Systems, devices and methods for delivering pulsed electric field ablation energy to endocardial tissue - Patents.com

Abstract

To provide systems, devices, and methods for electroporation ablation therapy.SOLUTION: The device includes a set of splines (3630) coupled to a catheter for medical ablation therapy. Each spline of the set of splines may include a set of electrodes (3640) formed on that spline. The set of splines may be configured for translation to transition between a first configuration and a second configuration. Each spline of the set of splines in the second configuration may have a petal-shape.SELECTED DRAWING: Figure 36C

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation-in-part of U.S. patent application Ser. No. 15 / 874,721, filed Jan. 18, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION," which claims the benefit of U.S. Provisional Application Ser. No. 62 / 529,268, filed Jul. 6, 2017, entitled "SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION." This application is also a continuation-in-part of PCT Application No. PCT / US2017 / 012099, filed on September 21, 2017, entitled "SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE," which was filed on January 4, 2017, and claims priority to U.S. Provisional Application No. 62 / 274,943, filed on January 5, 2016, and entitled "SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE." This application claims priority to U.S. patent application Ser. No. 15 / 711,266, entitled "SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE," which in turn claims priority to U.S. provisional application Ser. No. 62 / 491,910, filed April 28, 2017, entitled "SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE," and U.S. provisional application Ser. No. 62 / 529,268, filed July 6, 2017, entitled "SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION." The entire disclosures of each of the foregoing applications are incorporated by reference in their entirety. [Background technology]

[0002] While the generation of pulsed electric fields for tissue treatment has moved from laboratory to clinical applications over the past 20 years, the effects of brief pulses of high voltage and large electric fields on tissue have been investigated for over 40 years. The application of short-duration, high DC voltages to tissue generates localized high electric fields, typically in the range of several hundred volts per centimeter, which disrupt cell membranes by creating pores in the membrane. While the exact mechanism of this electrically driven pore generation, or electroporation, continues to be studied, it is believed that the application of relatively short, large electric fields causes instability in the lipid bilayer of the cell membrane, resulting in the appearance of a distribution of localized gaps or pores in the membrane. This electroporation can be irreversible if the electric field applied to the membrane is greater than a threshold, resulting in the pores either closing or remaining open, allowing biomolecular materials to be exchanged across the membrane, leading to necrosis and / or apoptosis (cell death). The surrounding tissue may then spontaneously heal.

[0003] Although pulsed DC voltage can drive electroporation under the proper conditions, there remains an unmet need for a thin, flexible, non-invasive device that selectively and effectively delivers high DC voltage electroporation ablation therapy to endocardial tissue in the desired region while minimizing damage to healthy tissue. Summary of the Invention

[0004] Described herein are systems, devices, and methods for ablating tissue by irreversible electroporation.

[0005] The device may include a first catheter defining a longitudinal axis and a lumen therethrough. A second catheter may extend from the distal end of the first catheter lumen. A set of splines may have a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter. Each spline may include a set of independently addressable electrodes formed on a surface of each spline. Each electrode may have an associated insulated conductor. The insulated conductor may be disposed in the body of each of the spline sets. The second catheter may be configured to translate along the longitudinal axis to transition between a first configuration and a second configuration. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, at least a portion of each spline of the spline set may extend distally relative to the distal end of the second catheter.

[0006] In some embodiments, the device may include a first catheter defining a longitudinal axis and a lumen therethrough. A second catheter may extend from the distal end of the first catheter lumen. A set of splines may have a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter. Each spline may include a set of independently addressable electrodes formed on a surface of each spline. An insulated conductor is associated with each electrode. The insulated conductor may be disposed in the body of each of the spline sets. The second catheter may be configured to translate along the longitudinal axis to transition between a first configuration and a second configuration. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, each spline of the spline set may have a longitudinal axis in a second configuration that is at an angle of less than about 80 degrees relative to the longitudinal axis of the first catheter.

[0007] In some embodiments, the device may include a first catheter defining a longitudinal axis and a lumen therethrough. A second catheter may extend from the distal end of the first catheter lumen. A set of splines may have a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter. Each spline may include a set of independently addressable electrodes formed on a surface of each spline. Each electrode may have an associated insulated conductor. The insulated conductor may be disposed in the body of each of the spline sets. The second catheter may be configured to translate along the longitudinal axis to transition between the first and second configurations. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, each spline of the spline set may form a loop and be twisted along its length, resulting in the spline having torsion along its length.

[0008] In some embodiments, each spline in the set of splines is represented by the following equation:

number

number

[0009] In some embodiments, the system may include a signal generator configured to generate a pulse waveform. The ablation device is coupled to the signal generator and configured to receive the pulse waveform. The ablation device may include a first catheter defining a longitudinal axis and a lumen therethrough. The second catheter may extend from the distal end of the first catheter lumen. A handle may be coupled to the second catheter. The set of splines may have a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter. Each spline may include a set of independently addressable electrodes formed on a surface of each of the splines. Each electrode may have an associated insulated conductor. The insulated conductor may be disposed in a body of each of the set of splines. The second catheter may be configured to translate along the longitudinal axis to transition between a first configuration and a second configuration. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, at least a portion of each spline of the set of splines may extend distally relative to the distal end of the second catheter.

[0010] In some embodiments, in the second configuration, at least one electrode of each spline of the set of splines may be distal to the distal end of the second catheter. In some embodiments, a proximal portion of the set of splines may be coupled to the first catheter within a first catheter lumen. In some embodiments, the second catheter may define a lumen therethrough, and a distal portion of the set of splines may be coupled to the second catheter within a second catheter lumen. In some embodiments, in the second configuration, each spline of the set of splines may not overlap with an adjacent spline.

[0011] In some embodiments, the set of splines may be deflected radially outward from the longitudinal axis in the second configuration. In some embodiments, the set of splines may be biased away from the longitudinal axis in the second configuration. In some embodiments, an actuator may be coupled to the set of splines and the distal cap. The actuator may be configured to transition the set of splines between the first configuration and the second configuration. In some embodiments, the sets of electrodes on adjacent splines may have opposite polarities. In some embodiments, the set of splines may form a shape having an effective cross-sectional diameter at its largest portion between about 10 mm and about 35 mm when deployed in the second configuration. In some embodiments, the set of splines may include between 3 splines and 14 splines. In some embodiments, each spline in the set of splines may have a diameter between about 1 mm and about 5 mm. In some embodiments, each electrode in the set of electrodes may have a diameter between about 1 mm and about 5 mm.

[0012] In some embodiments, the insulated conductor may be disposed in the body of the second catheter. The insulated conductor may be configured to maintain a potential of at least about 700 V without breakdown of its corresponding insulation. In some embodiments, a pulse waveform comprising a first level of the hierarchy of pulse waveforms may comprise a first set of pulses, each pulse having a pulse duration, with a first time interval separating successive pulses. A second level of the hierarchy of pulse waveforms may comprise a first set of multiple pulses as the second set of pulses, with a second pulse interval separating successive first set of pulses, with the second time interval being at least three times the duration of the first time interval. A third level of the hierarchy of pulse waveforms may comprise a second set of multiple pulses as the third set of pulses, with a third time interval separating successive second set of pulses, with the third time interval being at least 30 times the duration of the time intervals of the second level.

[0013] In some embodiments, a method for treating cardiac arrhythmia with irreversible electroporation may include advancing an ablation device into a patient's left atrium and transitioning the ablation device from a first configuration to a second configuration. The ablation device includes a first catheter defining a longitudinal axis and a lumen therethrough, a second catheter extending from a distal end of the first catheter lumen, and a second catheter extending from a distal end of the first catheter lumen.

[0014] and a set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline including a set of independently addressable electrodes formed on a surface of each spline, each electrode associated with an insulated conductor disposed in a body of each of the set of splines. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, at least a portion of each spline of the set of splines extends distally relative to the distal end of the second catheter. These steps may further include generating a set of pulse waveforms and delivering the set of pulse waveforms to a set of adjacent portions of the posterior wall of the left atrium via one or more splines of the set of splines of the ablation device in the second configuration to form a set of ablation zones.

[0015] In some embodiments, in the second configuration, the set of splines may form a loop and be twisted along its length, resulting in the splines having torsion along their length. In some embodiments, in the second configuration, each spline of the set of splines may have a longitudinal axis in the second configuration that is at an angle of less than about 80 degrees relative to the longitudinal axis of the first catheter. In some embodiments, each spline of the set of splines may be configured to satisfy the equation

number

number

[0016] In some embodiments, at least a portion of the set of splines may be advanced distally relative to the distal end of the second catheter by retracting the second catheter relative to the first catheter. In some embodiments, each insulated conductor may be configured to maintain a potential of at least about 700 V without its corresponding insulation breaking down.

[0017] In some embodiments, the set of splines may include a group of electrodes, and the group of electrodes may include a set of electrodes for each spline in the set of splines. The method may further include configuring a first electrode of the group of electrodes as an anode, configuring a second electrode of the group of electrodes as a cathode, and delivering a pulsed waveform to the first electrode and the second electrode.

[0018] In some embodiments, a first set of electrodes on a first spline of the set of splines may be configured as an anode and a second set of electrodes on a second spline of the set of splines may be configured as a cathode, and a pulse waveform may be delivered to the first set of electrodes and the second set of electrodes. [Brief explanation of the drawings]

[0019] [Figure 1] FIG. 1 is a block diagram of an electroporation system, according to an embodiment. [Figure 2] 1 is a perspective view of an ablation catheter, according to an embodiment. [Figure 3] FIG. 1 is a perspective view of an ablation catheter according to another embodiment. [Figure 4] FIG. 1 is a perspective view of an ablation catheter according to another embodiment. [Figure 5] FIG. 10 is a detailed perspective view of a distal portion of an ablation catheter according to another embodiment. [Figure 6] FIG. 10 is a side view of an ablation catheter according to another embodiment. [Figure 7] FIG. 10 is a side view of an ablation catheter according to another embodiment. [Figure 8A] 8A and 8B are side views of an ablation catheter according to another embodiment. [Figure 8B] 8A and 8B are front cross-sectional views of an ablation catheter according to another embodiment. [Figure 9A] FIG. 1B is a side view of an ablation catheter in a first configuration, according to another embodiment. [Figure 9B] FIG. 10 is a side view of an ablation catheter in a second expanded configuration, according to another embodiment. [Figure 9C] FIG. 10 is a side view of an ablation catheter in a third expanded configuration, according to another embodiment. [Figure 9D] FIG. 10 is a side view of an ablation catheter in a fourth expanded configuration, according to another embodiment. [Figure 9E] FIG. 10 is a side view of an ablation catheter in a fifth expanded configuration, according to another embodiment. [Figure 10] FIG. 1 is a perspective view of a balloon ablation catheter disposed in the left atrial cavity of the heart, according to another embodiment. [Figure 11] 1 is a cross-sectional view of a balloon ablation catheter disposed in the left atrial cavity of the heart, according to another embodiment. [Figure 12A] 12A and 12B are schematic diagrams of a return electrode of an ablation system, according to an embodiment. [Figure 12B]12A and 12B are schematic diagrams of a return electrode of an ablation system, according to an embodiment. [Figure 13] 1 illustrates a method of tissue ablation, according to an embodiment. [Figure 14] 1 illustrates a method of tissue ablation, according to an embodiment. [Figure 15] 3 is a diagrammatic illustration of the ablation catheter shown in FIG. 2 positioned in the left atrial chamber of the heart. [Figure 16] 4 is a diagrammatic illustration of the ablation catheter shown in FIG. 3 positioned in the left atrial chamber of the heart. [Figure 17] 5 is an illustration of two of the ablation catheters shown in FIG. 4 positioned in the left atrial chamber of the heart. [Figure 18] 6 is a diagrammatic illustration of the ablation catheter shown in FIG. 5 positioned in the left atrial chamber of the heart. [Figure 19A] 19A is a schematic perspective view of a set of electrodes disposed at the ostium of a pulmonary vein according to another embodiment. [Figure 19B] 19A and 19B are cross-sectional views illustrating a set of electrodes disposed at the ostium of a pulmonary vein according to another embodiment. [Figure 20A] 20A is a schematic perspective view illustrating an electric field generated by electrodes disposed at the ostium of a pulmonary vein, according to another embodiment. [Figure 20B] 20A and 20B are cross-sectional views illustrating an electric field generated by electrodes placed at the ostium of a pulmonary vein, according to another embodiment. [Figure 21] 1 is an exemplary waveform illustrating a series of voltage pulses with a defined pulse width for each pulse, according to an embodiment. [Figure 22] 10A-10C illustrate a schematic representation of a hierarchy of pulses showing pulse widths, spacing between pulses, and pulse groupings, according to an embodiment. [Figure 23] 1 provides a schematic diagram of a nested hierarchy of monophasic pulses showing different levels of nested hierarchy, according to an embodiment. [Figure 24]FIG. 1B is a schematic diagram of a nested hierarchy of biphasic pulses showing different levels of nested hierarchy, according to an embodiment. [Figure 25] 1A-1C are schematic illustrations of electrocardiogram and cardiac pacing signal time series along with atrial and ventricular refractory periods illustrating the time sequence of irreversible electroporation ablation, according to an embodiment; [Figure 26A] FIG. 1 is a perspective view of an ablation catheter according to another embodiment. [Figure 26B] FIG. 26B is a side view of the ablation catheter shown in FIG. 26A positioned in the left atrial cavity of the heart adjacent the pulmonary ostium. [Figure 26C] FIG. 26C is a top view of a simulation of the ablation catheter illustrated in FIG. 26B showing selective electrode actuation, according to an embodiment. [Figure 26D] 1 is an illustration of a simulation of tissue ablation at a lung ostium, according to an embodiment. [Figure 27A] 27A and 27B are side views of an ablation catheter in a second configuration, according to another embodiment. [Figure 27B] 27A and 27B are side views of an ablation catheter in a second configuration, according to another embodiment. [Figure 27C] 27A-27C are side views of an ablation catheter in accordance with another embodiment; [Figure 28] FIG. 10 is a side view of an ablation catheter according to another embodiment. [Figure 29A] 29A is a cross-sectional side view of an ablation catheter in a first configuration, according to another embodiment. [Figure 29B] 29A and 29B are cross-sectional views of an ablation catheter according to another embodiment. [Figure 29C]29A and 29B are cross-sectional views of an ablation catheter according to another embodiment.FIGS. 29C and 29D are another longitudinal side cross-sectional view of the ablation catheter in a third configuration. [Figure 29D] 29A and 29B are cross-sectional views of an ablation catheter according to another embodiment.FIGS. 29C and 29D are cross-sectional side views of an ablation catheter in a third configuration. [Figure 30] FIG. 10 is a side view of an ablation catheter according to another embodiment. [Figure 31A] 31A is a perspective view of an ablation catheter in a first configuration, according to another embodiment; [Figure 31B] 31A and 31B are perspective views of an ablation catheter in a second configuration, according to another embodiment. [Figure 32] 1 is a schematic cross-sectional view of an ablation catheter according to another embodiment. [Figure 33A] 33A is a perspective view of an ablation catheter according to another embodiment. [Figure 33B] Figure 33B is an illustration of an ablation catheter according to another embodiment. Figure 33B is a front view of the ablation catheter of Figure 33A. [Figure 33C] Figure 33C is an illustration of an ablation catheter according to another embodiment. Figure 33C is a cutaway perspective view of the splines of the ablation catheter of Figure 33A. [Figure 33D] Figure 33D is an illustration of an ablation catheter according to another embodiment. Figure 33A is a cross-sectional view of the splines of the ablation catheter of Figure 33A. [Figure 33E] Figure 33E is an illustration of an ablation catheter according to another embodiment. Figure 33E is a perspective view of the ablation catheter of Figure 33A positioned adjacent to tissue. [Figure 34A] 34A is a side view of a spline according to another embodiment, with a unit tangent vector . [Figure 34B] 34A and 34B are side views of a spline according to another embodiment, with two unit tangent vectors. [Figure 35] FIG. 10 is a side view of an ablation catheter according to another embodiment. [Figure 36A] 36A is a side view of an ablation catheter in a second configuration, according to another embodiment. [Figure 36B] 36A and 36B are side views of an ablation catheter according to another embodiment. [Figure 36C] 36A and 36B are side views of an ablation catheter according to another embodiment; [Figure 37A] 37A is a perspective view of an ablation catheter and the left atrium.FIG. 37A is a perspective view of an ablation catheter positioned in the left atrium. [Figure 37B] Figure 37A is a perspective view of the ablation catheter and the left atrium after tissue ablation. DETAILED DESCRIPTION OF THE INVENTION

[0020] Described herein are systems, devices, and methods for the selective and rapid application of pulsed electric fields to ablate tissue through irreversible electroporation. Generally, the systems, devices, and methods described herein can be used to generate high electric field strength in a desired targeted region and reduce peak electric field values ​​elsewhere to reduce unnecessary tissue damage and electrical arcing. The irreversible electroporation systems described herein may include a signal generator and processor configured to apply one or more voltage pulse waveforms to a selected set of electrodes of an ablation device to deliver energy to a targeted region (e.g., ablation energy for a set of tissue at the ostium of a pulmonary vein). The pulse waveforms disclosed herein can assist in the therapeutic treatment of various cardiac arrhythmias (e.g., atrial fibrillation). To deliver the pulse waveforms generated by the signal generator, one or more electrodes of the ablation device may have insulated conductors configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. The electrodes may be independently addressable, allowing each electrode to be controlled (e.g., deliver energy) independently of any other electrode of the device. In this way, the electrodes can synergistically deliver different energy waveforms at different times for electroporation of tissue.

[0021] As used herein, the term "electroporation" refers to the application of an electric field to a cell membrane, causing a change in 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, causing a temporary change in the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing reversible electroporation may undergo the temporary and / or intermittent formation of one or more pores in the 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, causing a permanent change in the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing irreversible electroporation may undergo the formation of one or more pores in the cell membrane that persist upon removal of the electric field.

[0022] The pulse waveforms for electroporation energy delivery disclosed herein may enhance the safety, efficiency, and effectiveness of energy delivery to tissue by lowering the electric field threshold associated with irreversible electroporation, resulting in more effective ablation lesions with reduced total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein may be hierarchical and nested. For example, the pulse waveforms may include hierarchical groupings of pulses with 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, entitled "SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE," the contents of which are incorporated herein by reference in their entirety.

[0023] In some embodiments, the system may further include a cardiac stimulator used to synchronize pulse waveform generation to the paced heartbeat. The cardiac stimulator may electrically pace the heart to ensure pacing capture and 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 disruption of the cardiac sinus rhythm. In some embodiments, the ablation device may include one or more catheters, guidewires, balloons, and electrodes. The ablation device may transition to different configurations (e.g., compact and expanded) to position the device within the cardiac cavity. In some embodiments, the system may optionally include one or more return electrodes.

[0024] Generally, to ablate tissue, one or more catheters may be minimally invasively advanced through the vasculature to the target site. In cardiac applications, the electrodes to which the voltage pulse waveform is delivered may be disposed on an epicardial or endocardial device. The methods described herein may include introducing a device into a cardiac chamber in the left atrium of the heart and positioning the device in contact with a pulmonary vein ostium. The pulse waveform may be generated and delivered to one or more electrodes of the device to ablate tissue. In some embodiments, the pulse waveform may be generated synchronously with a cardiac pacing signal to avoid disruption of the cardiac sinus rhythm. In some embodiments, the electrodes may be configured in an anode-cathode subset. The pulse waveform may include a hierarchical waveform to assist tissue ablation and reduce damage to healthy tissue.

[0025] I. System overview Disclosed herein are systems and devices configured for tissue ablation via the selective and rapid application of a voltage pulse waveform to assist tissue ablation, resulting in irreversible electroporation. Generally, the tissue ablation systems described herein may include a signal generator and an ablation device having one or more electrodes for selective and rapid application of a DC voltage to drive electroporation. As described herein, the systems and devices may be deployed epicardially and / or endocardially to treat atrial fibrillation. A voltage may be applied to a selected subset of electrodes, with independent subset selection for anode and cathode electrode selection. A pacing signal for cardiac stimulation may be generated, which may be used to generate a pulse waveform by a signal generator synchronized with the pacing signal.

[0026] Generally, the systems and devices described herein include one or more catheters configured to ablate tissue in the left atrial chamber of the heart. 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 optionally be coupled to an ablation device (110), as well as a pacing device (130) and / or an optional return electrode (140) (e.g., a return pad, shown here in dotted lines).

[0027] The signal generator (122) may be configured to generate a pulse waveform for irreversible electroporation of tissue, such as the ostium of a pulmonary vein. For example, the signal generator (122) may be a voltage pulse waveform generator and deliver the pulse waveform to the ablation device (110). A return electrode (140) may be coupled to the patient (e.g., disposed on the patient's back) to allow current to flow from the ablation device (110) through the patient to the return electrode (140), providing a safe current return path (not shown) from the patient. The processor (124) may incorporate data received from the memory (126), the cardiac stimulator (128), and the pacing device (130) to determine parameters (e.g., amplitude, width, duty cycle, etc.) of the pulse waveform generated by the signal generator (122). 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 configured to receive and / or deliver pulsed waveforms, as described in more detail below. For example, the ablation device (110) may be introduced into a cardiac cavity in the left atrium and positioned to align one or more electrodes (112) with the ostia of one or more pulmonary veins, after which the pulsed waveforms are delivered to ablate tissue. The ablation device (110) may include one or more electrodes (112), which in some embodiments may be a set of independently addressable electrodes. Each electrode may include an insulated conductor configured to maintain a potential of at least about 700 V without corresponding insulation breakdown. In some embodiments, the insulation of each conductor may maintain a potential difference of about 200 V to about 1,500 V across its thickness without breakdown. For example, the electrodes (112) may be grouped into one or more anode-cathode subsets, such as a subset including one anode and one cathode, a subset including two anodes and two cathodes, a subset including two anodes and one cathode, a subset including one anode and two cathodes, a subset including three anodes and one cathode, or a subset including three anodes and two cathodes.

[0029] The pacing device (130) may be suitably coupled to the patient (not shown) and configured to receive cardiac pacing signals generated by the cardiac stimulator (128) of the apparatus (120) for cardiac stimulation. A representation of the pacing signal may be transmitted by the cardiac stimulator (128) to the signal generator (122). Based on the pacing signal, a representation of a voltage pulse waveform may be selected, calculated, and / or otherwise identified by the processor (124) and generated by the signal generator (122). In some embodiments, the signal generator (122) is configured to generate the pulse waveform synchronously with the representation of the pacing signal (e.g., within a common refractory window). For example, in some embodiments, the common refractory window begins substantially immediately (or after a very small delay) after the ventricular pacing signal and lasts for a period of approximately 250 milliseconds or less thereafter. In such embodiments, the entire pulse waveform may be delivered within this period.

[0030] The processor (124) may be any suitable processing device configured to implement 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 implement 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, such as 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, etc.

[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), 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 communicate with other devices (not shown), for example, via one or more networks, each of which may be any type of network. A wireless network refers to any type of digital network that is not connected by any type of cable. However, wireless networks may connect to wired networks to connect to the Internet, other carrier voice and data networks, business networks, and personal networks. Wired networks are typically carried by copper twisted pair, coaxial cable, or fiber optic cable. There are various 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, and virtual private networks (VPNs). Hereinafter, a network refers to any combination of combined wireless, wired, public, and private data networks, typically interconnected via the Internet, to provide integrated networking and information access solutions.

[0033] Ablation devices The systems described herein may include one or more multi-electrode ablation devices configured to ablate tissue in the left atrial chamber of the heart to treat atrial fibrillation. Figure 2 is a perspective view of an ablation device (200) (e.g., structurally and / or functionally similar to the ablation device (110)) including a catheter (210) and a guidewire (220) slidable within the lumen of the catheter (210). The guidewire (220) may include a nonlinear distal portion (222), and the catheter (210) may be configured to be disposed over the guidewire (220) during use. The distal portion (222) of the guidewire (220) may be shaped to aid in placement of the catheter (210) in a patient's lumen. For example, the shape of the distal portion (222) of the guidewire (220) may be configured to be positioned at and / or near the ostium of a pulmonary vein, as described in more detail in Figure 15. The distal portion (222) of the guidewire (220) may include and / or be formed with an atraumatic shape that reduces trauma to tissue (e.g., prevents and / or reduces the possibility of tissue puncture). For example, the distal portion (222) of the guidewire (220) may include a nonlinear shape, such as a circle, a loop (as shown in FIG. 2), an ellipsoid, or any other geometric shape. In some embodiments, the guidewire (220) may be configured to be elastic such that a guidewire having a nonlinear shape conforms to the lumen of the catheter (210) when disposed in the catheter (210) and reforms or regains its nonlinear shape as it advances out of the catheter (210). In other embodiments, the catheter (210) may similarly be configured to be elastic, such as to aid in the advancement of the catheter (210) through a sheath (not shown). The distal portion (222) of the shaped guidewire (220) may be angled relative to the other portions of the guidewire (220) and the catheter (210). The catheter (210) and guidewire (220) may be sized for advancement into a cardiac cavity (e.g., the left atrium).The diameter of the distal portion (222) of the shaped guidewire (220) may be approximately the same as the diameter of the lumen in which the catheter (230) will be disposed.

[0034] The catheter (210) may be slidably advanced over the guidewire (220) so that it is disposed over the guidewire (220) during use. A distal portion (222) of the guidewire (220) disposed in the lumen (e.g., near the ostium of a pulmonary vein) may act as a backstop against the advancement of the distal portion of the catheter (210). The distal portion of the catheter (210) may include a set of electrodes (212) (e.g., structurally and / or functionally similar to the electrode(s) (112)) configured to contact the inner radial surface of the lumen (e.g., the ostium of a pulmonary vein). For example, the electrodes (212) may include a generally circular array of electrodes configured to contact the ostium of a pulmonary vein. As shown in FIG. 2, one or more electrodes (212) may include a series of metal bands or rings disposed along the catheter shaft and electrically connected together. For example, the ablation device (200) may include a single electrode with multiple bands, one or more electrodes, each with its own band, and combinations thereof. In some embodiments, the electrode (212) may be shaped to match the shape of the distal portion (222) of the guidewire (220). The catheter shaft may include flexible sections between the electrodes to enhance flexibility. In other embodiments, one or more of the electrodes (212) may include a helical winding to enhance flexibility.

[0035] Each of the electrodes of the ablation devices discussed herein may be connected to an insulated lead (not shown) that leads to a handle (not shown) coupled to the proximal portion of the catheter. The insulation of each lead may maintain a potential difference of at least 700 V across its thickness without breakdown. In other embodiments, the insulation of each lead may maintain a potential difference of between about 200 V and about 2000 V, including all values ​​and subranges therebetween, across its thickness without breakdown. This allows the electrodes to efficiently deliver electrical energy and ablate tissue via irreversible electroporation. The electrodes may receive a pulsed waveform, for example, generated by a signal generator (122), as discussed above with respect to FIG. 1. In other embodiments, the guidewire (220) may be separate from the ablation device (200) (e.g., the ablation device (200) includes a catheter (210) but not a guidewire (220)). For example, guidewire (220) may be advanced by itself into the heart cavity, and catheter (210) may then be advanced over guidewire (220) into the heart cavity.

[0036] FIG. 3 is a perspective view of another embodiment of an ablation device (300) (e.g., structurally and / or functionally similar to the ablation device (110)) including a catheter (310) with a set of electrodes (314) disposed along a distal portion (312) of the catheter (310). The distal portion (312) of the catheter (310) may be nonlinear and form a generally circular shape. The set of electrodes (314) may be disposed along the nonlinear distal portion (312) of the catheter (310) and may form a generally circular array of electrodes (314). In use, the electrodes (314) may be disposed at the ostium of a pulmonary vein to deliver a pulsed waveform to ablate tissue, as described in more detail with respect to FIG. 16 . The distal portion (312) of the shaped catheter (310) may be angled relative to other locations on the catheter (310). For example, the distal portion (312) of the catheter (310) may be approximately perpendicular to the adjacent portion of the catheter (310). In some embodiments, a handle (not shown) may be coupled to the proximal portion of the catheter (310) and may include a bending mechanism (e.g., one or more pull wires (not shown)) configured to alter the shape of the distal portion (312) of the catheter (310). For example, manipulation of the pull wires of the handle may increase or decrease the circumference of the circular shape of the distal portion (312) of the catheter (310). The diameter of the distal portion (312) of the catheter (310) may be altered to allow the electrode (314) to be positioned near and / or in contact with the pulmonary vein ostium (e.g., in contact with the inner radial surface of the pulmonary vein). The electrode (314) may include a series of metal bands or rings and may be independently addressable.

