System, apparatus, and method for delivery of pulsed electric field ablative energy to endocardial tissue

Abstract

To provide a system, device, and method for electroporation ablation therapy, including an inflatable member for positioning an ablation device within a pulmonary vein ostium.SOLUTION: An apparatus can include: first and second shafts moveable relative to one another; a first electrode 1809 and a second electrode 1811 configured to generate an electric field for ablating tissue; and an inflatable member 1806 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 and second shafts. In some embodiments, the inflatable member in the deployed configuration can engage a wall of a pulmonary vein ostium and direct the electric field generated by the first and second electrodes toward the wall.SELECTED DRAWING: Figure 12B

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 62 / 734,214, filed Sep. 20, 2018, the entire disclosure of which is incorporated herein by reference in its entirety. [Background technology]

[0002] While the generation of pulsed electric fields for tissue therapy has been moving from laboratory to clinical applications over the past 20 years, the effects of short pulses of high voltage and large electric fields on tissues have been investigated for over the past 40 years. The application of a short high DC voltage to tissue can generate localized high electric fields, typically in the range of hundreds of volts per centimeter, that disrupt cell membranes by generating pores within the membrane. Although the exact mechanism of this electrokinetic pore generation or electroporation continues to be studied, it is believed that the application of a relatively short and large electric field creates instability in the lipid bilayer within the cell membrane, causing the generation of a distribution of localized gaps or pores within the cell membrane. This electroporation can be irreversible if the applied electric field at the membrane is greater than a threshold value, which causes the pores to not close but remain open, thereby allowing the exchange of biomolecular material across the membrane resulting in necrosis and / or apoptosis (cell death). The surrounding tissue can then heal naturally.

[0003] While pulsed DC voltages can drive electroporation under appropriate circumstances, there remains an unmet need for a low-profile, flexible, atraumatic device that effectively delivers high DC voltage electroporation ablation therapy selectively to endocardial tissue in the region of interest while minimizing damage to healthy tissue. Summary of the Invention

[0004] Systems, devices, and methods for ablating tissue via irreversible electroporation are described herein. In some embodiments, the apparatus 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 along the longitudinal axis relative to the first shaft, 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 and second electrodes being configured to generate an electric field for ablating tissue, and an expandable member disposed between the first and second electrodes, the expandable member being configured to transition from a non-deployed configuration to a deployed configuration in response to the second shaft moving proximally relative to the first shaft, the expandable member in the deployed configuration being configured to engage a wall of the pulmonary vein ostium and direct an electric field generated by the first and second electrodes against the wall.

[0005] In some embodiments, the device can include a shaft having a longitudinal axis and defining an internal lumen; an expandable member disposed near a distal portion of the shaft, the expandable member configured to transition between an undeployed configuration and a deployed configuration, the expandable member including 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 the thicknesses of the proximal and distal portions of the wall; and first and second electrodes disposed on opposite sides of the expandable member along the longitudinal axis, the first and second electrodes configured to generate an electric field to ablate tissue.

[0006] In some embodiments, the system can include a signal generator configured to generate a pulsed waveform; and an ablation device coupled to the signal generator, the ablation device including first and second electrodes configured to receive the pulsed waveform and generate an electric field for ablation, and an expandable member formed from an insulating material and disposed between the first and second electrodes, the expandable member configured to transition between a non-deployed configuration in which the expandable member can be advanced to the pulmonary vein ostium and a deployed configuration in which the expandable member can engage a wall of the pulmonary vein ostium, the expandable member in the deployed configuration configured to direct an electric field against the wall.

[0007] In some embodiments, the method can include retracting an inner shaft of the ablation device relative to an outer shaft of the ablation device, the inner shaft being disposed within a lumen of the outer shaft; transitioning an expandable member of the ablation device from an undeployed configuration to a deployed configuration in which a side portion of the expandable member engages a wall of the pulmonary vein ostium in response to retracting the inner shaft relative to the outer shaft; and delivering a pulse waveform to first and second electrodes of the ablation device after the transition, whereby the first and second electrodes generate an electric field to ablate the wall of the pulmonary vein ostium, the first and second electrodes being disposed on opposite sides of the expandable member. [Brief description of the drawings]

[0008] [Figure 1] FIG. 1 is a block diagram of an electroporation system according to an embodiment. [Figure 2A] FIG. 2 is a side view of an ablation device in an expanded state, according to an embodiment. [Figure 2B] 2B is a side view of the ablation device shown in FIG. 2A in a contracted state, according to an embodiment. [Diagram 3] 1 is a cross-sectional side view of an ablation device positioned within a pulmonary vein, in accordance with an embodiment. [Figure 4A] 1 is a cross-sectional side view of an ablation device positioned within a pulmonary vein, in accordance with an embodiment. [Figure 4B] 4B is a perspective view of an ablation region associated with the ablation device shown in FIG. 4A when positioned within a pulmonary vein, in accordance with an embodiment. [Figure 5A] 1 is a cross-sectional side view of an ablation device positioned within a pulmonary vein, in accordance with an embodiment. [Figure 5B] FIG. 5B is a cross-sectional side view of the ablation device shown in FIG. 5A positioned within a pulmonary vein. [Figure 6A] 1 is a cross-sectional side view of an ablation device positioned within a pulmonary vein, in accordance with an embodiment. [Figure 6B] FIG. 6B is a cross-sectional side view of the ablation region of the ablation device shown in FIG. 6A positioned within a pulmonary vein. [Figure 7] FIG. 2 is a side view of an ablation device according to an embodiment. [Figure 8] FIG. 2 is a side view of an ablation device according to an embodiment. [Figure 9] 1 is a perspective view of an ablation device according to an embodiment. [Figure 10] 1 is a schematic side view of a portion of a wall of an expandable member of an ablation device according to an embodiment. [Figure 11] 1 is a schematic side view of a portion of a wall of an expandable member of an ablation device according to an embodiment. [Figure 12A] 1A-1D are different views of an ablation device according to an embodiment. [Figure 12B] 1A-1D are different views of an ablation device according to an embodiment. [Figure 13] FIG. 12C is a cross-sectional side view of the ablation device shown in FIGS. 12A and 12B. [Figure 14] FIG. 12C is a cross-sectional side view of an ablation region of the ablation device shown in FIGS. 12A and 12B. [Figure 15]4 is an example waveform illustrating a sequence of voltage pulses having a defined pulse width for each pulse, according to an embodiment. [Figure 16] 1 illustrates a schematic of a hierarchy of pulses showing pulse widths, spacing between pulses, and grouping of pulses, according to an embodiment. [Figure 17] 1 provides a schematic diagram of a nesting hierarchy of monophasic pulses illustrating different levels of nesting hierarchy, according to an embodiment. [Figure 18] FIG. 13 is a schematic diagram of a nesting hierarchy of biphasic pulses showing different levels of nesting hierarchy, according to an embodiment. [Figure 19] 1A-1C are schematic diagrams illustrating time sequences of electrocardiogram and cardiac pacing signals with atrial and ventricular refractory periods, illustrating the time window for irreversible electroporation ablation according to an embodiment; [Figure 20A] 1 illustrates a method for tissue ablation according to an embodiment. [Figure 20B] 1 illustrates a method for tissue ablation according to an embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Systems, devices, and methods for ablating tissue via irreversible electroporation are described herein. In general, an apparatus for delivering a pulse waveform to tissue may include a first catheter (e.g., 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., shaft) or lumen may be disposed within the lumen of the first catheter and within the chamber of the expandable / inflatable member, where the second catheter may be slidable relative to the first catheter. The 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 a first catheter, and the distal portion of the expandable / inflatable member may be coupled to a distal portion of a second catheter or lumen. The second catheter may have a lumen diameter sufficient to pass a guidewire through the lumen. The guidewire may provide mechanical support for the first and second catheters. In some embodiments, the first electrode may comprise a first electrode set, and the second electrode may comprise a second electrode set.

[0010] Generally, a system for delivering a pulse waveform to tissue may include a signal generator configured to generate a 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 to deliver energy to ablate tissue by irreversible electroporation. One or more electrodes may be formed proximal to the expandable / inflatable member on a surface of the first catheter.

[0011] In some embodiments, the system may include a signal generator configured to generate a pulse waveform. The 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 the second electrode relative to the first electrode. The system may include a cardiac stimulation device for generating a pacing signal and delivering the pulse waveform synchronized 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 an electrical potential of at least about 700V without dielectric breakdown of its corresponding insulation, the insulated electrical lead being disposed within a lumen of the catheter. In some embodiments, one or more of the electrodes may be independently addressable.

[0012] In some embodiments, the pulse waveform may include a first hierarchical level of pulse waveforms in the form of a first pulse set, each pulse having a pulse duration and a first time interval separating successive pulses. A second hierarchical level of pulse waveforms includes a plurality of the first pulse sets as a second pulse set, a second time interval separating successive first pulse sets, the second time interval being at least three times the duration of the first time interval. A third hierarchical level of pulse waveforms includes a plurality of the second pulse sets as a third pulse set, a third time interval separating successive second pulse sets, the third time interval being at least 30 times the duration of the time interval of the second level. In some of these embodiments, the pulse waveform includes a fourth hierarchical level of pulse waveforms includes a plurality of the third pulse sets as a fourth pulse set, a fourth time interval separating successive third pulse sets, the fourth time interval being at least 10 times the duration of the time interval of the third level.

[0013] In some embodiments, the distal portion of the ablation device may further include a radiopaque portion.In some embodiments, the second catheter defines a lumen therethrough.

