System, apparatus, and method for ventricular focal ablation

Abstract

To provide a system, a device, and a method for ablating tissues by irreversible electroporation ablation.SOLUTION: A system 100 for electroporation ablation therapy, an endocardial ablation device 110, and a method are disclosed. The system includes a pulse waveform signal generator 122 for medical ablation therapy. The endocardial ablation device includes an inflatable member and at least one electrode 112 for focal ablation pulse delivery to tissue. The signal generator may deliver voltage pulses to the ablation device in the form of a pulse waveform. The system may include a cardiac stimulator 128 for generation of a pacing signal and for sequenced delivery of pulse waveforms in synchrony with the pacing signal.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 62 / 557,390, filed Sep. 12, 2017, the entire contents of which are incorporated by reference herein. [Background technology]

[0002]

[0002] The generation of pulsed electric fields for tissue treatment has moved from laboratory to clinical applications in the past 20 years, but the effects of short pulses of high voltage and large electric fields on tissues have been investigated for over 40 years. The application of a short-term high DC voltage to tissue typically generates a localized high electric field in the range of several hundred volts per centimeter, which disrupts cell membranes by generating pores in the membrane. Although the exact mechanism of this electrically driven pore generation or electroporation continues to be investigated, it is believed that the application of a relatively short and large electric field causes instability in the lipid bilayer of the cell membrane, leading to the appearance of a distribution of localized gaps or pores in the cell membrane. This electroporation can be irreversible if the electric field applied to the membrane is greater than a threshold value, resulting in the pores not closing and remaining open, which allows biomolecular material to be exchanged across the membrane, causing necrosis and / or apoptosis (cell death). The surrounding tissue can then heal naturally.

[0003]

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

[0004]

[0004] Described herein are systems, devices, and methods for ablating tissue by irreversible electroporation. In general, an apparatus for delivering a pulse waveform to tissue may include a catheter shaft defining a longitudinal axis. An expandable member may be coupled to a distal end of the catheter shaft. The expandable member may have an exterior surface including a set of electrically conductive portions. A first set of electrodes may be formed on the surface of the catheter shaft. A second set of electrodes may be formed distal to the first set of electrodes on the surface of the catheter shaft. The second set of electrodes may be electrically coupled to the exterior surface of the expandable member and electrically insulated from the first set of electrodes.

[0005] In some embodiments, the apparatus may include a catheter defining a longitudinal axis. The expandable member may be coupled to a distal end of the catheter shaft. A first set of electrodes may be formed on a surface of the catheter shaft. A second electrode may be formed on the expandable member and may be electrically insulated from the first set of electrodes.

[0006] In some embodiments, the device may include a catheter defining a longitudinal axis. An expandable member may be coupled to a distal end of the catheter shaft. A first set of electrodes may be formed on the expandable member and disposed proximal to an equatorial plane of the expandable member. A second set of electrodes may be formed on the expandable member and disposed distal to an equatorial plane of the expandable member. The second set of electrodes may be electrically insulated from the first set of electrodes.

[0007] In some embodiments, the system may include a signal generator configured to generate a pulse waveform. The ablation device may be coupled to the signal generator and configured to receive the pulse waveform. The ablation device may include a handle, a catheter shaft defining a longitudinal axis, and an expandable member coupled to a distal end of the catheter shaft. The expandable member may have an exterior surface including a set of electrically conductive portions. A first set of electrodes may be formed on the surface of the catheter shaft. A second set of electrodes may be formed distal to the first set of electrodes on the surface of the catheter shaft. The second set of electrodes may be electrically coupled to the exterior surface of the expandable member and electrically insulated from the first set of electrodes.

[0008] In some embodiments, the device may include a catheter defining a longitudinal axis. An annular expandable member may be coupled to a distal end of the catheter shaft. The expandable member may define an annular expandable member lumen therethrough. A first electrode may be disposed at a distal end of the annular expandable member. The first electrode may have a substantially planar portion. A second electrode may extend from the annular expandable member lumen to the distal end and may be spaced apart from the first electrode.

[0009] In some embodiments, the first set of electrodes may have a polarity opposite to that of the second set of electrodes during delivery of the pulse waveform. In some embodiments, the first set of electrodes may have a polarity opposite to that of the second set of electrodes during delivery of the pulse waveform. In some embodiments, the first set of electrodes may have a polarity opposite to that of the second set of electrodes during delivery of the pulse waveform.

[0010] In some embodiments, the catheter shaft can include a deflectable portion formed between the first set of electrodes and the second set of electrodes. The deflectable portion can be configured to deflect a portion of the catheter including the second set of electrodes and the expandable member up to about 210 degrees relative to the longitudinal axis. In some embodiments, a fluid source can be coupled to the expandable member and configured to expand the expandable member.

[0011] In some embodiments, one or more of the electrodes of the first set of electrodes and one or more of the electrodes of the second set of electrodes may have an insulated conductor associated therewith, the insulated conductor may be configured to maintain a potential of at least about 700V without breakdown of its corresponding insulation, and the insulated conductor may be disposed within a lumen of the catheter shaft. In some embodiments, one or more of the electrodes of the first set of electrodes and one or more of the electrodes of the second set of electrodes may have an insulated conductor associated therewith, the insulated conductor may be configured to maintain a potential of at least about 700V without breakdown of its corresponding insulation, and the insulated conductor may be disposed within a lumen of the catheter shaft.

[0012] In some embodiments, one or more of the first set of electrodes and one or more of the second set of electrodes may be independently addressable. In some embodiments, one or more of the first set of electrodes and the second electrode may be independently addressable.

[0013] In some embodiments, the distal-most electrode of the first set of electrodes may be spaced about 2 mm to about 10 mm from the proximal-most electrode of the second set of electrodes. In some embodiments, the distal-most electrode of the first set of electrodes may be spaced at least about 5 mm from the proximal end of the expandable member. In some embodiments, the first set of electrodes may be formed on a portion of the catheter shaft having a length of about 1 mm to about 12 mm. In some embodiments, the expandable member has a cross-sectional diameter at its equatorial plane of about 5 mm to about 15 mm. In some embodiments, the expandable member may have a length up to about 22 mm. In some embodiments, each electrode of the first set of electrodes has a width of about 1 mm to about 5 mm, and adjacent electrodes of the first set of electrodes are spaced apart by about 1 mm to about 5 mm.

[0014]

[0014] In some embodiments, the expandable member may have an asymmetric shape in a proximal to distal direction. In some embodiments, the expandable member may have a bulbous shape. In some embodiments, the expandable member may have a polyhedral shape. In some embodiments, a biocompatible coating may be formed on an exterior surface of the expandable member. In some embodiments, the distal end of the catheter may extend into an interior volume of the expandable member. In some embodiments, a set of splines may be coupled to the catheter and an interior surface of the expandable member. The set of splines may be configured to translate along the longitudinal axis to transition between a first configuration in which the set of splines is approximately parallel to the longitudinal axis and a second configuration in which the set of splines is offset away from the longitudinal axis.

[0015]

[0015] In some embodiments, the pulse waveform may include a first level of a hierarchy of pulse waveforms in the form of a first set of pulses, each pulse having a pulse time duration, and a first time interval separating successive pulses. A second level of the hierarchy of pulse waveforms includes a plurality of the first set of pulses as the second set of pulses, and a second time interval separating successive first set of pulses, and the second time interval is at least three times the duration of the first time interval. A third level of the hierarchy of pulse waveforms includes a plurality of the second set of pulses as the third set of pulses, and a third time interval separating successive second set of pulses, and the third time interval is at least 30 times the duration of the time interval of the second level. In some embodiments, the pulse waveform comprises a fourth level of the hierarchy of pulse waveforms and includes a plurality of a third set of pulses as the fourth set of pulses, a fourth time interval separating consecutive third set pulses, and the fourth time interval being at least 10 times the duration of the time intervals of the third level.

[0016] In some embodiments, the distal portion of the catheter shaft further includes a radiopaque portion. In some embodiments, the catheter shaft defines a shaft lumen therethrough. In some embodiments, the first set of electrodes is formed on the distal portion of the catheter shaft.

[0017]

[0017] In some embodiments, no electrodes are formed on the exterior surface of the expandable member. In some embodiments, a conductive element may be formed on the surface of the expandable member. In some embodiments, the conductive element may include a set of spaced apart conductive stripes extending between the ends of the expandable member. In some embodiments, the conductive element may be electrically connected to a second set of electrodes. In some embodiments, each stripe of the set of stripes may intersect at one or more of the proximal and distal ends of the expandable member.

[0018] In some embodiments, the conductive elements may include an interlaced structure that defines a set of openings. In some embodiments, the first conductive element may be disposed on an exterior surface of the expandable member, and the second conductive element may be disposed on an interior surface of the expandable member. The first conductive element may have an opposite polarity to the second conductive element during delivery of the pulse waveform.

[0019] In some embodiments, a first conductive element may be disposed on an exterior surface of the expandable member and a second conductive element may be disposed on an interior surface of the expandable member. The first conductive element may have an opposite polarity to the second conductive element during delivery of the pulse waveform.

[0020] In some embodiments, the first set of electrodes may be disposed on an exterior surface of the catheter shaft, and one or more electrodes of the second set of electrodes may be disposed on an interior surface of the catheter shaft. In some embodiments, the second electrode may be configured to receive electrophysiology data. In some embodiments, the second electrode may be a distal electrode. In some embodiments, the second electrode may be the only electrode formed on the exterior surface of the inflatable member.

[0021] In some embodiments, the distal end of the expandable member may have a concave surface facing away from the proximal end of the expandable member. In some embodiments, the expandable member may have a set of curved surfaces. In some embodiments, at least one electrode of the second set of electrodes is formed on one surface of the expandable member. In some embodiments, one or more electrodes of the second set of electrodes may be concave.

[0022] In some embodiments, the expandable member may have a set of curved edges. In some embodiments, each electrode of the second set of electrodes may have a diameter of about 3 mm to about 15 mm. In some embodiments, the distal-most electrode of the first set of electrodes may be spaced at least about 3 mm from the proximal end of the expandable member. In some embodiments, the expandable member when expanded may have a cross-sectional diameter at its largest portion of about 6 mm to about 22 mm.

[0023] In some embodiments, the annular expandable member when expanded can have a diameter of about 10 mm to about 15 mm. In some embodiments, the second electrode can have a length of about 2 mm to about 10 mm. In some embodiments, the annular expandable member lumen can have a diameter of about 4 mm to about 15 mm.

[0024] In some embodiments, the second set of electrodes may be formed on the expandable member between the first set of electrodes and the second set of electrodes. In some embodiments, the second electrodes may be independently addressable. In some embodiments, each electrode of the second set of electrodes may be independently addressable.

[0025] In some embodiments, the second set of electrodes may be formed on the expandable member on an approximate plane that is approximately perpendicular to the longitudinal axis. In some embodiments, each electrode of the second set of electrodes may have a circular or elliptical shape. In some embodiments, the long axis of each electrode of the second set of electrodes having an elliptical shape may be substantially parallel to the longitudinal axis.

[0026] In some embodiments, the second set of electrodes can include a distal electrode formed at a distal end of the expandable member. In some embodiments, each electrode of the second set of electrodes can have a circular or elliptical shape. In some embodiments, the major axis of each electrode of the second set of electrodes having an elliptical shape, except for the distal electrode, is substantially parallel to the longitudinal axis.

[0027]

[0027] In some embodiments, a method of focal ablation via irreversible electroporation includes advancing an ablation device toward an endocardial wall. The ablation device may include a catheter shaft defining a longitudinal axis and an expandable member coupled to a distal end of the catheter shaft. The expandable member may have an exterior surface including a set of electrically conductive portions. A first set of electrodes may be formed on the surface of the catheter shaft. A second set of electrodes may be formed distal to the first set of electrodes on the surface of the catheter shaft. The second set of electrodes may be electrically coupled to the exterior surface of the expandable member and electrically insulated from the first set of electrodes. A pulse waveform may be generated. The pulse waveform may be delivered to the endocardial wall via the ablation device.

[0028]

[0028] In some embodiments, one of the first set of electrodes and the second set of electrodes can be configured as an anode. The other of the first set of electrodes and the second set of electrodes can be configured as a cathode. In some embodiments, the expandable member of the ablation device can be transitioned from a first configuration to a second configuration. In some embodiments, transitioning the expandable member from the first configuration to the second configuration includes injecting saline into the expandable member. In some embodiments, pulsed electric field ablation energy can be delivered through the first set of electrodes and the second set of electrodes of the ablation device. In some embodiments, the ablation device is configured to generate an electric field strength of about 200 V / cm to about 800 V / cm.

[0029]

[0029] In some embodiments, the ablation device may include a handle. The method may further include deflecting a portion of the ablation device using the handle. In some embodiments, first electrophysiology data of the endocardial wall may be recorded. Second electrophysiology data of the endocardial wall may be recorded after delivering the pulse waveform. In some embodiments, the first electrophysiology data and the second electrophysiology data may include intracardiac ECG signal data of the endocardial wall. In some embodiments, a diagnostic catheter may be advanced into the endocardial wall and the first electrophysiology data and the second electrophysiology data may be recorded using the diagnostic catheter. In some embodiments, the first electrophysiology data and the second electrophysiology data may be recorded using the ablation device in the second configuration.

[0030]

[0030] In some embodiments, the method may include creating a transseptal opening in the left atrium, advancing a guidewire and a sheath through the transseptal opening into the left atrium, and advancing an ablation device over the guidewire into the ventricle. In some embodiments, the method may include creating a first access site in the patient, advancing a guidewire through the first access site into the right atrium, advancing a dilator and a sheath over the guidewire into the right atrium, advancing a dilator from the right atrium into the left atrium through the atrial septum to create a transseptal opening, and dilating the transseptal opening using the dilator. In some embodiments, a second access site may be created in the patient for advancing a cardiac stimulator. In some embodiments, the method may include advancing a cardiac stimulator into the right ventricle, generating a pacing signal for cardiac stimulation of the heart using the cardiac stimulator, and applying the pacing signal to the heart using the cardiac stimulator, wherein a pulse waveform is generated synchronously with the pacing signal.

[0031] In some embodiments, the method may include imaging a radiopaque portion of the ablation device under fluoroscopy during one or more steps. In some embodiments, the first access site is the femoral vein. In some embodiments, the interatrial septum includes the fossa ovalis. In some embodiments, the endocardial wall is a ventricle.