[0037] In some embodiments, the pulse waveforms may be applied between electrodes (314) configured in anode-cathode sets. For example, adjacent or approximately diametrically opposed electrode pairs may operate together as an anode-cathode set. It should be understood that any of the pulse waveforms disclosed herein may be applied incrementally or sequentially to a sequence of anode-cathode electrodes.

[0038] FIG. 4 is a perspective view of yet another embodiment of an ablation device (400) (e.g., structurally and / or functionally similar to ablation device (110)) including a catheter (410) and a guidewire (420) having a shaped, nonlinear distal portion (422). The guidewire (420) may be slidable within the lumen of the catheter (410). The guidewire (420) may be advanced through the lumen of the catheter (410), and the distal portion (422) of the guidewire (420) may be generally circular in shape. The shape and / or diameter of the distal portion (422) of the guidewire (420) may be altered using a bending mechanism, as described above with respect to FIG. 3. The catheter (410) may be flexible so as to be bent. In some embodiments, the catheter (410) and / or guidewire (420) may be configured to be elastic so as to conform to the lumen in which they are disposed and assume a secondary shape as they advance out of the lumen. By altering the size of the guidewire 420 and manipulating the deflection of the catheter 410, the distal portion 422 of the guidewire 420 can be positioned at a target tissue site, such as the ostium of a pulmonary vein. The distal end 412 of the catheter 410 can be sealed except where the guidewire 420 begins to extend, such that the catheter 410 can electrically insulate the portion of the guidewire 420 that is within the lumen of the catheter 410. For example, in some embodiments, the distal end 412 of the catheter 410 can include a seal having an opening that allows the guidewire 420 to pass therethrough and forms a compressive hold (which may be fluid-tight) between the seal and the guidewire 420 upon application of force.

[0039] In some embodiments, the exposed distal portion (422) of the guidewire (420) may be coupled to an electrode and configured to receive a pulse waveform from a signal generator and deliver the pulse waveform to tissue during use. For example, the proximal end of the guidewire (420) may be coupled to a suitable lead and connected to the signal generator (122) of FIG. 1. The distal portion (422) of the guidewire (420) may be sized to be positioned at the ostium of a pulmonary vein. For example, the diameter of the distal portion (422) of the shaped guidewire (420) may be approximately the same as the diameter of the ostium of a pulmonary vein. The distal portion (422) of the shaped guidewire (420) may be angled relative to the rest of the guidewire (420) and catheter (410).

[0040] The guidewire (420) may comprise stainless steel, nitinol, platinum, or other suitable biocompatible materials. In some embodiments, the distal portion (422) of the guidewire (420) may include a platinum coil physically and electrically coupled to the guidewire (420). The platinum coil may be an electrode configured for delivery of a voltage pulse waveform. Platinum is radiopaque, and its use may increase flexibility and aid in the advancement and positioning of the ablation device (400) within the cardiac cavity.

[0041] Figure 5 is a detailed perspective view of a flower-shaped distal portion of an ablation device (500) (e.g., structurally and / or functionally similar to ablation device (110)) that includes a set of electrodes (520, 522, 524, 526) each extending from a pair of insulated lead segments (510, 512, 514, 516). Each pair of adjacent insulated lead segments coupled to an uninsulated electrode (e.g., lead segments (510, 512) and electrode (526)) forms a loop (Figure 5 shows a set of four loops). The set of loops at the distal end of ablation device (500) may be configured to deliver a pulsed waveform to tissue. The ablation device (500) may include a set of insulated conductor segments (510, 512, 514, 516) that branch at the distal end of the device (500) and connect to respective exposed electrodes (520, 522, 524, 526), ​​as shown in FIG. 5. The electrodes (520, 522, 524, 526) may include exposed portions of electrical conductors. In some embodiments, one or more of the electrodes (520, 522, 524, 526) may include platinum coils. One or more of the segments (510, 512, 514, 516) may be coupled to a bending mechanism (e.g., struts, pull wires, etc.) controlled from a handle (not shown) to control the size and / or shape of the distal portion of the device (500).

[0042] The electrodes (520, 522, 524, 526) may be flexible and form a compact first configuration for advancement into a cardiac cavity, such as adjacent the ostium of a pulmonary vein. Once positioned at a desired location, the electrodes (520, 522, 524, 526) may transition to an expanded second configuration to form a flower-shaped distal portion as they are advanced out of a lumen, such as a sheath, as shown in FIG. 5. In other embodiments, the insulated lead segments (510, 512, 514, 516) and electrodes (520, 522, 524, 526) are biased to expand outward (e.g., spring open) into the second configuration as they are advanced out of a lumen (e.g., a sheath) to carry the device (500). The electrodes (520, 522, 524, 526) may be independently addressable and may each have an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its thickness without breakdown.

[0043] In some embodiments, the ablation device (5000) may be configured to deliver a pulsed waveform to tissue during use via a set of electrodes (520, 522, 524, 526). In some embodiments, the pulsed waveform may be applied between electrodes (520, 522, 524, 526) configured as an anode-cathode set. For example, a pair of approximately diametrically opposed electrodes (e.g., electrodes (520, 524) and (522, 526)) may operate together as an anode-cathode pair. In other embodiments, adjacent electrodes may be configured as an anode-cathode pair. By way of example, one electrode (520) of a set of electrodes may be configured as an anode, and a second electrode (522) may be configured as a cathode.

[0044] 6-9E, 26A-27C, and 28 illustrate additional embodiments of ablation devices (e.g., structurally and / or functionally similar to ablation device 110) that may be configured to deliver a voltage pulse waveform using a set of electrodes to ablate tissue and electrically isolate a pulmonary vein. In some of these embodiments, the ablation device may be transitioned from a first configuration to a second configuration such that the electrodes of the ablation device expand outward to contact the lumen of the tissue (e.g., the ostium of the pulmonary vein).

[0045] FIG. 6 is a side view of an embodiment of an ablation device (600) including a catheter shaft (610) at the proximal end of the device (600), a distal cap (612) of the device (600), and a set of splines (614) coupled thereto. The distal cap (612) may include an atraumatic shape to reduce trauma to tissue. The proximal end of the set of splines (614) may be coupled to the distal end of the catheter shaft (610), and the distal end of the set of splines (614) may be tethered to the distal cap (612) of the device (600). The ablation device (600) may be configured to deliver a pulsed waveform to tissue during use via one or more splines of the set of splines (614). As used herein, "spline" and "spine" may be used interchangeably. In some embodiments, the apparatus may include a catheter defining a longitudinal axis.

[0046] Each spline (614) of the ablation device (600) may include one or more interconnected, or in some cases independently addressable, electrodes (616) formed on the surface of the spline (614). Each electrode (616) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its thickness without breakdown. Each spline (614) may include an insulated conductor for each electrode (616) formed in the body of the spline (e.g., within the lumen of the spline (614)). When the electrodes on a single spline are wired together, a single insulated conductor may carry strands connecting different electrodes on the spline. 6 shows a set of splines (614) where each spline (614) includes a pair of electrodes (616) that have approximately the same size, shape, and spacing as the electrodes (616) of the adjacent spline (614). In other embodiments, the size, shape, and spacing of the electrodes (616) may be different.

[0047] For each of the ablation devices described herein, and particularly for the ablation devices depicted in Figures 6-9E, 26A-27C, and 28, each spline of a spline set may include a flexible curvature. The minimum radius of curvature of the splines may range from about 1 cm or greater. For example, the spline set may form a delivery assembly at the distal portion of the ablation device and may be configured to transition between a first configuration in which the spline set is deflected radially outward from the longitudinal axis of the ablation device and a second configuration in which the spline set is aligned generally parallel to the longitudinal axis of the ablation device. In this manner, the splines may more easily conform to the geometry of the cardiac cavity. In general, the "basket" of splines may have an asymmetric shape along the length of the shaft, such that one end of the basket (the hypothetical distal end) is more bulging than the other end of the basket (the hypothetical proximal end). The delivery assembly may be disposed in a first configuration in contact with the pulmonary vein ostium and transition to a second configuration prior to delivery of the pulse waveform. In some of these embodiments, a handle may be coupled to the set of splines, and the handle is configured to actuate a transition of the set of splines between the first and second configurations. In some embodiments, the leads of at least two electrodes of the set of electrodes may be electrically coupled at or near a proximal portion of the ablation device, e.g., within the handle.

[0048] In one embodiment, each of the electrodes (616) on a spline (614) may be configured as an anode, while each of the electrodes (616) on an adjacent spline (614) may be configured as a cathode. In another embodiment, the electrodes (616) on one spline may alternate between anodes and cathodes, while the electrodes on an adjacent spline have the opposite configuration (e.g., cathodes and anodes). The ablation device (600) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (600) may include between 3 and 20 splines. In some embodiments, the ablation device (600) may include between 6 and 12 splines.

[0049] 7 is a side view of another embodiment of an ablation device (700) including a catheter shaft (710) at the proximal end of the device (700), a distal cap (712) of the device (700), and a set of splines (714) coupled thereto. The distal cap (712) may include an atraumatic shape. The proximal end of the set of splines (714) may be coupled to the distal end of the catheter shaft (710), and the distal end of the set of splines (714) may be tethered to the distal cap (712) of the device (700). Each spline (714) of the ablation device (700) may include one or more independently addressable electrodes (716) formed on the surface of the spline (714). Each electrode (716) may include an insulated conductor configured to maintain a potential of at least approximately 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 1500 V across its thickness without breakdown. Each spline (714) may include an insulated conductor for each electrode (716) formed in the body of the spline (714) (e.g., within the lumen of the spline (714)). The spline wires (718, 719) of a set may be electrically conductive and electrically coupled to adjacent electrodes (716) disposed on different splines (714), such as the electrodes (716) between a pair of splines (718, 719) of a spline set. For example, the spline wires (718, 719) may extend transversely to the longitudinal axis of the ablation device (700).

[0050] 7 shows a set of splines (714) in which each spline (714) includes a pair of electrodes (716) having approximately the same size, shape, and spacing as the electrodes (716) of the adjacent spline (714). In other embodiments, the size, shape, and spacing of the electrodes (716) may be different. For example, the electrode (716) electrically coupled to a first spline wire (718) may be a different size and / or shape than the electrode (716') electrically coupled to a second spline wire (719).

[0051] In some embodiments, the first spline wire (718) may include a first set of spline wires (720, 721, 722, 723), where each spline wire in the set of spline wires (720, 721, 722, 723) may couple electrodes (716) between different pairs of splines in the set of splines (714). In some of these embodiments, the set of spline wires (720, 721, 722, 723) may form a continuous loop between the electrodes (716) coupled thereto. Similarly, the second spline wire (719) may include a second set of spline wires (724, 725, 726), where each spline wire in the set of spline wires (724, 725, 726) may couple an electrode (716′) across the set of splines (714). The second set of spline wires (724, 725, 726) may couple different electrodes (716′) across a different set of splines (714) than the first set of spline wires (720, 721, 722, 723). In some of these embodiments, the first set of spline wires (720, 721, 722, 723) may form a first continuous loop between the electrodes (716) coupled thereto, and the second set of spline wires (724, 725, 726) may form a second continuous loop between the electrodes (716′) coupled thereto. The first continuous loop may be electrically isolated from the second continuous loop. In some of these embodiments, the electrode (716) coupled to the first continuous loop may be configured as an anode, and the electrode (716) coupled to the second continuous loop may be configured as a cathode. A pulse waveform may be delivered to the electrodes (716) of the first and second continuous loops. In some embodiments, the spline wires, e.g., 721, 722, 723, etc., can be replaced with similar electrical connections in the proximal portion of the device (e.g., in the device handle). For example, the electrodes 716 can all be electrically wired together in the handle of the device.

[0052] In another embodiment, the first spline wire (721) of the set of spline wires (720, 721, 722, 723) may couple the electrode (716) between the first spline (711) and the second spline (713) of the set of splines (714), and the second spline wire (720) of the set of spline wires (720, 721, 722, 723) may couple the electrode (716) between the first spline (711) and the third spline (715) of the set of splines (714). The electrodes (716) coupled by the first spline wire (721) and the second spline wire (720) may be configured as an anode and a cathode (or vice versa). In yet another embodiment, a first spline wire (721) of the set of spline wires (720, 721, 722, 723) may couple an electrode (716) between a first spline (711) and a second spline (713) of the set of spline wires (714), and a second spline wire (723) of the set of spline wires (720, 721, 722, 723) may couple an electrode (716) between a third spline (715) and a fourth spline (717) of the set of spline wires (714). A pulse waveform may be delivered to the electrode (716) coupled by the first spline wire (721) and the second spline wire (723). In some embodiments, instead of spline wires, the leads of at least two electrodes of the set of electrodes are electrically coupled at or near a proximal portion of the ablation device, such as in the handle.

[0053] In other embodiments, one or more of the spline wires (718, 719) may form a continuous loop between the electrically coupled electrodes (716). For example, the first set of spline wires (718) may form a first continuous loop between the electrodes (716) coupled thereto, and the second set of spline wires (719) may form a second continuous loop between the electrodes (716) coupled thereto. In this case, the first continuous loop may be electrically isolated from the second continuous loop. In one embodiment, each of the electrodes (716) coupled to the first set of spline wires (718) may be configured as an anode, while each of the electrodes (716) coupled to the second set of spline wires (719) may be configured as a cathode. Each group of electrically coupled electrodes (716) may be independently addressable. In some embodiments, instead of spline wires, the leads of at least two of the electrodes of a set of electrodes are electrically coupled at or near a proximal portion of the ablation device, such as in the handle.

[0054] In some embodiments, as discussed in more detail below with respect to Figures 8A-8B, the spline wire may be electrically coupled to a set of electrodes (e.g., two, three, four, five, etc.) without forming a continuous loop. For example, a discontinuous loop may be formed using two spline wires. In other embodiments, the size, shape, and spacing of the electrodes (716) may vary. The ablation device (700) may include any number of splines, e.g., three, four, five, six, seven, eight, nine, ten, twelve, fourteen, sixteen, eighteen, twenty, or more splines. In some embodiments, the ablation device (700) may include between three and twenty splines. For example, in one embodiment, the ablation device (700) may include between six and nine splines.

[0055] 8A and 8B are longitudinal side and front cross-sectional views, respectively, of an ablation catheter (800). FIG. 8A is a side view of an embodiment of an ablation device (800) including a catheter shaft (810) at the proximal end of the device (800), a distal cap (812) of the device (800), and a set of splines (814) coupled thereto. The distal cap (812) may include an atraumatic shape. The proximal end of the set of splines (814) may be coupled to the distal end of the catheter shaft (810), and the distal end of the set of splines (814) may be anchored to the distal cap (812) of the device (800). Each spline (814) of the ablation device (800) may include one or more independently addressable electrodes (816, 818) formed on the surface of the spline (814). Each electrode (816, 818) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its entire thickness, including all values ​​and subranges therebetween. Each spline (814) may include an insulated conductor for each electrode (816, 818) formed in the body of the spline (814) (e.g., within the lumen of the spline (814)). One or more spline wires (817, 819) may be electrically conductive and electrically couple adjacent electrodes (816, 818) disposed on different splines (814). For example, the spline wires (817, 819) may extend transversely to the longitudinal axis of the ablation device (800).

[0056] FIG. 8B is a front cross-sectional view of FIG. 8A taken along line 8B-8B. Each spline wire (817, 819, 821, 823) electrically couples a pair of adjacent electrodes (816, 818, 820, 822) on a different spline. In some embodiments, each coupled electrode pair may be electrically isolated from one another. In some embodiments, coupled electrode pairs may be configured with a common polarity. Adjacent electrode pairs may be configured with opposite polarities (e.g., a first electrode pair configured as an anode and an adjacent second electrode pair configured as a cathode). For example, electrode (816) coupled to the first set of spline wires (817) may be configured as an anode, while each of the electrodes (818) coupled to the second set of spline wires (819) may be configured as a cathode. In some embodiments, each electrode formed on spline (814) may share a common polarity (e.g., configured as an anode or a cathode). Each coupled electrode pair may be independently addressable. In some embodiments, the ablation device (800) may include an even number of splines. The ablation device (800) may include any number of splines, e.g., 4, 6, 8, 10, or more splines. In some embodiments, the ablation device may include 4 to 10 splines. For example, in one embodiment, the ablation device may include between 6 and 8 splines. As noted above, in some embodiments, the spline wires, e.g., 817, 819, etc., can be replaced with similar electrical connections in the proximal portion of the device (e.g., within the device handle). For example, the electrodes (816) can be electrically wired together within the device handle so that they are at the same potential during ablation.

[0057] 9A is a side view of yet another embodiment of an ablation device (900) including a catheter shaft (910) at the proximal end of the device (900), a distal cap (912) of the device (900), and a set of splines (914) coupled thereto. The distal cap (912) may include an atraumatic shape. The proximal end of the set of splines (914) may be coupled to the distal end of the catheter shaft (910), and the distal end of the set of splines (914) may be anchored to the distal cap (912) of the device (900). Each spline (914) of the ablation device (900) may include one or more independently addressable electrodes (916, 918) formed on the surface of the spline (914). Each electrode (916, 918) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its thickness without breakdown. Each spline (914) may include an insulated conductor for each electrode (916, 918) formed in the body of the spline (914) (e.g., within the lumen of the spline (914)). Figure 9A illustrates a set of splines (914) in which each spline (914) includes an electrode that is spaced or offset from the electrode of an adjacent spline (914). For example, a set of splines (914) including a first spline (920) and a second spline (922) adjacent to the first spline (920) in which the electrode (916) of the first spline (920) is disposed closer to the distal end (912) of the ablation device (900) than the electrode (918) of the second spline (922). In other embodiments, the size and shape of the electrodes (916, 918) may also vary.

[0058] In some embodiments, adjacent distal and proximal electrodes (916, 918) may form an anode-cathode pair. For example, the distal electrode (916) may be configured as an anode, and the proximal electrode (918) may be configured as a cathode. In some embodiments, the ablation device (900) may include between three and twelve splines. In FIG. 9A, one electrode (916, 918) is formed on the surface of each spline (914) such that each spline (914) includes one insulated conductor. This reduces the diameter of the spline's (914) lumen, allowing the spline (914) to be thicker and more mechanically robust. This may further reduce insulation breakdown, improving the reliability and lifespan of each spline (914) and the ablation device (900). The ablation device (900) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines. In some embodiments, the ablation device (900) may include between 3 and 20 splines. For example, in one embodiment, the ablation device (900) may include between 6 and 10 splines. Furthermore, in some embodiments, the shape of the spherical expansion structure (930) of the set of expanded splines (914) may be asymmetric, e.g., with its distal portion being more spherical or curved than its proximal portion (see, e.g., Figures 9B-9E). Such a spherical distal portion may assist in positioning the device at the ostium of the pulmonary vein.

[0059] With reference to Figures 9B-9E, it will be understood that components bearing similar reference numbers to those in Figure 9A (e.g., electrode (916) in Figure 9A and electrode (916') in Figure 9B) are structurally and / or functionally similar unless otherwise indicated. Figure 9B shows splined wires (914', 920', 922') forming an expanded structure (930') during use, such as during deployment. The cross-sectional area of ​​a first face (924A'), sometimes referred to as the proximal face, of the expanded structure (930') is different from the cross-sectional area at a second face (924B') of the expanded structure (930'). As shown in Figure 9B, in some embodiments, the cross-sectional area of ​​the expanded structure (930') at the second face (924B') is greater than the cross-sectional area at the first face (924A'). The terms "first plane" and "second plane," as used with respect to Figure 9B, may refer to planes perpendicular to the longitudinal axis of the catheter shaft (910'), formed up to about 1 cm, about 2 cm, and about 3 cm or more (including all values ​​and subranges therebetween) from the distal end of the catheter shaft (910') and the proximal end of the distal cap (912'), respectively. Similar to Figure 9A, the electrodes (916') of the first spline (920') are disposed closer to the distal cap (912') of the ablation device (900') than the electrodes (918') of the second spline (922').

[0060] FIG. 9C shows spline wires (914", 920", 922") forming an expanded structure (930") during use, such as during deployment. The cross-sectional area of ​​a first face (924A"), sometimes referred to as the proximal face, of the expanded structure (930") is different from the cross-sectional area of ​​a second face (924B") of the expanded structure (930"). As shown in FIG. 9C , in some embodiments, the cross-sectional area of ​​the expansion structure (930″) at the second plane (924B″) is greater than the cross-sectional area at the first plane (924A″). The terms “first plane” and “second plane” as used with respect to FIG. 9C may refer to planes perpendicular to the longitudinal axis of the catheter shaft (910″) that are formed up to about 1 cm, about 2 cm, and about 3 cm or more (including all values ​​and subranges therebetween) from the distal end of the catheter shaft (910″) and the proximal end of the distal cap (912″), respectively. Unlike FIGS. 9A and 9B , multiple electrodes may be present on each spline wire, with some electrodes being equidistant from the distal cap (912″). In this manner, relatively distal electrodes such as 932″ and 934″ may be juxtaposed to or proximal / lumen of a pulmonary vein ostium during use for ablation delivery to create a peri-ostial lesion around the pulmonary vein.

[0061] FIG. 9D shows spline wires (914''', 920''', 922''') forming an expanded structure (930''') during use, such as during deployment. The spline wires (914''', 920''', 922''') converge at their distal ends to a point (928''') within the expanded structure (930'''). As shown in FIG. 9D, in such a configuration, at least some of the electrodes (932''', 934''') on the spline wires (914''', 920''', 922''') may be at the distal end surface (926''') of the expanded structure (930'''). The term "distal end surface" as used with respect to FIG. 9D may refer to a plane perpendicular to the longitudinal axis of the catheter shaft (910''') that passes through the distal boundary of the expanded structure (930'''). In this manner, the expandable structure (930''') may be pressed against an endocardial surface, such as the posterior wall of the left atrium, to create lesions directly on the surface by activating appropriate electrodes on the distal end face using any suitable combination of polarities. For example, the distal electrodes (932''' and 934''') may be used against the endocardial surface to create lesions (e.g., spot lesions) via focal ablation.

[0062] Referring now to the creation of focal ablation lesions using ablation device (900'"), in some embodiments, electrodes (933, 935) (sometimes referred to as "proximal electrodes") and electrodes (932'", 934'") (sometimes referred to as "distal electrodes") may be operated at opposite polarities. Conduction between these electrodes through the blood pool generates an electric field that is applied as ablation energy to the endocardial surface present at distal end face (926'"), resulting in focal ablation. For example, the splined wires (914''', 920''', 922''') may form an expanded structure (930''') such that the distal electrodes (932''', 934''') are at or within the distal end face (926''') of the endocardial surface, while the proximal electrodes (933, 935) are outside the distal end face (926''') and, as a result, do not press against or contact the endocardial surface. In some embodiments, the distal electrodes (932''', 934''') may have the same polarity, while the adjacent proximal electrodes (935, 933) may have an opposite polarity to the distal electrodes (932''', 934''').

[0063] In some embodiments, the electrodes of the ablation device (900''') may have a length of about 0.5 mm to about 5.0 mm and a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 2.5 mm, inclusive of all values ​​and subranges therebetween. The splined wires (914''', 920''', 922''') in the expanded structure (930''') shown in FIG. 9D may have a cross-sectional dimension (e.g., diameter) of about 6.0 mm to about 30.0 mm, inclusive of all values ​​and subranges therebetween. The focal ablation lesions thus formed may have a diameter of about 0.5 cm to about 2.5 cm, inclusive of all values ​​and subranges therebetween.

[0064] In some embodiments, the distal electrodes (932''', 934''') may be configured with opposite polarities. In some embodiments, adjacent electrodes on the same spline may have the same polarity, such that the distal electrode (934''') may have the same polarity as the proximal electrode (933), and similarly, the distal electrode (932''') may have the same polarity as the proximal electrode (935). The electrodes (934''', 933) may have the opposite polarity as the electrodes (932''', 935).

[0065] In some embodiments, adjacent distal electrodes (934''') and proximal electrodes (933) may form an anode-cathode pair. For example, the distal electrodes (934''') may be configured as an anode, and the proximal electrodes (933) may be configured as a cathode. In another embodiment, the electrodes (2630) on one spline may alternate between anodes and cathodes, with the electrodes on adjacent splines having the opposite configuration (e.g., cathodes and anodes).

[0066] FIG. 9E shows spline wires (944, 940, 942) forming an expanded structure (950) during use, such as during deployment. The spline wires (944, 940, 942) converge at their distal ends at the proximal end of a distal cap (912'''') within the expanded structure (950). As shown in FIG. 9E, in such a configuration, at least some of the electrodes (952, 954) on the spline wires (944, 940) may be at the distal end face (946) of the expanded structure (950). The term "distal end face" as used with respect to FIG. 9E may refer to a plane that passes through the distal boundary of the expanded structure (950) and is perpendicular to the longitudinal axis of the catheter shaft (910''''). In this manner, the expandable structure (950) may be pressed against, for example, the posterior wall of the left atrium to directly create a lesion on the surface by activating appropriate electrodes on the distal end face (946) using any suitable combination of polarities. For example, electrodes 952 and 954 may be configured with opposite polarities. Compared to the expandable structure (930'''') of FIG. 9D , the expandable structure (950) of FIG. 9E has a more orthogonal (e.g., flattened) shape that may be pressed against, for example, the posterior wall of the left atrium for tissue ablation. In other words, the cross-sectional area of ​​the expandable structure (930'''') at the distal end face (926'''') is smaller than the cross-sectional area of ​​the expandable structure (950) at the distal end face (946). As another example, distal electrodes (952, 954) may be used against an endocardial surface to form a lesion (e.g., a spot lesion) via focal ablation, as generally described herein with respect to FIG. 9D .

[0067] For each ablation device described herein, each spline may comprise a polymer and define a lumen to form a hollow tube. One or more electrodes of the ablation devices described herein may have a diameter of about 0.2 mm to about 2.0 mm and a length of about 0.2 mm to about 5.0 mm. In some embodiments, the electrodes may have a diameter of about 1 mm and a length of about 1 mm. Because the electrodes are independently addressable, they can be energized in any sequence using pulse waveforms sufficient to ablate tissue by irreversible electroporation. For example, as discussed in further detail below, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms). It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver continuous / transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes (e.g., all distal electrodes) may be at the same potential, as may all other electrodes (e.g., all proximal electrodes). Thus, ablation can be rapidly delivered by simultaneously activating all electrodes. A variety of such electrode pair options exist and may be implemented based on convenience.

[0068] Figure 26A is a side view of an embodiment of an ablation device (2600) having a flower-like shape and including a catheter shaft (2610) at the proximal end of the device (2600), a distal cap (2612) of the device (2600), and a set of splines (2620) coupled thereto. As best shown in Figure 26B, the splined shaft (2614) may be coupled to a proximal handle (not shown) at its proximal end and to the distal cap (2612) at its distal end. In a preferred embodiment, the distance between the distal cap (2612) and the catheter shaft (2610) may be less than about 8 mm. The splined shaft (2614) and the distal cap (2612) may be translatable along the longitudinal axis (2616) of the ablation device (2600). The splined shaft (2614) and the distal cap (2612) may move together. The elongate shaft (2614) may be configured to slide within the lumen of the catheter shaft (2610). The distal cap (2612) may include an atraumatic shape to reduce trauma to tissue. The proximal end of each spline of the set of splines (2620) may pass through the distal end of the catheter shaft (2610) and be anchored to the catheter shaft within the catheter shaft lumen, and the distal end of each spline of the set of splines (2620) may be anchored to the distal cap (2612) of the device (2600). The ablation device (2600) may be configured to deliver a pulsed waveform to tissue during use via one or more splines of the set of splines (2620), for example, as disclosed in FIGS. 21-25.

[0069] Each spline 2620 of the ablation device 2600, in some embodiments, may include one or more interconnected electrodes 2630 formed on the surface of the spline 2620. In other embodiments, one or more of the electrodes 2630 on a given spline may be independently addressable. Each electrode 2630 may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its thickness without breakdown. Each spline 2620 may include an insulated conductor for each electrode 2630 within the body of the spline 2620 (e.g., within the lumen of the spline 2620). 26A shows a set of splines (2620) in which each spline includes a set of electrodes (2632 or 2634) having approximately the same size, shape, and spacing as the electrodes (2634 or 2632) of the adjacent spline (2620). In other embodiments, the size, shape, and spacing of the electrodes (2632, 2634) may be different. The thickness of each spline (2620) may vary based on the number of electrodes (2630) formed on each spline (2620), which may correspond to the number of insulated conductors on the spline (2620). The splines (2620) may be the same or different in material, thickness, and / or length.

