Systems, devices, and methods for focal zone ablation

Abstract

Systems, devices, and methods for focal region ablation are disclosed. Also described are devices for irreversible electroporation ablation of tissue, including a first shaft defining a longitudinal axis and a lumen, a second shaft disposed within the lumen and 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, a spline set, and a plurality of electrodes disposed within the second shaft. Each spline of the set of splines includes: a set of electrodes from a plurality of electrodes formed on the spline, each set of electrodes including: (1) a distal electrode such that the set of splines includes the set of distal electrodes; and (2) proximal electrodes such that the spline set 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 a distal end of the second shaft.

Description

[0001] This application is a divisional application of the patent application with application number "202080040775.5", application date "April 3, 2020", and titled "Systems, Devices and Methods for Focal Ablation".

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application is a continuation of U.S. Patent Application No. 16 / 375,561, filed April 4, 2019, which is a continuation-in-part of PCT Application No. PCT / US2019 / 014226, filed January 18, 2019. PCT Application No. PCT / US2019 / 014226 is a continuation-in-part of PCT Application No. PCT / US2018 / 029938, filed April 27, 2018, which is a continuation-in-part of U.S. Patent Application No. 15 / 874,721, filed January 18, 2018 (now issued as U.S. Patent No. 10,1304,23, filed September 21, 2017) and U.S. Patent Application No. 15 / 711,266 (now issued as U.S. Patent No. 10,172,673). U.S. Patent Application No. 15 / 874,721 claims priority to U.S. Provisional Application No. 62 / 529,268, filed on July 6, 2017. U.S. Patent Application No. 15 / 711,266 is a continuation-in-part of PCT Application No. PCT / US2017 / 012099, filed on January 4, 2017, which claims priority to U.S. Provisional Application No. 62 / 274,943, filed on January 5, 2016. U.S. Patent Application No. 15 / 711,266 also claims priority to U.S. Provisional Application No. 62 / 491,910, filed on April 28, 2017, and U.S. Provisional Application No. 62 / 529,268, filed on July 6, 2017. PCT Application No. PCT / US2019 / 014226 also claims priority to U.S. Provisional Application No. 62 / 744,495 filed on October 11, 2018 and U.S. Provisional Application No. 62 / 769,407 filed on November 19, 2018. The entire disclosure of each of the foregoing applications is incorporated herein by reference in its entirety. Background Art

[0004] The present invention relates to the generation of pulsed electric fields for tissue treatment, which has moved from the laboratory to clinical applications over the past two decades, and the effects of short pulses of high voltage and larger electric fields on tissues have been studied over the past four decades or more. The application of a brief high DC voltage to the tissue may generate a local high electric field, typically in the range of hundreds of volts per centimeter, which damages the cell membrane by generating holes in the cell membrane. Although the precise mechanism of this electrically driven pore generation or electroporation is still under investigation, it is believed that the application of a relatively brief and large electric field generates instabilities in the lipid bilayer of the cell membrane, resulting in a distribution of local gaps or holes in the cell membrane. If the electric field applied to the membrane is greater than a threshold value, so that the pores do not close and remain open, the electroporation can be irreversible, thereby allowing the exchange of biomolecular materials across the membrane leading to necrosis and / or apoptosis (cell death). Subsequently, the surrounding tissue can heal naturally.

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

[0006] Systems, devices, and methods for ablating tissue by irreversible electroporation are described herein. In some embodiments, a device may include a first shaft defining a longitudinal axis and an inner cavity, a second shaft disposed within the inner cavity and 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 spline group, each spline of the spline group comprising: a set of electrodes from the plurality of electrodes formed on the spline, each electrode set comprising: (1) a distal electrode, such that the spline group comprises the distal electrode set, and (2) a proximal electrode, such that the spline group comprises the proximal electrode set. 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 spline group may be configured to be converted to an expanded configuration, wherein the distal portion of each spline from the spline group is at an angle greater than about 70 degrees relative to the longitudinal axis.

[0007] In some embodiments, a device may include a first shaft defining a longitudinal axis and an inner cavity, a second shaft disposed within the inner cavity and 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 spline group, each spline of the spline group comprising: a set of electrodes from the plurality of electrodes formed on the spline, each electrode set comprising: (1) a distal electrode, such that the spline group comprises a distal electrode set, and (2) a proximal electrode, such that the spline group comprises a proximal electrode set. 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 spline group may be configured to be converted to an expanded configuration, the spline group defining a space therebetween that is larger in the expanded configuration of the spline group. An expandable member may be disposed distal to the distal end of the first shaft and in the space between the spline groups. When the spline group is in the expanded configuration, the expandable member may be configured to be converted to an expanded configuration.

[0008] In some embodiments, the expandable member may be arranged distally of the distal end of the first shaft and within the space between the spline groups. The expandable member may be configured to be converted to an expanded configuration. In some embodiments, the expandable member in the expanded configuration may substantially fill the space between the spline groups in its expanded configuration. The expandable member may be configured to be converted from a reduced configuration in which the outer surface of the expandable member is approximately parallel to the longitudinal axis to an expanded configuration in which the outer surface of the expandable member is curved radially outward from the longitudinal axis. The spline group may be configured to be converted to an expanded configuration in response to the expandable member being converted to the expanded configuration.

[0009] In some embodiments, when the spline group is in the expanded configuration, the distal portion of each spline from the spline group may be at an angle of at least about 70 degrees relative to the longitudinal axis. In some embodiments, the expandable member in the expanded configuration may form an asymmetric shape, wherein the outer diameter of the distal portion of the expandable member is greater than the outer diameter of the proximal portion of the expandable member. The expandable member in the expanded configuration may form a shape having an outer diameter at the largest portion between about 6 mm and about 24 mm. In some embodiments, when the spline group is in the expanded configuration, at least one electrode from the distal electrode set may be configured to contact a tissue surface and form a focal ablation lesion on the tissue surface having a diameter between about 0.5 cm and about 2.5 cm.

[0010] In some embodiments, at least a portion of the expandable member may be formed of 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 also includes an outer shaft. The first inner shaft and the second inner shaft may be configured to slide relative to the outer shaft, and the proximal portion of the expandable member may be coupled to the distal portion of the outer shaft. The distal portion of the expandable member may be coupled to the distal portion of the first inner shaft. In some of these embodiments, the first inner shaft may be configured to be coupled to a fluid source so that the fluid may be delivered to the expandable member via the inner cavity of the first inner shaft to convert the expandable member to an expanded configuration. The spline group may be configured to convert to an expanded configuration in response to the second inner shaft moving relative to the first inner shaft. The expandable member may define an inner cavity, and the second inner shaft may extend through the inner cavity of the expandable member.

[0011] In some embodiments, the expandable member may be configured to be in fluid communication with a fluid source. The fluid source may be configured to deliver fluid to the expandable member to convert the expandable member to an expanded configuration. In some embodiments, when the spline group is in an expanded configuration, the spline group may extend outwardly from the distal end of the first shaft by between about 6 mm and about 24 mm. The outer diameter of the first shaft is between about 1.5 mm and about 6.0 mm. The spline group may be configured to be converted to an expanded configuration in response to the second shaft moving relative to the first shaft along the longitudinal axis. When the spline group is in an expanded configuration, the distal electrode set may be at an angle of between about 70 degrees and about 180 degrees relative to the proximal electrode set.

[0012] The spline set in the expanded configuration may form an asymmetric shape, wherein the outer diameter of the distal portion is greater than the outer diameter of the proximal portion. The distal end of the second shaft may be separated from each distal electrode in the distal electrode set by up to about 6 mm. The distal end of the second shaft may have a cross-sectional diameter between about 0.7 mm and about 5 mm. The distal portion of the device may have an atraumatic shape. Each of the plurality of electrodes may surround the circumference of a corresponding spline from the spline set on which the electrode is disposed.

[0013] At least one distal electrode from the distal electrode set may be configured to be activated with a first polarity. At least one proximal electrode from the proximal electrode set may be configured to be activated with a second polarity opposite to the first polarity to jointly generate an electric field. The distal electrode set may be configured to be activated with a first polarity, and the proximal electrode set may be configured to be activated with a second polarity opposite to the first polarity.

[0014] The length of each electrode from a plurality of electrodes may be between about 0.5 mm and about 5 mm. Each electrode from a plurality of electrodes may be addressable independently of other electrodes from a plurality of electrodes. Each spline from a spline set may include an insulated electrical lead set arranged therein. Each insulated electrical lead from an insulated electrical lead set may be electrically coupled to at least one electrode in an electrode set formed on the spline and configured to maintain a voltage potential of at least about 700 V, and dielectric breakdown does not occur in its corresponding insulation. The diameter of each electrode from a plurality of electrodes may be between about 0.5 mm and about 3 mm. For each spline in a spline set, the distal most distal electrode may be separated from the proximal most proximal electrode by about 1 mm to about 40 mm.

[0015] Each spline from the spline group may include a plurality of proximal electrodes and at least one flexible portion, which is arranged between adjacent proximal electrodes from the plurality of proximal electrodes to increase the flexibility of the spline. The proximal electrode set may include at least one coil electrode. The electrode set of each spline in the spline group may include at least one electrode configured only for ablation and at least one electrode configured to receive an electrocardiogram (ECG) signal. In some of these embodiments, at least one electrode may be configured only for ablation, and the at least one electrode may be configured to receive an ECG signal, which is coupled to a separate insulated electrical lead.

[0016] In some embodiments, a method may include placing an ablation device within a cardiac chamber of a subject's heart, the ablation device defining a longitudinal axis and comprising a spline set. The spline set may be converted into an expanded configuration, wherein a distal portion of each spline of the spline set is angled greater than about 70 degrees relative to the longitudinal axis. An ablation pulse waveform may be delivered to a plurality of electrodes arranged on the spline set such that the spline set generates an electric field for ablating cardiac chamber tissue.

[0017] In some embodiments, a method may include arranging an ablation device in a cardiac chamber of a subject's heart, the ablation device defining a longitudinal axis and comprising a spline group, and an expandable member arranged in a space between the spline groups. The spline group can be converted into an expanded configuration, wherein a distal portion of each spline of the spline group is bent radially outward from the longitudinal axis. The expandable member can be converted into an expanded configuration. An ablation pulse waveform can be delivered to a plurality of electrodes arranged on the spline group so that the spline group generates an electric field for ablating cardiac chamber tissue.

[0018] In some embodiments, the electric field can be configured to form a focal ablation lesion having a diameter between about 0.5 cm and about 2.5 cm on a tissue surface. The ablation device can include a first shaft and a second shaft arranged within the first shaft and translatable relative to the first shaft. The spline group can be converted to an expanded configuration including: retracting a distal portion of the second shaft relative to the first shaft. In some of these embodiments, retracting the 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 embodiments, the tissue may include an endocardial surface of a heart chamber. In some of these embodiments, the heart chamber may be a ventricle.

[0019] In some embodiments, each spline from the spline group includes an electrode set from a plurality of electrodes, and the method further includes configuring a first electrode from the electrode set of at least one spline as an anode, configuring a second electrode from the electrode set of at least one spline as a cathode, and delivering an ablation pulse waveform to the first electrode and the second electrode.

[0020] In some embodiments, each spline from the spline group may include an electrode set from the plurality of electrodes. At least one electrode set may be configured for ablation, and at least one electrode set is used to receive electrophysiological data. Electrophysiological data from the heart may be recorded using a subset of electrodes from at least one electrode set. In some of these embodiments, the electrophysiological data may include intracardiac electrocardiogram (ECG) signal data of at least one pulmonary vein.

[0021] In some embodiments, a pacing device may be advanced into the right ventricle of the heart. A pacing signal may be generated for cardiac stimulation of the heart. A pacing signal may be applied to the heart using the pacing device, and the ablation pulse waveform may be generated synchronously with the pacing signal. In some of these embodiments, the ablation pulse waveform may include a time offset with respect to the pacing signal.

[0022] In some embodiments, the radiopaque portion of the ablation device can be visualized by fluoroscopy in one or more steps. A diagnostic catheter can be advanced into a heart chamber and electrophysiological data can be recorded using the diagnostic catheter. In some of these embodiments, after converting the spline set to a deployed configuration and converting the balloon to an inflated configuration, at least one spline from the spline set can 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.

[0023] In some embodiments, the ablation device may include a shaft defining an inner cavity in fluid communication with an expandable member, and converting the expandable member to an expanded configuration includes delivering fluid to the expandable member via the inner cavity of the shaft. The expandable member may be formed of an insulating material so that the expandable member acts as an insulator during delivery of the ablation pulse waveform. The expandable member may include a plurality of expansion portions, each of the plurality of expansion portions expanding independently of other expansion portions of the plurality of expansion portions. Converting the spline group to an expanded configuration may include converting the spline group so that the distal portion of each spline from the spline group is at an angle greater than about 70 degrees relative to the longitudinal axis.

[0024] In some embodiments, the ablation pulse waveform includes a first level of an ablation pulse waveform hierarchy, which may include a first pulse set, each pulse having a pulse duration, and a first time interval separating consecutive pulses. A second level of the ablation pulse waveform hierarchy may include a plurality of first pulse sets as second pulse sets, a second time interval separating consecutive first pulse sets, and the second time interval being at least three times the duration of the first time interval. A third level of the ablation pulse waveform hierarchy may include a plurality of second pulse sets as third pulse sets, a third time interval separating consecutive second pulse sets, and the third time interval being at least thirty times the duration of the second level time interval.

[0025] In some embodiments, the spline set transitions to the deployed configuration in response to the expandable member transitioning to the expanded configuration.

[0026] In some embodiments, a device may include a first shaft defining a longitudinal axis and a lumen, a second shaft that may be disposed within the lumen and having a distal portion extending from a distal end of the first shaft, a plurality of electrodes, and a spline set. Each spline in the spline set includes an electrode set from a plurality of electrodes formed on the spline. Each set of electrodes includes (1) a distal electrode, such that the spline set includes a distal electrode set; and (2) a proximal electrode, such that the spline set includes a proximal electrode set. 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.

[0027] In some embodiments, the spline group can be converted to multiple states between and including the undeployed configuration and the deployed configuration, wherein in each of the multiple states, the distal portion of each spline from the spline group is set to be at one of a corresponding multiple angles relative to the proximal portion of each spline from the spline group. A preselected portion of the multiple electrodes can be activated in each of the multiple states to generate an electric field for ablating a tissue wall by irreversible electroporation. In some embodiments, the spline group can be configured to ablate a tissue wall regardless of the orientation of the spline group relative to the tissue wall. In some embodiments, the preselected portion of the multiple electrodes includes electrodes from the multiple electrodes that are oriented closer to the tissue surface.

[0028] In some embodiments, the spline set can be transitioned to each of a plurality of states in response to the second shaft moving along the longitudinal axis relative to the first shaft. In some embodiments, when the spline set is in the deployed configuration, at least one electrode from the distal electrode set can be angled between about 70 degrees and about 180 degrees relative to at least one electrode from the proximal electrode set. In some embodiments, the distal end of the second shaft can be separated from each distal electrode in the distal electrode set by up to about 6 mm.

[0029] In some embodiments, at least one distal electrode from the distal electrode set can be configured to be activated with a first polarity, and at least one proximal electrode from the proximal electrode set can be configured to be activated with a second polarity opposite to the first polarity to jointly generate an electric field. In some embodiments, each spline from the spline set can include a plurality of proximal electrodes, and at least one flexible portion can be disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase spline flexibility.

[0030] In some embodiments, the first shaft is a first inner shaft, and the second shaft is a second inner shaft. The device may include an outer shaft. The first inner shaft and the second inner shaft may be configured to be slidable relative to the outer shaft. In some embodiments, each distal electrode from the distal electrode set may be at the same distance from the distal end of the second shaft. In some embodiments, when the spline group is in an expanded configuration. The spline group may extend outwardly from the distal end of the first shaft to a radial distance of about 6mm to about 24mm. In some embodiments, the outer diameter of the first shaft may be between about 1.5mm and about 6.0mm. In some embodiments, the cross-sectional diameter of the distal end of the second shaft may be between about 0.7mm and about 5mm.

[0031] In some embodiments, the second shaft may further include an annular lumen and an expandable member disposed distal to the distal end of the first shaft and within the space between the spline groups. The annular lumen of the second shaft may be coupled to the expandable member, and the expandable member may be configured to be converted to an expanded configuration by fluid pressure applied through the annular lumen.

[0032] In some embodiments, the spline set can be configured to be transitionable into a plurality of states in response to the expandable member transitioning into the expanded configuration.

[0033] In some embodiments, a device may include a first shaft defining a longitudinal axis and an inner cavity, a second shaft disposed within the inner cavity and having a distal portion extending from a distal end of the first shaft, a plurality of electrodes, and a spline set. Each spline in the spline set includes a set of electrodes from a plurality of electrodes formed on the spline. Each set of electrodes includes (1) a distal electrode, such that the spline set includes a distal electrode set; and (2) a proximal electrode, such that the spline set includes a proximal electrode set coupled to a proximal end of the distal end of the first shaft and coupled to a distal end of the distal end of the second shaft. The spline set can be converted into a plurality of states between and including an undeployed configuration and an deployed configuration, wherein an angle between a first unit tangent vector extending through a length of a distal portion of each spline from the spline set and a second unit tangent vector extending through a proximal portion of each spline from the spline set 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 for ablating a tissue wall by irreversible electroporation.

[0034] In some embodiments, when used for ventricular ablation or ablation of thicker tissue, the spline group can be converted to one or more states with an angle between about 90 degrees and about 180 degrees from a plurality of states. In some embodiments, when used for atrial ablation or ablation of thinner tissue, the spline group can be converted to one or more states with an angle between about 70 degrees and about 120 degrees from a plurality of states.

[0035] In some embodiments, the expandable member may be arranged distal to the distal end of the first shaft and located in the space between the spline groups. The expandable member may be configured to be converted to an expanded configuration. In some embodiments, the expandable member may be formed of an insulating material so that the expandable member may be configured to drive the electric field generated by the plurality of electrodes to an area outside the space between the spline groups. In some embodiments, the spline group may be configured to ablate the tissue wall regardless of the orientation of the spline group relative to the tissue wall. In some embodiments, in response to the second shaft moving along the longitudinal axis relative to the first shaft, the spline group may be converted to a plurality of states. In some embodiments, the distal end of the second shaft may be separated from each distal electrode from the distal electrode set by up to about 6 mm.

[0036] In some embodiments, at least one distal electrode from the distal electrode set can be configured to be activated with a first polarity, and at least one proximal electrode from the proximal electrode set can be configured to be activated with a second polarity opposite to the first polarity to jointly generate an electric field. In some embodiments, each spline from the spline set includes a plurality of proximal electrodes and at least one flexible portion disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase spline flexibility.

[0037] In some embodiments, a method may include positioning an ablation device at a first position within a cardiac chamber of a subject's heart, the ablation device defining a longitudinal axis and including a spline group, each spline in the spline group including a distal electrode and a proximal electrode formed on the spline. An inner shaft of the ablation device may translate relative to an outer shaft of the ablation device to convert the spline group to a state in which a distal portion of each spline of the spline group is at a first angle between about 70 degrees and about 180 degrees with a proximal portion of each spline of the spline group. Each spline from the spline group may have a distal end coupled to the inner shaft and a proximal end coupled to the outer shaft. A first ablation pulse waveform may be delivered to a distal electrode formed on at least one spline from the spline group and a proximal electrode formed on at least one spline from the spline group, such that the spline group generates a first electric field to ablate a first portion of a cardiac chamber tissue wall. The ablation device may be positioned at a second position within the cardiac chamber. A second ablation pulse waveform may be delivered to a distal electrode formed on at least one spline from the spline set and a proximal electrode formed on at least one spline from the spline set such that the spline set generates a second electric field to ablate a second portion of the tissue wall.

[0038] 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 on the tissue surface. In some embodiments, the ablation device also includes an expandable member arranged in the space between the spline groups. The method may also include converting the expandable member to an expanded configuration. At least one of the first ablation pulse waveform or the second ablation pulse waveform is delivered after the expandable member is converted to the expanded configuration. In some embodiments, the first and second positions are located in the 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 positions are located in the ventricle of the heart, and the first and second angles are between about 90 degrees and about 180 degrees. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 is a block diagram of an electroporation system according to an embodiment.

[0040] Figure 2 is a perspective view of an ablation catheter according to an embodiment.

[0041] Figure 3 is a perspective view of an ablation catheter according to other embodiments.

[0042] Figure 4 is a perspective view of an ablation catheter according to other embodiments.

[0043] Figure 5 is a detailed perspective view of a distal portion of an ablation catheter according to other embodiments.

[0044] Figure 6 is a side view of an ablation catheter according to other embodiments.

[0045] Figure 7 is a side view of an ablation catheter according to other embodiments.

[0046] Figures 8A-8B are views of ablation catheters according to other embodiments. Fig. 8A is a side view, and Figure 8B It is a front cross-sectional view.

[0047] Fig.9A is a side view of an ablation catheter in a first structure according to other embodiments. Fig. 9B is a side view of an ablation catheter in a second deployed configuration according to other embodiments. Fig. 9C is a side view of an ablation catheter in a third deployed configuration according to other embodiments. Fig.9D is a side view of an ablation catheter in a fourth deployed configuration according to other embodiments. Fig.9E is a side view of an ablation catheter in a fifth deployed configuration according to other embodiments.

[0048] Fig.10 is a perspective view of a balloon ablation catheter deployed within the left atrial chamber of a heart according to other embodiments.

[0049] Fig.11 is a cross-sectional view of a balloon ablation catheter deployed within the left atrial chamber of a heart according to other embodiments.

[0050] Figures 12A-12B is a schematic diagram of a return electrode of an ablation system according to an embodiment. Fig. 12A shows an unpowered electrode, and Fig. 12B The electrodes are shown powered.

[0051] Fig.13 A method for tissue ablation according to an embodiment is shown.

[0052] Fig.14 Methods for tissue ablation according to other embodiments are shown.

[0053] Fig.15 yes Figure 2 Illustration of an ablation catheter as depicted in FIG. 1 deployed within the left atrial chamber of a heart.

[0054] Fig.16 yes Figure 3 Illustration of an ablation catheter as depicted in FIG. 1 deployed within the left atrial chamber of a heart.

[0055] Fig.17 yes Figure 4 An illustration of two ablation catheters deployed within the left atrial chamber of the heart is depicted in FIG.

[0056] Fig.18 yes Figure 5 Illustration of an ablation catheter as depicted in FIG. 1 deployed within the left atrial chamber of a heart.

[0057] Figures 19A-19B is a schematic diagram of an electrode set disposed in a pulmonary vein ostium according to other embodiments. Fig.19A is a schematic perspective view, and Fig.19B is a cross-sectional view.

[0058] Figures 20A-20B is an illustrative view of an electric field generated by an electrode disposed in a pulmonary vein ostium according to other embodiments. Fig. 20A is a schematic perspective view, and Fig. 20B is a cross-sectional view.

[0059] Fig.21 is an example waveform illustrating a train of voltage pulses with a pulse width defined for each pulse in accordance with an embodiment.

[0060] Fig. 22 Schematically illustrates a hierarchy of pulses showing pulse width, inter-pulse interval, and pulse grouping according to an embodiment.

[0061] Fig.23 A schematic diagram of a monophasic pulse nesting hierarchy showing different levels of the nesting hierarchy is provided according to an embodiment.

[0062] Fig.24 is a schematic diagram of a biphasic pulse nesting hierarchy showing different levels of the nesting hierarchy, according to an embodiment.

[0063] Fig.25 The time series of an electrocardiogram and a cardiac pacing signal together with atrial and ventricular refractory periods according to an embodiment are schematically shown, and indicate the time window for irreversible electroporation ablation.

[0064] Fig.26A is a perspective view of an ablation catheter according to other embodiments. Fig.26B yes Fig.26ADepicted is a side view of an ablation catheter deployed in the left atrial chamber of the heart, near the pulmonary ostium. Fig.26C yes Fig.26B Depicted is a simulated top view of an ablation catheter showing selective electrode activation in accordance with an embodiment. Fig.26D is an illustration of a simulation of tissue ablation in a lung orifice, according to an embodiment.

[0065] Figures 27A-27C are each side views of an ablation catheter according to other embodiments. Fig.27A is a side view of the ablation catheter in a second configuration. Fig.27B is another side view of the ablation catheter in the second configuration. Fig.27C is yet another side view of the ablation catheter in a second configuration.

[0066] Fig.28 is a side view of an ablation catheter according to other embodiments.

[0067] Figures 29A-29D is a cross-sectional side view of an ablation catheter according to other embodiments. Fig.29A is a cross-sectional side view of the ablation catheter in a first configuration. Fig.29B is a cross-sectional side view of the ablation catheter in a third configuration. Fig.29C is another cross-sectional side view of the ablation catheter in a third configuration. Fig.29D is yet another cross-sectional side view of the ablation catheter in a third configuration.

[0068] Fig.30 is a side view of an ablation catheter according to other embodiments.

[0069] Figures 31A-31B is a perspective view of an ablation catheter according to other embodiments. Fig.31A is a perspective view of an ablation catheter in a first configuration. Fig.31B is a perspective view of the ablation catheter in a second configuration.

[0070] Fig.32 is a schematic cross-sectional view of an ablation catheter according to other embodiments.

[0071] Figures 33A-33E are illustrative views of ablation catheters according to other embodiments. Fig.33A is a perspective view of an ablation catheter. Fig.33B yes Fig.33A Front view of the ablation catheter. Fig.33C yes Fig.33A A cutaway perspective view of the spline of an ablation catheter. Fig.33D yes Fig.33A Cross-sectional view of the splines of an ablation catheter. Fig.33E Is located adjacent to the organization Fig.33A Perspective view of an ablation catheter.

[0072] Figures 34A-34B is a side view of a spline according to other embodiments. Fig.34A is a side view of the spline with unit tangent vector. Fig.34B is a side view with two unit tangent vectors.

[0073] Fig.35 is a side view of an ablation catheter in an undeployed configuration according to other embodiments.

[0074] Figures 36A-36C is a side view of an ablation catheter according to other embodiments. Fig.36A is a side view of the ablation catheter in a second configuration. Fig.36B is another side view of the ablation catheter in the second configuration. Fig.36C is a side view of an ablation catheter near tissue.

[0075] Figures 37A-37B is a perspective view of the ablation catheter and left atrium. Fig.37A is a perspective view of an ablation catheter deployed in the left atrium. Fig.37B is a perspective view of the left atrium after tissue ablation.

[0076] Figures 38A-38D are illustrative views of ablation catheters according to other embodiments. Fig.38A is a perspective view of an ablation catheter according to a first configuration. Fig.38B is another perspective view of an ablation catheter according to a second configuration.