[0032]

[0032] In some embodiments, the pulse waveform may include a first level of a hierarchy of pulse waveforms in the form of a first set of pulses, each pulse having a pulse time duration, and a first time interval separating successive pulses. A second level of the hierarchy of pulse waveforms includes a plurality of the first set of pulses as the second set of pulses, and a second time interval separating successive first set of pulses, and the second time interval is at least three times the duration of the first time interval. A third level of the hierarchy of pulse waveforms includes a plurality of the second set of pulses as the third set of pulses, and a third time interval separating successive second set of pulses, and the third time interval is at least 30 times the duration of the time interval of the second level. In some embodiments, the pulse waveform comprises a fourth level of the hierarchy of pulse waveforms and includes a plurality of a third set of pulses as the fourth set of pulses, a fourth time interval separating consecutive third set pulses, and the fourth time interval being at least 10 times the duration of the time intervals of the third level. [Brief description of the drawings]

[0033] [Figure 1] FIG. 1 is a block diagram of an electroporation system, according to an embodiment. [Figure 2A] 1A-1D are side views of an ablation device in various configurations, according to embodiments; [Figure 2B] FIG. 1 is a side view of an expanded ablation device. [Figure 2C] 13 is a side view of another embodiment of an expanded ablation device. [Figure 2D] 13 is a side view of another embodiment of an expanded ablation device. [Diagram 3] 1 is a side view of an ablation device according to another embodiment. [Figure 4A] 1 illustrates a method for tissue ablation, according to an embodiment. [Figure 4B] 1 illustrates a method for tissue ablation, according to an embodiment. [Figure 5A] 1A-1C are side and perspective views of an ablation device according to another embodiment; [Figure 5B] FIG. 5B is a cross-sectional side view of the ablation device depicted in FIG. 5A. [Figure 5C] 13A is a cross-sectional side view of another embodiment of an ablation device. [Figure 5D] FIG. 5D is a perspective view of the ablation device depicted in FIG. 5C. [Figure 5E] FIG. 5D is a cross-sectional side view of the ablation device depicted in FIG. 5C. [Figure 5F] 1 is a perspective view of another embodiment of an ablation device. [Figure 5G] FIG. 5F is a perspective view of the ablation device depicted in FIG. 5F. [Figure 5H] FIG. 5F is a perspective view of the ablation device depicted in FIG. 5F. [Figure 5I] 1 is a perspective view of another embodiment of an ablation device. [Figure 5J] FIG. 5I is a cross-sectional side view of the ablation device depicted in FIG. 5I. [Figure 6] 1 is an exemplary waveform illustrating a series of voltage pulses having a defined pulse width for each pulse, according to an embodiment. [Figure 7] 10A-10C illustrate a hierarchy of pulses, showing pulse widths, spacing between pulses, and grouping of pulses, according to an embodiment; [Figure 8] 1 provides a schematic, illustrative diagram of a nested hierarchy of monophasic pulses displaying different levels of nested hierarchy, according to an embodiment. [Figure 9]FIG. 1 is a schematic, illustrative diagram of a nested hierarchy of biphasic pulses displaying different levels of nested hierarchy, according to an embodiment. [Figure 10] 1A-1C are schematic illustrations of electrocardiogram and cardiac pacing signal time series showing atrial and ventricular refractory periods and a time window for irreversible electroporation ablation, according to an embodiment; [Figure 11] 1 is a side view of an ablation device according to another embodiment. [Figure 12] 1 is a side view of an ablation device according to another embodiment. [Figure 13] 1 is a side view of an ablation device according to another embodiment. [Figure 14] 1 is a side view of an ablation device according to another embodiment. [Figure 15] 1 is a side view of an ablation device according to another embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034]

[0048] Described herein are systems, devices, and methods for ablating tissue by irreversible electroporation. In general, a system for delivering a pulse waveform to tissue may include a signal generator configured to generate a pulse waveform, and an ablation device coupled to the signal generator and configured to receive the pulse waveform. The ablation device may include a conductive expandable member (e.g., a balloon) coupled to a distal end of a catheter shaft to deliver energy to ablate tissue by irreversible electroporation. A conductive metal pattern may be disposed on an exterior surface of the expandable member. One or more electrodes may be formed proximal to the expandable member on a surface of the catheter shaft. In some embodiments, the ablation device may be configured to deliver a pulse waveform to tissue during use via one or more electrodes and the expandable member forming a dipole. In some embodiments, capacitive voltage delivery may be provided using a biphasic waveform across the thickness of the expandable member wall. The embodiments of the ablation device described herein may deliver sufficient energy for irreversible electroporation to tissue through the expandable member of the ablation device functioning as an electrode. The expandable member is expandable such that an electric field and corresponding focal ablation lesion is generated. In some embodiments, the ablation device may form focal ablation lesions with a depth of about 2 mm to about 15 mm or more, which may be suitable for forming broad and deep ablations in the ventricular wall.

[0035]

[0049] In some embodiments, the ablation devices described herein may be useful for treating ventricular arrhythmias (e.g., reentrant ventricular tachycardia) that originate in the ventricles and in which the cardiac depolarization signal does not complete the normal circuit, but rather may cause the arrhythmia through an alternative circuit such as a loopback (e.g., a reentrant circuit). For example, the ablation devices described herein may be used for scar homogenization or "debulking," which may ablate one or more portions of scar tissue to electrically isolate and / or destroy the reentrant circuit. The systems, devices, and methods described herein may be used to create one or more focal ablation lesions using an endocardial approach, and in other embodiments, may be used with an epicardial approach.

[0036]

[0050] In some embodiments, the ablation device may include one or more electrodes configured to receive ECG signals and used to generate an anatomical map of the patient. For example, ECG recording electrodes may be disposed on one or more of the expandable member and the catheter shaft. This allows the ablation device to both map and ablate tissue, thereby reducing cost, complexity, and procedure time when a separate mapping catheter is not used.

[0037]

[0051] The systems, devices, and methods described herein may be used to generate large electric field magnitudes in a desired region of interest to generate irreversible electroporation. The irreversible electroporation system described herein may include a signal generator and a processor configured to apply one or more voltage pulse waveforms to a selected set of electrodes and an expandable member of an ablation device to deliver energy (e.g., ablation energy to a set of tissues in a ventricle) to the region of interest. The pulse waveforms disclosed herein may assist in therapeutic treatment of various cardiac arrhythmias (e.g., atrial fibrillation, reentrant ventricular arrhythmia, ventricular tachycardia, etc.). 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 700V without breakdown of their corresponding insulation. In some embodiments, at least some of the electrodes may be independently addressable such that each electrode may be controlled (e.g., 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.

[0038]

[0052] The term "electroporation" as used herein refers to the application of an electric field to a cell membrane to change the permeability of the cell membrane to the extracellular environment. The term "reversible electroporation" as used herein refers to the application of an electric field to a cell membrane to temporarily change the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing reversible electroporation may observe the temporary and / or intermittent formation of one or more pores in its cell membrane that close upon removal of the electric field. The term "irreversible electroporation" as used herein refers to the application of an electric field to a cell membrane to permanently change the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing irreversible electroporation may observe the formation of one or more pores in its cell membrane that persist upon removal of the electric field.

[0039]

[0053] The pulse waveforms for electroporation energy delivery disclosed herein can enhance the safety, efficiency, and effectiveness of energy delivery to tissue by reducing the electric field threshold associated with irreversible electroporation, thereby resulting in more effective ablation lesions with reduced total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein can be hierarchical and nested. For example, the pulse waveforms can include hierarchical groupings of pulses with related time scales. In some embodiments, the methods, systems, and devices disclosed herein can comprise 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.

[0040]

[0054] In some embodiments, the system may further include a cardiac stimulator used to synchronize the generation of the pulse waveform to the paced heartbeat. The cardiac stimulator may electrically pace the heart with the cardiac stimulator 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 sinus rhythm of the heart. In some embodiments, the ablation device may include one or more catheters, guidewires, expandable members, and electrodes. The ablation device may transition to different configurations (e.g., contracted and expanded) to position the device within the cardiac cavity.

[0041]

[0055] In general, to ablate tissue, one or more catheters may be minimally invasively advanced through the vasculature to a target location. The methods described herein may include introducing a device into a cardiac cavity in the left atrium of the heart and disposing the device in contact with a ventricle or other cardiac surface. A pulse waveform may be generated and delivered to one or more electrodes and conductive expandable members 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 aid in tissue ablation and reduce damage to healthy tissue.

[0042] I. System Summary

[0056] Disclosed herein are systems and devices configured for tissue ablation via selective and rapid application of a voltage pulse waveform to assist tissue ablation resulting in irreversible electroporation. In general, the system for ablating tissue described herein may include a signal generator and an ablation device having one or more electrodes and an expandable member for selective and rapid application of a DC voltage to drive electroporation. As described herein, the system and device may be deployed on the endocardium to treat atrial fibrillation. Suitable anode / cathode electrodes may be selected and a voltage pulse waveform may be applied to a subset of the electrodes. A pacing signal for cardiac stimulation may be generated and used to generate a pulse waveform by the signal generator in synchronization with the pacing signal.

[0043]

[0057] In general, the systems and devices described herein include one or more catheters configured to ablate tissue in a cardiac chamber. Figure 1 illustrates an ablation system (100) configured to deliver a voltage pulse waveform. The system (100) may include an apparatus (120) including a signal generator (122), a processor (124), a memory (126), and a cardiac stimulator (128). The apparatus (120) may be coupled to an ablation device (110) and, optionally, a pacing device (130).

[0044]

[0058] The signal generator (122) may be configured to generate a pulse waveform for irreversible electroporation of tissue, such as ventricular tissue, such as left ventricular tissue. For example, the signal generator (122) may be a voltage pulse waveform generator and may be configured to deliver the pulse waveform to the ablation device (110). The return electrode (140) in some embodiments may be coupled to the patient (e.g., placed on the patient's back) and current may flow from the ablation device (110), through the patient, and then to the return electrode (140). In other embodiments, the return electrode (140) may be part of the ablation device, such as an electrode dipole on the device. 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 for 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.

[0045]

[0059] In some embodiments, the ablation device (110) may include a catheter having an expandable member (e.g., a balloon) configured to deliver a pulsed waveform, as described in more detail below. In each of the embodiments described herein, the expandable member may be expanded using a gas, a liquid, a combination thereof, or the like. For example, the ablation device (110) may be introduced into the endocardial space, positioned to align the expandable member with a tissue surface, and then deliver a pulsed waveform to ablate the tissue. The ablation device (110) may include one or more electrodes (112), which in some embodiments may be independently addressable electrodes. Each electrode may include an insulated conductor configured to maintain a potential of at least about 700V without breakdown of its corresponding insulation. In some embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 3,000V across its thickness without breakdown. For example, the electrodes (112) may be grouped into one or more anode-cathode subsets, such as, for example, a subset including one proximal and one distal electrode. In some embodiments, the distal electrode may comprise at least a portion of the expandable member. As used herein, proximal is toward the handle of the ablation device and distal is toward the tip of the ablation device.

[0046]

[0060] When in use, the pacing device (130) may be suitably coupled to a patient (not shown) and configured to receive a cardiac pacing signal generated by a cardiac stimulator (128) of the apparatus (120) for cardiac stimulation. An indicator of the pacing signal may be transmitted by the cardiac stimulator (128) to the signal generator (122). Based on the pacing signal, an indicator 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) may be configured to generate a pulse waveform (e.g., within a common refractory window) in synchronization with the indicator of the pacing signal. 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 duration of about 250 milliseconds or less thereafter. In such embodiments, the entire pulse waveform may be delivered within this duration.

[0047]

[0061] 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.

[0048]

[0062] The memory (126) may include a database (not shown) and may be, for example, a random access memory (RAM), a memory buffer, a hard drive, an erasable programmable read only memory (EPROM), an electrically erasable read only memory (EEPROM), a read only memory (ROM), a flash memory, etc. The memory (126) may store instructions that cause the processor (124) to execute modules, processes, and / or functions associated with the system (100), such as pulse waveform generation and / or cardiac pacing.

[0049]

[0063] 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 may refer to any type of digital network that is not connected by any type of cable. However, a wireless network may connect to a wired network to interface with the Internet, other carriers' voice and data networks, business networks, and personal networks. Wired networks are typically carried over copper twisted pairs, coaxial cables, or fiber optic cables. There are many different types of wired networks, including wide area networks (WANs), metropolitan area networks (MANs), local area networks (LANs), campus area networks (CANs), global area networks (GANs), such as 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 through the Internet, to provide an integrated networking and information access solution.

[0050] Ablation Devices

[0064] The systems described herein may include one or more multi-electrode ablation devices configured to ablate tissue in a cardiac chamber to treat indications such as ventricular arrhythmias. FIG. 2A is a side view of an ablation device (200) (e.g., structurally and / or functionally similar to ablation device (110)) including a catheter shaft (210) and an expandable member (e.g., balloon) (240) coupled to a distal end of the catheter shaft (210). In some embodiments, the ablation device (200) is useful for forming lesions on endocardial surfaces via focal ablation, such as the interior surface of a cardiac chamber, as described herein. A distal portion of the expandable member (240) may include and / or be formed with a non-invasive shape that reduces trauma to tissue (e.g., prevents and / or reduces the possibility of tissue puncture). The catheter shaft (210) and the expandable member (240) may be sized for advancement into a cardiac chamber (e.g., the left ventricle). The catheter shaft (210) may be flexible so as to be deflectable, as shown and discussed in more detail with respect to FIG. 3. Any of the catheter shafts described herein may include a shaft lumen therethrough. A set of electrical leads and / or a fluid (e.g., saline) may be disposed within the shaft lumen. The expandable member (240) may be configured to transition between a first configuration (e.g., a contracted state) and a second configuration (e.g., an expanded state). In the first configuration, the expandable member (240) may have a diameter approximately the same as the diameter of the catheter shaft (210) to aid in advancing the ablation device (200) through the vasculature. For example, the expandable member (240) in the first configuration may be approximately parallel to the longitudinal axis (212) of the catheter shaft (210). For example, the expandable member (240) may be in a compressed or crimped configuration. In the second configuration, the expandable member (240) can have a cross-sectional diameter at its largest portion (e.g., at its equatorial plane) in the range of about 5 mm to about 15 mm. For example, the expandable member (240) when expanded can be biased away from the longitudinal axis.The expandable member (240), or a portion thereof, can include a conductive exterior surface (eg, FIG. 2C) that can be configured as an anode or cathode for delivering a pulse waveform to tissue.

[0051]

[0065] As shown in FIGS. 2A-2D, the one or more electrodes (220, 230) may include a series of metal bands or rings disposed along the surface of the catheter shaft (210). For example, the ablation device (200) may include a first set of electrodes (220) (e.g., one or more proximal electrodes) formed on the surface of a distal portion of the catheter shaft (210). In some embodiments, the one or more electrodes (220, 230) may be formed on the catheter shaft (210) along its entire circumference. In some embodiments, the one or more electrodes (220, 230) may be formed on the surface of only a portion of the circumference of the catheter shaft (210). For example, the electrodes (220) may surround the circumference of the catheter shaft (210). In some embodiments, the one or more electrodes may be completely covered by a thin layer of a dielectric coating for biphasic operation.

[0052]

[0066] In FIGS. 2A-2B, no electrodes are formed on the exterior surface of the expandable member (240). In some embodiments, the ablation device (200) may include a second set of electrodes (230) (e.g., a single distal electrode). The second set of electrodes (230) may be formed distal to the first set of electrodes (210) on the surface of the distal portion of the catheter shaft (210). In some embodiments, the electrodes (220, 230) may be shaped to conform to the shape of the catheter shaft (210). For example, the electrodes may be press-fit (e.g., crimped) into the catheter shaft (210) or attached using a conductive adhesive. The catheter shaft (210) may include a flexible portion (e.g., deflectable) between the electrodes (220, 230) to enhance flexibility and aid in deflecting the device (200) and advancing through the vasculature. In other embodiments, one or more of the electrodes (220, 230) may include spiral windings to enhance flexibility.

