CN112971969A

CN112971969A - Systems, devices, and methods for delivering pulsed electric field ablation energy to endocardial tissue

Info

Publication number: CN112971969A
Application number: CN202110157926.1A
Authority: CN
Inventors: R·维斯瓦纳萨安; A·齐恩格勒尔; G·朗; J-L·帕雅尔; B·哈谢伊
Original assignee: Farapulse Inc
Current assignee: Boston Scientific Scimed Inc
Priority date: 2017-04-28
Filing date: 2018-04-27
Publication date: 2021-06-18
Also published as: CN110662483B; JP2023082063A; CN116158839A; JP2020517355A; CN110662483A; EP3614912A1; EP3614912A4

Abstract

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

Description

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

The present application is a divisional application of the application entitled "system, device, and method for delivering pulsed electric field ablation energy to endocardial tissue" filed 2018, 4 and 27, and application No. 201880033278.5.

Cross Reference to Related Applications

The present application is a continuation-in-part application of U.S. patent application No. 15/874,721, entitled system, apparatus AND method FOR FOCAL ABLATION (SYSTEMS, DEVICES, AND METHODS FOR FOCAL ABLATION), filed on 18.1.2018, which claims the benefit of U.S. provisional application No. 62/529,268, filed on 6.7.2017, AND entitled system, apparatus AND method FOR FOCAL ABLATION. This application also claims priority OF U.S. patent application No. 15/711,266, filed on 21.9.2017 AND entitled system, device AND method FOR delivering PULSED electric field ablation ENERGY TO ENDOCARDIAL TISSUE (SYSTEMS, DEVICES, AND METHODS FOR DELIVERY OF PULSED electric field ablation ENERGY ELECTRIC FIELD associated ENERGY TO ENDOCARDIAL TISSUE), which is filed on 4.1.2017 AND entitled "system, device AND method FOR delivering PULSED electric field ablation ENERGY TO ENDOCARDIAL TISSUE," continuation-in-part OF PCT application No. PCT/US2017/012099, which claims priority OF U.S. provisional application No. 62/274,943, filed on 5.1.5.2016 AND entitled "system, device AND apparatus FOR delivering PULSED electric field ablation ENERGY TO ENDOCARDIAL TISSUE. U.S. patent application No. 15/711,266 also claims priority from U.S. provisional application No. 62/491,910, filed on 28.4.2017 and entitled "system, device and method for delivering pulsed electric field ablation energy to endocardial tissue", and priority from U.S. provisional application No. 62/529,268, filed on 6.7.2017 and entitled "system, device and method for focal ablation". The entire disclosure of each of the foregoing applications is incorporated by reference in its entirety.

Background

Over the last two decades, the generation of pulsed electric fields for tissue treatment has shifted from laboratories to clinical applications, while over the last forty years or more, the effect of short pulses of high voltage and large electric fields on tissue has been studied. The application of a brief high DC voltage to the tissue can generate a local high electric field, typically in the range of hundreds of volts per centimeter, that disrupts the cell membranes by creating pores in the cell membranes. While the precise mechanism of this electrically driven pore generation or electroporation continues to be investigated, it is believed that the application of a relatively brief and large electric field creates instability in the lipid bilayer in the cell membrane, resulting in the appearance of a local gap or pore distribution in the cell membrane. Such electroporation may be irreversible in the following cases: an applied electric field at the membrane above a threshold causes the pores to not close and remain open, thereby allowing biomolecular material to exchange across the membrane, resulting in necrosis and/or apoptosis (cell death). Subsequently, the surrounding tissue may heal naturally.

While pulsed DC voltages can drive electroporation under appropriate circumstances, there is still an unmet need for a thinner, flexible, atraumatic device that is effective in selectively delivering high DC voltage electroporation ablation therapy to endocardial tissue in a region of interest while minimizing damage to healthy tissue.

Disclosure of Invention

Systems, devices, and methods for ablating tissue by irreversible electroporation are described herein.

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

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

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

In some embodiments, each spline of the set of splines may have a rate of rotation u' controlled by the following equation: | } u' } dl > pi, where l is the arc length of the spline. In some embodiments, the rate of rotation u' of the spline is controlled by the following equation: u' ═ du/dl, where l is the arc length along the spline. The shape of each spline of the set of splines is controlled by the following equation: (u ″, b) dl ≠ 0, where b ═ u × u.

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

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

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

In some embodiments, the insulated electrical lead may be disposed in the body of the second catheter. The insulated electrical leads are configured to maintain a voltage potential of at least about 700V without dielectric breakdown of their corresponding insulation. In some embodiments, a pulse waveform comprising a first level of a hierarchy of the pulse waveforms may comprise a first set of pulses, each pulse having a pulse duration, a first time interval separated by consecutive pulses. A second stage of the hierarchy of the pulse waveforms may include a plurality of first set of pulses as a second set of pulses, a second time interval separating successive first set of pulses, the second time interval being at least three times a duration of the first time interval. A third stage of the hierarchy of the pulse waveforms may include a plurality of second set of pulses as a third set of pulses, a third time interval separating successive second set of pulses, the third time interval being at least thirty times a duration of the second stage time interval.

In some embodiments, a method of treating cardiac arrhythmia by irreversible electroporation can comprise the steps of: advancing an ablation device into a left atrium of a patient; transitioning the ablation device from a first configuration to a second configuration. The ablation device may include: a first catheter defining a longitudinal axis and a lumen therethrough; a second catheter extending from a distal end of the first catheter lumen; 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 comprising a set of independently addressable electrodes formed on a surface of each spline of the splines, each electrode having an insulated electrical lead associated therewith disposed in a body of each spline of the set of splines. In the first configuration, the set of splines may be substantially parallel to the longitudinal axis. In the second configuration, at least a portion of each spline of the set of splines extends distally of the distal end of the second catheter. The steps may further include generating a set of pulse waveforms and delivering the set of pulse waveforms through one or more splines of a set of splines of the ablation device in the second configuration to a set of adjoining portions of a posterior wall of the left atrium to form a set of ablation zones.

In some embodiments, in the second configuration, the set of splines may form a loop and twist along its length such that the splines have a twist along their length. In some embodiments, in the second configuration, each spline of the set of splines may have a longitudinal axis in the second configuration having an angle of less than about 80 degrees relative to the longitudinal axis of the first conduit. In some embodiments, each spline of the set of splines may have a rate of rotation u' controlled by the following equation: | } u' } dl > pi, where l is the arc length of the spline. In some embodiments, the rate of rotation u' of the spline is controlled by the following equation: u' ═ du/dl, where l is the arc length along the spline. In some embodiments, the shape of each spline of the set of splines may be controlled by the following equation: (u ″, b) dl ≠ 0, where b ═ u × u.

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

In some embodiments, the set of splines may comprise a set of electrodes, which may comprise the set of electrodes of each spline of the set of splines. The method may further comprise configuring a first electrode of the set of electrodes as an anode; configuring a second electrode of the set of electrodes as a cathode; and delivering the pulse waveform to the first electrode and the second electrode.

In some embodiments, a first set of electrodes of a first spline of the set of splines may be configured as anodes, a second set of electrodes of a second spline of the set of splines may be configured as cathodes, and the pulse waveforms may be delivered to the first set of electrodes and the second set of electrodes.

Drawings

Fig. 1 is a block diagram of an electroporation system according to an embodiment.

Fig. 2 is a perspective view of an ablation catheter according to an embodiment.

Fig. 3 is a perspective view of an ablation catheter according to other embodiments.

Fig. 4 is a perspective view of an ablation catheter according to other embodiments.

Fig. 5 is a detailed perspective view of a distal portion of an ablation catheter according to other embodiments.

Fig. 6 is a side view of an ablation catheter according to other embodiments.

Fig. 7 is a side view of an ablation catheter according to other embodiments.

Fig. 8A-8B are views of ablation catheters according to other embodiments. Fig. 8A is a side view, and fig. 8B is a front sectional view.

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

Fig. 10 is a perspective view of a balloon ablation catheter positioned in a left atrial chamber of a heart according to other embodiments.

Fig. 11 is a cross-sectional view of a balloon ablation catheter positioned in a left atrial chamber of a heart according to other embodiments.

Fig. 12A-12B are schematic illustrations of a return electrode of an ablation system according to an embodiment. Fig. 12A shows an unpowered electrode, and fig. 12B shows an energized electrode.

Fig. 13 illustrates a method for performing tissue ablation according to an embodiment.

Fig. 14 illustrates a method for performing tissue ablation according to other embodiments.

Fig. 15 is an illustration of the ablation catheter depicted in fig. 2 positioned in a left atrial chamber of the heart.

Fig. 16 is an illustration of the ablation catheter depicted in fig. 3 positioned in a left atrial chamber of a heart.

Fig. 17 is an illustration of two of the ablation catheters depicted in fig. 4 positioned in a left atrial chamber of the heart.

Fig. 18 is an illustration of the ablation catheter depicted in fig. 5 positioned in a left atrial chamber of the heart.

Fig. 19A-19B are schematic illustrations of a set of electrodes positioned in the ostium of a pulmonary vein according to other embodiments. Fig. 19A is a schematic perspective view, and fig. 19B is a sectional view.

Figures 20A-20B are schematic illustrations of electric fields generated by electrodes positioned in the ostium of a pulmonary vein according to other embodiments. Fig. 20A is a schematic perspective view, and fig. 20B is a sectional view.

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

Fig. 22 schematically illustrates a pulse hierarchy showing pulse widths, intervals between pulses, and pulse groupings, according to an embodiment.

Fig. 23 provides a schematic illustration of a nesting level showing monophasic pulses of different levels of the nesting level, according to an embodiment.

Fig. 24 is a schematic illustration of a nesting level showing biphasic pulses of different levels of the nesting level, according to an embodiment.

Fig. 25 schematically shows a time sequence of electrocardiogram and cardiac pacing signals and atrial and ventricular refractory periods, and indicates time windows for irreversible electroporation ablation, in accordance with an embodiment.

Fig. 26A is a perspective view of an ablation catheter according to other embodiments. Fig. 26B is a side view of the ablation catheter depicted in fig. 26A positioned in a left atrial chamber of the heart adjacent to the ostium. Fig. 26C is a top view of a simulation of the ablation catheter depicted in fig. 26B, illustrating selective electrode activation according to an embodiment. Fig. 26D is a simulated illustration of tissue ablation in the ostium of a lung according to an embodiment.

Fig. 27A-27C are respective side views of ablation catheters according to other embodiments. Fig. 27A is a side view of an ablation catheter in a second configuration. Fig. 27B is another side view of the ablation catheter in a second configuration. Fig. 27C is yet another side view of the ablation catheter in a second configuration.

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

Fig. 29A-29D are cross-sectional side views of ablation catheters according to other embodiments. Fig. 29A is a cross-sectional side view of the ablation catheter in a first configuration. Fig. 29B is a cross-sectional side view of the ablation catheter in a third configuration. Fig. 29C is another cross-sectional side view of the ablation catheter in a third configuration. Fig. 29D is yet another cross-sectional side view of the ablation catheter in a third configuration.

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

Fig. 31A-31B are perspective views of ablation catheters according to other embodiments. Fig. 31A is a perspective view of an ablation catheter in a first configuration. Fig. 31B is a perspective view of the ablation catheter in a second configuration.

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

Fig. 33A-33E are illustrative views of ablation catheters according to other embodiments. Fig. 33A is a perspective view of an ablation catheter. Fig. 33B is a front view of the ablation catheter of fig. 33A. Fig. 33C is a cut-away perspective view of the splines of the ablation catheter of fig. 33A. Fig. 33D is a cross-sectional view of the splines of the ablation catheter of fig. 33A. Fig. 33E is a perspective view of the ablation catheter of fig. 33A positioned adjacent tissue.

34A-34B are side views of splines according to other embodiments. FIG. 34A is a side view of a spline having a unit tangent vector. FIG. 34B is a side view of a spline having two unit tangent vectors.

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

Fig. 36A-36C are side views of ablation catheters according to other embodiments. Fig. 36A is a side view of an ablation catheter in a second configuration. Fig. 36B is another side view of the ablation catheter in a second configuration. Fig. 36C is a side view of the ablation catheter near tissue.

Fig. 37A-37B are perspective views of an ablation catheter and the left atrium. Fig. 37A is a perspective view of an ablation catheter positioned in the left atrium. FIG. 37B is a perspective view of the left atrium after tissue ablation has been performed.

Detailed Description

Systems, devices, and methods for selective and rapid application of pulsed electric fields to ablate tissue by irreversible electroporation are described herein. In general, the systems, devices, and methods described herein can be used to produce large electric field amplitudes at desired regions of interest and reduce peak electric field values elsewhere to reduce unnecessary tissue damage and arcing. The irreversible electroporation systems described herein can include a signal generator and a processor configured to apply one or more voltage pulse waveforms to a selected set of electrodes of an ablation device to deliver energy to a region of interest (e.g., ablation energy for a set of tissues in a pulmonary vein ostium). The pulse waveforms disclosed herein may help treat various arrhythmias (e.g., atrial fibrillation). To deliver the pulsed waveform generated by the signal generator, one or more electrodes of the ablation device may have insulated electrical leads configured to maintain a voltage potential of at least about 700V without dielectric breakdown of their corresponding insulation. The electrodes may be independently addressable such that each electrode may be controlled (e.g., deliver energy) independently of any other electrode of the device. In this way, the electrodes may be coordinated to deliver different energy waveforms with different timings to electroporate tissue.

As used herein, the term "electroporation" refers to the application of an electric field to a cell membrane to alter the permeability of the cell membrane to the extracellular environment. As used herein, the term "reversible electroporation" refers to the application of an electric field to a cell membrane to temporarily alter the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing reversible electroporation may observe the temporary and/or intermittent formation of one or more pores in its cell membrane that close upon removal of the electric field. As used herein, the term "irreversible electroporation" refers to the application of an electric field to a cell membrane to permanently alter the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing irreversible electroporation may observe the formation of one or more pores in its cell membrane that remain after the electric field is removed.

The pulse waveforms for electroporation energy delivery disclosed herein may enhance the safety, efficiency, and effectiveness of energy delivery to tissue by reducing the electric field threshold associated with irreversible electroporation, resulting in more effective ablative lesions with a reduction in the total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein may be hierarchical and have a nested structure. For example, the pulse waveform may contain hierarchical groupings of pulses having associated time scales. In some embodiments, the METHODS, SYSTEMS, AND devices disclosed herein may include one or more OF the METHODS, SYSTEMS, AND devices described in international application serial No. PCT/US 2016/057664, filed 2016, 19, AND entitled system, apparatus, AND method FOR delivering ABLATIVE ENERGY TO TISSUE (SYSTEMS, apparatus AND METHODS FOR delivering ablation ENERGY TO TISSUE), the contents OF which are incorporated herein by reference in their entirety.

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

Typically, to ablate tissue, one or more catheters may be advanced through the vasculature to a target location in a minimally invasive manner. In cardiac applications, the electrodes through which the voltage pulse waveform is delivered may be positioned on an epicardial device or an endocardial device. The methods described herein may include introducing a device into the endocardial space of the left atrium of the heart and placing the device in contact with the ostium of a pulmonary vein. A pulse waveform may be generated and delivered to one or more electrodes of the device to ablate tissue. In some embodiments, the pulse waveform may be generated in synchronization with a cardiac pacing signal to avoid disruption of cardiac sinus rhythm. In some embodiments, the electrodes may be configured in an anode-cathode subset. The pulse waveform may comprise a graded waveform to aid in tissue ablation and reduce damage to healthy tissue.

