Systems, devices and methods for delivering pulsed electric field ablation energy to endocardial tissue

Abstract

The present disclosure relates to systems, devices and methods for delivering pulsed electric field ablation energy to endocardial tissue. Systems, devices and methods for electroporation ablation therapy are disclosed, wherein the device comprises a set of splines coupled to a catheter for medical ablation therapy. Each spline in the set of splines can include a set of electrodes formed on the splines. The set of splines can be configured to translate to convert between a first configuration and a second configuration. Each spline in the set of splines in the second configuration can be petal-shaped.

Description

[0001] This application is a divisional application of a divisional application with an application date of April 27, 2018, application number of 202110157926.1, and invention name of “Systems, devices and methods for delivering pulsed electric field ablation energy to endocardial tissue”. The corresponding original application has an application date of April 27, 2018, application number of 201880033278.5, and invention name of “Systems, devices and methods for delivering pulsed electric field ablation energy to endocardial tissue”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application is a continuation-in-part of U.S. patent application No. 15 / 874,721, filed on January 18, 2018, and entitled “SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION,” which claims the benefit of U.S. Provisional Application No. 62 / 529,268, filed on July 6, 2017, and entitled “SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION.” This application also claims priority to U.S. patent application No. 15 / 711,266, filed on September 21, 2017 and entitled “SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE,” which is a continuation-in-part of PCT application No. PCT / US2017 / 012099, filed on January 4, 2017 and entitled “SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE,” which claims priority to U.S. Provisional Application No. 62 / 274,943, filed on January 5, 2016 and entitled “SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE.” 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 entitled “SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSE ELECTRIC FIELD ABLATION ENERGY TO ENDOCARDIAL TISSUE,” and claims priority to U.S. Provisional Application No. 62 / 529,268, filed on July 6, 2017, and entitled “SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION.” The entire disclosure of each of the foregoing applications is incorporated by reference in its entirety. Background Art

[0004] In the past two decades, the generation of pulsed electric fields for tissue treatment has been transferred from the laboratory to clinical applications, and in the past four decades or more, the effects of short pulses of high voltage and large electric fields on tissues have been studied. Applying a short high DC voltage to tissue can produce a local high electric field with a range of usually hundreds of volts per centimeter, which destroys the cell membrane by creating pores in the cell membrane. Although the precise mechanism of this electric drive pore generation or electroporation is still under study, it is believed that applying a relatively short and large electric field will produce instability in the lipid bilayer in the cell membrane, resulting in the distribution of local gaps or pores in the cell membrane. This electroporation may be irreversible in the following cases: the electric field applied at the membrane is greater than the threshold so that the pore is not closed and remains open, thereby allowing biomolecular materials to pass through the membrane for exchange, thereby causing necrosis and / or apoptosis (cell death). Subsequently, the surrounding tissue can heal naturally.

[0005] While pulsed DC voltage can drive electroporation under appropriate circumstances, there remains an unmet need for thinner, flexible, atraumatic devices that effectively deliver high DC voltage electroporation ablation therapy selectively to endocardial tissue in areas of interest while minimizing damage to healthy tissue. Summary of the invention

[0006] Described herein are systems, devices, and methods for ablating tissue by irreversible electroporation.

[0007] The device may include a first catheter, the first catheter defining a longitudinal axis and a lumen passing therethrough. A second catheter may extend from the distal end of the first catheter lumen. A set of splines may have a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter. Each spline may include a set of independently addressable electrodes formed on the surface of each spline in the splines. Each electrode may have an insulated electrical lead associated therewith. The insulated electrical lead may be placed in the body of each spline in the set of splines. The second catheter may be configured to translate along the longitudinal axis to convert between a first configuration and a second configuration. In the first configuration, the set of splines may be substantially parallel to the longitudinal axis. In the second configuration, at least a portion of each spline in the set of splines may extend distally of the distal end of the second catheter.

[0008] In some embodiments, the device may include a first catheter, the first catheter defining a longitudinal axis and a lumen passing therethrough. A second catheter may extend from the distal end of the first catheter lumen. A group of splines may have a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter. Each spline may include a group of independently addressable electrodes formed on the surface of each spline in the splines. Each electrode has an insulated electrical lead associated therewith. The insulated electrical lead may be placed in the body of each spline in the group of splines. The second catheter may be configured to translate along the longitudinal axis to convert between a first configuration and a second configuration. In the first configuration, the group of splines may be substantially parallel to the longitudinal axis. In the second configuration, each spline in the group of splines may have a longitudinal axis in the second configuration, the longitudinal axis having an angle of less than about 80 degrees relative to the longitudinal axis of the first catheter.

[0009] In some embodiments, the device may include a first catheter, the first catheter defining a longitudinal axis and a lumen passing therethrough. A second catheter may extend from the distal end of the first catheter lumen. A set of splines may have a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter. Each spline may include a set of independently addressable electrodes formed on the surface of each spline in the splines. Each electrode may have an insulated electrical lead associated therewith. The insulated electrical lead may be placed in the body of each spline in the set of splines. The second catheter may be configured to translate along the longitudinal axis to convert between a first configuration and a second configuration. In the first configuration, the set of splines may be substantially parallel to the longitudinal axis. In the second configuration, each spline in the set of splines may form a loop and twist along its length so that the spline has a torsion along its length.

[0010] In some embodiments, each spline in the set of splines may have a rotation rate u' governed by the following equation: ∫ | u ′}dl>π, where l is the arc length of the spline. In some embodiments, the rotation rate u' of the spline is controlled by the following equation: u'=du / dl, where l is the arc length along the spline. The shape of each spline in the group of splines is controlled by the following equation: ∫(u″·b)dl≠0, where b=u×u.

[0011] In some embodiments, the system may include a signal generator configured to generate a pulse waveform. The ablation device may be coupled to the signal generator and configured to receive the pulse waveform. The ablation device may include a first catheter, the first catheter defining a longitudinal axis and a lumen passing therethrough. A second catheter may extend from the distal end of the lumen of the first catheter. A handle may be coupled to the second catheter. A set of splines may have a proximal portion coupled to the distal end of the lumen of the first catheter and a distal portion coupled to the distal end of the second catheter. Each spline may include a set of independently addressable electrodes formed on the surface of each spline in the splines. Each electrode may have an insulated electrical lead associated therewith. The insulated electrical lead may be placed in the body of each spline in the set of splines. The second catheter may be configured to translate along the longitudinal axis to switch between a first configuration and a second configuration. In the first configuration, the set of splines may be substantially parallel to the longitudinal axis. In the second configuration, at least a portion of each spline in the set of splines may extend distally of the distal end of the second catheter.

[0012] In some embodiments, in the second configuration, at least one electrode of each spline in the set of splines may be distal to the distal end of the second catheter. In some embodiments, the proximal portion of the set of splines may be coupled to the first catheter within the lumen of the first catheter. In some embodiments, the second catheter may define a lumen therethrough, and the distal portion of the set of splines may be coupled to the second catheter within the lumen of the second catheter. In some embodiments, in the second configuration, each spline in the set of splines may not overlap with an adjacent spline.

[0013] In some embodiments, the group of splines can be bent radially outward from the longitudinal axis in the second configuration. In some embodiments, the group of splines can be offset away from the longitudinal axis in the second configuration. In some embodiments, an actuator can be coupled to the group of splines and a distal cap. The actuator can be configured to convert the group of splines between the first configuration and the second configuration. In some embodiments, the group of electrodes on adjacent splines can have opposite polarities. In some embodiments, when deployed in the second configuration, the group of splines can be formed into a shape with an effective cross-sectional diameter between about 10mm and about 35mm at its maximum portion. In some embodiments, the group of splines can include 3 to 14 splines. In some embodiments, the diameter of each spline in the group of splines can be between about 1mm and about 5mm. In some embodiments, the diameter of each electrode in the group of electrodes can be between about 1mm and about 5mm.

[0014] In some embodiments, the insulated electrical lead may be disposed in the body of the second conduit. The insulated electrical lead is configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In some embodiments, the pulse waveform of the first level of the hierarchy comprising the pulse waveform may include a first group of pulses, each pulse having a pulse duration, a first time interval separating consecutive pulses. The second level of the hierarchy of the pulse waveform may include a plurality of first groups of pulses as a second group of pulses, a second time interval separating consecutive first groups of pulses, the second time interval being at least three times the duration of the first time interval. The third level of the hierarchy of the pulse waveform may include a plurality of second groups of pulses as a third group of pulses, a third time interval separating consecutive second groups of pulses, the third time interval being at least thirty times the duration of the second level time interval.

[0015] In some embodiments, a method of treating arrhythmias by irreversible electroporation may include the following steps: advancing an ablation device into a left atrium of a patient; converting the ablation device from a first configuration to a second configuration. The ablation device may include: a first catheter defining a longitudinal axis and a lumen therethrough; a second catheter extending from a distal end of the lumen of the first catheter; and

[0016] A set of splines, the set of splines having a proximal portion coupled to the distal end of the lumen of the first catheter and a distal portion coupled to the distal end of the second catheter, each spline including a set of independently addressable electrodes formed on the surface of each spline in the splines, each electrode having an insulated electrical lead associated therewith, the insulated electrical lead disposed in the body of each spline in the set of splines. In the first configuration, the set of splines may be substantially parallel to the longitudinal axis. In the second configuration, at least a portion of each spline in the set of splines extends distally of the distal end of the second catheter. The steps may further include generating a set of pulse waveforms and delivering the set of pulse waveforms to a set of adjacent portions of the posterior wall of the left atrium through one or more splines in the set of splines of the ablation device in the second configuration to form a set of ablation zones.

[0017] In some embodiments, in the second configuration, the set of splines can form a loop and twist along its length so that the splines have a twist along its length. In some embodiments, in the second configuration, each spline in the set of splines can have a longitudinal axis in the second configuration that has an angle of less than about 80 degrees relative to the longitudinal axis of the first conduit. In some embodiments, each spline in the set of splines can have a rotation rate u' governed by the following equation: ∫|u ′}dl>π, where l is the arc length of the spline. In some embodiments, the rotation rate u' of the spline is controlled by the following equation: u'=du / dl, where l is the arc length along the spline. In some embodiments, the shape of each spline in the group of splines can be controlled by the following equation: ∫(u″·b)dl≠0, where b=u×u.

[0018] In some embodiments, at least a portion of the set of splines can be advanced distally of the distal end of the second catheter by retracting the second catheter relative to the first catheter. In some embodiments, each insulated electrical lead can be configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation.

[0019] In some embodiments, the group of splines may include an electrode group, the electrode group may include the group of electrodes for each spline in the group of splines. The method may further include configuring a first electrode in the electrode group as an anode; configuring a second electrode in the electrode group as a cathode; and delivering the pulse waveform to the first electrode and the second electrode.

[0020] In some embodiments, a first set of electrodes of a first spline in the group of splines can be configured as an anode, a second set of electrodes of a second spline in the group of splines can be configured as a cathode, and the pulse waveform can be delivered to the first set of electrodes and the second set of electrodes. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is a block diagram of an electroporation system according to an embodiment.

[0022] Figure 2 is a perspective view of an ablation catheter according to an embodiment.

[0023] Figure 3 is a perspective view of an ablation catheter according to other embodiments.

[0024] Figure 4 is a perspective view of an ablation catheter according to other embodiments.

[0025] Figure 5 is a detailed perspective view of a distal portion of an ablation catheter according to other embodiments.

[0026] Figure 6 is a side view of an ablation catheter according to other embodiments.

[0027] Figure 7 is a side view of an ablation catheter according to other embodiments.

[0028] Figure 8A-B are views of ablation catheters according to other embodiments. Fig. 8A is a side view, and Figure 8B is a front section view.

[0029] 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 expanded configuration according to other embodiments. Fig. 9C is a side view of an ablation catheter in a third expanded configuration according to other embodiments. Fig.9D is a side view of an ablation catheter in a fourth expanded configuration according to other embodiments. Fig.9E is a side view of an ablation catheter in a fifth expanded configuration according to other embodiments.

[0030] Fig.10 is a perspective view of a balloon ablation catheter positioned in the left atrial cavity of a heart according to other embodiments.

[0031] Fig.11 is a cross-sectional view of a balloon ablation catheter positioned in the left atrial cavity of a heart according to other embodiments.

[0032] Figure 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.

[0033] Fig.13 A method for performing tissue ablation according to an embodiment is shown.

[0034] Fig.14 Methods for performing tissue ablation according to other embodiments are shown.

[0035] Fig.15 It is located in the left atrium of the heart. Figure 2 Illustration of the depicted ablation catheter.

[0036] Fig.16 It is located in the left atrium of the heart. Figure 3 Illustration of the depicted ablation catheter.

[0037] Fig.17 It is located in the left atrium of the heart. Figure 4 Illustration of two of the depicted ablation catheters.

[0038] Fig.18 It is located in the left atrium of the heart. Figure 5 Illustration of the depicted ablation catheter.

[0039] Figure 19A-19Bis a schematic diagram of a set of electrodes placed in a pulmonary vein ostium according to other embodiments. Fig.19A is a schematic perspective view, and Fig.19B is a section view.

[0040] Figure 20A-20B is a schematic diagram of an electric field generated by an electrode positioned in a pulmonary vein ostium according to other embodiments. Fig. 20A is a schematic perspective view, and Fig. 20B is a section view.

[0041] Fig.21 is an example waveform showing the timing of voltage pulses with a pulse width defined for each pulse according to an embodiment.

[0042] Fig. 22 Schematically illustrated is a pulse hierarchy showing pulse width, spacing between pulses and pulse grouping according to an embodiment.

[0043] Fig.23 A schematic illustration of a nested hierarchy of monophasic pulses showing different levels of the nested hierarchy is provided according to an embodiment.

[0044] Fig.24 is a schematic illustration of a nested hierarchy of biphasic pulses showing different levels of the nested hierarchy, according to an embodiment.

[0045] Fig.25 The time series of an electrocardiogram and a cardiac pacing signal as well as atrial and ventricular refractory periods according to an embodiment are schematically shown, and the time window for irreversible electroporation ablation is indicated.

[0046] Fig.26A is a perspective view of an ablation catheter according to other embodiments. Fig.26B It is placed in the left atrium of the heart near the lung opening. Fig.26A A side view of the ablation catheter depicted. 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 a simulated illustration of tissue ablation in a lung ostium, according to an embodiment.

[0047] Figure 27A-27C are respective side views of ablation catheters 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 a second configuration. Fig.27C is yet another side view of the ablation catheter in a second configuration.

[0048] Fig.28 is a side view of an ablation catheter according to other embodiments.

[0049] Figure 29A-Figure 29D is a cross-sectional side view of an ablation catheter according to other embodiments. Fig.29A is a cross-sectional side view of an 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.

[0050] Fig.30 is a side view of an ablation catheter according to other embodiments.

[0051] Figure 31A-Figure 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.

[0052] Fig.32 is a schematic cross-sectional view of an ablation catheter according to other embodiments.

[0053] Figure 33A-Figure 33E is an explanatory diagram of an ablation catheter according to another embodiment. 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 cross-sectional perspective view of the splines of an ablation catheter. Fig.33D yes Fig.33A Cross-sectional view of the splines of an ablation catheter. Fig.33E Placed by neighboring organizations Fig.33A Perspective view of an ablation catheter.

[0054] Figure 34A-Figure 34B is a side view of a spline according to other embodiments. Fig.34A is a side view of a spline with unit tangent vector. Fig.34B is a side view of a spline with two unit tangent vectors.

[0055] Fig.35 is a side view of an ablation catheter according to other embodiments.

[0056] Figure 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 a second configuration. Fig.36C is a side view of an ablation catheter near tissue.

[0057] Figure 37A-Figure 37B is a perspective view of the ablation catheter and left atrium. Fig.37A is a perspective view of an ablation catheter positioned in the left atrium. Fig.37B is a perspective view of the left atrium after tissue ablation. DETAILED DESCRIPTION

[0058] Described herein are systems, devices, and methods for selectively and rapidly applying pulsed electric fields to ablate tissues by irreversible electroporation. In general, the systems, devices, and methods described herein can be used to generate large electric field amplitudes in desired areas of interest and reduce peak electric field values ​​elsewhere to reduce unnecessary tissue damage and arcing. The irreversible electroporation system described herein may include a signal generator and a processor, the signal generator and the processor being configured to apply one or more voltage pulse waveforms to a selected set of electrodes of an ablation device to deliver energy to the area of ​​interest (e.g., ablation energy for a group of tissues in the pulmonary vein ostium). The pulse waveforms disclosed herein can help treat 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 insulated electrical leads that are configured to maintain a voltage potential of at least about 700V without dielectric breakdown of the insulation corresponding thereto. The electrodes may be independently addressable so that each electrode can be controlled (e.g., delivered energy) independently of any other electrode of the device. In this way, the electrodes can coordinately deliver different energy waveforms with different timings to electroporate tissue.

[0059] As used herein, the term "electroporation" refers to the application of an electric field to a cell membrane to change the permeability of the cell membrane to the extracellular environment. As used herein, the term "reversible electroporation" refers to the application of an electric field to a cell membrane to temporarily change the permeability of the cell membrane to the extracellular environment. For example, cells subjected to reversible electroporation can observe one or more pores temporarily and / or intermittently formed in their cell membranes, which are closed after the electric field is removed. As used herein, the term "irreversible electroporation" refers to the application of an electric field to a cell membrane to permanently change the permeability of the cell membrane to the extracellular environment. For example, cells subjected to irreversible electroporation can observe one or more pores formed in their cell membranes, which still exist after the electric field is removed.

[0060] The pulse waveform for electroporation energy delivery disclosed herein can enhance the safety, efficiency and effectiveness of energy delivery to tissue by reducing the electric field threshold associated with irreversible electroporation, thereby producing more effective ablative damage 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 hierarchical groupings of pulses with associated time scales. In some embodiments, the methods, systems and devices disclosed herein may include one or more of the methods, systems and devices described in international application serial number PCT / US2016 / 057664, filed on October 19, 2016 and entitled "SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE", the contents of which are incorporated herein by reference in their entirety.

[0061] In some embodiments, the system may further include a cardiac stimulator, which is used to synchronize the generation of the pulse waveform with the paced heartbeat. The cardiac stimulator can use the cardiac stimulator to electrically pace the heart and ensure pacing capture to establish the periodicity and predictability of the cardiac cycle. A time window within the refractory period of the periodic cardiac cycle can be selected for voltage pulse waveform delivery. Therefore, the voltage pulse waveform can be delivered during the refractory period of the cardiac cycle to avoid interruption of the cardiac sinus rhythm. In some embodiments, the ablation device may include one or more catheters, guide wires, balloons, and electrodes. The ablation device can be converted into different configurations (e.g., compact and expanded) to position the device in the endocardial space. In some embodiments, the system may optionally include one or more return electrodes.

[0062] Typically, in order to ablate tissue, one or more catheters can be advanced through the vascular system to a target location in a minimally invasive manner. In cardiac applications, the electrodes through which the voltage pulse waveform is delivered can be placed on an epicardial device or an endocardial device. The method described herein may include introducing the device into the endocardial space of the left atrium of the heart and placing the device in contact with the pulmonary vein orifice. A pulse waveform 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 a cardiac pacing signal to avoid interruption of the heart's sinus rhythm. In some embodiments, the electrodes can be configured in the form of an anode-cathode subset. The pulse waveform can include a graded waveform to help tissue ablation and reduce damage to healthy tissue.

[0063] I. System

[0064] Overview

[0065] Disclosed herein are systems and devices configured for tissue ablation, which assist in tissue ablation by selectively and rapidly applying a voltage pulse waveform, thereby achieving irreversible electroporation. Generally, the system for ablating tissue described herein may include a signal generator and an ablation device, the ablation device having one or more electrodes, the one or more electrodes being used to selectively and rapidly apply a DC voltage to drive electroporation. As described herein, the system and device may be deployed at the epicardium and / or at the endocardium to treat atrial fibrillation. Voltage may be applied to a selected subset of the electrodes, with anode electrode selection and cathode electrode selection having independent subset selections. A pacing signal for cardiac stimulation may be generated by the signal generator in synchronization with the pacing signal and used to generate a pulse waveform.

[0066] Generally, the systems and devices described herein include one or more catheters configured to ablate tissue in the left atrial chamber of the heart. Figure 1 An ablation system (100) configured to deliver a voltage pulse waveform is shown. The system (100) may include an apparatus (120) comprising 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).