[0077] Fig.38C is an annotated perspective view of an ablation catheter. Fig.38D is a perspective view of an ablation catheter positioned adjacent to tissue.

[0078] Figures 39A-39D are illustrative views of ablation catheters according to other embodiments. Fig.39A is a perspective view of an ablation catheter in an expanded configuration. Fig.39B is another perspective view of an ablation catheter with an expandable member in a deflated configuration. Fig.39C is another perspective view of an ablation catheter with an expandable member in a deflated configuration. Fig.39D is an annotated perspective view of an ablation catheter with an expandable member in an expanded configuration.

[0079] Fig.40 is a side view of an ablation catheter positioned adjacent to tissue according to embodiments described herein. DETAILED DESCRIPTION

[0080] Described herein are systems, devices, and methods for selectively and rapidly applying pulsed electric fields to ablate tissues through irreversible electroporation. In general, the systems, devices, and methods described herein can be used to generate a larger electric field strength in a desired region of interest and reduce the peak electric field value elsewhere to reduce unintended tissue damage. The irreversible electroporation system described herein may include a signal generator and a processor configured to apply one or more voltage pulse waveforms to a selected set of electrodes of an ablation device to deliver energy to a region of interest (e.g., ablation energy for a group of tissues in the ostium of a pulmonary vein). The pulse waveforms disclosed herein may contribute to the treatment of various arrhythmias (e.g., atrial fibrillation). In order to deliver the pulse waveforms generated by the signal generator, one or more electrodes of the ablation device may have an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of the corresponding insulation. A subset of electrodes may be independently addressable so that the subset may be controlled (e.g., deliver energy) independently of any other electrode of the device. In this way, electrodes and / or subsets of electrodes may synergistically deliver different energy waveforms with different timings for electroporation of tissues.

[0081] 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, cells undergoing reversible electroporation can observe temporary and / or intermittent formation of one or more holes in their cell membranes, which are closed after the electric field is removed. 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, cells undergoing irreversible electroporation can observe the formation of one or more holes in their cell membranes, which persist after the electric field is removed.

[0082] The pulse waveform for electroporation energy delivery disclosed herein can improve the safety, efficiency and effectiveness of energy delivery to tissue by reducing the electric field threshold associated with irreversible electroporation, thereby producing more effective ablation lesions while reducing the total energy delivered. In some embodiments, the voltage pulse waveform disclosed herein can be hierarchical and have a nested structure. For example, the pulse waveform can include a hierarchical grouping of pulses with related time scales. In some embodiments, the methods, systems and devices disclosed herein may include one or more methods, systems and devices described in international application serial number PCT / US2016 / 057664, filed on October 19, 2016 and entitled "SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE", the entire contents of which are incorporated herein by reference in their entirety.

[0083] In some embodiments, the system may further include a cardiac stimulator for synchronizing the generation of a pulse waveform with a paced heartbeat. The cardiac stimulator may be used to electrically pace the heart with a cardiac stimulator and ensure pacing capture to establish periodicity and predictability of the cardiac cycle. A time window within the refractory period of a periodic cardiac cycle may be selected for voltage pulse waveform delivery. Therefore, the voltage pulse waveform may be delivered within the refractory period of the cardiac cycle to avoid disruption of the sinus rhythm of the heart. In some embodiments, the ablation device may include one or more catheters, guide wires, balloons, and electrodes. The ablation device may be converted to different configurations (e.g., compact and expanded) to position the device within the endocardial space. In some embodiments, the system may optionally include one or more return electrodes.

[0084] Typically, in order to ablate tissue, one or more catheters can be advanced to a target location through a blood vessel in a minimally invasive manner. In cardiac applications, the electrodes through which the voltage pulse waveform is delivered can be arranged on an epicardial device or an endocardial device. The methods described herein may include introducing the device into the endocardial space of the left atrium of the heart and positioning (e.g., arranging) the device in contact with the pulmonary vein orifice. Multiple pulse waveforms can be generated and delivered to one or more electrodes of the device to ablate tissue. In some embodiments, the pulse waveform can be generated synchronously with the pacing signal of the heart to avoid disturbance of the sinus rhythm of the heart. In some embodiments, the electrodes can be configured in an anode-cathode subset. The pulse waveform may include a hierarchical waveform to assist in tissue ablation and reduce damage to healthy tissue.

[0085] system

[0086] Overview

[0087] Disclosed herein are systems and devices configured to assist tissue ablation via selective and rapid application of voltage pulse waveforms to generate irreversible electroporation for tissue ablation. Typically, the system for ablating tissue described herein may include a signal generator and an ablation device having one or more electrodes to selectively and rapidly apply a DC voltage to drive electroporation. As described herein, the system and device may be deployed in the epicardium and / or endocardium to treat atrial fibrillation. Voltage may be applied to a selected subset of electrodes, which have independent subset selections for anode and cathode electrode selection. A pacing signal for cardiac stimulation may be generated and used to generate a pulse waveform by the signal generator in synchronization with the pacing signal.

[0088] Generally, the systems and devices described herein include one or more catheters configured for ablating tissue in the left atrial chamber of the heart. Figure 1 An ablation system (100) configured to deliver a voltage pulse waveform is shown. The system (100) may include an apparatus (120) including a signal generator (122), a processor (124), a memory (126), and a cardiac stimulator (128). The apparatus (120) may be coupled to an ablation device (110), and optionally to a pacing device (130) and / or an optional return electrode (140) (e.g., a return pad, shown here in dashed lines).

[0089] The signal generator (122) may be configured to generate a pulse waveform for irreversible electroporation of tissue (e.g., a pulmonary vein ostium). For example, the signal generator (122) may be a voltage pulse waveform generator and deliver the 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) to allow current to flow from the ablation device (110) through the patient and then to the return electrode (140) to provide a safe current return path from the patient (not shown). The processor (124) may incorporate data received from the memory (126), the cardiac stimulator (128), and the pacing device (130) to determine parameters (e.g., amplitude, width, duty cycle, etc.) of the pulse waveform to be generated by the signal generator (122). The memory (126) may further store instructions to cause the signal generator (122) to execute modules, processes, and / or functions associated with the system (100), such as pulse waveform generation and / or cardiac pacing synchronization. For example, the memory (126) may be configured to store pulse waveforms and / or cardiac pacing data for pulse waveform generation and / or cardiac pacing, respectively.

[0090] In some embodiments, the ablation device (110) may include a catheter configured to receive and / or deliver a pulse waveform as described in more detail below. For example, the ablation device (110) may 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 the pulse waveform to the ablated tissue. The ablation device (110) may include one or more electrodes (112), which in some embodiments may be a collection of independently addressable electrodes. Each electrode may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In some embodiments, the insulation on each electrical lead may maintain a potential difference of between about 200V and about 1500V across its thickness without dielectric breakdown. For example, the electrodes (112) may be grouped into one or more anode-cathode subsets, such as a subset including one anode and one cathode, a subset including two anodes and two cathodes, a subset including two anodes and one cathode, a subset including one anode and two cathodes, a subset including three anodes and one cathode, a subset including three anodes and two cathodes, and so on.

[0091] The pacing device (130) may be suitably coupled to a patient (not shown) and configured to receive a cardiac pacing signal generated by a cardiac stimulator (128) of the device (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, calculated and / or otherwise identified by the processor (124) and generated by the signal generator (122). In some embodiments, the signal generator (122) is configured to generate the pulse waveform synchronously with the indication of the pacing signal (e.g., within a common refractory window). For example, in some embodiments, the common refractory window may begin immediately after the ventricular pacing signal (or after a very small delay) and continue thereafter for a duration of approximately 250 ms or less. In these embodiments, the entire pulse waveform may be delivered within this duration.

[0092] The processor (124) can be any suitable processing device configured to run and / or execute a set of instructions or codes. The processor can be, for example, a general purpose processor, a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), a digital signal processor (DSP), etc. The processor can be configured to run and / or execute application processing and / or other modules, processes, and / or functions related to the system and / or a network associated therewith (not shown). The underlying device technology can be provided in various component types, for example, metal oxide semiconductor field effect transistor (MOSFET) technology such as complementary metal oxide semiconductor (CMOS), bipolar technology such as emitter coupled logic (ECL), polymer technology (e.g., silicon conjugated polymer and metal conjugated polymer metal structure), hybrid analog and digital, etc.

[0093] 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.

[0094] The system (100) can communicate with other devices (not shown) through, for example, one or more networks, each of which can be any type of network. A wireless network can refer to any type of digital network that is not connected by any type of cable. However, a wireless network can be connected to a wired network to connect to the Internet, other carrier voice and data networks, business networks, and personal networks. Wired networks are typically carried by copper twisted pair, coaxial cable, or fiber optic cable. There are many different types of wired networks, including wide area networks (WANs), metropolitan area networks (MANs), local area networks (LANs), campus networks (CANs), global area networks (GANs) (such as the Internet), and virtual private networks (VPNs). In the following, a network refers to any combination of combined wireless, wired, public, and private data networks that are typically interconnected by the Internet to provide a unified network and information access solution.

[0095] Ablation equipment

[0096] The systems described herein may include one or more multi-electrode ablation devices configured for ablating tissue within the left atrial chamber of the heart to treat atrial fibrillation. Figure 2is a perspective view of an ablation device (200) (e.g., similar in structure and / or function to ablation device (110)) including a catheter (210) and a guide wire (220) slidable within a lumen of the catheter (210). The guide wire (220) may include a non-linear distal portion (222), and the catheter (210) may be configured to be disposed over the guide wire (220) during use. The distal portion (222) of the guide wire (220) may be shaped to assist in placing the catheter (210) within a lumen of a patient. For example, the shape of the distal portion (222) of the guide wire (220) may be configured to be placed at and / or near the ostium of a pulmonary vein, as described with respect to Fig.15 The distal portion (222) of the guide wire (220) may include and / or be formed into an atraumatic shape to reduce damage to tissue (e.g., to prevent and / or reduce the possibility of tissue puncture). For example, the distal portion (222) of the guide wire (220) may include a non-linear shape, such as a circular, annular (e.g., Figure 2 ), elliptical, or any other geometric shape. In some embodiments, the guidewire (220) may be configured to be resilient such that the guidewire having a nonlinear shape may conform to the lumen of the catheter (210) when disposed in the catheter (210) and may reform / otherwise resume the nonlinear shape when pushed out of the catheter (210). In other embodiments, the catheter (210) may be similarly configured to be resilient, such as to assist in advancing the catheter (210) through a sheath (not shown). The shaped distal portion (222) of the guidewire (220) may be angled relative to the guidewire (220) and other portions of the catheter (210). The catheter (210) and guidewire (220) may be sized to advance into an endocardial space (e.g., the left atrium). The diameter of the shaped distal portion (222) of the guidewire (220) may be substantially the same as the diameter of the lumen in which the catheter (230) will be disposed.

[0097] The catheter (210) can be slidably advanced over a guidewire (220) so as to be disposed over the guidewire (220) during use. A distal portion (222) of the guidewire (220) disposed in an inner cavity (e.g., proximate a pulmonary vein ostium) can serve as a backstop for advancement of the distal portion of the catheter (210). The distal portion of the catheter (210) may include an electrode set (212) (e.g., similar in structure and / or function to (one or more) electrodes (112)) configured to contact a radially inner surface of the inner cavity (e.g., a pulmonary vein ostium). For example, the electrodes (212) may include an approximately annular arrangement of electrodes configured to contact the pulmonary vein ostium. As Figure 2As shown, one or more electrodes (212) may include a series of metal bands or rings arranged along the catheter shaft and electrically connected together. For example, the ablation device (200) may include a single electrode with multiple bands, one or more electrodes each having its own band, and combinations thereof. In some embodiments, the electrode (212) may be formed into a shape that conforms to the shape of the distal portion (222) of the guide wire (220). The catheter shaft may include a flexible portion between the electrodes to enhance flexibility. In other embodiments, one or more electrodes (212) may include a spiral winding to enhance flexibility.

[0098] Each electrode of the ablation device discussed herein can be connected to an insulated electrical lead (not shown) that leads to a handle (not shown) coupled to the proximal portion of the catheter. The insulation on each electrical lead can maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation on each electrical lead can maintain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. This enables the electrodes to effectively deliver electrical energy and ablate tissue by irreversible electroporation. The electrodes can, for example, receive a signal from a source as described above with respect to Figure 1 The pulse waveform generated by the signal generator (122) in question. In other embodiments, the guide wire (220) may be separate from the ablation device (200) (e.g., the ablation device (200) includes the catheter (210) but does not include the guide wire (220)). For example, the guide wire (220) itself may be advanced into the endocardial space, and then the catheter (210) may be advanced into the endocardial space above the guide wire (220).

[0099] Figure 3 is a perspective view of another embodiment of an ablation device (300) (e.g., similar in structure and / or function to ablation device (110)), which includes a catheter (310) having an electrode collection (314) disposed 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 electrode collection (314) can be arranged along the non-linear distal portion (312) of the catheter (310) to form a generally annular arrangement of electrodes (314). During use, the electrodes (314) can be arranged at the ostium of a pulmonary vein to deliver a pulse waveform to ablate tissue, as described with respect to Fig.16Described in more detail. 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 substantially 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, operation of the pull wires of the handle may increase or decrease the circumference of the annular 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 arranged near and / or in contact with the ostium of the pulmonary vein (e.g., in contact with the radial inner surface of the pulmonary vein). The electrode (314) may include a series of metal bands or rings and may be independently addressable.

[0100] In some embodiments, pulse waveforms may be applied between electrodes (314) configured in an anode and cathode set. For example, adjacent or approximately diametrically opposed pairs of electrodes may be activated together as an anode-cathode set. It should be understood that any pulse waveform disclosed herein may be applied stepwise or sequentially to a sequence of anode-cathode electrodes.

[0101] Figure 4 is a perspective view of yet another embodiment of an ablation device (400) (e.g., similar in structure and / or function to ablation device (110)), which includes a catheter (410) and a guide wire (420) having a shaped non-linear distal portion (422). The guide wire (420) is slidable within the lumen of the catheter (410). The guide wire (420) can be advanced through the lumen of the catheter (410), and the distal portion (422) of the guide wire (420) can be approximately annular. The shape and / or diameter of the distal portion (422) of the guide wire (420) can be used as described above with respect to Figure 3The catheter (410) can be modified by the bending mechanism described. The catheter (410) can be flexible so as to be able to deflect. In some embodiments, the catheter (410) and / or the guide wire (420) can be configured to be resilient so that it conforms to the inner cavity in which it is disposed and assumes a secondary shape when pushed out of the inner cavity. By modifying the size of the guide wire (420) and manipulating the deflection of the catheter (410), the distal portion (422) of the guide wire (420) can be positioned at a target tissue site, such as a pulmonary vein ostium. The distal end (412) of the catheter (410) can be sealed, except where the guide wire (420) extends from it, so that the catheter (410) can electrically insulate the portion of the guide wire (420) within the inner cavity of the catheter (410). For example, in some embodiments, the distal end (412) of the catheter (410) may include a seal having an opening that allows the guidewire (420) to pass when a force is applied to form a compressive hold (which may be fluid-tight) between the seal and the guidewire (420).

[0102] In some embodiments, the exposed distal portion (422) of the guide wire (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 guide wire (420) may be coupled to a suitable electrical lead and connected to Figure 1 The guide wire (420) may be configured to include a signal generator (122) configured to provide a pulmonary vein ostium. The distal portion (422) of the guide wire (420) may be sized to be positioned at the ostium of the pulmonary vein. For example, the diameter of the shaped distal portion (422) of the guide wire (420) may be approximately the same as the diameter of the ostium of the pulmonary vein. The shaped distal portion (422) of the guide wire (420) may be angled relative to the guide wire (420) and other portions of the catheter (410).

[0103] The guide wire (420) may include stainless steel, nickel titanium alloy, platinum or other suitable biocompatible materials. In some embodiments, the distal portion (422) of the guide wire (420) may include a platinum coil physically and electrically attached to the guide wire (420). The platinum coil may be an electrode configured to deliver a voltage pulse waveform. Platinum is radiopaque, and its use may increase flexibility to help advance and position the ablation device (400) within the endocardial space.

[0104] Figure 5Detailed perspective view of a flower-shaped distal portion of an ablation device (500) (e.g., similar in structure and / or function to ablation device (110)) including an electrode set (520, 522, 524, 526), ​​each of which extends from an insulated lead segment pair (510, 512, 514, 516). Each pair of adjacent insulated lead segments (e.g., lead segments (510, 512) and electrodes (526)) coupled to non-insulated electrodes forms a loop ( Figure 5 A set of four loops is shown). A set of loops at the distal portion of the ablation device (500) may be configured to deliver a pulse waveform to tissue. Figure 5 As shown, the ablation device (500) may include a collection of insulated lead segments (510, 512, 514, 516) that branch out at the distal end of the device (500) to connect to corresponding exposed electrodes (520, 522, 524, 526). The electrodes (520, 522, 524, 526) may include exposed portions of electrical conductors. In some embodiments, one or more electrodes (520, 522, 524, 526) may include a platinum coil. One or more segments (510, 512, 514, 516) may be coupled to a bending mechanism (e.g., a strut, a pull wire, etc.) controlled from a handle (not shown) to control the size and / or shape of the distal portion of the device (500).

[0105] The electrodes (520, 522, 524, 526) can be flexible and formed into a compact first configuration for advancement into an endocardial space, such as near a pulmonary vein ostium. Once deployed at a desired location, the electrodes (520, 522, 524, 526) can be transformed into an expanded second configuration when pushed out of an inner cavity, such as a sheath, to form a flower-shaped distal portion, such as Figure 5 As shown. In other embodiments, the insulated lead segments (510, 512, 514, 516) and electrodes (520, 522, 524, 526) can be biased to expand outward (e.g., spring open) to a second configuration when pushed out of the inner cavity (e.g., sheath) of the carrier device (500). The electrodes (520, 522, 524, 526) can be independently addressable, and each electrode has an insulated electrical lead that is configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead can maintain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown.

[0106] In some embodiments, the ablation device (5000) may be configured to deliver a pulse waveform to tissue via an electrode set (520, 522, 524, 526) during use. In some embodiments, a pulse waveform may be applied between electrodes (520, 522, 524, 526) configured as an anode set and a cathode set. For example, approximately diametrically opposite electrode pairs (e.g., electrodes (520, 524) and electrodes (522, 526)) may be activated together as an anode-cathode pair. In other embodiments, adjacent electrodes may be configured as an anode-cathode pair. For example, a first electrode (520) in the electrode set may be configured as an anode, and a second electrode (522) may be configured as a cathode.

[0107] Figure 6-9E , 26A-27C and 28 show additional embodiments of ablation devices (e.g., similar in structure and / or function to ablation device (110)) that can be configured to deliver a voltage pulse waveform using an electrode set to ablate tissue and electrically isolate a pulmonary vein. In some of these embodiments, the ablation device can be converted from a first configuration to a second configuration such that the electrodes of the ablation device are deployed outward to contact a tissue lumen (e.g., a pulmonary vein ostium).

[0108] Figure 6 is a side view of an embodiment of an ablation device (600) comprising a catheter shaft (610) located at the proximal end of the device (600), a distal cap (612) of the device (600), and a spline group (614) coupled thereto. The distal cap (612) may include a non-destructive shape to reduce trauma to tissue. The proximal end of the spline group (614) may be coupled to the distal end of the catheter shaft (610), and the distal end of the spline group (614) may be tethered to the distal cap (612) of the device (600). The ablation device (600) may be configured to deliver a pulse waveform to tissue via one or more splines in the spline group (614) during use. As used herein, the terms "spline" and "spine" may be used interchangeably. In some embodiments, the device may include a catheter defining a longitudinal axis.

[0109] Each spline (614) of the ablation device (600) may include one or more jointly wired, or in some cases, independently addressable electrodes (616) formed on the surface of the spline (614). Each electrode (616) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead may maintain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline (614) may include an insulated electrical lead for each electrode (616) formed in the body of the spline (614) (e.g., within the lumen of the spline (614)). If the electrodes on a single spline are connected together, the single insulated electrical lead may carry strands connected to different electrodes on the spline. Figure 6 A spline set (614) is shown, wherein each spline (614) includes a pair of electrodes (616) having substantially the same size, shape, and spacing as the electrodes (616) of adjacent splines (614). In other embodiments, the size, shape, and spacing of the electrodes (616) may vary.

[0110] For each ablation device described herein, and particularly in Figure 6-9E , 26A-27C and 28, each spline in the spline group may include a flexible curvature. The minimum radius of curvature of the spline may be in the range of about 1 cm or greater. For example, the spline group may form a delivery assembly at a distal portion of the ablation device and be configured to transition between a first configuration (in which the spline group is curved radially outward from the longitudinal axis of the ablation device) and a second configuration (in which the spline group is arranged approximately parallel to the longitudinal axis of the ablation device). In this way, the splines can more easily conform to the geometry of the endocardial space. Typically, the "basket" of the spline can have an asymmetric shape along the length of the axis, so that one end of the basket (such as the distal end) is more spherical than the other end of the basket (such as the proximal end). The delivery assembly can be arranged in a first configuration in contact with the ostium of the pulmonary vein and converted to the second configuration before delivering the pulse waveform. In some of these embodiments, a handle can be coupled to the spline group, and the handle is configured to affect the conversion of the spline group between the first configuration and the second configuration. In some embodiments, electrical leads of at least two electrodes of the electrode set may be electrically coupled at or near a proximal portion of the ablation device, such as, for example, within a handle.

[0111] In one embodiment, each electrode (616) on a spline (614) may be configured as an anode, while each electrode (616) on an adjacent spline (614) may be configured as a cathode. In another embodiment, the electrodes (616) on one spline may alternate between an anode and a cathode, wherein the electrodes of adjacent splines have an inverse configuration (e.g., a cathode and an anode). The ablation device (600) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (600) may include 3 to 20 splines. For example, the ablation device (600) may include 6 to 12 splines.

[0112] Figure 7 is a side view of another embodiment of an ablation device (700) comprising a catheter shaft (710) located at a proximal end of the device (700), a distal cap (712) of the device (700), and a set of splines (714) coupled thereto. The distal cap (712) may include an atraumatic shape. The proximal end of the set of splines (714) may be coupled to the distal end of the catheter shaft (710), and the distal end of the set of splines (714) may be tethered to the distal cap (712) of the device (700). Each spline (714) of the ablation device (700) may include one or more independently addressable electrodes (716) formed on a surface of the spline (714). Each electrode (716) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead can maintain 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 in the body of the spline (714) (e.g., within a lumen of the spline (714)). A set of spline wires (718, 719) can be conductive and electrically couple adjacent electrodes (716) arranged on different splines (714), such as electrodes (716) between a pair of splines (718, 719) of the set of splines. For example, the spline wires (718, 719) can extend in a transverse direction relative to the longitudinal axis of the ablation device (700).

[0113] Figure 7A set of splines (714) is shown, wherein each spline (714) includes a pair of electrodes (716) having substantially the same size, shape, and spacing as the electrodes (716) of adjacent splines (714). In other embodiments, the size, shape, and spacing of the electrodes (716) may be different. For example, an electrode (716) electrically coupled to a first spline line (718) may be different in size and / or shape than an electrode (716') electrically coupled to a second spline line (719).

[0114] In some embodiments, the first spline wires (718) may include a first set of spline wires (720, 721, 722, 723), wherein each spline wire of the set of spline wires (720, 721, 722, 723) may be coupled to an electrode (716) between different pairs of splines of the set of splines (714). In some of these embodiments, the set of spline wires (720, 721, 722, 723) may form a continuous loop between the electrodes (716) coupled thereto. Similarly, the second spline wires (719) may include a second set of spline wires (724, 725, 726), wherein each spline wire of the set of spline wires (724, 725, 726) may be coupled to an electrode (716') across the set of splines (714). The second set of spline wires (724, 725, 726) may couple different electrodes (716') across the spline (714) set compared to the first set of spline wires (720, 721, 722, 723). In some of these embodiments, the first set of spline wires (720, 721, 722, 723) may form a first continuous loop between the electrodes (716) coupled thereto, and the second set of spline wires (724, 725, 726) may form a second continuous loop between the electrodes (716') coupled thereto. The first continuous loop may be electrically isolated from the second continuous loop. In some of these embodiments, the electrode (716) coupled to the first continuous loop may be configured as an anode, and the electrode (716) coupled to the second continuous loop may be configured as a cathode. The pulse waveform may be delivered to the electrodes (716) of the first and second continuous loops. In some embodiments, spline wires such as 721, 722, 723 may be replaced by similar electrical connections in the proximal portion of the device (eg, in the device handle). For example, the electrodes 716 may all be electrically wired together in the handle of the device.

[0115] In another embodiment, a first spline wire (721) of a group of spline wires (720, 721, 722, 723) may be coupled to an electrode (716) between a first spline wire (711) and a second spline wire (713) of a group of spline wires (714), and a second spline wire (720) of a group of spline wires (720, 721, 722, 723) may be coupled to an electrode (716) between a first spline (711) and a third spline (715) of a group of spline wires (714). The electrode (716) coupled by the first spline wire (721) and the second spline wire (720) may be configured as an anode and a cathode (or vice versa). In yet another embodiment, a first spline wire (721) in a set of spline wires (720, 721, 722, 723) may be coupled to an electrode (716) between a first spline wire (711) and a second spline wire (713) in a set of spline wires (714), and a second spline wire (723) in a set of spline wires (720, 721, 722, 723) may be coupled to an electrode (716) between a third spline (715) and a fourth spline (717) in a set of spline wires (714). A pulse waveform may be delivered to the electrode (716) coupled by the first spline wire (721) and the second spline wire (723). In some embodiments, instead of spline wires, electrical leads of at least two electrodes in the electrode set are electrically coupled at or near a proximal portion of the ablation device, such as, for example, within a handle.

[0116] In other embodiments, one or more of the spline wires (718, 719) may form a continuous loop between the electrically coupled electrodes (716). For example, a first set of spline wires (718) may form a first continuous loop between the electrodes (716) coupled thereto, and a second set of spline wires (719) may form a second continuous loop between the electrodes (716) coupled thereto. In this case, the first continuous loop may be electrically isolated from the second continuous loop. In one embodiment, each of the electrodes (716) coupled to the first set of spline wires (718) may be configured as an anode, and each of the electrodes (716) coupled to the second set of spline wires (719) may be configured as a cathode. Each group of electrically coupled electrodes (716) is independently addressable. In some embodiments, instead of spline wires, electrical leads of at least two electrodes in the electrode set are electrically coupled at or near a proximal portion of the ablation device, such as, for example, within a handle.

[0117] In some embodiments, as described below with respect to Figures 8A-8BDiscussed in further detail, a spline wire may be electrically coupled to a collection of electrodes (e.g., 2, 3, 4, 5, etc.) without forming a continuous loop. For example, two spline wires may be used to form a discontinuous loop. In other embodiments, the size, shape, and spacing of the electrodes (716) may be different. The ablation device (700) may 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) may include 3 to 20 splines. For example, in one embodiment, the ablation device (700) may include 6 to 9 splines.