[0070] Each spline of the set of splines (2620) may include a flexible curvature such that it can be rotated or twisted to form a petal-shaped curve, such as that shown in FIGS. 26A-26C. The minimum radius of curvature of the splines in the petal-shaped configuration may range from about 7 mm to about 25 mm. For example, the set of splines may be configured to form a delivery assembly at a distal portion of the ablation device (2600) and transition between a first configuration in which the set of splines is aligned generally parallel to the longitudinal axis of the ablation device (2600) and a second configuration in which the set of splines is rotated or twisted about the longitudinal axis of the ablation device (2600) and biased generally away from the longitudinal axis. In the first configuration, each spline of the set of splines may lie in a plane with the longitudinal axis of the ablation device. In the second configuration, each spline in the set of splines may be biased away from the longitudinal axis to form a petal-like curve aligned generally perpendicular to the longitudinal axis. In this manner, the set of splines (2620) may be twisted and bent away from the longitudinal axis of the ablation device (2600) to more easily conform to the geometry of the cardiac chambers, particularly those adjacent the pulmonary ostium openings. The second configuration may resemble a flower shape when the ablation device is viewed from the front, as best shown in FIG. 26C . In some embodiments, each spline in the set of splines in the second configuration may be twisted and bent to form a petal-like curve that, when viewed from the front, exhibits an angle greater than 180 degrees between the proximal and distal ends of the curve. The set of splines may be further configured to transition from the second configuration to a third configuration in which the set of splines (2620) may be pressed against (e.g., contact) target tissue, such as tissue surrounding a pulmonary vein ostium.

[0071] In some embodiments, the splined shaft 2614 coupled to the set of splines 2620 may allow each spline of the set of splines 2620 to bend and twist relative to the catheter shaft 2610 as the splined shaft 2614 slides within the lumen of the catheter shaft 2610. For example, the set of splines 2620 may form a shape generally parallel to the longitudinal axis of the splined shaft 2614 when undeployed, and may be wrapped (e.g., spirally, twisted) about an axis 2660 parallel to the longitudinal axis of the splined shaft 2620 when fully deployed, or any intermediate shape in between (e.g., cage-like or barrel-like) as the splined shaft 2614 slides within the lumen of the catheter shaft 2610.

[0072] In some embodiments, a set of splines in a first configuration, such as splines (2620), may be wound around an axis (2660) parallel to the longitudinal axis of the catheter shaft (2610) along some portions of its length, while other portions may be otherwise generally parallel to the longitudinal axis of the catheter shaft (2610). The spline shaft (2614) may be retracted within the catheter shaft (2610) to transition the ablation device (2600) from the first configuration to a second configuration in which the splines (2620) are twisted, generally angled or offset with respect to (e.g., perpendicular to) the longitudinal axis of the catheter shaft (2610). As shown in the front view of FIG. 26C, each spline (2620) may form a twisted loop in this front view projection. In FIG. 26C, each spline (2620) has a set of electrodes (2630) with the same polarity. As shown in the front view of Figure 26C, each spline of a set of splines (2620) may form a twisted loop such that each spline overlaps one or more other splines. The number and spacing of electrodes (2630) and the rotational twist of the splines (2620) may be configured by suitably positioning the electrodes along each spline to prevent electrodes (2630) on one spline from overlapping electrodes on an adjacent overlapping spline (2620).

[0073] Splines with a set of anodic electrodes (2632) may operate together to deliver a pulse waveform for irreversible electroporation. Electrodes on other splines may operate together as cathodic electrodes, such as electrodes (2634) and (2635) on their respective splines, to form anodic-cathode pairings for delivering a pulse waveform for irreversible electroporation, as shown in FIG. 26C. The anodic-cathode pairings and pulse waveform delivery may be repeated sequentially across a set of such pairings.

[0074] For example, the splines (2620) may be activated sequentially in a clockwise or counterclockwise fashion. As another example, the cathode splines may be activated sequentially simultaneously with each successive anode spline activation until ablation is complete. In embodiments in which the electrodes on a given spline are separately wired, the order of activation within the electrodes of each spline may similarly vary. For example, the electrodes in a spline may be activated all at once or may be activated in a predetermined sequence.

[0075] The delivery assembly may be disposed in a first configuration prior to delivery of the pulse waveform and transition to a second configuration to contact the pulmonary vein ostium or sinus ostium. In some of these embodiments, a handle may be coupled to the splined shaft (2614), and the handle may be configured to actuate the transition of the set of splines between the first and second configurations. For example, the handle may translate the splined shaft (2614) and the distal cap (2612) relative to the catheter shaft (2610), thereby actuating the set of splines (2620) coupled to the distal cap to bend and twist them. The proximal ends of the splines (2620) may be secured to the splined shaft (2614), causing buckling of the splines (2620), resulting in bending and twisting of the splines (2620), for example, when the distal cap (2612) and splined shaft (2614) are pulled back relative to the catheter shaft (2610), which may be held by a user. For example, the distal end of the set of splines (2620) anchored to the distal cap (2612) may translate up to about 60 mm along the longitudinal axis of the ablation device to activate this change in configuration. In other words, translation of an actuation member in the handle can bend and twist the set of splines (2620). In some embodiments, actuation of a knob, wheel, or other rotary control mechanism in the device handle can translate the actuation member or spline shaft, thereby bending and twisting the splines (2620). In some embodiments, the leads of at least two electrodes of the set of electrodes (2630) can be electrically coupled at or near a proximal portion of the ablation device (2600), such as in the handle.

[0076] Retracting the splined shaft (2614) and distal cap (2612) may bring the set of splines (2620) closer together, as shown in FIG. 26B, where the set of splines (2620) is generally perpendicular to the longitudinal axis of the catheter shaft (2610). In some embodiments, each spline of the set of splines (2620) may be biased laterally up to about 3 cm away from the longitudinal axis of the splined shaft (2614). In some embodiments, the splined shaft (2614) may include a hollow lumen. In some embodiments, the cross-section of the splines may be asymmetric such that one bending plane of the spline perpendicular to the plane of the cross-section has greater bending stiffness than another bending plane. Such an asymmetric cross-section may be configured to exhibit relatively greater lateral stiffness, thereby allowing the splines to deploy with minimal overlap between the petal-shaped curves of each spline and its neighbors in the final or fully deployed configuration.

[0077] In one embodiment, each of the electrodes (2632) on a spline (2620) may be configured as an anode, while each of the electrodes (2634) on a different spline may be configured as a cathode. In another embodiment, the electrodes (2630) on one spline may alternate between anodes and cathodes, while the electrodes on another spline have the opposite configuration (e.g., cathodes and anodes).

[0078] In some embodiments, the spline electrodes may be electrically operated in a sequential manner to deliver a pulse waveform to each anode-cathode pairing. In some embodiments, the electrodes may be electrically wired together within the spline, while in alternative embodiments, the electrodes may be wired together within the handle of the device, so that they are at the same electrical potential during ablation. Similarly, in other embodiments, the size, shape, and spacing of the electrodes (2630) may vary. In some embodiments, adjacent distal and proximal electrodes may form an anode-cathode pair. For example, the distal electrode may be configured as an anode and the proximal electrode may be configured as a cathode.

[0079] The ablation device (2600) may include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2600) may include between 3 and 20 splines. In some embodiments, the ablation device (2600) may include between 4 and 12 splines.

[0080] Each spline of the set of splines (2620) may include a respective electrode (2630) having an atraumatic shape to reduce trauma to tissue. For example, the electrode (2630) may have an atraumatic shape that includes a contoured, flat, curved, and / or blunted portion configured to contact endocardial tissue. In some embodiments, the electrode (2630) may be located along any portion of the spline (2620) distal to the catheter shaft (2610). The electrodes (2630) may be the same or different in size, shape, and / or location along each spline.

[0081] In this manner, the electrodes in the second configuration may be held in close proximity to or placed against a portion of the atrial wall of the left atrium, as described herein, to directly create a lesion thereon by activating the appropriate electrodes using any suitable polarity combination. For example, a set of splines 2620 may be placed in contact with the atrial wall 2654 of the atrium 2652 adjacent to a pulmonary vein 2650 (e.g., an ostium or sinus ostium).

[0082] FIG. 26D is a schematic illustration of an ablation (2664) created by an ablation device (2600) on tissue, such as tissue surrounding a pulmonary vein ostium. For example, activation of one or more of the electrodes (2630) on one or more of the splines (2620) can create one or more corresponding ablation areas (2664) along the wall (2654) of the pulmonary vein ostium or ostium. In some embodiments, the contour of the ablation area (2664) in the pulmonary vein ostium can be about 2 cm to about 6 cm, or can be about 3.5 cm, in diameter. In this manner, a continuous transmural lesion can be created, resulting in electrical isolation of the pulmonary vein, which is the desired therapeutic outcome.

[0083] Alternatively, an ablation catheter with deployed electrodes may be positioned adjacent to or against a portion of the posterior wall of the left atrium, and by activation of a suitable electrode set, an appropriate pulse waveform may be delivered for irreversible electroporation energy delivery to ablate tissue.

[0084] In some embodiments, electrodes or subsets of electrodes may be independently addressable, so that the electrodes may be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, as discussed in further detail herein, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms). It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver continuous / transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes may be at the same potential, as may all other alternate electrodes. Thus, in some embodiments, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0085] In some embodiments, the distal-most portion of the ablation device may include a set of splines rather than a distal cap or another element extending the length of the catheter shaft. This may aid in positioning the set of splines relative to the tissue and reduce contact of other elements of the ablation device with the tissue, which may cause trauma to the tissue. For example, FIG. 35 is a side view of an embodiment of an ablation device (3500) including a first catheter (3510) (e.g., an outer catheter shaft) at the proximal end of the device (3500). The first catheter (3510) may define a longitudinal axis and a lumen therethrough. The second catheter (3520) may be slidably disposed within the first catheter lumen and extend from the distal end of the first catheter lumen. The second catheter (3520) may have a diameter smaller than the diameter of the first catheter (3510). The second catheter (3520) may define a lumen therethrough. For example, the lumen may provide a passageway for another device, such as a guidewire.

[0086] The set of splines (3530) may be coupled to the first catheter (3510) and the second catheter (3520). Specifically, a proximal end of the set of splines (3530) may be coupled to a distal end of the first catheter (3510), and a distal end of the set of splines (3530) may be coupled to a distal end of the second catheter (3520). The second catheter (3520) may be translatable along the longitudinal axis (3550) of the ablation device (3500). The proximal end of each spline of the set of splines (3530) may pass through the distal end of the first catheter (3510) and be anchored to the first catheter (3510) within the first catheter lumen. The distal end of each spline of the set of splines (3530) may pass through the distal end of the second catheter (3520) and be anchored to the second catheter (3520) within the second catheter lumen. In some embodiments, a junction (3522) may be formed between the distal end of the second catheter (3520) and the set of splines (3530). For example, a polymer reflow process may be used to form a smooth, atraumatic junction between the second catheter (3520) and the set of splines (3530). The ablation device (3500) may be configured to deliver a pulsed waveform to tissue during use via electrodes on one or more splines of the set of splines (3530), for example, as disclosed in FIGS.

[0087] Each spline (3530) of the ablation device (3500) may include one or more electrodes (3540) formed on the surface of the spline (3530). Each electrode (3540) may include an insulated conductor configured to maintain a potential of at least approximately 700 V without breakdown of the corresponding insulation. Each spline (3530) may include an insulated conductor for each electrode (3540) formed in the body of the spline (3530) (e.g., within the lumen of the spline (3530)). Figure 35 shows a set of splines where each spline (3530) includes a set of electrodes (3540) having approximately the same size, shape, and spacing as the electrodes (3540) of adjacent splines. In other embodiments, the size, shape, and spacing of the electrodes (3540) may be different.

[0088] The ablation device (3500) may be configured to deliver a set of voltage pulse waveforms using a set of electrodes (3540) to ablate tissue. In some of these embodiments, the ablation device (3500) may transition from a first configuration to a second configuration such that the splines (3530) of the ablation device (3500) deflect radially outward.

[0089] At least a portion of the set of splines (3530) may include a flexible curvature, for example, the proximal region (3522) and distal region (3526) of each spline (3530). The set of splines (3530) may form a delivery assembly at the distal portion of the ablation device (3500) and may be configured to transition between a first configuration in which the set of splines (3530) are aligned generally proximate to the longitudinal axis (3540) of the ablation device (3500) and a second configuration in which the set of splines (3530) bend radially outward from the longitudinal axis (3540) of the ablation device (3500) to form a basket-like and / or flower-like shape in which each spline forms a "petal." The spatial curvature shape of the splines in the second configuration may be described with reference to equations (1)-(3) corresponding to Figures 34A-34B. For example, in a fully deployed configuration, the integrated magnitude of the rotational velocity of each of the splines of the set of splines (3530) along the length of each spline may be greater than π degrees of arc.

[0090] In other embodiments, the spline "basket" may have an asymmetric shape along the length of the catheter, such that one end of the basket (let's say the distal end) is more bulging than the other end of the basket (let's say the proximal end). The delivery assembly may be advanced through the body cavity in a first configuration and transitioned to a second configuration prior to delivery of the pulse waveform. In some embodiments, a handle (not shown) may be coupled to the set of splines (3530), and the handle is configured to actuate the transition of the set of splines (3530) between the first and second configurations. In some embodiments, activation of one or more knobs, wheels, sliders, pull wires, and / or other control mechanisms within the handle may translate the second catheter (3520) relative to the first catheter (3510), causing bending of the splines (3530). In some embodiments, the leads of at least two electrodes of the set of electrodes (3540) may be electrically coupled at or near a proximal portion of the ablation device (3500), e.g., within the handle. For example, the handle may be configured to actuate and bend the set of splines (3530) by translating the second catheter (3512) relative to the first catheter (3510), as shown in FIG. 35. The distal ends of the splines (3530) may be secured to the distal end of the second catheter (3520), causing buckling of the splines (3530), resulting in bending movement of the splines (3530), for example, when the second catheter (3520) is retracted relative to the first catheter (3510). In other words, translation of the handle's actuation member may bend the set of splines (3530). In some embodiments, each spline of the set of splines (3530) may be biased laterally up to about 35 mm away from the longitudinal axis (3540) of the second catheter (3512). For example, the set of splines (3530) in the second configuration may form a shape with an effective cross-sectional diameter at its largest point of about 10 mm to about 35 mm. In the second configuration, the set of splines may be about 15 mm to about 50 mm in length.

[0091] In one embodiment, each of the electrodes on a spline may be configured as an anode, while each of the electrodes on a different spline may be configured as a cathode. That is, sets of electrodes on adjacent splines may have opposite polarities. In another embodiment, the electrodes on one spline may alternate between anode and cathode, while the electrodes on another spline have the opposite configuration (e.g., cathode and anode). In some embodiments, adjacent distal and proximal electrodes may form an anode-cathode pair. For example, the distal electrode may be configured as an anode, and the proximal electrode may be configured as a cathode.

[0092] In some embodiments, the electrodes may be electrically activated in a sequential manner to deliver a pulse waveform to each anode-cathode pairing. In some embodiments, the electrodes (3540) may be electrically wired together within the spline (3530), while in alternative embodiments, the electrodes may be wired together within the handle of the device (3500), so that the electrodes (3540) are at the same electrical potential during ablation. Similarly, in other embodiments, the size, shape, and spacing of the electrodes (3540) may vary. As another example, the splines (3530) may be activated sequentially in a clockwise or counterclockwise fashion. As another example, the cathode splines may be activated sequentially simultaneously with each successive anode spline activation until ablation is complete. In embodiments in which the electrodes (3540) on a given spline (3530) are separately wired, the order of activation within the electrodes (3540) of each spline (3530) may be varied as well. For example, the electrodes (3540) in the spline may be activated all at once or in a predetermined sequence.

[0093] The electrodes may be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. It should be understood that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver sufficient energy to electrically isolate one or more regions of cardiac tissue. In some embodiments, alternate electrodes (e.g., all distal electrodes) may be at the same potential, as may all other electrodes (e.g., all proximal electrodes). Thus, ablation can be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on their convenience.

[0094] Each of the splines (3530) may be composed of a polymer and define a lumen to form a hollow tube. The set of splines (3530) of the ablation device (3500) may have a diameter of about 1.0 mm to about 5.0 mm. The set of electrodes (3540) of the ablation device (3500) may have a diameter of about 1.0 mm to about 5.0 mm and a length of about 0.2 mm to about 5.0 mm.

[0095] The ablation device (3500) may include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (3500) may include between 3 and 16 splines. In some embodiments, the ablation device (3500) may include between 3 and 14 splines.

[0096] Each spline of the set of splines (3530) may include a respective electrode (3540) having an atraumatic shape to reduce trauma to tissue. For example, the electrode (3540) may have an atraumatic shape that includes a contoured, flat, curved, and / or blunted portion. In some embodiments, the electrode (3540) may be located along any portion of the spline (3530) distal to the first catheter (3510). The electrodes (3540) may be the same or different in size, shape, and / or location along each spline. The ablation device (3500) may include any number of electrodes per spline, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, or more, including all values ​​and subranges therebetween. In some embodiments, the ablation device (3500) may include 2 to 12 electrodes per spline.

[0097] FIGS. 34A and 34B are side views of a spline (3400) structurally and / or functionally similar to the splines described herein, such as those shown in FIGS. 36A-36C. FIG. 34A is a side view of a spline having a unit tangent vector . FIG. 34B is a side view of a spline having two unit tangent vectors. FIGS. 34A and 34B depict a spline (3400) having a flower petal-like shape, which may correspond to the shape of a spline in a second and / or third configuration, as described in detail herein. For simplicity, the spline (3400) is shown without other elements, such as electrodes. The curved spline (3400) includes a proximal end (3402) and a distal end (3404). At every point (3410) along the spline (3400), a unit tangent vector u (3420) may be defined. FIG. 34B shows the unit tangent vector u1 (3430) at the proximal end (3402) of the spline (3400) and the unit tangent vector u2 (3440) at the distal end (3404) of the spline (3400).

[0098] The rate of change of the unit tangent vector along the length of the spline may conform to the following equation:

number

[0099] The rate of change of the unit tangent vector u′ may be referred to as the rotational velocity of the unit tangent vector along the spline. Since u u = 1, the rotational velocity u′ is perpendicular to the unit tangent vector u.

[0100] In some embodiments, the splines described herein may transition to form a petal shape or may form a loop that is twisted along its length such that the spline has torsion along its length. The splines described herein have an integrated magnitude of rotational velocity that conforms to the following equation:

number

[0101] That is, the integrated magnitude of the rotational velocity of the spline is greater than the radian π, or 180 degrees. Since u and u' are perpendicular, u·u' = 0. Therefore, the vector b = u × u' is perpendicular to both u and u'.

[0102] In some embodiments, the shape of the spline is generally a space curve with torsion such that the derivative of the rotational rate generally has a component along b at least at some locations along the length of the spline, which conforms to the following equation:

number

[0103] In some embodiments of the devices described herein, the expanded splines of the set of splines may satisfy both equations (2) and (3).

[0104] 36A-36C are side views of an ablation catheter (3600) configured such that when the distal splines are fully deployed, the deployed spline set and electrode set extend distally of all other elements of the catheter (3600) to reduce trauma to tissue and aid in positioning and contact between the electrode set and tissue. FIG. 36A is a perspective view of an embodiment of an ablation device (3600) having a flower-like shape and including a first catheter (3610) at the proximal end of the device (3600). The first catheter (3610) may define a longitudinal axis (3650) and a lumen therethrough. A second catheter (3620) may be slidably disposed within the first catheter lumen and extend from the distal end of the first catheter lumen. The first catheter and second catheter, along with an actuation catheter handle, may comprise a single device. The set of splines (3630) may be coupled to the first catheter (3610) and the second catheter (3620). The second catheter (3620) may be translatable along the longitudinal axis (3650) of the ablation device (3600). A proximal end of each spline of the set of splines (3630) may pass through the distal end of the first catheter (3610) and be anchored to the first catheter (3610) within the first catheter lumen, and a distal end of each spline of the set of splines (3630) may be anchored to the distal end (3622) of the second catheter (3620), as described in more detail with respect to FIG. Because the ablation catheter (3600) does not include a distal cap or other protrusions extending from the distal end of the second catheter (3620), the device (3600) in the second configuration (e.g., a flower shape) may engage sensitive tissue, such as the thin heart, with a low risk of trauma from the device (3600). The ablation device (3600) may be configured to deliver a pulsed waveform to tissue during use via one or more electrodes of the set of splines (3630), for example, as disclosed in FIGS.

[0105] Each spline (3630) of the ablation device (3600), in some embodiments, may include one or more interconnected electrodes (3640) formed on the surface of the spline (3630). In other embodiments, one or more of the electrodes (3640) on a given spline may be an independently addressable electrode (3640). Each electrode (3640) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its thickness without breakdown. Each spline (3630) may include an insulated conductor for each electrode (3640) within the body of the spline (3630) (e.g., within the lumen of the spline (3630)). 36A-36C show a set of splines (3630) where each spline includes a set of electrodes (3640) having approximately the same size, shape, and spacing as the electrodes (3640) of an adjacent spline (3630). In other embodiments, the size, shape, and spacing of the electrodes (3640) may be different. The thickness of each spline (3630) may vary based on the number of electrodes (3640) formed on each spline (3630), which may correspond to the number of insulated conductors on the spline (3630). The splines (3630) may be the same or different in material, thickness, and / or length.

[0106] Each spline of the set of splines (3630) may include a flexible curvature such that it can be rotated or twisted to form a petal-shaped curve, such as that shown in FIGS. 26A-26C, 34A-34B, and 36A-36C. The minimum radius of curvature of the splines in the petal-shaped configuration may be about 7 mm to about 25 mm. For example, the set of splines may be configured to form a delivery assembly at a distal portion of the ablation device (3600) and transition between a first configuration in which the set of splines is aligned generally close to the longitudinal axis of the ablation device (3600) and a second configuration in which the set of splines is rotated or twisted about the longitudinal axis of the ablation device (3600) and biased generally away from the longitudinal axis. In the first configuration, each spline of the set of splines may lie in a plane with the longitudinal axis of the ablation device. In the second configuration, each spline in the set of splines may be biased away from the longitudinal axis to form a petal-like curve (e.g., a flower shape), where the longitudinal axis of the spline is aligned generally perpendicular to or at an acute angle with the longitudinal axis (3650). As described in detail herein, the shape (e.g., bend, curve) of the set of splines may satisfy equations (1)-(3). In this manner, the set of splines (3620) may be twisted and bent to bias away from the longitudinal axis of the ablation device (3600) so that the splines (3620) can more easily conform to the geometry of a cardiac cavity, such as the posterior wall and opening of the ostium. In some embodiments, each spline in the set of splines in the second configuration may be twisted and bent to form a petal-like curve that, when viewed from the front, exhibits an angle greater than 180 degrees between the proximal and distal ends of the curve.

[0107] In some embodiments, the second catheter (3620) coupled to the set of splines (3630) may allow each spline of the set of splines (3630) to bend and twist relative to the first catheter (3610) as the second catheter (3620) slides within the lumen of the first catheter (3610). For example, the set of splines (3630) may form a shape generally approximating the longitudinal axis of the second catheter (3620) when undeployed, may be wrapped (e.g., spirally, twisted) about the longitudinal axis (3650) when fully deployed, and may form any intermediate shape in between (such as a cage or barrel shape) as the second catheter (3620) slides within the lumen of the first catheter (3610).

[0108] In some embodiments, a set of splines in a first configuration, such as splines (3630), may be wound around the longitudinal axis (3650) of the first catheter (3610) for some portions along its length, while other portions may otherwise be generally parallel to the longitudinal axis of the first catheter (3610). A second catheter (3620) may be retracted within the first catheter (3610) to transition the ablation device (3600) from the first configuration to a second configuration, in which the splines (3630) are twisted to form a petal-like shape and are generally angled or offset (e.g., perpendicular, angled distally) with respect to the longitudinal axis (3650) of the first catheter (3610). When the second catheter (3622) is further retracted within the lumen of the first catheter (3610), the set of splines (3630) may extend further distally. As shown in Figures 36A-36C, each spline (3630) may form a twisted loop (eg, a petal shape where a set of splines together form a flower shape).

[0109] In the second configuration, the set of splines (3630) in the second configuration may form a flower shape and may be angled distally. Figure 36A shows a set of splines (3630) in which at least a portion of each spline of the set of splines (3630) extends distally relative to the distal end (3622) of the second catheter (3620). For example, Figure 36A shows that the distal portion of the spline intersects a plane (3660) (perpendicular to the longitudinal axis (3650)) that is distal to the distal end (3622) of the second catheter (3620). Thus, as the ablation device (3600) advances distally to contact tissue, the set of splines (3630) will contact before the first catheter (3610) and the second catheter (3620). This may reduce trauma to the tissue as the tissue may come into contact with the flexible set of splines without coming into contact with the relatively rigid second catheter (3622).

[0110] 36B shows a set of splines (3630) in a second configuration, forming a distal (e.g., leading) angle (3680) between the longitudinal axis (3670) of the splines (3630) and the longitudinal axis of the first catheter (3650). The longitudinal axis (3670) of the splines (3630) may be defined by a line formed between the apex of the splines (3630) and the midpoint between the proximal and distal ends of the splines (3630). In some embodiments, the distal angle may be less than about 80 degrees. For example, the distal angle may be 60 degrees or less.

[0111] In some embodiments, each spline of a set of splines (3620) may form a twisted loop such that each spline partially overlaps one or more other splines. The number and spacing of electrodes (3640) and the rotational twist of splines (3630) may be configured by suitably positioning the electrodes along each spline to prevent electrodes (3640) on one spline from overlapping electrodes on an adjacent overlapping spline.

[0112] Splines with a set of anodic electrodes may operate together to deliver a pulse waveform for irreversible electroporation. Electrodes on other splines may operate together as cathodic electrodes, such as the electrodes on their respective splines, to form anodic-cathode pairings for delivering a pulse waveform for irreversible electroporation. The anodic-cathode pairings and pulse waveform delivery may be repeated sequentially across a set of such pairings.

[0113] For example, the splines (3630) may be activated sequentially in a clockwise or counterclockwise fashion. As another example, the cathode splines may be activated sequentially simultaneously with each successive anode spline activation until ablation is complete. In embodiments in which the electrodes on a given spline are separately wired, the order of activation within the electrodes of each spline may similarly vary. For example, the electrodes in a spline may be activated all at once or may be activated in a predetermined sequence.

[0114] The delivery assembly may be disposed in a first configuration prior to delivery of the pulse waveform and transition to a second configuration to contact the ostium of a pulmonary vein or sinus. For example, FIG. 36C shows a distal-most portion of a set of splines (3630) in close proximity to and / or in contact with a tissue wall (3690), such as the posterior wall of the left atrium. The set of splines (3630) in FIG. 36C is in the second configuration, with at least a portion of each spline of the set of splines (3630) extending distally relative to the distal end (3622) of the second catheter (3620). The tissue (3690) may be a cardiac wall, such as the endocardial surface of the posterior wall of the left atrium. The distal end (3622) of the second catheter (3620) may be separated from the tissue (3690) by a first distance (3692). Thus, the ablation device (3600) in the second configuration can engage tissue (3690) in a non-invasive manner with reduced risk of penetration or other trauma, allowing the ablation device (3600) to be used to ablate even thin tissue structures, such as the posterior wall of the left atrium.

[0115] In some of these embodiments, a handle may be coupled to the second catheter (3620), and the handle may be configured to actuate a transition of the set of splines between a first configuration and a second configuration. For example, the handle may translate the second catheter (3620) relative to the first catheter (3610), thereby actuating the set of splines (3630) coupled to the second catheter (3620) to bend and twist them. The proximal ends of the splines (3630) may be fixed to the second catheter (3620), causing buckling of the splines (3630), resulting in bending and twisting of the splines (3630), for example, when the second catheter (3620) is pulled back relative to the first catheter (3610), which may be held by a user. For example, the distal end of the set of splines (3630) tethered to the second catheter (3620) may translate up to about 60 mm along the longitudinal axis of the ablation device to activate this change in configuration. In other words, translation of an actuation member in the handle can bend and twist the set of splines (3630). In some embodiments, actuation of a knob, wheel, or other rotary control mechanism in the device handle can translate the actuation member or second catheter, bending and twisting the splines (3630). In some embodiments, the leads of at least two electrodes in the set of electrodes (3640) can be electrically coupled at or near a proximal portion of the ablation device (3600), such as in the handle.