I. System for controlling a power supply

SUMMARY

Disclosed herein are systems and devices configured for tissue ablation that facilitate tissue ablation by selectively and rapidly applying voltage pulse waveforms to achieve irreversible electroporation. In general, the systems described herein for ablating tissue may include a signal generator and an ablation device having one or more electrodes for selectively and rapidly applying a DC voltage to drive electroporation. As described herein, the systems and devices may be deployed epicardially and/or endocardially to treat atrial fibrillation. Voltages may be applied to selected subsets of the electrodes, with anode electrode selection and cathode electrode selection having independent subset selection. A pacing signal for cardiac stimulation may be generated by the signal generator in synchronization with the pacing signal and used to generate the pulse waveform.

In general, the systems and devices described herein include one or more catheters configured to ablate tissue in the left atrial chamber of the heart. Fig. 1 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 be coupled to an ablation device (110), and optionally to a pacing device (130) and/or an optional return electrode (140) (e.g., a return pad, shown here in dashed lines).

The signal generator (122) may be configured to generate a pulse waveform for irreversible electroporation of tissue, such as, for example, the ostium of a pulmonary vein. For example, the signal generator (122) may be a voltage pulse waveform generator and deliver a pulse waveform to the ablation device (110). The return electrode (140) may be coupled to a patient (e.g., positioned on the patient's back) to allow current to flow from the ablation device (110) through the patient, and then to the return electrode (140) to provide a safe current return path from the patient (not shown). The processor (124) may combine data received from the memory (126), cardiac stimulator (128), and pacing device (130) to determine parameters (e.g., amplitude, width, duty cycle, etc.) of a pulse waveform to be generated by the signal generator (122). The memory (126) may further store instructions that cause the signal generator (122) to perform modules, processes, and/or functions associated with the system (100), such as pulse waveform generation and/or cardiac pacing synchronization. For example, the memory (126) may be configured to store pulse waveform data and/or cardiac pacing data for 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 a pulse waveform described in more detail below. For example, an ablation device (110) may be introduced into the endocardial space of the left atrium and positioned to align one or more electrodes (112) with one or more pulmonary vein ostia and then deliver a pulse waveform to ablate tissue. The ablation device (110) may include one or more electrodes (112), which in some embodiments may be a set of individually addressable electrodes. Each electrode may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In some embodiments, the insulation on each of the electrical leads may maintain a potential difference between about 200V to about 1,500V across its thickness without creating a dielectric breakdown. For example, the electrodes (112) may be grouped into one or more anode-cathode subsets, such as, for example, subsets comprising one anode and one cathode, subsets comprising two anodes and two cathodes, subsets comprising two anodes and one cathode, subsets comprising one anode and two cathodes, subsets comprising three anodes and one cathode, subsets comprising three anodes and two cathodes, and the like.

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

The processor (124) may be any suitable processing device configured to execute and/or execute a set of instructions or code. The processor may be, for example, a general purpose processor, a Field Programmable Gate Array (FPGA), an Application Specific Integrated Circuit (ASIC), a Digital Signal Processor (DSP), or the like. The processor may be configured to run and/or execute application processes and/or other modules, processes, and/or functions associated with the system and/or a network (not shown) associated therewith. The underlying device technologies may be provided in a variety of component types, such as Metal Oxide Semiconductor Field Effect Transistor (MOSFET) technologies (e.g., Complementary Metal Oxide Semiconductor (CMOS)), bipolar technologies (e.g., Emitter Coupled Logic (ECL)), polymer technologies (e.g., silicon-conjugated polymers and metal-conjugated polymer-metal structures), hybrid analog and digital, and so forth.

The memory (126) may contain a database (not shown) and may be, for example, Random Access Memory (RAM), memory buffers, hard drives, erasable programmable read-only memory (EPROM), electrically erasable read-only memory (EEPROM), read-only memory (ROM), flash memory, and 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) over, for example, one or more networks, each of which may be any type of network. A wireless network may refer to any type of digital network that is not connected by any type of cable. However, wireless networks may be connected to wired networks to interface with the internet, other carrier voice and data networks, business networks, and personal networks. Wired networks are typically carried by copper twisted pairs, coaxial cables, or fiber optic cables. There are many different types of wired networks, including Wide Area Networks (WANs), Metropolitan Area Networks (MANs), Local Area Networks (LANs), Campus Area Networks (CANs), Global Area Networks (GANs) (e.g., the internet), and Virtual Private Networks (VPNs). In the following, a network refers to any combination of wireless, wired, public and private data networks interconnected typically by the internet to provide a combination of unified networking and information access solutions.

Ablation device

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

The catheter (210) may be slidably advanced over the guidewire (220) for placement over the guidewire (220) during use. A distal portion (222) of a guidewire (220) positioned in a lumen (e.g., near an ostium of a pulmonary vein) can act as a stop for advancement of the distal portion of the catheter (210). A distal portion of a catheter (210) may include a set of electrodes (212) (e.g., structurally and/or functionally similar to one or more electrodes (112)) configured to contact an inner radial surface of a lumen (e.g., a pulmonary vein ostium). For example, the electrode (212) may comprise an approximately circular electrode arrangement configured to contact the ostium of the pulmonary vein. As shown in fig. 2, one or more of the electrodes (212) may comprise a series of metal bands or rings disposed along the catheter shaft and electrically connected together. For example, the ablation device (200) may contain a single electrode having multiple bands, one or more electrodes each having its own band, and combinations thereof. In some embodiments, the electrode (212) may be shaped to conform to the shape of the distal portion (222) of the guidewire (220). The catheter shaft may include a flexible portion between the electrodes for enhanced flexibility. In other embodiments, one or more of the electrodes (212) may contain a helical winding for enhanced flexibility.

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

Fig. 3 is a perspective view of another embodiment of an ablation device (300) (e.g., structurally and/or functionally similar to ablation device (110)) that includes a catheter (310) having a set of electrodes (314) disposed along a distal portion (312) of the catheter (310). The distal portion (312) of the catheter (310) may be non-linear and form an approximately circular shape. A set of electrodes (314) may be disposed along the non-linear distal portion (312) of the catheter (310) and may form a substantially circular arrangement of electrodes (314). In use, the electrode (314) may be positioned at a pulmonary vein ostium to deliver a pulse waveform to ablate tissue, as described in more detail with reference to fig. 16. The shaped distal portion (312) of the catheter (310) may be angled relative to other portions of the catheter (310). For example, the distal portion (312) of the catheter (310) may be substantially perpendicular to the proximal portion of the catheter (310). In some embodiments, a handle (not shown) may be coupled to a proximal portion of the catheter (310) and may contain a bending mechanism (e.g., one or more pull wires (not shown)) configured to modify the shape of the distal portion (312) of the catheter (310). For example, manipulating the pull wire of the handle may increase or decrease the circumference of the circular shape of the distal portion (312) of the catheter (310). The diameter of the distal portion (312) of the catheter (310) may be modified to allow the electrodes (314) to be positioned near and/or in contact with the pulmonary vein ostium (e.g., in contact with the inner radial surface of the pulmonary vein). The electrodes (314) may comprise a series of metal strips or rings and are independently addressable.

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

Fig. 4 is a perspective view of yet another embodiment of an ablation device (400) (e.g., structurally and/or functionally similar to ablation device (110)) including a catheter (410) and a guidewire (420) having a shaped nonlinear distal portion (422). A guidewire (420) is slidable within the lumen of the catheter (410). A guidewire (420) can be advanced through a lumen of the catheter (410), and a distal portion (422) of the guidewire (420) can be approximately circular. The shape and/or diameter of the distal portion (422) of the guidewire (420) may be modified using a bending mechanism as described above with reference to fig. 3. The catheter (410) may be flexible so as to be deflectable. In some embodiments, the catheter (410) and/or guidewire (420) may be configured to be elastic such that it conforms to a lumen in which it is positioned and assumes a second shape when advanced out of the lumen. By modifying the size of the guidewire (420) and manipulating the deflection of the catheter (410), a distal portion (422) of the guidewire (420) can be positioned at a target tissue site, such as the ostium of a pulmonary vein. The distal end (412) of the catheter (410) may be sealed (except where the guidewire (420) extends therefrom) such that the catheter (410) may electrically insulate the portion of the guidewire (420) within the lumen of the catheter (410). For example, in some embodiments, the distal end (412) of the catheter (410) may include a seal with an opening that allows the guidewire (420) to pass through when force is applied to form a compression retainer (which may be liquid-tight) between the seal and the guidewire (420).

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

The guidewire (420) may comprise stainless steel, nitinol, platinum, or other suitable biocompatible material. In some embodiments, the distal portion (422) of the guidewire (420) may contain a platinum coil physically and electrically attached to the guidewire (420). The platinum coil may be an electrode configured to deliver a voltage pulse waveform. Platinum is radiopaque, and its use may add flexibility to aid in the advancement and positioning of the ablation device (400) within the endocardial space.

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

The electrodes (520, 522, 524, 526) may be flexible and form a compact first configuration to be advanced into an endocardial space, such as adjacent a pulmonary vein ostium. Once positioned at the desired location, when the electrodes (520, 522, 524, 526) are advanced out of the lumen (e.g., sheath), the electrodes may be converted to the expanded second configuration to form the flower-shaped distal portion shown in fig. 5. In other embodiments, the insulated lead segments (510, 512, 514, 516) and electrodes (520, 522, 524, 526) may be biased to expand outward (e.g., spring open) into a second configuration when pushed out of a lumen (e.g., sheath) of the carrier device (500). The electrodes (520, 522, 524, 526) may be independently addressable, and each electrode has an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads may maintain a potential difference between about 200V to about 2000V across the thickness without creating a dielectric breakdown.

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

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

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

Each spline (614) of the ablation device (600) may include one or more electrodes (616) formed on the surface of the spline (614) that are commonly connected with a lead wire, or in some cases, independently addressable. Each electrode (616) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads may maintain a potential difference between about 200V to about 2000V across the thickness without creating a dielectric breakdown. Each spline (614) may contain an insulated electrical lead for each electrode (616) formed in the body of the spline (614) (e.g., within the lumen of the spline (614)). Where the electrodes on a single spline are wired together, a single insulated lead may carry a wire harness that connects to different electrodes on the spline. Fig. 6 shows a set of splines (614), where each spline (614) contains a pair of electrodes (616) that are about 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 be different.

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

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

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

Fig. 7 shows a set of splines (714) wherein each spline (714) contains a pair of electrodes (716) having about the same size, shape and spacing as the electrodes (716) of adjacent splines (714). In other embodiments, the size, shape, and spacing of the electrodes (716) may be different. For example, the electrode (716) electrically coupled to the first spline wire (718) may be different in size and/or shape from the electrode (716') electrically coupled to the second spline wire (719).

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

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

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

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

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

Fig. 8B is a front cross-sectional view of fig. 8A taken along line 8B-8B. Each spline lead (817, 819, 821, 823) electrically couples a pair of adjacent electrodes (816, 818, 820, 822) on different splines. In some embodiments, each coupled pair of electrodes may be electrically isolated from each other. In some embodiments, the coupled electrode pairs may be configured to have a common polarity. Adjacent pairs of electrodes may be configured to have opposite polarities (e.g., a first electrode pair is configured as an anode and an adjacent second electrode pair is configured as a cathode). For example, 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 as cathodes. In some embodiments, each electrode formed on the splines (814) may share a common polarity (e.g., configured as an anode or cathode). Each coupled pair of electrodes 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 contain 4 to 10 splines. For example, in one embodiment, the ablation device may contain 6 to 8 splines. As previously described, in some embodiments, the spline leads (e.g., 817, 819, etc.) may be replaced by similar electrical connections in the proximal portion of the device (e.g., in the device handle). For example, electrodes (816) may be electrically connected together with wires in the handle of the device such that the electrodes are at the same electrical potential during ablation.

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

In some embodiments, adjacent distal (916) and proximal (918) electrodes 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 contain 3 to 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 insulated electrical lead. The diameter of the spline (914) lumen can thus be reduced and allow the spline (914) to be thicker and mechanically stronger. Accordingly, dielectric breakdown of the insulation may be further reduced, thereby improving the reliability and longevity of each spline (914) and ablation device (900). The ablation device (900) may include any number of splines, such as 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines. In some embodiments, the ablation device (900) may contain 3 to 20 splines. For example, in one embodiment, the ablation device (900) may contain 6 to 10 splines. Further, in some embodiments, the shape of the bulbous expanded structure (930) of the expanded set of splines (914) may be asymmetric, e.g., with a distal portion thereof being more bulbous or rounded than a proximal portion thereof (e.g., see fig. 9B-9E). Such a spherical distal portion may help position the device at the ostium of the pulmonary vein.

Referring to fig. 9B-9E, it should be understood that, unless otherwise noted, components having reference numbers similar to those in fig. 9A (e.g., electrode (916) in fig. 9A and electrode (916') in fig. 9B) may be structurally and/or functionally similar. Fig. 9B shows the spline wires (914', 920', 922') forming an expanded structure (930') during use (e.g., when expanded). The cross-sectional area of the first plane (924A ') (sometimes also referred to as the proximal plane) of the expanded structure (930') is different from the cross-sectional area at the second plane (924B ') of the expanded structure (930'). As shown in fig. 9B, in some embodiments, the cross-sectional area of the expanded structure (930') at the second plane (924B ') is greater than its cross-sectional area at the first plane (924A '). As used with reference to fig. 9B, the terms "first plane" and "second plane" may refer to planes orthogonal to the longitudinal axis of the catheter shaft (910'), each plane formed up to about 1cm, about 2cm, and about 3cm or more (including all values and subranges therebetween) from the distal end of the catheter shaft (910') and the proximal end of the distal cap (912'), respectively. Similar to fig. 9A, the electrode (916') of the first spline (920') is disposed closer to the distal cap (912') of the ablation device (900') than the electrode (918') of the second spline (922').

Fig. 9C shows the spline wires (914 ", 920", 922 ") forming an expanded structure (930") during use (e.g., when expanded). The cross-sectional area of a first plane (924A ") (sometimes also referred to as a proximal plane) of the expanded structure (930") is different from the cross-sectional area at a second plane (924B ") of the expanded structure (930"). As shown in fig. 9C, in some embodiments, the cross-sectional area of the expanded structure (930 ") at the second plane (924B") is greater than its cross-sectional area at the first plane (924A "). As used with reference to fig. 9C, the terms "first plane" and "second plane" may refer to planes orthogonal to the longitudinal axis of the catheter shaft (910 "), each plane formed up to about 1cm, about 2cm, and about 3cm or more (including all values and subranges therebetween) from the distal end of the catheter shaft (910") and the proximal end of the distal cap (912 "), respectively. Unlike fig. 9A-9B, multiple electrodes may be present on each spline lead, and some electrodes may be equidistant from the distal cap (912 "). In this manner, relatively distal electrodes (e.g., 932 "and 934") may be placed at or proximal/sinus to the pulmonary vein ostium during delivery for ablation to create ostial circumferential lesions around the pulmonary veins.

Fig. 9D shows the spline wires (914 "', 920"', 922 "') forming an expanded structure (930"') during use (e.g., when expanded). The spline wires (914 "', 920" ', 922 "') converge at their distal ends to a point (928" ') located inside/within the expanded structure (930 "'). As shown in fig. 9D, in such a configuration, at least some of the electrodes (932 "', 934" ') on the spline wires (914 "', 920" ', 922 "') may be located in a distal plane (926" ') of the expanded structure (930 "'). As used with reference to fig. 9D, the term "distal plane" may refer to a plane orthogonal to the longitudinal axis of the catheter shaft (910 "') that passes through the distal boundary of the expanded structure (930"'). In this way, the expanded structure (930 "') may be pressed against, for example, an endocardial surface (e.g., the posterior left atrial wall) to create a lesion directly thereon by activating suitable electrodes in the distal plane using any suitable combination of polarities. For example, the distal electrodes (932 "', 934"') may be pressed against the endocardial surface and used to form a lesion (e.g., a spot lesion) by focal ablation.