[0014] In some embodiments, a method of ablation via irreversible electroporation includes advancing an ablation device toward a pulmonary vein ostium. The ablation device may include a first catheter, a second catheter or lumen, and an expandable / inflatable member coupled to a distal end of the catheter shaft. The inflatable member may be adjacent to electrodes mounted on the device proximal and distal to the inflatable member. A pulse waveform may be generated. The pulse waveform may be delivered to the pulmonary vein ostium via electrodes on the ablation device.

[0015] In some embodiments, the expandable / inflatable member of the ablation device may 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, which may induce mechanical expansion. In some embodiments, pulsed electric field ablation energy may be delivered through the first and second electrode sets of the ablation device. In some embodiments, the ablation device is configured to generate an electric field strength of about 200 V / cm to about 800 V / cm.

[0016] In some embodiments, the ablation device may include a handle. In some embodiments, the proximal electrode or a portion of the first catheter shaft proximal to the first electrode set may be deflectable, with the deflection controlled by a knob or other control mechanism on the handle. The method may further include deflecting a portion of the ablation device using the handle. For example, the second electrode may be moved relative to the first electrode, the shape of the expandable / inflatable member in the second configuration may be changed by injection of 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.

[0017] In some embodiments, the method may include creating a transseptal opening to the left atrium, advancing a guidewire and a steerable sheath through the transseptal opening into the left atrium, and advancing an ablation device over the guidewire into a pulmonary vein. In some embodiments, the method may include creating a first access site in the patient, advancing a guidewire through the first access site into the right atrium, advancing a dilator and a steerable sheath over the guidewire and into the right atrium, advancing a dilator from the right atrium through the atrial septum into the left atrium 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 advancing a pacing catheter into the right ventricle, generating a pacing signal for cardiac stimulation of the heart using a cardiac stimulation device, applying the pacing signal to the heart using the cardiac stimulation device, and then delivering a pulsed electric field voltage pulse waveform synchronously with the pacing signal once an ablation device having an expandable member is suitably positioned at the ostium of a pulmonary vein.

[0018] In some embodiments, the method may include fluoroscopically imaging a radiopaque portion of the ablation device during one or more steps. In some embodiments, the first access site is the femoral vein. In some embodiments, the interatrial septum includes the ovoid fossa.

[0019] In some embodiments, the pulse waveform may include a first hierarchical level of pulse waveforms in the form of a first pulse set, each pulse having a pulse duration and a first time interval separating successive pulses. A second hierarchical level of pulse waveforms includes a plurality of the first pulse sets as a second pulse set, a second time interval separating successive first pulse sets, the second time interval being at least three times the duration of the first time interval. A third hierarchical level of pulse waveforms includes a plurality of the second pulse sets as a third pulse set, a third time interval separating successive second pulse sets, the third time interval being at least 30 times the duration of the time interval of the second level. In some of these embodiments, the pulse waveform includes a fourth hierarchical level of pulse waveforms includes a plurality of the third pulse sets as a fourth pulse set, a fourth time interval separating successive third pulse sets, the fourth time interval being at least 10 times the duration of the time interval of the third level.

[0020] The systems, devices, and methods described herein may be used to produce large electric field magnitudes in desired regions of interest to produce irreversible electroporation. The irreversible electroporation systems described herein may include a signal generator and a processor configured to apply one or more voltage pulse waveforms to an electrode set to deliver energy to a region of interest. The pulse waveforms disclosed herein may be useful in the therapeutic treatment of cardiac arrhythmias, such as atrial fibrillation. To deliver the pulse waveforms generated by the signal generator, one or more electrodes of the ablation device may have insulated electrical leads configured to maintain a potential of at least about 700V without dielectric breakdown of their corresponding insulation. In some embodiments, at least some of the electrodes may be independently addressable, such that each electrode may be controlled (e.g., may deliver energy) independently of any other electrode of the device.

[0021] As used herein, the term "electroporation" refers to the application of 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 the application of an electric field to a cell membrane to temporarily change the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing reversible electroporation can be observed to temporarily and / or intermittently form one or more pores in its cell membrane that close upon removal of the electric field. As used herein, the term "irreversible electroporation" refers to the application of an electric field to a cell membrane to permanently change the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing irreversible electroporation can be observed to form one or more pores in its cell membrane that persist upon removal of the electric field.

[0022] The pulse waveforms for electroporation energy delivery disclosed herein may increase the safety, efficiency, and effectiveness of energy delivery to tissue by reducing the electric field threshold associated with irreversible electroporation, thereby resulting in more effective ablative lesions with reduced total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein may be hierarchical and may have a nested structure. For example, the pulse waveforms may include a hierarchical grouping of pulses having related time scales. In some embodiments, the methods, systems, and devices disclosed herein may include one or more of the methods, systems, and devices described in International Application No. PCT / US2016 / 057664, filed October 19, 2016, and entitled "SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE," and U.S. Patent Application No. 16 / 405,515, filed May 7, 2019, and entitled "SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE," the contents of each of which are incorporated by reference in their entirety herein.

[0023] In some embodiments, the system may further include a cardiac stimulator used to synchronize the generation of the pulse waveform to the paced heartbeat. The cardiac stimulator may electrically pace the heart with the cardiac stimulator and ensure pacing capture to establish periodicity and predictability of the cardiac cycle. A time window within the refractory period of the periodic cardiac cycle may be selected for voltage pulse waveform delivery. Thus, the voltage pulse waveform may be delivered during the refractory period of the cardiac cycle to avoid disturbance 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 change to different configurations (e.g., contract and expand) to position the device within the endocardial space.

[0024] In general, one or more catheters may be minimally invasively advanced to a target location via the vascular system to ablate tissue. The methods described herein may include introducing a device into an endocardial cavity of the heart and positioning the device at the ostium of a pulmonary vein. A pulse waveform may be generated and delivered to an electrode of the device to ablate tissue. In some embodiments, the pulse waveform may be generated synchronously with a cardiac pacing signal to avoid disturbance of the cardiac sinus rhythm. In some embodiments, the electrodes may be configured with an anode-cathode subset. The pulse waveform may include a hierarchical waveform to assist in tissue ablation and reduce damage to healthy tissue.

[0025] I. System Overview Disclosed herein are systems and devices configured for tissue ablation via selective and rapid application of voltage pulse waveforms to assist tissue ablation and effect irreversible electroporation. In general, the systems for ablating tissue described herein may include a signal generator and an ablation device having one or more electrodes and an expandable / inflatable member (e.g., a balloon) for selective and rapid application of DC voltage to drive electroporation. As described herein, the systems and devices may be deployed at the endocardium to treat cardiac arrhythmias. The voltage pulse waveform may be applied to a subset of electrodes with the selection of appropriate anode / cathode electrodes. A pacing signal for cardiac stimulation may be generated and used to generate a pulse waveform by the signal generator in synchronization with the pacing signal.

[0026] Generally, the systems and devices described herein include one or more catheters configured to ablate tissue in a cardiac chamber. Figure 1 shows an ablation system (100) configured to deliver a voltage pulse waveform. The system (100) may include an apparatus (120) including a signal generator (122), a processor (124), a memory (126), and a cardiac stimulator (128). The apparatus (120) may be coupled to an ablation device (110) and, optionally, to a pacing device (130).

[0027] The signal generator (122) may 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) may be a voltage pulse waveform generator and may be configured to deliver the pulse waveform to the ablation device (110). In some embodiments, the return electrode (140) may be coupled to the patient (e.g., placed on the patient's back) to allow current to flow from the ablation device (110) through the patient to the return electrode (140). In other embodiments, an electrode of the ablation device may function as a return such that a separate return electrode (140) may not be present. The processor (124) may incorporate data received from the memory (126) to determine parameters of the pulse waveform generated by the signal generator (122), while some parameters, such as voltage, may be input by a user. The memory (126) may further store instructions that 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 waveform and / or cardiac pacing data for pulse waveform generation and / or cardiac pacing, respectively.

[0028] 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, which is described in more detail below. In each of the embodiments described herein, the expandable / inflatable member may be inflated using, for example, saline, or in some cases, a non-conductive or very low conductive fluid (e.g., gas, liquid such as distilled water, deionized water, etc.). The fluid may be introduced through a lumen of the catheter coupled to the expandable / inflatable member. For example, the ablation device (110) may be introduced into the endocardial space, positioned at the ostium of a pulmonary vein, inflated such that the expandable member is well apposed or engaged to the wall of the pulmonary vein, and then a pulse waveform may be delivered to ablate tissue. The ablation device (110) may include one or more electrodes (112), which may be independently addressable electrodes in some embodiments. Each electrode may include an insulated electrical lead configured to maintain an electrical potential of at least about 700V without dielectric breakdown of its corresponding insulation. In some embodiments, the insulation of each of the electrical leads can sustain a potential difference of about 200V to about 3,000V across its thickness without dielectric breakdown. For example, the electrodes (112) may be grouped into one or more anode-cathode subsets, such as, for example, a subset including one proximal electrode and one distal electrode. In some embodiments, the distal electrode may comprise at least a portion of the expandable / inflatable member. As used herein, proximal is toward the handle of the ablation device and distal is toward the tip of the ablation device.