[0116] Retraction of the second catheter (3620) relative to the first catheter (3610) may cause the set of splines (3630) to approach each other, as shown in FIGS. 36A-36C. The set of splines (3630) may be more generally perpendicular or angled distally relative to the longitudinal axis (3650) of the first catheter (3610). In some embodiments, each spline of the set of splines (3630) may be biased laterally up to about 30 mm away from the longitudinal axis (3650). In some embodiments, the second catheter (3620) may include a hollow lumen. In some embodiments, the cross-section of the splines may be asymmetric, such that one bending plane of the spline perpendicular to the plane of the cross-section has a greater bending stiffness than a different bending plane. Such asymmetric cross-sections may be configured to exhibit relatively high lateral stiffness, such that in the final or fully deployed configuration, they may deploy with minimal overlap of the petal-shaped curve of each spline and its neighbors.

[0117] In one embodiment, each of the electrodes (3640) on a spline (3630) may be configured as an anode, while each of the electrodes (3640) on a different spline (3630) may be configured as a cathode. In another embodiment, the electrodes (3640) on one spline may alternate between anodes and cathodes, while the electrodes on another spline have the opposite configuration (e.g., cathodes and anodes).

[0118] In some embodiments, the spline electrodes may be electrically operated in a sequential manner to deliver a pulse waveform to each anode-cathode pairing. In some embodiments, the electrodes may be electrically wired together within the spline, while in alternative embodiments, the electrodes may be wired together within the handle of the device, so that they are at the same electrical potential during ablation. Similarly, in other embodiments, the size, shape, and spacing of the electrodes (3640) may vary. In some embodiments, adjacent distal and proximal electrodes may form an anode-cathode pair. For example, the distal electrode may be configured as an anode and the proximal electrode may be configured as a cathode.

[0119] The ablation device (3600) may include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (3600) may include between 3 and 20 splines. In some embodiments, the ablation device (3600) may include between 4 and 12 splines.

[0120] Each spline of the set of splines (3630) may include a respective electrode (3640) having an atraumatic shape to reduce trauma to tissue. For example, the electrode (3640) may have an atraumatic shape including a contoured, flat, curved, and / or blunted portion configured to contact endocardial tissue. In some embodiments, the electrode (3640) may be located along any portion of the spline (3630) distal to the first catheter (3610). The electrodes (3640) may be the same or different in size, shape, and / or location along each spline.

[0121] In this manner, the electrodes in the second configuration may be held in close proximity to or placed against a portion of the atrial wall of the left atrium, as described herein, to directly create lesions thereon by activating the appropriate electrodes using any suitable polarity combination. For example, a set of splines (3630) may be placed in contact with the atrial wall (3654) of the atrium (3652) adjacent the pulmonary vein (3650) (e.g., ostium or sinus ostium) and / or posterior wall.

[0122] 37A-37B are perspective views of an ablation catheter (3730) and the left atrium (3700). FIG. 37A is a perspective view of the ablation catheter (3730) disposed in the left atrium (3700). The left atrium (3700) includes a set of pulmonary veins (3720) and a posterior wall (3710). The ablation device (3730), which may be structurally and / or functionally similar to the ablation devices (3500, 3600) described herein, may be advanced into the left atrium (3700) and positioned adjacent to and / or in contact with the posterior wall (3710) of the left atrium (3700) without penetrating and / or causing trauma to the sensitive tissue of the posterior wall (3710). For example, the set of splines may extend distally relative to the distal end of the catheter coupled to the splines such that the flexible and atraumatic splines may abut or contact the posterior wall (3710) without any other portion of the device (3730) contacting the posterior wall (3710). In embodiments in which the distal-most portion of the device (3700) includes only the set of splines in the second configuration (e.g., having a flower shape), the deployed device may engage thin tissue structures, such as the heart wall, with minimal risk of trauma from the ablation device (3700). A set of pulse waveforms may be applied by electrodes of the ablation device (3700) having a flower shape to ablate tissue within the ablation zone (3740).

[0123] Figure 37B is a schematic perspective view of the left atrium (3700) after tissue ablation. The ablation device (3700) may be used to create a set of ablation zones (3740, 3742, 3744) in the posterior wall (3710) of the left atrium (3700). For example, by activating one or more electrodes on one or more of the splines of the ablation device (3730) and repeating this with catheter movement between completed ablations, the ablation zones (3740, 3742, 3744) may be created along the posterior wall (3710) of the left atrium (3700). In some embodiments, the ablation zones (3740, 3742, 3744) may partially overlap one another. These consecutive, overlapping ablation zones may approximately form a thick line of ablation (3746). One or more ablation lines may connect to other ablation lines (e.g., those generated around a pulmonary vein ostium or ostium) and / or ablation zones, thereby creating a box-shaped lesion. For example, a set of contiguous ablation zones may be formed by the ablation device (3730) to form a box-shaped lesion around the posterior wall (3710) of the left atrium (3700) that also surrounds one or more of the pulmonary veins (3720). In this manner, a continuous transmural lesion may be generated around all of the pulmonary veins, resulting in electrical isolation of the pulmonary veins and achieving the desired therapeutic outcome. In some embodiments, each ablation zone in the set of ablation zones (3740, 3742, 3744) may have a diameter of about 2 cm to about 6 cm. For example, an ablation zone may have a diameter of about 2.3 cm to about 4.0 cm.

[0124] In some embodiments, electrodes or subsets of electrodes may be independently addressable, so that the electrodes may be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver sufficient energy to electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes may be at the same potential, as may all other alternate electrodes. Thus, in some embodiments, ablation may be rapidly delivered with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0125] 27A and 27B are side views of an embodiment of an ablation device (2700) including a catheter shaft (2710) at a proximal end of the device (2700) and a set of splines (2720) coupled to the catheter shaft (2710) at a distal end of the device (2700). The ablation device (2700) may be configured to deliver a pulsed waveform to tissue during use via one or more splines of the set of splines (2720). Each spline (2720) of the ablation device (2700) may include one or more optionally independently addressable electrodes (2730) formed on a surface (e.g., a distal end) of the spline (2720). Each electrode (2730) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its thickness without breakdown. Each spline of the set of splines 2720 may include an insulated conductor of each electrode 2730 formed in the body of the spline 2720 (e.g., within the lumen of the spline 2720). In some embodiments, the electrodes 2730 may be formed at the distal end of their respective splines 2720.

[0126] The set of splines (2720) may form a delivery assembly at the distal portion of the ablation device (2700) and may be configured to transition between a first configuration and a second configuration. The set of splines (2720) in the first configuration may be generally parallel to the longitudinal axis of the ablation device (2700) and closely spaced together. The set of splines (2720) in the second configuration is depicted in FIGS. 27A and 27B, where the set of splines (2720) extend out from the distal end of the catheter shaft (2710) and are biased (e.g., curved) away from the longitudinal axis of the ablation device (2700) and the other splines (2720). In this manner, the splines (2720) may more easily conform to the geometry of the cardiac chamber. The delivery assembly may be disposed in the first configuration before delivering a pulse waveform to a portion of cardiac tissue, such as the posterior wall of the left atrium, or to a ventricle and transition to the second configuration. Such devices that deliver irreversible electroporative pulse waveforms can create large lesions for focal ablation.

[0127] The distal end of the set of splines 2720 can be configured to be biased away from the longitudinal axis of the distal end of the catheter shaft 2710 and away from the other splines. Each spline of the set of splines 2720 can include a flexible curvature. The minimum radius of curvature of the splines 2720 can be in the range of about 1 cm or greater.

[0128] In some embodiments, the proximal ends of the set of splines (2720) may be slidably coupled to the distal end of the catheter shaft (2710). Thus, the length of the set of splines (2720) may vary, as shown in FIGS. 27A and 27B. As the set of splines (2720) extends further out of the catheter shaft (2710), the distal ends of the set of splines (2720) may be biased further away from each other and the longitudinal axis of the catheter shaft (2710). The sets of splines (2720) may be slidably advanced out of the catheter shaft (2710) independently or in one or more groups. For example, the set of splines (2720) may be disposed within the catheter shaft (2710) in a first configuration. The splines (2720) may then be advanced out of the catheter shaft (2710) and transition to a second configuration. The splines (2720) may all advance together, or may advance such that the set of splines (2720) corresponding to the anode electrodes (2730) advances separately from the set of splines (2720) corresponding to the cathode electrodes (2730). In some embodiments, the splines (2720) may advance independently. In the second configuration, the electrodes (2730) are biased longitudinally and / or laterally away from the catheter shaft (2710) relative to the longitudinal axis of the distal end of the catheter shaft (2710). This may assist in the delivery and positioning of the electrodes (2730) relative to the endocardial surface. In some embodiments, each set of splines (2720) may extend up to about 5 cm from the distal end of the catheter shaft (2710).

[0129] In some embodiments, the set of splines (2720) may have a fixed length from the distal end of the catheter shaft (2710). The splines (2720) may extend equal or unequal lengths from the distal end of the catheter shaft (2710). For example, a spline with a larger radius of curvature than an adjacent spline may extend further from the catheter shaft (2710) than an adjacent spline. The set of splines (2720) is constrained by the lumen of the guide sheath so that the set of splines (2720) is substantially parallel to the longitudinal axis of the catheter shaft (2710) in the first configuration.

[0130] In some of these embodiments, a handle (not shown) may be coupled to the set of splines. The handle may be configured to actuate a transition between the first and second configurations of the set of splines. In some embodiments, the leads of at least two electrodes of the set of electrodes (2730) may be electrically coupled at or near a proximal portion of the ablation device, such as within the handle. In this case, the electrodes (2730) may be electrically wired together within the handle of the device (2700) so that the electrodes (2730) are at the same potential during ablation.

[0131] Each spline of the set of splines (2720) may include a respective electrode (2730) at the distal end of the set of splines (2720). The set of electrodes (2730) may include an atraumatic shape to reduce trauma to tissue. For example, the electrodes (2730) may have an atraumatic shape including a contoured, flat, curved, and / or blunted portion configured to contact endocardial tissue. In some embodiments, the electrodes (2730) may be located along any portion of the splines (2720) distal to the catheter shaft (2710). The electrodes (2730) may be the same or different in size, shape, and / or position along each spline.

[0132] In one embodiment, the electrodes (2730) on a spline (2720) may be configured as an anode, while the electrodes (2730) on an adjacent spline (2720) may be configured as a cathode. The ablation device (2700) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2700) may include between 3 and 20 splines. In some embodiments, the ablation device (2700) may include between 6 and 12 splines.

[0133] 27A and 27B are side views of an embodiment of an ablation device (2700) including a catheter shaft (2710) at a proximal end of the device (2700) and a set of splines (2720) coupled to the catheter shaft (2710) at a distal end of the device (2700). The ablation device (2700) may be configured to deliver a pulsed waveform to tissue during use via one or more splines of the set of splines (2720). Each spline (2720) of the ablation device (2700) may include one or more optionally independently addressable electrodes (2730) formed on a surface (e.g., a distal end) of the spline (2720). Each electrode (2730) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its thickness without breakdown. Each spline of the set of splines 2720 may include an insulated conductor of each electrode 2730 formed in the body of the spline 2720 (e.g., within the lumen of the spline 2720). In some embodiments, the electrodes 2730 may be formed at the distal end of their respective splines 2720.

[0134] The set of splines (2720) may form a delivery assembly at the distal portion of the ablation device (2700) and may be configured to transition between a first configuration and a second configuration. The set of splines (2720) in the first configuration may be generally parallel to the longitudinal axis of the ablation device (2700) and closely spaced together. The set of splines (2720) in the second configuration is depicted in FIGS. 27A and 27B, where the set of splines (2720) extend out from the distal end of the catheter shaft (2710) and are biased (e.g., curved) away from the longitudinal axis of the ablation device (2700) and the other splines (2720). In this manner, the splines (2720) may more easily conform to the geometry of the cardiac chamber. The delivery assembly may be disposed in the first configuration before delivering a pulse waveform to a portion of cardiac tissue, such as the posterior wall of the left atrium, or to a ventricle and transition to the second configuration. Such devices that deliver irreversible electroporative pulse waveforms can create large lesions for focal ablation.

[0135] The distal end of the set of splines 2720 can be configured to be biased away from the longitudinal axis of the distal end of the catheter shaft 2710 and away from the other splines. Each spline of the set of splines 2720 can include a flexible curvature. The minimum radius of curvature of the splines 2720 can be in the range of about 1 cm or greater.

[0136] In some embodiments, the proximal ends of the set of splines (2720) may be slidably coupled to the distal end of the catheter shaft (2710). Thus, the length of the set of splines (2720) may vary, as shown in FIGS. 27A and 27B. As the set of splines (2720) extends further out of the catheter shaft (2710), the distal ends of the set of splines (2720) may be biased further away from each other and the longitudinal axis of the catheter shaft (2710). The sets of splines (2720) may be slidably advanced out of the catheter shaft (2710) independently or in one or more groups. For example, the set of splines (2720) may be disposed within the catheter shaft (2710) in a first configuration. The splines (2720) may then be advanced out of the catheter shaft (2710) and transition to a second configuration. The splines (2720) may all advance together, or may advance such that the set of splines (2720) corresponding to the anode electrodes (2730) advances separately from the set of splines (2720) corresponding to the cathode electrodes (2730). In some embodiments, the splines (2720) may advance independently. In the second configuration, the electrodes (2730) are biased longitudinally and / or laterally away from the catheter shaft (2710) relative to the longitudinal axis of the distal end of the catheter shaft (2710). This may assist in delivery and positioning of the electrodes (2730) relative to the endocardial surface. In some embodiments, each set of splines (2720) may extend up to about 5 cm from the distal end of the catheter shaft (2710).

[0137] In some embodiments, the set of splines (2720) may have a fixed length from the distal end of the catheter shaft (2710). The splines (2720) may extend equal or unequal lengths from the distal end of the catheter shaft (2710). For example, a spline with a larger radius of curvature than an adjacent spline may extend further from the catheter shaft (2710) than an adjacent spline. The set of splines (2720) is constrained by the lumen of the guide sheath so that the set of splines (2720) is substantially parallel to the longitudinal axis of the catheter shaft (2710) in the first configuration.

[0138] In some of these embodiments, a handle (not shown) may be coupled to the set of splines. The handle may be configured to actuate a transition between the first and second configurations of the set of splines. In some embodiments, the leads of at least two electrodes of the set of electrodes (2730) may be electrically coupled at or near a proximal portion of the ablation device, such as within the handle. In this case, the electrodes (2730) may be electrically wired together within the handle of the device (2700) so that the electrodes (2730) are at the same potential during ablation.

[0139] Each spline of the set of splines (2720) may include a respective electrode (2730) at the distal end of the set of splines (2720). The set of electrodes (2730) may include an atraumatic shape to reduce trauma to tissue. For example, the electrodes (2730) may have an atraumatic shape including a contoured, flat, curved, and / or blunted portion configured to contact endocardial tissue. In some embodiments, the electrodes (2730) may be located along any portion of the splines (2720) distal to the catheter shaft (2710). The electrodes (2730) may be the same or different in size, shape, and / or position along each spline.

[0140] In one embodiment, the electrodes (2730) on a spline (2720) may be configured as an anode, while the electrodes (2730) on an adjacent spline (2720) may be configured as a cathode. The ablation device (2700) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2700) may include between 3 and 20 splines. In some embodiments, the ablation device (2700) may include between 6 and 12 splines.

[0141] In FIGS. 27A-27B, one electrode 2730 is formed on the surface of each spline 2720 such that each spline 2720 contains one insulated conductor. This reduces the diameter of the spline's lumen, allowing the spline to be thicker and more mechanically robust. This may further reduce insulation breakdown, improving the reliability and lifespan of each spline 2720 and the ablation device 2700. Furthermore, in some embodiments, the radius of curvature of the spline may vary over its length. For example, the radius of curvature may be monotonically increasing. Such a varying radius of curvature may aid in positioning the electrode 2730 at several locations in the endocardial tissue. The splines 2720 may be of the same or different material, thickness, and / or radius of curvature. For example, the thickness of each spline may decrease distally.

[0142] In this manner, the electrodes in the second configuration may be pressed against, for example, the posterior wall of the left atrium to directly create a localized or focal lesion thereon by activating the appropriate electrodes using any suitable polarity combination. For example, adjacent electrodes 2730 may be configured with opposite polarities.

[0143] Because electrodes or subsets of electrodes may be independently addressable, the electrodes may be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, as discussed in further detail herein, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms). It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver transmural lesions over a relatively large area of ​​endocardial tissue. In some embodiments, alternate electrodes may be at the same potential, as may all other alternate electrodes. Thus, ablation can be rapidly delivered with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0144] Referring to Figure 27C, unless otherwise indicated, components bearing similar reference numbers to those in Figures 27A-27B (e.g., electrode (2730) in Figures 27A-27B and electrode (2730') in Figure 27C) are understood to be structurally and / or functionally similar. Figure 27C shows a set of splines (2720'), each spline (2720') including a pair of electrodes (2730', 2740).

[0145] The ablation device (2700′) includes a catheter shaft (2710′) at a proximal end of the device (2700′) and a set of splines (2720′) coupled to the catheter shaft (2710′) at a distal end of the device (2700′). The ablation device (2700′) may be configured to deliver a pulsed waveform to tissue during use via one or more splines of the set of splines (2720′). Each spline (2720′) of the ablation device (2700′) may include one or more independently addressable electrodes (2730′, 2740) formed on the surface of the spline (2720′). Each electrode (2730′, 2740) may include an insulated conductor configured to maintain a potential of at least about 700 V without corresponding insulation breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its thickness without breakdown. Each spline of the set of splines 2720′ may include an insulated conductor for each electrode 2730′, 2740 formed in the body of the spline 2720′ (e.g., within the lumen of the spline 2720′). Each electrode 2730′, 2740 of a spline 2720′ may be substantially the same in size and shape. Furthermore, each electrode 2730′, 2740 of a spline 2720′ may be substantially the same in size, shape, and spacing as the electrodes 2730′, 2740 of an adjacent spline 2720′. In other embodiments, the size, shape, number, and spacing of the electrodes 2730′, 2740 may be different.

[0146] In some embodiments, the electrodes (2730′, 2740) of the ablation device (2700′) may have a length of about 0.5 mm to about 5.0 mm and a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 4.0 mm, inclusive of all values ​​and subranges therebetween. The splined wires (2720′) in the second configuration are spaced apart by an extent S at the distal end of the ablation device (2700′) from about 5.0 mm to about 20.0 mm from each other, inclusive of all values ​​and subranges therebetween. dand may extend outward from the distal end of the catheter shaft (2710′) to a length S of about 8.0 mm to about 20.0 mm, inclusive of all values ​​and subranges therebetween. l In some embodiments, the ablation device (2700') may include four splines, five splines, or six splines. In some embodiments, each spline may independently include one electrode, two electrodes, or more than two electrodes.

[0147] The set of splines (2720′) may form a delivery assembly at the distal portion of the ablation device (2700′) and may be configured to transition between a first configuration and a second configuration. The set of splines (2720′) in the first configuration may be generally parallel to the longitudinal axis of the ablation device (2700) and closely spaced together. The set of splines (2720′) in the second configuration is depicted in FIG. 27C , where the set of splines (2720′) extend out from the distal end of the catheter shaft (2710′) and are biased (e.g., curved) away from the longitudinal axis of the ablation device (2700′) and the other splines (2720′). In this way, the splines (2720′) may more easily conform to the geometry of the cardiac cavity. The delivery assembly may be disposed in a first configuration prior to delivery of the pulse waveform and transition to a second configuration to contact a region of endocardial tissue and create a large, localized lesion when delivering the pulse waveform for irreversible electroporation as disclosed herein. In some embodiments, electrode (2730′) in the second configuration depicted in FIG. 27C (sometimes referred to as the “distal electrode”) may be configured to contact and press against the endocardial tissue, while electrode (2740) in the second configuration (sometimes referred to as the “proximal electrode”) may not contact the endocardial tissue. In this manner, focal ablation of tissue is achieved by the electric field generated by the electrode due to conduction between the proximal and distal electrodes through the blood pool.

[0148] In some embodiments, the proximal ends of the set of splines (2720′) may be slidably coupled to the distal end of the catheter shaft (2710′). As the set of splines (2720′) extends further out of the catheter shaft (2710′), the distal ends of the set of splines (2720′) may be biased further away from each other and the longitudinal axis of the catheter shaft (2710′). The sets of splines (2720′) may be slidably advanced out of the catheter shaft (2710′) independently or in one or more groups. For example, the set of splines (2720′) may be disposed within the catheter shaft (2710′) in a first configuration. The splines (2720′) may then be advanced out of the catheter shaft (2710′) and transition to a second configuration. The splines (2720′) may all advance together, or may advance such that the set of splines (2720′) corresponding to the anode electrode (2730) advances separately from the set of splines (2720′) corresponding to the cathode electrodes (2730′, 2740). In some embodiments, the splines (2710′) may advance independently through their respective lumens (e.g., sheaths) of the catheter shaft (2710′). In the second configuration, the electrodes (2730′, 2740) are biased longitudinally and / or laterally away from the catheter shaft (2710′) relative to the longitudinal axis of the distal end of the catheter shaft (2710′). This may assist in delivery and positioning of the electrodes (2730′, 2740) relative to the endocardial surface. In some embodiments, each set of splines (2720′) may extend up to approximately 5 cm from the distal end of the catheter shaft (2710′).

[0149] In some embodiments, the distal electrode (2730') may have the same polarity, while the adjacent proximal electrode (2740) may have an opposite polarity to the distal electrode (2730'). In this manner, an electric field may be generated between the distal and proximal electrodes for focal ablation.

[0150] In some of these embodiments, a handle (not shown) may be coupled to the set of splines. The handle may be configured to actuate a transition between the first and second configurations of the set of splines. In some embodiments, the leads of at least two electrodes of the set of electrodes (2730′, 2740) may be electrically coupled at or near a proximal portion of the ablation device, such as within the handle. In some embodiments, the electrodes (2730′, 2740) may be electrically wired together within the handle of the device (2700′) so that the electrodes (2730′, 2740) are at the same electrical potential during ablation.

[0151] The set of electrodes (2730′, 2740) may include an atraumatic shape to reduce trauma to tissue. For example, the electrodes (2730′, 2740) may have an atraumatic shape including contoured, flat, curved, and / or blunted portions configured to contact endocardial tissue. In some embodiments, the electrodes (2730′, 2740) may be located along any portion of the spline (2720′) distal to the catheter shaft (2710′). The electrodes (2730′, 2740) may be the same or different in size, shape, and / or position along each spline. One or more of the splines (2720′) may include three or more electrodes.

[0152] In some embodiments, each of the electrodes (2730′) on a spline (2720′) may be configured as an anode, while each of the electrodes (2730′) on an adjacent spline (2720′) may be configured as a cathode. In another embodiment, each of the electrodes (2730′) on one spline may alternate between an anode and a cathode, with each of the electrodes on an adjacent spline having the opposite configuration (e.g., a cathode and an anode). In some embodiments, a subset of the electrodes may be electrically wired together within the handle of the device so that these electrodes are at the same potential during ablation. Similarly, in other embodiments, the size, shape, and spacing of the electrodes (2730) may vary. In some embodiments, adjacent distal and proximal electrodes (2730′) and (2740) may form an anode-cathode pair. For example, the distal electrode (2730′) may be configured as an anode, and the proximal electrode (2740) may be configured as a cathode.

[0153] The ablation device (2700') may include any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2700') may include between 3 and 20 splines. In some embodiments, the ablation device (2700') may include between 6 and 12 splines.

[0154] In Figure 27C, two electrodes (2730', 2740) are formed on the surface of each spline (2720') such that each spline (2720') includes two insulated conductors. The thickness of each spline may vary based on the number of electrodes formed on each spline (2720'), which may correspond to the number of insulated conductors in the spline (2720'). The splines (2720') may have the same or different materials, thicknesses, and / or radii of curvature. For example, the thickness of each spline (2720') may decrease distally.

[0155] In this manner, the electrodes in the second configuration may be positioned against a section of endocardial tissue to create a lesion directly thereon by activating the appropriate electrodes using any suitable polarity combination to deliver a pulse waveform for irreversible electroporation. For example, adjacent electrodes (2730', 2740) may be configured with opposite polarities.

[0156] Because the electrodes may be independently addressable, they may be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, as discussed in further detail herein, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms). It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver continuous / transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes may be at the same potential, as may all other alternate electrodes. Thus, ablation can be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0157] 28 is a side view of yet another embodiment of an ablation device 2800, including a catheter shaft 2810 at the proximal end of the device 2800, a distal cap 2812 of the device 2800, and a set of splines 2814 coupled thereto. In some embodiments, the ablation device 2800 is useful for creating lesions on the endocardial surface via focal ablation, as described herein.

[0158] The distal cap (2812) may include an atraumatic shape and one or more independently addressable electrodes (2816) (sometimes referred to as "distal electrodes"), as described in further detail herein. The proximal end of the set of splines (2814) may be coupled to the distal end of the catheter shaft (2810), and the distal end of the set of splines (2814) may be anchored to the distal cap (2812) of the device (2800). Each spline (2814) of the ablation device (2800) may include one or more independently addressable electrodes (2818) (sometimes referred to as "proximal electrodes") formed on the surface of the spline (2814). Each electrode (2816, 2818) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V, including all values ​​and subranges therebetween, across its entire thickness without breakdown. Each spline (2814) may include an insulated conductor for each electrode (2818) formed in the body of the spline (2814) (e.g., within the lumen of the spline (2814)). One or more of the splines (2818) may further include an insulated conductor for a distal electrode (2816). In some embodiments, the size and / or shape of the electrodes (2816, 2818) may differ from one another.

[0159] The configuration of the set of splines (2814) and the proximal electrode (2818) can control the depth, shape, and / or diameter / size of the focal ablation lesion created by the ablation device (2800). The ablation device (2800) may be configured to transition between a first configuration in which the set of splines (2814) are aligned generally parallel to the longitudinal axis of the ablation device (2800) and a second configuration in which the set of splines (2814) are deflected radially outward from the longitudinal axis of the ablation device (2800). It will be understood that the set of splines (2814) may transition continuously or in discrete steps to any intermediate configuration between the first and second configurations.

[0160] Actuating the electrodes using a predetermined configuration can result in targeted and precise focal ablation by controlling the size of the focal ablation spot based on the expansion of the splines (2814). For example, in some embodiments, the distal electrode (2816) can be configured with a first polarity and one or more proximal electrodes (2818) can be configured with a second polarity opposite the first polarity. When the proximal electrode (2818) of the ablation device (2800) is in the first configuration, a high-intensity electric field with a relatively small / more focused diameter results in a focal ablation lesion on the endocardial surface that is relatively smaller in diameter and deeper in depth. When the proximal electrode (2818) of the ablation device (2800) is in the second configuration, a relatively more dispersed electric field is generated, resulting in a focal ablation lesion on the endocardial surface that is relatively wider and shallower than when in the first configuration. In this manner, by varying the degree of expansion of the splines 2814, the depth, shape, and / or size of the lesion can be controlled without changing the ablation device 2800. Such an embodiment is useful for creating multiple lesions of various sizes and / or depths using the same ablation device.

[0161] The distal cap (2812) may be disposed to press against endocardial tissue, while the proximal electrode (2818) in either the first or second configuration may be configured not to contact endocardial tissue. It should be understood that the distal electrode (2816) need not contact endocardial tissue. In some of these embodiments, a handle (not shown) may be coupled to the set of splines (2814), and the handle is configured to actuate a transition of the set of splines (2814) between the first and second configurations. In some embodiments, the leads of at least two electrodes of the set of electrodes may be electrically coupled at or near a proximal portion of the ablation device (2800), such as within the handle.