[0053]

[0067] Each of the electrodes of any of the ablation devices discussed herein may be connected to an insulated conductor (not shown) that leads to a handle (not shown) coupled to a proximal portion of the catheter. The insulation of each of the conductors may maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 3,000V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. This allows the electrodes and the expandable member coupled thereto to effectively deliver electrical energy to ablate tissue through irreversible electroporation. The electrodes (220, 230) may receive a pulse waveform generated by a signal generator (122), for example, as described above with respect to FIG. 1.

[0054]

[0068] The first set of electrodes (220) may be electrically coupled together using one or more conductors. The second set of electrodes (230) may be electrically coupled together using a different set of conductors. The exterior surface of the expandable member (240) may include a set of electrically conductive portions and may be coupled to the second set of electrodes (230) and may be electrically insulated from the first set of electrodes (220). In some embodiments, the first set of electrodes (220) may be configured as an anode, and the second set of electrodes (230) and the expandable member (240) may be configured as a cathode. Thus, a dipole may be formed between the first set of electrodes (220) and the expandable member (240), resulting in an electric field capable of ablating tissue (e.g., myocardial cells on an interior surface or within a ventricle). The expandable member (240) and the first set of electrodes (220) may be electrically insulated from each other. For example, the second set of electrodes (230) and the first set of electrodes (220) can each be coupled to a respective insulated conductor, with each conductor having sufficient electrical insulation to maintain a potential difference of at least 700 V across its thickness therebetween without dielectric breakdown. In some embodiments, the first set of electrodes (220) can have an opposite polarity than the second set of electrodes (230) during delivery of the voltage pulse waveform.

[0055]

[0069] The first and second sets of electrodes (220, 230) may include atraumatic shapes to reduce trauma to tissue. For example, the electrodes (220, 230) may have atraumatic shapes that include rounded, planar, curved, and / or blunt portions. For example, the electrodes (220, 230) of FIGS. 2A-2D may be ring electrodes. In some embodiments, the first set of electrodes (220) may be positioned along any portion of the catheter shaft (210) proximal to the second set of electrodes (230). The second set of electrodes (230) may be positioned on a surface of the catheter shaft (240) and / or may be flush with a surface of the expandable member (240) so as to be electrically coupled to the expandable member (240). The electrodes (220, 230) may have the same or different sizes, shapes, and / or positions along the catheter shaft (210). The spacing between the electrodes of the first set of electrodes (220) can be configured to allow a distal portion (e.g., the deflectable portion) of the catheter shaft (210) to deflect a predetermined amount (e.g., deflection up to about 210 degrees). For example, the deflectable portion can be configured to deflect a portion of the catheter including the second set of electrodes (230) and the expandable member (240) up to about 210 degrees relative to the longitudinal axis.

[0056]

[0070] In some embodiments, the first set of electrodes (220) may include electrodes disposed along a portion of the catheter shaft (210) having a length of about 1 mm to about 12 mm from the proximal end to the distal end of the first set of electrodes (220). The first set of electrodes (220) may be spaced apart from one another and wired together via one or more insulated leads such that they function as a single electrode (e.g., an anode or a cathode) while the catheter shaft (210) remains flexible and facilitates deflection. In some embodiments, the first set of electrodes (220) may be spaced apart from the second set of electrodes (230) by a length of about 2 mm to about 10 mm.

[0057]

[0071] For each of the ablation devices discussed herein, the electrodes (220, 230) may comprise a biocompatible metal, such as titanium, palladium, gold, silver, platinum, or a platinum alloy. For example, the electrodes may preferably comprise platinum or a platinum alloy. In some embodiments, the proximal electrodes may have a biocompatible coating that allows for capacitive voltage delivery with a biphasic waveform. Each electrode (220, 230) may comprise a conductor having sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 3,000V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. The insulated conductors may run to a proximal handle portion of the ablation device (200) from where they may connect to a suitable electrical connector. The catheter shaft (210) may be made of a flexible polymeric material, such as Teflon, Nylon, Pebax, or the like.

[0058]

[0072] In some embodiments, one or more of the electrodes of the first and second sets of electrodes (220, 230) may be configured to receive or sense an ECG signal for recording electrophysiological data. The electrophysiological data may be used to generate an anatomical map that can be used to compare electrophysiological data recorded after energy delivery. The electrophysiological data may include intracardiac electrocardiogram signal data. The ablation device (200) may include one or more ECG signal electrodes. For example, one or more of the electrodes of the first set of electrodes (220) may be configured to receive an ECG signal. In some embodiments, the ECG signal electrode may be disposed on a surface of the distal end of the expandable member (240) (not shown). The ECG signal electrode may be coupled to its own insulated conductor. The ECG signal electrode may be electrically isolated from the expandable member (240), for example, using a ring of insulation around the ECG signal electrode that electrically insulates the ECG signal electrode from the conductive expandable member. In these embodiments, the ablation device may be used to record electrophysiology data in place of a mapping catheter before and / or after tissue ablation. In some embodiments, the ablation device (200) may include a position sensor that may generate position data of the ablation device positioned within the vasculature. The electrophysiology data and the position data may be used to generate an anatomical map of the electrophysiology data. In some embodiments, the position sensor may include an electromagnetic coil positioned at the distal end of the expandable member (240). In other embodiments, the position sensor may be positioned within a lumen of the catheter shaft (210).

[0059]

[0073] In some embodiments, the expandable member (240) may be coupled to the second set of electrodes (230) and may be configured to deliver a pulse waveform from the signal generator to tissue during use. The expandable member (240) may be coupled to a distal portion of the catheter shaft (210) and may be conductively configured to function as one half of an anode-cathode pair for delivering irreversible electroporation energy to tissue. The expandable member (240) may be configured to transition between a first configuration (e.g., the contracted expandable member of FIG. 2A) and a second configuration (e.g., the expanded expandable member of FIGS. 2B-2D). The expandable member (240) in the first configuration may be in a compact contracted state suitable for advancing through the vasculature. For example, the expandable member (240) in the first configuration may be substantially emptied of a fluid, such as saline. The expandable member (240) in the second configuration may hold a volume of saline that fills and expands the expandable member (240) to a predetermined size and shape (e.g., having a diameter that contacts the diameter of the ventricle). The expandable member (240) may transition to an intermediate configuration between the first and second configurations as needed, for example, to conform to a lumen or advance the device through the vasculature.

[0060]

[0074] In some embodiments, the inflatable members described herein may have an expandable structure and may be composed of materials including, but not limited to, polyvinyl chloride (PVC), polyethylene (PE), cross-linked polyethylene, polyolefins, polyolefin copolymers (POC), polyethylene terephthalate (PET), nylon, polymer blends, polyester, polyimide, polyamide, polyurethane, silicone, polydimethylsiloxane (PDMS), etc. The inflatable members may be embedded with other materials including, but not limited to, metals, insulators, Kevlar, nylon fibers, etc.

[0061]

[0075] The distal portion of the expandable member (240) disposed within the lumen (e.g., ventricle) may act as a backstop against the advancement of the distal portion of the catheter (200). By modifying the size of the expandable member (240) and manipulating the deflection of the catheter shaft (210), the expandable member (240) may be positioned at a target tissue site, such as near or in contact with the wall of the left ventricle. The distal portion of the catheter shaft (210) may include a pair of electrodes (220, 230) (e.g., structurally and / or functionally similar to the electrode(s) (112)) that may be configured to contact the inner radial surface of the tissue lumen (e.g., ventricle). In some embodiments, the cross-sectional diameter of the expandable member (240) when inflated, at its largest portion (e.g., at the equatorial plane) when inflated, may be from about 5 mm to about 15 mm. The length of the expandable member (240) when inflated may be up to about 22 mm. In some embodiments, the length of the expandable member (240) may be substantially the same between the first and second configurations.

[0062]

[0076] The proximal end of the expandable member (240) may be coupled to a suitable lead (e.g., via the second set of electrodes (230)) and connected to the signal generator (122) of FIG. 1. The expandable member (240) may be configured as a cathode and the first set of electrodes (220) may be configured as an anode, or vice versa. In some embodiments, as described in detail herein, the set of proximal electrodes (220) and the expandable member (240) may form a dipole. In this manner, the expandable member (240) in the second configuration may be positioned against the inner wall of the left ventricle to directly create a localized or focal lesion, for example, by activation of the first and second sets of electrodes (220, 230) using any suitable combination of polarities. For example, the first and second sets of electrodes (230, 240) may be configured with opposite polarities. In some embodiments, the ablation device can be configured to generate an electric field having a strength of at least about 200 V / cm.

[0063]

[0077] One or more biphasic signals may be applied to the bipoles such that tissue at a desired location in the ventricle may be ablated between the expandable member (240) and the first set of electrodes (220). For example, a biphasic pulse waveform may be delivered between the sets of electrodes of opposite polarity, resulting in a zone of irreversible electroporative ablation in the area around the expandable member.

[0064]

[0078] In some embodiments, the expandable member (240) when expanded may be configured to contact endocardial tissue, while the second set of electrodes in the second configuration (sometimes referred to as "proximal electrodes") may not contact endocardial tissue. The electric field generated by the ablation device (200) through conduction between the expandable member (240) and the proximal electrodes (220) through the blood pool and tissue may result in focal ablation of tissue via irreversible electroporation.

[0065]

[0079] In general, the expandable member (240) when expanded has an asymmetric shape in the proximal to distal direction, such that one end (e.g., the distal end) of the expandable member (240) may be more bulbous than the other end (e.g., the proximal end) of the expandable member (240). The expandable member (240) when expanded may be rotationally symmetric about the longitudinal axis of the catheter shaft (210). Such a bulbous distal portion may aid in positioning the device (200) within the ventricle and may further aid in controlling the size and depth of the focal ablation. In this manner, the expandable member (240) when expanded may be positioned against an endocardial surface, such as, for example, the interior surface of a ventricle, to directly create a lesion thereon by actuating the appropriate electrodes (220, 230) using any suitable combination of polarities. For example, the expandable member (240) may be positioned against an endocardial surface and used to form a lesion (e.g., a spot lesion) via focal ablation.

[0066]

[0080] In some embodiments, the exterior surface of the expandable member (240) may include a set of conductive (e.g., metallized) portions. In this configuration, a dipole may be formed between the exterior surface of the expandable member (240) and the first set of electrodes (220) (e.g., proximal electrodes). For example, the exterior surface of the expandable member (240) may include a deposition of a biocompatible metallic material (e.g., gold, silver, platinum), metal plating, printed metallic nanoparticle ink, etc. A portion of the expandable member may include a metal foil. The density of the metallic material disposed on the exterior surface of the expandable member (240) may be such as to ensure electrical coupling with the second set of electrodes (230) (e.g., distal ring electrodes). The second set of electrodes (230) may be electrically coupled to the set of electrically conductive portions of the exterior surface of the expandable member (240) such that the expandable member (240) is electrically coupled to the respective electrical leads. The electrode lead may be constructed with sufficient insulation and high dielectric strength so as to be suitable for delivery of the irreversible electroporation energy described herein.

[0067]

[0081] As shown in FIG. 2C, the ablation device (200') may include a catheter shaft (210') coupled at a distal end to an expandable member (e.g., balloon) (240'). The first set of electrodes (220') and the second set of electrodes (230') may be disposed on and / or flush with the surface of the catheter shaft (210'). In some embodiments, one or more portions of the expandable member (240') may be conductive. For example, the entire exterior surface of the expandable member (240') may be conductive, or a predetermined portion of the expandable member (240') may be conductive and coupled to the second set of electrodes (230'). As shown in FIG. 2C, the exterior surface of the expandable member may include another conductive element (e.g., pattern) (242') having a set of spaced apart conductive stripes extending in a proximal to distal direction between the ends of the expandable member (240'). The one or more conductive elements (242') may be electrically insulated from one another. The conductive stripes may be formed by techniques such as masked electrodeposition. In some embodiments, the conductive elements (242') may be symmetrically disposed on the expandable member (240'). Each stripe of the conductive elements (242') may be electrically coupled to a distal electrode (230'). The stripes may cross each other at the proximal and distal ends of the expandable member (240') and / or between the ends of the expandable member (240'). The expandable member (240') may be flexible and / or expandable between the metal stripes of the conductive elements (242'). The conductive elements (242') may be disposed (e.g., deposited) on the expandable member (240') in a manner that maintains electrical coupling with the electrical leads in the first configuration, the second configuration, and configurations therebetween. The conductive element (242') may provide stiffness and / or rigidity to the expandable member (240') and may aid in the advancement of the expandable member (240') through the vasculature. In some embodiments, the conductive element (242') may include one or more helical shaped metallic portions. In some embodiments, the conductive element (242') may include an interlaced structure (e.g., a mesh shape). For example, the interlaced structure may form a set of polygonal openings (e.g., apertures) including one or more of a circle, a parallelogram, a hexagon, etc.

[0068]

[0082] As shown in FIG. 2D, the ablation device (200'') may include a catheter shaft (210'') coupled at a distal end to an expandable member (e.g., balloon) (240''). A first set of electrodes (220'') may be disposed on an exterior surface of the catheter shaft (210''). A second set of electrodes (235'') may be disposed on an interior surface of the catheter shaft (210''). In some embodiments, one or more portions of the expandable member (240'') may include a metallic electrode portion (245'') (e.g., a second electrode). In some embodiments, the second electrode (245'') is the only electrode formed on the exterior surface of the expandable member. A portion (245'') of the expandable member surface (240'') may be metallic. For example, a portion (245'') of the expandable member (240'') may be a distal portion. In some embodiments, the expandable member (240'') may define an expandable member lumen (237'') that extends along a first longitudinal axis of the catheter shaft (210'') to a distal end of the expandable member (240''). A proximal end of a lead (239'') may be coupled to a distal electrode (235''), extend through the expandable member lumen (237''), and couple to an electrode portion (245'') at the distal end of the expandable member (240''). Thus, the electrode portion (245'') may be configured to deliver an irreversible electroporation voltage pulse. In some embodiments, the portion (245'') of the expandable member (240'') (e.g., formed of a metal) may be configured as an electrode of one polarity, while the first set of electrodes (220'') (e.g., the proximal electrode(s)) may be configured as an electrode(s) of the opposite polarity.

[0069]

[0083] In some embodiments, the metalized exterior surface of the expandable member discussed herein may be further covered by a layer of biocompatible material. The biocompatible coating may help prevent fibrin deposition due to high voltage energy delivery to tissue by the ablation device. In this configuration, a dipole may be formed between the exterior surface of the expandable member and the first set of electrodes (e.g., the proximal electrodes). However, the ablation device may be configured to deliver energy capacitively using one or more biphasic waveforms across the biocompatible coating on the expandable member.

[0070]

[0084] In some embodiments, the ablation device (200) may not include a second set of electrodes (230) (e.g., distal electrodes) disposed on the exterior surface of the catheter shaft (210). Instead, the expandable member (240) may be configured to include inner and outer metallized surfaces that sandwich the expandable member (240). The inner and outer metallized surfaces may include any combination of conductive elements (242) described herein. Electrical leads may be directly connected to the inner metallized surface of the expandable member (240). In this configuration, a dipole may be formed between the expandable member (240) and the first set of electrodes (220).