[0029] If used, the pacing device (130) may 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 may be transmitted by the cardiac stimulator (128) to the signal generator (122). Based on detection of the pacing signal by the generator, a voltage pulse waveform may be generated by the signal generator (122) for ablation delivery. In some embodiments, the signal generator (122) may be configured to generate the pulse waveform in synchronization with the indication of the pacing signal (e.g., such that the ablation delivery occurs during a refractory window of the heart chamber). In some embodiments, the refractory window may be a common refractory window of two heart chambers, such as the atrium and ventricle. For example, in some embodiments, the common refractory window may begin substantially immediately (or after a very short delay) after the ventricular pacing signal and continue thereafter for a duration of about 250 milliseconds or less. In such embodiments, the entire pulse waveform may be delivered within this duration.

[0030] The processor (124) may be any suitable processing device configured to run and / or execute a set of instructions or code. The processor may be, for example, a general purpose processor, a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), a digital signal processor (DSP), and / or the like. The processor may be configured to run and / or execute application processes and / or other modules, processes and / or functions associated with the system and / or its associated network (not shown). The underlying device technology may be provided in a variety of 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 structures), mixed analog and digital, and / or the like.

[0031] 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 electrically erasable read only memory (EEPROM), a read only memory (ROM), a flash memory, etc. The memory (126) may store instructions that 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.

[0032] The system (100) may be in communication with other devices (not shown) via one or more networks, each of which may be any type of network, for example. A wireless network may refer to any type of digital network that is not connected by any type of cable. However, a wireless network may connect to a wired network to interface with the Internet, other carrier voice and data networks, business networks, and personal networks. Wired networks are typically transmitted 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 area networks (CANs), global area networks (GANs), e.g., the Internet, virtual private networks (VPNs). Hereinafter, a network refers to any combination of wireless, wired, public, and private data networks, typically interconnected via the Internet, to provide a unified networking and information access solution.

[0033] Ablation Devices The systems described herein may include one or more multi-electrode ablation devices configured to ablate tissue in the pulmonary veins of the heart to treat indications such as arrhythmia. Figure 2A is a side view of an ablation device (200) (e.g., structurally and / or functionally similar to ablation device (110)) including a first catheter (203) (e.g., a catheter shaft or outer shaft) defining a lumen, a second catheter (210) (e.g., a tubular guidewire or inner shaft defining a lumen), and an expandable member (207). The second catheter (210) may be disposed within the lumen of the first catheter (203) and within a chamber of the expandable member (207) where the second catheter (210) may be slidable relative to the first catheter (203). The expandable member (e.g., balloon) (207) may be coupled to the second catheter (210) such that the second catheter may pass through the inner chamber of the expandable member (207). The first electrode (213) may be disposed on the surface of the distal portion (217) of the first catheter (203) and may be separate from or attached to the proximal portion of the expandable member (207). The second electrode (220) may be disposed on the distal portion (223) of the second catheter (210) and may be separate from or attached to the distal portion of the expandable member (207). The distal portion (223) of the second catheter (217) may be linearly movable and may be around the distal portion of the first catheter (203). In some embodiments, the second electrode (223) may be movable relative to the first electrode (213). A proximal portion of the expandable member (207) may be coupled to a distal portion of the first catheter (203).

[0034] The proximal end of the expandable member (207) may be attached proximally 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 expandable member (207). In FIGS. 2A-2B, a second catheter or tubular lumen (210) is shown extending from the distal end (217) of the first catheter (203) and out from the distal end of the expandable member (207). The second electrode (220) is disposed on a surface of the second catheter (210) proximal to the distal end (223) of the second catheter (210). The distal end of the expandable member (207) may be attached to the second catheter (210) just proximal to the second electrode (220).

[0035] In some embodiments, a handle (not shown) may be coupled to the proximal portion of the ablation device (200) and may include a bending mechanism (not shown) (e.g., knob, switch, pull wire) configured to deflect a portion of the second catheter (210) immediately proximal to the first catheter (203). For example, manipulation of a pull wire in the handle may increase or decrease the curvature of the distal portion of the first catheter. A fluid port may be attached to the handle for injection of a fluid such as distilled or deionized water to expand the expandable member. In embodiments, the handle may incorporate a deployment mechanism configured to advance and retract the second catheter or guidewire lumen (210) such that the distance between the first electrode (213) and the second electrode (220) may be changed. For example, the expandable member may be expanded within the vein after being suitably positioned within the pulmonary vein and well apposed. The first electrode (213) and the second electrode (220) may then be brought closer together by retracting the second catheter (210) relative to the first catheter (203). In this manner, the device may be configured for PEF ablation delivery.

[0036] The expandable member (207) may be configured to transition between a first configuration (e.g., the contracted expandable member of FIG. 2B) and a second configuration (e.g., the expanded expandable member of FIG. 2A). The expandable member (207) in the first configuration may be in a compact, contracted state suitable for advancement through the vasculature. For example, the expandable member (207) in the first configuration may be substantially free of fluid, such as sterile distilled or deionized water or saline. In some embodiments, fluid may enter the expandable member (207) through an injection port in a handle coupled to the ablation device. The expandable member (207) in the second configuration may hold a volume of saline or distilled or deionized water that fills and expands the expandable member (207) to an appropriate size and shape (e.g., having a diameter that contacts the diameter of a pulmonary vein) under pressure from a syringe or other injection device. The expandable member (207) may transition to an intermediate configuration between the first and second configurations as needed, for example, to conform to a lumen or to advance the device through the vasculature. In some embodiments, the expandable member may be pressurized using one or more of a manually operated syringe, a pump, an injection device, combinations thereof, and the like. In some embodiments, the injection pressure may be from about 2 psi to about 20 psi.

[0037] 2A and 2B show an ablation device having one proximal electrode (213) and one distal electrode (223), it should be understood that more electrodes may be used in other embodiments. For example, the first electrode (213) may include a set 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 set 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 from about 1 mm to about 6 mm, including all values ​​and subranges therebetween. The length of the electrodes (213, 220) (measured along the longitudinal axis of the first and second catheters) may be from about 1 mm to about 8 mm, including all values ​​and subranges therebetween. In some embodiments, the set of electrodes disposed on the surface of the first catheter (e.g., a set of two or more proximal electrodes (213)) may be spaced apart by about 0.5 mm to about 9 mm, including all values ​​and subranges therebetween. In some embodiments, the set of electrodes disposed on the surface of the second catheter (e.g., a set of two or more distal electrodes (220)) may be spaced apart by about 0.5 mm to about 9 mm, including all values ​​and subranges therebetween. In some embodiments, the expandable member in the second configuration (e.g., inflated, deployed) may have an outer diameter (e.g., maximum width) of about 20 mm to about 40 mm, including all values ​​and subranges therebetween. In some embodiments, the expandable member in the first configuration (e.g., in a contracted, undeployed state) may have a length (measured along the longitudinal axis of the second catheter) of about 10 mm to about 80 mm when the first and second electrodes (213, 220) are maximally separated, including all values ​​and subranges therebetween.

[0038] FIG. 3 illustrates an ablation device (300) (e.g., structurally and / or functionally similar to ablation devices (110, 200)) including an expandable member (305) in a second configuration (e.g., inflated) and coaxially deployed at a pulmonary vein ostium (301). The ablation device (300) includes a first electrode (311) coupled to a proximal end of the expandable member (305) and a second electrode (313) coupled to a distal end of the expandable member (305). A first catheter and a second catheter (e.g., a guidewire catheter defining a lumen) similar to those described herein are not shown in FIG. 3 for clarity. In FIG. 3, the second catheter or guidewire lumen (not shown) is retracted relative to the first catheter such that the first electrode (311) and the second electrode (313) are minimally separated. When the expandable member is in the second configuration and the first and second electrodes (311, 313) are retracted toward one another, the central region (308) of the expandable member (305) may similarly be retracted toward one another or may be retracted such that the proximal and distal ends of the expandable member (305) are brought closer together. In this manner, the first and second electrodes (311, 313) may be at least partially surrounded by the portion of the expandable member (305) (the balloon folded inwardly).

[0039] FIG. 4A is a cross-sectional side view of an ablation device (400) (e.g., structurally and / or functionally similar to ablation devices (110, 200, 300)) positioned at a pulmonary vein ostium (402). Specifically, the longitudinal axis of the ablation device (400) is positioned at an angle relative to the longitudinal axis of the pulmonary vein. FIG. 4B is a cross-sectional side view of an ablation region (408) of the ablation device shown in FIG. 4A positioned within a pulmonary vein (411). The ablation device (400) may include an expandable member (404) and a first electrode (e.g., an electrode proximal to the expandable member (404)) and a second electrode (e.g., an electrode distal to the expandable member (404)). The first and second electrodes may be configured as an anode-cathode pair for delivering ablation energy to tissue. The ablation region (408) may form a continuous annular shape over the pulmonary vein ostium (402) when the anode-cathode pair delivers energy above the threshold required to cause irreversible electroporation.

[0040] FIG. 5A is a cross-sectional side view of an ablation device (500) (e.g., structurally and / or functionally similar to ablation devices (110, 200, 300, 400)) positioned (e.g., coaxially deployed) within a pulmonary vein ostium (502). The ablation device (500) includes a first electrode (508) coupled to a proximal end of an expandable member (505) and a second electrode (509) coupled to a distal end of the expandable member (505). Alternatively or additionally, the first and second electrodes may be coupled to a distal portion of a first catheter proximal to the expandable member and a distal portion of a second catheter / guidewire lumen distal to the expandable member, respectively. A first catheter or outer shaft and a second catheter or inner shaft (e.g., guidewire lumen) similar to those described herein are not shown in FIGS. 5A-5B for clarity. In FIG. 5A, the expandable member (505) when expanded may form a frustum shape (e.g., a trapezoid shape when viewed in cross section). In some embodiments, the diameter of the expandable member (505) at its widest portion may be from about 20 mm to about 40 mm, including all values ​​and subranges therebetween. The length of the expandable member (505) when fully deployed (measured along the longitudinal axes of the first and second catheters) may be from about 3 mm to about 30 mm, including all values ​​and subranges therebetween. FIG. 5B is a cross-sectional side view of the ablation device (500) shown in FIG. 5A, where the longitudinal axis of the ablation device (500) is disposed at an angle relative to the longitudinal axis of the pulmonary vein (502).