[0162] In some embodiments, the distal electrode (2816) and the proximal electrode (2818) may form an anode-cathode pair. For example, the distal electrode (2816) may be configured as an anode, and each of the proximal electrodes (2818) may be configured as a cathode. In some embodiments, the ablation device (2800) may include 3 to 12 splines. The ablation device (2800) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines. In some embodiments, the ablation device (2800) may include 3 to 20 splines. For example, in one embodiment, the ablation device (2800) may include 6 to 10 splines. Furthermore, in some embodiments, the shape of the set of expanded splines (2814) may be asymmetric, e.g., with the distal portion thereof being more spherical or curved than the proximal portion thereof. Such a spherical distal portion (as well as the location of the proximal electrode) may assist in further control of the size and depth of the focal ablation.

[0163] The first plane (2822) depicted in FIG. 28 may refer to a plane perpendicular to the longitudinal axis of the catheter shaft (2810). The distal cap (2812) may be pressed against an endocardial surface within the first plane (2812), such as the luminal wall of a pulmonary vein, to directly create focal ablation lesions thereon by activating appropriate electrodes using any suitable polarity combination. For example, the distal electrode (2816) may be pressed against the endocardial surface and used to form focal ablation lesions (e.g., spot lesions). In some embodiments, one or more proximal electrodes (2818) may be configured with a polarity opposite that of the distal electrode (2816). Conversely, one or more of the proximal electrodes (2818) may be configured with the same polarity as the distal electrode (2816). In some embodiments, the proximal electrodes (2818) on different splines (2814) may alternate between anodes and cathodes.

[0164] In some embodiments, the distal electrode (2816) of the ablation device (2800) may have a length of about 0.5 mm to about 7.0 mm and a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 4.0 mm, inclusive of all values ​​and subranges therebetween. In some embodiments, the proximal electrode (2818) may have a length of about 0.5 mm to about 5.0 mm and a diameter of about 0.5 mm to about 2.5 mm, inclusive of all values ​​and subranges therebetween. The distal electrode (2816) may be spaced apart from the proximal electrode (2818) by a length of about 3.0 mm to about 12.0 mm, inclusive of all values ​​and subranges therebetween. The distal electrode (2816) disposed in the distal cap (2812) may be located apart from the distal end of the distal cap (2812) by a length of about 1.0 mm to about 4.0 mm, inclusive of all values ​​and subranges therebetween. In some embodiments, the distal end of the distal cap (2812) may include a distal electrode (2816). One or more focal ablation zones may be formed comprising a diameter of about 1.0 cm to about 2.0 cm, inclusive of all values ​​and subranges therebetween.

[0165] 29A-29D are side views of yet another embodiment of an ablation device (2900), including an outer catheter or sheath (2902) and a set of inner catheters (2910, 2920) slidable within the outer catheter lumen to extend from the distal end of the lumen. The outer catheter may define a longitudinal axis. The inner diameter of the outer catheter (2902) may be about 0.7 mm to about 3 mm, and the outer diameter of the outer catheter (2902) may be about 2 mm to about 5 mm. As best seen in FIGS. 29A and 29D, the ablation device (2900) includes a first catheter (2910) having a first proximal portion (2912), a first distal portion (2914), and a first electrode (2916) formed on the first distal portion (2914), e.g., on a surface of the first distal portion (2914). The first proximal portion (2912) may be coupled to the first distal portion (2914) via a first hinge (2918). The second catheter (2920) includes a second proximal portion (2922), a second distal portion (2924), and a second electrode (2926) formed on the second distal portion (2924). The second proximal portion (2922) may be coupled to the second distal portion (2924) via a second hinge (2928).

[0166] In some embodiments, the ablation device (2900), as described herein, is useful for creating lesions on the endocardial surface via focal ablation. The distal ends of the catheters (2910, 2920) and / or the electrodes (2916, 2922) may include atraumatic shapes to reduce trauma to tissue. For example, the distal ends of the catheters (2910, 2920) and / or the electrodes (2916, 2922) may have atraumatic shapes that include contoured, flat, curved, and / or blunted portions configured to contact endocardial tissue.

[0167] Each electrode (2916, 2926) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its entire thickness, including all values ​​and subranges therebetween, without breakdown. Each catheter (2910, 2920) may include an insulated conductor for each electrode (2916, 2926) formed in the body of the catheter (2910, 2920) (e.g., within the lumen of the catheter (2910, 2920)). Each of the electrodes (2916, 2926) may be connected to a corresponding insulated conductor that leads to a handle (not shown) coupled to the proximal portion of the catheter (2910, 2920). In some embodiments, the size, shape, and / or location of the electrodes (2916, 2926) may differ from one another.

[0168] In some embodiments, the configuration of the catheters (2910, 2920) and electrodes (2916, 2926) can control the depth, shape, and / or diameter / size of the focal ablation lesion created by the ablation device (2900). The first and second catheters (2910, 2920) can be configured to translate along the longitudinal axis of the outer catheter (2902). In some embodiments, the ablation device (2900) may be configured to transition between a first configuration (e.g., FIG. 29A) in which the set of catheters (2910, 2920) are arranged generally parallel to the longitudinal axis of the outer catheter (2902) and the distal portions of the catheters (2910, 2920) are disposed within the outer catheter (2902), a second configuration in which the electrodes (2916, 2926) exit the distal end (2903) of the outer catheter lumen (2902) and advance any suitable distance therefrom, and a third configuration (e.g., FIGS. 29B-29D) in which the distal portion of each catheter (2910, 2920) may rotate, twist, or bend about its corresponding hinge (2918, 2928) relative to the proximal portion of its corresponding catheter (2910, 2920). For example, as best shown in Figures 29B-29C, the first catheter (2910) may include a distal portion (2914) that is rotatable about a first hinge (2918), which may be configured to position the distal portion (2914) in multiple positions relative to the proximal portion (2912). The catheters (2910, 2912) in the second and third configurations may be angled away from each other so as to be biased away from the longitudinal axis of the outer catheter (2902). The distal ends of the proximal portions (2912, 2922) may form an angle along the longitudinal axis of about 5 degrees to about 75 degrees (e.g., Figure 29D). It is understood that the ablation device (2900) may transition to any intermediate configuration between the first, second, and third configurations continuously or in discrete steps.

[0169] In some embodiments, conduction between the electrodes through the blood pool and / or endocardial tissue results in the generation of an electric field and its application to the endocardial surface as ablation energy. The electrodes may be held in physical proximity to or placed in physical contact with a portion of the atrial wall of the left atrium, and lesions may be created thereon by activating one or more of the electrodes using any suitable polarity combination. In this manner, activating the electrodes using a predetermined configuration may result in targeted, precise focal ablation by controlling the focal ablation spot size based on the position and orientation of the electrodes (2916, 2926) relative to the proximal portions (2912, 2922) of the catheters (2910, 2920). For example, in some embodiments, the first electrode (2916) may be configured with a first polarity and the second electrode (2926) may be configured with a second polarity opposite the first polarity. When the electrodes (2916, 2926) are rotated so that they are relatively close to one another (e.g., when the proximal portion (2912) and distal portion (2914) form an acute angle (2950)), a relatively high intensity electric field with a relatively small / more focused diameter results in a focal ablation lesion on the endocardial surface with a relatively small diameter and good depth. By way of non-limiting example only, the acute angle formed at the articulating hinge may range from about 15 degrees to about 70 degrees. In some embodiments, the electric field strength within the focal ablation zone may be about 200 V / cm or greater. When the electrodes (2916, 2926) rotate about their corresponding hinges (2918, 2928) so that they are relatively farther apart from one another (e.g., when the proximal and distal portions (2912, 2914) form a larger angle), a more dispersed, lower intensity electric field is generated, resulting in a relatively wider, shallower focal ablation lesion on the endocardial surface. In this manner, by varying the degree of rotation of the electrodes (2916, 2926) relative to the proximal portions (2912, 2922) of the catheters (2910, 2920), the depth, shape, and / or size of the lesion can be controlled without replacing the ablation device (2900).Such an embodiment is useful for creating multiple lesions of various sizes, shapes, and / or depths using the same ablation device. For example, the lesions may have diameters of about 2 mm to about 3 cm, and depths of about 2 mm to about 12 mm. While the electrodes (2916, 2926) may be positioned so as to touch endocardial tissue, it should be understood that the electrodes (2916, 2926) need not touch endocardial tissue.

[0170] In some of these embodiments, a handle (not shown) may be coupled to the set of catheters (2910, 2920), and the handle is configured to actuate transitions of the catheters (2910, 2920) between a first configuration, a second configuration, and a third configuration. In some embodiments, activation of one or more knobs, wheels, sliders, pull wires, and / or other control mechanisms within the handle may result in translation of one or more catheters (2910, 2920) through the outer catheter (2902) and / or rotation of the distal portions (2914, 2924) of the catheters about hinges (2918, 2928).

[0171] 29B-29C depict a first catheter (2910) having an articulated distal portion (2914). The first catheter (2910) may include a proximal portion (2912) connected to the distal portion (2914) via a hinge (2918). The distal portion (2914) may include an electrode (2916), as described herein. In some embodiments, the hinge (2918) may include a rotatable wheel. In other embodiments, the hinge (2918) may include a portion of the proximal portion (2912) or distal portion (2914) that is more flexible than other portions of the catheter and has a reduced cross-sectional area relative to the first catheter (2910). In still other embodiments, the hinge (2918) may include a joint, a rotatable wheel, a ball and socket joint, a condylar joint, a saddle joint, a pivot, a track, or the like.

[0172] The rotatable wheel may be coupled to a wire (2917) (e.g., a pull wire). For example, the wire (2917) may be attached around a hinge (2918), and the distal portion (2914) may be attached to a portion of the hinge (2918). Thus, actuation (2930) of the wire (2917) (e.g., pulling one end of the wire proximally) may cause the wheel (2918) and the distal portion (2914) to rotate, resulting in the distal portion (2914) rotating relative to the proximal portion (2912) of the first catheter (2910). In some embodiments, the distal portion may rotate an angle of about 110 degrees to about 165 degrees relative to the proximal portion, and the length of the distal portion may be about 3 mm to about 12 mm. The proximal end of the wire (2917), in some embodiments, may be coupled to a handle (not shown) having two control mechanisms (e.g., one or more knobs, wheels, sliders). An operator may operate the control mechanisms to manipulate the wire (2917) and rotate the distal portion (2914) of the first catheter (2910) about the hinge (2918). The handle control mechanism may include a lock to fix the position of the distal portion (2914). Figure 29B depicts an embodiment of the first catheter (2910) having the distal portion (2914) between the second and third configurations. Figure 29C depicts an embodiment of the first catheter (2910) in the third configuration. The electrodes (2916, 2926) may be biased toward each other in the third configuration.

[0173] 29D depicts an embodiment of the ablation device (2900) in a third configuration, in which the distal portions of the first and second catheters (2910, 2920) extend out of the outer catheter or sheath (2902) and rotate to a desired (e.g., fully rotated, fully bent) position relative to the proximal portions (2912, 2922) of the catheters (2910, 2920). In some embodiments, the wires (2912, 2922) of each of the catheters (2910, 2920) may be coupled together at the handle, such that activation of a control mechanism can control the wires (2912, 2922) together to simultaneously rotate the distal portions (2914, 2924) of each of the catheters (2910, 2920) about their respective hinges (2918, 2928). In the second and third configurations, the first and second catheters (2910, 2920) may be biased away from the longitudinal axis of the outer catheter (2902).

[0174] As the first and second catheters (2910, 2920) extend out of the outer catheter (2902), one or more portions of the catheters (2910, 2920) may assume their natural (e.g., unconstrained) shape(s), such as a curved shape. The catheters (2910, 2920) may advance out of the outer catheter (2902) together or independently. In some embodiments, the proximal portions (2912, 2922) of the catheters (2910, 2920) may include a flexible curve such that the distal ends of the catheters (2910, 2920) can flare outward away from one another. The minimum radius of curvature of the catheters (2910, 2920) may be in the range of approximately 1 cm or greater. For example, the proximal portions (2912, 2922) may have a radius of curvature of approximately 1 cm or greater. In some embodiments, the distal portions (2914, 2924) may have a radius of curvature of about 1 cm or greater.

[0175] In some embodiments, the electrodes (2916, 2926) of the ablation device (2900) may have a length of about 0.5 mm to about 7.0 mm and a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 4.0 mm, inclusive of all values ​​and subranges therebetween. The electrodes (2916, 2926) of different catheters (2910, 2920) may be spaced apart from one another by a distance of about 3.0 mm to about 20 mm, inclusive of all values ​​and subranges therebetween. The electrodes (2916, 2926) may be located apart from the distal ends of their corresponding catheters (2910, 2920) by a distance of about 1.0 mm to about 4.0 mm, inclusive of all values ​​and subranges therebetween. In some embodiments, the distal ends of the catheters (2910, 2920) may include the electrodes (2916, 2926). One or more focal ablation lesions may be formed comprising a diameter of about 1.0 cm to about 2.0 cm, inclusive of all values ​​and subranges therebetween.

[0176] Figure 30 is a side view of another embodiment of an ablation device (3000), which includes an outer catheter or sheath (3010) defining a longitudinal axis and a set of four catheters (3020, 3030, 3040, 3050) slidable within the lumen (3010). Each of the catheters (3020, 3030, 3040, 3050) may include a proximal portion (3023, 3033, 3043, 3053), a distal portion (3024, 3034, 3044, 3054), and a hinge (3021, 3031, 3041, 3051) connecting the proximal portion (3023, 3033, 3043, 3053) to the distal portion (3024, 3034, 3044, 3054). Each of the distal portions (3024, 3034, 3044, 3054) may include an electrode (3022, 3032, 3042, 3052). The distal ends of the catheters (3020, 3030, 3040, 3050) and / or the electrodes (3022, 3032, 3042, 3052) may include atraumatic shapes (e.g., contoured, flat, curved, and / or blunted portions) to reduce trauma to tissue. Each of the catheters (3020, 3030, 3040, 3050) may include hinges (3021, 3031, 3041, 3051), as described in detail herein. It should be understood that the ablation device (3000) may include any number of catheters, including two, three, four, five, six, or more catheters.

[0177] Each electrode (3022, 3032, 3042, 3052) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its thickness therebetween, including all values ​​and subranges therebetween, without breakdown. Each catheter (3020, 3030, 3040, 3050) may include an insulated conductor for each electrode (3022, 3032, 3042, 3052) formed in the body of the catheter (3020, 3030, 3040, 3050) (e.g., within the lumen of the catheter (3020, 3030, 3040, 3050)). Each of the electrodes (3022, 3032, 3042, 3052) may be connected to a corresponding insulated conductor that leads to a handle (not shown) that is coupled to the proximal portion of the catheter. In some embodiments, the size, shape, and / or location of the electrodes (3022, 3032, 3042, 3052) may differ from one another.

[0178] In some embodiments, the configuration of the catheters (3020, 3030, 3040, 3050) and electrodes (3022, 3032, 3042, 3052) can control the depth, shape, and / or diameter / size of the focal ablation lesions created by the ablation device (3000). The set of catheters (3020, 3030, 3040, 3050) can be configured to translate along a longitudinal axis to transition between a first configuration, a second configuration, and a third configuration. In some embodiments, the ablation device (3000) may be configured in a first configuration in which a set of catheters (3020, 3030, 3040, 3050) are arranged generally parallel to the longitudinal axis of an outer catheter or sheath (3010), with distal portions of the catheters (3020, 3030, 3040, 3050) disposed within the outer catheter (3010); 11) and advanced any suitable distance therefrom, and a third configuration (e.g., FIG. 30) in which the distal portion of each catheter (3020, 3030, 3040, 3050) may be rotated, twisted, or bent about its corresponding hinge (3021, 3031, 3041, 3051) relative to the proximal portion of its corresponding catheter (3020, 3030, 3040, 3050). For example, the first catheter (3020) may include a distal portion (3024) that is rotatable about a first hinge (3021), which may be configured to position the distal portion (3024) in a plurality of positions relative to the proximal portion (3023), as discussed above with respect to FIGS. 29A-29D. It will be appreciated that the ablation device (3000) may transition continuously or in discrete steps to any intermediate configuration between the first, second, and third configurations. In the second configuration, the catheter set may be biased away from the longitudinal axis.

[0179] In some embodiments, one or more pulse waveforms may be applied between electrodes (3022, 3032, 3042, 3052) configured as an anode-cathode set. For example, adjacent or approximately opposite electrode pairs may operate together as an anode-cathode set. In FIG. 30, the first electrode (3022) may be configured as an anode and paired with the second electrode (3032) configured as a cathode. The third electrode (3042) may be configured as an anode and paired with the fourth electrode (3052) configured as a cathode. The first and second electrode pair (3022, 3032) may apply a first pulse waveform, followed sequentially by a second pulse waveform, using the third and fourth electrode pair (3042, 3052). In another embodiment, the pulse waveform may be applied to each of the electrodes simultaneously, where the second and third electrodes (3032, 3042) may be configured as anodes and the first and fourth electrodes (3022, 3052) may be configured as cathodes. It should be understood that any of the pulse waveforms disclosed herein may be applied progressively or sequentially to a sequence of anode-cathode electrodes. Some embodiments of the ablation device (3000) may have the same dimensions as those described above with respect to the ablation device (2900).

[0180] In other embodiments, one or more of the electrodes (3022, 3032, 3042, 3052) may be configured with a first electrical polarity, while one or more electrodes (not shown) disposed on the surface of the outer catheter shaft (3010) (not shown) may be configured with a second electrical polarity opposite the first electrical polarity.

[0181] 31A-31B are perspective views of yet another embodiment of an ablation device (3100), including an outer catheter or sheath (3110) defining a longitudinal axis and a catheter (3160) slidable within the outer catheter lumen. The catheter (3160) may extend from the distal end of the lumen. The catheter (3160) may include a proximal portion (3160), multiple distal portions (3122, 3132, 3142, 3152), and a joint (3162) connecting the proximal portion to each of the multiple distal portions. For example, the joint (3162) may include a hinge, a joint, a rotating wheel, a ball-and-socket joint, a condylar joint, a saddle joint, a pivot, a track, or the like. The distal portions (3122, 3132, 3142, 3152) are folded within the outer catheter (3110), and internal springs (not shown) connecting each portion are in a compressed configuration when each distal portion (3122, 3132, 3142, 3152) is folded. When the distal portions (3122, 3132, 3142, 3152) are unconstrained (i.e., when the inner catheter (3160) is deployed or pushed sufficiently away from the outer catheter (3110)), the springs assume their native or uncompressed configuration, causing the joints (3162) to fold, causing the distal portions (3122, 3132, 3142, 3152) to fold outward and assume a configuration approximately perpendicular to the longitudinal axis of the catheter. As shown in Figure 31B, the distal end of the catheter (3160) may be coupled to a set of electrodes (3120, 3130, 3140, 3150) via a joint (3162). In some embodiments, the joint (3162) may be coupled to a first distal portion (3122), a second distal portion (3132), a third distal portion (3142), and a fourth distal portion (3152). The electrodes (3120, 3130, 3140, 3150) may be disposed on the surface of each distal portion (3122, 3132, 3142, 3152). When the catheter (3160) exits the outer catheter (3110) and advances, the distal portions (3120, 3130, 3140, 3150) may assume their natural (e.g., unconstrained) shape so as to be approximately perpendicular to the longitudinal axis of the catheter (3160).

[0182] The electrodes (3120, 3130, 3140, 3150) may include a non-invasive shape (e.g., contoured, flat, curved, and / or blunted portions) to reduce trauma to tissue. Each electrode (3120, 3130, 3140, 3150) may include an insulated conductor configured to maintain a potential of at least about 700 V without breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V across its entire thickness without breakdown, including all values ​​and subranges therebetween. The catheter (3160) may include an insulated conductor for each electrode (3120, 3130, 3140, 3150) formed in the body (e.g., lumen) of the catheter (3160). Each of the electrodes (3120, 3130, 3140, 3150) may be connected to a corresponding insulated conductor that leads to a handle (not shown) that is coupled to the proximal portion of the catheter (3160). In some embodiments, the size, shape, and / or location of the electrodes (3120, 3130, 3140, 3150) may differ from one another.

[0183] The catheter (3160) may be configured to translate along the longitudinal axis to transition between the first configuration, the second configuration, and the third configuration. In some embodiments, the ablation device (3100) may be configured to transition between a first configuration (e.g., FIG. 31A) in which the set of electrodes (3120, 3130, 3140, 3150) is arranged within the outer catheter (3110) generally parallel to the longitudinal axis of the outer catheter (3110), a second configuration (not shown in FIG. 31A) in which the set of electrodes (3120, 3130, 3140, 3150) advances out of the distal end (3111) of the outer catheter lumen any suitable distance, and a third configuration (e.g., FIG. 31B) in which the electrodes (3120, 3130, 3140, 3150) may rotate, twist, or bend about their corresponding joints (3162) relative to the proximal portion of the catheter (3160). The transition from the first configuration to the second and third configurations may be made by advancing the catheter (3160) and electrodes (3120, 3130, 3140, 3150) out of the distal end of the outer catheter (3110). It will be understood that the ablation device (3100) may transition to any intermediate configuration between the first, second, and third configurations continuously or in discrete steps.

[0184] Figure 31B shows electrodes (3120, 3130, 3140, 3150) evenly spaced to form a plus ("+") shape. However, the angle between adjacent electrodes (3120, 3130, 3140, 3150) may be selected based on the desired focal ablation pattern. Similarly, the electrodes (3120, 3130, 3140, 3150) in Figure 31B are approximately perpendicular to the longitudinal axis of the catheter (3160), but may be adjusted based on a set of ablation parameters.

[0185] In some embodiments, one or more pulse waveforms may be applied between electrodes (3120, 3130, 3140, 3150) configured as an anode-cathode set. For example, adjacent or approximately opposite electrode pairs may operate together as an anode-cathode set. In FIG. 31B, a first electrode (3120) may be configured as an anode and paired with a third electrode (3140) configured as a cathode. A second electrode (3130) may be configured as an anode and paired with a fourth electrode (3150) configured as a cathode. The first and third electrode pair (3120, 3140) may apply a first pulse waveform, followed sequentially by a second pulse waveform, using the second and fourth electrode pair (3130, 3150). In another embodiment, the pulse waveform may be applied to each of the electrodes simultaneously, where the first and second electrodes (3120, 3130) may be configured as anodes and the third and fourth electrodes (3140, 3150) may be configured as cathodes. It should be understood that any of the pulse waveforms disclosed herein may be applied progressively or sequentially to a sequence of anode-cathode electrodes.

[0186] In other embodiments, one or more of the electrodes (3120, 3130, 3140, 3150) may be configured with a first electrical polarity, and one or more electrodes disposed on the surface of the outer catheter shaft (3110) may be configured with a second electrical polarity opposite to the first electrical polarity.

[0187] FIG. 32 is a cross-sectional schematic diagram of a high-intensity electric field generated by an ablation device (3200) for ablation of tissue, such as tissue in a ventricular chamber. For example, the ablation device (3200) may be disposed in the left ventricular chamber of the heart. The ablation device (3200) depicted in FIG. 32 may be similar to the ablation devices (3000, 3100) described with respect to FIGS. 30 and 31A-31B. In some embodiments, the electrodes (3210, 3220, 3230, 3240) may be apposed to the tissue wall when in the third configuration. In some embodiments, the electrodes (3210, 3220, 3230, 3240) of FIG. 32 may have a width of about 1 mm to about 3 mm and a length of about 3 mm to about 9 mm. For example, the electrodes (3210, 3220, 3230, 3240) may have a width of about 2 mm and a length of about 6 mm.

[0188] In some embodiments, the electrodes (3210, 3220, 3230, 3240) may form an anode-cathode pair. For example, the first electrode (3210) may be configured as an anode, and the third electrode (3230) may be configured as a cathode. The first and second electrodes (3210, 3230) may have a potential difference of up to approximately 1500 V. By activating one or more of the one or more catheter electrodes (3210, 3220, 3230, 3240), one or more ablation zones may be generated along a portion of the ventricular wall. The electric field contours (3350) are isointensity contours corresponding to the ablation zone (3350) having a field intensity threshold of approximately 460 V / cm when the first and third electrodes (3220, 3240) are activated. In some embodiments, the ablation zone (3350) may be about 12 mm wide and about 20 mm long. Alternatively, the ablation device may be placed adjacent to or against a portion of the posterior wall of the left atrium, and activation of one or more electrodes may deliver an appropriate pulse waveform for irreversible electroporation energy delivery to ablate tissue.

[0189] 33A is a perspective view of another embodiment of an ablation device / apparatus (3300) in the form of a catheter, including an outer shaft (3310) extending to the proximal end of the device (3300), an inner shaft (3320) extending from the distal end of the shaft lumen (3312) of the outer shaft (3310), and a set of splines (3330) coupled thereto. The inner shaft (3320) may be coupled to a handle (not shown) at its proximal end and disposed at its distal portion (e.g., its distal end) relative to a cap electrode (3322). The inner shaft (3320) and the set of splines (3330) may be translatable along the longitudinal axis (3324) of the ablation device (3300). In some embodiments, the inner shaft (3320) and the set of splines (3330) may move together or may translate independently. The inner shaft (3320) may be configured to slide within the lumen (3312) of the outer shaft (3310). The cap electrode (3322) may include an atraumatic shape to reduce trauma to tissue. For example, the cap electrode (3322) may have a flat, circular shape and / or a curved, blunted profile. The distal end of each spline of the set of splines (3330) may be anchored to a distal portion of the inner shaft (3320). The proximal portion of the set of splines (3330) may be attached to the outer shaft (3310). The ablation device (3300) may be configured to deliver a pulse waveform to tissue during use via the electrodes (3332, 3334) on the splines (3330) and the distal cap electrode (3322), as disclosed in FIGS. 21-25, for example.

[0190] Each spline in the set of splines (3330) may include a set of electrodes (3332, 3334) on the surface of that spline. Each set of electrodes may include distal electrodes (3332), such that the set of splines includes a set of distal electrodes (3332). Each of the distal electrodes (3332) is closest to the cap electrode (3322) compared to the other electrodes in its corresponding set of electrodes on the same spline (e.g., the set of proximal electrodes (3334)). Furthermore, in some embodiments, the distal electrodes (3332) may only have an outward-facing, exposed portion, i.e., a portion that does not face the interior space / volume defined by the set of splines. For example, if the distal electrodes (3332) are constructed from metal rings, a portion of each ring may be insulated so that only the outward-facing, exposed portion or “window” is exposed for delivery of ablation energy. The cap electrode (3322) and each distal electrode (3332) of the set of distal electrodes may collectively have the same polarity during use. This combination of closely spaced distal electrodes with outwardly facing windows and cap electrodes allows the distal end of the ablation device (3300) to generate and project a stronger electric field, thereby more effectively producing focal ablation lesions of tissue at a desired depth compared to any one of these electrodes alone.

[0191] Each spline (3330) of the ablation device (3300) may include at least one set of independently addressable electrodes (3332, 3334) on the surface of that spline (3330). A distal cap electrode (3322) may be formed at the distal end of the catheter device (3300). Each electrode (3322, 3332, 3334) may be coupled to an insulated lead, the corresponding insulation of which may be configured to maintain a potential of at least about 700 V without breakdown. In other embodiments, the insulation of each lead may maintain a potential difference of between about 200 V and about 2000 V across its thickness without breakdown. Each spline (3330) may include an insulated lead for each electrode (3332, 3334) within the body of the spline (3330) (e.g., within the lumen of the spline (3330)). Similarly, in some embodiments, the inner shaft (3320) may include insulated wires for the cap electrodes (3322). In other embodiments, a subset of the electrodes (3322, 3332, 3334) may be wired together. For example, the proximal electrodes (3334) of each spline of a set of splines (3330) may be wired together. As another example, all of the distal electrodes (3332) and cap electrodes (3322) may be wired together.

[0192] In some embodiments, the set of splines (3330) may be configured to transition between a first configuration in which the set of splines (3330) are aligned generally parallel to the longitudinal axis (3324) of the ablation device (3300) and a second configuration in which the distal end of each spline of the set of splines (3330) is deflected radially outward from the longitudinal axis (3324). In this manner, the set of distal electrodes (3332) and the cap electrodes (3322) may be shaped / oriented to form the second configuration shown in Figures 33A, 33B, and 33E. The cap electrodes (3322) may be spaced up to about 5 mm from each distal electrode of the set of distal electrodes (3332), including all values ​​and subranges therebetween. For example, the cap electrodes (3322) may be spaced from each distal electrode of the set of distal electrodes (3332) by about 0.5 mm to about 3 mm. In the second configuration, the distal portion of each spline of the set of splines 3330 may be angled 3336 from about 45 degrees to about 90 degrees relative to the longitudinal axis 3312, including all values ​​and subranges therebetween. For example, the distal portion of each spline of the set of splines 3330 in the second configuration may be angled 3336 from about 70 degrees to about 80 degrees relative to the longitudinal axis 3312. For example, in the second configuration, the set of cap electrodes 3322 and distal electrodes 3332 may take the shape of a "plus" sign when projected onto a plane perpendicular to the longitudinal axis 3324, as seen in the front view of FIG. 33B.

