System, device, and method for focal ablation

Abstract

To provide a device for selectively delivering high DC voltage electroporation ablation therapy to endocardial tissues in an area of interest while minimizing damage to healthy tissues.SOLUTION: A device includes: a first shaft defining a longitudinal axis and a lumen; a second shaft disposed within the lumen and having a distal portion that extends from a distal end of the first shaft; a plurality of electrodes configured to generate an electric field for ablating tissue; and a set of splines. Each spline of the set of splines includes a set of electrodes from the plurality of electrodes formed on that spline, each set of electrodes including: a distal electrode such that the set of splines includes a set of distal electrodes; and a proximal electrode such that the set of splines includes a set of proximal electrodes.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present disclosure relates to systems, devices, and methods for focal ablation. [Background technology]

[0002] While the generation of pulsed electric fields for tissue therapeutics has moved from the laboratory to clinical applications over the past 20 years, the effects of short pulses of high voltage and large electric fields on tissues have been investigated for over 40 years. Application of a short high DC voltage to tissue can generate localized high electric fields, typically in the range of several hundred volts per centimeter, which disrupt cell membranes by generating pores in them. Although the precise 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 generates instabilities in the lipid bilayer in the cell membrane, causing the generation of a distribution of localized gaps or pores in the cell membrane. This electroporation can be irreversible if the applied electric field at the membrane is greater than a threshold value, causing the pores to remain open rather than closing, thereby allowing the exchange of biomolecular materials across the membrane, leading to necrosis and / or apoptosis (cell death). The surrounding tissue can then heal naturally.

[0003] Although pulsed DC voltages can drive electroporation under certain conditions, there remains an unmet need for a thin, flexible, atraumatic device that effectively delivers high DC voltage electroporation ablation therapy selectively to endocardial tissue within a region of interest while minimizing damage to healthy tissue. Summary of the Invention

[0004] Described herein are systems, devices, and methods for ablating tissue through irreversible electroporation. In some embodiments, the device may include a first shaft defining a longitudinal axis and a lumen, a second shaft disposed within the lumen, the second shaft having a distal portion extending from a distal end of the first shaft, a plurality of electrodes configured to generate an electric field for ablating tissue, and a set of splines, each spline of the set of splines including a set of electrodes from the plurality of electrodes formed thereon, the electrodes of each set including (1) a distal electrode, such that the set of splines includes a set of distal electrodes, and (2) a proximal electrode, such that the set of splines includes a set of proximal electrodes. The proximal end may be coupled to the distal end of the first shaft. The distal end may be coupled to the distal end of the second shaft. The splines of one set can be configured to transition to an expanded configuration in which a distal portion of each spline from the one set is angled greater than about 70 degrees relative to the longitudinal axis.

[0005] In some embodiments, the device may include a first shaft defining a longitudinal axis and a lumen, a second shaft disposed within the lumen, the second shaft having a distal portion extending from a distal end of the first shaft, a plurality of electrodes configured to generate an electric field to ablate tissue, and a set of splines, each spline of the set of splines including a set of electrodes from the plurality of electrodes formed thereon, the electrodes of each set including (1) a distal electrode, such that the set of splines includes a set of distal electrodes, and (2) a proximal electrode, such that the set of splines includes a set of proximal electrodes. The proximal end may be coupled to the distal end of the first shaft. The distal end may be coupled to the distal end of the second shaft. The set of splines can be configured to transition to an expanded configuration, the set of splines defining spaces therebetween, the spaces being larger in the expanded configuration of the set of splines. An expandable member can be disposed distal to the distal end of the first shaft and in the spaces between the set of splines. The expandable member can be configured to transition to the expanded configuration when the set of splines are in the expanded configuration.

[0006] In some embodiments, the expandable member may be disposed distal to the distal end of the first shaft and in the space between the set of splines. The expandable member may be configured to transition to an expanded configuration. In some embodiments, the expandable members in the expanded configuration may substantially fill the space between the set of splines in their expanded configuration. The expandable members may be configured to transition from a contracted configuration to an expanded configuration, in which an outer surface of the expandable member is approximately parallel to the longitudinal axis and in which the outer surface of the expandable member curves radially outward from the longitudinal axis. The set of splines may be configured to transition to the expanded configuration in response to the expandable member transitioning to the expanded configuration.

[0007] In some embodiments, when the set of splines is in the expanded configuration, a distal portion of each spline from the set of splines can be angled at least about 70 degrees relative to the longitudinal axis. In some embodiments, the expandable member in the expanded configuration can form an asymmetric shape, where a distal portion of the expandable member has an outer diameter that is greater than an outer diameter of a proximal portion of the expandable member. The expandable member in the expanded configuration can form a shape having an outer diameter of between about 6 mm and about 24 mm at its largest portion. In some embodiments, when the set of splines is in the expanded configuration, at least one electrode from the set of distal electrodes can be configured to contact a tissue surface and form a focal ablation lesion above the tissue surface having a diameter of between about 0.5 cm and about 2.5 cm.

[0008] In some embodiments, at least a portion of the expandable member may be formed from an insulating material. The expandable member may include a radiopaque portion. The first shaft may be a first inner shaft, and the second shaft may be a second inner shaft. The device may further include an outer shaft. The first inner shaft and the second inner shaft may be configured to slide relative to the outer shaft, and a proximal portion of the expandable member may be coupled to a distal portion of the outer shaft. The distal portion of the expandable member may be coupled to a distal portion of the first inner shaft. In some of these embodiments, the first inner shaft may be configured to couple to a fluid source, such that fluid is delivered through a lumen of the first inner shaft into the expandable member to transition the expandable member to an expanded configuration. The set of splines may be configured to transition to an expanded configuration in response to the second inner shaft moving relative to the first inner shaft. The expandable member can define a lumen and the second inner shaft can extend through the lumen of the expandable member.

[0009] In some embodiments, the expandable member may be configured in fluid communication with a fluid source. The fluid source may be configured to deliver fluid to the expandable member to transition the expandable member to an expanded configuration. In some embodiments, when the set of splines is in the expanded configuration, the set of splines may extend outwardly from the distal end of the first shaft by between about 6 mm and about 24 mm. The first shaft may have an outer diameter between about 1.5 mm and about 6.0 mm. The set of splines may be configured to transition to the expanded configuration in response to the second shaft moving relative to the first shaft along the longitudinal axis. When the set of splines is in the expanded configuration, the set of distal electrodes may be angled between about 70 degrees and about 180 degrees relative to the set of proximal electrodes.

[0010] The set of splines in the expanded configuration can form an asymmetric shape, where the distal portion has an outer diameter that is greater than an outer diameter of the proximal portion. The distal end of the second shaft can be separated from each distal electrode from the set of distal electrodes by at most about 6 mm. The distal end of the second shaft can have a cross-sectional diameter between about 0.7 mm and about 5 mm. The distal portion of the device can have an atraumatic shape. Each electrode from the plurality of electrodes can surround a periphery of a respective spline from the set of splines on which the electrode is disposed.

[0011] At least one distal electrode from a set of distal electrodes can be configured to be activated with a first polarity. At least one proximal electrode from a set of proximal electrodes can be configured to be activated with a second polarity opposite the first polarity, collectively generating an electric field. A set of distal electrodes can be configured to be activated with a first polarity and a set of proximal electrodes can be configured to be activated with a second polarity opposite the first polarity.

[0012] Each electrode from the plurality of electrodes can have a length between about 0.5 mm and about 5 mm. Each electrode from the plurality of electrodes can be independently addressable from other electrodes from the plurality of electrodes. Each spline from a set of splines can include a set of insulated electrical leads disposed therein. Each insulated electrical lead from a set of insulated electrical leads can be electrically coupled to at least one electrode from a set of electrodes formed on the spline and can be configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. Each electrode from the plurality of electrodes can have a diameter between about 0.5 mm and about 3 mm. For each spline from a set of splines, a most distal electrode can be separated from a most distal proximal electrode by a value between about 1 mm and about 40 mm.

[0013] Each spline from the set of splines can include a plurality of proximal electrodes and at least one flexible portion, the at least one flexible portion being disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase spline flexibility. The set of proximal electrodes can include at least one coil electrode. The set of electrodes of each spline in the set of splines can include at least one electrode configured for ablation only and at least one electrode configured to receive electrocardiogram (ECG) signals. In some of these embodiments, at least one electrode can be configured for ablation only and at least one electrode can be configured to receive ECG signals and are coupled to separate insulated electrical leads.

[0014] In some embodiments, a method can include disposing an ablation device in a chamber of a subject's heart, the ablation device defining a longitudinal axis and including a set of splines. The set of splines can be transitioned to an expanded configuration, where a distal portion of each spline of the set of splines is angled greater than about 70 degrees relative to the longitudinal axis. An ablation pulse waveform can be delivered to a plurality of electrodes disposed on the set of splines, such that the set of splines generate an electric field to ablate tissue of the heart chamber.

[0015] In some embodiments, a method can include disposing an ablation device in a chamber of a subject's heart, the ablation device defining a longitudinal axis and including a set of splines and an expandable member, the expandable member disposed in spaces between the set of splines. The set of splines can be transitioned to an expanded configuration, where a distal portion of each spline of the set of splines bends radially outward from the longitudinal axis. The expandable member can be transitioned to the expanded configuration. An ablation pulse waveform can be delivered to a plurality of electrodes disposed on the set of splines, the set of splines configured to generate an electric field to ablate tissue of the heart chamber.

[0016] In some embodiments, the electric field can be configured to form focal ablation lesions having a diameter between about 0.5 cm and about 2.5 cm above the surface of the tissue. The ablation device can include a first shaft and a second shaft, the second shaft disposed within the first shaft and translatable relative to the first shaft. The set of splines can be transitioned to an expanded configuration, and includes retracting a distal portion of the second shaft relative to the first shaft. In some of these embodiments, retracting a distal portion of the second shaft relative to the first shaft includes using a handle coupled to at least one of the second shaft or the first shaft. In some of these embodiments, the tissue can include an endocardial surface of a heart chamber. In some of these embodiments, the heart chamber can be a ventricle.

[0017] In some embodiments, each spline from the set of splines includes a set of electrodes from the plurality of electrodes, and the method further comprises configuring a first electrode from the set of electrodes of at least one spline as an anode, configuring a second electrode from the set of electrodes of at least one spline as a cathode, and delivering an ablation pulse waveform to the first electrode and the second electrode.

[0018] In some embodiments, each spline from the set of splines can include a set of electrodes from the plurality of electrodes. At least one set of electrodes can be configured for ablation, and at least one set of electrodes can be configured to receive electrophysiology data. The electrophysiology data can be recorded from the heart using a subset of electrodes from the at least one set of electrodes. In some of these embodiments, the electrophysiology data can include intracardiac electrocardiogram (ECG) signal data of at least one pulmonary vein.

[0019] In some embodiments, a pacing device can be advanced into the right ventricle of the heart. A pacing signal can be generated for cardiac stimulation of the heart. The pacing signal can be applied to the heart using the pacing device, and an ablation pulse waveform can be generated synchronously with the pacing signal. In some of these embodiments, the ablation pulse waveform can include a time offset with respect to the pacing signal.

[0020] In some embodiments, a radiopaque portion of the ablation device may be fluoroscopically visualized during one or more steps. A diagnostic catheter may be advanced into the heart chamber and electrophysiology data may be recorded using the diagnostic catheter. In some of these embodiments, after transitioning the set of splines to an expanded configuration and after transitioning the balloon to an inflated configuration, at least one spline from the set of splines may be placed in contact with the endocardium of the heart chamber. In some of these embodiments, the at least one spline in contact with the endocardium forms a "C" shape.

[0021] In some embodiments, the ablation device can include a shaft defining a lumen in fluid communication with the expandable member, and transitioning the expandable member to the expanded configuration can include delivering fluid into the expandable member via the lumen of the shaft. The expandable member can be formed from an insulating material such that the expandable member acts as an insulator during delivery of the ablation pulse waveform. The expandable member can include a plurality of expandable portions, and each expandable portion from the plurality of expandable portions can be independently expandable from other expandable portions of the plurality of expandable portions. Transitioning the set of splines to the expanded configuration can include transitioning the set of splines such that a distal portion of each spline from the set of splines is angled greater than about 70 degrees relative to the longitudinal axis.

[0022] In some embodiments, the ablation pulse waveform comprises a first level of a hierarchy of ablation pulse waveforms and can include 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 ablation pulse waveforms can include a plurality of the first set of pulses as the second set of pulses, a second time interval separating successive first set pulses, the second time interval being at least three times the duration of the first time interval. A third level of the hierarchy of ablation pulse waveforms can include a plurality of the second set of pulses as the third set of pulses, a third time interval separating successive second set pulses, the third time interval being at least 30 times the duration of the second level time interval.

[0023] In some embodiments, transitioning the set of splines to the expanded configuration is responsive to transitioning the expandable member to the expanded configuration. In some embodiments, the device can include a first shaft defining a longitudinal axis and a lumen, a second shaft disposed within the lumen, the second shaft having a distal portion extending from a distal end of the first shaft, a plurality of electrodes, and a set of splines. Each spline of the set of splines includes a set of electrodes from the plurality of electrodes formed thereon. Each set of electrodes includes (1) distal electrodes, such that the set of splines includes a set of distal electrodes, and (2) proximal electrodes, such that the set of splines includes a set of proximal electrodes. The proximal end can be coupled to the distal end of the first shaft. The distal end can be coupled to the distal end of the second shaft.

[0024] In some embodiments, the set of splines may be transitionable between a plurality of states, including an undeployed configuration and an expanded configuration, and in the expanded configuration, a distal portion of each spline from the set of splines is set at one of a corresponding plurality of angles relative to a proximal portion of each spline from the set of splines in each of the plurality of states. A preselected portion of the plurality of electrodes may be activated in each of the plurality of states to generate an electric field for ablating the tissue wall by irreversible electroporation. In some embodiments, the set of splines may be configured to ablate the tissue wall independent of the orientation of the set of splines relative to the tissue wall. In some embodiments, the preselected portion of the plurality of electrodes includes an electrode from the plurality of electrodes oriented closer to the tissue surface.

[0025] In some embodiments, the set of splines can be transitionable into each of a plurality of states in response to the second shaft moving relative to the first shaft along the longitudinal axis. In some embodiments, when the set of splines is in the expanded configuration, at least one electrode from the set of distal electrodes can be angled at an angle between about 70 degrees and about 180 degrees relative to at least one electrode from the set of proximal electrodes. In some embodiments, the distal end of the second shaft can be separated from each distal electrode from the set of distal electrodes by at most about 6 mm.

[0026] In some embodiments, at least one distal electrode from a set of distal electrodes can be configured to be activated with a first polarity and at least one proximal electrode from a set of proximal electrodes can be configured to be activated with a second polarity opposite the first polarity, collectively generating an electric field. In some embodiments, each spline from a set of splines can include a plurality of proximal electrodes and at least one flexible portion, and the at least one flexible portion can be disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase spline flexibility.

[0027] In some embodiments, the first shaft is a first inner shaft and the second shaft is a second inner shaft. The device can include an outer shaft. The first inner shaft and the second inner shaft can be configured to slide relative to the outer shaft. In some embodiments, each distal electrode from the set of distal electrodes can be at the same distance from the distal end of the second shaft. In some embodiments, when the set of splines is in an expanded configuration, the set of splines can extend outward from the distal end of the first shaft a radial distance of between about 6 mm and about 24 mm. In some embodiments, the first shaft can have an outer diameter of between about 1.5 mm and about 6.0 mm. In some embodiments, the distal end of the second shaft can have a cross-sectional diameter of between about 0.7 mm and about 5 mm.

[0028] In some embodiments, the second shaft can further include an annular lumen and an expandable member, the expandable member disposed distal to the distal end of the first shaft and in the space between the set of splines. The annular lumen of the second shaft can be coupled to the expandable member, and the expandable member can be configured to transition to an expanded configuration by fluid pressure applied through the annular lumen.

[0029] In some embodiments, a set of splines can be configured to be transitionable to a plurality of states in response to the expandable member transitioning to the expanded configuration. In some embodiments, the device can include a first shaft defining a longitudinal axis and a lumen, a second shaft disposed within the lumen, the second shaft having a distal portion extending from a distal end of the first shaft, a plurality of electrodes, and a set of splines. Each spline of the set of splines includes a set of electrodes from the plurality of electrodes formed thereon. Each set of electrodes includes a set of electrodes including (1) distal electrodes, such that a set of splines includes a set of distal electrodes, and (2) proximal electrodes, such that a set of splines includes a set of proximal electrodes, a proximal end coupled to the distal end of the first shaft, and a distal end coupled to the distal end of the second shaft. The set of splines may be transitionable into a plurality of states between an undeployed configuration and an expanded configuration, including an undeployed configuration and an expanded configuration, where an angle between a first unit tangent vector extending through a length of a distal portion of each spline from the set of splines and a second unit tangent vector extending through a proximal portion of each spline from the set of splines varies between about 70 degrees and about 180 degrees. A preselected portion of the plurality of electrodes is activatable in each of the plurality of states to generate an electric field to ablate the tissue wall by irreversible electroporation.

[0030] In some embodiments, a set of splines can be transitioned to one or more states from a plurality of states with angles between about 90 degrees and about 180 degrees when used for ventricular ablation or to ablate thicker tissue. In some embodiments, a set of splines can be transitioned to one or more states from a plurality of states with angles between about 70 degrees and about 120 degrees when used for atrial ablation or to ablate thinner tissue.

[0031] In some embodiments, the expandable member may be disposed distal to the distal end of the first shaft and in the space between the set of splines. The expandable member may be configured to transition to an expanded configuration. In some embodiments, the expandable member may be formed from an insulating material such that the expandable member may be configured to drive an electric field generated by the plurality of electrodes to an area outside the space between the set of splines. In some embodiments, the set of splines may be configured to ablate the tissue wall independent of the orientation of the set of splines relative to the tissue wall. In some embodiments, the set of splines may be transitionable to a plurality of states in response to the second shaft moving relative to the first shaft along the longitudinal axis. In some embodiments, the distal end of the second shaft may be separated from each distal electrode from the set of distal electrodes by at most about 6 mm.

[0032] In some embodiments, at least one distal electrode from a set of distal electrodes can be configured to be activated with a first polarity and at least one proximal electrode from a set of proximal electrodes can be configured to be activated with a second polarity opposite the first polarity, collectively generating an electric field. In some embodiments, each spline from a set of splines includes a plurality of proximal electrodes and at least one flexible portion, the at least one flexible portion being disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase spline flexibility.

[0033] In some embodiments, the method can include positioning an ablation device at a first location within a chamber of a subject's heart, the ablation device defining a longitudinal axis and including a set of splines, each spline from the set including a distal electrode and a proximal electrode formed thereon. An inner shaft of the ablation device can be translated relative to an outer shaft of the ablation device to transition the set of splines to a predetermined state, in which a distal portion of each spline from the set of splines and a proximal portion of each spline from the set of splines are at a first angle between about 70 degrees and about 180 degrees. Each spline from the set of splines can have a distal end coupled to the inner shaft and a proximal end coupled to the outer shaft. A first ablation pulse waveform can be delivered to a distal electrode formed on at least one spline from the set of splines and to a proximal electrode formed on at least one spline from the set of splines, the set of splines configured to generate a first electric field for ablating a first portion of a tissue wall of the heart chamber. The ablation device can be positioned at a second location within the heart chamber. A second ablation pulse waveform can be delivered to a distal electrode formed on at least one spline from the set of splines and to a proximal electrode formed on at least one spline from the set of splines, the set of splines configured to generate a second electric field for ablating a second portion of the tissue wall.

[0034] In some embodiments, at least one of the first electric field or the second electric field is configured to form a focal ablation lesion having a diameter between about 0.5 cm and about 2.5 cm above the surface of the tissue. In some embodiments, the ablation device further includes an expandable member disposed in a space between the set of splines. The method can further include transitioning the expandable member to an expanded configuration. After the expandable member is transitioned to the expanded configuration, at least one of the first ablation pulse waveform or the second ablation pulse waveform is delivered. In some embodiments, the first and second locations are in an atrium of the heart, and the first and second angles are between about 70 degrees and about 120 degrees. In some embodiments, the first and second locations are in a ventricle of the heart, and the first and second angles are between about 90 degrees and about 180 degrees. [Brief description of the drawings]

[0035] [Figure 1] 1 is a block diagram of an electroporation system, according to an embodiment. [Diagram 2] 1 is a perspective view of an ablation catheter according to an embodiment. [Diagram 3] FIG. 13 is a perspective view of an ablation catheter according to another embodiment. [Figure 4] FIG. 13 is a perspective view of an ablation catheter according to another embodiment. [Diagram 5] FIG. 13 is a detailed perspective view of a distal portion of an ablation catheter according to another embodiment. [Figure 6] FIG. 13 is a side view of an ablation catheter according to another embodiment. [Figure 7] FIG. 13 is a side view of an ablation catheter according to another embodiment. [Figure 8A] FIG. 13 is a side view of an ablation catheter according to another embodiment. [Figure 8B] FIG. 13 is a front cross-sectional view of an ablation catheter according to another embodiment. [Figure 9A]FIG. 2 is a side view of an ablation catheter in a first configuration according to another embodiment. [Figure 9B] FIG. 13 is a side view of an ablation catheter in a second, expanded configuration, according to another embodiment. [Figure 9C] FIG. 11 is a side view of an ablation catheter in a third expanded configuration, according to another embodiment. [Figure 9D] FIG. 11 is a side view of an ablation catheter in a fourth expanded configuration according to another embodiment. [Figure 9E] FIG. 11 is a side view of an ablation catheter in a fifth expanded configuration, according to another embodiment. [Figure 10] 1 is a perspective view of a balloon ablation catheter disposed within the left atrial chamber of the heart, according to another embodiment. [Figure 11] 1 is a cross-sectional view of a balloon ablation catheter disposed within the left atrial chamber of the heart, according to another embodiment. [Figure 12A] 1 is a schematic diagram of a return electrode of an ablation system, according to an embodiment; [Figure 12B] 1 is a schematic diagram of a return electrode of an ablation system, according to an embodiment; [Figure 13] 1 illustrates a method for tissue ablation, according to an embodiment. [Figure 14] 13 illustrates a method for tissue ablation, according to another embodiment. [Figure 15] FIG. 3 is an illustration of the ablation catheter shown in FIG. 2 being positioned within the left atrial cavity of the heart. [Figure 16] FIG. 4 is an illustration of the ablation catheter shown in FIG. 3 being positioned within the left atrial cavity of the heart. [Figure 17] An illustration of two of the ablation catheters shown in Figure 4 being positioned within the left atrial cavity of the heart. [Figure 18]FIG. 6 is an illustration of the ablation catheter shown in Figure 5 being positioned within the left atrial cavity of the heart. [Figure 19A] FIG. 13 is an illustrative schematic perspective view of a set of electrodes disposed in a pulmonary vein ostium, according to another embodiment; [Figure 19B] 13 is an illustrative cross-sectional view of a set of electrodes disposed in a pulmonary vein ostium, according to another embodiment; [Figure 20A] FIG. 13 is an illustrative schematic perspective view of an electric field generated by an electrode disposed in a pulmonary vein ostium, according to another embodiment; [Figure 20B] 11 is an illustrative cross-sectional view of an electric field generated by an electrode disposed in a pulmonary vein ostium, in accordance with another embodiment; [Figure 21] FIG. 2 illustrates an example waveform showing a series of voltage pulses having a defined pulse width for each pulse, according to an embodiment. [Figure 22] 1A-1C are schematic diagrams illustrating a hierarchy of pulses showing pulse widths, spacing between pulses, and grouping of pulses, according to an embodiment; [Figure 23] FIG. 1 is a schematic illustration of a nesting hierarchy of monophasic pulses showing different levels of the nesting hierarchy, according to an embodiment. [Figure 24] FIG. 1 is a schematic illustration of a nesting hierarchy of biphasic pulses showing different levels of the nesting hierarchy, according to an embodiment. [Diagram 25] FIG. 13A-C are schematic illustrations of time sequences of electrocardiogram and cardiac pacing signals, along with atrial and ventricular refractory time periods, showing time windows for irreversible electroporation ablation, in accordance with an embodiment; [Figure 26A] FIG. 13 is a perspective view of an ablation catheter according to another embodiment. [Figure 26B] FIG. 26B is a side view of the ablation catheter shown in FIG. 26A positioned in the left atrial cavity of the heart adjacent to the ostium. [Figure 26C] FIG. 26C is a top view of a simulation of the ablation catheter shown in FIG. 26B illustrating selective electrode activation, according to an embodiment. [Figure 26D] 1 is a simulated illustration of tissue ablation in a lung ostium, according to an embodiment. [Figure 27A] 1A and 1B are respective side views of an ablation catheter according to another embodiment; [Figure 27B] 1A and 1B are respective side views of an ablation catheter according to another embodiment; [Figure 27C] 1A-1D are respective side views of an ablation catheter according to another embodiment; [Figure 28] FIG. 13 is a side view of an ablation catheter according to another embodiment. [Figure 29A] 1A and 1B are side cross-sectional views of an ablation catheter according to another embodiment; [Figure 29B] 13A and 13B are side cross-sectional views of an ablation catheter according to another embodiment; [Figure 29C] 13A and 13B are side cross-sectional views of an ablation catheter according to another embodiment;FIG. 14A and 14B are side cross-sectional views of an ablation catheter in a third configuration; [Figure 29D] 13A and 13B are side cross-sectional views of an ablation catheter according to another embodiment;FIG. 14A and 14B are yet another side cross-sectional view of an ablation catheter in a third configuration; [Diagram 30] FIG. 13 is a side view of an ablation catheter according to another embodiment. [Figure 31A] 1 is a perspective view of an ablation catheter according to another embodiment;FIG. 2 is a perspective view of an ablation catheter in a first configuration;FIG. [Figure 31B] 1 is a perspective view of an ablation catheter according to another embodiment;FIG. 2 is a perspective view of an ablation catheter in a second configuration;FIG. [Diagram 32] 1 is a schematic cross-sectional view of an ablation catheter according to another embodiment. [Figure 33A]1 is an illustrative view of an ablation catheter, according to another embodiment; [Figure 33B] 33A is a front view of the ablation catheter of FIG. 33A, according to another embodiment; [Figure 33C] 33A is an illustrative view of an ablation catheter according to another embodiment;FIG. 33B is a cutaway perspective view of the splines of the ablation catheter of FIG. [Figure 33D] 33A is an illustrative view of an ablation catheter according to another embodiment;FIG. 33B is a cross-sectional view of the splines of the ablation catheter of FIG. [Figure 33E] 33A is a perspective view of the ablation catheter of FIG. 33A disposed adjacent to tissue. [Figure 34A] 11A and 11B are side views of a spline and a spline with a unit tangent vector, according to another embodiment; [Figure 34B] 11 is a side view of a spline according to another embodiment, with two unit tangent vectors. [Diagram 35] FIG. 2 is a side view of an ablation catheter in an undeployed configuration, according to another embodiment. [Figure 36A] 1A and 1B are side views of an ablation catheter according to another embodiment; [Figure 36B] 1 is a side view of an ablation catheter according to another embodiment;FIG. 2 is another side view of the ablation catheter in a second configuration; [Figure 36C] 1A and 1B are side views of an ablation catheter according to another embodiment; [Figure 37A] 1 is a perspective view of an ablation catheter and the left atrium. 2 is a perspective view of an ablation catheter disposed in the left atrium. [Figure 37B] Oblique view of the ablation catheter and the left atrium. Oblique view of the left atrium after tissue ablation. [Figure 38A] 1 is an illustrative view of an ablation catheter according to another embodiment;FIG. 2 is a perspective view of an ablation catheter according to a first configuration; [Figure 38B] 1 is an illustrative view of an ablation catheter according to another embodiment;FIG. 2 is another perspective view of the ablation catheter according to a second configuration; [Figure 38C] 1 is an illustrative diagram of an ablation catheter according to another embodiment; [Figure 38D] 1 is an illustrative view of an ablation catheter according to another embodiment;FIG. 2 is a perspective view of an ablation catheter disposed adjacent to tissue; [Figure 39A] 1 is an illustrative view of an ablation catheter according to another embodiment;FIG. [Figure 39B] 1 is an illustrative view of an ablation catheter according to another embodiment;FIG. 2 is another perspective view of an ablation catheter with an expandable member in a contracted configuration; [Figure 39C] 1 is an illustrative view of an ablation catheter according to another embodiment;FIG. 2 is another perspective view of an ablation catheter with an expandable member in a contracted configuration; [Figure 39D] 1 is an illustrative diagram of an ablation catheter according to another embodiment.FIG. 2 is an annotated perspective view of an ablation catheter with an expandable member in an expanded configuration. [Diagram 40] 1 is a side view of an ablation catheter disposed adjacent to tissue according to an embodiment described herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] Described herein are systems, devices, and methods for selective and rapid application of pulsed electric fields to ablate tissue by irreversible electroporation. In general, the systems, devices, and methods described herein can be used to generate large electric field magnitudes in desired regions of interest and to reduce peak electric field values ​​elsewhere, so as to reduce unintended tissue damage. An irreversible electroporation system as described herein can include a signal generator and a processor, the processor configured to apply one or more voltage pulse waveforms to a selected set of electrodes of the ablation device to deliver energy to the region of interest (e.g., ablation energy for a set of tissue in a pulmonary vein ostium). The pulse waveforms disclosed herein can aid in the therapeutic treatment of various cardiac arrhythmias (e.g., atrial fibrillation). To deliver the pulse waveforms generated by the signal generator, one or more electrodes of the ablation device can have insulated electrical leads configured to sustain a voltage potential of at least about 700V without dielectric breakdown of the corresponding insulation. A subset of the electrodes may be independently addressable, such that the subset may be controlled (e.g., deliver energy) independently from any other electrodes of the device. In this manner, the electrodes and / or electrode subsets may synergistically deliver different energy waveforms at different times for electroporation of tissue.