[0118] Figures 8A-8B Side and front cross-sectional views, respectively, of the ablation catheter (800). Fig. 8A is a side view of an embodiment of an ablation device (800) comprising a catheter shaft (810) located 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) may comprise an atraumatic shape. The proximal end of the set of splines (814) may be coupled to the distal end of the catheter shaft (810), and the distal end of the set of splines (814) may be tethered to the distal cap (812) of the device (800). Each spline (814) of the ablation device (800) may comprise one or more independently addressable electrodes (816, 818) formed on a surface of the spline (814). Each electrode (816, 818) may comprise an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead can maintain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. Each spline (814) can include an insulated electrical lead for each electrode (816, 818) formed in the body of the spline (814) (e.g., within a lumen of the spline (814)). One or more spline wires (817, 819) can be conductive and electrically couple adjacent electrodes (816, 818) arranged on different splines (814). For example, the spline wires (817, 819) can extend in a lateral direction relative to the longitudinal axis of the ablation device (800).

[0119] Figure 8B It is taken along line 8B-8B Fig. 8A. Each spline wire (817, 819, 821, 823) electrically couples adjacent electrode pairs (816, 818, 820, 822) on different splines. In some embodiments, each coupled electrode pair can be electrically isolated from each other. In some embodiments, the coupled electrode pairs can be configured with a common polarity. Adjacent electrode pairs can be configured with opposite polarities (e.g., a first electrode pair configured as an anode and an adjacent second electrode pair configured as a cathode). For example, the electrode (816) coupled to the first group of spline wires (817) can be configured as an anode, and each of the electrodes (818) coupled to the second group of spline wires (819) can 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 a cathode). Each coupled electrode pair is 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, for example, 4, 6, 8, 10 or more splines. In some embodiments, the ablation device may include 4 to 10 splines. For example, in one embodiment, the ablation device may include 6 to 8 splines. As previously described, in some embodiments, spline wires such as 817, 819, etc. may be replaced by similar electrical connections in the proximal portion of the device (e.g., in the handle of the device). For example, the electrodes (816) may be electrically wired together in the handle of the device so that the electrodes are at the same electrical potential during ablation.

[0120] Fig.9A is a side view of another embodiment of an ablation device (900) comprising a catheter shaft (910) located at a proximal end of the device (900), a distal cap (912) of the device (900), and a set of splines (914) coupled thereto. The distal cap (912) may include an atraumatic shape. The proximal end of the spline (914) set may be coupled to the distal end of the catheter shaft (910), and the distal end of the spline (914) set may be tethered to the distal cap (912) of the device (900). Each spline (914) of the ablation device (900) may include one or more independently addressable electrodes (916, 918) formed on a surface of the spline (914). Each electrode (916, 918) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead can sustain a potential difference between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline (914) can include an insulated electrical lead for each electrode (916, 918) formed in the body of the spline (914) (e.g., within a lumen of the spline (914)). Fig.9AA set of splines (914) is shown, wherein each spline (914) includes an electrode that is spaced or offset from an electrode of an adjacent spline (914). For example, the set of splines (914) includes a first spline (920) and a second spline (922) adjacent to the first spline (920), wherein the electrode (916) of the first spline (920) is arranged closer to the distal end (912) of the ablation device (900) relative to the electrode (918) of the second spline (922). In other embodiments, the size and shape of the electrodes (916, 918) may also be different.

[0121] In some embodiments, adjacent distal electrodes (916) and proximal electrodes (918) may form an anode-cathode pair. For example, the distal electrode (916) may be configured as an anode and the proximal electrode (918) may be configured as a cathode. In some embodiments, the ablation device (900) may include 3 to 12 splines. Fig.9A In the present invention, an electrode (916, 918) is formed on the surface of each spline (914) so ​​that each spline (914) includes an insulated electrical lead. Therefore, the diameter of the inner cavity of the spline (914) can be reduced, allowing the spline (914) to be thicker and more mechanically strong. Therefore, the dielectric breakdown of the insulation can be further reduced, thereby improving the reliability and life of each spline (914) and the ablation device (900). The ablation device (900) may 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 (900) may include 3 to 20 splines. For example, in one embodiment, the ablation device (900) may include 6 to 10 splines. Additionally, in some embodiments, the shape of the spherical expansion structure (930) of the expansion spline (914) set may be asymmetrical, for example, with its distal portion being more spherical or rounded than its proximal portion (see, for example, Figure 9B-9E ). Such a bulbous distal portion may help position the device at the ostium of the pulmonary vein.

[0122] refer to Figure 9B-9E , it should be understood that unless otherwise indicated, Fig.9A Components in the same manner as the components with reference numbers (e.g., Fig.9A The electrode (916) and Fig. 9B The electrodes (916') in may be similar in structure and / or function. Fig. 9BThe spline lines (914', 920', 922') are shown forming an expanded structure (930') during use (such as when deployed). The first plane (924A') of the expanded structure (930'), sometimes also referred to as the proximal plane, has a cross-sectional area that is different from the cross-sectional area at the second plane (924B') of the expanded structure (930'). Fig. 9B As shown, in some embodiments, the cross-sectional area of ​​the expanded structure (930') at the second plane (924B') is greater than the cross-sectional area at the first plane (924A'). Fig. 9B The terms "first plane" and "second plane" as used herein may refer to planes orthogonal to the longitudinal axis of the catheter shaft (910'), each 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. Fig.9A Similarly, electrodes (916') of first splines (920') are disposed closer to distal cap (912') of ablation device (900') than electrodes (918') of second splines (922').

[0123] Fig. 9C The spline lines (914", 920", 922") are shown forming an expanded structure (930") during use, such as when deployed. A first plane (924A") of the expanded structure (930'), sometimes also referred to as a proximal plane, has a cross-sectional area that is different from a cross-sectional area at a second plane (924B") of the expanded structure (930'). Fig. 9C As shown, in some embodiments, the cross-sectional area of ​​the expanded structure (930") at the second plane (924B") is greater than the cross-sectional area at the first plane (924A"). Fig. 9C The terms "first plane" and "second plane" as used herein may refer to planes orthogonal to the longitudinal axis of the catheter shaft (910"), each formed at 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. Figures 9A-9B Differently, there may be multiple electrodes on each spline wire, and some electrodes may be equidistant from the distal cap (912"). In this way, during ablation delivery, relatively distal electrodes such as 932" and 934" may be located at the ostium or proximal / sinus of the pulmonary vein to create a peri-ostial lesion around the pulmonary vein.

[0124] Fig.9DThe spline lines (914'", 920'", 922') are shown forming an expanded structure (930'") during use (such as when deployed). The spline lines (914'", 920'", 922') converge at their distal ends to a point (928'") located inside / inside the expanded structure (930'"). Fig.9D As shown, in this configuration, at least some of the electrodes (932'", 934'") on the spline lines (914'", 920'", 922'") can be located in the distal plane (926'") of the expanded structure (930'"). Fig.9D The term "distal plane" as used may refer to a plane orthogonal to the longitudinal axis of the catheter shaft (910'") passing through the distal boundary of the deployment structure (930'"). In this manner, the deployment structure (930'") may be pressed against, for example, an endocardial surface (such as the posterior wall of the left atrium) so that a foci may be generated directly thereon by activating appropriate electrodes in the distal plane using any suitable polarity combination. For example, the distal electrodes (932'", 934'") may be pressed against the endocardial surface and used to form foci (e.g., spot foci) via focal ablation.

[0125] Referring now to the use of the ablation device (900'") to generate a focal ablation lesion, in some embodiments, electrodes (933, 935) (sometimes also referred to as "proximal electrodes") and electrodes (932'", 934'") (sometimes also referred to as "distal electrodes") can be activated with opposite polarities. Conduction between these electrodes through the blood pool results in the generation of an electric field, which is applied as ablative energy to the endocardial surface presented at the distal plane (926'") to cause focal ablation. For example, the spline wires (914'", 920'", 922'") can form an expanded structure (930'") such that the distal electrodes (932'", 934'") are located at or within the distal plane (926'") of the endocardial surface, and the proximal electrodes (933, 935) are located outside the distal plane (926'") and, therefore, do not press against or otherwise contact the endocardial surface. In some embodiments, the distal electrodes (932'", 934'") may have the same polarity, while the adjacent proximal electrodes (935, 933) may have an opposite polarity than the distal electrodes (932'", 934'").

[0126] In some embodiments, the electrodes of the ablation device (900'") may have a length between about 0.5 mm and about 5.0 mm and a cross-sectional dimension (eg, diameter) between about 0.5 mm and about 2.5 mm, including all values ​​and subranges therebetween. Fig.9DThe cross-sectional dimensions (e.g., diameter) of the spline lines (914'", 920'", 922'") in the expanded structure (930'") shown in the figure can be from about 6.0 mm to about 30.0 mm, including all values ​​and sub-ranges therebetween. The diameter of the focal ablation lesion formed in this manner can be between about 0.5 cm and about 2.5 cm, including all values ​​and sub-ranges therebetween.

[0127] In some embodiments, the distal electrodes (932'", 934'") may be configured with opposite polarities. In some embodiments, adjacent electrodes on the same spline may have the same polarity, such that the distal electrode (934'") may have the same polarity as the proximal electrode (933), and similarly, the distal electrode (932'") may have the same polarity as the proximal electrode (935). The electrodes (934'", 933) may have opposite polarities as the electrodes (932'", 935).

[0128] In some embodiments, adjacent distal electrodes (934'") and proximal electrodes (933) may form an anode-cathode pairing. For example, the distal electrode (934'") may be configured as an anode and the proximal electrode (933) may be configured as a cathode. In another embodiment, the electrodes (2630) on one spline may alternate between anode and cathode, and the electrodes of adjacent splines have reverse configurations (e.g., cathode and anode).

[0129] Fig.9E The spline wires (944, 940, 942) are shown forming an expanded structure (950) during use (such as when deployed). The spline wires (944, 940, 942) converge at their distal ends at the proximal end of the distal cap (912"") inside / inside the expanded structure (950). Fig.9E As shown, in this configuration, at least some of the electrodes (952, 954) on the spline lines (944, 940) can be located in the distal plane (946) of the deployed structure (950). Fig.9E The term "distal plane" as used herein may refer to a plane orthogonal to the longitudinal axis of the catheter shaft (910") passing through the distal boundary of the expanded structure (950). In this manner, the expanded structure (950) may be pressed against, for example, the posterior wall of the left atrium so as to create a foci directly thereon by activating appropriate electrodes in the distal plane (946) using any suitable polarity combination. For example, electrodes 952 and 954 may be configured to have opposite polarities. With respect to Fig.9D The expanded structure in (930""), Fig.9EThe expanded structure (950) in has a more orthogonal (e.g., flattened) shape that can 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 plane (926"") is smaller than the cross-sectional area of ​​the expanded structure (950) at the distal plane (946). As another example, the distal electrodes (952, 954) can be pressed against the endocardial surface and used to form foci (e.g., spot foci) via focal ablation, as described herein with respect to Fig.9D Usually described.

[0130] For each of the ablation devices described herein, each of the splines may include a polymer and define an inner cavity to form a hollow tube. One or more electrodes of the ablation device described herein may 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 electrode may include a diameter of about 1 mm and a length of about 1 mm. Since the electrodes are independently addressable, any pulse waveform sufficient to ablate the tissue by irreversible electroporation can be used to provide energy to the electrodes in any order. 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 understood that the size, shape, and spacing of the electrodes on and between the splines can be configured to deliver continuous / transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternating electrodes (e.g., all distal electrodes) can be at the same potential, and this is also true for all other electrodes (e.g., all proximal electrodes). Therefore, when all electrodes are activated simultaneously, ablation can be delivered quickly. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0131] Fig.26A is a perspective view of an embodiment of an ablation device (2600) having a flower-like shape and comprising 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. Fig.26BAs best shown, the spline shaft (2614) can be coupled to a proximal handle (not shown) at the proximal end and to a distal cap (2612) at the distal end. In a preferred embodiment, the distance between the distal cap (2612) and the catheter shaft (2610) can be less than about 8 mm. The spline shaft (2614) and the distal cap (2612) can translate along the longitudinal axis (2616) of the ablation device (2600). The spline shaft (2614) and the distal cap (2612) can move together. The spline shaft (2614) can be configured to slide within the inner cavity of the catheter shaft (2610). The distal cap (2612) can include an atraumatic shape to reduce damage to tissue. The proximal end of each spline of the spline (2620) set can pass through the distal end of the catheter shaft (2610) and be tethered to the catheter shaft within the inner lumen of the catheter shaft, and the distal end of each spline of the spline (2620) set can be tethered to the distal cap (2612) of the device (2600). The ablation device (2600) can be configured as follows: Figure 21-25 As disclosed in the examples of , during use a pulse waveform is delivered to tissue via one or more splines in the spline (2620) set.

[0132] In some embodiments, each spline (2620) of the ablation device (2600) may include one or more commonly connected electrodes (2630) formed on the surface of the spline (2620). In other embodiments, one or more electrodes (2630) on a given spline may be independently addressable electrodes (2630). Each electrode (2630) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead may maintain a potential difference between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline (2620) may include an insulated electrical lead for each electrode (2630) within the body of the spline (2620) (e.g., within the lumen of the spline (2620)). Fig.26A A set of splines (2620) is shown, wherein each spline includes a set of electrodes (2632 or 2634) having substantially 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) may vary based on the number of electrodes (2630) formed on each spline (2620), which may correspond to the number of insulated electrical leads in the spline (2620). The splines (2620) may have the same or different materials, thicknesses, and / or lengths.

[0133] Each spline in the set of splines (2620) may include a flexible curvature to allow rotation, or twist and bend and form a petal-shaped curve, such as Figures 26A-26CAs shown. The minimum radius of curvature of the splines in the petal-shaped configuration may be in the range of about 7 mm to about 25 mm. For example, the spline group may form a delivery assembly at the distal portion of the ablation device (2600) and be configured to convert between a first configuration in which the spline group is arranged generally parallel to the longitudinal axis of the ablation device (2600) and a second configuration in which the spline group is rotated around the longitudinal axis of the ablation device (2600), or twisted and bent, and generally deviates from the longitudinal axis of the ablation device (2600). In the first configuration, each spline in the spline group may be located in a plane with the longitudinal axis of the ablation device. In the second configuration, each spline in the spline group may deviate from the longitudinal axis to form a petal-shaped curve arranged generally perpendicular to the longitudinal axis. In this manner, the spline set (2620) twists, bends, and deviates from the longitudinal axis of the ablation device (2600), thereby allowing the spline set (2620) to more easily conform to the geometry of the endocardial space, particularly at the geometry of the opening adjacent to the pulmonary orifice. Fig.26C As best shown in , the second configuration can, for example, resemble the shape of a flower when the ablation device is viewed from the front. In some embodiments, each spline in the spline group in the second configuration can be twisted and bent to form a petal-like curve, showing an angle between the proximal and distal ends of the curve greater than about 180 degrees when viewed from the front. The spline group can also be configured to transform from the second configuration to a third configuration in which the spline (2620) group can be pressed against (e.g., in contact with) target tissue such as tissue surrounding a pulmonary vein ostium.

[0134] In some embodiments, when the spline shaft (2614) coupled to the spline set (2620) slides within the lumen of the catheter shaft (2610), the spline shaft (2614) can allow each spline in the spline set (2620) to bend and twist relative to the catheter shaft (2610). For example, the spline set (2620) can form a shape that is generally parallel to the longitudinal axis of the spline shaft (2614) when not deployed, can be wound (e.g., helically twisted) about an axis (2660) that is parallel to the longitudinal axis of the spline shaft (2620) when fully deployed, and can form any intermediate shape (such as a cage or barrel) therebetween as the spline shaft (2614) slides within the lumen of the catheter shaft (2610).

[0135] In some embodiments, a spline assembly, such as spline (2620), in a first configuration can be wound around an axis (2660) parallel to the longitudinal axis of the catheter shaft (2610) at certain portions along its length, but generally parallel to the longitudinal axis of the catheter shaft (2610) at other portions. The spline shaft (2614) can be retracted into the catheter shaft (2610) to convert the ablation device (2600) from the first configuration to a second configuration in which the spline (2620) is generally angled or offset (e.g., perpendicular) and twisted relative to the longitudinal axis of the catheter shaft (2610). Fig.26C As shown in the front view of , each spline (2620) can form a twisted loop in the front view projection. Fig.26C In the embodiment, each spline (2620) has a set of electrodes (2630) with the same polarity. Fig.26C As shown in the front view of the embodiment of the present invention, each spline in the set of splines (2620) can form a twisted loop so that each spline overlaps one or more other splines. The number and spacing of electrodes (2630), as well as the rotational twist of the splines (2620) can be configured by appropriately placing electrodes along each spline to prevent the electrodes (2630) on one spline from overlapping the electrodes of adjacent overlapping splines (2620).

[0136] The spline with the set of anode electrodes (2632) can be activated together to deliver a pulse waveform for irreversible electroporation. Electrodes on other splines can be activated together as cathode electrodes, such as electrodes (2634) and (2635) on their respective splines, to form an anode-cathode pair to deliver a pulse waveform for irreversible electroporation, such as Fig.26C The anode-cathode pairing and pulse waveform delivery can be repeated sequentially over a set of such pairings.

[0137] For example, the splines (2620) may be activated sequentially in a clockwise or counterclockwise manner. As another example, the cathode splines may be activated sequentially with corresponding sequential anode spline activation until ablation is complete. In embodiments where the electrodes on a given spline are wired separately, the activation order within the electrodes of each spline may also vary. For example, the electrodes in a spline may be activated all at once or in a predetermined order.

[0138] The delivery assembly can be arranged in a first configuration before delivering the pulse waveform and converted to a second configuration to contact the pulmonary vein ostium or sinus. In some of these embodiments, a handle can be coupled to the spline shaft (2614), and the handle is configured to affect the conversion of the spline group between the first configuration and the second configuration. For example, the handle can be configured to translate the spline shaft (2614) and the distal cap (2612) relative to the catheter shaft (2610), thereby actuating the spline (2620) group coupled to the distal cap and causing it to bend and twist. The proximal end of the spline (2620) can be fixed to the spline shaft (2614), thereby generating buckling of the spline (2620), resulting in bending and twisting motion of the spline (2620), for example, when the distal cap (2612) and the spline shaft (2614) are pulled back relative to the catheter shaft (2610) that can be held by the user. For example, the distal end of the spline (2620) group tethered to the distal cap (2612) can translate up to about 60 mm along the longitudinal axis of the ablation device to actuate a change in configuration. In other words, translation of the actuation member of the handle can bend and twist the spline (2620) group. In some embodiments, actuation of a knob, wheel, or other rotary control mechanism in the handle of the device can cause translation of the actuation mechanism or spline shaft and cause bending and twisting of the spline (2620). In some embodiments, the electrical leads of at least two electrodes of the electrode (2630) set can be electrically coupled at or near a proximal portion of the ablation device (2600), such as, for example, within the handle.

[0139] Retraction of the spline shaft (2614) and distal cap (2612) may bring the spline (2620) group closer together, such as Fig.26B As shown, wherein the spline (2620) group is generally perpendicular to the longitudinal axis of the catheter shaft (2610). In some embodiments, each spline in the spline (2620) group may be laterally offset from the longitudinal axis of the spline shaft (2614) by up to about 3 cm. In some embodiments, the spline shaft (2614) may include a hollow lumen. In some embodiments, the cross-section of the spline may be asymmetric so as to have a greater bending stiffness in one bending plane of the spline that is orthogonal to the plane of the cross-section than in a different bending plane. Such an asymmetric cross-section may be configured to present a relatively large lateral stiffness, so that the petal-shaped curves of each spline and its adjacent splines can be deployed in a manner with minimal overlap in a final or fully deployed configuration.

[0140] In one embodiment, each of the electrodes (2632) on a spline (2620) can be configured as an anode, while each electrode (2634) on a different spline can be configured as a cathode. In another embodiment, the electrodes (2630) on one spline can alternate between anode and cathode, and the electrodes of another spline have the opposite configuration (e.g., cathode and anode).

[0141] 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 within the splines, and in alternative embodiments, they can be wired together within the handle of the device so that the electrodes are at the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (2630) can also be different. In some embodiments, adjacent distal electrodes and proximal electrodes can form an anode-cathode pairing. For example, the distal electrode can be configured as an anode and the proximal electrode can be configured as a cathode.

[0142] The ablation device (2600) may include any number of splines, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2600) may include 3 to 20 splines. For example, the ablation device (2600) may include 4 to 12 splines.

[0143] Each spline in the set of splines (2620) may include a corresponding electrode (2630) having an atraumatic shape to reduce damage to tissue. For example, the electrode (2630) may have an atraumatic shape including a rounded, flat, curved, and / or blunted portion configured to contact endocardial tissue. In some embodiments, the electrode (2630) may be positioned along any portion of the splines (2620) that is distal to the catheter shaft (2610). The electrodes (2630) may have the same or different sizes, shapes, and / or positions along the corresponding splines.

[0144] In this way, the electrode in the second configuration can be held close to or placed against a portion of the atrial wall of the left atrium so as to generate a foci directly thereon by activating the appropriate electrode using any suitable polarity combination, as described herein. For example, the spline (2620) set can be placed in contact with the atrial wall (2654) of the atrium (2652) adjacent to the pulmonary vein (2650) (e.g., the ostium or sinus).

[0145] Fig.26D is a schematic diagram of an ablation (2664) generated by an ablation device (2600) on tissue, such as tissue surrounding a pulmonary vein ostium. For example, activating one or more electrodes (2630) on one or more splines (2620) can generate one or more corresponding ablation regions (2664) along a wall (2654) of a pulmonary vein sinus or ostium. In some embodiments, the contour of the ablation region (2664) in 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, a continuous transmural lesion can be generated, resulting in electrical isolation of the pulmonary veins, which is a desired treatment outcome.

[0146] Alternatively, the ablation catheter and its deployed electrodes may be placed adjacent to or against a portion of the posterior wall of the left atrium, and by activating the appropriate set of electrodes, a suitable pulse waveform may be delivered to deliver irreversible electroporation energy to ablate tissue.

[0147] In some embodiments, since the electrodes or subsets of electrodes are independently addressable, the electrodes can be energized in any order 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 herein. It should be understood that the size, shape, and spacing of the electrodes on and between the splines can be configured to deliver continuous / transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternating electrodes can be at the same potential, and this is also true for all other alternating electrodes. Therefore, in some embodiments, ablation can be delivered quickly with all electrodes activated simultaneously. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0148] In some embodiments, the distal-most portion of the ablation device may include a spline set rather than a distal cap or another element that extends the length of the catheter shaft. This may help position the spline set against the tissue and reduce contact of other elements of the ablation device with the tissue (which may cause damage to the tissue). For example, Fig.35 is a side view of an embodiment of an ablation device (3500) comprising a first catheter (3510) (e.g., an outer catheter shaft) located at a proximal end of the device (3500). The first catheter (3510) may define a longitudinal axis (3550) and a lumen therethrough. A second catheter (3520) may be slidably disposed within the lumen of the first catheter and extend from a distal end of the lumen of the first catheter. The diameter of the second catheter (3520) may be smaller than the diameter of the first catheter (3510). The second catheter (3520) may define a lumen therethrough. For example, the lumen may provide a passage for another device (such as a guide wire).

[0149] The spline (3530) group can be coupled to the first catheter (3510) and the second catheter (3520). Specifically, the proximal portion of the spline (3530) group can be coupled to the distal end of the first catheter (3510), and the distal portion of the spline (3530) group can be coupled to the distal end of the second catheter (3520). The second catheter (3520) can translate along the longitudinal axis (3550) of the ablation device (3500). The proximal end of each spline in the spline (3530) group can pass through the distal end of the first catheter (3510) and be tethered to the first catheter (3510) within the lumen of the first catheter. The distal end of each spline in the spline (3530) group can pass through the distal end of the second catheter (3520) and be tethered to the second catheter (3520) within the lumen of the second catheter. In some embodiments, a joint (3522) can be formed between the distal end of the second catheter (3520) and the spline (3530) group. For example, a polymer reflow process may be used to form a smooth, atraumatic joint between the second catheter (3520) and the spline (3530) set. The ablation device (3500) may be configured, for example Figure 21-2 As disclosed in the example of 6, during use, a pulse waveform is delivered to tissue via electrodes of one or more splines in a spline (3530) group.

[0150] Each spline (3530) of the ablation device (3500) may include one or more electrodes (3540) formed on a surface of the spline (3530). Each electrode (3540) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. Each spline (3530) may include an insulated electrical lead of each electrode (3540) formed in the body of the spline (3530) (e.g., within a lumen of the spline (3530)). Fig.35 A spline group is shown, where each spline (3530) includes a set of electrodes (3540) having approximately the same size, shape, and spacing as the electrodes (3540) of adjacent splines. In other embodiments, the size, shape, and spacing of the electrodes (3540) may vary.

[0151] 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 converted from a first configuration to a second configuration such that the splines (3530) of the ablation device (3500) are bent radially outward.

[0152] At least a portion of the spline (3530) group may include a flexible curvature. For example, a proximal region (3522) and a distal region (3526) of each spline (3530). The spline (3530) group may form a delivery assembly at a distal portion of the ablation device (3500) and may be configured to transition between a first configuration in which the spline (3530) group is arranged substantially closer to the longitudinal axis (3540) of the ablation device (3500) and a second configuration in which the spline (3530) group is radially outwardly curved from the longitudinal axis (3540) of the ablation device (3500) to form a basket-like and / or flower-like shape in which each spline forms a "petal". The spatially curved shape of the splines in the second configuration may be about Figures 34A-34B For example, in a fully deployed configuration, the integral magnitude of the rotational rate of each spline of the spline (3530) group along the length of each spline can be greater than π radians.

