JP7394766B2 - Systems, devices, and methods for focal ablation - Google Patents

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 62/529,268, filed July 6, 2017, and U.S. Patent Application No. 15, filed January 18, 2018. This is a continuation in part of No./874,721. This application is also a continuation in part of U.S. patent application Ser. This application is a continuation-in-part of PCT Application No. PCT/US2018/029938 filed on April 27, 2018. U.S. Patent Application No. 15/711,266 is a PCT application filed on January 4, 2017 that claims the benefit of U.S. Provisional Application No. 62/274,943, filed on January 5, 2016. This is a continuation-in-part of PCT/US2017/012099. U.S. patent application Ser. 529,268. This application also claims the benefit of U.S. Provisional Application No. 62/744,495, filed on October 11, 2018, and U.S. Provisional Application No. 62/769,407, filed on November 19, 2018. do. The entire disclosures of each of the aforementioned applications are incorporated herein by reference in their entirety.

Although the generation of pulsed electric fields for tissue treatment has moved from the laboratory to clinical applications over the past two decades, the effects of short pulses of high voltage and large electric fields on tissue have been investigated over the past four decades. has been done. Applying high DC voltages to tissue for short periods of time can generate locally high electric fields, typically in the range of several hundred volts per centimeter, that disrupt cell membranes by creating pores in them. Although the exact mechanism of this electrically driven pore generation or electroporation continues to be studied, applying large electric fields of relatively short duration can destabilize the lipid bilayer of cell membranes. , is thought to cause the appearance of localized gaps or pore distribution in the cell membrane. This electroporation can be irreversible if the electric field applied to the membrane is greater than a threshold, resulting in the pores closing or remaining open, thereby allowing the biomolecular material to penetrate the membrane. exchanged across the body, causing necrosis and/or apoptosis (cell death). The surrounding tissue may then heal on its own.

Although pulsed DC voltage can drive electroporation under the right circumstances, high DC voltage electroporation ablation therapy can be selected to target endocardial tissue in the area of interest with minimal damage to healthy tissue. However, there remains an unmet need for thin, flexible, non-invasive devices that deliver effectively.

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

In some embodiments, the device has a first shaft defining a longitudinal axis and a lumen, and a distal portion disposed within the lumen and extending from a distal end of the first shaft. a second shaft, a plurality of electrodes configured to generate an electric field for ablating tissue, and a set of splines, each spline of the set of splines having a plurality of electrodes formed thereon; a set of electrodes from the electrodes, each set of electrodes including (1) a distal electrode such that the set of splines includes a set of distal electrodes; and (2) a set of proximal electrodes such that the set of splines includes a set of proximal electrodes. a set of splines, including a proximal electrode, such as a proximal electrode. The proximal end may be coupled to the distal end of the first shaft. The distal end may be coupled to the distal end of the second shaft. The set of splines may be configured to transition to an expanded configuration, the set of splines defining a space therebetween, the space being larger in the expanded configuration of the set of splines. The expandable member may be disposed distal to the distal end of the first shaft and within the space between the sets of splines. The expandable member may be configured to be transitioned to the expanded configuration when the set of splines is in the expanded configuration.

In some embodiments, the expandable member may be disposed distal to the distal end of the first shaft and within the space between the sets of splines. The expandable member may be configured to transition to an expanded configuration. In some embodiments, the expandable member in the expanded configuration may substantially fill the space between the sets of splines in the expanded configuration. The expandable member transitions from a collapsed configuration in which the outer surface of the expandable member is substantially parallel to the longitudinal axis to an expanded configuration in which the outer surface of the expandable member deflects radially outwardly from the longitudinal axis. may be configured to do so. The set of splines may be configured to transition to an expanded configuration in response to transition of the expandable member to an expanded configuration.

In some embodiments, the distal portion of each spline from the set of splines may be angled at least about 70 degrees relative to the longitudinal axis when the set of splines is in the expanded configuration. In some embodiments, the expandable member in the expanded configuration may form an asymmetric shape in which the distal portion of the expandable member has a larger outer diameter than that of the proximal portion of the expandable member. The expandable member in the expanded configuration may form a shape having an outer diameter at its greatest portion from about 6 mm to about 24 mm. In some embodiments, when the set of splines is in the expanded configuration, at least one electrode from the set of distal electrodes contacts the tissue surface and has a diameter of about 0.5 cm to about 2.5 cm. The focal ablation lesion may be configured to form a focal ablation lesion on the tissue surface.

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

In some embodiments, the expandable member may be configured in fluid communication with a fluid source. The fluid source may be configured to deliver fluid to the expandable member to transition the expandable member to an expanded configuration. In some embodiments, when the set of splines is in the expanded configuration, the set of splines may extend outwardly from the distal end of the first shaft from about 6 mm to about 24 mm. The first shaft can have an outer diameter of about 1.5 mm to about 6.0 mm. The set of splines may be configured to transition to an expanded configuration in response to movement of the second shaft relative to the first shaft along the longitudinal axis. When the set of splines is in the expanded configuration, the set of distal electrodes may be angled at about 90 degrees to about 180 degrees relative to the set of proximal electrodes.

A set of splines in an expanded configuration may form an asymmetric shape with the distal portion having a larger outer diameter than that of the proximal portion. The distal end of the second shaft may be spaced up to about 6 mm from each distal electrode from the set of distal electrodes. The distal end of the second shaft can have a cross-sectional diameter of about 1 mm to about 5 mm. The distal portion of the device may have an atraumatic shape. Each electrode from the plurality of electrodes may circumscribe a respective spline from the set of splines on which it is disposed.

At least one distal electrode from the set of distal electrodes may be configured to operate with a first polarity. At least one proximal electrode from the set of proximal electrodes can be configured to operate at a second polarity opposite the first polarity to collectively generate an electric field. The set of distal electrodes may be configured to operate at a first polarity and the set of proximal electrodes may be configured to operate at a second polarity opposite the first polarity.

Each electrode from the plurality of electrodes can have a length of about 0.5 mm to about 5 mm. Each electrode from the plurality of electrodes may be independently addressable from other electrodes of the plurality of electrodes. Each spline from the set of splines may include a set of insulated conductors disposed therein. Each insulated conductor from the set of insulated conductors is electrically coupled to at least one electrode from the set of electrodes formed on the spline and capable of carrying a potential of at least about 700 V without breakdown of the corresponding insulation. may be configured to maintain. Each electrode from the plurality of electrodes can have a diameter of about 0.5 mm to about 3 mm. For each spline from the set of splines, the most distal electrode may be separated from the most distal proximal electrode by about 1 mm to about 40 mm.

Each spline from the set of splines includes a plurality of proximal electrodes and at least one flexible member disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase the flexibility of the spline. may include a portion. The set of proximal electrodes may include at least one coil electrode. Each spline electrode set within the spline set may include at least one electrode configured only for ablation and at least one electrode configured to receive an electrocardiogram (ECG) signal. In some of these embodiments, at least one electrode may be configured solely for ablation and at least one electrode may be configured to receive ECG signals, which combine to Separate the conductors.

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

In some embodiments, the method may include disposing an ablation device within a ventricular cavity of a subject's heart, the ablation device defining a longitudinal axis, a set of splines, and a cross-section between the sets of splines. It includes an expandable member disposed within the space. The set of splines can be transitioned to an expanded configuration in which a distal portion of each spline in the set of splines deflects radially outwardly from the longitudinal axis. The expandable member may transition to an expanded configuration. An ablation pulse waveform can be delivered to a plurality of electrodes disposed on the set of splines such that the set of splines generates an electric field to ablate tissue in the ventricular cavity.

In some embodiments, the electric field may be configured to create a focal ablation lesion on the tissue surface having a diameter of about 0.5 cm to about 2.5 cm. The ablation device may include a first shaft and a second shaft disposed within the first shaft and translatable relative to the first shaft. The set of splines can be moved to an expanded configuration, including retracting a distal portion of the second shaft relative to the first shaft. In some of these embodiments, retracting the distal portion of the second shaft relative to the first shaft is coupled to at least one of the second shaft or the first shaft. This includes using a handle that is In some embodiments, the tissue may include the endocardial surface of the ventricular cavity. In some of these embodiments, the ventricular cavity may be a ventricle.

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

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

In some embodiments, a pacing device may be advanced into the right ventricle of the heart. A pacing signal for cardiac stimulation of the heart can be generated. A pacing device can be used to apply a pacing signal to the heart, and an ablation pulse waveform is generated in synchronization with the pacing signal. In some of these embodiments, the ablation pulse waveform may include a time offset with respect to the pacing signal.

In some embodiments, a radiopaque portion of the ablation device may be visualized under fluoroscopy during one or more steps. A diagnostic catheter may be advanced into the ventricular cavity and electrophysiology data may be recorded using the diagnostic catheter. In some of these embodiments, after transitioning the set of splines to the expanded configuration and transitioning the balloon to the expanded configuration, at least one of the splines from the set of splines is in contact with the endocardium of the ventricular cavity. Splines can be placed. In some of these embodiments, at least one spline in contact with the endocardium forms a "C" shape.