[0037] 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 can be observed to have a 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 can be observed to have a temporary and / or intermittent formation of one or more pores in its cell membrane that persist upon removal of the electric field.

[0038] Pulse waveforms for electroporation energy delivery as disclosed herein can enhance the safety, efficiency and effectiveness of energy delivery to tissue by reducing the electric field threshold associated with irreversible electroporation, thus producing more effective ablative damage by reducing the total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein can be hierarchical and can have a nested structure. For example, the pulse waveforms can include a hierarchical grouping of pulses having 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, entitled "SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE," filed on October 19, 2016, the contents of which are incorporated herein by reference in their entirety.

[0039] In some embodiments, the system can further include a cardiac stimulator used to synchronize the generation of the pulse waveform to the paced heartbeat. The cardiac stimulator can electrically pace the heart by 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 regular cardiac cycle can be selected for the voltage pulse waveform delivery. Thus, the voltage pulse waveform can be delivered within the refractory period of the cardiac cycle to avoid disturbance of the sinus rhythm of the heart. In some embodiments, the ablation device can include one or more catheters, guidewires, balloons, and electrodes. The ablation device can transform into different configurations (e.g., compact and expanded configurations) to position the device within the endocardial space. In some embodiments, the system can optionally include one or more return electrodes.

[0040] In general, to ablate tissue, one or more catheters may be advanced through the vasculature in a minimally invasive manner to a target location. In cardiac applications, electrodes (through which voltage pulse waveforms are delivered) may be disposed on an epicardial device or on an endocardial device. The methods described herein may include introducing a device into an endocardial space of the left atrium of the heart and positioning (e.g., disposing) the device in contact with a pulmonary vein ostium. Multiple pulse waveforms may be generated and delivered to one or more electrodes of the device to ablate tissue. In some embodiments, the pulse waveforms may be generated synchronously with a cardiac pacing signal to avoid disturbance of the cardiac sinus rhythm. In some embodiments, the electrodes may be configured in an anode-cathode subset. The pulse waveforms may include hierarchical waveforms to aid in tissue ablation and reduce damage to healthy tissue.

[0041] system Overview Disclosed herein are systems and devices configured for tissue ablation via selective and rapid application of a voltage pulse waveform to assist in tissue ablation, resulting in irreversible electroporation. In general, the systems for ablating tissue described herein can include a signal generator and an ablation device, the ablation device having one or more electrodes for selective and rapid application of a DC voltage to drive electroporation. As described herein, the systems and devices can be deployed epicardially and / or endocardially to treat atrial fibrillation. A voltage can be applied to a selected subset of the electrodes, with independent subset selection for anode and cathode electrode selection. A pacing signal for cardiac stimulation can be generated and used to generate a pulse waveform by the signal generator in synchronization with the pacing signal.

[0042] Generally, the systems and devices described herein include one or more catheters configured to ablate tissue in the left atrial chamber of the heart. FIG. 1 illustrates an ablation system (100) configured to deliver a voltage pulse waveform. The system (100) can include an apparatus (120) including a signal generator (122), a processor (124), a memory (126), and a cardiac stimulator (128). The apparatus (120) can be coupled to an ablation device (110) and can optionally be coupled to a pacing device (130) and / or an optional return electrode (140) (e.g., a return pad, illustrated here by a dotted line).

[0043] The signal generator (122) may be configured to generate a pulse waveform for irreversible electroporation of tissue (e.g., pulmonary vein ostia, etc.). For example, the signal generator (122) may be a voltage pulse waveform generator and may deliver a pulse waveform to the ablation device (110). The return electrode (140) may be coupled to the patient (e.g., disposed on the patient's back) and allow current to flow from the ablation device (110) through the patient and then to the return electrode (140) and provide a safe current return path (not shown) from the patient. The processor (124) may incorporate data received from the memory (126), the cardiac stimulator (128), and the pacing device (130) and determine parameters (e.g., amplitude, width, duty cycle, etc.) of the pulse waveform to be generated by the signal generator (122). The memory (126) may further store instructions for causing the signal generator (122) to execute modules, processes, and / or functions associated with the system (100), such as pulse waveform generation and / or cardiac pacing synchronization, etc. For example, the memory (126) may be configured to store pulse waveforms and / or cardiac pacing data for pulse waveform generation and / or cardiac pacing, respectively.

[0044] In some embodiments, the ablation device (110) can include a catheter configured to receive and / or deliver a pulsed waveform, as described in more detail below. For example, the ablation device (110) can be introduced into the endocardial space of the left atrium and positioned to align one or more electrodes (112) with one or more pulmonary vein ostia, and then deliver a pulsed waveform to ablate tissue. The ablation device (110) can include one or more electrodes (112), which in some embodiments can be a set of independently addressable electrodes. Each electrode can include an insulated electrical lead, which is configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In some embodiments, the insulation on each of the electrical leads is capable of sustaining a potential difference of between about 200V and about 1,500V across its thickness without dielectric breakdown. For example, the electrodes (112) may be grouped into one or more anode-cathode subsets, such as, for example, a subset including one anode and one cathode, a subset including two anodes and two cathodes, a subset including two anodes and one cathode, a subset including one anode and two cathodes, a subset including three anodes and one cathode, and / or a subset including three anodes and two cathodes.

[0045] The pacing device (130) may be suitably coupled to a patient (not shown) and may be configured to receive a cardiac pacing signal generated by a cardiac stimulator (128) of the apparatus (120) for cardiac stimulation. An indication of the pacing signal may be transmitted by the cardiac stimulator (128) to the signal generator (122). Based on the pacing signal, an indication of a voltage pulse waveform may be selected, computed, and / or otherwise identified by the processor (124) and generated by the signal generator (122). In some embodiments, the signal generator (122) is configured to generate a pulse waveform in synchronization with an indication of the pacing signal (e.g., within a common refractory window). For example, in some embodiments, the common refractory window may begin substantially immediately (or after a very small delay) following the ventricular pacing signal and continue thereafter for a duration of approximately 250 ms or less. In such embodiments, the entire pulse waveform may be delivered within this duration.

[0046] The processor (124) may be any suitable processing device configured to run and / or execute a set of instructions or code. The processor may be, for example, a general purpose processor, a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), and / or a digital signal processor (DSP), etc. The processor may be configured to run and / or execute application processes and / or other modules, processes, and / or functions associated with the system and / or its associated network (not shown). The underlying device technology may be provided in a variety of component types, such as, for example, metal oxide semiconductor field effect transistor (MOSFET) technology such as complementary metal oxide semiconductor (CMOS), bipolar technology such as emitter coupled logic (ECL), polymer technology (e.g., silicon conjugated polymer and metal conjugated polymer metal structures), and / or mixed analog and digital.

[0047] The memory (126) may include a database (not shown) and may be, for example, a random access memory (RAM), a memory buffer, a hard drive, an erasable programmable read-only memory (EPROM), an electrically erasable read-only memory (EEPROM), a read-only memory (ROM), flash memory, etc. The memory (126) may store instructions to cause the processor (124) to execute modules, processes, and / or functions associated with the system (100), such as pulse waveform generation and / or cardiac pacing.

[0048] The system (100) may be in communication 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 be connected to a wireline network, such as to interface with the Internet, other carrier voice and data networks, business networks, and personal networks. Wireline networks are typically carried over copper twisted pairs, coaxial cables, or fiber optic cables. There are many different types of wireline 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, network refers to any combination of combined wireless, wireline, public and private data networks that are typically interconnected through the Internet to provide a unified networking and information access solution.

[0049] Ablation Devices The systems described herein can include one or more multi-electrode ablation devices configured to ablate tissue in the left atrial chamber of the heart to treat atrial fibrillation. FIG. 2 is a perspective view of an ablation device (200) (e.g., structurally and / or functionally similar to ablation device (110)) that includes a catheter (210) and a guidewire (220) that is slidable within a lumen of the catheter (210). The guidewire (220) can include a non-straight distal portion (222), and the catheter (210) can be configured to be disposed over the guidewire (220) during use. The distal portion (222) of the guidewire (220) can be shaped to aid in placement of the catheter (210) within a lumen of a patient. For example, the shape of the distal portion (222) of the guidewire (220) may be configured for placement at and / or near the ostium of a pulmonary vein, as described in more detail with respect to FIG. 15. The distal portion (222) of the guidewire (220) 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). For example, the distal portion (222) of the guidewire (220) can include a non-linear shape, such as a circle, a loop (as illustrated in FIG. 2), an ellipsoid, or any other geometric shape. In some embodiments, guidewire (220) may be configured to be elastic such that the guidewire, having a non-linear shape, can conform to the lumen of catheter (210) when disposed therein, and reform / otherwise resume the non-linear shape when advanced from catheter (210). In other embodiments, catheter (210) may be similarly configured to be elastic, such as to aid in the advancement of catheter (210) through a sheath (not shown).The shaped distal portion (222) of the guidewire (220) may be angled relative to the other portions of the guidewire (220) and the catheter (210). The catheter (210) and the guidewire (220) may be sized for advancement into the endocardial space (e.g., the left atrium). The diameter of the shaped distal portion (222) of the guidewire (220) can be approximately the same as the diameter of the lumen in which the catheter (230) will be disposed.

[0050] The catheter (210) may be slidably advanced over the guidewire (220) and is adapted to be disposed over the guidewire (220) during use. A distal portion (222) of the guidewire (220) disposed within the lumen (e.g., near the pulmonary vein ostium) may act as a backstop for the advancement of the distal portion of the catheter (210). The distal portion of the catheter (210) may include a set of electrodes (212) (e.g., structurally and / or functionally similar to the electrodes (112)) configured to contact a radially inner surface of the lumen (e.g., the pulmonary vein ostium). For example, the electrodes (212) may include a roughly circular arrangement of electrodes configured to contact the pulmonary vein ostium. As shown in FIG. 2, the one or more electrodes (212) may include a series of metallic bands or rings disposed along the catheter shaft and may be electrically connected together. For example, the ablation device (200) can include a single electrode with multiple bands, one or more electrodes, each with its own band, and combinations thereof. In some embodiments, the electrode (212) can be shaped to match the shape of the distal portion (222) of the guidewire (220). The catheter shaft can include flexible sections between the electrodes to enhance flexibility. In other embodiments, the electrode or electrodes (212) can include helical windings to enhance flexibility.

[0051] Each of the electrodes of the ablation devices discussed herein may be connected to an insulated electrical lead (not shown), which leads to a handle (not shown) that is coupled to a proximal portion of the catheter. The insulation of each of the electrical leads is capable of sustaining a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation of each of the electrical leads is capable of sustaining a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown (including all values ​​and subranges therebetween). This allows the electrodes to effectively deliver electrical energy and ablate tissue through irreversible electroporation. The electrodes may receive a pulsed waveform, for example, generated by a signal generator (122), as discussed above with respect to FIG. 1. In other embodiments, the guidewire (220) may be separate from the ablation device (200) (e.g., the ablation device (200) includes a catheter (210) but does not include a guidewire (220)). For example, guidewire (220) may be advanced by itself into the endocardial space, after which catheter (210) may be advanced over guidewire (220) into the endocardial space.

[0052] FIG. 3 is a perspective view of another embodiment of an ablation device (300) (e.g., structurally and / or functionally similar to ablation device (110)) that includes a catheter (310) having a set of electrodes (314), the set of electrodes (314) being provided along a distal portion (312) of the catheter (310). The distal portion (312) of the catheter (310) can be non-linear and form an approximately circular shape. The set of electrodes (314) can be disposed along the non-linear distal portion (312) of the catheter (310) to form a generally circular arrangement of electrodes (314). During use, the electrodes (314) can be disposed at the ostium of a pulmonary vein to deliver a pulsed waveform to ablate tissue, as described in more detail with respect to FIG. 16. The shaped distal portion (312) of the catheter (310) may be angled relative to other portions of the catheter (310). For example, the distal portion (312) of the catheter (310) may be approximately perpendicular to adjacent portions of the catheter (310). In some embodiments, a handle (not shown) may be coupled to the proximal portion of the catheter (310) and may include a bending mechanism (e.g., one or more pull wires (not shown)) configured to modify the shape of the distal portion (312) of the catheter (310). For example, movement of the pull wires of the handle may increase or decrease the circumference of the circular shape of the distal portion (312) of the catheter (310). The diameter of the distal portion (312) of the catheter (310) may be modified to allow the electrode (314) to be disposed near and / or in contact with the pulmonary vein ostium (e.g., in contact with a radially inner surface of the pulmonary vein). The electrodes (314) may include a series of metallic bands or rings and may be independently addressable.

[0053] In some embodiments, a pulse waveform may be applied between electrodes (314) configured in an anode and cathode set. For example, adjacent or approximately diametrically opposed electrode pairs may be activated together as an anode-cathode set. It should be appreciated that any of the pulse waveforms disclosed herein may be applied incrementally or sequentially over a series of anode-cathode electrodes.

[0054] FIG. 4 is a perspective view of yet another embodiment of an ablation device (400) (e.g., structurally and / or functionally similar to ablation device (110)) including a catheter (410) and a guidewire (420) having a shaped, non-straight distal portion (422). The guidewire (420) may be slidable within the lumen of the catheter (410). The guidewire (420) may be advanced through the lumen of the catheter (410), and the distal portion (422) of the guidewire (420) may be shaped to be approximately circular. The shape and / or diameter of the distal portion (422) of the guidewire (420) may be modified using a bending mechanism, as described above with respect to FIG. 3. The catheter (410) may be flexible and adapted to be deflectable. In some embodiments, the catheter (410) and / or guidewire (420) may be configured to be elastic so that they conform to the lumen in which they are disposed and assume a secondary shape when advanced from the lumen. By modifying the size of the guidewire (420) and manipulating the deflection of the catheter (410), the distal portion (422) of the guidewire (420) may be positioned at a target tissue site, such as, for example, the ostium of a pulmonary vein. The distal end (412) of the catheter (410) may be sealed except where the guidewire (420) extends, allowing the catheter (410) to electrically insulate the portion of the guidewire (420) within the lumen of the catheter (410). For example, in some embodiments, the distal end (412) of the catheter (410) can include a seal having an opening that allows passage of a guidewire (420) upon application of force, forming a compression hold (which can be fluid-tight) between the seal and the guidewire (420).

[0055] In some embodiments, the exposed distal portion (422) of the guidewire (420) may be coupled to an electrode and configured to receive a pulse waveform from a signal generator and deliver the pulse waveform to tissue during use. For example, the proximal end of the guidewire (420) may be coupled to a suitable lead and connected to the signal generator (122) of FIG. 1. The distal portion (422) of the guidewire (420) may be sized such that it may be positioned at the pulmonary vein ostium. For example, the diameter of the shaped distal portion (422) of the guidewire (420) may be approximately the same as the diameter of the pulmonary vein ostium. The shaped distal portion (422) of the guidewire (420) may be angled relative to the rest of the guidewire (420) and the catheter (410).

[0056] The guidewire (420) can comprise stainless steel, nitinol, platinum, or other suitable biocompatible materials. In some embodiments, the distal portion (422) of the guidewire (420) can include a platinum coil that is physically and electrically attached to the guidewire (420). The platinum coil can be an electrode configured for delivery of a voltage pulse waveform. Platinum is radiopaque, and its use can increase flexibility and aid in the advancement and positioning of the ablation device (400) within the endocardial space.

[0057] 5 is a detailed perspective view of a flower-shaped distal portion of an ablation device (500) (e.g., structurally and / or functionally similar to ablation device (110)) that includes a set of electrodes (520, 522, 524, 526) extending from a pair of insulated lead segments (510, 512, 514, 516), respectively. Each pair of adjacent insulated lead segments (e.g., lead segments (510, 512) and electrodes (526)) that are coupled to a non-insulated electrode form a loop (FIG. 5 illustrates a set of four loops). The set of loops in the distal portion of the ablation device (500) can be configured to deliver a pulse waveform to tissue. The ablation device (500) can include a set of insulated lead segments (510, 512, 514, 516) that branch at a distal end of the device (500) and connect to respective exposed electrodes (520, 522, 524, 526) as shown in FIG. 5. The electrodes (520, 522, 524, 526) can include exposed portions of electrical conductors. In some embodiments, one or more of the electrodes (520, 522, 524, 526) can include platinum coils. One or more of the segments (510, 512, 514, 516) can be coupled to a bending mechanism (e.g., struts, pull wires, etc.) controlled from a handle (not shown) to control the size and / or shape of the distal portion of the device (500).

[0058] The electrodes (520, 522, 524, 526) may be flexible and capable of forming a compact first configuration for advancement into the endocardial space (e.g., adjacent a pulmonary vein ostium). Once positioned at a desired location, the electrodes (520, 522, 524, 526) may be deformed to an expanded second configuration and form a flower-shaped distal portion when advanced out of a lumen (e.g., a sheath, etc.), as shown in FIG. 5. In other embodiments, the insulated lead segments (510, 512, 514, 516) and electrodes (520, 522, 524, 526) may be biased to expand (e.g., fling) outwardly into the second configuration when advanced out of a lumen (e.g., a sheath) carrying the device (500). The electrodes (520, 522, 524, 526) may be independently addressable and may each have an insulated electrical lead configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads is capable of sustaining a potential difference of between about 200 V and about 2000 V across its thickness without dielectric breakdown.

[0059] In some embodiments, the ablation device (5000) may be configured to deliver a pulsed waveform to tissue via a set of electrodes (520, 522, 524, 526) during use. In some embodiments, the pulsed waveform may be applied between electrodes (520, 522, 524, 526) configured in an anode and cathode set. For example, a roughly diametrically opposed pair of electrodes (e.g., electrodes (520, 524) and (522, 526)) may be activated together as an anode-cathode pair. In other embodiments, adjacent electrodes may be configured as an anode-cathode pair. By way of example, a first electrode (520) of a set of electrodes may be configured as an anode and a second electrode (522) may be configured as a cathode.

[0060] 6-9E, 26A-27C, and 28 illustrate additional embodiments of ablation devices (e.g., structurally and / or functionally similar to ablation device (110)) that can be configured to deliver a voltage pulse waveform using a set of electrodes to ablate tissue and to electrically isolate a pulmonary vein. In some of these embodiments, the ablation device can be transformed from a first configuration to a second configuration such that the electrodes of the ablation device expand outwardly to contact the lumen of the tissue (e.g., the ostium of the pulmonary vein).

[0061] FIG. 6 is a side view of an embodiment of an ablation device (600) including a catheter shaft (610) at a proximal end of the device (600) and a distal cap (612) of the device (600) and a set of splines (614) coupled thereto. The distal cap (612) can include an atraumatic shape to reduce trauma to tissue. A proximal end of the set of splines (614) can be coupled to a distal end of the catheter shaft (610) and a distal end of the set of splines (614) can be tethered to the distal cap (612) of the device (600). The ablation device (600) can be configured to deliver a pulsed waveform to tissue during use via one or more splines of the set of splines (614). As used herein, the terms "spline" and "spine" may be used interchangeably. In some embodiments, the device can include a catheter defining a longitudinal axis.

[0062] Each spline (614) of the ablation device (600) can include one or more commonly wired, or in some cases, independently addressable, electrodes (616) formed on a surface of the spline (614). Each electrode (616) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads is capable of sustaining a potential difference of between about 200 V and about 2000 V across its thickness without dielectric breakdown. Each spline (614) can include an insulated electrical lead of each electrode (616) formed within the body of the spline (614) (e.g., within the lumen of the spline (614)). In the case where the electrodes on a single spline are wired together, a single insulated lead can carry strands that connect to the different electrodes on the splines. Figure 6 illustrates a set of splines (614) where each spline (614) includes a pair of electrodes (616) that have approximately the same size, shape, and spacing as the electrodes (616) on the adjacent spline (614). In other embodiments, the size, shape, and spacing of the electrodes (616) may differ.

[0063] For each of the ablation devices described herein, and particularly for the ablation devices described in Figures 6-9E, 26A-27C, and 28, each spline of a set of splines can include a flexible curvature. The minimum radius of curvature of the splines can be in the range of about 1 cm or greater. For example, the set of splines can form a delivery assembly at a distal portion of the ablation device and can be configured to transform between a first configuration and a second configuration, where in the first configuration the set of splines are curved radially outward from the longitudinal axis of the ablation device and in the second configuration the set of splines are generally disposed parallel to the longitudinal axis of the ablation device. In this manner, the splines can more easily conform to the geometry of the endocardial space. In general, the "basket" of splines can have an asymmetric shape along the shaft length such that one end of the basket (e.g., a distal end) is more bulbous than the other end of the basket (e.g., a proximal end). The delivery assembly can be disposed in a first configuration in contact with the pulmonary vein ostium and transformed to a second configuration prior to delivery of the pulse waveform. In some of these embodiments, a handle can be coupled to the set of splines, and the handle can be configured to affect transformation of the set of splines between the first and second configurations. In some embodiments, the electrical leads of at least two electrodes of the set of electrodes can be electrically coupled at or near a proximal portion of the ablation device (e.g., in the handle).

[0064] In one embodiment, each of the electrodes (616) on a spline (614) can be configured as an anode, while each of the electrodes (616) on an adjacent spline (614) can be configured as a cathode. In another embodiment, the electrodes (616) on one spline can alternate between an anode and a cathode, with the electrodes on an adjacent spline having the opposite configuration (e.g., cathode and anode). The ablation device (600) can include any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (600) can include between 3 and 20 splines. For example, the ablation device (600) can include between 6 and 12 splines.

[0065] FIG. 7 is a side view of another embodiment of an ablation device (700) including a catheter shaft (710) at a proximal end of the device (700) and a distal cap (712) of the device (700) and a set of splines (714) coupled thereto. The distal cap (712) can include an atraumatic shape. The proximal end of the set of splines (714) can be coupled to the distal end of the catheter shaft (710) and the distal end of the set of splines (714) can be tethered to the distal cap (712) of the device (700). Each spline (714) of the ablation device (700) can include one or more independently addressable electrodes (716) formed on a surface of the spline (714). Each electrode (716) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200V and about 1500V across its thickness without dielectric breakdown. Each spline (714) can include an insulated electrical lead for each electrode (716) formed within the body of the spline (714) (e.g., within the lumen of the spline (714)). A set of spline wires (718, 719) can be electrically conductive and can electrically couple adjacent electrodes (716) disposed on different splines (714) (e.g., electrodes (716) between a pair of splines (718, 719) of a set of splines). For example, the spline wires (718, 719) can extend transversely to the longitudinal axis of the ablation device (700).

[0066] 7 illustrates a set of splines (714), where each spline (714) includes a pair of electrodes (716) that have approximately the same size, shape, and spacing as the electrodes (716) of an adjacent spline (714). In other embodiments, the size, shape, and spacing of the electrodes (716) may be different. For example, the electrode (716) electrically coupled to a first spline wire (718) may be different in size and / or shape from the electrode (716') electrically coupled to a second spline wire (719).

[0067] In some embodiments, the first spline wire (718) can include a first set of spline wires (720, 721, 722, 723), where each spline wire in the set of spline wires (720, 721, 722, 723) can connect electrodes (716) between different pairs of splines in the set of splines (714). In some of these embodiments, a set of spline wires (720, 721, 722, 723) can form a continuous loop between the electrodes (716) connected thereto. Similarly, the second spline wire (719) can include a second set of spline wires (724, 725, 726), where each spline wire in the set of spline wires (724, 725, 726) can traverse the set of splines (714) to connect electrodes (716'). The second set of spline wires (724, 725, 726) can traverse the set of splines (714) to connect different electrodes (716') than the first set of spline wires (720, 721, 722, 723). In some of these embodiments, the first set of splined wires (720, 721, 722, 723) can form a first continuous loop between the electrodes (716) coupled thereto, and the second set of splined wires (724, 725, 726) can form a second continuous loop between the electrodes (716') coupled thereto. The first continuous loop can be electrically isolated from the second continuous loop. In some of these embodiments, the electrode (716) coupled to the first continuous loop can be configured as an anode, and the electrode (716) coupled to the second continuous loop can be configured as a cathode. A pulse waveform can be delivered to the electrodes (716) of the first and second continuous loops.In some embodiments, the spline wires (e.g., 721, 722, 723, etc.) may be replaced by similar electrical connections in the proximal portion of the device (e.g., in the device handle). For example, the electrodes 716 may all be electrically wired together in the handle of the device.

[0068] In another embodiment, a first spline wire (721) of a set of spline wires (720, 721, 722, 723) can connect the electrodes (716) between the first spline (711) and the second spline (713) of the set of splines (714), and a second spline wire (720) of the set of spline wires (720, 721, 722, 723) can connect the electrodes (716) between the first spline (711) and the third spline (715) of the set of splines (714). The electrodes (716) connected by the first spline wire (721) and the second spline wire (720) can be configured as an anode and a cathode (or vice versa). In yet another embodiment, a first spline wire (721) of a set of spline wires (720, 721, 722, 723) can connect electrodes (716) between a first spline (711) and a second spline (713) of a set of splines (714), and a second spline wire (723) of a set of spline wires (720, 721, 722, 723) can connect electrodes (716) between a third spline (715) and a fourth spline (717) of the set of splines (714). A pulse waveform can be delivered to electrodes (716) connected by the first spline wire (721) and the second spline wire (723). In some embodiments, instead of spline wires, the electrical leads of at least two of a set of electrodes are electrically coupled at or near the proximal portion of the ablation device (e.g., in the handle).

[0069] In other embodiments, one or more of the spline wires (718, 719) can form a continuous loop between the electrodes (716) that are electrically coupled to them. For example, a first set of spline wires (718) can form a first continuous loop between the electrodes (716) that are coupled to it, and a second set of spline wires (719) can form a second continuous loop between the electrodes (716) that are coupled to it. In this case, the first continuous loop can be electrically isolated from the second continuous loop. In one embodiment, each of the electrodes (716) that are coupled to the first set of spline wires (718) can be configured as an anode, while each of the electrodes (716) that are coupled to the second set of spline wires (719) can be configured as a cathode. Each group of electrically coupled electrodes (716) can be independently addressable. In some embodiments, instead of spline wires, the electrical leads of at least two of a set of electrodes are electrically coupled at or near the proximal portion of the ablation device (e.g., in the handle).

[0070] In some embodiments, as discussed in more detail below with respect to FIGS. 8A-8B, the spline wire can be electrically coupled to a set of electrodes (e.g., 2, 3, 4, 5, etc.) without forming a continuous loop. For example, a non-continuous loop can be formed using two spline wires. In other embodiments, the size, shape, and spacing of the electrodes (716) can vary. The ablation device (700) can include any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines. In some embodiments, the ablation device (700) can include between 3 and 20 splines. For example, in one embodiment, the ablation device (700) can include between 6 and 9 splines.

[0071] 8A-8B are side and front cross-sectional views, respectively, of an ablation catheter (800). FIG. 8A is a side view of an embodiment of an ablation device (800) including a catheter shaft (810) at a proximal end of the device (800), a distal cap (812) of the device (800) and a set of splines (814) coupled thereto. The distal cap (812) can include an atraumatic shape. The proximal end of the set of splines (814) can be coupled to the distal end of the catheter shaft (810), and the distal end of the set of splines (14) can be tethered to the distal cap (812) of the device (800). Each spline (814) of the ablation device (800) can include one or more independently addressable electrodes (816, 818) formed on a surface of the spline (814). Each electrode (816, 818) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads is capable of sustaining a potential difference of between about 200 V and about 2000 V across its thickness without dielectric breakdown (including all values ​​and subranges therebetween). Each spline (814) can include an insulated electrical lead of each electrode (816, 818) formed within the body of the spline (814) (e.g., within the lumen of the spline (814)). One or more of the spline wires (817, 819) can be electrically conductive and can electrically couple adjacent electrodes (816, 818) disposed on different splines (814). For example, the spline wires (817, 819) can extend transversely to the longitudinal axis of the ablation device (800).

[0072] FIG. 8B is a front cross-sectional view of FIG. 8A taken along line 8B-8B. Each spline wire (817, 819, 821, 823) electrically couples a pair of adjacent electrodes (816, 818, 820, 822) on a different spline. In some embodiments, each coupled electrode pair may be electrically isolated from one another. In some embodiments, coupled electrode pairs may be configured with a common polarity. Adjacent electrode pairs may be configured with opposite polarities (e.g., a first electrode pair may be configured as an anode and an adjacent second electrode pair may be configured as a cathode). For example, the electrode (816) coupled to the first set of spline wires (817) may be configured as an anode, while each of the electrodes (818) coupled to the second set of spline wires (819) may be configured as a cathode. In some embodiments, each electrode formed on the spline (814) can share a common polarity (e.g., configured as an anode or cathode). Each linked electrode pair can be independently addressable. In some embodiments, the ablation device (800) can include an even number of splines. The ablation device (800) can include any number of splines, e.g., four, six, eight, ten, or more splines. In some embodiments, the ablation device can include four to ten splines. For example, in one embodiment, the ablation device can include six to eight splines. As shown above, in some embodiments, the spline wires (e.g., 817, 819, etc.) can be replaced by similar electrical connections in the proximal portion of the device (e.g., in the device handle). For example, the electrodes (816) can be electrically wired together in the handle of the device such that the electrodes are at the same electrical potential during ablation.