[0067] The signal generator (122) can be configured to generate a pulse waveform for irreversible electroporation of tissue (such as, for example, a pulmonary vein ostium). For example, the signal generator (122) can be a voltage pulse waveform generator and deliver the pulse waveform to the ablation device (110). The return electrode (140) can be coupled to the patient (e.g., placed on the patient's back) to allow current to flow from the ablation device (110) through the patient and then to the return electrode (140) to provide a safe current return path from the patient (not shown). The processor (124) can combine 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) can further store instructions that cause the signal generator (122) to execute modules, processes, and / or functions associated with the system (100) (such as pulse waveform generation and / or cardiac pacing synchronization). For example, the memory (126) may be configured to store pulse waveform data and / or cardiac pacing data for use in pulse waveform generation and / or cardiac pacing, respectively.

[0068] In some embodiments, the ablation device (110) may include a catheter configured to receive and / or deliver a pulse waveform 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 a pulse waveform to ablate the tissue. The ablation device (110) may include one or more electrodes (112), which in some embodiments may be a set of independently addressable electrodes. Each electrode may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without causing dielectric breakdown of its corresponding insulation. In some embodiments, the insulation on each of the electrical leads may maintain a potential difference between about 200V and about 1,500V across its thickness without causing dielectric breakdown. For example, the electrodes (112) can be grouped into one or more anode-cathode subsets, such as, for example, a subset comprising one anode and one cathode, a subset comprising two anodes and two cathodes, a subset comprising two anodes and one cathode, a subset comprising one anode and two cathodes, a subset comprising three anodes and one cathode, a subset comprising three anodes and two cathodes, and the like.

[0069] The pacing device (130) can 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 can be transmitted by the cardiac stimulator (128) to the signal generator (122). Based on the pacing signal, an indication of a voltage pulse waveform can 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 a pulse waveform synchronously with the indication of the pacing signal (e.g., within a common refractory period window). For example, in some embodiments, the common refractory period window can begin substantially immediately after the ventricular pacing signal (or after a very small delay) and last for approximately 250 milliseconds or less thereafter. In such embodiments, the entire pulse waveform can be delivered within this duration.

[0070] 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 processes and / or other modules, processes and / or functions associated with the system and / or a network associated therewith (not shown). The underlying device technology can be provided in a variety of component types, such as metal oxide semiconductor field effect transistor (MOSFET) technology (such as complementary metal oxide semiconductor (CMOS)), bipolar technology (such as emitter coupled logic (ECL)), polymer technology (e.g., silicon conjugated polymer and metal conjugated polymer-metal structure), hybrid analog and digital, etc.

[0071] The memory (126) may include a database (not shown) and may be, for example, a random access memory (RAM), a memory buffer, a hard drive, an erasable programmable read-only memory (EPROM), an electrically erasable read-only memory (EEPROM), a read-only memory (ROM), flash memory, etc. The memory (126) may store instructions that cause the processor (124) to execute modules, processes, and / or functions associated with the system (100), such as pulse waveform generation and / or cardiac pacing.

[0072] 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 interface with the Internet, other operator voice and data networks, business networks, and personal networks. Wired networks are usually carried by copper twisted pairs, coaxial cables, or optical fiber cables. There are many different types of wired networks, including wide area networks (WANs), metropolitan area networks (MANs), local area networks (LANs), campus area networks (CANs), global area networks (GANs) (such as the Internet), and virtual private networks (VPNs). In the following, a network refers to any combination of wireless, wired, public, and private data networks that are usually interconnected by the Internet to provide a combination of unified networking and information access solutions.

[0073] Ablation Device

[0074] The systems described herein may include one or more multi-electrode ablation devices configured to ablate tissue in the left atrial chamber of the heart to treat atrial fibrillation. Figure 2is a perspective view of an ablation device (200) (e.g., similar in structure and / or function to ablation device (110)), comprising a catheter (210) and a guidewire (220) slidable within a lumen of the catheter (210). The guidewire (220) may include a nonlinear distal portion (222), and the catheter (210) may be configured to rest on the guidewire (220) during use. The distal portion (222) of the guidewire (220) may be shaped to facilitate placement of the catheter (210) within a lumen of a patient. For example, the shape of the distal portion (222) of the guidewire (220) may be configured to be placed in and / or near the ostium of a pulmonary vein, as described with reference to FIG. Fig.15 The distal portion (222) of the guidewire (220) may include and / or be formed to have an atraumatic shape that reduces trauma to tissue (e.g., prevents and / or reduces the possibility of tissue puncture). For example, the distal portion (222) of the guidewire (220) may include a non-linear shape, such as a circular, annular (e.g., Figure 2 ), elliptical, or any other geometric shape. In some embodiments, the guidewire (220) can be configured to be elastic so that the guidewire having a nonlinear shape can conform to the lumen of the catheter (210) when placed in the catheter (210) and reform / otherwise regain the nonlinear shape when the catheter (210) is pushed out. In other embodiments, the catheter (210) can be similarly configured to be elastic, such as to help advance the catheter (210) through a sheath (not shown). The shaped distal portion (222) of the guidewire (220) can be angled relative to the guidewire (220) and other portions of the catheter (210). The catheter (210) and the guidewire (220) can be sized to be advanced into the endocardial space (e.g., the left atrium). The diameter of the shaped distal portion (222) of the guidewire (220) can be approximately the same as the diameter of the lumen into which the catheter (230) is to be placed.

[0075] The catheter (210) can be slidably advanced over the guidewire (220) so as to be positioned on the guidewire (220) during use. The distal portion (222) of the guidewire (220) positioned in the lumen (e.g., near the ostium of a pulmonary vein) can act as a stop for advancement of the distal portion of the catheter (210). The distal portion of the catheter (210) can include a set of electrodes (212) (e.g., structurally and / or functionally similar to one or more electrodes (112)), which are configured to contact an inner radial surface of the lumen (e.g., the ostium of a pulmonary vein). For example, the electrodes (212) can include an approximately circular electrode arrangement configured to contact the ostium of a pulmonary vein. As Figure 2As shown, one or more electrodes (212) may include a series of metal bands or metal 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 to conform to the shape of the distal portion (222) of the guide wire (220). The catheter shaft may include a flexible portion between the electrodes for enhancing flexibility. In other embodiments, one or more electrodes (212) may include a spiral winding for enhancing flexibility.

[0076] Each of the electrodes of the ablation device discussed herein can be connected to an insulated electrical lead (not shown), thereby coupling a handle (not shown) to the proximal portion of the catheter. The insulation on each of the electrical leads can maintain a potential difference of at least 700V across its thickness without causing dielectric breakdown. In other embodiments, the insulation on each of the electrical leads can maintain a potential difference of between about 200V and about 2000V across its thickness without causing dielectric breakdown, including all values ​​and subranges therebetween. This allows the electrodes to effectively deliver electrical energy and ablate tissue by irreversible electroporation. The electrodes can, for example, receive a pulse waveform generated by a signal generator (122), as described above with reference to Figure 1 In other embodiments, the guidewire (220) can be separate from the ablation device (200) (e.g., the ablation device (200) includes the catheter (210) but does not include the guidewire (220)). For example, the guidewire (220) can be advanced into the endocardial space by itself, and thereafter, the catheter (210) can be advanced into the endocardial space over the guidewire (220).

[0077] 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)), the ablation device comprising a catheter (310) having a set of electrodes (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 set of electrodes (314) can be positioned along the non-linear distal portion (312) of the catheter (310) and can form a generally circular arrangement of electrodes (314). During use, the electrodes (314) can be positioned at the ostium of a pulmonary vein to deliver a pulse waveform to ablate tissue, as described with reference to FIG. Fig.16More detailed description. The shaped distal portion (312) of the catheter (310) can be angled relative to other portions of the catheter (310). For example, the distal portion (312) of the catheter (310) can be substantially perpendicular to the adjacent portion of the catheter (310). In some embodiments, a handle (not shown) can be coupled to the proximal portion of the catheter (310) and can include a bending mechanism (e.g., one or more pull wires (not shown)) that is configured to modify the shape of the distal portion (312) of the catheter (310). For example, operating the pull wire of the handle can increase or decrease the circumference of the circular shape of the distal portion (312) of the catheter (310). The diameter of the distal portion (312) of the catheter (310) can be modified to allow the electrode (314) to be placed near and / or in contact with the pulmonary vein orifice (e.g., in contact with the inner radial surface of the pulmonary vein). The electrode (314) can include a series of metal bands or metal rings and be independently addressable.

[0078] In some embodiments, the pulse waveforms may be applied between electrodes (314) configured in an anode and cathode group. For example, adjacent or approximately diametrically opposed electrode pairs may be activated together as an anode-cathode group. It should be understood that any of the pulse waveforms disclosed herein may be applied progressively or sequentially to a series of anode-cathode electrodes.

[0079] 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)), the ablation device comprising a catheter (410) and a guidewire (420) having a shaped nonlinear distal portion (422). The guidewire (420) can slide within the lumen of the catheter (410). The guidewire (420) can be advanced through the lumen of the catheter (410), and the distal portion (422) of the guidewire (420) can be approximately circular. The shape and / or diameter of the distal portion (422) of the guidewire (420) can be used as described above with reference to Figure 3The bending mechanism is modified. The catheter (410) can be flexible so as to be deflectable. In some embodiments, the catheter (410) and / or the guide wire (420) can be configured to be elastic so that it conforms to the lumen into which it is placed and assumes a second shape when pushed out of the lumen. 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 for the location from which the guide wire (420) extends) so that the catheter (410) can electrically insulate the portion of the guide wire (420) within the lumen 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 a guidewire (420) to pass through when force is applied to form a compression retainer (which may be fluid-tight) between the seal and the guidewire (420).

[0080] In some embodiments, the exposed distal portion (422) of the guidewire (420) can be coupled to an electrode and configured to receive a pulse waveform from a signal generator and deliver the pulse waveform to tissue during use. For example, the proximal end of the guidewire (420) can be coupled to a suitable lead and connected to Figure 1 The signal generator (122) of the guidewire (420) can be configured to be sized so that it can be positioned at the ostium of the pulmonary vein. For example, the diameter of the shaped distal portion (422) of the guidewire (420) can be approximately the same as the diameter of the ostium of the pulmonary vein. The shaped distal portion (422) of the guidewire (420) can be angled relative to the guidewire (420) and other portions of the catheter (410).

[0081] The guide wire (420) may comprise stainless steel, nitinol, platinum or other suitable biocompatible materials. In some embodiments, the distal portion (422) of the guide wire (420) may comprise 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.

[0082] Figure 5 Detailed 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)), the ablation device comprising a set of electrodes (520, 522, 524, 526), ​​each electrode extending from a pair of insulated lead segments (510, 512, 514, 516). Each pair of adjacent insulated lead segments coupled to uninsulated electrodes (e.g., lead segments (510, 512) and electrode (526)) forms a loop ( Figure 5A set of four loops is shown. The set of loops at the distal portion of the ablation device (500) can be configured to deliver a pulse waveform to tissue. The ablation device (500) can include a set of insulated lead segments (510, 512, 514, 516) that branch at the distal end of the device (500) to connect to corresponding exposed electrodes (520, 522, 524, 526), ​​such as Figure 5 As shown. The electrodes (520, 522, 524, 526) may include exposed portions of electrical conductors. In some embodiments, one or more of the electrodes (520, 522, 524, 526) may include platinum coils. One or more segments (510, 512, 514, 516) may be coupled to a bending mechanism (e.g., a strut, a pull wire, etc.) controlled by a handle (not shown) to control the size and / or shape of the distal portion of the device (500).

[0083] The electrodes (520, 522, 524, 526) can be flexible and formed into a compact first configuration for advancement into the endocardial space, such as adjacent to the ostium of a pulmonary vein. Once positioned at the desired location, when the electrodes (520, 522, 524, 526) are advanced out of a lumen (such as a sheath), the electrodes can be transformed into an expanded second configuration to form a Figure 5 The flower-shaped distal portion 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) into a second configuration when pushed out of a lumen (e.g., a sheath) of the carrier (500). The electrodes (520, 522, 524, 526) can be independently addressable, and each electrode has 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 of the electrical leads can maintain a potential difference between about 200V and about 2000V across the thickness without dielectric breakdown.

[0084] In some embodiments, the ablation device (5000) can be configured to deliver a pulse waveform to tissue through the group of electrodes (520, 522, 524, 526) during use. In some embodiments, the pulse waveform can be applied between electrodes (520, 522, 524, 526) configured in an anode group and a cathode group. For example, an electrode pair that is approximately diametrically opposed (e.g., electrodes (520, 524) and (522, 526)) can be activated together as an anode-cathode pair. In other embodiments, adjacent electrodes can be configured as an anode-cathode pair. As an example, the first electrode (520) in the group of electrodes can be configured as an anode, and the second electrode (522) can be configured as a cathode.

[0085] Figure 6-9E , 26A-27C and 28 show additional embodiments of ablation devices (e.g., structurally and / or functionally similar to ablation device (110)), which can be configured to deliver a voltage pulse waveform using a set of electrodes to ablate tissue and electrically isolate the pulmonary veins. 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 extend outward to contact the lumen of the tissue (e.g., the ostium of the pulmonary vein).

[0086] Figure 6 6 is a side view of an embodiment of an ablation device (600), the ablation device comprising a catheter shaft (610) at the proximal end of the device (600), a distal cap (612) of the device (600), and a set of splines (614) coupled thereto. The distal cap (612) may include an anti-damage shape to reduce trauma to tissue. The proximal end of the set of splines (614) may be coupled to the distal end of the catheter shaft (610), and the distal end of the set of splines (614) may be tethered to the distal cap (612) of the device (600). The ablation device (600) may be configured to deliver a pulse waveform to tissue through one or more splines in the set of splines (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.

[0087] Each spline (614) of the ablation device (600) can include one or more electrodes (616) formed on the surface of the spline (614) that are connected together by wires, or in some cases, independently addressable electrodes. Each electrode (616) can include an insulated electrical lead that is configured to maintain a voltage potential of at least about 700V without causing dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can maintain a potential difference between about 200V and about 2000V across the thickness without causing dielectric breakdown. Each spline (614) can 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)). In the case where the electrodes on a single spline are connected together by wires, the single insulated lead can carry the bundle of wires connected to the different electrodes on the spline. Figure 6 A set of splines (614) is shown, wherein each spline (614) includes a pair of electrodes (616) having approximately 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.

[0088] For each of the ablation devices described herein and in particular Figure 6-9E , 26A-27C and 28, each spline in the group of splines may include a flexible curvature. The minimum radius of curvature of the spline may range from about 1 cm or greater. For example, the group of splines may form a delivery assembly at a distal portion of the ablation device and be configured to transition between a first configuration and a second configuration, in which the group of splines bends radially outward from the longitudinal axis of the ablation device and in which the group of splines is arranged to be substantially parallel to the longitudinal axis of the ablation device. In this way, the splines may more easily conform to the geometry of the endocardial space. Typically, the "basket" of the splines may have an asymmetric shape along the length of the axis, such that one end of the basket (e.g., the distal end) is more spherical than the other end of the basket (e.g., the proximal end). The delivery assembly may be placed in contact with the pulmonary vein ostium in the first configuration and converted to the second configuration before delivering the pulse waveform. In some of these embodiments, a handle may be coupled to the group of splines, and the handle may be configured to affect the conversion of the group of splines between the first configuration and the second configuration. In some embodiments, electrical leads of at least two electrodes in the set of electrodes can be electrically coupled at or near a proximal portion of the ablation device, such as, for example, within the handle.

[0089] In one embodiment, each of the electrodes (616) on a spline (614) can be configured as an anode, while each of the electrodes (616) on an adjacent spline (614) can be configured as a cathode. In another embodiment, the electrodes (616) on one spline can alternate between anode and cathode, with the electrodes on adjacent splines having the opposite configuration (e.g., cathode and anode). The ablation device (600) can include any number of splines, such as 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (600) can include 3 to 20 splines. For example, the ablation device (600) can include 6 to 12 splines.

[0090] Figure 7 7 is a side view of another embodiment of an ablation device (700), the ablation device comprising a catheter shaft (710) at the proximal end of the device (700), a distal cap (712) of the device (700), and a set of splines (714) coupled thereto. The distal cap (712) may include an atraumatic shape. The proximal end of the set of splines (714) may be coupled to the distal end of the catheter shaft (710), and the distal end of the set of splines (714) may be tethered to the distal cap (712) of the device (700). Each spline (714) of the ablation device (700) may include one or more independently addressable electrodes (716) formed on the surface of the spline (714). Each electrode (716) may include an insulated 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 of the electrical leads can maintain a potential difference of between about 200V and about 1500V across the 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 the lumen of the spline (714)). A set of spline wires (718, 719) can be conductive and electrically couple adjacent electrodes (716) disposed on different splines (714) (e.g., 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).

[0091] Figure 7A set of splines (714) is shown, wherein each spline (714) includes a pair of electrodes (716) having approximately 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 wire (718) may be different in size and / or shape than an electrode (716') electrically coupled to a second spline wire (719).

[0092] In some embodiments, the first spline conductors (718) may include a first set of spline conductors (720, 721, 722, 723), wherein each spline conductor in the set of spline conductors (720, 721, 722, 723) may couple an electrode (716) between different pairs of splines in the set of splines (714). In some of these embodiments, the set of spline conductors (720, 721, 722, 723) may form a continuous loop between the electrodes (716) coupled thereto. Similarly, the second spline conductors (719) may include a second set of spline conductors (724, 725, 726), wherein each spline conductor in the set of spline conductors (724, 725, 726) may couple an electrode (716') across the set of splines (714). The second group of spline conductors (724, 725, 726) can be coupled to different electrodes (716') across the group of spline conductors (714) compared to the first group of spline conductors (720, 721, 722, 723). In some of these embodiments, the first group of spline conductors (720, 721, 722, 723) can form a first continuous loop between the electrodes (716) coupled thereto, and the second group of spline conductors (724, 725, 726) can form a second continuous loop between the electrodes (716') coupled thereto. The first continuous loop can be electrically isolated from the second continuous loop. In some of these embodiments, the electrode (716) coupled to the first continuous loop can be configured as an anode, and the electrode (716) coupled to the second continuous loop can be configured as a cathode. The pulse waveform can be delivered to the electrodes (716) of the first continuous loop and the second continuous loop. In some embodiments, the spline wires (such as 721, 722, 723, etc.) can be replaced by similar electrical connections in the proximal portion of the device (e.g., in the device handle). For example, the electrodes 716 can all be electrically connected together with wires in the handle of the device.

[0093] In another embodiment, a first spline wire (721) in the set of spline wires (720, 721, 722, 723) can couple the electrode (716) between the first spline (711) and the second spline (713) in the set of splines (714), and a second spline wire (720) in the set of spline wires (720, 721, 722, 723) can couple the electrode (716) between the first spline (711) and the third spline (715) in the set of splines (714). The electrode (716) coupled by the first spline wire (721) and the second spline wire (720) can be configured as an anode and a cathode (or vice versa). In yet another embodiment, a first spline wire (721) in the set of spline wires (720, 721, 722, 723) can couple an electrode (716) between a first spline (711) and a second spline (713) in the set of splines (714), and a second spline wire (723) in the set of spline wires (720, 721, 722, 723) can couple an electrode (716) between a third spline (715) and a fourth spline (717) in the set of splines (714). A pulse waveform can 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 leads, electrical leads of at least two electrodes in the set of electrodes are electrically coupled at or near a proximal portion of the ablation device, such as, for example, within a handle.

[0094] In other embodiments, one or more of the spline wires (718, 719) can form a continuous loop between the electrically coupled electrodes (716). For example, a first group of spline wires (718) can form a first continuous loop between the electrodes (716) coupled thereto, and a second group of spline wires (719) can form a second continuous loop between the electrodes (716) coupled thereto. In this case, the first continuous loop can be electrically isolated from the second continuous loop. In one embodiment, each of the electrodes (716) coupled to the first group of spline wires (718) can be configured as an anode, while each of the electrodes (716) coupled to the second group of spline wires (719) can be configured as a cathode. Each group of electrically coupled electrodes (716) can be independently addressable. In some embodiments, instead of spline leads, the electrical leads of at least two of the electrodes in the group of electrodes are electrically coupled at or near the proximal portion of the ablation device, such as, for example, within a handle.