[0071]

[0085] Activation of the first and second sets of electrodes using a given configuration of the expandable member can provide precise focal ablation of targets by controlling focal ablation spot size based on expansion of the expandable member. As described herein, focal ablation of tissue can be used to treat ventricular arrhythmias. For example, when the expandable member of the ablation device is partially filled with saline, a high intensity electric field with a relatively small / more concentrated diameter results in a focal ablation lesion with a relatively small diameter and shallow depth. When the expandable member of the ablation device is in a second configuration (e.g., fully expanded), a relatively large and more distributed electric field is generated, resulting in a relatively wide and deeper focal ablation lesion. In this manner, by varying the degree of expansion of the expandable member, the depth and / or size of the lesion can be controlled with a single ablation device. Such an embodiment is useful for creating multiple lesions of various sizes and / or depths using the same ablation device. Saline can be used to expand the expandable member and not for conduction. If the expandable member (which is non-porous) is punctured or otherwise damaged, the saline can safely leak out of the expandable member.

[0072]

[0086] In some embodiments, the distal end of the catheter shaft (210) may extend into the internal cavity of the expandable member (240) to aid in the advancement of the ablation device (200) through the vasculature and to provide stiffness and support to the distal end of the ablation device (200). The added stiffness may further provide additional tactile feedback to the operator. For example, the distal end of the catheter shaft (210) coupled to the distal end of the expandable member (240) may provide sufficient support and stiffness in advancing the expandable member (240) through a transseptal puncture. In some embodiments, the distal end of the catheter shaft (210) may include a set of splines in the expandable member that are offset away from the longitudinal axis of the catheter shaft (210) and connect together at the distal end of the expandable member (240). For example, a set of splines may be coupled to the interior surface of the catheter shaft (210) and the expandable member (240) and configured to translate along the longitudinal axis to transition between a first configuration in which the set of splines is approximately parallel to the longitudinal axis and a second configuration in which the set of splines is offset away from the longitudinal axis. The set of splines may form a basket-like shape to provide stiffness and support to the expandable member. In some embodiments, the distal end of the catheter shaft (210) may be configured with a predetermined stiffness that is different from the stiffness of the catheter shaft (210) proximal to the expandable member (240). For example, the distal end of the catheter shaft (210) within the expandable member (240) may be stiffer than the deflectable portion of the catheter shaft (210).

[0073]

[0087] In some embodiments, one or more distal portions of the catheter shaft (210) may include a radiopaque portion. For example, the distal portion of the catheter shaft (210) may include a radiopaque platinum coil within the cavity of the expandable member (240). The radiopaque portion may be imaged under fluoroscopy to assist the operator in positioning and placing the ablation device (200) within one or more body cavities of the patient. The radiopaque portion may include a set of marker bands. In some embodiments, one or more splines of the distal portion (e.g., distal end) of the catheter shaft (210) may include a radiopaque portion (not shown) formed on the surface of the spline. Additionally or alternatively, a position sensor may be coupled to the distal end of the catheter shaft (210) within the expandable member (240).

[0074]

[0088] 3 is a side view of another embodiment of an ablation device (300) (e.g., structurally and / or functionally similar to ablation devices (110, 200)) including a catheter shaft (310) having a first set of electrodes (320) and an expandable member (e.g., balloon) (340) provided proximal to a second set of electrodes (330). The first set of electrodes may be formed on a surface of a distal portion of the catheter shaft (310). In use, the electrodes (320, 330) may be positioned in a cardiac chamber to deliver a pulsed waveform to ablate tissue (350), as described in more detail herein.

[0075]

[0089] In some embodiments, a handle (not shown) may be coupled to a proximal portion of the ablation device (300) and may include a bending mechanism (e.g., one or more pull wires (not shown)) configured to change the shape of the distal portion (310) of the catheter shaft. For example, manipulation of the pull wires of the handle may increase or decrease the curvature (e.g., bending of the catheter shaft (310)) of the deflectable portion (312) of the distal portion of the catheter shaft (310). In some embodiments, the catheter (300) may have a deflectable portion (312) proximal to the second set of electrodes (330) and / or the first set of electrodes (320). The deflectable portion may be configured to deflect up to about 210 degrees relative to the longitudinal axis of the catheter shaft (310). The curvature of the deflectable portion (312) of the catheter shaft (310) may be modified such that the electrodes (320, 330) and expandable member (340) are positioned near and / or in contact with the tissue surface (350) (e.g., in contact with the inner radial surface of the ventricle). In this manner, apposition of the ablation device (300) to the tissue may be provided in a desired position and orientation (e.g., the expandable member may be perpendicular, angled, or parallel to the tissue surface).

[0076]

[0090] In some embodiments, the pulse waveform may be applied between the first set of electrodes (320) and the expandable member (340) comprised of an anode set and a cathode set. It should be understood that any of the pulse waveforms disclosed herein may be applied incrementally or continuously to the anode-cathode pairs of the set. In some embodiments, the first set of electrodes (320) may have an opposite polarity to the second set of electrodes (330) during delivery of the voltage pulse waveform. The electrodes (320, 330) may comprise a series of metal bands or rings and may be independently addressable in some embodiments. In some embodiments, the leads of at least two electrodes of the first set of electrodes (320) may be electrically coupled at or near a proximal portion of the ablation device, such as in the handle.

[0077]

[0091] FIG. 5A is a side view of an ablation device (500) (e.g., structurally and / or functionally similar to ablation device (110)) including a catheter shaft (510) and an expandable member (e.g., balloon) (540) coupled to a distal end of the catheter shaft (510). In some embodiments, the ablation device (500) is useful for forming lesions on an endocardial surface (555) via focal ablation. FIG. 5B illustrates spatial zones (530, 532) that may correspond to tissue ablation zones of electric field intensity high enough to generate focal ablation lesions on the tissue surface (555). As shown in FIG. 5A, the expandable member (540) may generally be configured as a second electrode and may have a portion (545) that may be at least partially metallic. In some embodiments, the first set of electrodes (520) of the ablation device (500) may be configured as a cathode and the second electrode (545) may be configured as an anode, or vice versa. In some embodiments, the first set of electrodes (520) may have an opposite polarity to the second electrode (545) during delivery of the voltage pulse waveform. The first set of electrodes (520) may be formed on the surface of the distal portion of the catheter shaft (510). The planar distal second electrode (545) of the expandable member (540) may be positioned against a tissue surface, such as a ventricular wall (555). The expandable member (540) in the second configuration may have a circular cross-section. For example, the expandable member (545) may have a diameter of about 12 mm, and a potential difference of about 2,000 V may be applied between the anode (520) and cathode (545) electrodes. In some embodiments, the first set of electrodes (520) may each have a width of about 3 mm and a spacing between adjacent electrodes of about 3 mm, hi some embodiments, the distal-most electrode of the first set of electrodes (520) may be separated from the expandable member (540) by at least about 5 mm.

[0078]

[0092] 5B illustrates first and second spatial zones (530, 532) corresponding to a field strength of at least about a magnitude of 460 V / cm when a potential difference of about 2,000 V is applied between the anode (520) and the cathode (545) and the distal planar electrode (545) is positioned against a tissue wall (555). The second spatial zone (532), which overlaps the tissue wall (555), can have a depth of about 7 mm and a width of about 20 mm.

[0079]

[0093] In some embodiments, the ablation device (500') may include an expandable member (540') having a distal portion with a concave surface facing away from a proximal end of the expandable member (540'). As shown in Figures 5C and 5D, the expandable member (540') may include a first curved portion (544') and a second curved portion (545'). The first curved portion (544') may include a portion of the expandable member (540') configured to contact an endocardial surface (555'), as shown in Figure 5E.

[0080]

[0094] In some embodiments, for example as shown in FIG. 5C, the expandable member (540') may include an expandable member lumen (537') extending along a first longitudinal axis of the catheter shaft (510') from the distal end of the catheter shaft (510') to the distal end of the expandable member (540'). The proximal end of the lead (539') may be coupled to a second set of electrodes (535') (e.g., a distal electrode) and extend through the expandable member lumen (537') to couple to an electrode portion (545') at the distal end (540') of the expandable member. Thus, the electrode portion (545') may be configured to deliver an irreversible electroporation voltage pulse. The first set of electrodes (520') and portion (545') may be configured with opposite polarity.

[0081]

[0095] FIG. 5D is a perspective view of the expandable member (540') of FIG. 5C having a metal recess (545') covering substantially the entire distal surface of the expandable member (540'). For example, the expandable member (545') may have a diameter of about 12 mm, and a potential difference of, for example, about 2,000 V may be applied between the expandable member (545') (e.g., an anode) and the first set of electrodes (520') (e.g., a cathode). In some embodiments, the first set of electrodes (520') may have a width of about 3 mm and a spacing of about 3 mm therebetween. The distal-most electrode of the first set of electrodes (520') may be separated from the expandable member (540') by about 5 mm. The first set of electrodes (520') may have a width of about 3 mm and a spacing of about 3 mm therebetween. The distal most electrode of the first set of electrodes (520') may be approximately 7 mm away from the expandable member (540'). These dimensions are provided as examples for illustrative purposes only, and other values ​​may be selected as deemed convenient for clinical application.

[0082]

[0096] 5E illustrates first and second spatial zones (530', 532') corresponding to electric field strength sufficient to generate focal ablation lesions. The second ablation zone (532') may correspond to a tissue ablation zone when the expandable member (540') is positioned against a tissue wall (555'). In some embodiments, the second set of electrodes (535') and the portion (545') of the expandable member (540') (e.g., including a metal) may be configured as electrodes of one polarity, while the first set of electrodes (520') (e.g., the proximal electrode(s)) may be configured as electrode(s) of the opposite polarity. 5E illustrates first and second spatial zones (530', 532') corresponding to a field intensity having a magnitude of at least about 460 V / cm when a potential difference of about 2,000 V is applied between the anode (520') and cathode (545') electrodes and the distal curved electrode portion (545') (e.g., concave) is positioned against a tissue wall (555'). The second spatial zone (532') overlapping the tissue wall (555') can have a depth of about 5 mm and a width of about 21 mm. In some variations, the second spatial zone (532') can have a depth of up to about 10 mm and a width of up to about 30 mm.

[0083]

[0097] 5F and 5G show an ablation device (500'') (e.g., structurally and / or functionally similar to ablation device (110)) including a catheter shaft (510'') and an expandable member (540'') coupled to a distal end of the catheter shaft (510''). In some embodiments, the ablation device (500'') is useful for creating lesions on an endocardial surface via focal ablation. In some embodiments, the expandable member (540'') may have a multi-sided shape. In some embodiments, the multi-sided shape may generally have one or more second electrodes (504'') disposed on portions of one or more faces (511'') of the multi-sided shape. A first set of electrodes (520') may be disposed on the catheter shaft (510'). The expandable member (540') may generally have one or more second electrode portions (504'') that may be configured as electrodes of the second set of electrodes and may include metal. The expandable member (540'') in the second configuration may have a polyhedral shape with one or more faces (511''). The second electrode portions (504'') may be electrically wired together to function as a single electrode or wired separately as independent electrodes. FIG. 5F shows a dodecahedral shaped expandable member (540'') having second electrode portions (504') on six faces (511''). In some embodiments, the first set of electrodes (520'') may have an opposite polarity than the second electrode portions (504'') during delivery of the voltage pulse waveform. In some embodiments, one or more faces (511'') of the polyhedron may have a curved surface.

[0084]

[0098] In some embodiments, one or more of the second electrode portions (504'') of the second set of electrodes may be configured to receive an ECG signal, as described herein. The strength and / or pattern of the ECG signal received by the one or more second electrode portions (504'') may be used to determine the level of contact of each of the second electrode portions (504'') with tissue (e.g., a heart chamber wall). The electrode portions (504'') of the second set may be selected using the ECG signal to be configured as an anode or a cathode. Thus, one or more second electrode portions (504'') disposed on corresponding faces (511'') of the expandable member (540'') may be used for tissue ablation based on ECG signal strength corresponding to tissue contact. In some embodiments, the edges of the faces (511'') (e.g., polyhedral surfaces) may be rounded to form a "soft" surface.

[0085]

[0099] In some embodiments, one or more of the second set of electrodes (504'') disposed on the surface (511'') may form pockets configured to contact the tissue surface of those surfaces (511''). The edges (515'') of these surfaces (511'') may have a greater stiffness than the surface (511'') itself, and the expandable member (540'') in the second configuration may form a polyhedral shape (511'') having one or more concave sides.

[0086]

[0100] FIG. 5G is another perspective view of an ablation device (500'') having an expandable member (540'') having a generally polyhedral shape with metalized electrodes (504'') disposed on a portion of one or more faces (511'', 512'', 513'', 514'') of the expandable member (540''). In some embodiments of the present invention, the catheter shaft (510'') may define a catheter shaft lumen (not shown) configured to inject saline to expand the expandable member (540''). Leads may also be disposed within the catheter shaft lumen and configured to connect to the one or more electrodes (504''). The edges (515'') of the faces (511'', 512'', 513'', 514'') may be rounded and have a greater stiffness than the surfaces of the faces such that a concave face is formed when in the second configuration. In some embodiments, the diameter of the expandable member (540') in the second configuration can be from about 6 mm to about 22 mm. The first set of electrodes (520'') can be separated from the proximal end of the expandable member (540'') by at least about 3 mm or more. The metalized electrode portion (504'') can have a diameter of from about 6 mm to about 15 mm. In some embodiments, the edge (522''') of one or more faces (511''') of the expandable member (540''') can be curved. As shown in FIG. 5H, one or more electrode portions (504''') of the second set of electrodes can be disposed on a face (511''') of the expandable member (540'''). The curved edge (522''') (e.g., a polyhedral surface) can form a soft surface (511''').

[0087]

[0101] FIG. 5I illustrates an ablation device (500'''') (e.g., structurally and / or functionally similar to ablation device (110)) including a catheter shaft (510'''') and an expandable member (e.g., balloon) (540'''') coupled to a distal end of the catheter shaft (510''''). In some embodiments, the ablation device (500'''') is useful for forming lesions on an endocardial surface via focal ablation. In some embodiments, the expandable member (540'''') may define an annular expandable member lumen (533'''') (e.g., having an annular shape) and may include a distal surface (545'''') with a first electrode portion. The distal surface (545'''') may have a substantially planar portion. A second electrode (535'''') (needle) may be disposed within the expandable member lumen (533'''') and may extend distally from the expandable member lumen (533'''') along a longitudinal axis of the expandable member (540''''). The expandable member (540'''') may have a planar distal surface (545'''') that may be metalized and configured as a first electrode. An annular space defined by the expandable member lumen (533'''') may separate the second electrode (535'''') from the annular expandable member (540'''') to prevent flash arcing when the second electrode (535'''') and the first electrode portion (545'''') are polarized with opposite electrical polarities. For example, the needle may have a length of about 8 mm to about 10 mm. The expandable member (540'''') may have a diameter of about 12 mm. The expandable member lumen (533'''') can have a diameter of about 4 mm to about 8 mm.