[0073] FIG. 9A is a side view of yet another embodiment of an ablation device (900) including a catheter shaft (910) at a proximal end of the device (900) and a distal cap (912) of the device (900) and a set of splines (914) coupled thereto. The distal cap (912) can include an atraumatic shape. A proximal end of the set of splines (914) can be coupled to a distal end of the catheter shaft (910) and a distal end of the set of splines (914) can be tethered to the distal cap (912) of the device (900). Each spline (914) of the ablation device (900) can include one or more independently addressable electrodes (916, 918) formed on a surface of the spline (914). Each electrode (916, 918) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200 V and about 2000 V across its thickness without dielectric breakdown. Each spline (914) can include an insulated electrical lead of each electrode (916, 918) formed within the body of the spline (914) (e.g., within the lumen of the spline (914)). FIG. 9A illustrates a set of splines (914) where each spline (914) includes an electrode that is spaced apart or offset from the electrodes of adjacent splines (914). For example, one set of splines (914) may include a first spline (920) and a second spline (922) adjacent the first spline (920), where the electrode (916) of the first spline (920) is disposed closer to the distal end (912) of the ablation device (900) than the electrode (918) of the second spline (922). In other embodiments, the size and shape of the electrodes (916, 918) may be different as well.

[0074] In some embodiments, the adjacent distal electrode (916) and proximal electrode (918) can form an anode-cathode pair. For example, the distal electrode (916) can be configured as an anode and the proximal electrode (918) can be configured as a cathode. In some embodiments, the ablation device (900) can include three to twelve splines. In FIG. 9A, one electrode (916, 918) is formed on the surface of each spline (914) such that each spline (914) includes one insulated electrical lead. Thus, the lumen of the spline (914) can be reduced in diameter, allowing the spline (914) to be thicker and more mechanically robust. Thus, dielectric breakdown of the insulation can be further reduced, thereby improving the reliability and lifespan of each spline (914) and the ablation device (900). The ablation device (900) can include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines. In some embodiments, the ablation device (900) can include 3 to 20 splines. For example, in one embodiment, the ablation device (900) can include 6 to 10 splines. Moreover, in some embodiments, the shape of the bulbous expanded structures (930) of the expanded set of splines (914) can be asymmetric, e.g., the distal portion is more bulbous or rounded than the proximal portion (see, e.g., FIGS. 9B-9E). Such bulbous distal portions can aid in positioning the device at the ostium of the pulmonary vein.

[0075] 9B-9E, it is understood that components with similar reference numbers as in FIG. 9A (e.g., electrode (916) in FIG. 9A and electrode (916') in FIG. 9B) may be structurally and / or functionally similar unless otherwise indicated. FIG. 9B illustrates spline wires (914', 920', 922') that form an expanded structure (930') during use (e.g., when deployed). A first plane (924A') (sometimes referred to as a proximal plane) of the expanded structure (930') has a different cross-sectional area than a second plane (924B') of the expanded structure (930'). As illustrated in FIG. 9B, in some embodiments, the cross-sectional area of ​​the expanded structure (930') in the second plane (924B') is greater than in the first plane (924A'). The terms "first plane" and "second plane" as used with respect to Figure 9B can refer to planes perpendicular to the longitudinal axis of the catheter shaft (910'), which are formed up to about 1 cm, about 2 cm, and about 3 cm or more (including all values ​​and subranges therebetween) from the distal end of the catheter shaft (910') and the proximal end of the distal cap (912'), respectively. Similar to Figure 9A, the electrodes (916') of the first spline (920') are disposed closer to the distal cap (912') of the ablation device (900') than the electrodes (918') of the second spline (922').

[0076] FIG. 9C illustrates spline wires (914'', 920'', 922'') forming an expanded structure (930'') during use (e.g., when deployed). A first plane (924A'') (sometimes referred to as a proximal plane) of the expanded structure (930'') has a different cross-sectional area than a second plane (924B'') of the expanded structure (930''). As illustrated in FIG. 9C, in some embodiments, the cross-sectional area of ​​the expanded structure (930'') in the second plane (924B'') is greater than in the first plane (924A''). The terms "first plane" and "second plane" as used with respect to FIG. 9C may refer to planes perpendicular to the longitudinal axis of the catheter shaft (910''), which are formed up to about 1 cm, about 2 cm, and about 3 cm or more (including all values ​​and subranges therebetween) from the distal end of the catheter shaft (910'') and from the proximal end of the distal cap (912''), respectively. Unlike FIGS. 9A-9B, multiple electrodes may be present on each splined wire, with some electrodes being equidistant from the distal cap (912''). In this manner, the relatively distal electrodes (e.g., 932'' and 934'') may be juxtaposed to the pulmonary vein ostium or proximal / antrum of the pulmonary vein ostium during use for ablation delivery to generate circumferential lesions of the ostium around the pulmonary vein.

[0077] FIG. 9D illustrates spline wires (914''', 920''', 922''') forming an expanded structure (930''') during use (e.g., when deployed). The spline wires (914''', 920''', 922''') converge at their distal ends to points (928''''), which are inside / within the expanded structure (930''''). As illustrated in FIG. 9D, in such a configuration, at least some of the electrodes (932''', 934''') on the spline wires (914'''', 920'''', 922'''') can be within the distal end plane (926''') of the expanded structure (930''''). The term "distal end plane" as used with respect to FIG. 9D can refer to a plane that passes through the distal boundary of the expanded structure (930''') and is perpendicular to the longitudinal axis of the catheter shaft (910'''). In this manner, the expanded structure (930''') can be pressed against, for example, an endocardial surface (e.g., the posterior wall of the left atrium) to directly generate lesions thereon by activation of appropriate electrodes in the distal end plane using any suitable combination of polarities. For example, distal electrodes (932'''', 934'''') can be pressed against the endocardial surface and used to create lesions via focal ablation (e.g., spot lesions).

[0078] Turning now to the generation of focal ablation lesions using ablation device (900'''), in some embodiments, electrodes (933, 935) (sometimes referred to as the "proximal electrodes") and electrodes (932''', 934''') (sometimes referred to as the "distal electrodes") may be activated with opposite polarity. Conduction between these electrodes through the blood pool results in the generation of an electric field and the application of the electric field as ablative energy to the endocardial surface present at the distal end plane (926'''), resulting in focal ablation. For example, the spline wires (914''', 920''', 922''') can form an expanded structure (930''') such that the distal electrodes (932''', 934''') are at or within the distal end plane (926'''') of the endocardial surface, while the proximal electrodes (933, 935) are outside of the distal end plane (926''') and thus do not press against or otherwise contact the endocardial surface. In some embodiments, the distal electrodes (932''', 934''') can have the same polarity, while the adjacent proximal electrodes (935, 933) can have an opposite polarity as the distal electrodes (932''', 934''').

[0079] In some embodiments, the electrodes of the ablation device (900''') can have a length of about 0.5 mm to about 5.0 mm and a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 2.5 mm, including all values ​​and subranges therebetween. The splined wires (914'''', 920'''', 922'''') of the expanded structure (930''') illustrated in FIG. 9D can have a cross-sectional dimension (e.g., diameter) of about 6.0 mm to about 30.0 mm, including all values ​​and subranges therebetween. The focal ablation lesions thus formed can have a diameter of about 0.5 cm to about 2.5 cm, including all values ​​and subranges therebetween.

[0080] In some embodiments, distal electrodes (932''', 934''') can be configured with opposite polarity. In some embodiments, adjacent electrodes on the same spline can have the same polarity, such that distal electrode (934''') can have the same polarity as proximal electrode (933), and similarly, distal electrode (932''') can have the same polarity as proximal electrode (935). Electrodes (934'''', 933) can have the opposite polarity as electrodes (932'''', 935).

[0081] In some embodiments, adjacent distal electrode (934''') and proximal electrode (933) can form an anode-cathode pair. For example, distal electrode (934''') can be configured as an anode and proximal electrode (933) can be configured as a cathode. In another embodiment, electrodes (2630) on the splines can alternate between anodes and cathodes, with electrodes on adjacent splines having the opposite configuration (e.g., cathode and anode).

[0082] FIG. 9E illustrates spline wires (944, 940, 942) that form an expanded structure (950) during use (e.g., when deployed). The spline wires (944, 940, 942) converge at their distal ends to the proximal end of the distal cap (912'''') inside / within the expanded structure (950). As illustrated in FIG. 9E, in such a configuration, at least some of the electrodes (952, 954) on the spline wires (944, 940) can be in the distal end plane (946) of the expanded structure (950). The term "distal end plane" as used with respect to FIG. 9E can refer to a plane that passes through the distal boundary of the expanded structure (950) and is perpendicular to the longitudinal axis of the catheter shaft (910''''). In this manner, the expanded structure (950) may be pressed against, for example, the posterior wall of the left atrium to directly generate a lesion thereon by activation of appropriate electrodes in the distal end plane (946) using any suitable combination of polarities. For example, electrodes 952 and 954 may be configured with opposite polarities. Relative to the expanded structure (930'''') in FIG. 9D, the expanded structure (950) in FIG. 9E has a more orthogonal (e.g., flattened) shape that may be pressed against, for example, the posterior wall of the left atrium for tissue ablation. In other words, the cross-sectional area of ​​the expanded structure (930'''') at the distal end plane (926'''') is smaller than the cross-sectional area of ​​the expanded structure (950) at the distal end plane (946). As another example, the distal electrodes (952, 954) may be pressed against an endocardial surface and used to form a lesion via focal ablation (e.g., spot lesion), as generally described herein with respect to FIG. 9D.

[0083] For each of the ablation devices described herein, each of the splines can include a polymer and can define a lumen to form a hollow tube. One or more electrodes of the ablation devices described herein can include a diameter of about 0.2 mm to about 2.0 mm and a length of about 0.2 mm to about 5.0 mm. In some embodiments, the electrodes can include a diameter of about 1 mm and a length of about 1 mm. Because the electrodes can be independently addressable, the electrodes can be excited in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes can deliver different sets of pulses (e.g., hierarchical pulse waveforms), as discussed in further detail below. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines can be configured to deliver sequential / percutaneous energy and electrically isolate one or more pulmonary veins. In some embodiments, the alternate electrodes (e.g., all distal electrodes) can be at the same potential, as can all other electrodes (e.g., all proximal electrodes). Thus, ablation can be delivered quickly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and can be implemented based on convenience.

[0084] FIG. 26A is a perspective view of an embodiment of an ablation device (2600) having a flower-like shape and including a catheter shaft (2610) at the proximal end of the device (2600), a distal cap (2612) of the device (2600), and a set of splines (2620) coupled thereto. As best shown in FIG. 26B, the splined shaft (2614) can be coupled at the proximal end to a proximal handle (not shown) and at the distal end to the distal cap (2612). In a preferred embodiment, the distance between the distal cap (2612) and the catheter shaft (2610) can be less than about 8 mm. The splined shaft (2614) and the distal cap (2612) can be translatable along the longitudinal axis (2616) of the ablation device (2600). The splined shaft (2614) and the distal cap (2612) can move together. The splined shaft (2614) can be configured to slide within the lumen of the catheter shaft (2610). The distal cap (2612) can include an atraumatic shape to reduce trauma to tissue. A proximal end of each spline of the set of splines (2620) can pass through a distal end of the catheter shaft (2610) and can be coupled to the catheter shaft within the catheter shaft lumen, and a distal end of each spline of the set of splines (2620) can be coupled to the distal cap (2612) of the device (2600). The ablation device (2600) can be configured to deliver a pulsed waveform to tissue during use, for example, as disclosed in FIGS. 21-25, via one or more splines of the set of splines (2620).

[0085] Each spline (2620) of the ablation device (2600) can, in some embodiments, include one or more commonly wired electrodes (2630) formed on a surface of the spline (2620). In other embodiments, one or more of the electrodes (2630) on a given spline can be an independently addressable electrode (2630). Each electrode (2630) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline (2620) can include an insulated electrical lead of each electrode (2630) within the body of the spline (2620) (e.g., within the lumen of the spline (2620)). FIG. 26A illustrates a set of splines (2620), where each spline includes a set of electrodes (2632 or 2634) that have approximately the same size, shape, and spacing as the electrodes (2634 or 2632) of an adjacent spline (2620). In other embodiments, the size, shape, and spacing of the electrodes (2632, 2634) may be different. The thickness of each spline (2620) can vary based on the number of electrodes (2630) formed on each spline (2620), which can correspond to the number of insulated electrical leads in the spline (2620). The splines (2620) can have the same or different materials, thicknesses, and / or lengths.

[0086] Each spline of the set of splines (2620) can include a flexible curvature to rotate or twist and bend to form a petal-shaped curve, such as that shown in FIGS. 26A-26C. The minimum radius of curvature of the splines in the petal-shaped configuration can range from about 7 mm to about 25 mm. For example, the set of splines can form a delivery assembly at a distal portion of the ablation device (2600) and can be configured to transform between a first configuration and a second configuration, where the set of splines are generally parallel to the longitudinal axis of the ablation device (2600) and where the set of splines are generally biased away from the longitudinal axis of the ablation device (2600), by rotating or twisting and bending. In a first configuration, each spline of the set of splines can be in a plane with the longitudinal axis of the ablation device. In a second configuration, each spline of the set of splines can be biased away from the longitudinal axis to form a petal-like curve that is generally disposed perpendicular to the longitudinal axis. In this manner, the set of splines (2620) twist, bend, and bias away from the longitudinal axis of the ablation device (2600), thus allowing the splines (2620) to more easily conform to the geometry of the endocardial space and, in particular, adjacent the opening of the ostium. As best shown in FIG. 26C, the second configuration can resemble, for example, a flower shape when the ablation device is viewed from the front. In some embodiments, each spline in the set of splines in the second configuration can twist and bend to form a petal-like curve that, when viewed from the front, exhibits an angle between the proximal and distal ends of the curve that is greater than about 180 degrees.The set of splines may be further configured to transform from the second configuration to a third configuration, where the set of splines (2620) may be imprinted against (e.g., in contact with) a target tissue, such as tissue surrounding a pulmonary vein ostium.

[0087] In some embodiments, the splined shaft (2614) coupled to the set of splines (2620) can allow each spline of the set of splines (2620) to bend and twist relative to the catheter shaft (2610) as the splined shaft (2614) slides through the lumen of the catheter shaft (2610). For example, the set of splines (2620) can form a shape generally parallel to the longitudinal axis of the splined shaft (2614) when undeployed, and can be wrapped (e.g., helically twisted) around an axis (2660) parallel to the longitudinal axis of the splined shaft (2620) when fully deployed, forming any intermediate shape therebetween (e.g., a cage or barrel, etc.) as the splined shaft (2614) slides through the lumen of the catheter shaft (2610).

[0088] In some embodiments, a set of splines in a first configuration (e.g., splines (2620)) may be wound around an axis (2660) that is parallel to the longitudinal axis of the catheter shaft (2610) at some portions along its length, but may otherwise be generally parallel to the longitudinal axis of the catheter shaft (2610) at other locations. The spline shaft (2614) may be retracted into the catheter shaft (2610) to transform the ablation device (2600) from the first configuration to a second configuration, in which the splines (2620) are generally angled or offset (e.g., perpendicular) to the longitudinal axis of the catheter shaft (2610) and twisted. As shown in the front view of FIG. 26C, each spline (2620) may form a twisted loop in this front view projection. In FIG. 26C, each spline (2620) has a set of electrodes (2630) with the same polarity. As shown in the front view of FIG. 26C, each spline of a set of splines (2620) can form a twisted loop such that each spline overlaps one or more other splines. The number and spacing of the electrodes (2630) and the rotational twist of the splines (2620) can be configured by appropriate placement of the electrodes along each spline to prevent overlap of the electrodes (2630) on one spline with the electrodes of an adjacent overlapping spline (2620).

[0089] Splines with one set of anodic electrodes (2632) can be activated together to deliver a pulse waveform for irreversible electroporation. Electrodes on other splines can be activated together as cathodic electrodes, such as electrodes (2634) and (2635) on their respective splines, to form an anode-cathode pairing for delivery of a pulse waveform for irreversible electroporation, as shown in FIG. 26C. The anode-cathode pairing and pulse waveform delivery can be repeated sequentially across a set of such pairings.

[0090] For example, the splines (2620) may be activated sequentially in a clockwise or counterclockwise fashion. As another example, the cathode splines may be activated sequentially with each sequential anode spline activation until ablation is completed. In embodiments in which the electrodes on a given spline are separately wired, the order of activation among the electrodes of each spline may be varied as well. For example, the electrodes in a spline may be activated all at once or in a predetermined sequence.

[0091] The delivery assembly can be disposed in a first configuration prior to delivery of the pulse waveform and transformed into a second configuration to contact the pulmonary vein ostium or sinus. In some of these embodiments, a handle can be coupled to the splined shaft (2614), and the handle can be configured to affect transformation of the set of splines between the first and second configurations. For example, the handle can be configured to translate the splined shaft (2614) and the distal cap (2612) relative to the catheter shaft (2610), thereby actuating a set of splines (2620) coupled to the distal cap, causing them to bend and twist. The proximal ends of the splines (2620) may be secured to the splined shaft (2614), such that when the distal cap (2612) and splined shaft (2614) are pulled back relative to the catheter shaft (2610), which may be held by a user, for example, the splines (2620) buckle, resulting in bending and twisting of the splines (2620). For example, the distal ends of a set of splines (2620) coupled to the distal cap (2612) may be translated up to about 60 mm along the longitudinal axis of the ablation device to actuate this change in configuration. In other words, translation of an actuation member of the handle may bend and twist the set of splines (2620). In some embodiments, actuation of a knob, wheel, or other rotational control mechanism in the device handle can result in translation of the actuation member or splined shaft, which can result in bending and twisting of the splines (2620). In some embodiments, the electrical leads of at least two of a set of electrodes (2630) can be electrically coupled at or near a proximal portion of the ablation device (2600), such as in the handle.

[0092] Retraction of the splined shaft (2614) and distal cap (2612) together can move the set of splines (2620) closer together, as shown in FIG. 26B, where the set of splines (2620) are generally perpendicular to the longitudinal axis of the catheter shaft (2610). In some embodiments, each spline of the set of splines (2620) can be biased laterally away from the longitudinal axis of the splined shaft (2614) by up to about 3 cm. In some embodiments, the splined shaft (2614) can include a hollow lumen. In some embodiments, the cross-section of the splines can be asymmetric, such that one bending plane of the splines perpendicular to the plane of the cross-section has a greater bending stiffness than a different bending plane. Such asymmetric cross-sections can be configured to exhibit relatively high lateral stiffness, thereby enabling them to be deployed with minimal overlap of the petal-shaped curves of each spline and its neighbors in a final or fully deployed configuration.

[0093] In one embodiment, each of the electrodes (2632) on a spline (2620) may be configured as an anode, while each of the electrodes (2634) on a different spline may be configured as a cathode. In another embodiment, the electrodes (2630) on one spline may alternate between anodes and cathodes, while the electrodes on another spline have the opposite configuration (e.g., cathode and anode).

[0094] In some embodiments, the spline electrodes can be electrically activated in a sequential manner to deliver a pulse waveform with each anode-cathode pairing. In some embodiments, the electrodes can be electrically wired together in the spline, while in alternative embodiments, they can be wired together in the handle of the device, such that the electrodes are at the same electrical potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (2630) can be different as well. In some embodiments, adjacent distal and proximal electrodes can form an anode-cathode pair. For example, the distal electrode can be configured as an anode and the proximal electrode can be configured as a cathode.

[0095] The ablation device (2600) can include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (2600) can include between 3 and 20 splines. For example, the ablation device (2600) can include between 4 and 12 splines.

[0096] Each of the splines of the set of splines (2620) can include a respective electrode (2630) having an atraumatic shape to reduce trauma to tissue. For example, the electrodes (2630) can have an atraumatic shape including rounded, flat, curved, and / or blunted portions configured to contact endocardial tissue. In some embodiments, the electrodes (2630) can be positioned along any portion of the splines (2620) distal to the catheter shaft (2610). The electrodes (2630) can have the same or different sizes, shapes, and / or locations along each spline.

[0097] In this manner, the electrodes in the second configuration may be held near or placed against a section of the atrial wall of the left atrium to directly create lesions thereon by activation of the appropriate electrodes using any suitable polarity combination, as described herein. For example, one set of splines (2620) may be placed in contact with the atrial wall (2654) of the atrium (2652) adjacent a pulmonary vein (2650) (e.g., an ostium or sinus).

[0098] FIG. 26D is a schematic illustration of an ablation (2664) generated by an ablation device (2600) on tissue (such as tissue surrounding a pulmonary vein ostium). For example, activation of one or more of the electrodes (2630) on one or more of the splines (2620) can generate one or more corresponding ablation areas (2664) along the walls (2654) of the pulmonary vein sinus or pulmonary vein ostium. In some embodiments, the contour of the ablation area (2664) within the pulmonary vein ostium can have a diameter between about 2 cm and about 6 cm, and can be about 3.5 cm. In this manner, continuous percutaneous lesions can be generated, resulting in electrical isolation of the pulmonary vein, which is the desired therapeutic outcome.

[0099] Alternatively, an ablation catheter with its deployed electrodes can be placed adjacent to or against a section of the posterior wall of the left atrium and by activation of the appropriate electrode set, a suitable pulse waveform can be delivered for irreversible electroporation energy delivery to ablate tissue.

[0100] In some embodiments, since the electrodes or a subset of electrodes may be independently addressable, the electrodes may be excited in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms) as discussed in further detail herein. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver sequential / percutaneous energy and electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes may be at the same potential, as well as all other alternating electrodes. Thus, in some embodiments, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0101] In some embodiments, the distal most portion of the ablation device can include a set of splines rather than a distal cap or another element that extends the length of the catheter shaft. This can aid in positioning the set of splines relative to the tissue and can also reduce contact of other elements of the ablation device with the tissue, which can cause trauma to the tissue. For example, FIG. 35 is a side view of an embodiment of an ablation device (3500) including a first catheter (3510) (e.g., an outer catheter shaft) at a proximal end of the device (3500). The first catheter (3510) can define a longitudinal axis (3550) and a lumen therethrough. A second catheter (3520) can be slidably disposed within the first catheter lumen and can extend from a distal end of the first catheter lumen. The second catheter (3520) can have a diameter smaller than the diameter of the first catheter (3510). The second catheter (3520) can define a lumen therethrough. For example, the lumen can provide passage for another device, such as a guidewire, or the like.

[0102] The set of splines (3530) may be coupled to the first catheter (3510) and the second catheter (3520). In particular, a proximal portion of the set of splines (3530) may be coupled to a distal end of the first catheter (3510) and a distal portion of the set of splines (3530) may be coupled to a distal end of the second catheter (3520). The second catheter (3520) may be translatable along the longitudinal axis (3550) of the ablation device (3500). A proximal end of each spline of the set of splines (3530) may pass through the distal end of the first catheter (3510) and may be tethered to the first catheter (3510) within the first catheter lumen. A distal end of each spline of the set of splines (3530) can pass through a distal end of the second catheter (3520) and can be coupled to the second catheter (3520) within the second catheter lumen. In some embodiments, a joint (3522) can be formed between the distal end of the second catheter (3520) and the set of splines (3530). For example, a polymer reflow process can be used to form a smooth, atraumatic joint between the second catheter (3520) and the set of splines (3530). The ablation device (3500) can be configured to deliver a pulsed waveform (e.g., as disclosed in FIGS. 21-26) to tissue during use via electrodes of one or more splines of the set of splines (3530).

[0103] Each spline (3530) of the ablation device (3500) can include one or more electrodes (3540) formed on a surface of the spline (3530). Each electrode (3540) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. Each spline (3530) can include an insulated electrical lead of each electrode (3540) within the body of the spline (3530) (e.g., within the lumen of the spline (3530)). FIG. 35 illustrates a set of splines, where each spline (3530) includes a set of electrodes (3540) having approximately the same size, shape, and spacing as the electrodes (3540) of adjacent splines. In other embodiments, the size, shape, and spacing of the electrodes (3540) can be different.

[0104] The ablation device (3500) can be configured to deliver a set of voltage pulse waveforms using a set of electrodes (3540) to ablate tissue. In some of these embodiments, the ablation device (3500) can be transformed from a first configuration to a second configuration such that the splines (3530) of the ablation device (3500) bend radially outward.

[0105] At least a portion of the set of splines (3530) can include a flexible curvature, such as a proximal region (3522) and a distal region (3526) of each spline (3530). The set of splines (3530) can form a delivery assembly at a distal portion of the ablation device (3500) and can be configured to transform between a first configuration and a second configuration, where in the first configuration the set of splines (3530) are generally disposed closer to the longitudinal axis (3540) of the ablation device (3500) and in the second configuration the set of splines (3530) bend radially outward from the longitudinal axis (3540) of the ablation device (3500) to form a basket-like and / or flower-like shape, where each spline forms a "petal." The space curve shapes of the splines in the second configuration may be described with respect to equations (1)-(3) corresponding to Figures 34A-B. For example, in a fully deployed configuration, the integrated magnitude of the rotation rate of each of the splines of the set of splines (3530) along the length of each spline may be greater than π radians.

[0106] In other embodiments, the "basket" of splines can have an asymmetric shape along the catheter length, such that one end of the basket (e.g., the distal end) is more bulbous than the other end of the basket (e.g., the proximal end). The delivery assembly can be advanced through a body lumen in a first configuration and transformed to a second configuration prior to delivery of the pulse waveform. In some embodiments, a handle (not shown) can be coupled to the set of splines (3530), and the handle can be configured to affect transformation of the set of splines (3530) between the first and second configurations. In some embodiments, actuation of one or more knobs, wheels, sliders, pull wires, and / or other control mechanisms in the handle can result in translation of the second catheter (3520) relative to the first catheter (3510), which can result in bending of the splines (3530). In some embodiments, the electrical leads of at least two of the set of electrodes (3540) can be electrically coupled at or near a proximal portion of the ablation device (3500) (e.g., in a handle, etc.). For example, the handle can be configured to translate the second catheter (3512) relative to the first catheter (3510), thereby actuating the set of splines (3530) and causing them to bend, as shown in FIG. 35. The distal end of the splines (3530) can be fixed to the distal end of the second catheter (3520), thereby causing buckling of the splines (3530), for example, when the second catheter (3520) is pulled back relative to the first catheter (3510), resulting in a bending movement of the splines (3530). In other words, translation of the actuating member of the handle can bend the set of splines (3530). In some embodiments, each spline of a set of splines (3530) can be biased laterally away from the longitudinal axis (3540) of the second catheter (3512) by up to about 35 mm.For example, a set of splines (3530) in the second configuration can form a shape having an effective cross-sectional diameter at its largest portion between about 10 mm and about 35 mm. In the second configuration, a set of splines can have a length between about 15 mm and about 50 mm.

[0107] In one embodiment, each of the electrodes on a spline can be configured as an anode while each of the electrodes on a different spline can be configured as a cathode. That is, one set of electrodes on adjacent splines can have opposite polarities. In another embodiment, the electrodes on one spline can alternate between anode and cathode while the electrodes on another spline have the opposite configuration (e.g., cathode and anode). In some embodiments, adjacent distal and proximal electrodes can form an anode-cathode pair. For example, the distal electrode can be configured as an anode and the proximal electrode can be configured as a cathode.

[0108] In some embodiments, the electrodes are electrically activated in a sequential manner, allowing each anode-cathode pairing to deliver a pulse waveform. In some embodiments, the electrodes (3540) can be electrically wired together within the splines (3530), while in alternative embodiments, they can be wired together within the handle of the device (3500) such that the electrodes (3540) are at the same electrical potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3540) can be different as well. As another example, the splines (3530) can be activated sequentially in a clockwise or counterclockwise fashion. As another example, the cathode splines can be activated sequentially with each sequential anode spline activation until ablation is completed. In embodiments in which the electrodes (3540) on a given spline (3530) are separately wired, the order of activation among the electrodes (3540) of each spline (3530) may be varied as well. For example, the electrodes (3540) in a spline may be activated all at once or in a predetermined sequence.

[0109] The electrodes may be excited in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver energy and electrically isolate one or more regions of cardiac tissue. In some embodiments, the alternate electrodes (e.g., all distal electrodes) may be at the same potential, as well as all other electrodes (e.g., all proximal electrodes). Thus, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0110] Each of the splines (3530) can be constructed from a polymer and can define a lumen to form a hollow tube. The set of splines (3530) of the ablation device (3500) can have a diameter between about 1.0 mm and about 5.0 mm. The set of electrodes (3540) of the ablation device (3500) can have a diameter between about 1.0 mm and about 5.0 mm and a length between about 0.2 mm and about 5.0 mm.

[0111] The ablation device (3500) can include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (3500) can include between 3 and 16 splines. For example, the ablation device (3500) can include between 3 and 14 splines.