In some embodiments, the ablation device can include a shaft defining a lumen in fluid communication with the expandable member, and transitioning the expandable member to the expanded configuration directs fluid into the lumen of the shaft. and delivery through the lumen and into the expandable member. The expandable member may be formed from an insulating material such that the expandable member acts as an insulator during delivery of the ablation pulse waveform. The expandable member may include a plurality of expandable portions, each expandable portion of the plurality of expandable portions being independently inflatable from other expandable portions of the plurality of expandable portions. be. Transitioning the set of splines to the expanded configuration includes transitioning the set of splines such that a distal portion of each spline from the set of splines is angled at more than 70 degrees to a longitudinal axis. include.

In some embodiments, an ablation pulse waveform that includes a first level of a hierarchy of ablation pulse waveforms may include a first set of pulses, each pulse having a pulse duration and a first time interval. separates consecutive pulses. A second level of the hierarchy of ablation pulse waveforms may include a first set of a plurality of pulses as a second set of pulses, a second time interval separating the first set of consecutive pulses; The second time interval is at least three times the duration of the first time interval. A third level of the hierarchy of ablation pulse waveforms may include a second set of a plurality of pulses as a third set of pulses, a third time interval separating the second set of consecutive pulses; The third time interval is at least 30 times the duration of the second level time interval.

In some embodiments, transitioning the set of splines to the expanded configuration is responsive to transitioning the expandable member to the expanded configuration.

1 is a block diagram of an electroporation system, according to an embodiment. FIG. FIG. 2 is a perspective view of an ablation catheter, according to an embodiment. FIG. 7 is a perspective view of an ablation catheter, according to another embodiment. FIG. 7 is a perspective view of an ablation catheter, according to another embodiment. FIG. 7 is a detailed perspective view of a distal portion of an ablation catheter, according to another embodiment. FIG. 7 is a side view of an ablation catheter, according to another embodiment. FIG. 7 is a side view of an ablation catheter, according to another embodiment. FIG. 3 is an illustration of an ablation catheter, according to another embodiment. FIG. 8A is a side view. FIG. 3 is an illustration of an ablation catheter, according to another embodiment. FIG. 8B is a front sectional view. FIG. 7 is a side view of an ablation catheter in a first configuration, according to another embodiment. FIG. 7 is a side view of an ablation catheter in a second expanded configuration, according to another embodiment. FIG. 7 is a side view of an ablation catheter in a third expanded configuration, according to another embodiment. FIG. 7 is a side view of an ablation catheter in a fourth expanded configuration, according to another embodiment. FIG. 7 is a side view of an ablation catheter in a fifth expanded configuration, according to another embodiment. FIG. 7 is a perspective view of a balloon ablation catheter disposed in the left atrial cavity of a heart, according to another embodiment. FIG. 3 is a cross-sectional view of a balloon ablation catheter disposed in the left atrial cavity of a heart, according to another embodiment. FIG. 2 is a schematic diagram of a return electrode of an ablation system, according to an embodiment. Figure 12A shows the electrodes not energized. FIG. 2 is a schematic diagram of a return electrode of an ablation system, according to an embodiment. Figure 12B shows the energized electrodes. 3 illustrates a method of tissue ablation, according to an embodiment. 4 illustrates a method of tissue ablation, according to another embodiment. 3 is an illustration of the ablation catheter shown in FIG. 2 disposed in the left atrial cavity of the heart; FIG. 4 is an illustration of the ablation catheter shown in FIG. 3 disposed in the left atrial cavity of the heart. 5 is an illustration of two of the ablation catheters shown in FIG. 4 disposed in the left atrial cavity of the heart; FIG. 6 is an illustration of the ablation catheter shown in FIG. 5 disposed in the left atrial cavity of the heart. FIG. 6 is an illustration of a set of electrodes disposed at a pulmonary vein ostium, according to another embodiment. FIG. 19A is a schematic perspective view, and FIG. 19B is a cross-sectional view. FIG. 6 is an illustration of a set of electrodes disposed at a pulmonary vein ostium, according to another embodiment. FIG. 19A is a schematic perspective view, and FIG. 19B is a cross-sectional view. FIG. 6 is an illustration of an electric field generated by an electrode disposed at a pulmonary vein ostium, according to another embodiment. FIG. 20A is a schematic perspective view. FIG. 6 is an illustration of an electric field generated by an electrode disposed at a pulmonary vein ostium, according to another embodiment. FIG. 20B is a cross-sectional view. 3 is an example waveform showing a sequence of voltage pulses with a defined pulse width for each pulse, according to an embodiment. 3 schematically depicts a hierarchy of pulses showing pulse widths, inter-pulse spacing, and groupings of pulses, according to an embodiment; FIG. 2 provides a schematic diagram of a nested hierarchy of monophasic pulses displaying different levels of nested hierarchy, according to an embodiment; FIG. 1 is a schematic diagram of a nested hierarchy of biphasic pulses displaying different levels of nested hierarchy, according to an embodiment; FIG. In accordance with embodiments, a time series of electrocardiogram and cardiac pacing signals with atrial and ventricular refractory periods is schematically illustrated, and a time series of irreversible electroporation ablation is illustrated. FIG. 7 is a perspective view of an ablation catheter, according to another embodiment. FIG. 26B is a side view of the ablation catheter depicted in FIG. 26A positioned in the left atrial cavity of the heart adjacent to the pulmonary ostium. 26B is a top view of a simulation of the ablation catheter depicted in FIG. 26B showing selective electrode actuation, according to embodiments; FIG. 2 is an illustration of a simulation of tissue ablation in the lung ostium, according to an embodiment; FIG. 3A and 3B are side views of an ablation catheter according to other embodiments. FIG. 27A is a side view of the ablation catheter in a second configuration. 3A and 3B are side views of an ablation catheter according to other embodiments. FIG. 27B is another side view of the ablation catheter in a second configuration. 3A and 3B are side views of an ablation catheter according to other embodiments. FIG. 27C is yet another side view of the ablation catheter in a second configuration. FIG. 7 is a side view of an ablation catheter, according to another embodiment. FIG. 7 is a side cross-sectional view of an ablation catheter, according to another embodiment. FIG. 29A is a side cross-sectional view of the ablation catheter in a first configuration. FIG. 7 is a side cross-sectional view of an ablation catheter, according to another embodiment. FIG. 29B is a side cross-sectional view of the ablation catheter in a third configuration. FIG. 7 is a side cross-sectional view of an ablation catheter, according to another embodiment. FIG. 29C is another side cross-sectional view of the ablation catheter in a third configuration. FIG. 7 is a side cross-sectional view of an ablation catheter, according to another embodiment. FIG. 29D is yet another side cross-sectional view of the ablation catheter in a third configuration. FIG. 7 is a side view of an ablation catheter, according to another embodiment. FIG. 7 is a perspective view of an ablation catheter, according to another embodiment. FIG. 31A is a perspective view of the ablation catheter in a first configuration. FIG. 7 is a perspective view of an ablation catheter, according to another embodiment. FIG. 31B is a perspective view of the ablation catheter in a second configuration. FIG. 3 is a cross-sectional schematic illustration of an ablation catheter, according to another embodiment. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 33A is a perspective view of an ablation catheter. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 33B is a front view of the ablation catheter of FIG. 33A. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 33C is a cutaway perspective view of the spline of the ablation catheter of FIG. 33A. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 33D is a cross-sectional view of the spline of the ablation catheter of FIG. 33A. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 33E is a perspective view of the ablation catheter of FIG. 33A disposed adjacent tissue. FIG. 7 is a side view of a spline, according to another embodiment. FIG. 34A is a side view of a spline with unit tangent vector. FIG. 7 is a side view of a spline, according to another embodiment. FIG. 34B is a side view with two unit tangent vectors. FIG. 7 is a side view of an ablation catheter in an undeployed configuration, according to another embodiment. FIG. 7 is a side view of an ablation catheter, according to another embodiment. FIG. 36A is a side view of the ablation catheter in a second configuration. FIG. 7 is a side view of an ablation catheter, according to another embodiment. FIG. 36B is another side view of the ablation catheter in a second configuration. FIG. 7 is a side view of an ablation catheter, according to another embodiment. FIG. 36C is a side view of the ablation catheter near tissue. FIG. 2 is a perspective view of an ablation catheter and left atrium. FIG. 37A is a perspective view of an ablation catheter placed in the left atrium. FIG. 2 is a perspective view of an ablation catheter and left atrium. FIG. 37B is a perspective view of the left atrium after tissue ablation. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 38A is a perspective view of an ablation catheter in a first configuration. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 38B is another perspective view of the ablation catheter in a second configuration. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 38C is an annotated perspective view of an ablation catheter. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 38D is a perspective view of an ablation catheter positioned adjacent tissue. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 39A is a perspective view of an ablation catheter in an expanded configuration. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 39B is another perspective view of an ablation catheter including an expandable member in a deflated configuration. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 39C is another perspective view of an ablation catheter including an expandable member in a deflated configuration. FIG. 7 is an illustration of an ablation catheter according to another embodiment. FIG. 39D is an annotated perspective view of an ablation catheter including an expandable member in an expanded configuration.