[0088]

[0102] 5J illustrates spatial zone (532'''') corresponding to a field intensity of at least about 460 V / cm magnitude when a potential difference of about 2,000 V is applied between electrode (535'''') and electrode portion (545'''') and planar distal electrode (545'''') is positioned at tissue wall (555''''). Spatial zone (532'''') overlapping tissue wall (555'''') can have a depth of about 10 mm and a width of about 14 mm.

[0089]

[0103] FIG. 11 is a side view of another embodiment of an ablation device (1100) (e.g., structurally and / or functionally similar to ablation devices (110, 200, 300, 500, 500', 500'', 500'''') including a catheter shaft (1110) having a first set of electrodes (1120) and an expandable member (e.g., balloon) (1140) provided proximal to a second set of electrodes (1130, 1132). The first set of electrodes (1120) may be formed on a surface of a distal portion of the catheter shaft (1110). That is, the first set of electrodes (1120) may be formed on a surface of a distal end of the catheter shaft (1110). The second set of electrodes (1130, 1132) may be formed on a surface of the distal end of the expandable member (1140) and may be electrically insulated from the first set of electrodes (1120). In some embodiments, the major axis (e.g., longitudinal axis) of the second electrode (1132) may be substantially parallel to the longitudinal axis of the catheter shaft (1110) and / or the expandable member (1140).

[0090]

[0104] In some embodiments, the ablation device (1100) is useful for creating lesions on endocardial surfaces via focal ablation, such as on the interior surface of a ventricle. In use, the electrodes (1120, 1130, 1132) can be positioned in the ventricle to deliver pulse waveforms to ablate tissue, as described in more detail herein. The distal portion of the expandable member (1140) can 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). The catheter shaft (1110) and expandable member (1140) can be sized for advancement into the endocardial space (e.g., the left ventricle). The catheter shaft (1110) can be flexible so as to be deflectable. For example, the deflectable portion of the catheter shaft (1110) may be configured to deflect a portion of the catheter (1100) including the second set of electrodes (1130, 1132) and the expandable member (1140) up to about 210 degrees relative to the longitudinal axis. The expandable member (1140) may be configured to transition between a first configuration (e.g., a contracted state) and a second configuration (e.g., an expanded state). In the first configuration, the expandable member (1140) may have a diameter approximately the same as the diameter of the catheter shaft (1110) to aid in advancing the ablation device (1100) through the vasculature. For example, the expandable member (1140) in the first configuration may be approximately parallel to the longitudinal axis of the catheter shaft (1110). The expandable member (1140) in the second configuration may be biased away from the longitudinal axis. The first set of electrodes (1120) may be structurally and / or functionally similar to the electrodes (220, 230) described with respect to Figures 2A-2D.

[0091]

[0105] The first set of electrodes (1120) may be electrically coupled together using one or more conductors. The second set of electrodes (1130, 1132) may be electrically coupled together using a different set of conductors. In some embodiments, the expandable member (1140) may be electrically coupled to the second set of electrodes (1130, 1132). A voltage pulse waveform delivered to the electrically coupled expandable member (1140) between the first set of electrodes (1120) and the second set of electrodes (1130, 1132) may be used to form a lesion (e.g., a spot lesion) via focal ablation of a predetermined size and shape. In some embodiments, the first set of electrodes (1120) may be configured as an anode while the second set of electrodes (1130, 1132) and the expandable member (240) may be configured as a cathode, or vice versa. Thus, a dipole may be formed between the first set of electrodes (1120) and the expandable member (1140), resulting in an electric field that may ablate tissue (e.g., myocardial cells on an interior surface or within a ventricle). The expandable member (1140) and the first set of electrodes (1120) may be electrically insulated from one another. For example, the second set of electrodes (1130, 1132) and the first set of electrodes (1120) may each be coupled to a respective insulated conductor, each conductor having sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness between them without dielectric breakdown.

[0092]

[0106] The first and second sets of electrodes (1120, 1130, 1132) may include atraumatic shapes to reduce trauma to tissue. For example, the first set of electrodes (1120) may be ring electrodes. In some embodiments, the first set of electrodes (1120) may be positioned along any portion of the catheter shaft (1110) proximal to the second set of electrodes (1130, 1132). The first set of electrodes (1120) may be spaced apart from one another and wired together via one or more insulated leads to function as a single electrode (e.g., an anode or a cathode) while the catheter shaft (1110) remains flexible and facilitates deflection. The second set of electrodes (1130, 1132) may be positioned on a surface of the expandable member (1140) and / or may be flush with the surface of the expandable member (1140) to be electrically coupled to the expandable member (1140). The second set of electrodes (1130, 1132) may have the same or different size, shape, and / or location along the expandable member (1140).

[0093]

[0107] For example, the second set of electrodes (1130, 1132) may include a distal tip electrode (1130) and a set of generally circular or elliptical shaped electrodes (1132) arranged around the expandable member (1140). For example, the second set of electrodes (1130) may be formed on the expandable member (1140) on an approximate plane that is generally perpendicular to the longitudinal axis. In some embodiments, each electrode of the second set of electrodes (1130, 1132) may be wired together. In other embodiments, a subset of the electrodes of the second set of electrodes (1130, 1132) may be electrically wired together while the other subset may be independently addressable. In some embodiments, the distal tip electrode (1132) may be electrically isolated from the first set of electrodes (1120). In some embodiments, each electrode of the second set of electrodes (1130, 1132) may be independently addressable. The distal tip electrode (1132) may be formed on a distal portion of the expandable member (1440) and may be electrically insulated from the first set of electrodes (1120). The distal tip electrode (1132) may have a diameter in the range of about 3 mm to about 10 mm.

[0094]

[0108] In some embodiments, one or more of the first and second sets of electrodes (1120, 1132) may be configured to receive or sense ECG signals for recording electrophysiological data. The ablation device (1100) may include one or more ECG signal electrodes. For example, one or more of the second set of electrodes (1130, 1132) may be configured to receive ECG signals. These ECG signal electrodes, such as the distal tip electrode (1130), may be coupled to their own insulated conductors. The ECG signal electrodes may be electrically insulated from the expandable member (1140), for example, using a ring of insulation around the ECG signal electrodes. In these embodiments, the ablation device may be used to record electrophysiological data before and / or after tissue ablation, instead of a mapping catheter.

[0095]

[0109] One or more biphasic signals may be applied to the dipole to ablate tissue between the expandable member (1140) and the first set of electrodes (1120) at a desired location in the ventricle. In some embodiments, the expandable member (1140) in the second configuration may be configured to contact endocardial tissue, while the first set of electrodes (1130) in the second configuration may not contact endocardial tissue. The electric field generated by the ablation device (1100) through conduction between the expandable member (1140) and the first set of electrodes (1120) through the blood pool and tissue may result in focal ablation of tissue via irreversible electroporation. The expandable member (1140) when expanded has an asymmetric shape in the proximal to distal direction, such that one end (e.g., the distal end) of the expandable member (1140) may be more bulbous than the other end (e.g., the proximal end) of the expandable member (1140). The expandable member (1140) when expanded can be rotationally symmetric about the longitudinal axis of the catheter shaft (1110). In this configuration, the expandable member (1140) can contact the endocardial surface and can be used to form lesions (e.g., spot lesions) via focal ablation.

[0096]

[0110] In some embodiments, the catheter shaft (1110) may include a deflectable portion between the first set of electrodes (1120) and the second set of electrodes (1130) in the same manner as shown in Figure 3. The deflectable portion may be configured to deflect up to about 210 degrees relative to the longitudinal axis of the catheter shaft (1110). In some embodiments, an actuator (e.g., a fluid source) may be coupled to the expandable member and configured to transition the expandable member between a first configuration (e.g., a deflated state) and a second configuration (e.g., an inflated state), for example, by using pressurized saline.

[0097]

[0111] FIG. 12 is a side view of another embodiment of an ablation device (1200) (e.g., structurally and / or functionally similar to ablation devices (110, 200, 300, 500, 500', 500'', 500'''', 1100) including a catheter shaft (1210) having a first set of electrodes (1220) and an expandable member (e.g., balloon) (1240) provided proximal to a second set of electrodes (1230). The first set of electrodes (1220) may be formed on a surface of a distal portion of the catheter shaft (1210). That is, the first set of electrodes (1220) may be formed on a surface of the distal end of the catheter shaft (1210). The second set of electrodes (1230) may be formed on a surface of the distal end of the expandable member (1240) and may be electrically insulated from the first set of electrodes (1220). In some embodiments, the ablation device (1200) is useful for forming lesions on endocardial surfaces via focal ablation, such as the interior surface of a ventricle. In use, the electrodes (1220, 1230) may be positioned in the ventricle to deliver a pulse waveform to ablate tissue, as described in more detail herein. The distal portion of the expandable member (1240) may include and / or be formed with an atraumatic shape that reduces trauma to tissue. The catheter shaft (1210) and the expandable member (1240) may be sized for advancement into the endocardial space (e.g., the left ventricle). The catheter shaft (1210) may be flexible so as to be deflectable. For example, the deflectable portion of the catheter shaft (1210) may be configured to deflect a portion of the catheter (1200) including the second set of electrodes (1230) and the expandable member (1240) up to about 210 degrees relative to the longitudinal axis. The expandable member (1240) may be configured to transition between a first configuration (e.g., a contracted state) and a second configuration (e.g., an expanded state). In the first configuration, the expandable member (1240) may have a diameter approximately the same as that of the catheter shaft (1210) to aid in advancing the ablation device (1200) through the vasculature. For example, the expandable member (1240) in the first configuration may be approximately parallel to the longitudinal axis of the catheter shaft (1210).The expandable member (1240) when expanded may be biased away from the longitudinal axis. The first set of electrodes (1220) may be structurally and / or functionally similar to the electrodes (220, 230) described with respect to Figures 2A-2D.

[0098]

[0112] The first set of electrodes (1220) may be electrically coupled to each other using one or more conductors. One or more of the second set of electrodes (1230) may be electrically coupled together using a different set of conductors. A voltage pulse waveform delivered between the first set of electrodes (1220) and the second set of electrodes (1230) may be used to form a lesion (e.g., a spot lesion) via focal ablation of a predetermined size and shape. In some embodiments, the first set of electrodes (1220) may be configured as an anode while the second set of electrodes (1230) may be configured as a cathode, or vice versa. Thus, a dipole may be formed between the first set of electrodes (1220) and the second set of electrodes (1230), and an electric field may be generated that may ablate tissue (e.g., myocardial cells on an interior surface or within a ventricle). The second set of electrodes (1230) and the first set of electrodes (1220) may be electrically insulated from one another. For example, the second set of electrodes (1230) and the first set of electrodes (1220) may each be coupled to a respective insulated conductor, each conductor having sufficient electrical insulation to maintain a potential difference of at least 700 V across its thickness therebetween without dielectric breakdown.

[0099]

[0113] The first and second sets of electrodes (1220, 1230) may include atraumatic shapes to reduce trauma to tissue. For example, the first set of electrodes (1220) may be ring electrodes. In some embodiments, the first set of electrodes (1220) may be disposed along any portion of the catheter shaft (1210) proximal to the second set of electrodes (1230). The first set of electrodes (1220) may be spaced apart from one another and wired together via one or more insulated leads to function as a single electrode (e.g., an anode or a cathode) while the catheter shaft (1210) remains flexible and facilitates deflection. The second set of electrodes (1230) may be disposed on a surface of the expandable member (1240) and / or may be flush with the surface of the expandable member (1240) to be electrically coupled to the expandable member (1240). The second set of electrodes (1230) may have the same or different size, shape, and / or location along the expandable member (1240).

[0100]

[0114] For example, the second set of electrodes (1230) may include a generally circular set of electrodes disposed about the circumference of the expandable member (1240). In some embodiments, each electrode in the second set of electrodes (1230) may be wired together. In other embodiments, a subset of the electrodes in the second set of electrodes (1230) may be electrically wired together, while other subsets may be independently addressable.

[0101]

[0115] In some embodiments, one or more of the first and second sets of electrodes (1220) may be configured to receive or sense ECG signals for recording electrophysiological data. The ablation device (1200) may include one or more ECG signal electrodes. For example, one or more of the second set of electrodes (1230) may be configured to receive ECG signals. These ECG signal electrodes may be coupled to their own insulated conductors. In these embodiments, the ablation device may be used to record electrophysiological data before and / or after tissue ablation, in place of a mapping catheter.

[0102]

[0116] One or more biphasic signals may be applied to the dipole formed by the first set of electrodes (122) and the second set of electrodes (1230) to ablate tissue distal to or surrounding the expandable member (1240) at a desired location in the ventricle. For example, a biphasic pulse waveform may be delivered between the set of electrodes, resulting in a zone of irreversible electroporative ablation in the area around the expandable member. The expandable member (1240) when expanded may have an asymmetric shape in the proximal to distal direction, such that one end (e.g., the distal end) of the expandable member (1240) may be more bulbous than the other end (e.g., the proximal end) of the expandable member (1240). The expandable member (1240) when expanded may be rotationally symmetric about the longitudinal axis of the catheter shaft (1210). In this configuration, the expandable member (1240) may be positioned on the endocardial surface and used to create a lesion (e.g., a spot lesion) via focal ablation. The electrode lead may be constructed with sufficient insulation and high dielectric strength so as to be suitable for delivery of the irreversible electroporation energy described herein.

[0103]

[0117] In some embodiments, the catheter shaft (1210) may include a deflectable portion, in some embodiments between the first set of electrodes (1220) and the second set of electrodes (1230), or in other embodiments proximal to the first set of electrodes (1220). The deflectable portion may be configured to deflect up to about 210 degrees relative to a longitudinal axis of the catheter shaft (1210). In some embodiments, an actuator (e.g., a fluid source) may be coupled to the expandable member and configured to transition the expandable member between a first configuration (e.g., a deflated state) and a second configuration (e.g., an inflated state), for example, by using pressurized saline.

[0104]

[0118] FIG. 13 is a side view of another embodiment of an ablation device (1300) (e.g., structurally and / or functionally similar to ablation devices (110, 200, 300, 500, 500', 500'', 500'''', 1100, 1200) including a catheter shaft (1310) having a first set of electrodes (1320) and an expandable member (e.g., balloon) (1340) provided proximal to a second set of electrodes (1330, 1332). The first set of electrodes (1320) may be formed on a surface of a distal portion of the catheter shaft (1310). That is, the first set of electrodes (1320) may be formed on a surface of a distal end of the catheter shaft (1310). The second set of electrodes (1330, 1332) may be formed on a surface of the distal end of the expandable member (1340) and may be electrically insulated from the first set of electrodes (1320). In some embodiments, the major axis (e.g., longitudinal axis) of the second electrode (1332) may be substantially parallel to the longitudinal axis of the catheter shaft (1310) and / or the expandable member (1340).