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

In some embodiments, the length of the electrodes of the ablation device (900 "') may be about 0.5mm to about 5.0mm, and the cross-sectional dimension (e.g., diameter) may be about 0.5mm to about 2.5mm, including all values and subranges therebetween. The cross-sectional dimension (e.g., diameter) of the spline wires (914 "', 920"', 922 "') in the expanded configuration (930"') shown in fig. 9D may be about 6.0mm to about 30.0mm, including all values and subranges therebetween. The focal ablation lesion formed in this manner may have a diameter between about 0.5cm and about 2.5cm, including all values and subranges therebetween.

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

In some embodiments, adjacent distal (934 "') and proximal (933) electrodes 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 anode and cathode, with the electrodes of adjacent splines having opposite configurations (e.g., cathode and anode).

Fig. 9E shows a spline conductor (944, 940, 942) forming an expanded configuration (950) during use (e.g., when deployed). The spline lead (944, 940, 942) converges at its distal end at the proximal end of a distal cap (912 "") inside/within the expanded structure (950). As shown in fig. 9E, in this configuration, at least some electrodes (952, 954) on spline leads (944, 940) may be located in a distal plane (946) of expanded structure (950). As used with reference to fig. 9E, the term "distal plane" may refer to a plane orthogonal to the longitudinal axis of the catheter shaft (910 ""), which passes through the distal boundary of the expanded structure (950). In this manner, the expanded structure (950) may be pressed against, for example, the posterior left atrial wall to create lesions directly thereon by activating suitable electrodes in the distal plane (946) using any suitable combination of polarities. For example,

electrodes

952 and 954 may be configured to have opposite polarities. Relative to the expanded structure (930 "") of fig. 9D, the expanded structure (950) of fig. 9E has a more orthogonal (e.g., flattened) shape that can be pressed against, for example, the posterior wall of the left atrium for tissue ablation. In other words, the cross-sectional area of the expanded structure (930 "") at the distal plane (926 "") is smaller than the cross-sectional area of the expanded structure (950) at the distal plane (946). As another example, the distal electrodes (952, 954) may be pressed against the endocardial surface and used to form a lesion (e.g., a spot lesion) by focal ablation, as generally described herein with respect to fig. 9D.

For each of the ablation devices described herein, each of the splines may comprise a polymer and define a lumen to form a hollow tube. One or more electrodes of the ablation devices described herein may comprise a diameter of about 0.2mm to about 2.0mm and a length of about 0.2mm to about 5.0 mm. In some embodiments, the electrode may comprise a diameter of about 1mm and a length of about 1 mm. Since the electrodes may be independently addressable, the electrodes may be energized in any order using any pulse shape sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., a stepped pulse waveform), as discussed in further detail below. It should be understood that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver continuous/transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternating electrodes (e.g., all distal electrodes) may be at the same potential, and so on for all other electrodes (e.g., all proximal electrodes). Thus, ablation can be delivered quickly with all electrodes activated simultaneously. There are a variety of such electrode pairing options, and they may be implemented based on their convenience.

Fig. 26A is a perspective view of an embodiment of an ablation device (2600) having a flower-like shape and including a catheter shaft (2610) at a proximal end of the device (2600), a distal cap (2612) of the device (2600), and a set of splines (2620) coupled thereto. As best shown in fig. 26B, the spline shaft (2614) may be coupled at a proximal end to a proximal handle (not shown) and at a distal end to a distal cap (2612). 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 translate along a longitudinal axis (2616) of the ablation device (2600). The spline shaft (2614) and distal cap (2612) may move together. The spline shaft (2614) may be configured to slide within a lumen of the catheter shaft (2610). The distal cap (2612) may include an atraumatic shape to reduce trauma to tissue. A proximal end of each spline of the set of splines (2620) may pass through a distal end of the catheter shaft (2610) and may be tethered to the catheter shaft within the catheter shaft tube lumen, and a distal end of each spline of the set of splines (2620) may be tethered to a distal cap (2612) of the device (2600). The ablation device (2600) can be configured to deliver a pulse waveform to tissue through one or more splines of the set of splines (2620) during use, as disclosed in, for example, fig. 21-25.

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

Each spline of the set of splines (2620) may contain a flexible curvature to rotate or twist and bend and form a petaloid curve, as shown in fig. 26A-26C. The minimum radius of curvature of the splines in the petal configuration may range from about 7mm to about 25 mm. For example, the set of splines may form a delivery assembly at a distal portion of the ablation device (2600), and be configured to transition between a first configuration in which the set of splines is arranged substantially parallel to a longitudinal axis of the ablation device (2600), and a second configuration in which the set of splines is rotated about the longitudinal axis of the ablation device (2600), or twisted and bent and substantially biased away from the longitudinal axis. In the first configuration, each spline of the set of splines may lie in a plane with the longitudinal axis of the ablation device. In the second configuration, each spline of the set of splines may be offset away from the longitudinal axis to form a petal-like curve arranged generally perpendicular to the longitudinal axis. In this manner, the set of splines (2620) are twisted, bent, and biased away from the longitudinal axis of the ablation device (2600), thereby allowing the splines (2620) to more easily conform to the geometry of the endocardial space and specifically adjacent to the ostium opening. When the ablation device is viewed from the front, as best shown in fig. 26C, the second configuration may resemble a flower shape, for example. In some embodiments, each spline of the set of splines in the second configuration may twist and bend to form a petal-like curve that, when viewed from the front, exhibits an angle of more than 180 degrees between a proximal end and a distal end of the curve. The set of splines further may be configured to transition from a second configuration to a third configuration in which the set of splines (2620) may imprint (e.g., contact) target tissue, such as tissue surrounding a pulmonary vein ostium.

In some embodiments, spline shaft (2614) coupled to the set of splines (2620) may allow each spline of the set of splines (2620) to bend and twist relative to catheter shaft (2610) as spline shaft (2614) slides within the lumen of catheter shaft (2610). For example, the set of splines (2620) may form a shape that is substantially parallel to the longitudinal axis of spline shaft (2614) when undeployed, may be wound (e.g., helically twisted) about an axis (2660) that is parallel to the longitudinal axis of spline shaft (2620) when fully deployed, and form any intermediate shape (e.g., cage or barrel) between spline shaft (2614) as it slides within the lumen of catheter shaft (2610).

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

The splines with a set of anode electrodes (2632) may be activated together to deliver a pulse waveform for irreversible electroporation. As shown in fig. 26C, the electrodes on the other splines may be activated together as a cathode electrode (e.g., electrodes (2634) and (2635) on their respective splines) to form an anode-cathode pairing in order to deliver a pulse waveform for irreversible electroporation. The anode-cathode pairing and pulse waveform delivery may be sequentially repeated through a set of such pairings.

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

The delivery assembly may be positioned in the first configuration prior to delivery of the pulse waveform and may be transitioned to the second configuration to contact the pulmonary vein ostium or sinus. In some of these embodiments, a handle may be coupled to a splined shaft (2614), and the handle is configured to affect a transition of the set of splines between the first configuration and the second configuration. For example, the handle can be configured to translate the spline shaft (2614) and the distal cap (2612) relative to the catheter shaft (2610) to thereby actuate the set of splines (2620) coupled to the distal cap and bend and twist the set of splines. The proximal end of spline (2620) may be secured to spline shaft (2614), thereby creating flexing of spline (2620) resulting in bending and twisting motion of spline (2620), for example, when distal cap (2612) and spline shaft (2614) are pulled back relative to catheter shaft (2610) that may be held by a user. For example, the distal end of the set of splines (2620) tethered to the distal cap (2612) can translate up to about 60mm along the longitudinal axis of the ablation device to actuate this configuration change. In other words, translation of the actuating member of the handle may bend and twist the set of splines (2620). In some embodiments, actuation of a knob, wheel, or other rotational control mechanism in the device handle can cause the actuation member or spline shaft to translate and cause the spline (2620) to bend and twist. In some embodiments, the electrical leads of at least two electrodes of the set of electrodes (2630) may be electrically coupled at or near a proximal portion of the ablation device (2600), as, for example, within the handle.

Retraction of the splined shaft (2614) and distal cap (2612) may bring the set of splines (2620) closer together, as shown in fig. 26B, where the set of splines (2620) are generally perpendicular to the longitudinal axis of the catheter shaft (2610). In some embodiments, each spline of the set of splines (2620) may be laterally offset up to about 3cm away from the longitudinal axis of spline shaft (2614). In some embodiments, spline shaft (2614) may contain a hollow lumen. In some embodiments, the cross-section of the splines may be asymmetric so as to have a greater bending stiffness in one bending plane of the spline than in a different bending plane orthogonal to the plane of the cross-section. Such an asymmetric cross-section may be configured to exhibit relatively greater lateral stiffness and thus may be deployed in a final or fully deployed configuration with minimal overlap of the petal-like curves of each spline and its adjacent splines.

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

In some embodiments, the splined electrodes may be electrically activated in a sequential manner to deliver a pulsed waveform with each anode-cathode pairing. In some embodiments, the electrodes may be electrically connected together within the splines with wires, while in alternative embodiments, the electrodes may be connected together with wires in the handle of the device such that the electrodes are at the same electrical potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (2630) may also be different. In some embodiments, 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) may comprise any number of splines, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values and subranges therebetween. In some embodiments, the ablation device (2600) may contain 3 to 20 splines. For example, the ablation device (2600) may contain 4 to 12 splines.

Each of the splines of the set of splines (2620) may contain a respective electrode (2630) having an atraumatic shape to reduce trauma to tissue. For example, the electrode (2630) may have an atraumatic shape comprising a rounded, flattened, curved, and/or blunt head portion configured to contact endocardial tissue. In some embodiments, the electrode (2630) may be positioned along any portion of the spline (2620) distal to the catheter shaft (2610). The electrodes (2630) may have the same or different sizes, shapes, and/or locations along the respective splines.

In this way, the electrodes in the second configuration may be held close to or placed against a portion of the atrial wall of the left atrium to create a lesion directly on the portion by activating the appropriate electrodes using any suitable combination of polarities, as described herein. For example, the set of splines (2620) may be placed in contact against an atrial wall (2654) of an atrium (2652) adjacent to a pulmonary vein (2650) (e.g., ostium or sinus).

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

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

In some embodiments, since the electrodes or subsets of electrodes may be independently addressable, the electrodes may be energized in any order using any pulse shape sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., a stepped pulse waveform), as discussed in further detail herein. It should be understood that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver continuous/transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternating electrodes may be at the same potential, and so on for all other alternating electrodes. Thus, in some embodiments, ablation may be delivered quickly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on their convenience.

In some embodiments, the distal-most portion of the ablation device may contain a set of splines instead of a distal cap or another element that extends the length of the catheter shaft. This may help position the set of splines against tissue and reduce contact with tissue by other elements of the ablation device that may cause trauma to the tissue. For example, fig. 35 is a side view of an embodiment of an ablation device (3500) including a first catheter (3510) (e.g., an outer catheter shaft) at a proximal end of the device (3500). The first catheter (3510) can define a longitudinal axis (3550) and a lumen therethrough. A second catheter (3520) may be slidably disposed within the first catheter lumen and extend from a distal end of the first catheter lumen. The diameter of the second conduit (3520) may be smaller than the diameter of the first conduit (3510). The second catheter (3520) can define a lumen therethrough. For example, the lumen may provide a channel for another device (e.g., a guidewire).

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

Each spline (3530) of the ablation device (3500) can include one or more electrodes (3540) formed on the surface of the spline (3530). Each electrode (3540) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. Each spline (3530) can contain insulated electrical leads for each electrode (3540) formed in the body of the spline (3530) (e.g., within the lumen of the spline (3530)). Fig. 35 shows a set of splines, where each spline (3530) contains a set of electrodes (3540) that have about the same size, shape, and spacing as the electrodes (3540) of adjacent splines. In other embodiments, the size, shape, and spacing of the electrodes (3540) can be different.

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

At least a portion of the set of splines (3530) may include a flexible curvature. For example, a proximal region (3522) and a distal region (3526) of each spline (3530). The set of splines (3530) may form a delivery assembly at a distal portion of the ablation device (3500), and may be configured to transition between a first configuration in which the set of splines (3530) is disposed substantially closer to a longitudinal axis (3540) of the ablation device (3500), and a second configuration in which the set of splines (3530) curve radially outward from the longitudinal axis (3540) of the ablation device (3500) to form a basket-like and/or flower-like shape in which each spline forms a "petal". The spatial curve shape of the spline in the second configuration may be described with reference to equations (1) - (3) corresponding to fig. 34A-34B. For example, in a fully deployed configuration, the integrated magnitude of the rate of rotation of each of the splines in the set of splines (3530) along the length of each spline may be greater than pi radians.

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

In one embodiment, each of the electrodes on a spline may be configured as an anode, while each of the electrodes on a different spline may be configured as a cathode. That is, the sets of electrodes on adjacent splines may have opposite polarities. In another embodiment, the electrodes on one spline may alternate between anodes and cathodes while the electrodes of the other spline have the opposite configuration (e.g., cathode and anode). In some embodiments, 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 be electrically activated in a sequential manner to deliver a pulsed waveform with each anode-cathode pair. In some embodiments, the electrodes (3540) can be electrically connected together with wires within the splines (3530), while in alternative embodiments, the electrodes can be wired together in the handle of the device (3500) such that the electrodes (3540) are at the same electrical potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3540) may also be different. As another example, the splines (3530) may be sequentially activated in a clockwise or counterclockwise manner. As another example, the cathodic splines may be sequentially activated along with a corresponding sequential anodic spline activation until ablation is complete. In embodiments where the electrodes (3540) on a given spline (3530) are separately connected with a wire, the order of activation within the electrodes (3540) of each spline (3530) may also vary. For example, the electrodes (3540) in the splines may be activated all at once or in a predetermined sequence.

The electrodes may be energized in any order using any pulse shape sufficient to ablate tissue by irreversible electroporation. It should be understood that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver energy to electrically isolate one or more regions of cardiac tissue. In some embodiments, alternating electrodes (e.g., all distal electrodes) may be at the same potential, and so on for all other electrodes (e.g., all proximal electrodes). Thus, ablation can be delivered quickly with all electrodes activated simultaneously. There are a variety of such electrode pairing options, and they may be implemented based on their convenience.

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

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

Each of the splines in the set of splines (3530) may contain a respective electrode (3540) having an atraumatic shape to reduce trauma to tissue. For example, the electrode (3540) may have an atraumatic shape that includes rounded, flat, curved, and/or blunt portions. In some embodiments, the electrode (3540) can be positioned along any portion of the spline (3530) distal to the first catheter (3510). The electrodes (3540) may have the same or different size, shape, and/or location along the respective splines. The ablation device (3500) may contain any number of electrodes, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 or more electrodes per spline, including all values and subranges therebetween. In some embodiments, the ablation device (3500) may contain 2 to 12 electrodes per spline.

Fig. 34A-34B are side views of a spline (3400) similar in structure and/or function to the splines described herein, such as the spline shown in fig. 36A-36C. FIG. 34A is a side view of a spline having a unit tangent vector. FIG. 34B is a side view of a spline having two unit tangent vectors. Fig. 34A-34B depict splines (3400) having a petal-like shape, and may correspond to the shape of the splines in the second configuration and/or the third configuration, as described in detail herein. For simplicity, spline (3400) is shown without other elements, such as electrodes. The curved spline (3400) includes a proximal end (3402) and a distal end (3404). A unit tangent vector u (3420) may be defined at each point (3410) along spline (3400). FIG. 34B shows a unit tangent vector u at the proximal end (3402) of spline (3400) ₁(3430) And a unit tangent vector u at the distal end (3404) of the spline (3400)₂(3440)。

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

u'＝du/dl (1)

where l is the arc length along the spline.

