JP2020517355A5 - - Google Patents

Description

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

Cross-references to related applications This application is filed on July 6, 2017 and claims the interests of US Provisional Application No. 62 / 529,268 entitled "SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION". This is a partial continuation application of US Patent Application No. 15 / 874,721, filed on January 18, 2018, entitled "SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION". This application was also filed on January 5, 2016, "SYSTEMS, APPARATUSES".
AND DEVICES FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE ”claimed priority over US Provisional Application No. 62 / 274,943, filed on January 4, 2017, and filed on January 4, 2017. METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE ”is a partial continuation of the PCT application No. PCT / US2017 / 012099, filed on September 21, 2017, and filed on September 21, 2017. METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE ”claims priority over US Patent Application No. 15 / 711,266. U.S. Patent Application No. 15 / 711,266 was also filed on April 28, 2017 and was entitled "SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED ELECTRIC FIELD ABLATIVE ENERGY TO ENDOCARDIAL TISSUE". Claims priority to US Provisional Application Nos. 62 / 491,910, and US Provisional Application No. 62 / 529,268, filed July 6, 2017, entitled "SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABRATION". The entire disclosure of each of the aforementioned applications is incorporated by reference in its entirety.

The generation of pulsed electric fields for tissue treatment has moved from the laboratory to clinical applications in the last 20 years, but the effects of short pulses of high voltage and large electric fields on tissues have been investigated over the past 40 years. Has been done. When a high DC voltage is applied to a tissue for a short period of time, a high electric field is locally generated in the range of several hundred volts per centimeter, and pores are formed in the cell membrane to destroy the cell membrane. The exact mechanism of this electrically driven pore formation or electroporation has been continuously studied, but by applying a large electric field for a relatively short period of time, the lipid bilayer of the cell membrane is made unstable. It is believed to result in the appearance of local gaps or pore distribution in the cell membrane. This electroporation can be irreversible if the electric field applied to the membrane is greater than the threshold, resulting in pores closing or remaining open, which causes the biomolecular material to leave the membrane. It is exchanged across and causes necrosis and / or apoptosis (cell death). The surrounding tissue may then heal spontaneously.

Pulsed DC voltage can drive electroporation under the right conditions, but high DC voltage electroporation ablation therapy is selected for endocardial tissue in the area of interest with minimal damage to healthy tissue. The demand for thin, flexible, non-invasive devices that deliver effectively is still unmet.

This specification describes systems, devices, and methods for ablating tissue by irreversible electroporation.

The device may include a first catheter that defines the longitudinal axis and the lumen through it. The 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 each surface of the spline. Insulated conductors may be associated with each electrode. Insulated conductors may be placed on each fuselage of the set of splines. The second catheter may be configured to translate along the longitudinal axis to transition between the first and second configurations. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, at least a portion of each spline in the set of splines may extend distal to the distal end of the second catheter.

In some embodiments, the device may include a first catheter that defines the longitudinal axis and the lumen through it. The 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 each surface of the spline. An insulating wire is associated with each electrode. Insulated conductors may be placed on each fuselage of the set of splines. The second catheter may be configured to translate along the longitudinal axis to transition between the first and second configurations. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, each spline in the set of splines may have a longitudinal axis in the second configuration that has an angle of less than about 80 degrees with respect to the longitudinal axis of the first catheter.

In some embodiments, the device may include a first catheter that defines the longitudinal axis and the lumen through it. The 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 each surface of the spline. Insulated conductors may be associated with each electrode. Insulated conductors may be placed on each fuselage of the set of splines. The second catheter may be configured to translate along the longitudinal axis to transition between the first and second configurations. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, each spline in the set of splines may form a loop and be twisted along its length so that the spline has torsion along its length. ..

に準拠する回転速度ｕ′を有してもよく、式中、ｌはスプラインの弧長である。いくつかの実施形態では、スプラインの回転速度ｕ′は、等式ｕ′＝ｄｕ／ｄｌに準拠し、式中、ｌはスプラインに沿った弧長である。スプラインのセットの各スプラインの形状は、等式

に準拠し、式中、ｂ＝ｕ×ｕである。 In some embodiments, each spline in a set of splines has the following equation:

May have a rotational speed u'according to, where in the equation l is the arc length of the spline. In some embodiments, the rotational speed u'of the spline conforms to the equation u'= du / dl, where l is the arc length along the spline. The shape of each spline in a set of splines is an equation

In the equation, b = u × u.

In some embodiments, the system may include a signal generator configured to generate a pulse waveform. The ablation device is configured to couple to a signal generator and receive a pulse waveform. The ablation device may include a first catheter that defines the longitudinal axis and the lumen through it. The second catheter may extend from the distal end of the first catheter lumen. The handle may be coupled to a second catheter. 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 each surface of the spline. Insulated conductors may be associated with each electrode. Insulated conductors may be placed on each fuselage of the set of splines. The second catheter may be configured to translate along the longitudinal axis to transition between the first and second configurations. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, at least a portion of each spline in the set of splines may extend distal to the distal end of the second catheter.

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 through it, and the distal portion of the set of splines binds to the second catheter within the second catheter lumen. You may. In some embodiments, in the second configuration, each spline in a set of splines does not have to overlap adjacent splines.

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

In some embodiments, the insulated conductor may be disposed on the body of the second catheter. The insulated conductor may be configured to maintain a potential of at least about 700 V without dielectric breakdown of its corresponding insulation. In some embodiments, the pulse waveform comprising the first level of the pulse waveform hierarchy may include a first set of pulses, where each pulse has a pulse duration and the first time interval is continuous. Separate the pulses. The second level of the pulse waveform hierarchy contains the first set of multiple pulses as the second set of pulses, the second pulse interval separates the first set of successive pulses, and the second. The time interval may be at least three times the duration of the first time interval. The third level of the pulse waveform hierarchy includes a second set of multiple pulses as a third set of pulses, separating the second set of pulses with consecutive third time intervals, and a third. The time interval may be at least 30 times the duration of the second level time interval.

In some embodiments, the method of treating cardiac arrhythmia by irreversible electroporation involves moving the ablation device forward into the patient's left atrium and moving the ablation device from the first configuration to the second configuration. And may be included. The ablation device includes a first catheter that defines the longitudinal axis and a lumen through it, and a second catheter that extends from the distal end of the first catheter lumen.

A set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, with each spline on its respective surface of the spline. A set of splines, which comprises a set of independently addressable electrodes formed, each electrode having an insulated lead associated with it, and an insulated lead arranged on each fuselage of the set of splines. It may be included. In the first configuration, the set of splines may be generally parallel to the longitudinal axis. In the second configuration, at least a portion of each spline in the set of splines extends distal to the distal end of the second catheter. These steps generate a set of pulse waveforms and a set of pulse waveforms to a set of adjacent portions of the posterior wall of the left atrium, one or more sets of splines of the ablation device in the second configuration. Delivery via splines may further include forming a set of ablation zones.

に準拠する回転速度ｕ′を有してもよく、式中、ｌはスプラインの弧長である。いくつかの実施形態では、スプラインの回転速度ｕ′は、等式ｕ′＝ｄｕ／ｄｌに準拠し、式中、ｌはスプラインに沿った弧長である。いくつかの実施形態では、スプラインのセットの各スプラインの形状は、等式

に準拠してもよく、式中、ｂ＝ｕ×ｕである。 In some embodiments, in the second configuration, the set of splines may form a loop and is twisted along its length so that the spline torsions along its length. Will have. In some embodiments, in the second configuration, each spline in the set of splines has a longitudinal axis in the second configuration that has an angle of less than about 80 degrees with respect to the longitudinal axis of the first catheter. You may have. In some embodiments, each spline in a set of splines is an equation.

May have a rotational speed u'according to, where in the equation l is the arc length of the spline. In some embodiments, the rotational speed u'of the spline conforms to the equation u'= du / dl, where l is the arc length along the spline. In some embodiments, the shape of each spline in a set of splines is an equation.

In the equation, b = u × u.

In some embodiments, at least a portion of the set of splines may advance distally to the distal end of the second catheter by retracting the second catheter with respect to the first catheter. Good. In some embodiments, each insulating wire may be configured to maintain a potential of at least about 700V without dielectric breakdown of its corresponding insulation.

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

In some embodiments, the first set of spline electrodes in a set of splines may be configured as an anode, and the second set of electrodes in a second spline in a set of splines may be a cathode. The pulse waveform may be delivered to the first set of electrodes and the second set of electrodes.

FIG. 5 is a block diagram of an electroporation system according to an embodiment. It is a perspective view of the ablation catheter according to an embodiment. It is a perspective view of the ablation catheter according to another embodiment. It is a perspective view of the ablation catheter according to another embodiment. FIG. 3 is a detailed perspective view of the distal portion of the ablation catheter according to another embodiment. It is a side view of the ablation catheter according to another embodiment. It is a side view of the ablation catheter according to another embodiment. FIG. 5 is a diagram of an ablation catheter according to another embodiment. FIG. 8A is a side view. FIG. 5 is a diagram of an ablation catheter according to another embodiment. FIG. 8B is a front sectional view. It is a side view of the ablation catheter in the first structure according to another embodiment. It is a side view of the ablation catheter in the second expansion structure according to another embodiment. It is a side view of the ablation catheter in the third expansion structure according to another embodiment. It is a side view of the ablation catheter in the 4th expansion structure according to another embodiment. It is a side view of the ablation catheter in the fifth expansion structure according to another embodiment. FIG. 5 is a perspective view of a balloon ablation catheter disposed in the left atrial space of the heart according to another embodiment. FIG. 5 is a cross-sectional view of a balloon ablation catheter disposed in the left atrial space of the heart according to another embodiment. It is the schematic of the return electrode of the ablation system according to an embodiment. FIG. 12A shows an electrode that is not energized. It is the schematic of the return electrode of the ablation system according to an embodiment. FIG. 12B shows an energized electrode. The method of tissue ablation according to the embodiment is shown. The method of tissue ablation according to the embodiment is shown. FIG. 2 is an illustration of an ablation catheter illustrated in FIG. 2 located in the left atrial space of the heart. FIG. 3 is an illustration of an ablation catheter illustrated in FIG. 3 located in the left atrial space of the heart. It is an illustration of two of the ablation catheters illustrated in FIG. 4 located in the left atrial space of the heart. FIG. 5 is an illustration of an ablation catheter illustrated in FIG. 5 located in the left atrial space of the heart. It is explanatory drawing of the set of the electrode arranged in the pulmonary vein opening by another embodiment. FIG. 19A is a schematic perspective view. It is explanatory drawing of the set of the electrode arranged in the pulmonary vein opening by another embodiment. FIG. 19B is a cross-sectional view. It is explanatory drawing of the electric field generated by the electrode arranged in the pulmonary vein opening by another embodiment. FIG. 20A is a schematic perspective view. It is explanatory drawing of the electric field generated by the electrode arranged in the pulmonary vein opening by another embodiment. FIG. 20B is a cross-sectional view. It is an exemplary waveform showing a series of voltage pulses having a defined pulse width for each pulse according to the embodiment. The pulse hierarchy indicating the pulse width, the interval between pulses, and the grouping of pulses according to the embodiment is shown schematically. Provided is a schematic diagram of a monophasic pulse nested hierarchy displaying different levels of nested hierarchy according to an embodiment. FIG. 5 is a schematic diagram of a biphasic pulse nested hierarchy displaying different levels of nested hierarchy according to an embodiment. In embodiments, the timeline of the electrocardiogram and cardiac pacing signals is schematically shown along with the atrial and ventricular refractory periods and the time sequence of irreversible electroporation ablation. It is a perspective view of the ablation catheter according to another embodiment. It is a side view of the ablation catheter illustrated in FIG. 26A disposed in the left atrial space of the heart adjacent to the pulmonary ostium. FIG. 6 is a top view of a simulation of an ablation catheter illustrated in FIG. 26B showing selective electrode operation according to an embodiment. It is an illustration of the simulation of tissue ablation in the lung ostium according to the embodiment. It is each side view of the ablation catheter according to another embodiment. FIG. 27A is a side view of the ablation catheter in the second configuration. It is each side view of the ablation catheter according to another embodiment. FIG. 27B is another side view of the ablation catheter in the second configuration. It is each side view of the ablation catheter according to another embodiment. FIG. 27C is yet another side view of the ablation catheter in the second configuration. It is a side view of the ablation catheter according to another embodiment. FIG. 5 is a cross-sectional view of an ablation catheter according to another embodiment. FIG. 29A is a longitudinal side view of the ablation catheter in the first configuration. FIG. 5 is a cross-sectional view of an ablation catheter according to another embodiment. FIG. 29B is a longitudinal side view of the ablation catheter in the third configuration. FIG. 5 is a cross-sectional view of an ablation catheter according to another embodiment. FIG. 29C is another longitudinal side view of the ablation catheter in the third configuration. FIG. 5 is a cross-sectional view of an ablation catheter according to another embodiment. FIG. 29D is yet another longitudinal side view of the ablation catheter in the third configuration. It is a side view of the ablation catheter according to another embodiment. It is a perspective view of the ablation catheter according to another embodiment. FIG. 31A is a perspective view of the ablation catheter in the first configuration. It is a perspective view of the ablation catheter according to another embodiment. FIG. 31B is a perspective view of the ablation catheter in the second configuration. FIG. 3 is a schematic cross-sectional view of an ablation catheter according to another embodiment. It is explanatory drawing of the ablation catheter by another embodiment. FIG. 33A is a perspective view of the ablation catheter. It is explanatory drawing of the ablation catheter by another embodiment. FIG. 33B is a front view of the ablation catheter of FIG. 33A. It is explanatory drawing of the ablation catheter by another embodiment. FIG. 33C is a notched perspective view of the spline of the ablation catheter of FIG. 33A. It is explanatory drawing of the ablation catheter by another embodiment. FIG. 33D is a cross-sectional view of the spline of the ablation catheter of FIG. 33A. It is explanatory drawing of the ablation catheter by another embodiment. FIG. 33E is a perspective view of the ablation catheter of FIG. 33A disposed adjacent to the tissue. It is a side view of the spline by another embodiment. FIG. 34A is a unit tangent vector. It is a side view of a spline accompanied by. It is a side view of the spline by another embodiment. FIG. 34B is a side view with two unit tangent vectors. It is a side view of the ablation catheter according to another embodiment. It is a side view of the ablation catheter according to another embodiment. FIG. 36A is a side view of the ablation catheter in the second configuration. It is a side view of the ablation catheter according to another embodiment. FIG. 36B is another side view of the ablation catheter in the second configuration. It is a side view of the ablation catheter according to another embodiment. FIG. 36C is a side view of the ablation catheter near the tissue. It is a perspective view of an ablation catheter and a left atrium. FIG. 37A is a perspective view of an ablation catheter disposed in the left atrium. It is a perspective view of an ablation catheter and a left atrium. FIG. 37B is a perspective view of the left atrium after tissue ablation.

As used herein, systems, devices, and methods for the selective and rapid application of pulsed electric fields to ablate tissue by irreversible electroporation are described. In general, the systems, devices, and methods described herein generate large electric field strengths in the desired region of interest and reduce peak electric field values elsewhere, resulting in unwanted tissue damage and electricity. Can be used to reduce arc discharge. The irreversible electroporation system described herein applies one or more voltage pulse waveforms to a selected set of electrodes in an ablation device to apply energy to the region of interest (eg, to the pulmonary vein ostium). It may include a signal generator and processor configured to deliver (ablation energy) for a set of tissues. The pulse waveforms disclosed herein can support the therapeutic treatment of various cardiac arrhythmias (eg, atrial fibrillation). To deliver the pulse waveform generated by the signal generator, one or more electrodes of the ablation device are configured to maintain a potential of at least about 700 V without dielectric breakdown of the corresponding insulation. It may have a lead wire. The electrodes may be independently addressable so that each electrode can be controlled (eg, deliver energy) independently of any other electrode in the device. In this way, the electrodes can deliver different energy waveforms synergistically at different times due to electroporation of the tissue.

As used herein, the term "electroporation" refers to the application of an electric field to a cell membrane and refers to altering 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 the cell membrane, which temporarily alters the permeability of the cell membrane to the extracellular environment. For example, cells undergoing reversible electroporation may follow the temporary and / or intermittent formation of one or more pores within the cell membrane that close when the electric field is removed. As used herein, the term "irreversible electroporation" refers to the application of an electric field to the cell membrane, which permanently alters the permeability of the cell membrane to the extracellular environment. For example, cells undergoing irreversible electroporation may follow the formation of one or more pores within the cell membrane that persists upon removal of the electric field.

The pulse waveforms for electroporation energy delivery disclosed herein enhance the safety, efficiency, and effectiveness of energy delivery to tissues by lowering the electric field threshold associated with irreversible electroporation. It can result in a more effective excision affected area with a reduction in the total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein are hierarchical and may have a nested structure. For example, the pulse waveform may include a hierarchical grouping of pulses with associated timescales. In some embodiments, the methods, systems, and devices disclosed herein are "SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE.
It may include one or more of the methods, systems, and devices described in the international application PCT / US2016 / 057664 filed on October 19, 2016, entitled "ENERGY TO TISSUE", the contents of which are referenced. Is incorporated herein by all means.

In some embodiments, the system can further include a cardiac stimulator used to synchronize the generation of pulse waveforms with the paced heartbeat. The cardiac stimulator can electrically pace the heart with the cardiac stimulator, ensuring capture of the pacing and establishing the periodicity and predictability of the cardiac cycle. The time window within the refractory period of the periodic cardiac cycle may be selected for voltage pulse waveform delivery. Therefore, a voltage pulse waveform can be delivered during the refractory period of the cardiac cycle to avoid disruption of the sinus rhythm of the heart. In some embodiments, the ablation device may include one or more catheters, guidewires, balloons, and electrodes. The ablation device may move to different configurations (eg, compact and dilated) to position the device within the intracardiac lumen. In some embodiments, the system may optionally include one or more return electrodes.

In general, to ablate tissue, one or more catheters can advance minimally invasively through the vascular structure to the target site. For cardiac applications, the electrodes to which the voltage pulse waveform is delivered may be disposed on the epicardial or endocardial device. The methods described herein may include introducing the device into the intracardiac lumen of the left atrium of the heart and disposing the device in contact with the pulmonary venous ostium. The pulse waveform can be generated and delivered to one or more electrodes of the device to ablate the tissue. In some embodiments, the pulse waveform can be generated in synchronization with the pacing signal of the heart to avoid disruption of the sinus rhythm of the heart. In some embodiments, the electrode may consist of an anode-cathode subset. The pulse waveform may include a hierarchical waveform to assist tissue ablation and reduce damage to healthy tissue.

I. System Overview This specification discloses systems and devices configured for tissue ablation through selective and rapid application of voltage pulse waveforms to assist tissue ablation resulting in irreversible electrical perforation. In general, the tissue ablation systems described herein include a signal generator and an ablation device having one or more electrodes for the selective and rapid application of DC voltage to drive electroporation. It may be included. As described herein, systems and devices may be deployed in the epicardium and / or endocardium to treat atrial fibrillation. The voltage may be applied to a selected subset of electrodes and there is an independent subset selection for the selection of the anode and cathode electrodes. A pacing signal for cardiac stimulation may be generated and used by the signal generator to generate a pulse waveform in synchronization with the pacing signal.

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

The signal generator (122) may be configured to generate pulse waveforms for irreversible electroporation of tissues such as the pulmonary vein ostium. For example, the signal generator (122) is a voltage pulse waveform generator, which may deliver the pulse waveform to the ablation device (110). By coupling the return electrode (140) to the patient (eg, by disposing it on the patient's back), an electric current flows from the ablation device (110) through the patient to the return electrode (140) and from the patient. It is possible to provide a safe current feedback path (not shown). The processor (124) incorporates the data received from the memory (126), the cardiac stimulator (128), and the pacing device (130) to generate pulse waveform parameters (eg, amplitude) by the signal generator (122). , Width, duty cycle, etc.). The memory (126) further stores instructions that cause the signal generator (122) to perform modules, processes, and / or functions related to the system (100), such as pulse waveform generation and / or cardiac pacing synchronization. You may. For example, the memory (126) may be configured to store pulse waveforms and / or cardiac pacing data for pulse waveform generation and / or cardiac pacing, respectively.

In some embodiments, the ablation device (110) may include a catheter configured to receive and / or deliver the pulse waveform described in more detail below. For example, the ablation device (110) is introduced into the intracardiac lumen of the left atrium and is positioned to align one or more electrodes (112) to one or more pulmonary venous ostium and then produces a pulse waveform. It may be delivered 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 insulating wire configured to maintain a potential of at least about 700 V without the corresponding insulation breaking down. In some embodiments, each insulation of the conductor may maintain a potential difference of about 200V to about 1,500V over its entire thickness without dielectric breakdown. For example, the electrode (112) is, for example, a subset containing one anode and one cathode, a subset containing two anodes and two cathodes, a subset containing two anodes and one cathode, one anode and two. It may be grouped into one or more anode-cathode subsets, such as a subset containing one cathode and a subset containing three anodes and one cathode, and a subset containing three anodes and two cathodes.

The pacing device (130) is configured to be suitably coupled to the patient (not shown) and to receive a cardiac pacing signal generated by the cardiac stimulator (128) of the device (120) for cardiac stimulation. May be good. The display of the pacing signal may be transmitted by the cardiac stimulator (128) to the signal generator (122). Based on the pacing signal, the display of the voltage pulse waveform may be selected, calculated, and / or otherwise identified by the processor (124) and generated by the signal generator (122). In some embodiments, the signal generator (122) is configured to generate a pulse waveform in synchronization with the display of the pacing signal (eg, within a common refractory window). For example, in some embodiments, the common refractory window begins substantially immediately after the ventricular pacing signal (or after a very small delay) and then lasts for a period of about 250 ms or less. In such an embodiment, the entire pulse waveform may be delivered within this period.

The processor (124) may be any suitable processing device configured to execute and / or execute a set of instructions or codes. The processor may be, for example, a general purpose processor, a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), a digital signal processor (DSP), and / or the like. The processor may be configured to perform and / or perform application processes and / or other modules, processes and / or functions associated with the system and / or its associated network (not shown). The underlying device technologies include metal oxide semiconductor field effect transistor (MOSFET) technologies such as complementary metal oxide semiconductors (CMOS), bipolar technologies such as emitter-coupled logic (ECL), and polymer technologies (eg, silicon-conjugated polymers and). It may be provided in various component types, such as metal-conjugated polymer metal structures), a mixture of analog and digital.

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

The system (100) may communicate with other devices (not shown) via, for example, one or more networks, each of which may be any type of network. A wireless network refers to any type of digital network that is not connected by any type of cable. However, wireless networks may connect to wired networks to connect to the Internet, voice and data networks of other carriers, business networks, and personal networks. Wired networks are typically carried by twisted pair of copper wires, coaxial cable, or fiber optic cable. Wide Area Network (WAN), Metropolitan Area Network (MAN), Local Area Network (LAN), Campus Area Network (CAN), Global Area Network (GAN), For example, Internet, and Virtual Private Network (VPN). There are various types of wired networks. Hereinafter, network refers to any combination of combined wireless, wired, public, and private data networks, typically interconnected via the Internet, to provide an integrated networking and information access solution. ..

Ablation Devices The systems described herein may include one or more multi-electrode ablation devices configured to ablate tissue in the left atrial space of the heart to treat atrial fibrillation. FIG. 2 is structural and / or functional to an ablation device (200) (eg, an ablation device (110)) that includes a catheter (210) and a guide wire (220) that is slidable within the lumen of the catheter (210). It is a perspective view of (similar to). The guide wire (220) may include a non-linear distal portion (222) and the catheter (210) may be configured to be disposed on the guide wire (220) during use. The distal portion (222) of the guide wire (220) may be shaped to assist in the placement of the catheter (210) in the patient's lumen. For example, the shape of the distal portion (222) of the guide wire (220) may be configured to be located at and / or near the pulmonary vein ostium, as described in more detail in FIG. .. The distal portion (222) of the guide wire (220) comprises a non-invasive shape that reduces trauma to the tissue (eg, prevents and / or reduces the possibility of tissue puncture) and / or is non-invasive. It may be formed in a shape. For example, the distal portion (222) of the guide wire (220) may include non-linear shapes such as circles, loops (as shown in FIG. 2), ellipsoids, or any other geometry. .. In some embodiments, the guidewire (220) coincides with the lumen of the catheter (210) when a guidewire having a non-linear shape is placed on the catheter (210) and from the catheter (210). It may be configured to be elastic so that it reshapes or restores the non-linear shape as it exits and advances. In other embodiments, the catheter (210) may also be configured to be elastic (not shown), such as to assist in advancing the catheter (210) through the sheath. The distal portion (222) of the molded guide wire (220) may be angled with respect to the guide wire (220) and the rest of the catheter (210). The catheter (210) and guide wire (220) may be sized for advancement into the cardiac lumen (eg, left atrium). The diameter of the distal portion (222) of the molded guide wire (220) may be approximately the same as the diameter of the lumen in which the catheter (230) will be placed.

The catheter (210) may slidably advance over the guide wire (220) so that it is disposed over the guide wire (220) during use. The distal portion (222) of the guide wire (220) disposed in the lumen (eg, near the pulmonary vein opening) can act as a backstop for advancing the distal portion of the catheter (210). The distal portion of the catheter (210) is structural to an electrode (212) (eg, electrode (s) (112) configured to contact the medial radial surface of the lumen (eg, pulmonary vein ostium). And / or functionally similar) sets may be included. For example, the electrode (212) may include a nearly circular array of electrodes configured to contact the pulmonary vein ostium. As shown in FIG. 2, the one or more electrodes (212) include a series of metal bands or rings arranged along the catheter shaft, both of which may be electrically connected. For example, the ablation device (200) may include a single electrode having multiple bands, one or more electrodes in which each electrode has its own band, and combinations thereof. In some embodiments, the electrode (212) may be shaped to match the shape of the distal portion (222) of the guide wire (220). The catheter shaft may include flexible portions between the electrodes to enhance flexibility. In other embodiments, the one or more electrodes (212) may include a spiral to enhance flexibility.

Each of the electrodes of the ablation device discussed herein may be connected to an insulated wire (not shown) that connects to a handle (not shown) attached to the proximal portion of the catheter. Each insulation of the conductor may maintain a potential difference of at least 700 V over its entire thickness without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200V and about 2000V over the entire thickness in between, including all values and subranges in between, without dielectric breakdown. Good. This allows the electrodes to efficiently deliver electrical energy and ablate tissue by irreversible electroporation. The electrodes may receive, for example, the pulse waveform generated by the signal generator (122), as discussed above with respect to FIG. In other embodiments, the guide wire (220) may be separate from the ablation device (200) (eg, the ablation device (200) includes a catheter (210) but includes a guide wire (220). Absent). For example, the guide wire (220) may itself advance into the cardiac lumen, after which the catheter (210) may advance into the cardiac lumen on the guide wire (220).

FIG. 3 is structural to an ablation device (300) (eg, an ablation device (110)) comprising a catheter (310) in which a set of electrodes (314) is provided along the distal portion (312) of the catheter (310). And / or functionally similar) another embodiment perspective view. The distal portion (312) of the catheter (310) is non-linear and may form an approximately circular shape. The set of electrodes (314) may be disposed along the non-linear distal portion (312) of the catheter (310) or may form a nearly circular array of electrodes (314). During use, the electrode (314) may be placed in the pulmonary venous ostium to deliver a pulsed waveform and ablate the tissue, as described in more detail with respect to FIG. The distal portion (312) of the molded catheter (310) may be angled with respect to other positions of the catheter (310). For example, the distal portion (312) of the catheter (310) may be approximately perpendicular to the adjacent position of the catheter (310). In some embodiments, the handle (not shown) may be attached to the proximal portion of the catheter (310) and is configured to modify the shape of the distal portion (312) of the catheter (310). It may include a bending mechanism (eg, one or more pull wires (not shown)). For example, manipulating the pull wire on the handle can increase or decrease the circular shape outer circumference of the distal portion (312) of the catheter (310). By modifying the diameter of the distal portion (312) of the catheter (310), the electrode (314) is placed near the pulmonary vein opening and / or in contact with the pulmonary vein opening (eg, the medial radial surface of the pulmonary vein). It may be possible to dispose of it (in contact with). The electrode (314) may include a series of metal bands or rings and can be addressed independently.

In some embodiments, the pulse waveform can be applied between electrodes (314) composed of a set of anode and cathode. For example, adjacent or nearly opposite electrode pairs may work together as an anode-cathode set. It should be understood that any of the pulse waveforms disclosed herein can be applied incrementally or continuously to the anode-cathode electrode sequence.