[0105]

[0119] In some embodiments, the ablation device (1300) is useful for creating lesions on endocardial surfaces via focal ablation, such as on the interior surface of a ventricle. In use, the electrodes (1320, 1330, 1332) can be positioned in the ventricle to deliver a pulse waveform to ablate tissue, as described in more detail herein. The distal portion of the expandable member (1340) can include and / or be formed with an atraumatic shape that reduces trauma to tissue. The catheter shaft (1310) and the expandable member (1340) can be sized for advancement into the endocardial space (e.g., the left ventricle). The catheter shaft (1310) can be flexible so as to be deflectable. For example, the deflectable portion of the catheter shaft (1310) can be configured to deflect a portion of the catheter (1300) including the second set of electrodes (1330, 1332) and the expandable member (1340) up to about 210 degrees relative to the longitudinal axis. The expandable member (1340) may be configured to transition between a first configuration (e.g., a contracted state) and a second configuration (e.g., an expanded state). In the first configuration, the expandable member (1340) may have a diameter approximately the same as the diameter of the catheter shaft (1310) to aid in advancing the ablation device (1300) through the vasculature. For example, the expandable member (1340) in the first configuration may be approximately parallel to the longitudinal axis of the catheter shaft (1310). The expandable member (1340) when expanded may be biased away from the longitudinal axis. The first set of electrodes (1320) may be structurally and / or functionally similar to the electrodes (220, 230) described with respect to FIGS. 2A-2D.

[0106]

[0120] The first set of electrodes (1320) may be electrically coupled together using one or more conductors. The second set of electrodes (1330, 1332) may be electrically coupled together using a different set of conductors. A voltage pulse waveform delivered between the first set of electrodes (1320) and the second set of electrodes (1330, 1332) may form a lesion (e.g., a spot lesion) via focal ablation of a predetermined size and shape. In some embodiments, the first set of electrodes (1320) may be configured as an anode while the second set of electrodes (1330, 1332) may be configured as a cathode, or vice versa. The second set of electrodes (1330, 1332) and the first set of electrodes (1320) may be electrically isolated from each other. For example, the second set of electrodes (1330, 1332) and the first set of electrodes (1320) can each be coupled to a respective insulated conductor, each conductor having sufficient electrical insulation to maintain a potential difference of at least 700 V across its thickness therebetween without dielectric breakdown.

[0107]

[0121] The first and second sets of electrodes (1320, 1330, 1332) may include atraumatic shapes to reduce trauma to tissue. For example, the first set of electrodes (1320) may be ring electrodes. In some embodiments, the first set of electrodes (1320) may be disposed along any portion of the catheter shaft (1310) proximal to the second set of electrodes (1330, 1332). The first set of electrodes (1320) may be spaced apart from one another and wired together via one or more insulated leads to function as a single electrode (e.g., an anode or a cathode) while the catheter shaft (1310) remains flexible and facilitates deflection. The second set of electrodes (1330, 1332) may be disposed on a surface of the expandable member (1340) and / or may be flush with the surface of the expandable member (1340) to be electrically coupled to the expandable member (1340). The second set of electrodes (1330, 1332) may have the same or different size, shape, and / or location along the expandable member (1340).

[0108]

[0122] For example, the second set of electrodes (1330, 1332) may include a distal tip electrode (1330) and a set of generally oval shaped electrodes (1332) arranged around the expandable member (1340). For example, the second set of electrodes (1330) may be formed on the expandable member (1340) on an approximate plane that is generally perpendicular to the longitudinal axis. In some embodiments, the longitudinal axis of each electrode (1332) may be substantially parallel to the longitudinal axis of the catheter shaft (1310) and / or the expandable member (1340). In some embodiments, each electrode of the second set of electrodes (1330, 1332) may be wired together. In other embodiments, a subset of the electrodes of the second set of electrodes (1330, 1332) may be electrically wired together while the other subset (e.g., the distal tip electrodes) may be independently addressable. In some embodiments, the distal tip electrode (1332) may be electrically isolated from the first set of electrodes (1320). In some embodiments, each electrode of the second set of electrodes (1330, 1332) may be independently addressable. The distal tip electrode (1330) may be formed at a distal portion of the expandable member (1340) and may be electrically isolated from the first set of electrodes (1320).

[0109]

[0123] In some embodiments, one or more of the first and second sets of electrodes (1320, 1330, 1332) may be configured to receive or sense ECG signals for recording electrophysiological data. The ablation device (1300) may include one or more ECG signal electrodes. For example, one or more of the second set of electrodes (1330, 1332) may be configured to receive ECG signals. These ECG signal electrodes, such as the distal tip electrode (1330), may be coupled to their own insulated conductors. In these embodiments, the ablation device may be used to record electrophysiological data before and / or after tissue ablation, in place of a mapping catheter.

[0110]

[0124] The expandable member (1340) when expanded may have an asymmetric shape in the proximal to distal direction, such that one end (e.g., the distal end) of the expandable member (1340) may be more bulbous than the other end (e.g., the proximal end) of the expandable member (1340). The expandable member (1340) when expanded may be rotationally symmetric about the longitudinal axis of the catheter shaft (1310). In this configuration, the expandable member (1340) may be positioned on the endocardial surface and used to form a lesion (e.g., a spot lesion) via focal ablation. The electrode lead may be constructed with sufficient insulation and high dielectric strength so as to be suitable for delivery of the irreversible electroporation energy described herein.

[0111]

[0125] In some embodiments, the catheter shaft (1310) may include a deflectable portion between the first set of electrodes (1320) and the second set of electrodes (1330) or proximal to the first set of electrodes (1320). The deflectable portion may be configured to deflect up to about 210 degrees relative to a longitudinal axis of the catheter shaft (1310). In some embodiments, an actuator (e.g., a fluid source) may be coupled to the expandable member and configured to transition the expandable member between a first configuration (e.g., a deflated state) and a second configuration (e.g., an inflated state), for example, by using pressurized saline.

[0112]

[0126] FIG. 14 is a side view of another embodiment of an ablation device (1400) (e.g., structurally and / or functionally similar to ablation devices (110, 200, 300, 500, 500', 500'', 500'''', 1100, 1200, 1300) including a catheter shaft (1410) having a first set of electrodes (1420) and an expandable member (e.g., balloon) (1440) provided proximal to a second set of electrodes (1430, 1432). The first set of electrodes (1420) may be formed on a surface of a proximal portion of the expandable member (1440). For example, the first set of electrodes (1420) may be formed proximal to the equatorial plane of the expandable member (1440). As used herein, the equatorial plane of the expandable member (1440) refers to the plane that intersects the maximum cross-sectional diameter of the expandable member (1440) when expanded. That is, the proximal portion of the expandable member (1440) is proximal to the cross-sectional diameter of the expandable member (1440) at its maximum portion. The second set of electrodes (1430, 1432) may be formed on a surface of the expandable member (1440) distal to the equatorial plane and may be electrically insulated from the first set of electrodes (1420). In some embodiments, the major axes (e.g., longitudinal axes) of the first set of electrodes (1420) and the second set of electrodes (1432) may be substantially parallel to the longitudinal axis of the catheter shaft (1410) and / or the expandable member (1440).

[0113]

[0127] In some embodiments, the ablation device (1400) is useful for creating lesions on endocardial surfaces via focal ablation, such as the interior surface of a ventricle. In use, the electrodes (1420, 1430, 1432) can be positioned in the ventricle to deliver a pulse waveform to ablate tissue, as described in more detail herein. The distal portion of the expandable member (1440) can include and / or be formed with an atraumatic shape that reduces trauma to tissue. The catheter shaft (1410) and expandable member (1440) can be sized for advancement into the endocardial space (e.g., the left ventricle). The catheter shaft (1410) can be flexible so as to be deflectable. For example, the deflectable portion of the catheter shaft (1410) may be configured to deflect a portion of the catheter (1400) including the first and second sets of electrodes (1420, 1430, 1432) and the expandable member (1440) up to about 210 degrees relative to the longitudinal axis. The expandable member (1440) may be configured to transition between a first configuration (e.g., a contracted state) and a second configuration (e.g., an expanded state). In the first configuration, the expandable member (1440) may have a diameter approximately the same as the diameter of the catheter shaft (1410) to aid in advancing the ablation device (1400) through the vasculature. For example, the expandable member (1440) in the first configuration may be approximately parallel to the longitudinal axis of the catheter shaft (1410). The expandable member (1440) when expanded may be biased away from the longitudinal axis.

[0114]

[0128] The first set of electrodes (1420) may be electrically coupled together using one or more conductors. The second set of electrodes (1430, 1432) may be electrically coupled together using a different set of conductors. Thus, a dipole may be formed between the first set of electrodes (1420) and the second set of electrodes (1430, 1432), resulting in an electric field that may ablate tissue (e.g., myocardial cells on an interior surface or within a ventricle). For example, the second set of electrodes (1430, 1432) and the first set of electrodes (1420) may each be coupled to a respective insulated conductor, each conductor having sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness between them without dielectric breakdown.

[0115]

[0129] The first and second sets of electrodes (1420, 1430, 1432) may include atraumatic shapes to reduce trauma to tissue. For example, the first set of electrodes (1420) may have a set of approximately oval shaped electrodes (1420) arranged around the expandable member (1440). In some embodiments, the first set of electrodes (1420) may be arranged along any portion of the expandable member (1440) proximal to the second set of electrodes (1430, 1432). The first set of electrodes (1420) may be spaced apart from one another and wired together via one or more insulated leads to function as a single electrode (e.g., an anode or a cathode). The second set of electrodes (1430, 1432) may be arranged at a distal end of the expandable member (1430, 1432) and electrically insulated from the first set of electrodes (1420).

[0116]

[0130] The first and second sets of electrodes (1420, 1430, 1432) may have the same or different sizes, shapes, and / or positions along the expandable member (1440). For example, one or more of the first and second sets of electrodes (1420, 1430, 1432) may have a generally oval shape. For example, the second set of electrodes (1430, 1432) may include a distal tip electrode (1430) and a set of generally oval shaped electrodes (1432) disposed about the expandable member (1440). In some embodiments, the longitudinal axis of each electrode (1420, 1432) may be substantially parallel to the longitudinal axis of the catheter shaft (1410) and / or the expandable member (1440). In some embodiments, each electrode of the second set of electrodes (1430, 1432) may be wired together. In other embodiments, a subset of the electrodes in the second set of electrodes (1430, 1432) may be electrically wired together while the other subset (e.g., the distal tip electrode) may be independently addressable. In some embodiments, the distal tip electrode (1432) may be electrically isolated from the first set of electrodes (1420). In some embodiments, one or more electrodes in the first and second sets of electrodes (1420, 1430, 1432) may be independently addressable. The distal tip electrode (1430) may be formed in a distal portion of the expandable member (1440).

[0117]

[0131] In some embodiments, one or more of the first and second sets of electrodes (1420, 1430, 1432) may be configured to receive or sense ECG signals for recording electrophysiological data. The ablation device (1400) may include one or more ECG signal electrodes. For example, one or more of the second set of electrodes (1430, 1432) may be configured to receive ECG signals. These ECG signal electrodes, such as the distal tip electrode (1430), may be coupled to their own insulated conductors. In these embodiments, the ablation device may be used to record electrophysiological data before and / or after tissue ablation, in place of a mapping catheter.

[0118]

[0132] In some embodiments, the first and second sets of electrodes (1420, 1430, 1432) may be configured to deliver a pulse waveform from the signal generator to tissue during use. The expandable member (1440) may be coupled to a distal portion of the catheter shaft (1410) and may be configured to deliver irreversible electroporation energy to tissue. The first and second sets of electrodes (1420) and (1430, 1432) may have opposite electrical polarities during delivery of the pulse waveform.

[0119]

[0133] The electric field generated by the ablation device (1400) by conduction between the second set of electrodes (1430, 1432) and the first set of electrodes (1420) through the blood pool and tissue can result in focal ablation of tissue via irreversible electroporation. The expandable member (1440) when expanded has an asymmetric shape in the proximal to distal direction, such that one end (e.g., the distal end) of the expandable member (1440) can be more bulbous than the other end (e.g., the proximal end) of the expandable member (1440). The expandable member (1440) when expanded can be rotationally symmetric about the longitudinal axis of the catheter shaft (1410). In this configuration, the expandable member (1440) can be positioned on an endocardial surface and used to form a lesion (e.g., a spot lesion) via focal ablation. The electrode lead may be constructed with sufficient insulation and high dielectric strength so as to be suitable for delivery of the irreversible electroporation energy described herein.

[0120]

[0134] In some embodiments, the catheter shaft (1410) may include a deflectable portion, such as a distal portion of the catheter shaft (1410). The deflectable portion may be configured to deflect up to about 210 degrees relative to a longitudinal axis of the catheter shaft (1410). In some embodiments, an actuator (e.g., a fluid source) may be coupled to the expandable member and configured to transition the expandable member between a first configuration (e.g., a deflated state) and a second configuration (e.g., an expanded state), for example, by using pressurized saline.

[0121]

[0135] FIG. 15 is a side view of another embodiment of an ablation device (1500) (e.g., structurally and / or functionally similar to ablation devices (110, 200, 300, 500, 500', 500'', 500'''', 1100, 1200, 1300, 1400)) including a catheter shaft (1510) having a first set of electrodes (1520) and an expandable member (e.g., balloon) (1540) provided proximal to a second set of electrodes (1530, 1532, 1534). The first set of electrodes (1510) may be formed on a surface of a distal portion of the catheter shaft (1510). That is, the first set of electrodes (1520) may be formed on a surface of a distal end of the catheter shaft (1510). The second set of electrodes (1530, 1532, 1534) may be formed on a surface of the expandable member (1540) and may be electrically insulated from the first set of electrodes (1520). In some embodiments, the major axes (e.g., longitudinal axes) of the second electrodes (1532, 1534) may be substantially parallel to the longitudinal axis of the catheter shaft (1510) and / or the expandable member (1540).

[0122]

[0136] In some embodiments, the ablation device (1500) is useful for creating lesions on endocardial surfaces via focal ablation, such as the interior surface of a ventricle. In use, the electrodes (1520, 1530, 1532, 1534) can be positioned in the ventricle to deliver pulse waveforms to ablate tissue, as described in more detail herein. The distal portion of the expandable member (1540) can include and / or be formed with an atraumatic shape that reduces trauma to tissue. The catheter shaft (1510) and expandable member (1540) can be sized for advancement into the endocardial space (e.g., the left ventricle). The catheter shaft (1510) can be flexible so as to be deflectable. For example, the deflectable portion of the catheter shaft (1510) may be configured to deflect a portion of the catheter (1500) including the second set of electrodes (1530, 1532, 1534) and the expandable member (1540) up to about 210 degrees relative to the longitudinal axis. The expandable member (1540) may be configured to transition between a first configuration (e.g., a contracted state) and a second configuration (e.g., an expanded state). In the first configuration, the expandable member (1540) may have a diameter approximately the same as the diameter of the catheter shaft (1510) to aid in advancing the ablation device (1500) through the vasculature. For example, the expandable member (1540) in the first configuration may be approximately parallel to the longitudinal axis of the catheter shaft (1510). The expandable member (1540) when expanded may be biased away from the longitudinal axis. The first set of electrodes (1520) may be structurally and / or functionally similar to the electrodes (220, 230) described with respect to Figures 2A-2D.