Systems, devices, and methods are described herein for selective and rapid application of pulsed electric fields to ablate tissue by irreversible electroporation. In general, the systems, devices, and methods described herein generate large electric field strengths in desired areas of interest and reduce peak electric field values elsewhere to reduce unintended tissue damage. can be used to make The irreversible electroporation system described herein applies a signal generator and one or more voltage pulse waveforms to a selected set of electrodes of an ablation device to deliver energy (e.g. , ablation energy for a set of tissues located at a pulmonary vein ostium). The pulse waveforms disclosed herein can support therapeutic treatment of various cardiac arrhythmias (eg, atrial fibrillation). To deliver the pulse waveform generated by the signal generator, one or more electrodes of the ablation device are insulated conductive wires configured to maintain an electrical potential of at least about 700 V without breakdown of the corresponding insulation. It may have. A subset of electrodes may be independently addressable such that the subset can be controlled (eg, deliver energy) independently of any other electrodes of the device. In this manner, the electrodes and/or electrode subsets may synergistically deliver different energy waveforms at different times for tissue electroporation.

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, cells undergoing reversible electroporation may be observed to have transient and/or intermittent formation of one or more pores in the 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, cells undergoing irreversible electroporation may be observed to form one or more pores within the cell membrane that persist even after removal of the electric field.

The pulse waveforms for electroporation energy delivery disclosed herein increase the safety, efficiency, and effectiveness of energy delivery to tissue by lowering the electric field threshold associated with irreversible electroporation. can result in more effective ablation of the lesion with a reduction in total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein are hierarchical and may have a nested structure. For example, a pulse waveform may include hierarchical groupings of pulses with associated timescales. In some embodiments, the methods, systems, and devices disclosed herein are disclosed in the International Patent Application Publication No. 2003-100000, filed October 19, 2016, entitled "SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE." It may include one or more of the methods, systems, and devices described in application no. PCT/US2016/057664, the contents of which are incorporated herein by reference in their entirety.

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

Generally, to ablate tissue, one or more catheters may be advanced through the vasculature to a target site in a minimally invasive manner. In cardiac applications, the electrodes through which the voltage pulse waveforms are delivered may be disposed on epicardial or endocardial devices. The methods described herein may include introducing a device into the endocardial cavity of the left atrium of the heart and placing the device in contact with a pulmonary vein ostium. 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 can be generated in synchronization with the heart's pacing signal to avoid disrupting the heart's sinus rhythm. In some embodiments, the electrodes may be configured in an anode-cathode subset. The pulse waveform may include a hierarchical waveform to assist in tissue ablation and reduce damage to healthy tissue.

System Overview Disclosed herein are systems and devices configured for tissue ablation through selective and rapid application of voltage pulse waveforms to assist in tissue ablation, resulting in irreversible electroporation. Generally, the systems for ablating tissue described herein include a signal generator and an ablation device having one or more electrodes for selective and rapid application of a DC voltage to drive electroporation. May include. As described herein, systems and devices may be deployed in the epicardium and/or endocardium to treat atrial fibrillation. Voltages may be applied to selected subsets of electrodes, with independent subset selection for selection of anode and cathode electrodes. A pacing signal for cardiac stimulation may be generated and used to generate a pulse waveform by a signal generator in synchronization with the pacing signal.

Generally, the systems and devices described herein include one or more catheters configured to ablate tissue in the left atrial cavity 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) that includes a signal generator (122), a processor (124), a memory (126), and a heart stimulator (128). Apparatus (120) may be coupled to an ablation device (110) and optionally a pacing device (130) and/or an optional return electrode (140) (e.g., a return pad shown here in dotted line) .

The signal generator (122) may be configured to generate a pulse waveform for irreversible electroporation of tissue, such as a pulmonary vein ostium. For example, signal generator (122) may be a voltage pulse waveform generator and deliver a pulse waveform to ablation device (110). The return electrode (140) is coupled to the patient (e.g., disposed on the patient's back), allowing electrical current to flow from the ablation device (110) through the patient to the return electrode (140), allowing for safe removal from the patient. It is possible to provide a current return path (not shown). Processor (124) incorporates data received from memory (126), cardiac stimulator (128), and pacing device (130) to determine parameters (e.g., amplitude) of pulse waveforms generated by signal generator (122). , width, duty cycle, etc.). The memory (126) further stores instructions that cause the signal generator (122) to perform modules, processes, and/or functions associated with the system (100), such as generating pulse waveforms and/or synchronizing cardiac pacing. You can. For example, memory (126) may be configured to store pulse waveforms and/or cardiac pacing data for pulse waveform generation and/or cardiac pacing, respectively.

In some embodiments, ablation device (110) may include a catheter configured to receive and/or deliver pulse waveforms described in more detail below. For example, after the ablation device (110) is introduced into the endocardial cavity of the left atrium and positioned to align the one or more electrodes (112) with one or more pulmonary vein ostia, the pulse waveform may be delivered to ablate the tissue. Ablation device (110) may include one or more electrodes (112), which in some embodiments may be a set of independently addressable electrodes. Each electrode may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In some embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 1,500V across its thickness without breakdown. For example, the electrodes (112) may include, for example, a subset including one anode and one cathode, a subset including two anodes and two cathodes, a subset including two anodes and one cathode, one anode and two cathodes. The anode-cathode subsets may be grouped into one or more anode-cathode subsets, such as a subset containing three anodes and one cathode, a subset containing three anodes and two cathodes, and a subset containing three anodes and two cathodes.

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

Processor (124) may be any suitable processing device configured to implement 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), and/or the like. The processor may be configured to implement and/or execute application processes and/or other modules, processes and/or functions associated with the system and/or its associated network (not shown). The underlying device technologies include metal oxide semiconductor field effect transistor (MOSFET) technologies such as complementary metal oxide semiconductors (CMOS), bipolar technologies such as emitter-coupled logic (ECL), polymer technologies (e.g. silicon conjugated polymers and They may be provided in a variety of component types, such as metal conjugated polymer metal structures), a mix of analog and digital.

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

System (100) may, for example, communicate with other devices (not shown) via one or more networks, each of which may be any type of network. A wireless network refers to any type of digital network that is not connected by any type of cable. However, wireless networks may connect to wired networks to interface with the Internet, voice and data networks of other carriers, business networks, and personal networks. Wired networks are typically carried by twisted pairs of copper wire, coaxial cable, or fiber optic cable. Wide Area Networks (WANs), Metropolitan Area Networks (MANs), Local Area Networks (LANs), Campus Area Networks (CANs), Global Area Networks (GANs), and many more, including the Internet, and Virtual Private Networks (VPNs). There are different types of wired networks. Hereinafter, network refers to any combination of combined wireless, wired, public, and private data networks that are interconnected, typically via the Internet, to provide an integrated networking and information access solution. .

Ablation Devices The systems described herein may include one or more multi-electrode ablation devices configured to ablate tissue in the left atrial cavity of the heart to treat atrial fibrillation. FIG. 2 shows an ablation device (200) including a catheter (210) and a guidewire (220) slidable within the lumen of the catheter (210) (e.g., structural and/or functional components of the ablation device (110)). FIG. Guidewire (220) may include a non-linear distal portion (222), and catheter (210) may be configured to be disposed over guidewire (220) during use. Distal portion (222) of guidewire (220) may be shaped to assist in placement of catheter (210) in a patient's lumen. For example, the shape of the distal portion (222) of the guidewire (220) may be configured to be placed at and/or near the pulmonary vein ostium, as illustrated in more detail in FIG. The distal portion (222) of the guidewire (220) includes a non-invasive shape that reduces trauma to the tissue (e.g., prevents and/or reduces the possibility of tissue puncture) and/or includes a non-invasive shape. It may be formed in any shape. For example, the distal portion (222) of the guidewire (220) may include a non-linear shape, such as a circle, a loop (as shown in FIG. 2), an ellipsoid, or any other geometric shape. . In some embodiments, the guidewire (220) has a non-linear shape that matches the lumen of the catheter (210) when disposed in the catheter (210) and The non-linear shape may be configured to be elastic so as to reshape/otherwise recover the non-linear shape upon exiting and advancing. In other embodiments, catheter (210) may also be configured to be resilient, such as to assist advancement of catheter (210) through a sheath (not shown). Shaped distal portion (222) of guidewire (220) may be angled relative to guidewire (220) and other portions of catheter (210). Catheter (210) and guidewire (220) may be sized for advancement into the endocardial space (eg, left atrium). The diameter of the shaped distal portion (222) of the guidewire (220) may be approximately the same as the diameter of the lumen in which the catheter (230) will be disposed.

Catheter (210) may be slidably advanced over guidewire (220) such that it is disposed over guidewire (220) during use. A distal portion (222) of guidewire (220) disposed in the lumen (eg, near the pulmonary vein ostium) may act as a backstop to advancement of the distal portion of catheter (210). The distal portion of the catheter (210) is structurally connected to an electrode (212) (e.g., electrode(s) (112)) configured to contact the inner radial surface of the lumen (e.g., pulmonary vein ostium). and/or functionally similar). For example, electrode (212) may include a generally circular array of electrodes configured to contact a pulmonary vein ostium. As shown in FIG. 2, the one or more electrodes (212) may include a series of metal bands or rings disposed along the catheter shaft and electrically connected together. For example, ablation device (200) may include a single electrode with multiple bands, one or more electrodes with each electrode having its own band, and combinations thereof. In some embodiments, electrode (212) may be shaped to match the shape of distal portion (222) of guidewire (220). The catheter shaft may include flexible portions between the electrodes to enhance flexibility. In other embodiments, one or more electrodes (212) may include helical turns to enhance flexibility.