[0112] Each of the splines of the set of splines (3530) can include a respective electrode (3540) having an atraumatic shape to reduce trauma to tissue. For example, the electrodes (3540) can have an atraumatic shape including rounded, flat, curved, and / or blunted portions. In some embodiments, the electrodes (3540) can be positioned along any portion of the splines (3530) distal to the first catheter (3510). The electrodes (3540) can have the same or different sizes, shapes, and / or locations along each spline. The ablation device (3500) can include any number of electrodes per spline, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, or more electrodes (including all values ​​and subranges therebetween). In some embodiments, the ablation device (3500) can include between 2 and 12 electrodes per spline.

[0113] 34A-34B are side views of a spline (3400) structurally and / or functionally similar to the splines described herein, such as the splines shown in FIGS. 36A-36C. FIG. 34A is a side view of a spline with a unit tangent vector. FIG. 34B is a side view of a spline with two unit tangent vectors. FIGS. 34A-34B show a spline (3400) having a petal-like shape, which may correspond to the shape of the spline in the second and / or third configurations as described in detail herein. For simplicity, the spline (3400) is shown without other elements, such as electrodes. The curved spline (3400) includes a proximal end (3402) and a distal end (3404). At every point (3410) along the spline (3400), a unit tangent vector u (3420) may be defined. FIG. 34B shows the unit tangent vector u at the proximal end (3402) of the spline (3400). 1(3430), and the unit tangent vector u at the distal end (3404) of the spline (3400). 2 (3440) is shown.

[0114] The rate of change of a unit tangent vector along the length of a spline may be governed by the following formula: u'=du / dl (1) where l is the arc length along the spline.

[0115] The rate of change of the unit tangent vector u' can be referred to as the curl of the unit tangent vector along the spline. Since u u = 1, the curl u' is perpendicular to the unit tangent vector u.

[0116] In some embodiments, a spline as described herein may be shifted to form a petal shape and may form loops that are twisted along its length, such that the spline has torsion along its length. A spline as described herein has an integrated magnitude of rotation rate governed by the following inequality: ∫|u'|}dl>π (2) That is, the integrated magnitude of the spline's rotation is greater than π radians (in other words, 180 degrees). Since u and u' are perpendicular, u·u' = 0. Therefore, the vector b = uxu' is perpendicular to both u and u'.

[0117] In some embodiments, the shape of the spline is generally a space curve with torsion such that at least some places along the length of the spline, the derivative of the rotation rate has a component along b that is governed by the following equation: ∫(u''·b)dl≠0 (3) In some embodiments of the devices described herein, the expanded splines of a set of splines can satisfy both equation (2) and equation (3).

[0118] 36A-36C are side views of an ablation catheter (3600) configured to have a set of splines deployed when the distal splines are fully deployed and a set of electrodes that extend distally of all other elements of the catheter (3600) to reduce trauma to tissue and aid in positioning and contact between the set of electrodes and tissue. FIG. 36A is a perspective view of an embodiment of an ablation device (3600) having a flower-like shape and including a first catheter (3610) at a proximal end of the device (3600). The first catheter (3610) can define a longitudinal axis (3650) and a lumen therethrough. A second catheter (3620) may be slidably disposed within the first catheter lumen and may extend from a distal end of the first catheter lumen. The first catheter and the second catheter may comprise a single device along with a catheter handle for actuation. A set of splines (3630) may be coupled to the first catheter (3610) and the second catheter (3620). The second catheter (3620) may be translatable along a longitudinal axis (3650) of the ablation device (3600). A proximal end of each of the splines of the set of splines (3630) may pass through a distal end of the first catheter (3610) and may be coupled to the first catheter (3610) within the first catheter lumen, and a distal end of each of the splines of the set of splines (3630) may be coupled to a distal end (3622) of the second catheter (3620), as described in detail with respect to FIG 35. Because the ablation catheter (3600) does not include a distal cap or other protrusion extending from the distal end of the second catheter (3620), the device (3600) in the second configuration (e.g., flower shape) is capable of engaging sensitive tissue, such as a thin heart wall, with reduced risk of trauma from the device (3600).The ablation device (3600) can be configured to deliver a pulsed waveform (e.g., as disclosed in Figures 21-26) to tissue during use via one or more electrodes on a set of splines (3630).

[0119] Each spline (3630) of the ablation device (3600) can, in some embodiments, include one or more commonly wired electrodes (3640) formed on a surface of the spline (3630). In other embodiments, one or more of the electrodes (3640) on a given spline can be an independently addressable electrode (3640). Each electrode (3640) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline (3630) can include an insulated electrical lead of each electrode (3640) within the body of the spline (3630) (e.g., within the lumen of the spline (3630)). 36A-36C illustrate a set of splines (3630), where each spline includes a set of electrodes (3640) having approximately the same size, shape, and spacing as the electrodes (3640) of adjacent splines (3630). In other embodiments, the size, shape, and spacing of the electrodes (3640) may be different. The thickness of each spline (3630) can vary based on the number of electrodes (3640) formed on each spline (3630), which can correspond to the number of insulated electrical leads in the spline (3630). The splines (3630) can have the same or different materials, thicknesses, and / or lengths.

[0120] Each spline of the set of splines (3630) can include a flexible curvature to rotate or twist and bend to form a petal-shaped curve, such as those shown in FIGS. 26A-C, 34A-B, and 36A-C. The minimum radius of curvature of the splines in the petal-shaped configuration can be between about 7 mm and about 25 mm. For example, the set of splines can form a delivery assembly at a distal portion of the ablation device (3600) and can be configured to transform between a first configuration and a second configuration, where in the first configuration the splines of the set are generally disposed closer to the longitudinal axis of the ablation device (3600) and in the second configuration the splines of the set rotate or twist and bend to generally bias away from the longitudinal axis of the ablation device (3600). In a first configuration, each spline of the set of splines can be in a plane with the longitudinal axis of the ablation device. In a second configuration, each spline of the set of splines can be biased away from the longitudinal axis to form a petal-like curve (e.g., a flower shape) where the longitudinal axis of the splines is disposed generally perpendicular to the longitudinal axis (3650) or has an acute angle with respect to the longitudinal axis (3650). As described in detail herein, the shape (e.g., bend, curve) of the set of splines can satisfy Equations (1)-(3). In this manner, the set of splines (3620) twist, bend, and bias away from the longitudinal axis of the ablation device (3600), thus allowing the splines (3620) to more easily conform to the geometry of the endocardial space (e.g., the posterior wall and opening of the ostium, etc.).In some embodiments, each spline in the set of splines in the second configuration can twist and bend to form a petal-like curve that, when viewed from the front, exhibits an angle between the proximal and distal ends of the curve that is greater than about 180 degrees.

[0121] In some embodiments, the second catheter (3620) coupled to the set of splines (3630) can allow each spline of the set of splines (3630) to bend and twist relative to the first catheter (3610) as the second catheter (3620) slides through the lumen of the first catheter (3610). For example, the set of splines (3630) can form a shape generally closer to the longitudinal axis of the second catheter (3620) when undeployed, can be wrapped (e.g., helically twisted) around the fully deployed longitudinal axis (3650), and can form any intermediate shape therebetween (e.g., a cage or barrel, etc.) as the second catheter (3620) slides through the lumen of the first catheter (3610).

[0122] In some embodiments, a set of splines in the first configuration (e.g., splines (3630)) may be wrapped around the longitudinal axis (3650) of the first catheter (3610) at some portions along its length, but may otherwise be generally parallel to the longitudinal axis of the first catheter (3610) at other locations. The second catheter (3620) can be retracted into the first catheter (3610) to transform the ablation device (3600) from the first configuration to a second configuration, in which the splines (3630) twist to form a petal-like shape and are generally angled or offset (e.g., perpendicular, angled distally) relative to the longitudinal axis (3650) of the first catheter (3610). As the second catheter (3622) is retracted further into the lumen of the first catheter (3610), the set of splines (3630) can extend further distally. As shown in Figures 36A-36C, each spline (3630) can form a twisting loop (e.g., a petal shape where the set of splines together form a flower shape).

[0123] In the second configuration, the set of splines (3630) in the second configuration can form a flower shape and can be angled distally. FIG. 36A shows a set of splines (3630) with at least a portion of each spline of the set of splines (3630) extending distally of the distal end (3622) of the second catheter (3620). For example, FIG. 36A shows that the distal portion of the splines intersects with a plane (3660) (perpendicular to the longitudinal axis (3650)) distal to the distal end (3622) of the second catheter (3620). Thus, when the ablation device (3600) is advanced distally and contacts tissue, the set of splines (3630) will contact in front of the first catheter (3610) and the second catheter (3620). This can reduce trauma to the tissue because the tissue can contact the flexible set of splines without having to contact the relatively stiff second catheter (3622).

[0124] 36B shows that the set of splines (3630) in the second configuration form a distal (e.g., forward) angle (3680) between the longitudinal axis (3670) of the splines (3630) and the longitudinal axis (3650) of the first catheter. The longitudinal axis (3670) of the splines (3630) may be defined by a line formed between the apex of the splines (3630) and a midpoint between the proximal and distal ends of the splines (3630). In some embodiments, the distal angle can be less than about 80 degrees. For example, the distal angle can be about 60 degrees or less.

[0125] In some embodiments, each spline of a set of splines (3620) can form a twisted loop such that each spline partially overlaps one or more other splines. The number and spacing of the electrodes (3640) and the rotational twist of the splines (3630) can be configured by appropriate placement of the electrodes along each spline to prevent overlap of the electrodes (3640) on one spline with the electrodes of an adjacent overlapping spline.

[0126] Splines having one set of anodic electrodes can be activated together to deliver a pulse waveform for irreversible electroporation. Electrodes on other splines can be activated together as cathodic electrodes, such as the electrodes on their respective splines, to form an anode-cathode pairing for delivery of a pulse waveform for irreversible electroporation. The anode-cathode pairing and pulse waveform delivery can be repeated sequentially across a set of such pairings.

[0127] For example, the splines (3630) may be activated sequentially in a clockwise or counterclockwise fashion. As another example, the cathode splines may be activated sequentially with each sequential anode spline activation until ablation is completed. In embodiments in which the electrodes on a given spline are separately wired, the order of activation among the electrodes of each spline may be varied as well. For example, the electrodes in a spline may be activated all at once or in a predetermined sequence.

[0128] The delivery assembly may be disposed in a first configuration prior to delivery of the pulse waveform and transformed into a second configuration to contact a pulmonary vein ostium or sinus. For example, FIG. 36C shows a distal-most portion of a set of splines (3630) adjacent to and / or in contact with a tissue wall (3690), such as the posterior wall of the left atrium. The set of splines (3630) in FIG. 36C is in a second configuration in which at least a portion of each spline of the set of splines (3630) extends distally of the distal end (3622) of the second catheter (3620). The tissue (3690) may be a cardiac wall, such as the endocardial surface of the posterior wall of the left atrium. The distal end (3622) of the second catheter (3620) may be separated from the tissue (3690) by a first distance (3692). Thus, the ablation device (3600) in the second configuration is able to engage tissue (3690) in an atraumatic manner with reduced risk of perforation or other trauma, and thus may be used to ablate even thin tissue structures, such as the posterior wall of the left atrium.

[0129] In some of these embodiments, a handle may be coupled to the second catheter (3620), and the handle may be configured to affect deformation of the set of splines between a first configuration and a second configuration. For example, the handle may be configured to translate the second catheter (3620) relative to the first catheter (3610), thereby actuating a set of splines (3630) coupled to the second catheter (3620), causing them to bend and twist. The proximal ends of the splines (3630) may be fixed to the second catheter (3620), thereby causing buckling of the splines (3630), resulting in bending and twisting movement of the splines (3630), when the second catheter (3620) is pulled back relative to the first catheter (3610), which may be held by a user, for example. For example, the distal end of the set of splines (3630) coupled to the second catheter (3620) can be translated up to about 60 mm along the longitudinal axis of the ablation device to actuate this change in configuration. In other words, translation of the actuation member of the handle can bend and twist the set of splines (3630). In some embodiments, actuation of a knob, wheel, or other rotational control mechanism in the device handle can result in translation of the actuation member or the second catheter, resulting in bending and twisting of the splines (3630). In some embodiments, the electrical leads of at least two of the set of electrodes (3640) can be electrically coupled at or near the proximal portion of the ablation device (3600) (e.g., in the handle).

[0130] Retraction of the second catheter (3620) relative to the first catheter (3610) can move the set of splines (3630) closer together, as shown in FIGS. 36A-36C. The set of splines (3630) can also be generally perpendicular or angled distally to the longitudinal axis (3650) of the first catheter (3610). In some embodiments, each spline of the set of splines (3630) can be biased laterally away from the longitudinal axis (3650) by up to about 30 cm. In some embodiments, the second catheter (3620) can include a hollow lumen. In some embodiments, the cross-section of the splines can be asymmetric, such that one bending plane of the splines perpendicular to the plane of the cross-section has a greater bending stiffness than a different bending plane. Such asymmetric cross-sections can be configured to exhibit relatively high lateral stiffness, thereby enabling them to be deployed with minimal overlap of the petal-shaped curves of each spline and its neighbors in a final or fully deployed configuration.

[0131] In one embodiment, each of the electrodes (3640) on a spline (3630) may be configured as an anode, while each of the electrodes (3640) on a different spline (3630) may be configured as a cathode. In another embodiment, the electrodes (3640) on one spline may alternate between anodes and cathodes, while the electrodes on another spline have the opposite configuration (e.g., cathodes and anodes).

[0132] In some embodiments, the spline electrodes can be electrically activated in a sequential manner to deliver a pulse waveform with each anode-cathode pairing. In some embodiments, the electrodes can be electrically wired together in the spline, while in alternative embodiments, they can be wired together in the handle of the device, such that the electrodes are at the same electrical potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3640) can be different as well. In some embodiments, adjacent distal and proximal electrodes can form an anode-cathode pair. For example, the distal electrode can be configured as an anode and the proximal electrode can be configured as a cathode.

[0133] The ablation device (3600) can include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (3600) can include between 3 and 20 splines. For example, the ablation device (3600) can include between 4 and 12 splines.

[0134] Each of the splines of the set of splines (3630) can include a respective electrode (3640) having an atraumatic shape to reduce trauma to tissue. For example, the electrodes (3640) can have an atraumatic shape including rounded, flat, curved, and / or blunted portions configured to contact endocardial tissue. In some embodiments, the electrodes (3640) can be positioned along any portion of the splines (3630) distal to the first catheter (3610). The electrodes (3640) can have the same or different sizes, shapes, and / or locations along each spline.

[0135] In this manner, the electrodes in the second configuration may be held near or placed against a section of the atrial wall of the left atrium to directly create lesions thereon by activation of the appropriate electrodes using any suitable polarity combination, as described herein. For example, one set of splines (3630) may be placed in contact with the atrial wall (3654) of the atrium (3652) adjacent the pulmonary vein (3650) (e.g., ostium or sinus) and / or posterior wall.

[0136] 37A-37B are perspective views of an ablation catheter (3730) and the left atrium (3700). FIG. 37A is a perspective view of an ablation catheter (3730) disposed within the left atrium (3700). The left atrium (3700) includes a set of pulmonary veins (3720) and a posterior wall (3710). The ablation device (3730), which can be structurally and / or functionally similar to the ablation devices (3500, 3600) described herein, can be advanced into the left atrium (3700) and positioned adjacent to and / or in contact with the posterior wall (3710) of the left atrium (3700) without perforating and / or causing trauma to sensitive tissue of the posterior wall (3710). For example, a set of splines can extend distal to the distal end of the catheter coupled to the splines such that the flexible and atraumatic splines can abut or contact the rear wall (3710) without any other portion of the device (3730) contacting the rear wall (3710). In an embodiment in which the most distal portion of the device (3700) includes only one set of splines in the second configuration (e.g., having a flower shape), the deployed device can engage thin tissue structures such as heart walls with minimal risk of trauma from the ablation device (3700). A set of pulse waveforms can be applied by the electrodes of the ablation device (3700) having a flower shape to ablate tissue within the ablation zone (3740).

[0137] FIG. 37B is a schematic diagram of a perspective view of the left atrium (3700) after tissue ablation. The ablation device (3700) can be used to generate a set of ablation zones (3740, 3742, 3744) on the posterior wall (3710) of the left atrium (3700). For example, activation of one or more of the electrodes on one or more of the splines of the ablation device (3730), repeated by movement of the catheter between complete ablations, can generate a set of ablation zones (3740, 3742, 3744) along the posterior wall (3710) of the left atrium (3700). In some embodiments, the ablation zones (3740, 3742, 3744) can partially overlap one another. These successive overlapping ablation zones can form approximately a thick line of ablation (3746). One or more ablation lines can connect to other ablation lines (e.g., generated around a pulmonary vein sinus or pulmonary vein ostium) and / or ablation zones, thereby creating a box lesion. For example, a set of contiguous ablation zones can be formed by the ablation device (3730) to create a box lesion around the posterior wall (3710) of the left atrium (3700), which can also surround one or more of the pulmonary veins (3720). In this manner, contiguous percutaneous lesions can be generated around all of the pulmonary veins, resulting in electrical isolation of the pulmonary veins and providing the desired therapeutic outcome. In some embodiments, each ablation zone of the set of ablation zones (3740, 3742, 3744) can have a diameter between about 2 cm and about 6 cm. For example, the ablation zones can have a diameter between about 2.3 cm and about 4.0 cm.

[0138] In some embodiments, since the electrodes or a subset of electrodes are independently addressable, the electrodes may be excited in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver sufficient energy to electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes may be at the same potential, as well as all other alternating electrodes. Thus, in some embodiments, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0139] 27A-B are side views of an embodiment of an ablation device (2700) including a catheter shaft (2710) at a proximal end of the device (2700) and a set of splines (2720) coupled to the catheter shaft (2710) at a distal end of the device (2700). The ablation device (2700) can be configured to deliver a pulsed waveform to tissue during use via one or more splines of the set of splines (2720). Each spline (2720) of the ablation device (2700) can include one or more, possibly independently addressable, electrodes (2730) formed on a surface (e.g., a distal end) of the spline (2720). Each electrode (2730) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200 V and about 2000 V across its thickness without dielectric breakdown. Each spline of a set of splines (2720) can include an insulated electrical lead of a respective electrode (2730) formed within the body of the spline (2720) (e.g., within the lumen of the spline (2720)). In some embodiments, the electrodes (2730) can be formed at the distal ends of their respective splines (2720).

[0140] The set of splines (2720) can form a delivery assembly at the distal portion of the ablation device (2700) and can be configured to change between a first configuration and a second configuration. The set of splines (2720) in the first configuration can be generally parallel to the longitudinal axis of the ablation device (2700) and spaced apart from one another. The set of splines (2720) in the second configuration is shown in FIGS. 27A-B, where the set of splines (2720) extend out from the distal end of the catheter shaft (2710) and are biased (e.g., curved) away from the longitudinal axis of the ablation device (2700) and the other splines (2720). In this manner, the splines (2720) can more easily conform to the geometry of the endocardial space. The delivery assembly can be disposed in a first configuration prior to delivery of the pulse waveform and transformed into a second configuration against a section of cardiac tissue, such as the posterior wall of the left atrium or ventricle, etc. Such devices delivering irreversible electroporation pulse waveforms are capable of generating large lesions for focal ablation.

[0141] The distal end of a set of splines (2720) can be configured to bias away from a longitudinal axis of the distal end of the catheter shaft (2710) and away from the other splines. Each spline of the set of splines (2720) can include a flexible curvature. The minimum radius of curvature of the splines (2720) can be in the range of about 1 cm or greater.

[0142] In some embodiments, the proximal end of the set of splines (2720) can be slidably coupled to the distal end of the catheter shaft (2710). Thus, the length of the set of splines (2720) can be varied as shown in FIGS. 27A and 27B. As the set of splines (2720) is extended further out of the catheter shaft (2710), the distal ends of the set of splines (2720) can be further biased away from each other and from the longitudinal axis of the catheter shaft (2710). The set of splines (2720) can be slidably advanced out of the catheter shaft (2710) independently or in one or more groups. For example, the set of splines (2720) can be disposed in the catheter shaft (2710) in a first configuration. The splines (2720) can then be advanced out of the catheter shaft (2710) and transformed into a second configuration. The splines (2720) can be advanced all together or advanced such that a set of splines (2720) corresponding to the anode electrodes (2730) is advanced separately from a set of splines (2720) corresponding to the cathode electrodes (2730). In some embodiments, the splines (2720) can be advanced independently. In the second configuration, the electrodes (2730) are biased away from the catheter shaft (2710) longitudinally and / or transversely relative to the longitudinal axis of the distal end of the catheter shaft (2710). This can aid in the delivery and positioning of the electrodes (2730) relative to the endocardial surface. In some embodiments, each of a set of splines (2720) can extend up to about 5 cm from the distal end of the catheter shaft (2710).

[0143] In some embodiments, the set of splines (2720) can have a fixed length from the distal end of the catheter shaft (2710). The splines (2720) can extend from the distal end of the catheter shaft (2710) at equal or unequal lengths. For example, a spline having a larger radius of curvature than an adjacent spline can extend farther from the catheter shaft (2710) than an adjacent spline. The set of splines (2720) can be constrained by a lumen of the guide sheath such that the set of splines (2720) is substantially parallel to the longitudinal axis of the catheter shaft (2710) in the first configuration.

[0144] In some of these embodiments, a handle (not shown) may be coupled to the set of splines. The handle may be configured to affect deformation of the set of splines between a first configuration and a second configuration. In some embodiments, the electrical leads of at least two of the set of electrodes (2730) may be electrically coupled at or near a proximal portion of the ablation device (e.g., in the handle). In this case, the electrodes (2730) may be electrically wired together in the handle of the device (2700) such that the electrodes (2730) are at the same electrical potential during ablation.

[0145] Each of the splines of the set of splines (2720) can include a respective electrode (2730) at a distal end of the set of splines (2720). The set of electrodes (2730) can include an atraumatic shape to reduce trauma to tissue. For example, the electrodes (2730) can have an atraumatic shape that includes rounded, flat, curved, and / or blunted portions configured to contact endocardial tissue. In some embodiments, the electrodes (2730) can be positioned along any portion of the splines (2720) distal to the catheter shaft (2710). The electrodes (2730) can have the same or different sizes, shapes, and / or locations along each spline.

[0146] In one embodiment, the electrode (2730) on a spline (2720) may be configured as an anode, while the electrode (2730) on an adjacent spline (2720) may be configured as a cathode. The ablation device (2700) may include any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (2700) may include between 3 and 20 splines. For example, the ablation device (2700) may include between 6 and 12 splines.

[0147] 27A-B are side views of an embodiment of an ablation device (2700) including a catheter shaft (2710) at a proximal end of the device (2700) and a set of splines (2720) coupled to the catheter shaft (2710) at a distal end of the device (2700). The ablation device (2700) can be configured to deliver a pulsed waveform to tissue during use via one or more splines of the set of splines (2720). Each spline (2720) of the ablation device (2700) can include one or more, possibly independently addressable, electrodes (2730) formed on a surface (e.g., a distal end) of the spline (2720). Each electrode (2730) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200 V and about 2000 V across its thickness without dielectric breakdown. Each spline of a set of splines (2720) can include an insulated electrical lead of a respective electrode (2730) formed within the body of the spline (2720) (e.g., within the lumen of the spline (2720)). In some embodiments, the electrodes (2730) can be formed at the distal ends of their respective splines (2720).

[0148] The set of splines (2720) can form a delivery assembly at the distal portion of the ablation device (2700) and can be configured to change between a first configuration and a second configuration. The set of splines (2720) in the first configuration can be generally parallel to the longitudinal axis of the ablation device (2700) and spaced apart from one another. The set of splines (2720) in the second configuration is shown in FIGS. 27A-B, where the set of splines (2720) extend out from the distal end of the catheter shaft (2710) and are biased (e.g., curved) away from the longitudinal axis of the ablation device (2700) and the other splines (2720). In this manner, the splines (2720) can more easily conform to the geometry of the endocardial space. The delivery assembly can be disposed in a first configuration prior to delivery of the pulse waveform and transformed into a second configuration against a section of cardiac tissue, such as the posterior wall of the left atrium or ventricle, etc. Such devices delivering irreversible electroporation pulse waveforms are capable of generating large lesions for focal ablation.

[0149] The distal end of a set of splines (2720) can be configured to bias away from a longitudinal axis of the distal end of the catheter shaft (2710) and away from the other splines. Each spline of the set of splines (2720) can include a flexible curvature. The minimum radius of curvature of the splines (2720) can be in the range of about 1 cm or greater.

[0150] In some embodiments, the proximal end of the set of splines (2720) can be slidably coupled to the distal end of the catheter shaft (2710). Thus, the length of the set of splines (2720) can be varied as shown in FIGS. 27A and 27B. As the set of splines (2720) is extended further out of the catheter shaft (2710), the distal ends of the set of splines (2720) can be further biased away from each other and from the longitudinal axis of the catheter shaft (2710). The set of splines (2720) can be slidably advanced out of the catheter shaft (2710) independently or in one or more groups. For example, the set of splines (2720) can be disposed in the catheter shaft (2710) in a first configuration. The splines (2720) can then be advanced out of the catheter shaft (2710) and transformed into a second configuration. The splines (2720) can be advanced all together or advanced such that a set of splines (2720) corresponding to the anode electrodes (2730) is advanced separately from a set of splines (2720) corresponding to the cathode electrodes (2730). In some embodiments, the splines (2720) can be advanced independently. In the second configuration, the electrodes (2730) are biased away from the catheter shaft (2710) longitudinally and / or transversely relative to the longitudinal axis of the distal end of the catheter shaft (2710). This can aid in the delivery and positioning of the electrodes (2730) relative to the endocardial surface. In some embodiments, each of a set of splines (2720) can extend up to about 5 cm from the distal end of the catheter shaft (2710).

[0151] In some embodiments, the set of splines (2720) can have a fixed length from the distal end of the catheter shaft (2710). The splines (2720) can extend from the distal end of the catheter shaft (2710) at equal or unequal lengths. For example, a spline having a larger radius of curvature than an adjacent spline can extend farther from the catheter shaft (2710) than an adjacent spline. The set of splines (2720) can be constrained by a lumen of the guide sheath such that the set of splines (2720) is substantially parallel to the longitudinal axis of the catheter shaft (2710) in the first configuration.

[0152] In some of these embodiments, a handle (not shown) may be coupled to the set of splines. The handle may be configured to affect deformation of the set of splines between a first configuration and a second configuration. In some embodiments, the electrical leads of at least two of the set of electrodes (2730) may be electrically coupled at or near a proximal portion of the ablation device (e.g., in the handle). In this case, the electrodes (2730) may be electrically wired together in the handle of the device (2700) such that the electrodes (2730) are at the same electrical potential during ablation.

[0153] Each of the splines of the set of splines (2720) can include a respective electrode (2730) at a distal end of the set of splines (2720). The set of electrodes (2730) can include an atraumatic shape to reduce trauma to tissue. For example, the electrodes (2730) can have an atraumatic shape that includes rounded, flat, curved, and / or blunted portions configured to contact endocardial tissue. In some embodiments, the electrodes (2730) can be positioned along any portion of the splines (2720) distal to the catheter shaft (2710). The electrodes (2730) can have the same or different sizes, shapes, and / or locations along each spline.

[0154] In one embodiment, the electrode (2730) on a spline (2720) may be configured as an anode, while the electrode (2730) on an adjacent spline (2720) may be configured as a cathode. The ablation device (2700) may include any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (2700) may include between 3 and 20 splines. For example, the ablation device (2700) may include between 6 and 12 splines.

[0155] In FIG. 27A-B, an electrode (2730) is formed on the surface of each spline (2720) such that each spline (2720) includes an insulated electrical lead. Thus, the lumen of the spline (2720) may be reduced in diameter, allowing the spline (2720) to be thicker and more mechanically robust. Thus, dielectric breakdown of the insulation may be further reduced, thereby improving the reliability and lifespan of each spline (2720) and the ablation device (2700). Moreover, in some embodiments, the radius of curvature of the spline may vary over the length of the spline. For example, the radius of curvature may be monotonically increasing. Such a variable radius of curvature may aid in positioning of the electrode (2730) at several locations of the endocardial tissue. The splines (2720) may have the same or different materials, thicknesses, and / or radii of curvature. For example, the thickness of each spline can decrease distally.

[0156] In this manner, the electrodes in the second configuration may be pressed against, for example, the posterior wall of the left atrium to directly generate focal or localized lesions thereon by activation of the appropriate electrodes using any suitable polarity combination, for example, adjacent electrodes (2730) may be configured with opposite polarities.

[0157] Because the electrodes or subsets of electrodes may be independently addressable, the electrodes may be excited in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms), as discussed in further detail herein. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver percutaneous lesions over a relatively large area of ​​endocardial tissue. In some embodiments, alternate electrodes may be at the same potential, as well as all other alternating electrodes. Thus, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0158] With reference to Figure 27C, it will be understood that components with similar reference numbers as in Figures 27A-B (e.g., electrode (2730) in Figures 27A-B and electrode (2730') in Figure 27C) can be structurally and / or functionally similar unless otherwise indicated. Figure 27C illustrates a set of splines (2720'), where each spline (2720') includes a pair of electrodes (2730', 2740).