[0193] In some embodiments, the inner shaft (3320) may be retracted a predetermined amount within the outer catheter lumen (3312) to transition the ablation device (3300) from a first configuration to a second configuration. It is understood that the set of splines (3330) may transition continuously or in discrete steps to any intermediate configuration between the first and second configurations. The set of splines (3330) may form a shape generally parallel to the longitudinal axis (3324) of the inner shaft (3320) when undeployed, and may form a basket-like or spherical shape when the distal ends of the set of splines (3330) are deflected radially outward from the longitudinal axis (3324).

[0194] 33A, 33B, and 33E show a set of splines (3330), where each spline of the set includes a distal electrode (3332) and one or more proximal electrodes (3334) that vary in one or more of size, shape, number, and spacing. For example, FIG. 33A shows one distal electrode (3332) and two proximal electrodes (3334) for each spline of the set of splines (3330). In some embodiments, each proximal electrode (3334) may be formed on the surface of that spline (3330) along its entire circumference, i.e., around the entire thickness of the spline. In some embodiments, each distal electrode (3332) may be formed on a portion of the circumference of that spline. That is, as shown in Figures 33C and 33D, a distal electrode (3332) may be partially on the circumference of its corresponding spline and not cover the entire circumference of its corresponding spline (3330). For example, a distal electrode (3332) may surround the circumference of its corresponding spline and be partially covered by an insulating layer such that only a portion (e.g., a window) of the distal electrode (3332) is exposed. In some embodiments, one or more electrodes may be completely covered by a thin insulating layer for two-stage operation. In some embodiments, a set of distal electrodes (3332) of a set of splines (3330) may form an angle (3333) of about 30 degrees to about 300 degrees, inclusive of all values ​​and subranges therebetween, around the center of its corresponding spline (3330). For example, the set of distal electrodes 3332 of a set of splines 3330 may form an angle 3333 of about 60 degrees to about 120 degrees around the center of its corresponding spline 3330. In this way, a significant percentage of the electric field generated by the set of distal electrodes 3332 in the second configuration may be directed forward and projected toward the target tissue to assist in focal ablation, rather than away from the target tissue and into the blood.

[0195] In this manner, the distal electrodes (3332) may be configured to face in a particular direction. For example, Figures 33A and 33E show the set of distal electrodes (3332) and the cap electrodes (3322) facing generally forward at the distal end of the device (3300) in a second configuration in which the distal ends of the set of splines (3330) are deflected radially outward from the longitudinal axis (3324). Furthermore, the distal electrodes (3332) may be disposed at the distal ends of the splines (3330) such that the distal electrodes (3332) of the set of splines (3330) are disposed near the cap electrodes (3322).

[0196] In some embodiments, each spline of a set of splines (3330) may include a set of electrodes (3332, 3334) having approximately the same size, shape, number, and spacing as the corresponding electrodes (3332, 3334) of an adjacent spline. The thickness of each spline (3330) may vary based on the number of electrodes (3332, 3334) formed on each spline (3330), which may correspond to the number of insulated conductors in the spline (3330). The splines (3330) may be the same or different in material, thickness, and / or length.

[0197] In some embodiments, the cap electrode (3322) and the set of electrodes (3332, 3334) may be configured as an anode-cathode set. For example, the cap electrode (3322) and each distal electrode of the set of distal electrodes (3332) may be collectively configured as an anode, and all proximal electrodes (3334) may be collectively configured as a cathode (or vice versa). In some embodiments, the set of distal electrodes (3332) and the set of proximal electrodes (3334) may have opposite polarities. For example, the set of distal electrodes (3332) and proximal electrodes (3334) for a given spline may have opposite polarities. The set of cap electrodes (3322) and distal electrodes (3332) may have the same polarity. As discussed herein, all distal electrodes (3332) and cap electrodes (3322) may be wired together. In some embodiments, the cap electrode and the set of electrodes (3332, 3334) of one or more splines of the set of splines (3330) may operate together to deliver a pulse waveform for irreversible electroporation. In other embodiments, the delivery of the pulse waveform may be repeated sequentially across a predetermined subset of the set of electrodes (3332, 3334).

[0198] In some embodiments, the set of distal electrodes (3332) may be spaced from the cap electrodes (3322) by up to 3 mm from the distal end of each spline (3330). In some embodiments, the set of distal electrodes (3332) may be spaced from the set of proximal electrodes (3334) by about 1 mm to about 20 mm. In some embodiments, each electrode in the set of electrodes (3332, 3334) may have a diameter of about 0.5 mm to about 3 mm. In some embodiments, the cap electrode (3322) may have a cross-sectional diameter of about 1 mm to about 5 mm. In some embodiments, each electrode in the set of electrodes (3332, 3334) may have a length of about 0.5 mm to about 5 mm. In some embodiments, the set of splines (3330) in the second configuration may have an expanded cross-sectional diameter (i.e., the effective diameter of the expanded or second configuration at its largest portion) of about 6 mm to about 24 mm. In some embodiments, the set of splines (3300) may extend from about 6 mm to about 30 mm from the distal end (3312) of the outer shaft (3310). In some embodiments, the outer shaft (3310) may have an outer diameter of about 1.5 mm to about 6.0 mm.

[0199] The ablation devices (3300) described herein may be disposed in a first configuration prior to delivery of a pulse waveform and transition to a second configuration to contact a tissue surface (e.g., the interior wall of the left atrium or ventricle, and / or the like). In some of these embodiments, a handle (not shown) may be coupled to the catheter (3300) and the set of splines (3330), the handle configured to actuate the transition of the set of splines (3330) between the first and second configurations. For example, the handle may be configured to translate the inner shaft (3320) relative to the outer shaft (3310). For example, retracting the inner shaft (3320) into the lumen (3312) of the outer shaft (3310) may deploy the set of splines (3330) to assume the spherical shape shown herein. In some embodiments, activating a knob, wheel, or other control mechanism within the device handle may translate the inner shaft (3324) and deploy the set of splines (3330). In some embodiments, the leads of at least two electrodes of a set of electrodes (3322, 3332, 3334) may be electrically coupled at or near a proximal portion of the ablation device (3300), for example, in the handle.

[0200] Additionally, the catheter handle (not shown) may include a mechanism for deflecting or guiding the distal portion of the catheter device 3300. For example, a pull wire may extend from the catheter handle to one end of the distal portion of the device 3300 at or near the distal end of the outer shaft 3310, and tension on the pull wire deflects the distal portion of the device 3300. Deflection of the device 3300 may assist a user in positioning the device 3300 in a controlled manner at a preferred anatomical location. In some embodiments, the distal cap electrode 3322 may be electrically wired separately from the spline electrode 3332. In this manner, intracardiac ECG signals may be recorded from only the distal cap electrode 3322. In some embodiments, one or more distal spline electrodes 3332 may be electrically wired separately to monitor intracardiac ECG signals from each such electrode 3332. In some embodiments, some distal spline electrodes (3332) may be used for ECG monitoring, while other distal spline electrodes (3332) may be used for ablation energy delivery. It should be understood that any of the ablation devices described herein may be used with separately electrically wired electrodes for monitoring intracardiac ECG signals from each such electrode. In some embodiments, some electrodes of one or more splines of a set of splines may be used for ECG monitoring, while other electrodes may be used for ablation energy delivery.

[0201] The ablation device (3300) may include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (3300) may include between 3 and 20 splines. In some embodiments, the ablation device (3300) may include between 4 and 12 splines.

[0202] Each spline of the set of splines (3300) may include a respective electrode (3332, 3334) having an atraumatic, generally curved shape to reduce trauma to tissue. In this manner, the distal electrode in the second configuration may be held in close proximity to or positioned against a portion of the atrial wall of the left atrium, as described herein, to create a lesion thereon by activating the appropriate electrode using any suitable polarity combination. For example, the cap electrode (3322) and distal electrode (3332) of the set of splines (3330) may be positioned in contact with or in close proximity to the tissue wall (3350), as shown in FIG. 33E, in a generally perpendicular or generally oblique orientation relative to the tissue wall. This configuration of the distal electrodes (3322, 3332) allows for the creation of a localized lesion at a desired depth even when the ablation device (3300) in the deployed configuration abuts the tissue wall (3350) at an angle (e.g., obliquely).

[0203] In some embodiments, electrodes or subsets of electrodes may be independently addressable, so that the electrodes may be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, as discussed in further detail herein, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms). It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver continuous / transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes may be at the same potential, as may all other alternate electrodes. Thus, in some embodiments, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0204] In some embodiments, the ablation devices (2900, 3000, 3100, 3200) may include two to six catheters. The ablation devices (2900, 3000, 3100, 3200) may include any number of catheters, e.g., two, three, four, five, six, or more catheters. For example, in some embodiments, the ablation devices (2900, 3000, 3100, 3200) may include three to six catheters. In some embodiments, the catheters of the ablation devices (2900, 3000, 3100, 3200) may include two to six distal segments. The catheters may include any number of distal segments, e.g., two, three, four, five, six, or more distal segments. For example, in some embodiments, the catheters may include two to four distal segments. Additionally, in some embodiments, the shape (eg, curvature, length, size) of the catheter may be asymmetric to aid in controlling the depth, shape, and / or size of the focal ablation.

[0205] In some embodiments, the electrodes may form an anode-cathode pair. For example, a first electrode may be configured as an anode and a second electrode may be configured as a cathode. In some embodiments, subsets of the electrodes may be independently addressable, and the electrodes may be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms).

[0206] In all of the embodiments described above, and without limitation, the ablation catheter may itself be a steerable device with pull wires to control deflection by a suitable mechanism in the catheter handle, as known to those skilled in the art.

[0207] balloon In some embodiments, the ablation device may include one or more balloons to deliver energy to ablate tissue by irreversible electroporation. Figure 10 depicts an embodiment of a balloon ablation device (1010) (e.g., structurally and / or functionally similar to the ablation device (110)) disposed in the left atrial cavity (1000) of the heart. The ablation device (1010) may include a first balloon (1012) and a second balloon (1014) that may be configured to be disposed in the ostium (1002) of a pulmonary vein (1004). The first balloon (1012) in an expanded (e.g., inflated) configuration may have a larger diameter than the second balloon (1014) in an expanded configuration. This allows the second balloon (1014) to be advanced and positioned further into the pulmonary vein (1014), while the first balloon (1012) is positioned at and / or near the ostium (1002) of the pulmonary vein (1004). The inflated second balloon serves to stabilize the first balloon at the ostium of the pulmonary vein. In some embodiments, the first balloon (1012) and the second balloon (1014) may be filled with any suitable conductive fluid, such as saline. The first balloon (1012) and the second balloon (1014) may be electrically insulated from one another. For example, each balloon (1012, 1014) may have an associated insulated conductor, each conductor having sufficient electrical insulation to maintain a potential difference of at least 700 V across its thickness without breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference across its thickness between about 200 V and about 2500 V, including all values ​​and subranges therebetween. For example, the conductors of the second balloon (1014) may be insulated as they extend through the first balloon (1012).

[0208] In some embodiments, the first and second balloons (1012, 1014) may form an anode-cathode pair. For example, in one embodiment, the first and second balloons may carry electrically isolated saline fluid, and the first balloon (1012) may be configured as a cathode and the second balloon (1014) may be configured as an anode, or vice versa, where electrical energy may be capacitively coupled across the balloons or the saline-filled electrode. The device (1010) may receive a pulsed waveform to be delivered to the tissue (1002). For example, one or more biphasic signals may be applied so that tissue may be ablated between the first balloon (1012) and the second balloon (1014) at a desired location in the pulmonary vein (1004). The first and second balloons (1012, 1014) may confine the electric field substantially between the first balloon (1012) and the second balloon (1014) to reduce the electric field and damage to tissue away from the ostium (1002) of the pulmonary vein (1004). In another embodiment, one or both of the electrodes (1018) and the electric field (1019) disposed proximal and distal to the first balloon, respectively, may be used as electrodes of one polarity, while the fluid in the first balloon may act as an electrode of the opposite polarity. A biphasic pulse waveform may then be delivered between these electrodes of opposite polarity by capacitive coupling across the balloons to create a zone of irreversible electroporative ablation in the area surrounding the first balloon. In some embodiments, one or more of the balloons (1012, 1014) may include a wire mesh.

[0209] 11 is a cross-sectional view of another embodiment of a balloon ablation device (1110) (e.g., structurally and / or functionally similar to ablation device (1010)) disposed in the left atrial cavity (1100) and right atrial cavity (1104) of a heart. The ablation device (1110) may include a balloon (1112) that may be configured to be advanced into and disposed in the right atrial cavity (1104). For example, the balloon (1112) may be disposed in contact with the septum (1106) of the heart. The balloon (1112) may be filled with saline. The device (1110) may further include an electrode (1120) that may be advanced from the right atrial cavity (1104) through the balloon (1112) and septum (1106) into the left atrial cavity (1100). For example, the electrode 1120 may extend from the balloon 1112, puncture the septum 1106, and advance into the left atrial cavity 1100. As the electrode 1120 advances into the left atrial cavity 1100, the distal portion of the electrode 1120 may deform to form a predetermined shape. For example, the distal portion of the electrode 1120 may include a nonlinear shape, such as a circle, an ellipsoid, or any other geometric shape. In FIG. 11 , the distal portion of the electrode 1120 forms a loop that may surround one or more ostia of a pulmonary vein 1102 in the left atrial cavity 1100. In other embodiments, the distal portion of the electrode 1120 may have a diameter approximately the same as the ostia of the pulmonary vein 1102.

[0210] The balloon 1112 and the electrode 1120 may be electrically insulated from one another. For example, the balloon 1112 and the electrode 1120 may each include an insulated conductor 1114, 1122, each conductor 1114, 1122, with sufficient electrical insulation to maintain a potential difference of at least 700 V across its thickness without breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2000 V, including all values ​​and subranges therebetween, across its thickness without breakdown. The conductor 1122 of the electrode 1120 may be insulated through the balloon 1112. In some embodiments, the saline in the balloon 1112 and the electrode 1120 may form an anode-cathode pair. For example, the balloon 1112 may be configured as a cathode, and the electrode 1120 may be configured as an anode. The device 1110 may receive a pulsed waveform delivered to the ostium of the pulmonary vein 1102. For example, a biphasic signal may be applied to ablate tissue. The pulsed waveform creates a strong electric field around the electrode 1120, and a current is applied to the balloon 1112 via capacitive coupling to complete the circuit. In some embodiments, the electrode 1120 may comprise a high-gauge wire, and the balloon 1112 may comprise a wire mesh.

[0211] In another embodiment, the electrode (1120) may be advanced through the pulmonary vein (1102) and disposed at one or more of the pulmonary vein ostia without advancing through the balloon (1112) and / or septum (1106). The balloon (1112) and electrode (1120) may be configured as a cathode-anode pair and receive a pulse waveform in a manner similar to that discussed above.

[0212] Return electrode Some embodiments of the ablation systems described herein may further include a return electrode or a distributed set of return electrodes coupled to the patient to reduce the risk of unintended damage to healthy tissue. Figures 12A-12B are schematic diagrams of a set of return electrodes (1230) (e.g., return pads) of an ablation system disposed on a patient (1200). A set of four ostia of pulmonary veins (1210) in the left atrium is shown in Figures 12A-12B. The electrodes (1220) of the ablation device may be positioned around one or more of the ostia of the pulmonary veins (1210). In some embodiments, the set of return electrodes (1230) may be disposed on the back of the patient (1200) so that current passes from the electrodes (1220) through the patient (1200) and returns to the return electrodes (1230).

[0213] For example, one or more return electrodes may be disposed on the patient's (1200) skin. In one embodiment, eight return electrodes (1230) may be positioned on the patient's back to surround the pulmonary vein ostia (1210). A conductive gel may be applied between the return electrodes (1230) and the skin to improve contact. It should be understood that any of the ablation devices described herein may be used with one or more return electrodes (1230). In Figures 12A-12B, electrodes (1220) are disposed around four ostia (1210).

[0214] 12B shows energized electrodes 1220 forming an electric field 1240 around the ostium 1210 of a pulmonary vein. Return electrodes 1230 then receive the monophasic and / or biphasic waveforms delivered by the electrodes 1220. In some embodiments, the number of return electrodes 1230 may be approximately inversely proportional to the surface area of ​​the return electrodes 1230.

[0215] For each ablation device discussed herein, the electrodes (e.g., ablation electrode, return electrode) may comprise a biocompatible metal such as titanium, palladium, silver, platinum, or a platinum alloy. For example, the electrodes may preferably comprise platinum or a platinum alloy. Each electrode may include a conductor having sufficient electrical insulation to maintain a potential difference of at least 700 V across its thickness without breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference of between about 200 V and about 2500 V across its thickness, including all values ​​and subranges therebetween. The insulated conductors run to the proximal handle portion of the catheter, from which they can be connected to an appropriate electrical connector. The catheter shaft may be made of a flexible polymeric material such as Teflon, nylon, or Pebax.

[0216] II. Method Also described herein are methods for ablating tissue in a heart cavity using the above-described systems and devices. The heart cavity may be the left atrial cavity and may include its associated pulmonary vein. Generally, the methods described herein include introducing a device and positioning it in contact with one or more pulmonary vein ostium or cavity regions. A pulse waveform may be delivered to one or more electrodes 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 levels of hierarchy to reduce total energy delivery. Tissue ablation performed in this manner may be delivered with less energy delivered in synchronization with the paced heartbeat to reduce damage to healthy tissue. It should be understood that any of the ablation devices described herein can be used to ablate tissue, as needed, using the methods described below.

[0217] In some embodiments, the ablation devices described herein may be used for focal ablation of cardiac mechanisms / structures identified as causing arrhythmias. For example, a cardiac electrophysiology diagnostic catheter (e.g., a mapping catheter) may be used to map cardiac structures, such as rotors, that can subsequently be ablated by focal ablation using any of the ablation devices described herein. Focal ablation may create, for example, spot lesions that neutralize the rotor while sparing surrounding tissue. In some embodiments, one or more focal ablation lesions may be formed in combination with one or more boxes or lines to treat cardiac arrhythmias. As a non-limiting example, in some embodiments, a system may include one or more mapping catheters, one or more ablation catheters useful for creating focal ablation lesions (e.g., the ablation devices shown in Figures 9D, 9E, 27A-27C, 28, 29, 30, 31, and 32), and one or more catheters useful for creating box-shaped and / or linear lesions (e.g., the ablation devices shown in Figures 3-8, 9A-9C, 10-12, and 26A-26B).

[0218] 13 is a method (1300) for one embodiment of a tissue ablation process. In some embodiments, the voltage pulse waveforms described herein may be applied during the refractory period of the cardiac cycle to avoid disruption of the heart's sinus rhythm. The method (1300) includes, in steps, introducing a device (e.g., an ablation device such as the ablation device (110) and / or any of the ablation devices (200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 2900, 3000, 3100)) into a cardiac cavity of the left atrium (1302). The device may be advanced and disposed in contact with a pulmonary vein ostium (1304). For example, electrodes of the ablation device may form a generally circular array of electrodes disposed in contact with an inner radial surface at the pulmonary vein ostium. In some embodiments, a pacing signal for cardiac stimulation of the heart may be generated (1306). A pacing signal may then be applied to the heart (1308). For example, the heart may be electrically paced by a cardiac stimulator to ensure pacing capture and establish periodicity and predictability of the cardiac cycle. One or more of atrial pacing and ventricular pacing may be applied. An indication of the pacing signal may be transmitted to a signal generator (1310). A time window during the refractory period of the cardiac cycle during which one or more voltage pulse waveforms may be delivered may then be defined. In some embodiments, the refractory time window follows the pacing signal. For example, a common refractory time window may be between the atrial refractory time window and the ventricular refractory time window.

[0219] The pulse waveforms may be generated synchronously with the pacing signal (1312). For example, the voltage pulse waveforms may be applied at a common refractory time window. In some embodiments, the pulse waveforms may be generated with a time offset relative to the display of the pacing signal. For example, the start of the refractory time window may be offset from the pacing signal by a time offset. The voltage pulse waveform(s) may be applied over a series of heartbeats spanning a corresponding common refractory time window. The generated pulse waveforms may be delivered to tissue (1314). In some embodiments, the pulse waveforms may be delivered to the ostia of pulmonary veins in the patient's heart via one or more splines of a set of splines of the ablation device. In other embodiments, the voltage pulse waveforms described herein may be selectively delivered to a subset of electrodes, such as an anode-cathode subset, for pulmonary vein isolation and ablation. For example, a first electrode of a group of electrodes may be configured as an anode and a second electrode of the group of electrodes may be configured as a cathode. These steps may be repeated for the desired number of ablated pulmonary vein ostia or cavity regions (eg, one, two, three, or four ostia).

[0220] In some embodiments, the hierarchical voltage pulse waveforms with nested structures and time interval hierarchies described herein are useful for irreversible electroporation, providing control and selectivity across different tissue types. Figure 14 is a flowchart (1400) of another embodiment of a tissue ablation process. The method (1400) includes introducing a device (e.g., an ablation device such as any of the ablation devices (200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 2900, 3000, 3100)) into a cardiac cavity of the left atrium (1402). The device may be advanced to be disposed at a pulmonary vein ostium (1404). In embodiments in which the device may include first and second configurations (e.g., compact and expanded), the device may be introduced in the first configuration and transition to the second configuration to contact tissue at or near the pulmonary vein ostium or ostium (1406). The device may include electrodes, which may be configured in anode-cathode subsets as discussed in detail above 1408. For example, a subset of the device's electrodes may be selected as anodes, while another subset of the device's electrodes may be selected as cathodes, and a voltage pulse waveform may be applied between the anodes and cathodes.

[0221] The pulse waveform may be generated by a signal generator (e.g., signal generator 122) and may include multiple levels in a hierarchy (1410). Various hierarchical waveforms may be generated using the signal generators disclosed herein. For example, a pulse waveform may include a first level of a hierarchy of pulse waveforms including a first set of pulses. Each pulse has a pulse duration and a first time interval separating successive pulses. A second level of the hierarchy of pulse waveforms may include a first set of multiple pulses as a second set. A second time interval may separate the first set of successive pulses. The second time interval may be at least three times the duration of the first time interval. A third level of the hierarchy of pulse waveforms may include a second set of multiple pulses as a third set of pulses. A third time interval may separate the second set of successive pulses. The third time interval may be at least 30 times the duration of the time intervals of the second level.

[0222] While the examples herein identify distinct monophasic and biphasic waveforms, it should be understood that combination waveforms can also be generated in which some portions of the waveform hierarchy are monophasic and other portions are biphasic. Hierarchically structured voltage pulse waveforms may be applied across different anode-cathode subsets (optionally with a time delay). As described above, one or more waveforms applied to the anode-cathode subsets may be applied during the refractory period of the cardiac cycle. The pulse waveforms may be delivered to the tissue (1412). It should be understood that the steps described in Figures 13 and 14 may be combined and modified as needed.

[0223] 15-18 depict an embodiment of a method for ablating tissue in an atrial chamber of a heart as described above using an ablation device described herein (e.g., FIGS. 2-5). FIG. 15 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial chamber of a heart using an ablation device (1500) corresponding to the ablation device (210) depicted in FIG. 2. A left atrial chamber (1502) having four pulmonary veins (1504) is depicted, and the ablation device (1500) may be used to sequentially ablate tissue to electrically isolate one or more of the pulmonary veins (1504). As shown in FIG. 15, the ablation device (1500) may be introduced into a cardiac chamber, such as the left atrial chamber (1502), using a transseptal approach (e.g., extending from the right atrial chamber through the septum to the left atrial chamber (1502)). The ablation device 1500 may include a catheter 1510 and a guidewire 1520 slidable within the lumen of the catheter 1510. A distal portion of the catheter 1510 may include a set of electrodes 1512. A distal portion 1522 of the guidewire 1520 may be advanced into the left atrial cavity 1502 so as to be disposed near the ostium of a pulmonary vein 1504. The catheter 1510 may then be advanced over the guidewire 1520 to position the electrodes 1512 near the ostium of the pulmonary vein 1504. When the electrodes 1512 contact the ostium of the pulmonary vein 1504, the electrodes 1512 may be configured as an anode-cathode subset. Voltage pulse waveforms generated by a signal generator (not shown) may be delivered to tissue using electrodes (1512) in synchronization with the paced heartbeat and / or may include waveform hierarchy. After completing tissue ablation in one of the pulmonary veins (1504), the catheter (1510) and guidewire (1520) may be repositioned in another pulmonary vein (1504) to ablate tissue in one or more of the remaining pulmonary veins (1504).

[0224] Figure 16 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial cavity of a heart using an ablation device (1600) corresponding to the ablation device (310) depicted in Figure 3. A left atrial cavity (1602) having four pulmonary veins (1604) is depicted, and the ablation device (1600) can be used to sequentially ablate tissue to electrically isolate one or more of the pulmonary veins (1604). As shown in Figure 16, the ablation device (1600) can be introduced into a cardiac cavity, such as the left atrial cavity (1602), using a transseptal approach. The ablation device (1600) can include a sheath (1610) and a catheter (1620) slidable within the lumen of the sheath (1610). A distal portion (1622) of the catheter (1620) can include a set of electrodes. A distal portion (1622) of the catheter (1620) may be advanced into the left atrial cavity (1602) such that the electrodes are disposed near the ostia of the pulmonary veins (1604). Once the electrodes contact the ostia of the pulmonary veins (1604), the electrodes may be configured in an anode-cathode subset. Voltage pulse waveforms generated by a signal generator (not shown) may be delivered to tissue using the electrodes in synchronization with the paced heartbeat and / or may include waveform hierarchy. After completing tissue ablation in a pulmonary vein (1604), the catheter (1620) may be repositioned in another pulmonary vein (1604) to ablate tissue in one or more of the remaining pulmonary veins (1604).

[0225] Figure 17 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial cavity of a heart using an ablation device corresponding to the ablation device (410) depicted in Figure 4. A left atrial cavity (1702) having four pulmonary veins (1704) is depicted, and the ablation device (1700) can be used to ablate tissue to electrically isolate one or more of the pulmonary veins (1704). As shown in Figure 17, the ablation device (1700) can be introduced into a cardiac cavity, such as the left atrial cavity (1702), using a transseptal approach. The ablation device (1700) can include a sheath (1710) and multiple catheters (1720, 1721) slidable within the lumen of the sheath (1710). Each of the catheters (1720, 1721) may include a respective guidewire (1722, 1723) slidable within the catheter (1720, 1721). Distal portions of the guidewires (1722, 1723) may include electrodes configured to deliver a voltage pulse waveform. Each of the catheters (1720, 1721) and the corresponding guidewire (1722, 1723) may be advanced into the left atrial cavity (1702) so as to be disposed near the respective ostia of the pulmonary vein (1704). When the guidewire electrodes (1722, 1723) contact the ostia of the pulmonary vein (1704), the electrodes may be configured as an anode-cathode subset. For example, the first guidewire (1722) may be configured as an anode, and the second guidewire (1723) may be configured as a cathode. In this configuration, a voltage pulse waveform generated by a signal generator (not shown) may be delivered for ablation and simultaneous isolation of a pair of pulmonary veins (1704). Additionally or alternatively, the voltage pulse waveform may be delivered to tissue using electrodes synchronous with a paced heartbeat and / or may include waveform hierarchy. After completing tissue ablation in two of the pulmonary veins (1704), the catheters (1720, 1721) may be repositioned to ablate tissue in the remaining two pulmonary veins (1704).In some embodiments, the sheath (1710) may include three or four catheters disposed in the pulmonary veins (1704).