Each of the electrodes of the ablation devices discussed herein may be connected to an insulated lead wire (not shown) that leads to a handle (not shown) coupled to the proximal portion of the catheter. The insulation of each of the conductive wires may maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 2000V, including all values and subranges therebetween, throughout the thickness therebetween without breakdown. . This allows the electrode to efficiently deliver electrical energy and ablate tissue by irreversible electroporation. The electrodes may receive pulse waveforms generated by, for example, a signal generator (122), as discussed above with respect to FIG. 1. In other embodiments, guidewire (220) may be separate from ablation device (200) (e.g., ablation device (200) includes catheter (210) but does not include guidewire (220)). do not have). For example, guidewire (220) may be advanced into the endocardial space by itself, and then catheter (210) may be advanced over guidewire (220) into the endocardial space. Good too.

FIG. 3 shows an ablation device (300) including a catheter (310) with a set of electrodes (314) provided along a distal portion (312) of the catheter (310) (e.g., structurally attached to the ablation device (110)). and/or functionally similar). The distal portion (312) of the catheter (310) may be non-linear and form a generally circular shape. A set of electrodes (314) may be disposed along a non-linear distal portion (312) of catheter (310) that may form a generally circular array of electrodes (314). In use, electrode (314) may be disposed at the pulmonary vein ostium to deliver a pulse waveform to ablate tissue, as described in more detail with respect to FIG. 16. The distal portion (312) of the shaped catheter (310) may be angled relative to other positions of the catheter (310). For example, distal portion (312) of catheter (310) may be substantially perpendicular to an adjacent location of catheter (310). In some embodiments, a handle (not shown) may be coupled to a proximal portion of catheter (310) and configured to modify the shape of distal portion (312) of catheter (310). A bending mechanism (eg, one or more pull wires (not shown)) may also be included. For example, manipulation of a pull wire in 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) is modified to place the electrode (314) near and/or in contact with the pulmonary vein ostium (e.g., on the inner radial surface of the pulmonary vein). (in contact with). Electrodes (314) include a series of metal bands or rings and may be independently addressable.

In some embodiments, the pulse waveform may be applied between electrodes (314) configured in an anode and cathode set. For example, adjacent or substantially diametrically opposed pairs of electrodes may operate together as an anode-cathode set. It is to be understood that any of the pulse waveforms disclosed herein can be applied to the anode-cathode electrode sequence progressively or sequentially.

FIG. 4 shows an ablation device (400) including a catheter (410) and a guidewire (420) having a shaped non-linear distal portion (422) (e.g., structural and/or functional additions to the ablation device (110)). FIG. 3 is a perspective view of yet another embodiment (similar to . Guidewire (420) may be slidable within the lumen of catheter (410). Guidewire (420) may be advanced through the lumen of catheter (410), and the distal portion (422) of guidewire (420) may be generally circular in shape. The shape and/or diameter of the distal portion (422) of the guidewire (420) may be modified using a bending mechanism, as described above with respect to FIG. Catheter (410) may be flexible so that it can be bent. In some embodiments, catheter (410) and/or guidewire (420) conform to the lumen in which they are disposed and assume a secondary shape as they are advanced out of the lumen. It may be configured to be elastic. By varying the size of guidewire (420) and manipulating the deflection of catheter (410), distal portion (422) of guidewire (420) may be positioned at a target tissue site, such as a pulmonary vein ostium. The distal end (412) of catheter (410) is connected to guidewire (420) such that catheter (410) can electrically isolate the portion of guidewire (420) that is within the lumen of catheter (410). may be sealed except where it extends. For example, in some embodiments, distal end (412) of catheter (410) may include a seal that allows passage of guidewire (420) when a force is applied. and has an opening that forms a compressive hold (which may be liquid tight) between the seal and the guidewire (420).

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

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

FIG. 5 shows an ablation device (500) (e.g., an ablation device (110 FIG. 3 is a detailed perspective view of the distal portion of the flower-shaped portion of the flower-shaped structure (structurally and/or functionally similar to ); Each pair of adjacent insulated conductor segments coupled to uninsulated electrodes (e.g., conductor segments (510, 512) and electrode (526)) forms a loop (FIG. 5 shows a set of four loops). . A set of loops at the distal end of the ablation device (500) may be configured to deliver pulse waveforms to tissue. The ablation device (500) includes insulated conductor segments (510) that bifurcate at the distal end of the device (500) to connect to respective exposed electrodes (520, 522, 524, 526), as shown in FIG. , 512, 514, 516). The electrodes (520, 522, 524, 526) may include exposed portions of electrical conductor. In some embodiments, one or more of the electrodes (520, 522, 524, 526) may include a platinum coil. One or more segments (510, 512, 514, 516) include a bending mechanism (e.g., controlled from a handle (not shown) to control the size and/or shape of the distal portion of the device (500). (posts, pull wires, etc.).

The electrodes (520, 522, 524, 526) may be flexible and form a compact first configuration for advancement into the endocardial cavity, such as adjacent the pulmonary vein ostium. . Once positioned at the desired location, the electrodes (520, 522, 524, 526) are advanced into an expanded second configuration as they are advanced out of a lumen, such as a sheath, as shown in FIG. It may transition to form a flower-shaped distal portion. In other embodiments, the insulated lead segments (510, 512, 514, 516) and electrodes (520, 522, 524, 526) are energized as they advance out of the lumen (e.g., sheath); Expand outwardly (eg, pop open) into the second configuration to carry the device (500). The electrodes (520, 522, 524, 526) may be independently addressable and each insulator configured to maintain a potential of at least about 700V without breakdown of the corresponding insulator. It may also include a conducting wire. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 2000V across its thickness without breakdown.

In some embodiments, the ablation device (5000) may be configured to deliver pulse waveforms to tissue during use via a set of electrodes (520, 522, 524, 526). In some embodiments, pulse waveforms may be applied between electrodes (520, 522, 524, 526) configured in an anode and cathode set. For example, a pair of substantially diametrically opposed electrodes (eg, electrodes (520, 524) and (522, 526)) may operate together as an anode-cathode pair. In other embodiments, adjacent electrodes may be configured as anode-cathode pairs. By way of 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.

6-9E, 26A-27C, and 28 illustrate an ablation device (e.g., , structurally and/or functionally similar to ablation device (110)). In some of these embodiments, the ablation device is moved from the first configuration to the second configuration such that the electrodes of the ablation device expand outwardly to contact the tissue lumen (e.g., pulmonary vein ostium). It may be moved to the configuration.

FIG. 6 shows an ablation device (600) that includes a catheter shaft (610) at the proximal end of the device (600), a distal cap (612) of the device (600), and a set of splines (614) coupled thereto. ) is a side view of an embodiment of the present invention. Distal cap (612) may include an atraumatic feature 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 coupled to the distal cap (612) of the device (600). ) may be moored. Ablation device (600) may be configured to deliver a pulse waveform to tissue during use through one or more splines of set of splines (614). As used herein, "spline" and "spine" may be used interchangeably. In some embodiments, the device may include a catheter defining a longitudinal axis.

Each spline (614) of the ablation device (600) has one or more interconnected, wired, or in some cases independently addressable electrodes (616) formed on the surface of the spline (614). ) may also be included. Each electrode (616) can include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 2000V across its thickness without breakdown. Each spline (614) may include an insulated lead for each electrode (616) formed in the body of the spline (614) (eg, within the lumen of the spline (614)). If the electrodes on a single spline are wired together, a single insulated conductor may carry strands connecting different electrodes on the spline. FIG. 6 shows a set of splines (614) where each spline (614) includes a pair of electrodes (616) having approximately the same size, shape, and spacing as the electrodes (616) of an adjacent spline (614). In other embodiments, the size, shape, and spacing of electrodes (616) may vary.

For each of the ablation devices described herein, and particularly those described in FIGS. 6-9E, 26A-27C, and 28, each spline of the set of splines may include a flexible curvature. . The minimum radius of curvature of the spline can range from about 1 cm or more. For example, the set of splines may form a delivery assembly at a distal portion of the ablation device, with the set of splines deflecting radially outwardly from the longitudinal axis of the ablation device; The second configuration may be configured to transition between a second configuration arranged generally parallel to a longitudinal axis of the ablation device. In this way, the spline can more easily match the geometry of the endocardial cavity. Generally, a spline "basket" has an asymmetrical shape along the length of the shaft such that one end of the basket (let's say the distal end) is more bulbous than the other end of the basket (let's say the proximal end). may have. The delivery assembly may be disposed in a first configuration in contact with a pulmonary vein ostium and transitioned 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 effect a transition between a first configuration and a second configuration of the set of splines. be done. In some embodiments, the 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 in 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 on an adjacent spline having an opposite configuration (eg, cathode and anode). The ablation device (600) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, including all values and subranges in between. , 12, 14, 16, 18, 20, or more splines. In some embodiments, ablation device (600) may include 3 to 20 splines. For example, ablation device (600) may include 6 to 12 splines.