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

In some embodiments, a spline that can be transformed to form a petal shape as described herein can form a loop that twists along its length such that the spline has twists along its length. The spline as described herein has an integrated amplitude of the rate of rotation controlled by the following inequality:

∫|u′|}dl>π (2)

that is, the integrated magnitude of the rotational rate of the spline is greater than π radians, or equivalent to 180 degrees. Since u and u 'are perpendicular, u · u' is 0. Thus, the vector b is perpendicular to both u and u'.

In some embodiments, the shape of the spline is generally a space curve with twist, such that the derivative of the rate of rotation generally has a component along b at least at some locations along the length of the spline, the component being controlled by the following equation:

∫(u″·b)dl≠0 (3)

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

Fig. 36A-36C are side views of an ablation catheter (3600) configured with a set of splines deployed and a set of electrodes extending distally of all other elements of the catheter (3600) when the distal splines are fully deployed to reduce trauma to tissue and aid in positioning and contact between the set of electrodes and tissue. Fig. 36A is a perspective view of an embodiment of an ablation device (3600) having a flower-like shape and containing a first catheter (3610) at a proximal end of the device (3600). The first catheter (3610) may define a longitudinal axis (3650) and a lumen therethrough. A second catheter (3620) may be slidably disposed within the first catheter lumen and extend from a distal end of the first catheter lumen. The first and second conduits and the conduit handle for actuating may comprise a single device. A set of splines (3630) may be coupled to the first conduit (3610) and the second conduit (3620). The second catheter (3620) may be translatable along a longitudinal axis (3650) of the ablation device (3600). A proximal end of each spline of the set of splines (3630) may pass through a distal end of the first catheter (3610) and be tethered to the first catheter (3610) within the first catheter lumen, and a distal end of each spline of the set of splines (3630) may be tethered to a distal end (3622) of the second catheter (3620), as described in detail with reference to fig. 35. Since the ablation catheter (3600) does not include a distal cap or other protrusion extending from the distal end of the second catheter (3620), the device (3600) in the second configuration (e.g., flower-shaped) may engage sensitive tissue (such as a thin heart wall) with reduced risk of trauma from the device (3600). The ablation device (3600) may be configured for delivering a pulse waveform to tissue through one or more electrodes on the set of splines (3630) during use, as disclosed in, for example, fig. 21-26.

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

Each spline of the set of splines (3630) may contain a flexible curvature to rotate or twist and bend and form a petaloid curve, as shown in fig. 26A-26C, 34A-34B, and 36A-36C. The minimum radius of curvature of the splines in the petal configuration may be between about 7mm and about 25 mm. For example, the set of splines may form a delivery assembly at a distal portion of the ablation device (3600) and be configured to transition between a first configuration in which the set of splines is disposed generally closer to a longitudinal axis of the ablation device (3600) and a second configuration in which the set of splines is rotated about the longitudinal axis of the ablation device (3600) or twisted and bent and generally biased away from the longitudinal axis. In the first configuration, each spline of the set of splines may lie in a plane with the longitudinal axis of the ablation device. In the second configuration, each spline of the set of splines may be offset away from the longitudinal axis to form a petal-like curve (e.g., a flower shape) in which the longitudinal axes of the splines are arranged substantially perpendicular to longitudinal axis (3650) or at an acute angle relative to the longitudinal axis. As described in detail herein, the shape (e.g., curved, curvilinear) of the set of splines may satisfy equations (1) - (3). In this manner, the set of splines (3620) twists and bends and is biased away from the longitudinal axis of the ablation device (3600), allowing the splines (3620) to more easily conform to the geometry of the endocardial space (e.g., posterior wall and ostium openings). In some embodiments, each spline of the set of splines in the second configuration may twist and bend to form a petal-like curve that, when viewed from the front, exhibits an angle of more than 180 degrees between a proximal end and a distal end of the curve.

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

In some embodiments, the set of splines (e.g., splines 3630) in the first configuration may wrap around the longitudinal axis (3650) of the first conduit (3610) along some portion of its length, but other locations may be otherwise generally parallel to the longitudinal axis of the first conduit (3610). The second catheter (3620) may be retracted into the first catheter (3610) to transition the ablation device (3600) from a first configuration to a second configuration in which the splines (3630) are twisted to form a petal-like shape and are generally angled or offset (e.g., perpendicular, angled in a distal direction) relative to the longitudinal axis (3650) of the first catheter (3610). As the second catheter (3622) is further retracted into the lumen of the first catheter (3610), the set of splines (3630) may extend further distally. As shown in fig. 36A-36C, each spline (3630) may form a twisted loop (e.g., a petal shape, where the 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 and may be angled in a distal direction. Fig. 36A depicts the set of splines (3630), at least a portion of each spline of the set of splines (3630) extending distally of a distal end (3622) of the second catheter (3620). For example, fig. 36A shows that the distal portion of the spline intersects a plane (3660) (perpendicular to the longitudinal axis (3650)) distal to the distal end (3622) of the second catheter (3620). Thus, when the ablation device (3600) is advanced in a distal direction to contact tissue, the set of splines (3630) will contact before the first catheter (3610) and the second catheter (3620). This may reduce trauma to the tissue, as the tissue may contact the flexible set of splines without having to contact the relatively stiff second catheter (3622).

Fig. 36B shows the set of splines (3630) in the second configuration forming a distal (e.g., forward) angle (3680) between a longitudinal axis (3670) of the splines (3630) and a longitudinal axis of the first catheter (3650). A longitudinal axis (3670) of spline (3630) may be defined by a line formed between an apex of spline (3630) and a midpoint between a proximal end and a distal end of spline (3630). 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 of the set of splines (3620) may form a twisted loop such that each spline partially overlaps one or more other splines. The number and spacing of electrodes (3640) and the rotational twist of splines (3630) may be configured by appropriately placing electrodes along each spline to prevent electrodes (3640) on one spline from overlapping electrodes of adjacent overlapping splines.

The splines with a set of anodic electrodes may be activated together to deliver a pulse waveform for irreversible electroporation. The electrodes on the other splines may be activated together as a cathodic electrode (e.g., the electrode on its corresponding spline) to form an anode-cathode pairing in order to deliver a pulse waveform for irreversible electroporation. The anode-cathode pairing and pulse waveform delivery may be sequentially repeated through a set of such pairings.

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

The delivery assembly may be positioned in the first configuration prior to delivery of the pulse waveform and may be transitioned to the second configuration to contact the pulmonary vein ostium or sinus. For example, fig. 36C depicts a distal-most portion of the set of splines (3630) in close proximity to and/or in contact with a tissue wall (3690) (e.g., the posterior left atrial wall). The set of splines (3630) in fig. 36C is in a second configuration in which at least a portion of each spline of the set of splines (3630) extends distally of the distal end (3622) of the second catheter (3620). The tissue (3690) may be an endocardial surface of a heart wall, such as a posterior wall of a left atrium. The distal end (3622) of the second catheter (3620) may be spaced a first distance (3692) from the tissue (3690). Thus, the ablation device (3600) in the second configuration may engage tissue (3690) in an atraumatic manner with reduced risk of perforation or other trauma. Accordingly, the ablation device (3600) may be used to ablate even thin tissue structures, such as the posterior left atrial wall.

In some of these embodiments, a handle may be coupled to a second catheter (3620), and the handle is configured to affect a transition of the set of splines between the first configuration and the second configuration. For example, the handle may be configured to translate the second conduit (3620) relative to the first conduit (3610) to actuate the set of splines (3630) coupled to the second conduit (3620) and bend and twist the set of splines. The proximal end of spline (3630) may be fixed to second catheter (3620), thereby creating flexion of spline (3630) resulting in bending and twisting motion of spline (3630), for example, when second catheter (3620) is pulled back relative to first catheter (3610) which may be gripped by a user. For example, the distal end of the set of splines (3630) tethered to the second catheter (3620) can be translated along the longitudinal axis of the ablation device by up to about 60mm to actuate this configuration change. In other words, translation of the actuating member of the handle may bend and twist the set of splines (3630). In some embodiments, actuation of a knob, wheel, or other rotational control mechanism in the device handle may cause the actuation member or second conduit to translate and cause splines (3630) to bend and twist. In some embodiments, electrical leads of at least two electrodes of the set of electrodes (3640) may be electrically coupled at or near a proximal portion of the ablation device (3600), as, for example, within the handle.

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

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

In some embodiments, the splined electrodes may be electrically activated in a sequential manner to deliver a pulsed waveform with each anode-cathode pairing. In some embodiments, the electrodes may be electrically connected together within the splines with wires, while in alternative embodiments, the electrodes may be connected together with wires in the handle of the device such that the electrodes are at the same electrical potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3640) may also be different. In some embodiments, 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) may include any number of splines, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values and subranges therebetween. In some embodiments, the ablation device (3600) may contain 3 to 20 splines. For example, the ablation device (3600) may contain 4 to 12 splines.

Each of the splines in the set of splines (3630) may include a respective electrode (3640) having an atraumatic shape to reduce trauma to tissue. For example, the electrode (3640) may have an atraumatic shape including rounded, flattened, curved, and/or blunt portions configured to contact endocardial tissue. In some embodiments, the electrode (3640) may be positioned along any portion of the spline (3630) distal to the first catheter (3610). Electrodes (3640) may have the same or different size, shape and/or location along the respective splines.

In this way, the electrodes in the second configuration may be held close to or placed against a portion of the atrial wall of the left atrium to create a lesion directly on the portion by activating the appropriate electrodes using any suitable combination of polarities, as described herein. For example, the set of splines (3630) may be placed in contact against an atrial wall (3654) and/or a posterior wall of an atrium (3652) adjacent to a pulmonary vein (3650) (e.g., ostium or sinus).

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

Fig. 37B is a schematic diagram of a perspective view of the left atrium (3700) after tissue ablation. The ablation device (3700) can be used to create a set of ablation zones (3740, 3742, 3744) on the posterior wall (3710) of the left atrium (3700). For example, repeated activation of one or more of the electrodes on one or more of the splines of the ablation device (3730) as the catheter is moved between complete ablations may create the set of ablated regions (3740, 3742, 3744) along the posterior wall (3710) of the left atrium (3700). In some embodiments, the ablation regions (3740, 3742, 3744) may partially overlap each other. These successive overlapping ablation zones may approximately form an ablation bold line (3746). One or more ablation lines may be connected to other ablation lines and/or ablation zones (e.g., created around the pulmonary sinus or ostium) to thereby create a box-like lesion. For example, a series of successive ablation zones may be formed by the ablation device (3730) to form a box-like lesion around the posterior wall (3710) of the left atrium (3700) that also encircles one or more of the pulmonary veins (3720). In this way, a continuous transmural lesion may be created around all pulmonary veins, resulting in electrical isolation of the pulmonary veins to provide a desired therapeutic effect. In some embodiments, each ablation region in a set of ablation regions (3740, 3742, 3744) can be between about 2cm and about 6cm in diameter. For example, the diameter of the ablation zone may be between about 2.3cm and about 4.0 cm.

In some embodiments, since the electrodes or subsets of electrodes may be independently addressable, the electrodes may be energized in any order using any pulse shape sufficient to ablate tissue by irreversible electroporation. It should be understood that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver sufficient energy to electrically isolate one or more pulmonary veins. In some embodiments, alternating electrodes may be at the same potential, and so on for all other alternating electrodes. Thus, in some embodiments, ablation may be delivered quickly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on their convenience.

Fig. 27A-27B are side views of an embodiment of an ablation device (2700) including a catheter shaft (2710) at a proximal end of the device (2700) and a set of splines (2720) coupled to the catheter shaft (2710) at a distal end of the device (2700). The ablation device (2700) may be configured to deliver a pulse waveform to tissue through one or more splines of the set of splines (2720) during use. Each spline (2720) of ablation device (2700) may include one or more, possibly independently addressable, electrodes (2730) formed on a surface (e.g., distal end) of spline (2720). Each electrode (2730) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads may maintain a potential difference between about 200V to about 2000V across the thickness without creating a dielectric breakdown. Each spline of the set of splines (2720) may include an insulated electrical lead for each electrode (2730) formed in a body of the spline (2720) (e.g., within a 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 a distal portion of the ablation device (2700) and configured to transition between a first configuration and a second configuration. The set of splines (2720) in the first configuration is substantially parallel to a longitudinal axis of the ablation device (2700) and may be closely spaced together. The set of splines (2720) is depicted in a second configuration in fig. 27A-27B, wherein the set of splines (2720) extend out of the distal end of the catheter shaft (2710) and are biased (e.g., bent) away from the longitudinal axis of the ablation device (2700) and the other splines (2720). In this way, the splines (2720) may more easily conform to the geometry of the endocardial space. The delivery assembly may be positioned in the first configuration prior to delivering the pulse waveform, and may transition to the second configuration to reach a portion of cardiac tissue (e.g., a posterior wall of a left atrium or a ventricle). Such a device delivering irreversible electroporation pulse waveforms can create larger lesions for focal ablation.

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

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). Thus, the length of the set of splines (2720) may vary, as shown in fig. 27A and 27B. As the set of splines (2720) further extends outward from the catheter shaft (2710), the distal ends of the set of splines (2720) may be further biased away from each other and the longitudinal axis of the catheter shaft (2710). The set of splines (2720) may be slidably advanced out of the catheter shaft (2710) independently or in one or more sets. For example, the set of splines (2720) may be disposed within a catheter shaft (2710) in the first configuration. The splines (2720) may then be pushed out of the catheter shaft (2710) and converted to the second configuration. The splines (2720) may advance together or advance such that 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). In some embodiments, splines (2720) may be independently advanced. In the second configuration, the electrode (2730) is longitudinally and/or laterally offset from the catheter shaft (2710) relative to a longitudinal axis of the distal end of the catheter shaft (2710). This may facilitate delivery and positioning of the electrode (2730) against the endocardial surface. In some embodiments, each spline of the set of splines (2720) may extend up to about 5cm from the distal end of the catheter shaft (2710).

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

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

Each of the splines of the set of splines (2720) may include a respective electrode (2730) at a distal end of the set of splines (2720). The set of electrodes (2730) may include an atraumatic shape to reduce trauma to tissue. For example, the electrode (2730) may have an atraumatic shape including rounded, flattened, curved, and/or blunt portions configured to contact endocardial tissue. In some embodiments, the electrode (2730) may be positioned along any portion of the spline (2720) distal to the catheter shaft (2710). The electrodes (2730) may have the same or different size, shape, and/or location along the respective splines.

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

In fig. 27A-27B, an electrode (2730) is formed on the surface of each spline (2720) such that each spline (2720) contains an insulated electrical lead. The diameter of the spline (2720) lumen may thus be reduced, and allow the spline (2720) to be thicker and mechanically stronger. Accordingly, dielectric breakdown of the insulation may be further reduced, thereby improving reliability and longevity of each spline (2720) and ablation device (2700). Further, 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 variable radii of curvature may help position the electrode (2730) at some location in the endocardial tissue. Splines (2720) may be of the same or different material, thickness, and/or radius of curvature. For example, the thickness of each spline may decrease distally.

In this way, the electrodes in the second configuration may be pressed against, for example, the posterior left atrial wall to create a localized or focal lesion directly on the posterior left atrial wall by activating the appropriate electrodes using any suitable combination of polarities. For example, adjacent electrodes (2730) may be configured with opposite polarities.

Since the electrodes or subsets of electrodes may be independently addressable, the electrodes may be energized in any order using any pulse shape sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., a stepped pulse waveform), as discussed in further detail herein. It will be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver transmural lesions over a relatively wide area of endocardial tissue. In some embodiments, alternating electrodes may be at the same potential, and so on for all other alternating electrodes. Thus, ablation can be delivered quickly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on their convenience.

Referring to fig. 27C, it should be understood that, unless otherwise specified, components having reference numbers similar to those in fig. 27A-27B (e.g., electrode (2730) in fig. 27A-27B and electrode (2730') in fig. 27C) may be structurally and/or functionally similar. Fig. 27C shows a set of splines (2720'), where each spline (2720') contains a pair of electrodes (2730', 2740).