[0123]

[0137] The first set of electrodes (1520) may be electrically coupled together using one or more conductors. The proximal electrode (1534) of the second set of electrodes and the distal electrode (1532, 1530) of the second set of electrodes may each be electrically wired separately using a different set of conductors. In some embodiments, the first set of electrodes (1520) may be configured as an anode while the second set of electrodes (1530, 1532, 1534) may be configured as a cathode, or vice versa. In alternative embodiments, the first set of electrodes (1520) and the proximal electrode (1534) of the second set of electrodes may be configured as an anode while the distal electrode (1532, 1530) of the second set of electrodes may be configured as a cathode, or vice versa. For example, the proximal electrode of the second set of electrodes (1534), the distal electrode of the second set of electrodes (1532, 1530), and the first set of electrodes (1520) can each be coupled to a respective insulated conductor, each conductor having sufficient electrical insulation to maintain a potential difference of at least 700 V across its thickness without dielectric breakdown.

[0124]

[0138] The first and second sets of electrodes (1520, 1530, 1532, 1534) may include atraumatic shapes to reduce trauma to tissue. For example, the first set of electrodes (1520) may be ring electrodes. In some embodiments, the first set of electrodes (1520) may be positioned along any portion of the catheter shaft (1510) proximal to the second set of electrodes (1530, 1532, 1534). The first set of electrodes (1520) may be spaced apart from one another and wired together via one or more insulated leads to function as a single electrode (e.g., an anode or a cathode) while the catheter shaft (1510) remains flexible and facilitates deflection. The second set of electrodes (1530, 1532, 1534) may be positioned on a superficial surface of the expandable member (1540) and / or be flush with the surface of the expandable member (1540). The second set of electrodes (1530, 1532) may have the same or different size, shape, and / or location along the expandable member (1540).

[0125]

[0139] For example, the second set of electrodes (1530, 1532, 1534) may include a distal tip electrode (1530) and a set of generally oval shaped electrodes (1532, 1534) arranged around the expandable member (1540). In some embodiments, the major axis (e.g., longitudinal axis) of each electrode (1532, 1534) may be substantially parallel to the longitudinal axis of the catheter shaft (1510) and / or the expandable member (1540). In some embodiments, the distal tip electrode (1532) may be electrically isolated from the first set of electrodes (1520). In some embodiments, each electrode of the second set of electrodes (1530, 1532, 1534) may be independently addressable. A distal tip electrode (1530) may be formed on a distal portion of the expandable member (1540) and may be electrically insulated from the first set of electrodes (1520).

[0126]

[0140] In some embodiments, the second set of electrodes may be electrically coupled to the first set of electrodes. For example, the first set of electrodes (1520) and the proximal electrode (1534) of the second set of electrodes may be electrically coupled together using one or more electrical leads. In some embodiments, the proximal electrode (1534) may be formed proximal to the maximum cross-sectional diameter of the expandable member (1540) when expanded. That is, the proximal portion of the expandable member (1540) is proximal to the cross-sectional diameter of the expandable member (1540) at its maximum portion. In this configuration, the distal electrode (1530, 1532) of the second set of electrodes may be configured to contact tissue in the second configuration, while the first set of electrodes (1520) and the proximal electrode (1534) of the second set of electrodes may be configured to be out of contact with tissue in the second configuration.

[0127]

[0141] In some embodiments, one or more of the first and second sets of electrodes (1520, 1530, 1532, 1534) may be configured to receive or sense ECG signals for recording electrophysiological data. The ablation device (1500) may include one or more ECG signal electrodes. For example, one or more of the second set of electrodes (1530, 1532, 1534) may be configured to receive ECG signals. These ECG signal electrodes, such as the distal tip electrode (1530), may be coupled to their own insulated conductors. In these embodiments, the ablation device may be used to record electrophysiological data before and / or after tissue ablation, in place of a mapping catheter.

[0128]

[0142] The expandable member (1540) when expanded may have an asymmetric shape in the proximal to distal direction, such that one end (e.g., the distal end) of the expandable member (1540) may be more bulbous than the other end (e.g., the proximal end) of the expandable member (1540). The expandable member (1540) when expanded may be rotationally symmetric about the longitudinal axis of the catheter shaft (1510). In this configuration, the expandable member (1540) may be positioned on the endocardial surface and used to form a lesion (e.g., a spot lesion) via focal ablation. The electrode lead may be constructed with sufficient insulation and high dielectric strength so as to be suitable for delivery of the irreversible electroporation energy described herein.

[0129]

[0143] In some embodiments, the catheter shaft (1510) may include a deflectable portion between the first set of electrodes (1520) and the second set of electrodes (1530). In other embodiments, the deflectable portion may be proximal to the first set of electrodes (1520). The deflectable portion may be configured to deflect up to about 210 degrees relative to the longitudinal axis of the catheter shaft (1510). In some embodiments, an actuator (e.g., a fluid source) may be coupled to the expandable member and configured to transition the expandable member between a first configuration (e.g., a deflated state) and a second configuration (e.g., an inflated state), for example, by using pressurized saline.

[0130]

[0144] In the embodiments described herein with respect to Figures 11-15, the first set of electrodes may be spaced from the second set of electrodes by about 2 mm to about 10 mm. In some embodiments, the first set of electrodes may be formed on a portion of the catheter shaft having a length of about 2 mm to about 12 mm. In some embodiments, the expandable member when expanded may have a shape having an effective cross-sectional diameter at its largest portion of about 5 mm to about 15 mm. In some embodiments, the expandable member may have a length of up to about 22 mm. For example, the expandable member may have substantially the same length in the first configuration and the second configuration. In some embodiments, one or more electrodes of the first set of electrodes may have a width of about 1 mm to about 5 mm and may be spaced apart by about 1 mm to about 5 mm. In some embodiments, the most distal electrode of the first set of electrodes may be spaced apart by at least about 5 mm from the proximal end of the expandable member when expanded.

[0131] II. Method

[0145] Also described herein are methods for ablating tissue in a cardiac chamber using the above systems and devices. The cardiac chamber may include one or more of the right ventricle, the left ventricle, and / or the right atrium, the left atrium. In general, the methods described herein include introducing and positioning a device in contact with one or more chambers, such as a ventricle. A pulse waveform may be delivered by one or more electrodes and an expandable member (e.g., a balloon) of the device to ablate tissue. In some embodiments, a cardiac pacing signal may synchronize the delivered pulse waveform with the cardiac cycle. Additionally or alternatively, the pulse waveform may include multiple levels of hierarchy to reduce total energy delivery. Tissue ablation performed in this manner may be delivered with less energy delivery in synchronization with the paced heartbeat to reduce damage to healthy tissue. It should be understood that any of the ablation devices described herein may be used to ablate tissue, as appropriate, using the methods described below.

[0132]

[0146] In some embodiments, the ablation devices described herein may be used for focal ablation of cardiac features / structures identified as causing arrhythmias. For example, cardiac electrophysiology diagnostic catheters (such as mapping catheters) may be used to map cardiac structures such as reentrant circuits and ventricular scar tissue, which can then be ablated through focal ablation using any of the ablation devices described herein. Focal ablation may create, for example, spot lesions that neutralize reentrant circuits while sparing surrounding tissue. In some embodiments, one or more focal ablation lesions may be formed in combination with one or more box-shaped or linear lesions to treat cardiac arrhythmias. As a non-limiting example, in some embodiments, the system may include one or more mapping catheters, one or more ablation devices (e.g., as shown in Figures 2A-2C and 3) useful for creating lesions via focal ablation.

[0133]

[0147] Generally, as shown in FIGS. 4A-4B, the method (400) includes the introduction of a device (e.g., an ablation device (110, 200, 300, 500, 500', 500'', 500'''', 1100, 1200, 1300, 1400, 1500) into the endocardial space of a ventricle. The ablation device may be introduced in a first configuration and may transition to a second configuration within the ventricle. Once positioned within the ventricle, a voltage pulse waveform may be applied to tissue during a refractory period of the cardiac cycle. Electrophysiology data of the ventricle may be recorded to determine the effectiveness of the ablation.

[0134]

[0148] The method (400) may begin with creating an access site in a patient (402). For example, to access the left ventricle for treatment, an antegrade delivery approach may be used, in which case a first access site may be via the patient's femoral vein. A guidewire may be advanced to the access site via the femoral vein and advanced into the patient's right atrium (404). A dilator and a deflectable sheath may be advanced over the guidewire into the right atrium (406). The sheath may be configured to deflect, for example, up to about 210 degrees. The dilator may be advanced from the right atrium to the left atrium through the septum to create a transseptal opening (408). For example, a dilator may be advanced from the right atrium through the atrial septum into the left atrium to create a transseptal opening. The atrial septum may include the patient's fossa ovalis. The transseptal opening may be dilated using the dilator (410). For example, a dilator may be advanced out of the sheath and used to poke the fossa ovalis and create a transseptal opening (assuming the patient is heparinized). Alternatively, a transseptal needle (e.g., a Brockenbrough needle) may be used to create a transseptal opening. A sheath may be advanced (412) from the right atrium into the left atrium through the transseptal opening. An ablation device may be advanced (414) over a guidewire through the mitral valve and into the left ventricle. Alternatively, the left ventricle may be accessed by a retrograde approach, in which case the first access site may be via the patient's femoral artery, and the guidewire and ablation device may be advanced through the patient's aorta and then through the aortic valve into the left ventricle. For treatment of the right ventricle, the first access site may again be via the patient's femoral vein, and the guidewire and ablation device may be advanced into the patient's right atrium and then through the tricuspid valve into the right ventricle.

[0135]

[0149] In some embodiments, the ablation device may include a catheter shaft lumen and a set of insulated conductors extending through the shaft lumen. The catheter shaft may include one or more electrodes formed on a surface of the shaft. In some embodiments, the one or more electrodes may be disposed on one or more portions of the expandable member. For example, the electrodes may be disposed on a distal end of the expandable member. The one or more electrodes may be configured to receive electrophysiology signals from the ventricle. In the method of FIGS. 4A-4B, the ablation device may be configured to record electrophysiology data of the ventricle. In some embodiments, the ablation device may transition (416) from a first configuration within the ventricle (e.g., the left ventricle) to a second configuration to enable the ablation device to record electrophysiology data. In some embodiments, the expandable member may be transitioned between the first and second configurations using a handle of the ablation device. For example, the handle may include a saline flow control mechanism that controls a volume of saline within the expandable member. The handle may further include a saline volume indicator to indicate the configuration of the expandable member. The ablation device in the second configuration can be configured to record electrophysiological data using the ablation device 418. For example, one or more electrodes on the catheter shaft and the expandable member can be configured to receive ECG signals to record the electrophysiological data.

[0136]

[0150] In other embodiments, a separate diagnostic bias (e.g., a mapping catheter) may be used to record electrophysiology data of the ventricle to be treated. The electrophysiology data may be used to generate an anatomical map that may be used to compare electrophysiology data recorded after energy delivery (e.g., ablation). The diagnostic bias may be advanced to the selected ventricle via the femoral or jugular vein. In these embodiments, instead of advancing the ablation device into the selected ventricle, a diagnostic device (e.g., a second catheter) may be advanced over the guidewire into the right ventricle (through the tricuspid valve) or into the ventricle (through the left atrium and mitral valve) after step (412). The second catheter may be used to record electrophysiology data of one or more ventricles. Once complete, the diagnostic bias may be withdrawn from the body over the guidewire, and then an ablation device may be advanced over the guidewire into the selected ventricle.

[0137]

[0151] 4A-4B, a second access site may be created in the patient for advancing a cardiac stimulation lead or catheter into the patient's heart. For example, the second access site may be via the patient's jugular vein. A device for cardiac stimulation may be advanced (420) through the second access site (e.g., near the apex of the right ventricle) into the right ventricle. A pacing signal may be generated by the cardiac stimulator and applied to the heart for cardiac stimulation of the heart. An indication of the pacing signal may be transmitted from the cardiac stimulator to the signal generator. In some embodiments, an operator may confirm pacing capture and determine that the ventricle is responding to the pacing signal as intended. For example, pacing capture may be confirmed on an ECG display on the signal generator. Confirmation of pacing capture is a safety feature in that ablation is delivered synchronously with pacing due to the enforced periodicity of the pacing Q waves.

[0138]

[0152] The ablation device may be advanced toward the target ventricle to deliver a pulse waveform configured for tissue ablation (422). In particular, the ablation device in a second configuration may be advanced toward the ventricle of the heart to contact a tissue surface. The sheath may be deflected as needed to direct the ablation device toward the target ventricle. The expandable member may be transitioned to a second configuration in which the expandable member expands to contact the expandable member against the ventricle at a predetermined location. Once the ablation device is positioned at a predetermined location within the heart to deliver one or more pulse waveforms, an extension cable may be used to electrically couple a signal generator to a proximal end of the handle of the ablation device. After pacing the right ventricle using the pacing device (424), the ablation device may be used to deliver a pulse waveform to the ventricle to ablate tissue in a portion of the target ventricle (426). The pulse waveform may be delivered synchronously with the pacing signal.

[0139]

[0153] As detailed in the figures (e.g., Figs. 5A-5J), the ablation device can be configured to generate an electric field intensity in a region of the myocardial tissue of the ventricle (e.g., can be a reentrant circuit, etc.) large enough to cause irreversible electroporation in the tissue. For example, the expandable member of the ablation device of Fig. 5D can be used to generate a set of high intensity electric field lines that can contact the tissue surface and penetrate the ventricle to a depth of about 5 mm to about 8 mm, as shown by spatial zone (532) in Fig. 5E, forming one or more focal ablation lesions. The ablation zones corresponding to the spatial zones (532) can be wide and deep. The size of the expandable member can be modified to control the depth and intensity of the electric field. This allows the energy to be delivered more efficiently, thus enabling tissue ablation with a minimum of total energy delivered.

[0140]

[0154] Although examples of ablation devices configured for delivery of irreversible electroporation pulsed electric field therapy have been described herein, the examples described herein are provided for illustrative purposes only, and those skilled in the art may devise other variations without departing from the scope of the present invention. For example, various materials, polyhedral sides, electrode diameters, device dimensions, voltage levels, proximal electrodes, and other such details are possible and can be implemented as convenient for the application at hand without departing from the scope of the present invention. The catheter shaft can undergo various deflections by controlling the deflection from the catheter handle. Metalized electrode portions disposed on the expandable member embodiments can be used for ECG signal recording or irreversible electroporation therapy delivery or both.

[0141]

[0155] As discussed herein, the pulse waveform may be generated by a signal generator coupled to the ablation device. The signal generator may be electrically coupled to a proximal end of a handle of the ablation device. For example, an extension cable may electrically couple the signal generator to the proximal end of the handle. In some embodiments, the pulse waveform may include a time offset with respect to the pacing signal. In some embodiments, the pulse waveform may include a first level of a hierarchy of pulse waveforms that includes a first set of pulses. Each pulse has a pulse time duration and a first time interval that separates successive pulses. A second level of the hierarchy of pulse waveforms may include a plurality of the first set of pulses as a second set of pulses. The second time interval may separate successive first set of pulses. The second time interval may be at least three times the duration of the first time interval. A third level of the hierarchy of pulse waveforms may include a plurality of the second set of pulses as a third set of pulses. The third time interval may separate successive second set of pulses. The third time interval may be at least 30 times the duration of the second level time interval. A fourth level of the hierarchy of pulse waveforms may include a plurality of the third set of pulses as a fourth set of pulses. A fourth time interval may separate consecutive third set pulses. The fourth time interval may be at least 10 times the duration of the third level time interval.