[0095] In some embodiments, as described below with reference to Figures 8A-8BAs discussed in further detail, a spline wire can be electrically coupled to a set of electrodes (e.g., 2, 3, 4, 5, etc.) without forming a continuous loop. For example, two spline wires can be used to form a discontinuous loop. In other embodiments, the size, shape, and spacing of the electrodes (716) can be different. The ablation device (700) can include any number of splines, such as 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20 or more splines. In some embodiments, the ablation device (700) can include 3 to 20 splines. For example, in one embodiment, the ablation device (700) can include 6 to 9 splines.

[0096] Figures 8A-8B 1 and 2 are side cross-sectional views and front cross-sectional views of the ablation catheter (800), respectively. Fig. 8A 8 is a side view of an embodiment of an ablation device (800), the ablation device comprising a catheter shaft (810) at the proximal end of the device (800), a distal cap (812) of the device (800), and a set of splines (814) coupled thereto. The distal cap (812) may include an atraumatic shape. The proximal end of the set of splines (814) may be coupled to the distal end of the catheter shaft (810), and the distal end of the set of splines (14) may be tethered to the distal cap (812) of the device (800). Each spline (814) of the ablation device (800) may include one or more independently addressable electrodes (816, 818) formed on the surface of the spline (814). Each electrode (816, 818) may include an insulated 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 of the electrical leads can maintain a potential difference between about 200V and about 2000V across its thickness, including all values ​​and subranges therebetween, without producing dielectric breakdown. 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 the lumen of the spline (814)). One or more spline wires (817, 819) can be conductive and electrically couple adjacent electrodes (816, 818) disposed on different splines (814). For example, the spline wires (817, 819) can extend in a transverse direction relative to the longitudinal axis of the ablation device (800).

[0097] Figure 8B It was taken along line 8B-8B Fig. 8AA front cross-sectional view of . Each spline wire (817, 819, 821, 823) electrically couples a pair of adjacent electrodes (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 to have a common polarity. Adjacent pairs of electrodes can be configured to have opposite polarities (e.g., a first electrode pair is configured as an anode and an adjacent second electrode pair is configured as a cathode). For example, an electrode (816) coupled to a first set of spline wires (817) can be configured as an anode, while each of the electrodes (818) coupled to a second set of spline wires (819) can be configured as a cathode. In some embodiments, each electrode formed on a spline (814) can share a common polarity (e.g., configured as an anode or a cathode). Each coupled electrode pair can be independently addressable. In some embodiments, the ablation device (800) can include an even number of splines. The ablation device (800) may include any number of splines, such as 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, the 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 connected together with wires in the handle of the device so that the electrodes are at the same electrical potential during ablation.

[0098] Fig.9Ais a side view of yet another embodiment of an ablation device (900), the ablation device comprising a catheter shaft (910) at the proximal end of the device (900), a distal cap (912) of the device (900), and a set of splines (914) coupled thereto. The distal cap (912) may include an atraumatic shape. The proximal end of the set of splines (914) may be coupled to the distal end of the catheter shaft (910), and the distal end of the set of splines (914) may be 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 the 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 of the electrical leads can sustain a potential difference across the thickness of between about 200 V and about 2000 V 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 the lumen of the spline (914)). Fig.9A A set of splines (914) is shown, wherein each spline (914) includes an electrode that is spaced apart 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 positioned 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.

[0099] In some embodiments, adjacent distal electrodes (916) and proximal electrodes (918) can form an anode-cathode pair. For example, the distal electrode (916) can be configured as an anode and the proximal electrode (918) can be configured as a cathode. In some embodiments, the ablation device (900) can include 3 to 12 splines. Fig.9AIn the embodiment of 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. The diameter of the spline (914) lumen can therefore be reduced, allowing the spline (914) to be thicker and more mechanically strong. Therefore, 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) can include any number of splines, such as 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20 or more splines. In some embodiments, the ablation device (900) can include 3 to 20 splines. For example, in one embodiment, the ablation device (900) can include 6 to 10 splines. Additionally, in some embodiments, the shape of the spherical expanded structure (930) of the expanded set of splines (914) may be asymmetrical, such that its distal portion is more spherical or rounded than its proximal portion (see, e.g., Figure 9B-9E ). This bulbous distal portion can help position the device at the ostium of the pulmonary vein.

[0100] refer to Figure 9B-9E It should be understood that unless otherwise specified, the reference numerals and Fig.9A Components with similar reference numerals in FIG. Fig.9A The electrode (916) and Fig. 9B The electrodes (916') in can be similar in structure and / or function. Fig. 9B The splined wires (914', 920', 922') are shown forming an expanded structure (930') during use (e.g., when deployed). The cross-sectional area of ​​the expanded structure (930') in a first plane (924A') (sometimes also referred to as a proximal plane) is different from the cross-sectional area at a 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 its cross-sectional area at the first plane (924A'). Fig. 9B As used herein, the terms "first plane" and "second plane" may refer to planes orthogonal to the longitudinal axis of the catheter shaft (910'), each plane being 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 , the electrode ( 916 ′) of the first spline ( 920 ′) is positioned closer to the distal cap ( 912 ′) of the ablation device ( 900 ′) than the electrode ( 918 ′) of the second spline ( 922 ′).

[0101] Fig. 9C The splined wires (914", 920", 922") are shown forming an expanded structure (930") during use (e.g., when deployed). The cross-sectional area of ​​the expanded structure (930") in a first plane (924A") (sometimes also referred to as a proximal plane) is different from the cross-sectional area of ​​the expanded structure (930") at a second plane (924B") . Fig. 9C As shown, in some embodiments, the cross-sectional area of ​​the expanded structure (930") at the second plane (924B") is greater than its cross-sectional area at the first plane (924A"). Fig. 9C As used herein, the terms "first plane" and "second plane" may refer to planes orthogonal to the longitudinal axis of the catheter shaft (910"), each plane being 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. Figures 9A-9B Differently, multiple electrodes may be present on each splined wire and some electrodes may be equidistant from the distal cap (912"). In this way, relatively distal electrodes (such as 932" and 934") may be positioned at or proximal to the ostium / sinus of a pulmonary vein during ablation delivery to create a circumferential lesion around the pulmonary vein.

[0102] Fig.9D 1. Splined wires (914'", 920'", 922'") are shown forming an expanded structure (930'") during use (e.g., when deployed). The splined wires (914'", 920'", 922'") converge at their distal ends to a point (928'") located inside / within the expanded structure (930'). Fig.9D As shown, in this configuration, at least some of the electrodes (932"', 934"') on the spline wires (914"', 920"', 922"') can be located in the distal plane (926"') of the expanded structure (930"'). As shown in reference Fig.9D As used herein, the term "distal plane" can refer to a plane orthogonal to the longitudinal axis of the catheter shaft (910'"), which plane passes through the distal boundary of the expanded structure (930'"). In this manner, the expanded structure (930'") can be pressed against, for example, an endocardial surface (such as the posterior wall of the left atrium) to directly create a lesion thereon by activating a suitable electrode in the distal plane using any suitable polarity combination. For example, the distal electrodes (932'", 934'") can be pressed against the endocardial surface and used to form a lesion (e.g., a spot lesion) by focal ablation.

[0103] Referring now to the use of ablation device (900'") to produce focal ablation lesions, 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 and the application of the electric field as ablative energy to the endocardial surface at the distal plane (926'"), thereby resulting in focal ablation. For example, the spline wires (914'", 920'", 922') can form an extended structure (930'") such that the distal electrodes (932'", 934'") are located at or within the distal plane (926'") of the endocardial surface, while 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 to the distal electrodes (932'", 934'").

[0104] In some embodiments, the electrodes of the ablation device (900'") may have a length of about 0.5 mm to about 5.0 mm and a cross-sectional dimension (eg, diameter) of about 0.5 mm to about 2.5 mm, including all values ​​and subranges therebetween. Fig.9D The cross-sectional dimensions (e.g., diameter) of the splined wires (914'", 920'", 922'") in the expanded structure (930'") shown can be between about 6.0 mm and about 30.0 mm, including all values ​​and subranges 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 subranges therebetween.

[0105] In some embodiments, the distal electrodes (932'", 934'") can be configured to have opposite polarities. In some embodiments, adjacent electrodes on the same spline can have the same polarity, so that the distal electrode (934'") can have the same polarity as the proximal electrode (933), and similarly the distal electrode (932'") can have the same polarity as the proximal electrode (935). The electrodes (934'", 933) can have opposite polarities as the electrodes (932'", 935).

[0106] In some embodiments, adjacent distal electrodes (934'") and proximal electrodes (933) can form an anode-cathode pair. For example, the distal electrode (934'") can be configured as an anode and the proximal electrode (933) can be configured as a cathode. In another embodiment, the electrodes (2630) on one spline can alternate between anode and cathode, with the electrodes of adjacent splines having opposite configurations (e.g., cathode and anode).

[0107] Fig.9E The splined wires (944, 940, 942) are shown forming an expanded structure (950) during use (e.g., when deployed). The splined wires (944, 940, 942) converge at their distal ends at the proximal end of a distal cap (912") inside / within the expanded structure (950). Fig.9E As shown, in this configuration, at least some of the electrodes (952, 954) on the spline wires (944, 940) can be located in the distal plane (946) of the expanded structure (950). Fig.9E As used herein, the term "distal plane" may refer to a plane orthogonal to the longitudinal axis of the catheter shaft (910"), which plane passes 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 to create a lesion 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 (930””) in Fig.9E The expanded structure (950) in has a more orthogonal (e.g., flat) 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 a lesion (e.g., a spot lesion) by focal ablation, as described herein with respect to Fig.9D Roughly described.

[0108] For each ablation device described herein, each spline in the spline can include a polymer and define a lumen to form a hollow tube. One or more electrodes of the ablation device described herein can include a diameter of about 0.2 mm to about 2.0 mm and a length of about 0.2 mm to about 5.0 mm. In some embodiments, the electrode can include a diameter of about 1 mm and a length of about 1 mm. 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 groups of electrodes can deliver different groups of pulses (e.g., graded 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, ablation can be delivered quickly when all electrodes are activated simultaneously. There are a variety of such electrode pairing options, and the options can be implemented based on their convenience.

[0109] 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.26B As best shown in , 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 lumen of the catheter shaft (2610). The distal cap (2612) can include an anti-traumatic shape to reduce trauma to tissue. The proximal end of each spline in the set of splines (2620) can pass through the distal end of the catheter shaft (2610) and can be tethered to the catheter shaft within the lumen of the catheter shaft, and the distal end of each spline in the set of splines (2620) can be tethered to the distal cap (2612) of the device (2600). The ablation device (2600) can be configured to deliver a pulse waveform to tissue during use through one or more splines in the set of splines (2620), such as, for example Figure 21-25 As disclosed in.

[0110] In some embodiments, each spline (2620) of the ablation device (2600) can include one or more electrodes (2630) formed on the surface of the spline (2620) connected together by a wire. In other embodiments, one or more of the electrodes (2630) on a given spline can be independently addressable electrodes (2630). Each electrode (2630) 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 of the electrical leads can maintain a potential difference between about 200V and about 2000V across the thickness without dielectric breakdown. Each spline (2620) can 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 approximately the same size, shape, and spacing as the electrodes (2634 or 2632) of an adjacent spline (2620). In other embodiments, the size, shape, and spacing of the electrodes (2632, 2634) may be different. The thickness of each spline (2620) may vary based on the number of electrodes (2630) formed on each spline (2620), which number 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.

[0111] Each spline in the set of splines (2620) may include a flexible curvature to allow rotation, or to twist and bend and form a petal-like curve, such as Figures 26A-26CAs shown. The minimum radius of curvature of the splines in a petal-like configuration can range from about 7 mm to about 25 mm. For example, the group of splines can form a delivery assembly at a distal portion of an ablation device (2600) and be configured to transition between a first configuration and a second configuration, wherein the first configuration wherein the group of splines is arranged approximately parallel to the longitudinal axis of the ablation device (2600) and the second configuration wherein the group of splines rotates about the longitudinal axis of the ablation device (2600), or twists and bends and is approximately offset away from the longitudinal axis. In the first configuration, each spline in the group of splines can be located in a plane with the longitudinal axis of the ablation device. In the second configuration, each spline in the group of splines can be offset away from the longitudinal axis to form a petal-like curve arranged approximately perpendicular to the longitudinal axis. In this manner, the set of splines (2620) are twisted, bent, and offset away from the longitudinal axis of the ablation device (2600), thereby allowing the splines (2620) to more easily conform to the geometry of the endocardial space and specifically adjacent to the ostial opening. Fig.26C As best shown, the second configuration may, for example, resemble the shape of a flower. In some embodiments, each spline in the set of splines in the second configuration may twist and bend to form a petal-like curve that exhibits an angle of more than 180 degrees between the proximal and distal ends of the curve when viewed from the front. The set of splines may further be configured to transition from the second configuration to a third configuration in which the set of splines (2620) may impress (e.g., contact) target tissue, such as tissue surrounding a pulmonary vein ostium.

[0112] In some embodiments, the spline shaft (2614) coupled to the set of splines (2620) can allow each spline in the set of splines (2620) to bend and twist relative to the catheter shaft (2610) as the spline shaft (2614) slides within the lumen of the catheter shaft (2610). For example, the set of splines (2620) can form a shape that is generally parallel to the longitudinal axis of the spline shaft (2614) when not deployed, can wrap (e.g., twist helically) around an axis (2660) that is parallel to the longitudinal axis of the spline shaft (2620) when fully deployed, and form any intermediate shape (such as a cage or cylinder) therebetween as the spline shaft (2614) slides within the lumen of the catheter shaft (2610).

[0113] In some embodiments, the set of splines (e.g., splines (2620)) in the first configuration can be wound about an axis (2660) that is parallel to the longitudinal axis of the catheter shaft (2610) for some portion along its length, but other portions can be generally parallel to the longitudinal axis of the catheter shaft (2610) in other ways. 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 splines (2620) are 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 this 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) and the rotational twist of splines (2620) can be configured by appropriately placing electrodes along each spline to prevent electrodes (2630) on one spline from overlapping electrodes of adjacent overlapping splines (2620).

[0114] A spline with a set of anode electrodes (2632) can be activated together to deliver a pulse waveform for irreversible electroporation. Fig.26C As shown, electrodes on other splines can be activated together as cathode electrodes (such as electrodes (2634) and (2635) 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 through a set of such pairings.

[0115] For example, the splines (2620) can be activated sequentially in a clockwise or counterclockwise manner. As another example, the cathode splines can be activated sequentially with the corresponding sequential anode spline activation until ablation is complete. In embodiments where the electrodes on a given spline are connected separately with wires, the activation sequence within the electrodes of each spline can also vary. For example, the electrodes in a spline can be activated all at once or in a predetermined sequence.

[0116] The delivery assembly can be arranged in the first configuration before delivering the pulse waveform, and can be converted to the second configuration to contact the pulmonary vein orifice 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 group of splines 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 group of splines (2620) coupled to the distal cap and bending and twisting the group of splines. The proximal end of the spline (2620) can be fixed to the spline shaft (2614), thereby generating the buckling of the spline (2620), thereby causing the bending and twisting movement 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 set of splines (2620) tethered to the distal cap (2612) can translate up to about 60 mm along the longitudinal axis of the ablation device to actuate such a configuration change. In other words, translation of the actuation member of the handle can bend and twist the set of splines (2620). In some embodiments, actuation of a knob, wheel, or other rotary control mechanism in the handle of the device can cause the actuation member or spline shaft to translate and cause the splines (2620) to bend and twist. In some embodiments, the electrical leads of at least two of the electrodes in the set of electrodes (2630) can be electrically coupled at or near a proximal portion of the ablation device (2600), such as, for example, within the handle.

[0117] Retraction of the spline shaft (2614) and distal cap (2612) may bring the set of splines (2620) closer together, as Fig.26B 2610). In some embodiments, each spline in the group of splines (2620) can be laterally offset away from the longitudinal axis of the spline shaft (2614) by up to about 3 cm. In some embodiments, the spline shaft (2614) can include a hollow lumen. In some embodiments, the cross-section of the spline can 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 can be configured to present a relatively large lateral stiffness and thereby can be deployed with minimal overlap of the petal-shaped curves of each spline and its adjacent spline in the final or fully deployed configuration.

[0118] In one embodiment, each of the electrodes (2632) on a spline (2620) can be configured as an anode, while each of the electrodes (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, while the electrodes of another spline have the opposite configuration (e.g., cathode and anode).

[0119] 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 connected together with wires within the spline, while in alternative embodiments, the electrodes can be connected together with wires in 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 pair. For example, the distal electrode can be configured as an anode and the proximal electrode can be configured as a cathode.

[0120] The ablation device (2600) may include any number of splines, such as 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.

[0121] Each of the splines in the set of splines (2620) can include a corresponding electrode (2630) having an atraumatic shape to reduce trauma to tissue. For example, the electrode (2630) can have an atraumatic shape including a rounded, flat, curved, and / or blunt tip portion configured to contact endocardial tissue. In some embodiments, the electrode (2630) can be positioned along any portion of the splines (2620) distal to the catheter shaft (2610). The electrode (2630) can have the same or different sizes, shapes, and / or positions along the corresponding splines.

[0122] In this way, the electrode in the second configuration can be held proximate to or placed against a portion of the atrial wall of the left atrium so as to create a lesion directly on the portion by activating the appropriate electrode using any suitable polarity combination, as described herein. For example, the set of splines (2620) can be placed in contact against an atrial wall (2654) of an atrium (2652) adjacent to a pulmonary vein (2650) (e.g., ostium or antrum).

[0123] Fig.26Dis a schematic illustration of an ablation (2664) produced by an ablation device (2600) on tissue, such as tissue surrounding a pulmonary vein ostium. For example, activating one or more of the electrodes (2630) on one or more of the splines (2620) can produce one or more corresponding ablation regions (2664) along the wall (2654) of the pulmonary vein antrum or ostium. In some embodiments, the diameter of the contour of the ablation region (2664) in the pulmonary vein ostium can be between about 2 cm and about 6 cm, and can be about 3.5 cm. In this way, a continuous transmural lesion can be produced, resulting in electrical isolation of the pulmonary veins, which is a desired therapeutic effect.

[0124] 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 an appropriate set of electrodes, an appropriate pulse waveform may be delivered for irreversible electroporation energy delivery to ablate tissue.

[0125] In some embodiments, since the electrodes or subsets of 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 groups of electrodes can deliver different groups of pulses (e.g., graded 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 when all electrodes are activated simultaneously. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0126] In some embodiments, the distal-most portion of the ablation device may include a set of splines rather than a distal cap or another element that extends the length of the catheter shaft. This may help position the set of splines against the tissue and reduce contact with tissue by other elements of the ablation device that may cause trauma 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) at the proximal end of the device (3500). The first catheter (3510) can define a longitudinal axis (3550) and a lumen therethrough. A second catheter (3520) can be slidably disposed within the first catheter lumen and extend from a distal end of the first catheter lumen. The diameter of the second catheter (3520) can be smaller than the diameter of the first catheter (3510). The second catheter (3520) can define a lumen therethrough. For example, the lumen can provide a passage for another device (e.g., a guidewire).

[0127] A set of splines (3530) can be coupled to a first catheter (3510) and a second catheter (3520). Specifically, a proximal portion of the set of splines (3530) can be coupled to the distal end of the first catheter (3510), and a distal portion of the set of splines (3530) 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 set of splines (3530) 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 set of splines (3530) 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 set of splines (3530). For example, a polymer reflow process can be used to form a smooth, atraumatic joint between the second catheter (3520) and the set of splines (3530). The ablation device (3500) can be configured to deliver a pulse waveform to tissue during use through an electrode of one or more splines in the set of splines (3530), such as, for example Figure 21-2 6 disclosed.

[0128] Each spline (3530) of the ablation device (3500) can include one or more electrodes (3540) formed on a surface of the spline (3530). Each electrode (3540) can include an insulated electrical lead configured to sustain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. Each spline (3530) can include an insulated electrical lead of each electrode (3540) formed in the body of the spline (3530) (e.g., within the lumen of the spline (3530)). Fig.35 A set of splines is shown, wherein each spline (3530) contains a set of electrodes (3540) having approximately the same size, shape, and spacing as the electrodes (3540) of an adjacent spline. In other embodiments, the size, shape, and spacing of the electrodes (3540) may be different.

[0129] 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.