[0153] In other embodiments, the "basket" of the spline may have an asymmetric shape along the length of the catheter, such that one end of the basket (referred to as the distal end) is more spherical than the other end of the basket (referred to as the proximal end). The delivery assembly may be advanced through a body cavity in a first configuration and converted to a second configuration prior to delivering a pulse waveform. In some embodiments, a handle (not shown) may be coupled to the spline (3530) set and the handle is configured to affect the conversion of the spline (3530) set between the first configuration and the second configuration. In some embodiments, actuation of one or more knobs, wheels, sliders, pull wires and / or other control mechanisms in the handle may cause translation of the second catheter (3520) relative to the first catheter (3510) and cause the spline (3530) to bend. In some embodiments, the electrical leads of at least two electrodes of the electrode (3540) set may be electrically coupled at or near a proximal portion of the ablation device (3500), such as, for example, within the handle. For example, the handle may be configured to translate the second catheter (3512) relative to the first catheter (3510), thereby actuating and bending the spline (3530) set, such as Fig.35 As shown. The distal end of the spline (3530) can be fixed to the distal end of the second catheter (3520), thereby generating flexion of the spline (3530), resulting in a bending movement of the spline (3530), for example, when the second catheter (3520) is pulled back relative to the first catheter (3510). In other words, the translation of the handle actuation member can bend the spline (3530) group. In some embodiments, each spline in the spline (3530) group can be laterally offset from the longitudinal axis (3540) of the second catheter (3512) by up to about 35mm. For example, the spline (3530) group in the second configuration can be formed into a shape having an effective cross-sectional diameter at its largest portion between about 10mm and about 35mm. In the second configuration, the length of the spline group can be between about 15mm and about 50mm.

[0154] In one embodiment, each electrode on a spline may be configured as an anode, while each electrode on a different spline may be configured as a cathode. That is, the electrode sets on adjacent splines may have opposite polarities. In another embodiment, the electrodes on one spline may alternate between an anode and a cathode, and the electrodes of another spline have a reverse configuration (e.g., a cathode and an anode). In some embodiments, adjacent distal electrodes and proximal electrodes may form an anode-cathode pairing. For example, the distal electrode may be configured as an anode, and the proximal electrode may be configured as a cathode.

[0155] In some embodiments, the electrodes may be electrically activated in a sequential manner to deliver a pulse waveform with each anode-cathode pairing. In some embodiments, the electrodes (3540) may be electrically wired together within the spline (3530), and in alternative embodiments, they may be electrically wired together within the handle of the device (3500) so that the electrodes (3540) are at the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3540) may also be different. As another example, the splines (3530) may be activated sequentially in a clockwise or counterclockwise manner. As another example, the cathode splines may be activated sequentially with the corresponding sequential anode spline activation until the ablation is completed. In embodiments where the electrodes (3540) on a given spline (3530) are wired separately, the activation order within the electrodes (3540) of each spline (3530) may also vary. For example, the electrodes (3540) in the spline may be activated all at once or in a predetermined order.

[0156] Any pulse waveform sufficient to ablate tissue by irreversible electroporation can be used to provide energy to the electrodes in any order. It should be understood that the size, shape and spacing of the electrodes on and between the splines can be configured to deliver energy to electrically isolate one or more areas of cardiac tissue. In some embodiments, alternating electrodes (e.g., all distal electrodes) can be at the same potential, and this is also true for all other electrodes (e.g., all proximal electrodes). Therefore, when all electrodes are activated simultaneously, ablation can be delivered quickly. There are multiple such electrode pairing options, and they can be implemented based on their convenience.

[0157] Each of the splines (3530) may be composed of a polymer and define an inner lumen to form a hollow tube. The splines (3530) group of the ablation device (3500) may have a diameter that may be between about 1.0 mm and about 5.0 mm. The electrodes (3540) set of the ablation device (3500) may have a diameter that may be between about 1.0 mm and about 5.0 mm, and a length that may be between about 0.2 mm and about 5.0 mm.

[0158] The ablation device (3500) may include any number of splines, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (3500) may include 3 to 16 splines. For example, the ablation device (3500) may include 3 to 14 splines.

[0159] Each spline in the spline (3530) group may include a corresponding electrode (3540) having an atraumatic shape to reduce damage to tissue. For example, the electrode (3540) may have an atraumatic shape including a rounded, flat, curved, and / or blunted portion. In some embodiments, the electrode (3540) may be positioned along any portion of the spline (3530) that is distal to the first catheter (3510). The electrodes (3540) may have the same or different sizes, shapes, and / or positions along the corresponding splines. The ablation device (3500) may include any number of electrodes, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 or more electrodes per spline, including all values ​​and sub-ranges therebetween. In some embodiments, the ablation device (3500) may include 2 to 12 electrodes per spline.

[0160] Figures 34A-34B is a side view of a spline (3400) similar in structure and / or function to that described herein, such as Figures 36A-36C The spline shown in . Fig.34A is a side view of the spline with unit tangent vector. Fig.34B is a side view of a spline with two unit tangent vectors. Figures 34A-34B A spline (3400) having a petal-like shape is depicted, and may correspond to the shape of the splines in the second configuration and / or the third configuration 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 each point (3410) along the spline (3400), a unit tangent vector u (3420) may be defined. Fig.34B A unit tangent vector u1 (3430) at the proximal end (3402) of the spline (3400) and a unit tangent vector u2 (3440) at the distal end (3404) of the spline (3400) are shown.

[0161] The rate of change of the unit tangent vector along the length of the spline is controlled by the following equation:

[0162] u'=du / dl(1)

[0163] where l is the arc length along the spline.

[0164] The rate of change of the unit tangent vector u' can be called the rotation rate of the unit tangent vector along the spline. Since u·u=1, the rotation rate u' is perpendicular to the unit tangent vector u.

[0165] In some embodiments, a spline as described herein can be transformed into a petal shape or can form a loop that twists along its length so that the spline has a twist along its length. A spline as described herein has an integral magnitude of the rotation rate governed by the inequality:

[0166] ∫|u'|}dl>π(2)

[0167] That is, the integrated magnitude of the rate of rotation of the spline is greater than π radians, or equivalently 180 degrees. Since u and u' are perpendicular, u·u' = 0. Therefore, the vector b = ux u' is perpendicular to u and u'.

[0168] In some embodiments, the shape of the spline is generally a space curve with a twist so that the derivative of the rotation rate generally has a component along b at least at some location along the length of the spline, governed by the following equation:

[0169] ∫(u"·b)dl≠0(3)

[0170] In some embodiments of the apparatus described herein, the deployed splines of the spline set may satisfy equations (2) and (3) simultaneously.

[0171] Figures 36A-36C is a side view of an ablation catheter (3600) configured with a deployed spline group and an electrode assembly extending distally from all other elements of the catheter (3600) when the distal splines are fully deployed, thereby reducing damage to tissue and facilitating positioning and contact between the electrode assembly and tissue. Fig.36A is a perspective view of an embodiment of an ablation device (3600) having a flower-like shape and comprising a first catheter (3610) located at a proximal end of the device (3600). The first catheter (3610) may define a longitudinal axis (3650) and an inner cavity therethrough. A second catheter (3620) may be slidably disposed within the inner cavity of the first catheter and extend from a distal end of the inner cavity of the first catheter. The first catheter and the second catheter and a catheter handle for actuation may comprise a single device. A spline (3630) set may be coupled to the first catheter (3610) and the second catheter (3620). The second catheter (3620) may translate along the longitudinal axis (3650) of the ablation device (3600). The proximal end of each spline of the spline (3630) group can pass through the distal end of the first catheter (3610) and be tethered to the first catheter (3610) within the lumen of the first catheter, and the distal end of each spline of the spline (3630) group can be tethered to the distal end (3622) of the second catheter (3620), as described 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) can engage sensitive tissue, such as a thin heart wall, while reducing the risk of damage from the device (3600). The ablation device (3600) can be configured, such as Figure 21-2 6, during use, a pulse waveform is delivered to tissue via one or more electrodes on the spline (3630) set.

[0172] In some embodiments, each spline (3630) of the ablation device (3600) may include one or more commonly connected electrodes (3640) formed on the surface of the spline (3630). In other embodiments, one or more electrodes (3640) on a given spline may be independently addressable electrodes (3640). Each electrode (3640) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead may maintain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline (3630) may include an insulated electrical lead for each electrode (3640) within the body of the spline (3630) (e.g., within the lumen of the spline (3630)). Figures 36A-36C A set of splines (3630) is shown, wherein 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) may vary based on the number of electrodes (3640) formed on each spline (3630), which may correspond to the number of insulated electrical leads in the spline (3630). The splines (3630) may have the same or different materials, thicknesses, and / or lengths.

[0173] Each spline in the set of splines (3630) may include a flexible curvature to allow rotation, twisting and bending and forming a petal-shaped curve, such as Figures 26A-26C, 34A-34B and 36A-36C. The minimum radius of curvature of the splines in the petal-like configuration may be between about 7 mm and about 25 mm. For example, the spline group may form a delivery assembly at a distal portion of the ablation device (3600) and be configured to transition between a first configuration in which the spline group is arranged generally closer to the longitudinal axis of the ablation device (3600) and a second configuration in which the spline group is rotated about the longitudinal axis of the ablation device (3600), or twisted and bent, and generally offset from the longitudinal axis of the ablation device (3600). In the first configuration, each spline in the spline group may be located in a plane with the longitudinal axis of the ablation device. In the second configuration, each spline in the spline group may be offset from the longitudinal axis to form a petal-like curve (e.g., a flower shape), wherein the longitudinal axis of the spline is arranged generally perpendicular to the longitudinal axis (3650) or has an acute angle relative to the longitudinal axis (3650). As described in detail herein, the shape (e.g., bend, curve) of the spline group can satisfy equations (1)-(3). In this manner, the spline (3620) group twists, bends, and deviates from the longitudinal axis of the ablation device (3600), thereby allowing the spline (3620) group to more easily conform to the geometry of the endocardial space, such as the orifice and posterior wall of the pulmonary orifice. In some embodiments, each spline in the spline group in the second configuration can be twisted and bent to form a petal-like curve that exhibits an angle of greater than about 180 degrees between the proximal and distal ends of the curve when viewed from the front.

[0174] In some embodiments, when the second catheter (3620) coupled to the set of splines (3630) slides within the lumen of the first catheter (3610), the second catheter (3620) may allow each spline of the set of splines (3630) to bend and twist relative to the first catheter (3610). For example, the set of splines (3630) may form a shape that is generally closer to the longitudinal axis of the second catheter (3620) when undeployed, and wrap (e.g., spiral, twist) around the longitudinal axis (3650) when fully deployed, and form any intermediate shape therebetween (such as a cage or barrel) as the second catheter (3620) slides within the lumen of the first catheter (3610).

[0175] In some embodiments, the spline group in the first configuration, such as the spline (3630), may be wrapped around the longitudinal axis (3650) of the first catheter (3610) at certain portions along its length, but generally parallel to the longitudinal axis of the first catheter (3610) at other portions. The second catheter (3620) can be retracted into the first catheter (3610) to convert the ablation device (3600) from the first configuration to a second configuration, in which the splines (3630) are twisted to form a petal-like shape and are generally angled or offset (e.g., perpendicular, angled in the distal direction) relative to the longitudinal axis (3650) of the first catheter (3610). When the second catheter (3622) is further retracted into the inner cavity of the first catheter (3610), the spline (3630) group may extend further distally. Figures 36A-36C As shown, each spline (3630) may form a twisted ring (eg, a petal shape, where groups of splines together form a flower shape).

[0176] In the second configuration, the set of splines (3630) in the second configuration may form a flower shape and may be angled in the distal direction. Fig.36A A spline (3630) set is depicted having at least a portion of each spline of the spline (3630) set extending distally of the distal end (3622) of the second catheter (3620). For example, Fig.36A The distal portion of the splines is shown intersecting a plane (3660) located distal to the distal end (3622) of the second catheter (3620) (perpendicular to the longitudinal axis (3650)). Thus, when the ablation device (3600) is advanced in the distal direction to contact tissue, the spline (3630) set will contact before the first catheter (3610) and the second catheter (3620). This can reduce damage to the tissue because the tissue can contact the flexible spline set without having to contact the relatively stiff second catheter (3622).

[0177] Fig.36B The spline (3630) set in a second configuration is shown, the spline (3630) set forming a distal (e.g., forward) angle (3680) between the longitudinal axis (3670) of the spline (3630) and the longitudinal axis of the first catheter (3650). The longitudinal axis (3670) of the spline (3630) can be defined by a line formed between the apex of the spline (3630) and the midpoint between the proximal and distal ends of the spline (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.

[0178] In some embodiments, each spline in the 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 electrodes (3640) and the rotational twist of the splines (3630) can be configured by appropriately placing the electrodes along each spline to prevent the electrodes (3640) on one spline from overlapping the electrodes of adjacent overlapping splines.

[0179] Splines with anode electrode sets can be activated together to deliver pulse waveforms for irreversible electroporation. Electrodes on other splines can be activated together as cathode electrodes, such as electrodes on their corresponding splines, to form an anode-cathode pairing to deliver a pulse waveform for irreversible electroporation. Anode-cathode pairing and pulse waveform delivery can be repeated sequentially on a set of such pairs.

[0180] For example, the splines (3630) may be activated sequentially in a clockwise or counterclockwise manner. As another example, the cathode splines may be activated sequentially with corresponding sequential anode spline activation until ablation is complete. In embodiments where the electrodes on a given spline are wired separately, the activation order within the electrodes of each spline may also vary. For example, the electrodes in a spline may be activated all at once or in a predetermined order.

[0181] Prior to delivering the pulse waveform, the delivery assembly may be arranged in a first configuration and converted to a second configuration to contact the ostium or sinus of a pulmonary vein. Fig.36C The distal-most portion of the spline (3630) set is depicted in close proximity and / or contact with a tissue wall (3690), such as the posterior wall of the left atrium. Fig.36C The spline (3630) group in the second configuration is in a second configuration, wherein at least a portion of each spline of the spline (3630) group extends distally of the distal end (3622) of the second catheter (3620). The tissue (3690) can be a heart wall, such as the endocardial surface of the posterior wall of the left atrium. The distal end (3622) of the second catheter (3620) can be separated from the tissue (3690) by a first distance (3692). Therefore, the ablation device (3600) in the second configuration can engage the tissue (3690) in an atraumatic manner, thereby reducing the risk of perforation or other damage. Therefore, the ablation device (3600) can be used to ablate even thin tissue structures, such as the posterior wall of the left atrium.

[0182] In some of these embodiments, a handle may be coupled to the second catheter (3620), and the handle is configured to affect a transition of the spline group 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 the spline (3630) group coupled to the second catheter (3620) and causing it to bend and twist. The proximal end of the spline (3630) may be fixed to the second catheter (3620), thereby generating a flexion of the spline (3630), which results in a bending and twisting motion of the spline (3630), for example, when the second catheter (3620) is pulled back relative to the first catheter (3610) that can be held by a user. For example, the distal end of the spline (3630) group tethered to the second catheter (3620) may be translated up to about 60 mm along the longitudinal axis of the ablation device to actuate the change in the configuration. In other words, translation of the actuation member of the handle may bend and twist the spline (3630) group. In some embodiments, actuation of a knob, wheel, or other rotary control mechanism in the device handle can result in translation of the actuation member or second catheter and in bending and twisting of the spline (3630). In some embodiments, electrical leads of at least two electrodes of the electrode (3640) set can be electrically coupled at or near a proximal portion of the ablation device (3600), such as, for example, within the handle.

[0183] Retraction of the second conduit (3620) relative to the first conduit (3610) may bring the set of splines (3630) closer together, such as Figures 36A-36C As shown. The spline (3630) group is further substantially perpendicular or angled distally relative to the longitudinal axis (3650) of the first catheter (3610). In some embodiments, each spline in the spline (3630) group may be laterally offset from the longitudinal axis (3650) by up to about 30 mm. In some embodiments, the second catheter (3620) may include a hollow lumen. In some embodiments, the cross-section of the spline may be asymmetric so as to have a greater bending stiffness in one bending plane of the spline orthogonal to the plane of the cross-section than in a different bending plane. Such an asymmetric cross-section may be configured to present a relatively large lateral stiffness, so that the petal-shaped curves of each spline and its adjacent splines can be deployed in a final or fully deployed configuration with minimal overlap.

[0184] In one embodiment, each electrode (3640) on a spline (3630) may be configured as an anode, while each electrode (3640) on a different spline (3630) may be configured as a cathode. In another embodiment, the electrodes (3640) on one spline may alternate between anode and cathode, and the electrodes of another spline have the opposite configuration (e.g., cathode and anode).

[0185] 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 within the spline, and in alternative embodiments, they can be electrically wired together within the handle of the device so that the electrodes are at the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3640) can also be different. In some embodiments, adjacent distal electrodes 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.

[0186] The ablation device (3600) may include any number of splines, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (3600) may include 3 to 20 splines. For example, the ablation device (3600) may include 4 to 12 splines.

[0187] Each spline in the set of splines (3630) may include a corresponding electrode (3640) having an atraumatic shape to reduce damage to tissue. For example, the electrode (3640) may have an atraumatic shape including a rounded, flat, curved, and / or blunted portion configured to contact endocardial tissue. In some embodiments, the electrode (3640) may be positioned along any portion of the splines (3630) that is distal to the first catheter (3610). The electrodes (3640) may have the same or different sizes, shapes, and / or positions along the corresponding splines.

[0188] In this way, the electrodes in the second configuration can be held close to or placed against a portion of the atrial wall of the left atrium so as to generate a foci directly thereon by activating the appropriate electrodes using any suitable polarity combination, as described herein. For example, the spline (3630) set can be placed in contact with the atrial wall (3654) of the atrium (3652) adjacent to the pulmonary vein (3650) (e.g., the ostium or sinus) and / or the posterior wall.

[0189] Figures 37A-37B is a perspective view of the ablation catheter (3730) and the left atrium (3700). Fig.37Ais a perspective view of an ablation catheter (3730) disposed in the left atrium (3700). The left atrium (3700) includes a set of pulmonary veins (3720) and a posterior wall (3710). The ablation device (3730) can be similar in structure and / or function to the ablation devices (3500, 3600) described herein, which can be advanced into the left atrium (3700) and positioned near and / or in contact with the posterior wall (3710) of the left atrium (3700) without perforating and / or causing damage to sensitive tissue of the posterior wall (3710). For example, the spline group can extend distally of the distal end of the catheter coupled to the spline so that the flexible and non-damaging spline can be adjacent to or in contact with the posterior wall (3710) and no other portion of the device (3730) is in contact with the posterior wall (3710). In embodiments where the distal-most portion of the device (3700) includes only a set of splines in the second configuration (e.g., having a flower shape), the deployed device may engage thinner tissue structures, such as a heart wall, where the risk of damage from the ablation device (3700) is minimized. A pulse waveform may be applied by an electrode of the ablation device (3700) having a flower shape to ablate tissue within the ablation zone (3740).

[0190] Fig.37B Schematic diagram of a perspective view of the left atrium (3700) after tissue ablation. The ablation device (3700) can be used to generate a collection of ablation zones (3740, 3742, 3744) on the posterior wall (3710) of the left atrium (3700). For example, repeated activation of one or more electrodes on one or more splines of the ablation device (3730) as the catheter moves between complete ablations can generate a collection 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 each other. These adjacent overlapping ablation zones can approximate a thicker ablation line (3746). One or more ablation lines can be connected to other ablation lines (e.g., generated around the pulmonary vein sinus or orifice) and / or ablation zones to produce a box-shaped lesion. For example, a collection of continuous ablation zones can be formed by the ablation device (3730) to form a box-shaped lesion around the posterior wall (3710) of the left atrium (3700), which also surrounds one or more pulmonary veins (3720). In this way, a continuous transmural lesion can be generated around all pulmonary veins, which results in electrical isolation of the pulmonary veins to provide the desired treatment results. In some embodiments, the diameter of each ablation zone in the collection of ablation zones (3740, 3742, 3744) can be between about 2 cm and about 6 cm. For example, the diameter of the ablation zone can be between about 2.3 cm and about 4.0 cm.

[0191] In some embodiments, because the electrodes or subsets of electrodes are independently addressable, the electrodes can be energized in any order using any pulse waveform sufficient to ablate tissue by irreversible electroporation. It should be understood that the size, shape, and spacing of the electrodes on and between the splines can be configured to deliver sufficient energy to electrically isolate one or more pulmonary veins. In some embodiments, the alternating electrodes can be at the same potential, and the same is true for all other alternating electrodes. Therefore, in some embodiments, ablation can be delivered quickly with all electrodes activated simultaneously. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0192] Figures 27A-27B is a side view of an embodiment of an ablation device (2700), the ablation device (2700) comprising a catheter shaft (2710) located at a proximal end of the device (2700) and a spline (2720) group coupled to the catheter shaft (2710) at a distal end of the device (2700). The ablation device (2700) may be configured to deliver a pulse waveform to tissue via one or more splines in the spline (2720) group during use. Each spline (2720) of the ablation device (2700) may include one or more electrodes (2730) formed on a surface (e.g., a distal end) of the spline (2720) that may be independently addressable. Each electrode (2730) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead can sustain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline of the set of splines (2720) may include an insulated electrical lead for each electrode (2730) formed in the body of the spline (2720) (e.g., within the lumen of the spline (2720)). In some embodiments, the electrodes (2730) may be formed at the distal end of their respective splines (2720).

[0193] The set of splines (2720) may form a delivery assembly at the distal end of the ablation device (2700) and may be configured to transition between a first configuration and a second configuration. The set of splines (2720) in the first configuration are generally parallel to the longitudinal axis of the ablation device (2700) and may be closely spaced together. Figures 27A-27B, a spline (2720) group in a second configuration is depicted, wherein the spline (2720) group extends outward from the distal end of the catheter shaft (2710) and deviates (e.g., bends) from the longitudinal axis of the ablation device (2700) and 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 arranged in a first configuration prior to delivering a pulse waveform and converted to a second configuration to a portion of cardiac tissue, such as the posterior wall of the left atrium or the ventricle. Such a device that delivers an irreversible electroporation pulse waveform can generate larger lesions for focal ablation.

[0194] The distal end of the spline (2720) group can be configured to deviate from the longitudinal axis of the distal end of the catheter shaft (2710) and from other splines. Each spline in the spline (2720) group can include a flexible curvature. The minimum radius of curvature of the spline (2720) can be in the range of about 1 cm or greater.

[0195] In some embodiments, the proximal end of the spline (2720) set can be slidably coupled to the distal end of the catheter shaft (2710). Thus, the length of the spline (2720) set can be as long as Fig.27A and 27B As shown in the variation. When the spline (2720) group extends further outward from the catheter shaft (2710), the distal ends of the spline (2720) group may further deviate from each other and deviate from the longitudinal axis of the catheter shaft (2710). The spline (2720) group can be slidably pushed out from the catheter shaft (2710) independently or in the form of one or more groups. For example, in a first configuration, the spline (2720) group can be arranged in the catheter shaft (2710). The spline (2720) can then be pushed out of the catheter shaft (2710) and converted to a second configuration. The spline (2720) can be pushed together, or pushed so that the spline (2720) group corresponding to the anode electrode (2730) and the spline (2720) group corresponding to the cathode electrode (2730) are pushed separately. In some embodiments, the spline (2720) can be pushed independently. In a second configuration, the electrode (2730) is offset longitudinally and / or laterally from the catheter shaft (2710) relative to the longitudinal axis of the distal end of the catheter shaft (2710). This may facilitate delivery and positioning of the electrode (2730) relative to the endocardial surface. In some embodiments, each of the spline (2720) set may extend up to about 5 cm from the distal end of the catheter shaft (2710).

[0196] In some embodiments, the spline (2720) group 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 further from the catheter shaft (2710) than an adjacent spline. The spline (2720) group can be constrained by the lumen of the guide sheath so that the spline (2720) group is substantially parallel to the longitudinal axis of the catheter shaft (2710) in the first configuration.

[0197] In some of these embodiments, a handle (not shown) may be coupled to the spline set. The handle may be configured to affect a transition of the spline set between a first configuration and a second configuration. In some embodiments, electrical leads of at least two electrodes of the electrode (2730) set may be electrically coupled at or near a proximal portion of the ablation device, such as, for example, within a handle. In this case, the electrodes (2730) may be electrically wired together in a handle of the device (2700) so that the electrodes (2730) are at the same electrical potential during ablation.

[0198] Each spline of the spline (2720) group may include a corresponding electrode (2730) located at the distal end of the spline (2720) group. The electrode (2730) set may include an atraumatic shape to reduce damage to tissue. For example, the electrode (2730) may have an atraumatic shape that includes a rounded, flat, curved, and / or blunted portion configured to contact endocardial tissue. In some embodiments, the electrode (2730) may be positioned along any portion of the spline (2720) located distal to the catheter shaft (2710). The electrodes (2730) may have the same or different sizes, shapes, and / or positions along the corresponding splines.

[0199] In one embodiment, an electrode (2730) on a spline (2720) may be configured as an anode, while an electrode (2730) on an adjacent spline (2720) may be configured as a cathode. The ablation device (2700) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2700) may include 3 to 20 splines. For example, the ablation device (2700) may include 6 to 12 splines.

[0200] Figures 27A-27Bis a side view of an embodiment of an ablation device (2700), the ablation device (2700) comprising a catheter shaft (2710) located at a proximal end of the device (2700) and a spline (2720) group coupled to the catheter shaft (2710) at a distal end of the device (2700). The ablation device (2700) may be configured to deliver a pulse waveform to tissue via one or more splines in the spline (2720) group during use. Each spline (2720) of the ablation device (2700) may include one or more electrodes (2730) formed on a surface (e.g., a distal end) of the spline (2720) that may be independently addressable. Each electrode (2730) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead can sustain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline of the set of splines (2720) may include an insulated electrical lead for each electrode (2730) formed in the body of the spline (2720) (e.g., within the lumen of the spline (2720)). In some embodiments, the electrodes (2730) may be formed at the distal end of their respective splines (2720).

[0201] The spline (2720) group may form a delivery assembly at a distal portion of the ablation device (2700) and may be configured to transition between a first configuration and a second configuration. The spline (2720) group in the first configuration is generally parallel to the longitudinal axis of the ablation device (2700) and may be closely spaced together. The spline (2720) group in the second configuration may be configured to transition between a first configuration and a second configuration. Figures 27A-27B As shown, a spline (2720) group extends outward from the distal end of the catheter shaft (2710) and deviates (e.g., bends) from the longitudinal axis of the ablation device (2700) and other splines (2720). In this way, the splines (2720) can more easily conform to the geometry of the endocardial space. The delivery assembly can be arranged in a first configuration before delivering a pulse waveform and converted to a second configuration to a portion of cardiac tissue, such as the posterior wall of the left atrium or the ventricle. This device that delivers an irreversible electroporation pulse waveform can generate larger lesions for focal ablation.

[0202] The distal end of the spline (2720) group can be configured to deviate from the longitudinal axis of the distal end of the catheter shaft (2710) and from other splines. Each spline in the spline (2720) group can include a flexible curvature. The minimum radius of curvature of the spline (2720) can be in the range of about 1 cm or greater.