[0041] FIG. 6A is a cross-sectional side view of an ablation device (600) (e.g., structurally and / or functionally similar to ablation devices (110, 200, 300, 400, 500)) positioned (e.g., coaxially deployed) within a pulmonary vein ostium (603). The ablation device (600) includes a first electrode (609) coupled to a proximal end of an expandable member (606) and a second electrode (611) coupled to a distal end of the expandable member (606). Additionally or alternatively, the first and second electrodes may be coupled to a distal portion of a first catheter / outer shaft proximal to the expandable member and a distal portion of a second catheter / guidewire lumen distal to the expandable member, respectively. A first catheter / outer shaft or outer shaft and a second catheter (e.g., an inner shaft defining a lumen) similar to those described herein are not shown in FIGS. 6A-6B for clarity. The expandable member (606) in the expanded configuration may form a diamond shape in side view, as shown in FIG. 6A. FIG. 6B is a cross-sectional view of the ablation region (610) of the ablation device (600) shown in FIG. 6A positioned within a pulmonary vein (603). The first and second electrodes (609, 611) may be configured as an anode-cathode pair for delivering ablation energy to tissue. The ablation region (610) may form an annular shape over the pulmonary vein ostium (603) when the anode-cathode pair delivers energy above the threshold required to cause irreversible electroporation.

[0042] FIG. 7 is a schematic cross-sectional side view of an ablation device (700) (e.g., structurally and / or functionally similar 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 a lumen, a second catheter (705) (e.g., an inner shaft defining a lumen), and an expandable member (710). The second catheter (705) may be disposed within a lumen of the first catheter (703) and within a chamber of the expandable member (710) where the second catheter (705) may be slidable relative to the first catheter (703). The expandable member (e.g., balloon) (710) may be coupled to the second catheter (705) such that the second catheter (705) may pass through the inner chamber of the expandable member (710). The first electrode (707) may be disposed on a surface of a distal portion of the first catheter (703) and immediately proximal to the expandable member (710). The second electrode (709) may be disposed on a distal portion (712) of the second catheter (705) and immediately distal to the expandable member (710). The second catheter (705) may be linearly slidable relative to the first catheter (703). Thus, the second electrode (709) may be linearly slidable relative to the first electrode (707). The proximal portion of the expandable member (710) may be coupled to a distal portion of the first catheter (703). In FIG. 7, the expandable member (710) may form a generally diamond shape.

[0043] 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., knob, switch, pull wire) 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) may be varied. For example, the first electrode (707) and the second electrode (709) may be brought closer together by retracting the second catheter (705) relative to the first catheter (703). In FIG. 7, a central portion (713) of the distal end of the expandable member (710) is shown as retracted toward the proximal end of the expandable member (710).

[0044] When suitably expanded, the proximal main portion (715) and the distal main portion (719) of the expandable member (710) may be angled relative to the longitudinal axis of the first catheter (703) such that a surface of the expandable member (710) forms an angle (731) relative to the longitudinal axis of greater than about 45 degrees. In some embodiments, the intermediate portion (721) of the expandable member (710) may be relatively short compared to the main portions (715, 719).

[0045] FIG. 7 illustrates an ablation device having one proximal electrode (707) and one distal electrode (709), although it should be understood that more electrodes may be used in other embodiments. For example, the first electrode (707) may include a set of electrodes (e.g., two or more proximal electrodes). Similarly, the second electrode (709) may include a set of electrodes (e.g., two or more distal electrodes). In some embodiments, the diameter of the electrodes (707, 709) may be from about 1 mm to about 6 mm, including all values ​​and subranges therebetween. The length of the electrodes (707, 709) (measured along the longitudinal axis of the first and second catheters) may be from about 1 mm to about 8 mm, including all values ​​and subranges therebetween. In some embodiments, the set of electrodes (e.g., a set of two or more proximal electrodes (707)) disposed on the surface of the first catheter (703) may be spaced apart by about 0.5 mm to about 9 mm, including all values ​​and subranges therebetween. In some embodiments, the set of electrodes (e.g., a set of two or more distal electrodes (709)) disposed on the surface of the second catheter (705) may be spaced apart from about 0.5 mm to about 9 mm, including all values ​​and subranges therebetween. In some embodiments, the expandable member (710) in the second configuration (e.g., inflated) may have an outer diameter of about 20 mm to about 40 mm, including all values ​​and subranges therebetween. In some embodiments, the expandable member (710) in the first configuration (e.g., in a contracted, undeployed state) may have a length (measured along the longitudinal axis of the second catheter) of about 10 mm to about 80 mm when the first and second electrodes (707, 709) are maximally separated, including all values ​​and subranges therebetween. In a fully deployed state with the second catheter (705) retracted for minimal separation between the first and second electrodes (707, 709), the length of the expandable member (710) (measured along the longitudinal axis of the first catheter (703)) can be from about 3 mm to about 30 mm, including all values ​​and subranges therebetween.

[0046] FIG. 8 is a schematic cross-sectional side view of an ablation device (800) (e.g., structurally and / or functionally similar 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 a lumen, a second catheter (805) (e.g., an inner shaft defining a guidewire lumen), and an expandable member (810). The second catheter (805) may be disposed within a lumen of the first catheter (803) and within a chamber of the expandable member (810) where the second catheter (805) may be slidable relative to the first catheter (803). The expandable member (e.g., balloon) (810) may be coupled to the second catheter (805) such that the second catheter (805) may pass through the inner chamber of the expandable member (810). The first electrode (807) may be disposed on a surface of a distal portion of the first catheter (803) and immediately proximal to the expandable member (810). The second electrode (809) may be disposed on a distal portion (812) of the second catheter (805) and immediately distal to the expandable member (810). The second catheter (805) may be linearly slidable relative to the first catheter (803). Thus, the second electrode (809) may be slidable relative to the first electrode (807). A proximal portion of the expandable member (810) may be coupled to the first catheter (803), and a distal portion of the expandable member (810) may be coupled to the second catheter (805) such that the second catheter (805) may pass through the internal chamber of the expandable member (810).

[0047] In some embodiments, the ablation device (800) may include a handle (not shown) coupled to a proximal portion of the ablation device (800) and may include a mechanism (not shown) (e.g., knob, switch, pull wire) configured to advance and retract the second catheter (805) such that the distance between the first electrode (807) and the second electrode (809) may be varied. For example, the first electrode (807) and the second electrode (809) may be brought closer together by retracting the second catheter or guidewire (805) relative to the first catheter (803). In FIG. 8, a central portion (813) of the distal end of the expandable member (810) is shown as being retracted toward the proximal end of the expandable member (810) using the handle and bending mechanism described herein.

[0048] When suitably expanded, the proximal (815) and distal (819) main portions of the expandable member (810) may be gently curved with surfaces locally at an angle relative to the longitudinal axis of the first catheter (803) such that the surface of the expandable member (810) locally forms an angle (831) relative to the longitudinal axis. In some embodiments, the intermediate portion (821) of the expandable member (810) may be relatively short in length compared to the main portions (815, 819). In some embodiments, the main portions (815, 819) may be steeply and gently curved relative to the longitudinal axis (825) of the first catheter (803). In FIG. 8, the local tangent plane (829) to the surface of the expandable member (i.e., the component of the local tangent plane in the plane defined by the radial and axial directions) may form an angle (831) with the longitudinal axis (825) that is greater than about 45 degrees.

[0049] In some embodiments, the intermediate portion (821) of the expandable member (810) may be relatively short in length compared to the main portions (815, 819). When the expandable member (810) is expanded (e.g., suitably pressurized), the intermediate portion (821) may protrude as shown in FIG. 8. In some embodiments, the intermediate portion (821) of the expandable member (810) may be constructed of a thinner material compared to the main portions (815, 819). For example, the wall thickness of the expandable member (810) at the main portions (815, 819) may be at least 20% greater than the wall thickness of the intermediate portion (821). In some embodiments, the wall thickness of the expandable member (810) at the main portions (815, 819) may be at least 50% greater than the wall thickness of the intermediate portion (821). In some embodiments, the wall thickness of the expandable member (810) at the main portions (815, 819) may be at least 100% greater than the wall thickness of the intermediate portion (821).

[0050] Figure 10 is a schematic side view of a portion of an unexpanded expandable member wall (1000), including a proximal portion (1003), an intermediate portion (1005), and a distal portion (1007). Figure 10 illustrates diagrammatically 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 intermediate portion (1012).