[0142]

[0156] One or more electrodes of the ablation device in the second configuration may be configured to receive electrophysiology signals of the target ventricle and may be used to record electrophysiology data of the target ventricle 428. The electrophysiology data may be compared to baseline data recorded prior to ablation to determine whether the ablation was successful 430.

[0143]

[0157] In other embodiments, the ablation device may be withdrawn from the heart over the guidewire, and a mapping catheter may be advanced over the guidewire to record post-ablation electrophysiology data of the target ventricle. If the ablation is not successful based on the electrophysiology data and predetermined criteria (430-No), the process may return to step 426 for delivery of additional pulse waveforms. The pulse waveform parameters may be the same or may be changed in subsequent ablation cycles.

[0144]

[0158] If analysis of the electrophysiology data indicates that ablation of the ventricular portion was successful (e.g., the tissue portion is electrically silent) (430-YES), a decision may be made on another target ventricular portion to ablate (432). Another target ventricular portion may be selected (424) and when the other ventricular portion has been ablated, the process may return to step 422. When switching between target ventricles, the expandable member may be at least partially deflated and the ablation device may be advanced toward another portion of tissue. If the other portion is not to be ablated (432-NO), the ablation device, cardiac stimulator, sheath, guidewire, etc. may be removed from the patient (436).

[0145]

[0159] In other embodiments, a diagnostic device (e.g., a mapping catheter) may be used to record electrophysiology data of the ventricle after the ablation device delivers a pulse waveform to tissue. In these embodiments, after steps 426 or 436, the ablation device may be withdrawn from the patient over the guidewire and a diagnostic device may be advanced over the guidewire into the ventricle to record electrophysiology data of the target ventricle that has undergone tissue ablation.

[0146]

[0160] It should be noted that for any of the steps described herein, the radiopaque portions of the ablation device may be imaged under fluoroscopy to assist the operator. For example, visual confirmation may be performed through fluoroscopic imaging to visually confirm that the expandable member in the second configuration is in contact with the ventricle or the apposition of the expandable member and electrodes to the ventricle. Imaging from multiple angles may be used to confirm positioning.

[0147]

[0161] It will be understood that the examples and descriptions in this disclosure serve for illustrative purposes, and that deviations and variations, such as the characteristics of the expandable member, the number of electrodes, etc., can be constructed and developed in accordance with the teachings herein without departing from the scope of the invention.

[0148] Pulse Waveform

[0162] Disclosed herein are methods, systems, and devices for 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 in any of the systems (100), devices (e.g., 200, 300), and methods (e.g., 400) described herein. Some embodiments relate to pulsed high voltage waveforms with sequenced delivery schemes for delivering energy to tissue through a set of electrodes. In some embodiments, peak electric field values ​​can be reduced and / or minimized while maintaining a sufficiently large electric field strength in the area where tissue ablation is desired. In some embodiments, a system useful for irreversible electroporation includes a signal generator and a processor that can be configured to apply a pulsed voltage waveform to a selected plurality of electrodes or a subset of electrodes of an ablation device. In some embodiments, the processor is configured to control inputs whereby a subset of anode-cathode pairs of selected electrodes can be triggered sequentially based on a predefined sequence, and 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.

[0149]

[0163] 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 having various associated timescales. Furthermore, the associated timescales and pulse widths, as well as the number of pulses and hierarchical groupings, may be selected to satisfy one or more of a set of Diophantine inequalities involving the frequency of cardiac pacing.

[0150]

[0164] The pulsed waveforms for electroporation energy delivery disclosed herein may 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 field of electroporation, including the therapeutic treatment of various cardiac arrhythmias.

[0151]

[0165] FIG. 6 shows a pulse voltage waveform in the form of a series of rectangular double pulses, with each pulse, such as pulses (600) 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, about 150 microseconds, including all values ​​and subranges in between. The pulse waveform in FIG. 6 shows a set of monophasic pulses with all pulses having the same polarity (all positive in FIG. 6 when measured from a zero baseline). In some embodiments, such as irreversible electroporation applications, the height (600) of each pulse or the voltage amplitude (600) of the pulse can be in the range of about 400 volts, about 1,000 volts, about 5,000 volts, about 10,000 volts, about 15,000 volts, including all values ​​and subranges in between. As shown in Figure 6, pulses (600) are separated from adjacent pulses by a time interval (602), sometimes referred to as a first time interval. The first time interval can be about 3 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.

[0152]

[0166] FIG. 7 introduces a pulse waveform with a hierarchy of nested pulses. FIG. 7 shows a series of monophasic pulses such as pulses (700) having a pulse width / pulse time duration w separated by a time interval (sometimes referred to as a first time interval) such as (702) of duration t1 between successive pulses, a number m1 of which are arranged to form a group of pulses (710) (sometimes referred to as a first set of pulses). The waveform further has a number m2 of such groups of pulses (sometimes referred to as a second set of pulses) separated by a time interval (712) of duration t2 between successive groups (sometimes referred to as a second time interval). The collection of a number m2 of such pulse groups, marked by (720) in FIG. 7, 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 t1 between pulses can range from microseconds to hundreds of microseconds, including all values ​​and subranges in between. In some embodiments, the time interval t2 can be at least three times greater than the time interval t1, in some embodiments, the ratio t2 / t1 can be in the range of about 3 to about 300, including all values ​​and subranges therebetween.

[0153]

[0167] FIG. 8 further illustrates the structure of a nested pulse hierarchical waveform. In this figure, a series of m1 pulses (individual pulses not shown) form a group (800) of pulses (e.g., a first set of pulses). A series of m2 such groups separated by an inter-group time interval (810) of duration t2 (e.g., a second time interval) between one group and the next form a packet (e.g., a second set of pulses). A series of m3 such packets separated by a time interval (812) of duration t3 (e.g., a third time interval) between one packet and the next form the next level in the hierarchy, labeled superpacket (820) (e.g., a third set of pulses). In some embodiments, the time interval t3 can be at least about 30 times greater than the time interval t2. In some embodiments, the time interval t3 can be at least about 50 times greater than the time interval t2. In some embodiments, the ratio t3 / t2 can be in the range of about 30 to about 800, including all values ​​and 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.

[0154]

[0168] FIG. 9 provides an example of a biphasic waveform sequence with a hierarchical structure. In the example shown, a biphasic pulse such as (900) has a positive voltage portion and a negative voltage portion to complete one cycle of the pulse. There is a time delay (902) (e.g., a first time interval) between adjacent cycles of duration t1 and adjacent cycles of n1, and such cycles form a group (910) of pulses (e.g., a first set of pulses). A series of n2 such groups separated by an inter-group time interval (912) (e.g., a second time interval) of duration t2 between one group and the next form a packet (920) (e.g., a second set of pulses). The figure also shows a second packet (930) with a time delay (932) (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 the biphasic pulse can be anywhere in the range of 500 volts to 7,000 volts or more, including all values ​​and subranges therebetween. The pulse width / pulse time duration can range from nanoseconds or subnanoseconds to tens of microseconds, and the delay t1 can range from 0 to several microseconds. The intergroup time interval t2 can be at least 10 times greater than the pulse width. In some embodiments, the time interval t3 can be at least about 20 times greater than the time interval t2. In some embodiments, the time interval t3 can be at least 50 times greater than the time interval t2.

[0155]

[0169] The embodiments disclosed herein include waveforms structured as hierarchical waveforms, including waveform elements / pulses at various levels of the hierarchy. An individual pulse, such as (700) of FIG. 7, comprises a first level of the hierarchy and has an associated pulse time 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 a group of pulses / second set of pulses (710) of FIG. 7. Other parameters associated with the waveform include a total time duration of the second set of pulses (not shown), a total number of first level elements / first set of pulses, and a second time interval between successive first level elements that describe the second level structure / second set of pulses. In some embodiments, the total time duration of the second set of pulses can be from about 20 microseconds to about 10 milliseconds, including all values ​​and subranges in between. A group of sets, second set of pulses, or elements of the second level structure form a third level of the hierarchy, such as a packet of groups / third set of pulses (720) of FIG. 7. Among other parameters are the total time 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 time duration of the third set of pulses can be between about 60 microseconds and about 200 milliseconds, including all values ​​and subranges therebetween. The general repeating or nested structure of the waveform can continue to multiple higher levels, such as a 10 or more level structure.

[0156]

[0170] For example, the pulse waveform may include a fourth level of the hierarchy of pulse waveforms and may include a plurality of third set pulses as the fourth set of pulses, a fourth pulse interval separating consecutive third set pulses, and the fourth time interval being at least 10 times the duration of the time intervals of the third level.

[0157]

[0171] In some embodiments, hierarchical waveforms with nested structures and time interval hierarchies described herein are useful for irreversible electroporation ablation energy delivery and provide sufficient control and selectivity for application in different tissue types. A variety of hierarchical waveforms can be generated using a suitable pulse generator. Although the examples herein identify monophasic and biphasic waveforms separately for clarity, it should be understood that combination waveforms can also be generated / implemented where one portion of the waveform hierarchy is monophasic and another portion is biphasic.

[0158]

[0172] In some embodiments, the ablation pulse waveforms described herein are applied during the refractory period of the cardiac cycle to avoid disruption of the sinus rhythm of the heart. In some embodiments, the treatment method includes electrically pacing the heart with a cardiac stimulator to ensure pacing capture, establish periodicity and predictability of the cardiac cycle, and then define a time window within the refractory period within the cardiac cycle during which one or more pulse ablation waveforms can be delivered. FIG. 10 shows an example in which both atrial and ventricular pacing are applied (e.g., pacing leads or catheters are placed in the right atrium and right ventricle, respectively). FIG. 10 shows, with time on the horizontal axis, a series of ventricular pacing signals such as (1000) and (1010), and a series of atrial pacing signals (1020, 1030), along with a series of ECG waveforms (1040, 1042) driven by the pacing signals. As indicated by the thick arrows in FIG. 10, there are atrial refractory time windows (1022) and ventricular refractory time windows (1002) following the atrial pacing signal (1022) and the ventricular pacing signal (1000), respectively. As shown in FIG. 10, there are time periods of duration T rA common refractory time window (1050) of pulses may be defined. In some embodiments, the electroporation ablation waveform(s) may be applied during this common refractory time window (1050). The start of this refractory time window (1022) is offset from the pacing signal (1000) by a time offset (1004), as shown in FIG. 10. In some embodiments, the time offset (1004) may be less than about 25 milliseconds. At the next heartbeat, the similarly defined common refractory time window (1052) is the next time window available for application of the ablation waveform(s). In this manner, the ablation waveform(s) may be applied over a series of heartbeats, with 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 for a given set of electrodes, a series of packets are applied over a series of heartbeats.

[0159]

[0173] As used herein, the terms "about" and / or "approximately" when used in conjunction with numerical values ​​and / or ranges generally refer to numerical values ​​and / or ranges near the recited numerical values ​​and / or ranges. 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.

[0160]

[0174] Some embodiments described herein relate to computer storage products with non-transitory computer-readable media (also referred to as non-transitory processor-readable media) having instructions or computer code for performing various computer-implemented operations. The computer-readable media (or processor-readable media) is non-transitory in the sense that it does not itself include a transitory propagating signal (e.g., a propagating electromagnetic wave that carries information over a transmission medium such as space or a cable). The media and computer code (which may also be referred to as 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, magnetic tapes, optical storage media such as compact disks / digital video disks (CD / DVD), compact disk read-only memories (CD-ROMs), and holographic devices, magneto-optical storage media such as optical disks, carrier wave signal processing modules, and hardware devices specially configured to store and execute program code, such as application-specific integrated circuits (ASICs), programmable logic devices (PLDs), read-only memories (ROMs), random access memory (RAM) devices, etc. Other embodiments described herein relate to computer program products, which may include, for example, instructions and / or computer code disclosed herein.

[0161]

[0175] 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) may be expressed in a variety of software languages ​​(e.g., computer code), including C, C++, Java, Ruby, Visual Basic, and / or other object-oriented, procedural, or other programming languages ​​and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, machine instructions such as those produced by a compiler, code used to generate 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.

[0162]

[0176] The specific examples and descriptions herein are exemplary in nature and embodiments may be developed by one of ordinary skill in the art based on the teachings herein without departing from the scope of the invention, which is limited only by the appended claims.

Claims

1. An apparatus comprising: a catheter shaft defining a longitudinal axis; an expandable member coupled to a distal end of the catheter shaft; a first set of electrodes formed on the expandable member and positioned proximal to an equatorial plane of the expandable member; a second set of electrodes formed on the expandable member and positioned distal to the equatorial plane of the expandable member, the second set of electrodes being electrically insulated from the first set of electrodes.

2. 10. The device of claim 1, wherein the first set of electrodes has a polarity opposite to that of the second set of electrodes during delivery of a pulse waveform.

3. 3. The device of claim 1 or 2, wherein the catheter shaft includes a deflectable section formed between the first set of electrodes and the second set of electrodes, the deflectable section configured to deflect a portion of the catheter shaft including the second set of electrodes and the expandable member up to 210 degrees relative to the longitudinal axis.

4. The apparatus of any one of claims 1 to 3, further comprising a fluid source coupled to the expandable member and configured to inflate the expandable member.

5. 5. The device of claim 1, wherein one or more of the first set of electrodes and one or more of the second set of electrodes have an insulated conductor associated therewith, the insulated conductor configured to maintain an electrical potential of at least 700V without breakdown of its corresponding insulation, the insulated conductor disposed within a lumen of the catheter shaft.

6. 6. The apparatus of claim 1, wherein one or more electrodes of the first set of electrodes and one or more electrodes of the second set of electrodes are independently controllable.

7. 7. Apparatus according to any preceding claim, wherein the distal most electrode of the first set of electrodes is spaced between 4mm and 10mm from the proximal most electrode of the second set of electrodes.

8. An apparatus according to any preceding claim, wherein the expandable member has a cross-sectional diameter at the equatorial plane of between 5mm and 15mm.

9. An apparatus according to any preceding claim, wherein the expandable member has a length of up to 22mm.

10. The device of any one of claims 1 to 9, wherein the expandable member has an asymmetric shape in the proximal to distal direction.

11. The device of any one of claims 1 to 10, wherein the expandable member has a bulbous shape.

12. The device of any one of claims 1 to 11, further comprising a biocompatible coating formed on an exterior surface of the expandable member.

13. The apparatus of any one of claims 1 to 12, wherein the distal end of the catheter shaft extends within the interior volume of the expandable member.

14. An apparatus according to any preceding claim, wherein each electrode of the second set of electrodes has a circular or elliptical shape.

15. The device described in claim 14, wherein the long axis of each electrode of the second set of electrodes having an elliptical shape is substantially parallel to the longitudinal axis.

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