FIG. 4 is structural and / or functional to an ablation device (400) (eg, ablation device (110)) including a catheter (410) with a molded non-linear distal portion (422) and a guide wire (420). It is a perspective view of still another embodiment (similar to). The guide wire (420) may be slidable within the lumen of the catheter (410). The guide wire (420) may advance through the lumen of the catheter (410), and the distal portion (422) of the guide wire (420) may have a substantially circular shape. The shape and / or diameter of the distal portion (422) of the guide wire (420) may be modified using a bending mechanism as described above with respect to FIG. The catheter (410) may be flexible so that it can be bent. In some embodiments, the catheters (410) and / or the guide wires (420) match the lumen in which they are placed and take a secondary shape as they exit and advance out of the lumen. It may be configured to be elastic. 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 the target tissue site, such as the pulmonary vein ostium. The distal end (412) of the catheter (410) is provided with a guide wire (420) so that the catheter (410) can electrically insulate the portion of the guide wire (420) within the lumen of the catheter (410). It may be sealed except where it begins to extend. For example, in some embodiments, the distal end (412) of the catheter (410) may include a seal, which allows the passage of the guide wire (420) when a force is applied. It has an opening that forms a compression hold (which may be liquidtight) between the seal and the guide wire (420).

In some embodiments, the distal portion (422) of the exposed guidewire (420) may be coupled to an electrode, receiving a pulse waveform from the signal generator and delivering the pulse waveform to the tissue during use. It may be configured to do so. For example, the proximal end of the guide wire (420) may be coupled to a suitable conductor and connected to the signal generator (122) of FIG. The distal portion (422) of the guide wire (420) can be sized so that it can be positioned at the pulmonary vein ostium. For example, the diameter of the distal portion (422) of the molded guide wire (420) may be approximately the same as the diameter of the pulmonary vein opening. The distal portion (422) of the molded guide wire (420) may be angled with respect to the guide wire (420) and the rest of the catheter (410).

The guide wire (420) may include stainless steel, nitinol, platinum, or other suitable biocompatible material. In some embodiments, the distal portion (422) of the guide wire (420) may include a platinum coil physically and electrically connected to the guide wire (420). The platinum coil may be an electrode configured for delivery of voltage pulse waveforms. Platinum is radiopaque and its use may increase flexibility and assist in advancing and positioning the ablation device (400) in the cardiac lumen.

FIG. 5 includes an ablation device (500) (eg, an ablation device (110), including a set of electrodes (520, 522, 524, 526), each extending from a pair of insulated lead segments (510, 512, 514, 516). ) Is structurally and / or functionally similar to)) is a detailed perspective view of the distal portion of the flower shape. Each pair of adjacent insulated wire segments coupled to an uninsulated electrode (eg, wire segment (510, 512) and electrode (526)) forms a loop (Figure 5 shows a set of four loops). .. The set of loops at the distal end of the ablation device (500) may be configured to deliver the pulse waveform to the tissue. The ablation device (500) is an insulated lead segment (510) that branches at the distal end of the device (500) and connects to each exposed electrode (520, 522, 524, 526), as shown in FIG. It may include a set of 512, 514, 516). The electrodes (520, 522, 524, 526) may include exposed portions of the electrical conductor. In some embodiments, one or more of the electrodes (520, 522, 524, 526) may include a platinum coil. One or more segments (510, 512, 514, 516) are bending mechanisms (eg, not shown) controlled from handles (not shown) to control the size and / or shape of the distal portion of the device (500). It may be connected to a support (pull wire, etc.).

The electrodes (520, 522, 524, 526) are flexible and may form a compact first configuration for advancement into the cardiac lumen, such as adjacent to the pulmonary vein ostium. When placed in the desired location, the electrodes (520, 522, 524, 526) have an expanded second configuration as they move out of a lumen, such as a sheath, as shown in FIG. It may migrate to form the distal part of the flower shape. In other embodiments, the insulated conductor segments (510, 512, 514, 516) and electrodes (520, 522, 524, 526) are urged as they move forward out of the lumen (eg, sheath). It expands outward (eg, bounces open) to form a second configuration that carries the device (500). The electrodes (520, 522, 524, 526) may be independently addressable and are each insulated conductor configured to maintain a potential of at least about 700 V without dielectric breakdown of the corresponding insulation. May have. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 2000 V over its entire thickness without dielectric breakdown.

In some embodiments, the ablation device (5000) may be configured to deliver a pulse waveform to the tissue during use via a set of electrodes (520, 522, 524, 526). In some embodiments, the pulse waveform can be applied between electrodes (520, 522, 524, 526) composed of a set of anode and cathode. For example, the approximately opposite electrode pairs (eg, electrodes (520, 524) and (522, 526)) may operate together as an anode-cathode pair. In other embodiments, the adjacent electrodes may be configured as an anode-cathode pair. As an example, one electrode (520) in a set of electrodes may be configured as an anode and a second electrode (522) may be configured as a cathode.

FIGS. 6-9E, 26A-27C, and 28 are ablation devices that can be configured to ablate tissue and deliver a voltage pulse waveform using a set of electrodes to electrically insulate the pulmonary veins (eg,). , An additional embodiment of an ablation device (110) that is structurally and / or functionally similar). In some of these embodiments, the ablation device is moved from a first configuration to a second configuration so that the electrodes of the ablation device expand outward to contact the lumen of the tissue (eg, the pulmonary vein opening). It may be migrated.

FIG. 6 includes an ablation device (600) including a catheter shaft (610) at the proximal end of the device (600), a distal cap (612) of the device (600), and a spline (614) attached thereto. It is a side view of the embodiment of. The distal cap (612) may include a non-invasive shape to reduce trauma to the 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 the distal cap (612) of the device (600). ) May be connected. The ablation device (600) may be configured to deliver a pulse waveform to the tissue during use via one or more splines in a set of splines (614). As used herein, "spline" and "spine" may be used interchangeably. In some embodiments, the device may include a catheter defining a longitudinal axis.

Each spline (614) of the ablation device (600) is connected and wired one or more connected to each other formed on the surface of the spline (614), or in some cases independently addressable electrodes (616). May include. Each electrode (616) can include an insulating wire configured to maintain a potential of at least about 700 V without dielectric breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 2000 V over its entire thickness without dielectric breakdown. Each spline (614) may include an insulating conductor of each electrode (616) formed in the fuselage of the spline (614) (eg, in the lumen of the spline (614)). If the electrodes on a single spline are routed together, the single insulated wire may hold strands that connect to different electrodes on the spline. FIG. 6 shows a set of splines (614), including a pair of electrodes (616) in which each spline (614) has 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.

For each of the ablation devices described herein, and especially for the ablation devices described in FIGS. 6-9E, 26A-27C, and 28, each spline in the set of splines may include a flexible curve. .. The minimum radius of curvature of the spline can be in the range of about 1 cm or more. For example, a set of splines may form a delivery assembly at the distal portion of the ablation device, with a first configuration in which the set of splines flex radially outward from the longitudinal axis of the ablation device, and a set of splines. It may be configured to transition to and from a second configuration that is arranged approximately parallel to the longitudinal axis of the ablation device. In this way, the splines can be more easily matched by the geometry of the intracardiac lumen. In general, a spline "basket" has an asymmetric shape along the length of the shaft so that one end of the basket (probably the distal end) bulges from the other end of the basket (probably the proximal end). Can have. The delivery assembly may be disposed in contact with the pulmonary venous ostium in the first configuration and transition to the second configuration prior to delivery of the pulse waveform. In some of these embodiments, the handle may be coupled to a set of splines, the handle being configured to trigger a transition between the first and second configurations of the set of splines. Will be done. In some embodiments, the conductors of at least two electrodes in a set of electrodes may be electrically coupled at or near the proximal portion of the ablation device, for example in a handle.

In one embodiment, each of the electrodes (616) on the spline (614) may be configured as an anode, while each of the electrodes (616) on the adjacent spline (614) may be configured as a cathode. .. In another embodiment, the electrodes (616) on one spline may alternate between the anode and the cathode, and the electrodes on the adjacent splines have the opposite configuration (eg, cathode and anode). The ablation device (600) has an arbitrary number of splines, including all values and subranges in between, eg, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18 , 20 or more splines may be included. In some embodiments, the ablation device (600) may include 3 to 20 splines. In some embodiments, the ablation device (600) may include 6-12 splines.

FIG. 7 includes an ablation device (700) including a catheter shaft (710) located at the proximal end of the device (700), a distal cap (712) of the device (700), and a spline (714) attached thereto. It is a side view of another embodiment of. The distal cap (712) may include a non-invasive 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 the distal cap (712) of the device (700). ) May be connected. 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 insulating wire configured to maintain a potential of at least about 700 V without dielectric breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 1500 V over its entire thickness without dielectric breakdown. Each spline (714) may include an insulating conductor of each electrode (716) formed in the fuselage of the spline (714) (eg, in the lumen of the spline (714)). The set of spline wires (718, 719) is conductive and adjacent electrodes (714) disposed on different splines (714), such as the electrodes (716) between a pair of splines (718, 719) in the set of splines. It may be electrically coupled to 716). For example, the spline wires (718, 719) may extend laterally with respect to the longitudinal axis of the ablation device (700).

FIG. 7 shows a set of splines (714) including a pair of electrodes (716) in which each spline (714) has 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 vary. For example, the electrode (716) electrically coupled to the first spline wire (718) differs in size and / or shape from the electrode (716') electrically coupled to the second spline wire (719). You may.

In some embodiments, the first spline wire (718) may include a first set of spline wires (720, 721, 722, 723) of the spline wires (720, 721, 722, 723). Each spline wire in the set may couple electrodes (716) between different pairs of splines in the set of splines (714). In some of these embodiments, the set of spline wires (720, 721, 722, 723) may form a continuous loop between the electrodes (716) coupled to it. Similarly, the second spline wire (719) may include a second set of spline wires (724, 725, 726), and each spline wire in the set of spline wires (724, 725, 726) is a spline. Electrodes (716') across the set of (714) may be coupled. A second set of spline wires (724, 725, 726) couples different electrodes (716') across a different set of splines (714) than the first set of spline wires (720, 721, 722, 723). You may. In some of these embodiments, the first set of spline wires (720, 721, 722, 723) may form a first continuous loop between the electrodes (716) coupled to it, the spline wires. A second set of (724, 725, 726) may form a second continuous loop between the electrodes (716') coupled to it. The first continuous loop may be electrically isolated from the second continuous loop. In some of these embodiments, the electrode (716) coupled to the first continuous loop may be configured as an anode and the electrode (716) coupled to the second continuous loop may be configured as a cathode. Good. The pulse waveform may be delivered to the electrodes (716) of the first and second continuous loops. In some embodiments, spline wires, such as 721, 722, 723, etc., can be replaced with similar electrical connections in the proximal part of the device (eg, in the device handle). For example, all electrodes 716 can be electrically wired together within the handle of the device.

In another embodiment, the first spline wire (721) of the set of spline wires (720, 721, 722, 723) is the first spline (711) and the second spline (711) of the set of splines (714). The electrode (716) between the spline wire (713) may be coupled and the second spline wire (720) in the set of spline wires (720, 721, 722, 723) is the first in the set of splines (714). The electrode (716) between the spline (711) and the third spline (715) may be coupled. The electrode (716) coupled by the first spline wire (721) and the second spline wire (720) may be configured as an anode and cathode (or vice versa). In yet another embodiment, the first spline wire (721) of the set of spline wires (720, 721, 722, 723) is the first spline (711) and the second spline of the set of splines (714). The electrode (716) to and from (713) may be coupled and the second spline wire (723) of the set of spline wires (720, 721, 722, 723) is the second of the set of splines (714). An electrode (716) between the 3rd spline (715) and the 4th spline (717) may be coupled. The pulse waveform may be delivered to the electrode (716) coupled by the first spline wire (721) and the second spline wire (723). In some embodiments, instead of spline wires, the conductors of at least two electrodes in a set of electrodes are electrically coupled at or near the proximal portion of the ablation device, for example in a handle.

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

In some embodiments, as discussed in more detail below with respect to FIGS. 8A-8B, the spline wires do not form continuous loops and are electrodes (eg, 2, 3, 4, 5, etc. ) May be electrically coupled to the set. For example, the discontinuous loop may be formed using two spline wires. In other embodiments, the size, shape, and spacing of the electrodes (716) may vary. The ablation device (700) has an arbitrary number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 12, 14, 16, and 18. , 20 or more splines may be included. In some embodiments, the ablation device (700) may include 3 to 20 splines. For example, in one embodiment, the ablation device (700) may include 6-9 splines.

8A and 8B are a longitudinal side view and a front sectional view of the ablation catheter (800), respectively. FIG. 8A includes an ablation device (800) including a catheter shaft (810) located at the proximal end of the device (800), a distal cap (812) of the device (800), and a spline (814) attached thereto. It is a side view of the embodiment of. The distal cap (812) may include a non-invasive 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 the distal cap (812) of the device (800). ) May be moored. 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 insulating wire configured to maintain a potential of at least about 700 V without dielectric breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200V and about 2000V over the entire thickness between them, including all values and subranges between them. Each spline (814) may include an insulating conductor of each electrode (816, 818) formed in the fuselage of the spline (814) (eg, in the lumen of the spline (814)). The one or more spline wires (817, 819) are conductive and may electrically couple adjacent electrodes (816, 818) disposed on different splines (814). For example, the spline wires (817, 819) may extend laterally with respect to the longitudinal axis of the ablation device (800).

FIG. 8B is a front sectional view of FIG. 8A along the line 8B-8B. 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 may be electrically isolated from each other. In some embodiments, the coupled electrode pairs may be configured with a common polarity. Adjacent electrode pairs may be configured with opposite polarities (eg, a first electrode pair configured as an anode and an adjacent second electrode pair configured as a cathode). For example, the electrodes (816) coupled to the first set of spline wires (817) may be configured as anodes, while each of the electrodes (818) coupled to the second set of spline wires (819) may be configured. It may be configured as a cathode. In some embodiments, each electrode formed on the spline (814) may share a common polarity (eg, configured as an anode or cathode). Each coupled electrode pair may be independently addressable. In some embodiments, the ablation device (800) may include an even number of splines. The ablation device (800) may include any number of splines, such as 4, 6, 8, 10, or more splines. In some embodiments, the ablation device may include 4-10 splines. For example, in one embodiment, the ablation device may include between 6 and 8 splines. As shown above, in some embodiments, spline wires, such as 817, 819, etc., can be replaced with similar electrical connections in the proximal part of the device (eg, in the device handle). For example, the electrodes (816) can be electrically wired together within the handle of the device so that these electrodes have the same potential during ablation.

FIG. 9A includes an ablation device (900) including a catheter shaft (910) at the proximal end of the device (900), a distal cap (912) of the device (900), and a spline (914) attached thereto. It is a side view of still another embodiment of. The distal cap (912) may include a non-invasive 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 the distal cap (912) of the device (900). ) May be moored. 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 insulating wire configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 2000 V over its entire thickness without dielectric breakdown. Each spline (914) may include an insulating conductor of each electrode (916, 918) formed in the fuselage of the spline (914) (eg, in the lumen of the spline (914)). FIG. 9A shows a set of splines (914), including electrodes in which each spline (914) is separated or offset from the electrodes of adjacent splines (914). For example, the electrode (916) of the first spline (920) is placed closer to the distal end (912) of the ablation device (900) than the electrode (918) of the second spline (922). A set of splines (914) that includes a first spline (920) and a second spline (922) adjacent to the first spline (920). In other embodiments, the size and shape of the electrodes (916, 918) may also vary.

In some embodiments, adjacent distal electrodes (916) and proximal electrodes (918) may form an anode-cathode pair. For example, the distal electrode (916) may be configured as an anode and the proximal electrode (918) may be configured as a cathode. In some embodiments, the ablation device (900) may include 3-12 splines. In FIG. 9A, one electrode (916, 918) is formed on the surface of each spline (914) such that each spline (914) contains one insulating wire. This can reduce the diameter of the lumen of the spline (914), making the spline (914) thicker and more mechanically robust. As a result, the reliability and life of each spline (914) and ablation device (900) can be improved by further reducing the dielectric breakdown of the insulation. The ablation device (900) has an arbitrary number of splines, for example, 3, 4, 5, 6, 7, 8, 9, 10, 12, 12, 14, 16, and 18. , 20 or more splines may be included. In some embodiments, the ablation device (900) may include 3 to 20 splines. For example, in one embodiment, the ablation device (900) may include 6-10 splines. Moreover, in some embodiments, the shape of the spherical expansion structure (930) of the set of expanded splines (914) is, for example, with its distal portion more spherical or curvilinear than its proximal portion. , May be asymmetric (see, eg, FIGS. 9B-9E). Such a spherical distal portion assists in the oral positioning of the device's pulmonary veins.

With reference to FIGS. 9B-9E, unless otherwise indicated, components with reference numbers similar to those in FIG. 9A (eg, electrodes (916) in FIG. 9A and electrodes (916') in FIG. 9B) are , Structurally and / or functionally similar. FIG. 9B shows spline wires (914', 920', 922') forming an extended structure (930') during use, such as during deployment. The cross-sectional area of the first plane (924A') of the extended structure (930'), sometimes referred to as the proximal plane, is the cross-sectional area of the extended structure (930') on the second plane (924B'). Is different. As shown in FIG. 9B, in some embodiments, the cross-sectional area of the extended structure (930') on the second plane (924B') is greater than the cross-sectional area on the first plane (924A'). .. The terms "first plane" and "second plane" used with respect to FIG. 9B are maximal from the distal end of the catheter shaft (910') and the proximal end of the distal cap (912'), respectively. Refers to the plane orthogonal to the longitudinal axis of the catheter shaft (910'), each formed at about 1 cm, about 2 cm, and about 3 cm, or more (including all values and subranges in between). obtain. Similar to FIG. 9A, the electrode (916') of the first spline (920') is the distal cap (912') of the ablation device (900') compared to the electrode (918') of the second spline (922'). ′) Closer to each other.

FIG. 9C shows spline wires (914 ″, 920 ″, 922 ″) forming an extended structure (930 ″) during use, such as during deployment. The cross-sectional area of the first plane (924A ″) of the extended structure (930 ″), sometimes referred to as the proximal plane, is the cross-sectional area of the extended structure (930 ″) on the second plane (924B ″). Is different. As shown in FIG. 9C, in some embodiments, the cross-sectional area of the extended structure (930 ″) on the second plane (924B ″) is greater than the cross-sectional area on the first plane (924A ″). The terms "first plane" and "second plane" used with respect to FIG. 9C are from the distal end of the catheter shaft (910 ″) and the proximal end of the distal cap (912 ″), respectively. A plane orthogonal to the longitudinal axis of the catheter shaft (910 ″), each formed up to about 1 cm, about 2 cm, and about 3 cm, or more (including all values and subranges in between). Can be pointed out. Unlike FIGS. 9A and 9B, multiple electrodes may be present on each spline wire and some electrodes may be equidistant from the distal cap (912 ″). In this way, relatively distal electrodes such as 932 ″ and 934 ″ are juxtaposed to the pulmonary vein ostium or proximal / cavity thereof during use for ablation delivery and mouth around the pulmonary vein. Peripheral affected areas may be generated.

FIG. 9D shows spline wires (914 ″ ″, 920 ″ ″, 922 ″ ″) forming an extended structure (930 ″ ″) during use, such as during deployment. Spline wires (914 ″ ″, 920 ″ ″, 922 ″ ″) are focused at their distal end relative to a point (928 ″ ″) inside / inside the extension structure (930 ″ ″). As shown in FIG. 9D, in such a configuration, at least some electrodes (932 ″ ″, 934 ″ ″) on the spline wires (914 ″ ″, 920 ″ ″, 922 ″ ″). May be on the distal end face (926 ″ ″) of the extended structure (930 ″ ″). The term "distal end face" as used with respect to FIG. 9D refers to a plane that passes through the distal boundary of the extended structure (930 ″ ″) and is orthogonal to the longitudinal axis of the catheter shaft (910 ″ ″). May be good. In this way, the extended structure (930 ″'') is pressed against the endocardial surface, such as the posterior wall of the left atrium, and is suitable for the distal end face using any suitable combination of polarities. By activating the electrodes, the affected area can be created directly on the surface. For example, distal electrodes (932 ″ ″, 934 ″ ″) may be used by pressing against the endocardial surface to form an affected area (eg, a spot affected area) via focal ablation.

Reference here to the generation of focal ablation affected areas using an ablation device (900 ″''), in some embodiments, electrodes (933, 935) (sometimes referred to as “proximal electrodes”) and The electrodes (932 ″ ″, 934 ″ ″) (sometimes referred to as “distal electrodes”) may operate in opposite polarities. Conduction between these electrodes through the blood pool creates an electric field that is applied as ablation energy to the endocardial surface present at the distal end face (926 ″ ″), resulting in focal ablation. For example, in spline wires (914 ″ ″, 920 ″ ″, 922 ″ ″), the distal electrodes (932 ″ ″, 934 ″ ″) are the distal end faces (926 ″ ″) of the endocardial surface. ) Or within it, while the proximal electrodes (933, 935) are outside the distal end face (926 ″ ″) and, as a result, are not pressed against or contact the endocardial surface. As such, an extended structure (930 ″ ″) may be formed. In some embodiments, the distal electrodes (932 ″ ″, 934 ″ ″) may have the same polarity, while the adjacent proximal electrodes (935, 933) are distal electrodes (935, 933). It may have the opposite polarity to 932 ″ ″, 934 ″ ″).

In some embodiments, the electrodes of the ablation device (900 ″'') are about 0.5 mm to about 5.0 mm in length, including all values and subranges in between, and cross-sectional dimensions (eg, diameter). ) May be about 0.5 mm to about 2.5 mm. The spline wires (914 ″ ″, 920 ″ ″, 922 ″ ″) in the extended structure (930 ″ ″) shown in FIG. 9D have cross-sectional dimensions (including all values and subranges between them). For example, the diameter) may be about 6.0 mm to about 30.0 mm. The focal ablation affected area thus formed may be about 0.5 cm to about 2.5 cm in diameter, including all values and partial ranges in between.

In some embodiments, the distal electrodes (932 ″ ″, 934 ″ ″) may be configured with opposite polarities. In some embodiments, adjacent electrodes on the same spline may have the distal electrode (934 ″ ″) having the same polarity as the proximal electrode (933), as well as the distal electrode (932 ″ ″). ) May have the same polarity as the proximal electrode (935). The electrode (934 ″ ″, 933) may have the opposite polarity to the electrode (932 ″ ″, 935).

In some embodiments, the adjacent distal electrode (934 ″'') and proximal electrode (933) may form an anode-cathode pair. For example, the distal electrode (934 ″'') may be configured as an anode and the proximal electrode (933) may be configured as a cathode. In another embodiment, the electrodes (2630) on one spline may alternate between the anode and the cathode, and the electrodes on the adjacent splines have the opposite configuration (eg, cathode and anode).

FIG. 9E shows spline wires (944, 940, 942) forming an extended structure (950) during use, such as during deployment. Spline wires (944, 940, 942) are focused at their distal ends at the proximal ends of the distal caps (912 ″ ″ ″) inside / inside the expansion structure (950). As shown in FIG. 9E, in such a configuration, at least some electrodes (952, 954) on the spline wire (944, 940) are on the distal end face (946) of the extended structure (950). May be good. The term "distal end face" as used with respect to FIG. 9E may refer to a plane that passes through the distal boundary of the extension structure (950) and is orthogonal to the longitudinal axis of the catheter shaft (910 ″ ″). .. In this way, the extended structure (950) is pressed against the posterior wall of the left atrium, for example, to actuate the appropriate electrodes on the distal end face (946) using any suitable combination of polarities. The affected area can be generated directly on top. For example, the electrodes 952 and 954 may be configured with opposite polarities. Compared to the extended structure (930 ″ ″) of FIG. 9D, the extended structure (950) of FIG. 9E is more orthogonal (eg flat) that can be pressed against, for example, the posterior wall of the left atrium for tissue ablation. ) Has a shape. In other words, the cross-sectional area of the extended structure (930 ″ ″ ″) at the distal end face (926 ″ ″) is smaller than the cross-sectional area of the extended structure (950) at the distal end face (946). As another example, as generally described herein with respect to FIG. 9D, a distal electrode (952, 954) is used by pressing against the endocardial surface and is used via focal ablation to the affected area (eg, spot affected area). ) May be formed.

For each ablation device described herein, each spline may contain a polymer and the lumen may be defined to form a hollow tube. One or more electrodes of the ablation device described herein may have a diameter of about 0.2 mm to about 2.0 mm and a length of about 0.2 mm to about 5.0 mm. In some embodiments, the electrodes may be about 1 mm in diameter and about 1 mm in length. Since the electrodes can be addressed independently, the electrodes can be energized in any sequence using a pulse waveform sufficient to ablate the tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms), as discussed in more detail below. It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver continuous / through-wall energy to electrically insulate one or more pulmonary veins. .. In some embodiments, the alternative electrodes (eg, all distal electrodes) can be at the same potential, and so can all other electrodes (eg, all proximal electrodes). Therefore, ablation can act on all electrodes simultaneously for rapid delivery. There are various options for such electrode pairs and they may be implemented based on their convenience.

FIG. 26A shows a set of a catheter shaft (2610) at the proximal end of the device (2600), a distal cap (2612) of the device (2600), and a spline (2620) attached to it, which has a flower-like shape. It is a side view of the embodiment of the ablation device (2600) including. As best shown in FIG. 26B, the spline shaft (2614) may be coupled to the proximal handle (not shown) at the proximal end and to the distal cap (2612) at the distal end. In a preferred embodiment, the distance between the distal cap (2612) and the catheter shaft (2610) may be less than about 8 mm. The spline shaft (2614) and distal cap (2612) may be translatable along the longitudinal axis (2616) of the ablation device (2600). The spline shaft (2614) and the distal cap (2612) may move together. The elongated shaft (2614) may be configured to slide within the lumen of the catheter shaft (2610). The distal cap (2612) may include a non-invasive shape to reduce trauma to the tissue. The proximal end of each spline in the set of splines (2620) may pass through the distal end of the catheter shaft (2610) and be anchored to the catheter shaft within the lumen of the catheter shaft, or the set of splines (2620). The distal end of each spline may be moored to the distal cap (2612) of the device (2600). The ablation device (2600) is configured to deliver a pulse waveform to the tissue during use via one or more splines in a set of splines (2620), eg, as disclosed in FIGS. 21-25. May be good.

Each spline (2620) of the ablation device (2600) may include, in some embodiments, one or more connected and wired electrodes (2630) formed on the surface of the spline (2620). In other embodiments, one or more of the electrodes (2630) on a given spline may be independently addressable electrodes (2630). Each electrode (2630) may include an insulating wire configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 2000 V over its entire thickness without dielectric breakdown. Each spline (2620) may include an insulating conductor of each electrode (2630) in the body of the spline (2620) (eg, in the lumen of the spline (2620)). FIG. 26A shows a set of splines (2620), including a set of electrodes (2632 or 2634) in which each spline has approximately the same size, shape, and spacing as the electrodes (2634 or 2632) of the adjacent spline (2620). .. In other embodiments, the electrodes (2632, 2634) may vary in size, shape, and spacing. The thickness of each spline (2620) may vary based on the number of electrodes (2630) formed on each spline (2620), which may correspond to the number of insulated conductors of the spline (2620). Splines (2620) may be the same or different in material, thickness, and / or length.

Each spline in the set of splines (2620) may include a flexible curve so that it can be rotated or twisted and bent to form a petal-shaped curve, such as that shown in FIGS. 26A-26C. Good. The minimum radius of curvature of the spline in the petal-shaped configuration may range from about 7 mm to about 25 mm. For example, a set of splines forms a delivery assembly at the distal portion of the ablation device (2600), with a first configuration in which the set of splines is generally aligned parallel to the longitudinal axis of the ablation device (2600) and the splines. The set is configured to rotate or be twisted and bent around the longitudinal axis of the ablation device (2600) to transition to and from a second configuration that is generally urged away from the longitudinal axis. You may. In the first configuration, each spline in the set of splines may be in one plane with the longitudinal axis of the ablation device. In the second configuration, each spline in the set of splines may be urged away from the longitudinal axis to form a petal-like curve that is generally aligned perpendicular to the longitudinal axis. In this way, the set of splines (2620) is twisted and bent and urged away from the longitudinal axis of the ablation device (2600) so that the splines (2620) are placed in the cardiac lumen, especially the pulmonary ostium. The geometric shape of the part adjacent to the opening of the can be easily matched. The second configuration may resemble the shape of a flower when viewed from the front, for example, as best shown in FIG. 26C. In some embodiments, each spline in the set of splines in the second configuration may be twisted and bent to form a petal-like curve, which is viewed from the front. In some cases, the angle between the proximal and distal ends of the curve indicates more than 180 degrees. The set of splines moves from a second configuration to a third configuration in which the set of splines (2620) can be pressed (eg, in contact with) a target tissue, such as the tissue surrounding the pulmonary venous ostium. May be further configured.