[0226] Figure 18 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial cavity of a heart using an ablation device 1800 corresponding to the ablation device 500 depicted in Figure 5. A left atrial cavity 1802 having four pulmonary veins 1804 is depicted, and the ablation device 1800 can be used to sequentially ablate tissue to electrically isolate one or more of the pulmonary veins 1804. As shown in Figure 18, the ablation device can be introduced into a cardiac cavity, such as the left atrial cavity 1802, using a transseptal approach. The ablation device can include a sheath 1820 and a catheter 1810 slidable within the lumen of the sheath 1820. A distal portion 1812 of the catheter 1810 can be flower-shaped, as discussed in detail with respect to Figure 5. The distal portion 1812 of the catheter 1810 may be advanced into the left atrial cavity 1802 in a compact first configuration and disposed near the ostium of a pulmonary vein 1804. The distal portion 1812 of the catheter 1810 may then transition to an expanded second configuration to form the flower-shaped distal portion shown in FIG. 18 such that the distal portion 1812 of the catheter 1810 is disposed near the ostium of the pulmonary vein 1804. When the electrodes contact the ostium of the pulmonary vein 1804, the electrodes may be configured in an anode-cathode subset. Voltage pulse waveforms generated by a signal generator (not shown) may be delivered to tissue using the electrodes in synchronization with the paced heartbeat and / or may include waveform hierarchy. After completing tissue ablation in a pulmonary vein (1804), the catheter (1810) may be repositioned in another pulmonary vein (1804) to ablate tissue in one or more of the remaining pulmonary veins (1804).

[0227] Any of the methods described herein (e.g., FIGS. 13-18) may further include coupling a return electrode (e.g., one or more return electrodes (1230) depicted in FIGS. 12A-12B) to the patient's back configured to safely remove current from the patient during application of the voltage pulse waveform.

[0228] 19A-20B depict embodiments of electrodes disposed in contact around the ostium of a pulmonary vein and the electric field generated thereby. FIG. 19A is a schematic representation (1900) of an embodiment of a set of electrodes (1910) disposed at the ostium of a pulmonary vein (1904). The left atrial cavity (1902) may include a blood pool (1906), and the pulmonary vein (1904) may include a blood pool (1908). The left atrial cavity (1902) and the pulmonary vein (1904) may each have a wall thickness of up to approximately 4 mm.

[0229] FIG. 19B is another schematic representation (1900) of a set of electrodes (1910) radially disposed along the inner surface of a pulmonary vein (1904). The pulmonary vein (1904) may include an arterial wall (1905) containing a blood pool (1908). Adjacent electrodes (1910) may be spaced a predetermined distance (1911) apart. In some embodiments, the pulmonary vein (1904) may have an inner diameter of approximately 16 mm. In FIGS. 19A-19B, the electrodes (1910) may have a length of approximately 10 mm and be spaced approximately 4 mm apart from one another. It should be understood that the electrodes (1910) may, in other embodiments, be any of the electrodes disclosed herein. For example, the electrodes (1910) may include the flower-shaped distal electrodes of FIG. 5 and / or the generally circular array of electrodes depicted in FIG. 3.

[0230] 20A-20B are schematic representations (2000) of an embodiment of an electric field (2020) generated by a set of electrodes (2010) disposed at the ostium of a pulmonary vein (2002). While FIG. 20A shows a perspective view of the outer wall of the pulmonary vein (2002) and the left atrial cavity (2004), FIG. 20B shows a cross-sectional view thereof. The shaded electric field (2020) indicates when the electric field (2020) exceeds a threshold value when adjacent electrodes (2010) deliver energy (e.g., a voltage pulse waveform) to ablate tissue. For example, the electric field (2020) represents a potential difference of 1500 V applied between adjacent electrodes (2010). Under this applied voltage, the electric field (2020) strength may be sufficient to at least exceed a threshold of 500 V / cm within the shaded capacitive electric field (2020) and produce irreversible ablation in cardiac tissue. By arranging pulse waveforms across adjacent pairs of electrodes (2010) as described in detail above, the pulmonary vein (2002) ostium can be ablated to electrically isolate the pulmonary vein (2002) from the left atrial cavity (2004).

[0231] Pulse waveform Disclosed herein are methods, systems, and devices for the selective and rapid application of pulsed electric fields / waveforms to achieve tissue ablation by irreversible electroporation. The pulse waveform(s) disclosed herein can be used with the systems (100), devices (e.g., 200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 1230, 1500, 1600, 1700, 1800, 1910, 2010, 2900, 3000, 3100), and methods (e.g., 1300, 1400) disclosed herein. Some embodiments are directed to pulsed high-voltage waveforms in conjunction with sequenced delivery schemes for delivering energy to tissue via a set of electrodes. In some embodiments, peak electric field values ​​can be reduced and / or minimized while maintaining a sufficiently high electric field strength in the area where tissue ablation is desired. This also reduces the likelihood of excessive tissue damage or electrical arcing and localized high temperatures. In some embodiments, a system useful for irreversible electroporation includes a signal generator and a processor that can be configured to apply a pulse voltage waveform to a selected plurality of electrodes or a subset of electrodes of an ablation device. In some embodiments, the processor is configured to control inputs such that a selected subset of anode-cathode electrode pairs can be sequentially triggered based on a predetermined sequence; in one embodiment, the sequenced delivery can be triggered from a cardiac stimulator and / or a pacing device. In some embodiments, to avoid disruption of the heart's sinus rhythm, the ablation pulse waveform is applied during the refractory period of the cardiac cycle. One example way 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 within the refractory period within this cardiac cycle during which the ablation waveform is delivered.

[0232] In some embodiments, the pulse voltage waveforms disclosed herein are hierarchical in organization and have a nested structure. In some embodiments, the pulse waveforms include hierarchical groupings of pulses with various associated timescales. Furthermore, the associated timescales and pulse widths, as well as the number of pulses and hierarchical groupings, can be selected to satisfy one or more of a set of Diophantine inequalities involving the frequency of cardiac pacing.

[0233] The pulse waveforms for electroporation energy delivery disclosed herein can enhance the safety, efficiency, and effectiveness of energy delivery by lowering the electric field threshold associated with irreversible electroporation, resulting in more effective ablation lesions with reduced total energy delivered, which may expand the clinical application of electroporation to include the therapeutic treatment of various cardiac arrhythmias.

[0234] FIG. 21 shows a pulse voltage waveform in the form of a series of rectangular double pulses, with each pulse, such as pulse (2100), associated with a pulse width or duration. The pulse width / duration can be about 0.5 microseconds, about 1 microsecond, about 5 microseconds, about 10 microseconds, about 25 microseconds, about 50 microseconds, about 100 microseconds, about 125 microseconds, about 140 microseconds, or about 150 microseconds, including all values ​​and subranges therebetween. The pulse waveform in FIG. 21 shows a set of monophasic pulses in which all pulses have the same polarity (all positive in FIG. 21, measured from a zero baseline). In some embodiments, such as irreversible electroporation applications, the height (2100) of each pulse or the voltage amplitude (2100) of the pulse can range from about 400 volts, about 1,000 volts, about 5,000 volts, about 10,000 volts, or about 15,000 volts, including all values ​​and subranges therebetween. As shown in Figure 21, pulses (2100) are separated from adjacent pulses by a time interval (2102), also referred to as a first time interval. The first time interval can be about 10 microseconds, 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 produce irreversible electroporation.

[0235] FIG. 22 introduces a pulse waveform with a hierarchical structure of nested pulses. FIG. 22 shows a series of monophasic pulses, such as pulses (2200) of pulse width / pulse duration w, separated by a time interval (also referred to as a first time interval), such as duration t1 (2202), between successive pulses, m1 of which are arranged to form a group of pulses (2210) (also referred to as a first set of pulses). The waveform further includes m2 groups of pulses (also referred to as a second set of pulses), separated by a time interval (2212) (also referred to as a second time interval) of duration t2 between successive groups. A group of pulses, such as the set of m2 marked by (2220) in FIG. 22, constitutes the next level of the hierarchy, which may be referred to as a packet and / or a third set of pulses. Both the pulse width and the time interval between pulses, t1, may range from microseconds to hundreds of microseconds, including all values ​​and subranges in between. In some embodiments, the time interval, t2, may be at least three times greater than the time interval, t1. In some embodiments, the ratio t2 / t1 can be in the range of about 3 to about 300, including all values ​​and subranges therebetween.

[0236] FIG. 23 further illustrates the structure of a nested pulse hierarchical waveform. In this figure, a series of m pulses (individual pulses not shown) forms a group of pulses (2300) (e.g., a first set of pulses). A series of m such groups separated by an inter-group time interval (2310) of duration t (e.g., a second time interval) between one group and the next form a packet 132 (e.g., a second set of pulses). A series of m such packets separated by a time interval (2312) of duration t (e.g., a third time interval) between one packet and the next level form a superpacket (e.g., a third set of pulses) at the next level of the hierarchy, labeled (2320) in the figure. In some embodiments, time interval t may be at least about 30 times greater than time interval t. In some embodiments, time interval t may be at least 50 times greater than time interval t. In some embodiments, the ratio t / t 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 range anywhere from 500 volts to 7,000 volts or more, including all values ​​and subranges therebetween.

[0237] FIG. 24 provides an example of a biphasic waveform sequence with a hierarchical structure. In the illustrated example, a biphasic pulse, such as (2400), has a positive voltage portion and a negative voltage portion to complete one cycle of the pulse. There is a time delay (2402) (e.g., a first time interval) between adjacent cycles of duration t1 and n1, and such cycles form a group of pulses (2410) (e.g., a first set of pulses). A series of n2 groups, separated by an inter-group time interval (2412) (e.g., a second time interval) of duration t2 between one group and the next, form a packet (2420) (e.g., a second set of pulses). The figure also shows a second packet (2430) with a time delay (2432) (e.g., a third time interval) of duration t3 between packets. As with monophasic pulses, higher-level hierarchical structures can also be formed. The amplitude of each pulse or the voltage amplitude of a biphasic pulse may range anywhere from 500 volts to 7,000 volts or more, including all values ​​and subranges therebetween. The pulse width / pulse duration may range from nanoseconds or subnanoseconds to tens of microseconds, and the delay t1 may range from 0 to several microseconds. The inter-group 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.

[0238] The embodiments disclosed herein may include waveforms structured as hierarchical waveforms, including waveform elements / pulses at various levels of the hierarchy. Individual pulses, such as (2200) in FIG. 22, comprise a first level of the hierarchy and have an associated pulse duration and a first time interval between successive pulses. A set of pulses, or elements of the first level structure, form a second level of the hierarchy, such as the group of pulses / second set of pulses (2210) in FIG. 22. Other parameters associated with the waveform include the total duration of the second set of pulses (not shown), the total number of first level elements / first set of pulses, and the second time interval between successive first level elements that describe the second level structure / second set of pulses. In some embodiments, the total duration of the second set of pulses may be between about 20 microseconds and about 10 milliseconds, including all values ​​and subranges therebetween. A set of groups, second sets of pulses, or elements of the second level structure form a third level of the hierarchy, such as the third set of packets / pulses (2220) in FIG. 22. Among other parameters are the total duration of the third set of pulses (not shown), the total number of second level elements / second set of pulses, and the third time interval between successive second level elements describing the third level structure / third set of pulses. In some embodiments, the total duration of the third set of pulses may be between about 60 microseconds and about 200 milliseconds, including all values ​​and subranges therebetween. The general repeating or nested structure of the waveform may continue to multiple higher levels, such as a 10-level or greater structure.

[0239] In some embodiments, hierarchical waveforms with nested structures and time interval hierarchies described herein are useful for irreversible electroporation ablation energy delivery, providing sufficient control and selectivity for application in different tissue types. A variety of hierarchical waveforms can be generated using an appropriate pulse generator. While the examples herein identify monophasic and biphasic waveforms separately for clarity, it should be understood that combination waveforms in which some portions of a waveform hierarchy are monophasic and other portions are biphasic can also be generated / implemented.

[0240] In some embodiments, the ablation pulse waveforms described herein are applied during the refractory period of the cardiac cycle to avoid disruption of the heart's sinus rhythm. In some embodiments, the treatment method includes electrically pacing the heart with a cardiac stimulator to ensure pacing capture and establish periodicity and predictability of the cardiac cycle, and then defining a time window within the refractory period within the cardiac cycle during which one or more pulse ablation waveforms can be delivered. FIG. 25 illustrates an example in which both atrial and ventricular pacing are applied (e.g., using pacing leads or catheters located in the right atrium and right ventricle, respectively). With time on the horizontal axis, FIG. 25 illustrates a series of ventricular pacing signals, such as (2500) and (2510), and a series of atrial pacing signals (2520, 2530), along with a series of ECG waveforms (2540, 2542) driven by the pacing signals. As indicated by the thick arrows in FIG. 25, there are atrial refractory time windows (2522) and ventricular refractory time windows (2502) following the atrial pacing signal (2522) and the ventricular pacing signal (2500), respectively. As shown in FIG. 25, the time period T r A common refractory time window (2550) may be defined to be within the refractory time windows (2522, 2502) of both the atrium and the ventricle. In some embodiments, electroporation ablation waveform(s) may be applied during this common refractory time window (2550). The start of this refractory time window (2522) is offset from the pacing signal (2500) by a time offset (2504), as shown in FIG. 25 . In some embodiments, the time offset (2504) may be less than approximately 25 milliseconds. At the next heartbeat, the similarly defined common refractory time window (2552) is the next time window available for application of the ablation waveform. In this manner, the ablation waveform(s) are applied over a series of heartbeats, each heartbeat remaining within the common refractory time window. In one embodiment, each packet of pulses defined above in the pulse waveform hierarchy may be applied over a series of heartbeats, such that a series of packets is applied to a given set of electrodes over a series of heartbeats.

[0241] It should be understood that the examples and illustrations in this disclosure are for illustrative purposes and that deviations and modifications, such as the number of splines, number of electrodes, etc., can be constructed and deployed in accordance with the present teachings without departing from the scope of the present invention.

[0242] 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 stated 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.

[0243] Some embodiments described herein relate to computer storage products with non-transitory computer-readable media (also called non-transitory processor-readable media) having instructions or computer code for performing various computer-implemented operations. The computer-readable media (or processor-readable media) are non-transitory in the sense that they do not themselves comprise transitory propagating signals (e.g., propagating electromagnetic waves that carry information over a transmission medium such as space or a cable). The media and computer code (also called code or algorithms) are designed and constructed for a specific purpose. Examples of non-transitory computer-readable media include, but are not limited to, magnetic storage media such as hard disks, floppy disks, and magnetic tape; optical storage media such as compact disks / digital video disks (CDs / DVDs); compact disk read-only memories (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 memory (ROMs), and random access memory (RAM) devices. Other embodiments described herein relate to computer program products that may include, for example, instructions and / or computer code disclosed herein.

[0244] The systems, devices, and / or methods described herein may be implemented by software (executed in 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) can be expressed in various 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 generated by a compiler, code used to create web services, and files containing high-level instructions executed by a computer using an interpreter. Other examples of computer code include, but are not limited to, control signals, encryption code, and compression code.

[0245] The specific examples and descriptions herein are exemplary in nature and enable one skilled in the art to develop embodiments based on the teachings herein without departing from the scope of the invention, which is limited only by the appended claims.

[0246] The above-described embodiment has the features described in the following supplementary notes. (Appendix 1) 1. An apparatus comprising: a first catheter defining a longitudinal axis and a lumen therethrough; a second catheter extending from the distal end of the first catheter lumen; a set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline including a set of electrodes formed on a surface of each of the splines, each electrode having an insulated wire associated therewith, the insulated wire being disposed in a body of each of the set of splines; the second catheter is configured to translate along the longitudinal axis to transition between a first configuration and a second configuration; In the first configuration, the set of splines is generally parallel to the longitudinal axis; In the second configuration, at least a portion of each spline of the set of splines extends distally relative to the distal end of the second catheter.

[0247] (Appendix 2) 1. An apparatus comprising: a first catheter defining a longitudinal axis and a lumen therethrough; a second catheter extending from the distal end of the first catheter lumen; a set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline including a set of electrodes formed on a surface of each of the splines, each electrode having an insulated wire associated therewith, the insulated wire being disposed in a body of each of the set of splines; the second catheter is configured to translate along the longitudinal axis to transition between a first configuration and a second configuration; In the first configuration, the set of splines is generally parallel to the longitudinal axis; wherein in the second configuration, each spline of the set of splines has a longitudinal axis in the second configuration that is at an angle of less than about 80 degrees relative to the longitudinal axis of the first catheter.

[0248] (Appendix 3) 1. An apparatus comprising: a first catheter defining a longitudinal axis and a lumen therethrough; a second catheter extending from the distal end of the first catheter lumen; a set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline including a set of electrodes formed on a surface of each of the splines, each electrode having an insulated wire associated therewith, the insulated wire being disposed in a body of each of the set of splines; the second catheter is configured to translate along the longitudinal axis to transition between a first configuration and a second configuration; In the first configuration, the set of splines is generally close to the longitudinal axis; In the second configuration, each spline of the set of splines forms a loop and is twisted along its length, such that the spline has torsion along its length.

[0249] (Appendix 4) 4. The apparatus of claim 3, wherein each spline of the set of splines is petal-shaped.

[0250] (Appendix 5) 4. The apparatus of claim 3, wherein each spline of the set of splines has a local unit tangent vector and a rotational velocity defined by the derivative of the unit tangent vector with respect to arc length, such that the rotational velocity integrated along the length of the spline is at least π radians.

[0251] (Appendix 6) 6. The apparatus of claim 5, wherein the geometry of the curve defined by the at least one spline is the geometry of a space curve with torsion.

[0252] (Appendix 7) 4. The device of any one of claims 1 to 3, wherein in the second configuration, at least one electrode on each spline of the set of splines is distal to the distal end of the second catheter.

[0253] (Appendix 8) 4. The device of any one of claims 1 to 3, wherein the proximal portion of the set of splines is coupled to the first catheter within a first catheter lumen.

[0254] (Appendix 9) 4. The apparatus of any one of claims 1-3, wherein the second catheter defines a lumen therethrough, and the distal portion of the set of splines is coupled to the second catheter within the second catheter lumen.

[0255] (Appendix 10) 4. The apparatus of any one of appendixes 1 to 3, wherein in the second configuration, each spline of the set of splines does not overlap with an adjacent spline.

[0256] (Appendix 11) 4. The apparatus of any one of clauses 1 to 3, wherein the set of splines deflects radially outward from the longitudinal axis in the second configuration.

[0257] (Appendix 12) 4. The apparatus of any one of claims 1 to 3, wherein the set of splines is biased away from the longitudinal axis in the second configuration.

[0258] (Appendix 13) 4. The device of any one of claims 1 to 3, further comprising an actuator coupled to the set of splines and the second catheter, the actuator configured to transition the set of splines between the first configuration and the second configuration.

[0259] (Appendix 14) 4. The apparatus of any one of claims 1 to 3, wherein the sets of electrodes on adjacent splines have opposite polarities.

[0260] (Appendix 15) 4. The device of any one of claims 1 to 3, wherein the set of splines, when deployed in the second configuration, forms a shape having an effective cross-sectional diameter at its largest cross section of about 10 mm to about 35 mm.

[0261] (Appendix 16) 4. The apparatus of any one of appendixes 1 to 3, wherein the set of splines includes between 3 splines and 14 splines.

[0262] (Appendix 17) 4. The apparatus of any one of claims 1 to 3, wherein each spline of the set of splines has a diameter of about 1 mm to about 5 mm.

[0263] (Appendix 18) 4. The device of any one of appendixes 1 to 3, wherein each electrode of the set of electrodes has a diameter of about 1 mm to about 5 mm.

[0264] (Appendix 19) 4. The device of claim 1, wherein the insulated conductor is disposed in the body of the second catheter, the insulated conductor configured to maintain a potential of at least about 700 V without breakdown of its corresponding insulation.

[0265] (Appendix 20) 1. A system comprising: a signal generator configured to generate a pulse waveform; an ablation device coupled to the signal generator and configured to receive the pulse waveform, the ablation device comprising: a first catheter defining a longitudinal axis and a lumen therethrough; a second catheter extending from the distal end of the first catheter lumen; a handle coupled to the second catheter; a set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline including a set of electrodes formed on a surface of each of the splines, each electrode having an insulated wire associated therewith, the insulated wire being disposed in a body of each of the set of splines; the second catheter is configured to translate along the longitudinal axis to transition between a first configuration and a second configuration; In the first configuration, the set of splines is generally close to the longitudinal axis; In the second configuration, at least a portion of each spline of the set of splines extends distally relative to the distal end of the second catheter.

[0266] (Appendix 21) 21. The system of claim 20, wherein in the second configuration, at least one electrode on each spline of the set of splines is distal to the distal end of the second catheter.

[0267] (Appendix 22) 21. The system of claim 20, wherein the proximal portion of the set of splines is coupled to the first catheter within a first catheter lumen.

[0268] (Appendix 23) 21. The system of claim 20, wherein the second catheter defines a lumen therethrough, and the distal portion of the set of splines is coupled to the second catheter within the second catheter lumen.

[0269] (Appendix 24) 21. The system of claim 20, wherein in the second configuration, each spline in the set of splines does not overlap with an adjacent spline.

[0270] (Appendix 25) 21. The system of claim 20, wherein the set of splines deflects radially outward from the longitudinal axis in the second configuration.

[0271] (Appendix 26) 21. The system of claim 20, wherein the set of splines is biased away from the longitudinal axis in the second configuration.

[0272] (Appendix 27) 21. The system of claim 20, further comprising an actuator coupled to the set of splines and the second catheter, the actuator configured to transition the set of splines between the first configuration and the second configuration.

[0273] (Appendix 28) 21. The system of claim 20, wherein the sets of electrodes on adjacent splines have opposite polarities.

[0274] (Appendix 29) 21. The system of claim 20, wherein the set of splines, when deployed in the second configuration, forms a shape having an effective cross-sectional diameter at its largest cross section of about 10 mm to about 35 mm.

[0275] (Appendix 30) 21. The system of claim 20, wherein the set of splines includes between 3 splines and 14 splines.

[0276] (Appendix 31) 21. The system of claim 20, wherein each spline of the set of splines has a diameter of about 1 mm to about 5 mm.

[0277] (Appendix 32) 21. The system of claim 20, wherein each electrode of the set of electrodes has a diameter of about 1 mm to about 5 mm.

[0278] (Appendix 33) 21. The system of claim 20, wherein the insulated conductor is disposed in the body of the second catheter, the insulated conductor configured to maintain a potential of at least about 700 V without breakdown of its corresponding insulation.

[0279] (Appendix 34) The pulse waveform is a first level of the hierarchy of pulse waveforms including a first set of pulses, each pulse having a pulse duration and a first time interval separating successive pulses; a second level of the hierarchy of pulse waveforms including the first set of pulses as a second set of pulses, wherein a second time interval separates consecutive first set of pulses, the second time interval being at least three times the duration of the first time interval; and a third level of the hierarchy of pulse waveforms including a second set of pulses as a third set of pulses, wherein a third time interval separates consecutive second set of pulses, the third time interval being at least 30 times the duration of the second time interval.

[0280] (Appendix 35) 1. A method for treating cardiac arrhythmia by irreversible electroporation, comprising: advancing an ablation device into a left atrium of a patient, said ablation device comprising: a first catheter defining a longitudinal axis and a lumen therethrough; a second catheter extending from the distal end of the first catheter lumen; a set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline including a set of electrodes formed on a surface of each of the splines, each electrode having an insulated wire associated therewith, the insulated wire being disposed in a body of each of the set of splines; In the first configuration, the set of splines is generally close to the longitudinal axis; advancing an ablation device in the second configuration such that at least a portion of each spline of the set of splines extends distally relative to the distal end of the second catheter; transitioning the ablation device from a first configuration to a second configuration; generating a set of pulse waveforms; delivering the set of pulse waveforms to a set of adjacent portions of the posterior wall of the left atrium via one or more splines of a set of splines of the ablation device in the second configuration to form a set of ablation zones.

[0281] (Appendix 36) 36. The method of claim 35, wherein, in the second configuration, each spline of the set of splines forms a loop and is twisted along its length, such that the spline has torsion along its length.

[0282] (Appendix 37) 36. The method of claim 35, wherein in the second configuration, each spline of the set of splines has the longitudinal axis in a second configuration that is at an angle of less than about 80 degrees relative to the longitudinal axis of the first catheter.

[0283] (Appendix 38) 36. The method of claim 35, wherein each spline of the set of splines has a rotational velocity defined by the derivative with respect to the arc length of a unit tangent vector such that the rotational velocity integrated along the length of the spline is at least π radians.

[0284] (Appendix 39) 39. The method of claim 38, wherein the geometry of the curve defined by the at least one spline is the geometry of a space curve with torsion.

[0285] (Appendix 40) 36. The method of claim 35, further comprising advancing at least a portion of the set of splines distally relative to the distal end of the second catheter by retracting the second catheter relative to the first catheter.

[0286] (Appendix 41) 36. The method of claim 35, wherein each insulated conductor is configured such that its corresponding insulation maintains a potential of at least about 700 V without breakdown.

[0287] (Appendix 42) the set of splines includes a group of electrodes, the group of electrodes includes the set of electrodes for each spline of the set of splines, and the method comprises: configuring a first electrode of the group of electrodes as an anode; configuring a second electrode of the group of electrodes as a cathode; 36. The method of claim 35, comprising delivering the pulse waveform to the first electrode and the second electrode.

[0288] (Appendix 43) configuring a first set of electrodes of a first spline of the set of splines as an anode; configuring a second set of electrodes of a second spline of the set of splines as a cathode; 36. The method of claim 35, comprising delivering the pulse waveform to the first set of electrodes and the second set of electrodes.

[0289] (Appendix 44) 2. The apparatus of claim 1, wherein each spline of the set of splines is petal-shaped.

[0290] (Appendix 45) 3. The apparatus of claim 2, wherein each spline of the set of splines is petal-shaped.

[0291] (Appendix 46) 1. An apparatus comprising: an outer catheter defining a longitudinal axis and a lumen therethrough; a set of catheters, each extending from a distal end of the outer catheter lumen, each catheter including a proximal portion, a distal portion, and a hinge joining the proximal portion to the distal portion, the distal portion of each catheter including an electrode such that the set of catheters includes a set of electrodes, and each catheter of the set of catheters configured to translate along the longitudinal axis to transition between a first configuration, a second configuration, and a third configuration; In the first configuration, each catheter of the set of catheters is generally parallel to the longitudinal axis; In the second configuration, each catheter of the set of catheters is biased away from the longitudinal axis; In the third configuration, the distal portion of each catheter of the set of catheters rotates about its corresponding hinge.

[0292] (Appendix 47) 47. The apparatus of claim 46, wherein a first electrode of the set of electrodes has a polarity opposite to a polarity of a second electrode of the set of electrodes.

[0293] (Appendix 48) 48. The apparatus of claim 47, wherein insulated conductors are associated with the first and second electrodes, the insulated conductors are disposed in the bodies of the first and second catheters, and the insulated conductors are configured to maintain a potential of at least about 700 V without breakdown of their corresponding insulation.

[0294] (Appendix 49) 47. The apparatus of claim 46, wherein the distal portion of each catheter of the set of catheters is biased away from the longitudinal axis in the second configuration.

[0295] (Appendix 50) 47. The apparatus of claim 46, wherein the first and second electrodes are biased toward each other in the third configuration.

[0296] (Appendix 51) 47. The apparatus of claim 46, wherein in the third configuration, the proximal portion of each catheter is biased away from the longitudinal axis and each electrode in the set of electrodes is biased toward the longitudinal axis.

[0297] (Appendix 52) 47. The apparatus of claim 46, wherein the proximal portion of each catheter of the set of catheters has a radius of curvature of about 1 cm or greater.

[0298] (Appendix 53) 47. The device of claim 46, wherein the distal portion of each catheter of the set of catheters has a length of about 3 mm to about 12 mm.

[0299] (Appendix 54) 48. The device of claim 47, wherein the first and second electrodes have a length of about 1 mm to about 7 mm.

[0300] (Appendix 55) 47. The device of claim 46, wherein the distance between the distal portions of each catheter of the set of catheters in the third configuration is between about 1 mm and about 7 mm.

[0301] (Appendix 56) 47. The device of claim 46, wherein each catheter includes a wire coupled to the hinge.

[0302] (Appendix 57) 47. The device of claim 46, wherein the set of catheters includes two to four catheters.

[0303] (Appendix 58) 47. The device of claim 46, wherein the set of catheters includes 3 to 6 catheters.

[0304] (Appendix 59) 59. The apparatus of claim 58, wherein the proximal portion of each catheter of the set of catheters has a radius of curvature of about 1 cm or greater.