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

In some embodiments, the electrodes (2730', 2740) of the ablation device (2700') may be about 0.5mm to about 5.0mm in length and the cross-sectional dimension (e.g., diameter) may be about 0.5mm to about 4.0mm, including all values and subranges therebetween. The splined leads (2720') in the second configuration can be splayed apart from each other at the distal end of the ablation device (2700') to an extent S of about 5.0mm to about 20.0mm_d(including all values and subranges therebetween), and may extend a length S from the distal end of the catheter shaft (2710') of about 8.0mm to about 20.0mm_lIncluding all values and subranges therebetween. In some embodiments, the ablation device (2700') can include 4 splines, 5 splines, or 6 splines. In some embodiments, each spline may independently contain 1 electrode, 2 electrodes, or 3 or more electrodes.

The set of splines (2720') may form a delivery assembly at a distal portion of the ablation device (2700') and configured to transition between a first configuration and a second configuration. The set of splines (2720') in the first configuration are substantially parallel to a longitudinal axis of the ablation device (2700) and may be closely spaced together. The set of splines (2720') in a second configuration is depicted in fig. 27C, wherein the set of splines (2720') extend out of the distal end of the catheter shaft (2710') and are biased (e.g., bent) away from the longitudinal axis of the ablation device (2700') and the other splines (2720 '). In this way, the splines (2720') may more easily conform to the geometry of the endocardial space. The delivery assembly may be positioned in the first configuration prior to delivery of the pulse waveform, and may be transitioned to the second configuration to contact a region of endocardial tissue in order to create a large focal lesion when delivering the pulse waveform for irreversible electroporation as disclosed herein. In some embodiments, the electrode in the second configuration (2730') (also sometimes referred to as a "distal electrode") depicted in fig. 27C may be configured to contact and press against endocardial tissue, while the electrode in the second configuration (2740) (also sometimes referred to as a "proximal electrode") may not contact 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 results in 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') further extends outwardly from the catheter shaft (2710'), the distal ends of the set of splines (2720') may be further biased away from each other and the longitudinal axis of the catheter shaft (2710'). The set of splines (2720') may be slidably advanced out of the catheter shaft (2710') independently or in one or more sets. For example, the set of splines (2720') may be disposed within the catheter shaft (2710') in the first configuration. The splines (2720') may then be pushed out of the catheter shaft (2710') and converted to the second configuration. The splines (2720') may advance together or advance such that 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', 2740). In some embodiments, the splines (2710') may be independently advanced through a respective lumen (e.g., sheath) of the catheter shaft (2710'). In the second configuration, the electrodes (2730', 2740) are longitudinally and/or laterally offset from the catheter shaft (2710') relative to a longitudinal axis of the distal end of the catheter shaft (2710 '). This may facilitate delivery and positioning of the electrodes (2730', 2740) against the endocardial surface. In some embodiments, each spline of the set of splines (2720') may extend up to about 5cm from the distal end of the catheter shaft (2710').

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

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

The set of electrodes (2730', 2740) may include an atraumatic shape to reduce trauma to tissue. For example, the electrodes (2730', 2740) may have an atraumatic shape including rounded, flattened, curved, and/or blunt portions configured to contact endocardial tissue. In some embodiments, the electrodes (2730', 2740) may be positioned along any portion of the splines (2720') distal to the catheter shaft (2710). The electrodes (2730', 2740) may have the same or different size, shape, and/or location along the respective splines. One or more of the splines (2720') may contain three or more electrodes.

In some embodiments, each of the electrodes (2730') on a spline (2720') can be configured as an anode, while each of the electrodes (2730') on adjacent splines (2720') can be configured as a cathode. In another embodiment, each of the electrodes (2730') on one spline may alternate between an anode and a cathode, with each of the electrodes of adjacent splines having an opposite configuration (e.g., cathode and anode). In some embodiments, the electrode subsets may be electrically connected together with wires in the handle of the device such that the electrodes are at the same electrical potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (2730) may also be different. In some embodiments, adjacent distal (2730') and proximal (2740) electrodes 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') may include any number of splines, such as 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, or more splines, including all values and subranges therebetween. In some embodiments, the ablation device (2700') can include 3 to 20 splines. For example, ablation device (2700) may contain 6 to 12 splines.

In fig. 27C, two electrodes (2730', 2740) are formed on the surface of each spline (2720') such that each spline (2720') contains two insulated electrical leads. 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 electrical leads in the spline (2720'). The splines (2720') may be of the same or different material, thickness and/or radius of curvature. For example, the thickness of each spline (2720') may decrease distally.

In this way, the electrodes in the second configuration may be placed against a portion of endocardial tissue to create a lesion directly on the portion by activating the appropriate electrodes using any suitable combination of polarities in order to deliver a pulse waveform for irreversible electroporation. For example, adjacent electrodes (2730', 2740) may be configured with opposite polarities.

Since the electrodes may be independently addressable, the electrodes may be energized in any order using any pulse shape sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., a stepped pulse waveform), as discussed in further detail herein. It should be understood that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver continuous/transmural energy to electrically isolate one or more pulmonary veins. In some embodiments, alternating electrodes may be at the same potential, and so on for all other alternating electrodes. Thus, ablation can be delivered quickly with all electrodes activated simultaneously. A variety of such electrode pairing options exist and may be implemented based on their convenience.

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

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

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

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

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

In some embodiments, the distal electrode (2816) and the proximal electrode (2818) may form an anode-cathode pair. For example, the distal electrodes (2816) may be configured as anodes and each of the proximal electrodes (2818) may be configured as cathodes. In some embodiments, the ablation device (2800) may contain 3 to 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. In some embodiments, the ablation device (2800) may contain 3 to 20 splines. For example, in one embodiment, the ablation device (2800) may contain 6 to 10 splines. Further, in some embodiments, the shape of the expanded set of splines (2814) may be asymmetric, e.g., with a distal portion that is more spherical or rounded than a proximal portion thereof. Such a spherical distal portion (and proximal electrode positioning) may help to further control the size and depth of the focal ablation.

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

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

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

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

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

In some embodiments, the configuration of the catheter (2910, 2920) and the electrode (2916, 2926) may control the depth, shape, and/or diameter/size of the focal ablation lesion created by the ablation device (2900). The first conduit (2910) and the second conduit (2920) may be configured to translate along a longitudinal axis of the outer conduit (2902). In some embodiments, the ablation device (2900) may be configured to transition between a first configuration in which the set of catheters (2910, 2920) is arranged substantially parallel to a longitudinal axis of the outer catheter (2902) and a distal portion of the catheters (2910, 2920) is disposed within the outer catheter (2902) (e.g., fig. 29A); in the second configuration, the electrodes (2916, 2926) are pushed out of the distal end (2903) of the outer catheter lumen (2902) and any suitable distance away from the distal end; in the third configuration, the distal portion of each catheter (2910, 2920) may rotate, twist, or bend relative to the proximal portion of its corresponding catheter (2910, 2920) about its corresponding hinge (2918, 2928) (e.g., fig. 29B-29D). For example, as best shown in fig. 29B-29C, the first catheter (2910) may include a distal portion (2914) rotatable about a first hinge (2918) that may be configured to position the distal portion (2914) at a plurality of positions relative to the proximal portion (2912). The conduits (2910, 2912) in the second and third configurations may be angled away from each other to bias away from a longitudinal axis of the outer conduit (2902). The distal end of the proximal portion (2912, 2922) may form an angle of between about 5 degrees and about 75 degrees with respect to the longitudinal axis (e.g., fig. 29D). It should be understood that the ablation device (2900) may be transitioned to any intermediate configuration between the first, second, and third configurations, either continuously or in discrete steps.

In some embodiments, conduction between the electrodes through the blood pool and/or the endocardial tissue causes an electric field to be generated and applied to the endocardial surface as an ablative property. The electrodes may be held close to or placed in physical contact against a portion of the atrial wall of the left atrium to create a lesion on the portion by activating one or more of the electrodes using any suitable combination of polarities. In this way, activating the electrodes using the predetermined configuration can provide targeted, unambiguous and precise focal ablation by controlling the focal ablation spot size based on the position and orientation of the electrodes (2916, 2926) relative to the proximal portion (2912, 2922) of the catheter (2910, 2920). For example, in some embodiments, the first electrode (2916) may be configured to have a first polarity and the second electrode (2926) may be configured to have a second polarity opposite the first polarity. When the electrodes (2916, 2926) are rotated such that they are relatively close to each other (e.g., when the proximal portion (2912) and the distal portion (2914) form an acute angle (2950)), a relatively higher intensity electric field with a relatively smaller/more focused diameter results in a focal ablation lesion of relatively smaller diameter and good depth on the endocardial surface. For purely illustrative purposes, and not by way of limitation, the acute angle formed at the hinged hinge may range between about 15 degrees and about 70 degrees. In some embodiments, the electric field strength in the focal ablation zone may be about 200V/cm or higher. As the electrodes (2916, 2926) rotate about their respective hinges (2918, 2928) such that they are relatively farther from each other (e.g., as the proximal portion (2912) and distal portion (2914) form a larger angle), a relatively more dispersed and lower intensity electric field is generated, resulting in a relatively wider and shallower focal ablation lesion on the endocardial surface. In this manner, by varying the degree of rotation of the electrode (2916, 2926) relative to the proximal portion (2912, 2922) of the catheter (2910, 2920), the depth, shape, and/or size of the lesion can be controlled without turning off the ablation device (2900). Such an aspect may be used to create multiple lesions of different sizes, shapes, and/or depths using the same ablation device. For example, the lesion diameter may be about 2mm to about 3cm, and the lesion depth may be between about 2mm and about 12 mm. Although the electrodes (2916, 2926) may be positioned to contact endocardial tissue, it should be understood that the electrodes (2916, 2926) need not contact endocardial tissue.

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

Fig. 29B-29C depict a first catheter (2910) having an articulated distal portion (2914). The first conduit (2910) may include a proximal portion (2912) coupled to a distal portion (2914) by a hinge (2918). The distal portion (2914) may contain an electrode (2916) as described herein. In some embodiments, the hinge (2918) may include a rotatable wheel. In other embodiments, the hinge (2918) may include a portion of the proximal portion (2912) or the distal portion (2914) that is more flexible than other portions of the first catheter (2910), the portion having a reduced cross-sectional area relative to the catheter. In still other embodiments, the hinge (2918) may include a joint, a rotatable wheel, a ball joint, a condylar joint, a saddle joint, a pivot, a track, or the like.

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

Fig. 29D depicts an embodiment of the ablation device (2900) in the third configuration, in which the distal portions of the first catheter (2910) and the second catheter (2920) extend out of the outer catheter or sheath (2902) and are rotated to a desired position (e.g., fully rotated, fully articulated) relative to the proximal portions (2912, 2922) of the catheters (2910, 2920). In some embodiments, the wires (2912, 2922) of each of the catheters (2910, 2920) may be coupled together at the handle such that actuation of the control mechanism controls the wires (2912, 2922) together such that the distal portion (2914, 2924) of each of the catheters (2910, 2920) may simultaneously rotate about its respective hinge (2918, 2928). In the second and third configurations, the first and second conduits (2910, 2920) may be biased away from a longitudinal axis of the outer conduit (2902).

When the first and second conduits (2910, 2920) extend out of the outer conduit (2902), one or more portions of the conduits (2910, 2920) may assume their natural (e.g., unconstrained) one or more shapes (such as curved shapes). The conduits (2910, 2920) may be pushed out of the outer conduit (2902) together or independently. In some embodiments, the proximal portion (2912, 2922) of the catheter (2910, 2920) may include a flexible curvature such that the distal ends of the catheter (2910, 2920) may be configured to splay apart from one another. The minimum radius of curvature of the conduit (2910, 2920) may range from about 1cm or more. For example, the radius of curvature of the proximal portion (2912, 2922) may be about 1cm or greater. In some embodiments, the radius of curvature of the distal portion (2914, 2924) may be about 1cm or greater.

In some embodiments, the electrodes (2916, 2926) of the ablation device (2900) may comprise a length of about 0.5mm to about 7.0mm and a cross-sectional dimension (e.g., diameter) of about 0.5mm to about 4.0mm, including all values and subranges therebetween. The electrodes (2916, 2926) of the different conduits (2910, 2920) may be spaced apart from each other by a distance of about 3.0mm to about 20mm, including all values and subranges therebetween. The electrodes (2916, 2926) may be located about 1.0mm to about 4.0mm from the distal end of their respective conduits (2910, 2920), including all values and subranges therebetween. In some embodiments, the distal end of the catheter (2910, 2920) may contain an electrode (2916, 2926). One or more focal ablation lesions comprising a diameter of about 1.0cm to about 2.0cm, including all values and subranges therebetween, can be formed.

Fig. 30 is a side view of another embodiment of an ablation device (3000) including an outer catheter or sheath (3010) defining a longitudinal axis and a set of four catheters (3020, 3030, 3040, 3050) slidable within a lumen (3010). Each of the catheters (3020, 3030, 3040, 3050) may include a proximal portion (3023, 3033, 3043, 3053), a distal portion (3024, 3034, 3044, 3054), and a hinge (3021, 3031, 3041, 3051) coupling the proximal portion (3023, 3033, 3043, 3053) to the distal portion (3024, 3034, 3044, 3054). Each of the distal portions (3024, 3034, 3044, 3054) may include an electrode (3022, 3032, 3042, 3052). The distal end of the catheter (3020, 3030, 3040, 3050) and/or the electrode (3022, 3032, 3042, 3052) may include an atraumatic shape (e.g., rounded, flattened, curved, and/or blunt portions) to reduce trauma to tissue. Each of the conduits (3020, 3030, 3040, 3050) may include a hinge (3021, 3031, 3041, 3051), as described in detail herein. It should be understood that the ablation device (3000) may contain any number of catheters, including a set of 2, 3, 4, 5, 6, or more catheters.

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

In some embodiments, the configuration of the catheter (3020, 3030, 3040, 3050) and the electrode (3022, 3032, 3042, 3052) may control the depth, shape, and/or diameter/size of the focal ablation lesion created by the ablation device (3000). The set of conduits (3020, 3030, 3040, 3050) may be configured to translate along the longitudinal axis to transition between a first configuration, a second configuration, and a third configuration. In some embodiments, the ablation device (3000) may be configured to transition between a first configuration in which the set of catheters (3020, 3030, 3040, 3050) is arranged substantially parallel to the longitudinal axis of the outer catheter or sheath (3010) and a distal portion of the catheters (3020, 3030, 3040, 3050) is disposed within the outer catheter (3010); in the second configuration, the electrodes (3022, 3032, 3042, 3052) are pushed out of the distal end (3011) of the outer catheter (3010) lumen and any suitable distance away from the distal end; in the third configuration, the distal portion of each catheter (3020, 3030, 3040, 3050) may rotate, twist, or bend relative to the proximal portion of its corresponding catheter (3020, 3030, 3040, 3050) about its corresponding hinge (3021, 3031, 3041, 3051) (e.g., fig. 30). For example, a first catheter (3020) may include a distal portion (3024) rotatable about a first hinge (3021), which may be configured to position the distal portion (3024) at a plurality of positions relative to the proximal portion (3023), as discussed above with reference to fig. 29A-29D. It should be understood that the ablation device (3000) may be converted to any intermediate configuration between the first, second, and third configurations, either continuously or in discrete steps. In the second configuration, the set of conduits may be biased away from the longitudinal axis.