[0130] At least a portion of the group of splines (3530) may include a flexible curvature. For example, a proximal region (3522) and a distal region (3526) of each spline (3530). The group of splines (3530) may form a delivery assembly at a distal portion of the ablation device (3500) and may be configured to transition between a first configuration and a second configuration, wherein the group of splines (3530) is arranged generally closer to the longitudinal axis (3540) of the ablation device (3500) and wherein the group of splines (3530) bends radially outward from the longitudinal axis (3540) of the ablation device (3500) to form a basket-like and / or flower-like shape in which each spline forms a "petal". Reference may be made to the description corresponding to the embodiment of the present invention. Figures 34A-34B The spatial curve shape of the spline in the second configuration is described by equations (1)-(3). For example, in the fully expanded configuration, the integral amplitude of the rotation rate of each of the splines in the set of splines (3530) along the length of each spline can be greater than π radians.

[0131] In other embodiments, the "basket" of the splines can have an asymmetric shape along the length of the catheter, such that one end of the basket (e.g., the distal end) is more spherical than the other end of the basket (e.g., the proximal end). The delivery assembly can be advanced through the body cavity in the first configuration and converted to the second configuration prior to delivering the pulse waveform. In some embodiments, a handle (not shown) can be coupled to the set of splines (3530), and the handle is configured to affect the conversion of the set of splines (3530) 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 can cause the second catheter (3520) to translate relative to the first catheter (3510) and cause the splines (3530) to bend. In some embodiments, the electrical leads of at least two electrodes in the set of electrodes (3540) can 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 set of splines (3530), such as Fig.35As shown. The distal end of the spline (3530) can be fixed to the distal end of the second catheter (3520), thereby generating a flexion of the spline (3530), thereby causing 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 actuating member of the handle can bend the group of splines (3530). In some embodiments, each spline in the group of splines (3530) can be laterally offset away from the longitudinal axis (3540) of the second catheter (3512) by up to about 35mm. For example, the group of splines (3530) in the second configuration can be formed in a shape with an effective cross-sectional diameter between about 10mm and about 35mm at its largest portion. In the second configuration, the length of the group of splines can be between about 15mm and about 50mm.

[0132] In one embodiment, each of the electrodes on a spline can be configured as an anode, while each of the electrodes on different splines can be configured as a cathode. That is, the groups of electrodes on adjacent splines can have opposite polarities. In another embodiment, the electrodes on one spline can alternate between an anode and a cathode, while the electrodes of another spline have opposite configurations (e.g., a cathode and an anode). 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.

[0133] In some embodiments, the electrodes can be electrically activated in a sequential manner to deliver a pulse waveform with each anode-cathode pairing. In some embodiments, the electrodes (3540) can be electrically connected together with wires within the spline (3530), while in alternative embodiments, the electrodes can be connected together with wires in 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) can also be different. As another example, the splines (3530) can be activated sequentially in a clockwise or counterclockwise manner. As another example, the cathode splines can 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 connected separately with wires, the activation order within the electrodes (3540) of each spline (3530) can also vary. For example, the electrodes (3540) in the spline can be activated all at once or in a predetermined order.

[0134] 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 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 so can all other electrodes (e.g., all proximal electrodes). Therefore, ablation can be delivered quickly when all electrodes are activated simultaneously. There are a variety of such electrode pairing options, and the options can be implemented based on their convenience.

[0135] Each of the splines (3530) can be comprised of a polymer and define a lumen to form a hollow tube. The diameter of the set of splines (3530) of the ablation device (3500) can be between about 1.0 mm and about 5.0 mm. The diameter of the set of electrodes (3540) of the ablation device (3500) can be between about 1.0 mm and about 5.0 mm, and the length can be between about 0.2 mm and about 5.0 mm.

[0136] The ablation device (3500) may include any number of splines, such as 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.

[0137] Each of the splines in the group of splines (3530) can include a corresponding electrode (3540) having an atraumatic shape to reduce trauma to the tissue. For example, the electrode (3540) can have an atraumatic shape that includes a round, flat, curved, and / or blunt tip portion. In some embodiments, the electrode (3540) can be positioned along any portion of the spline (3530) distal to the first catheter (3510). The electrode (3540) can have the same or different size, shape, and / or position along the corresponding spline. The ablation device (3500) can include any number of electrodes, such as 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) can include 2 to 12 electrodes per spline.

[0138] Figures 34A-34B is a side view of a spline (3400) that is structurally and / or functionally similar to the splines described herein, such as Figures 36A-36C Spline shown. Fig.34A is a side view of a 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 a spline in a second configuration and / or a third configuration, as described in detail herein. For simplicity, the spline (3400) is shown without other elements, such as electrodes. The curved spline (3400) includes a proximal end (3402) and a distal end (3404). A unit tangent vector u (3420) may be defined at each point (3410) along the spline (3400). 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.

[0139] The rate of change of the unit tangent vector along the length of the spline can be controlled by the following equation:

[0140] u' = du / dl (1)

[0141] Where l is the arc length along the spline.

[0142] The rate of change of the unit tangent vector u' can be referred to as the rotation rate of the unit tangent vector along the spline. The rotation rate u' is perpendicular to the unit tangent vector u because u·u=1.

[0143] In some embodiments, a spline that can be transformed to form a petal shape as described herein 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 that is governed by the following inequality:

[0144] ∫|u ′ |}dl>π (2)

[0145] That is, the integral 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 = u x u' is perpendicular to both u and u'.

[0146] 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 position along the length of the spline, which is governed by the following equation:

[0147] ∫(u″·b)dl≠0 (3)

[0148] In some embodiments of the devices described herein, the expanded splines of the set of splines may satisfy both equations (2) and (3).

[0149] Figures 36A-36C is a side view of an ablation catheter (3600) configured to have a set of splines expanded when the distal splines are fully expanded and a set of electrodes extending distally of all other elements of the catheter (3600) to reduce trauma to the tissue and to facilitate positioning and contact between the set of electrodes and the 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) at the proximal end of the device (3600). The first catheter (3610) can define a longitudinal axis (3650) and a lumen therethrough. A second catheter (3620) can be slidably disposed within the first catheter lumen and extend from the distal end of the first catheter lumen. The first catheter and the second catheter and a catheter handle for actuation can comprise a single device. A set of splines (3630) can be coupled to the first catheter (3610) and the second catheter (3620). The second catheter (3620) can translate along the longitudinal axis (3650) of the ablation device (3600). The proximal end of each spline in the set of splines (3630) 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 in the set of splines (3630) can be tethered to the distal end (3622) of the second catheter (3620), as described with reference 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 (e.g., thin heart walls) with reduced risk of trauma from the device (3600). The ablation device (3600) can be configured to deliver a pulse waveform to tissue during use via one or more electrodes on the set of splines (3630), such as, for example Figure 21-2 6 disclosed.

[0150] In some embodiments, each spline (3630) of the ablation device (3600) can include one or more electrodes (3640) formed on the surface of the spline (3630) connected together by a wire. In other embodiments, one or more of the electrodes (3640) on a given spline can be independently addressable electrodes (3640). Each electrode (3640) 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 of the electrical leads can maintain a potential difference between about 200V and about 2000V across the thickness without dielectric breakdown. Each spline (3630) can 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 contains 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 number 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.

[0151] Each spline in the set of splines (3630) may include a flexible curvature to allow rotation, or to twist and bend and form a petal-like curve, such as Figures 26A-26C , Figures 34A-34B and Figures 36A-36CAs shown. The minimum radius of curvature of the splines in the petal-like configuration can be between about 7 mm and about 25 mm. For example, the group of splines can form a delivery assembly at a distal portion of the ablation device (3600) and be configured to transition between a first configuration and a second configuration, in which the group of splines is arranged generally closer to the longitudinal axis of the ablation device (3600) and in which the group of splines is rotated around the longitudinal axis of the ablation device (3600), or twisted and bent and generally offset away from the longitudinal axis. In the first configuration, each spline in the group of splines can be located in a plane with the longitudinal axis of the ablation device. In the second configuration, each spline in the group of splines can be offset away from the longitudinal axis to form a petal-like curve (e.g., a flower shape) in which 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. As described in detail herein, the shape (e.g., bend, curve) of the set of splines can satisfy equations (1)-(3). In this way, the set of splines (3620) twists and bends and is offset away from the longitudinal axis of the ablation device (3600), thereby allowing the splines (3620) to more easily conform to the geometry of the endocardial space (such as the posterior wall and the ostial opening). In some embodiments, each spline in the set of splines in the second configuration can be twisted and bent to form a petal-like curve that, when viewed from the front, exhibits an angle of more than 180 degrees between the proximal and distal ends of the curve.

[0152] In some embodiments, the second catheter (3620) coupled to the set of splines (3630) can allow each of the splines in the set of splines (3630) to bend and twist relative to the first catheter (3610) as the second catheter (3620) slides within the lumen of the first catheter (3610). For example, the set of splines (3630) can form a shape that is generally closer to the longitudinal axis of the second catheter (3620) when not deployed, and wrap (e.g., twist helically) around the longitudinal axis (3650) when fully deployed, and form any intermediate shape (such as a cage or cylinder) therebetween as the second catheter (3620) slides within the lumen of the first catheter (3610).

[0153] In some embodiments, the set of splines (such as splines 3630) in the first configuration can be wrapped around the longitudinal axis (3650) of the first catheter (3610) along some portions of their length, but other portions can be generally parallel to the longitudinal axis of the first catheter (3610) in other ways. 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). As the second catheter (3622) is further retracted into the lumen of the first catheter (3610), the set of splines (3630) can extend further distally. Figures 36A-36C As shown, each spline (3630) can form a twisted loop (e.g., a petal shape, where the group of splines together form a flower shape).

[0154] In the second configuration, the set of splines (3630) in the second configuration may form a flower shape and may be angled in a distal direction. Fig.36A The set of splines (3630) is depicted, with at least a portion of each spline in the set of splines (3630) 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) (perpendicular to the longitudinal axis (3650)) distal to the distal end (3622) of the second catheter (3620). Thus, when the ablation device (3600) is advanced in the distal direction to contact tissue, the set of splines (3630) will contact before the first catheter (3610) and the second catheter (3620). This can reduce trauma to the tissue because the tissue can contact the flexible set of splines without having to contact the relatively stiff second catheter (3622).

[0155] Fig.36B The set of splines (3630) in the second configuration is shown, the set of splines forming a distal (e.g., forward) angle (3680) between the longitudinal axis (3670) of the splines (3630) and the longitudinal axis of the first catheter (3650). The longitudinal axis (3670) of the splines (3630) can be defined by a line formed between the apex of the splines (3630) and the midpoint between the proximal and distal ends of the splines (3630). In some embodiments, the distal angle can be less than about 80 degrees. For example, the distal angle can be 60 degrees or less.

[0156] 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 appropriate placement of electrodes along each spline to prevent an electrode (3640) on one spline from overlapping an electrode of an adjacent overlapping spline.

[0157] A spline with a set of anode electrodes 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 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 through a set of such pairings.

[0158] For example, the splines (3630) can be activated sequentially in a clockwise or counterclockwise manner. As another example, the cathode splines can be activated sequentially with the corresponding sequential anode spline activation until ablation is complete. In embodiments where the electrodes on a given spline are connected separately with wires, the activation sequence within the electrodes of each spline can also vary. For example, the electrodes in a spline can be activated all at once or in a predetermined sequence.

[0159] The delivery assembly can be positioned in the first configuration prior to delivering the pulse waveform and can be switched to the second configuration to contact the ostium or sinus of a pulmonary vein. Fig.36C A distal-most portion of the set of splines (3630) is depicted as being in close proximity to and / or contacting a tissue wall (3690) (eg, the posterior wall of the left atrium). Fig.36C The group of splines (3630) in the second catheter (3620) is in a second configuration in which at least a portion of each spline in the group of splines (3630) 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). Thus, the ablation device (3600) in the second configuration can engage the tissue (3690) in an atraumatic manner with a reduced risk of perforation or other trauma. Thus, the ablation device (3600) can be used to ablate even thinner tissue structures, such as the posterior wall of the left atrium.

[0160] In some of these embodiments, a handle can be coupled to the second catheter (3620), and the handle is configured to affect the conversion of the group of splines between the first configuration and the second configuration. For example, the handle can be configured to translate the second catheter (3620) relative to the first catheter (3610), thereby actuating the group of splines (3630) coupled to the second catheter (3620) and causing the group of splines to bend and twist. The proximal end of the spline (3630) can be fixed to the second catheter (3620), thereby generating flexion of the spline (3630), thereby causing bending and twisting movement 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 group of splines (3630) tethered to the second catheter (3620) can be translated up to about 60 mm along the longitudinal axis of the ablation device to actuate such a configuration change. In other words, translation of the actuation member of the handle can bend and twist the set of splines (3630). In some embodiments, actuation of a knob, wheel, or other rotational control mechanism in the device handle can cause the actuation member or second catheter to translate and cause the splines (3630) to bend and twist. In some embodiments, electrical leads of at least two electrodes in the set of electrodes (3640) can be electrically coupled at or near a proximal portion of the ablation device (3600), such as, for example, within the handle.

[0161] Retraction of the second conduit (3620) relative to the first conduit (3610) may bring the set of splines (3630) closer together, as Figures 36A-36C As shown. The group of splines (3630) is further approximately perpendicular or angled distally relative to the longitudinal axis (3650) of the first catheter (3610). In some embodiments, each spline in the group of splines (3630) can be laterally offset away from the longitudinal axis (3650) by up to about 30 mm. In some embodiments, the second catheter (3620) can include a hollow lumen. In some embodiments, the cross-section of the spline can 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 can be configured to present a relatively large lateral stiffness, and thereby can be deployed with minimal overlap of the petal-shaped curves of each spline and its adjacent spline in the final or fully deployed configuration.

[0162] In one embodiment, each of the electrodes (3640) on a spline (3630) can be configured as an anode, while each of the electrodes (3640) on a different spline (3630) can be configured as a cathode. In another embodiment, the electrodes (3640) on one spline can alternate between anode and cathode, while the electrodes of another spline have the opposite configuration (e.g., cathode and anode).

[0163] 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 connected together with wires within the spline, while in alternative embodiments, the electrodes can be connected together with wires in 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.

[0164] The ablation device (3600) may include any number of splines, such as 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.

[0165] Each of the splines in the set of splines (3630) can include a corresponding electrode (3640) having an atraumatic shape to reduce trauma to tissue. For example, the electrode (3640) can have an atraumatic shape including a rounded, flat, curved, and / or blunt tip portion configured to contact endocardial tissue. In some embodiments, the electrode (3640) can be positioned along any portion of the splines (3630) distal to the first catheter (3610). The electrode (3640) can have the same or different sizes, shapes, and / or positions along the corresponding splines.

[0166] In this way, the electrode in the second configuration can be held proximate to or placed against a portion of the atrial wall of the left atrium so as to create a lesion directly on the portion by activating the appropriate electrode using any suitable polarity combination, as described herein. For example, the set of splines (3630) can be placed in contact with the atrial wall (3654) and / or posterior wall of the atrium (3652) adjacent to a pulmonary vein (3650) (e.g., ostium or antrum).

[0167] Figures 37A-37B is a perspective view of the ablation catheter (3730) and the left atrium (3700). Fig.37A is a perspective view of an ablation catheter (3730) positioned 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 structurally and / or functionally similar to the ablation devices (3500, 3600) described herein, can be advanced into the left atrium (3700), and positioned adjacent to and / or in contact with the posterior wall (3710) of the left atrium (3700) without perforating and / or traumatizing sensitive tissue of the posterior wall (3710). For example, the set of splines can extend distally of the distal end of the catheter coupled to the splines so that the flexible and damage-resistant splines can be adjacent to or in contact with the posterior wall (3710) without any other portion of the device (3730) contacting the posterior wall (3710). In embodiments where the distal-most portion of the device (3700) includes only the set of splines in the second configuration (e.g., having a flower shape), the deployed device can engage thin tissue structures (such as a heart wall) with minimal risk of trauma from the ablation device (3700). A set of pulse waveforms can be applied by electrodes of the ablation device (3700) having a flower shape to ablate tissue within the ablation zone (3740).

[0168] Fig.37BSchematic diagram of a perspective view of the left atrium (3700) after tissue ablation. The ablation device (3700) can be used to produce a set 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 of the splines of the ablation device (3730) as the catheter moves between complete ablations can produce the set of ablation zones (3740, 3742, 3744) along the posterior wall (3710) of the left atrium (3700). In some embodiments, the ablation zones (3740, 3742, 3744) can partially overlap each other. These continuous overlapping ablation zones can approximately form an ablation thick line (3746). One or more ablation lines can be connected to other ablation lines and / or ablation zones (e.g., produced around the pulmonary vein sinus or mouth) to thereby produce a box-shaped lesion. For example, a set 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) that also surrounds one or more of the pulmonary veins (3720). In this way, a continuous transmural lesion can be created around all of the pulmonary veins, resulting in electrical isolation of the pulmonary veins to provide the desired therapeutic effect. In some embodiments, the diameter of each ablation zone in a set 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.

[0169] In some embodiments, since the electrodes or subsets of electrodes can be 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 enough energy to electrically isolate one or more pulmonary veins. In some embodiments, the 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.

[0170] Figures 27A-27Bis a side view of an embodiment of an ablation device (2700) comprising a catheter shaft (2710) at the proximal end of the device (2700) and a set of splines (2720) 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 through one or more splines in the set of splines (2720) during use. Each spline (2720) of the ablation device (2700) can include one or more electrodes (2730) that may be independently addressable formed on a surface (e.g., distal end) of the spline (2720). Each electrode (2730) 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 of the electrical leads can sustain a potential difference between about 200V and about 2000V across the thickness without dielectric breakdown. Each spline in the set of splines (2720) can 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) can be formed at the distal end of their respective splines (2720).

[0171] The set of splines (2720) 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 set of splines (2720) in the first configuration are generally parallel to a longitudinal axis of the ablation device (2700) and may be closely spaced together. Figures 27A-27B , wherein the group of splines (2720) is depicted in a second configuration, wherein the group of splines (2720) extends beyond the distal end of the catheter shaft (2710) and is offset (e.g., bent) away 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 positioned in the first configuration prior to delivering a pulse waveform, and can be converted to the second configuration to reach a portion of cardiac tissue (such as the posterior wall of the left atrium or the ventricle). This device for delivering an irreversible electroporation pulse waveform can produce larger lesions for focal ablation.

[0172] The distal end of the set of splines (2720) can be configured to be offset away from the longitudinal axis of the distal end of the catheter shaft (2710) and offset away from the other splines. Each spline in the set of splines (2720) can include a flexible curvature. The minimum radius of curvature of the splines (2720) can range from about 1 cm or greater.

[0173] In some embodiments, the proximal end of the set of splines (2720) can be slidably coupled to the distal end of the catheter shaft (2710). Thus, the length of the set of splines (2720) can vary, such as Fig.27A and 27B As shown. As the group of splines (2720) further extends outward from the catheter shaft (2710), the distal ends of the group of splines (2720) can be further offset away from each other and the longitudinal axis of the catheter shaft (2710). The group of splines (2720) can be independently or in one or more groups slidably pushed out of the catheter shaft (2710). For example, the group of splines (2720) can be placed in the catheter shaft (2710) in the first configuration. The splines (2720) can then be pushed out of the catheter shaft (2710) and converted into a second configuration. The splines (2720) can be pushed together or pushed forward so that the group of splines (2720) corresponding to the anode electrode (2730) is pushed separately from the group of splines (2720) corresponding to the cathode electrode (2730). In some embodiments, the splines (2720) can be pushed forward independently. In the second configuration, the electrode (2730) is longitudinally and / or laterally offset away from the catheter shaft (2710) relative to the longitudinal axis of the distal end of the catheter shaft (2710). This can facilitate delivery and positioning of the electrode (2730) against the endocardial surface. In some embodiments, each spline in the set of splines (2720) can extend up to about 5 cm from the distal end of the catheter shaft (2710).

[0174] In some embodiments, the group of splines (2720) can have a fixed length extending 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 radius of curvature greater than an adjacent spline can extend further from the catheter shaft (2710) than an adjacent spline. The group of splines (2720) can be constrained by the lumen of the guide sheath so that the group of splines (2720) is substantially parallel to the longitudinal axis of the catheter shaft (2710) in the first configuration.

[0175] In some of these embodiments, a handle (not shown) can be coupled to the set of splines. The handle can be configured to affect a transition of the set of splines between the first configuration and the second configuration. In some embodiments, electrical leads of at least two electrodes in the set of electrodes (2730) can be electrically coupled at or near a proximal portion of the ablation device, such as, for example, within the handle. In this case, the electrodes (2730) can be electrically connected together with wires in the handle of the device (2700) so that the electrodes (2730) are at the same electrical potential during ablation.