[0203] In some embodiments, the proximal end of the spline (2720) set is slidably coupled to the distal end of the catheter shaft (2710). Thus, the length of the spline (2720) set can be as long as Fig.27A and 27BAs shown in the variation. When the spline (2720) group extends further outward from the catheter shaft (2710), the distal ends of the spline (2720) group may further deviate from each other and deviate from the longitudinal axis of the catheter shaft (2710). The spline (2720) group can be independently or in the form of one or more groups slidably pushed out from the catheter shaft (2710). For example, in a first configuration, the spline (2720) group can be arranged in the catheter shaft (2710). The spline (2720) can then be pushed out of the catheter shaft (2710) and converted to a second configuration. The spline (2720) can be pushed together, or pushed so that the spline (2720) group corresponding to the anode electrode (2730) and the spline (2720) group corresponding to the cathode electrode (2730) are pushed separately. In some embodiments, the spline (2720) can be pushed independently. In a second configuration, the electrode (2730) is longitudinally and / or laterally offset from the catheter shaft (2710) relative to the longitudinal axis of the distal end of the catheter shaft (2710). This may facilitate delivery and positioning of the electrode (2730) relative to the endocardial surface. In some embodiments, each spline of the spline (2720) set may extend up to about 5 cm from the distal end of the catheter shaft (2710).

[0204] In some embodiments, the spline (2720) group 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 further from the catheter shaft (2710) than an adjacent spline. The spline (2720) group can be constrained by the lumen of the guide sheath so that the spline (2720) group is substantially parallel to the longitudinal axis of the catheter shaft (2710) in the first configuration.

[0205] In some of these embodiments, a handle (not shown) may be coupled to the spline set. The handle may be configured to affect a transition of the spline set between a first configuration and a second configuration. In some embodiments, electrical leads of at least two electrodes of the electrode (2730) set may be electrically coupled at or near a proximal portion of the ablation device, such as, for example, within a handle. In this case, the electrodes (2730) may be electrically wired together in the handle of the device (2700) so that the electrodes (2730) are at the same electrical potential during ablation.

[0206] Each spline of the spline (2720) group may include a corresponding electrode (2730) located at the distal end of the spline (2720) group. The electrode (2730) set may include an atraumatic shape to reduce damage to tissue. For example, the electrode (2730) may have an atraumatic shape, including a round, flat, curved and / or blunted portion configured to contact endocardial tissue. In some embodiments, the electrode (2730) may be positioned along any portion of the spline (2720) located at the distal end of the catheter shaft (2710). The electrodes (2730) may have the same or different sizes, shapes and / or positions along the corresponding splines.

[0207] In one embodiment, an electrode (2730) on a spline (2720) may be configured as an anode, while an electrode (2730) on an adjacent spline (2720) may be configured as a cathode. The ablation device (2700) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2700) may include 3 to 20 splines. For example, the ablation device (2700) may include 6 to 12 splines.

[0208] exist Figures 27A-27B In the present invention, an electrode (2730) is formed on the surface of each spline (2720) so that each spline (2720) includes an insulated electrical lead. Therefore, the diameter of the inner cavity of the spline (2720) can be reduced, allowing the spline (2720) to be thicker and mechanically stronger. Therefore, the dielectric breakdown of the insulation can be further reduced, thereby improving the reliability and life of each spline (2720) and the ablation device (2700). In addition, in some embodiments, the radius of curvature of the spline can vary with the length of the spline. For example, the radius of curvature may increase monotonically. Such a variable radius of curvature can help to position the electrode (2730) at certain locations of the endocardial tissue. The splines (2720) can have the same or different materials, thicknesses and / or radii of curvature. For example, the thickness of each spline may decrease from the distal end.

[0209] In this manner, the electrodes in the second configuration can be pressed against, for example, the posterior wall of the left atrium to generate a local or focal lesion directly thereon by activating the appropriate electrodes using any suitable polarity combination. For example, adjacent electrodes (2730) can be configured to have opposite polarities.

[0210] Since the electrodes or subsets of electrodes are independently addressable, the electrodes can be energized in any order 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 herein. It should be understood that the size, shape, and spacing of the electrodes on and between the splines can be configured to deliver transmural lesions over a relatively wide area of ​​endocardial tissue. In some embodiments, alternating electrodes can be at the same potential, and this is also true for all other alternating electrodes. Therefore, with all electrodes activated simultaneously, ablation can be performed quickly. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0211] refer to Fig.27C , it should be understood that unless otherwise indicated, Figures 27A-27B Components in the same manner as the components with reference numbers (e.g., Figures 27A-27B The electrodes (2730) and Fig.27C The electrodes (2730') in can be similar in structure and / or function. Fig.27C A set of splines (2720') is shown, wherein each spline (2720') includes a pair of electrodes (2730', 2740).

[0212] The ablation device (2700') includes a catheter shaft (2710') located at the proximal end of the device (2700') and a spline (2720') group coupled to the catheter shaft (2710') at the distal end of the device (2700'). The ablation device (2700') can be configured to deliver a pulse waveform to tissue via one or more splines in the spline (2720') group during use. Each spline (2720') of the ablation device (2700') can include one or more independently addressable electrodes (2730', 2740) formed on the surface of the spline (2720'). Each electrode (2730', 2740) can include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead can maintain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline of the spline (2720') group may include an insulated electrical lead for each electrode (2730', 2740) formed within the body of the spline (2720') (e.g., within the inner cavity of the spline (2720')). Each electrode (2730', 2740) of the spline (2720') can have approximately the same size and shape. In addition, each electrode (2730', 2740) of the spline (2720') can have approximately the same size, shape, and spacing as the electrodes (2730', 2740) of the adjacent spline (2720'). In other embodiments, the size, shape, number, and spacing of the electrodes (2730', 2740) can be different.

[0213] In some embodiments, the electrodes (2730', 2740) of the ablation device (2700') may have a length between about 0.5 mm and about 5.0 mm, and a cross-sectional dimension (e.g., diameter) between about 0.5 mm and about 4.0 mm, including all values ​​and subranges therebetween. The spline lines (2720') in the second configuration may be flared to each other at the distal end of the ablation device (2700') to a range Sd between about 5.0 mm and about 20.0 mm (including all values ​​and subranges therebetween), and may extend from the distal end of the catheter shaft (2710') to a length Sl between about 8.0 mm and about 20.0 mm (including all values ​​and subranges therebetween). In some embodiments, the ablation device (2700') may include 4 splines, 5 splines, or 6 splines. In some embodiments, each spline may independently include 1 electrode, 2 electrodes, or 3 or more electrodes.

[0214] The spline (2720') group may form a delivery assembly at a distal portion of the ablation device (2700') and may be configured to transition between a first configuration and a second configuration. The spline (2720') group in the first configuration is generally parallel to the longitudinal axis of the ablation device (2700) and may be closely spaced together. The spline (2720') group in the second configuration may be configured to transition between a first configuration and a second configuration. Fig.27C As shown, a spline (2720') group extends outward from the distal end of the catheter shaft (2710') and deviates (e.g., bends) from the longitudinal axis of the ablation device (2700') and other splines (2720'). In this way, the splines (2720'") can more easily conform to the geometry of the endocardial space. As disclosed herein, the delivery assembly can be arranged in a first configuration before delivering a pulse waveform and converted to a second configuration to contact an endocardial tissue area to generate a larger focal lesion when delivering a pulse waveform for irreversible electroporation. In some embodiments, Fig.27C The electrode (2730'") in the depicted second configuration (sometimes referred to as the "distal electrode") may be configured to contact and press against the endocardial tissue, while at the same time 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 electrodes due to conduction between the proximal and distal electrodes through the blood pool results in focal ablation of the tissue.

[0215] In some embodiments, the proximal end of the spline (2720') group can be slidably coupled to the distal end of the catheter shaft (2710'). As the spline (2720') group extends further outward from the catheter shaft (2710'), the distal ends of the spline (2720') group can be further offset from each other and away from the longitudinal axis of the catheter shaft (2710'). The spline (2720') group can be slidably pushed out of the catheter shaft (2710') individually or in one or more groups. For example, in a first configuration, the spline (2720'") group can be arranged within the catheter shaft (2710'). The spline (2720') can then be pushed out of the catheter shaft (2710') and converted to a second configuration. The splines (2720') can be pushed together, or pushed so that the spline (2720') group corresponding to the anode electrode (2730) is pushed separately from the spline (2720') group corresponding to the cathode electrodes (2730', 2740). In some embodiments, the spline (271 In some embodiments, the splines of the spline group (2720') can extend up to about 5 cm from the distal end of the catheter shaft (2710').

[0216] In some embodiments, the distal electrodes (2730') may have the same polarity, while the adjacent proximal electrodes (2740) may have the opposite polarity as the distal electrodes (2730'). In this manner, an electric field for focal ablation may be generated between the distal and proximal electrodes.

[0217] In some of these embodiments, a handle (not shown) may be coupled to the spline set. The handle may be configured to affect a transition of the spline set between a first configuration and a second configuration. In some embodiments, electrical leads of at least two electrodes of the electrode (2730', 2740) set may be electrically coupled at or near a proximal portion of the ablation device, such as, for example, within a handle. In some embodiments, the electrodes (2730', 2740) may be electrically wired together in a handle of the device (2700') so that the electrodes (2730', 2740) are at the same electrical potential during ablation.

[0218] The electrode (2730', 2740) set may include a non-invasive shape to reduce damage to tissue. For example, the electrode (2730', 2740) may have a non-invasive shape, which includes a round, flat, curved and / or blunted portion configured to contact endocardial tissue. In some embodiments, the electrode (2730', 2740) may be positioned along any portion of the spline (2720') located distal to the catheter shaft (2710'). The electrodes (2730', 2740) may have the same or different sizes, shapes and / or positions along the corresponding splines. One or more splines (2720') may include three or more electrodes.

[0219] In some embodiments, each electrode (2730') on a spline (2720') may be configured as an anode, while each electrode (2730') on an adjacent spline (2720') may be configured as a cathode. In another embodiment, each electrode (2730') on one spline may alternate between an anode and a cathode, and each electrode of an adjacent spline has an inverse configuration (e.g., a cathode and an anode). In some embodiments, a subset of electrodes may be electrically wired together in the device handle so that the electrodes are at the same electrical potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (2730) may also vary. In some embodiments, adjacent distal electrodes (2730') and proximal electrodes (2740) may form an anode-cathode pair. For example, a distal electrode (2730') may be configured as an anode, and a proximal electrode (2740) may be configured as a cathode.

[0220] 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 3 to 20 splines. For example, the ablation device (2700) may include 6 to 12 splines.

[0221] exist Fig.27C In the embodiment of the present invention, two electrodes (2730', 2740) are formed on the surface of each spline (2720') so that each spline (2720') includes two insulated electrical leads. The thickness of each spline can vary based on the number of electrodes formed on each spline (2720'), which number 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.

[0222] In this manner, the electrodes in the second configuration can be placed against a portion of the endocardial tissue to create a foci directly thereon by activating the appropriate electrodes using any suitable polarity combination to deliver a pulse waveform for irreversible electroporation. For example, adjacent electrodes (2730', 2740) can be configured to have opposite polarities.

[0223] Since the electrodes can be independently addressable, any pulse waveform sufficient to ablate tissue by irreversible electroporation can be used to energize the electrodes in any order. For example, different electrode sets can deliver different pulse sets (e.g., hierarchical pulse waveforms), as discussed in further detail herein. It should be understood that the size, shape, and spacing of the electrodes on and between the splines can be configured to deliver continuous / transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternating electrodes can be at the same potential, and this is also true for all other alternating electrodes. Therefore, with all electrodes activated simultaneously, ablation can be delivered quickly. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0224] Fig.28 2 is a side view of another embodiment of an ablation device (2800) comprising 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 used to form a lesion on an endocardial surface via focal ablation, as described herein.

[0225] The distal cap (2812) may include an atraumatic shape and one or more independently addressable electrodes (2816) (sometimes also referred to as "distal electrodes"), as described in further detail herein. The proximal end of the spline (2814) group may be coupled to the distal end of the catheter shaft (2810), and the distal end of the spline (2814) group may be tethered to the distal cap (2812) of the device (2800). Each spline (2814) of the ablation device (2800) may include one or more independently addressable electrodes (2818) (sometimes also referred to as "proximal electrodes") formed on the surface of the spline (2814). Each electrode (2816, 2818) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead can maintain 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 for each electrode (2818) formed in the body of the spline (2814) (e.g., within a lumen of the spline (2814)). One or more splines (2818) can further include an insulated electrical lead for a distal electrode (2816). In some embodiments, the size and / or shape of the electrodes (2816, 2818) can be different from one another.

[0226] The configuration of the spline (2814) set and the proximal electrode (2818) can control the depth, shape and / or diameter / size of a focal ablation lesion generated by the ablation device (2800). The ablation device (2800) can be configured to transition between a first configuration in which the spline (2814) set is arranged generally parallel to the longitudinal axis of the ablation device (2800) and a second configuration in which the spline (2814) set curves radially outward from the longitudinal axis of the ablation device (2800). It should be understood that the spline (2814) set can be transitioned to any intermediate configuration between the first configuration and the second configuration, either continuously or in discrete steps.

[0227] Activation of the electrodes using a predetermined configuration can provide targeted and precise focal ablation by controlling the focal ablation spot size based on the expansion of the spline (2814). For example, in some embodiments, the distal electrode (2816) can be configured to have a first polarity, and one or more proximal electrodes (2818) can be configured to have a second polarity opposite to the first polarity. When the proximal electrode (2818) of the ablation device (2800) is in the first configuration, a high-intensity electric field with a relatively smaller / more focused diameter results in a focal ablation lesion with a relatively smaller diameter and greater depth on the endocardial surface. When the proximal electrode (2818) of the ablation device (2800) is in the second configuration, a relatively more dispersed electric field is generated, resulting in a focal ablation lesion on the endocardial surface that is relatively wider and shallower than in the first configuration. In this way, by varying the degree of expansion of the spline (2814), the depth, shape and / or size of the lesion can be controlled without disconnecting the ablation device (2800). These aspects can be used to create multiple lesions of varying sizes and / or depths using the same ablation device.

[0228] The distal cap (2812) can be configured to press against endocardial tissue, while the proximal electrode (2818) in the first or second configuration can be configured to not contact the endocardial tissue. It should be understood that the distal electrode (2816) does not need to contact the endocardial tissue. In some of these embodiments, a handle (not shown) can be coupled to the spline (2814) group and the handle is configured to affect the conversion of the spline (2814) group between the first configuration and the second configuration. In some embodiments, the electrical leads of at least two electrodes of the electrode set can be electrically coupled at or near the proximal portion of the ablation device (2800), such as, for example, within the handle.

[0229] In some embodiments, the distal electrode (2816) and the proximal electrode (2818) may form an anode-cathode pair. For example, the distal electrode (2816) may be configured as an anode and each proximal electrode (2818) may be configured as a cathode. In some embodiments, the ablation device (2800) may include 3 to 12 splines. The ablation device (2800) may include any number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20 or more splines. In some embodiments, the ablation device (2800) may include 3 to 20 splines. For example, in one embodiment, the ablation device (2800) may include 6 to 10 splines. In addition, in some embodiments, the shape of the expanded spline set (2814) may be asymmetric, for example, its distal portion is more spherical or rounded than its proximal portion. Such a spherical distal portion (and the proximal electrode positioning) may help further control the size and depth of focal ablation.

[0230] Fig.28 The depicted first plane (2822) may refer to a plane orthogonal to the longitudinal axis of the catheter shaft (2810). The distal cap (2812) may be pressed against, for example, an endocardial surface located within the first plane (2812), such as the luminal wall of a pulmonary vein, so as to directly generate a focal ablation lesion by activating the appropriate electrode using any suitable polarity combination. For example, the distal electrode (2816) may be pressed against the endocardial surface and used to form a focal ablation lesion (e.g., a spot lesion). In some embodiments, one or more proximal electrodes (2818) may be configured to have a polarity opposite to that of the distal electrode (2816). Conversely, one or more proximal electrodes (2818) may be configured to have the same polarity as the distal electrode (2816). In some embodiments, the proximal electrodes (2818) on different splines (2814) may alternate between anodes and cathodes.

[0231] In some embodiments, the distal electrode (2816) of the ablation device (2800) may include a length between about 0.5 mm and about 7.0 mm and a cross-sectional dimension (e.g., diameter) between about 0.5 mm and about 4.0 mm, including all values ​​and subranges therebetween. In some embodiments, the proximal electrode (2818) may include a length between about 0.5 mm and about 5.0 mm and a diameter between about 0.5 mm and about 2.5 mm, including all values ​​and subranges therebetween. The distal electrode (2816) may be separated from the proximal electrode (2818) by a length between about 3.0 mm and about 12.0 mm, including all values ​​and subranges therebetween. The distal electrode (2816) disposed on the distal cap (2812) may be located 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) may include the distal electrode (2816). One or more focal ablation zones can be formed comprising a diameter between about 1.0 cm and about 2.0 cm, including all values ​​and subranges therebetween.

[0232] Figures 29A-29D is a side view of another embodiment of an ablation device (2900) comprising an outer catheter or sheath (2902) and a collection of inner catheters (2910, 2920) slidable within a lumen of the outer catheter so as to extend from a distal end of the lumen. The outer catheter may define a longitudinal axis. The inner diameter of the outer catheter (2902) may be between about 0.7 mm and about 3 mm, and the outer diameter of the outer catheter (2902) may be between about 2 mm and about 5 mm. Fig.29A , 29DAs seen, the ablation device (2900) includes a first catheter (2910) having a first proximal portion (2912), a first distal portion (2914), and a first electrode (2916) formed on the first distal portion (2914) (e.g., such as 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).

[0233] In some embodiments, as described herein, the ablation device (2900) can be used to form a lesion on the endocardial surface via focal ablation. The distal end of the catheter (2910, 2920) and / or the electrode (2916, 2922) can include an atraumatic shape to reduce damage to the tissue. For example, the distal end of the catheter (2910, 2920) and / or the electrode (2916, 2922) can have an atraumatic shape, including a rounded, flat, curved, and / or blunted portion configured to contact endocardial tissue.

[0234] Each electrode (2916, 2926) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead may maintain a potential difference between about 200V and about 2000V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. Each catheter (2910, 2920) may include an insulated electrical lead for each electrode (2916, 2926) formed in the body of the catheter (2910, 2920) (e.g., within the lumen of the catheter (2910, 2920)). Each electrode (2916, 2926) may be connected to a corresponding insulated electrical lead that leads to a handle (not shown) coupled to the proximal portion of the catheter (2910, 2920). In some embodiments, the size, shape, and / or position of the electrodes (2916, 2926) may differ from one another.

[0235] In some embodiments, the configuration of the catheters (2910, 2920) and electrodes (2916, 2926) can control the depth, shape, and / or diameter / size of a focal ablation lesion generated by the ablation device (2900). The first and second catheters (2910, 2920) can be configured to translate along the longitudinal axis of the outer catheter (2902). In some embodiments, the ablation device (2900) can be configured to transition between the following configurations: a first configuration in which the catheter set (2910, 2920) is arranged generally parallel to the longitudinal axis of the outer catheter (2902), and the distal portions of the catheters (2910, 2920) are arranged within the outer catheter (2902) (e.g., Fig.29A ); a second configuration in which the electrodes (2916, 2926) are pushed out and away from the distal end (2903) of the outer catheter lumen (2902) at any suitable distance; and a third configuration in which the distal portion of each catheter (2910, 2920) can be rotated, twisted, or bent (e.g., Figures 29B-29D ). For example, Figures 29B-29C As best shown in FIG. 1 , the first catheter (2910) may include a distal portion (2914) that is rotatable about a first hinge (2918), which may be configured to position the distal portion (2914) relative to the proximal portion (2912) in a plurality of positions. The catheters (2910, 2912) in the second and third configurations may be angled away from each other, thereby offset from the longitudinal axis of the outer catheter (2902). The distal ends of the proximal portions (2912, 2922) may form an angle of between about 5 degrees and about 75 degrees relative to the longitudinal axis (e.g., Fig.29D ). It should be understood that the ablation device (2900) may be converted to any intermediate configuration between the first, second and third configurations, either continuously or in discrete steps.

[0236] In some embodiments, conduction between the electrodes through the blood pool and / or endocardial tissue results in the generation of an electric field, and the electric field is applied to the endocardial surface as ablative energy. The electrode may be held close to or in physical contact with a portion of the atrial wall of the left atrium so as to generate a focus by activating one or more electrodes using any suitable polarity combination. In this way, activation of the electrodes using a predetermined configuration can provide targeted and precise focal ablation by controlling the focal ablation spot size based on the position and orientation of the electrodes (2916, 2926) relative to the proximal portion (2912, 2922) of the catheter (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 to the first polarity. When the electrodes (2916, 2926) are rotated so that they are relatively close to each other (e.g., when the proximal portion (2912) and the distal portion (2914) form an acute angle (2950)), a relatively high intensity electric field with a relatively smaller / more focused diameter results in a focal ablation lesion of relatively small diameter and good depth on the endocardial surface. Purely for non-limiting illustrative purposes, the acute angle formed at the articulated hinge may range from about 15 degrees to about 70 degrees. In some embodiments, the electric field strength in the focal ablation zone may be about 200 V / cm or more. When the electrodes (2916, 2926) are rotated about their corresponding hinges (2918, 2928) so that they are relatively far from each other (e.g., when the proximal portion (2912) and the distal portion (2914) form a larger angle), a relatively dispersed and lower intensity electric field is generated, resulting in a focal ablation lesion of relatively wide and shallower diameter on the endocardial surface. In this manner, by varying the degree of rotation of the electrodes (2916, 2926) relative to the proximal portions (2912, 2922) of the catheters (2910, 2920), the depth, shape, and / or size of the lesion can be controlled without disconnecting the ablation device (2900). These aspects are useful for producing multiple lesions of different sizes, shapes, and / or depths using the same ablation device. For example, the diameter of the lesion can be between about 2 mm and about 3 cm, and the depth of the lesion can be between about 2 mm and about 12 mm. Although the electrodes (2916, 2926) can be arranged to contact the endocardial tissue, it should be understood that the electrodes (2916, 2926) need not contact the endocardial tissue.

[0237] In some of these embodiments, a handle (not shown) may be coupled to the set of catheters (2910, 2920), and the handle is configured to effect transition of the catheters (2910, 2920) between the first, second, and third configurations. In some embodiments, actuation of one or more knobs, wheels, sliders, pullwires, and / or other control mechanisms in the handle may result in translation of one or more catheters (2910, 2920) through the outer catheter (2902) and / or rotation of the distal portions (2914, 2924) of the catheters about the hinges (2918, 2928).

[0238] Figures 29B-29C A first catheter (2910) having an articulated distal portion (2914) is depicted. The first catheter (2910) may include a proximal portion (2912) coupled to the distal portion (2914) via a hinge (2918). The distal portion (2914) may include an electrode (2916) as described herein. In some embodiments, the hinge (2918) may include a rotatable wheel. In other embodiments, the hinge (2918) may include a portion of the proximal portion (2912) or the distal portion (2914) having a reduced cross-sectional area relative to the first catheter (2910) that is more flexible than other portions of the catheter. In yet another embodiment, the hinge (2918) may include a joint, a rotatable wheel, a ball and socket joint, a condylar joint, a saddle joint, a pivot, and a track, among others.

[0239] The rotatable wheel may be coupled to a wire (2917) (e.g., a pull wire). For example, the wire (2917) may be attached around a hinge (2918), and the distal portion (2914) may be attached to a portion of the hinge (2918). Thus, actuation (2930) of the wire (2917) (e.g., pulling one end of the wire proximally) may in turn rotate the wheel (2918) and the distal portion (2914), causing the distal portion (2914) to rotate relative to the proximal portion (2912) of the first catheter (2910). In some embodiments, the distal portion may be rotated relative to the proximal portion at an angle of about 110 degrees to about 165 degrees, and the length of the distal portion may be between about 3 mm and about 12 mm. In some embodiments, the proximal end of the wire (2917) may be coupled to a handle (not shown) having a control mechanism (e.g., one or more knobs, wheels, sliders). The operator may operate the control mechanism to manipulate the guide wire (2917) to rotate the distal portion (2914) of the first catheter (2910) about the hinge (2918). The control mechanism of the handle may include a lock for fixing the position of the distal portion (2914). Fig.29B An embodiment of a first catheter (2910) is depicted having a distal portion (2914) positioned between a second configuration and a third configuration. Fig.29CAn embodiment of a first catheter (2910) in a third configuration is depicted.The electrodes (2916, 2926) may be offset toward each other in the third configuration.

[0240] Fig.29D An embodiment of an ablation device (2900) in a third configuration is depicted, wherein the distal portions of the first and second catheters (2910, 2920) extend outward from the outer catheter or sheath (2902) and rotate to a desired position (e.g., fully rotated, fully articulated) relative to the proximal portions (2912, 2922) of the catheters (2910, 2920). In some embodiments, the wires (2912, 2922) of each catheter (2910, 2920) can be coupled together at the handle so that actuation of the control mechanism controls the wires (2912, 2922) together so that the distal portions (2914, 2924) of each catheter (2910, 2920) can rotate simultaneously about their respective hinges (2918, 2928). In the second and third configurations, the first and second catheters (2910, 2920) can be offset from the longitudinal axis of the outer catheter (2902).

[0241] When the first and second catheters (2910, 2920) extend outward from the outer catheter (2902), one or more portions of the catheters (2910, 2920) can assume their natural (e.g., unconstrained) (one or more) shapes, such as curved shapes. The catheters (2910, 2920) can be pushed 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 so that the distal ends of the catheters (2910, 2920) can be configured to open away from each other. The minimum radius of curvature of the catheters (2910, 2920) can be in the range of about 1 cm or more. For example, the proximal portions (2912, 2922) can have a radius of curvature of about 1 cm or more. In some embodiments, the distal portions (2914, 2924) can have a radius of curvature of about 1 cm or more.

[0242] In some embodiments, the electrodes (2916, 2926) of the ablation device (2900) may include a length between about 0.5 mm and about 7.0 mm and a cross-sectional dimension (e.g., diameter) between about 0.5 mm and about 4.0 mm, including all values ​​and subranges therebetween. The electrodes (2916, 2926) of different catheters (2910, 2920) may be separated from each other by a distance between about 3.0 mm and about 20 mm, including all values ​​and subranges therebetween. The electrodes (2916, 2926) may be located about 1.0 mm to about 4.0 mm away from the distal end of their corresponding catheters (2910, 2920), including all values ​​and subranges therebetween. In some embodiments, the distal end of the catheter (2910, 2920) may include the electrodes (2916, 2926). One or more focal ablation lesions may be formed having a diameter between about 1.0 cm and about 2.0 cm, including all values ​​and subranges therebetween.