In some embodiments, the spline shaft (2614) coupled to the set of splines (2620) allows each spline in the set of splines (2620) to be placed in the lumen of the catheter shaft (2610) by the spline shaft (2614). When sliding, it may be able to bend and twist with respect to the catheter shaft (2610). For example, a set of splines (2620) forms a shape that is generally parallel to the longitudinal axis of the spline shaft (2614) when undeployed, and in the longitudinal direction of the spline shaft (2620) when fully deployed. When wound around an axis (2660) parallel to the axis (eg, spirally twisted) and the spline shaft (2614) slides within the lumen of the catheter shaft (2610), any intermediate between them. Shapes (such as cages or barrels) may be formed.

In some embodiments, a set of splines in a first configuration, such as a spline (2620), has an axis (2660) parallel to the longitudinal axis of the catheter shaft (2610) at some point along its length. It may be wound as a center, but the other parts may be otherwise generally parallel to the longitudinal axis of the catheter shaft (2610). The spline shaft (2614) may be housed in the catheter shaft (2610) to move the ablation device (2600) from the first configuration to the second configuration, in which spline (2620) is generally angled (eg, vertically) or twisted with respect to the longitudinal axis of the catheter shaft (2610). As shown in the front view of FIG. 26C, each spline (2620) may form a twisted loop in this front view projection. In FIG. 26C, each spline (2620) has a set of electrodes (2630) having the same polarity. As shown in the front view of FIG. 26C, each spline in a set of splines (2620) may form a twisted loop such that each spline overlaps one or more other splines. The number and distance of the electrodes (2630), as well as the rotational twist of the splines (2620), is configured by the suitable placement of the electrodes along each spline so that the electrodes (2630) on one spline are adjacent. It can be prevented from overlapping with the electrodes of the overlapping splines (2620).

Splines with a set of anode electrodes (2632) may work together to deliver a pulse waveform for irreversible electroporation. The electrodes on the other splines (2634) so as to form an anode-cathode pair to deliver the pulse waveform for irreversible electroporation, as shown in FIG. 26C. ) And (2)
It may operate together as a cathode electrode such as 635). Anode-cathode pairing and pulsed waveform delivery can be repeated continuously over a set of such pairings.

For example, the spline (2620) may operate continuously in a clockwise or counterclockwise fashion. As another example, the cathode splines may operate continuously at the same time as each successive anode spline operation until the ablation is complete. In embodiments where the electrodes on a given spline are wired separately, the order of operation within the electrodes of each spline may vary as well. For example, the electrodes in the spline may be activated all at once or in a predetermined sequence.

The delivery assembly may be disposed in the first configuration prior to delivering the pulse waveform and may transition to the second configuration to contact the pulmonary vein or sinus ostium. In some of these embodiments, the handle may be coupled to the spline shaft (2614) so that the handle triggers a transition between the first and second configurations of the set of splines. It is composed of. For example, the handle activates a set of splines (2620) attached to the distal cap by translating the spline shaft (2614) and the distal cap (2612) with respect to the catheter shaft (2610) and pulls them together. You may bend and twist. The proximal end of the spline (2620) is secured to the spline shaft (2614), causing buckling of the spline (2620), resulting in, for example, the distal cap (2612) and the spline shaft (2614). Bending and twisting movements of the spline (2620) can occur when pulled back against the catheter shaft (2610) that can be held by the user. For example, the distal end of a set of splines (2620) moored to the distal cap (2612) may translate up to about 60 mm along the longitudinal axis of the ablation device to trigger this change in configuration. .. In other words, the translation of the actuating member of the handle can bend and twist the set of splines (2620). In some embodiments, activating a knob, wheel, or other rotary control mechanism within the device handle can translate the activation member or spline shaft and bend and twist the spline (2620). In some embodiments, the conductors of at least two electrodes in the set of electrodes (2630) may be electrically coupled at or near the proximal portion of the ablation device (2600), for example in a handle.

By retracting the spline shaft (2614) and the distal cap (2612), the set of splines (2620) may be close together, which means that the set of splines (2620) is the longitudinal axis of the catheter shaft (2610). As shown in FIG. 26B, which is generally perpendicular to. In some embodiments, each spline in a set of splines (2620) may be laterally urged up to about 3 cm away from the longitudinal axis of the spline shaft (2614). In some embodiments, the spline shaft (2614) may include a hollow lumen. In some embodiments, the cross section of the spline may be asymmetric so that it has greater bending stiffness in one bending plane of the spline orthogonal to the plane of the cross section than in different bending planes. Such an asymmetric cross section may be configured to exhibit relatively high lateral stiffness, whereby in the final or fully unfolded configuration, the petal-shaped curve of each spline and its neighbors. It can be deployed with minimal overlap.

In one embodiment, each of the electrodes (2632) on the spline (2620) may be configured as an anode, while each of the electrodes (2634) on a different spline may be configured as a cathode. In another embodiment, the electrodes (2630) on one spline may alternate between the anode and the cathode, and the electrodes on the other spline have the opposite configuration (eg, cathode and anode).

In some embodiments, the spline electrodes may operate electrically in a continuous fashion to deliver a pulse waveform at each anode-cathode pair. In some embodiments, the electrodes may be electrically wired together in the spline, while in alternative embodiments, the electrodes may be wired together in the handle of the device, resulting in These electrodes will be at the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (2630) may be different as well. In some embodiments, the adjacent distal and proximal electrodes may form an anode-cathode pair. For example, the distal electrode may be configured as an anode and the proximal electrode may be configured as a cathode.

The ablation device (2600) has any number of splines, including all values and subranges in between, eg, 2, 3, 4, 5, 6, 6, 7, 8, 9. It may include 10, 12, 14, 16, 18, 20, or more splines. In some embodiments, the ablation device (2600) can include 3 to 20 splines. In some embodiments, the ablation device (2600) may include 4-12 splines.

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

In this way, the electrodes in the second configuration are held close to or placed close to a portion of the atrial wall of the left atrium, as described herein, in any case. The affected area can be formed directly on it by activating the appropriate electrode using a suitable combination of polarities. For example, a set of splines (2620) may be placed in contact with the atrial wall (2654) of the atrial (2652) adjacent to the pulmonary vein (2650) (eg, mouth or sinus).

FIG. 26D is a schematic diagram of the ablation (2664) generated by the ablation device (2600) on tissues such as the tissue surrounding the pulmonary vein ostium. For example, the activation of one or more of the electrodes (2630) on one or more of the splines (2620) causes one or more corresponding ablation areas (2664) to become the pulmonary vein sinus ostium or mouth wall (2654). Can be generated along. In some embodiments, the outer shape of the ablation area (2664) in the pulmonary vein ostium may have a diameter of about 2 cm to about 6 cm or about 3.5 cm. In this way, a continuous penetrating lesion can be created, resulting in electrical insulation of the pulmonary veins, which is the desired therapeutic result.

Alternatively, the electrode-deployed ablation catheter may be positioned adjacent to or relative to a portion of the posterior wall of the left atrium, and with the action of a suitable electrode set, the appropriate pulse waveform is irreversible. It may be delivered for perforation energy delivery to ablate the tissue.

In some embodiments, the electrodes or subset of electrodes can be addressed independently, so that the electrodes use any pulse waveform sufficient to ablate the tissue by irreversible electroporation. Can be energized in sequence. For example, as discussed in more detail herein, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms). It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver continuous / through-wall energy to electrically insulate one or more pulmonary veins. .. In some embodiments, the alternative electrodes may have the same potential and may be the same for all other alternative electrodes. Thus, in some embodiments, the ablation can be delivered rapidly with all electrodes activated simultaneously. There are various options for such electrode pairs and they may be implemented based on their convenience.

In some embodiments, the most distal 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 assists in the positioning of the set of splines to the tissue and can reduce the contact of other elements of the ablation device with the tissue, which can cause trauma to the tissue. For example, FIG. 35 is a side view of an embodiment of an ablation device (3500) comprising a first catheter (3510) (eg, an outer catheter shaft) at the proximal end of the device (3500). The first catheter (3510) may define the longitudinal axis and the lumen through it. The second catheter (3520) is slidably disposed within the first catheter lumen and may extend from the distal end of the first catheter lumen. The diameter of the second catheter (3520) may be smaller than the diameter of the first catheter (3510). The second catheter (3520) may define a lumen through which it passes. For example, the lumen may provide a passage to another device, such as a guide wire.

A set of splines (3530) may be coupled to a first catheter (3510) and a second catheter (3520). Specifically, the proximal end of the set of splines (3530) may be coupled to the distal end of the first catheter (3510) and the distal end of the set of splines (3530) may be the second. It may be attached to the distal end of the catheter (3520). The second catheter (3520) may be translatable along the longitudinal axis (3550) of the ablation device (3500). The proximal end of each spline in the set of splines (3530) may pass through the distal end of the first catheter (3510) and be anchored in the first catheter (3510) within the lumen of the first catheter. Good. The distal end of each spline in the set of splines (3530) may pass through the distal end of the second catheter (3520) and be moored to the second catheter (3520) within the lumen of the second catheter. Good. In some embodiments, a junction (3522) may be formed between the distal end of the second catheter (3520) and a set of splines (3530). For example, a polymer reflow process may be used to form a smooth, non-invasive junction between the second catheter (3520) and the set of splines (3530). The ablation device (3500) is configured to deliver a pulse waveform to the tissue during use via the electrodes of one or more splines in a set of splines (3530), eg, as disclosed in FIGS. 21-26. May be done.

Each spline (3530) of the ablation device (3500) may include one or more electrodes (3540) formed on the surface of the spline (3530). Each electrode (3540) may include an insulating wire configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. Each spline (3530) may include an insulating conductor of each electrode (3540) formed in the fuselage of the spline (3530) (eg, in the lumen of the spline (3530)). FIG. 35 shows a set of splines, including a set of electrodes (3540) in which each spline (3530) has approximately the same size, shape, and spacing as the electrodes (3540) of adjacent splines. In other embodiments, the size, shape, and spacing of the electrodes (3540) may vary.

The ablation device (3500) is an electrode (35) for ablating tissue.
The set of 40) may be configured to deliver a set of voltage pulse waveforms. In some of these embodiments, the ablation device (3500) may transition from a first configuration to a second configuration such that the spline (3530) of the ablation device (3500) flexes radially outward. Good.

At least a portion of the set of splines (3530) may include flexible curvature. For example, the proximal region (3522) and the distal region (3526) of each spline (3530). The set of splines (3530) may form a delivery assembly in the distal portion of the ablation device (3500), with the set of splines (3530) generally approaching the longitudinal axis (3540) of the ablation device (3500). Each spline transitions between a first configuration arranged in a row and a second configuration in which a set of splines (3530) flexes radially outward from the longitudinal axis (3540) of the ablation device (3500). May be configured to form basket-like and / or flower-like shapes that form "petals". The spline spatial curve shape of the second configuration can be described with respect to equations (1)-(3) corresponding to FIGS. 34A-34B. For example, in a fully expanded configuration, the integrated magnitude of each rotational speed of a set of splines (3530) along the length of each spline may be greater than radian π.

In another embodiment, the "basket" of the spline is along the length of the catheter so that one end of the basket (probably the distal end) bulges from the other end of the basket (probably the proximal end). It can have an asymmetrical shape. The delivery assembly may advance through the fuselage cavity in the first configuration and transition to the second configuration prior to delivery of the pulse waveform. In some embodiments, a handle (not shown) may be coupled to a set of splines (3530), the handle being between a first configuration and a second configuration of the set of splines (3530). It is configured to trigger the transition. In some embodiments, the activation of one or more knobs, wheels, sliders, pullwires, and / or other control mechanisms within the handle causes the second catheter (3520) to relative to the first catheter (3510). Translation can result in bending of the spline (3530). In some embodiments, the conductors of at least two electrodes in a set of electrodes (3540) may be electrically coupled at or near the proximal portion of the ablation device (3500), for example in a handle. For example, the handle activates a set of splines (3530) and bends them by translating the second catheter (3512) relative to the first catheter (3510), as shown in FIG. It may be configured in. Fixing the distal end of the spline (3530) to the distal end of the second catheter (3520) causes buckling of the spline (3530), resulting in, for example, the second catheter (3520). Bending motion of the spline (3530) can occur when pulled back with respect to the first catheter (3510). In other words, the translation of the actuating member of the handle can bend the set of splines (3530). In some embodiments, each spline in a set of splines (3530) may be laterally urged up to about 35 mm away from the longitudinal axis (3540) of the second catheter (3512). For example, the set of splines (3530) in the second configuration may form a shape having an effective cross-sectional diameter of about 10 mm to about 35 mm at the maximum portion. In the second configuration, the set of splines may be from about 15 mm to about 50 mm in length.

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

In some embodiments, the electrodes may operate electrically in a continuous fashion to deliver a pulse waveform at each anode-cathode pair. In some embodiments, the electrodes (3540) may be electrically wired together within the spline (3530), while in alternative embodiments the electrodes are together within the handle of the device (3500). It may be wired so that these electrodes (3540) have the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3540) may be different as well. As another example, the spline (3530) may operate continuously in a clockwise or counterclockwise fashion. As another example, the cathode splines may operate continuously at the same time as each successive anode spline operation until the ablation is complete. In embodiments in which the electrodes (3540) on a given spline (3530) are wired separately, the order of operation within the electrodes (3540) of each spline (3530) may vary as well. For example, the electrodes (3540) in the spline may operate all at once, or may operate in a predetermined sequence.

The electrodes can be energized in any sequence using any pulse waveform sufficient to ablate the tissue by irreversible electroporation. It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver sufficient energy to electrically insulate one or more areas of heart tissue. .. In some embodiments, the alternative electrodes (eg, all distal electrodes) can be at the same potential, and so can all other electrodes (eg, all proximal electrodes). Therefore, ablation can act on all electrodes simultaneously for rapid delivery. There are various options for such electrode pairs and they may be implemented based on their convenience.

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

The ablation device (3500) has any number of splines, including all values and subranges in between, eg, 2, 3, 4, 5, 6, 6, 7, 8, 9. It may include 10, 12, 14, 16 or more splines. In some embodiments, the ablation device (3500) can include 3 to 16 splines. In some embodiments, the ablation device (3500) may include 3-14 splines.

Each of the splines in the set of splines (3530) may include an respective electrode (3540) having a non-invasive shape to reduce trauma to the tissue. For example, the electrode (3540) may have a non-invasive shape, including curved, flat, curved, and / or blunted portions. In some embodiments, the electrode (3540) may be located along any portion of the spline (3530) distal to the first catheter (3510). The electrodes (3540) may be the same or different in size, shape, and / or position along their respective splines. The ablation device (3500) has any number of electrodes, eg, 2, 3, 4, 5, 6, 6, 7, 8 per spline, including all values and subranges in between. , 9, 10, 12, or more electrodes may be included. In some embodiments, the ablation device (3500) may include 2-12 electrodes per spline.

34A and 34B are side views of splines (3400) that are structurally and / or functionally similar to the splines described herein, such as the splines shown in FIGS. 36A-36C. FIG. 34A is a unit tangent vector. It is a side view of the spline having. FIG. 34B is a side view of a spline having two unit tangent vectors. FIGS. 34A and 34B depict a spline (3400) having a flower petal-like shape, which is in a second configuration and / or a third configuration, as described in detail herein. It can correspond to the shape of the spline. For simplicity, splines (3400) are shown without other elements such as electrodes. The curved spline (3400) includes the proximal end (3402) and the distal end (3404). The unit tangent vector u (3420) may be defined at all points (3410) along the spline (3400). FIG. 34B shows the unit tangent vector u _{1 (3430) at the proximal end (3402) of the spline (3400) and the unit tangent vector u 2} (3440) at the distal end (3404) of the spline (3400). ..

式中、ｌは、スプラインに沿った弧長である。 The rate of change of the unit tangent vector along the length of the spline may conform to the following equation.

In the formula, l is the arc length along the spline.

The rate of change of the unit tangent vector u'may be referred to as the rotation speed of the unit tangent vector along the spline. Since u · u = 1, the rotation speed u ′ is perpendicular to the unit tangent vector u.

In some embodiments, the splines described herein may migrate to form petal shapes or loops, in which the splines are torsioned along their length. Twisted along its length to have. The splines described herein have an integrated magnitude of rotational speed according to the following equation.

That is, the integrated magnitude of the spline rotation speed is greater than the radian π, that is, 180 degrees. Since u and u'are vertical, u · u'= 0. Therefore, the vector b = u × u ′ is perpendicular to both u and u ′.

In some embodiments, the shape of the spline is generally a spatial curve with torsion such that the derivative of the rotational speed generally has a component along b at some position along the length of the spline. Yes, this conforms to the following equation.

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

36A-36C show a set of deployed splines when the distal splines are fully deployed to reduce trauma to the tissue and assist in positioning and contact between the set of electrodes and the tissue. And a side view of an ablation catheter (3600) configured such that a set of electrodes extends distal to all other elements of the catheter (3600). FIG. 36A is a perspective view of an embodiment of an ablation device (3600) having a flower-like shape and including a first catheter (3610) at the proximal end of the device (3600). The first catheter (3610) may define the longitudinal axis (3650) and the lumen through it. The second catheter (3620) is slidably disposed within the first catheter lumen and may extend from the distal end of the first catheter lumen. The first catheter and the second catheter may constitute a single device together with a catheter handle for activation. A set of splines (3630) may be coupled to a first catheter (3610) and a second catheter (3620). The second catheter (3620) may be translatable along the longitudinal axis (3650) of the ablation device (3600). The proximal end of each spline in the set of splines (3630) may pass through the distal end of the first catheter (3610) and be anchored in the first catheter (3610) within the lumen of the first catheter. Well, the distal end of each spline in the set of splines (3630) may be anchored to the distal end (3622) of the second catheter (3620), which is described in more detail with respect to FIG. 35. That's right. The ablation catheter (3600) does not include a distal cap or other protrusion extending from the distal end of the second catheter (3620), so the device (3600) in the second configuration (eg, flower shape). Can engage sensitive tissues such as the thin heart with a low risk of trauma from the device (3600). The ablation device (3600) is configured to deliver a pulse waveform to the tissue during use via one or more electrodes of a set of splines (3630), eg, as disclosed in FIGS. 21-26. May be good.

Each spline (3630) of the ablation device (3600) may include, in some embodiments, one or more connected and wired electrodes (3640) formed on the surface of the spline (3630). In other embodiments, one or more of the electrodes (3640) on a given spline may be independently addressable electrodes (3640). Each electrode (3640) may include an insulating wire configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 2000 V over its entire thickness without dielectric breakdown. Each spline (3630) may include an insulating lead wire for each electrode (3640) within the body of the spline (3630) (eg, in the lumen of the spline (3630)). 36A-36C show a set of splines (3630), including a set of electrodes (3640) in which each spline has 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 vary. The thickness of each spline (3630) may vary based on the number of electrodes (3640) formed on each spline (3630), which may correspond to the number of insulated conductors of the spline (3630). The splines (3630) may be the same or different in material, thickness, and / or length.

Each spline in the set of splines (3630) is rotated or twisted to form a petal-shaped curve, such as that shown in FIGS. 26A-26C, 34A-34B, and 36A-36C. , May include flexible curves. The minimum radius of curvature of the spline in the petal-shaped configuration may be from about 7 mm to about 25 mm. For example, a set of splines forms a delivery assembly at the distal portion of the ablation device (3600), with a first configuration in which the set of splines is generally aligned with the longitudinal axis of the ablation device (3600). A set of splines is configured to rotate or be twisted and bent around the longitudinal axis of the ablation device (3600) to transition to and from a second configuration that is generally urged away from the longitudinal axis. May be done. In the first configuration, each spline in the set of splines may be in one plane with the longitudinal axis of the ablation device. In the second configuration, each spline in the set of splines may be urged away from the longitudinal axis to form a petal-like curve (eg, a flower shape), where the longitudinal axis of the spline. Are generally arranged perpendicular to the longitudinal axis (3650) or have sharp angles. As described in detail herein, the shape of the set of splines (eg, bends, curves) can satisfy equations (1)-(3). In this way, the set of splines (3620) is twisted and bent and urged away from the longitudinal axis of the ablation device (3600), causing the splines (3620) to open the posterior wall and opening of the lung ostium. The geometric shape of the intracardiac cavity such as the part makes it easier to match. In some embodiments, each spline in the set of splines in the second configuration may be twisted and bent to form a petal-like curve, which is viewed from the front. In some cases, the angle between the proximal and distal ends of the curve indicates more than 180 degrees.

In some embodiments, the second catheter (3620) coupled to the set of splines (3630) allows each spline in the set of splines (3630) to be squeezed by the second catheter (3620) into the first catheter (3610). ) May be able to bend and twist with respect to the first catheter (3610) as it slides in the lumen. For example, a set of splines (3630) forms a shape that is generally close to the longitudinal axis of the second catheter (3620) when undeployed, and the longitudinal axis (3650) when fully deployed. When the second catheter (3620) slides in the lumen of the first catheter (3610), it is wound around (eg, spirally, twisted), and any intermediate shape (cage-like) between them. Alternatively, a barrel shape or the like may be formed.

In some embodiments, the set of splines in the first configuration, such as the spline (3630), is centered on the longitudinal axis (3650) of the first catheter (3610) in some part along its length. It may be rolled up, but the other part may be otherwise generally parallel to the longitudinal axis of the first catheter (3610). The second catheter (3620) may be housed in the first catheter (3610) to shift the ablation device (3600) from the first configuration to the second configuration. In the configuration, the spline (3630) is twisted to form a petal-like shape and is angled with respect to the longitudinal axis (3650) of the first catheter (3610) (eg, vertically and distally). ) Generally angled or offset. If the second catheter (3622) is further retracted into the lumen of the first catheter (3610), the set of splines (3630) may extend further distally. As shown in FIGS. 36A-36C, each spline (3630) may form a twisted loop (eg, a petal shape in which a set of splines together form a flower shape).

In the second configuration, the set of splines (3630) in the second configuration may form a flower shape or may be angled distally. FIG. 36A shows a set of splines (3630) in which at least a portion of each set of splines (3630) extends distally to the distal end (3622) of the second catheter (3620). Shown. For example, in FIG. 36A, the distal portion of the spline intersects a plane (3660) (perpendicular to the longitudinal axis (3650)) that is distal to the distal end (3622) of the second catheter (3620). Indicates to do. Thus, when the ablation device (3600) advances distally and contacts the tissue, the set of splines (3630) contacts in front of the first catheter (3610) and the second catheter (3620). It will be. This allows the tissue to come into contact with a set of flexible splines without contacting the relatively rigid second catheter (3622), which can reduce trauma to the tissue.

FIG. 36B shows a second configuration forming a distal (eg, anterior) angle (3680) between the longitudinal axis (3670) of the spline (3630) and the longitudinal axis of the first catheter (3650). Shows a set of splines (3630) at. The longitudinal axis (3670) of the spline (3630) is defined by a line formed between the apex of the spline (3630) and the midpoint between the proximal and distal ends of the spline (3630). May be good. In some embodiments, the distal angle may be less than about 80 degrees. For example, the distal angle may be 60 degrees or less.

In some embodiments, each spline in a set of splines (3620) may form a twisted loop such that each spline partially overlaps one or more other splines. The number and distance of the electrodes (3640), as well as the rotational twist of the splines (3630), is configured by appropriately placing the electrodes along each spline, with the electrodes (3640) on one spline adjacent It can prevent overlapping with the electrodes of the overlapping splines.

Splines with a set of anode electrodes may work together to deliver a pulse waveform for irreversible electroporation. The electrodes on the other splines act together as cathode electrodes, such as the electrodes on their respective splines, to form an anode-cathode pair to deliver the pulse waveform for irreversible electroporation. May be good. Anode-cathode pairing and pulsed waveform delivery can be repeated continuously over a set of such pairings.

For example, the spline (3630) may operate continuously in a clockwise or counterclockwise fashion. As another example, the cathode splines may operate continuously at the same time as each successive anode spline operation until the ablation is complete. In embodiments where the electrodes on a given spline are wired separately, the order of operation within the electrodes of each spline may vary as well. For example, the electrodes in the spline may be activated all at once or in a predetermined sequence.

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

In some of these embodiments, the handle may be coupled to a second catheter (3620), which triggers a transition between the first and second configurations of the set of splines. It is configured to do. For example, the handle activates a set of splines (3630) attached to the second catheter (3620) by translating the second catheter (3620) relative to the first catheter (3610) and they. May be bent and twisted. Immobilization of the proximal end of the spline (3630) to the second catheter (3620) causes buckling of the spline (3630), resulting in, for example, the second catheter (3620) being held by the user. Bending and twisting movements of the spline (3630) can occur when pulled back against a possible first catheter (3610). For example, the distal end of a set of splines (3630) moored to a second catheter (3620) may translate up to about 60 mm along the longitudinal axis of the ablation device to trigger this configuration change. Good. In other words, the translation of the actuating member of the handle can bend and twist the set of splines (3630). In some embodiments, activating a knob, wheel, or other rotary control mechanism within the device handle can translate the activation member or second catheter and bend and twist the spline (3630). In some embodiments,
The conductors of at least two electrodes in the set of electrodes (3640) may be electrically coupled at or near the proximal portion of the ablation device (3600), for example in a handle.

Storage of the second catheter (3620) relative to the first catheter (3610) allows the sets of splines (3630) to approach each other, as shown in FIGS. 36A-36C. The set of splines (3630) is more generally perpendicular or distal to the longitudinal axis (3650) of the first catheter (3610). In some embodiments, each spline in a set of splines (3630) may be laterally urged up to about 30 mm away from the longitudinal axis (3650). In some embodiments, the second catheter (3620) may include a hollow lumen. In some embodiments, the cross section of the spline may be asymmetric so that it has greater bending stiffness in one bending plane of the spline orthogonal to the plane of the cross section than in different bending planes. Such an asymmetric cross section may be configured to exhibit relatively high lateral stiffness, whereby in the final or fully unfolded configuration, the petal-shaped curve of each spline and its neighbors. It can be deployed with minimal overlap.

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

In some embodiments, the spline electrodes may operate electrically in a continuous fashion to deliver a pulse waveform at each anode-cathode pair. In some embodiments, the electrodes may be electrically wired together in the spline, while in alternative embodiments, the electrodes may be wired together in the handle of the device, resulting in These electrodes will be at the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3640) may be different as well. In some embodiments, the adjacent distal and proximal electrodes may form an anode-cathode pair. For example, the distal electrode may be configured as an anode and the proximal electrode may be configured as a cathode.

The ablation device (3600) has any number of splines, including all values and subranges in between, eg, 2, 3, 4, 5, 6, 7, 8, 9, 9. It may include 10, 12, 14, 16, 18, 20, or more splines. In some embodiments, the ablation device (3600) may include 3 to 20 splines. In some embodiments, the ablation device (3600) may include 4-12 splines.

Each of the splines in the set of splines (3630) may include an respective electrode (3640) having a non-invasive shape to reduce trauma to the tissue. For example, the electrode (3640) may have a non-invasive shape that includes a curvilinear, flat, curved, and / or blunted portion configured to contact the endocardial tissue. .. In some embodiments, the electrode (3640) may be located along any portion of the spline (3630) distal to the first catheter (3610). The electrodes (3640) may be the same or different in size, shape, and / or position along their respective splines.

In this way, the electrodes in the second configuration are held close to or placed close to a portion of the atrial wall of the left atrium, as described herein, in any case. The affected area can be formed directly on it by activating the appropriate electrode using a suitable combination of polarities. For example, a set of splines (3630) may be placed in contact with the atrial wall (3654) of the pulmonary vein (3650) (eg, mouth or sinus) and / or the atrial (3652) adjacent to the posterior wall. Good.

37A-37B are perspective views of the ablation catheter (3730) and the left atrium (3700). FIG. 37A is a perspective view of an ablation catheter (3730) disposed in the left atrium (3700). The left atrium (3700) contains a set of pulmonary veins (3720) and a posterior wall (3710). The ablation device (3730) may be structurally and / or functionally similar to the ablation device (3500, 3600) described herein, advancing into the left atrium (3700) and It may be positioned in close proximity to and / or in contact with the posterior wall (3710) of the left atrium (3700) without penetrating the sensitive tissue of the posterior wall (3710) and / or causing trauma to the tissue. .. For example, in a set of splines, a flexible and non-invasive spline may be adjacent to or in contact with the posterior wall (3710) without any other part of the device (3730) contacting the posterior wall (3710). To obtain it, it may extend distal to the distal end of the catheter attached to the spline. In embodiments that include only a set of splines in which the most distal portion of the device (3700) is in a second configuration (eg, having a flower shape), the deployed device is at risk of trauma from the ablation device (3700). Can engage thin tissue structures such as the heart wall with minimal. A set of pulse waveforms may be applied by the electrodes of an ablation device (3700) having a flower shape to ablate the tissue within the ablation zone (3740).