FIG. 7 shows an ablation device (700) that includes a catheter shaft (710) at the proximal end of the device (700), a distal cap (712) of the device (700), and a set of splines (714) coupled thereto. ) is a side view of another embodiment of the invention. Distal cap (712) may include an atraumatic feature. 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 coupled to the distal cap (712) of the device (700). ) may be moored. 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 conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 1500V across its thickness without breakdown. Each spline (714) may include an insulated lead for each electrode (716) formed in the body of the spline (714) (eg, within the lumen of the spline (714)). The set of spline wires (718, 719) are electrically conductive and have adjacent electrodes ( 716). For example, spline wires (718, 719) may extend transversely to the longitudinal axis of ablation device (700).

FIG. 7 shows a set of splines (714) where each spline (714) includes a pair of electrodes (716) having approximately the same size, shape, and spacing as the electrodes (716) of an adjacent spline (714). In other embodiments, the size, shape, and spacing of electrodes (716) may vary. 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). You can.

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

In another embodiment, the first spline wire (721) of the set of spline wires (720, 721, 722, 723) is connected to the first spline (711) and the second spline ( The second spline wire (720) of the set of spline wires (720, 721, 722, 723) may be coupled to the first spline wire (716) of the set of spline wires (713). The electrode (716) between the third spline (711) and the third spline (715) may be coupled. The electrode (716) coupled by the first spline wire (721) and the second spline wire (720) may be configured as an anode and a cathode (or vice versa). In yet another embodiment, the first spline wire (721) of the set of spline wires (720, 721, 722, 723) is connected to the first spline (711) and the second spline of the set of splines (714). (713) and the second spline wire (723) of the set of spline wires (720, 721, 722, 723) is the second spline wire (723) of the set of spline wires (714). The electrode (716) between the third spline (715) and the fourth spline (717) may be coupled. 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 spline wires, the 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 in the handle.

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

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

8A and 8B are side and front cross-sectional views, respectively, of an ablation catheter (800). FIG. 8A shows an ablation device (800) including a catheter shaft (810) at the proximal end of the device (800), a distal cap (812) of the device (800), and a set of splines (814) coupled thereto. FIG. 2 is a side view of an embodiment of the invention. Distal cap (812) may include an atraumatic feature. 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 coupled to the distal cap (812) of the device (800). ) may be moored. Each spline (814) of the ablation device (800) may include one or more independently addressable electrodes (816, 818) formed on the surface of the spline (814). Each electrode (816, 818) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 2000V, including all values and subranges therebetween, throughout the thickness therebetween without breakdown. . Each spline (814) may include an insulated lead for each electrode (816, 818) formed in the body of the spline (814) (eg, within the lumen of the spline (814)). One or more spline wires (817, 819) may be electrically conductive and electrically couple adjacent electrodes (816, 818) disposed on different splines (814). For example, spline wires (817, 819) may extend transversely to the longitudinal axis of ablation device (800).

FIG. 8B is a front cross-sectional view of FIG. 8A taken along line 8B-8B. Each spline wire (817, 819, 821, 823) electrically couples a pair of adjacent electrodes (816, 818, 820, 822) on a different spline. In some embodiments, each coupled electrode pair may be electrically isolated from each other. In some embodiments, the coupled electrode pairs may be configured with a common polarity. Pairs of adjacent electrodes may be configured with opposite polarity (eg, a first pair of electrodes configured as an anode and a second adjacent pair of electrodes 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) It may also be configured as a cathode. In some embodiments, each electrode formed on spline (814) may share a common polarity (eg, configured as an anode or a cathode). Each coupled electrode pair may be independently addressable. In some embodiments, ablation device (800) may include an even number of splines. Ablation device (800) may include any number of splines, such as 4, 6, 8, 10, or more splines. In some embodiments, the ablation device may include 4-10 splines. For example, in one embodiment, an ablation device may include 6 to 8 splines. As indicated above, in some embodiments, the spline wires, eg, 817, 819, etc., can be replaced with similar electrical connections in the proximal portion of the device (eg, within the device handle). For example, electrodes (816) can be electrically wired together within the handle of the device so that the electrodes are at the same potential during ablation.

FIG. 9A shows an ablation device (900) including a catheter shaft (910) at the proximal end of the device (900), a distal cap (912) of the device (900), and a set of splines (914) coupled thereto. FIG. 4 is a side view of yet another embodiment of the invention. Distal cap (912) may include an atraumatic feature. 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 coupled to the distal cap (912) of the device (900). ) may be moored. Each spline (914) of the ablation device (900) may include one or more independently addressable electrodes (916, 918) formed on the surface of the spline (914). Each electrode (916, 918) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 2000V across its thickness without breakdown. Each spline (914) may include an insulated lead for each electrode (916, 918) formed in the body of the spline (914) (eg, within the lumen of the spline (914)). FIG. 9A shows a set of splines (914) where each spline (914) includes electrodes that are spaced apart or offset from the electrodes of adjacent splines (914). For example, the electrode (916) of the first spline (920) is disposed closer to the distal end (912) of the ablation device (900) compared to the electrode (918) of the second spline (922). A set of splines (914) including a first spline (920) and a second spline (922) adjacent the first spline (920). In other embodiments, the size and shape of the electrodes (916, 918) may also vary.

In some embodiments, adjacent distal electrode (916) and proximal electrode (918) may form an anode-cathode pair. For example, distal electrode (916) may be configured as an anode and proximal electrode (918) may be configured as a cathode. In some embodiments, ablation device (900) may include 3-12 splines. In FIG. 9A, one electrode (916, 918) is formed on the surface of each spline (914) such that each spline (914) includes one insulated conductor. This reduces the diameter of the lumen of spline (914) and may make spline (914) thicker and more mechanically robust. As a result, the reliability and lifetime of each spline (914) and ablation device (900) may be improved by further reducing dielectric breakdown of the insulation. The ablation device (900) may include any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18 , 20, or more splines. In some embodiments, ablation device (900) may include 3-20 splines. For example, in one embodiment, ablation device (900) may include 6 to 10 splines. Additionally, in some embodiments, the shape of the bulbous expanded structure (930) of the set of expanded splines (914) is such that its distal portion is more bulbous or curved than its proximal portion. (see, eg, FIGS. 9B-9E). Such a bulbous distal portion assists in positioning the device at the ostium of the pulmonary vein.

Referring to FIGS. 9B-9E, unless otherwise indicated, components with reference numbers similar to those in FIG. 9A (e.g., electrode (916) in FIG. 9A and electrode (916') in FIG. 9B) are , may be structurally and/or functionally similar. FIG. 9B shows spline wires (914', 920', 922') forming expanded structure (930') during use, such as during deployment. The first surface (924A'), which may also be referred to as the proximal surface, of the expansion structure (930') is different from the cross-sectional area at the second surface (924B') of the expansion structure (930'). It has a cross-sectional area. As shown in FIG. 9B, in some embodiments, the cross-sectional area of the expanded structure (930') at the second side (924B') is greater than the cross-sectional area at the first side (924A'). . The terms "first surface" and "second surface" as used with respect to FIG. 9B refer to the maximum 1 cm, about 2 cm, and about 3 cm, or more (including all values and subranges therebetween), respectively, perpendicular to the longitudinal axis of catheter shaft (910'). obtain. Similar to FIG. 9A, the electrode (916') of the first spline (920') is larger than the distal cap (912') of the ablation device (900') compared to the electrode (918') of the second spline (922'). ’).

Figure 9C shows the spline wires (914'', 920'', 922'') forming an expanded structure (930'') during use, such as during deployment. The first surface (924A''), which may also be referred to as the proximal surface, of the expansion structure (930'') is different from the cross-sectional area at the second surface (924B'') of the expansion structure (930''). It has a cross-sectional area. As shown in FIG. 9C, in some embodiments, the cross-sectional area of the expanded structure (930'') at the second side (924B'') is greater than the cross-sectional area at the first side (924A''). The terms "first surface" and "second surface" as used with respect to FIG. a plane perpendicular to the longitudinal axis of the catheter shaft (910″) each formed at a maximum of about 1 cm, about 2 cm, and about 3 cm, or more, including all values and subranges therebetween; Unlike FIGS. 9A and 9B, multiple electrodes may be present on each spline wire, and some electrodes may be equidistant from the distal cap (912''). In this way, relatively distal electrodes such as 932'' and 934'' can be placed around the pulmonary vein ostium or apposed to its proximal/lumen during use for ablation delivery. A surrounding affected area may also be generated.

Figure 9D shows the spline wires (914''', 920''', 922''') forming an expanded structure (930''') during use, such as during deployment. The spline wires (914''', 920''', 922''') converge at their distal ends to a point (928''') within/within the expansion structure (930'''). In such a configuration, at least some of the electrodes (932''', 934''') on the spline wires (914''', 920''', 922''') are shown in FIG. 9D. may be on the distal end surface (926''') of the expansion structure (930'''). The term "distal end surface" as used with respect to FIG. 9D refers to the surface perpendicular to the longitudinal axis of catheter shaft (910''') that passes through the distal boundary of expansion structure (930'''). Good too. In this way, the expansion structure (930′′′) can be pressed against an endocardial surface, such as the posterior wall of the left atrium, and the appropriate polarization of the distal end surface can be achieved using any suitable combination of polarities. A lesion can be created directly on the surface by actuating the electrodes. For example, distal electrodes (932''', 934''') may be used to press against the endocardial surface to create lesions (eg, spot lesions) via focal ablation.