[0159] The ablation device (2700') includes a catheter shaft (2710') at a proximal end of the device (2700') and a set of splines (2720') coupled to the catheter shaft (2710') at a distal end of the device (2700'). The ablation device (2700') can be configured to deliver a pulsed waveform to tissue during use via one or more splines of the set of splines (2720'). Each spline (2720') of the ablation device (2700') can include one or more independently addressable electrodes (2730', 2740) formed on a surface of the spline (2720'). Each electrode (2730', 2740) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads is capable of sustaining a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline of a set of splines (2720') can include an insulated electrical lead of a respective electrode (2730', 2740) formed within the body of the spline (2720') (e.g., within the lumen of the spline (2720')). The electrodes (2730', 2740) of each spline (2720') can have approximately the same size and shape. Moreover, the electrodes (2730', 2740) of each spline (2720') can have approximately the same size, shape, and spacing as the electrodes (2730', 2740) of an adjacent spline (2720'). In other embodiments, the size, shape, number, and spacing of the electrodes (2730', 2740) can be different.

[0160] In some embodiments, the electrodes (2730', 2740) of the ablation device (2700') can have a length of about 0.5 mm to about 5.0 mm and a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 4.0 mm, including all values ​​and subranges therebetween. The spline wires (2720') in the second configuration can diverge from one another at the distal end of the ablation device (2700') in a range Sd of about 5.0 mm to about 20.0 mm, including all values ​​and subranges therebetween, and can extend from the distal end of the catheter shaft (2710') over a length Sl of about 8.0 mm to about 20.0 mm, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2700') can include four splines, five splines, or six splines. In some embodiments, each spline can independently include one electrode, two electrodes, or three or more electrodes.

[0161] The set of splines (2720') can form a delivery assembly at the distal portion of the ablation device (2700') and can be configured to change between a first configuration and a second configuration. The set of splines (2720') in the first configuration can be generally parallel to the longitudinal axis of the ablation device (2700) and spaced apart from one another. The set of splines (2720') in the second configuration is shown in FIG. 27C, where the set of splines (2720') extend out from the distal end of the catheter shaft (2710') and are biased (e.g., curved) away from the longitudinal axis of the ablation device (2700') and the other splines (2720'). In this way, the splines (2720') can more easily conform to the geometry of the endocardial space. The delivery assembly may be disposed in a first configuration prior to delivery of the pulse waveform and may be transformed into a second configuration to contact a region of endocardial tissue and generate large focal lesions upon delivery of the pulse waveform for irreversible electroporation as disclosed herein. In some embodiments, the electrode (2730') in the second configuration shown in FIG. 27C (sometimes referred to as the "distal electrode") may be configured to contact and press against the endocardial tissue, while the electrode (2740) in the second configuration (sometimes referred to as the "proximal electrode") may not contact the endocardial tissue. In this manner, the electric field generated by the electrode due to conduction between the proximal and distal electrodes through the blood pool results in focal ablation of the tissue.

[0162] In some embodiments, the proximal end of the set of splines (2720') can be slidably coupled to the distal end of the catheter shaft (2710'). As the set of splines (2720') is extended further out of the catheter shaft (2710'), the distal ends of the set of splines (2720') can be further biased away from each other and from the longitudinal axis of the catheter shaft (2710'). The set of splines (2720') can be slidably advanced out of the catheter shaft (2710') independently or in one or more groups. For example, the set of splines (2720') can be disposed in the catheter shaft (2710') in a first configuration. The splines (2720') can then be advanced out of the catheter shaft (2710') and transformed into a second configuration. The splines (2720') may be advanced all together or may be advanced such that a set of splines (2720') corresponding to the anode electrodes (2730) is advanced separately from a set of splines (2720') corresponding to the cathode electrodes (2730', 2740). In some embodiments, the splines (2710') may be advanced independently through their respective lumens (e.g., sheaths) of the catheter shaft (2710'). In the second configuration, the electrodes (2730', 2740) are biased away from the catheter shaft (2710') longitudinally and / or transversely relative to the longitudinal axis of the distal end of the catheter shaft (2710'). This may aid in the delivery and positioning of the electrodes (2730', 2740) relative to the endocardial surface. In some embodiments, each of a set of splines (2720') can extend up to about 5 cm from the distal end of the catheter shaft (2710').

[0163] In some embodiments, the distal electrode (2730') can have the same polarity while the adjacent proximal electrode (2740) can have an opposite polarity to the distal electrode (2730'). In this manner, an electric field can be generated between the distal and proximal electrodes for focal ablation.

[0164] In some of these embodiments, a handle (not shown) may be coupled to the set of splines. The handle may be configured to affect deformation of the set of splines between a first configuration and a second configuration. In some embodiments, the electrical leads of at least two of the set of electrodes (2730', 2740) may be electrically coupled at or near a proximal portion of the ablation device (e.g., in the handle, etc.). In some embodiments, the electrodes (2730', 2740) may be electrically wired together in the handle of the device (2700') such that the electrodes (2730', 2740) are at the same electrical potential during ablation.

[0165] The set of electrodes (2730', 2740) can include an atraumatic shape to reduce trauma to tissue. For example, the electrodes (2730', 2740) can have an atraumatic shape including rounded, flat, curved, and / or blunted portions configured to contact endocardial tissue. In some embodiments, the electrodes (2730', 2740) can be positioned along any portion of the splines (2720') at the distal end of the catheter shaft (2710'). The electrodes (2730', 2740) can have the same or different sizes, shapes, and / or locations along each spline. One or more of the splines (2720') can include three or more electrodes.

[0166] In some embodiments, each of the electrodes (2730') on a spline (2720') may be configured as an anode, while each of the electrodes (2730') on an adjacent spline (2720') may be configured as a cathode. In another embodiment, each of the electrodes (2730') on a spline may alternate between an anode and a cathode, with each of the electrodes on an adjacent spline having the opposite configuration (e.g., a cathode and an anode). In some embodiments, a subset of the electrodes may be electrically wired together in the handle of the device, such that these electrodes are at the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (2730) may be different as well. In some embodiments, adjacent distal electrodes (2730') and proximal electrodes (2740) may form an anode-cathode pair. For example, the distal electrode (2730') may be configured as an anode, and the proximal electrode (2740) may be configured as a cathode.

[0167] The ablation device (2700') can include any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (2700') can include between 3 and 20 splines. For example, the ablation device (2700) can include between 6 and 12 splines.

[0168] In FIG. 27C, two electrodes (2730', 2740) are formed on the surface of each spline (2720'), such that each spline (2720') includes two insulated electrical leads. The thickness of each spline (2720') can vary based on the number of electrodes formed on each spline (2720'), which can correspond to the number of insulated electrical leads in the spline (2720'). The splines (2720') can have the same or different materials, thicknesses, and / or radii of curvature. For example, the thickness of each spline (2720') can decrease distally.

[0169] In this manner, the electrodes in the second configuration may be placed against a section of endocardial tissue to directly create lesions thereon by activation of the appropriate electrodes using any suitable polarity combination for delivery of a pulse waveform for irreversible electroporation. For example, adjacent electrodes (2730', 2740) may be configured with opposite polarities.

[0170] Since the electrodes may be independently addressable, the electrodes may be excited in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms) as discussed in further detail herein. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver sequential / percutaneous energy and electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes may be at the same potential, as well as all other alternating electrodes. Thus, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0171] 28 is a side view of yet another embodiment of an ablation device (2800) including a catheter shaft (2810) at a proximal end of the device (2800), a distal cap (2812) of the device (2800) and a set of splines (2814) coupled thereto. In some embodiments, the ablation device (2800) is useful for forming lesions on the endocardial surface via focal ablation, as described herein.

[0172] The distal cap (2812) can include an atraumatic shape and one or more independently addressable electrodes (2816) (sometimes referred to as "distal electrodes"), as described in further detail herein. A proximal end of a set of splines (2814) can be coupled to a distal end of the catheter shaft (2810), and a distal end of a set of splines (2814) can be tethered to the distal cap (2812) of the device (2800). Each spline (2814) of the ablation device (2800) can include one or more independently addressable electrodes (2818) (sometimes referred to as "proximal electrodes") formed on a surface of the spline (2814). Each electrode (2816, 2818) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown (including all values ​​and subranges therebetween). Each spline (2814) can include an insulated electrical lead of each electrode (2818) formed within the body of the spline (2814) (e.g., within the lumen of the spline (2814)). One or more of the splines (2818) can further include an insulated electrical lead of a distal electrode (2816). In some embodiments, the size and / or shape of the electrodes (2816, 2818) can be different from one another.

[0173] The configuration of the set of splines (2814) and the proximal electrode (2818) can control the depth, shape, and / or diameter / size of the focal ablation lesions generated by the ablation device (2800). The ablation device (2800) can be configured to transform between a first configuration and a second configuration, in which the set of splines (2814) are disposed generally parallel to the longitudinal axis of the ablation device (2800) and in which the set of splines (2814) are curved radially outward from the longitudinal axis of the ablation device (2800). It is understood that the set of splines (2814) can be transformed, either continuously or in discrete steps, to any intermediate configuration between the first and second configurations.

[0174] Activation of the electrodes using a predefined configuration can provide targeted and precise focal ablation by controlling focal ablation spot size based on the expansion of the splines (2814). For example, in some embodiments, the distal electrode (2816) can be configured with a first polarity and one or more proximal electrodes (2818) can be configured with a second polarity opposite the first polarity. When the proximal electrode (2818) of the ablation device (2800) is in the first configuration, a high intensity electric field having a relatively smaller / more focused diameter results in focal ablation lesions on the endocardial surface that are relatively smaller in diameter and have a greater depth. When the proximal electrode (2818) of the ablation device (2800) is in the second configuration, a relatively more dispersed electric field is generated, resulting in focal ablation lesions on the endocardial surface that are relatively wider and shallower than those of the first configuration. In this manner, by varying the extent of expansion of the splines (2814), the depth, shape, and / or size of the lesion may be controlled without switching out the ablation device (2800). Such an embodiment is useful for creating multiple lesions of varying sizes and / or depths using the same ablation device.

[0175] The distal cap (2812) may be disposed to press against endocardial tissue, while the proximal electrodes (2818) in either the first or second configuration may be configured not to contact endocardial tissue. It should be appreciated that the distal electrodes (2816) need not contact endocardial tissue. In some of these embodiments, a handle (not shown) may be coupled to the set of splines (2814), and the handle may be configured to affect deformation of the set of splines (2814) between the first and second configurations. In some embodiments, the electrical leads of at least two electrodes of the set of electrodes may be electrically coupled at or near a proximal portion of the ablation device (2800) (e.g., in a handle, etc.).

[0176] In some embodiments, the distal electrode (2816) and the proximal electrode (2818) can form an anode-cathode pair. For example, the distal electrode (2816) can be configured as an anode and each of the proximal electrodes (2818) can be configured as a cathode. In some embodiments, the ablation device (2800) can include between three and twelve splines. The ablation device (2800) can include any number of splines, for example, three, four, five, six, seven, eight, nine, ten, twelve, fourteen, sixteen, eighteen, twenty, or more splines. In some embodiments, the ablation device (2800) can include between three and twenty splines. For example, in one embodiment, the ablation device (2800) can include between six and ten splines. Moreover, in some embodiments, the shape of the expanded set of splines (2814) can be asymmetric, for example, with its distal portion being more bulbous or rounded than its proximal portion. Such a bulbous distal portion (and proximal electrode positioning) can help to further control the size and depth of the focal ablation.

[0177] The first plane (2822) shown in FIG. 28 can refer to a plane perpendicular to the longitudinal axis of the catheter shaft (2810). The distal cap (2812) can be pressed against an endocardial surface (e.g., the luminal wall of a pulmonary vein, etc.) lying within the first plane (2812) to directly generate focal ablation lesions thereon by activation of appropriate electrodes using any suitable polarity combination. For example, the distal electrode (2816) can be pressed against the endocardial surface and used to form focal ablation lesions (e.g., spot lesions). In some embodiments, one or more of the proximal electrodes (2818) can be configured with a polarity opposite that of the distal electrode (2816). Conversely, one or more of the proximal electrodes (2818) can be configured with the same polarity as the distal electrode (2816). In some embodiments, the proximal electrodes (2818) on different splines (2814) can alternate between anodes and cathodes.

[0178] In some embodiments, the distal electrode (2816) of the ablation device (2800) can include a length of about 0.5 mm to about 7.0 mm and a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 4.0 mm, including all values ​​and subranges therebetween. In some embodiments, the proximal electrode (2818) can include a length of about 0.5 mm to about 5.0 mm and a diameter of about 0.5 mm to about 2.5 mm, including all values ​​and subranges therebetween. The distal electrode (2816) can be separated from the proximal electrode (2818) by a length of about 3.0 mm to about 12.0 mm, including all values ​​and subranges therebetween. The distal electrode (2816), disposed on the distal cap (2812), can be positioned about 1.0 mm to about 4.0 mm away from the distal end of the distal cap (2812), including all values ​​and subranges therebetween. In some embodiments, the distal end of the distal cap (2812) can include a distal electrode (2816). One or more focal ablation zones can be formed to include a diameter of about 1.0 cm to about 2.0 cm (including all values ​​and subranges therebetween).

[0179] 29A-29D are side views of yet another embodiment of an ablation device (2900) including an outer catheter or sheath (2902) and a set of inner catheters (2910, 2920) that are slidable within the outer catheter lumen and extend from a distal end of the lumen. The outer catheter can define a longitudinal axis. The inner diameter of the outer catheter (2902) can be from about 0.7 mm to about 3 mm, and the outer diameter of the outer catheter (2902) can be from about 2 mm to about 5 mm. As best seen in Figures 29A-D, the ablation device (2900) includes a first catheter (2910) having a first proximal portion (2912), a first distal portion (2914), and a first electrode (2916), the first electrode (2916) being formed, for example, on (e.g., on a surface of) the first distal portion (2914). The first proximal portion (2912) can be coupled to the first distal portion (2914) via a first hinge (2918). The second catheter (2920) includes a second proximal portion (2922), a second distal portion (2924), and a second electrode (2926) formed on the second distal portion (2924). The second proximal portion (2922) can be coupled to the second distal portion (2924) via a second hinge (2928).

[0180] In some embodiments, the ablation device (2900) is useful for forming lesions on the endocardial surface via focal ablation, as described herein. The distal ends of the catheters (2910, 2920) and / or the electrodes (2916, 2922) can include an atraumatic shape to reduce trauma to tissue. For example, the distal ends of the catheters (2910, 2920) and / or the electrodes (2916, 2922) can have an atraumatic shape that includes rounded, flat, curved, and / or blunted portions that are configured to contact endocardial tissue.

[0181] Each electrode (2916, 2926) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown (including all values ​​and subranges therebetween). Each catheter (2910, 2920) can include an insulated electrical lead of each electrode (2916, 2926) formed within the body of the catheter (2910, 2920) (e.g., within the lumen of the catheter (2910, 2920)). Each of the electrodes (2916, 2926) can be connected to a corresponding insulated electrical lead that leads to a handle (not shown) that is coupled to a proximal portion of the catheter (2910, 2920). In some embodiments, the size, shape, and / or location of the electrodes (2916, 2926) may differ from one another.

[0182] In some embodiments, the configuration of the catheters (2910, 2920) and electrodes (2916, 2926) can control the depth, shape, and / or diameter / size of focal ablation lesions generated by the ablation device (2900). The first and second catheters (2910, 2920) can be configured for translation along the longitudinal axis of the outer catheter (2902). In some embodiments, the ablation device (2900) can be configured to transform between a first configuration, a second configuration, and a third configuration, where in the first configuration, a set of catheters (2910, 2920) are positioned generally parallel to the longitudinal axis of the outer catheter (2902) and distal portions of the catheters (2910, 2920) are disposed within the outer catheter (2902) (e.g., FIG. 29A); in the second configuration, the electrodes (2916, 2926) can be configured for translation along the longitudinal axis of the outer catheter (2902). (2916, 2926) have been advanced outwardly away from the distal end (2903) of the outer catheter lumen (2902) by any suitable distance; in the third configuration, the distal portion of each catheter (2910, 2920) can rotate, twist, or bend about its corresponding hinge (2918, 2928) relative to the proximal portion of its corresponding catheter (2910, 2920) (e.g., FIGS. 29B-29D). For example, as best shown in FIGS. 29B-29C, a first catheter (2910) can include a distal portion (2914) that is rotatable about a first hinge (2918), which can be configured to position the distal portion (2914) relative to the proximal portion (2912) in a plurality of positions. The catheters (2910, 2912) in the second and third configurations can be angled away from one another to bias them away from the longitudinal axis of the outer catheter (2902). The distal ends of the proximal portions (2912, 2922) can form an angle between about 5 degrees and about 75 degrees with respect to the longitudinal axis (e.g., FIG. 29D).It will be understood that the ablation device (2900) may be transformed, either continuously or in discrete steps, to any intermediate configuration between the first, second, and third configurations.

[0183] In some embodiments, conduction between the electrodes through the blood pool and / or endocardial tissue results in electric field generation and application of the electric field as ablative energy to the endocardial surface. The electrodes may be held near or placed in physical contact with a section of the atrial wall of the left atrium to generate lesions thereon by activation of one or more of the electrodes using any suitable polarity combination. In this manner, activation of the electrodes using a predetermined configuration can provide targeted and precise focal ablation by controlling focal ablation spot size based on the position and orientation of the electrodes (2916, 2926) relative to the proximal portions (2912, 2922) of the catheters (2910, 2920). For example, in some embodiments, the first electrode (2916) may be configured with a first polarity and the second electrode (2926) may be configured with a second polarity opposite the first polarity. When the electrodes (2916, 2926) are rotated relatively closer to one another (e.g., when the proximal portion (2912) and the distal portion (2914) form an acute angle (2950)), a relatively higher intensity electric field with a relatively smaller / more focused diameter results in a focal ablation lesion on the endocardial surface that is relatively smaller in diameter and has good depth. Purely for non-limiting illustrative purposes, the acute angle formed at the articulating hinge can range between about 15 degrees to about 70 degrees. In some embodiments, the electric field strength in the focal ablation zone can be about 200 V / cm or greater. When the electrodes (2916, 2926) are rotated about their corresponding hinges (2918, 2928) relatively farther away from one another (e.g., when the proximal portion (2912) and distal portion (2914) form a larger angle), a relatively more dispersed and lower strength electric field is generated, resulting in a focal ablation lesion on the endocardial surface that is relatively wider and shallower.In this manner, by varying the extent of rotation of the electrodes (2916, 2926) relative to the proximal portions (2912, 2922) of the catheters (2910, 2920), the depth, shape, and / or size of the lesion may be controlled without switching out the ablation device (2900). Such an embodiment is useful for creating multiple lesions of various sizes, shapes, and / or depths using the same ablation device. For example, the lesion diameter may be about 2 mm to about 3 cm, and the lesion depth may be between about 2 mm and about 12 mm. Although the electrodes (2916, 2926) may be disposed to touch endocardial tissue, it should be appreciated that the electrodes (2916, 2926) need not contact endocardial tissue.

[0184] In some of these embodiments, a handle (not shown) may be coupled to a set of catheters (2910, 2920), and the handle may be configured to affect deformation of the catheters (2910, 2920) between the first, second, and third configurations. In some embodiments, actuation of one or more knobs, wheels, sliders, pull wires, and / or other control mechanisms in the handle can result in translation of one or more catheters (2910, 2920) through the outer catheter (2902) and / or rotation of distal portions (2914, 2924) of the catheters about hinges (2918, 2928).

[0185] 29B-C show a first catheter (2910) having an articulating distal portion (2914). The first catheter (2910) can include a proximal portion (2912) that is coupled to a distal portion (2914) via a hinge (2918). The distal portion (2914) can include an electrode (2916), as described herein. In some embodiments, the hinge (2918) can include a rotatable wheel. In other embodiments, the hinge (2918) can include a portion of the proximal portion (2912) or distal portion (2914) that has a reduced cross-sectional area relative to the first catheter (2910), making it more flexible than other portions of the catheter. In yet other embodiments, the hinge (2918) can include a joint, a rotatable wheel, a ball and socket joint, a condyloid joint, a saddle joint, a pivot, a track, and the like.

[0186] The rotatable wheel can be coupled to a wire (2917) (e.g., a pull wire). For example, the wire (2917) can be attached around a hinge (2918) and the distal portion (2914) can be attached to a portion of the hinge (2918). Thus, actuation (2930) of the wire (2917) (e.g., pulling one end of the wire proximally) can in turn rotate the wheel (2918) and the distal portion (2914), such that the distal portion (2914) rotates relative to the proximal portion (2912) of the first catheter (2910). In some embodiments, the distal portion can rotate relative to the proximal portion by an angle of about 110 degrees to about 165 degrees, and the length of the distal portion can be about 3 mm to about 12 mm. The proximal end of the wire (2917), in some embodiments, may be coupled to a handle (not shown) having a control mechanism (e.g., one or more knobs, wheels, sliders). An operator can operate the control mechanism to manipulate the wire (2917) and rotate the distal portion (2914) of the first catheter (2910) about the hinge (2918). The control mechanism of the handle can include a lock to fix the position of the distal portion (2914). FIG. 29B illustrates an embodiment of the first catheter (2910) having the distal portion (2914) between the second and third configurations. FIG. 29C illustrates an embodiment of the first catheter (2910) in the third configuration. The electrodes (2916, 2926) can be biased toward each other in the third configuration.

[0187] 29D shows an embodiment of an ablation device (2900) in a third configuration, in which the distal portions of the first and second catheters (2910, 2920) are extended out of an outer catheter or sheath (2902) and rotated (e.g., fully rotated, fully articulated) to a desired position relative to the proximal portions (2912, 2922) of the catheters (2910, 2920). In some embodiments, the wires (2912, 2922) of the catheters (2910, 2920) can be coupled together at a handle such that actuation of a control mechanism controls the wires (2912, 2922) together such that the distal portions (2914, 2924) of the catheters (2910, 2920) can be rotated simultaneously about their respective hinges (2918, 2928). In the second and third configurations, the first and second catheters (2910, 2920) can be biased away from the longitudinal axis of the outer catheter (2902).

[0188] When the first and second catheters (2910, 2920) are extended out of the outer catheter (2902), one or more portions of the catheters (2910, 2920) can assume their natural (e.g., unconstrained) shape (e.g., curved shape, etc.). The catheters (2910, 2920) can be advanced out of the outer catheter (2902) together or independently. In some embodiments, the proximal portions (2912, 2922) of the catheters (2910, 2920) can include a flexible curvature such that the distal ends of the catheters (2910, 2920) can be configured to flare away from one another. The minimum radius of curvature of the catheters (2910, 2920) can be in the range of about 1 cm or greater. For example, the proximal portions (2912, 2922) can have a radius of curvature of about 1 cm or greater. In some embodiments, the distal portions (2914, 2924) can have a radius of curvature of about 1 cm or greater.

[0189] In some embodiments, the electrodes (2916, 2926) of the ablation device (2900) can include a length of about 0.5 mm to about 7.0 mm and a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 4.0 mm, including all values ​​and subranges therebetween. The electrodes (2916, 2926) of different catheters (2910, 2920) can be separated from each other by a distance of about 3.0 mm to about 20 mm, including all values ​​and subranges therebetween. The electrodes (2916, 2926) can be positioned about 1.0 mm to about 4.0 mm away from the distal end of its corresponding catheter (2910, 2920), including all values ​​and subranges therebetween. In some embodiments, the distal ends of the catheters (2910, 2920) can include the electrodes (2916, 2926). One or more focal ablative lesions may be formed having diameters ranging from about 1.0 cm to about 2.0 cm (including all values ​​and subranges therebetween).

[0190] FIG. 30 is a side view of another embodiment of an ablation device (3000) including an outer catheter or sheath (3010) defining a longitudinal axis and a set of four catheters (3020, 3030, 3040, 3050) slidable within the lumen (3010). Each of the catheters (3020, 3030, 3040, 3050) can include a proximal portion (3023, 3033, 3043, 3053), a distal portion (3024, 3034, 3044, 3054), and a hinge (3021, 3031, 3041, 3051) connecting the proximal portion (3023, 3033, 3043, 3053) to the distal portion (3024, 3034, 3044, 3054). Each of the distal portions (3024, 3034, 3044, 3054) can include an electrode (3022, 3032, 3042, 3052). The distal ends of the catheters (3020, 3030, 3040, 3050) and / or the electrodes (3022, 3032, 3042, 3052) can include an atraumatic shape (e.g., rounded, flat, curved, and / or blunted portions) to reduce trauma to tissue. Each of the catheters (3020, 3030, 3040, 3050) can include a hinge (3021, 3031, 3041, 3051), as described in detail herein. It should be appreciated that the ablation device (3000) can include any number of catheters, including a set of two, three, four, five, six, or more catheters.

[0191] Each electrode (3022, 3032, 3042, 3052) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown (including all values ​​and subranges therebetween). Each catheter (3020, 3030, 3040, 3050) can include an insulated electrical lead of each electrode (3022, 3032, 3042, 3052) formed within the body of the catheter (3020, 3030, 3040, 3050) (e.g., within the lumen of the catheter (3020, 3030, 3040, 3050)). Each of the electrodes (3022, 3032, 3042, 3052) may be connected to a corresponding insulated electrical lead that leads to a handle (not shown) that is coupled to a proximal portion of the catheter. In some embodiments, the size, shape, and / or location of the electrodes (3022, 3032, 3042, 3052) may differ from one another.

[0192] In some embodiments, the configuration of the catheters (3020, 3030, 3040, 3050) and electrodes (3022, 3032, 3042, 3052) can control the depth, shape, and / or diameter / size of the focal ablation lesions generated by the ablation device (3000). A set of catheters (3020, 3030, 3040, 3050) can be configured to translate along a longitudinal axis and transition between first, second, and third configurations. In some embodiments, the ablation device (3000) may be configured to transform between a first configuration, a second configuration, and a third configuration, where in the first configuration, a set of catheters (3020, 3030, 3040, 3050) are arranged generally parallel to a longitudinal axis of an outer catheter or sheath (3010), with distal portions of the catheters (3020, 3030, 3040, 3050) disposed within the outer catheter (3010); 2, 3042, 3052) are advanced any suitable distance out of the distal end (3011) of the outer catheter (3010) lumen; in the third configuration, the distal portion of each catheter (3020, 3030, 3040, 3050) is allowed to rotate, twist, or bend about its corresponding hinge (3021, 3031, 3041, 3051) relative to the proximal portion of its corresponding catheter (3020, 3030, 3040, 3050) (e.g., FIG. 30). For example, the first catheter (3020) can include a distal portion (3024) rotatable about a first hinge (3021), which can be configured to position the distal portion (3024) relative to the proximal portion (3023) in a plurality of positions, as discussed above with respect to Figures 29A-29D. It is understood that the ablation device (3000) can be transformed into any intermediate configuration between the first, second, and third configurations, either continuously or in discrete steps. In the second configuration, the set of catheters can be biased away from the longitudinal axis.

[0193] In some embodiments, one or more pulse waveforms may be applied between electrodes (3022, 3032, 3042, 3052) that are configured as an anode and cathode set. For example, adjacent or roughly opposite electrode pairs may be activated together as an anode-cathode set. In FIG. 30, a first electrode (3022) may be configured as an anode and paired with a second electrode (3032) that is configured as a cathode. A third electrode (3042) may be configured as an anode and paired with a fourth electrode (3052) that is configured as a cathode. The first and second electrode (3022, 3032) pair may apply a first pulse waveform, followed sequentially by a second pulse waveform using the third and fourth electrode (3042, 3052) pair. In another embodiment, the pulse waveform may be applied to each of the electrodes simultaneously, where the second and third electrodes (3032, 3042) may be configured as an anode and the first and fourth electrodes (3022, 3052) may be configured as a cathode. It should be appreciated that any of the pulse waveforms disclosed herein may be applied progressively or sequentially over a series of anode-cathode electrodes. Some embodiments of the ablation device (3000) can have the same dimensions as those described above with respect to the ablation device (2900).

[0194] In other embodiments, one or more of the electrodes (3022, 3032, 3042, 3052) may be configured with a first electrical polarity, while one or more electrodes (not shown) disposed on a surface of the outer catheter shaft (3010) (not shown) may be configured with a second electrical polarity opposite the first electrical polarity.

[0195] 31A-31B are perspective views of yet another embodiment of an ablation device (3100) including an outer catheter or sheath (3110) defining a longitudinal axis and a catheter (3160) slidable within the outer catheter lumen. The catheter (3160) can extend from a distal end of the lumen. The catheter (3160) can include a proximal portion (3160), a plurality of distal portions (3122, 3132, 3142, 3152), and an articulation portion (3162) connecting the proximal portion to each of the plurality of distal portions. For example, the articulation portion (3162) can include a hinge, a joint, a rotatable wheel, a ball-and-socket joint, a condyloid joint, a saddle joint, a pivot, a track, and the like. The distal portions (3122, 3132, 3142, 3152) are folded into the outer catheter (3110) such that when each distal portion (3122, 3132, 3142, 3152) is folded, internal springs (not shown) connecting each portion are in a stressed configuration. When the distal portions (3122, 3132, 3142, 3152) are unconstrained (i.e., when the inner catheter (3160) is deployed or pushed sufficiently far from the outer catheter (3110)), the springs assume their natural or unstressed configuration, resulting in articulation of the articulation portion (3162) when the distal portions (3122, 3132, 3142, 3152) articulate outwardly and assume a configuration approximately perpendicular to the longitudinal axis of the catheter. As shown in Figure 3 IB, the distal end of the catheter (3160) may be coupled to a set of electrodes (3120, 3130, 3140, 3150) via an articulation section (3162). In some embodiments, the articulation section (3162) may be coupled to a first distal portion (3122), a second distal portion (3132), a third distal portion (3142), and a fourth distal portion (3152). The electrodes (3120, 3130, 3140, 3150) may be disposed on a surface of the respective distal portions (3122, 3132, 3142, 3152).When the catheter (3160) is advanced out of the outer catheter (3110), the distal portions (3120, 3130, 3140, 3150) are allowed to assume their natural (e.g., unconstrained) shape, such that they are approximately perpendicular to the longitudinal axis of the catheter (3160).