FIG. 37B is a schematic perspective view of the left atrium (3700) after tissue ablation. An ablation device (3700) may be used to generate a set of ablation zones (3740, 3742, 3744) on the posterior wall (3710) of the left atrium (3700). For example, by activating one or more of the electrodes on one or more of the splines of the ablation device (3730) and repeating this with the movement of the catheter between the completed ablation, the ablation zones (3740, 3742, 3744) may be generated along the posterior wall (3710) of the left atrium (3700). In some embodiments, the ablation zones (3740, 3742, 3744) may partially overlap each other. These continuous and overlapping ablation zones can approximately form a thick line of ablation (3746). One or more ablation lines may connect to other ablation lines (eg, those generated around the pulmonary vein sinus ostium or mouth) and / or ablation zones, thereby creating a box-shaped affected area. For example, a set of continuous ablation zones is formed by an ablation device (3730) with a box-shaped affected area around the posterior wall (3710) of the left atrium (3700) that also surrounds one or more of the pulmonary veins (3720). It may be formed. In this way, a continuous perforator affected area is created around all the pulmonary veins, resulting in electrical insulation of the pulmonary veins and the desired therapeutic result can be obtained. In some embodiments, each ablation zone in the set of ablation zones (3740, 3742, 3744) may have a diameter of about 2 cm to about 6 cm. For example, the ablation zone may have a diameter of about 2.3 cm to about 4.0 cm.

In some embodiments, the electrodes or subset of electrodes can be addressed independently, so that the electrodes use any pulse waveform sufficient to ablate the tissue by irreversible electroporation. Can be energized in sequence. It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver sufficient energy to electrically insulate one or more pulmonary veins. In some embodiments, the alternative electrodes may have the same potential and may be the same for all other alternative electrodes. Thus, in some embodiments, the ablation can be delivered rapidly with all electrodes activated simultaneously. There are various options for such electrode pairs and they may be implemented based on their convenience.

27A and 27B are side views of an embodiment of the ablation device (2700), where the ablation device (2700) has a catheter shaft (2710) at the proximal end of the device (2700) and a distal end of the device (2700). Includes a set of splines (2720) coupled to the catheter shaft (2710) at the ends. The ablation device (2700) may be configured to deliver a pulse waveform to the tissue during use via one or more splines in a set of splines (2720). Each spline (2720) of the ablation device (2700) may include one or more optionally independently addressable electrodes (2730) formed on the surface (eg, distal end) of the spline (2720). .. Each electrode (2730) may include an insulating wire configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 2000 V over its entire thickness without dielectric breakdown. Each spline in a set of splines (2720) may include an insulating conductor of each electrode (2730) formed in the fuselage of the spline (2720) (eg, in the lumen of the spline (2720)). In some embodiments, the electrodes (2730) may be formed at the distal ends of their respective splines (2720).

The set of splines (2720) may form a delivery assembly at the distal portion of the ablation device (2700) or may be configured to transition between a first configuration and a second configuration. The set of splines (2720) in the first configuration is generally parallel to the longitudinal axis of the ablation device (2700) and may be close together and separated. A set of splines (2720) in the second configuration is depicted in FIGS. 27A and 27B, where the set of splines (2720) extends out of the distal end of the catheter shaft (2710) and extends. It is urged (eg, curved) away from the longitudinal axis of the ablation device (2700) and other splines (2720). In this way, the splines (2720) can be more easily matched by the geometry of the intracardiac lumen. The delivery assembly may be disposed in the first configuration prior to delivering the pulse waveform and may transition to a second configuration to a portion of cardiac tissue such as the posterior wall of the left atrium or to the ventricles. Such a device that delivers an irreversible electroporation pulse waveform can produce a large affected area for focal ablation.

The distal end of a set of splines (2720) may be configured to be urged away from the longitudinal axis of the distal end of the catheter shaft (2710) and away from other splines. .. Each spline in the set of splines (2720) may include a flexible curve. The minimum radius of curvature of the spline (2720) may be in the range of about 1 cm or more.

In some embodiments, the proximal end of the set of splines (2720) may be slidably coupled to the distal end of the catheter shaft (2710). Therefore, the length of the set of splines (2720) may vary, as shown in FIGS. 27A and 27B. As the set of splines (2720) extends further out of the catheter shaft (2710), the distal ends of the set of splines (2720) are urged further away from each other and the longitudinal axis of the catheter shaft (2710). You may. The set of splines (2720) may be slidably advanced out of the catheter shaft (2710), either independently or in groups of one or more. For example, the set of splines (2720) may be disposed within the catheter shaft (2710) in the first configuration. The spline (2720) may then exit the catheter shaft (2710) and move forward to move to a second configuration. The splines (2720) may all move forward together, or the anode electrode (2730).
The set of splines (2720) corresponding to the cathodic electrode (2730) may be advanced separately from the set of splines (2720) corresponding to the cathode electrode (2730). In some embodiments, the spline (2720) may move forward independently. In the second configuration, the electrode (2730) is urged longitudinally and / or laterally away from the catheter shaft (2710) with respect to the longitudinal axis of the distal end of the catheter shaft (2710). This may assist in the delivery and positioning of the electrode (2730) with respect to the endocardial surface. In some embodiments, each set of splines (2720) may extend up to about 5 cm from the distal end of the catheter shaft (2710).

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

In some of these embodiments, the handles (not shown) may be coupled to a set of splines. The handle may be configured to trigger a transition between the first and second configurations of the set of splines. In some embodiments, the conductors of at least two electrodes in a set of electrodes (2730) may be electrically coupled at or near the proximal portion of the ablation device, for example in a handle. In this case, the electrodes (2730) can be both electrically wired within the handle of the device (2700) so that these electrodes (2730) have the same potential during ablation.

Each spline in a set of splines (2720) may include its own electrode (2730) at the distal end of the set of splines (2720). The (2730) set of electrodes may include a non-invasive shape to reduce trauma to the tissue. For example, the electrode (2730) may have a non-invasive shape that includes a curvilinear, flat, curved, and / or blunted portion configured to contact the endocardial tissue. .. In some embodiments, the electrode (2730) may be located along any portion of the spline (2720) distal to the catheter shaft (2710). The electrodes (2730) may be the same or different in size, shape, and / or position along their respective splines.

In one embodiment, the electrode (2730) on the spline (2720) may be configured as the anode, while the electrode (2730) on the adjacent spline (2720) may be configured as the cathode. The ablation device (2700) has any number of splines, including all values and subranges in between, eg, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18 , 20 or more splines may be included. In some embodiments, the ablation device (2700) may include 3 to 20 splines. In some embodiments, the ablation device (2700) may include 6-12 splines.

27A and 27B are side views of an embodiment of the ablation device (2700), where the ablation device (2700) has a catheter shaft (2710) at the proximal end of the device (2700) and a distal end of the device (2700). Includes a set of splines (2720) coupled to the catheter shaft (2710) at the ends. The ablation device (2700) may be configured to deliver a pulse waveform to the tissue during use via one or more splines in a set of splines (2720). Each spline (2720) of the ablation device (2700) may include one or more optionally independently addressable electrodes (2730) formed on the surface (eg, distal end) of the spline (2720). .. Each electrode (2730) may include an insulating wire configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 2000 V over its entire thickness without dielectric breakdown. Each spline in a set of splines (2720) may include an insulating conductor of each electrode (2730) formed in the fuselage of the spline (2720) (eg, in the lumen of the spline (2720)). In some embodiments, the electrodes (2730) may be formed at the distal ends of their respective splines (2720).

The set of splines (2720) may form a delivery assembly at the distal portion of the ablation device (2700) or may be configured to transition between a first configuration and a second configuration. The set of splines (2720) in the first configuration is generally parallel to the longitudinal axis of the ablation device (2700) and may be close together and separated. A set of splines (2720) in the second configuration is depicted in FIGS. 27A and 27B, where the set of splines (2720) extends out of the distal end of the catheter shaft (2710) and extends. It is urged (eg, curved) away from the longitudinal axis of the ablation device (2700) and other splines (2720). In this way, the splines (2720) can be more easily matched by the geometry of the intracardiac lumen. The delivery assembly may be disposed in the first configuration prior to delivering the pulse waveform and may transition to a second configuration to a portion of cardiac tissue such as the posterior wall of the left atrium or to the ventricles. Such a device that delivers an irreversible electroporation pulse waveform can produce a large affected area for focal ablation.

The distal end of a set of splines (2720) may be configured to be urged away from the longitudinal axis of the distal end of the catheter shaft (2710) and away from other splines. .. Each spline in the set of splines (2720) may include a flexible curve. The minimum radius of curvature of the spline (2720) may be in the range of about 1 cm or more.

In some embodiments, the proximal end of the set of splines (2720) may be slidably coupled to the distal end of the catheter shaft (2710). Therefore, the length of the set of splines (2720) may vary, as shown in FIGS. 27A and 27B. As the set of splines (2720) extends further out of the catheter shaft (2710), the distal ends of the set of splines (2720) are urged further away from each other and the longitudinal axis of the catheter shaft (2710). You may. The set of splines (2720) may be slidably advanced out of the catheter shaft (2710), either independently or in groups of one or more. For example, the set of splines (2720) may be disposed within the catheter shaft (2710) in the first configuration. The spline (2720) may then exit the catheter shaft (2710) and move forward to move to a second configuration. The splines (2720) may all advance together, or the set of splines (2720) corresponding to the anode electrode (2730) advances separately from the set of splines (2720) corresponding to the cathode electrode (2730). You may move forward as you do. In some embodiments, the spline (2720) may move forward independently. In the second configuration, the electrode (2730) is urged longitudinally and / or laterally away from the catheter shaft (2710) with respect to the longitudinal axis of the distal end of the catheter shaft (2710). This may assist in delivery and positioning of the electrode (2730) with respect to the endocardial surface. In some embodiments, each set of splines (2720) may extend up to about 5 cm from the distal end of the catheter shaft (2710).

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

In some of these embodiments, the handles (not shown) may be coupled to a set of splines. The handle may be configured to trigger a transition between the first and second configurations of the set of splines. In some embodiments, the conductors of at least two electrodes in a set of electrodes (2730) may be electrically coupled at or near the proximal portion of the ablation device, for example in a handle. In this case, the electrodes (2730) can be both electrically wired within the handle of the device (2700) so that these electrodes (2730) have the same potential during ablation.

Each spline in a set of splines (2720) may include its own electrode (2730) at the distal end of the set of splines (2720). The (2730) set of electrodes may include a non-invasive shape to reduce trauma to the tissue. For example, the electrode (2730) may have a non-invasive shape that includes a curvilinear, flat, curved, and / or blunted portion configured to contact the endocardial tissue. .. In some embodiments, the electrode (2730) may be located along any portion of the spline (2720) distal to the catheter shaft (2710). The electrodes (2730) may be the same or different in size, shape, and / or position along their respective splines.

In one embodiment, the electrode (2730) on the spline (2720) may be configured as the anode, while the electrode (2730) on the adjacent spline (2720) may be configured as the cathode. The ablation device (2700) has any number of splines, including all values and subranges in between, eg, 3, 4, 5, 6, 7, 8, 9, 10 , 12, 14, 16, 18, 20, or more splines may be included. In some embodiments, the ablation device (2700) may include 3 to 20 splines. In some embodiments, the ablation device (2700) may include 6-12 splines.

In FIGS. 27A-27B, one electrode (2730) is formed on the surface of each spline (2720) such that each spline (2720) contains one insulating wire. This can reduce the diameter of the lumen of the spline (2720), making the spline (2720) thicker and more mechanically robust. As a result, the reliability and life of each spline (2720) and ablation device (2700) can be improved by further reducing the dielectric breakdown of the insulation. Moreover, in some embodiments, the radius of curvature of the spline may vary over the length of the spline. For example, the radius of curvature may increase monotonically. Such a variable radius of curvature may assist in the positioning of the electrodes (2730) at several locations in the endocardial tissue. The splines (2720) may have the same or different materials, thicknesses, and / or radii of curvature. For example, the thickness of each spline may decrease distally.

In this way, the electrodes in the second configuration are localized onto it, for example by being pressed against the posterior wall of the left atrium and activating the appropriate electrodes using any suitable combination of polarities. Alternatively, a localized affected area can be directly generated. For example, the adjacent electrodes (2730) may be configured with opposite polarities.

Since the electrodes or subset of electrodes can be addressed independently, the electrodes can be energized in any sequence using any pulse waveform sufficient to ablate the tissue by irreversible electroporation. For example, as discussed in more detail herein, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms). It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver the affected area through the wall over a relatively large area of endocardial tissue. In some embodiments, the alternative electrodes may have the same potential and may be the same for all other alternative electrodes. Therefore, ablation can act on all electrodes simultaneously for rapid delivery. There are various options for such electrode pairs and they may be implemented based on their convenience.

Reference to FIG. 27C, unless otherwise indicated, components with reference numbers similar to those of FIGS. 27A-27B (eg, electrodes (2730) of FIGS. 27A-27B and electrodes (2730') of FIGS. 27C). ) Is understood to be structurally and / or functionally similar. FIG. 27C shows a set of splines (2720'), each spline (2720') containing a pair of electrodes (2730', 2740).

The ablation device (2700') is a spline (2720') in which the catheter shaft (2710') is coupled to the catheter shaft (2710') at the proximal end of the device (2700') and to the catheter shaft (2710') at the distal end of the device (2700'). Includes a set of. The ablation device (2700') may be configured to deliver a pulse waveform to the tissue during use via one or more splines in a set of splines (2720'). Each spline (2720') of the ablation device (2700') may include one or more independently addressable electrodes (2730', 2740) formed on the surface of the spline (2720'). Each electrode (2730', 2740) may include an insulating wire configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 2000 V over its entire thickness without dielectric breakdown. Each spline in a set of splines (2720') contains an insulating lead wire for each electrode (2730', 2740) formed in the fuselage of the spline (2720') (eg, in the lumen of the spline (2720')). It may be. The electrodes (2730', 2740) of the spline (2720') may be approximately the same in size and shape. Further, each electrode (2730', 2740) of the spline (2720') may be 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) may vary.

In some embodiments, the electrodes (2730', 2740) of the ablation device (2700') are about 0.5 mm to about 5.0 mm in length and cross-sectional dimensions, including all values and subranges in between. (For example, the diameter) may be about 0.5 mm to about 4.0 mm. The spline wires (2720') in the second configuration are at the distal end of the ablation device (2700') about 5.0 mm to about 20.0 mm (including all values and subranges between) from each other. may be spread out to the extent _{S d,} from the distal end of the catheter shaft (2710 '), all values and including the subranges about 8.0mm~ about 20.0mm length _{S l} Bun'nobe between May be present. In some embodiments, the ablation device (2700') may include 4 splines, 5 splines, or 6 splines. In some embodiments, each spline is independently one electrode, two electrodes,
Alternatively, it may include three or more electrodes.

The set of splines (2720') may form a delivery assembly at the distal portion of the ablation device (2700') or may be configured to transition between a first configuration and a second configuration. Good. The set of splines (2720') in the first configuration is generally parallel to the longitudinal axis of the ablation device (2700) and may be close together and separated. A set of splines (2720') in the second configuration is depicted in FIG. 27C, where the set of splines (2720') extends out of the distal end of the catheter shaft (2710'). Is urged (eg, curved) away from the longitudinal axis of the ablation device (2700') and other splines (2720'). In this way, the splines (2720') can be more easily matched by the geometry of the intracardiac lumen. The delivery assembly is disposed in the first configuration prior to delivering the pulse waveform, transitions to the second configuration, contacts the area of endocardial tissue and is irreversible as disclosed herein. Large localized affected areas may be generated when delivering pulse waveforms for target electrical perforation. In some embodiments, the electrode (2730') (sometimes referred to as the "distal electrode") in the second configuration depicted in FIG. 27C is in contact with and pressed against the endocardial tissue. However, the electrode (2740) in the second configuration (sometimes referred to as the "proximal electrode") may not come into contact with the endocardial tissue. In this way, the electric field generated by the electrodes due to conduction between the proximal and distal electrodes through the blood pool provides focal ablation of the tissue.

In some embodiments, the proximal end of the set of splines (2720') may be slidably coupled to the distal end of the catheter shaft (2710'). As the set of splines (2720') extends further out of the catheter shaft (2710'), the distal ends of the set of splines (2720') are further separated from each other and the longitudinal axis of the catheter shaft (2710'). May be urged. The set of splines (2720') may be slidably advanced out of the catheter shaft (2710'), either independently or in groups of one or more. For example, a set of splines (2720') may be disposed within the catheter shaft (2710') in the first configuration. The spline (2720') may then exit the catheter shaft (2710') and move forward to move to a second configuration. The splines (2720') may all move forward together, or a set of splines (2720') corresponding to the anode electrodes (2730) of the splines (2720') corresponding to the cathode electrodes (2730', 2740). You may move forward so that you move forward separately from the set. In some embodiments, the spline (2710') may advance independently through the respective lumen (eg, sheath) of the catheter shaft (2710'). In the second configuration, the electrodes (2730', 2740) are urged longitudinally and / or laterally away from the catheter shaft (2710') with respect to the longitudinal axis of the distal end of the catheter shaft (2710'). To. This may assist in delivery and positioning of the electrodes (2730', 2740) with respect to the endocardial surface. In some embodiments, each of the sets of splines (2720') may extend up to about 5 cm from the distal end of the catheter shaft (2710').

In some embodiments, the distal electrode (2730') may have the same polarity, while the adjacent proximal electrode (2740) has the opposite polarity to the distal electrode (2730'). You may. In this way, an electric field can be generated between the distal and proximal electrodes due to focal ablation.

In some of these embodiments, the handles (not shown) may be coupled to a set of splines. The handle may be configured to trigger a transition between the first and second configurations of the set of splines. In some embodiments, the electrodes (2730', 27
The conductors of at least two electrodes in the set of 40) may be electrically coupled at or near the proximal portion of the ablation device, for example in a handle. In some embodiments, the electrodes (2730', 2740) are both electrically wired within the handle of the device (2700') so that these electrodes (2730', 2740) have the same potential during ablation. obtain.

The set of electrodes (2730', 2740) may include a non-invasive shape to reduce trauma to the tissue. For example, the electrodes (2730', 2740) have a non-invasive shape that includes curved, flat, curved, and / or blunted portions that are configured to contact the endocardial tissue. You may. In some embodiments, the electrodes (2730', 2740) may be located along any portion of the spline (2720') distal to the catheter shaft (2710'). The electrodes (2730', 2740) may be the same or different in size, shape, and / or position along their respective splines. One or more of the splines (2720') may include three or more electrodes.

In some embodiments, each of the electrodes (2730') on the spline (2720') may be configured as an anode, while each of the electrodes (2730') on the adjacent spline (2720') is a cathode. It may be configured as. In another embodiment, each of the electrodes (2730') on one spline may alternate between anode and cathode, and each of the electrodes of adjacent splines may have the opposite configuration (eg, cathode and anode). And). In some embodiments, a subset of electrodes can be electrically wired together within the handle of the device so that these electrodes have the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (2730) may be different as well. In some embodiments, the adjacent distal electrode (2730') and proximal electrode (2740) may form an anode-cathode pair. For example, the distal electrode (2730') may be configured as an anode and the proximal electrode (2740) may be configured as a cathode.

The ablation device (2700') can be any number of splines, including all values and subranges in between, eg, 3, 4, 5, 6, 7, 8, 9, 10 It may include, 12, 14, 16, 18, 20, or more splines. In some embodiments, the ablation device (2700') may include 3 to 20 splines. In some embodiments, the ablation device (2700') may include 6-12 splines.

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

In this way, the electrodes in the second configuration are placed relative to the section of endocardial tissue and use any suitable polarity combination to deliver the pulse waveform for irreversible electroporation. By activating the appropriate electrode, the affected area can be formed directly on it. For example, adjacent electrodes (2730', 2740) may be configured with opposite polarities.

Since the electrodes can be addressed independently, the electrodes can be energized in any sequence using any pulse waveform sufficient to ablate the tissue by irreversible electroporation. For example, as discussed in more detail herein, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms). It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver continuous / through-wall energy to electrically insulate one or more pulmonary veins. .. In some embodiments, the alternative electrodes may have the same potential and may be the same for all other alternative electrodes. Therefore, ablation can act on all electrodes simultaneously for rapid delivery. There are various options for such electrode pairs and they may be implemented based on their convenience.

FIG. 28 includes an ablation device (2800) including a catheter shaft (2810) at the proximal end of the device (2800), a distal cap (2812) of the device (2800), and a spline (2814) attached thereto. It is a side view of still another embodiment of. In some embodiments, the ablation device (2800) is useful for forming the affected area on the endocardial surface via focal ablation, as described herein.

The distal cap (2812), as described in more detail herein, has a non-invasive shape and one or more independently addressable electrodes (2816) (referred to as "distal electrodes"). In some cases) may be included. The proximal end of the set of splines (2814) may be coupled to the distal end of the catheter shaft (2810), and the distal end of the set of splines (2814) may be the distal cap (2812) of the device (2800). ) May be moored. Each spline (2814) of the ablation device (2800) is sometimes referred to as one or more independently addressable electrodes (2818) (sometimes referred to as "proximal electrodes") formed on the surface of the spline (2814). ) May be included. Each electrode (2816, 2818) may include an insulating wire configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200V and about 2000V over the entire thickness in between, including all values and subranges in between, without dielectric breakdown. Good. Each spline (2814) may include an insulating conductor of each electrode (2818) formed in the fuselage of the spline (2814) (eg, in the lumen of the spline (2814)). One or more of the splines (2818) may further include an insulating lead wire of the distal electrode (2816). In some embodiments, the sizes and / or shapes of the electrodes (2816, 2818) may differ from each other.

The set of splines (2814) and the configuration of the proximal electrodes (2818) can control the depth, shape, and / or diameter / size of the focal ablation affected area produced by the ablation device (2800). The ablation device (2800) has a first configuration in which a set of splines (2814) is arranged generally parallel to the longitudinal axis of the ablation device (2800), and a set of splines (2814) is the length of the ablation device (2800). It may be configured to transition from a directional axis to a second configuration that flexes outward in the radial direction. It is understood that the set of splines (2814) may be transitioned to any intermediate configuration between the first configuration and the second configuration in continuous or separate steps.

Activating the electrodes using a given configuration can result in targeted and accurate focal ablation by controlling the size of the focal ablation spot based on the expansion of the spline (2814). For example, in some embodiments, the distal electrode (2816) may be configured with a first polarity, and one or more proximal electrodes (2818) may have a second polarity opposite to the first polarity. It may be composed of polarities. When the proximal electrode (2818) of the ablation device (2800) is in the first configuration, a high intensity electric field with a relatively small / more concentrated diameter causes the heart to be relatively small in diameter and deeper in depth. The affected area of focal ablation on the surface of the endocardium is obtained. When the proximal electrode (2818) of the ablation device (2800) is in the second configuration, a relatively more dispersed electric field is generated, which makes it relatively wider and shallower than in the first configuration. The affected area of focal ablation on the surface of the endocardium is obtained. In this way, by varying the degree of expansion of the spline (2814), the depth, shape, and / or size of the affected area can be controlled without replacing the ablation device (2800). Such an embodiment is useful for creating multiple affected areas of various sizes and / or depths using the same ablation device.

The distal cap (2812) may be arranged to press against the endocardial tissue, while the proximal electrode (2818) in either the first or second configuration is the endocardium. It may be configured so that it does not come into contact with the tissue. It should be understood that the distal electrode (2816) does not need to be in contact with the endocardial tissue. In some of these embodiments, a handle (not shown) may be coupled to a set of splines (2814), the handle being a first configuration and a second configuration of the set of splines (2814). It is configured to trigger a transition between and. In some embodiments, the conductors of at least two electrodes in the set of electrodes may be electrically coupled at or near the proximal portion of the ablation device (2800), for example in a handle.

In some embodiments, the distal electrode (2816) and the proximal electrode (2818) may form an anode-cathode pair. For example, the distal electrode (2816) may be configured as an anode and each of the proximal electrodes (2818) may be configured as a cathode. In some embodiments, the ablation device (2800) can include 3-12 splines. The ablation device (2800) may include any number of splines, such as 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines. it can. In some embodiments, the ablation device (2800) can include 3 to 20 splines. For example, in one embodiment, the ablation device (2800) may include 6-10 splines. Further, in some embodiments, the shape of the set of extended splines (2814) may be asymmetric, for example, with its distal portion more spherical or curvilinear than its proximal portion. Such a spherical distal portion (as well as the position of the proximal electrode) may assist in further control of the size and depth of focal ablation.

The first plane (2822) depicted in FIG. 28 may point to a plane orthogonal to the longitudinal axis of the catheter shaft (2810). The distal cap (2812) is pressed against the endocardial surface within a first plane (2812), such as the luminal wall of the pulmonary vein, and is suitable using any suitable combination of polarities. The focal ablation affected area may be directly generated on the electrode by activating the electrode. For example, the distal electrode (2816) may be pressed against the endocardial surface to form a focal ablation affected area (eg, a spot affected area). In some embodiments, the one or more proximal electrodes (2818) may be configured with a polarity opposite to that of the distal electrode (2816). Conversely, one or more of the proximal electrodes (2818) may be configured with the same polarity as the distal electrodes (2816). In some embodiments, the proximal electrodes (2818) on different splines (2814) may alternate at the anode and cathode.

In some embodiments, the distal electrode (2816) of the ablation device (2800) is about 0.5 mm to about 7.0 mm in length and cross-sectional dimensions (eg, including all values and partial ranges in between). , Diameter) may be from about 0.5 mm to about 4.0 mm. In some embodiments, the proximal electrode (2818) has a length of about 0.5 mm to about 5.0 mm and a diameter of about 0.5 mm to about 2. It may be 5 mm. The distal electrode (2816) may be about 3.0 mm to about 12.0 mm long away from the proximal electrode (2818), including all values and subranges in between. Distal electrode (2816) disposed on the distal cap (2812) is about 1.0 mm to about 4. mm, including all values and partial ranges from the distal end of the distal cap (2812). It may be located at a distance of 0 mm. In some embodiments, the distal end of the distal cap (2812) may include a distal electrode (2816). The one or more focal ablation zones may be formed to include a diameter of about 1.0 cm to about 2.0 cm, including all values and subranges in between.

29A-29D are side views of yet another embodiment of the ablation device (2900) so that the ablation device (2900) extends from the lateral catheter or sheath (2902) and the distal end of the lumen. Includes a set of inner catheters (2910, 2920) that are slidable within the outer catheter lumen. The lateral catheter may demarcate the longitudinal axis. The inner diameter of the outer catheter (2902) may be from about 0.7 mm to about 3 mm, and the outer diameter of the outer catheter (2902) may be from about 2 mm to about 5 mm. As most commonly seen in FIGS. 29A, 29D, the ablation device (2900) has a first proximal portion (2912), a first distal portion (2914), and, for example, a first distal portion (2914). Includes a first catheter (2910) having a first electrode (2916) formed on a first distal portion (2914), such as the surface of a. The first proximal portion (2912) may be coupled to the first distal portion (2914) via a first hinge (2918). The second catheter (2920) has a second electrode (2926) formed in the second proximal portion (2922), the second distal portion (2924), and the second distal portion (2924). including. The second proximal portion (2922) may be coupled to the second distal portion (2924) via a second hinge (2928).

In some embodiments, the ablation device (2900) is useful for forming the affected area on the endocardial surface via focal ablation, as described herein. The distal end and / or electrode (2916, 2922) of the catheter (2910, 2920) may include a non-invasive shape to reduce trauma to the tissue. For example, the distal end and / or electrodes (2916, 2922) of the catheter (2910, 2920) are curved, flat, curved, and / or blunted, configured to contact endocardial tissue. It may have a non-invasive shape including the portion that has been removed.

Each electrode (2916, 2926) may include an insulating wire configured to maintain a potential of at least about 700 V without dielectric breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200V and about 2000V over the entire thickness in between, including all values and subranges in between, without dielectric breakdown. Good. Each catheter (2910, 2920) may include an insulating conductor of each electrode (2916, 2926) formed in the body of the catheter (2910, 2920) (eg, in the lumen of the catheter (2910, 2920)). .. Each of the electrodes (2916, 2926) may be connected to a corresponding insulated wire leading to a handle (not shown) attached to the proximal portion of the catheter (2910, 2920). In some embodiments, the sizes, shapes, and / or locations of the electrodes (2916, 2926) may differ from each other.

In some embodiments, the configuration of the catheters (2910, 2920) and electrodes (2916, 2926) controls the depth, shape, and / or diameter / size of the focal ablation affected area produced by the ablation device (2900). obtain. The first and second catheters (2910, 2920) may be configured to migrate along the longitudinal axis of the lateral catheter (2902). In some embodiments, the ablation device (2900) has a set of catheters (2910, 2920) arranged generally parallel to the longitudinal axis of the lateral catheter (2902), with the distal portion of the catheter (2910, 2920) A first configuration (eg, FIG. 29A) disposed within the lateral catheter (2902) and electrodes (2916, 2926) exit from the distal end (2903) of the lateral catheter lumen (2902), wherein A second configuration in which the distal portion of each catheter (2910, 2920) advances with respect to the proximal portion of its corresponding catheter (2910, 2920) and its corresponding hinge. It may be configured to transition to and from a third configuration (eg, FIGS. 29B-29D) that can rotate, twist, or bend around (2918, 2928). For example, as best shown in FIGS. 29B-29C, the first catheter (2910) is configured to position the distal portion (2914) in multiple positions relative to the proximal portion (2912). It may also include a distal portion (2914) that is rotatable about a first hinge (2918). The catheters (2910, 2912) in the second and third configurations may be angled away from each other so that they are urged away from the longitudinal axis of the outer catheter (2902). The distal ends of the proximal portions (2912, 2922) may form an angle along the longitudinal axis of about 5 to about 75 degrees (eg, FIG. 29D). It is understood that the ablation device (2900) may transition to any intermediate configuration between the first configuration, the second configuration, and the third configuration in continuous or separate steps.