[0243] Fig.30 1 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 an inner lumen (3010). Each of the catheters (3020, 3030, 3040, 3050) may include a proximal portion (3023, 3033, 3043, 3053), a distal portion (3024, 3034, 3044, 3054), and a hinge (3021, 3031, 3041, 3051) coupling the proximal portion (3023, 3033, 3043, 3053) to the distal portion (3024, 3034, 3044, 3054). Each of the distal portions (3024, 3034, 3044, 3054) may include electrodes (3022, 3032, 3042, 3052). The distal ends of the catheters (3020, 3030, 3040, 3050) and / or the electrodes (3022, 3032, 3042, 3052) may include a non-invasive shape (e.g., a round, flat, curved and / or blunted portion) to reduce damage to tissue. Each of the catheters (3020, 3030, 3040, 3050) may include a hinge (3021, 3031, 3041, 3051) as described in detail herein. It should be understood that the ablation device (3000) may include any number of catheters, including a catheter collection of 2, 3, 4, 5, 6 or more catheters.

[0244] Each electrode (3022, 3032, 3042, 3052) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead may maintain a potential difference between about 200V and about 2000V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. Each of the catheters (3020, 3030, 3040, 3050) may include an insulated electrical lead for each electrode (3022, 3032, 3042, 3052) formed in the body of the catheter (3020, 3030, 3040, 3050) (e.g., within the lumen of the catheter (3020, 3030, 3040, 3050)). Each of the electrodes (3022, 3032, 3042, 3052) can be connected to a corresponding insulated electrical lead leading to a handle (not shown) coupled to the proximal portion of the catheter. In some embodiments, the size, shape and / or position of the electrodes (3022, 3032, 3042, 3052) can be different from each other.

[0245] 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 a focal ablation lesion generated by the ablation device (3000). The set of catheters (3020, 3030, 3040, 3050) can be configured to translate along a longitudinal axis to transition between first, second, and third configurations. In some embodiments, the ablation device (3000) can be configured to switch between the following configurations: a first configuration in which the catheters (3020, 3030, 3040, 3050) are collectively arranged substantially parallel to the longitudinal axis of the outer catheter or sheath (3010), and the distal portions of the catheters (3020, 3030, 3040, 3050) are arranged within the outer catheter (3010); and a second configuration in which the electrodes (3022, 3032, 3042, 3050) are arranged substantially parallel to the longitudinal axis of the outer catheter or sheath (3010). 2) pushed out and away from the distal end (3011) of the lumen of the outer catheter (3010) at any suitable distance; and a third configuration in which the distal portion of each of the catheters (3020, 3030, 3040, 3050) can be rotated, twisted or bent (e.g., Fig.30 For example, the first catheter (3020) may include a distal portion (3024) that is rotatable about a first hinge (3021), and the distal portion (3024) may be configured to position the distal portion (3024) relative to the proximal portion (3023) in a plurality of positions, as described above with respect to Figures 29A-29D It should be understood that the ablation device (3000) can be converted to any intermediate configuration between the first, second and third configurations, either continuously or in discrete steps. In the second configuration, the catheter set can be offset from the longitudinal axis.

[0246] In some embodiments, one or more pulse waveforms may be applied between electrodes (3022, 3032, 3042, 3052) configured in an anode group and a cathode group. For example, adjacent or approximately diametrically opposed electrode pairs may be activated together as an anode-cathode group. Fig.30 In one embodiment, the first electrode (3022) may be configured as an anode and paired with a second electrode (3032) configured as a cathode. The third electrode (3042) may be configured as an anode and paired with a fourth electrode (3052) configured as a cathode. The first and second electrode (3022, 3032) pairs may apply a first pulse waveform, followed sequentially by applying a second pulse waveform using the third and fourth electrode (3042, 3052) pairs. In another embodiment, the pulse waveform may be applied to each electrode simultaneously, wherein the second and third electrodes (3032, 3042) may be configured as anodes and the first and fourth electrodes (3022, 3052) may be configured as cathodes. It should be understood that any pulse waveform disclosed herein may be applied stepwise or sequentially to a sequence of anode-cathode electrodes. Some embodiments of the ablation device (3000) may have the same dimensions as the ablation device (2900) described above.

[0247] In other embodiments, one or more electrodes (3022, 3032, 3042, 3052) may be configured with a first electrical polarity, and one or more electrodes (not shown) arranged on the surface of the outer catheter shaft (3010) (not shown) may be configured with a second electrical polarity opposite to the first electrical polarity.

[0248] Figures 31A-31Bis a perspective view of yet another embodiment of an ablation device (3100) comprising an outer catheter or sheath (3110) defining a longitudinal axis and a catheter (3160) slidable within a lumen of the outer catheter. The catheter (3160) may extend distally from the lumen. The catheter (3160) may include a proximal portion (3160), a plurality of distal portions (3122, 3132, 3142, 3152), and an articulation (3162) coupling the proximal portion to each of the plurality of distal portions. For example, the articulation (3162) may include a hinge, a joint, a rotatable wheel, a ball and socket joint, a condylar joint, a saddle joint, a pivot, a track, and the like. The distal portions (3122, 3132, 3142, 3152) are folded back within the outer catheter (3110), and when each distal portion (3122, 3132, 3142, 3152) is folded, an internal spring (not shown) connected to each portion is 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 far enough out of the outer catheter (3110)), the spring adopts its inherent or unstressed configuration, resulting in articulation of the hinge (3162), so that the distal portions (3122, 3132, 3142, 3152) articulate outwardly and assume a configuration approximately perpendicular to the longitudinal axis of the catheter. Fig.31B As shown, the distal end of the catheter (3160) can be coupled to a set of electrodes (3120, 3130, 3140, 3150) via a hinge (3162). In some embodiments, the hinge (3162) can 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) can be arranged on the surface of the corresponding distal portions (3122, 3132, 3142, 3152). When the catheter (3160) is pushed out of the outer catheter (3110), the distal portions (3120, 3130, 3140, 3150) can assume their natural (e.g., unconstrained) shape so as to be approximately perpendicular to the longitudinal axis of the catheter (3160).

[0249] The electrodes (3120, 3130, 3140, 3150) may include a non-invasive shape (e.g., round, flat, curved and / or blunted portions) to reduce damage to tissue. Each electrode (3120, 3130, 3140, 3150) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead may maintain a potential difference between about 200V and about 2000V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. The catheter (3160) may include an insulated electrical lead of each electrode (3120, 3130, 3140, 3150) formed in the body (e.g., lumen) of the catheter (3160). Each electrode (3120, 3130, 3140, 3150) can be connected to a corresponding insulated electrical lead that leads to a handle (not shown) coupled to the proximal portion of the catheter (3160). In some embodiments, the size, shape and / or position of the electrodes (3120, 3130, 3140, 3150) can be different from each other.

[0250] The catheter (3160) can be configured to translate along the longitudinal axis to transition between first, second, and third configurations. In some embodiments, the ablation device (3100) can be configured to transition between the following configurations: a first configuration in which the electrode set (3120, 3130, 3140, 3150) is arranged substantially parallel to the longitudinal axis of the outer catheter (3110) and is within the outer catheter (3110) (e.g., Fig.31A ); a second configuration in which the electrode (3120, 3130, 3140, 3150) set is pushed out and away from the distal end (3111) of the outer catheter lumen at any suitable distance (not shown in Figure 31a); and a third configuration in which the electrodes (3120, 3130, 3140, 3150) can be rotated, twisted or bent (for example, about their corresponding hinges (3162)) relative to the proximal portion of the catheter (3160) Fig.31B ). The conversion from the first configuration to the second and third configurations can be performed by pushing the catheter (3160) and electrodes (3120, 3130, 3140, 3150) out of the distal end of the outer catheter (3110). It should be understood that the ablation device (3100) can be converted to any intermediate configuration between the first, second and third configurations continuously or in discrete steps.

[0251] Fig.31BElectrodes (3120, 3130, 3140, 3150) are shown evenly spaced to form a plus sign ("+") shape. However, the angle between adjacent electrodes (3120, 3130, 3140, 3150) can be selected based on the desired focal ablation pattern. Similarly, Fig.31B The electrodes (3120, 3130, 3140, 3150) are approximately perpendicular to the longitudinal axis of the catheter (3160), but can be adjusted based on a set of ablation parameters.

[0252] In some embodiments, one or more pulse waveforms may be applied between electrodes (3120, 3130, 3140, 3150) configured in an anode group and a cathode group. For example, adjacent or approximately diametrically opposed electrode pairs may be activated together as an anode-cathode group. Fig.31B In the embodiment of the present invention, the first electrode (3120) can be configured as an anode and paired with a third electrode (3140) configured as a cathode. The second electrode (3130) can be configured as an anode and paired with a fourth electrode (3150) configured as a cathode. The first and third electrode (3120, 3140) pair can apply a first pulse waveform, followed sequentially by applying a second pulse waveform using the second and fourth electrodes (3130, 3150). In another embodiment, the pulse waveform can be applied to each electrode simultaneously, wherein the first and second electrodes (3120, 3130) can be configured as anodes and the third and fourth electrodes (3140, 3150) can be configured as cathodes. It should be understood that any pulse waveform disclosed herein can be applied stepwise or sequentially to a sequence of anode-cathode electrodes.

[0253] In other embodiments, one or more electrodes (3120, 3130, 3140, 3150) may be configured with a first electrical polarity, and one or more electrodes arranged on the surface of the outer catheter shaft (3110) may be configured with a second electrical polarity opposite to the first electrical polarity.

[0254] Fig.32 is a cross-sectional schematic diagram of a high intensity electric field generated by an ablation device (3200) for ablating tissue, such as tissue in a ventricular chamber. For example, ablation device (3200) may be placed in the endocardial space of the left ventricle of a heart. Fig.32 The ablation device (3200) depicted in Fig.30 and 31A -31B those ablation devices (3000, 3100). In some embodiments, when in the third configuration, the electrodes (3210, 3220, 3230, 3240) can be placed near the tissue wall. In some embodiments, Fig.32The electrodes (3210, 3220, 3230, 3240) 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) may have a width of about 2 mm and a length of about 6 mm.

[0255] In some embodiments, the electrodes (3210, 3220, 3230, 3240) may form an anode-cathode pair. For example, the first electrode (3210) may be configured as an anode and the third electrode (3230) may be configured as a cathode. The first and second electrodes (3210, 3230) may have a potential difference of up to about 1500V. Activation of one or more electrodes (3210, 3220, 3230, 3240) of one or more catheters may generate one or more ablation zones along a portion of a heart chamber wall. The electric field profile (3350) is an isoamplitude line corresponding to an ablation zone (3350) having an electric field strength threshold of about 460v / cm when the first and third electrodes (3220, 3240) are activated. In some embodiments, the ablation zone (3350) may have a width of up to about 12mm and a length of up to about 20mm. Alternatively, the ablation device may be placed adjacent to or against a portion of the posterior wall of the left atrium and, by activating one or more electrodes, an appropriate pulse waveform is delivered for delivering irreversible electroporation energy to ablate tissue.

[0256] Fig.33A is a perspective view of another embodiment of an ablation device / apparatus (3300) in the form of a catheter, the ablation device / apparatus (3300) comprising an outer shaft (3310) extending to the proximal end of the device (3300), an inner shaft (3320) extending from the distal end of the shaft lumen (3312) of the outer shaft (3310), and a spline (3330) group coupled thereto. The inner shaft (3320) may be coupled to a handle (not shown) at the proximal end and arranged to a cap electrode (3322) at a distal portion (e.g., distal end). The inner shaft (3320) and the spline (3330) group may be translated along the longitudinal axis (3324) of the ablation device (3300). In some embodiments, the inner shaft (3320) and the spline (3330) group may be movable together or independently translatable. The inner shaft (3320) may be configured to slide within the lumen (3312) of the outer shaft (3310). The cap electrode (3322) may include an atraumatic shape to reduce damage to tissue. For example, the cap electrode (3322) may have a flat, annular, and / or rounded and blunt profile. The distal end of each spline in the spline (3330) group may be tethered to the distal portion of the inner shaft (3320). The proximal portion of the spline (3330) group may be attached to the outer shaft (3310). The ablation device (3300) may be configured as follows: Figure 21-25As shown, during use, a pulse waveform is delivered to tissue via electrodes (3332, 3334) on spline (3330) and distal cap electrode (3322).

[0257] Each spline of the spline (3330) group may include a set of electrodes (3332, 3334) on the surface of the spline. Each electrode set may include a distal electrode (3332) such that the spline group 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 electrode set on the same spline (e.g., the set of proximal electrodes (3334)). In addition, in some embodiments, the distal electrode (3332) may have only an exposed portion facing outward, that is, a portion facing away from the internal space / volume defined by the spline group. For example, if the distal electrode (3332) is composed of a metal ring, a portion of each ring may be insulated so that only the exposed portion or "window" facing outward is exposed for delivering ablation energy. The cap electrode (3322) and each distal electrode (3332) in the distal electrode set may have the same polarity during use. This combination of closely placed distal electrodes and cap electrodes with outwardly facing windows allows the distal end of the ablation device (3300) to generate and project a stronger electric field and thereby more effectively create a focal ablation lesion of tissue at a desired depth than using either of these electrodes alone.

[0258] Each spline (3330) of the ablation device (3300) may include at least a set of independently addressable electrodes (3332, 3334) on the surface of the spline (3330). A distal cap electrode (3322) may be formed at the distal end of the catheter device (3300). Each electrode (3322, 3332, 3334) may be coupled to an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead may maintain a potential difference of between about 200V and about 2000V across its thickness without dielectric breakdown. Each spline (3330) may 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) may include insulated electrical leads for the cap electrodes (3322). In other embodiments, a subset of the electrodes (3322, 3332, 3334) may be wired together. For example, the proximal electrodes (3334) of each spline in the set of splines (3330) may be wired together. As another example, all distal electrodes (3332) and the cap electrodes (3322) may be wired together.

[0259] In some embodiments, the spline (3330) set can be configured to transition between a first configuration in which the spline (3330) set is arranged substantially 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 spline (3330) set is curved radially outward from the longitudinal axis (3324). In this manner, the distal electrode (3332) set and the cap electrode (3322) can be shaped / oriented to form a Fig.33A , 33B and 33E. The cap electrode (3322) may be separated from each distal electrode of the distal electrode (3332) set by up to about 5 mm, including all values ​​and subranges therebetween. For example, the cap electrode (3322) may be separated from each distal electrode of the distal electrode (3332) set by between about 0.5 mm and about 3 mm. In the second configuration, the distal portion of each spline of the spline (3330) group may be at an angle (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 spline of the spline (3330) group in the second configuration may be at an angle (3336) between about 70 degrees and about 80 degrees relative to the longitudinal axis (3312). For example, in the second configuration, when the cap electrode (3322) and the distal electrode (3332) are collectively projected onto a plane perpendicular to the longitudinal axis (3324), they may appear in the shape of a "plus" symbol, such as Fig.33B shown in the front view.

[0260] In some embodiments, the inner shaft (3320) can be retracted into the outer catheter lumen (3312) by a predetermined amount to convert the ablation device (3300) from a first configuration to a second configuration. It should be understood that the spline (3330) group can be converted to any intermediate configuration between the first configuration and the second configuration continuously or in discrete steps. When not deployed, the spline (3330) group can form a shape that is generally parallel to the longitudinal axis (3324) of the inner shaft (3320), and when the distal end of the spline (3330) group is bent radially outward from the longitudinal axis (3324), a basket-like or spherical shape can be formed.

[0261] Fig.33A , 33B 33E shows a spline (3330) set, wherein each spline of the spline (3330) set includes one or more proximal electrodes (3334) and distal electrodes (3332) that differ in one or more of size, shape, number, and spacing. For example, Fig.33AOne distal electrode (3332) and two proximal electrodes (3334) are shown for each spline of the spline (3330) group. In some embodiments, each proximal electrode (3334) may be formed on the surface of its spline (3330) along its entire circumference (i.e., around the entire thickness of the spline). In some embodiments, each distal electrode (3332) may be formed on the surface of a portion of the circumference of its spline. That is, as Fig.33C and 33D As shown, the distal electrode (3332) may be partially located on the circumference of its corresponding spline and not cover the entire circumference of its spline (3330). For example, the distal electrode (3332) may surround the circumference of its corresponding spline and be partially covered by an insulating layer so that only a portion (e.g., a window) of the distal electrode (3332) is exposed. In some embodiments, one or more electrodes may be completely covered by a thin insulating layer for biphasic operation. In some embodiments, the distal electrode (3332) set of the spline (3330) group may subtend an angle (3333) between about 30 degrees and about 300 degrees around the center of its corresponding spline (3330), including all values ​​and subranges therebetween. For example, the distal electrode (3332) set of the spline (3330) group may subtend an angle (3333) between about 60 degrees and about 120 degrees around the center of its corresponding spline (3330). In this way, a significant portion 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 to assist in focal ablation, rather than away from the target tissue and projected into the blood.

[0262] In this manner, the distal electrode (3332) can be configured to face a particular direction. For example, Fig.33A and 33E In a second configuration, the distal electrode (3332) set and the cap electrode (3322) are shown facing generally forward at the distal end of the device (3300) when the distal end of the spline (3330) set is bent radially outward from the longitudinal axis (3324). In addition, the distal electrode (3332) can be arranged at the distal end of its spline so that the distal electrode (3332) of the spline (3330) set is arranged adjacent to the cap electrode (3322).

[0263] In some embodiments, each spline of the group of splines (3330) may include a set of electrodes (3332, 3334) having approximately the same size, shape, number, and spacing as the corresponding electrodes (3332, 3334) of the adjacent splines. The thickness of each spline (3330) may vary based on the number of electrodes (3332, 3334) formed on each spline (3330), which may correspond to the number of insulated electrical leads in the spline (3330). The splines (3330) may have the same or different materials, thicknesses, and / or lengths.

[0264] In some embodiments, the cap electrode (3322) and the electrode (3332, 3334) set may be configured in an anode-cathode group. For example, each distal electrode in the cap electrode (3322) and the distal electrode (3332) set may be configured as an anode, and all proximal electrodes (3334) may be configured as cathodes (or vice versa). In some embodiments, the distal electrode (3332) set and the proximal electrode (3334) set may have opposite polarities. For example, the distal electrode (3332) and the proximal electrode (3334) set for a given spline may have opposite polarities. The cap electrode (3322) and the distal electrode (3332) set may have the same polarity. As discussed herein, the distal electrode (3332) set and the cap electrode (3322) may be wired together. In some embodiments, a set of electrodes (3332, 3334) of one or more splines (3332, 3334) of a cap electrode and spline (3330) set can be activated together to deliver a pulse waveform for irreversible electroporation. In other embodiments, pulse waveform delivery can be repeated sequentially on a predetermined subset of the set of electrodes (3332, 3334).

[0265] In some embodiments, the distal electrode (3332) set may be separated from the cap electrode (3322) by up to 3 mm from the distal end of each spline (3330). In some embodiments, the distal electrode (3332) set may be separated from the proximal electrode (3334) set by between about 1 mm and about 20 mm. In some embodiments, each electrode of the electrode (3332, 3334) set may include a diameter between about 0.5 mm and about 3 mm. In some embodiments, the cap electrode (3322) may include a cross-sectional diameter between about 1 mm and about 5 mm. In some embodiments, each electrode in the electrode (3332, 3334) set may have a length between about 0.5 mm and about 5 mm. In some embodiments, the spline (3330) set in the second configuration may have an expanded cross-sectional diameter (i.e., the effective diameter of the expanded configuration or the second configuration at its largest portion) between about 6 mm and about 24 mm. In some embodiments, the spline (3300) set may extend from the distal end (3312) of the outer shaft (3310) between about 6 mm and about 30 mm. In some embodiments, the outer shaft (3310) may have an outer diameter between about 1.5 mm and about 6.0 mm.

[0266] The ablation device (3300) as described herein can be arranged in a first configuration prior to delivering a pulse waveform and converted to 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) can be coupled to the catheter (3300) and the spline (3330) group, and the handle is configured to affect the conversion of the spline (3330) group between the first configuration and the second configuration. For example, the handle can be configured to translate the inner shaft (3320) relative to the outer shaft (3310). For example, retracting the inner shaft (3320) into the inner cavity (3312) of the outer shaft (3310) can deploy the spline (3330) group into the bulb-like shape shown herein. In some embodiments, actuation of a knob, wheel, or other control mechanism in the device handle can cause translation of the inner shaft (3324) and cause deployment of the spline (3330) group. In some embodiments, electrical leads of at least two electrodes in the set of electrodes (3322, 3332, 3334) may be electrically coupled at or near a proximal portion of the ablation device (3300), such as, for example, within a handle.

[0267] In addition, the catheter handle (not shown) may include a mechanism for deflecting or steering the distal portion of the catheter device (3300). For example, a pull wire may 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), wherein tensioning of the pull wire causes deflection of the distal portion of the device (3300). The deflection of the device (3300) can help the user position the device (3300) in a controlled manner at an appropriate anatomical position. In some embodiments, the distal cap electrode (3322) can be electrically connected separately from the distal spline electrode (3332). In this way, the intracardiac ECG signal can be recorded only from the distal cap electrode (3322). In some embodiments, one or more distal spline electrodes (3332) can be electrically connected separately to monitor the intracardiac ECG signal 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 to deliver ablation energy. It should be understood that any ablation device described herein may be used with separately electrically wired electrodes to monitor intracardiac ECG signals from each such electrode. In some embodiments, some electrodes on one or more splines of a spline set may be used for ECG monitoring, while other electrodes may be used to deliver ablation energy.

[0268] The ablation device (3300) may include any number of splines, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (3300) may include 3 to 20 splines. For example, the ablation device (3300) may include 4 to 12 splines.

[0269] Each spline of the spline (3300) group may include a corresponding electrode (3332, 3334) having an atraumatic, generally circular shape to reduce damage to tissue. In this manner, as described herein, the distal electrode in the second configuration may be held close to or placed against a portion of the atrial wall of the left atrium so as to generate a foci thereon by activating the appropriate electrode using any suitable polarity combination. For example, the cap electrode (3322) and distal electrode (3332) of the spline (3330) group may be placed in contact with or close to the tissue wall (3350) in an orientation that is approximately perpendicular or generally oblique to the tissue wall, as described herein. Fig.33E The configuration of the distal electrodes (3322, 3332) allows for the creation of a focal lesion at a desired depth even when the ablation device (3300) in the deployed configuration is adjacent to the tissue wall (3350) at an angle (eg, obliquely).

[0270] In some embodiments, Figures 33A-33E The ablation device (3300) shown in FIG. 3 may be configured for focal ablation and may include an atraumatic distal portion or cap (3322) that does not include a distal electrode.

[0271] Fig.38Ais a perspective view of another embodiment of an ablation device / apparatus (3800) in the form of a catheter, the ablation device / apparatus (3800) comprising an outer shaft (3810) (e.g., a first shaft) extending to the proximal end of the device (3800), an inner shaft (3820) (e.g., a second shaft) extending from the distal end of the shaft lumen (3812) of the outer shaft (3810), and a set of splines (3830) coupled thereto. The ablation device / apparatus (3800) may include components and / or functions similar to those of the ablation device / apparatus (3300), but the ablation device / apparatus (3800) does not include a cap electrode. The inner shaft (3820) may be coupled to a handle (not shown) at a proximal end and have a distal end disposed near or adjacent to a distal portion (3822) (e.g., a distal end). For example, the distal portion (3822) may be coupled to the distal end of the inner shaft (3820). The proximal end of the spline (3830) group can be coupled to the 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 spline (3830) group can translate along the 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 spline (3830) group can move together. The spline can be flexible. When the inner shaft translates relative to the outer shaft (3810), the spline can be converted between configurations (e.g., deployed, not deployed). The inner shaft (3820) can be configured to slide within the inner cavity (3812) of the outer shaft (3810). The distal portion (3822) can include a non-destructive shape to reduce damage to tissue. For example, the distal portion (3822) can have a flat, annular and / or circular and blunt profile. In some embodiments, the distal portion (3822) may include a cap. Figures 38A-38D , the distal portion (3822) does not include an electrode. The distal end of each spline in the spline (3830) group can be tethered to and / or coupled to the distal portion (e.g., the distal end) of the inner shaft (3820). The proximal portion of the spline (3830) group can be attached to and / or coupled to the outer shaft (3810). The ablation device (3800) can be configured as follows: Figure 21-25 As disclosed in the example of , during use, a pulse waveform is delivered to tissue via electrodes (3832, 3834) on the spline (3830).

[0272] The ablation device / apparatus may include a plurality of electrodes configured to generate an electric field for ablating tissue. Each spline in the spline (3830) group may include a set of electrodes (3832, 3834) from a plurality of electrodes formed on the surface of the spline. Each electrode set may include a distal electrode (3832), such that the spline group includes a set of distal electrodes (3832). Each distal electrode (3832) is closest to the distal portion (3822) relative to other electrodes (e.g., a set of proximal electrodes (3834)) of its corresponding electrode set on the same spline. Each electrode set may include a proximal electrode, such that the spline group includes a set of proximal electrodes (3834). In some embodiments, the electrode (3832, 3834) sets may each extend around the circumference of its spline. For example, the distal electrode (3832) may be formed of a metal ring surrounding the circumference of its spline. In some embodiments, each distal electrode (3832) in the distal electrode set may have the same polarity during use. This combination of closely placed distal electrodes allows the distal end of the ablation device (3800) to generate and project a stronger electric field and thereby more effectively create a focal ablation lesion of tissue at a desired depth than using any of these electrodes alone. In other embodiments, at least two distal electrodes may have the same electrical polarity for ablation delivery.

[0273] Each spline (3830) of the ablation device (3800) may include at least a set of independently addressable electrodes (3832, 3834) on the surface of the spline (3830). Each electrode (3832, 3834) may be coupled to an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead may maintain a potential difference of between about 200V and about 3000V across its thickness without dielectric breakdown. Each spline (3830) may include an insulated electrical lead for 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) may include an insulated electrical lead for one or more distal electrodes (3832). In other embodiments, a subset of electrodes (3832, 3834) may be wired together. For example, the proximal electrodes (3834) of each spline in the spline (3830) group may be wired together. As another example, all distal electrodes (3832) may be wired together.

[0274] In some embodiments, the spline (3830) group can be configured to transition to a plurality of states between and including an undeployed configuration and an expanded configuration, wherein in each of the plurality of states, a distal portion of each spline from the spline group is disposed at one of a corresponding plurality of angles relative to a proximal portion of each spline from the spline group. In some embodiments, the spline (3830) group can be configured to transition to each of the plurality of states in response to movement of the inner shaft (3820) relative to the outer shaft (3810) along the longitudinal axis (3824). For example, the spline (3830) group can be configured to transition to each of the plurality of states. Fig.38A The first configuration (eg, undeployed configuration) shown (wherein the spline (3830) set is arranged generally parallel to the longitudinal axis (3824) of the ablation device (3800) and as shown in FIG. Fig.38B The embodiment of the present invention is a schematic diagram of a second configuration (e.g., an expanded configuration, a basket configuration, a deployed configuration) in which the distal portion (3804) of each spline of the set of splines (3830) is curved radially outward from the longitudinal axis (3824). In other words, the distal portion (3804) of the splines (3830) is curved relative to the proximal portion (3802) of the splines (3830), such as with respect to Fig.38B and 38C As described in more detail, 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 greater in the expanded configuration of the spline set than in the first configuration.