In some embodiments, one or more pulse waveforms may be applied between electrodes (3022, 3032, 3042, 3052) configured in an anode set and a cathode set. For example, adjacent or approximately diametrically opposed pairs of electrodes may be activated together as an anode-cathode set. In fig. 30, the first electrode (3022) may be configured as an anode and may be paired with the 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 first electrode (3022) and second electrode (3032) pair may use the third electrode (3042) and fourth electrode (3052) pair to apply a first pulse waveform followed by the sequential application of a second pulse waveform. In another embodiment, a pulse waveform may be simultaneously applied to each of the electrodes, wherein the second electrode (3032) and the third electrode (3042) may be configured as anodes and the first electrode (3022) and the fourth electrode (3052) may be configured as cathodes. It should be understood that any of the pulse waveforms disclosed herein may be applied to a series of anode-cathode electrodes, either progressively or sequentially. Some embodiments of the ablation device (3000) may have the same dimensions as described above with respect to the ablation device (2900).

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

Fig. 31A-31B are perspective views of yet another embodiment of an ablation device (3100) including an outer catheter or sheath (3110) defining a longitudinal axis and a catheter (3160) slidable within a lumen of the outer catheter. A catheter (3160) may extend from the distal end of the lumen. A catheter (3160) may include a proximal portion (3160), a plurality of distal portions (3122, 3132, 3142, 3152), and a hinge (3162) coupling the proximal portion to each of the plurality of distal portions. For example, the articulation (3162) may comprise a hinge, joint, rotatable wheel, ball joint, condyloid joint, saddle joint, pivot, track, or the like. The distal portions (3122, 3132, 3142, 3152) are folded back within the outer catheter (3110) and when each distal portion (3122, 3132, 3142, 3152) is folded, an internal spring (not shown) connected to each portion is in a stressed configuration. When the distal portion (3122, 3132, 3142, 3152) is unconstrained (i.e., when the inner catheter (3160) is deployed or pushed far enough out of the outer catheter (3110)), the spring assumes its natural or unstressed configuration, resulting in articulation of the articulation member (3162), after which the distal portion (3122, 3132, 3142, 3152) articulates outwardly and assumes a configuration that is substantially perpendicular to the longitudinal axis of the catheter. As shown in fig. 31B, the distal end of the catheter (3160) may be coupled to a set of electrodes (3120, 3130, 3140, 3150) by a hinge (3162). In some embodiments, the hinge (3162) may be coupled to the first distal portion (3122), the second distal portion (3132), the third distal portion (3142), and the fourth distal portion (3152). The electrodes (3120, 3130, 3140, 3150) may be disposed on a surface of the respective distal portion (3122, 3132, 3142, 3152). The distal portion (3120, 3130, 3140, 3150) may assume its natural (e.g., unconstrained) shape so as to be substantially perpendicular to the longitudinal axis of the catheter (3160) as the catheter (3160) is advanced out of the outer catheter (3110).

The electrodes (3120, 3130, 3140, 3150) may include atraumatic shapes (e.g., rounded, flattened, curved, and/or blunt portions) to reduce trauma to tissue. Each electrode (3120, 3130, 3140, 3150) may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In other embodiments, the insulation on each of the electrical leads may maintain a potential difference between about 200V and about 2000V across its thickness, including all values and subranges therebetween, without creating a dielectric breakdown. The catheter (3160) may include insulated electrical leads for each electrode (3120, 3130, 3140, 3150) formed in the body (e.g., lumen) of the catheter (3160). Each of the electrodes (3120, 3130, 3140, 3150) may be connected to a corresponding insulated electrical lead, resulting in a handle (not shown) being coupled to a proximal portion of the catheter (3160). In some embodiments, the size, shape, and/or location of the electrodes (3120, 3130, 3140, 3150) may be different from one another.

The conduit (3160) may be configured to translate along the longitudinal axis to transition between a first configuration, a second configuration, and a third configuration. In some embodiments, the ablation device (3100) may be configured to transition between a first configuration in which the set of electrodes (3120, 3130, 3140, 3150) are arranged substantially parallel to a longitudinal axis of the outer catheter (3110) and within the outer catheter (3110) (e.g., fig. 31A); in the second configuration, the set of electrodes (3120, 3130, 3140, 3150) is pushed out of the distal end (3111) of the outer catheter lumen and any suitable distance away from the distal end (not shown in fig. 31A); in the third configuration, the electrodes (3120, 3130, 3140, 3150) may rotate, twist, or bend about their corresponding hinges (3162) relative to the proximal portion of the catheter (3160) (e.g., fig. 31B). The transition from the first configuration to the second and third configurations may be performed by pushing the catheter (3160) and the electrode (3120, 3130, 3140, 3150) out of the distal end of the outer catheter (3110). It should be understood that the ablation device (3100) may be convertible to any intermediate configuration between the first, second, and third configurations, either continuously or in discrete steps.

Fig. 31B shows the electrodes (3120, 3130, 3140, 3150) evenly spaced to form a plus ("+") shape. However, the angle between adjacent electrodes (3120, 3130, 3140, 3150) may be selected based on the desired focal ablation pattern. Similarly, the electrodes (3120, 3130, 3140, 3150) in fig. 31B are generally 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 may be applied between electrodes (3120, 3130, 3140, 3150) configured in an anode set and a cathode set. For example, adjacent or approximately diametrically opposed pairs of electrodes may be activated together as an anode-cathode set. In fig. 31B, the first electrode (3120) may be configured as an anode, and may be 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 first (3120) and third (3140) electrode pairs may apply the first pulse waveform using the second (3130) and fourth (3150) electrode pairs, and then sequentially apply the second pulse waveform. In another embodiment, the pulse waveform may be applied to each of the electrodes simultaneously, wherein the first electrode (3120) and the second electrode (3130) may be configured as anodes, and the third electrode (3140) and the fourth electrode (3150) may be configured as cathodes. It should be understood that any of the pulse waveforms disclosed herein may be applied to a series of anode-cathode electrodes, either progressively or sequentially.

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

Fig. 32 is a schematic cross-sectional view of a high intensity electric field generated by ablation device (3200) for ablating tissue, such as tissue in a ventricular chamber. For example, the ablation device (3200) may be positioned in an endocardial space of a left ventricle of a heart. The ablation device (3200) depicted in fig. 32 may be similar to those ablation devices (3000, 3100) described with reference to fig. 30 and 31A-31B. In some embodiments, the electrodes (3210, 3220, 3230, 3240) may be juxtaposed to the tissue wall when in the third configuration. In some embodiments, the electrode (3210, 3220, 3230, 3240) of fig. 32 may be between about 1mm to about 3mm wide and between about 3mm and about 9mm long. For example, the electrodes (3210, 3220, 3230, 3240) may be about 2mm wide and about 6mm long.

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 electrode (3210) and the second electrode (3230) may have a potential difference of up to about 1500V. Activation of one or more of the electrodes (3210, 3220, 3230, 3240) of the one or more catheters may create one or more ablation zones along a portion of the heart chamber wall. The electric field curve (3350) is a constant amplitude line corresponding to an ablation zone (3350) having an electric field strength threshold of about 460V/cm when the first electrode (3220) and the third electrode (3240) are activated. In some embodiments, the ablation zone (3350) may be up to about 12mm in width and up to about 20mm in length. Alternatively, the ablation device may be placed adjacent to or against a portion of the posterior wall of the left atrium, and by activating one or more electrodes, an appropriate pulse waveform may be delivered for irreversible electroporation energy delivery to ablate tissue.

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

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

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

In some embodiments, the set of splines (3330) may be configured to transition between a first configuration in which the set of splines (3330) is arranged substantially parallel to a longitudinal axis (3324) of the ablation device (3300) and a second configuration in which a distal end of each spline of the set of splines (3330) curves radially outward from the longitudinal axis (3324). In this manner, the set of distal electrodes (3332) and cap electrodes (3322) may be shaped/oriented to form the second configuration shown in fig. 33A, 33B, and 33E. The cap electrode (3322) may be spaced apart from each distal electrode in the set of distal electrodes (3332) by up to about 5mm, including all values and subranges therebetween. For example, the cap electrode (3322) may be spaced apart from each distal electrode in the set of distal electrodes (3332) by about 0.5mm to about 3 mm. In the second configuration, the distal portion of each spline of the set of splines (3330) may be at an angle (3336) of between about 45 degrees and about 90 degrees relative to the longitudinal axis (3312), including all values and subranges therebetween. For example, the distal portion of each spline of the set of splines (3330) in the second configuration may be at an angle (3336) of between about 70 degrees and about 80 degrees relative to the longitudinal axis (3312). For example, in the second configuration, when the cap electrode (3322) and the set of distal electrodes (3332) are projected onto a plane perpendicular to the longitudinal axis (3324), they may take the shape of a "plus" symbol, as shown in the front view in fig. 33B.

In some embodiments, the inner shaft (3320) may be retracted into the outer catheter lumen (3312) by a predetermined amount to transition the ablation device (3300) from the first configuration to the second configuration. It should be appreciated that the set of splines (3330) may be converted to any intermediate configuration between the first configuration and the second configuration, either continuously or in discrete steps. The set of splines (3330) may form a shape when undeployed that is substantially parallel to a longitudinal axis (3324) of the inner shaft (3320), and may form a basket or ball shape when the distal end of the set of splines (3330) is bent radially outward from the longitudinal axis (3324).

Fig. 33A, 33B, and 33E illustrate a set of splines (3330), wherein each spline of the set of splines (3330) contains a distal electrode (3332) and one or more proximal electrodes (3334) that differ in one or more of size, shape, number, and spacing. For example, fig. 33A shows one distal electrode (3332) and two proximal electrodes (3334) for each spline of the set of splines (3330). In some embodiments, each proximal electrode (3334) may be formed on the surface of its spline (3330) along its entire circumference (i.e., around the entire thickness of the spline). In some embodiments, each distal electrode (3332) may be formed on a surface of a portion of a circumference of a spline thereof. That is, as shown in fig. 33C and 33D, the distal electrode (3332) may be partially on the circumference of its corresponding spline and not cover the entire circumference of its spline (3330). For example, the distal electrode (3332) may surround the circumference of its corresponding spline and be partially covered by an insulating layer such that only a portion (e.g., a window) of the distal electrode (3332) is exposed. In some embodiments, one or more electrodes may be completely covered by a thin insulating layer for biphasic operation. In some embodiments, the set of distal electrodes (3332) of the set of splines (3330) may make an angle (3333) of between about 30 degrees to about 300 degrees, including all values and subranges therebetween, about the center of its corresponding spline (3330). For example, the set of distal electrodes (3332) of the set of splines (3330) may be angled (3333) between about 60 degrees to about 120 degrees about a center of their corresponding splines (3330). In this way, a substantial portion of the electric field generated by the set of distal electrodes (3332) in the second configuration may be directed in an anterior direction and projected into the target tissue to assist in focal ablation, rather than directed away from the target tissue and projected into the blood.

In this way, the distal electrode (3332) may be configured to face in a particular direction. For example, fig. 33A and 33E show the set of distal electrodes (3332) and cap electrodes (3322) facing generally forward at the distal end of the device (3300) in the second configuration when the distal end of the set of splines (3330) is bent radially outward from the longitudinal axis (3324). Further, a distal electrode (3332) may be disposed at a distal end of its splines such that the distal electrode (3332) of the set of splines (3330) is disposed proximate to the cap electrode (3322).

In some embodiments, each spline of the set of splines (3330) may contain a set of electrodes (3332, 3334) that are about the same size, shape, number, and spacing as the corresponding electrodes (3332, 3334) of an adjacent spline. The thickness of each spline (3330) may vary based on the number of electrodes (3332, 3334) formed on each spline (3330), which may correspond to the number of insulated electrical leads in the spline (3330). Splines (3330) may be of the same or different materials, thicknesses, and/or lengths.

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

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

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

In addition, the catheter handle (not shown) may contain a mechanism for deflecting or manipulating the distal portion of the catheter device (3300). For example, a pull wire may extend from the catheter handle to one side of a distal portion of the device (3300) at or near the distal end of the outer shaft (3310), the tensioning of the pull wire causing the distal portion of the device (3300) to deflect. Deflection of the device (3300) may assist a user in positioning the device (3300) at a suitable anatomical location in a controlled manner. In some embodiments, the distal cap electrode (3322) may be electrically connected with a wire separately from the distal spline electrode (3332). In this way, intracardiac ECG signals may be recorded from only the distal cap electrode (3322). In some embodiments, one or more distal splined electrodes (3332) can be separately electrically connected with a lead to monitor intracardiac ECG signals from each such electrode (3332). In some embodiments, some distal splined electrodes (3332) may be used for ECG monitoring, while other distal splined electrodes (3332) may be used for delivering ablation energy. It should be understood that any of the ablation devices described herein may be used with electrodes that are separately electrically connected with a lead to monitor intracardiac ECG signals from each such electrode. In some embodiments, some electrodes on one or more of the splines in a set of splines may be used for ECG monitoring, while other electrodes may be used for delivering ablation energy.

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

Each of the splines of the set of splines (3300) may contain a respective electrode (3332, 3334) having an atraumatic (generally circular) shape to reduce trauma to tissue. In this way, the distal electrode in the second configuration may be held close to or placed against a portion of the atrial wall of the left atrium to create a lesion thereon by activating the appropriate electrodes using any suitable combination of polarities, as described herein. For example, as shown in fig. 33E, the cap electrode (3322) and the distal electrode (3332) of the set of splines (3330) may be placed in contact against or abutting the tissue wall (3350) in an orientation that is generally perpendicular or generally oblique to the tissue wall. The configuration of the distal electrodes (3322, 3332) allows for focal lesions to be created at a desired depth even when the ablation device (3300) in the deployed configuration abuts the tissue wall (3350) at an angle (e.g., obliquely).

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

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 subsets of electrodes may be independently addressable, and the electrodes may be energized in any order using any pulse shape sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (e.g., a stepped pulse waveform).

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

Balloon

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

In some embodiments, the first balloon (1012) and the second balloon (1014) may form an anode-cathode pair. For example, in one embodiment, the first and second balloons may carry an electrically separate body of saline fluid, and the first balloon (1012) may be configured as a cathode and the second balloon (1014) may be configured as an anode, or vice versa, wherein electrical energy may be capacitively coupled across the balloons or the saline-filled electrodes. The device (1010) may receive a pulse waveform to be delivered to the tissue (1002). For example, one or more biphasic signals may be applied such that tissue between the first balloon (1012) and the second balloon (1014) may be ablated at a desired location in the pulmonary vein (1004). The first balloon (1012) and the second balloon (1014) may substantially confine the electric field between the first balloon (1012) and the second balloon (1014) to reduce the electric field and damage to tissue distal to the ostium (1002) of the pulmonary vein (1004). In another embodiment, one or both of electrode (1018) and electrode (1019) disposed proximal and distal, respectively, to the first balloon may be used as electrodes of one polarity, while the fluid in the first balloon may be used as electrodes of the opposite polarity. A biphasic pulse waveform may then be delivered between these oppositely polarized electrodes by capacitive coupling across the balloon, creating an irreversible electroporation ablation zone 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 a cross-sectional view of another embodiment of a balloon ablation device (1110) (e.g., structurally and/or functionally similar to ablation device (1010)) positioned in a left atrial chamber (1100) and a right atrial chamber (1104) of a heart. The ablation device (1110) may include a balloon (1112) that may be configured to be advanced into and positioned in the right atrial lumen (1104). For example, the balloon (1112) may be placed in contact with a septum (1106) of the heart. The balloon (1112) may be filled with saline. The device (1110) may further include an electrode (1120) that may be advanced from the right atrial chamber (1104), through the balloon (1112) and septum (1106), and into the left atrial chamber (1100). For example, electrodes (1120) may extend from balloon (1112) and pierce septum (1106) and advance into left atrial chamber (1100). Once the electrode (1120) is advanced into the left atrial chamber (1100), the distal portion of the electrode (1120) may be modified to form a predetermined shape. For example, the distal portion of the electrode (1120) may comprise a non-linear shape, such as a circle, an ellipse, or any other geometric shape. In fig. 11, the distal portion of the electrode (1120) forms a loop that may surround a single ostium or two or more ostia of the pulmonary vein (1102) in the left atrial chamber (1100). In other embodiments, the distal portion of the electrode (1120) may have about the same diameter as the ostium of the pulmonary vein (1102).