[0051] 11 is a schematic side view of a portion of a wall (1700) of an expandable member of an ablation device, including a proximal portion (1703), an intermediate portion (1705), and a distal portion (1707) arranged along a longitudinal or central axis (1710) of the expandable member. Any of the expandable members described herein (e.g., expandable members 207, 305, 404, 505, 606, etc.) can have walls structurally and / or functionally similar to the wall (1700) shown in FIG. A proximal portion (1703) of the wall (1700) can have a length L1 extending along the longitudinal axis (1710), an intermediate portion (1705) of the wall (1700) can have a length L2 extending along the longitudinal axis (1710), and a distal portion (1707) of the wall (1700) can have a length L3 extending along the longitudinal axis (1710). L1 and L3 can be greater than L2, and the ratios of L1 / L2 and L3 / L2 are greater than 3.

[0052] 11, the proximal portion (1703) of the expandable member wall (1700) can have a maximum thickness D1, the intermediate 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 one another (or approximately equal to one another), and the thickness D2 of the intermediate portion (1705) can be about one-third or less of the thicknesses D1 and D3.

[0053] FIG. 8 illustrates an ablation device having one proximal electrode (807) and one distal electrode (809), although it should be understood that more electrodes may be used in other embodiments. For example, the first electrode (807) may include a set of electrodes (e.g., two or more proximal electrodes). Similarly, the second electrode (809) may include a set of electrodes (e.g., two or more distal electrodes). In some embodiments, the diameter of the electrodes (807, 809) may be from about 1 mm to about 6 mm, including all values ​​and subranges therebetween. The length of the electrodes (807, 809) (measured along the longitudinal axis of the first and second catheters) may be from about 1 mm to about 8 mm, including all values ​​and subranges therebetween. In some embodiments, the set of electrodes (e.g., a set of two or more proximal electrodes (807)) disposed on the surface of the first catheter (803) may be spaced apart by about 0.5 mm to about 9 mm, including all values ​​and subranges therebetween. In some embodiments, the set of electrodes (e.g., a set of two or more distal electrodes (809)) disposed on the surface of the second catheter (805) may be spaced apart from about 0.5 mm to about 9 mm, including all values ​​and subranges therebetween. In some embodiments, the expandable member (810) in the second configuration (e.g., inflated) may have an outer diameter of about 20 mm to about 40 mm, including all values ​​and subranges therebetween. In some embodiments, the expandable member (810) in the first configuration (e.g., in a contracted, undeployed state) may have a length (measured along the longitudinal axis of the second catheter) of about 10 mm to about 80 mm when the first and second electrodes (807, 809) are maximally separated, including all values ​​and subranges therebetween. In a fully deployed state with the second catheter (805) retracted for minimal separation between the first and second electrodes (807, 809), the length of the expandable member (810) (measured along the longitudinal axis of the first catheter (803)) can be from about 3 mm to about 30 mm, including all values ​​and subranges therebetween.

[0054] FIG. 9 is a perspective view of an ablation device (900) (e.g., structurally and / or functionally similar to ablation devices (110, (801)). Specifically, ablation device (900) corresponds to a perspective view of ablation device (800) shown in FIG. 8. Ablation device (900) includes a first catheter (903) (e.g., an outer catheter shaft) defining a lumen, and a second catheter (e.g., an inner shaft or guidewire lumen) (the distal end of which is shown at (912)). The first catheter (903) may include a first electrode (907) and an expandable member (910). The second catheter may be disposed within a lumen of the first catheter (903) and within a chamber of the expandable member (910) through which the second catheter may be slidable relative to the first catheter (903). The expandable member (e.g., a balloon) (910) may be coupled to the second catheter such that the second catheter may pass through the inner chamber of the expandable member (910). The first electrode (907) may be coupled to the first catheter (903). The second electrode (909) may be disposed on a surface of a distal portion of the first catheter (903) and separate from the expandable member (910). The second electrode (909) may be disposed on a distal portion of the first catheter (903) and separate from the expandable member (910). The second catheter may be linearly slidable relative to the first catheter (903). Thus, the second electrode (909) may be slidable relative to the first electrode (907). The proximal portion of the expandable member (910) may be coupled to a distal portion of the first catheter (903). The proximal main portion (915) and the distal main portion (919) of the expandable member (910) may be gently curved with surfaces locally at an angle relative to the longitudinal axis of the first catheter (903). In some embodiments, the intermediate portion (921) of the expandable member (910) may be relatively short in length compared to the main portions (915, 919). In some embodiments, the main portions (915, 919) may be steeply and gently curved relative to the longitudinal axis of the first catheter (903).

[0055] 12A and 12B show different views of an ablation device (1800), which may include structurally and / or functionally similar components to those of other ablation devices described herein. The ablation device (1800) may include a first electrode (1809) coupled to a proximal end of an expandable member (1806) and a second electrode (1811) coupled to a distal end of the expandable member (1806). In some embodiments, the second electrode (1811) may be coupled to an inner catheter or inner shaft or guidewire lumen, which may be attached to a proximal handle (not shown) for deploying 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 attracted to the first electrode (1809) and the expandable member (1806) expands. Once deployed, the ablation device (1800) can be locked in place using an appropriate locking mechanism, for example a locking mechanism located in the handle.

[0056] The expandable member (1806) in the expanded and deployed configuration can form a conical shape as shown in Figures 12A and 12B. In the deployed configuration, shown in more detail in Figure 13, the expandable member (1806) can have a circular side (e.g., side portion) having a maximum width W, a height H, and a radius of curvature R. In some embodiments, for example, when the expandable member (1806) is designed for use in the pulmonary veins of the 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.

[0057] In some embodiments, the first and second electrodes (1809, 1811) may be structurally similar. For example, each of the first and second electrodes (1809, 1811) may 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) may have a circular or atraumatic shape, for example, as shown in FIG. 14. An inner shaft or guidewire lumen may be used to pass a guidewire internally to aid in engagement with the pulmonary vein so that the catheter may be delivered over the guidewire to the target anatomical structure.

[0058] In some embodiments, a proximal portion of the expandable member (1806) in a deployed configuration may be angled relative to a longitudinal axis of the ablation device (1800) by angle A1, and a distal portion of the expandable member (1806) may be angled relative to a longitudinal axis of the ablation device (1800) by angle A2. In some embodiments, angle A2 may be greater than angle A1 such that the expandable member (1806) when deployed has an asymmetric shape. For example, in some embodiments, angle A1 may be in the range of about 50 degrees to about 75 degrees, while angle A2 may be about 80 degrees to about 90 degrees.

[0059] FIG. 14 illustrates a cross-sectional side view of an ablation device (1900), including components structurally and / or functionally similar to those of other ablation devices described herein, while positioned, for example, at a pulmonary vein ostium (1901) of the heart. Specifically, similar to the ablation device (1800), the ablation device (1900) includes two electrodes (1909, 1911) disposed on opposite sides of an expandable member (1906). The electrode (1911) disposed at the distal end of the expandable member (1906) can have a rounded or atraumatic tip (1911a). When deployed, the expandable member (1906) of the ablation device (1900) can have sides that engage the walls (1902) of the pulmonary vein ostium (1901) and can hold the ablation device (1900) against the pulmonary vein ostium (1901). 14, the ablation device (1900) may be held with its longitudinal axis generally aligned with the longitudinal axis of the pulmonary vein ostium (1901), with the proximal side of the expandable member (1906) facing the heart chamber blood pool (1903). Alternatively, the ablation device (1900) may be held in other orientations relative to the pulmonary vein ostium (1901), resulting in different ablation regions within the surrounding tissue.

[0060] 14, the electrodes (1909, 1911) can result in an ablation region (1920), for example, when configured as an anode-cathode pair for delivering ablation energy via irreversible electroporation as described further herein. The expandable member (1906) can be formed from an insulating material and, when oriented and shaped, can direct the electric field generated by the electrodes (1909, 1911) to the walls (1902) of the pulmonary vein ostium (1901).

[0061] Each of the ablation devices described herein (110, 200, 300, 400, 500, 600, 700, 800, 900, 1800, 1900, etc.) may, in some embodiments, include a handle (not shown) that may be coupled to a proximal portion of the ablation device and may include a mechanism (e.g., knob, switch, pull wire) configured to change the position of the second electrode relative to the first electrode. For example, the first and second electrodes may be brought closer together by retracting the second catheter or 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 embodiments, the device tracks over a guidewire positioned in a pulmonary vein through a steerable sheath, and deflection of the sheath can provide steering control for positioning the guidewire and the expandable member of the ablation catheter in the pulmonary vein. The expandable member may be inflated through a fluid port attached to the catheter handle, and distilled or deionized water may be injected under pressure. In this manner, apposition of the ablation device to tissue may be provided in a desired location and orientation (e.g., at the ostium of a pulmonary vein).

[0062] The ablation devices described herein may be useful for forming lesions on endocardial surfaces, such as the inner surface of a pulmonary vein, as described herein. The distal portion of the expandable member may include and / or be formed with an atraumatic shape that reduces tissue trauma (e.g., prevents and / or reduces the possibility of tissue puncture). The expandable member may be sized to advance into the endocardial cavity. A set of electrical leads and / or fluid (e.g., saline) may be positioned within the lumen of the first catheter.

[0063] In some embodiments, the electrodes may be shaped to conform to the shape of the catheter in which they are placed. For example, the electrodes may be press-fit (e.g., crimped) into the first catheter or outer shaft, or may be attached using an adhesive to electrical leads attached to the electrodes. The first catheter may include a flexible portion (e.g., may be deflectable) to increase flexibility and allow the device to deflect.