[0275] Fig.38C is a perspective view of a spline (3830) with two unit tangent vectors. Fig.38A and 38B A set of splines (3830) having a basket-like or pyramid-like shape is depicted, and may correspond to the shape of the splines in the second configuration. At each point along the splines (3830), a unit tangent vector u may be defined. Fig.38CA first unit tangent vector u1 (3840) at the distal portion (3804) of the spline (3830) and a second unit tangent vector u2 (3844) at the proximal portion (3802) of the spline (3830) are shown. For example, the unit tangent vector u1 (3840) corresponds to the distal electrode (3832) and extends in the distal direction of the distal electrode (3832). Similarly, the unit tangent vector u2 (3844) corresponds to the proximal electrode (3832) and extends in the distal direction of the proximal electrode (3832). The first line (3842) is tangent to the distal electrode (3832), and the second line (3846) is tangent to the proximal electrode (3834). The intersection of the first line (3842) and the second line (3846) forms a Fig.38C Angle (3848) shown.

[0276] In some embodiments, the spline (3830) set can be configured to transition to a plurality of states between and including an undeployed configuration and a deployed configuration, wherein an angle between a first unit tangent vector u1 (3840) extending through a length of a distal portion of each spline from the spline (3830) set and a second unit tangent vector u2 (3844) extending through a proximal portion of each spline from the spline (3830) set varies between about 70 degrees and about 180 degrees. A preselected portion of the plurality of electrodes (3832, 3834) can be configured to be activated in each of the plurality of states to generate an electric field for ablating a tissue wall by irreversible electroporation.

[0277] The dot product of the unit vectors u1 and u2 is equal to the cosine of the angle (3848). In some embodiments, the dot product of the corresponding unit tangent vectors is negative. That is, the angle (3848) between the distal electrode (3832) and the proximal electrode (3834) is between about 90 degrees and about 180 degrees.

[0278] Depending on the particular application, the distal electrode (3432) and the proximal electrode (3834) can be at different angles. For example, the inner shaft (3820) can be retracted to different positions relative to the outer shaft (3810) to form different angles between the distal electrode (3432) and the proximal electrode (3834). The adjustability of the angle between the distal electrode (3432) and the proximal electrode (3834) can be advantageous for accommodating different applications. For example, when performing atrial ablation, the distal electrode (3432) and the proximal electrode (3834) can be at a smaller angle relative to each other, for example, at an angle of less than about 90 degrees, so that the spline (3830) group forms an expanded structure with a more rounded distal portion. The following description Fig.40A more detailed view of the deployed configuration is provided. In such a deployment, the angle between the unit vectors u1 and u2 can be about 70 degrees or greater. Alternatively, when performing ventricular ablation, the distal electrode (3432) and the proximal electrode (3834) can be at a greater angle to each other, for example, at an angle between about 90 degrees and about 180 degrees, so that the spline (3830) group forms an deployed configuration with a more orthogonal or flatter distal end. Fig.38D As shown, a flatter distal end may allow the distal end of the ablation device (3800) to be generally closer to the endocardial surface (bringing a greater number of distal electrodes closer to the tissue surface) and be used to form lesions via focal ablation.

[0279] In this manner, the distal electrode (3832) collection can be shaped / oriented to form Fig.38B , 38C and the second configuration shown in 38D. The distal portion (3822) may be separated from each distal electrode of the distal electrode (3832) set by, for example, up to about 6 mm, including all values ​​and subranges therebetween. For example, the distal portion (3822) may be separated from each distal electrode of the distal electrode (3832) set by between about 0.5 mm and about 3 mm. In the second configuration, the distal portion (3804) of each spline of the spline (3830) set may be at an angle (3836) between about 90 degrees and about 180 degrees relative to the proximal portion (3802), including all values ​​and subranges therebetween. The distal portion (3804) is generally linear in the second configuration, depending in part on the length and stiffness of the distal electrode (3832) set. For example, in the second configuration, when the distal portion (3804) is positioned similar to Fig.33B When the front view of the device / apparatus (3300) is shown projected onto a plane perpendicular to the longitudinal axis (3824), the distal portion (3822) and the collection of distal electrodes (3832) can appear in the shape of a "+" symbol (e.g., an "X" or cross).

[0280] In some embodiments, the inner shaft (3820) can be retracted into the outer catheter lumen (3812) by a predetermined amount to convert the ablation device (3800) from a first configuration to a second configuration. It should be understood that the spline (3830) group can be converted to any intermediate configuration between the first configuration and the second configuration continuously or in discrete steps. When not deployed, the spline (3830) group can form a shape that is generally parallel to the longitudinal axis (3824) of the inner shaft (3820), and when the distal portion of the spline (3830) group is bent radially outward from the longitudinal axis (3824) and angled relative to the proximal portion (3802) of the spline, a basket or pyramidal shape can be formed.

[0281] Fig.38A , 38B, 38C and 38D show a spline (3830) group, wherein each spline of the spline (3830) group includes a distal electrode (3832) and a plurality of proximal electrodes (3834). In some embodiments, different numbers 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 One distal electrode (3832) and two proximal electrodes (3834) are shown for each spline of the spline (3830) group. In some embodiments, each spline in the spline (3830) group may include multiple proximal electrodes (3834). The proximal electrodes (3834) may form a proximal electrode area of ​​a given length, but by being divided into a group of electrode segments of shorter lengths, the proximal electrodes (3834) are able to achieve flexibility of the proximal portion (3802) of the spline (3830). In some embodiments, each proximal electrode (3834) may be formed on the surface of its spline (3830) along its entire circumference (e.g., around the entire circumference of the spline). In some embodiments, each distal electrode (3832) may be formed on the surface of its spline (3830) along its entire circumference. That is, the distal electrode (3832) may cover (e.g., extend around, surround) the entire circumference of its spline (3830). Additionally or alternatively, one or more proximal electrodes (3834) may include a coil electrode that enables flexibility of the proximal portion (3802) of the spline (3830). For example, in one embodiment, multiple proximal electrodes (3834) may be replaced with a single proximal electrode (3834) having a coiled configuration that is sufficiently flexible to enable the device / apparatus (3800) to transition between its first configuration and its second (deployed) configuration.

[0282] The distal electrode (3832) set can be configured to face a particular direction. For example, Fig.38B , 38C 38D shows that in a second configuration when the distal portion (3822) of the spline (3830) set is bent radially outward from the longitudinal axis (3824), the distal electrode (3832) set and the distal portion (3822) face generally forward at the distal end of the device (3800). In addition, the distal electrode (3832) can be arranged at the distal end of its spline so that the distal electrode (3832) of the spline (3830) set is arranged near the distal portion (3822) of the device (3800).

[0283] In some embodiments, each spline of the set of splines (3830) may include a set of electrodes (3832, 3834) having substantially the same size, shape, number, and spacing as corresponding electrodes (3832, 3834) of adjacent splines. The thickness of each spline (3830) may vary based on the number of electrodes (3832, 3834) formed on each spline (3830), which number may correspond to the number of insulated electrical leads in the spline (3830). The splines (3830) may have the same or different materials, thicknesses, and / or lengths.

[0284] In some embodiments, the set of electrodes (3832, 3834) of each spline of the group of splines (3830) can have substantially the same size, shape, number, and spacing as the corresponding electrodes (3832, 3834) of adjacent splines. 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.

[0285] In some embodiments, each spline of the spline (3830) group may include a plurality of proximal electrodes (3834). The proximal electrodes (3834) may form a proximal electrode region of a given length, but by being divided into a group of electrode segments of shorter lengths, the proximal electrodes (3834) are able to achieve flexibility of the proximal portion (3802) of the spline (3830). In some embodiments, at least one flexible portion is arranged between adjacent side 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 the distal electrode set may be at the same distance from the distal end of the inner shaft (3820).

[0286] The electrode set (3832, 3834) may be appropriately polarized to deliver high voltage pulses corresponding to pulsed electric field (PEF) ablation energy, which may be applied to tissue to cause cell death through irreversible electroporation. In some embodiments, at least one distal electrode from the distal electrode set may be configured to be activated with a first polarity, and at least one proximal electrode from the proximal electrode set may be configured to be activated with a second polarity opposite to the first polarity to jointly generate 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, thereby defining a bipolar pairing of electrodes for delivering PEF ablation energy. In general, a bipolar-like sequence may be defined for PEF ablation delivery. As another example, all distal electrodes (3832) may have one electrical polarity, while all proximal electrodes (3834) may have an opposite electrical polarity.

[0287] In some embodiments, the electrode set (3832, 3834) may be configured as an anode-cathode group. For example, each distal electrode of the distal electrode (3832) set may be configured as an anode, and the proximal electrode (3834) set may be configured as a cathode (or vice versa). In some embodiments, the distal electrode (3832) set and the proximal electrode (3834) set may have opposite polarities. For example, the distal electrode (3832) and proximal electrode (3834) sets for a given spline may have opposite polarities. The distal electrode (3832) set may have the same polarity. As discussed herein, the distal electrode (3832) set may be wired together. In some embodiments, the electrode (3832, 3834) sets of one or more splines in the spline (3830) set may be activated together to deliver a pulse waveform for irreversible electroporation. For example, a preselected portion of the plurality of electrodes may be activatable 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, pulse waveform delivery may be repeated sequentially on a predetermined subset of the set of electrodes (3832, 3834). For example, a particular activation sequence may include activating the distal electrodes (3432) of half of the spline (3830) (e.g., Figures 38A-38D ) and a proximal electrode (3834) that activates half of the splines (3830) (e.g., Figures 38A-38D ). Depending on the desired direction of the electric field generated by the electrodes (3832, 3834), the activated distal electrode (3832) and the proximal electrode (3834) can be offset from each other (e.g., the distal electrode (3832) can be located on adjacent splines (3830) as the proximal electrode (3834), or the distal electrode (3832) can be offset from the proximal electrode (3834) at an angle (e.g., 90 degrees). In some embodiments, the spline group can be configured to ablate a tissue wall regardless of the orientation of the spline group relative to the tissue wall. In some embodiments, a preselected portion of the plurality of electrodes may include electrodes from the plurality of electrodes oriented close to the tissue surface.

[0288] In some embodiments, the distal electrode (3832) set may be separated from the distal portion (3822) by up to 6 mm from the distal end of each spline (3830). In some embodiments, the distal electrode (3832) set may be separated from the proximal electrode (3834) set by between about 1 mm and about 20 mm. In some embodiments, each electrode of the electrode (3832, 3834) set may include a diameter 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 between about 0.7 mm and about 5 mm. In some embodiments, each electrode in the electrode (3832, 3834) set may have a length between about 0.5 mm and about 5 mm. In some embodiments, the spline (3830) group in the second configuration (e.g., the expanded configuration) may have an expanded cross-sectional diameter (i.e., the effective diameter of the expanded configuration or the second configuration at a plane corresponding to its largest portion) between about 6 mm and about 24 mm. In some embodiments, the spline (3800) set may extend between about 6 mm and about 24 mm from the distal end (3812) of the outer shaft (3810). For example, when the spline (3830) set is in the expanded configuration, the spline (3830) set may extend outwardly from the distal end of the outer shaft (3810) a radial distance between about 6 mm and about 24 mm. In some embodiments, the outer shaft (3810) may have an outer diameter between about 1.5 mm and about 6.0 mm.

[0289] The ablation device (3800) as described herein can be arranged in a first configuration prior to delivering a pulse waveform and converted to 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) can be coupled to the catheter (3800) and the spline (3830) group, and the handle is configured to affect the conversion of the spline (3830) group between the first configuration and the second configuration. For example, the handle can be configured to translate the inner shaft (3820) relative to the outer shaft (3810). For example, retracting the inner shaft (3820) into the inner cavity (3812) of the outer shaft (3810) can deploy the spline (3830) group into a basket-like or pyramid-like shape as shown herein. In some embodiments, actuation of a knob, wheel, or other control mechanism in the device handle can cause translation of the inner shaft (3824) and cause deployment of the spline (3830) group. In some embodiments, electrical leads of at least two electrodes of the electrode set (3832, 3834) may be electrically coupled at or near a proximal portion of the ablation device (3800), such as, for example, within a handle.

[0290] In addition, the catheter handle (not shown) may include a mechanism for deflecting or steering the distal portion (3804) of the catheter device (3800). For example, a pull wire may 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), wherein tensioning of the pull wire causes deflection of the distal portion (3804) of the device (3800). The deflection of the device (3800) can help the user position the device (3800) in a suitable anatomical position in a controlled manner. In some embodiments, one or more distal spline electrodes (3832) can be separately electrically wired to monitor intracardiac ECG signals from each such electrode (3832). In some embodiments, some distal spline electrodes (3832) can be used for ECG monitoring, while other distal spline electrodes (3832) can be used to deliver ablation energy. In some embodiments, some proximal spline electrodes (3834) can be separately wired for intracardiac ECG monitoring. It should be understood that any ablation device described herein can be used with electrodes that are separately electrically wired to monitor intracardiac ECG signals from each such electrode. In some embodiments, some electrodes on one or more splines of a spline set can be used for ECG monitoring, while other electrodes can be used to deliver ablation energy.

[0291] The ablation device (3800) may include any number of splines, e.g., 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) may include 3 to 20 splines. For example, the ablation device (3800) may include 4 to 12 splines.

[0292] Each spline in the spline (3800) group may include a corresponding electrode (3832, 3834) having an atraumatic, generally circular shape to reduce damage to tissue. In this manner, as described herein, the distal electrode in the second configuration may be held close to or placed against a portion of the atrial wall of the left atrium, or generally, any atrium or ventricle, so as to generate a foci thereon by activating the appropriate electrode using any suitable polarity combination. For example, the distal portion (3822) of the spline (3830) group and / or the distal electrode (3832) may be placed in contact with or proximate to the tissue wall (3850) in an orientation that is approximately perpendicular or generally oblique to the tissue wall, as described herein. Fig.38D The configuration of the distal electrode (3832) allows for the creation of a focal lesion at a desired depth even when the ablation device (3800) in the deployed configuration is adjacent to the tissue wall (3850) at an angle (eg, obliquely).

[0293] As described above, in some embodiments, the angle between the distal electrode (3832) and the proximal electrode (3834) can vary based on a particular application. More specifically, the spline (3830) group can be configured to transition to a plurality of states between and including an undeployed configuration and an expanded configuration, wherein the angle between a first unit tangent vector u1 (3840) extending through the length of the distal portion of each spline from the spline (3830) group and a second unit tangent vector u2 (3844) extending through the proximal portion of each spline from the spline (3830) group varies between about 70 degrees and about 180 degrees. For example, when the device is used 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, so that the deployed structure of the spline (3830) has a flatter distal end to be suitable for being generally positioned closer to the tissue and providing a larger surface area to form a deeper focal lesion. Alternatively, when the device is used for atrial ablation and / or ablation of thinner tissue, the spline group can be converted from multiple states to one or more states with an angle between about 70 degrees and about 90 degrees or between about 70 degrees and about 120 degrees, including all sub-ranges 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 sub-ranges and values ​​therebetween). Such a shape enables the spline (3830) to be placed in different orientations relative to the tissue surface. For example, Fig.40 As depicted, an ablation device (4000) including a set of splines (4030) can be placed so that the splines (4030) are oriented transversely relative to a tissue wall (4050). Each spline (4030) can have at least one distal electrode (4032) and at least one proximal electrode (4034). As depicted, the distal electrode (4032) can be at an angle (4048) less than about 90 degrees relative to the proximal electrode (4034), that is, a unit tangent vector u1 extending through the distal electrode (4032) can be at an angle (4048) less than about 90 degrees relative to a unit tangent vector u2 extending through the proximal electrode (4034). In one 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. Regardless of the orientation of the splines (4030) relative to the tissue wall (4050), the same set of electrodes (4032, 4034) may be activated to ablate tissue. Alternatively, different sets of electrodes may be activated to ablate tissue depending on which splines (4030) are oriented closer to the tissue surface.

[0294] Fig.39A is a perspective view of another embodiment of an ablation device / apparatus (3900) in the form of a catheter, the device / apparatus (3900) comprising an outer shaft (3910) extending to the proximal end of the device (3900), a first inner shaft (3920) and a second inner shaft (3921) extending from the distal end of the shaft lumen (3912) of the outer shaft (3910), a spline (3930) set, and an expandable member (3950). The ablation device (3900) may have components that are functionally and / or structurally similar to other ablation devices described herein, such as the ablation device (3800). The second inner shaft (3921) may extend from the distal end of the first inner shaft (3920) and be coupled to the spline (3930) set. The ablation device / apparatus (3900) may include components and / or functions similar to the ablation devices / 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 to a catheter handle (not shown) at respective proximal ends. The distal end of the second inner shaft (3921) can be coupled to the distal portion (3922). The proximal portion of the expandable 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 arranged distal to the distal end of the outer shaft (3910) and in the space between the spline (3930) group.

[0295] Optionally, the 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). The proximal portion of each spline of the spline (3930) group may be coupled to the distal portion of the outer shaft (3910). The distal portion of each spline in the spline (3930) group 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 arranged in the space between the spline (3930) groups so as to be surrounded by the spline (3930) group. In some embodiments, the expandable member (3950) is translatable separately from the spline (3930) group, for example, the expandable member (3950) is movable relative to the spline (3930) group. In these embodiments, the expandable member (3950) can be moved to a specific predetermined position relative to the spline (3930) group. In some embodiments, the expandable member (3950) can be coupled to a shaft or other structure that is different from the first inner shaft (3920), the second inner shaft (3921), and / or the distal portion (3922). For example, the expandable member (3950) can be coupled to a third inner shaft (not depicted). In some embodiments, the expandable member defines a lumen, and the second inner shaft (3921) can extend through the lumen of the expandable member.

[0296] The first inner shaft (3920), the second inner shaft (3921), and the spline (3930) group can translate along the longitudinal axis (3924) of the ablation device (3900). In some embodiments, the spline group can be configured to convert to multiple states in response to the expandable member converting to the expanded configuration. For example, the spline (3930) group can be configured to convert to the expanded configuration in response to the second inner shaft (3921) moving relative to the first inner shaft (3920). As another example, the spline (3930) group can be configured to convert to the 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 spline (3930) group can move together. The spline (3930) can be flexible. When the first and second inner shafts (3920, 3921) translate relative to the outer shaft (3910), the spline can be converted between configurations (e.g., deployed, not deployed). The first inner shaft (3920) and the second inner shaft (3921) can be configured to slide within the inner cavity (3912) of the outer shaft (3910). The spline (3930) set can be translated by moving the second inner shaft (3921) relative to the outer shaft (3910) using an actuation mechanism such as a handle.

[0297] The distal portion (3922) may include a non-invasive shape to reduce damage to tissue. For example, the distal portion (3922) may have a flat, annular and / or rounded and blunted profile. In some embodiments, the distal portion (3922) may include a cap. In Figures 39A-39D, the distal portion (3922) does not include an electrode. This allows the shape, profile, and size of the distal portion (3922) to be configurable and / or reduced. The distal end of each spline in the spline (3930) group can be tethered to and / or coupled to the distal portion of the second inner shaft (3921). The proximal portion of the spline (3930) group can be attached to and / or coupled to the outer shaft (3910). The ablation device (3900) can be configured, such as Figure 21-25 As shown, during use, a pulse waveform is delivered to tissue via electrodes (3932, 3934) on spline (3930).

[0298] The ablation device / apparatus may include a plurality of electrodes configured to generate an electric field for ablating tissue. Each spline in the spline (3930) group may include a set of electrodes (3932, 3934) from a plurality of electrodes formed on the surface of the spline. Each electrode set may include a distal electrode (3932), such that the spline group includes a set of distal electrodes (3932). Each of the distal electrodes (3932) is closest to the distal portion (3922) relative to other electrodes (e.g., a set of proximal electrodes (3934)) of its corresponding electrode set on the same spline. Each electrode set may include a proximal electrode, such that the spline group includes a set of proximal electrodes (3934). In some embodiments, the electrode sets (3932, 3934) may each extend around the circumference of their splines. For example, the distal electrode (3932) may be formed of a metal ring surrounding the circumference of its spline. In some embodiments, each distal electrode (3932) in the distal electrode set may have the same polarity in common during use. This combination of closely placed distal electrodes allows the distal end of the ablation device (3900) to generate and project a stronger electric field, thereby more effectively creating a focal ablation lesion of tissue at a desired depth than any one of these electrodes alone. In other embodiments, at least two distal electrodes may have the same electrical polarity for ablation delivery.

[0299] Each spline (3930) of the ablation device (3900) may include at least an independently addressable set of electrodes (3932, 3934) on the surface of the spline (3930). Each electrode (3932, 3934) may be coupled to an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each electrical lead may maintain a potential difference of between about 200V and about 3000V across its thickness without dielectric breakdown. Each spline (3930) may include an insulated electrical lead for 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) may include an insulated electrical lead for one or more distal electrodes (3932). In other embodiments, a subset of electrodes (3932, 3934) may be wired together. For example, the proximal electrodes (3934) of each spline in the set of splines (3930) may be wired together. As another example, all distal electrodes (3932) may be wired together.

[0300] In some embodiments, the spline (3930) group can be configured to transition to a plurality of states between and including an undeployed configuration and an deployed configuration, wherein in each of the plurality of states, a distal portion of each spline from the spline group is at one of a corresponding plurality of angles relative to a proximal portion of each spline from the spline group. In some embodiments, the spline (3930) group 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 spline (3930) group can be configured to transition to one or more of the plurality of states. Fig.39C The first configuration shown in which the spline (3930) group is arranged generally parallel to the longitudinal axis (3924) of the ablation device (3900) and the Fig.39A , 39B The spline (3930) can be configured to transition between a second configuration (e.g., an expanded configuration, a basket configuration, a deployed configuration) shown in FIG39D (in which the distal portion (3904) of each spline of the spline (3930) is curved radially outward from the longitudinal axis (3924). That is, the distal portion (3904) of the spline (3930) is curved relative to the proximal portion (3902) of the spline (3930), such as with respect to FIG39D. 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-like or pyramid-like shape. Fig.39C As shown, when the set of splines (3930) is in the first configuration, expandable member (3950) is in the deflated configuration. The set of splines (3930) in the second configuration may define a space therebetween that is greater in the expanded configuration of the set of splines than in the first configuration.

[0301] Fig.39D is a perspective view of a spline (3930) with two unit tangent vectors. Fig.39A and 39B A set of splines (3930) having a basket-like or pyramid-like shape is depicted, and may correspond to the shape of the splines in the second configuration. At each point along the splines (3930), a unit tangent vector u may be defined. Fig.39DA unit tangent vector u1 (3940) at the distal portion (3904) of the spline (3930) and a unit tangent vector u2 (3944) at the proximal portion (3902) of the spline (3930) are shown. For example, the unit tangent vector u1 (3940) corresponds to the distal electrode (3932) and extends in the distal direction of the distal electrode (3932). Similarly, the unit tangent vector u2 (3944) corresponds to the proximal electrode (3934) and extends in the distal direction of the proximal electrode (3932). The first line (3942) is tangent to the distal electrode (3932), and the second line (3946) is tangent to the proximal electrode (3934). The intersection of the first line (3942) and the second line (3946) forms a Fig.39D The first angle (3948) is shown. Similarly, the intersection of the first line (3942) and the longitudinal axis (3924) forms a second angle (3960).

[0302] In some embodiments, the dot product of the unit vectors u1 and u2 is equal to the cosine of the angle (3948). In some embodiments, the dot product of the respective unit tangent vectors 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 a second configuration (e.g., an expanded configuration), a 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. Fig.39D shown.

[0303] In this manner, the distal electrode (3932) collection can be shaped / oriented to form Fig.39A , 39B and the second configuration shown in 39D. The distal portion (3922) can be separated from each distal electrode of the set of distal electrodes (3932) by up to about 6 mm, including all values ​​and subranges therebetween. For example, the distal portion (3922) can be separated from each distal electrode 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 spline (3930) set can be angled relative to the proximal portion (3902) between about 90 degrees and about 180 degrees, including all values ​​and subranges therebetween.

[0304] The distal portion (3904) is generally linear in the second configuration, depending in part on the length and stiffness of the distal electrode (3932) set. For example, in the second configuration, when the distal portion (3904) is substantially linear, the distal portion (3904) is substantially linear. Fig.33BWhen the front view of the device / apparatus (3300) is shown projected onto a plane perpendicular to the longitudinal axis (3924), the distal portion (3922) and the collection of distal electrodes (3932) can appear in the shape of a "+" symbol (e.g., an "X" or cross).

[0305] In some embodiments, the second inner shaft (3921) can be retracted into the catheter outer lumen (3912) by a predetermined amount to convert the ablation device (3900) from the first configuration to the second configuration. It should be understood that the spline (3930) group can be converted to any intermediate configuration between the first and second configurations continuously or in discrete steps. When not deployed, the spline (3930) group can form a shape that is generally parallel to the longitudinal axis (3924), and when the distal portion of the spline (3930) group is bent radially outward from the longitudinal axis (3924) and angled relative to the proximal portion (3902) of the spline, the spline (3930) group can form a basket-like or pyramid-like shape.

[0306] In some embodiments, the expandable member (3950) may be configured to Fig.39B and 39C The deflated configuration shown, in which the outer surface of the expandable member (3950) is arranged approximately parallel to the longitudinal axis (3924) of the ablation device (3900), and Fig.39A and 39D The expandable member (3950) can be configured to convert between the expanded configuration shown in the figure (wherein the outer surface of the expandable member (3950) is bent radially outward from the longitudinal axis (3924) when the spline group is in the expanded configuration). In some embodiments, the spline (3930) group is configured to convert to the expanded configuration in response to the expandable member converting to the expanded configuration. In the expanded configuration - wherein the expandable member (3950) is arranged distal to the distal end of the outer shaft (3910) and in the space between the spline (3930) groups, the expandable member (3950) is configured to drive the electric field generated by the multiple electrodes out of the space between the spline groups so that the electric field can form a larger foci in the tissue. In some embodiments, the expandable member (3950) in the expanded configuration substantially fills the space between the spline groups in its expanded configuration. When the expandable member (3950) is in the deflated configuration, the spline (3930) group can be in a first configuration ( Fig.39C ) or the second configuration ( Fig.39B ).

[0307] In some embodiments, the expandable member in the expanded configuration may form an asymmetric shape (e.g., Fig.39A , 39D ), wherein the outer diameter of the distal portion of the expandable member is greater than the outer diameter of the proximal portion of the expandable member.

