured to transition from an undeployed configuration to a deployed configuration in response to proximal movement of the second axis relative to the first axis, the inflatable member in the deployed configuration being configured to engage a wall of a pulmonary vein ostium and direct an electric field generated by the first electrode and the second electrode toward the wall.

2. The device of claim 1, wherein the inflatable member comprises a wall having: proximal part; distal part; as well as An intermediate portion is disposed between the proximal portion and the distal portion of the wall, the intermediate portion having a minimum thickness that is less than the thickness of the proximal portion and the distal portion of the wall.

3. The device of claim 2, wherein the length of each of the proximal portion and the distal portion of the inflatable member along the longitudinal axis is greater than the length of the intermediate portion along the longitudinal axis.

4. A device comprising: a shaft having a longitudinal axis and defining an inner lumen; an inflatable member disposed proximate a distal portion of the shaft, the inflatable member configured to transition between an undeployed configuration and a deployed configuration, the inflatable member comprising a wall having a proximal portion, a distal portion, and an intermediate portion disposed between the proximal and distal portions of the wall, the intermediate portion having a minimum thickness that is less than a thickness of the proximal and distal portions of the wall; as well as A first electrode and a second electrode are disposed on opposite sides of the inflatable member along the longitudinal axis, the first electrode and the second electrode being configured to generate an electric field for ablating tissue.

5. The device of claim 4, wherein the inflatable member in the deployed configuration is configured to engage a wall of a pulmonary vein ostium, and the inflatable member is formed of an insulating material so that the inflatable member in the deployed configuration directs the electric field generated by the first electrode and the second electrode toward the wall of the pulmonary vein ostium.

6. The device of any of the preceding claims, wherein the inflatable member in the deployed configuration comprises at least a proximal portion or a distal portion at an angle greater than about 45 degrees relative to the longitudinal axis.

7. A device according to any one of claims 3 or 4, wherein the minimum thickness of the intermediate portion is less than about one-third of the thickness of at least the proximal portion or the distal portion of the wall.

8. The device of any one of claims 2-5 or 7, wherein the ratio of the length of the proximal portion to the length of the middle portion and the ratio of the length of the distal portion to the length of the middle portion are greater than about three.

9. A device according to any of the preceding claims, wherein the inflatable member in the deployed configuration has a cross-sectional shape having a width less than about 40 mm, a height less than about 25 mm, and a side having a radius of curvature less than about 15 mm.

10. The device of any of the preceding claims, wherein the inflatable member in the deployed configuration has a cross-sectional shape having a maximum width of between about 20 mm and about 40 mm.

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