Referring now to the creation of focal ablation lesions using an ablation device (900′′′), some embodiments include electrodes (933, 935) (sometimes referred to as “proximal electrodes”) and The electrodes (932''', 934''') (sometimes referred to as "distal electrodes") may operate with opposite polarity. Conduction between these electrodes through the blood pool generates an electric field that is applied as ablation energy to the endocardial surface present at the distal end face (926'''), resulting in focal ablation. For example, the spline wires (914''', 920''', 922''') have distal electrodes (932''', 934''') on the distal end surface (926''') of the endocardial surface. ), while the proximal electrodes (933, 935) are outside the distal end face (926''') and, as a result, are not pressed against the endocardial surface or otherwise An extended structure (930''') may be formed so as not to contact it. In some embodiments, the distal electrodes (932''', 934''') may have the same polarity, while the adjacent proximal electrodes (935, 933) 932''', 934''').

In some embodiments, the electrode of the ablation device (900''') has a length of about 0.5 mm to about 5.0 mm, a cross-sectional dimension (e.g., a diameter ) may be about 0.5 mm to about 2.5 mm. The spline wires (914''', 920''', 922''') in the expanded structure (930''') shown in FIG. 9D have cross-sectional dimensions ( For example, the diameter) may be about 6.0 mm to about 30.0 mm. The focal ablation lesion thus formed may have a diameter of about 0.5 cm to about 2.5 cm, including all values and subranges therebetween.

In some embodiments, the distal electrodes (932''', 934''') may be configured with opposite polarity. In some embodiments, adjacent electrodes on the same spline may have the same polarity as the distal electrode (934''') and the proximal electrode (933), as well as the distal electrode (932'''). ) may have the same polarity as the proximal electrode (935). Electrodes (934''', 933) may have opposite polarity to electrodes (932''', 935).

In some embodiments, adjacent distal electrode (934''') and proximal electrode (933) may form an anode-cathode pair. For example, distal electrode (934''') may be configured as an anode and 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 on an adjacent spline having an opposite configuration (eg, cathode and anode).

FIG. 9E shows spline wires (944, 940, 942) forming expanded structure (950) during use, such as during deployment. The spline wires (944, 940, 942) converge at their distal ends at the proximal end of the distal cap (912'''') within/within the expansion structure (950). In such a configuration, at least some electrodes (952, 954) on the spline wires (944, 940) are at the distal end surface (946) of the expansion structure (950), as shown in FIG. 9E. Good too. The term "distal end surface" as used with respect to FIG. 9E may refer to a surface perpendicular to the longitudinal axis of catheter shaft (910'''') that passes through the distal boundary of expansion structure (950). . In this way, the expansion structure (950) can be pressed against the posterior wall of the left atrium, for example, by activating the appropriate electrodes on the distal end face (946) using any suitable combination of polarities. The affected area can be generated directly on top. For example, electrodes 952 and 954 may be configured with opposite polarities. Compared to the expanded structure (930''''') of FIG. 9D, the expanded structure (950) of FIG. 9E has a more orthogonal (e.g., a flattened ) has a shape. In other words, the cross-sectional area of the expansion structure (930'''') at the distal end surface (926''''') is less than the cross-sectional area of the expansion structure (950) at the distal end surface (946). As another example, as generally described herein with respect to FIG. ) may be formed.

For each of the ablation devices described herein, each of the splines may include a polymer and define a lumen to form a hollow tube. One or more electrodes of the ablation devices described herein may have a diameter of about 0.2 mm to about 2.0 mm and a length of about 0.2 mm to about 5.0 mm. In some embodiments, the electrodes may be about 1 mm in diameter and about 1 mm in length. Because the electrodes are independently addressable, they can be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms), as discussed in more detail below. It should be appreciated 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, alternate electrodes (eg, all distal electrodes) can be at the same potential, and so can all other electrodes (eg, all proximal electrodes). Therefore, 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. 26A shows a catheter shaft (2610) having a flower-like shape and at the proximal end of the device (2600), a distal cap (2612) of the device (2600), and a set of splines (2620) coupled thereto. 26 is a perspective view of an embodiment of an ablation device (2600), including FIG. As best shown in FIG. 26B, splined 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 preferred embodiments, the distance between distal cap (2612) and catheter shaft (2610) may be less than about 8 mm. Splined shaft (2614) and distal cap (2612) may be translatable along longitudinal axis (2616) of ablation device (2600). Splined shaft (2614) and distal cap (2612) may move together. Spline shaft (2614) may be configured to slide within the lumen of catheter shaft (2610). Distal cap (2612) may include an atraumatic feature to reduce trauma to tissue. The proximal end of each spline of the set of splines (2620) may pass through the distal end of the catheter shaft (2610) and be anchored to the catheter shaft within the catheter shaft lumen, and the proximal end of each spline of the set of splines (2620) The distal end of each spline may be anchored to a distal cap (2612) of the device (2600). Ablation device (2600) is configured to deliver a pulse waveform to tissue during use via one or more splines of set of splines (2620), for example as disclosed in FIGS. 21-25. Good too.

Each spline (2620) of the ablation device (2600) may, in some embodiments, include one or more interconnected wired electrodes (2630) formed on the surface of the spline (2620). In other embodiments, one or more of the electrodes (2630) on a given spline may be independently addressable electrodes (2630). Each electrode (2630) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 2000V across its thickness without breakdown. Each spline (2620) may include an insulated lead for each electrode (2630) within the body of the spline (2620) (eg, within the lumen of the spline (2620)). FIG. 26A shows a set of splines (2620) where each spline includes a set of electrodes (2632 or 2634) having approximately the same size, shape, and spacing as the electrodes (2634 or 2632) of an adjacent spline (2620). . In other embodiments, the size, shape, and spacing of the electrodes (2632, 2634) may be different. The thickness of each spline (2620) may vary based on the number of electrodes (2630) formed on each spline (2620), which may correspond to the number of insulated conductors in the spline (2620). Splines (2620) may be the same or different in material, thickness, and/or length.

Each spline of the set of splines (2620) may include a flexible curvature such that it can be rotated or twisted and bent to form a petal-shaped curve such as that shown in FIGS. 26A-26C. good. The minimum radius of curvature of the splines in a petal-shaped configuration may range from about 7 mm to about 25 mm. For example, a set of splines may form a delivery assembly at a distal portion of ablation device (2600), and a first configuration in which the set of splines is arranged generally parallel to a longitudinal axis of ablation device (2600); of the ablation device (2600) are configured to rotate or twist and bend about the longitudinal axis of the ablation device (2600) to transition between a second configuration biased generally away from the longitudinal axis. You can. In a first configuration, each spline of the set of splines may lie in a plane with a longitudinal axis of the ablation device. In a second configuration, each spline of the set of splines may be biased 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 and bent and biased away from the longitudinal axis of the ablation device (2600), causing the splines (2620) to move into the endocardial cavity, particularly the lungs. The geometry of the portion adjacent the mouth opening can be more easily matched. The second configuration may, for example, resemble a flower shape when the ablation device is viewed from the front, as best shown in FIG. 26C. In some embodiments, each spline in the set of splines in the second configuration may be twisted and bent to form a petal-like curve, which petal-like curve when viewed from the front. In some cases the angle between the proximal and distal ends of the curve is greater than 180 degrees. The set of splines is further configured to transition from the second configuration to a third configuration in which the set of splines (2620) may be pressed against (e.g., come into contact with) target tissue, such as tissue surrounding a pulmonary vein ostium. may be configured.

In some embodiments, a spline shaft (2614) coupled to a set of splines (2620) allows the spline shaft (2614) to connect each spline of the set of splines (2620) within the lumen of the catheter shaft (2610). As it slides, it may be allowed to bend and twist relative to the catheter shaft (2610). For example, when undeployed, the set of splines (2620) form a shape that is generally parallel to the longitudinal axis of spline shaft (2614) and when fully deployed, the set of splines (2620) forms a shape that is generally parallel to the longitudinal axis of spline shaft (2620). When splined shaft (2614) is wound (e.g., helically, twisted) about axis (2660) parallel to the axis and slides within the lumen of catheter shaft (2610), any intermediate point between It may also form a shape (such as a cage or barrel).