[0308] 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 spline (3930) set in the second configuration and / or convert the expandable member (3950) to an expanded, deployed configuration. In some embodiments, a fluid source in fluid communication with the expandable member (3950) can be used to convert the expandable member (3950) from its deflated configuration to its expanded configuration. For example, the first inner shaft (3920) can be configured to be coupled (e.g., in fluid communication) to a fluid source (not shown) such that a fluid can be delivered to the expandable member (3950) via the lumen of the first inner shaft (3920) to convert the expandable member (3950) to the expanded configuration. In some embodiments, the expandable member (3950) in the expanded configuration can conform to the shape formed by the spline (3930) set in the second configuration. That is, the expanded or unfolded expandable member (3950) can form a spherical, basket-like, or pyramidal shape. In some embodiments, the expandable member (3950) can be unfolded so that the outer surface of the expandable member (3950) engages with an area of ​​the spline (3930) group. It should be understood that the expandable member (3950) can be converted to any intermediate configuration between the collapsed and expanded configurations, either continuously or in discrete steps. In some embodiments, converting the expandable member (3950) from the collapsed configuration to the expanded configuration applies a force to the spline (3930) group that converts the spline group from a first configuration to a second configuration. For example, the expandable member (3950) can expand to engage with an area of ​​the spline (3930) group to apply an outward force to the spline (3930) group, causing the configuration of the spline (3930) group to change from its first configuration (i.e., Fig.39C ) to its second configuration (i.e., Fig.39D deployment configuration shown).

[0309] In some embodiments, the expandable member as described herein may have an expandable structure and may be composed of any of a variety of insulating or dielectric materials, including but not limited to polyvinyl chloride (PVC), polyethylene (PE), cross-linked polyethylene, polyolefins, polyolefin copolymers (POC), polyethylene terephthalate (PET), polyester, nylon, polymer blends, polyester, polyimide, polyamide, polyurethane, silicone, polydimethylsiloxane (PDMS), PEBAX, etc. Preferred embodiments may be composed of polyurethane or silicone. In some embodiments, one or more portions of the expandable member may include a radiopaque portion. In some embodiments, a fluid may, for example, be passed through the lumen of the first inner shaft (3920) or another shaft or structure coupled to the expandable member (3950) to expand the expandable member (3950). For example, the expandable member (3950) may be expanded through a fluid port attached to a catheter handle, wherein a fluid such as distilled water or deionized water may be injected under pressure.

[0310] Together with the use of a liquid (e.g., distilled or deionized water, saline air, or other liquids and / or gases) to expand the expandable member, the expandable member acts as an effective insulator during delivery of the pulsed electric field waveform and drives the electric field to areas outside the expandable member or balloon and to areas surrounding the balloon. This combination of the expandable member and the spline set allows the distal end of the ablation device (3900) to project or deliver a stronger electric field at a greater distance from the ablation device (3900) and thereby more effectively generate focal ablation lesions of tissue at a desired depth than with the spline set alone. Thus, the device (3900) in the second configuration and the expanded configuration ( Fig.39A and 39D ) can effectively form a lesion in tissue with less power by redirecting the electric field generated by the electrode set (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 spline (3930) group is in the expanded configuration, at least one electrode from the distal electrode (3932) set is configured to contact the tissue surface and form a focal ablation lesion having a diameter between about 0.5 cm and about 2.5 cm on the tissue surface.

[0311] In some embodiments, different numbers 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.39ATwo distal electrodes (3932) and three proximal electrodes (3934) are shown for each spline of the spline (3930) group. In some embodiments, each spline in the spline (3930) group may 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 collection of electrode segments of shorter lengths, the proximal electrodes (3934) are able to achieve flexibility of the proximal portion (3902) of the spline (3930). In some embodiments, at least one flexible portion is arranged between adjacent side electrodes from multiple proximal electrodes to increase the flexibility of the spline at the location of multiple proximal electrodes. Each proximal electrode (3934) may be formed on the surface of its spline (3930) along its entire circumference (e.g., around the entire circumference of the spline) and / or around a portion of its entire circumference. Each distal electrode (3932) may be formed on the surface of its spline (3930) along its entire circumference and / or around a portion of its entire circumference. When the proximal and distal electrodes (3932, 3934) extend along the entire circumference, the proximal and distal electrodes (3932, 3934) may cover (e.g., extend around, surround) the entire circumference of its spline (3930). Additionally or alternatively, one or more proximal electrodes (3934) may include at least one coil electrode that enables flexibility of the proximal portion (3902) of the spline (3930). For example, in one embodiment, multiple proximal electrodes (3934) may be replaced with a single proximal electrode (3934) having a sufficiently flexible curled configuration to enable the device / apparatus (3900) to transition between its first configuration and second (deployed) configuration.

[0312] The distal electrode (3932) set can be configured to face a particular direction. For example, Fig.39B , 39C 39D shows that in a second configuration when the distal portion (3904) of the spline (3930) set is bent radially outward from the longitudinal axis (3924), the distal electrode (3932) set and the distal portion (3922) face generally forward at the distal end of the device (3900). In addition, the distal electrode (3932) can be arranged at the distal end of its spline so that the distal electrode (3932) of the spline (3930) set is arranged near the distal portion (3922) of the device (3900).

[0313] In some embodiments, the set of electrodes (3932, 3934) of each spline in the set of splines (3930) can have approximately the same size, shape, number, and spacing as the corresponding electrodes (3932, 3934) of adjacent splines. The thickness of each spline (3930) can vary based on the number of electrodes (3932, 3934) formed on each spline (3930), which number 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.

[0314] The electrode set (3932, 3934) may be appropriately polarized to deliver high voltage pulses corresponding to pulsed electric field (PEF) ablation energy, which may be applied to tissue to cause cell death by irreversible electroporation. In some embodiments, at least one distal electrode from the distal electrode set may be configured to be activated with a first polarity, and at least one proximal electrode from the proximal electrode set may be configured to be activated with a second polarity opposite to the first polarity to jointly generate 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, thereby defining a bipolar pairing of electrodes for delivering PEF ablation energy. In general, a bipolar-like sequence may be defined for PEF ablation delivery. As another example, all distal electrodes (3932) may have one electrical polarity, while all proximal electrodes (3934) may have an opposite electrical polarity.

[0315] In some embodiments, the electrode (3932, 3934) set may be configured as an anode-cathode set. For example, each distal electrode of the distal electrode (3932) set may be configured as an anode, and the proximal electrode (3934) set may be configured as a cathode (or vice versa). In some embodiments, the distal electrode (3932) set and the proximal electrode (3934) set may have opposite polarities. For example, for a given spline, the distal electrode (3932) and the proximal electrode (3934) set may have opposite polarities. The distal electrode (3932) set may have the same polarity. As discussed herein, the distal electrode (3932) set may be wired together. In some embodiments, the electrode (3932, 3934) sets of one or more splines in the spline (3930) set may be activated together to deliver a pulse waveform for irreversible electroporation. For example, a preselected portion of the plurality of electrodes may be activatable in each of the plurality of states to generate an electric field for ablating a tissue wall (e.g., a heart chamber) by irreversible electroporation. In other embodiments, pulse waveform delivery may be repeated sequentially on a predetermined subset of the set of electrodes (3932, 3934). For example, a particular activation sequence may include activating the distal electrode (3932) of one half of the spline (3930) (e.g., Figures 39A-39D ) and a proximal electrode (3934) that activates half of the splines (3930) (e.g., Figures 39A-39D ). Depending on the desired electric field generated by the electrodes (3932, 3934), the activated distal electrode (3932) and the proximal electrode (3934) can be offset from each other (e.g., the distal electrode (3932) can be located on adjacent splines (3930) as the proximal electrode (3934) or the distal electrode (3932) can be offset from the proximal electrode (3934) at an angle (e.g., approximately 90 degrees). In some embodiments, the spline group can be configured to ablate a tissue wall regardless of the orientation of the spline group relative to the tissue wall. In some embodiments, a preselected portion of the plurality of electrodes can include electrodes from the plurality of electrodes oriented to be proximal to the tissue surface.

[0316] In some embodiments, the distal electrode (3932) set may be separated from the distal portion (3922) by up to 6 mm from the distal end of each spline (3930). In some embodiments, the distal electrode (3932) set may be separated from the proximal electrode (3934) set by between about 1 mm and about 20 mm. In some embodiments, each electrode of the electrode set (3932, 3934) may include a diameter between about 0.5 mm and about 3 mm. In some embodiments, the distal end of the distal portion (3922) and / or the second inner shaft (3921) may include a cross-sectional diameter between about 0.7 mm and about 5 mm. In some embodiments, each electrode in the electrode (3932, 3934) set may have a length between about 0.5 mm and about 5 mm. In some embodiments, the spline (3930) set in the second configuration may have an expanded cross-sectional diameter (i.e., the effective diameter of the expanded configuration or the second configuration in a plane corresponding to its largest portion) between about 6 mm and about 24 mm. In some embodiments, in the undeployed configuration, the spline (3900) set may extend between about 6 mm and about 30 mm from the distal end (3912) of the outer shaft (3910). In some embodiments, the outer shaft (3910) may have an outer diameter between about 1.5 mm and about 6.0 mm.

[0317] The ablation device (3900) as described herein can be arranged in a first configuration prior to delivering a pulse waveform and converted to 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) can be coupled to the catheter (3900) and the spline (3930) group, and the handle is configured to affect the conversion of the spline (3930) group between the first configuration and the second configuration. For example, the handle can 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) can deploy the spline (3930) group into a basket-like or pyramid-like shape as shown herein. In some embodiments, actuation of a knob, wheel, or other control mechanism in the device handle can cause translation of the first and second inner shafts (3920, 3921) and cause deployment of the spline (3930) group. In some embodiments, the electrical leads of at least two electrodes in the set of electrodes (3932, 3934) may be electrically coupled at or near a proximal portion of the ablation device (3900), such as, for example, within a handle.

[0318] In addition, the catheter handle (not shown) may include a mechanism for deflecting or steering the distal portion (3904) of the catheter device (3900). For example, a pull wire may extend from the catheter handle to a side of the distal portion (3904) of the device (3900) at or near the distal end of the outer shaft (3910), wherein tensioning of the pull wire causes deflection of the device (3900). The deflection of the device (3900) may help a user position the device (3900) in an appropriate anatomical position in a controlled manner. For example, the device (3900) may be slidably disposed within a steerable sheath (not shown) for delivering the device (3900) to a desired location such as a cardiac chamber. Once in the chamber, the device (3900) may be further deflected or steered to enter the desired location for delivering ablation energy.

[0319] In some embodiments, one or more distal spline electrodes (3932) may be separately electrically wired to receive and / or monitor intracardiac electrocardiogram (ECG) signals from each such electrode (3932). For example, an electrode configured for ablation and another electrode configured to receive 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 to deliver ablation energy. In some embodiments, some proximal spline electrodes (3934) may be separately wired for intracardiac ECG monitoring. It should be understood that any ablation device described herein may be used with separately electrically wired electrodes to monitor intracardiac ECG signals from each such electrode. In some embodiments, some electrodes on one or more splines of a spline group may be used for ECG monitoring, while other electrodes may be used to deliver ablation energy, whereas in other embodiments, only some electrodes may be used for ECG monitoring, while all electrodes may be used to deliver ablation energy.

[0320] An illustrative method of using an ablation device (3900) including an expandable member (3950) may include the step of positioning (e.g., placing) the ablation device (3900) at a first position within a cardiac chamber of a subject's heart. The spline (3930) group can be converted to an expanded configuration in which a distal portion of each spline of the spline group is bent radially outward from the longitudinal axis (3924). Converting the spline (3930) group to the expanded configuration includes: retracting a distal portion of the second shaft relative to the first axis. Retracting the distal portion of the second shaft relative to the first axis may 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 convert the spline group to a state in which a distal portion of each spline of the spline group and a proximal portion of each spline of the spline group are at a first angle between about 70 degrees and about 180 degrees.

[0321] The expandable member (3950) can be converted to an expanded configuration. An ablation pulse waveform can be delivered to a plurality of electrodes (3932, 3934) arranged on the spline (3930) set so that the spline (3930) set generates an electric field for ablating tissue of the heart chamber, wherein the expandable member (3950) directs the electric field toward the tissue.

[0322] In some embodiments, a first ablation pulse waveform can be delivered to a distal electrode formed on at least one spline from the spline set and a proximal electrode formed on at least one spline from the spline set, such that the spline set generates a first electric field for ablating a first portion of a tissue wall of a cardiac chamber. The ablation device can be positioned at a second location within the cardiac chamber. A second ablation pulse waveform can be delivered to a distal electrode formed on at least one spline from the spline set and a proximal electrode formed on at least one spline from the spline set, such that the spline set generates a second electric field for ablating a second portion of the tissue wall.

[0323] In some embodiments, the first and second locations are located in an atrium of the heart, and the first and second angles are between about 70 degrees to about 90 degrees or between about 70 degrees to about 120 degrees, including all subranges and values ​​therebetween. In some embodiments, the first and second locations are located in a ventricle of the heart, and the first and second angles are between about 90 degrees to about 180 degrees.

[0324] In some embodiments, at least one of the first electric field and 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 on the tissue surface. A first electrode from at least one splined electrode set can be configured as an anode. A second electrode from at least one splined electrode set can be configured as a cathode. An ablation pulse waveform can be delivered to the first electrode and the second electrode.

[0325] At least one electrode set may be configured for ablation, and at least one electrode set may be configured for receiving electrophysiological data. Electrophysiological data from the heart may be recorded using at least one electrode set. The electrophysiological data may include intracardiac electrocardiogram (ECG) signal data of at least one pulmonary vein.

[0326] The tissue includes an endocardial surface of a heart chamber. In some applications, the heart chamber is a ventricle, and in other applications it may be an atrium. In some embodiments, a pacing device may be advanced into the right ventricle or other heart region of the heart. A pacing signal may be generated for cardiac stimulation of the heart. A pacing signal may be applied to the heart using the pacing device while an ablation pulse waveform is generated synchronously with the pacing signal. The ablation pulse waveform may include a time offset with respect to the pacing signal. A radiopaque portion of the ablation device may be visualized fluoroscopically in one or more steps.

[0327] In some embodiments, the catheter can be advanced into a cardiac chamber of the heart and electrophysiological data can be recorded using recording electrodes. After the spline group is converted to an expanded configuration and the balloon is converted to an expanded configuration, at least one spline in the spline group can be placed in contact with the endocardial surface. At least one spline in contact with the endocardium can form a "C" shape. As described herein, the ablation device (3900) may include a shaft defining an inner cavity in fluid communication with an expandable member (3950). The expandable member converted to an expanded configuration includes delivering a fluid to the expandable member via the inner cavity of the shaft. The expandable member may be formed of an insulating material so that the expandable member acts as an insulator during delivery of the ablation pulse waveform.

[0328] The expandable member may include a plurality of expandable portions. Each expandable portion from the plurality of expandable portions may expand independently of other expandable portions in the plurality of expandable portions.

[0329] In some embodiments, converting the spline set to the deployed configuration may include converting the spline set so that the distal portion of each spline in the spline set is angled greater than about 70 degrees relative to the longitudinal axis. In some embodiments, converting the spline set to the deployed configuration is in response to converting the expandable member to the expanded configuration.

[0330] The ablation device (3900) may include any number of splines, e.g., 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) may include 3 to 20 splines. For example, the ablation device (3900) may include 4 to 12 splines.

[0331] Each spline of the spline (3900) group may include a corresponding electrode (3932, 3934) having an atraumatic, generally circular shape to reduce damage to tissue. In this manner, as described herein, the distal electrode (3932) in the second configuration may be held close to or placed against a portion of an atrial wall of the left ventricle, or more generally, any atrium or ventricle, so as to generate a foci thereon by activating the appropriate electrode using any suitable polarity combination. For example, the distal portion (3922) of the spline (3930) group and / or the distal electrode (3932) may be in contact with or in proximity to a tissue wall (3950), similar to Fig.38D As shown, the distal electrode (3932) is positioned in an approximately perpendicular or generally oblique orientation to the tissue wall. The configuration of the distal electrode (3932) allows for the creation of a focal lesion at a desired depth even when the ablation device (3900) in the deployed configuration is adjacent to the tissue wall (3950) at an angle (e.g., obliquely).

[0332] In some embodiments, since the electrodes or subsets of electrodes are independently addressable, the electrodes can be energized in any order 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 herein. It should be understood that the size, shape, and spacing of the electrodes on and between the splines can be configured to deliver continuous / transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternating electrodes can be at the same potential, and this is also true for all other alternating electrodes. Therefore, in some embodiments, ablation can be delivered quickly with all electrodes activated simultaneously. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0333] In some embodiments, the ablation device (e.g., 2900, 3000, 3100, 3200) may include 2 to 6 catheters. The ablation device (e.g., 2900, 3000, 3100, 3200) may include any number of catheters, for example, 2, 3, 4, 5, 6, or more catheters. For example, in some embodiments, the ablation device (e.g., 2900, 3000, 3100, 3200) may include 3 to 6 catheters. In some embodiments, the catheter of the ablation device (e.g., 2900, 3000, 3100, 3200) may include 2 to 6 distal portions. The catheter may include any number of distal portions, for example, 2, 3, 4, 5, 6, or more distal portions. For example, in some embodiments, the catheter may include 2 to 4 distal portions. In addition, in some embodiments, the shape (e.g., curvature, length, size) of the catheter may be asymmetric to help control the depth, shape, and / or size of the focal ablation.

[0334] In some embodiments, the electrodes may form an anode-cathode pairing. For example, a first electrode may be configured as an anode and a second electrode may be configured as a cathode. In some embodiments, subsets of electrodes are independently addressable and the electrodes may be energized in any order 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).

[0335] In all of the above and non-limiting embodiments, the ablation catheter itself may be a steerable device with a pull wire for controlling the deflection by an appropriate mechanism in the catheter handle, as known to those skilled in the art.

[0336] Balloon

[0337] In some embodiments, an ablation device may include one or more balloons for delivering energy to ablate tissue via irreversible electroporation. Fig.10An embodiment of a balloon ablation device (1010) (e.g., similar in structure and / or function to ablation device (110)) is depicted being arranged in a left atrial chamber (1000) of a heart. The ablation device (1010) may include a first balloon (1012) and a second balloon (1014), which may be configured to be arranged in an orifice (1002) of a pulmonary vein (1004). The diameter of the first balloon (1012) in the deployed (e.g., inflated) configuration may be greater than the diameter of the second balloon (1014) in the deployed configuration. This allows the second balloon (1014) to be advanced and arranged further into the pulmonary vein (1014), and the first balloon (1012) may be arranged near and / or at the orifice (1002) of the pulmonary vein (1004). The inflated second balloon is used to stabilize the position of the first balloon at the orifice of the pulmonary vein. In some embodiments, the first balloon (1012) and the second balloon (1014) can be filled with any suitable conductive fluid, such as saline. The first balloon (1012) and the second balloon (1014) can be electrically isolated from each other. For example, each balloon (1012, 1014) can include an insulated electrical lead associated therewith, wherein each lead has sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation on each electrical lead can maintain a potential difference of between about 200V and about 2500V across its thickness without dielectric breakdown, including all values ​​and sub-ranges therebetween. For example, the lead of the second balloon (1014) can be insulated when it extends through the first balloon (1012).

[0338] In some embodiments, the first and second balloons (1012, 1014) may form an anode-cathode pairing. For example, in one embodiment, the first and second balloons may carry electrically separated saline fluids, and the first balloon (1012) may be configured as a cathode and the second balloon (1014) may be configured as an anode, or vice versa, wherein electrical energy may be capacitively coupled across the balloon or saline-filled electrodes. The device (1010) may receive a pulse waveform to be delivered to the tissue (1002). For example, one or more biphasic signals may be applied so that tissue may be ablated between the first balloon (1012) and the second balloon (1014) at a desired location in the pulmonary vein (1004). The first and second balloons (1012, 1014) may 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 orifice (1002) of the pulmonary vein (1004). In another embodiment, one or both of the electrodes (1018) and (1019) disposed proximally and distally of the first balloon, respectively, may be used as electrodes of one polarity, and the fluid in the first balloon may be used as an electrode of the opposite polarity. A biphasic pulse waveform may then be delivered between these electrodes of opposite polarity by capacitive coupling across the balloon, thereby forming an irreversible electroporation ablation zone in the area surrounding the first balloon. In some embodiments, one or more balloons (1012, 1014) may include a wire mesh.

[0339] Fig.11 is a cross-sectional view of another embodiment of a balloon ablation device (1110) (e.g., similar in structure and / or function to ablation device (1010)) disposed in a left atrial chamber (1100) and a right atrial chamber (1104) of a heart. The ablation device (1110) may include a balloon (1112), which may be configured to be advanced into and disposed in the right atrial chamber (1104). For example, the balloon (1112) may be disposed in contact with a septum (1106) of the heart. The balloon (1112) may be filled with saline. The device (1110) may also include an electrode (1120), which may be advanced from the right atrial chamber (1104) through the balloon (1112) and the septum (1106) into the left atrial chamber (1100). For example, the electrode (1120) may extend from the balloon (1112) and pass through the septum (1106) and advance into the left atrial chamber (1100). Once the electrode (1120) is advanced into the left atrial chamber (1100), the 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. Fig.11In one embodiment, the distal portion of the electrode (1120) forms a ring that can surround a single orifice or two or more orifices of a pulmonary vein (1102) in the left atrial chamber (1100). In other embodiments, the distal portion of the electrode (1120) can have approximately the same diameter as the orifice of the pulmonary vein (1102).

[0340] The balloon (1112) and the electrode (1120) can be electrically isolated from each other. For example, the balloon (1112) and the electrode (1120) can each include an insulated electrical lead (1114, 1122), respectively, wherein each lead (1114, 1122) has sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation on each electrical lead can maintain a potential difference 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 by 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) can be configured as a cathode, and the electrode (1120) can be configured as an anode. The device (1110) can receive a pulse waveform to be delivered to the orifice of the pulmonary vein (1102). For example, a biphasic waveform can be applied to ablate tissue. The pulse waveform can generate a strong electric field around the electrode (1120), while the current is applied to the balloon (1112) via capacitive coupling to complete the circuit. In some embodiments, the electrode (1120) can include a fine gauge wire and the balloon (1112) can include a wire mesh.

[0341] In another embodiment, the electrode (1120) may be advanced through the pulmonary vein (1102) and disposed in one or more pulmonary vein ostia without being advanced through the balloon (1112) and / or the septum (1106). The balloon (1112) and electrode (1120) may be configured as a cathode-anode pair and receive a pulse waveform in the same manner as discussed above.

[0342] Return electrode

[0343] Some embodiments of ablation systems as described herein may also include a return electrode or a distributed collection of return electrodes coupled to the patient to reduce the risk of inadvertent damage to healthy tissue. Figures 12A-12B 1 is a schematic diagram of a set of return electrodes (1230) (eg, return pads) of an ablation system arranged on a patient (1200). A set of four orifices of a left atrial pulmonary vein (1210) such as Figures 12A-12BThe electrodes (1220) of the ablation device may be positioned around one or more ostia of the pulmonary vein (1210). In some embodiments, a set of return electrodes (1230) may be arranged 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).

[0344] For example, one or more return electrodes may be arranged on the skin of the patient (1200). In one embodiment, eight return electrodes (1230) may be positioned on the patient's back so as to surround the pulmonary vein orifices (1210). A conductive gel may be applied between the return electrodes (1230) and the skin to improve contact. It should be understood that any ablation device described herein may be used with one or more return electrodes (1230). In Figures 12A-12B, the electrodes (1220) are arranged around four orifices (1210).

[0345] Fig. 12B An energized electrode (1220) is shown forming an electric field (1240) around an orifice (1210) of a pulmonary vein. Return electrodes (1230) may in turn receive the pulsed monophasic and / or biphasic waveforms delivered by electrodes (1220). In some embodiments, the number of return electrodes (1230) may be approximately inversely proportional to the surface area of ​​the return electrodes (1230).

[0346] For each ablation device discussed herein, the electrode (e.g., ablation electrode, return electrode) may include a biocompatible metal such as titanium, palladium, silver, platinum, or a platinum alloy. For example, the electrode may preferably include platinum or a platinum alloy. Each electrode may include an electrical lead having sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation on each electrical lead may maintain a potential difference of between about 200V and about 2500V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. The insulated electrical leads may reach the proximal handle portion of the catheter, from which they may be connected to a suitable electrical connector. The catheter shaft may be made of a flexible polymer material such as polytetrafluoroethylene, nylon, Pebax, etc.

[0347] method

[0348] Also described herein are methods for ablating tissue within a cardiac chamber using the above-described systems and devices. The cardiac chamber may be a left atrial chamber, and include its associated pulmonary veins. Typically, the methods described herein include introducing and arranging a device in contact with one or more pulmonary vein ostia or sinus regions. A pulse waveform may be delivered by one or more electrodes of the device to ablate tissue. In some embodiments, a cardiac pacing signal may synchronize the delivered pulse waveform with the cardiac cycle. Additionally or alternatively, the pulse waveform may include multiple le...

Claims

1. A device comprising: a first shaft defining a longitudinal axis and an inner lumen; as well as a second shaft disposed within the lumen and having a distal portion extending from the distal end of the first shaft; Multiple electrodes; A spline group, each spline in the spline group comprising: an electrode set from the plurality of electrodes formed on the spline, each electrode set comprising: (1) a distal electrode, such that the spline set comprises a distal electrode set, and (2) a proximal electrode, such that the spline set comprises a proximal electrode set; 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 spline group is convertible into a plurality of states between and including an undeployed configuration and a deployed configuration, wherein, in each of the plurality of states, a distal portion of each spline from the spline group is arranged to be at one of a corresponding plurality of angles relative to a proximal portion of each spline from the spline group, 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 according to claim 1, wherein: The spline set is configured to ablate the tissue wall regardless of an orientation of the spline set relative to the tissue wall.

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

4. The device according to claim 1, wherein: The spline set 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. The device according to claim 1, wherein: When the spline set is in the deployed configuration, at least one electrode from the distal electrode set is angled between about 70 degrees and about 180 degrees relative to at least one electrode from the proximal electrode set.

6. The device according to 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. The device according to claim 1, wherein: At least one distal electrode from the distal electrode set is configured to be activated with a first polarity, and at least one proximal electrode from the proximal electrode set is configured to be activated with a second polarity opposite to the first polarity to jointly generate the electric field.

8. The device according to claim 1, wherein: Each spline from the set of splines includes a plurality of proximal electrodes and at least one flexible portion disposed between adjacent proximal electrodes from the plurality of proximal electrodes for increasing spline flexibility.

9. The device according to 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, wherein the first inner shaft and the second inner shaft are configured to slide relative to the outer shaft.

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

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