[0176] Each of the splines in the set of splines (2720) can include a corresponding electrode (2730) at the distal end of the set of splines (2720). The set of electrodes (2730) can include an atraumatic shape to reduce trauma to tissue. For example, the electrode (2730) can have an atraumatic shape that includes a rounded, flat, curved, and / or blunt portion configured to contact endocardial tissue. In some embodiments, the electrode (2730) can be positioned along any portion of the splines (2720) distal to the catheter shaft (2710). The electrode (2730) can have the same or different size, shape, and / or position along the corresponding splines.

[0177] In one embodiment, an electrode (2730) on a spline (2720) can be configured as an anode, while an electrode (2730) on an adjacent spline (2720) can be configured as a cathode. The ablation device (2700) can include any number of splines, such as 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2700) can include 3 to 20 splines. For example, the ablation device (2700) can include 6 to 12 splines.

[0178] Figures 27A-27B is a side view of an embodiment of an ablation device (2700) comprising a catheter shaft (2710) at the proximal end of the device (2700) and a set of splines (2720) 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 through one or more splines in the set of splines (2720) during use. Each spline (2720) of the ablation device (2700) can include one or more electrodes (2730) that may be independently addressable formed on a surface (e.g., distal end) of the spline (2720). Each electrode (2730) 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 of the electrical leads can sustain a potential difference between about 200V and about 2000V across the thickness without dielectric breakdown. Each spline in the set of splines (2720) can 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) can be formed at the distal end of their respective splines (2720).

[0179] The set of splines (2720) 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 set of splines (2720) in the first configuration are generally parallel to a longitudinal axis of the ablation device (2700) and may be closely spaced together. Figures 27A-27B , wherein the group of splines (2720) is depicted in a second configuration, wherein the group of splines (2720) extends beyond the distal end of the catheter shaft (2710) and is offset (e.g., bent) away 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 positioned in the first configuration prior to delivering a pulse waveform, and can be converted to the second configuration to reach a portion of cardiac tissue (such as the posterior wall of the left atrium or the ventricle). This device for delivering an irreversible electroporation pulse waveform can produce larger lesions for focal ablation.

[0180] The distal end of the set of splines (2720) can be configured to be offset away from the longitudinal axis of the distal end of the catheter shaft (2710) and offset away from the other splines. Each spline in the set of splines (2720) can include a flexible curvature. The minimum radius of curvature of the splines (2720) can range from about 1 cm or greater.

[0181] In some embodiments, the proximal end of the set of splines (2720) can be slidably coupled to the distal end of the catheter shaft (2710). Thus, the length of the set of splines (2720) can vary, such as Fig.27A and 27BAs shown. As the group of splines (2720) further extends outward from the catheter shaft (2710), the distal ends of the group of splines (2720) can be further offset away from each other and the longitudinal axis of the catheter shaft (2710). The group of splines (2720) can be independently or in one or more groups slidably pushed out of the catheter shaft (2710). For example, the group of splines (2720) can be placed in the catheter shaft (2710) in the first configuration. The splines (2720) can then be pushed out of the catheter shaft (2710) and converted into a second configuration. The splines (2720) can be pushed together or pushed forward so that the group of splines (2720) corresponding to the anode electrode (2730) is pushed separately from the group of splines (2720) corresponding to the cathode electrode (2730). In some embodiments, the splines (2720) can be pushed forward independently. In the second configuration, the electrode (2730) is longitudinally and / or laterally offset away from the catheter shaft (2710) relative to the longitudinal axis of the distal end of the catheter shaft (2710). This can facilitate delivery and positioning of the electrode (2730) against the endocardial surface. In some embodiments, each spline in the set of splines (2720) can extend up to about 5 cm from the distal end of the catheter shaft (2710).

[0182] In some embodiments, the group of splines (2720) can have a fixed length extending 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 radius of curvature greater than an adjacent spline can extend further from the catheter shaft (2710) than an adjacent spline. The group of splines (2720) can be constrained by the lumen of the guide sheath so that the group of splines (2720) is substantially parallel to the longitudinal axis of the catheter shaft (2710) in the first configuration.

[0183] In some of these embodiments, a handle (not shown) can be coupled to the set of splines. The handle can be configured to affect a transition of the set of splines between the first configuration and the second configuration. In some embodiments, electrical leads of at least two electrodes in the set of electrodes (2730) can be electrically coupled at or near a proximal portion of the ablation device, such as, for example, within the handle. In this case, the electrodes (2730) can be electrically connected together with wires in the handle of the device (2700) so that the electrodes (2730) are at the same electrical potential during ablation.

[0184] Each of the splines in the set of splines (2720) can include a corresponding electrode (2730) at the distal end of the set of splines (2720). The set of electrodes (2730) can include an atraumatic shape to reduce trauma to tissue. For example, the electrode (2730) can have an atraumatic shape that includes a rounded, flat, curved, and / or blunt portion configured to contact endocardial tissue. In some embodiments, the electrode (2730) can be positioned along any portion of the splines (2720) distal to the catheter shaft (2710). The electrode (2730) can have the same or different size, shape, and / or position along the corresponding splines.

[0185] In one embodiment, an electrode (2730) on a spline (2720) can be configured as an anode, while an electrode (2730) on an adjacent spline (2720) can be configured as a cathode. The ablation device (2700) can include any number of splines, such as 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values ​​and subranges therebetween. In some embodiments, the ablation device (2700) can include 3 to 20 splines. For example, the ablation device (2700) can include 6 to 12 splines.

[0186] 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. The diameter of the spline (2720) lumen can therefore 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 over the length of the spline. For example, the radius of curvature can increase monotonically. Such a variable radius of curvature can help position the electrode (2730) at some 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 can decrease distally.

[0187] In this way, the electrodes in the second configuration can be pressed against, for example, the posterior wall of the left atrium to produce a localized or focal lesion directly on the posterior wall of the left atrium by activating the appropriate electrodes using any suitable polarity combination. For example, adjacent electrodes (2730) can be configured to have opposite polarities.

[0188] Since the electrodes or subsets of 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 groups of electrodes can deliver different groups of pulses (e.g., graded 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 on 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, ablation can be delivered quickly when all electrodes are activated simultaneously. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0189] refer to Fig.27C It should be understood that unless otherwise specified, the reference numerals and Figures 27A-27B Components with similar reference numerals in FIG. 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') contains a pair of electrodes (2730', 2740).

[0190] The ablation device (2700') includes a catheter shaft (2710') at the proximal end of the device (2700') and a set of splines (2720') 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 through one or more splines in the set of splines (2720') 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 causing dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads can maintain a potential difference between about 200V and about 2000V across the thickness without dielectric breakdown. Each spline in the set of splines (2720') can include an insulated electrical lead for each electrode (2730', 2740) formed in the body of the spline (2720') (e.g., within the lumen of the spline (2720')). Each electrode (2730', 2740) of the spline (2720') can have approximately the same size and shape. In addition, each electrode (2730', 2740) in 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.

[0191] In some embodiments, the length of the electrodes (2730', 2740) of the ablation device (2700') can be about 0.5 mm to about 5.0 mm, and the cross-sectional dimension (e.g., diameter) can be about 0.5 mm to about 4.0 mm, including all values ​​and subranges therebetween. The spline wires (2720') in the second configuration can be flared to about 5.0 mm to about 20.0 mm at the distal end of the ablation device (2700'). d (including all values ​​and subranges therebetween), and may extend a length S of about 8.0 mm to about 20.0 mm from the distal end of the catheter shaft (2710'). l , 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.

[0192] The set of splines (2720') 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 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. Fig.27C , the group of splines (2720') is depicted in a second configuration, wherein the group of splines (2720') extends beyond the distal end of the catheter shaft (2710') and is offset (e.g., bent) away 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 positioned in the first configuration prior to delivering a pulse waveform, and can be converted to the second configuration to contact an area of ​​endocardial tissue so as to produce a large focal lesion when delivering a pulse waveform for irreversible electroporation as disclosed herein. In some embodiments, Fig.27C The electrode (2730') depicted in the second configuration (sometimes also referred to as the "distal electrode") can be configured to contact and press against the endocardial tissue, while the electrode (2740) in the second configuration (sometimes also referred to as the "proximal electrode") can not contact the endocardial tissue. In this way, the electric field generated by the electrodes due to conduction between the proximal electrode and the distal electrode through the blood pool causes focal ablation of the tissue.

[0193] In some embodiments, the proximal end of the group of splines (2720') can be slidably coupled to the distal end of the catheter shaft (2710'). As the group of splines (2720') further extends outward from the catheter shaft (2710'), the distal end of the group of splines (2720') can be further offset away from each other and the longitudinal axis of the catheter shaft (2710'). The group of splines (2720') can be slidably pushed out of the catheter shaft (2710') independently or in one or more groups. For example, the group of splines (2720') can be placed in the catheter shaft (2710') in the first configuration. The splines (2720') can then be pushed out of the catheter shaft (2710') and converted into a second configuration. The splines (2720') can be advanced or advanced together so that the group of splines (2720') corresponding to the anode electrode (2730) is advanced separately from the group of splines (2720') corresponding to the cathode electrode (2730', 2740). In some embodiments, the splines (2710') can be independently advanced through the corresponding lumen (e.g., sheath) of the catheter shaft (2710'). In the second configuration, the electrodes (2730', 2740) are longitudinally and / or laterally offset away from the catheter shaft (2710') relative to the longitudinal axis of the distal end of the catheter shaft (2710'). This can facilitate the delivery and positioning of the electrodes (2730', 2740) against the endocardial surface. In some embodiments, each spline in the group of splines (2720') can extend up to about 5 cm from the distal end of the catheter shaft (2710').

[0194] In some embodiments, the distal electrodes (2730') can have the same polarity, while the adjacent proximal electrodes (2740) can have the opposite polarity to the distal electrodes (2730'). In this way, an electric field can be generated between the distal and proximal electrodes for focal ablation.

[0195] In some of these embodiments, a handle (not shown) can be coupled to the set of splines. The handle can be configured to affect a transition of the set of splines between the first configuration and the second configuration. In some embodiments, electrical leads of at least two electrodes in the set of electrodes (2730', 2740) can be electrically coupled at or near a proximal portion of the ablation device, such as, for example, within the handle. In some embodiments, the electrodes (2730', 2740) can be electrically connected together with wires in the handle of the device (2700') so that the electrodes (2730', 2740) are at the same electrical potential during ablation.

[0196] The group of electrodes (2730', 2740) can include an anti-injury shape to reduce trauma to tissue. For example, the electrodes (2730', 2740) can have an anti-injury shape that includes a round, flat, curved and / or blunt tip portion configured to contact endocardial tissue. In some embodiments, the electrodes (2730', 2740) can be positioned along any portion of the splines (2720') distal to the catheter shaft (2710). The electrodes (2730', 2740) can have the same or different sizes, shapes and / or positions along the corresponding splines. One or more splines in the splines (2720') can include three or more electrodes.

[0197] In some embodiments, each of the electrodes (2730') on the spline (2720') can be configured as an anode, while each of the electrodes (2730') on the adjacent spline (2720') can be configured as a cathode. In another embodiment, each of the electrodes (2730') on one spline can alternate between an anode and a cathode, and each of the electrodes on adjacent splines has an opposite configuration (e.g., a cathode and an anode). In some embodiments, a subset of electrodes can be electrically connected together with a wire in 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 (2730) can also be different. In some embodiments, adjacent distal electrodes (2730') and proximal electrodes (2740) can form an anode-cathode pair. For example, the distal electrode (2730') can be configured as an anode, and the proximal electrode (2740) can be configured as a cathode.

[0198] The ablation device (2700') may include any number of splines, such as 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.

[0199] 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') contains 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.

[0200] In this way, the electrodes in the second configuration can be placed against a portion of endocardial tissue to create a lesion directly on the portion 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.

[0201] 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 groups of electrodes can deliver different groups of pulses (e.g., graded 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, ablation can be delivered quickly when all electrodes are activated simultaneously. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0202] Fig.28 is a side view of yet another embodiment of an ablation device (2800) comprising a catheter shaft (2810) at the proximal end of the device (2800), a distal cap (2812) of the device (2800), and a set of splines (2814) coupled thereto. In some embodiments, the ablation device (2800) can be used to form lesions on the endocardial surface by focal ablation, as described herein.

[0203] The distal cap (2812) can 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 set of splines (2814) can be coupled to the distal end of the catheter shaft (2810), and the distal end of the set of splines (2814) can be tethered to the distal cap (2812) of the device (2800). Each spline (2814) of the ablation device (2800) can include one or more independently addressable electrodes (2818) (sometimes also referred to as "proximal electrodes") formed on the surface of the spline (2814). Each electrode (2816, 2818) 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 of the electrical leads can maintain a potential difference between about 200V and about 2000V across its thickness, including all values ​​and subranges therebetween, without dielectric breakdown. Each spline (2814) can include an insulated electrical lead for each electrode (2818) formed in the body of the spline (2814) (e.g., within the lumen of the spline (2814)). One or more of the splines (2818) can further include the insulated electrical lead for the distal electrode (2816). In some embodiments, the size and / or shape of the electrodes (2816, 2818) can be different from each other.

[0204] The configuration of the set of splines (2814) and the proximal electrode (2818) can control the depth, shape and / or diameter / size of the focal ablation lesion produced by the ablation device (2800). The ablation device (2800) can be configured to transition between a first configuration in which the set of splines (2814) is arranged generally parallel to the longitudinal axis of the ablation device (2800) and a second configuration in which the set of splines (2814) is bent radially outward from the longitudinal axis of the ablation device (2800). It should be understood that the set of splines (2814) can be transitioned to any intermediate configuration between the first configuration and the second configuration, either continuously or in discrete steps.

[0205] Activating 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 the focal ablation lesion generated in the first configuration. In this manner, by varying the degree of expansion of the splines (2814), the depth, shape and / or size of the lesion may be controlled without shutting down the ablation device (2800). This aspect may be used to create multiple lesions of varying sizes and / or depths using the same ablation device.

[0206] The distal cap (2812) can be positioned to press against the endocardial tissue, while the proximal electrode (2818) in the first configuration or the second configuration can be configured not to 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 group of splines (2814), and the handle is configured to affect the conversion of the group of splines (2814) between the first configuration and the second configuration. In some embodiments, the electrical leads of at least two electrodes in the group of electrodes can be electrically coupled at or near the proximal portion of the ablation device (2800), such as, for example, within the handle.

[0207] In some embodiments, the distal electrode (2816) and the proximal electrode (2818) can form an anode-cathode pair. For example, the distal electrode (2816) can be configured as an anode and each of the proximal electrodes (2818) can be configured as a cathode. In some embodiments, the ablation device (2800) can include 3 to 12 splines. The ablation device (2800) can include any number of splines, such as 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20 or more splines. In some embodiments, the ablation device (2800) can include 3 to 20 splines. For example, in one embodiment, the ablation device (2800) can include 6 to 10 splines. In addition, in some embodiments, the shape of the extended set of splines (2814) can be asymmetric, such as having a distal portion that is more spherical or rounded than a proximal portion. This bulbous distal portion (as well as proximal electrode positioning) can help further control the size and depth of focal ablations.

[0208] Fig.28 The first plane (2822) depicted in the figure may refer to a plane orthogonal to the longitudinal axis of the catheter shaft (2810). The distal cap (2812) may be pressed against an endocardial surface, for example, located within the first plane (2812) (such as the lumen wall of a pulmonary vein) so as to produce a focal ablation lesion directly on the endocardial surface by activating a suitable electrode using any suitable polarity combination. For example, the distal electrode (2816) may be pressed against the endocardial surface and may be 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 of the 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.

[0209] In some embodiments, the distal electrode (2816) of the ablation device (2800) can include a length of about 0.5 mm to about 7.0 mm and a cross-sectional dimension (e.g., diameter) of about 0.5 mm to about 4.0 mm, including all values ​​and subranges therebetween. In some embodiments, the proximal electrode (2818) can include a length of about 0.5 mm to about 5.0 mm and a diameter of about 0.5 mm to about 2.5 mm, including all values ​​and subranges therebetween. The distal electrode (2816) can be separated from the proximal electrode (2818) by a length of about 3.0 mm to about 12.0 mm, including all values ​​and subranges therebetween. The distal electrode (2816) disposed on the distal cap (2812) can be located at a position of about 1.0 mm to about 4.0 mm from the distal end of the distal cap (2812), including all values ​​and subranges therebetween. In some embodiments, the distal end of the distal cap (2812) can include the distal electrode (2816). One or more focal ablation zones may be formed comprising a diameter of about 1.0 cm to about 2.0 cm, including all values ​​and subranges therebetween.

[0210] Figures 29A-29D is a side view of yet another embodiment of an ablation device (2900) comprising an outer catheter or sheath (2902) and a set 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 about 0.7 mm to about 3 mm, and the outer diameter of the outer catheter (2902) may be about 2 mm to about 5 mm. Fig.29A , 29D As best shown, 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).

[0211] In some embodiments, the ablation device (2900) can be used to form lesions on the endocardial surface by focal ablation, as described herein. The distal end of the catheter (2910, 2920) and / or the electrode (2916, 2922) can include an atraumatic shape to reduce trauma to the tissue. For example, the distal end of the catheter (2910, 2920) and / or the electrode (2916, 2922) can have an atraumatic shape that includes a rounded, flat, curved, and / or blunt portion configured to contact endocardial tissue.

[0212] Each electrode (2916, 2926) 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 of the electrical leads can 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) can 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 of the electrodes (2916, 2926) can be connected to the corresponding insulated electrical lead, resulting in a handle (not shown) being 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.

[0213] 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 produced by the ablation device (2900). The first catheter (2910) and the second catheter (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 a first configuration, a second configuration, and a third configuration, in which the set of catheters (2910, 2920) are arranged to be substantially parallel to the longitudinal axis of the outer catheter (2902), and the distal portions of the catheters (2910, 2920) are disposed within the outer catheter (2902) (e.g., Fig.29A ); in the second configuration, the electrodes (2916, 2926) are pushed out of the distal end (2903) of the outer catheter lumen (2902) and away from the distal end by any suitable distance; in the third configuration, 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) can include a distal portion (2914) that can rotate about a first hinge (2918), which can be configured to position the distal portion (2914) at a plurality of positions relative to the proximal portion (2912). The catheters (2910, 2912) in the second and third configurations can be angled away from each other to offset away from the longitudinal axis of the outer catheter (2902). The distal ends of the proximal portions (2912, 2922) can form an angle between about 5 degrees and about 75 degrees relative to the longitudinal axis (e.g., Fig.29D ). It should be understood that the ablation device (2900) may be transformed into any intermediate configuration between the first configuration, the second configuration, and the third configuration, either continuously or in discrete steps.

[0214] In some embodiments, conduction between the electrodes through the blood pool and / or endocardial tissue generates an electric field and applies the electric field to the endocardial surface as ablative energy. The electrode can be kept close to a portion of the atrial wall of the left atrium or placed in physical contact with the portion so as to cause damage to the portion by activating one or more of the electrodes using any suitable polarity combination. In this way, activating 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) can be configured to have a first polarity, and the second electrode (2926) can be configured to have 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. For purely non-limiting illustrative purposes, the acute angle formed at the hinged hinge can range between about 15 degrees and about 70 degrees. In some embodiments, the electric field strength in the focal ablation zone can 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 farther from each other (e.g., when the proximal portion (2912) and the distal portion (2914) form a larger angle), a relatively more dispersed and lower intensity electric field is generated, resulting in a relatively wider and shallower focal ablation lesion on the endocardial surface. In this way, by changing the degree of rotation of the electrodes (2916, 2926) relative to the proximal portion (2912, 2922) of the catheter (2910, 2920), the depth, shape and / or size of the lesion can be controlled without turning off the ablation device (2900). This aspect can be used to produce multiple lesions of different sizes, shapes and / or depths using the same ablation device. For example, the lesion diameter can be about 2 mm to about 3 cm, and the lesion depth can be between about 2 mm and about 12 mm. While electrodes (2916, 2926) may be positioned to contact endocardial tissue, it should be understood that electrodes (2916, 2926) need not contact endocardial tissue.