[0196] The electrodes (3120, 3130, 3140, 3150) can include an atraumatic shape (e.g., rounded, flat, curved, and / or blunted portions) to reduce trauma to tissue. Each electrode (3120, 3130, 3140, 3150) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown (including all values ​​and subranges therebetween). The catheter (3160) can include an insulated electrical lead of each electrode (3120, 3130, 3140, 3150) within the body (e.g., lumen) of the catheter (3160). Each of the electrodes (3120, 3130, 3140, 3150) may be connected to a corresponding insulated electrical lead that leads to a handle (not shown) that is coupled to a proximal portion of the catheter (3160). In some embodiments, the size, shape, and / or location of the electrodes (3120, 3130, 3140, 3150) may differ from one another.

[0197] The catheter (3160) may be configured to translate along a longitudinal axis to transition between a first, second, and third configuration. In some embodiments, the ablation device (3100) may be configured to transform between a first configuration, a second configuration, and a third configuration, where in the first configuration, a set of electrodes (3120, 3130, 3140, 3150) are disposed within the outer catheter (3110) generally parallel to the longitudinal axis of the outer catheter (3110) (e.g., FIG. 31A); In the third configuration, the electrodes (3120, 3130, 3140, 3150) can be advanced any suitable distance away from the distal end (3111) of the outer catheter lumen (not shown in FIG. 31A); in the third configuration, the electrodes (3120, 3130, 3140, 3150) can rotate, twist, or bend about their corresponding articulation portions (3162) relative to the proximal portion of the catheter (3160) (e.g., FIG. 31B). Transitions from the first configuration to the second and third configurations can be performed by advancing the catheter (3160) and the electrodes (3120, 3130, 3140, 3150) out of the distal end of the outer catheter (3110). It is understood that the ablation device (3100) can be transformed into any intermediate configuration between the first, second, and third configurations, either continuously or in discrete steps.

[0198] FIG. 31B illustrates the electrodes (3120, 3130, 3140, 3150) spaced evenly apart to form a plus ("+") shape. However, the angle between adjacent electrodes (3120, 3130, 3140, 3150) may be selected based on the desired focal ablation pattern. Similarly, the electrodes (3120, 3130, 3140, 3150) in FIG. 31B are approximately perpendicular to the longitudinal axis of the catheter (3160), but may be adjusted based on a set of ablation parameters.

[0199] In some embodiments, one or more pulse waveforms may be applied between electrodes (3120, 3130, 3140, 3150) configured as an anode and cathode set. For example, adjacent or roughly opposite electrode pairs may be activated together as an anode-cathode set. In FIG. 31B, a first electrode (3120) may be configured as an anode and paired with a third electrode (3140) configured as a cathode. A second electrode (3130) may be configured as an anode and paired with a fourth electrode (3150) configured as a cathode. The first and third electrode (3120, 3140) pair may apply a first pulse waveform, followed sequentially by a second pulse waveform using the second and fourth electrode (3130, 3150) pair. In another embodiment, the pulse waveform may be applied to each of the electrodes simultaneously, where the first and second electrodes (3120, 3130) may be configured as anodes and the third and fourth electrodes (3140, 3150) may be configured as cathodes. It should be appreciated that any of the pulse waveforms disclosed herein may be applied progressively or sequentially onto a series of anode-cathode electrodes.

[0200] In other embodiments, one or more of the electrodes (3120, 3130, 3140, 3150) can be configured with a first electrical polarity and one or more electrodes disposed on a surface of the outer catheter shaft (3110) can be configured with a second electrical polarity opposite the first electrical polarity.

[0201] FIG. 32 is a schematic cross-sectional view of a high intensity electric field generated by an ablation device (3200) for ablation of tissue (such as tissue in a ventricular cavity). For example, the ablation device (3200) may be disposed in the endocardial space of the left ventricle of the heart. The ablation device (3200) shown in FIG. 32 may be similar to those ablation devices (3000, 3100) described with respect to FIG. 30 and FIG. 31A-B. In some embodiments, the electrodes (3210, 3220, 3230, 3240) may be apposed to a tissue wall when in the third configuration. In some embodiments, the electrodes (3210, 3220, 3230, 3240) of FIG. 32 may have a width between about 1 mm and about 3 mm and a length between about 3 mm and about 9 mm. For example, the electrodes (3210, 3220, 3230, 3240) can have a width of about 2 mm and a length of about 6 mm.

[0202] In some embodiments, the electrodes (3210, 3220, 3230, 3240) can form an anode-cathode pair. For example, the first electrode (3210) can be configured as an anode and the third electrode (3230) can be configured as a cathode. The first and second electrodes (3210, 3230) can have a potential difference of up to about 1500V. Activation of one or more of the catheter electrodes (3210, 3220, 3230, 3240) can generate one or more ablation zones along a portion of the wall of the heart chamber. The electric field contours (3350) are lines of equal magnitude that correspond to the ablation zones (3350) having a field strength threshold of about 460V / cm when the first and third electrodes (3220, 3240) are activated. In some embodiments, the ablation zone (3350) can have a width of up to about 12 mm and a length of up to about 20 mm. Alternatively, the ablation device can be placed adjacent to or against a section of the posterior wall of the left atrium and upon activation of one or more electrodes, a suitable pulse waveform can be delivered for irreversible electroporation energy delivery to ablate tissue.

[0203] 33A is a perspective view of another embodiment of an ablation device / apparatus (3300) in the form of a catheter including an outer shaft (3310) extending to a proximal end of the device (3300), an inner shaft (3320) extending from a distal end of a shaft lumen (3312) of the outer shaft (3310) and a set of splines (3330) coupled thereto. The inner shaft (3320) may be coupled to a handle (not shown) at a proximal end and disposed at a distal portion (e.g., distal end) to a cap electrode (3322). The inner shaft (3320) and the set of splines (3330) may be translatable along a longitudinal axis (3324) of the ablation device (3300). In some embodiments, the inner shaft (3320) and the set of splines (3330) can move together or can be translated independently. The inner shaft (3320) can be configured to slide within the lumen (3312) of the outer shaft (3310). The cap electrode (3322) can include an atraumatic shape to reduce trauma to tissue. For example, the cap electrode (3322) can have a flat circular shape and / or a rounded, blunt profile. A distal end of each spline of the set of splines (3330) can be coupled to a distal portion of the inner shaft (3320). A proximal portion of the set of splines (3330) can be attached to the outer shaft (3310). The ablation device (3300) can be configured to deliver a pulsed waveform to tissue during use via the electrodes (3332, 3334) on the splines (3330) and the distal cap electrode (3322), for example as disclosed in Figures 21-25.

[0204] Each spline of the set of splines (3330) can include a set of electrodes (3332, 3334) on the surface of the spline. Each set of electrodes can include distal electrodes (3332), such that a set of splines includes a set of distal electrodes (3332). Each of the distal electrodes (3332) is closest to the cap electrode (3322) relative to the other electrodes of its corresponding set of electrodes on the same spline (e.g., a set of proximal electrodes (3334)). Moreover, in some embodiments, the distal electrodes (3332) can have only an outwardly exposed portion (i.e., a portion that faces away from the interior space / volume defined by the set of splines). For example, if the distal electrodes (3332) are constructed from metal rings, a portion of each ring can be insulated such that only an outwardly exposed portion or "window" is exposed for delivery of ablation energy. The cap electrode (3322) and each distal electrode (3332) of a set of distal electrodes can collectively have the same polarity during use. This combination of closely spaced distal and cap electrodes with outwardly facing windows allows the distal end of the ablation device (3300) to generate and project a stronger electric field, thereby more effectively generating focal ablation lesions of tissue at a desired depth compared to any one of these electrodes alone.

[0205] Each spline (3330) of the ablation device (3300) can include at least one set of independently addressable electrodes (3332, 3334) on a surface of the spline (3330). A distal cap electrode (3322) can be formed at a distal end of the catheter device (3300). Each electrode (3322, 3332, 3334) can be coupled to an insulated electrical lead configured to sustain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads is capable of sustaining a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline (3330) can include an insulated electrical lead for each electrode (3332, 3334) within the body of the spline (3330) (e.g., within the lumen of the spline (3330)). Similarly, in some embodiments, the inner shaft (3320) can include an insulated electrical lead for the cap electrode (3322). In other embodiments, a subset of the electrodes (3322, 3332, 3334) can be jointly wired. For example, the proximal electrodes (3334) of each spline of a set of splines (3330) can be jointly wired. As another example, all of the distal electrodes (3332) and the cap electrodes (3322) can be jointly wired.

[0206] In some embodiments, the set of splines (3330) may be configured to transform between a first configuration in which the set of splines (3330) are disposed generally parallel to the longitudinal axis (3324) of the ablation device (3300) and a second configuration in which the distal end of each spline of the set of splines (3330) bends radially outward from the longitudinal axis (3324). In this manner, the set of distal electrodes (3332) and the cap electrodes (3322) may be shaped / oriented to form the second configuration shown in Figures 33A, 33B, and 33E. The cap electrodes (3322) may be separated from each distal electrode of the set of distal electrodes (3332) by at most about 5 mm (including all values ​​and subranges therebetween). For example, the cap electrode (3322) may be separated from each of the distal electrodes of the set of distal electrodes (3332) by between about 0.5 mm and about 3 mm. In the second configuration, the distal portion of each of the splines of the set of splines (3330) may be angled (3336) between about 45 degrees and about 90 degrees relative to the longitudinal axis (3312), including all values ​​and subranges therebetween. For example, the distal portion of each of the splines of the set of splines (3330) in the second configuration may be angled (3336) between about 70 degrees and about 80 degrees relative to the longitudinal axis (3312). For example, in the second configuration, the cap electrode (3322) and the set of distal electrodes (3332) may take the shape of a "plus" sign when projected onto a plane perpendicular to the longitudinal axis (3324), as can be seen in the front view of FIG. 33B.

[0207] In some embodiments, the inner shaft (3320) can be retracted a predetermined amount into the outer catheter lumen (3312) to transform the ablation device (3300) from a first configuration to a second configuration. It is understood that the set of splines (3330) can be transformed to any intermediate configuration between the first and second configurations, either continuously or in discrete steps. The set of splines (3330) can form a shape generally parallel to the longitudinal axis (3324) of the inner shaft (3320) when undeployed, and can form a basket-like or bulb-like shape when the distal end of the set of splines (3330) is bent radially outward from the longitudinal axis (3324).

[0208] 33A, 33B, and 33E illustrate a set of splines (3330), where each spline of the set of splines (3330) includes a distal electrode (3332) and one or more proximal electrodes (3334) that differ in one or more of size, shape, number, and spacing. For example, FIG. 33A illustrates one distal electrode (3332) and two proximal electrodes (3334) for each spline of the set of splines (3330). In some embodiments, each proximal electrode (3334) may be formed on a surface of the spline (3330) along its entire periphery (i.e., around the entire thickness of the spline). In some embodiments, each distal electrode (3332) may be formed on a surface of a portion of the periphery of the spline. That is, as shown in FIG. 33C and FIG. 33D, a distal electrode (3332) can partially overlie the periphery of its corresponding spline and not cover the entire periphery of its spline (3330). For example, a distal electrode (3332) can surround the periphery of its corresponding spline and can be partially covered by a layer of insulation such that only a portion (e.g., a window) of the distal electrode (3332) is exposed. In some embodiments, one or more electrodes can be completely covered by a thin layer of insulation for biphasic operation. In some embodiments, a set of distal electrodes (3332) of a set of splines (3330) can subtend an angle (3333) between about 30 degrees and about 300 degrees (including all values ​​and subranges therebetween) about the center of its corresponding spline (3330). For example, a set of distal electrodes (3332) of a set of splines (3330) may subtend an angle (3333) between about 60 degrees and about 120 degrees about the center of its corresponding spline (3330).In this manner, a significant proportion of the electric field generated by the set of distal electrodes (3332) in the second configuration can be directed in a forward direction and projected into the target tissue, assisting in focal ablation into the blood, rather than away from the target tissue.

[0209] In this manner, the distal electrodes (3332) may be configured to face in a particular direction. For example, Figures 33A and 33E show a set of distal electrodes (3332) and a cap electrode (3322) that face generally forward at the distal end of the device (3300) in a second configuration, when the distal ends of the set of splines (3330) are bent radially outward from the longitudinal axis (3324). Moreover, the distal electrodes (3332) may be disposed at the distal ends of the splines such that the distal electrodes (3332) of the set of splines (3330) are disposed near the cap electrodes (3322).

[0210] In some embodiments, each spline of a set of splines (3330) can include a set of electrodes (3332, 3334) having approximately the same size, shape, number, and spacing as the corresponding electrodes (3332, 3334) of an adjacent spline. The thickness of each spline (3330) can vary based on the number of electrodes (3332, 3334) formed on each spline (3330), which can correspond to the number of insulated electrical leads in the spline (3330). The splines (3330) can have the same or different materials, thicknesses, and / or lengths.

[0211] In some embodiments, the cap electrode (3322) and the set of electrodes (3332, 3334) may be configured as an anode-cathode set. For example, the cap electrode (3322) and each of the set of distal electrodes (3332) may be collectively configured as an anode, and all of the proximal electrodes (3334) may be collectively configured as a cathode (or vice versa). In some embodiments, the set of distal electrodes (3332) and the set of proximal electrodes (3334) may have opposite polarities. For example, the distal electrodes (3332) and the set of proximal electrodes (3334) for a given spline may have opposite polarities. The cap electrodes (3322) and the set of distal electrodes (3332) may have the same polarity. As discussed herein, the set of distal electrodes (3332) and the cap electrodes (3322) may be jointly wired. In some embodiments, the cap electrodes and the set of electrodes (3332, 3334) of one or more splines of the set of splines (3330) can be activated together to deliver a pulse waveform for irreversible electroporation. In other embodiments, the pulse waveform delivery can be repeated sequentially on a predetermined subset of the set of electrodes (3332, 3334).

[0212] In some embodiments, the set of distal electrodes (3332) may be separated from the cap electrodes (3322) by at most 3 mm from the distal end of the respective splines (3330). In some embodiments, the set of distal electrodes (3332) may be separated from the set of proximal electrodes (3334) by between about 1 mm and about 20 mm. In some embodiments, each electrode of the set of electrodes (3332, 3334) may include a diameter of between about 0.5 mm and about 3 mm. In some embodiments, the cap electrodes (3322) may include a cross-sectional diameter of between about 1 mm and about 5 mm. In some embodiments, each electrode of the set of electrodes (3332, 3334) may have a length of between about 0.5 mm and about 5 mm. In some embodiments, the set of splines (3330) in the second configuration can have an expanded cross-sectional diameter (i.e., the effective diameter in the expanded or second configuration at its largest portion) of between about 6 mm and about 24 mm. In some embodiments, the set of splines (3300) can extend from the distal end (3312) of the outer shaft (3310) by between about 6 mm and about 30 mm. In some embodiments, the outer shaft (3310) can have an outer diameter of between about 1.5 mm and about 6.0 mm.

[0213] An ablation device (3300) as described herein may be disposed in a first configuration prior to delivery of a pulse waveform and transformed into a second configuration to contact a tissue surface (e.g., the inner wall of the left atrium or ventricle, etc.). In some of these embodiments, a handle (not shown) may be coupled to the catheter (3300) and the set of splines (3330), and the handle may be configured to affect transformation of the set of splines (3330) between the first and second configurations. For example, the handle may be configured to translate the inner shaft (3320) relative to the outer shaft (3310). For example, retracting the inner shaft (3320) into the lumen (3312) of the outer shaft (3310) may deploy the set of splines (3330) into the bulbous shape illustrated herein. In some embodiments, actuation of a knob, wheel, or other control mechanism in the device handle can result in translation of the inner shaft (3324), which can result in deployment of a set of splines (3330). In some embodiments, the electrical leads of at least two of a set of electrodes (3322, 3332, 3334) can be electrically coupled at or near a proximal portion of the ablation device (3300) (e.g., in the handle).

[0214] Moreover, the catheter handle (not shown) can include a mechanism for deflecting or steering the distal portion of the catheter device (3300). For example, a pull wire can extend from the catheter handle to one side of the distal portion of the device (3300) at or near the distal end of the outer shaft (3310), and tensioning the pull wire results in deflection of the distal portion of the device (3300). Deflection of the device (3300) can assist the user in positioning the device (3300) in a controlled manner and at the appropriate anatomical location. In some embodiments, the distal cap electrode (3322) can be electrically wired separately from the distal spline electrode (3332). In this manner, intracardiac ECG signals can be recorded only from the distal cap electrode (3322). In some embodiments, one or more distal spline electrodes (3332) may be separately electrically wired for monitoring of intracardiac ECG signals from each such electrode (3332). In some embodiments, some distal spline electrodes (3332) may be used for ECG monitoring, while other distal spline electrodes (3332) may be used for delivery of ablation energy. It should be appreciated that any of the ablation devices described herein may be used with separately electrically wired electrodes for monitoring of intracardiac ECG signals from each such electrode. In some embodiments, some electrodes on one or more splines of a set of splines may be used for ECG monitoring, while other electrodes may be used for delivery of ablation energy.

[0215] The ablation device (3300) can include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 20, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (3300) can include between 3 and 20 splines. For example, the ablation device (3300) can include between 4 and 12 splines.

[0216] Each of the splines of the set of splines (3300) can include a respective electrode (3332, 3334) having an atraumatic generally rounded shape to reduce trauma to the tissue. In this manner, the distal electrode in the second configuration can be held near or placed against a section of the atrial wall of the left atrium to generate lesions thereon by activation of the appropriate electrodes using any suitable polarity combination, as described herein. For example, the cap electrode (3322) and the distal electrode (3332) of the set of splines (3330) can be placed in contact with or adjacent to the tissue wall (3350) in either an approximately perpendicular orientation to the tissue wall or in a generally oblique orientation to the tissue wall, as shown in FIG. 33E. The configuration of the distal electrodes (3322, 3332) enables the generation of localized damage at a desired depth even when the ablation device (3300) in the deployed configuration abuts the tissue wall (3350) at a predetermined angle (e.g., obliquely).

[0217] In some embodiments, the ablation device (3300) shown in Figures 33A-33E can be configured for focal ablation and can include an atraumatic distal portion or cap (3322) that does not include a distal electrode.

[0218] FIG. 38A is a perspective view of another embodiment of an ablation device / apparatus (3800) in the form of a catheter that includes an outer shaft (3810) (e.g., a first shaft) extending to a proximal end of the device (3800), an inner shaft (3820) (e.g., a second shaft) extending from a distal end of a shaft lumen (3812) of the outer shaft (3810), and a set of splines (3830) coupled thereto. The ablation device / apparatus (3800) can include similar components and / or functionality as the ablation device / apparatus (3300), but the ablation device / apparatus (3800) does not include a cap electrode. The inner shaft (3820) can be coupled to a handle (not shown) at a proximal end and can have a distal end disposed near or adjacent to a distal portion (3822) (e.g., a distal end). For example, the distal portion (3822) can be coupled to a distal end of the inner shaft (3820). A proximal end of the set of splines (3830) can be coupled to a distal end of the outer shaft (3810) and can extend from the distal end of the outer shaft (3810). The inner shaft (3820) and the set of splines (3830) can be translatable along a longitudinal axis (3824) of the ablation device (3800) (e.g., the longitudinal axis of the outer shaft (3810)). In some embodiments, the inner shaft (3820) and the set of splines (3830) can move together. The splines can be flexible. The splines can transition between configurations (e.g., deployed configuration, undeployed configuration) when the inner shaft is translated relative to the outer shaft (3810). The inner shaft (3820) can be configured to slide within the lumen (3812) of the outer shaft (3810). The distal portion (3822) can include an atraumatic shape to reduce trauma to tissue. For example, the distal portion (3822) can have a flat circular shape and / or a rounded, blunt profile.In some embodiments, the distal portion (3822) can include a cap. In FIGS. 38A-38D, the distal portion (3822) does not include an electrode. A distal end of each spline of the set of splines (3830) can be tethered and / or coupled to a distal portion (e.g., distal end) of the inner shaft (3820). A proximal portion of the set of splines (3830) can be attached and / or coupled to the outer shaft (3810). The ablation device (3800) can be configured to deliver a pulsed waveform to tissue during use via electrodes (3832, 3834) on the splines (3830), for example as disclosed in FIGS. 21-25.

[0219] The ablation device / apparatus can include a plurality of electrodes configured to generate an electric field to ablate tissue. Each spline of the set of splines (3830) can include a set of electrodes (3832, 3834) from a plurality of electrodes formed on a surface of the spline. Each set of electrodes can include distal electrodes (3832), such that a set of splines includes a set of distal electrodes (3832). Each of the distal electrodes (3832) is closest to a distal portion (3822) relative to other electrodes of its corresponding set of electrodes on the same spline (e.g., a set of proximal electrodes (3834)). Each set of electrodes can include proximal electrodes, such that a set of splines includes a set of proximal electrodes (3834). In some embodiments, the set of electrodes (3832, 3834) can each extend around a perimeter of the spline. For example, the distal electrode (3832) may be constructed from a metallic ring that surrounds the periphery of the spline. In some embodiments, each distal electrode (3832) of a set of distal electrodes may collectively have the same polarity during use. This combination of closely spaced distal electrodes allows the distal end of the ablation device (3300) to generate and project a stronger electric field, thereby more effectively generating focal ablation lesions of tissue at a desired depth compared to any one of these electrodes alone. In other embodiments, at least two distal electrodes may have the same electrical polarity for ablation delivery.

[0220] Each spline (3830) of the ablation device (3800) can include at least one set of independently addressable electrodes (3832, 3834) on a surface of the spline (3830). Each electrode (3832, 3834) can be coupled to an insulated electrical lead configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200 V and about 3000 V across its thickness without dielectric breakdown. Each spline (3830) can include an insulated electrical lead of each electrode (3832, 3834) within the body of the spline (3830) (e.g., within the lumen of the spline (3830)). In some embodiments, the inner shaft (3820) can include insulated electrical leads for one or more of the distal electrodes (3832). In other embodiments, a subset of the electrodes (3832, 3834) can be jointly wired. For example, the proximal electrodes (3834) of each spline of a set of splines (3830) can be jointly wired. As another example, all of the distal electrodes (3832) can be jointly wired.

[0221] In some embodiments, the set of splines (3830) can be configured to transition between a plurality of states (including an undeployed configuration and an expanded configuration) where in the expanded configuration a distal portion of each spline from the set is set at one of a corresponding plurality of angles relative to a proximal portion of each spline from the set in each of the plurality of states. In some embodiments, the set of splines (3830) can be configured to transition to each of a plurality of states in response to the inner shaft (3820) moving relative to the outer shaft (3810) along the longitudinal axis (3824). For example, the set of splines (3830) may be configured to transform between a first configuration (e.g., undeployed configuration) shown in FIG. 38A in which the set of splines (3830) are disposed generally parallel to the longitudinal axis (3824) of the ablation device (3800), and a second configuration (e.g., expanded, basket, deployed configuration) shown in FIG. 38B in which a distal portion (3804) of each spline of the set of splines (3830) bends radially outward from the longitudinal axis (3824). That is, the distal portion (3804) of the splines (3830) forms a bend relative to the proximal portion (3802) of the splines (3830), as described in more detail with reference to FIG. 38B and FIG. 38C. In some embodiments, the inner shaft (3820) can be pulled toward the outer shaft (3810) (e.g., moved proximally relative to the outer shaft (3810)) to deploy the device (3800) in the second configuration. The set of splines (3830) in the second configuration can define a space therebetween that is larger in the expanded configuration of the set of splines than in the first configuration.

[0222] FIG. 38C is a perspective view of a spline (3830) with two unit tangent vectors. FIGS. 38A and 38B show a set of splines (3830) having a basket or pyramid-like shape, which can correspond to the shape of the spline in the second configuration. At every point along the spline (3830), a unit tangent vector u can be defined. FIG. 38C shows a first unit tangent vector u at the distal portion (3804) of the spline (3830). 1 (3840), and a second unit tangent vector u at the proximal portion (3802) of the spline (3830). 2 (3844) is shown. For example, the unit tangent vector u 1 (3840) corresponds to the distal electrode (3832) and extends in the distal direction of the distal electrode (3832). Similarly, the unit tangent vector u 2 A first line (3844) corresponds to the proximal electrode (3832) and extends distally of the proximal electrode (3832). A first line (3842) is tangent to the distal electrode (3832) and a second line (3846) is tangent to the proximal electrode (3834). The intersection of the first line (3842) and the second line (3846) forms an angle (3848), as shown in FIG. 38C.

[0223] In some embodiments, the set of splines (3830) may be configured to transition between (including) a non-deployed configuration and an expanded configuration, where in the expanded configuration, a first unit tangent vector u extending through the length of a distal portion of each spline from the set of splines (3830) may be configured to transition between (including) a non-deployed configuration and an expanded configuration. 1 (3840), and a second unit tangent vector u extending through the proximal portion of each spline from the set of splines (3830). 2 The angle between (3844) varies between about 70 degrees and about 180 degrees. Preselected portions of the plurality of electrodes (3832, 3834) can be configured to activate in each of a plurality of states to generate an electric field to ablate the tissue wall by irreversible electroporation.

[0224] Unit vector u 1 and u 2 The dot product of is equal to the cosine of the angle (3848). In some embodiments, the dot product of each unit tangent vector is negative, i.e., the angle (3848) between the distal electrode (3832) and the proximal electrode (3834) is between about 90 degrees and about 180 degrees.

[0225] The distal electrode (3432) and the proximal electrode (3834) may be angled at different degrees depending on the particular application. For example, the inner shaft (3820) can be retracted to different positions relative to the outer shaft (3810) to create different angles between the distal electrode (3432) and the proximal electrode (3834). Adjustability of the angle between the distal electrode (3432) and the proximal electrode (3834) may be advantageous to accommodate different applications. For example, when performing atrial ablation, the distal electrode (3432) and the proximal electrode (3834) may be angled less relative to one another (e.g., angled less than about 90 degrees), such that one set of splines (3830) forms an expanded structure with a more rounded distal portion. FIG. 40 (described below) provides a more detailed view of this expanded structure. In such an expansion, the unit vector u 1 Tou 2The angle between the distal electrode (3432) and the proximal electrode (3834) can be about 70 degrees or more. Alternatively, when performing ventricular ablation, the distal electrode (3432) and the proximal electrode (3834) can be angled more with respect to one another (e.g., angled between about 90 degrees and about 180 degrees) such that one set of splines (3830) forms an expanded structure with a more orthogonal or flattened distal end. As shown in FIG. 38D, a more flattened distal end can allow the distal end of the ablation device (3800) to be closer overall to the endocardial surface (with a greater number of distal electrodes closer to the tissue surface) and to be used to form lesions via focal ablation.

[0226] In this manner, the set of distal electrodes (3832) may be shaped / oriented to form a second configuration shown in Figures 38B, 38C, and 38D. The distal portion (3822) may be separated from each of the distal electrodes of the set of distal electrodes (3832), for example, by at most about 6 mm, including all values ​​and subranges therebetween. For example, the distal portion (3822) may be separated from each of the distal electrodes of the set of distal electrodes (3832) by between about 0.5 mm and about 3 mm. In the second configuration, the distal portion (3804) of each spline of the set of splines (3830) may be angled (3836) between about 90 degrees and about 180 degrees, including all values ​​and subranges therebetween, relative to the proximal portion (3802). The distal portion (3804) can be generally linear in the second configuration, depending in part on the length and stiffness of the set of distal electrodes (3832). For example, in the second configuration, the distal portion (3822) and the set of distal electrodes (3832) can take the shape of a "plus" sign (e.g., an "X" or cross) when projected onto a plane perpendicular to the longitudinal axis (3824), in a manner similar to the front view of the device / apparatus (3300) shown in FIG.

[0227] In some embodiments, the inner shaft (3820) can be retracted into the outer catheter lumen (3812) a predetermined amount to transform the ablation device (3800) from a first configuration to a second configuration. It is understood that the set of splines (3830) can be transformed to any intermediate configuration between the first and second configurations, either continuously or in discrete steps. The set of splines (3830) can form a shape generally parallel to the longitudinal axis (3824) of the inner shaft (3820) when undeployed, and can form a basket-like or pyramid-like shape when the distal portion of the set of splines (3830) is bent radially outward from the longitudinal axis (3824) and forms a predetermined angle with the proximal portion (3802) of the splines.