[0064] Each of the electrodes of the ablation devices discussed herein may be connected to an insulated electrical lead (not shown) that leads to a handle (not shown) coupled to a proximal portion of the first catheter. The insulation of each of the electrical leads may maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation of each of the electrical leads may maintain a potential difference of about 200V to about 3,000V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. This allows the electrodes and expandable members coupled to the electrodes to effectively deliver electrical energy to ablate tissue via irreversible electroporation. The electrodes may receive a pulsed waveform generated by a signal generator (122), for example, as discussed above with respect to FIG. 1.

[0065] For each of the ablation devices discussed herein, the electrodes may comprise a biocompatible metal, such as titanium, palladium, gold, silver, platinum, or a platinum alloy. For example, the electrodes may preferably comprise platinum or a platinum alloy. In some embodiments, the proximal electrodes may have a biocompatible coating that allows for 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 insulation of each of the electrical leads may maintain a potential difference of about 200V to about 3,000V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. The insulated electrical leads may extend to a proximal handle portion of the ablation device where they may be connected to a suitable electrical connector. The first catheter may be made of a flexible polymeric material, such as Teflon, Nylon, Pebax, etc.

[0066] In some embodiments, the inflatable members described herein may have an expandable structure and may be constructed from any of a variety of insulating or dielectric materials, including, but not limited to, polyvinyl chloride (PVC), polyethylene (PE), cross-linked polyethylene, polyolefin, polyolefin copolymer (POC), polyethylene terephthalate (PET), polyester, nylon, polymer blends, polyester, polyimide, polyamide, polyurethane, silicone, polydimethylsiloxane (PDMS), PEBAX, and the like. Preferred embodiments may be constructed from polyurethane or silicone. In conjunction with the use of distilled or deionized water to inflate the inflatable member, the inflatable member acts as an effective insulator during delivery of the pulsed electric field waveform, driving an electric field to the outside of the inflatable member or balloon and to the area surrounding the balloon.

[0067] II. Method Also described herein are methods for ablating tissue in pulmonary veins (e.g., left atrial pulmonary veins) using the above systems and devices. Generally, the methods described herein include introducing and positioning a device at the pulmonary vein ostium. A pulse waveform may 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 may synchronize the delivered pulse waveform with the cardiac cycle. Additionally or alternatively, the pulse waveform may include multiple hierarchical levels to reduce total energy delivery. The tissue ablation performed may thus be delivered in synchronization with the paced heartbeat and with less energy delivery to reduce damage to healthy tissue. It should be understood that any of the ablation devices described herein may be used to ablate tissue, optionally using the methods discussed below.

[0068] Generally, and as shown in FIGS. 20A-20B, the method (1600) includes introducing a device (e.g., an ablation device (e.g., an ablation device such as 110, 200, 300, 400, 500, 600, 700, 800, 900, etc.) into the endocardial cavity of a pulmonary vein. The ablation device may be introduced in a first or contracted configuration and transitioned to a second or expanded configuration within the pulmonary vein ostium. Once positioned, a voltage pulse waveform may be applied to the tissue during a refractory period of the cardiac cycle. Electrophysiological data of the cardiac chamber may be recorded to determine the effectiveness of the ablation.

[0069] The method (1600) may begin with creating an access site in a patient (1602). For example, a first access site may be via the patient's femoral vein. A guidewire may be advanced (1604) into the access site via the femoral vein and into the patient's right atrium. A dilator and a deflectable sheath may be advanced (1606) over the guidewire and into the right atrium. The sheath may be configured to deflect, for example, up to about 180 degrees or more. To create a transseptal opening, a dilator may be advanced (1608) from the right atrium through the septum into the left atrium. For example, to create a transseptal opening, a dilator may be advanced from the right atrium through the atrial septum into the left atrium. The atrial septum may include the patient's oval fossa. The transseptal opening may be dilated (1610) using the dilator. For example, a dilator may be advanced out of the sheath and used to puncture the fossa ovalis to create a transseptal opening (assuming the patient has been treated with heparin). Alternatively, a transseptal needle (e.g., a Brockenbrough needle) may be used to create the transseptal opening. The sheath may be advanced (1612) from the right atrium through the transseptal opening into the left atrium. An ablation device may be advanced (1614) over the guidewire into the left atrium, with a second catheter or guidewire lumen of the ablation device following over the guidewire.

[0070] 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 thin microcatheter having a circular distal shape with electrodes attached thereto may be introduced through a second catheter or guidewire lumen into a pulmonary vein and used to record intracardiac ECG data to confirm successful ablation.

[0071] 20A-20B, a second access site may be created in the patient for advancing a lead or catheter for cardiac stimulation into the patient's heart. For example, the second access site may be via the patient's jugular vein. A device for cardiac stimulation may be advanced 1620 into the right ventricle through the second access site (e.g., near the apex of the right ventricle). A pacing signal may be generated by the cardiac stimulation device and applied to the heart for cardiac stimulation of the heart. An indication of the pacing signal may be transmitted from the cardiac stimulation device to the signal generator. In some embodiments, an operator may confirm pacing capture and determine that the ventricle is responding to the pacing signal as intended. For example, pacing capture may be confirmed on an ECG display on the signal generator. Confirmation of pacing capture is a safety feature in that ablation is delivered synchronously with pacing through the mandatory periodicity of Q waves throughout the pacing. Similarly, in some embodiments, an additional pacing catheter may be used, for example, to pace the right atrium in addition to the right ventricle, and ablation may be delivered during a common refractory window of both heart chambers.

[0072] The ablation device may be advanced toward the target pulmonary vein to deliver a pulse waveform configured for tissue ablation (1622). Specifically, the ablation device in a second configuration may be advanced toward a pulmonary vein of the heart to engage a tissue surface. The sheath may be deflected, if necessary, to direct the ablation device toward the target vein. The expandable member may transition to a second configuration in which the expandable member expands to contact the expandable member against the pulmonary vein. Once the ablation device is in place within the heart and has delivered one or more pulse waveforms, an extension cable may be used to electrically couple a signal generator to a proximal end of the handle of the ablation device. After pacing the right ventricle using the pacing device (1624), a pulse waveform may be delivered to the target site using the ablation device to ablate tissue. The pulse waveform may be delivered synchronously with the pacing signal.

[0073] Although examples of ablation devices configured for delivery of irreversible electroporative pulsed electric field therapy are described herein, the examples described herein are provided for illustrative purposes only, and one skilled in the art may devise other variations without departing from the scope of the present invention. For example, various and varied materials, polyhedral sides, electrode diameters, device dimensions, 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 present invention. In embodiments in which the distal shaft of the catheter is deflectable, the catheter shaft may undergo various deflections by controlling the deflection from the catheter handle.

[0074] As discussed herein, the pulse waveform may be generated by a signal generator coupled to the ablation device. The signal generator may be electrically coupled to a proximal end of a 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 the pacing signal. In some embodiments, the pulse waveform may include a first hierarchical level of pulse waveforms including a first pulse set. Each pulse has a pulse duration and a first time interval separating successive pulses. A second hierarchical level of pulse waveforms may include a plurality of the first pulse sets as the second pulse set. The second time interval may separate successive first pulse sets. The second time interval may be at least three times the duration of the first time interval. A third hierarchical level of pulse waveforms may include a plurality of the second pulse sets as the third pulse set. The third time interval may separate successive second pulse sets. The third time interval may be at least 30 times the second level time interval. A fourth hierarchical level of the pulse waveform may include a plurality of the third pulse sets as the fourth pulse set. A fourth time interval may separate consecutive third pulse sets. The fourth time interval may be at least 10 times the third level time interval.

[0075] In other embodiments, the ablation device may be withdrawn from the heart over the guidewire, and a mapping catheter may be advanced over the guidewire to record post-ablation electrophysiological data of the target site. If the ablation is not successful based on the electrophysiological data and predetermined criteria (1630-No), the process may return to step 1626 for delivery of additional pulse waveforms. The pulse waveform parameters may be the same or may change for subsequent ablation cycles.

[0076] If analysis of the electrophysiological data indicates that the ablation was successful (e.g., the tissue portion is electrically silent) (1630-YES), another target portion to ablate may be determined (1632) (e.g., another pulmonary vein). Another target portion may be selected (1624) and the process may return to step 1622 if another portion is to be ablated. When switching target tissue, the expandable member may be at least partially deflated and the ablation device may be advanced toward another portion of the tissue. If no other portions are ablated (1632-NO), the ablation device, pacing catheter, sheath, guidewire, etc. may be removed from the patient (1636).

[0077] It should be noted that for any of the steps described herein, the radiopaque portions of the ablation device may be imaged fluoroscopically to assist the operator. For example, visual confirmation may be performed through fluoroscopic imaging that the expandable member in the second configuration is in contact with and approximately centered on the vein via a radiopaque marker band located on the distal portion of the device.

[0078] It will be appreciated that the embodiments and figures of the present disclosure are for illustrative purposes only, and that developments and variations in the characteristics of the expandable member, the number of electrodes, and the like may be constructed and developed in accordance with the teachings herein without departing from the scope of the present invention.