The balloon (1112) and the electrode (1120) may be electrically isolated from each other. For example, balloon (1112) and electrode (1120) may each contain insulated electrical leads (1114, 1122), each lead (1114, 1122) having sufficient electrical insulation to maintain an electrical potential difference of at least 700V across its thickness without creating a dielectric breakdown. In other embodiments, the insulation on each of the electrical leads may maintain a potential difference between about 200V and about 2,000V across its thickness, including all values and subranges therebetween, without producing dielectric breakdown. The leads (1122) of the electrodes (1120) may be insulated by the balloon (1112). In some embodiments, the saline in the balloon (1112) and the electrodes (1120) may form an anode-cathode pair. For example, balloon (1112) may be configured as a cathode and electrode (1120) may be configured as an anode. The device (1110) may receive a pulse waveform to be delivered to the ostium of the pulmonary vein (1102). For example, a biphasic signal may be applied to ablate tissue. The pulse waveform may generate a strong electric field around the electrode (1120) while current is applied to the balloon (1112) through capacitive coupling to complete the circuit. In some embodiments, the electrode (1120) may comprise a fine-diameter wire, and the balloon (1112) may comprise a wire mesh.

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

Return electrode

Some embodiments of an ablation system as described herein may further include a return electrode or a set of distributed return electrodes coupled to the patient to reduce the risk of accidental injury to healthy tissue. Fig. 12A-12B are schematic illustrations of a set of return electrodes (1230) (e.g., return pads) of an ablation system positioned on a patient (1200). A set of four ostia of the pulmonary veins (1210) of the left atrium is shown in fig. 12A-12B. An electrode (1220) of the ablation device may be positioned around one or more ostia of the pulmonary veins (1210). In some embodiments, a set of return electrodes (1230) may be placed on the back of the patient (1200) to allow current to pass from the electrodes (1220) through the patient (1200) and then to the return electrodes (1230).

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

Figure 12B shows powered electrode (1220) forming an electric field (1240) around the ostium (1210) of the pulmonary vein. The return electrode (1230) may in turn receive a pulsed 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 of the ablation devices discussed herein, the electrodes (e.g., ablation electrodes, return electrodes) may comprise a biocompatible metal, such as titanium, palladium, silver, platinum, or a platinum alloy. For example, the electrode may preferably comprise platinum or a platinum alloy. Each electrode may comprise an electrical lead having sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness without causing dielectric breakdown. In other embodiments, the insulation on each of the electrical leads may maintain a potential difference between about 200V and about 2500V across its thickness, including all values and subranges therebetween, without creating a dielectric breakdown. Insulated electrical leads may extend to a proximal handle portion of the catheter, from which they may be connected to a suitable electrical connector. The catheter shaft may be made of a flexible polymeric material such as teflon, nylon, Pebax, and the like.

Process II

Also described herein are methods for ablating tissue in a heart cavity using the above-described systems and devices. The heart chamber may be the left atrial chamber and contain its associated pulmonary veins. In general, the methods described herein involve introducing and positioning a device in contact with one or more pulmonary vein ostia or sinus regions. The pulse waveform may be delivered by one or more electrodes of the device to ablate tissue. In some embodiments, the cardiac pacing signal may synchronize the delivered pulse waveform with the cardiac cycle. Additionally or alternatively, the pulse waveform may contain multiple levels of hierarchy to reduce total energy delivery. Tissue ablation so performed may be delivered in synchrony with pacing the heart beat, with less energy delivered to reduce damage to healthy tissue. It should be understood that any of the ablation devices described herein may be used to ablate tissue using the methods discussed below as appropriate.

In some embodiments, the ablation devices described herein may be used to locally ablate cardiac features/structures identified as causing arrhythmias. For example, a cardiac electrophysiology diagnostic catheter (e.g., a mapping catheter) can be used to map cardiac structures (e.g., rotors) that can then be ablated by focal ablation using any of the ablation devices described herein. For example, focal ablation may create spot lesions that neutralize the rotor while sparing surrounding tissue. In some embodiments, one or more focal ablation lesions may be formed in combination with one or more box-like or wire-like lesions to treat cardiac arrhythmias. By way of non-limiting example, in some embodiments, the system may include one or more mapping catheters, one or more ablation catheters for creating lesions by focal ablation (e.g., the ablation devices shown in fig. 9D, 9E, 27A-27C, 28, 29, 30, 31, 32), and one or more catheters for creating box-like and/or wire-like lesions (e.g., the ablation devices shown in fig. 3-8, 9A-9C, 10-12, 26A-26B).

Fig. 13 is a method (1300) for one embodiment of a tissue ablation procedure. In some embodiments, the voltage pulse waveforms described herein may be applied during the refractory period of a cardiac cycle to avoid cardiac sinus rhythm disruption. The method (1300) includes introducing a device (e.g., an ablation device, such as any of the ablation device (110) and/or the ablation device (200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 2900, 3000, 3100)) into an endocardial space of the left atrium at step (1302). The device may be advanced to be placed in contact with the pulmonary vein ostium (1304). For example, the electrodes of the ablation device may form an approximately circular arrangement of electrodes that are positioned in contact with the inner radial surface at the ostium of the pulmonary vein. In some embodiments, a pacing signal may be generated for cardiac stimulation of the heart (1306). The pacing signal may then be applied to the heart (1308). For example, the heart may be electrically paced with a cardiac stimulator to ensure pacing capture, thereby establishing the periodicity and predictability of the cardiac cycle. One or more of atrial and ventricular pacing may be applied. An indication of the pacing signal may be transmitted to a signal generator (1310). A time window within the refractory period of the cardiac cycle may then be defined within which one or more voltage pulse waveforms may be delivered. In some embodiments, the refractory period time window may follow the pacing signal. For example, a common refractory period time window may be located between the atrial refractory period time window and the ventricular refractory period 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 period time window. In some embodiments, a pulse waveform may be generated that has a time offset relative to the indication of the pacing signal. For example, the beginning of the refractory period time window may be offset from the pacing signal by a time offset. One or more voltage pulse waveforms may be applied over a series of heartbeats over a corresponding common refractory period time window. The generated pulse waveform may be delivered to tissue (1314). In some embodiments, the pulse waveform may be delivered to the pulmonary vein ostium of the patient's heart through one or more splines of a set of splines of the ablation device. In other embodiments, the voltage pulse waveforms described herein may be selectively delivered to a subset of electrodes, such as an anode-cathode subset for ablating and isolating pulmonary veins. For example, a first electrode of the set of electrodes may be configured as an anode and a second electrode of the set of electrodes may be configured as a cathode. These steps may be repeated as many times as desired to ablate the pulmonary vein ostia or sinus region (e.g., 1, 2, 3, or 4 ostia).

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

The pulse waveform may be generated by a signal generator (e.g., signal generator 122) and may contain multiple levels in a hierarchy (1410). As disclosed herein, a variety of hierarchical waveforms may be generated by a signal generator. For example, the pulse waveform may include a first stage of a pulse waveform hierarchy that includes a first set of pulses. Each pulse has a pulse duration and a first time interval separating successive pulses. A second stage of the pulse waveform hierarchy may contain a plurality of the first set of pulses as a second set of pulses. The second time interval may be separated by a consecutive first set of pulses. The second time interval may be at least three times the duration of the first time interval. A third stage of the pulse waveform hierarchy may contain a plurality of the second set of pulses as a third set of pulses. The third time interval may separate consecutive pulses of the second set. The third time interval may be at least thirty times the duration of the second time interval.

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

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

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

Fig. 17 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in a left atrial chamber of a heart using an ablation device corresponding to the ablation device (410) depicted in fig. 4. The left atrial lumen (1702) is depicted as having four pulmonary veins (1704), and the ablation device (1700) may be used to ablate tissue to electrically isolate one or more of the pulmonary veins (1704). As shown in fig. 17, an ablation device (1700) may be introduced into an endocardial space, such as the left atrial chamber (1702), using a transseptal approach. The ablation device (1700) may include a sheath (1710) and a plurality of catheters (1720, 1721) slidable within a lumen of the sheath (1710). Each of the catheters (1720, 1721) can include a respective guidewire (1722, 1723) slidable within the catheter (1720, 1721). A distal portion of the guidewire (1722, 1723) may include electrodes configured to deliver a voltage pulse waveform. Each of the catheters (1720, 1721) and corresponding guidewire (1722, 1723) may be advanced into the left atrial chamber (1702) to be positioned adjacent a respective ostium of a pulmonary vein (1704). Once the guidewire electrodes (1722, 1723) are in contact with the ostium of the pulmonary vein (1704), the electrodes may be configured in an anode-cathode subset. For example, the first wire (1722) may be configured as an anode and the second wire (1723) may be configured as a cathode. In this configuration, a voltage pulse waveform generated by a signal generator (not shown) may be delivered to ablate and simultaneously isolate the pair of pulmonary veins (1704). Additionally or alternatively, the voltage pulse waveform may be delivered to tissue and/or contain a waveform hierarchy in synchronization with pacing a heartbeat using the electrodes. After tissue ablation of two of the pulmonary veins (1704) is completed, the catheter (1720, 1721) can be repositioned to ablate tissue at the two remaining 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 a left atrial chamber of a heart using an ablation device (1800) corresponding to the ablation device (500) depicted in fig. 5. The left atrial lumen (1802) is depicted with four pulmonary veins (1804) and an ablation device (1800) may be used to sequentially ablate tissue to electrically isolate one or more of the pulmonary veins (1804). As shown in fig. 18, an ablation device may be introduced into an endocardial space, such as the left atrial chamber (1802), using a transseptal approach. The ablation device may include a sheath (1820) and a catheter (1810) slidable within a lumen of the sheath (1820). The distal portion (1812) of the catheter (1810) may be flower-shaped, as discussed in detail with reference to fig. 5. The distal portion (1812) of the catheter (1810) may be advanced into the left atrial chamber (1802) in a compact first configuration and positioned near the ostium of the pulmonary vein (1804). The distal portion (1812) of the catheter (1810) may then be transitioned to the expanded second configuration to form a flower-shaped distal portion as shown in fig. 18 such that the distal portion (1812) of the catheter (1810) is positioned adjacent to the ostium of the pulmonary vein (1804). Once the electrodes are in contact with the ostium of the pulmonary vein (1804), the electrodes may be configured in an anode-cathode subset. A voltage pulse waveform generated by a signal generator (not shown) may be delivered to tissue and/or contain a waveform hierarchy in synchronization with pacing a heartbeat using the electrodes. After completing the tissue ablation in the pulmonary veins (1804), the catheter (1810) may be repositioned at another pulmonary vein (1804) to ablate tissue in one or more of the remaining pulmonary veins (1804).

It should be understood that any of the methods described herein (e.g., fig. 13-18) may further include coupling a return electrode (e.g., one or more return electrodes (1230) described in fig. 12A-12B) to the back of the patient and configured to safely remove current from the patient during application of the voltage pulse waveform.

Figures 19A-20B depict embodiments of electrodes and resulting electric fields placed in contact around the ostium of a pulmonary vein. Fig. 19A is a schematic (1900) of an embodiment of a set of electrodes (1910) positioned in the ostium of a pulmonary vein (1904). The left atrial lumen (1902) may contain a blood pool (1906), and the pulmonary vein (1904) may contain a blood pool (1908). The left atrial lumen (1902) and the pulmonary veins (1904) may each have a wall thickness of up to about 4 mm.

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

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

Pulse waveform

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

In some embodiments, the pulsed voltage waveforms disclosed herein are hierarchical in organization and have a nested structure. In some embodiments, the pulse waveform includes pulse level groupings with various associated timescales. In addition, the associated timescale and pulse width, as well as the number of pulses and the hierarchical grouping, may be selected to satisfy one or more of a set of drop map (diaphanine) inequalities relating to cardiac pacing rates.

The pulse waveforms for electroporation energy delivery disclosed herein may enhance the safety, efficiency, and effectiveness of energy delivery by lowering the electric field threshold associated with irreversible electroporation, resulting in more effective ablative lesions with a reduction in the total energy delivered. This in turn may broaden the clinical application area of electroporation, including the treatment of various arrhythmias.

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

Fig. 22 describes a pulse waveform with a nested pulse hierarchy. FIG. 22 shows a series of monophasic pulses, such as pulses (2200) having a pulse width/pulse duration w, which consists of a time interval (sometimes also referred to as a first time interval), such as a duration t between successive pulses₁(2202)), the number of pulses m₁Arranged to form groups of pulses (2210) (sometimes also referred to as first group of pulsesPunching). Further, the waveform has m₂Groups of such pulses (sometimes also referred to as second group of pulses) consisting of the duration t between successive groups₂Is separated by a time interval (2212) (sometimes also referred to as a second time interval). M marked with (2220) in FIG. 22₂The set of such groups of pulses constitutes the next level of the hierarchy, which may be referred to as a packet and/or a third group of pulses. Pulse width and time interval t between pulses₁Both may range from microseconds to hundreds of microseconds, including all values and subranges therebetween. In some embodiments, time interval t₂Can be compared with the time interval t₁At least three times greater. In some embodiments, the ratio t₂/t₁May range between about 3 and about 300 inclusive of all values and subranges therebetween.

Fig. 23 further illustrates the structure of nested pulse level waveforms. In this figure, a series of m₁The pulses (individual pulses not shown) form a pulse group (2300) (e.g., a first group of pulses). By the duration t between one group and the next₂2310) (e.g., a second time interval) are separated by a series of m₂One such group forms group 132 (e.g., the second group of pulses). By the duration t between one packet and the next₃Time interval (2312) (e.g., a third time interval) of (a)₃This type of packet forms the next level in the hierarchy, labeled as a super packet (2320) in the figure (e.g., a third set of pulses). In some embodiments, time interval t₃Can be compared with the time interval t₂At least about thirty times greater. In some embodiments, time interval t₃Can be compared with the time interval t₂At least fifty times greater. In some embodiments, the ratio t₃/t₂May range between about 30 and about 800, including all values and subranges therebetween. The amplitude of the individual voltage pulses in the pulse level may range from 500 volts to 7,000 volts or more, including all values and subranges therebetween.

Fig. 24 provides an example of a biphasic waveform sequence having a hierarchical structure. In the example shown in the figures, A biphasic pulse such as (2400) has a positive voltage portion and a negative voltage portion to complete one cycle of the pulse. Duration t₁Has a time delay (2402) (e.g., a first time interval) between adjacent cycles, and n₁Each such period forms a pulse group (2410) (e.g., a first group of pulses). By the duration t between one group and the next₂Is spaced apart by a series of n inter-group time intervals (2412) (e.g., a second time interval)₂This group forms a packet (2420) (e.g., a second set of pulses). Also shown is a second packet (2430), with a duration t between packets₃Time delay (2432) (e.g., third time interval). Higher level hierarchies can also be formed, just like monophasic pulses. The amplitude of each pulse or voltage amplitude of the biphasic pulse may range from 500 volts to 7,000 volts or more, including all values and subranges therebetween. The pulse width/pulse duration may range from a few nanoseconds or even sub-nanoseconds to tens of microseconds, with a delay t₁May range from zero to several microseconds. Inter-group time interval t₂May be at least ten times greater than the pulse width. In some embodiments, time interval t₃Can be compared with the time interval t ₂At least about twenty times greater. In some embodiments, time interval t₃Can be compared with the time interval t₂At least fifty times greater.