[0228] 38A, 38B, 38C, and 38D illustrate a set of splines (3830), where each spline of the set of splines (3830) includes a distal electrode (3832) and multiple proximal electrodes (3834). In some embodiments, a different number of proximal electrodes (3834) and / or proximal electrodes (3834) or distal electrodes (3832) that differ in one or more of size, shape, number, and spacing may be used. For example, FIG. 38A illustrates one distal electrode (3832) and two proximal electrodes (3834) for each spline of the set of splines (3830). In some embodiments, each spline of the set of splines (3830) can include multiple proximal electrodes (3834). The proximal electrodes (3834) can form a proximal electrode region of a given length, but by being divided into a set of shorter length electrode segments, the proximal electrodes (3834) allow for flexibility of the proximal portion (3802) of the spline (3830). In some embodiments, each proximal electrode (3834) can be formed on a surface of the spline (3830) along its entire periphery (e.g., around the entire periphery of the spline). In some embodiments, each distal electrode (3832) can be formed on a surface of the spline (3830) along its entire periphery. That is, the distal electrodes (3832) can cover (e.g., extend around, surround) the entire periphery of the spline (3830). Additionally or alternatively, one or more of the proximal electrodes (3834) can comprise coil electrodes, which can allow for flexibility of the proximal portion (3802) of the spline (3830). For example, in an embodiment, the multiple proximal electrodes (3834) can be replaced with a single proximal electrode (3834) having a coiled configuration, the coiled configuration being sufficiently flexible to allow the device / apparatus (3800) to transition between its first and second (deployed) configurations.

[0229] The set of distal electrodes (3832) may be configured to face in a particular direction. For example, Figures 38B, 38C, and 38D show a set of distal electrodes (3832) and distal portion (3822) facing generally forward at the distal end of the device (3800) in a second configuration when the distal portion (3822) of the set of splines (3830) is bent radially outward from the longitudinal axis (3824). Moreover, the distal electrodes (3832) may be disposed at the distal ends of the splines such that the distal electrodes (3832) of the set of splines (3830) are disposed near the distal portion (3822) of the device (3800).

[0230] In some embodiments, each spline of a set of splines (3830) can include a set of electrodes (3832, 3834) having approximately the same size, shape, number, and spacing as the corresponding electrodes (3832, 3834) of an adjacent spline. The thickness of each spline (3830) can vary based on the number of electrodes (3832, 3834) formed on each spline (3830), which can correspond to the number of insulated electrical leads in the spline (3830). The splines (3830) can have the same or different materials, thicknesses, and / or lengths.

[0231] In some embodiments, the electrodes (3832, 3834) of a set of each spline of a set of splines (3830) can have approximately the same size, shape, number, and spacing as the corresponding electrodes (3832, 3834) of an adjacent spline. The thickness of each spline (3830) can vary based on the number of electrodes (3832, 3834) formed on each spline (3830), which can correspond to the number of insulated electrical leads in the spline (3830). The splines (3830) can have the same or different materials, thicknesses, and / or lengths.

[0232] In some embodiments, each spline of the set of splines (3830) can include a plurality of proximal electrodes (3834). The proximal electrodes (3834) can form a proximal electrode region of a given length, but are divided into a set of shorter length electrode segments, allowing flexibility of the proximal portion (3802) of the spline (3830). In some embodiments, at least one flexible portion is disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase the flexibility of the spline at the location of the plurality of proximal electrodes. In some embodiments, each distal electrode (3832) from a set of distal electrodes can be the same distance from the distal end of the inner shaft (3820).

[0233] The set of electrodes (3832, 3834) may be appropriately polarized to deliver high voltage pulses corresponding to pulsed electric field (PEF) ablation energy that may be applied to tissue to cause irreversible electroporation cell death. In some embodiments, at least one distal electrode from a set of distal electrodes may be configured to be activated with a first polarity and at least one proximal electrode from a set of proximal electrodes may be configured to be activated with a second polarity opposite the first polarity, collectively generating an electric field. For example, a subset of the distal electrodes (3832) may have one electrical polarity, while a subset of the proximal electrodes (3834) may have an opposite electrical polarity, thus defining an electrode bipole pairing for delivery of PEF ablation energy. In general, a series of similar bipoles may be defined for PEF ablation delivery. As another example, all of the distal electrodes (3832) can have one electrical polarity, while all of the proximal electrodes (3834) can have the opposite electrical polarity.

[0234] In some embodiments, a set of electrodes (3832, 3834) may be configured as an anode-cathode set. For example, each of the distal electrodes of a set of distal electrodes (3832) may be collectively configured as an anode and the proximal electrodes of a set of proximal electrodes (3834) may be collectively configured as a cathode (or vice versa). In some embodiments, a set of distal electrodes (3832) and a set of proximal electrodes (3834) may have opposite polarities. For example, the distal electrodes (3832) and a set of proximal electrodes (3834) for a given spline may have opposite polarities. A set of distal electrodes (3832) may have the same polarity. As discussed herein, a set of distal electrodes (3832) may be jointly wired. In some embodiments, the electrodes (3832, 3834) of a set of one or more splines of a set of splines (3830) can be activated together to deliver a pulse waveform for irreversible electroporation. For example, a preselected portion of the electrodes can be activated in each of a plurality of states to generate an electric field for ablating a tissue wall (e.g., a heart chamber) by irreversible electroporation. In other embodiments, the pulse waveform delivery can be repeated sequentially on a predetermined subset of the electrodes (3832, 3834) of the set. For example, a particular activation sequence may include activating the distal electrodes (3432) of half the splines (3830) (e.g., two of the four splines (3830) shown in FIGS. 38A-38D) and activating the proximal electrodes (3834) of half the splines (3830) (e.g., two of the four splines (3830) shown in FIGS. 38A-38D).Depending on the direction of the electric field generated by the desired electrodes (3832, 3834), the activated distal electrode (3832) and proximal electrode (3834) may be offset from one another (e.g., the distal electrode (3832) can be on an adjacent spline (3830) from the proximal electrode (3834), or the distal electrode (3832) may be offset at a predetermined angle (e.g., 90 degrees) from the proximal electrode (3834). In some embodiments, a set of splines may be configured to ablate a tissue wall independent of the orientation of the set of splines relative to the tissue wall. In some embodiments, the preselected portion of the plurality of electrodes may include electrodes from the plurality of electrodes oriented near the tissue surface.

[0235] In some embodiments, the set of distal electrodes (3832) may be separated from the distal portion (3822) by at most 6 mm from the distal end of the respective spline (3830). In some embodiments, the set of distal electrodes (3832) may be separated from the set of proximal electrodes (3834) by between about 1 mm and about 20 mm. In some embodiments, each electrode of the set of electrodes (3832, 3834) may include a diameter of between about 0.5 mm and about 3 mm. In some embodiments, the distal portion (3822) of the inner shaft (3820) may include a cross-sectional diameter of between about 0.7 mm and about 5 mm. In some embodiments, each electrode of the set of electrodes (3832, 3834) may have a length of between about 0.5 mm and about 5 mm. In some embodiments, the set of splines (3830) in the second configuration (e.g., expanded configuration) can have an expanded cross-sectional diameter (i.e., the effective diameter in the expanded or second configuration at a plane corresponding to its largest portion) between about 6 mm and about 24 mm. In some embodiments, the set of splines (3800) can extend from the distal end (3812) of the outer shaft (3810) by a value between about 6 mm and about 24 mm. For example, when the set of splines (3830) is in the expanded configuration, the set of splines (3830) can extend outward from the distal end of the outer shaft (3810) by a radial distance between about 6 mm and about 24 mm. In some embodiments, the outer shaft (3810) can have an outer diameter between about 1.5 mm and about 6.0 mm.

[0236] An ablation device (3800) as described herein may be disposed in a first configuration prior to delivery of a pulse waveform and transformed into a second configuration to contact a tissue surface (e.g., the inner wall of the left atrium or ventricle, etc.). In some of these embodiments, a handle (not shown) may be coupled to the catheter (3800) and the set of splines (3830), and the handle may be configured to affect transformation of the set of splines (3830) between the first and second configurations. For example, the handle may be configured to translate the inner shaft (3820) relative to the outer shaft (3810). For example, retracting the inner shaft (3820) into the lumen (3812) of the outer shaft (3810) may deploy the set of splines (3830) into a basket or pyramid-like shape as illustrated herein. In some embodiments, actuation of a knob, wheel, or other control mechanism in the device handle can result in translation of the inner shaft (3824), which can result in deployment of a set of splines (3830). In some embodiments, the electrical leads of at least two of a set of electrodes (3832, 3834) can be electrically coupled at or near a proximal portion of the ablation device (3800) (e.g., in the handle).

[0237] Moreover, the catheter handle (not shown) can include a mechanism for deflecting or steering the distal portion (3804) of the catheter device (3800). For example, a pull wire can extend from the catheter handle to one side of the distal portion (3804) of the device (3800) at or near the distal end of the outer shaft (3810), and tensioning the pull wire results in deflection of the distal portion (3804) of the device (3800). Deflection of the device (3800) can assist the user in positioning the device (3800) in a controlled manner and at the appropriate anatomical location. In some embodiments, one or more distal spline electrodes (3832) can be separately electrically wired for monitoring of intracardiac ECG signals from each such electrode (3832). In some embodiments, some distal spline electrodes (3832) may be used for ECG monitoring, while other distal spline electrodes (3832) may be used for delivery of ablation energy. In some embodiments, some proximal spline electrodes (3834) may be separately wired for intracardiac ECG monitoring. It should be appreciated that any of the ablation devices described herein may be used with separately electrically wired electrodes for monitoring of intracardiac ECG signals from each such electrode. In some embodiments, some electrodes on one or more splines of a set of splines may be used for ECG monitoring, while other electrodes may be used for delivery of ablation energy.

[0238] The ablation device (3800) can include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 20, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (3800) can include between 3 and 20 splines. For example, the ablation device (3800) can include between 4 and 12 splines.

[0239] Each of the splines of the set of splines (3800) can include a respective electrode (3832, 3834) having an atraumatic generally rounded shape to reduce trauma to tissue. In this manner, the distal electrode in the second configuration can be held near or placed against a section of the atrial wall of the left atrium, or more generally, any atrial or ventricular cavity, to generate lesions thereon by activation of the appropriate electrodes using any suitable polarity combination, as described herein. For example, the distal portion (3822) and / or the distal electrode (3832) of the set of splines (3830) can be placed in contact with or adjacent to the tissue wall (3850), either in an approximately perpendicular orientation to the tissue wall, or in a generally oblique orientation to the tissue wall, as shown in FIG. 38D. The configuration of the distal electrode (3832) enables the generation of localized damage at a desired depth even when the ablation device (3800) in the deployed configuration abuts the tissue wall (3850) at a predetermined angle (e.g., obliquely).

[0240] As mentioned above, in some embodiments, the angle between the distal electrode (3832) and the proximal electrode (3834) can vary based on the particular application. More specifically, the set of splines (3830) can be configured to transition between (including) a plurality of states between an undeployed configuration and an expanded configuration, where in the expanded configuration, a first unit tangent vector u extending through the length of the distal portion of each spline from the set of splines (3830) is 1 (3840), and a second unit tangent vector u extending through the proximal portion of each spline from the set of splines (3830). 2(3844) varies between about 70 degrees and about 180 degrees. For example, when using the device for ventricular ablation and / or to penetrate thicker tissue, the angle between the distal electrode (3832) and the proximal electrode (2834) can be between about 90 degrees and about 180 degrees, with the expanded structure of the splines (3830) having a flatter distal end that is generally more suitable for positioning closer to the tissue and providing a larger surface area for forming a deeper focal lesion. Alternatively, when the device is being used for atrial ablation and / or to ablate thinner tissue, a set of splines can be transitioned from a plurality of states to one or more states where the angle is between about 70 degrees and about 90 degrees, or between about 70 degrees and about 120 degrees (including all subranges and values ​​therebetween). For example, the angle between the distal electrode (3832) and the proximal electrode (2834) can be lower (e.g., between about 70 degrees and about 90 degrees, between about 70 degrees and about 120 degrees (including all subranges and values ​​therebetween)). Such a shape allows the splines (3830) to be placed at different orientations relative to the tissue surface. For example, as shown in FIG. 40, an ablation device (4000) including a set of splines (4030) can be placed such that the splines (4030) are oriented laterally relative to the tissue wall (4050). Each spline (4030) can have at least one distal electrode (4032) and at least one proximal electrode (4034). As shown, the distal electrode (4032) may be angled relative to the proximal electrode (4034) at an angle (4048) of less than about 90 degrees, i.e., the unit tangent vector u extending through the distal electrode (4032) may be angled relative to the proximal electrode (4034) at an angle (4048) of less than about 90 degrees. 1 is a unit tangent vector u that extends through the proximal electrode (4034) at an angle (4048) of less than about 90 degrees. 2In an embodiment, the angle (4048) can be about 70 degrees. A preselected set of electrodes (4032, 4034) on the splines (4030) can then be activated to ablate tissue. The same set of electrodes (4032, 4034) can be activated to ablate tissue regardless of the orientation of the splines (4030) relative to the tissue wall (4050). Alternatively, a different set of electrodes can be activated to ablate tissue depending on which splines (4030) are oriented closer to the tissue surface.

[0241] FIG. 39A is a perspective view of another embodiment of an ablation device / apparatus (3900) in the form of a catheter, including an outer shaft (3910) extending to a proximal end of the device (3900), a first inner shaft (3920) and a second inner shaft (3921) extending from a distal end of a shaft lumen (3912) of the outer shaft (3910), a set of splines (3930), and an expandable member (3950). The ablation device (3900) can have functionally and / or structurally similar components as other ablation devices described herein (e.g., ablation device (3800)). A second inner shaft (3921) can extend from a distal end of the first inner shaft (3920) and couple to a set of splines (3930). The ablation device / apparatus (3900) can include similar components and / or functionality as the ablation device / apparatus (3300, 3800). In some embodiments, the ablation device / apparatus (3900) does not include a cap electrode formed on the distal portion (3922). The first inner shaft (3920), the second inner shaft (3921), and the outer shaft (3910) can be coupled at their respective proximal ends to a catheter handle (not shown). The distal end of the second inner shaft (3921) can be coupled to the distal portion (3922). The proximal portion of the inflatable member (3950) (e.g., expandable member, balloon) can be coupled to the distal portion of the first inner shaft (3920). For example, the expandable member (3950) can be disposed distal to the distal end of the outer shaft (3910) and in the space between the set of splines (3930).

[0242] Optionally, a distal portion of the expandable member (3950) may be coupled to one or more of the distal portion (3922) and the distal portion of the second inner shaft (3921). A proximal portion of each spline of the set of splines (3930) may be coupled to a distal portion of the outer shaft (3910). A distal portion of each spline of the set of splines (3930) may be coupled to one or more of the distal portion (3922) and the distal portion of the second inner shaft (3921). The expandable member (3950) may be disposed in a space between the set of splines (3930) such that it is surrounded by the set of splines (3930). In some embodiments, the expandable member (3950) may be translatable separately from the set of splines (3930), e.g., the expandable member (3950) may be movable relative to the set of splines (3930). In such embodiments, the expandable member (3950) may be moved to a specific, predetermined position relative to the set of splines (3930). In some embodiments, the expandable member (3950) may be coupled to a shaft or other structure different from the first inner shaft (3920), the second inner shaft (3921), and / or the distal portion (3922). For example, the expandable member (3950) may be coupled to a third inner shaft (not shown). In some embodiments, the expandable member defines a lumen, and the second inner shaft (3921) may extend through the lumen of the expandable member.

[0243] The first inner shaft (3920), the second inner shaft (3921), and the set of splines (3930) can be translatable along the longitudinal axis (3924) of the ablation device (3900). In some embodiments, the set of splines can be configured to transition to a plurality of states in response to the expandable member transitioning to an expanded configuration. For example, the set of splines (3930) can be configured to transition to an expanded configuration in response to the second inner shaft (3921) moving relative to the first inner shaft (3920). As another example, the set of splines (3930) can be configured to transition to an expanded configuration in response to the second inner shaft (3921) moving relative to the longitudinal axis (3924). In some embodiments, the first inner shaft (3920), the second inner shaft (3921), and the set of splines (3930) can move together. The splines (3930) can be flexible. The splines can transition between configurations (e.g., deployed, undeployed) when the first and second inner shafts (3920, 3921) are translated relative to the outer shaft (3910). The first inner shaft (3920) and the second inner shaft (3921) can be configured to slide into the lumen (3912) of the outer shaft (3910). A set of splines (3930) can be translated by moving the second inner shaft (3921) relative to the outer shaft (3910), for example, using an actuation mechanism of the handle.

[0244] The distal portion (3922) can include an atraumatic shape to reduce trauma to tissue. For example, the distal portion (3922) can have a flat circular shape and / or a rounded, blunt profile. In some embodiments, the distal portion (3922) can include a cap. In FIGS. 39A-39D, the distal portion (3922) does not include an electrode. This can allow the shape, profile, and size of the distal portion (3922) to be configurable and / or reduced. A distal end of each spline of the set of splines (3930) can be coupled and / or connected to a distal portion of the second inner shaft (3921). A proximal portion of the set of splines (3930) can be attached and / or connected to the outer shaft (3910). The ablation device (3900) can be configured to deliver a pulsed waveform to tissue during use via electrodes (3932, 3934) on the splines (3930), for example as disclosed in Figures 21-25.

[0245] The ablation device / apparatus can include a plurality of electrodes configured to generate an electric field to ablate tissue. Each spline of the set of splines (3930) can include a set of electrodes (3932, 3934) from a plurality of electrodes formed on a surface of the spline. Each set of electrodes can include distal electrodes (3932), such that a set of splines includes a set of distal electrodes (3932). Each of the distal electrodes (3932) is closest to a distal portion (3922) relative to other electrodes of its corresponding set of electrodes on the same spline (e.g., a set of proximal electrodes (3934)). Each set of electrodes can include proximal electrodes, such that a set of splines includes a set of proximal electrodes (3934). In some embodiments, the set of electrodes (3932, 3934) can each extend around a perimeter of the spline. For example, the distal electrode (3932) may be constructed from a metallic ring that surrounds the periphery of the spline. In some embodiments, each distal electrode (3932) of a set of distal electrodes can collectively have the same polarity during use. This combination of closely spaced distal electrodes allows the distal end of the ablation device (3900) to generate and project a stronger electric field, thereby more effectively generating focal ablation lesions of tissue at a desired depth compared to any one of these electrodes alone. In other embodiments, at least two distal electrodes can have the same electrical polarity for ablation delivery.

[0246] Each spline (3930) of the ablation device (3900) can include at least one set of independently addressable electrodes (3932, 3934) on a surface of the spline (3930). Each electrode (3932, 3934) can be coupled to an insulated electrical lead configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200 V and about 3000 V across its thickness without dielectric breakdown. Each spline (3930) can include an insulated electrical lead of each electrode (3932, 3934) within the body of the spline (3930) (e.g., within the lumen of the spline (3930)). In some embodiments, the inner shaft (3920) can include insulated electrical leads for one or more of the distal electrodes (3932). In other embodiments, a subset of the electrodes (3932, 3934) can be jointly wired. For example, the proximal electrodes (3934) of each spline of a set of splines (3930) can be jointly wired. As another example, all of the distal electrodes (3932) can be jointly wired.

[0247] In some embodiments, the set of splines (3930) can be configured to transition between a plurality of states (including an undeployed configuration and an expanded configuration) where in the expanded configuration a distal portion of each spline from the set is set at one of a corresponding plurality of angles relative to a proximal portion of each spline from the set in each of the plurality of states. In some embodiments, the set of splines (3930) can be configured to transition to one or more of the plurality of states in response to movement of the inner shaft (3920) relative to the outer shaft (3910) along the longitudinal axis (3924). For example, the set of splines (3930) may be configured to transform between a first configuration, shown in FIG. 39C, in which the set of splines (3930) are disposed generally parallel to the longitudinal axis (3924) of the ablation device (3900), and a second configuration (e.g., expanded, basket, deployed) shown in FIGs. 39A, 39B, and 39D, in which a distal portion (3904) of each spline of the set of splines (3930) bends radially outward from the longitudinal axis (3924), i.e., the distal portion (3904) of the splines (3930) forms a bend relative to a proximal portion (3902) of the splines (3930), as described in more detail with respect to FIG. 39D. In some embodiments, the first and second inner shafts (3920, 3921) can be pulled toward the outer shaft (3910) (e.g., moved proximally relative to the outer shaft (3910)) to deploy the device (3900) in the second configuration. The set of splines (3930) in the second configuration can have a basket or pyramid-like shape. As shown in FIG. 39C, when the set of splines (3930) is in the first configuration, the expandable member (3950) is in a contracted configuration.The set of splines (3930) in the second configuration can define a space therebetween, the space being larger in the expanded configuration of the set of splines than in the first configuration.

[0248] FIG. 39D is a perspective view of a spline (3930) with two unit tangent vectors. FIGS. 39A and 39B show a set of splines (3930) with a basket or pyramid-like shape, which can correspond to the shape of the spline in the second configuration. At every point along the spline (3930), a unit tangent vector u can be defined. FIG. 39D shows the unit tangent vector u at the distal portion (3904) of the spline (3930). 1 (3940), and the unit tangent vector u in the proximal part (3902) of the spline (3930). 2 (3944) is shown. For example, the unit tangent vector u 1 (3940) corresponds to the distal electrode (3932) and extends in the distal direction of the distal electrode (3932). Similarly, the unit tangent vector u 2 39D , a first line (3942) is tangent to the distal electrode (3932) and a second line (3946) is tangent to the proximal electrode (3934). The intersection of the first line (3942) and the second line (3946) forms a first angle (3948), as shown in FIG. 39D. Similarly, the intersection of the first line (3942) and the longitudinal axis (3924) forms a second angle (3960).

[0249] In some embodiments, the unit vector u 1 and u 2The dot product of is equal to the cosine of the angle (3948). In some embodiments, the dot product of each unit tangent vector is negative. That is, the first angle (3948) between the distal electrode (3932) and the proximal electrode (3934) is between about 90 degrees and about 180 degrees. In the second configuration (e.g., the expanded configuration), the second angle (3960) between the distal portion of each spline (e.g., the distal electrode (3932)) and the longitudinal axis (3924) is at least about 70 degrees, as shown in FIG. 39D.

[0250] In this manner, the set of distal electrodes (3932) may be shaped / oriented to form the second configuration shown in Figures 39A, 39B, and 39D. The distal portion (3922) may be separated from each of the distal electrodes of the set of distal electrodes (3932) by at most about 6 mm, including all values ​​and subranges therebetween. For example, the distal portion (3922) may be separated from each of the distal electrodes of the set of distal electrodes (3932) by between about 0.5 mm and about 3 mm. In the second configuration, the distal portion (3904) of each spline of the set of splines (3930) may be angled between about 90 degrees and about 180 degrees, including all values ​​and subranges therebetween, relative to the proximal portion (3902).

[0251] The distal portion (3904) can be generally linear in the second configuration, depending in part on the length and stiffness of the set of distal electrodes (3932). For example, in the second configuration, the distal portion (3922) and the set of distal electrodes (3932) can take the shape of a "plus" sign (e.g., an "X" or cross) when projected onto a plane perpendicular to the longitudinal axis (3924), in a manner similar to the front view of the device / apparatus (3300) shown in FIG.

[0252] In some embodiments, the second inner shaft (3921) can be retracted a predetermined amount into the outer catheter lumen (3912) to transform the ablation device (3900) from the first configuration to the second configuration. It is understood that the set of splines (3930) can be transformed to any intermediate configuration between the first and second configurations, either continuously or in discrete steps. The set of splines (3930) can form a shape generally parallel to the longitudinal axis (3924) when undeployed, and can form a basket-like or pyramid-like shape when the distal portion of the set of splines (3930) is bent radially outward from the longitudinal axis (3924) and forms a predetermined angle with the proximal portion of the splines (3902).

[0253] In some embodiments, the expandable member (3950) can be configured to transform between a contracted configuration, shown in Figures 39B and 39C, and an expanded configuration, shown in Figures 39A and 39D, where in the contracted configuration, an outer surface of the expandable member (3950) is disposed approximately parallel to the longitudinal axis (3924) of the ablation device (3900), and in the expanded configuration, the outer surface of the expandable member (3950) curves radially outward from the longitudinal axis (3924) when the set of splines is in the expanded configuration. In some embodiments, the set of splines (3930) are configured to transition to the expanded configuration in response to the expandable member transitioning to the expanded configuration. In an expanded configuration, in which the expandable member (3950) is disposed distal to the distal end of the outer shaft (3910) and in the space between the set of splines (3930), the expandable member (3950) is configured to drive an electric field generated by the electrodes from the space between the set of splines such that the electric field can create a larger lesion in the tissue. In some embodiments, the expandable member (3950) in the expanded configuration substantially fills the space between the set of splines in their expanded configuration. The set of splines (3930) can be in a first configuration (FIG. 39C) or a second configuration (FIG. 39B) when the expandable member (3950) is in a contracted configuration.

[0254] In some embodiments, the expandable member in the expanded configuration can form an asymmetric shape (e.g., FIGS. 39A, 39D) in which a distal portion of the expandable member has an outer diameter that is larger than an outer diameter of a proximal portion of the expandable member.

[0255] In some embodiments, the first and second inner shafts (3920, 3921) can be pulled toward the outer shaft (3910) (e.g., moved proximally relative to the outer shaft (3910)) to deploy the set of splines (3930) in the second configuration and / or to transform the expandable member (3950) to an expanded, expanded configuration. In some embodiments, a fluid source in fluid communication with the expandable member (3950) can be used to transform the expandable member (3950) from its contracted configuration to its expanded configuration. For example, the first inner shaft (3920) can be configured to couple to (e.g., be in fluid communication with) a fluid source (not shown) such that a fluid is delivered through a lumen of the first inner shaft (3920) into the expandable member (3950) to transition the expandable member (3950) to the expanded configuration. In some embodiments, the expanded member (3950) in the expanded configuration can conform to a shape formed by the set of splines (3930) in the second configuration. That is, the expanded or expanded expandable member (3950) can form a bulbous shape, a basket shape, or a pyramid-like shape. In some embodiments, the expandable member (3950) can expand such that an outer surface of the expandable member (3950) engages an area of ​​the set of splines (3930). It is understood that the expandable member (3950) can be transformed to any intermediate configuration between the contracted configuration and the expanded configuration, either continuously or in discrete steps. In some embodiments, transitioning the expandable member (3950) from the contracted configuration to the expanded configuration applies a force to the set of splines (3930) that transitions the set of splines from the first configuration to the second configuration.For example, the expandable member (3950) can expand to engage a region of the set of splines (3930) and apply an outward force to the set of splines (3930), causing the set of splines (3930) to change configuration from its first configuration (i.e., the undeployed configuration shown in FIG. 39C) to its second configuration (i.e., the deployed configuration shown in FIG. 39D).

[0256] In some embodiments, the inflatable member as described herein can have an expandable structure and can be constructed from any of a variety of insulating or dielectric materials, including, but not limited to, polyvinyl chloride (PVC), polyethylene (PE), cross-linked polyethylene, polyolefin, polyolefin copolymer (POC), polyethylene terephthalate (PET), polyester, nylon, polymer blends, polyester, polyimide, polyamide, polyurethane, silicone, polydimethylsiloxane (PDMS), and PEBAX. Preferred embodiments can be constructed from polyurethane or silicone. In some embodiments, one or more portions of the inflatable member can comprise radiopaque portions. In some embodiments, a fluid can inflate the inflatable member (3950), for example, through a lumen of the first inner shaft (3920) or another shaft or structure coupled to the inflatable member (3950). For example, the inflatable member (3950) can be inflated through a fluid port attached to the catheter handle, and a fluid, such as distilled or deionized water, can be injected under pressure.

[0257] In conjunction with the use of a fluid (e.g., distilled or deionized water, saline, air, or other liquids and / or gases) to inflate the expandable member, the expandable member acts as an effective insulator during delivery of the pulsed electric field waveform, driving the electric field to areas outside of the expandable member or balloon, and to areas surrounding the balloon. This combination of the expandable member and a set of splines allows the distal end of the ablation device (3900) to project or deliver a stronger electric field at greater distances from the ablation device (3900), thereby more effectively generating focal ablation lesions of tissue at a desired depth, as compared to only a set of splines. Thus, the device (3900) in the second expanded configuration (FIGS. 39A and 39D) is able to efficiently form lesions in tissue with less power by redirecting the electric field generated by the set of electrodes (3932, 3934) away from the expandable member (3950) and the second inner shaft (3921) and toward the tissue to be ablated. In some embodiments, when the set of splines (3930) is in the expanded configuration, at least one electrode from the set of distal electrodes (3932) is configured to contact the tissue surface and form a focal ablation lesion above the tissue surface having a diameter between about 0.5 cm and about 2.5 cm.

[0258] In some embodiments, a different number of proximal electrodes (3934) and / or proximal electrodes (3934) or distal electrodes (3932) that differ in one or more of size, shape, number, and spacing may be used. For example, FIG. 39A illustrates two distal electrodes (3932) and three proximal electrodes (3934) for each spline of a set of splines (3930). In some embodiments, each spline of a set of splines (3930) can include multiple proximal electrodes (3934). The proximal electrodes (3934) can form a proximal electrode area of ​​a given length, but by being divided into a set of shorter length electrode segments, the proximal electrodes (3934) allow flexibility in the proximal portion (3902) of the spline (3930). In some embodiments, at least one flexible portion is disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase the flexibility of the spline at the location of the plurality of proximal electrodes. Each proximal electrode (3934) may be formed on the surface of the spline (3930) along its entire periphery (e.g., around the entire periphery of the spline) and / or around a portion of its entire periphery. Each distal electrode (3932) may be formed on the surface of the spline (3930) along its entire periphery and / or around a portion of its entire periphery. When the proximal and distal electrodes (3932, 3934) extend along the entire periphery, they may cover (e.g., extend around, surround) the entire periphery of the spline (3930). Additionally or alternatively, the one or more proximal electrodes (3934) can comprise at least one coil electrode, which can enable flexibility of the proximal portion (3902) of the spline (3930).For example, in one embodiment, the multiple proximal electrodes (3934) may be replaced with a single proximal electrode (3934) having a coiled configuration that is sufficiently flexible to allow the device / apparatus (3900) to transition between its first configuration and its second (deployed) configuration.