In some embodiments, a set of splines in a first configuration, such as splines (2620), has an axis (2660) that is parallel to the longitudinal axis of catheter shaft (2610) for some portion along its length. Although it may be centrally wrapped, other portions may otherwise be generally parallel to the longitudinal axis of catheter shaft (2610). Spline shaft (2614) may be retracted into catheter shaft (2610) to transition ablation device (2600) from a first configuration to a second configuration, in which the spline shaft (2620) is generally angled or offset (eg, perpendicularly) with respect to the longitudinal axis of catheter shaft (2610) and twisted. As shown in the front view of FIG. 26C, each spline (2620) may form a twisted loop in this front view projection. In FIG. 26C, each spline (2620) has a set of electrodes (2630) with the same polarity. As shown in the front view of FIG. 26C, each spline of the set of splines (2620) may form twisted loops such that each spline overlaps one or more other splines. The number and spacing of the electrodes (2630) and the rotated twist of the splines (2620) are configured by suitably placing the electrodes along each spline so that the electrodes (2630) on one spline are Overlapping of the electrodes of the overlapping splines (2620) may be prevented.

A spline with a set of anodic electrodes (2632) may operate together to deliver a pulse waveform for irreversible electroporation. The electrodes on the other splines (2634 ) and (2635) may act together as cathode electrodes. Anode-cathode pairing and pulsed waveform delivery may be repeated sequentially over a set of such pairings.

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

The delivery assembly may be disposed in a first configuration prior to delivering a pulse waveform and transitioned to a second configuration to contact a pulmonary vein or sinus ostium. In some of these embodiments, a handle may be coupled to the splined shaft (2614), the handle configured to effect the transition between a first configuration and a second configuration of the set of splines. It is composed of For example, the handle can activate a set of splines (2620) coupled to the distal cap by translating the spline shaft (2614) and distal cap (2612) relative to the catheter shaft (2610), causing them to You can bend and twist it. The proximal end of spline (2620) is secured to spline shaft (2614), causing buckling of spline (2620) such that, for example, distal cap (2612) and spline shaft (2614) Bending and twisting motion of splines (2620) may occur when pulled back relative to catheter shaft (2610), which may be held by a user. For example, the distal end of the set of splines (2620) tethered to the distal cap (2612) may translate up to about 60 mm along the longitudinal axis of the ablation device to initiate this change in configuration. . In other words, translation of the activation member of the handle may bend and twist the set of splines (2620). In some embodiments, actuation of a knob, wheel, or other rotary control mechanism within the device handle may translate the actuation member or spline shaft to bend and twist the splines (2620). In some embodiments, the 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), such as in the handle.

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

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

In some embodiments, the spline electrode may be electrically actuated in a sequential manner to deliver a pulsed waveform at each anode-cathode pairing. In some embodiments, the electrodes may be electrically wired together within the spline, while in alternative embodiments the electrodes may be wired together within the handle of the device, resulting in These electrodes will be at the same potential during ablation. In other embodiments, the size, shape, and spacing of electrodes (2630) may vary as well. 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) can generate any number of splines, e.g., 2, 3, 4, 5, 6, 7, 8, 9, including all values and subranges in between. , 10, 12, 14, 16, 18, 20, or more splines. In some embodiments, ablation device (2600) may include 3-20 splines. For example, ablation device (2600) may include 4 to 12 splines.

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

In this manner, the electrode in the second configuration may be held close to or placed against a portion of the atrial wall of the left atrium, as described herein, to provide for any A lesion can be created directly thereon by actuating the appropriate electrodes using a suitable polarity combination. For example, a set of splines (2620) may be placed in contact with an atrial wall (2654) of an atrium (2652) adjacent a pulmonary vein (2650) (eg, an ostium or sinus ostium).

FIG. 26D is a schematic illustration of an ablation (2664) produced by the ablation device (2600) on tissue, such as tissue surrounding a pulmonary vein ostium. For example, actuation of one or more of the electrodes (2630) on one or more of the splines (2620) causes one or more corresponding ablation areas (2664) to can be generated along. In some embodiments, the profile of the ablation area (2664) in the pulmonary vein ostium may be about 2 cm to about 6 cm, or about 3.5 cm in diameter. In this way, a continuous transmural lesion may be created, resulting in electrical isolation of the pulmonary veins, which is a desirable therapeutic outcome.

Alternatively, an ablation catheter with electrodes deployed may be placed adjacent to or against a portion of the posterior wall of the left atrium, and actuation of a suitable electrode set causes an appropriate pulse waveform to be generated irreversibly. It may be delivered for penetrating energy delivery to ablate tissue.

In some embodiments, the electrodes or subsets of electrodes may be independently addressable so that the electrodes can be used at any time using any pulse waveform sufficient to ablate tissue by irreversible electroporation. It can be energized in this sequence. For example, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms), as discussed in further detail herein. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver continuous/transmural energy to electrically isolate one or more pulmonary veins. . In some embodiments, alternate electrodes may be at the same potential, and so can all other alternate electrodes. Thus, in some embodiments, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pair options exist and may be implemented based on their convenience.

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

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

Each spline (3530) of the ablation device (3500) may include one or more electrodes (3540) formed on the surface of the spline (3530). Each electrode (3540) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. Each spline (3530) may include an insulated lead for each electrode (3540) formed in the body of the spline (3530) (eg, within the lumen of the spline (3530)). FIG. 35 shows a set of splines where each spline (3530) includes a set of electrodes (3540) having approximately the same size, shape, and spacing as the electrodes (3540) of an adjacent spline. In other embodiments, the size, shape, and spacing of the electrodes (3540) may vary.

Ablation device (3500) may be configured to deliver a set of voltage pulse waveforms using a set of electrodes (3540) to ablate tissue. In some of these embodiments, the ablation device (3500) transitions from the first configuration to the second configuration such that the splines (3530) of the ablation device (3500) deflect radially outward. good.

At least a portion of the set of splines (3530) may include flexible curvature. For example, the proximal region (3522) and distal region (3526) of each spline (3530). The set of splines (3530) may form a delivery assembly in the distal portion of the ablation device (3500), with the set of splines (3530) generally proximate the longitudinal axis (3540) of the ablation device (3500). transitioning between a first configuration in which the set of splines (3530) are arranged in a manner such that each spline may be configured to form a basket-like and/or flower-like shape forming "petals". The spatial curve shape of the spline in the second configuration may be described with respect to equations (1)-(3) corresponding to FIGS. 34A-34B. For example, in a fully deployed configuration, the integrated magnitude of the rotational speed of each spline in the set of splines (3530) along the length of each spline may be greater than π arcuate degrees.

In other embodiments, the "basket" of splines extends along the length of the catheter such that one end of the basket (the distal end) is more bulbous than the other end of the basket (the proximal end). may have an asymmetrical shape. The delivery assembly may be advanced through the body cavity in a first configuration and transition to a second configuration prior to delivery of the pulse waveform. In some embodiments, a handle (not shown) may be coupled to the set of splines (3530), where the handle is connected between a first configuration and a second configuration of the set of splines (3530). configured to trigger the transition. In some embodiments, activation of one or more knobs, wheels, sliders, pull wires, and/or other control mechanisms in the handle causes the second catheter (3520) to move relative to the first catheter (3510). translation may result in bending of the spline (3530). In some embodiments, the 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), such as in the handle. For example, the handle may cause a set of splines (3530) to be activated and bent by translating the second catheter (3512) relative to the first catheter (3510), as shown in FIG. may be configured. The distal end of spline (3530) is secured to the distal end of second catheter (3520), causing buckling of spline (3530) such that, for example, second catheter (3520) Bending motion of spline (3530) may occur when pulled back relative to first catheter (3510). In other words, translation of the activation member of the handle may bend the set of splines (3530). In some embodiments, each spline of the set of splines (3530) may be biased laterally away from the longitudinal axis (3540) of the second catheter (3512) up to about 35 mm. For example, the set of splines (3530) in the second configuration may form a shape with an effective cross-sectional diameter at its largest portion of about 10 mm to about 35 mm. In a second configuration, the set of splines may be about 15 mm to about 50 mm in length.

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, sets of electrodes on adjacent splines may have opposite polarities. In another embodiment, the electrodes on one spline may alternate between anode and cathode, and the electrodes on another spline have the opposite configuration (eg, 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 actuated in a sequential manner to deliver a pulsed waveform at each anode-cathode pairing. In some embodiments, the electrodes (3540) may be electrically wired together within the spline (3530), while in alternative embodiments the electrodes are wired together within the handle of the device (3500). The electrodes (3540) may be wired so that they are at the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3540) may vary as well. As another example, spline (3530) may operate continuously in a clockwise or counterclockwise manner. As another example, the cathode spline may be operated sequentially simultaneously with each successive anode spline operation until ablation is complete. In embodiments where the electrodes (3540) on a given spline (3530) are wired separately, the order of actuation within the electrodes (3540) of each spline (3530) may vary as well. For example, the electrodes (3540) in the spline may be activated all at once or in a predetermined sequence.

The electrodes may be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver sufficient energy to electrically isolate one or more regions of cardiac tissue. . In some embodiments, alternate electrodes (eg, all distal electrodes) can be at the same potential, and so can all other electrodes (eg, all proximal electrodes). Therefore, ablation can be delivered quickly with all electrodes activated simultaneously. A variety of such electrode pair options exist and may be implemented based on their convenience.

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

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

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

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

The rate of change of the unit tangent vector along the length of the spline may conform to the following equation:
u′=du/dl (1)
where l is the arc length along the spline.