In some embodiments, conduction between the electrodes through the blood pool and / or endocardial tissue results in the generation of an electric field and the application of an electric field as ablation energy to the endocardial surface. The electrode is held physically close to or in physical contact with a portion of the atrial wall of the left atrium and is placed in physical contact with it, using any suitable polarity combination of one of the electrodes. By activating one or more, an affected area can be created on it. In this way, by activating the electrodes using a predetermined configuration, the focal ablation spot size is adjusted to the position and orientation of the electrodes (2916, 2926) with respect to the proximal portion (2912, 2922) of the catheter (2910, 2920). Targeted and accurate focal ablation can be achieved by controlling based on. For example, in some embodiments, the first electrode (2916) may be configured with a first polarity and the second electrode (2926) may have a second polarity opposite to the first polarity. It may be configured. Comparison when the electrodes (2916, 2926) rotate so that they are relatively close to each other (eg, when the proximal and distal parts (2914) form an acute angle (2950)). A relatively high intensity electric field with a smaller / more concentrated diameter results in a focal ablation affected area on the endocardial surface with a relatively small diameter and good depth. For non-limiting purposes only, the acute angles formed in the articulated hinges may range from about 15 degrees to about 70 degrees. In some embodiments, the electric field strength in the focal ablation zone may be about 200 V / cm or higher. When the electrodes (2916, 2926) rotate around their corresponding hinges (2918, 2928) so that they are relatively separated from each other (eg, proximal portion (2912) and distal portion (2914)). (When forming a larger angle), a relatively dispersed, lower intensity electric field is generated, resulting in a relatively wider, shallower, focal ablation affected area on the endocardial surface. In this way, the depth, shape, and / or size of the affected area is ablated by varying the degree of rotation of the electrodes (2916, 2926) with respect to the proximal portion (2912, 2922) of the catheter (2910, 2920). It can be controlled without replacing the device (2900). Such an embodiment is useful for creating multiple affected areas of various sizes, shapes, and / or depths using the same ablation device. For example, the diameter of the affected area may be about 2 mm to about 3 cm, and the depth of the affected area may be about 2 mm to about 12 mm. It should be understood that the electrodes (2916, 2926) may be arranged to touch the endocardial tissue, but the electrodes (2916, 2926) do not need to come into contact with the endocardial tissue.

In some of these embodiments, the handle (not shown) may be coupled to a set of catheters (2910, 2920), where the handle is a first configuration, second, of the catheter (2910, 2920). And the transition between the third configurations. In some embodiments, one or more catheters (2910, 2920) through the lateral catheter (2902) by activation of one or more knobs, wheels, sliders, pullwires, and / or other control mechanisms within the handle. ), And / or rotation of the distal portion (2914, 2924) of the catheter around the hinge (2918, 2928) can occur.

Figures 29B-29C depict a first catheter (2910) having a distal portion (2914) with joints. The first catheter (2910) may include a proximal portion (2912) that is hinged (2918) to the distal portion (2914). The distal portion (2914) may include an electrode (2916) as described herein. In some embodiments, the hinge (2918) may include a rotary wheel. In other embodiments, the hinge (2918) is more flexible than the rest of the catheter, has a reduced cross-sectional area compared to the first catheter (2910), the proximal portion (2912) or distal. The portion (2914) may be included. In yet other embodiments, the hinge (2918) may include fittings, rotary wheels, ball and socket fittings, condyle fittings, saddle fittings, swivel shafts, trajectories and the like.

The rotary wheel may be coupled to a wire (2917) (eg, a pull wire). For example, the wire (2917) may be attached around the hinge (2918) and the distal portion (2914) may be attached to a portion of the hinge (2918). Thus, activation (2930) of the wire (2917) (eg, pulling one end of the wire proximally) may cause the wheel (2918) and distal portion (2914) to rotate, resulting in the distal portion. (2914) rotates relative to the proximal portion (2912) of the first catheter (2910). In some embodiments, the distal portion may rotate by an angle of about 110 degrees to about 165 degrees with respect to the proximal portion, and the length of the distal portion may be from about 3 mm to about 12 mm. .. The proximal end of the wire (2917) may, in some embodiments, be coupled to a handle (not shown) having two control mechanisms (eg, one or more knobs, wheels, sliders). The operator may operate the control mechanism to operate the wire (2917) and rotate the distal portion (2914) of the first catheter (2910) around the hinge (2918). The control mechanism of the handle may include locking to secure the position of the distal portion (2914). FIG. 29B depicts an embodiment of a first catheter (2910) having a distal portion (2914) between a second configuration and a third configuration. FIG. 29C depicts an embodiment of a first catheter (2910) in a third configuration. The electrodes (2916, 2926) may be urged towards each other in the third configuration.

FIG. 29D depicts an embodiment of an ablation device (2900) in a third configuration, where the distal portion of the first and second catheters (2910, 2920) is an lateral catheter or sheath (2902). ) And extends to the desired (eg, fully rotated, fully bent) position relative to the proximal portion (2912, 2922) of the catheter (2910, 2920). In some embodiments, the respective wires (2912, 2922) of the catheter (2910, 2920) may be coupled together at the handle so that upon activation of the control mechanism, the wires (2912, 2922) are Controlled together, each distal portion (2914, 2924) of the catheter (2910, 2920) can rotate simultaneously about their respective hinges (2918, 2928). In the second and third configurations, the first and second catheters (2910, 2920) may be urged away from the longitudinal axis of the lateral catheter (2902).

When the first and second catheters (2910, 2920) extend out of the lateral catheter (2902), one or more portions of the catheters (2910, 2920) are of their natural (eg, curved shape, etc.). , Unconstrained) shape (s) may be taken. The catheters (2910, 2920) are together or independently of the lateral catheter (2902).
You may go out of and move forward. In some embodiments, the proximal portion (2912, 2922) of the catheter (2910, 2920) is flexible so that the distal ends of the catheter (2910, 2920) can spread out apart from each other. It may include a curve. The minimum radius of curvature of the catheters (2910, 2920) may be in the range of about 1 cm or more. For example, the proximal portion (2912, 2922) may have a radius of curvature of about 1 cm or more. In some embodiments, the distal portions (2914, 2924) may have a radius of curvature of about 1 cm or more.

In some embodiments, the electrodes (2916, 2926) of the ablation device (2900) are about 0.5 mm to about 7.0 mm in length and cross-sectional dimensions (eg, including all values and subranges in between). , Diameter) may be from about 0.5 mm to about 4.0 mm. The electrodes (2916, 2926) of the different catheters (2910, 2920) may be separated from each other by a distance of about 3.0 mm to about 20 mm, including all values and subranges between them. Electrodes (2916, 2926) may be located approximately 1.0 mm to approximately 4.0 mm away from the distal end of their corresponding catheters (2910, 2920), including all values and partial ranges in between. .. In some embodiments, the distal end of the catheter (2910, 2920) may include an electrode (2916, 2926). The one or more focal ablation affected areas may be formed to include a diameter of about 1.0 cm to about 2.0 cm, including all values and subranges in between.

FIG. 30 is a side view of another embodiment of the ablation device (3000), which slides in the lumen (3010) with an outer catheter or sheath (3010) defining a longitudinal axis. Includes a set of four movable catheters (3020, 3030, 3040, 3050). Each of the catheters (3020, 3030, 3040, 3050) has a proximal portion (3023, 3033, 3043, 3053), a distal portion (3024, 3034, 3044, 3054), and a proximal portion (3023, 3033, 3043). , 3053) may include hinges (3021, 3031, 3041, 3051) that connect to the distal portion (3024, 3034, 3044, 3054). Each of the distal portions (3024, 3034, 3044, 3054) may include electrodes (3022, 3032, 3042, 3052). The distal ends and / or electrodes (3022, 3032, 3042, 3052) of the catheters (3020, 3030, 3040, 3050) have a non-invasive shape (eg, curved, flat) to reduce trauma to the tissue. , Curved and / or blunted portions). Each of the catheters (3020, 3030, 3040, 3050) may include hinges (3021, 3031, 3041, 3051) as described in detail herein. It should be understood that the ablation device (3000) may include any number of catheters, including 2, 3, 4, 5, 6, or more catheters.

Each electrode (3022, 3032, 3042, 3052) may include an insulating wire configured to maintain a potential of at least about 700 V without dielectric breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200V and about 2000V over the entire thickness in between, including all values and subranges in between, without dielectric breakdown. Good. Each catheter (3020, 3030, 3040, 3050) is an electrode formed on the body of the catheter (3020, 3030, 3040, 3050) (eg, in the lumen of the catheter (3020, 3030, 3040, 3050)). Insulated conductors (3022, 3032, 3042, 3052) may be included. Each of the electrodes (3022, 3032, 3042, 3052) may be connected to a corresponding insulated wire leading to a handle (not shown) attached to the proximal portion of the catheter. In some embodiments, the sizes, shapes, and / or locations of the electrodes (3022, 3032, 3042, 3052) may differ from each other.

In some embodiments, the depth, shape, and focal ablation affected area produced by the ablation device (3000), depending on the configuration of the catheters (3020, 3030, 3040, 3050) and electrodes (3022, 3032, 3042, 3052) / Or diameter / size can be controlled. Even if the set of catheters (3020, 3030, 3040, 3050) is configured to translate along the longitudinal axis to transition between the first configuration, the second configuration, and the third configuration. Good. In some embodiments, the ablation device (3000) has a set of catheters (3020, 3030, 3040, 3050) arranged generally parallel to the longitudinal axis of the outer catheter or sheath (3010) and catheters (3020, 3030). , 3040, 3050), the first configuration in which the distal portion is located within the outer catheter (3010), and the electrodes (3022, 3032, 3042, 3052) are the distal ends of the outer catheter (3010) lumen. A second configuration that exits (3011) and advances at any suitable distance from it, and the distal portion of each catheter (3020, 3030, 3040, 3050) is the corresponding catheter (3020, 3030). , 3040, 3050) with respect to a third configuration (eg, 3040, 3050) that can rotate, twist, or bend about its corresponding hinges (3021, 3031, 3041, 3051). It may be configured to transition to and from FIG. 30). For example, the first catheter (3020) may be configured to position the distal portion (3024) in multiple positions with respect to the proximal portion (3023), as discussed above with respect to FIGS. 29A-29D. It may include a distal portion (3024) that is rotatable about a good first hinge (3021). It is understood that the ablation device (3000) may transition to any intermediate configuration between the first configuration, the second configuration, and the third configuration in continuous or separate steps. In the second configuration, the catheter set may be urged away from the longitudinal axis.

In some embodiments, one or more pulse waveforms can be applied between electrodes (3022, 3032, 3042, 3052) composed of a set of anode and cathode. For example, adjacent or nearly opposite electrode pairs may work together as an anode-cathode set. In FIG. 30, the first electrode (3022) may be configured as an anode and may be paired with a second electrode (3032) configured as a cathode. The third electrode (3042) may be configured as an anode and may be paired with a fourth electrode (3052) configured as a cathode. The pair of the first and second electrodes (3022, 3032) uses the pair of the third and fourth electrodes (3042, 3052) to form a first pulse waveform, followed by a second pulse waveform in succession. May be applied. In another embodiment, the pulse waveform may be applied to each of the electrodes simultaneously, where the second and third electrodes (3032, 3042) may be configured as anodes, the first and fourth. Electrodes (3022, 3052) may be configured as cathodes. It should be understood that any of the pulse waveforms disclosed herein can be applied incrementally or continuously to the anode-cathode electrode sequence. Some embodiments of the ablation device (3000) may have the same dimensions as described above for the ablation device (2900).

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

31A-31B are perspective views of yet another embodiment of the ablation device (3100), wherein the ablation device (3100) is the outer catheter or sheath (3110) defining the longitudinal axis and the outer catheter lumen. Includes a slidable catheter (3160). The catheter (3160) may extend from the distal end of the lumen. The catheter (3160) may also include a proximal portion (3160), a plurality of distal portions (3122, 3132, 3142, 3152), and a joint (3162) that connects the proximal portion to each of the plurality of distal portions. Good. For example, the joint (3162) may include hinges, fittings, rotary wheels, ball and socket fittings, condyle fittings, saddle fittings, swivel shafts, trajectories and the like. The distal part (3122, 3132, 3142, 3152) is folded back in the outer catheter (3110), and the internal spring (not shown) connecting the parts is the respective distal part (3122, 3132, 3142, 3152). ) Becomes a compressed configuration when folded. When the distal portions (3122, 3132, 3142, 3152) are not constrained (ie, when the medial catheter (3160) is deployed or pushed far enough away from the lateral catheter (3110)), the springs are their original. In a non-compressed configuration, the joint (3162) bends, and the distal portion (3122, 3132, 3142, 3152) bends outward, approximately along the longitudinal axis of the catheter. Take a vertical configuration. As shown in FIG. 31B, the distal end of the catheter (3160) may be coupled to a set of electrodes (3120, 3130, 3140, 3150) via a joint (3162). In some embodiments, the joint (3162) has a first distal portion (3122), a second distal portion (3132), a third distal portion (3142), and a fourth distal portion. It may be combined with (3152). Electrodes (3120, 3130, 3140, 3150) may be disposed on the surface of their respective distal portions (3122, 3132, 3142, 3152). As the catheter (3160) exits and advances from the lateral catheter (3110), their natural parts (3120, 3130, 3140, 3150) are approximately perpendicular to the longitudinal axis of the catheter (3160). (For example, it may take an unconstrained shape).

Electrodes (3120, 3130, 3140, 3150) may include non-invasive shapes (eg, curved, flat, curved, and / or blunted portions) to reduce trauma to tissue. Each electrode (3120, 3130, 3140, 3150) may include an insulating conductor configured to maintain a potential of at least about 700 V without dielectric breakdown of the corresponding insulation. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200V and about 2000V over the entire thickness in between, including all values and subranges in between, without dielectric breakdown. Good. The catheter (3160) may include insulated conductors of each electrode (3120, 3130, 3140, 3150) formed in the body (eg lumen) of the catheter (3160). Each of the electrodes (3120, 3130, 3140, 3150) may be connected to a corresponding insulated wire leading to a handle (not shown) attached to the proximal portion of the catheter (3160). In some embodiments, the sizes, shapes, and / or locations of the electrodes (3120, 3130, 3140, 3150) may differ from each other.

The catheter (3160) may be configured to translate along the longitudinal axis to transition between the first configuration, the second configuration, and the third configuration. In some embodiments, the ablation device (3100) has a set of electrodes (3120, 3130, 3140, 3150) arranged in the outer catheter (3110) generally parallel to the longitudinal axis of the outer catheter (3110). The first configuration (eg, FIG. 31A) and the set of electrodes (3120, 3130, 3140, 3150) advance out of the distal end (3111) of the lateral catheter lumen by any suitable distance. Can rotate about a second configuration (not shown in FIG. 31A) and its corresponding joint (3162) relative to the proximal portion of the electrode (3120, 3130, 3140, 3150) catheter (3160). Alternatively, it may be configured to transition to and from a third configuration (eg, FIG. 31B) that can be twisted or bent. The transition from the first configuration to the second and third configurations is performed by advancing the catheter (3160) and electrodes (3120, 3130, 3140, 3150) out of the distal end of the lateral catheter (3110). You may be disappointed. It is understood that the ablation device (3100) may transition to any intermediate configuration between the first configuration, the second configuration, and the third configuration in continuous or separate steps.

FIG. 31B shows electrodes (3120, 3130, 3140, 3150) that are evenly spaced to form a positive (“+”) shape. However, the angle between adjacent electrodes (3120, 3130, 3140, 3150) may be selected based on the desired focal ablation pattern. Similarly, the electrodes (3120, 3130, 3140, 3150) in FIG. 31B are substantially perpendicular to the longitudinal axis of the catheter (3160), but may be adjusted based on a set of ablation parameters.

In some embodiments, one or more pulse waveforms can be applied between electrodes (3120, 3130, 3140, 3150) composed of a set of anode and cathode. For example, adjacent or nearly opposite electrode pairs may work together as an anode-cathode set. In FIG. 31B, the first electrode (3120) may be configured as an anode and paired with a third electrode (3140) configured as a cathode. The second electrode (3130) may be configured as an anode and may be paired with a fourth electrode (3150) configured as a cathode. The pair of first and third electrodes (3120, 3140) uses the pair of second and fourth electrodes (3130, 3150) to make a first pulse waveform, followed by a second pulse waveform in succession. May be applied. In another embodiment, the pulse waveform may be applied to each of the electrodes simultaneously, where the first and second electrodes (3120, 3130) may be configured as anodes, the third and fourth. Electrodes (3140, 3150) may be configured as cathodes. It should be understood that any of the pulse waveforms disclosed herein can be applied incrementally or continuously to the anode-cathode electrode sequence.

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

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

In some embodiments, the electrodes (3210, 3220, 3230, 3240) may form an anode-cathode pair. For example, the first electrode (3210) may be configured as an anode and the third electrode (3230) may be configured as a cathode. The first and second electrodes (3210, 3230) may have a potential difference of up to about 1500 V. Activating one or more of the electrodes (3210, 3220, 3230, 3240) of one or more catheters can create one or more ablation zones along a portion of the wall of the ventricle. The isobaric line (3350) is an isobaric line corresponding to an ablation zone (3350) having an electric field strength threshold of about 460 V / cm when the first and third electrodes (3220, 3240) are activated. In some embodiments, the ablation zone (3350) may be about 12 mm wide and about 20 mm long. Alternatively, the ablation device may be placed adjacent to or relative to a portion of the posterior wall of the left atrium, and by actuation of one or more electrodes, the appropriate pulse waveform is irreversible electroporation energy delivery. May be delivered for ablation of tissue.

FIG. 33A shows the outer shaft (3310) extending to the proximal end of the device (3300), the inner shaft (3320) extending from the distal end of the shaft lumen (3312) of the outer shaft (3310), and it. FIG. 3 is a perspective view of another embodiment of an ablation device / device (3300) in the form of a catheter, comprising a set of coupled splines (3330). The inner shaft (3320) may be coupled to a handle (not shown) at the proximal end and disposed distal to the cap electrode (3322) (eg, the distal end). The set of inner shaft (3320) and spline (3330) may be translatable along the longitudinal axis (3324) of the ablation device (3300). In some embodiments, the set of inner shaft (3320) and spline (3330) may move together or translate independently. The inner shaft (3320) may be configured to slide within the lumen (3312) of the outer shaft (3310). The cap electrode (3322) may include a non-invasive shape to reduce trauma to the tissue. For example, the cap electrode (3322) may have a flat circular shape and / or a curvilinear, blunted outer shape. The distal end of each spline in the set of splines (3330) may be moored to the distal portion of the medial shaft (3320). The proximal portion of the set of splines (3330) may be attached to the outer shaft (3310). The ablation device (3300) tissue the pulse waveform during use via the electrodes (3332, 3334) on the spline (3330) and the distal cap electrode (3322), for example as disclosed in FIGS. 21-25. May be configured to deliver to.

Each spline in a set of splines (3330) may include a set of electrodes (3332, 3334) on the surface of the spline. Each set of electrodes may include a distal electrode (3332), just as a set of splines includes a set of distal electrodes (3332). Each of the distal electrodes (3332) is closest to the cap electrode (3322) as compared to other electrodes in its corresponding set of electrodes on the same spline (eg, a set of proximal electrodes (3334)). Moreover, in some embodiments, the distal electrode (3332) may have only an outwardly exposed portion, i.e., a portion that does not confront the inner space / volume defined by the set of splines. Good. For example, if the distal electrode (3332) is constructed from metal rings, a portion of each ring is insulated so that only the outwardly exposed parts or "windows" are exposed for the delivery of ablation energy. You may be. The cap electrode (3322) of the set of distal electrodes and each distal electrode (3332) may jointly have the same polarity during use. This combination of closely placed distal electrodes, with outward-facing windows and cap electrodes, causes the distal end of the ablation device (3300) to generate and fire a stronger electric field, thereby causing these. Compared with only one of the electrodes, the focal ablation affected area of the tissue can be produced more effectively at the desired depth.

Each spline (3330) of the ablation device (3300) may include at least one set of independently addressable electrodes (3332, 3334) on the surface of the spline (3330). The distal cap electrode (3322) may be formed at the distal end of the catheter device (3300). Each electrode (3322, 3332, 3334) may be coupled to an insulating conductor configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200 V and about 2000 V over its entire thickness without dielectric breakdown. Each spline (3330) may include insulating conductors of each electrode (3332, 3334) in the body of the spline (3330) (eg, in the lumen of the spline (3330)). Similarly, in some embodiments, the inner shaft (3320) may include an insulating wire for the cap electrode (3322). In other embodiments, the electrodes (3322, 3332, 333)
The subset of 4) may be connected and wired. For example, the proximal electrodes (3334) of each spline in a set of splines (3330) may be connected and wired. As another example, all distal electrodes (3332) and cap electrodes (3322) may be connected and wired.

In some embodiments, the set of splines (3330) is the first configuration in which the set of splines (3330) is arranged generally parallel to the longitudinal axis (3324) of the ablation device (3300), and the spline (3330). ) May be configured such that the distal end of each spline transitions from the longitudinal axis (3324) to a second configuration that flexes radially outward. In this way, the set of distal electrodes (3332) and cap electrode (3322) can be shaped / oriented to form the second configuration shown in FIGS. 33A, 33B, and 33E. The cap electrode (3322) may be separated from each distal electrode in the set of distal electrodes (3332) by up to about 5 mm, including all values and subranges in between. For example, the cap electrode (3322) may be about 0.5 mm to about 3 mm away from each distal electrode in the set of distal electrodes (3332). In the second configuration, the distal portion of each spline in the set of splines (3330) is about 45 to about 90 degrees with respect to the longitudinal axis (3312), including all values and partial ranges in between. The angle (3336) may be attached. For example, the distal portion of each spline in the set of splines (3330) in the second configuration may be angled (3336) from about 70 degrees to about 80 degrees with respect to the longitudinal axis (3312). Good. For example, in the second configuration, when the set of cap electrodes (3322) and distal electrodes (3332) is projected onto a plane perpendicular to the longitudinal axis (3324), as seen in the front view of FIG. 33B. Can take the form of a "plus" sign.

In some embodiments, the medial shaft (3320) is housed in the lateral catheter lumen (3312) by a predetermined amount to shift the ablation device (3300) from the first configuration to the second configuration. You may. It is understood that the set of splines (3330) may be transitioned to any intermediate configuration between the first configuration and the second configuration in continuous or separate steps. The set of splines (3330) forms a shape generally parallel to the longitudinal axis (3324) of the inner shaft (3320) when undeployed, and the distal end of the set of splines (3330) is the longitudinal axis (3324). ) May form a basket-like or spherical shape when flexing outward in the radial direction.

33A, 33B, and 33E show a set of splines (3330), where each spline in the set of splines (3330) is of size, shape, number, and spacing with the distal electrode (3332). Includes one or more proximal electrodes (3334) that differ in one or more of the. For example, FIG. 33A shows one distal electrode (3332) and two proximal electrodes (3334) for each spline in a set of splines (3330). In some embodiments, each proximal electrode (3334) may be formed on the surface of the spline (3330) along its entire perimeter, i.e., around the entire thickness of the spline. In some embodiments, each distal electrode (3332) may be formed on the surface of a portion of the outer circumference of the spline. That is, as shown in FIGS. 33C and 33D, the distal electrode (3332) may be partially on the outer circumference of the corresponding spline and may not cover the entire outer circumference of the spline (3330). For example, the distal electrode (3332) may surround the perimeter of its corresponding spline and be partially covered with an insulating layer such that only a portion (eg, window) of the distal electrode (3332) is exposed. In some embodiments, the one or more electrodes may be completely covered with a thin insulating layer for two-step operation. In some embodiments, a set of distal electrodes (3332) of a set of splines (3330) is about 30 around the center of its corresponding spline (3330), including all values and subranges in between. An angle (3333) of degrees to about 300 degrees may be made. For example, a set of distal electrodes (3332) in a set of splines (3330) has its corresponding spline (33).
An angle (3333) of about 60 degrees to about 120 degrees may be formed around the center of 30). In this way, a significant proportion of the electric field generated by the set of distal electrodes (3332) in the second configuration is directed forward rather than away from the target tissue into the blood and targeted. Can be fired at the tissue to assist in focal ablation.

In this way, the distal electrode (3332) may be configured to point in a particular direction. For example, in FIGS. 33A and 33E, a second set of distal electrodes (3332) and a cap electrode (3322) flexes radially outward from the longitudinal axis (3324) at the distal end of the set of splines (3330). In the configuration of, it is shown that the device (3300) is generally facing forward at the distal end. In addition, the distal electrode (3332) is located at the distal end of the spline so that the distal electrode (3332) of the set of splines (3330) is located near the cap electrode (3322). May be good.

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

In some embodiments, the set of cap electrodes (3322) and electrodes (3332, 3334) may consist of an anode-cathode set. For example, each distal electrode in a set of cap electrode (3322) and distal electrode (3332) may be collectively configured as an anode, and all proximal electrodes (3334) are collectively configured as a cathode. It may (or vice versa). In some embodiments, the set of distal electrodes (3332) and the set of proximal electrodes (3334) may have opposite polarities. For example, a set of distal electrodes (3332) and proximal electrodes (3334) for a given spline may have opposite polarities. The set of cap electrode (3322) and distal electrode (3332) may have the same polarity. As discussed herein, all distal electrodes (3332) and cap electrodes (3322) may be connected and wired. In some embodiments, the cap electrode and the set of one or more spline electrodes (3332, 3334) of the set of splines (3330) work together to produce a pulse waveform for irreversible electroporation. It may be delivered. In other embodiments, the delivery of the pulse waveform may be repeated continuously over a predetermined subset of the set of electrodes (3332, 3334).

In some embodiments, the set of distal electrodes (3332) may be up to 3 mm from the distal end of each spline (3330) and away from the cap electrode (3322). In some embodiments, the set of distal electrodes (3332) may be about 1 mm to about 20 mm away from the set of proximal electrodes (3334). In some embodiments, each electrode in the set of electrodes (3332, 3334) may have a diameter of about 0.5 mm to about 3 mm. In some embodiments, the cap electrode (3322) may have a cross-sectional diameter of about 1 mm to about 5 mm. In some embodiments, each electrode in the set of electrodes (3332, 3334) may be about 0.5 mm to about 5 mm in length. In some embodiments, the set of splines (3330) in the second configuration has an extended cross-sectional diameter (ie, the effective diameter of the extended configuration or the second configuration at its maximum) of about 6 mm to about. It may be 24 mm. In some embodiments, the set of splines (3300) may extend from the distal end (3312) of the outer shaft (3310) by about 6 mm to about 30 mm. In some embodiments, the outer shaft (3310) may have an outer diameter of about 1.5 mm to about 6.0 mm.

The ablation device (3300) described herein is disposed in the first configuration prior to delivering the pulse waveform and transitions to the second configuration on the tissue surface (eg, left atrium or ventricle). It may come into contact with the inner wall and / or the like. In some of these embodiments, a handle (not shown) may be coupled to a set of catheter (3300) and spline (3330), the handle being the first configuration of the set of splines (3330). It is configured to trigger the transition between and the second configuration. For example, the handle may be configured to translate the inner shaft (3320) with respect to the outer shaft (3310). For example, by storing the inner shaft (3320) in the lumen (3312) of the outer shaft (3310), a set of splines (3330) is unfolded into the spherical shape shown herein. May be good. In some embodiments, the inner shaft (3324) may be translated and a set of splines (3330) may be deployed by activating knobs, wheels, or other control mechanisms within the device handle. In some embodiments, the conductors of at least two electrodes in a set of electrodes (3322, 3332, 3334) are electrically coupled in or near the proximal portion of the ablation device (3300), for example in a handle. May be good.

In addition, the catheter handle (not shown) may include a mechanism for deflecting or guiding the distal portion of the catheter device (3300). For example, the pullwire may extend from the catheter handle to one end of the distal portion of the device (3300) at or near the distal end of the outer shaft (3310), and the tension of the pullwire causes the device (3300) to move away. The position part is biased. The deflection of the device (3300) can help the user position the device (3300) in a suitable anatomical position in a controlled manner. In some embodiments, the distal cap electrode (3322) may be electrically wired separately from the spline electrode (3332). In this way, the intracardiac ECG signal can be recorded only from the distal cap electrode (3322). In some embodiments, one or more distal spline electrodes (3332) may be electrically wired separately to monitor intracardiac ECG signals from each of such electrodes (3332). Good. In some embodiments, some distal spline electrodes (3332) may be used to monitor the ECG, while other distal spline electrodes (3332) are used to deliver ablation energy. May be good. It should be understood that any of the ablation devices described herein can be used with separately electrically wired electrodes to monitor the intracardiac ECG signal from each of such electrodes. In some embodiments, some electrodes of one or more splines in a set of splines may be used to monitor the ECG, while other electrodes are used to deliver ablation energy. May be good.