[0215] In some of these embodiments, a handle (not shown) can be coupled to the set of catheters (2910, 2920), and the handle is configured to affect transition of the catheters (2910, 2920) between the first configuration, the second configuration, and the third configuration. In some embodiments, actuation of one or more knobs, wheels, sliders, pullwires, and / or other control mechanisms in the handle can cause one or more catheters (2910, 2920) to translate through the outer catheter (2902) and / or the distal portions (2914, 2924) of the catheters to rotate about the hinges (2918, 2928).

[0216] Figures 29B-29C A first catheter (2910) having a hinged distal portion (2914) is depicted. The first catheter (2910) may include a proximal portion (2912) coupled to the distal portion (2914) by 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) that is more flexible than other portions of the first catheter (2910), the portion having a cross-sectional area that is reduced relative to the catheter. In yet other embodiments, the hinge (2918) may include a joint, a rotatable wheel, a ball joint, a condylar joint, a saddle joint, a pivot, a track, etc.

[0217] The rotatable wheel can be coupled to a wire (2917) (e.g., a pull wire). For example, the wire (2917) can be attached around a hinge (2918), and the distal portion (2914) can be attached to a portion of the hinge (2918). Thus, actuation (2930) of the wire (2917) (e.g., pulling one end of the wire proximally) can in turn rotate the wheel (2918) and the distal portion (2914), such that the distal portion (2914) rotates relative to the proximal portion (2912) of the first catheter (2910). In some embodiments, the distal portion can rotate at an angle of about 110 degrees to about 165 degrees relative to the proximal portion, and the length of the distal portion can be about 3 mm to about 12 mm. In some embodiments, the proximal end of the wire (2917) can 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 to fix the position of the distal portion (2914). Fig.29BAn embodiment of a first catheter (2910) is depicted having a distal portion (2914) between the second configuration and the third configuration. Fig.29C An embodiment of the first catheter (2910) is depicted in the third configuration. In the third configuration, the electrodes (2916, 2926) may be biased toward each other.

[0218] Fig.29D An embodiment of the ablation device (2900) in the third configuration is depicted, wherein the distal portions of the first catheter (2910) and the second catheter (2920) extend out of the outer catheter or sheath (2902) and are rotated 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 of the catheters (2910, 2920) can be coupled together at the handle so that actuation of the control mechanism controls the wires (2912, 2922) together, thereby allowing the distal portions (2914, 2924) of each of the catheters (2910, 2920) to rotate simultaneously about their respective hinges (2918, 2928). In the second and third configurations, the first conduit (2910) and the second conduit (2920) may be offset away from the longitudinal axis of the outer conduit (2902).

[0219] When the first catheter (2910) and the second catheter (2920) extend out of the outer catheter (2902), one or more portions of the catheters (2910, 2920) may assume their natural (e.g., unconstrained) one or more shapes (e.g., curved shapes). The catheters (2910, 2920) may be pushed out of the outer catheter (2902) together or independently. In some embodiments, the proximal portions (2912, 2922) of the catheters (2910, 2920) may include a flexible curvature so that the distal ends of the catheters (2910, 2920) may be configured to open to each other. The minimum radius of curvature of the catheters (2910, 2920) may range from about 1 cm or more. For example, the radius of curvature of the proximal portions (2912, 2922) may be about 1 cm or more. In some embodiments, the radius of curvature of the distal portions (2914, 2924) may be about 1 cm or more.

[0220] In some embodiments, the electrodes (2916, 2926) of the ablation device (2900) can include a length of about 0.5 mm to about 7.0 mm and a cross-sectional size (e.g., diameter) of about 0.5 mm to about 4.0 mm, including all values ​​and subranges therebetween. The electrodes (2916, 2926) of different catheters (2910, 2920) can be spaced apart from each other by a distance of about 3.0 mm to about 20 mm, including all values ​​and subranges therebetween. The electrodes (2916, 2926) can be located at a position of about 1.0 mm to about 4.0 mm 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) can include the electrodes (2916, 2926). One or more focal ablation lesions having a diameter of about 1.0 cm to about 2.0 cm, including all values ​​and subranges therebetween, can be formed.

[0221] Fig.30 1 is a side view of another embodiment of an ablation device (3000) comprising an outer catheter or sheath (3010) defining a longitudinal axis and a set of four catheters (3020, 3030, 3040, 3050) slidable within the lumen (3010). Each of the catheters (3020, 3030, 3040, 3050) may include a proximal portion (3023, 3033, 3043, 3053), a distal portion (3024, 3034, 3044, 3054), and a hinge (3021, 3031, 3041, 3051) 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 an electrode (3022, 3032, 3042, 3052). The distal ends of the catheters (3020, 3030, 3040, 3050) and / or the electrodes (3022, 3032, 3042, 3052) may include an atraumatic shape (e.g., a rounded, flat, curved, and / or blunt tip portion) to reduce trauma 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 set of 2, 3, 4, 5, 6, or more catheters.

[0222] Each electrode (3022, 3032, 3042, 3052) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads may maintain a potential difference between about 200 V and about 2000 V across its thickness, including all values ​​and subranges therebetween, without dielectric breakdown. Each catheter (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, resulting in 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.

[0223] In some embodiments, the configuration of the catheters (3020, 3030, 3040, 3050) and electrodes (3022, 3032, 3042, 3052) can control the depth, shape and / or diameter / size of the focal ablation lesion produced by the ablation device (3000). The set of catheters (3020, 3030, 3040, 3050) can be configured to translate along the longitudinal axis to transition between a first configuration, a second configuration, and a third configuration. In some embodiments, the ablation device (3000) can be configured to switch between a first configuration, a second configuration, and a third configuration, wherein in the first configuration, the set of catheters (3020, 3030, 3040, 3050) are 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 disposed within the outer catheter (3010); in the second configuration, the electrodes (3022 , 3032, 3042, 3052) are pushed out of the distal end (3011) of the lumen of the outer catheter (3010) and pushed away from the distal end by any suitable distance; in the third configuration, the distal portion of each catheter (3020, 3030, 3040, 3050) can be rotated, twisted or bent (for example, Fig.30For example, the first catheter (3020) may include a distal portion (3024) rotatable about a first hinge (3021), wherein the first hinge may be configured to position the distal portion (3024) at a plurality of positions relative to the proximal portion (3023), as described above with reference to Figures 29A-29D It should be understood that the ablation device (3000) can be converted into any intermediate configuration between the first configuration, the second configuration and the third configuration continuously or in discrete steps. In the second configuration, the set of catheters can be biased away from the longitudinal axis.

[0224] 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 the embodiment of the present invention, the first electrode (3022) can be configured as an anode and can be paired with a second electrode (3032) configured as a cathode. The third electrode (3042) can be configured as an anode and can be paired with a fourth electrode (3052) configured as a cathode. The first electrode (3022) and the second electrode (3032) pair can use the third electrode (3042) and the fourth electrode (3052) pair to apply a first pulse waveform, and then apply a second pulse waveform in sequence. In another embodiment, the pulse waveform can be applied to each of the electrodes simultaneously, wherein the second electrode (3032) and the third electrode (3042) can be configured as an anode, and the first electrode (3022) and the fourth electrode (3052) can be configured as a cathode. It should be understood that any of the pulse waveforms disclosed herein can be applied progressively or sequentially to a series of anode-cathode electrodes. Some embodiments of the ablation device (3000) can have the same dimensions as described above with respect to the ablation device (2900).

[0225] In other embodiments, one or more of the electrodes (3022, 3032, 3042, 3052) can be configured to have a first electrical polarity, and one or more electrodes (not shown) disposed on the surface of the outer catheter shaft (3010) (not shown) can be configured to have a second electrical polarity opposite to the first electrical polarity.

[0226] 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 from a distal end of 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 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 unfolded or pushed far enough away from the outer catheter (3110)), the spring assumes its natural or unstressed configuration, resulting in articulation of the hinge (3162), after which the distal portions (3122, 3132, 3142, 3152) articulate outwardly and assume a configuration that is generally 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 placed 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, thereby being approximately perpendicular to the longitudinal axis of the catheter (3160).

[0227] The electrodes (3120, 3130, 3140, 3150) may include an atraumatic shape (e.g., a rounded, flat, curved, and / or blunt tip portion) to reduce trauma 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 of the electrical leads 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 for each electrode (3120, 3130, 3140, 3150) formed in the body (e.g., lumen) of the catheter (3160). Each of the electrodes (3120, 3130, 3140, 3150) may be connected to a corresponding insulated electrical lead, resulting in 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) may differ from one another.

[0228] The catheter (3160) can be configured to translate along the longitudinal axis to transition between a first configuration, a second configuration, and a third configuration. In some embodiments, the ablation device (3100) can be configured to transition between a first configuration, a second configuration, and a third configuration, in which the set of electrodes (3120, 3130, 3140, 3150) are arranged substantially parallel to the longitudinal axis of the outer catheter (3110) and within the outer catheter (3110) (e.g., Fig.31A ); In the second configuration, the set of electrodes (3120, 3130, 3140, 3150) are pushed out of the distal end (3111) of the outer catheter lumen and pushed away from the distal end by any suitable distance ( Fig.31A ); in the third configuration, the electrodes (3120, 3130, 3140, 3150) can be rotated, twisted or bent (e.g., Fig.31B ). The conversion from the first configuration to the second configuration and the third configuration can be performed by pushing the catheter (3160) and the 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 configuration, the second configuration and the third configuration continuously or in discrete steps.

[0229] 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 generally perpendicular to the longitudinal axis of the catheter (3160), but can be adjusted based on a set of ablation parameters.

[0230] 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 can be paired with a third electrode (3140) configured as a cathode. The second electrode (3130) can be configured as an anode and can be paired with a fourth electrode (3150) configured as a cathode. The first electrode (3120) and the third electrode (3140) pair can use the second electrode (3130) and the fourth electrode (3150) pair to apply a first pulse waveform, and then apply a second pulse waveform in sequence. In another embodiment, the pulse waveform can be applied to each of the electrodes at the same time, wherein the first electrode (3120) and the second electrode (3130) can be configured as an anode, and the third electrode (3140) and the fourth electrode (3150) can be configured as a cathode. It should be understood that any of the pulse waveforms disclosed herein can be applied progressively or sequentially to a series of anode-cathode electrodes.

[0231] In other embodiments, one or more of the electrodes (3120, 3130, 3140, 3150) can be configured to have a first electrical polarity, and one or more electrodes disposed on the surface of the outer catheter shaft (3110) can be configured to have a second electrical polarity opposite to the first electrical polarity.

[0232] 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 cavity. For example, ablation device (3200) may be positioned in the endocardial space of the left ventricle of a heart. Fig.32 The ablation device (3200) depicted in Fig.30 and Figures 31A-31B In some embodiments, when the electrodes (3210, 3220, 3230, 3240) are in the third configuration, they can be apposed to the tissue wall. In some embodiments, Fig.32 The width of the electrodes (3210, 3220, 3230, 3240) may be between about 1 mm and about 3 mm, and the length may be between about 3 mm and about 9 mm. For example, the width of the electrodes (3210, 3220, 3230, 3240) may be about 2 mm, and the length may be about 6 mm.

[0233] In some embodiments, the electrodes (3210, 3220, 3230, 3240) can form an anode-cathode pair. For example, the first electrode (3210) can be configured as an anode and the third electrode (3230) can be configured as a cathode. The first electrode (3210) and the second electrode (3230) can have a potential difference of up to about 1500V. Activation of one or more of the electrodes (3210, 3220, 3230, 3240) of one or more catheters can produce one or more ablation zones along a portion of a cardiac chamber wall. The electric field curve (3350) is an isoamplitude line corresponding to an ablation zone (3350) with an electric field strength threshold of about 460V / cm when the first electrode (3220) and the third electrode (3240) are activated. In some embodiments, the width of the ablation zone (3350) can be up to about 12mm and the length can be 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 may be delivered for irreversible electroporation energy delivery to ablate tissue.

[0234] Fig.33Ais a perspective view of another embodiment of an ablation device / apparatus (3300) in the form of a catheter, the ablation device / apparatus 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 set of splines (3330) coupled thereto. The inner shaft (3320) can be coupled to a handle (not shown) at the proximal end and positioned to a cap electrode (3322) at a distal portion (e.g., distal end). The inner shaft (3320) and the set of splines (3330) can translate along the longitudinal axis (3324) of the ablation device (3300). In some embodiments, the inner shaft (3320) and the set of splines (3330) can move together or can translate independently. The inner shaft (3320) can be configured to slide within the lumen (3312) of the outer shaft (3310). The cap electrode (3322) can include an atraumatic shape to reduce trauma to tissue. For example, the cap electrode (3322) can have a flat, rounded shape and / or a rounded and blunt profile. The distal end of each spline in the set of splines (3330) can be tethered to the distal portion of the inner shaft (3320). The proximal portion of the set of splines (3330) can be attached to the outer shaft (3310). The ablation device (3300) can be configured to deliver a pulse waveform to tissue during use via the electrodes (3332, 3334) on the splines (3330) and the distal cap electrode (3322), such as, for example Figure 21-25 As disclosed in.

[0235] Each spline in the group of splines (3330) can include a group of electrodes (3332, 3334) on the surface of the spline. Each group of electrodes can include a distal electrode (3332) so that the group of splines includes a group of distal electrodes (3332). Each distal electrode in the distal electrodes (3332) is closest to the cap electrode (3322) relative to other electrodes in its corresponding group of electrodes on the same spline (e.g., the group of proximal electrodes (3334)). In addition, in some embodiments, the distal electrode (3332) can have only an exposed portion facing outward, that is, a portion that faces away from the internal space / volume defined by the group of splines. For example, if the distal electrode (3332) is constructed of a metal ring, a portion of each ring can be insulated so that only the exposed portion or "window" facing outward is exposed to deliver ablation energy. The cap electrode (3322) and each distal electrode (3332) in the group of distal electrodes can have the same polarity in common during use. This combination of closely placed distal electrodes with outward-facing windows and cap electrodes allows the distal end of the ablation device (3300) to generate and project a stronger electric field and thereby more effectively produce focal ablation lesions of tissue at a desired depth than either of these electrodes alone.

[0236] Each spline (3330) of the ablation device (3300) can include at least one set of independently addressable electrodes (3332, 3334) on the surface of the spline (3330). A distal cap electrode (3322) can be formed at the distal end of the catheter device (3300). Each electrode (3322, 3332, 3334) can 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 of the electrical leads can maintain a potential difference between about 200V and about 2000V across the thickness without dielectric breakdown. Each spline (3330) can include an insulated electrical lead for each electrode (3332, 3334) within the body of the spline (3330) (e.g., within the lumen of the spline (3330)). Likewise, in some embodiments, the inner shaft (3320) can include insulated electrical leads for the cap electrodes (3322). In other embodiments, a subset of the electrodes (3322, 3332, 3334) can be connected together with a wire. For example, the proximal electrodes (3334) of each spline in the set of splines (3330) can be connected together with a wire. As another example, all distal electrodes (3332) and the cap electrodes (3322) can be connected together with a wire.

[0237] In some embodiments, the set of splines (3330) can be configured to transition between a first configuration in which the set of splines (3330) are arranged generally parallel to the longitudinal axis (3324) of the ablation device (3300) and a second configuration in which the distal end of each spline in the set of splines (3330) is bent radially outward from the longitudinal axis (3324). In this manner, the set of distal electrodes (3332) and the cap electrode (3322) can be shaped / oriented to form Fig.33A , Fig.33B and Fig.33EThe second configuration shown. The cap electrode (3322) can be spaced at most about 5 mm from each distal electrode in the group of distal electrodes (3332), including all values ​​and sub-ranges therebetween. For example, the cap electrode (3322) can be spaced at about 0.5 mm to about 3 mm from each distal electrode in the group of distal electrodes (3332). In the second configuration, the distal portion of each spline in the group of splines (3330) can be at an angle (3336) between about 45 degrees and about 90 degrees relative to the longitudinal axis (3312), including all values ​​and sub-ranges therebetween. For example, the distal portion of each spline in the group of splines (3330) in the second configuration can 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 set of distal electrodes (3332) are projected onto a plane perpendicular to the longitudinal axis (3324), they can take on the shape of a "plus" symbol, such as Fig.33B shown in the front view.

[0238] 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 the first configuration to the second configuration. It should be understood that the set of splines (3330) can be converted to any intermediate configuration between the first configuration and the second configuration continuously or in discrete steps. The set of splines (3330) can form a shape that is generally parallel to the longitudinal axis (3324) of the inner shaft (3320) when not deployed, and can form a basket-like or spherical shape when the distal end of the set of splines (3330) is bent radially outward from the longitudinal axis (3324).

[0239] Fig.33A , Fig.33B and Fig.33E A set of splines (3330) is shown, wherein each spline in the set of splines (3330) includes a distal electrode (3332) and one or more proximal electrodes (3334), the one or more proximal electrodes differing in one or more of size, shape, number, and spacing. For example, Fig.33A One distal electrode (3332) and two proximal electrodes (3334) are shown for each spline in the set of splines (3330). In some embodiments, each proximal electrode (3334) can 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) can be formed on the surface of a portion of the circumference of its spline. That is, as Fig.33C and Fig.33DAs shown, the distal electrode (3332) can be partially located on the circumference of its corresponding spline and does not cover the entire circumference of its spline (3330). For example, the distal electrode (3332) can 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 can be completely covered by a thin insulating layer for biphasic operation. In some embodiments, the group of distal electrodes (3332) of the group of splines (3330) can be around the center of its corresponding spline (3330) at an angle (3333) between about 30 degrees and about 300 degrees, including all values ​​and sub-ranges therebetween. For example, the group of distal electrodes (3332) of the group of splines (3330) can be around the center of its corresponding spline (3330) at an angle (3333) between about 60 degrees and about 120 degrees. 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 being directed away from the target tissue and projected into the blood.

[0240] In this way, the distal electrode (3332) can be configured to face a particular direction. For example, Fig.33A and 33E The set of distal electrodes (3332) and the cap electrode (3322) are shown facing generally forward at the distal end of the device (3300) in the second configuration when the distal end of the set of splines (3330) is bent radially outward from the longitudinal axis (3324). In addition, the distal electrode (3332) can be positioned at the distal end of its splines such that the distal electrode (3332) of the set of splines (3330) is positioned proximate to the cap electrode (3322).

[0241] In some embodiments, each spline in the set of splines (3330) can include a set of electrodes (3332, 3334) having approximately the same size, shape, number, and spacing as corresponding electrodes (3332, 3334) of adjacent splines. The thickness of each spline (3330) can vary based on the number of electrodes (3332, 3334) formed on each spline (3330), which number can correspond to the number of insulated electrical leads in the spline (3330). The splines (3330) can have the same or different materials, thicknesses, and / or lengths.

[0242] In some embodiments, the cap electrode (3322) and the group of electrodes (3332, 3334) can be configured in the form of an anode-cathode group. For example, the cap electrode (3322) and each distal electrode in the group of distal electrodes (3332) can be configured together as an anode, and all proximal electrodes (3334) can be configured together as a cathode (or vice versa). In some embodiments, the group of distal electrodes (3332) and the group of proximal electrodes (3334) can have opposite polarities. For example, the distal electrode (3332) and the group of proximal electrodes (3334) for a given spline can have opposite polarities. The cap electrode (3322) and the group of distal electrodes (3332) can have the same polarity. As discussed herein, the group of distal electrodes (3332) and the cap electrode (3322) can be connected together with a wire. In some embodiments, the cap electrode and the set of electrodes (3332, 3334) of one or more of the set of splines (3330) 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).

[0243] In some embodiments, the set of distal electrodes (3332) can be spaced apart from the cap electrode (3322) by up to 3 mm from the distal end of each spline (3330). In some embodiments, the set of distal electrodes (3332) can be spaced apart from the set of proximal electrodes (3334) by about 1 mm to about 20 mm. In some embodiments, each electrode in the set of electrodes (3332, 3334) can include a diameter between about 0.5 mm and about 3 mm. In some embodiments, the cap electrode (3322) can include a cross-sectional diameter between about 1 mm and about 5 mm. In some embodiments, the length of each electrode in the set of electrodes (3332, 3334) can be about 0.5 mm to about 5 mm. In some embodiments, the expanded cross-sectional diameter (i.e., the expanded or second configuration effective diameter at its largest portion) of the set of splines (3330) in the second configuration can be between about 6 mm and about 24 mm. In some embodiments, the set of splines (3300) may extend from about 6 mm to about 30 mm from the distal end (3312) of the outer shaft (3310). In some embodiments, the outer diameter of the outer shaft (3310) may be between about 1.5 mm and about 6.0 mm.