[0079] Pulse Waveform Disclosed herein are methods, systems, and devices for selective and rapid application of pulsed electric fields / waveforms to effect tissue ablation with irreversible electroporation. The pulsed waveform(s) disclosed herein can be used in any of the systems (100), devices (e.g., 200, 300, 400, 500, 600, 700, 800, 900), and methods (e.g., 1600) described herein. Some embodiments relate to pulsed high voltage waveforms along with sequenced delivery schemes for delivering energy to tissue through a set of electrodes. In some embodiments, peak electric field values ​​can be reduced and / or minimized while a sufficiently large electric field magnitude can be maintained in the area where tissue ablation is desired. In some embodiments, a system useful for irreversible electroporation includes a signal generator and a processor that can be configured to apply a pulsed voltage waveform to a selected plurality or subset of electrodes of an ablation device. In some embodiments, the processor is configured to control inputs whereby selected pairs of the anode-cathode subset of electrodes may be triggered either simultaneously or sequentially based on a predefined sequence, in one embodiment, the sequenced delivery may be triggered from a cardiac stimulator and / or pacing device. In some embodiments, the ablation pulse waveform may be applied during the refractory period of the cardiac cycle to avoid disruption of the sinus rhythm of the heart. One example of how to do this is to electrically pace the heart with a cardiac stimulator, ensure pacing capture to establish periodicity and predictability of the cardiac cycle, and then define a time window well within the refractory period of this cardiac cycle during which the ablation waveform is delivered.

[0080] In some embodiments, the pulse voltage waveforms disclosed herein are hierarchically organized and have a nested structure. In some embodiments, the pulse waveforms include a hierarchical grouping of pulses having various associated time scales. Furthermore, the associated time scales and pulse widths, as well as the number of pulses and the hierarchical grouping, may be selected to satisfy one or more of a set of Diophantine inequalities that include the frequency of cardiac pacing.

[0081] The pulse waveforms for electroporation energy delivery disclosed herein may increase the safety, efficiency, and effectiveness of energy delivery by reducing the electric field threshold associated with irreversible electroporation, resulting in more effective ablation of lesions with reduced total energy delivered.

[0082] FIG. 15 shows a pulse voltage waveform in the form of a sequence of rectangular double pulses, with each pulse, such as pulse (1100), associated with a pulse width or duration. The pulse width / duration can be about 0.5 microseconds, about 1 microseconds, 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. The pulse waveform in FIG. 15 shows a set of monophasic pulses in which the polarity of all pulses is the same (all positive in FIG. 15 when measured from a zero baseline). In some embodiments, such as 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. As shown in Figure 15, pulses (1100) are separated from adjacent pulses by a time interval (1102), sometimes referred to as a first time interval. By way of 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 effect irreversible electroporation.

[0083] FIG. 16 introduces a pulse waveform with a hierarchical structure of nested pulses. FIG. 16 shows a series of monophasic pulses, such as pulses (1200) having a pulse width / pulse duration w, separated by a time interval (sometimes also referred to as a first time interval), such as (1202) of duration t1 between successive pulses, the number m1 of which is arranged to form a pulse group (1210) (sometimes also referred to as a first pulse set). Further, the waveform has a number m2 of such pulse groups (sometimes also referred to as a second pulse set), separated by a time interval (1212) (sometimes also referred to as a second time interval) of duration t2 between successive groups. The collection of m2 such pulse groups, marked by (1220) in FIG. 16, constitutes the next hierarchical level, which may be referred to as a packet and / or a third pulse set. Both the pulse width and the time interval t1 between pulses may be in the range of microseconds to hundreds of microseconds, including all values ​​and subranges therebetween. In some embodiments, the time interval t2 may be at least 3 times greater than the time interval t1. In some embodiments, the ratio of t2 / t1 may be in the range of about 3 to about 300, including all values ​​and subranges therebetween.

[0084] FIG. 17 further details the structure of the nested pulse hierarchical waveform. In this figure, a series of m1 pulses (individual pulses not shown) form a pulse group (1300) (e.g., a first pulse set). A series of m2 separated by an inter-group time interval (1310) of duration t2 (e.g., a second time interval) between one group and the next form a packet (e.g., a second pulse set). A series of m3 such packets separated by a time interval (1312) of duration t3 (e.g., a third time interval) between one packet and the next form a superpacket (e.g., a third pulse set), labeled (1320) in the figure, which is the next level in the hierarchy. In some embodiments, the time interval t3 may be at least about 30 times greater than the time interval t2. In some embodiments, the time interval t3 may be at least 50 times greater than the time interval t2. In some embodiments, the ratio of t3 / t2 may be in the range of about 30 to about 800, including all values ​​and subranges therebetween. The amplitude of the individual voltage pulses within the pulse hierarchy can be anywhere within the range of 500 volts to 7,000 volts or more, including all values ​​and subranges therebetween.

[0085] FIG. 18 provides an example of a biphasic waveform sequence with a hierarchical structure. 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 pulse set). 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 packet (1420) (e.g., a second pulse set). The figure also shows a second packet (1430) with a time delay (1432) (e.g., a third time interval) of duration t3 between packets. As with the monophasic pulses, higher levels of hierarchical structures can also be formed. The amplitude of each pulse or the voltage amplitude of the biphasic pulse may be anywhere in the range of 500 volts to 7,000 volts or more, including all values ​​and subranges therebetween. The pulse width / pulse duration may be in the range of nanoseconds or even subnanoseconds to tens of microseconds, while the delay t1 may be in the range of zero to several microseconds. The intergroup time interval t2 may be at least 10 times greater than the pulse width. In some embodiments, the time interval t3 may be at least about 20 times greater than the time interval t2. In some embodiments, the time interval t3 may be at least 50 times greater than the time interval t2.

[0086] The embodiments disclosed herein include waveforms structured as hierarchical waveforms that include waveform elements / pulses at various hierarchical levels. An individual pulse, such as (1200) of FIG. 16, comprises a first hierarchical level and has an associated pulse duration and a first time interval between successive pulses. A set of pulses, or elements of the first level structure, forms a second hierarchical level, such as a pulse group / second pulse set (1210) of FIG. 16. Among other parameters, parameters such as the total duration of the second pulse set (not shown), the total number of first level elements / first pulse sets, and a second time interval between successive first level elements that describe the second level structure / second pulse set are associated with the waveform. In some embodiments, the total duration of the second pulse set can be from about 20 microseconds to about 10 milliseconds, including all values ​​and subranges therebetween. A set of groups, second pulse sets, or sets of elements of the second level structure form a third hierarchical level, such as a packet of groups / third pulse set (1220) of FIG. 16. Among other parameters are the total duration of the third pulse set (not shown), the total number of second level elements / second pulse sets, and the third time interval between successive second level elements that describe the third level structure / third pulse set. The generally repetitive or nested structure of the waveform can continue to multiple higher levels, such as 10 or more structure levels.

[0087] For example, the pulse waveform may include a fourth hierarchical level of pulse waveforms and may include a plurality of third pulse sets as the fourth pulse set, with a fourth time interval separating consecutive third pulse sets and the fourth time interval being at least 10 times the duration of the time intervals of the third level.

[0088] In some embodiments, the hierarchical waveforms with nesting structure and time interval hierarchy described herein are useful for irreversible electroporation ablation energy delivery and provide a good level of control and selectivity for application in different tissue types. A variety of hierarchical waveforms can be generated using a suitable pulse generator. Although the examples herein specify separate monophasic and biphasic waveforms for clarity, it should be noted that combination waveforms can also be generated / performed, where some parts of the waveform hierarchy are monophasic and other parts are biphasic.

[0089] In some embodiments, the ablation pulse waveforms described herein may be applied during the refractory period of the cardiac cycle to avoid disturbance of the sinus rhythm of the heart. In some embodiments, the treatment method includes electrically pacing the heart with a cardiac stimulation device 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 cardiac cycle during which one or more ablation waveforms may be delivered. FIG. 19 shows an example in which both atrial and ventricular pacing is applied (e.g., pacing leads or catheters are located in the right atrium and right ventricle, respectively). Representing time on the horizontal axis, FIG. 19 shows a series of ventricular pacing signals, such as (1500) and (1510), as well as a series of atrial pacing signals (1520, 1530), along with a series of ECG waveforms (1540, 1542) driven by the pacing signals. As indicated by the bold arrows in FIG. 19, there is an atrial refractory window (1522) and a ventricular refractory window (1502) following the atrial pacing signal (1522) and the ventricular pacing signal (1500), respectively. As shown in FIG. 19, a common refractory window (1550) of duration Tr may be defined that is within both the atrial and ventricular refractory windows (1522, 1502). In some embodiments, the electroporation ablation waveform(s) may be applied during this common refractory window (1550). The start of this refractory window (1522) is offset from the pacing signal (1500) by a time offset (1504), as shown in FIG. 19. The time offset (1504) may be less than about 25 milliseconds in some embodiments. At the next cardiac beat, the similarly defined common refractory window (1552) is the next window of time available for application of the ablation waveform(s). In this manner, the ablation waveform(s) may be applied over a series of cardiac beats, remaining within the common refractory window at each cardiac beat. In one embodiment, each packet of pulses defined above in the pulse waveform hierarchy may be applied over one cardiac beat, such that a series of packets are applied to a given electrode set over a series of cardiac beats.

[0090] As used herein, the terms "about" and / or "approximately" when used in conjunction with a numerical value and / or range generally refer to a numerical value and / or range that is close to the recited numerical value and / or range. In some cases, the terms "about" and "approximately" may mean within ±10% of the recited value. For example, in some cases, "about 100 [units]" may mean within ±10% of 100 (e.g., 90 to 110). The terms "about" and "approximately" may be used interchangeably.