[0305] (Appendix 60) 1. An apparatus comprising: an outer catheter defining a longitudinal axis and a lumen therethrough; a catheter extending from a distal end of the outer catheter lumen, the catheter including a proximal portion, a set of distal portions, and a set of hinges connecting the proximal portion to the set of distal portions, the set of distal portions each including an electrode to define a set of electrodes; the catheter is configured to translate along the longitudinal axis to transition between a first configuration, a second configuration, and a third configuration; In the first configuration, the set of distal portions are generally parallel to the longitudinal axis; In the second configuration, each electrode of the set of electrodes advances away from the distal end of the outer catheter lumen; The device, in the third configuration, is configured such that each electrode of the set of electrodes is biased away from the longitudinal axis.

[0306] (Appendix 61) 61. The device of claim 60, wherein the electrodes on opposing distal portions have opposite polarities.

[0307] (Appendix 62) 61. The apparatus of claim 60, wherein each electrode of the set of electrodes has an associated insulated conductor, the insulated conductors disposed in the catheter body, and the insulated conductors are configured to maintain a potential of at least about 700 V without breakdown of their corresponding insulation.

[0308] (Appendix 63) 61. The device of claim 60, wherein the catheter comprises about 2 to about 4 distal portions.

[0309] (Appendix 64) 61. The device of claim 60, wherein the one or more distal portions are naturally biased to be approximately perpendicular to the longitudinal axis in the third configuration.

[0310] (Appendix 65) 1. A method for focal ablation by irreversible electroporation, comprising: generating a pulse waveform; delivering the pulse waveform to cardiac tissue of the patient via a set of electrodes of a set of catheters of an ablation device, each catheter comprising: A method comprising: a proximal portion, a distal portion, and a hinge connecting the proximal portion to the distal portion.

[0311] (Appendix 66) advancing the catheter set disposed within the lumen of an outer catheter away from the distal end of the outer catheter; 66. The method of claim 65, further comprising rotating each distal portion of the set of catheters about its corresponding hinge.

[0312] (Appendix 67) 66. The method of claim 65, further comprising disposing the ablation device within a cardiac cavity in the left atrium of the heart and in contact with an ostium of a pulmonary vein.

[0313] (Appendix 68) 66. The method of claim 65, wherein the ablation device is configured to generate an electric field strength of about 400 V / cm to about 600 V / cm.

[0314] (Appendix 69) 66. The method of claim 65, wherein each electrode of the set of electrodes has an associated insulated conductor, the insulated conductors disposed in the catheter body, and each insulated conductor is configured to maintain a potential of at least about 700 V without breakdown of its corresponding insulation.

[0315] (Appendix 70) 1. An apparatus comprising: a catheter shaft defining a longitudinal axis and a shaft lumen therethrough; a set of splines extending from a distal end of the shaft lumen, each spline including a set of independently addressable proximal electrodes formed on a surface of each of the splines, each electrode having an associated insulated conductor disposed in a body of each of the one or more splines; a distal cap coupled to a distal portion of each spline of the set of splines, the distal cap including independently addressable distal electrodes formed on a surface of the distal cap, the set of splines configured to translate along the longitudinal axis to transition between a first configuration and a second configuration, the distal electrodes disposed on a distal end face of the second configuration that is generally perpendicular to the longitudinal axis, and the set of proximal electrodes disposed outside the distal end face.

[0316] (Appendix 71) 71. The apparatus of claim 70, wherein the distal electrode has a polarity opposite to the polarity of at least one proximal electrode of the set of proximal electrodes.

[0317] (Appendix 72) 71. The apparatus of claim 70, wherein the set of splines are deflected radially outward from the longitudinal axis in the second configuration and the set of splines are aligned generally parallel to the longitudinal axis in the first configuration.

[0318] (Appendix 73) 71. The apparatus of claim 70, wherein the insulated conductors are configured to maintain a potential of at least about 700 V without breakdown of their corresponding insulation.

[0319] (Appendix 74) 71. The apparatus of claim 70, wherein the sets of electrodes on adjacent splines have opposite polarities.

[0320] (Appendix 75) 71. The device of claim 70, wherein the distal electrode has a length of about 0.5 mm to about 7.0 mm and a cross-sectional diameter of about 0.5 mm to about 4.0 mm.

[0321] (Appendix 76) 71. The device of claim 70, wherein each electrode of the set of electrodes has a length of about 0.5 mm to about 5.0 mm and a cross-sectional diameter of about 0.5 mm to about 2.5 mm.

[0322] (Appendix 77) 71. The device of claim 70, wherein the distance between the distal electrode and the distal end of the distal cap is about 1.0 mm to about 4.0 mm.

[0323] (Appendix 78) 1. An apparatus comprising: a catheter shaft defining a longitudinal axis and a shaft lumen therethrough; a set of splines extending from a distal end of the shaft lumen, each spline including a set of independently addressable electrodes formed on a surface of each of the one or more splines, with an insulated conductor associated with each electrode of the set of electrodes, the insulated conductor being disposed on a body of each of the one or more splines; the set of splines is configured to translate along the longitudinal axis to transition between a first configuration and a second configuration, the set of splines in the first configuration being generally parallel to the longitudinal axis and a distal end of the set of splines in the second configuration being biased away from the longitudinal axis.

[0324] (Appendix 79) 79. The apparatus of claim 78, wherein each spline of the set of splines has a radius of curvature of about 1 cm or greater.

[0325] (Appendix 80) 79. The apparatus of claim 78, wherein each spline of the set of splines has a monotonically increasing radius of curvature.

[0326] (Appendix 81) 79. The apparatus of claim 78, wherein each spline in the set of splines is configured to translate independently along the longitudinal axis.

[0327] (Appendix 82) 79. The device of claim 78, wherein the distal end of each spline of the set of splines is configured to extend from about 8.0 mm to about 20.0 mm from the distal end of the shaft lumen.

[0328] (Appendix 83) 79. The apparatus of claim 78, wherein a distal end of each spline of the set of splines is configured to extend a maximum of about 5 cm from the distal end of the shaft lumen.

[0329] (Appendix 84) 80. The apparatus of claim 78, wherein the insulated conductors are configured to maintain a potential of at least about 700 V without breakdown of their corresponding insulation.

[0330] (Appendix 85) 79. The device of claim 78, wherein the distance between the distal ends of the sets of splines in the second configuration is between about 5.0 mm and about 20.0 mm.

[0331] (Appendix 86) 79. The apparatus of claim 78, wherein the distal electrode of each spline of the set of splines has an opposite polarity to the corresponding proximal electrode.

[0332] (Appendix 87) 1. An apparatus comprising: a catheter shaft defining a longitudinal axis and a shaft lumen therethrough; a set of splines extending from a distal end of the shaft lumen, each spline including a set of proximal electrodes formed on a surface of each of the one or more splines, with an insulated conductor associated with each electrode of the set of proximal electrodes, the insulated conductor being disposed on a body of each of the one or more splines; a distal cap coupled to a distal portion of each spline of the set of splines, the distal cap including at least one independently addressable distal electrode, the set of splines configured to translate along the longitudinal axis to transition between a first configuration and a second configuration, the set of splines in the first configuration being generally parallel to the longitudinal axis and the set of splines in the second configuration being deflected radially outward from the longitudinal axis.

[0333] (Appendix 88) 88. The apparatus of claim 87, wherein the at least one distal electrode has an opposite polarity to at least one electrode in the set of proximal electrodes for each spline in the set of splines.

[0334] (Appendix 89) 88. The apparatus of claim 87, wherein the at least one distal electrode is configured as an anode and at least one electrode in the set of proximal electrodes for each spline in the set of splines is configured as a cathode.

[0335] (Appendix 90) 88. The apparatus of claim 87, wherein the sets of proximal electrodes on adjacent splines have opposite polarities.

[0336] (Appendix 91) 88. The device of claim 87, wherein the at least one distal electrode has a length of about 0.5 mm to about 7 mm and a cross-sectional diameter of about 0.5 mm to about 4.0 mm.

[0337] (Appendix 92) 88. The device of claim 87, wherein the set of proximal electrodes has a length of about 0.5 mm to about 5.0 mm and a cross-sectional diameter of about 0.5 mm to about 2.5 mm.

[0338] (Appendix 93) 88. The device of claim 87, wherein the distance between the at least one distal electrode and the set of proximal electrodes is between about 3.0 mm and about 12.0 mm.

[0339] (Appendix 94) 88. The device of claim 87, wherein the distance between the at least one distal electrode and the distal end of the distal cap is between about 1.0 mm and about 4.0 mm.

[0340] (Appendix 95) 1. A method for treating cardiac arrhythmia by irreversible electroporation, comprising: generating a pulse waveform; delivering the pulse waveform to a portion of a ventricular wall of the patient's heart through one or more splines of a set of splines of an ablation device, each spline comprising: The method includes a set of electrodes formed on a surface of the spline, each electrode of the set of electrodes having an insulated conductor associated therewith, the insulated conductor being disposed in a body of the spline.

[0341] (Appendix 96) 96. The method of claim 95, further comprising disposing the ablation device within a cardiac cavity in the left atrium of the heart and in contact with an ostium of a pulmonary vein.

[0342] (Appendix 97) 96. The method of claim 95, wherein each insulated conductor is configured such that its corresponding insulation maintains a potential of at least about 700 V without breakdown.

[0343] (Appendix 98) the set of splines includes a group of electrodes, the group of electrodes includes the set of electrodes for each spline of the set of splines, and the method comprises: configuring a first electrode of the group of electrodes as an anode; configuring a second electrode of the group of electrodes as a cathode; 96. The method of claim 95, comprising delivering the pulse waveform to the first electrode and the second electrode.

[0344] (Appendix 99) configuring a first set of electrodes of a first spline of the set of splines as an anode; configuring a second set of electrodes of a second spline of the set of splines as a cathode; 96. The method of claim 95, comprising delivering the pulse waveform to the first set of electrodes and the second set of electrodes.

[0345] (Appendix 100) 1. An apparatus comprising: a catheter defining a longitudinal axis; a set of splines coupled to the catheter, each spline of the set of splines including a set of electrodes formed thereon, each set of electrodes including a distal electrode having an exposed portion, such that the set of splines includes a set of distal electrodes; cap electrodes formed at the distal end of the catheter, each distal electrode being closest to the cap electrode compared to other electrodes of its corresponding set of electrodes on the same spline, the cap electrode and each distal electrode of each of the sets of distal electrodes having the same electrical polarity in use, and the set of splines being translated along the longitudinal axis to a first configuration, wherein the set of splines is generally parallel to the longitudinal axis; a first configuration, wherein a distal portion of each spline of the set of splines deflects radially outward from the longitudinal axis and the cap electrode is spaced at most about 3 mm from each distal electrode of the set of distal electrodes.

[0346] (Appendix 101) 101. The device of claim 100, wherein the exposed portion of each distal electrode of the set of distal electrodes is exposed along a portion of the circumference of its corresponding spline.

[0347] (Appendix 102) 101. The device of claim 100, wherein the exposed portion of each of the distal electrodes faces outward from the longitudinal axis in the first configuration.

[0348] (Appendix 103) 101. The device of claim 100, wherein the exposed portion of each distal electrode of the set of distal electrodes forms an angle of about 30 degrees to about 300 degrees around the center of its corresponding spline.

[0349] (Appendix 104) 101. The device of claim 100, wherein the set of distal electrodes has a diameter of about 0.5 mm to about 3 mm.

[0350] (Appendix 105) 101. The apparatus of claim 100, wherein the cap electrode has a cross-sectional diameter of about 1 mm to about 5 mm.

[0351] (Appendix 106) 101. The apparatus of claim 100, wherein each set of electrodes has a set of proximal electrodes, the distal electrode, and the set of proximal electrodes for a given spline having opposite electrical polarities for ablation delivery.

[0352] (Appendix 107) 101. The apparatus of claim 100, wherein the cap electrode and the set of distal electrodes are collectively configured as an anode.

[0353] (Appendix 108) 101. The device of claim 100, wherein each distal electrode of the set of distal electrodes has a length of about 0.5 mm to about 5 mm.

[0354] (Appendix 109) 101. The device of claim 100, wherein the set of splines, when deployed in the second configuration, forms a shape having an effective cross-sectional diameter at its largest point of about 6 mm to about 24 mm.

[0355] (Appendix 110) 101. The device of claim 100, further comprising an outer shaft defining a lumen therethrough, the set of splines extending from about 6 mm to about 30 mm from a distal end of the lumen.

[0356] (Appendix 111) 101. The apparatus of claim 100, wherein the insulated conductors are configured to maintain a potential of at least about 700 V without their corresponding insulation breaking down.

[0357] (Appendix 112) 101. The apparatus of claim 100, wherein the cap electrodes are independently addressable.

[0358] (Appendix 113) 101. The apparatus of claim 100, wherein the cap electrode and each electrode of the set of electrodes are independently addressable.

[0359] (Appendix 114) 101. The apparatus of claim 100, wherein an insulated conductor is associated with each electrode of the set of electrodes, the insulated conductor being disposed in a body of each of the one or more splines.

[0360] (Appendix 115) 1. An apparatus comprising: a catheter defining a longitudinal axis; a set of splines coupled to the catheter, each spline of the set of splines including a set of electrodes formed thereon, each set of electrodes including a distal electrode having an exposed portion such that the set of splines includes a set of distal electrodes, the exposed portion of each distal electrode of the set of distal electrodes forming an angle with respect to its corresponding spline of between about 30 degrees and about 300 degrees around a center of the corresponding spline; a cap electrode formed at the distal end of the catheter, wherein the set of splines translates along the longitudinal axis to a first configuration, wherein the set of splines is generally parallel to the longitudinal axis; a second configuration in which a distal portion of each spline of the set of splines is deflected radially outward from the longitudinal axis.

[0361] (Appendix 116) 116. The device of claim 115, wherein the cap electrode is spaced a maximum of about 3 mm from each distal electrode of the set of distal electrodes.

[0362] (Appendix 117) 116. The apparatus of claim 115, wherein each distal electrode of the set of distal electrodes partially surrounds the outer periphery of its corresponding spline.

[0363] (Appendix 118) 116. The device of claim 115, wherein the exposed portion of each of the set of distal electrodes faces outward from the longitudinal axis in the first configuration.

[0364] (Appendix 119) 116. The device of claim 115, wherein the set of distal electrodes has a diameter of about 0.5 mm to about 3 mm.

[0365] (Appendix 120) 16. The apparatus of claim 115, wherein the cap electrode has a cross-sectional diameter of about 1 mm to about 5 mm.

[0366] (Appendix 121) 116. The apparatus of claim 115, wherein each set of electrodes has a set of proximal electrodes, the distal electrode, and the set of proximal electrodes for a given spline having opposite electrical polarities during ablation energy delivery.

[0367] (Appendix 122) 116. The apparatus of claim 115, wherein the cap electrode and the set of distal electrodes are collectively configured as an anode.

[0368] (Appendix 123) 116. The device of claim 115, wherein each distal electrode of the set of distal electrodes has a length of about 0.5 mm to about 5.0 mm.

[0369] (Appendix 124) 116. The apparatus of claim 115, wherein the set of splines, when deployed in the second configuration, forms a shape having an effective cross-sectional diameter at its largest section of about 6 mm to about 24 mm.

[0370] (Appendix 125) 116. The device of claim 115, further comprising an outer shaft defining a lumen therethrough, the set of splines extending from about 6 mm to about 24 mm from a distal end of the lumen.

[0371] (Appendix 126) 116. The apparatus of claim 115, wherein the insulated conductors are configured to maintain a potential of at least about 700 V without breakdown of their corresponding insulation.

[0372] (Appendix 127) 116. The apparatus of claim 115, wherein the cap electrodes are independently addressable.

[0373] (Appendix 128) 116. The apparatus of claim 115, wherein the cap electrode and each electrode of the set of electrodes are independently addressable.

[0374] (Appendix 129) 116. The apparatus of claim 115, wherein an insulated conductor is associated with each electrode of the set of electrodes, the insulated conductor being disposed in a body of each of the one or more splines.

[0375] (Appendix 130) 1. An apparatus comprising: a catheter shaft defining a longitudinal axis; a set of splines coupled to the catheter shaft, each spline of the set of splines including a set of electrodes formed thereon, each set of electrodes including a distal electrode, such that the set of splines includes a set of distal electrodes; a cap electrode formed at the distal end of the catheter, wherein the set of splines translates along the longitudinal axis to a first configuration, wherein the set of splines is generally parallel to the longitudinal axis; a first configuration in which a distal portion of each spline of the set of splines is deflected radially outward from the longitudinal axis, the cap electrode is spaced a maximum of about 3 mm from each distal electrode of the set of distal electrodes, and the distal portion of each spline of the set of splines is angled between about 60 degrees and about 90 degrees relative to the longitudinal axis.

[0376] (Appendix 131) 131. The device of claim 130, wherein each distal electrode of the set of distal electrodes has an exposed portion that forms an angle of about 30 degrees to about 300 degrees around the center of its corresponding spline.

[0377] (Appendix 132) 1. An apparatus comprising: a catheter shaft defining a longitudinal axis and a shaft lumen therethrough; a set of splines extending from a distal end of the shaft lumen, each spline of the set of splines including a set of electrodes formed on a surface of the spline; a distal cap coupled to a distal portion of each spline of the set of splines, the set of splines configured to translate along the longitudinal axis to transition between a first configuration and a second configuration, the first configuration including the distal cap coupled to the distal end of the catheter shaft a first distance and the second configuration including the distal cap coupled to the distal end of the catheter shaft a second distance, the ratio of the first distance to the second distance being between about 5:1 and about 25:1.

[0378] (Appendix 133) 1. An apparatus comprising: a catheter shaft defining a longitudinal axis and a shaft lumen therethrough; a set of splines extending from a distal end of the shaft lumen, each spline of the set of splines including a set of electrodes formed on a surface of the spline; a distal cap coupled to a distal portion of each spline of the set of splines, the set of splines configured to translate along the longitudinal axis to transition between a first configuration and a second configuration, wherein in the first configuration each spline lies in a cylindrical surface that is generally parallel to the longitudinal axis of the catheter shaft, and in the second configuration at least a portion of each spline of the set of splines has a radius of curvature of between about 7 mm and about 25 mm.

[0379] (Appendix 134) 1. An apparatus comprising: a catheter shaft defining a longitudinal axis and a shaft lumen therethrough; a set of splines extending from a distal end of the shaft lumen, each spline of the set of splines including a set of electrodes formed on a surface of the spline; a distal cap coupled to a distal portion of each spline of the set of splines, the set of splines configured to translate along the longitudinal axis to transition between a first configuration and a second configuration, wherein in the first configuration each spline lies substantially in a plane that intersects the longitudinal axis of the catheter shaft, and in the second configuration each spline forms a loop having a first concave curved surface facing the distal cap, a second concave curved surface facing the longitudinal axis, and a third concave curved surface facing the distal end of the shaft lumen.

[0380] (Appendix 135) The apparatus of any one of clauses 132, 185, 198, and 208, wherein the first configuration includes a set of splines arranged to rotate helically about the longitudinal axis.

[0381] (Appendix 136) 136. The apparatus of claim 135, wherein each spline of the set of splines has a non-zero helix angle of less than about 5 degrees.

[0382] (Appendix 137) 136. The apparatus of claim 135, wherein each spline of the set of splines has a non-zero helix angle of less than about 2 degrees.

[0383] (Appendix 138) 136. The apparatus of claim 135, wherein each spline of the set of splines has a non-zero helix angle of less than about 1 degree.

[0384] (Appendix 139) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of splines in the second configuration are arranged as sets of non-overlapping loops.

[0385] (Appendix 140) The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of splines in the second configuration are arranged as a set of electrically isolated loops.

[0386] (Appendix 141) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of splines in the second configuration include a radius of curvature that varies along the length of the splines.

[0387] (Appendix 142) 198. The device of any one of clauses 132, 185, 198, and 208, wherein the set of splines in the second configuration are configured to abut a tissue wall, and the sets of electrodes on at least two of the splines are configured to generate an electric field against the tissue wall, the electric field being comprised of a magnitude and a tangential component of field lines, the tangential component being greater than half of the magnitude across a majority of the tissue wall between the at least two splines.

[0388] (Appendix 143) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein each spline of the set of splines in the second configuration is biased away from the longitudinal axis by a maximum of about 30 mm.

[0389] (Appendix 144) 9. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of splines in the second configuration has a diameter of about 10 mm to about 50 mm.

[0390] (Appendix 145) 9. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of splines in the second configuration has a diameter of about 25 mm to about 3 mm.

[0391] (Appendix 146) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of splines in the second configuration has a diameter of approximately 30 mm.

[0392] (Appendix 147) 209. The device of any one of clauses 132, 185, 198, and 208, wherein the set of splines and the distal cap are configured to translate together along the longitudinal axis by up to about 60 mm.

[0393] (Appendix 148) 19. The apparatus of any one of clauses 132, 185, 198, and 208, wherein each of the distal portions of the set of splines is fixed to the distal cap.

[0394] (Appendix 149) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein each spline of the set of splines in the second configuration includes an elliptical cross-section.

[0395] (Appendix 150) 150. The device of claim 149, wherein the elliptical cross section comprises a major axis length of about 1 mm to about 2.5 mm and a minor axis length of about 0.4 mm to about 1.2 mm.

[0396] (Appendix 151) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of splines includes between 3 splines and 20 splines.

[0397] (Appendix 152) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of splines includes five splines.

[0398] (Appendix 153) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of splines includes eight splines.

[0399] (Appendix 154) Each spline in the set of splines is about 0.2 mm 2 ~about 15mm 2 209. The apparatus of any one of clauses 132, 185, 198, and 208, having a cross-sectional area of

[0400] (Appendix 155) 19. The apparatus of any one of clauses 132, 185, 198, and 208, wherein each spline of the set of splines defines a spline lumen therein.

[0401] (Appendix 156) 156. The apparatus of claim 155, wherein an insulated conductor is associated with the set of electrodes for each spline in the set of splines, the insulated conductor being disposed within the spline lumen of each spline in the set of splines.

[0402] (Appendix 157) 156. The apparatus of claim 155, wherein the insulated conductors are configured to maintain a potential of at least about 700 V without their corresponding insulation breaking down.

[0403] (Appendix 158) 19. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of electrodes for each spline in the set of splines includes at least one electrode configured for ablation and at least one electrode configured to receive an ECG signal.

[0404] (Appendix 159) 159. The device of claim 158, wherein at least one electrode configured for ablation and at least one electrode configured to receive ECG signals are coupled and separate insulated conductors.

[0405] (Appendix 160) 160. The apparatus of claim 159, wherein the set of electrodes includes four electrodes configured for ablation and one electrode configured to receive the ECG signal.

[0406] (Appendix 161) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of electrodes for each spline in the set of splines is coupled to a corresponding insulated conductor.

[0407] (Appendix 162) The apparatus of any one of clauses 132, 185, 198, and 208, wherein each spline of the set of splines in the second configuration includes an apex relative to the longitudinal axis.

[0408] (Appendix 163) 163. The apparatus of claim 162, wherein the set of electrodes is non-uniformly distributed relative to the vertices of each spline of the set of splines.

[0409] (Appendix 164) 163. The device of claim 162, wherein the sets of electrodes are distributed proximal and distal to the apex in a 1:3 ratio.

[0410] (Appendix 165) 163. The device of claim 162, wherein the sets of electrodes are distributed proximal and distal to the apex in a 1:2 ratio.

[0411] (Appendix 166) 163. The device of claim 162, wherein the sets of electrodes are distributed proximal and distal to the apex in a 2:3 ratio.

[0412] (Appendix 167) 19. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of electrodes for each spline is wired together.

[0413] (Appendix 168) The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of electrodes for each spline is wired in series.

[0414] (Appendix 169) 19. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of electrodes comprises a non-invasive configuration.

[0415] (Appendix 170) 19. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of electrodes comprises an elliptical cross-section.

[0416] (Appendix 171) 171. The device of claim 170, wherein the elliptical cross-section comprises a major axis length of about 1 mm to about 4 mm and a minor axis length of about 0.4 mm to about 3 mm.

[0417] (Appendix 172) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the set of electrodes includes between 2 electrodes and 64 electrodes.

[0418] (Appendix 173) Each electrode of the set of electrodes is about 0.5 mm 2 ~about 20mm 2 209. The device of any one of clauses 132, 185, 198, and 208, having a surface area of

[0419] (Appendix 174) 209. The apparatus of any one of clauses 132, 185, 198, and 208, wherein a first set of electrodes of a first spline of the set of splines is configured as an anode and a second set of electrodes of a second spline of the set of splines is configured as a cathode.

[0420] (Appendix 175) 175. The apparatus of claim 174, wherein the first spline is not adjacent to the second spline.

[0421] (Appendix 176) 175. The device of claim 174, wherein the first set of electrodes includes one electrode and the second set of electrodes includes at least two electrodes.

[0422] (Appendix 177) 9. The apparatus of any one of clauses 132, 185, 198, and 208, wherein one electrode on each spline of the set of splines is alternatively configured for ablation and for receiving ECG signals.

[0423] (Appendix 178) 198. The device of any one of clauses 132, 185, 198, and 208, wherein the distance between the distal cap and the catheter shaft is less than about 8 mm.

[0424] (Appendix 179) 198. The device of any one of clauses 132, 185, 198, and 208, wherein the distal cap comprises an atraumatic shape.

[0425] (Appendix 180) 9. The apparatus of any one of clauses 132, 185, 198, and 208, wherein the distal cap defines a cap lumen therein.

[0426] (Appendix 181) 9. The device of any one of clauses 132, 185, 198, and 208, wherein the catheter shaft has a diameter of about 6 French to about 15 French.

[0427] (Appendix 182) 19. The device of any one of clauses 132, 185, 198, and 208, wherein one or more of the distal portion of the catheter shaft and ...

Claims

1. An apparatus comprising: a catheter shaft defining a longitudinal axis and a shaft lumen therethrough; a set of splines extending from a distal end of the shaft lumen, each spline of the set of splines including a set of electrodes formed on a surface of the spline; and a distal cap coupled to a distal portion of each spline of the set of splines, wherein the set of splines is configured to translate along the longitudinal axis to transition between a first configuration and a second configuration, the first configuration including the distal cap coupled to a distal end of the catheter shaft a first distance and the second configuration including the distal cap coupled to the distal end of the catheter shaft a second distance, the set of splines and the distal cap configured to translate together up to 60 mm along the longitudinal axis, and the set of splines in the second configuration configured to prevent overlap of electrodes of one spline with electrodes of an adjacent overlapping spline.

2. The apparatus of claim 1 , wherein the first arrangement includes a set of the splines arranged to rotate helically about the longitudinal axis.

3. The apparatus of claim 1 or 2, wherein the set of splines in the second configuration include a radius of curvature that varies along the length of the splines.

4. 4. The device of claim 1, wherein the set of splines in the second configuration is configured to abut a tissue wall, and the set of electrodes on at least two of the splines is configured to generate an electric field comprised of a magnitude and a tangential component of field lines relative to the tissue wall, the tangential component being greater than half of the magnitude in a majority of the tissue wall between the at least two splines.

5. An apparatus as claimed in any preceding claim, wherein the set of splines in the second configuration has a diameter of between 25mm and 35mm.

6. The device of any one of claims 1 to 5, wherein the set of splines and the distal cap are configured to be translated by activating a knob, wheel, or rotary control mechanism.

7. The apparatus of any one of claims 1 to 6, wherein each of the distal portions of the set of splines is fixed to the distal cap.

8. An apparatus as claimed in any preceding claim, wherein each spline of the set of splines in the second configuration comprises an elliptical cross-section.

9. 9. The apparatus of claim 1, wherein the set of electrodes for each spline in the set of splines includes at least one electrode configured for ablation and at least one electrode configured to receive an ECG signal.

10. 10. The device of claim 9, wherein the at least one electrode configured for ablation and the at least one electrode configured for receiving ECG signals are coupled to separate insulated conductors.

11. The device of claim 10 , wherein the set of electrodes includes four electrodes configured for ablation and one electrode configured to receive the ECG signal.

12. 12. The apparatus of claim 11, wherein a first set of electrodes of a first spline of the set of splines is configured as an anode and a second set of electrodes of a second spline of the set of splines is configured as a cathode.

13. The apparatus of claim 12 , wherein the first spline is not adjacent to the second spline.

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