[0244] The ablation device (3300) as described herein can be positioned in the first configuration prior to delivering the pulse waveform, and can be converted to the 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 group of splines (3330), and the handle is configured to affect the conversion of the group of splines (3330) 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 lumen (3312) of the outer shaft (3310) can expand the group of splines (3330) into the spherical shape shown herein. In some embodiments, actuation of a knob, wheel, or other control mechanism in the device handle can cause the inner shaft (3324) to translate and cause the group of splines (3330) to expand. 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 the handle.

[0245] In addition, the catheter handle (not shown) may include a mechanism for deflecting or manipulating the distal portion of the catheter device (3300). For example, a pull line 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), and the tensioning of the pull line causes the distal portion of the device (3300) to deflect. The deflection of the device (3300) can help the user to position the device (3300) at a suitable anatomical position in a controlled manner. In some embodiments, the distal cap electrode (3322) may be electrically connected to the distal spline electrode (3332) separately with a wire. In this way, the intracardiac ECG signal may be recorded only from the distal cap electrode (3322). In some embodiments, one or more distal spline electrodes (3332) may be electrically connected to the distal spline electrode (3332) separately with a wire to monitor the intracardiac ECG signal from each such electrode (3332). In some embodiments, some distal spline electrodes (3332) can be used for ECG monitoring, while other distal spline electrodes (3332) can be used to deliver ablation energy. It should be understood that any of the ablation devices described herein can be used with electrodes that are separately electrically connected with wires to monitor intracardiac ECG signals from each such electrode. In some embodiments, some electrodes on one or more splines in a set of splines can be used for ECG monitoring, while other electrodes can be used to deliver ablation energy.

[0246] The ablation device (3300) may include any number of splines, such as 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.

[0247] Each of the splines in the set of splines (3300) can include a respective electrode (3332, 3334) having an atraumatic (typically circular) shape to reduce trauma to tissue. In this manner, the distal electrode in the second configuration can be held proximate to or placed against a portion of the atrial wall of the left atrium to create a lesion on the portion by activating the appropriate electrode using any suitable polarity combination, as described herein. For example, Fig.33E As shown, the cap electrode (3322) and the distal electrode (3332) of the set of splines (3330) can be placed in contact with or in close proximity to the tissue wall (3350) in an orientation that is generally perpendicular or generally oblique to the tissue wall. The configuration of the distal electrodes (3322, 3332) allows for the creation of focal lesions at a desired depth even when the ablation device (3300) in the deployed configuration abuts the tissue wall (3350) at an angle (e.g., obliquely).

[0248] In some embodiments, since the electrodes or subsets of 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 groups of electrodes can deliver different groups of pulses (e.g., graded 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 when all electrodes are activated simultaneously. There are a variety of such electrode pairing options, and they can be implemented based on their convenience.

[0249] In some embodiments, the ablation device (2900, 3000, 3100, 3200) may include 2 to 6 catheters. The ablation device (2900, 3000, 3100, 3200) may include any number of catheters, such as 2, 3, 4, 5, 6 or more catheters. For example, in some embodiments, the ablation device (2900, 3000, 3100, 3200) may include 3 to 6 catheters. In some embodiments, the catheter of the ablation device (2900, 3000, 3100, 3200) may include 2 to 6 distal portions. The catheter may include any number of distal portions, such as 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 focal ablation.

[0250] In some embodiments, the electrodes may form an anode-cathode pair. For example, the first electrode may be configured as an anode and the second electrode may be configured as a cathode. In some embodiments, subsets of the electrodes may be independently addressable and the electrodes may be energized in any order using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different groups of electrodes may deliver different groups of pulses (e.g., graded pulse waveforms).

[0251] In all of the previously described embodiments, but without limitation, the ablation catheter itself may be a steerable device with pull wires for controlling deflection via a suitable mechanism in the catheter handle, as is well known to those skilled in the art.

[0252] Balloon

[0253] In some embodiments, the 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., structurally and / or functionally similar to ablation device (110)) positioned in a left atrial chamber (1000) of a heart is depicted. The ablation device (1010) may include a first balloon (1012) and a second balloon (1014), which may be configured to be positioned in the ostium (1002) of a pulmonary vein (1004). The first balloon (1012) in an expanded (e.g., inflated) configuration may have a larger diameter than the second balloon (1014) in an expanded configuration. This allows the second balloon (1014) to be advanced and positioned further into the pulmonary vein (1014), while the first balloon (1012) may be positioned near and / or at the ostium (1002) of the pulmonary vein (1004). The inflated second balloon is used to stabilize the position of the first balloon at the ostium 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, for example, 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, each 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 of the electrical leads can maintain a potential difference of between about 200V and about 2500V across its thickness without dielectric breakdown, including all values ​​and subranges therebetween. For example, the lead of the second balloon (1014) can be insulated when it extends through the first balloon (1012).

[0254] In some embodiments, the first balloon (1012) and the second balloon (1014) can form an anode-cathode pair. For example, in one embodiment, the first balloon and the second balloon can carry an electrically separate body of saline fluid, and the first balloon (1012) can be configured as a cathode and the second balloon (1014) can be configured as an anode, or vice versa, where electrical energy can be capacitively coupled across the balloon or saline-filled electrodes. The device (1010) can receive a pulse waveform to be delivered to the tissue (1002). For example, one or more biphasic signals can be applied so that tissue between the first balloon (1012) and the second balloon (1014) can be ablated at a desired location in the pulmonary vein (1004). The first balloon (1012) and the second balloon (1014) can substantially confine the electric field between the first balloon (1012) and the second balloon (1014) to reduce the electric field and damage to tissue away from the mouth (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, can be used as electrodes of one polarity, while the fluid in the first balloon can be used as an electrode of the opposite polarity. A biphasic pulse waveform can then be delivered between these electrodes of opposite polarity via capacitive coupling across the balloon, thereby creating an irreversible electroporation ablation zone in the area surrounding the first balloon. In some embodiments, one or more of the balloons (1012, 1014) can include a wire mesh.

[0255] Fig.11 is a cross-sectional view of another embodiment of a balloon ablation device (1110) (e.g., structurally and / or functionally similar to ablation device (1010)) positioned in a left atrial chamber (1100) and a right atrial chamber (1104) of a heart. The ablation device (1110) may include a balloon (1112) that may be configured to be advanced into and positioned in the right atrial chamber (1104). For example, the balloon (1112) may be positioned in contact with the septum (1106) of the heart. The balloon (1112) may be filled with saline. The device (1110) may further include an electrode (1120) that may be advanced from the right atrial chamber (1104) through the balloon (1112) and the septum (1106) and into the left atrial chamber (1100). For example, the electrode (1120) can extend from the balloon (1112) and pierce the septum (1106) and advance into the left atrial cavity (1100). Once the electrode (1120) is advanced into the left atrial cavity (1100), the distal portion of the electrode (1120) can be modified to form a predetermined shape. For example, the distal portion of the electrode (1120) can include a non-linear shape, such as a circle, an ellipse, or any other geometric shape. Fig.11In one embodiment, the distal portion of the electrode (1120) forms a loop that may surround a single ostium or two or more ostiums of a pulmonary vein (1102) in the left atrial chamber (1100). In other embodiments, the distal portion of the electrode (1120) may have approximately the same diameter as the ostium of the pulmonary vein (1102).

[0256] 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), each lead (1114, 1122) 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 of the electrical leads can maintain a potential difference of between about 200V and about 2,000V 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 ostium of the pulmonary vein (1102). For example, a biphasic signal 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) through capacitive coupling to complete the circuit. In some embodiments, the electrode (1120) can include a thin-gauge wire and the balloon (1112) can include a wire mesh.

[0257] In another embodiment, the electrode (1120) may be advanced through the pulmonary vein (1102) and positioned in one or more of the 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.

[0258] Return electrode

[0259] Some embodiments of ablation systems as described herein may further include a return electrode or a distributed set of return electrodes coupled to the patient to reduce the risk of inadvertent damage to healthy tissue. Figures 12A-12B is a schematic diagram of a set of return electrodes (1230) (eg, return pads) of an ablation system positioned on a patient (1200). Figures 12A-12BA set of four ostia of a pulmonary vein (1210) in the left atrium is shown. 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 placed on the back of the patient (1200) to allow current to pass from the electrodes (1220) through the patient (1200) and then to the return electrodes (1230).

[0260] For example, one or more return electrodes may be placed on the skin of the patient (1200). In one embodiment, eight return electrodes (1230) may be positioned on the patient's back to surround the pulmonary vein ostia (1210). Conductive gel may be applied between the return electrodes (1230) and the skin to improve contact. It should be understood that any of the ablation devices described herein may be used with one or more return electrodes (1230). Figures 12A-12B In the embodiment, electrodes (1220) are arranged around four ports (1210).

[0261] Fig. 12B An energized electrode (1220) is shown forming an electric field (1240) around the ostium (1210) of a pulmonary vein. The return electrode (1230) may in turn receive the pulsed monophasic and / or biphasic waveform delivered by the electrode (1220). In some embodiments, the number of return electrodes (1230) may be roughly inversely proportional to the surface area of ​​the return electrode (1230).

[0262] For each of the ablation devices discussed herein, the electrodes (e.g., ablation electrodes, return electrodes) may comprise a biocompatible metal, such as titanium, palladium, silver, platinum, or a platinum alloy. For example, the electrode may preferably comprise platinum or a platinum alloy. Each electrode may comprise 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 of the electrical leads 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 extend to the proximal handle portion of the catheter, from which the insulated electrical leads may be connected to a suitable electrical connector. The catheter shaft may be made of a flexible polymeric material, such as Teflon, nylon, Pebax, etc.

[0263] II. Methods

[0264] Also described herein are methods for ablating tissue in a cardiac chamber using the above-described systems and devices. The cardiac chamber may be a left atrial cavity and include its associated pulmonary veins. Typically, the methods described herein include introducing and placing 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 levels of hierarchy to reduce total energy delivery. Tissue ablation performed in this manner may be delivered in synchronization with the paced heartbeat, and less energy is delivered to reduce damage to healthy tissue. It should be understood that any of the ablation devices described herein may be used to ablate tissue appropriately using the methods discussed below.

[0265] In some embodiments, the ablation devices described herein can be used to focally ablate cardiac features / structures identified as causing arrhythmias. For example, a cardiac electrophysiology diagnostic catheter (e.g., a mapping catheter) can be used to map a cardiac structure (such as a rotor), which can then be ablated by focal ablation using any of the ablation devices described herein. For example, focal ablation may produce spot lesions that neutralize the rotor while leaving surrounding tissue unharmed. In some embodiments, one or more focal ablation lesions can be formed in combination with one or more box-shaped or linear lesions to treat arrhythmias. As a non-limiting example, in some embodiments, a system may include one or more mapping catheters, one or more ablation catheters for producing lesions by focal ablation (e.g., Fig.9D , 9E , ablation devices shown in 27A-27C, 28, 29, 30, 31, 32) and one or more catheters for creating box-shaped and / or linear lesions (e.g., Figure 3 -8, 9A-9C, 10-12, and the ablation devices shown in 26A-26B).

[0266] Fig.13A method (1300) of one embodiment for a tissue ablation procedure. In some embodiments, a voltage pulse waveform as described herein may be applied during a refractory period of a cardiac cycle to avoid interruption of a cardiac sinus rhythm. The method (1300) includes introducing a device (e.g., an ablation device, such as any of the ablation devices (110) and / or ablation devices (200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 2900, 3000, 3100)) into the endocardial space of the left atrium at step (1302). The device may be advanced to be positioned in contact with a pulmonary vein ostium (1304). For example, the electrodes of the ablation device may form an approximately circular arrangement of electrodes positioned in contact with an inner radial surface at the pulmonary vein ostium. In some embodiments, a pacing signal may be generated for cardiac stimulation of the heart (1306). The pacing signal may then be applied to the heart (1308). For example, the heart can be electrically paced with a cardiac stimulator to ensure pacing capture, thereby establishing periodicity and predictability of the cardiac cycle. One or more of atrial and ventricular pacing can be applied. An indication of a pacing signal can be transmitted to a signal generator (1310). A time window within the refractory period of the cardiac cycle can then be defined, within which one or more voltage pulse waveforms can be delivered. In some embodiments, the refractory time window can follow the pacing signal. For example, a common refractory time window can be located between the atrial refractory time window and the ventricular refractory time window.

[0267] The pulse waveform may be generated synchronously with the pacing signal (1312). For example, the voltage pulse waveform may be applied in a common refractory time window. In some embodiments, a pulse waveform may be generated with a time offset relative to an indication of the pacing signal. For example, the start of the refractory time window may be offset by a time offset from the pacing signal. One or more voltage pulse waveforms may be applied to a series of heartbeats on the corresponding common refractory time window. The generated pulse waveform may be delivered to the tissue (1314). In some embodiments, the pulse waveform may be delivered to the pulmonary vein ostium of the patient's heart through one or more splines in a set of splines of the ablation device. In other embodiments, the voltage pulse waveform described herein may be selectively delivered to an electrode subset, such as an anode-cathode subset for ablation and isolation of the pulmonary vein. For example, a first electrode in an electrode group may be configured as an anode, and a second electrode in an electrode group may be configured as a cathode. These steps may be repeated as many times as desired to ablate the pulmonary vein ostium or sinus region (e.g., 1, 2, 3, or 4 ostiums).

[0268] In some embodiments, hierarchical voltage pulse waveforms having nested structures and time interval hierarchies as described herein can be used for irreversible electroporation to provide control and selectivity in different tissue types. Fig.14 1400 is a flowchart of another embodiment of a tissue ablation process. The method (1400) includes introducing a device (e.g., an ablation device, such as any of ablation devices (200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 2900, 3000, 3100)) into the endocardial space of the left atrium (1402). The device can be advanced to be positioned in the ostium of a pulmonary vein (1404). In embodiments where the device can include a first configuration and a second configuration (e.g., compact and expanded), the device can be introduced in the first configuration and converted to the second configuration to contact tissue at or near the ostium or ostium of a pulmonary vein (1406). As discussed in detail above, the device can include electrodes and can be configured in the form of an anode-cathode subset (1408). For example, a subset of the electrodes of the device may be selected as anodes, while another subset of the electrodes of the device may be selected as cathodes, with a voltage pulse waveform applied between the anodes and cathodes.

[0269] The pulse waveform may be generated by a signal generator (e.g., signal generator 122) and may include multiple levels in a hierarchy (1410). As disclosed herein, multiple levels of waveforms may be generated by a signal generator. For example, a pulse waveform may include a first level of a pulse waveform hierarchy, the first level including a first group of pulses. Each pulse has a pulse duration and a first time interval separating consecutive pulses. A second level of the pulse waveform hierarchy may include a plurality of the first group of pulses as a second group of pulses. A second time interval may separate consecutive first group pulses. The second time interval may be at least three times the duration of the first time interval. A third level of the pulse waveform hierarchy may include a plurality of the second group of pulses as a third group of pulses. A third time interval may separate consecutive second group pulses. The third time interval may be at least thirty times the duration of the second time interval.

[0270] It should be understood that while the examples herein identify separate monophasic and biphasic waveforms, it should be understood that combined waveforms may also be generated in which some portions of the waveform hierarchy are monophasic and other portions are biphasic. The voltage pulse waveforms having the hierarchy may be applied to the different anode-cathode subsets (optionally with time delays). As described above, one or more of the waveforms applied to the anode-cathode subsets may be applied during a refractory period of the cardiac cycle. The pulse waveforms may be delivered to the tissue (1412). It should be understood that Fig.13 and Fig.14 The steps described in can be combined and modified appropriately.

[0271] Figure 15-18 Depicted are methods for using the methods described herein (e.g., Figure 2-5) is an embodiment of a method for ablating tissue in the left atrial cavity of the heart as described above. Fig.15 is used to use the corresponding Figure 2 A cross-sectional view of an embodiment of a method of ablating tissue disposed in a left atrial chamber of a heart using an ablation device (1500) as depicted in the ablation device (210) of FIG. The left atrial chamber (1502) is depicted as having four pulmonary veins (1504), and the ablation device (1500) can be used to sequentially ablate tissue to electrically isolate one or more of the pulmonary veins (1504). Fig.15 As shown, the ablation device (1500) can be introduced into an endocardial space such as the left atrial cavity (1502) using a transseptal approach (e.g., extending from the right atrial cavity through the septum and into the left atrial cavity (1502)). The ablation device (1500) can include a catheter (1510) and a guidewire (1520) that can slide within the lumen of the catheter (1510). The distal portion of the catheter (1510) can include a set of electrodes (1512). The distal portion (1522) of the guidewire (1520) can be advanced into the left atrial cavity (1502) to be positioned near the ostium of the pulmonary vein (1504). The catheter (1510) can then be advanced over the guidewire (1520) to position the electrode (1512) near the ostium of the pulmonary vein (1504). Once the electrodes (1512) are in contact with the mouth of the pulmonary veins (1504), the electrodes (1512) can be configured in the form of an anode-cathode subset. A voltage pulse waveform generated by a signal generator (not shown) can be delivered to tissue and / or contain waveform levels using the electrodes (1512) in synchronization with the pacing heartbeat. After completing tissue ablation in one of the pulmonary veins (1504), the catheter (1510) and guidewire (1520) can be repositioned at another pulmonary vein (1504) to ablate tissue in one or more of the remaining pulmonary veins (1504).

[0272] Fig.16 is used to use the corresponding Figure 3 A cross-sectional view of an embodiment of a method of ablating tissue disposed in a left atrial chamber of a heart using an ablation device (1600) as depicted in the ablation device (310) of FIG. The left atrial chamber (1602) is depicted as having four pulmonary veins (1604), and the ablation device (1600) can be used to sequentially ablate tissue to electrically isolate one or more of the pulmonary veins (1604). Fig.16As shown, the ablation device (1600) can be introduced into an endocardial space such as a left atrial cavity (1602) using a transseptal approach. The ablation device (1600) can include a sheath (1610) and a catheter (1620) that can slide within the lumen of the sheath (1610). The distal portion (1622) of the catheter (1620) can include a set of electrodes. The distal portion (1622) of the catheter (1620) can be advanced into the left atrial cavity (1602) to place the electrodes near the mouth of the pulmonary vein (1604). Once the electrodes are in contact with the mouth of the pulmonary vein (1604), the electrodes can be configured in the form of an anode-cathode subset. The voltage pulse waveform generated by a signal generator (not shown) can be delivered to the tissue and / or include waveform levels using the electrodes in synchronization with the pacing heartbeat. After completing ablation of tissue in a pulmonary vein ( 1604 ), catheter ( 1620 ) may be repositioned at another pulmonary vein ( 1604 ) to ablate tissue in one or more of the remaining pulmonary veins ( 1604 ).

[0273] Fig.17 is used to use the corresponding Figure 4 A cross-sectional view of an embodiment of a method of ablating tissue disposed in a left atrial chamber of a heart is depicted by an ablation device (410). The left atrial chamber (1702) is depicted as having four pulmonary veins (1704), and the ablation device (1700) can be used to ablate tissue to electrically isolate one or more of the pulmonary veins (1704). Fig.17As shown, the ablation device (1700) can be introduced into an endocardial space such as a left atrial cavity (1702) using a transseptal approach. The ablation device (1700) can include a sheath (1710) and a plurality of catheters (1720, 1721) that can slide in the lumen of the sheath (1710). Each of the catheters (1720, 1721) can include a corresponding guide wire (1722, 1723) that can slide in the catheter (1720, 1721). The distal portion of the guide wire (1722, 1723) can include an electrode configured to deliver a voltage pulse waveform. Each of the catheters (1720, 1721) and the corresponding guide wire (1722, 1723) can be advanced into the left atrial cavity (1702) to be placed near the corresponding mouth of the pulmonary vein (1704). Once the guidewire electrodes (1722, 1723) are in contact with the mouth of the pulmonary vein (1704), the electrodes can be configured in the form of an anode-cathode subset. For example, the first guidewire (1722) can be configured as an anode, and the second guidewire (1723) can be configured as a cathode. In this configuration, a voltage pulse waveform generated by a signal generator (not shown) can be delivered to ablate and simultaneously isolate the pair of pulmonary veins (1704). Additionally or alternatively, the voltage pulse waveform can be delivered to the tissue and / or include waveform levels using electrodes synchronously with the pacing heartbeat. After completing tissue ablation of two pulmonary veins in the pulmonary vein (1704), the catheter (1720, 1721) can be repositioned to ablate the tissue at the two remaining pulmonary veins (1704). In some embodiments, the sheath (1710) can include three or four catheters placed in the pulmonary veins (1704).