[0259] The set of distal electrodes (3932) may be configured to face in a particular direction. For example, Figures 39B, 39C, and 39D show a set of distal electrodes (3932) and distal portion (3922) facing generally forward at the distal end of the device (3900) in a second configuration when the distal portion (3904) of the set of splines (3930) is bent radially outward from the longitudinal axis (3924). Moreover, the distal electrodes (3932) may be disposed at the distal ends of the splines such that the distal electrodes (3932) of the set of splines (3930) are disposed near the distal portion (3922) of the device (3900).

[0260] In some embodiments, the electrodes (3932, 3934) of a set of each spline of a set of splines (3930) can have approximately the same size, shape, number, and spacing as the corresponding electrodes (3932, 3934) of an adjacent spline. The thickness of each spline (3930) can vary based on the number of electrodes (3932, 3934) formed on each spline (3930), which can correspond to the number of insulated electrical leads in the spline (3930). The splines (3930) can have the same or different materials, thicknesses, and / or lengths.

[0261] The set of electrodes (3932, 3934) may be appropriately polarized to deliver high voltage pulses corresponding to pulsed electric field (PEF) ablation energy that may be applied to tissue to cause irreversible electroporation cell death. In some embodiments, at least one distal electrode from a set of distal electrodes may be configured to be activated with a first polarity and at least one proximal electrode from a set of proximal electrodes may be configured to be activated with a second polarity opposite the first polarity, collectively generating an electric field. For example, a subset of the distal electrodes (3932) may have one electrical polarity, while a subset of the proximal electrodes (3934) may have an opposite electrical polarity, thus defining an electrode bipole pairing for delivery of PEF ablation energy. Generally, a series of similar bipoles may be defined for PEF ablation delivery. As another example, all of the distal electrodes (3932) can have one electrical polarity, while all of the proximal electrodes (3934) can have the opposite electrical polarity.

[0262] In some embodiments, a set of electrodes (3932, 3934) may be configured as an anode-cathode set. For example, each of the distal electrodes of a set of distal electrodes (3932) may be collectively configured as an anode and the proximal electrodes of a set of proximal electrodes (3934) may be collectively configured as a cathode (or vice versa). In some embodiments, a set of distal electrodes (3932) and a set of proximal electrodes (3934) may have opposite polarities. For example, the distal electrodes (3932) and a set of proximal electrodes (3934) for a given spline may have opposite polarities. A set of distal electrodes (3932) may have the same polarity. As discussed herein, a set of distal electrodes (3932) may be jointly wired. In some embodiments, the electrodes (3932, 3934) of a set of one or more splines of a set of splines (3930) can be activated together to deliver a pulse waveform for irreversible electroporation. For example, a preselected portion of the electrodes can be activated in each of a plurality of states to generate an electric field for ablating a tissue wall (e.g., a heart chamber) by irreversible electroporation. In other embodiments, the pulse waveform delivery can be repeated sequentially on a predetermined subset of the electrodes (3932, 3934) of the set. For example, a particular activation sequence may include activating the distal electrodes (3432) of half the splines (3930) (e.g., two of the four splines (3930) shown in Figures 39A-39D) and activating the proximal electrodes (3934) of half the splines (3930) (e.g., two of the four splines (3930) shown in Figures 39A-39D).Depending on the electric field generated by the desired electrodes (3932, 3934), the distal electrode (3932) and the proximal electrode (3934) to be activated may be offset from one another (e.g., the distal electrode (3932) can be on an adjacent spline (3930) from the proximal electrode (3934), or the distal electrode (3932) may be offset at a predetermined angle (e.g., about 90 degrees) from the proximal electrode (3934). In some embodiments, a set of splines may be configured to ablate a tissue wall independent of the orientation of the set of splines relative to the tissue wall. In some embodiments, the preselected portion of the plurality of electrodes may include electrodes from the plurality of electrodes oriented near the tissue surface.

[0263] In some embodiments, the set of distal electrodes (3932) may be separated from the distal portion (3922) by at most 6 mm from the distal end of the respective spline (3930). In some embodiments, the set of distal electrodes (3932) may be separated from the set of proximal electrodes (3934) by between about 1 mm and about 20 mm. In some embodiments, each electrode of the set of electrodes (3932, 3934) may include a diameter of between about 0.5 mm and about 3 mm. In some embodiments, the distal portion (3922) and / or the distal end of the second inner shaft (3921) may include a cross-sectional diameter of between about 0.7 mm and about 5 mm. In some embodiments, each electrode of the set of electrodes (3932, 3934) may have a length of between about 0.5 mm and about 5 mm. In some embodiments, the set of splines (3930) in the second configuration can have an expanded cross-sectional diameter (i.e., the effective diameter of the expanded or second configuration at the plane corresponding to its largest portion) of between about 6 mm and about 24 mm. In some embodiments, in the undeployed configuration, the set of splines (3900) can extend from the distal end (3912) of the outer shaft (3910) by between about 6 mm and about 30 mm. In some embodiments, the outer shaft (3910) can have an outer diameter of between about 1.5 mm and about 6.0 mm.

[0264] An ablation device (3900) as described herein may be disposed in a first configuration prior to delivery of a pulse waveform and transformed into a second configuration to contact a tissue surface (e.g., the inner wall of the left atrium or ventricle, etc.). In some of these embodiments, a handle (not shown) may be coupled to the catheter (3900) and the set of splines (3930), and the handle may be configured to affect transformation of the set of splines (3930) between the first and second configurations. For example, the handle may be configured to translate the first inner shaft (3920) and the second inner shaft (3921) relative to the outer shaft (3910). For example, retracting the first and second inner shafts (3920, 3921) into the lumen (3912) of the outer shaft (3910) may deploy the set of splines (3930) into a basket or pyramid-like shape as illustrated herein. In some embodiments, actuation of a knob, wheel, or other control mechanism in the device handle can result in translation of the first and second inner shafts (3920, 3921), which can result in deployment of the set of splines (3930). In some embodiments, the electrical leads of at least two of the set of electrodes (3932, 3934) can be electrically coupled at or near a proximal portion of the ablation device (3900) (e.g., in the handle).

[0265] Moreover, the catheter handle (not shown) can include a mechanism for deflecting or steering the distal portion (3904) of the catheter device (3900). For example, a pull wire can extend from the catheter handle to one side of the distal portion (3904) of the device (3900) at or near the distal end of the outer shaft (3910), and tensioning the pull wire results in deflection of the device (3900). Deflection of the device (3900) can assist the user in positioning the device (3900) in a controlled manner and at the appropriate anatomical location. For example, the device (3900) can be slidably disposed within a steerable sheath (not shown) that is used to deliver the device (3900) to a desired location, such as a heart chamber. Once within the heart chamber, the device (3900) can be further deflected or steered to access a desired site and deliver ablation energy.

[0266] In some embodiments, one or more distal spline electrodes (3932) may be separately electrically wired for receiving and / or monitoring intracardiac electrocardiogram (ECG) signals from each such electrode (3932). For example, an electrode configured for ablation and another electrode configured for receiving ECG signals may be coupled to separate insulated electrical leads. In some embodiments, some distal spline electrodes (3932) may be used for ECG monitoring while other distal spline electrodes (3932) may be used for delivery of ablation energy. In some embodiments, some proximal spline electrodes (3934) may be separately wired for intracardiac ECG monitoring. It should be appreciated that any of the ablation devices described herein may be used with separately electrically wired electrodes for monitoring intracardiac ECG signals from each such electrode. In some embodiments, some electrodes on one or more splines of a set of splines may be used for ECG monitoring while other electrodes may be used for delivery of ablation energy, while in other embodiments, only some electrodes may be used for ECG monitoring while all electrodes may be used for delivery of ablation energy.

[0267] An illustrative method of using an ablation device (3900) including an expandable member (3950) can include positioning (e.g., disposing) the ablation device (3900) at a first location within a chamber of a subject's heart. The set of splines (3930) can be transitioned to an expanded configuration in which a distal portion of each spline of the set of splines bends radially outward from the longitudinal axis (3924). Transitioning the set of splines (3930) to the expanded configuration can include retracting a distal portion of a second shaft relative to the first shaft. Retracting a distal portion of the second shaft relative to the first shaft can include using a handle coupled to at least one of the second shaft or the first shaft. Translating the inner shaft of the ablation device relative to the outer shaft of the ablation device can transition the set of splines to a predetermined state in which a distal portion of each spline of the set and a proximal portion of each spline of the set are at a first angle between about 70 degrees and about 180 degrees.

[0268] The expandable member (3950) can be transitioned to an expanded configuration, and an ablation pulse waveform can be delivered to the electrodes (3932, 3934) disposed on a set of splines (3930) configured to generate an electric field to ablate tissue in the heart chamber, and the expandable member (3950) can direct the electric field toward the tissue.

[0269] In some embodiments, a first ablation pulse waveform can be delivered to a distal electrode formed on at least one spline from the set of splines and a proximal electrode formed on at least one spline from the set of splines, such that the set of splines generates a first electric field for ablating a first portion of a tissue wall of the heart chamber. The ablation device can be positioned at a second location within the heart chamber. A second ablation pulse waveform can be delivered to a distal electrode formed on at least one spline from the set of splines and a proximal electrode formed on at least one spline from the set of splines, such that the set of splines generates a second electric field for ablating a second portion of the tissue wall.

[0270] In some embodiments, the first and second locations are in an atrium of the heart and the first and second angles are between about 70 degrees and about 90 degrees, or between about 70 degrees and about 120 degrees, including all subranges and values ​​therebetween. In some embodiments, the first and second locations are in a ventricle of the heart and the first and second angles are between about 90 degrees and about 180 degrees.

[0271] In some embodiments, at least one of the first and second electric fields is configured to form a focal ablation lesion having a diameter between about 0.5 cm and about 2.5 cm above a surface of the tissue. A first electrode from the set of electrodes of the at least one spline can be configured as an anode. A second electrode from the set of electrodes of the at least one spline can be configured as a cathode. An ablation pulse waveform can be delivered to the first electrode and the second electrode.

[0272] At least one set of electrodes may be configured for ablation, and at least one set of electrodes may be configured to receive electrophysiological data. The electrophysiological data may be recorded from the heart using the at least one set of electrodes. The electrophysiological data may include intracardiac electrocardiogram (ECG) signal data of at least one pulmonary vein.

[0273] The tissue includes an endocardial surface of a heart chamber. In some applications, the heart chamber is a ventricle, and in other applications, it can be an atrium. In some embodiments, a pacing device can be advanced into the right ventricle or other cardiac region of the heart. A pacing signal can be generated for cardiac stimulation of the heart. The pacing signal can be applied to the heart using a pacing device with an ablation pulse waveform generated synchronously with the pacing signal. The ablation pulse waveform can include a time offset with respect to the pacing signal. A radiopaque portion of the ablation device can be visualized fluoroscopically during one or more steps.

[0274] In some embodiments, the catheter can be advanced into a chamber of the heart and electrophysiology data can be recorded using recording electrodes. After transitioning the set of splines to the expanded configuration and transitioning the balloon to the inflated configuration, at least one spline from the set of splines can be placed in contact with an endocardial surface. The at least one spline in contact with the endocardial surface can form a "C" shape. As described herein, the ablation device (3900) can include a shaft defining a lumen in fluid communication with the expandable member (3950). Transitioning the expandable member to the expanded configuration includes delivering a fluid into the expandable member via the lumen of the shaft. The expandable member can be formed from an insulating material such that the expandable member acts as an insulator during delivery of the ablation pulse waveform.

[0275] The expandable member can include a plurality of expandable portions, each of which can be expandable independently of other expandable portions of the plurality of expandable portions.

[0276] In some embodiments, transitioning the set of splines to the expanded configuration can include transitioning the set of splines such that a distal portion of each spline from the set is angled greater than about 70 degrees relative to the longitudinal axis. In some embodiments, transitioning the set of splines to the expanded configuration is responsive to transitioning the expandable member to the expanded configuration.

[0277] The ablation device (3900) can include any number of splines, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 20, or more splines (including all values ​​and subranges therebetween). In some embodiments, the ablation device (3900) can include between 3 and 20 splines. For example, the ablation device (3900) can include between 4 and 12 splines.

[0278] Each of the splines of the set of splines (3900) can include a respective electrode (3932, 3934) having an atraumatic generally rounded shape to reduce trauma to tissue. In this manner, the distal electrode (3932) in the second configuration can be held near or placed against a section of the atrial wall of the left ventricle, or more generally, any atrial or ventricular cavity, to generate lesions thereon by activation of the appropriate electrodes using any suitable polarity combination, as described herein. For example, the distal portion (3922) and / or the distal electrode (3932) of the set of splines (3930) can be placed in contact with or adjacent to the tissue wall (3950) in either an approximately perpendicular orientation to the tissue wall, or in a generally oblique orientation to the tissue wall, similar to that shown in FIG. 38D. The configuration of the distal electrode (3932) enables the generation of localized damage at a desired depth even when the ablation device (3900) in the deployed configuration abuts the tissue wall (3950) at a predetermined angle (e.g., obliquely).

[0279] In some embodiments, since the electrodes or a subset of electrodes may be independently addressable, the electrodes may be excited in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., hierarchical pulse waveforms) as discussed in further detail herein. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver sequential / percutaneous energy and electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes may be at the same potential, as well as all other alternating electrodes. Thus, in some embodiments, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on convenience.

[0280] In some embodiments, an ablation device (e.g., 2900, 3000, 3100, 3200) can include two to six catheters. An ablation device (e.g., 2900, 3000, 3100, 3200) can include any number of catheters, e.g., two, three, four, five, six, or more catheters. For example, in some embodiments, an ablation device (e.g., 2900, 3000, 3100, 3200) can include three to six catheters. In some embodiments, a catheter of an ablation device (e.g., 2900, 3000, 3100, 3200) can include two to six distal portions. A catheter can include any number of distal portions, e.g., two, three, four, five, six, or more distal portions. For example, in some embodiments, a catheter can include two to four distal portions. Moreover, in some embodiments, the shape (e.g., curvature, length, size) of the catheter can be asymmetrical to help control the depth, shape, and / or size of the focal ablation.

[0281] In some embodiments, the electrodes can form an anode-cathode pair. For example, a first electrode can be configured as an anode and a second electrode can be configured as a cathode. In some embodiments, subsets of the electrodes can be independently addressable, and the electrodes can be excited in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes can deliver different sets of pulses (e.g., hierarchical pulse waveforms).

[0282] In all of the embodiments described above, and without limitation, the ablation catheter itself can be a steerable device with pull wires to control deflection through an appropriate mechanism in the catheter handle, as known to those of skill in the art.

[0283] balloon In some embodiments, the ablation device can include one or more balloons for delivering energy to ablate tissue by irreversible electroporation. FIG. 10 illustrates an embodiment of a balloon ablation device (1010) (e.g., structurally and / or functionally similar to the ablation device (110)) disposed in a left atrial cavity (1000) of a heart. The ablation device (1010) can include a first balloon (1012) and a second balloon (1014), which can be configured to be disposed in an ostium (1002) of a pulmonary vein (1004). The first balloon (1012) in an expanded (e.g., inflated) configuration can have a larger diameter than the second balloon (1014) in an expanded configuration. This allows the second balloon (1014) to be advanced further into and disposed in the pulmonary vein (1014), while the first balloon (1012) may be disposed near and / or at the mouth (1002) of the pulmonary vein (1004). The inflated second balloon serves to stabilize the positioning of the first balloon at the mouth of the pulmonary vein. In some embodiments, the first balloon (1012) and the second balloon (1014) may be filled with any suitable conductive fluid (e.g., saline, etc.). The first balloon (1012) and the second balloon (1014) may be electrically isolated from each other. For example, each balloon (1012, 1014) may include an insulated electrical lead associated therewith, each lead having sufficient electrical insulation to sustain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation on each of the electrical leads is capable of sustaining a potential difference of between about 200 V and about 2500 V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. For example, the lead of the second balloon (1014) may be insulated as it extends through the first balloon (1012).

[0284] In some embodiments, the first and second balloons (1012, 1014) can form an anode-cathode pair. For example, in one embodiment, the first and second balloons can carry electrically separate bodies of saline fluid, and the first balloon (1012) can be configured as a cathode and the second balloon (1014) can be configured as an anode, or vice versa, where electrical energy can be capacitively coupled across the balloons or the saline-filled electrodes. The device (1010) can receive a pulse waveform to be delivered to the tissue (1002). For example, one or more of a biphasic signal can be applied such that tissue can be ablated between the first balloon (1012) and the second balloon (1014) at a desired location in the pulmonary vein (1004). The first and second balloons (1012, 1014) can substantially confine the electric field between the first and second balloons (1012, 1014) to reduce the electric field and damage to tissue away from the ostium (1002) of the pulmonary vein (1004). In another embodiment, one or both of the electrodes (1018) and (1019), respectively disposed proximal and distal to the first balloon, can be used as electrodes of one polarity, while the fluid in the first balloon can act as an electrode of the opposite polarity. A biphasic pulse waveform can then be delivered between these electrodes of opposite polarity by capacitive coupling across the balloon, resulting in a zone of irreversible electroporation ablation in the area around the first balloon. In some embodiments, one or more of the balloons (1012, 1014) can include a wire mesh.

[0285] 11 is a cross-sectional view of another embodiment of a balloon ablation device (1110) (e.g., structurally and / or functionally similar to ablation device (1010)) disposed in the left atrial cavity (1100) and the right atrial cavity (1104) of a heart. The ablation device (1110) can include a balloon (1112) that can be configured to be advanced into and disposed in the right atrial cavity (1104). For example, the balloon (1112) can be disposed in contact with the septum (1106) of the heart. The balloon (1112) can be filled with saline. The device (1110) may further include an electrode (1120), which may be advanced from the right atrial cavity (1104) through the balloon (1112) and the septum (1106) into the left atrial cavity (1100). For example, the electrode (1120) may extend from the balloon (1112), puncture through the septum (1106), and be advanced into the left atrial cavity (1100). As the electrode (1120) is advanced into the left atrial cavity (1100), a distal portion of the electrode (1120) may be modified to form a predetermined shape. For example, the distal portion of the electrode (1120) may include a non-linear shape, such as a circle, an ellipsoid, or any other geometric shape. 11, the distal portion of the electrode (1120) forms a loop that can encircle a single or more ostia of a pulmonary vein (1102) in the left atrial cavity (1100). In other embodiments, the distal portion of the electrode (1120) can have approximately the same diameter as the ostia of the pulmonary vein (1102).

[0286] The balloon (1112) and the electrode (1120) can be electrically isolated from one another. For example, the balloon (1112) and the electrode (1120) can each include an insulated electrical lead (1114, 1122), each lead (1114, 1122) having sufficient electrical insulation to sustain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation on each of the electrical leads can sustain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown (including all values ​​and subranges therebetween). The lead (1122) of the electrode (1120) can be insulated through the balloon (1112). In some embodiments, the saline in the balloon (1112) and the electrode (1120) can form an anode-cathode pair. For example, the balloon (1112) may be configured as a cathode and the electrode (1120) may be configured as an anode. The device (1110) may receive a pulsed waveform to be delivered to the ostium of the pulmonary vein (1102). For example, a biphasic waveform may be applied to ablate tissue. The pulsed waveform may generate a strong electric field around the electrode (1120) while a current is applied to the balloon (1112) via capacitive coupling to complete the circuit. In some embodiments, the electrode (1120) may include a fine gauge wire and the balloon (1112) may include a wire mesh.

[0287] In another embodiment, the electrode (1120) may be advanced through the pulmonary vein (1102) and disposed in one or more of the pulmonary vein ostia without being advanced through the balloon (1112) and / or septum (1106). The balloon (1112) and electrode (1120) may be configured as a cathode-anode pair and capable of receiving a pulse waveform in the same manner as discussed above.

[0288] Return electrode Some embodiments of the ablation system as described herein may further include a return electrode or a distributed set of return electrodes coupled to the patient to reduce the risk of unintended damage to healthy tissue. FIGS. 12A-12B are schematic diagrams of a set of return electrodes (1230) (e.g., return pads) of an ablation system disposed on a patient (1200). A set of four ostia of the pulmonary veins (1210) in the left atrium are illustrated in FIGS. 12A-12B. The electrodes (1220) of the ablation device may be positioned around one or more of the ostia of the pulmonary veins (1210). In some embodiments, the set of return electrodes (1230) may be disposed on the back of the patient (1200) to allow current to flow from the electrodes (1220) through the patient (1200) and then to the return electrodes (1230).

[0289] For example, one or more return electrodes may be disposed on the skin of the patient (1200). In one embodiment, eight return electrodes (1230) may be positioned on the patient's back to surround the pulmonary vein ostia (1210). A conductive gel may be applied between the return electrodes (1230) and the skin to improve contact. It should be appreciated that any of the ablation devices described herein may be used with one or more return electrodes (1230). In F...

Claims

1. An apparatus, comprising: a first shaft defining a longitudinal axis and a lumen; a second shaft disposed within the lumen, the second shaft having a distal portion extending from a distal end of the first shaft; A plurality of electrodes; One set of splines and Equipped with Each spline in the set of splines comprises: a set of electrodes from the plurality of electrodes formed on the splines, each set of electrodes including (1) distal electrodes, such that the set of splines includes a set of distal electrodes, and (2) proximal electrodes, such that the set of splines includes a set of proximal electrodes; a proximal end coupled to the distal end of the first shaft; a distal end coupled to the distal end of the second shaft; Including, the set of splines are transitionable between a plurality of states including an undeployed configuration and an expanded configuration, wherein in the expanded configuration a distal portion of each spline from the set of splines is set at one of a corresponding plurality of angles relative to a proximal portion of each spline from the set of splines in each of the plurality of states, and a preselected portion of the plurality of electrodes is activatable in each of the plurality of states to generate an electric field for ablating a tissue wall by irreversible electroporation.

2. The device of claim 1 , wherein the set of splines is configured to ablate the tissue wall independent of an orientation of the set of splines relative to the tissue wall.

3. The device of claim 1 , wherein the preselected portion of the plurality of electrodes includes electrodes from the plurality of electrodes that are oriented closer to a tissue surface.

4. The apparatus of claim 1 , wherein the set of splines is transitionable into each of the plurality of states in response to movement of the second shaft relative to the first shaft along the longitudinal axis.

5. 2. The device of claim 1, wherein when the set of splines is in the expanded configuration, at least one electrode from the set of distal electrodes is angled at an angle between about 70 degrees and about 180 degrees relative to at least one electrode from the set of proximal electrodes.

6. The device of claim 1 , wherein the distal end of the second shaft is separated from each distal electrode from the set of distal electrodes by at most about 6 mm.

7. 2. The device of claim 1, wherein at least one distal electrode from the set of distal electrodes is configured to be activated with a first polarity and at least one proximal electrode from the set of proximal electrodes is configured to be activated with a second polarity opposite the first polarity, collectively generating the electric field.

8. 2. The device of claim 1, wherein each spline from the set of splines includes a plurality of proximal electrodes and at least one flexible portion, the at least one flexible portion being disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase spline flexibility.

9. 2. The device of claim 1, wherein the first shaft is a first inner shaft and the second shaft is a second inner shaft, the device further comprising an outer shaft, the first inner shaft and the second inner shaft configured to slide relative to the outer shaft.

10. The device of claim 1 , wherein each distal electrode from the set of distal electrodes is the same distance from the distal end of the second shaft.

11. 2. The device of claim 1, wherein when the set of splines is in the expanded configuration, the set of splines extends outward from the distal end of the first shaft a radial distance of between about 6 mm and about 24 mm.

12. The device of claim 1 , wherein the first shaft has an outer diameter of between about 1.5 mm and about 6.0 mm.

13. The device of claim 1 , wherein the distal end of the second shaft has a cross-sectional diameter of between about 0.7 mm and about 5 mm.

14. 2. The device of claim 1, wherein the second shaft further comprises an annular lumen and an expandable member, the expandable member disposed distal to the distal end of the first shaft and in a space between the set of splines, the annular lumen of the second shaft coupled to the expandable member, and the expandable member configured to transition to an expanded configuration by fluid pressure applied through the annular lumen.

15. The apparatus of claim 14 , wherein the set of splines is configured to be transitionable between the plurality of states in response to the expandable member transitioning to the expanded configuration.

16. An apparatus, comprising: a first shaft defining a longitudinal axis and a lumen; a second shaft disposed within the lumen, the second shaft having a distal portion extending from a distal end of the first shaft; A plurality of electrodes; One set of splines and Equipped with Each spline in the set of splines comprises: a set of electrodes from the plurality of electrodes formed on the splines, each set of electrodes including (1) distal electrodes, such that the set of splines includes a set of distal electrodes, and (2) proximal electrodes, such that the set of splines includes a set of proximal electrodes; a proximal end coupled to the distal end of the first shaft; a distal end coupled to the distal end of the second shaft; Including, the set of splines are transitionable into a plurality of states including an undeployed configuration and an expanded configuration, wherein in the expanded configuration an angle between a first unit tangent vector extending through a length of a distal portion of each spline from the set of splines and a second unit tangent vector extending through a proximal portion of each spline from the set of splines varies between about 70 degrees and about 180 degrees, and a preselected portion of the plurality of electrodes are activatable in each of the plurality of states to generate an electric field for ablating a tissue wall by irreversible electroporation.

17. 17. The device of claim 16, wherein the set of splines is transitioned to one or more states from the plurality of states where the angle is between about 90 degrees and about 180 degrees when used for ventricular ablation or to ablate thicker tissue.

18. 17. The device of claim 16, wherein the set of splines is transitioned to one or more states from the plurality of states where the angle is between about 70 degrees and about 120 degrees when used for atrial ablation or to ablate thinner tissue.

19. 17. The device of claim 16, further comprising an expandable member disposed distal to the distal end of the first shaft and in a space between the set of splines, the expandable member configured to transition to an expanded configuration.

20. 20. The apparatus of claim 19, wherein the expandable member is formed from an insulating material such that the expandable member is configured to drive the electric field generated by the plurality of electrodes to an area outside of the spaces between the set of splines.

21. The apparatus of claim 16 , wherein the set of splines is configured to ablate the tissue wall independent of an orientation of the set of splines relative to the tissue wall.

22. 20. The apparatus of claim 18, wherein the set of splines is transitionable into the plurality of states in response to movement of the second shaft relative to the first shaft along the longitudinal axis.

23. 20. The device of claim 18, wherein the distal end of the second shaft is separated from each distal electrode from the set of distal electrodes by at most about 6 mm.

24. 20. The device of claim 18, wherein at least one distal electrode from the set of distal electrodes is configured to be activated with a first polarity and at least one proximal electrode from the set of proximal electrodes is configured to be activated with a second polarity opposite the first polarity, collectively generating the electric field.

25. 20. The device of claim 18, wherein each spline from the set of splines includes a plurality of proximal electrodes and at least one flexible portion, the at least one flexible portion being disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase spline flexibility.

26. positioning an ablation device at a first location within a chamber of a subject's heart, the ablation device defining a longitudinal axis and including a set of splines, each spline from the set of splines including a distal electrode and a proximal electrode formed thereon; translating an inner shaft of the ablation device relative to an outer shaft of the ablation device to transition the set of splines to a predetermined state, wherein in the predetermined state a distal portion of each spline of the set of splines and a proximal portion of each spline of the set of splines are at a first angle between about 70 degrees and about 180 degrees, each spline from the set of splines having a distal end coupled to the inner shaft and a proximal end coupled to the outer shaft; delivering a first ablation pulse waveform to a distal electrode formed on at least one spline from the set of splines and to a proximal electrode formed on at least one spline from the set of splines, the set of splines configured to generate a first electric field for ablating a first portion of a tissue wall of the heart chamber; positioning the ablation device at a second location within the heart chamber; delivering a second ablation pulse waveform to a distal electrode formed on at least one spline from the set of splines and to a proximal electrode formed on at least one spline from the set of splines, the set of splines configured to generate a second electric field for ablating a second portion of the tissue wall; A method for providing the above.

27. 27. The method of claim 26, wherein at least one of the first electric field or the second electric field is configured to form a focal ablative lesion on a surface of the tissue having a diameter between about 0.5 cm and about 2.5 cm.

28. the ablation device further comprising an expandable member disposed in a space between the set of splines, the method further comprising transitioning the expandable member to an expanded configuration; 27. The method of claim 26, wherein at least one of the first ablation pulse waveform or the second ablation pulse waveform is delivered after the expandable member is transitioned to the expanded configuration.

29. 27. The method of claim 26, wherein the first and second locations are within an atrium of the heart and the first and second angles are between about 70 degrees and about 120 degrees.

30. 27. The method of claim 26, wherein the first and second locations are within a ventricle of the heart and the first and second angles are between about 90 degrees and about 180 degrees.

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