The ablation device (3300) has any number of splines, including all values and subranges in between, eg, 2, 3, 4, 5, 6, 6, 7, 8, 9. It may include 10, 12, 14, 16, 17, 20, or more splines. In some embodiments, the ablation device (3300) may include 3 to 20 splines. In some embodiments, the ablation device (3300) may include 4-12 splines.

Each of the splines in the set of splines (3300) may include respective electrodes (3332, 3334) that are non-invasive and generally curved in shape to reduce trauma to the tissue. In this way, the distal electrode in the second configuration is held close to or placed close to a portion of the atrial wall of the left atrium, as described herein. An affected area can be formed on it by activating a suitable electrode using any suitable combination of polarities. For example, the cap electrode (3322) and distal electrode (3332) of a set of splines (3330) are oriented approximately perpendicular or generally oblique to the tissue wall, as shown in FIG. 33E, the tissue wall (3350). ) May be placed in contact with or very close to. This configuration of the distal electrodes (3322, 3332) allows the ablation device (3300) in the deployed configuration to abut at an angle (eg, at an angle) to the tissue wall (3350) as desired. It is possible to generate a localized affected area at a depth of.

In some embodiments, the electrodes or subset of electrodes can be addressed independently, so that the electrodes use any pulse waveform sufficient to ablate the tissue by irreversible electroporation. Can be energized in sequence. For example, as discussed in more detail herein, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms). It should be understood that the size, shape, and spacing of the electrodes on and between splines may be configured to deliver continuous / through-wall energy to electrically insulate one or more pulmonary veins. .. In some embodiments, the alternative electrodes may have the same potential and may be the same for all other alternative electrodes. Therefore, in some embodiments, the ablation can be delivered rapidly with all electrodes activated simultaneously. There are various options for such electrode pairs and they may be implemented based on their convenience.

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, eg, 2, 3, 4, 5, 6, or more catheters. For example, in some embodiments, the ablation device (2900, 3000, 3100, 3200) may include 3-6 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 2-4 distal portions. Moreover, in some embodiments, the shape of the catheter (eg, curvature, length, size) may be asymmetric to assist in controlling the depth, shape, and / or size of focal ablation.

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, the subset of electrodes may be addressable independently and the electrodes are in any sequence using any pulse waveform sufficient to ablate the tissue by irreversible electroporation. It may be energized with. For example, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms).

In all embodiments described above, and without limitation, the ablation catheter itself controls deflection by a suitable mechanism within the catheter handle, as known to those of skill in the art. It may be a movable device with a pull wire.

Balloons In some embodiments, the ablation device may include one or more balloons to deliver energy and ablate tissue by irreversible electroporation. FIG. 10 depicts an embodiment of a balloon ablation device (1010) disposed in the left atrial space (1000) of the heart (eg, structurally and / or functionally similar to the ablation device (110)). There is. The ablation device (1010) may include a first balloon (1012) and a second balloon (1014) that may be configured to be disposed in the mouth (1002) of the pulmonary vein (1004). The first balloon (1012) in the expanded (eg, inflated) configuration may be larger in diameter than the second balloon (1014) in the expanded configuration. As a result, the second balloon (1014) is inserted into the pulmonary vein (1).
The first balloon (1012) can be placed further back in 014), while the first balloon (1012) can be placed in and / or near the mouth (1002) of the pulmonary vein (1004). The inflated second balloon functions to stabilize the positioning of the first balloon at the mouth of the pulmonary vein. In some embodiments, the first balloon (1012) and the second balloon (1014) may be filled with any suitable conductive fluid, such as saline. The first balloon (1012) and the second balloon (1014) may be electrically isolated from each other. For example, each balloon (1012, 1014) may be associated with an insulating wire, and each wire is sufficiently electrically insulated to maintain a potential difference of at least 700 V across its thickness without dielectric breakdown. Has sex. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200V and about 2500V over the entire thickness between them, including all values and subranges between them. For example, the conductor of the second balloon (1014) may be insulated as it extends through the first balloon (1012).

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

FIG. 11 is structurally and / or functionally similar to a balloon ablation device (1110) (eg, ablation device (1010)) disposed in the left atrial space (1100) and right atrial space (1104) of the heart. ) Is a cross-sectional view of another embodiment. The ablation device (1110) may include a balloon (1112) that may be configured to be positioned forward in the right atrial space (1104). For example, the balloon (1112) may be placed 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) capable of advancing from the right atrial space (1104) through the balloon (1112) and the septum (1106) into the left atrial space (1100). For example, the electrode (1120) may extend from the balloon (1112) and puncture the septum (1106) to advance into the left atrial space (1100). As the electrode (1120) advances into the left atrial space (1100), the distal portion of the electrode (1120) may deform to form a predetermined shape. For example, the distal portion of the electrode (1120) may include a non-linear shape, such as a circle, an ellipsoid, or any other geometry. In FIG. 11, the distal portion of the electrode (1120) forms a loop that may surround one or more mouths of the pulmonary vein (1102) of the left atrial space (1100). In other embodiments, the distal portion of the electrode (1120) may be approximately the same diameter as the mouth of the pulmonary vein (1102).

The balloon (1112) and the electrode (1120) may be electrically isolated from each other. For example, the balloon (1112) and the electrode (1120) may each contain insulating conductors (1114, 1122), each of which has a total thickness of at least 700 V without dielectric breakdown. It has sufficient electrical insulation to maintain the potential difference. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200V and about 2000V over the entire thickness in between, including all values and subranges in between, without dielectric breakdown. Good. The conductor (1122) of the electrode (1120) may be insulated through the balloon (1112). In some embodiments, the saline solution in the balloon (1112) and the electrode (1120) may form an anode-cathode pair. For example, the balloon (1112) may be configured as a cathode and the electrode (1120) may be configured as an anode. The device (1110) may receive a pulse waveform delivered to the mouth of the pulmonary vein (1102). For example, a biphasic signal may be applied to ablate the tissue. The pulse waveform creates a strong electric field around the electrode (1120) and a current is applied to the balloon (1112) via capacitive coupling to complete the circuit. In some embodiments, the electrode (1120) may include a high gauge wire and the balloon (1112) may include a wire mesh.

In another embodiment, the electrode (1120) advances through the pulmonary vein (1102) without advancing through the balloon (1112) and / or the septum (1106) and out of the pulmonary vein ostium. It may be arranged in one or more. The balloon (1112) and the electrode (1120) are configured as a cathode-anode pair and may receive pulse waveforms in the same manner as discussed above.

Return Electrodes Some embodiments of the ablation system described herein further include a distributed set of return electrodes or return electrodes coupled to the patient to reduce the risk of unintended damage to healthy tissue. It may be included. 12A-12B are schematic views of a set of return electrodes (1230) (eg, return pads) of an ablation system disposed on a patient (1200). A set of four mouths of the pulmonary vein (1210) in the left atrium is shown in FIGS. 12A-12B. The electrodes (1220) of the ablation device may be located around one or more of the mouths of the pulmonary veins (1210). In some embodiments, a set of return electrodes (1230) is placed on the back of the patient (1200) such that an electric current passes from the electrode (1220) through the patient (1200) and then returns to the return electrode (1230). You may.

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 back of the patient so as to surround the pulmonary vein opening (1210). A conductive gel may be applied between the return electrode (1230) and the skin to improve contact. It should be understood that any of the ablation devices described herein can be used with one or more return electrodes (1230). In FIGS. 12A-12B, the electrodes (1220) are arranged around the four mouths (1210).

FIG. 12B shows an energized electrode (1220) forming an electric field (1240) around the mouth of the pulmonary vein (1210). The return electrode (1230) then receives the monophasic and / or biphasic waveform delivered by the electrode (1220). In some embodiments, the number of return electrodes (1230) may be approximately inversely proportional to the surface area of the return electrodes (1230).

For each ablation device discussed herein, the electrodes (eg, ablation electrodes, return electrodes) may include biocompatible metals such as titanium, palladium, silver, platinum or platinum alloys. For example, the electrodes may preferably contain platinum or a platinum alloy. Each electrode may include a wire that is sufficiently electrically insulating to maintain a potential difference of at least 700 V over its entire thickness without dielectric breakdown. In other embodiments, the insulation of each conductor may maintain a potential difference between about 200V and about 2500V over the entire thickness between them, including all values and subranges between them. The insulated wire runs to the proximal handle portion of the catheter, from which it can be connected to the appropriate electrical connector. The catheter shaft may be made of a flexible polymeric material such as Teflon®, nylon, Pevacs or the like.

II. Methods Also described herein are methods for ablating tissue in the cardiac cavity using the systems and devices described above. The cardiac cavity may be the left atrial cavity and may include its associated pulmonary veins. In general, the methods described herein include introducing a device and disposing it in contact with one or more pulmonary venous ostium or cavity areas. The pulse waveform can be delivered to one or more electrodes of the device to ablate the tissue. In some embodiments, the cardiac pacing signal may synchronize the delivered pulse waveform with the cardiac cycle. Additional or alternative, the pulse waveform may include multiple levels of the hierarchy to reduce total energy delivery. Tissue ablation performed in this way may be delivered with less energy delivery in synchronization with the paced heartbeat to reduce damage to healthy tissue. It should be appreciated that any of the ablation devices described herein can be used to ablate tissue as needed using the methods described below.

In some embodiments, the ablation devices described herein may be used for focal ablation of cardiac mechanisms / structures identified as the cause of arrhythmias. For example, a cardiac electrophysiology diagnostic catheter (eg, a mapping catheter) is used to map a cardiac structure such as a rotor that can later be ablated by focal ablation using any of the ablation devices described herein. May be good. Focal ablation can create, for example, spot affected areas that invalidate the rotor while protecting surrounding tissue. In some embodiments, one or more focal ablation affected areas may be formed in combination with one or more boxes or lines to treat cardiac arrhythmias. As a non-limiting example, in some embodiments, the system is one or more mapping catheters, one or more ablation catheters useful for creating the affected area by focal ablation (eg, FIGS. 9D, 9E, 27A-27C). , 28, 29, 30, 31, 32), and one or more catheters useful for creating box-shaped and / or linear affected areas (eg, FIGS. 3-8, 9A-9C, 10-12). , 26A-26B).

FIG. 13 is a method (1300) for one embodiment of the tissue ablation process. In some embodiments, the voltage pulse waveforms described herein may be applied during the refractory period of the cardiac cycle to avoid disruption of cardiac sinus rhythm. The method (1300) is a step in the device (eg, ablation device (110) and / or ablation device (200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 2900, 3000, 3100). It involves introducing an ablation device, such as one of the above, into the intracardiac lumen of the left atrium (1302). The device can be advanced and placed in contact with the pulmonary vein opening (1304). For example, the electrodes of the ablation device may form a substantially circular array of electrodes arranged in contact with the medial radial surface at the pulmonary vein ostium. In some embodiments, pacing signals for cardiac stimulation of the heart may be generated (1306). The pacing signal may then be applied to the heart (13).
08). For example, the heart may be electrically paced by a cardiac stimulator to ensure pacing capture and establish the periodicity and predictability of the cardiac cycle. One or more of atrial pacing and ventricular pacing may be applied. The display of the pacing signal may be transmitted to the signal generator (1310). A time window during the refractory period of the cardiac cycle may then be defined in which one or more voltage pulse waveforms can be delivered. In some embodiments, the refractory time window follows a pacing signal. For example, a common refractory time window may be between the atrial refractory time window and the ventricular refractory time window.

The pulse waveform may be generated in synchronization with the pacing signal (1312). For example, the voltage pulse waveform may be applied in a common refractory time window. In some embodiments, the pulse waveform may be generated with a time offset with respect to the display of the pacing signal. For example, the start of the refractory time window may be offset from the pacing signal by a time offset. The voltage pulse waveform (s) may be applied over a series of heartbeats across a 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 venous ostium of the patient's heart via one or more splines in a set of splines in the ablation device. In other embodiments, the voltage pulse waveforms described herein may be selectively delivered to an electrode subset, such as an anode-cathode subset, for pulmonary vein insulation and ablation. For example, the first electrode in the group of electrodes may be configured as an anode and the second electrode in the group of electrodes may be configured as a cathode. These steps may be repeated for the desired number of ablated pulmonary vein ostium or cavity area (eg, one, two, three, or four mouths).

In some embodiments, the layered voltage pulse waveforms with nested structures and time interval layers described herein are useful for irreversible electroporation and provide control and selectivity in different tissue types. .. FIG. 14 is a flowchart (1400) of another embodiment of the tissue ablation process. The method (1400) uses a device (eg, an ablation device such as one of the ablation devices (200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 2900, 3000, 3100)). Including introduction into the intracardiac lumen of the left atrium (1402). The device can be advanced and placed in the pulmonary vein ostium (1404). In embodiments where the device may include first and second configurations (eg, compact and expanded), the device is introduced in the first configuration and transitions to the second configuration to the pulmonary vein sinus ostium or mouth or its mouth. Tissue may be contacted in the vicinity (1406). The device may include electrodes and may consist of an anode-cathode subset, as discussed in detail above (1408). For example, a subset of the electrodes of the device may be selected as the anode, while another subset of the electrodes of the device may be selected as the cathode, and a voltage pulse waveform is applied between the anode and the cathode.

The pulse waveform may be generated by a signal generator (eg, signal generator 122) or may include multiple levels in the hierarchy (1410). The signal generators disclosed herein can be used to generate various layered waveforms. For example, the pulse waveform may include a first level of a hierarchy of pulse waveforms, including a first set of pulses. Each pulse has a pulse duration and a first time interval that separates successive pulses. The second level of the pulse waveform hierarchy may include the first set of multiple pulses as the second set. The second time interval may separate the first set of successive pulses. The second time interval can be at least three times the duration of the first time interval. The third level of the pulse waveform hierarchy may include a second set of multiple pulses as a third set of pulses. The third time interval may separate a second set of contiguous pulses. The third time interval can be at least 30 times the duration of the second level time interval.

Although the examples herein identify distinct monophasic and biphasic waveforms, it should be appreciated that combined waveforms can also be generated in which part of the waveform hierarchy is monophasic and the other is biphasic. Voltage pulse waveforms with a hierarchical structure may be applied across different anode-cathode subsets (optionally with time delay). As mentioned above, one or more waveforms applied to the anode-cathode subset may be applied during the refractory period of the cardiac cycle. The pulse waveform may be delivered to the tissue (1412). It should be understood that the steps described in FIGS. 13 and 14 may be modified in combination as needed.

15-18 are embodiments of methods for ablating tissue in the atrial space of the heart as described above using the ablation devices described herein (eg, FIGS. 2-5). Is drawn. FIG. 15 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial space of the heart using an ablation device (1500) corresponding to the ablation device (210) depicted in FIG. Is. A left atrial space (1502) with four pulmonary veins (1504) is depicted, and an ablation device (1500) continuously ablates tissue to electrify one or more of the pulmonary veins (1504). Can be used to insulate. As shown in FIG. 15, the ablation device (1500) uses the transseptal method (eg, extending from the right atrial space through the septum to the left atrial space (1502)) to the left atrium. It may be introduced into a cardiac lumen such as the cavity (1502). The ablation device (1500) may include a catheter (1510) and a guide wire (1520) slidable within the lumen of the catheter (1510). The distal portion of the catheter (1510) may include a set of electrodes (1512). The distal portion (1522) of the guide wire (1520) may advance into the left atrial space (1502) so that it is located near the mouth of the pulmonary vein (1504). The catheter (1510) may then advance over the guide wire (1520) to place the electrode (1512) near the mouth of the pulmonary vein (1504). When the electrode (1512) contacts the mouth of the pulmonary vein (1504), the electrode (1512) may consist of an anode-cathode subset. The voltage pulse waveform generated by the signal generator (not shown) may be delivered to the tissue using electrodes (1512) in synchronization with the paced heartbeat and / or may include a waveform hierarchy. .. After completing tissue ablation in one of the pulmonary veins (1504), the catheter (1510) and guidewire (1520) are repositioned to another pulmonary vein (1504) and the remaining pulmonary veins (1504). Tissues may be ablated in one or more of them.

FIG. 16 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial space of the heart using an ablation device (1600) corresponding to the ablation device (310) depicted in FIG. Is. A left atrial space (1602) with four pulmonary veins (1604) is depicted, and an ablation device (1600) continuously ablates tissue to electrify one or more of the pulmonary veins (1604). Can be used to insulate. As shown in FIG. 16, the ablation device (1600) may be introduced into a cardiac lumen such as the left atrial space (1602) using the transseptal method. The ablation device (1600) may include a sheath (1610) and a catheter (1620) slidable within the lumen of the sheath (1610). The distal portion (1622) of the catheter (1620) may include a set of electrodes. The distal portion (1622) of the catheter (1620) may advance into the left atrial space (1602) such that the electrodes are located near the mouth of the pulmonary vein (1604). When the electrode contacts the mouth of the pulmonary vein (1604), the electrode may consist of an anode-cathode subset. The voltage pulse waveform generated by the signal generator (not shown) may be delivered to the tissue using electrodes in synchronization with the paced heartbeat and / or may include a waveform hierarchy. After completing tissue ablation in the pulmonary vein (1604), the catheter (1620) is repositioned to another pulmonary vein (1604) to ablate the tissue in one or more of the remaining pulmonary veins (1604). You may.

FIG. 17 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial space of the heart using an ablation device corresponding to the ablation device (410) depicted in FIG. A left atrial space (1702) with four pulmonary veins (1704) is depicted, and the ablation device (1700) ablate the tissue and electrically insulate one or more of the pulmonary veins (1704). Can be used to As shown in FIG. 17, the ablation device (1700) may be introduced into a cardiac lumen such as the left atrial space (1702) using the transseptal method. The ablation device (1700) may include a sheath (1710) and a plurality of catheters (1720, 1721) slidable within the lumen of the sheath (1710). Each of the catheters (1720, 1721) may include a respective guide wire (1722, 1723) slidable within the catheter (1720, 1721). The distal portion of the guide wires (1722, 1723) may include electrodes configured to deliver a voltage pulse waveform. Each of the catheters (1720, 1721) and the corresponding guide wires (1722, 1723) advance into the left atrial space (1702) so that they are located near the respective mouths of the pulmonary veins (1704). You may. When the guidewire electrodes (1722, 1723) come into contact with the mouth of the pulmonary vein (1704), the electrodes can consist of an anode-cathode subset. For example, the first guide wire (1722) may be configured as an anode and the second guide wire (1723) may be configured as a cathode. In this configuration, the voltage pulse waveform generated by the signal generator (not shown) may be delivered for simultaneous insulation of a pair of ablation and pulmonary veins (1704). Additional or alternative, the voltage pulse waveform may be delivered to the tissue using electrodes in synchronization with the paced heartbeat and / or may include a waveform hierarchy. After completing tissue ablation in two of the pulmonary veins (1704), the catheters (1720, 1721) may be repositioned to ablate the tissue in the remaining two pulmonary veins (1704). In some embodiments, the sheath (1710) may include three or four catheters disposed in the pulmonary vein (1704).

FIG. 18 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial space of the heart using an ablation device (1800) corresponding to the ablation device (500) depicted in FIG. Is. A left atrial space (1802) with four pulmonary veins (1804) is depicted, and an ablation device (1800) continuously ablates tissue to electrify one or more of the pulmonary veins (1804). Can be used to insulate. As shown in FIG. 18, the ablation device may be introduced into a cardiac lumen such as the left atrial space (1802) using the transseptal method. The ablation device may include a sheath (1820) and a catheter (1810) slidable within the lumen of the sheath (1820). The distal portion (1812) of the catheter (1810) may be in the shape of a flower, as discussed in detail with respect to FIG. The distal portion (1812) of the catheter (1810) may advance into the left atrial space (1802) in a compact first configuration and be located near the mouth of the pulmonary vein (1804). The distal portion (1812) of the catheter (1810) then transitions to an expanded second configuration, with the distal portion (1812) of the catheter (1810) located near the mouth of the pulmonary vein (1804). As provided, a flower-shaped distal portion shown in FIG. 18 may be formed. When the electrode contacts the mouth of the pulmonary vein (1804), the electrode may consist of an anode-cathode subset. The voltage pulse waveform generated by the signal generator (not shown) may be delivered to the tissue using electrodes in synchronization with the paced heartbeat and / or may include a waveform hierarchy. After completing tissue ablation in the pulmonary vein (1804), the catheter (1810) is repositioned in another pulmonary vein (1804) to ablate the tissue in one or more of the remaining pulmonary veins (1804). You may.

Any of the methods described herein (eg, FIGS. 13-18) are return electrodes (eg, FIGS. 12A–12A) configured to safely remove current from the patient during application of a voltage pulse waveform. It may further include coupling one or more return electrodes (1230) depicted on 12B) to the back of the patient.

19A-20B depict embodiments of electrodes arranged in contact with the perimeter of the mouth of the pulmonary vein and the electric field generated from them. FIG. 19A is a schematic representation (1900) of an embodiment of a set of electrodes (1910) disposed in the mouth of a pulmonary vein (1904). The left atrial space (1902) may include a blood pool (1906) and the pulmonary vein (1904) may include a blood pool (1908). The left atrial space (1902) and pulmonary vein (1904) may each have a wall thickness of up to about 4 mm.

FIG. 19B is another schematic representation (1900) of a set of electrodes (1910) arranged along the medial surface of the pulmonary vein (1904) in the radial direction. The pulmonary vein (1904) may include an arterial wall (1905) that houses a blood pool (1908). Adjacent electrodes (1910) may be separated by a predetermined distance (1911). In some embodiments, the pulmonary vein (1904) may have an inner diameter of about 16 mm. In FIGS. 19A-19B, the electrodes (1910) have a length of about 10 mm and may be separated from each other by about 4 mm. It should be understood that the electrode (1910) may be any of the electrodes disclosed herein in other embodiments. For example, the electrode (1910) may include an electrode in the distal portion of the flower shape of FIG. 5 and / or a generally circular array of electrodes depicted in FIG.

20A-20B are schematic representations (2000) of embodiments of an electric field (2020) generated by a set of electrodes (2010) disposed in the mouth of a pulmonary vein (2002). FIG. 20A is a perspective view of the outer walls of the pulmonary vein (2002) and the left atrial space (2004), whereas FIG. 20B is a cross-sectional view thereof. The shaded electric field (2020) indicates the case where the electric field (2020) exceeds the threshold when the adjacent electrode (2010) delivers energy (eg, a voltage pulse waveform) to ablate the tissue. For example, the electric field (2020) represents a potential difference of 1500 V applied between adjacent electrodes (2010). Under this applied voltage, the electric field (2020) intensity may be at least above the threshold of 500 V / cm within the shaded capacitive electric field (2020), sufficient to generate irreversible ablation in the heart tissue. By arranging the pulse waveforms over adjacent pairs of electrodes (2010) as detailed above, the pulmonary vein (2002) ostium is ablated and the pulmonary vein (2002) is electrified from the left atrial space (2004). Can be insulated.

Pulsed Waveforms Methods, systems, and devices for the selective and rapid application of pulsed electric fields / waveforms to achieve tissue ablation by irreversible electroporation are disclosed herein. The pulse waveforms (s) disclosed herein are the systems (100), devices (eg, 200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 1230) disclosed herein. 1500, 1600, 1700, 1800, 1910, 2010, 2900, 3000, 3100), and methods (eg, 1300, 1400). Some embodiments are directed to pulsed high voltage waveforms, along with a sequenced delivery scheme for delivering energy to the tissue through a set of electrodes. In some embodiments, the peak electric field value can be reduced and / or minimized, while at the same time maintaining a sufficiently large electric field strength in the region where tissue ablation is desired. It also reduces the possibility of excessive tissue damage or electric arcing, and local high temperatures. In some embodiments, a system useful for irreversible electroporation includes a signal generator and processor that may be configured to apply a pulsed voltage waveform to a plurality of selected electrodes or a subset of electrodes of the ablation device. In some embodiments, the processor is configured to control the input so that the anode-cathode subset pairs of the selected electrodes can be continuously triggered based on a predetermined sequence. And in one embodiment, the sequenced delivery can be triggered from a cardiac stimulator and / or a pacing device. In some embodiments, the ablation pulse waveform is applied during the refractory period of the cardiac cycle to avoid disruption of the sinus rhythm of the heart. An example method of doing this is to electrically pace the heart with a cardiac stimulator to ensure capture of the pacing and establish the periodicity and predictability of the cardiac cycle, after which the ablation waveform is delivered. Cycle It is to clarify the time window within the refractory period in the cycle.

In some embodiments, the pulsed voltage waveforms disclosed herein are hierarchical in mechanism and have a nested structure. In some embodiments, the pulse waveform comprises a hierarchical grouping of pulses with various related timescales. In addition, the relevant timescales and pulse widths, as well as the number of pulses and hierarchical groupings, may be selected to satisfy one or more of the set of Diophantus inequalities involving the frequency of cardiac pacing.

The pulse waveforms for electroporation energy delivery disclosed herein are delivered with increased safety, efficiency, and effectiveness of energy delivery by lowering the electric field threshold associated with irreversible electroporation. It can result in a more effective excision affected area with a reduction in total energy. This can expand the clinical application of electroporation, including therapeutic treatment of various cardiac arrhythmias.

FIG. 21 shows a pulse voltage waveform in the form of a series of rectangular double pulses, where each pulse, such as pulse (2100), is associated with a pulse width or duration. Pulse width / duration, including all values and subranges in between, is about 0.5 microseconds, about 1 microsecond, about 5 microseconds, about 10 microseconds, about 25 microseconds, about 50 microseconds, It can be about 100 microseconds, about 125 microseconds, about 140 microseconds, about 150 microseconds. The pulse waveform in FIG. 21 shows a set of monophasic pulses in which the polarities of all pulses are the same (measured from zero baseline, all are positive in FIG. 21). In some embodiments, such as irreversible electroporation applications, the height of each pulse (2100) or the voltage amplitude of each pulse (2100) is about 400 volts, about 1 including all values and subranges in between. It can be in the range of 000 volt, about 5,000 volt, about 10,000 volt, about 15,000 volt. As shown in FIG. 21, the pulse (2100) is separated from the adjacent pulse by a time interval (2102), also called the first time interval. The first time interval is about 10 microseconds, about 50 microseconds, about 100 microseconds, about 200 microseconds, about 200 microseconds, including all values and subranges in between, to generate irreversible electrical perforations. It can be 500 microseconds, about 800 microseconds, about 1 millisecond.

FIG. 22 introduces a pulse waveform having a hierarchical structure of nested pulses. FIG. 22 shows a series of pulses _{such as pulse width / pulse duration w (2200) separated between successive pulses at time intervals such as period t 1} (2202) (also referred to as the first time interval). It represents a monophasic pulse, the number m _{1 of which} is arranged to form a group of pulses (2210) (also called the first set of pulses). In addition, the waveform is _{a few m 2 of} a group of pulses (also called a second set of pulses) separated by a time interval (2212) (also called a second time interval) _{of period t 2 between successive groups.} Has. _{A group of pulses, such as the set of m 2} marked by (2220) in FIG. 22, constitutes the next level of hierarchy, which can be called a third set of packets and / or pulses. Both the time interval t ₁ is between pulse width and the pulse may be in the range of hundreds of microseconds microseconds, including all values and subranges therebetween. In some embodiments, the time interval t ₂ may be at least three times greater than the time interval t _1. In some embodiments, the ratio t ₂ / t ₁ can be in the range of about 3 to about 300, including all values and subranges in between.

FIG. 23 describes in more detail the structure of the nested pulse layered waveform. In this figure, a series of m ₁ pulses (each pulse is not shown), to form a group of pulses (2300) (e.g., a first set of pulses). _{A series of groups such as m 2} separated by an intergroup time interval (2310) for _{a period t 2} (eg, a second time interval) between one group and the next are packets 132 (eg, for example). A second set of pulses) is formed. Duration t ₃ between one packet and the next level _(e.g., the third time interval) packets, such as a series of m ₃ separated by a time interval of (2312) comprises a layer of the next level, FIG. To form a superpacket (eg, a third set of pulses) labeled (2320). In some embodiments, the time interval t ₃ may be at least about 30 times larger than the time interval t _2. In some embodiments, the time interval t ₃ may be at least 50 times greater than the time interval t _2. In some embodiments, the ratio t ₃ / t ₂ can be in the range of about 30 to about 800, including all values and subranges in between. The amplitude of the individual voltage pulses within the pulse hierarchy can be in the range of 500 volts to 7,000 volts or more, including all values and subranges in between.