[0091] Some embodiments described herein relate to computer storage products having non-transitory computer-readable media (which may also be referred to as non-transitory processor-readable media) having instructions or computer code for performing various computer-implemented operations. The computer-readable media (or processor-readable media) is non-transitory in the sense that it does not itself include a transitory propagating signal (e.g., a propagating electromagnetic wave that carries information on a transmission medium such as space or cable). The media and computer code (which may also be referred to as code or algorithms) may be designed and constructed for a specific purpose(s). 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 / DVDs), compact disk read-only memory (CD-ROMs), and holographic devices; magneto-optical storage media such as optical disks; carrier wave signal processing modules; and hardware devices specially 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 computer program products, which may include, for example, instructions and / or computer code disclosed herein.

[0092] The systems, devices, and / or methods described herein may be implemented by software (executed on hardware), hardware, or a combination thereof. Hardware modules may include, for example, general-purpose processors (or microprocessors or microcontrollers), field programmable gate arrays (FPGAs), and / or application-specific integrated circuits (ASICs). Software modules (executed on hardware) may be expressed in a variety of software languages ​​(e.g., computer code), including C, C++, Java, Ruby, Visual Basic, 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 compilation, code used to generate 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, encryption code, and compression code.

[0093] (Additional Note) As a preferred embodiment, the technical ideas that can be understood from the above embodiment will be described below. [Appendix 1] 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 along the longitudinal axis relative to the first shaft; 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 and second electrodes configured to generate an electric field to ablate tissue; and an expandable member disposed between the first electrode and the second electrode, the expandable member configured to transition from a non-deployed configuration to a deployed configuration in response to the second shaft moving proximally relative to the first shaft, the expandable member in the deployed configuration configured to engage a wall of a pulmonary vein ostium and direct the electric field generated by the first and second electrodes against the wall, the expandable member including a wall, the wall comprising: A proximal portion; A distal portion; an intermediate portion disposed between the proximal and distal portions of the wall, the intermediate portion having a minimum thickness less than the thicknesses of the proximal and distal portions of the wall; having A device wherein a length of each of the proximal and distal portions of the expandable member along the longitudinal axis is greater than a length of the intermediate portion along the longitudinal axis, and wherein the expandable member when in the deployed configuration has a longitudinal distance along the longitudinal axis between the proximal and distal portions, the longitudinal distance being greater than a length of the intermediate portion along the longitudinal axis. [Appendix 2] a shaft having a longitudinal axis and defining a lumen; an expandable member disposed near a distal portion of the shaft, the expandable member configured to transition between an undeployed configuration and a deployed configuration, the expandable member including a wall, the wall including a proximal portion having a proximal portion length, a distal portion having a distal portion length, and an intermediate portion disposed between the proximal and distal portions of the wall and having an intermediate portion length, the intermediate portion having a minimum thickness less than thicknesses of the proximal and distal portions of the wall, a ratio of the proximal portion length to the intermediate portion length and a ratio of the distal portion length to the intermediate portion length are greater than 3, the expandable member when in the deployed configuration has a longitudinal distance along the longitudinal axis between the proximal and distal portions, the longitudinal distance being greater than a length along the longitudinal axis of the intermediate portion; and first and second electrodes disposed on opposite sides of the expandable member along the longitudinal axis, the first and second electrodes configured to generate an electric field to ablate tissue. [Appendix 3] 3. The device of claim 2, wherein the expandable member in the deployed configuration is configured to engage a wall of a pulmonary vein ostium, the expandable member being formed from an insulating material such that the expandable member in the deployed configuration directs the electric field generated by the first and second electrodes toward the wall of the pulmonary vein ostium. [Appendix 4] 4. The device of any one of claims 1 to 3, wherein the expandable member in the deployed configuration comprises at least a proximal or distal portion angled at greater than 45 degrees relative to the longitudinal axis. [Appendix 5] 3. The device of any one of claims 1 or 2, wherein the minimum thickness of the intermediate portion is less than one-third of the thickness of at least the proximal or distal portion of the wall. [Appendix 6] 6. The device of any one of claims 1-5, wherein the expandable member in the deployed configuration has a cross-sectional shape having a width of less than 40 mm, a height of less than 25 mm, and a side portion having a radius of curvature of less than 15 mm. [Appendix 7] 7. The device of any one of claims 1 to 6, wherein the expandable member in the deployed configuration has a cross-sectional shape with a maximum width between 20 mm and 40 mm. [Appendix 8] 8. The device of any one of claims 1-7, wherein the first electrode is attached to a proximal portion of the expandable member and the second electrode is attached to a distal portion of the expandable member. [Appendix 9] 9. The apparatus of any one of claims 1 to 8, wherein each of the first and second electrodes has an outer diameter of 1 mm to 7 mm, and a length along the longitudinal axis of 1 mm to 15 mm. [Appendix 10] 10. The device of any one of claims 1 to 9, wherein the second electrode has a circular distal end. The specific examples and descriptions herein are exemplary in nature and embodiments may be developed by one of ordinary skill in the art based on the material taught herein without departing from the scope of the invention, which is limited only by the appended claims.

Claims

1. 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 along the longitudinal axis relative to the first shaft; 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 and second electrodes configured to generate an electric field to ablate tissue; and an expandable member disposed between the first electrode and the second electrode, the expandable member 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 expandable member in the deployed configuration configured to engage a wall of a pulmonary vein ostium and direct the electric field generated by the first and second electrodes toward the wall.

2. The inflatable member is a wall, a proximal portion; a distal portion; and 10. The device of claim 1, comprising a wall having an intermediate portion disposed between the proximal and distal portions of the wall, the intermediate portion having a minimum thickness less than the thicknesses of the proximal and distal portions of the wall.

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

4. A shaft having a longitudinal axis and defining an inner lumen; an expandable member disposed near a distal portion of the shaft, the expandable member configured to transition between an undeployed configuration and a deployed configuration, the expandable member including 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 the thicknesses of the proximal and distal portions of the wall; first and second electrodes disposed on opposite sides of the expandable member along the longitudinal axis, the first and second electrodes configured to generate an electric field to ablate tissue.

5. The device described in claim 4, wherein the expandable member in the expanded configuration is configured to engage with a wall of a pulmonary vein ostium, and wherein the expandable member is formed from an insulating material such that the expandable member in the expanded configuration directs the electric field generated by the first and second electrodes toward the wall of the pulmonary vein ostium.

6. A device described in any one of claims 1 to 5, wherein the expandable member in the deployed configuration includes at least a proximal or distal portion angled at more than about 45 degrees relative to the longitudinal axis.

7. A device as described in claim 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 or distal portion of the wall.

8. A device described in any one of claims 2 to 5 or 7, wherein the ratio of the length of the proximal portion to the length of the intermediate portion, and the ratio of the length of the distal portion to the length of the intermediate portion, are greater than approximately 3.

9. An apparatus as described in any one of claims 1 to 8, wherein the inflatable member in the expanded configuration has a cross-sectional shape having a width of less than about 40 mm, a height of less than about 25 mm, and side portions with a radius of curvature of less than about 15 mm.

10. A device as described in any one of claims 1 to 9, wherein the inflatable member in the deployed configuration has a cross-sectional shape with a maximum width of about 20 mm to about 40 mm.

11. A device described in any one of claims 1 to 10, wherein the first electrode is attached to a proximal portion of the expandable member and the second electrode is attached to a distal portion of the expandable member.

12. A device described in any one of claims 1 to 11, wherein each of the first and second electrodes has an outer diameter of about 1 mm to 7 mm and a length along the longitudinal axis of about 1 mm to about 15 mm.

13. An apparatus as described in any one of claims 1 to 12, wherein the second electrode has a circular distal end.

14. A device described in any one of claims 2 to 5 or 7, wherein the length of each of the proximal and distal portions of the expandable member along the longitudinal axis is greater than the length of the intermediate portion along the longitudinal axis.

15. An apparatus as described in any one of claims 1 to 14, wherein the expandable member is fluidly connected to an injection device, and the expandable member is configured to transition from the undeployed configuration to the deployed configuration in response to injection of fluid from the injection device.

16. The device described in claim 15, wherein the fluid injection is delivered at an injection pressure of about 2 psi to about 20 psi.

17. A signal generator configured to generate a pulse waveform; an ablation device coupled to the signal generator, the ablation device comprising: first and second electrodes configured to receive the pulse waveform and generate an electric field for ablation; and and an ablation device including an expandable member formed from an insulating material and disposed between the first electrode and the second electrode, the expandable member configured to transition between an undeployed configuration in which the expandable member may be advanced into a pulmonary vein ostium and a deployed configuration in which the expandable member may engage a wall of the pulmonary vein ostium, the expandable member in the deployed configuration being configured to direct the electric field toward the wall.

18. The ablation device, a first shaft having a longitudinal axis and defining a lumen; 18. The system of claim 17, further comprising: a second shaft extending through the lumen, the second shaft being movable relative to the first shaft to move proximal and distal ends of the expandable member along the longitudinal axis toward one another to transition the expandable member from the undeployed configuration to the deployed configuration.

19. The system described in claim 18, further comprising a handle connected to a proximal portion of the ablation device, the handle including a mechanism configured to move the second shaft relative to the first shaft.

20. The system described in claim 19, wherein the handle further includes a locking mechanism configured to lock the position of the second shaft relative to the first shaft to maintain the expandable member in the deployed configuration.

21. A system described in any one of claims 17 to 20, further comprising an injection device configured to pressurize the expandable member to transition the expandable member from the undeployed configuration to the deployed configuration.

22. A system described in any one of claims 17 to 21, wherein the expandable member in the deployed configuration has a cross-sectional shape having a width of less than about 40 mm, a height of less than about 25 mm, and side portions with a radius of curvature of less than about 15 mm.

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