Embodiments disclosed herein include waveforms structured as hierarchical waveforms that include waveform elements/pulses at different levels of the hierarchy. An individual pulse, such as (2200) in fig. 22, contains the first level of the hierarchy and has an associated pulse duration and a first time interval between successive pulses. A set of pulses or elements of the first level structure form a second level of the hierarchy, such as pulse set/second set of pulses (2210) in fig. 22. Among other parameters associated with the waveform are parameters describing the second level structure/second set of pulses, such as 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 time interval between successive first level elements. In some embodiments, the total duration of the second set of pulses may be between about 20 microseconds and about 10 milliseconds, including all values and subranges therebetween. A group of groups, a second set of pulses, or elements of the second level structure form a third level of the hierarchy, such as the group grouping/third set of pulses in fig. 22 (2220). Among other parameters, there are parameters describing the total duration of the third set of pulses (not shown) of the third level structure/third set of pulses, the total number of second level elements/second set of pulses, and the third time interval between successive second level elements. In some embodiments, the total duration of the third set of pulses may be between about 60 microseconds and about 200 milliseconds, including all values and subranges therebetween. The general iterative or nested structure of waveforms may continue to reach a higher multiple level structure, such as a ten level structure or more.

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

In some embodiments, the ablation pulse waveforms described herein are applied during the refractory period of the cardiac cycle to avoid cardiac sinus rhythm disruption. In some embodiments, the method of treatment includes electrically pacing the heart with a cardiac stimulator to ensure pacing capture in order to establish periodicity and predictability of cardiac cycles, and then defining a time window within a refractory period of a cardiac cycle in which one or more pulse ablation waveforms may be delivered. Fig. 25 shows an example where both atrial and ventricular pacing is applied (e.g., pacing leads or catheters in the right atrium and right ventricle, respectively). For time represented on the horizontal axis, fig. 25 shows a series of ventricular pacing signals (e.g., (2500) and (2510)) and a series of atrial pacing signals (2520, 2530) driven by the pacing signals, as well as a series of ECG waveforms (2540, 2542). As indicated by the thick arrows in FIG. 25, stores An atrial refractory period time window (2522) and a ventricular refractory period time window (2502) that track the atrial pacing signal (2522) and the ventricular pacing signal (2500), respectively. As shown in fig. 25, duration T_rMay be defined to lie within an atrial refractory period time window (2522) and a ventricular refractory period time window (2502). In some embodiments, one or more electroporation ablation waveforms may be applied in this common refractory period time window (2550). As shown in fig. 25, the start of the refractory period time window (2522) is offset from the pacing signal (2500) by a time offset (2504). In some embodiments, the time offset (2504) may be less than about 25 milliseconds. On the next heartbeat, a similarly defined common refractory period time window (2552) is the next time window available for application of one or more ablation waveforms. In this way, the one or more ablation waveforms may be applied over a series of heartbeats, each heartbeat remaining within a common refractory period time window. In one embodiment, for a given set of electrodes, each pulse packet as defined above in the pulse waveform hierarchy may be applied over a heartbeat, such that a series of packets are applied over a series of heartbeats.

It is to be understood that the examples and illustrations in this disclosure are for illustrative purposes and that deviations and variations, such as the number of splines, the number of electrodes, etc., may be constructed and arranged in accordance with the teachings herein without departing from the scope of this disclosure.

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

Some embodiments described herein relate to a computer storage product with a non-transitory computer-readable medium (which may also be referred to as a non-transitory processor-readable medium) having instructions or computer code thereon for performing various computer-implemented operations. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not itself contain a transitory propagating signal (e.g., a propagating electromagnetic wave carrying information on a transmission medium such as space or cable). The media and computer code (also can be referred to as code or algorithms) may be designed and constructed for the specific purpose or purposes. Examples of non-transitory computer readable media include, but are not limited to: magnetic storage media such as hard disks, floppy disks, and magnetic tape; optical storage media such as compact discs/digital video discs (CD/DVD), compact disc read-only memories (CD-ROM), and holographic devices; magneto-optical storage media such as optical disks; a carrier signal processing module; and hardware devices that are particularly configured to store and execute program code, such as Application Specific Integrated Circuits (ASICs), Programmable Logic Devices (PLDs), Read Only Memory (ROM), and Random Access Memory (RAM) devices. Other embodiments described herein relate to a computer program product that may contain, for example, the instructions and/or computer code disclosed herein.

The systems, devices, and/or methods described herein may be performed by software (executed on hardware), hardware, or a combination thereof. The hardware modules may comprise, for example, a general purpose processor (or microprocessor or microcontroller), a Field Programmable Gate Array (FPGA), and/or an Application Specific Integrated Circuit (ASIC). Software modules (executing on hardware) may be expressed in various software languages (e.g., computer code) including C, C + +,

Ruby、Visual

and/or other object-oriented, procedural, or other programming language and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions that are executed by a computer using an interpreter, machine instructions (such as those produced by a compiler), code for generating a Web service, and code containing higher level instructionsThe order file. Additional examples of computer code include, but are not limited to, control signals, encrypted code, and compressed code.

The specific examples and descriptions herein are illustrative in nature, and that those skilled in the art may develop embodiments based on the materials taught herein without departing from the scope of the invention, which is defined solely by the claims appended hereto.

Claims

1. An apparatus, comprising:

a catheter shaft defining a longitudinal axis and a shaft lumen therethrough;

a set of splines extending from a distal end of the shaft lumen, each spline of the set of splines comprising a set of electrodes formed on a surface of the spline; and

a distal cap coupled to a distal portion of each spline of the set of splines, the set of splines configured to translate along the longitudinal axis to transition between a first configuration and a second configuration, wherein in the first configuration each spline lies substantially in a plane that intersects the longitudinal axis of the catheter shaft, wherein in the second configuration each spline forms a loop having a first concave curve facing the distal cap, a second concave curve facing the longitudinal axis, and a third concave curve facing the distal end of the shaft lumen,

wherein the set of splines in the second configuration is arranged as a set of non-overlapping loops.

2. The apparatus of claim 1, wherein the first configuration includes the set of splines arranged to helically rotate about the longitudinal axis.

3. The apparatus of claim 2, wherein each spline of the set of splines has a non-zero helix angle of less than about 5 degrees.

4. The apparatus of claim 1, wherein the set of splines in the second configuration is arranged as a set of electrically isolated loops.

5. The apparatus of claim 1, wherein the set of splines in the second configuration includes a radius of curvature that varies along a spline length.

6. The apparatus of claim 1, wherein the set of splines in the second configuration is configured to abut a tissue wall, wherein the set of electrodes on at least two of the splines is configured to generate an electric field comprising a magnitude and a tangential component of electric field lines with respect to the tissue wall, wherein the tangential component is greater than half of the magnitude of a substantial portion of the tissue wall between the at least two splines.

7. The apparatus of claim 1, wherein each of the distal portions of the set of splines is fixed to the distal cap.

8. The apparatus of claim 1, wherein each spline of the set of splines in the second configuration includes an elliptical cross-section.

9. The apparatus of claim 8, wherein the elliptical cross-section includes a major axis length of between about 1mm and about 2.5mm and a minor axis length of between about 0.4mm and about 1.2 mm.

10. The apparatus of claim 1, wherein a cross-sectional area of each spline of the set of splines is between about 0.2mm²And about 15mm²In the meantime.

11. The apparatus of claim 1, wherein each spline of the set of splines defines a spline lumen therethrough.

12. The apparatus of claim 11, wherein the set of electrodes of each spline of the set of splines includes an insulated electrical lead associated therewith disposed in the spline lumen of each spline of the set of splines.

13. The apparatus of claim 11, wherein the insulated electrical leads are configured to maintain a voltage potential of at least about 700V without dielectric breakdown of their corresponding insulation.

14. The apparatus of claim 1, wherein the set of electrodes of each spline of the set of splines comprises at least one electrode configured for ablation and at least one electrode configured for receiving an ECG signal.

15. The device of claim 14, wherein the at least one electrode configured for ablation and the at least one electrode configured for receiving the ECG signal are coupled to separate insulated electrical leads.

16. The apparatus of claim 1, wherein the set of electrodes of each spline of the set of splines is coupled to a corresponding insulated electrical lead.

17. The apparatus of claim 1, wherein each spline of the set of splines in the second configuration includes an apex relative to the longitudinal axis.

18. The apparatus of claim 17, wherein the set of electrodes is unevenly distributed relative to the apex of each spline of the set of splines.

19. The apparatus of claim 17, wherein the set of electrodes is distributed proximal and distal to the apex at a ratio of 1: 3.

20. The apparatus of claim 1, wherein the set of electrodes of each spline are commonly connected with a wire.

21. The apparatus of claim 1, wherein the set of electrodes of each spline are connected in series with a wire.

22. The apparatus of claim 1, wherein the set of electrodes includes an atraumatic shape.

23. The apparatus of claim 1, wherein the set of electrodes includes an elliptical cross-section.

24. The apparatus of claim 23, wherein the elliptical cross-section includes a major axis length between about 1mm and about 4mm and a minor axis length between about 0.4mm and about 3 mm.

25. The apparatus of claim 1, wherein the surface area of each electrode in the set of electrodes is between about 0.5mm²And about 20mm²In the meantime.

26. The apparatus of claim 1, wherein a first set of electrodes of a first spline of the set of splines is configured as an anode and a second set of electrodes of a second spline of the set of splines is configured as a cathode.

27. An apparatus, comprising:

a handle;

a catheter shaft coupled to the proximal end of the handle, the catheter shaft defining a longitudinal axis and a shaft lumen therethrough;

a distal cap coupled to a distal portion of each spline of the set of splines, the set of splines configured to translate along the longitudinal axis to transition between a first configuration and a second configuration, the first configuration including the distal cap coupled to a distal end of the catheter shaft at a first distance and the second configuration including the distal cap coupled to the distal end of the catheter shaft at a second distance, and a ratio of the first distance to the second distance is between about 5:1 and about 25: 1.

28. A system, comprising:

a signal generator configured to generate a pulse waveform;

a cardiac stimulator coupled to the signal generator and configured to, during use, generate a pacing signal for cardiac stimulation and transmit an indication of the pacing signal to the signal generator;

the signal generator is further configured to generate the pulse waveform in synchronization with the indication of the pacing signal; and

an ablation device coupled to the signal generator and configured to receive the pulse waveform, the ablation device comprising:

a handle;

a catheter shaft coupled to a proximal end of the handle, the catheter shaft defining a first longitudinal axis and a shaft lumen therethrough;

a set of splines coupled to the catheter shaft, a distal portion of each spline of the set of splines extending distally from the distal end of the catheter shaft, each spline of the set of splines comprising a set of electrodes formed on a surface of each spline of the set of splines, each spline of the set of splines having an elliptical cross-section; and

A distal cap coupled to the distal portion of each spline of the set of splines, the distal portions each comprising a helical shape about the first longitudinal axis, the handle configured to translate the set of splines along the first longitudinal axis to shift the set of splines between a first configuration comprising the set of splines arranged substantially parallel to the first longitudinal axis and a second configuration comprising the set of splines forming a loop having a first concave curve facing the distal cap, a second concave curve facing the longitudinal axis and a third concave curve facing the distal end of the shaft lumen.

29. An apparatus, comprising:

a catheter shaft defining a longitudinal axis and a shaft lumen therethrough;

a distal cap coupled to a distal portion of each spline of the set of splines, the distal portion of each spline of the set of splines configured to translate along the longitudinal axis to transition the set of splines between a first configuration and a second configuration, respectively, wherein in the first configuration, the set of splines is substantially parallel to the longitudinal axis of the catheter shaft, and wherein in the second configuration, a radius of curvature of at least a portion of each spline of the set of splines is between about 7mm and about 25 mm.

30. The apparatus of claim 29, wherein each spline of the set of splines in the second configuration has a shape of more than half a turn of a deformed helix.

31. The apparatus of claim 29, wherein the set of splines in the second configuration is configured to abut a tissue wall, wherein the set of electrodes on at least two of the splines is configured to generate an electric field comprising a magnitude and a tangential component of electric field lines with respect to the tissue wall, wherein the tangential component is greater than half of the magnitude of a substantial portion of the tissue wall between the at least two splines.

32. The apparatus of claim 29, wherein each spline of the set of splines in the second configuration comprises an elliptical cross-section, and wherein the elliptical cross-section comprises a major axis length of between about 1mm and about 2.5mm and a minor axis length of between about 0.4mm and about 1.4 mm.

33. The apparatus of claim 29, wherein the set of electrodes of each spline of the set of splines includes an insulated electrical lead associated therewith and configured to maintain a voltage potential of at least about 700V without creating a dielectric breakdown.

34. The apparatus of claim 29, wherein the set of electrodes of each spline of the set of splines comprises at least one electrode configured for ablation and at least one electrode configured for measuring electrophysiological data.

35. A system, comprising:

a signal generator configured to generate an ablation pulse waveform;

a pacing device coupled to the signal generator and configured to generate a pacing signal for cardiac stimulation during use and to transmit an indication of the pacing signal to the signal generator;

a catheter shaft defining a longitudinal axis and a shaft lumen therethrough;

36. The apparatus of claim 35, wherein each spline of the set of splines in the second configuration has a shape of more than half a turn of a deformed helix.

37. The apparatus of claim 35, wherein the set of splines in the second configuration is configured to abut a tissue wall, wherein the set of electrodes on at least two of the splines is configured to generate an electric field comprising a magnitude and a tangential component of electric field lines with respect to the tissue wall, wherein the tangential component is greater than half of the magnitude of a substantial portion of the tissue wall between the at least two splines.

38. An apparatus, comprising:

a catheter shaft defining a longitudinal axis and a shaft lumen therethrough;

a distal cap coupled to a distal portion of each spline of the set of splines, the distal portion of each spline of the set of splines configured to translate along the longitudinal axis to transition the set of splines between a first configuration and a second configuration, respectively, the first configuration including the distal cap coupled to a distal end of the catheter shaft at a first distance and the second configuration including the distal cap coupled to the distal end of the catheter shaft at a second distance, and a ratio of the first distance to the second distance is between about 5:1 and about 25: 1.

39. An apparatus, comprising:

a catheter shaft defining a longitudinal axis and a shaft lumen therethrough;

a set of splines extending from a distal end of the shaft lumen, a distal portion of each spline of the set of splines extending distally from the distal end of the catheter shaft, each spline of the set of splines comprising a set of electrodes formed on a surface of the spline, the set of splines configured to transition between a first configuration and a second configuration, wherein the set of splines in the first configuration are arranged substantially parallel to the longitudinal axis and each spline of the set of splines in the second configuration has a radius of curvature that decreases and then increases along a length of the spline.

40. The apparatus of claim 39, wherein when the set of splines is in the second configuration, a radius of curvature of at least a portion of each spline of the set of splines is between about 7mm and about 25 mm.

41. The apparatus of claim 39, wherein the set of splines in the second configuration is arranged as a set of non-overlapping loops.

42. The apparatus of claim 39, wherein when the set of splines is in the first configuration, a distal end of each spline of the set of splines is disposed at a first distance from a distal end of the catheter shaft, and when the set of splines is in the second configuration, a distal end of each spline of the set of splines is disposed at a second distance from a distal end of the catheter shaft, and a ratio of the first distance to the second distance is between about 5:1 and about 25: 1.

43. The apparatus of claim 39, wherein the set of electrodes of each spline of the set of splines includes an insulated electrical lead associated therewith, and the insulated electrical lead is configured to maintain a voltage potential of at least about 700V without creating a dielectric breakdown.

44. The apparatus of claim 39, wherein each spline of the set of splines comprises an elliptical cross-section, and the elliptical cross-section comprises a long axis length of between about 1mm and about 2.5mm and a short axis length of between about 0.4mm and about 1.4 mm.

45. The apparatus as claimed in claim 39, wherein when said set of splines is in said second configuration, each spline of said set of splines has a helix angle of less than about 10 degrees relative to said longitudinal axis.

46. The apparatus of claim 39, wherein the set of electrodes formed on each spline in the set of splines comprises at least one electrode configured for ablation and at least one electrode configured for measuring electrophysiological data.