FIG. 24 provides an example of a biphasic waveform sequence having a hierarchical structure. 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) (eg, the first time interval) between the adjacent cycle of period t _{1 and} the adjacent cycle of n ₁ , such a cycle is a group of pulses (2410) (eg, the first of the pulses). Set) is formed. One group and inter-group interval duration t ₂ between the following groups (2412) (e.g., the second time interval) group, such as a series of n ₂ separated by the packet (2420) ( For example, it forms a second set of pulses). The figure also illustrates time delay period _{t 3} between packets (2432) (e.g., the third time interval) a second packet with a (2430). As with monophasic pulses, higher levels of hierarchy can be formed. The amplitude of each pulse or the voltage amplitude of the biphasic pulse may be in the range of 500 volt to 7,000 volt or more, including all values and subranges in between. Pulse width / pulse duration can range from a few tens of microseconds nanoseconds or sub-nanosecond delay t ₁ can range from 0 to a few microseconds. The time interval t ₂ between groups may be at least 10 times larger than the pulse width. In some embodiments, the time interval t ₃ may be at least about 20 times greater than the time interval t _2. In some embodiments, the time interval t ₃ may be at least 50 times greater than the time interval t _2.

The embodiments disclosed herein can include waveforms structured as hierarchical waveforms that include waveform elements / pulses at various levels of the hierarchy. Individual pulses, such as (2200) in FIG. 22, include the first level of the hierarchy and have a related pulse duration and a first time interval between consecutive pulses. The set of pulses, or elements of the first level structure, form a second level in the hierarchy, such as the group of pulses / second set of pulses (2210) in FIG. Other parameters associated with the waveform include the total duration of the second set of pulses (not shown), the total number of first level elements / first set of pulses, and the second level structure. / There is a second time interval between successive first level elements that describe the second set of pulses, and so on. In some embodiments, the total duration of the second set of pulses can be between about 20 microseconds and about 10 ms, including all values and subranges in between. Elements of a set of groups, a second set of pulses, or a second level structure form a third level in a hierarchy, such as a third set of packets / pulses (2220) in FIG. 22. Among other parameters, the total duration of the third set of pulses (not shown), the total number of the second set of second level elements / pulses, and the third level structure / third of the pulses. There is a third time interval between consecutive second level elements that describe the set, and so on. In some embodiments, the total duration of the third set of pulses may be between about 60 microseconds and about 200 ms, including all values and subranges in between. The general repeating or nested structure of the waveform can continue at higher multiple levels, such as structures of 10 levels or higher.

In some embodiments, the hierarchical waveforms with nested structures and time interval hierarchies described herein are useful for irreversible electroporation ablation energy delivery and with sufficient control for use in different tissue types. Provides selectivity. Various layered waveforms can be generated using a suitable pulse generator. In the examples herein, monophasic and biphasic waveforms are individually identified for clarity, but some combined waveforms are monophasic in part of the waveform hierarchy and biphasic in other parts. Please understand that it can be generated / implemented.

In some embodiments, the ablation pulse waveforms described herein are applied during the refractory period of the cardiac cycle to avoid disruption of cardiac sinus rhythm. In some embodiments, the procedure involves electrically pacing the heart with a cardiac stimulator to ensure pacing capture, establishing the periodicity and predictability of the cardiac cycle, and then one or more pulses. It involves defining a time window within the refractory period within the cardiac cycle in which the ablation waveform can be delivered. FIG. 25 shows an example where both atrial pacing and ventricular pacing are applied (eg, using pacing leads or catheters located in the right atrium and right ventricle, respectively). With time on the horizontal axis, FIG. 25 shows a series of ventricular pacing signals such as (2500) and (2510), and a series of ECG waveforms driven by a series of atrial pacing signals (2520, 2530). It is shown together with (2540, 2542). As shown by the thick arrows in FIG. 25, there is an atrial refractory time window (2522) and a ventricular refractory time window (2502) following the atrial pacing signal (2522) and the ventricular pacing signal (2500), respectively. As shown in FIG. 25, the period _{T r} common refractory time window (2550) may be defined to be within both the atrial and ventricular refractory time window (2522,2502). In some embodiments, an electroporation ablation waveform (s) can be applied to this common refractory time window (2550). The start of this refractory time window (2522) is offset from the pacing signal (2500) by a time offset (2504), as shown in FIG. In some embodiments, the time offset (2504) may be less than about 25 ms. In the next heartbeat, a similarly defined common refractory time window (2552) is the next time window that can be used to apply the ablation waveform. In this way, the ablation waveform (s) are applied over a series of heartbeats, each heartbeat staying within a common refractory time window. In one embodiment, each packet of pulses defined above in the pulse waveform hierarchy can be applied over a heartbeat, such that a series of packets is applied over a series of heartbeats for a given set of electrodes.

It should be understood that the examples and illustrations in the present disclosure serve exemplary purposes and that deviations and variations such as the number of splines, the number of electrodes, etc. can be constructed and developed in accordance with the present teachings without departing from the scope of the invention.

As used herein, the terms "about" and / or "approximately" when used in conjunction with numbers and / or ranges generally refer to numbers and / or ranges that are close to the numbers and / or ranges listed. Point to. In some cases, the terms "about" and "approximately" may mean within ± 10% of the stated value. For example, in some cases, "about 100 [units]" may mean within ± 10% of 100 (eg, 90-110). The terms "about" and "approximately" may be used interchangeably.

Some embodiments described herein are computers with non-transient computer-readable media (also referred to as non-transient processor-readable media) that carry instructions or computer code to perform various computer-implemented operations. Regarding storage products. Computer-readable media (or processor-readable media) are non-transient in the sense that they themselves do not contain transient propagating signals (eg, propagating electromagnetic waves that carry information over transmission media such as space and cables). Media and computer code (also called code or algorithms) are designed and built for specific purposes. Examples of non-temporary computer-readable media include magnetic storage media such as hard disks, floppy disks, and magnetic tapes, optical storage media such as compact discs / digital video discs (CD / DVD), and compact disc read-only memory (CD-. ROM), holographic devices, optical magnetic storage media such as optical disks, carrier signal processing modules, application-specific integrated circuits (ASIC), programmable logic devices (PLD), read-only memory (ROM), random access memory. Includes, but is not limited to, hardware devices specifically configured to store and execute program code, such as (RAM) devices. Other embodiments described herein relate to, for example, computer program products that may include instructions and / or computer code disclosed herein.

The systems, devices, and / or methods described herein may be performed by software (running on hardware), hardware, or a combination thereof. Hardware modules may include, for example, general purpose processors (or microprocessors or microcontrollers), field programmable gate arrays (FPGAs), and / or application specific integrated circuits (ASICs). Software modules (running on hardware) include C, C ++, Java®, Ruby, Visual Basic®, and / or other object-oriented, procedural, or other programming languages and development tools. It can be expressed in various software languages including (eg, computer code). Examples of computer code include microcode or microinstructions, machine instructions such as those generated by a compiler, code used to generate web services, and high-level instructions executed by a computer that uses an interpreter. Includes, but is not limited to. Other examples of computer code include, but are not limited to, control signals, encryption codes, and compression codes.

The specific examples and descriptions herein are exemplary in nature and will be appreciated by those skilled in the art on the basis of the materials taught herein without departing from the scope of the invention, which is limited solely by the appended claims. Can develop embodiments.

The embodiments described above have the features described in the following appendices.
(Appendix 1)
It ’s a device,
A first catheter that defines the longitudinal axis and the lumen through it,
A second catheter extending from the distal end of the first catheter lumen,
A set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline being a respective spline. Includes a set of splines, including a set of electrodes formed on the surface of the spline, each electrode having an insulated wire associated with it, the insulating wire being disposed on each body of the set of splines. ,
The second catheter is configured to translate along the longitudinal axis to transition between the first and second configurations.
In the first configuration, the set of splines is generally parallel to the longitudinal axis.
In the second configuration, an apparatus in which at least a portion of each spline in the set of splines extends distal to the distal end of the second catheter.

(Appendix 2)
It ’s a device,
A first catheter that defines the longitudinal axis and the lumen through it,
A second catheter extending from the distal end of the first catheter lumen,
A set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline being a respective spline. Includes a set of splines, including a set of electrodes formed on the surface of the spline, each electrode having an insulated wire associated with it, the insulating wire being disposed on each body of the set of splines. ,
The second catheter is configured to translate along the longitudinal axis to transition between the first and second configurations.
In the first configuration, the set of splines is generally parallel to the longitudinal axis.
In the second configuration, each spline in the set of splines has a longitudinal axis in the second configuration having an angle of less than about 80 degrees with respect to the longitudinal axis of the first catheter. apparatus.

(Appendix 3)
It ’s a device,
A first catheter that defines the longitudinal axis and the lumen through it,
A second catheter extending from the distal end of the first catheter lumen,
A set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline being a respective spline. Includes a set of splines, including a set of electrodes formed on the surface of the spline, each electrode having an insulated wire associated with it, the insulating wire being disposed on each body of the set of splines. ,
The second catheter is configured to translate along the longitudinal axis to transition between the first and second configurations.
In the first configuration, the set of splines is generally in close proximity to the longitudinal axis.
In the second configuration, each spline in the set of splines forms a loop and is twisted along its length so that the spline has torsion along its length. ,apparatus.

(Appendix 4)
The device according to Appendix 3, wherein each spline in the set of splines is petal-shaped.

(Appendix 5)
The rotational speed is the unit such that each spline in the set of splines has a local unit tangential vector and a rotational speed, and the rotational speed integrated along the length of the spline is at least π radians. The device according to Appendix 3, defined by a derivative of the arc length of the tangent vector.

(Appendix 6)
The device of Appendix 5, wherein the curve geometry defined by at least one spline is the geometry of a spatial curve with torsion.

(Appendix 7)
The second configuration, wherein at least one electrode of each spline in the set of splines is distal to the distal end of the second catheter, according to any one of Appendix 1-3. Equipment.

(Appendix 8)
The device according to any one of Appendix 1-3, wherein the proximal portion of the set of splines is coupled to the first catheter within the lumen of the first catheter.

(Appendix 9)
Appendix 1 The second catheter defines a lumen through which the distal portion of the set of splines is coupled to the second catheter within the second catheter lumen. The device according to any one of ~ 3.

(Appendix 10)
The device according to any one of Supplementary notes 1 to 3, wherein in the second configuration, each spline in the set of splines does not overlap the adjacent spline.

(Appendix 11)
The device according to any one of Supplementary notes 1 to 3, wherein the set of splines bends outward in the radial direction from the longitudinal axis in the second configuration.

(Appendix 12)
The device according to any one of Appendix 1-3, wherein the set of splines is urged away from the longitudinal axis in the second configuration.

(Appendix 13)
It further comprises a set of splines and an actuator coupled to the second catheter, which is configured to transfer the set of splines between the first configuration and the second configuration. , The apparatus according to any one of Appendix 1 to 3.

(Appendix 14)
The device according to any one of Appendix 1-3, wherein the set of electrodes on adjacent splines has opposite polarities.

(Appendix 15)
13. apparatus.

(Appendix 16)
The device according to any one of Appendix 1-3, wherein the set of splines comprises 3 to 14 splines.

(Appendix 17)
The device according to any one of Appendix 1-3, wherein each spline in the set of splines has a diameter of about 1 mm to about 5 mm.

(Appendix 18)
The device according to any one of Appendix 1 to 3, wherein each electrode in the set of electrodes has a diameter of about 1 mm to about 5 mm.

(Appendix 19)
The insulated conductors are disposed on the body of the second catheter, and the insulated conductors are configured such that the corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. The device according to any one of 3.

(Appendix 20)
It ’s a system,
With a signal generator configured to generate a pulse waveform,
The ablation device comprises an ablation device coupled to the signal generator and configured to receive the pulse waveform.
A first catheter that defines the longitudinal axis and the lumen through it,
A second catheter extending from the distal end of the first catheter lumen,
The handle attached to the second catheter and
A set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline being a respective spline. Includes a set of splines, including a set of electrodes formed on the surface of the spline, each electrode having an insulated wire associated with it, the insulating wire being disposed on each body of the set of splines. ,
The second catheter is configured to translate along the longitudinal axis to transition between the first and second configurations.
In the first configuration, the set of splines is generally in close proximity to the longitudinal axis.
In the second configuration, a system in which at least a portion of each spline in the set of splines extends distal to the distal end of the second catheter.

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

(Appendix 22)
20. The system of Appendix 20, wherein the proximal portion of the set of splines is coupled to the first catheter within the lumen of the first catheter.

(Appendix 23)
Appendix 20. The second catheter defines a lumen through which the distal portion of the set of splines is coupled to the second catheter within the second catheter lumen. The system described in.

(Appendix 24)
20. The system of Appendix 20, wherein in the second configuration, each spline in the set of splines does not overlap adjacent splines.

(Appendix 25)
20. The system of Appendix 20, wherein the set of splines flexes radially outward from the longitudinal axis in the second configuration.

(Appendix 26)
20. The system of Appendix 20, wherein the set of splines is urged away from the longitudinal axis in the second configuration.

(Appendix 27)
It further comprises a set of splines and an actuator coupled to the second catheter, which is configured to transfer the set of splines between the first configuration and the second configuration. , The system according to Appendix 20.

(Appendix 28)
20. The system of Appendix 20, wherein the set of electrodes on adjacent splines has opposite polarities.

(Appendix 29)
The system according to Appendix 20, wherein the set of splines forms a shape having an effective cross-sectional diameter of about 10 mm to about 35 mm in maximum cross-section when deployed in the second configuration.

(Appendix 30)
20. The system of Appendix 20, wherein the set of splines comprises 3 to 14 splines.

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

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

(Appendix 33)
The insulating conductor is disposed on the body of the second catheter, and the insulating conductor is configured to maintain a potential of at least about 700 V without dielectric breakdown of the corresponding insulation, see Appendix 20. Described system.

(Appendix 34)
The pulse waveform is
The pulse waveform at the first level of the hierarchy of the pulse waveform containing the first set of pulses, where each pulse has a pulse duration and the first time interval separates successive pulses. The first level of the hierarchy and
A second level of the hierarchy of said pulse waveforms that includes a first set of multiple pulses as a second set of pulses, with a second time interval separating the first set of contiguous pulses. The second level of the layer of the pulse waveform, wherein the second time interval is at least three times the period of the first time interval.
A third level of the hierarchy of said pulse waveforms that includes a second set of multiple pulses as a third set of pulses, with a third time interval separating the second set of contiguous pulses. 20. The system of Appendix 20, wherein the third time interval is at least thirty times the duration of the second time interval, including a third level of the hierarchy of the pulse waveform.

(Appendix 35)
It is a treatment method for cardiac arrhythmia by irreversible electroporation.
The ablation device is advanced into the patient's left atrium.
A first catheter that defines the longitudinal axis and the lumen through it,
A second catheter extending from the distal end of the first catheter lumen,
A set of splines having a proximal portion coupled to the distal end of the first catheter lumen and a distal portion coupled to the distal end of the second catheter, each spline being a respective spline. Includes a set of electrodes formed on the surface of the spline, each electrode having an insulated wire associated with it, the insulated wire being disposed on each fuselage of the set of splines, and a set of splines. ,
In the first configuration, the set of splines is generally in close proximity to the longitudinal axis.
In the second configuration, advancing the ablation device, in which at least a portion of each spline in the set of splines extends distally to the distal end of the second catheter.
Moving the ablation device from the first configuration to the second configuration
Generating a set of pulse waveforms and
The set of pulse waveforms is delivered to a set of adjacent portions of the posterior wall of the left atrium via one or more splines of the set of splines of the ablation device in the second configuration of the ablation zone. Methods, including forming a set.

(Appendix 36)
In the second configuration, each spline in the set of splines forms a loop and is twisted along its length so that the spline has a torsion along its length. The method according to Appendix 35.

(Appendix 37)
In the second configuration, each spline in the set of splines has the longitudinal axis in a second configuration having an angle of less than about 80 degrees with respect to the longitudinal axis of the first catheter. The method according to Appendix 35.

(Appendix 38)
The rotational speed relates to the arc length of the unit tangent vector such that each spline in the set of splines has a rotational speed and the rotational speed integrated along the length of the spline is at least π radians. 35. The method of Appendix 35, defined by the derivative.

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

(Appendix 40)
It further comprises advancing at least a portion of the set of splines distal to the distal end of the second catheter by retracting the second catheter relative to the first catheter. , The method according to Appendix 35.

(Appendix 41)
35. The method of Appendix 35, wherein each insulating conductor is configured such that its corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown.

(Appendix 42)
The set of splines comprises a group of electrodes, the group of electrodes comprises a set of the electrodes of each spline of the set of splines, the method.
The first electrode of the group of electrodes is configured as an anode, and
The second electrode of the group of electrodes is configured as a cathode, and
35. The method of Appendix 35, comprising delivering the pulse waveform to the first electrode and the second electrode.

(Appendix 43)
The configuration of the first set of electrodes of the first spline of the set of splines as an anode and
A second set of electrodes of the second spline of the set of splines is configured as a cathode.
35. The method of Appendix 35, comprising delivering the pulse waveform to a first set of electrodes and a second set of electrodes.

(Appendix 44)
The device according to Appendix 1, wherein each spline in the set of splines is petal-shaped.

(Appendix 45)
The device according to Appendix 2, wherein each spline in the set of splines is petal-shaped.

(Appendix 46)
It ’s a device,
An outer catheter that defines the longitudinal axis and the lumen through it,
A set of catheters, each extending from the distal end of the lateral catheter lumen, each catheter having a proximal portion, a distal portion, and a hinge connecting the proximal portion to the distal portion. The distal portion of each catheter comprises an electrode such that the set of catheters comprises a set of electrodes so that each catheter of the set of catheters translates along the longitudinal axis. It comprises a set of catheters configured to transition between one configuration, a second configuration, and a third configuration.
In the first configuration, each catheter in the set of catheters is generally parallel to the longitudinal axis.
In the second configuration, each catheter in the set of catheters is urged away from the longitudinal axis.
In the third configuration, a device in which the distal portion of each catheter in the set of catheters rotates around its corresponding hinge.

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

(Appendix 48)
Insulated conductors are associated with the first and second electrodes, the insulated conductors are disposed on the fuselage of the first and second catheters, and the insulated conductors do not undergo dielectric breakdown of their corresponding insulation. 47. The apparatus of Appendix 47, which is configured to maintain a potential of at least about 700 V.

(Appendix 49)
46. The device of Appendix 46, wherein the distal portion of each catheter in the set of catheters is urged away from the longitudinal axis in the second configuration.

(Appendix 50)
46. The device of Appendix 46, wherein the first and second electrodes are urged toward each other in the third configuration.

(Appendix 51)
In the third configuration, the proximal portion of each catheter is urged away from the longitudinal axis and each electrode in the set of electrodes is urged towards the longitudinal axis. The device described in.

(Appendix 52)
46. The device of Appendix 46, wherein the proximal portion of each catheter in the set of catheters has a radius of curvature of about 1 cm or more.

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

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

(Appendix 55)
46. The apparatus of Appendix 46, wherein the distance between the distal portions of each catheter in the set of catheters in the third configuration is from about 1 mm to about 7 mm.

(Appendix 56)
46. The device of Appendix 46, wherein each catheter comprises a wire coupled to the hinge.

(Appendix 57)
46. The device of Appendix 46, wherein the set of catheters comprises 2-4 catheters.

(Appendix 58)
46. The device of Appendix 46, wherein the set of catheters comprises 3 to 6 catheters.

(Appendix 59)
58. The apparatus of Appendix 58, wherein the proximal portion of each catheter in the set of catheters has a radius of curvature of about 1 cm or more.

(Appendix 60)
It ’s a device,
An outer catheter that defines the longitudinal axis and the lumen through it,
A catheter that extends from the distal end of the lateral catheter lumen, wherein the catheter connects the proximal portion, the distal portion set, and the proximal portion to the distal portion set.
Each set of distal portions comprises a set of hinges, each comprising a catheter, comprising an electrode and defining a set of electrodes.
The catheter is configured to translate along the longitudinal axis to transition between the first configuration, the second configuration, and the third configuration.
In the first configuration, the set of distal portions is generally parallel to the longitudinal axis.
In the second configuration, each electrode in the set of electrodes advances away from the distal end of the lateral catheter lumen.
In the third configuration, a device configured such that each electrode in the set of electrodes is urged away from the longitudinal axis.

(Appendix 61)
60. The device of Appendix 60, wherein the electrodes in opposite distal portions have opposite polarities.

(Appendix 62)
An insulated wire is associated with each electrode in the set of electrodes, the insulated wire is disposed on the body of the catheter, and the insulated wire maintains a potential of at least about 700 V without dielectric breakdown of its corresponding insulation. 60. The apparatus according to Appendix 60, which is configured to do so.

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

(Appendix 64)
60. The device of Appendix 60, wherein the one or more distal portions are naturally urged so that they are substantially perpendicular to the longitudinal axis in the third configuration.

(Appendix 65)
It is a focal ablation method by irreversible electroporation.
Generating pulse waveforms and
Each catheter comprises delivering the pulse waveform to the patient's heart tissue via a set of electrodes in a set of catheters for the ablation device.
A method comprising a proximal portion, a distal portion, and a hinge connecting the proximal portion to the distal portion.

(Appendix 66)
To advance the set of catheters disposed within the lumen of the lateral catheter away from the distal end of the lateral catheter.
65. The method of Appendix 65, further comprising rotating each distal portion of the set of catheters around its corresponding hinge.

(Appendix 67)
65. The method of Appendix 65, further comprising disposing the ablation device in contact with the pulmonary vein opening in the intracardiac lumen of the left atrium of the heart.

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

(Appendix 69)
An insulating lead is associated with each electrode in the set of electrodes, the insulated lead is placed on the body of the catheter, and each insulated lead maintains a potential of at least about 700 V without dielectric breakdown of its corresponding insulation. 65. The method of Appendix 65, which is configured to do so.

(Appendix 70)
It ’s a device,
A catheter shaft that defines the longitudinal axis and the shaft lumen through it,
A set of splines extending from the distal end of the shaft cavity, each spline containing a set of independently addressable proximal electrodes formed on each surface of the spline, at each electrode. A set of splines, wherein an insulated wire is associated and the insulated wire is disposed on each fuselage of the one or more splines.
With a distal cap coupled to the distal portion of each spline in the set of splines, the distal cap comprises an independently addressable distal electrode formed on the surface of the distal cap. The set of splines is configured to translate along the longitudinal axis to transition between the first and second configurations, with the distal electrodes generally perpendicular to the longitudinal axis. A device that is disposed on the distal end face of the second configuration, wherein the set of proximal electrodes is disposed outside the distal end face.

(Appendix 71)
The device according to Appendix 70, wherein the distal electrode has a polarity opposite to that of at least one proximal electrode in the set of proximal electrodes.

(Appendix 72)
The set of splines flexes radially outward from the longitudinal axis in the second configuration, and the set of splines is arranged generally parallel to the longitudinal axis in the first configuration. The device according to Appendix 70.

(Appendix 73)
The device according to Appendix 70, wherein the insulated conductor is configured such that its corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown.

(Appendix 74)
The device of Appendix 70, wherein the set of electrodes on adjacent splines has opposite polarities.

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

(Appendix 76)
The apparatus according to Appendix 70, wherein each electrode in the set of electrodes has a length of about 0.5 mm to about 5.0 mm and a cross-sectional diameter of about 0.5 mm to about 2.5 mm.

(Appendix 77)
The device according to Appendix 70, wherein the distance between the distal electrode and the distal end of the distal cap is from about 1.0 mm to about 4.0 mm.

(Appendix 78)
It ’s a device,
A catheter shaft that defines the longitudinal axis and the shaft lumen through it,
A set of splines extending from the distal end of the shaft cavity, wherein each spline comprises a set of independently addressable electrodes formed on the respective surface of the one or more splines. Each electrode in a set of electrodes comprises a set of splines, wherein the insulated conductor is associated with each of the fuselage of the one or more splines.
The set of splines is configured to translate along the longitudinal axis to transition between the first configuration and the second configuration, and the set of splines in the first configuration A device that is generally parallel to the longitudinal axis and the distal end of the set of splines in the second configuration is urged away from the longitudinal axis.

(Appendix 79)
The device according to Appendix 78, wherein each spline in the set of splines has a radius of curvature of about 1 cm or more.

(Appendix 80)
The device of Appendix 78, wherein each spline in the set of splines has a radius of curvature that increases monotonically.

(Appendix 81)
The device according to Appendix 78, wherein each spline in the set of splines is configured to translate independently along the longitudinal axis.

(Appendix 82)
58. The apparatus of Appendix 78, wherein the distal end of each spline in the set of splines is configured to extend from about 8.0 mm to about 20.0 mm from the distal end of the shaft lumen.

(Appendix 83)
The device of Appendix 78, wherein the distal end of each spline in the set of splines is configured to extend up to about 5 cm from the distal end of the shaft lumen.

(Appendix 84)
The device according to Appendix 78, wherein the insulated conductor is configured such that its corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown.

(Appendix 85)
The device according to Appendix 78, wherein the distance between the distal ends of the set of splines in the second configuration is from about 5.0 mm to about 20.0 mm.

(Appendix 86)
The device of Appendix 78, wherein the distal electrode of each spline in the set of splines has the opposite polarity of the corresponding proximal electrode.

(Appendix 87)
It ’s a device,
A catheter shaft that defines the longitudinal axis and the shaft lumen through it,
A set of splines extending from the distal end of the shaft cavity, each spline comprising a set of proximal electrodes formed on the respective surface of the one or more splines, of said proximal electrode. A set of splines, wherein an insulating wire is associated with each electrode of the set and the insulating wire is disposed on each fuselage of the one or more splines.
The set of splines comprises a distal cap coupled to the distal portion of each spline of the set of splines, the distal cap comprising at least one independently addressable distal electrode, and the set of splines is the first. The set of splines in the first configuration is configured to translate along the longitudinal axis to transition between the first configuration and the second configuration with respect to the longitudinal axis. A device that is generally parallel and in which the set of splines in the second configuration flex outward radially outward from the longitudinal axis.

(Appendix 88)
The device according to Appendix 87, wherein the at least one distal electrode has the opposite polarity to at least one electrode in the set of proximal electrodes for each spline in the set of splines.

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

(Appendix 90)
87. The device of Appendix 87, wherein the set of proximal electrodes on adjacent splines has opposite polarities.

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

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

(Appendix 93)
87. The apparatus of Appendix 87, wherein the distance between the at least one distal electrode and the set of proximal electrodes is from about 3.0 mm to about 12.0 mm.

(Appendix 94)
The device according to Appendix 87, wherein the distance between the at least one distal electrode and the distal end of the distal cap is from about 1.0 mm to about 4.0 mm.

(Appendix 95)
It is a treatment method for cardiac arrhythmia by irreversible electroporation.
Generating pulse waveforms and
Each spline comprises delivering the pulse waveform to a portion of the ventricular wall of the patient's heart by one or more splines of a set of splines in the ablation device.
A method comprising a set of electrodes formed on the surface of the spline, each electrode of the set of electrodes being associated with an insulating wire, the insulating wire being disposed on the body of the spline.

(Appendix 96)
95. The method of Appendix 95, further comprising disposing the ablation device in contact with the pulmonary vein opening in the intracardiac lumen of the left atrium of the heart.

(Appendix 97)
25. The method of Appendix 95, wherein each insulating conductor is configured such that its corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown.

(Appendix 98)
The set of splines comprises a group of electrodes, the group of electrodes comprises a set of the electrodes of each spline of the set of splines, the method.
The first electrode of the group of electrodes is configured as an anode, and
The second electrode of the group of electrodes is configured as a cathode, and
95. The method of Appendix 95, comprising delivering the pulse waveform to the first electrode and the second electrode.

(Appendix 99)
The configuration of the first set of electrodes of the first spline of the set of splines as an anode and
A second set of electrodes of the second spline of the set of splines is configured as a cathode.
95. The method of Appendix 95, comprising delivering the pulse waveform to a first set of electrodes and a second set of electrodes.

(Appendix 100)
It ’s a device,
A catheter that defines the longitudinal axis and
A set of splines coupled to the catheter, where each spline in the set of splines contains a set of electrodes formed on the spline, each set of electrodes is a set of splines that sets a set of distal electrodes. With a set of splines, including a distal electrode with an exposed portion, to include,
With a cap electrode formed at the distal end of the catheter, each distal electrode is closest to the cap electrode as compared to the other electrodes in its corresponding set of electrodes on the same spline. Each distal electrode of the cap electrode and each set of the distal electrodes has the same electrical polarity during use, and the set of splines translates along the longitudinal axis.
The first configuration, wherein the set of splines is substantially parallel to the longitudinal axis.
In the second configuration, the distal portion of each spline in the set of splines flexes radially outward from the longitudinal axis, and the cap electrode is from each distal electrode in the set of distal electrodes. A device configured to transition between and a second configuration, up to about 3 mm apart.