[0274] Fig.18 is used to use the corresponding Figure 5 A cross-sectional view of an embodiment of a method of ablating tissue disposed in a left atrial chamber of a heart using an ablation device (1800) as depicted in the ablation device (500) of FIG. The left atrial chamber (1802) is depicted as having four pulmonary veins (1804), and the ablation device (1800) can be used to sequentially ablate tissue to electrically isolate one or more of the pulmonary veins (1804). Fig.18 As shown, the ablation device can be introduced into an endocardial space such as the left atrial cavity (1802) using a transseptal approach. The ablation device can include a sheath (1820) and a catheter (1810) that can slide within the lumen of the sheath (1820). The distal portion (1812) of the catheter (1810) can be flower-shaped, as shown in FIG. Figure 5The distal portion (1812) of the catheter (1810) can be advanced into the left atrial cavity (1802) in a compact first configuration and positioned near the ostium of the pulmonary vein (1804). The distal portion (1812) of the catheter (1810) can then be converted to an expanded second configuration to form a Fig.18 The flower-shaped distal portion shown allows the distal portion (1812) of the catheter (1810) to be placed near the mouth of the pulmonary vein (1804). Once the electrode is in contact with the mouth of the pulmonary vein (1804), the electrode can be configured in the form of an anode-cathode subset. The voltage pulse waveform generated by the signal generator (not shown) can be delivered to the tissue and / or contain waveform levels using the electrode in synchronization with the pacing heartbeat. After completing the tissue ablation in the pulmonary vein (1804), the catheter (1810) can be repositioned at another pulmonary vein (1804) to ablate tissue in one or more of the remaining pulmonary veins (1804).

[0275] It should be understood that this article (for example, Figure 13-18 Any of the methods described in the claims may further include placing a return electrode (e.g., Figures 12A-12B One or more return electrodes (1230) described in the invention are coupled to the patient's back and are configured to safely remove current from the patient's body during application of the voltage pulse waveform.

[0276] Figures 19A-20B Depicted are embodiments of electrodes positioned to make contact around a pulmonary vein ostium and the electric field generated thereby. Fig.19A 1 is a schematic diagram of an embodiment of a set of electrodes (1910) positioned in the ostium of a pulmonary vein (1904). The left atrial chamber (1902) may contain a blood pool (1906), and the pulmonary vein (1904) may contain a blood pool (1908). The left atrial chamber (1902) and the pulmonary vein (1904) may each have a wall thickness of up to about 4 mm.

[0277] Fig.19B 1900 is another schematic diagram of the set of electrodes (1910) radially disposed along the inner surface of a pulmonary vein (1904). The pulmonary vein (1904) may include an arterial wall (1905) containing a pool of blood (1908). Adjacent electrodes (1910) may be spaced apart by a predetermined distance (1911). In some embodiments, the pulmonary vein (1904) may have an inner diameter of approximately 16 mm. Figures 19A-19B In the embodiment, the electrodes (1910) may have a length of about 10 mm and be spaced about 4 mm apart from each other. It should be understood that in other embodiments, the electrodes (1910) may be any of the electrodes disclosed herein. For example, the electrodes (1910) may include Figure 5 The flower-shaped distal portion of the electrode and / or Figure 3 A generally circular arrangement of electrodes is depicted.

[0278] Figures 20A-20B is a schematic diagram (2000) of an embodiment of an electric field (2020) generated by a set of electrodes (2010) positioned in the ostium of a pulmonary vein (2002). Fig. 20A is a perspective view, and Fig. 20B is a cross-sectional view of the pulmonary vein (2002) and outer wall of the left atrial chamber (2004). The shaded electric field (2020) shows the situation where the electric field (2020) exceeds a threshold when adjacent electrodes (2010) deliver energy (e.g., a voltage pulse waveform) to ablate tissue. For example, the electric field (2020) represents a potential difference of 1500V applied between adjacent electrodes (2010). At this applied voltage, the amplitude of the electric field (2020) is at least above the threshold of 500V / cm within the shaded volume electric field (2020) and can be sufficient to produce irreversible ablation in cardiac tissue. As described in detail above, by sequencing the pulse waveforms on the adjacent electrode pairs (2010), the ostia of the pulmonary veins (2002) can be ablated to electrically isolate the pulmonary veins (2002) from the left atrial chamber (2004).

[0279] Pulse waveform

[0280] Disclosed herein are methods, systems, and devices for selectively and rapidly applying pulsed electric fields / waveforms to achieve tissue ablation by irreversible electroporation. One or more pulse waveforms disclosed herein may be used with any of the systems (100), devices (e.g., 200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 1230, 1500, 1600, 1700, 1800, 1910, 2010, 2900, 3000, 3100) and methods (e.g., 1300, 1400) described herein. Some embodiments relate to pulsed high voltage waveforms and sequential delivery schemes for delivering energy to tissue via electrode groups. In some embodiments, the peak electric field value can be reduced and / or minimized while maintaining a sufficiently large electric field amplitude in the area where tissue ablation is desired. This also reduces the possibility of excessive tissue damage or arcing, and localized high temperatures are increased. In some embodiments, a system for irreversible electroporation includes a signal generator and a processor that can be configured to apply a pulse voltage waveform to a selected plurality of electrodes or a subset of electrodes of an ablation device. In some embodiments, the processor is configured to control an input whereby a selected anode-cathode subset pair of electrodes can be sequentially triggered based on a predetermined order, and in one embodiment, sequential delivery can be triggered from a cardiac stimulator and / or pacing device. In some embodiments, an ablation pulse waveform can be applied during a refractory period of the cardiac cycle to avoid interruption of the heart's sinus rhythm. An example method of achieving this is to electrically pace the heart with a cardiac stimulator and ensure pacing capture to establish periodicity and predictability of the cardiac cycle, and then to well define a time window within the refractory period of this periodic cycle for delivering the ablation waveform.

[0281] In some embodiments, the pulse voltage waveforms disclosed herein are hierarchical in organization and have a nested structure. In some embodiments, the pulse waveforms contain hierarchical groupings of pulses with various associated time scales. In addition, the associated time scales and pulse widths and the number of pulses and hierarchical groupings can be selected to satisfy one or more inequalities in a set of Diophantine inequalities related to cardiac pacing frequency.

[0282] The pulse waveforms for electroporation energy delivery disclosed herein can enhance the safety, efficiency, and effectiveness of energy delivery by lowering the electric field threshold associated with irreversible electroporation, thereby producing more effective ablative lesions while reducing the total energy delivered. This in turn can broaden the clinical application areas of electroporation, including the treatment of various arrhythmias.

[0283] Fig.21A pulsed voltage waveform is shown in the form of a rectangular double pulse train, each pulse (such as pulse (2100)) is associated with a pulse width or duration. The pulse width / duration can be about 0.5 microseconds, about 1 microsecond, about 5 microseconds, about 10 microseconds, about 25 microseconds, about 50 microseconds, about 100 microseconds, about 125 microseconds, about 140 microseconds, about 150 microseconds, including all values ​​and subranges therebetween. Fig.21 The pulse waveform of FIG. 1 shows a set of monophasic pulses, in which all pulses have the same polarity (in Fig.21 In some embodiments, such as for irreversible electroporation applications, the height of each pulse (2100) or the voltage amplitude of the pulse (2100) can range from about 400 volts, about 1,000 volts, about 5,000 volts, about 10,000 volts, about 15,000 volts, including all values ​​and subranges therebetween. Fig.21 As shown, pulses (2100) are separated from adjacent pulses by a time interval (2102), which is sometimes referred to as a first time interval. The first time interval can be about 10 microseconds, about 50 microseconds, about 100 microseconds, about 200 microseconds, about 500 microseconds, about 800 microseconds, about 1 millisecond, including all values ​​and subranges therebetween, to produce irreversible electroporation.

[0284] Fig. 22 A pulse waveform with a nested pulse hierarchy is introduced. Fig. 22 A series of monophasic pulses, such as pulses (2200) having a pulse width / pulse duration w, are shown, the pulses being separated by time intervals (sometimes also referred to as first time intervals) such as (2202) of duration t1 between consecutive pulses, the number m1 of the pulses being arranged to form a pulse group (2210) (sometimes also referred to as a first group of pulses). In addition, the waveform has m2 such pulse groups (sometimes also referred to as a second group of pulses), the pulse groups being separated by time intervals (2212) of duration t2 between consecutive groups (sometimes also referred to as a second time interval). Fig. 22 The set of m2 such pulse groups, labeled (2220) in the figure, constitutes the next level of the hierarchy, which may be referred to as a grouping and / or third group of pulses. Both the pulse width and the time interval t1 between pulses may range from microseconds to hundreds of microseconds, including all values ​​and subranges therebetween. In some embodiments, the time interval t2 may be at least three times greater than the time interval t1. In some embodiments, the ratio t2 / t1 may range from about 3 to about 300, including all values ​​and subranges therebetween.

[0285] Fig.23The structure of the nested pulse hierarchy waveform is further described. In this figure, a series of m1 pulses (individual pulses not shown) form a pulse group (2300) (e.g., a first group of pulses). A series of m2 such groups separated by an inter-group time interval (2310) of duration t2 between one group and the next (e.g., a second time interval) form a grouping 132 (e.g., a second group of pulses). A series of m3 such groups separated by an inter-group time interval (2312) of duration t3 between one group and the next (e.g., a third time interval) form the next level in the hierarchy, labeled as a super grouping (2320) in the figure (e.g., a third group of pulses). In some embodiments, the time interval t3 can be at least about thirty times greater than the time interval t2. In some embodiments, the time interval t3 can be at least fifty times greater than the time interval t2. In some embodiments, the ratio t3 / t2 can range between about 30 and about 800, including all values ​​and sub-ranges therebetween. The amplitude of the individual voltage pulses in the pulse hierarchy can range from 500 volts to 7,000 volts or more, including all values ​​and sub-ranges therebetween.

[0286] Fig.24 An example of a biphasic waveform sequence having a hierarchical structure is provided. In the example shown in the figure, a biphasic pulse such as (2400) has a positive voltage portion and a negative voltage portion to complete one cycle of the pulse. There is a time delay (2402) (e.g., a first time interval) between adjacent cycles of duration t1, and n1 such cycles form a pulse group (2410) (e.g., a first group of pulses). A series of n2 such groups separated by an inter-group time interval (2412) (e.g., a second time interval) of duration t2 between one group and the next group forms a group (2420) (e.g., a second group of pulses). A second group (2430) is also shown in the figure, and there is a time delay (2432) (e.g., a third time interval) of duration t3 between the groups. Just like the monophasic pulses, a higher level of hierarchy can also be formed. The amplitude of each pulse or the voltage amplitude of the biphasic pulse can range from 500 volts to 7,000 volts or more, including all values ​​and sub-ranges therebetween. The pulse width / pulse duration may range from a few nanoseconds or even a few sub-nanoseconds to tens of microseconds, while the delay t1 may range from zero to a few microseconds. The inter-group time interval t2 may be at least ten times greater than the pulse width. In some embodiments, the time interval t3 may be at least about twenty times greater than the time interval t2. In some embodiments, the time interval t3 may be at least fifty times greater than the time interval t2.

[0287] Embodiments disclosed herein include waveforms structured as hierarchical waveforms that include waveform elements / pulses at different levels of the hierarchy. Fig. 22(2200)) in comprises a first level of the hierarchy and has associated pulse durations and a first time interval between consecutive pulses. A group of pulses or elements of the first level structure forms a second level of the hierarchy, such as Fig. 22 The parameters associated with the waveform are, among other parameters, parameters describing the second level structure / second level pulse group (not shown), such as the total duration of the second level pulse group (not shown), the total number of first level elements / first level pulse group, and the second time interval between consecutive first level elements. In some embodiments, the total duration of the second level pulse group can be between about 20 microseconds and about 10 milliseconds, including all values ​​and subranges therebetween. A group, second group of pulses, or elements of the second level structure form a third level of the hierarchy, such as Fig. 22 The third level structure / third group of pulses is grouped in a group / third group of pulses (2220). Among other parameters, there are parameters describing the total duration of the third group of pulses (not shown) of the third level structure / third group of pulses, the total number of second level elements / second group of pulses, and the third time interval between consecutive second level elements. In some embodiments, the total duration of the third group of pulses can be between about 60 microseconds and about 200 milliseconds, including all values ​​and subranges therebetween. The general iterative or nested structure of waveforms can continue to reach higher multiple levels, such as a ten-level structure or more.

[0288] In some embodiments, hierarchical waveforms with nested structures and time interval hierarchies as described herein can be used for irreversible electroporation ablation energy delivery, thereby providing a good degree of control and selectivity for application in different tissue types. A variety of hierarchical waveforms can be generated by a suitable pulse generator. It should be understood that although the examples herein identify separate monophasic and biphasic waveforms for clarity, it should be noted that combined waveforms can also be generated / implemented in which some portions of the waveform hierarchy are monophasic and other portions are biphasic.

[0289] In some embodiments, the ablation pulse waveforms described herein are applied during the refractory period of the cardiac cycle to avoid interruption of the heart's sinus rhythm. In some embodiments, the treatment method comprises electrically pacing the heart with a cardiac stimulator to ensure pacing capture, so as to establish periodicity and predictability of the cardiac cycle, and then defining a time window within the refractory period of the cardiac cycle to which one or more pulsed ablation waveforms can be delivered. Fig.25 An example is shown in which both atrial and ventricular pacing are applied (e.g., pacing leads or catheters are located in the right atrium and right ventricle, respectively). For the time represented on the horizontal axis, Fig.25 A series of ventricular pacing signals (such as (2500) and (2510)) driven by a pacing signal and a series of atrial pacing signals (2520, 2530) and a series of ECG waveforms (2540, 2542) are shown. Fig.25As shown by the thick arrows, there are an atrial refractory period time window (2522) and a ventricular refractory period time window (2502) for tracking the atrial pacing signal (2522) and the ventricular pacing signal (2500) respectively. Fig.25 As shown, the duration T r The common refractory time window (2550) can be defined as being within the atrial refractory time window (2522) and the ventricular refractory time window (2502). In some embodiments, one or more electroporation ablation waveforms can be applied within this common refractory time window (2550). Fig.25 As shown, the start of this refractory time window (2522) is offset from the pacing signal (2500) by a time offset (2504). In some embodiments, the time offset (2504) can be less than about 25 milliseconds. At the next heartbeat, a similarly defined common refractory time window (2552) is the next time window available for applying one or more ablation waveforms. In this way, the one or more ablation waveforms can be applied over a series of heartbeats, with each heartbeat remaining within the common refractory time window. In one embodiment, for a given electrode group, each pulse grouping as defined above in the pulse waveform hierarchy can be applied over a heartbeat, such that a series of groups are applied over a series of heartbeats.

[0290] It should be understood that the examples and illustrations in this disclosure are for illustrative purposes, and that deviations and variations, such as the number of splines, the number of electrodes, etc., may be constructed and deployed according to the teachings herein without departing from the scope of the invention.

[0291] As used herein, when used in conjunction with a numerical value and / or range, the terms "about" and / or "approximately" generally refer to those numerical values ​​and / or ranges that are close to the numerical value and / or range. In some cases, the terms "about" and "approximately" can mean within ±10% of the value. For example, in some cases, "about 100 [units]" can mean within ±10% of 100 (e.g., 90 to 110). The terms "about" and "approximately" can be used interchangeably.

[0292] Some embodiments described herein relate to a computer storage product having a non-transitory computer-readable medium (also referred to as a non-transitory processor-readable medium) having instructions or computer code thereon for performing various computer-implemented operations. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not itself contain a transitory propagating signal (e.g., a propagating electromagnetic wave that carries information over a transmission medium such as space or a cable). The media and computer code (also referred to as code or algorithm) may be designed and constructed for a specific purpose or purposes. Examples of non-transitory computer-readable media include, but are not limited to: magnetic storage media such as hard disks, floppy disks, and magnetic tapes; optical storage media such as compact disks / digital video disks (CD / DVD), compact disk read-only memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical disks; carrier signal processing modules; and hardware devices that are specifically configured to store and execute program code, such as application specific integrated circuits (ASICs), programmable logic devices (PLDs), read-only memories (ROMs), and random access memory (RAM) devices. Other embodiments described herein relate to a computer program product, which may include, for example, the instructions and / or computer codes disclosed herein.

[0293] The systems, devices and / or methods described herein may be implemented by software (implemented on hardware), hardware or a combination thereof. Hardware modules may include, for example, a general purpose processor (or microprocessor or microcontroller), a field programmable gate array (FPGA) and / or an application specific integrated circuit (ASIC). Software modules (implemented on hardware) may be expressed in various software languages ​​(e.g., computer code), including C, C++, Ruby, Visual and / or other object-oriented, procedural or other programming languages ​​and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions executed by a computer using an interpreter, machine instructions (such as those generated by a compiler), code for generating Web services, and files containing higher-level instructions. Additional examples of computer code include, but are not limited to, control signals, encrypted code, and compressed code.

[0294] The specific examples and descriptions herein are exemplary in nature and one skilled in the art may develop embodiments based on the teachings herein without departing from the scope of the present invention, which is limited only by the appended claims.

Claims

1. A catheter for ablation of endocardial tissue by irreversible electroporation, the catheter comprising: a catheter shaft defining a longitudinal axis and having a proximal end, a distal end opposite the proximal end, and a shaft lumen therethrough; distal cap; a splined shaft disposed within the shaft lumen and having a distal end coupled to the distal cap; a set of splines extending from the distal end of the catheter shaft, each spline in the set of splines including a set of ablation electrodes disposed thereon, wherein each of the splines has a proximal end and a distal end, and wherein the proximal end of each spline is coupled to the distal end of the catheter shaft and the distal end of each spline is coupled to the distal cap, wherein the spline shaft and the distal cap are translatable along the axial axis between a first spline shaft position defining a first configuration of the set of splines and a second spline shaft position defining a second configuration of the set of splines, and the spline shaft is retracted into the catheter shaft to transition the catheter from the first configuration to the second configuration, and wherein, in the first configuration, the set of splines are wound about an axis parallel to the longitudinal axis of the catheter shaft in some portions along their length, but are otherwise generally parallel to the longitudinal axis in other portions, and Wherein, in the second configuration, In a front view of the catheter, each spline in the set of splines forms a twisted loop, so that each spline overlaps one or more other splines, and wherein the ablation electrodes are positioned along each spline to prevent overlap of any ablation electrode on a corresponding spline with any ablation electrode on an adjacent overlapping spline when the set of splines is in the second configuration.

2. The catheter of claim 1 , further comprising an actuator coupled to the set of splines and the distal cap, wherein: The actuator is configured to transition the set of splines between the first configuration and the second configuration.

3. The catheter according to any one of claims 1 or 2, wherein: The set of ablation electrodes on adjacent splines are configured to have opposite polarities in use.

4. The catheter according to any one of claims 1 to 3, wherein: One or more of the ablation electrodes on each spline are connected together by a wire.

5. The catheter according to any one of claims 1 to 3, wherein: One or more of the ablation electrodes on a given spline can be independently addressed.

6. The catheter according to any one of claims 1 to 5, wherein: The set of splines includes 4 to 12 splines.

7. The catheter according to any one of claims 1 to 6, wherein: Each spline in the set of splines has a diameter between about 1 mm and about 5 mm.

8. The catheter according to any one of claims 1 to 7, wherein: Each ablation electrode in the set of ablation electrodes has a diameter between about 0.2 mm and about 2.0 mm.

9. The catheter according to any one of claims 1 to 8, wherein: Each ablation electrode in the set of ablation electrodes has a length between about 0.2 mm and about 5.0 mm.

10. The catheter according to any one of claims 1 to 9, wherein: In the second configuration each spline is laterally offset away from the longitudinal axis by up to 3 cm.

11. The catheter according to any one of claims 1 to 10, wherein: The spline shaft has a hollow lumen.

12. The catheter according to any one of claims 1 to 11, wherein: Each spline has an asymmetric cross-section to have a greater bending stiffness in one bending plane with the spline than in a different bending plane.

13. The catheter according to any one of claims 1 to 12, wherein: The proximal end of each spline is secured to the catheter shaft within the shaft lumen.

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