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

(Appendix 102)
The device according to Appendix 100, wherein each of the exposed portions of the distal electrode faces outward as viewed from the longitudinal axis in the first configuration.

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

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

(Appendix 105)
The device according to Appendix 100, wherein the cap electrode has a cross-sectional diameter of about 1 mm to about 5 mm.

(Appendix 106)
Addendum 100, wherein each set of electrodes has a set of proximal electrodes, said distal electrode, and said set of proximal electrodes for a given spline having opposite electrical polarities for ablation delivery. apparatus.

(Appendix 107)
The device according to Appendix 100, wherein the cap electrode and the set of the distal electrodes are collectively configured as an anode.

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

(Appendix 109)
The apparatus according to Appendix 100, wherein the set of splines forms a shape having an effective cross-sectional diameter of about 6 mm to about 24 mm at the maximum portion when deployed in the second configuration.

(Appendix 110)
The device of Appendix 100, further comprising an outer shaft defining a lumen through which the set of splines extends from about 6 mm to about 30 mm from the distal end of the lumen.

(Appendix 111)
The device according to Appendix 100, wherein the insulated conductor is configured such that its corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown.

(Appendix 112)
The device according to Appendix 100, wherein the cap electrode can be addressed independently.

(Appendix 113)
The device according to Appendix 100, wherein the cap electrode and each electrode in the set of electrodes can be addressed independently.

(Appendix 114)
The device of Appendix 100, wherein an insulating wire is associated with each electrode in the set of electrodes, and the insulating wire is disposed on each fuselage of the one or more splines.

(Appendix 115)
It ’s a device,
A catheter that defines the longitudinal axis and
A set of splines coupled to the catheter, wherein each spline in the set of splines contains a set of electrodes formed on the spline, and each set of electrodes is a set of splines that comprises a set of distal electrodes. The exposed portion of each distal electrode in the set of distal electrodes comprises a distal electrode having an exposed portion, such as about 30 degrees to about 300 degrees around the center of its corresponding spline. A set of splines that make an angle to the spline,
With a cap electrode formed at the distal end of the catheter, the set of splines translates along the longitudinal axis.
A first configuration, wherein the set of splines is generally parallel to the longitudinal axis.
A second configuration is configured such that the distal portion of each spline in the set of splines transitions between a second configuration that flexes radially outward from the longitudinal axis. ,apparatus.

(Appendix 116)
The device of Appendix 115, wherein the cap electrode is up to about 3 mm away from each distal electrode in the set of distal electrodes.

(Appendix 117)
The device of Appendix 115, wherein each distal electrode in the set of distal electrodes partially surrounds the outer circumference of its corresponding spline.

(Appendix 118)
11. The apparatus of Appendix 115, wherein each of the exposed portions of the set of distal electrodes faces outward as viewed from the longitudinal axis in the first configuration.

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

(Appendix 120)
The device according to Appendix 115, wherein the cap electrode has a cross-sectional diameter of about 1 mm to about 5 mm.

(Appendix 121)
Addendum 115, wherein each set of electrodes has a set of proximal electrodes, said distal electrode, and said set of proximal electrodes for a given spline having opposite electrical polarities during ablation energy delivery. apparatus.

(Appendix 122)
The device according to Appendix 115, wherein the cap electrode and the set of the distal electrodes are collectively configured as an anode.

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

(Appendix 124)
The device according to Appendix 115, wherein the set of splines forms a shape having an effective cross-sectional diameter of about 6 mm to about 24 mm in the maximum section when deployed in the second configuration.

(Appendix 125)
The device of Appendix 115, further comprising an outer shaft defining a lumen through which the set of splines extends from about 6 mm to about 24 mm from the distal end of the lumen.

(Appendix 126)
The device according to Appendix 115, wherein the insulated conductor is configured to maintain a potential of at least about 700 V without dielectric breakdown of its corresponding insulation.

(Appendix 127)
The device according to Appendix 115, wherein the cap electrodes can be addressed independently.

(Appendix 128)
The device according to Appendix 115, wherein the cap electrode and each electrode in the set of electrodes can be addressed independently.

(Appendix 129)
The device of Appendix 115, wherein an insulating wire is associated with each electrode in the set of electrodes, and the insulating wire is disposed on each fuselage of the one or more splines.

(Appendix 130)
It ’s a device,
A catheter shaft that defines the longitudinal axis,
A set of splines coupled to the catheter shaft, where each spline in the set of splines contains a set of electrodes formed on the spline, each set of electrodes is a set of the set of splines is a set of distal electrodes. With a set of splines, including the distal electrodes,
With a cap electrode formed at the distal end of the catheter, the set of splines translates along the longitudinal axis.
A first configuration, wherein the set of splines is generally parallel to the longitudinal axis.
In the second configuration, the distal portion of each spline in the set of splines flexes radially outward from the longitudinal axis, and the cap electrode is from each distal electrode in the set of distal electrodes. A maximum of about 3 mm apart so that the distal portion of each spline in the set of splines transitions between a second configuration, which is at an angle of about 60 to about 90 degrees with respect to the longitudinal axis. The device, which is configured in.

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

(Appendix 132)
It ’s a device,
A catheter shaft that defines the longitudinal axis and the shaft lumen through it,
A set of splines that extends from the distal end of the shaft lumen, wherein each spline in the set of splines contains a set of electrodes formed on the surface of the spline.
With a distal cap coupled to the distal portion of each spline in the set of splines, the set of splines translates along the longitudinal axis to form a first configuration and a second configuration. The first configuration comprises the distal cap coupled to the distal end of the catheter shaft at a first distance, the second configuration being said of said catheter shaft. A device comprising the distal cap coupled to the distal end at a second distance, wherein the ratio of the first distance to the second distance is about 5: 1 to about 25: 1.

(Appendix 133)
It ’s a device,
A catheter shaft that defines the longitudinal axis and the shaft lumen through it,
A set of splines that extends from the distal end of the shaft lumen, wherein each spline in the set of splines contains a set of electrodes formed on the surface of the spline.
With a distal cap coupled to the distal portion of each spline of the set of splines, the set of splines translates along the longitudinal axis to form a first configuration and a second configuration. In the first configuration, each spline is on a cylindrical surface that is generally parallel to the longitudinal axis of the catheter shaft, and in the second configuration, of the set of splines. A device in which at least a portion of each spline has a radius of curvature of about 7 mm to about 25 mm.

(Appendix 134)
It ’s a device,
A catheter shaft that defines the longitudinal axis and the shaft lumen through it,
A set of splines that extends from the distal end of the shaft lumen, wherein each spline in the set of splines contains a set of electrodes formed on the surface of the spline.
With a distal cap coupled to the distal portion of each spline of the set of splines, the set of splines translates along the longitudinal axis to form a first configuration and a second configuration. In the first configuration, each spline is substantially in a plane intersecting the longitudinal axis of the catheter shaft, and in the second configuration, each spline is configured to transition between. On the first concave curved surface facing the distal cap and on the longitudinal axis
A device for forming a loop having a facing second concave curved surface and a third concave curved surface facing the distal end of the shaft lumen.

(Appendix 135)
The device according to any one of Supplementary 132, 185, 198, and 208, wherein the first configuration comprises a set of the splines arranged to rotate spirally around the longitudinal axis. ..

(Appendix 136)
The device of Appendix 135, wherein each spline in the set of splines has a nonzero helix angle of less than about 5 degrees.

(Appendix 137)
The device of Appendix 135, wherein each spline in the set of splines has a nonzero helix angle of less than about 2 degrees.

(Appendix 138)
The device of Appendix 135, wherein each spline in the set of splines has a nonzero helix angle of less than about 1 degree.

(Appendix 139)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines in the second configuration is arranged as a set of non-overlapping loops.

(Appendix 140)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines in the second configuration is arranged as a set of electrically isolated loops.

(Appendix 141)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines in the second configuration comprises a radius of curvature that varies along the length of the spline.

(Appendix 142)
The set of splines in the second configuration is configured to abut against the tissue wall, and the set of electrodes in at least two of the splines has the strength of the electric field lines and the strength of the electric field with respect to the tissue wall. Addendum 132, 185, 198, and 208, configured to generate an electric field composed of tangential components, wherein the tangent component exceeds half of the strength in most of the tissue wall between the at least two splines. The device according to any one of.

(Appendix 143)
The description in any one of Appendix 132, 185, 198, and 208, wherein each spline in the set of splines in the second configuration is urged up to about 30 mm away from the longitudinal axis. apparatus.

(Appendix 144)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines in the second configuration has a diameter of about 10 mm to about 50 mm.

(Appendix 145)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines in the second configuration has a diameter of about 25 mm to about 3 mm.

(Appendix 146)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines in the second configuration has a diameter of about 30 mm.

(Appendix 147)
32. One of Appendix 132, 185, 198, and 208, wherein the set of splines and the distal cap are configured to translate together up to about 60 mm along the longitudinal axis. apparatus.

(Appendix 148)
The device according to any one of Appendix 132, 185, 198, and 208, wherein each of the distal portions of the set of splines is secured to the distal cap.

(Appendix 149)
The device according to any one of Appendix 132, 185, 198, and 208, wherein each spline in the set of splines in the second configuration comprises an elliptical cross section.

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

(Appendix 151)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines comprises 3 to 20 splines.

(Appendix 152)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines comprises five splines.

(Appendix 153)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines comprises eight splines.

(Appendix 154)
Each spline in the set of splines is about 0.2 mm ² ~ About 15mm ² The device according to any one of Appendix 132, 185, 198, and 208, which has a cross-sectional area of.

(Appendix 155)
The device according to any one of Appendix 132, 185, 198, and 208, wherein each spline in the set of splines defines a spline lumen therein.

(Appendix 156)
155, wherein an insulating lead is associated with the set of electrodes for each spline in the set of splines, and the insulated lead is disposed within the spline lumen of each spline in the set of splines. Equipment.

(Appendix 157)
The device according to Appendix 155, wherein the insulated conductor is configured such that its corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown.

(Appendix 158)
Addendum 132, wherein the set of electrodes for each spline in the set of splines comprises at least one electrode configured for ablation and at least one electrode configured to receive an ECG signal. 185, 198, and 208.

(Appendix 159)
158. The apparatus of Appendix 158, wherein at least one electrode configured for the ablation and at least one electrode configured to receive the ECG signal are coupled to separate the insulated conductor.

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

(Appendix 161)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of electrodes for each spline in the set of splines is coupled to a corresponding insulating wire.

(Appendix 162)
The spline of the set of splines in the second configuration according to any one of Appendix 132, 185, 198, and 208, wherein each spline contains a vertex with respect to the longitudinal axis.
apparatus.

(Appendix 163)
The device according to Appendix 162, wherein the set of electrodes is unevenly distributed with respect to the apex of each spline in the set of splines.

(Appendix 164)
162. The device of Appendix 162, wherein the set of electrodes is distributed proximally and distally to the apex in a ratio of 1: 3.

(Appendix 165)
162. The device of Appendix 162, wherein the set of electrodes is distributed proximally and distally to the apex in a ratio of 1: 2.

(Appendix 166)
162. The device of Appendix 162, wherein the set of electrodes is distributed proximally and distally to the apex in a ratio of 2 to 3.

(Appendix 167)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of electrodes for each spline is connected and wired.

(Appendix 168)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of electrodes for each spline is routed in series.

(Appendix 169)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of electrodes comprises a non-invasive shape.

(Appendix 170)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of electrodes comprises an elliptical cross section.

(Appendix 171)
The apparatus according to Appendix 170, wherein the elliptical cross section comprises a major axis length of about 1 mm to about 4 mm and a minor axis length of about 0.4 mm to about 3 mm.

(Appendix 172)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of electrodes comprises 2 electrodes to 64 electrodes.

(Appendix 173)
Each electrode in the set of electrodes is about 0.5 mm ² ~ About 20mm ² The device according to any one of Appendix 132, 185, 198, and 208, which has a surface area of.

(Appendix 174)
The first set of electrodes of the first spline of the set of splines is configured as the anode and the second set of electrodes of the second spline of the set of splines is configured as the cathode, Appendix 132, 185, 198, and 208.

(Appendix 175)
174. The device of Appendix 174, wherein the first spline is not adjacent to the second spline.

(Appendix 176)
174. The apparatus of Appendix 174, wherein the first set of electrodes comprises one electrode and the second set of electrodes comprises at least two electrodes.

(Appendix 177)
The device according to any one of Appendix 132, 185, 198, and 208, wherein one electrode of each spline in the set of splines is configured alternative for ablation and ECG signal reception.

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

(Appendix 179)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the distal cap comprises a non-invasive shape.

(Appendix 180)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the distal cap defines a cap lumen therein.

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

(Appendix 182)
The device according to any one of Appendix 132, 185, 198, and 208, wherein one or more of the distal portions and distal caps of the catheter shaft comprises a radiation impervious portion.

(Appendix 183)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the set of splines comprises a radiation opaque portion formed on the surface of the set of splines.

(Appendix 184)
The device according to any one of Appendix 132, 185, 198, and 208, wherein the catheter shaft comprises a length of about 60 cm to about 85 cm.

(Appendix 185)
It ’s a device,
With the handle
A catheter shaft coupled to the proximal end of the handle, wherein the catheter shaft defines a longitudinal axis and a shaft lumen passing through the catheter shaft.
A set of splines that extends from the distal end of the shaft lumen, wherein each spline in the set of splines contains a set of electrodes formed on the surface of the spline.
With a distal cap coupled to the distal portion of each spline in the set of splines, the set of splines translates along the longitudinal axis to form a first configuration and a second configuration. The first configuration comprises the distal cap coupled to the distal end of the catheter shaft at a first distance, the second configuration being said of said catheter shaft. A device comprising the distal cap coupled to the distal end at a second distance, wherein the ratio of the first distance to the second distance is about 5: 1 to about 25: 1.

(Appendix 186)
The handle is coupled to the set of splines and the distal cap, the handle defines a second longitudinal axis and a handle lumen passing through, and the handle is disposed in the handle lumen. 185, 198, and 208, wherein the apparatus comprises a translational member.

(Appendix 187)
Addendum 186, wherein the translational member translates along the second longitudinal axis to shift a set of splines between the first configuration and the second configuration. The device described in.

(Appendix 188)
187. The apparatus of Appendix 187, wherein the translational member is configured to rotate around the second longitudinal axis to transition between a locked configuration and an unlocked configuration.

(Appendix 189)
The locking configuration fixes the set of splines and the translational position of the distal cap to the catheter shaft, and the unlocking configuration causes the set of splines and the distal cap to relative to the catheter shaft. 188. The device according to Appendix 188, which enables translation.

(Appendix 190)
186. The device of Appendix 186, wherein the translational member comprises a locking member.

(Appendix 191)
189. The device of Appendix 189, wherein the locking member comprises a protrusion.

(Appendix 192)
The device according to Appendix 189, wherein the handle lumen defines a translational groove and a plurality of locking grooves, each of which intersects the translational groove.

(Appendix 193)
191. Addendum 191 wherein the locking member is configured to translate along the translational groove to shift a set of splines between the first configuration and the second configuration. apparatus.

(Appendix 194)
The device according to any one of Appendix 185, 198, and 208, further comprising an electrical cable coupled to the handle.

(Appendix 195)
194. The device of Appendix 194, wherein the proximal end of the electrical cable comprises one or more connectors.

(Appendix 196)
186. The device of Appendix 186, wherein the translational member defines a guidewire lumen through which the translational member passes.

(Appendix 197)
185, 198, and 208, wherein the handle comprises a flash port.

(Appendix 198)
It ’s a system,
With a signal generator configured to generate a pulse waveform,
A cardiac stimulator that is configured to couple to the signal generator to generate a pacing signal for cardiac stimulation during use and to transmit a display of the pacing signal to the signal generator.
(The signal generator is further configured to generate the pulse waveform in synchronization with the display of the pacing signal).
The ablation device comprises an ablation device coupled to the signal generator and configured to receive the pulse waveform.
With the handle
A catheter shaft coupled to the proximal end of the handle, wherein the catheter shaft defines a first longitudinal axis and a shaft lumen passing through the catheter shaft.
A set of splines coupled to the catheter shaft, wherein the distal portion of each spline in the set of splines extends distally from the distal end of the catheter shaft, and each spline in the set of splines extends. A set of splines and a set of splines, including a set of electrodes formed on the surface of each spline of the set of splines.
Each spline set comprises a distal cap coupled to said distal portion of each spline, the distal portion each comprising a spiral shape centered on the first longitudinal axis, said handle. , The first configuration is configured such that the set of splines is translated along the first longitudinal axis to shift the set of splines between the first configuration and the second configuration. Includes a set of the splines arranged substantially parallel to the first longitudinal axis, wherein the second configuration is arranged substantially perpendicular to the first longitudinal axis. System, including a set of.

(Appendix 199)
The system according to any one of Appendix 198 and 208, further comprising a guide wire, wherein the ablation device is configured to be disposed on the guide wire during use.

(Appendix 200)
The system according to any one of Appendix 198 and 208, further comprising a bendable sheath that is configured to bend at least about 180 degrees.

(Appendix 201)
The system according to any one of Appendix 198 and 208, further comprising an expander configured to dilate the transseptal opening.

(Appendix 202)
The system according to Appendix 201, wherein the dilator is configured to create the transseptal opening.

(Appendix 203)
The system according to any one of Appendix 198 and 208, further comprising an extension cable configured to electrically couple the electrodes of the set of splines to the signal generator.

(Appendix 204)
The system according to any one of Appendix 198 and 208, further comprising a diagnostic device configured to receive electrophysiological data of the left atrium.

(Appendix 205)
The system according to any one of Appendix 198 and 208, wherein the electrophysiological data comprises at least one pulmonary vein in the left atrium.

(Appendix 206)
The system according to any one of Appendix 198 and 208, wherein the signal generator is configured to generate the pulse waveform with a time offset with respect to the display of the pacing signal.

(Appendix 207)
The pulse waveform is
The pulse waveform at the first level of the hierarchy of the pulse waveform containing the first set of pulses, where each pulse has a pulse duration and the first time interval separates successive pulses. The first level of the hierarchy and
A second level of the hierarchy of said pulse waveforms that includes a first set of multiple pulses as a second set of pulses, with a second time interval separating the first set of contiguous pulses. The second level of the layer of the pulse waveform, wherein the second time interval is at least three times the period of the first time interval.
A third level of the hierarchy of said pulse waveforms that includes a second set of multiple pulses as a third set of pulses, with a third time interval separating the second set of contiguous pulses. One of appendices 198 and 208, comprising, at least 30 times the period of the second time interval, the third level of the layer of the pulse waveform. The system described in.

(Appendix 208)
It is a treatment method for atrial fibrillation by irreversible electroporation.
Creating a transseptal opening in the left atrium and
To advance the guide wire and sheath into the left atrium through the transseptal opening and
By advancing the ablation device into the left atrium on the guide wire, the ablation device
A catheter shaft that defines the longitudinal axis and the shaft lumen through it,
A set of splines coupled to the catheter shaft, wherein the distal portion of each spline in the set of splines extends distally from the distal end of the catheter shaft, and each spline in the set of splines extends. Includes a set of electrodes formed on the surface of each spline in the set of splines, the set of splines translates along the longitudinal axis and transitions between the first configuration and the second configuration. The first configuration comprises a set of the splines arranged substantially parallel to the longitudinal axis, and the second configuration is substantially perpendicular to the longitudinal axis. To advance the ablation device, including the set of the arranged splines,
To shift the ablation device from the first configuration to the second configuration,
Recording the first electrophysiological data of the left atrium and
To advance the ablation device toward the pulmonary veins of the set of pulmonary veins,
Delivering the pulse waveform to the pulmonary vein using the ablation device,
A method comprising recording a second electrophysiological data of the left atrium after delivering the pulse waveform.

(Appendix 209)
The ablation device is such that upon delivery of the pulse waveform, it produces a set of circumferential electric field lines that are generally parallel to the second longitudinal axis of the set of cardiomyocytes arranged circumferentially on the atrial wall. The method according to Appendix 208, which is configured.

(Appendix 210)
Creating a first access site in the patient and
To advance the guide wire through the first access site into the right atrium,
To advance the dilator and sheath onto the guide wire into the right atrium.
To create the transseptal opening by advancing the dilator through the atrial septum from the right atrium into the left atrium.
The method of Appendix 208, further comprising expanding the transseptal opening using the dilator.

(Appendix 211)
The method of Appendix 208, further comprising creating a second access site in the patient to advance the cardiac stimulator.

(Appendix 212)
To advance the cardiac stimulator into the right ventricle,
Generating a pacing signal for cardiac stimulation of the heart using the cardiac stimulator and
The method of Appendix 211, further comprising applying the pacing signal to the heart using the cardiac stimulator, wherein the pulse waveform is generated in synchronization with the pacing signal.

(Appendix 213)
The method of Appendix 208, wherein the first and second electrophysiological data include intracardiac ECG signal data of at least one pulmonary vein.

(Appendix 214)
The method of Appendix 208, wherein the first and second electrophysiological data are recorded using the ablation device in the second configuration.

(Appendix 215)
Appendix 208, further comprising advancing the diagnostic catheter into the left atrium and recording the first and second electrophysiological data using the diagnostic catheter. Method.

(Appendix 216)
215. The method of Appendix 215, wherein the diagnostic catheter advances through the jugular vein.

(Appendix 217)
The method of Appendix 208, wherein the ablation device disposed in the left atrium transitions from the first configuration to the second configuration without contacting the atrial wall and the pulmonary veins.

(Appendix 218)
The method of Appendix 208, further comprising disposing the ablation device in the intracardiac lumen of the left atrium, wherein the ablation device is in contact with the pulmonary vein ostium.

(Appendix 219)
218. The method of Appendix 218, wherein the set of splines in contact with the pulmonary vein opening forms a "C" shape.

(Appendix 220)
Further, the first set of electrodes of the first spline of the set of splines is configured as an anode, and the second set of electrodes of the second spline of the set of splines is configured as a cathode. Included, the method of Appendix 208.

(Appendix 221)
The method of Appendix 220, wherein the first spline is not adjacent to the second spline.

(Appendix 222)
221. The method of Appendix 221 wherein the first set of electrodes comprises one electrode and the second set of electrodes comprises at least two electrodes.

(Appendix 223)
The method of Appendix 208, further comprising imaging a radiation opaque portion of the ablation device under fluoroscopy during one or more steps.

(Appendix 224)
The method according to Appendix 208, wherein the first access site is the femoral vein.

(Appendix 225)
The method of Appendix 210, wherein the atrial septum comprises a foramen ovale.

(Appendix 226)
The method of Appendix 208, further comprising generating the pulse waveform using a signal generator coupled to the ablation device.

(Appendix 227)
Further comprising migrating the set of splines from the second configuration after ablation of the pulmonary veins and advancing the ablation device towards another pulmonary vein of the set of pulmonary veins. The method according to Appendix 208.

(Appendix 228)
The pulse waveform is
The pulse waveform at the first level of the hierarchy of the pulse waveform containing the first set of pulses, where each pulse has a pulse duration and the first time interval separates successive pulses. The first level of the hierarchy and
A second level of the hierarchy of said pulse waveforms that includes a first set of multiple pulses as a second set of pulses, with a second time interval separating the first set of contiguous pulses. The second level of the layer of the pulse waveform, wherein the second time interval is at least three times the period of the first time interval.
A third level of the hierarchy of said pulse waveforms that includes a second set of multiple pulses as a third set of pulses, with a third time interval separating the second set of contiguous pulses. The method of Appendix 208, wherein the third time interval comprises at least a third level of the hierarchy of the pulse waveform, which is at least 30 times the duration of the second time interval.

(Appendix 229)
The method of Appendix 208, wherein the pulse waveform comprises a time offset with respect to the pacing signal.

(Appendix 230)
The ablation device comprises a handle, the catheter shaft is coupled to the proximal end of the handle, the method.
Using the handle, the set of splines is translated along the first longitudinal axis to transfer the set of splines between the first configuration and the second configuration. The method according to Appendix 208, further comprising.

(Appendix 231)
230. The method of Appendix 230, further comprising rotating the handle to shift the ablation device between locked and unlocked configurations.

(Appendix 232)
The locking configuration fixes the translational position of the set of splines with respect to the catheter shaft, and the unlocking configuration allows the set of splines to translate with respect to the catheter shaft, see Appendix 231. The method described.

(Appendix 233)
230. The method of Appendix 230, further comprising electrically coupling a signal generator to said proximal end of the handle.

(Appendix 234)
230. The method of Appendix 230, wherein the signal generator is electrically coupled to said proximal end of the handle using an extension cable.

(Appendix 235)
The method according to Appendix 208, wherein the pulse waveform is from about 900 V to about 1200 V.

(Appendix 236)
The method of Appendix 208, further comprising visually confirming that the set of splines in the second configuration is not in contact with the pulmonary veins.

(Appendix 237)
The method of Appendix 208, further comprising visually confirming that the juxtaposition of the set of splines is in contact with the pulmonary veins.

(Appendix 238)
The configuration of the first set of electrodes of the first spline of the set of splines as an anode and
A second set of electrodes of the second spline of the set of splines is configured as a cathode.
The method of Appendix 208, further comprising delivering the pulse waveform to a first set of the electrodes and a second set of the electrodes.

Claims (22)

It ’s a device,
A catheter shaft that defines the longitudinal axis and the shaft lumen through it,
A set of splines that extends from the distal end of the shaft lumen, wherein each spline in the set of splines contains a set of electrodes formed on the surface of the spline.
With a distal cap coupled to the distal portion of each spline of the set of splines, the set of splines translates along the longitudinal axis to form a first configuration and a second configuration. In the first configuration, each spline is substantially in a plane comprising the longitudinal axis of the catheter shaft, and in the second configuration, each spline is said to be said. A loop is formed having a first recess facing the distal cap, a second recess facing the longitudinal axis, and a third recess facing the distal end of the shaft lumen. Device. The device according to claim 1, wherein in the second configuration, each spline has a deformed spiral shape. The device of claim 2, wherein each spline in the set of splines has a non-zero spiral angle of less than about 5 degrees. The device of claim 1, wherein the set of splines in the second configuration is arranged as a set of non-overlapping loops. The device of claim 1, wherein the set of splines in the second configuration is arranged as a set of electrically isolated loops. The device of claim 1, wherein the set of splines in the second configuration comprises a radius of curvature that varies along the length of the spline. The device of claim 1, wherein each spline in the set of splines in the second configuration is urged up to about 30 mm away from the longitudinal axis. The device of claim 1, wherein the set of splines in the second configuration has a diameter of about 10 mm to about 50 mm. The set of splines in the second configuration is configured to abut against the tissue wall, and the set of electrodes in at least two of the splines has the strength of the electric field lines and the strength of the electric field with respect to the tissue wall. Any one of claims 1-8, configured to generate an electric field composed of tangent components, wherein the tangent component exceeds half of the strength in most of the tissue wall between the at least two splines. The device described in the section. The device of any one of claims 1-9, wherein the set of splines and the distal cap are configured to translate together up to about 60 mm along the longitudinal axis. The device according to any one of claims 1 to 10, wherein each of the distal portions of the set of splines is secured to the distal cap. The device according to any one of claims 1 to 11, wherein each spline in the set of splines in the second configuration comprises an elliptical cross section. 12. The apparatus of claim 12, wherein the elliptical cross section comprises a major axis length of about 1 mm to about 2.5 mm and a minor axis length of about 0.4 mm to about 1.2 mm. The device according to any one of claims 1 to 13, wherein the set of splines comprises 3 to 20 splines. Each spline in the set of splines is about 0.2 mm ² ~ About 15mm ² The apparatus according to any one of claims 1 to 14, which has a cross-sectional area of. Each spline in the set of splines defines a spline lumen therein.
An insulating lead is associated with the set of electrodes for each spline in the set of splines, and the insulated lead is disposed within the spline lumen of each spline in the set of splines.
The apparatus according to any one of claims 1 to 15, wherein the insulated conductor is configured such that its corresponding insulation maintains a potential of at least about 700 V without dielectric breakdown. Each electrode in the set of electrodes is about 0.5 mm ² ~ About 20mm ² The apparatus according to any one of claims 1 to 16, which has a surface area of. 1 of claim, wherein the first set of electrodes of the first spline of the set of splines is configured as an anode and the second set of electrodes of the second spline of the set of splines is configured as a cathode. The apparatus according to any one of 17 to 17. The device of claim 18, wherein the first spline is not adjacent to the second spline. 18. The apparatus of claim 18, wherein the first set of electrodes comprises one electrode and the second set of electrodes comprises at least two electrodes. In the first configuration, the distal cap is attached to the distal end of the catheter shaft at a first distance, and in the second configuration, the distal cap is attached to the distal end of the catheter shaft. The device according to claim 1, wherein the device is coupled at a distance of 2 and the ratio of the first distance to the second distance is about 5: 1 to about 25: 1. The device of claim 1, wherein in the second configuration, at least a portion of each spline in the set of splines has a radius of curvature of about 7 mm to about 25 mm.