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

In some embodiments, the splines described herein may transition to form a petal shape and may form loops that allow the spline to torsion along its length. twisted along its length so that it has a The splines described herein have an integral magnitude of rotational speed that conforms to the following inequality:

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

In some embodiments, the shape of the spline is generally a spatial curve with torsion such that the derivative of rotational velocity generally has a component along b at at least some locations along the length of the spline. , which conforms to the following equation:

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

FIGS. 36A-36C show the set of splines deployed when the distal spline is fully deployed to reduce trauma to the tissue and assist in positioning and contact between the set of electrodes and the tissue. FIG. 3A is a side view of an ablation catheter (3600) configured such that the set of electrodes and electrodes extend distally of all other elements of the catheter (3600). FIG. 36A is a perspective view of an embodiment of an ablation device (3600) having a flower-like shape and including a first catheter (3610) at the proximal end of the device (3600). The first catheter (3610) may define 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 catheter and the second catheter, along with the catheter handle for activation, may constitute a single device. A set of splines (3630) may be coupled to the first catheter (3610) and the second catheter (3620). The second catheter (3620) may be translatable along the longitudinal axis (3650) of the ablation device (3600). The proximal end of each spline in the set of splines (3630) passes through the distal end of the first catheter (3610) and is anchored to the first catheter (3610) within the first catheter lumen. Often, the distal end of each spline of the set of splines (3630) may be anchored to the distal end (3622) of the second catheter (3620), as described in more detail with respect to FIG. That's right. Ablation catheter (3600) does not include a distal cap or other protrusion extending from the distal end of second catheter (3620) so that device (3600) is in a second configuration (e.g., flower-shaped). may engage sensitive tissue, such as thin heart walls, with low risk of trauma from the device (3600). The ablation device (3600) is configured to deliver a pulse waveform to tissue during use, such as as disclosed in FIGS. 21-26, through one or more electrodes of a set of splines (3630). Good too.

Each spline (3630) of the ablation device (3600) may, in some embodiments, include one or more interconnected wired electrodes (3640) formed on the surface of the spline (3630). In other embodiments, one or more of the electrodes (3640) on a given spline may be independently addressable electrodes (3640). Each electrode (3640) may include an insulated conductor wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 2000V across its thickness without breakdown. Each spline (3630) may include an insulated lead for each electrode (3640) within the body of the spline (3630) (eg, within the lumen of the spline (3630)). 36A-36C illustrate a set of splines (3630), each spline including a set of electrodes (3640) having approximately the same size, shape, and spacing as the electrodes (3640) of an adjacent spline (3630). In other embodiments, the size, shape, and spacing of the electrodes (3640) may vary. The thickness of each spline (3630) may vary based on the number of electrodes (3640) formed on each spline (3630), which may correspond to the number of insulated conductors in the spline (3630). Splines (3630) may be the same or different in material, thickness, and/or length.

Each spline of the set of splines (3630) is rotated or twisted and bent to form a petal-shaped curve, such as those shown in FIGS. 26A-26C, 34A-34B, and 36A-36C. , may include flexible curvature. The minimum radius of curvature of the spline in a petal-shaped configuration may be from about 7 mm to about 25 mm. For example, a first configuration in which the set of splines forms a delivery assembly at a distal portion of the ablation device (3600), the set of splines being arranged generally proximate a longitudinal axis of the ablation device (3600); The set of splines is configured to rotate or twist and bend about the longitudinal axis of the ablation device (3600) to transition to and from a second configuration biased generally away from the longitudinal axis. may be done. In a first configuration, each spline of the set of splines may lie in a plane with a longitudinal axis of the ablation device. In a second configuration, each spline of the set of splines may be biased away from the longitudinal axis to form a petal-like curve (e.g., a flower shape), where the longitudinal axis of the spline are generally perpendicular to the longitudinal axis (3650) or have an acute angle. As described in detail herein, the shape of the set of splines (eg, bends, curves) may satisfy Equations (1)-(3). In this manner, the set of splines (3620) are twisted and bent and biased away from the longitudinal axis of the ablation device (3600), thereby causing the splines (3620) to The geometry of the endocardial cavity, such as the In some embodiments, each spline in the set of splines in the second configuration may be twisted and bent to form a petal-like curve, which petal-like curve when viewed from the front. In some cases the angle between the proximal and distal ends of the curve is greater than 180 degrees.

In some embodiments, a second catheter (3620) coupled to the set of splines (3630) connects each spline of the set of splines (3630) with the second catheter (3620) connecting the first catheter (3610) with the second catheter (3620). ) may be able to bend and twist relative to the first catheter (3610) as it slides within the lumen of the first catheter (3610). For example, the set of splines (3630) form a shape generally proximate the longitudinal axis of the second catheter (3620) when undeployed, and when fully deployed, the set of splines (3630) form a shape generally proximate the longitudinal axis (3650) of the second catheter (3620). When the second catheter (3620) is slid within the lumen of the first catheter (3610), the second catheter (3620) may be wound (e.g., spirally, twisted) around the or barrel-shaped).

In some embodiments, the set of splines in a first configuration, such as splines (3630), is centered about the longitudinal axis (3650) of the first catheter (3610) for some portion along its length. Although it may be coiled, the other portion may otherwise be generally parallel to the longitudinal axis of the first catheter (3610). The second catheter (3620) may be retracted into the first catheter (3610) to transition the ablation device (3600) from the first configuration to the second configuration. In the configuration, the splines (3630) are twisted to form a petal-like shape and angled distally (e.g., vertically) with respect to the longitudinal axis (3650) of the first catheter (3610). ) generally angled or offset. As the second catheter (3622) is retracted further into the lumen of the first catheter (3610), the set of splines (3630) may extend further distally. As shown in FIGS. 36A-36C, each spline (3630) may form a twisted loop (eg, a petal shape, 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 shows a set of splines (3630) where at least a portion of each spline in the set of splines (3630) extends distally with respect to the 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)) that is distal to the distal end (3622) of the second catheter (3620). Show that. Thus, as the ablation device (3600) is advanced distally to contact tissue, the set of splines (3630) contacts the front of the first catheter (3610) and the second catheter (3620). It turns out. This may reduce trauma to the tissue since the tissue may contact the set of flexible splines without contacting the relatively rigid second catheter (3622).

FIG. 36B shows a second configuration forming a distal (e.g., anterior) angle (3680) between the longitudinal axis (3670) of the spline (3630) and the longitudinal axis of the first catheter (3650). The set of splines (3630) in FIG. A longitudinal axis (3670) of spline (3630) is defined by a line formed between the apex of spline (3630) and the midpoint between the proximal and distal ends of spline (3630). Good too. 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 twisted loops such that each spline partially overlaps one or more other splines. The number and spacing of the electrodes (3640) and the rotated twist of the splines (3630) are configured by suitably placing the electrodes along each spline so that the electrodes (3640) on one spline are Overlapping of overlapping spline electrodes can be prevented.

A spline with a set of anodic electrodes may operate together to deliver a pulse waveform for irreversible electroporation. The electrodes on the other splines act together as cathode electrodes, such as the electrodes on their respective splines, to form an anode-cathode pairing for delivering pulse waveforms for irreversible electroporation. Good too. Anode-cathode pairing and pulsed waveform delivery may be repeated sequentially over a set of such pairings.

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

The delivery assembly may be disposed in a first configuration prior to delivering a pulse waveform and transitioned to a second configuration to contact a pulmonary vein or sinus ostium. For example, FIG. 36C shows the most distal portion of the set of splines (3630) in close proximity to and/or in contact with a tissue wall (3690), such as the posterior wall of the left atrium. . The set of splines (3630) of FIG. 36C includes a second catheter (3630) in which at least a portion of each spline of the set of splines (3630) extends distally with respect to the distal end (3622) of the second catheter (3620). It is in the configuration of 2. The tissue (3690) may be the wall of the heart, such as the endocardial surface of the posterior wall of the left atrium. A distal end (3622) of second catheter (3620) may be spaced from tissue (3690) by a first distance (3692). Thus, ablation device (3600) in the second configuration may engage tissue (3690) in a non-invasive manner with reduced risk of penetration or other trauma. Thus, the ablation device (3600) can be used to ablate even thin tissue structures, such as the posterior wall of the left atrium.

In some of these embodiments, a handle may be coupled to the second catheter (3620), the handle activating the transition between the first and second configurations of the set of splines. configured to do so. For example, the handle may actuate a set of splines (3630) coupled to the second catheter (3620) by translating the second catheter (3620) relative to the first catheter (3610) to You can bend and twist it. The proximal end of spline (3630) is secured to second catheter (3620), causing buckling of spline (3630) such that, for example, second catheter (3620) is not held by a user. Bending and twisting motion of the splines (3630) may occur when pulled back relative to the first catheter (3610), which may be moved. For example, the distal end of the set of splines (3630) tethered to the second catheter (3620) may be translated up to approximately 60 mm along the longitudinal axis of the ablation device to initiate this configuration change. good. In other words, translation of the activation member of the handle may bend and twist the set of splines (3630). In some embodiments, activating a knob, wheel, or other rotary control mechanism within the device handle may translate the activation member or second catheter to bend and twist splines (3630). In some embodiments, the 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), such as in the handle.

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

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

In some embodiments, the spline electrode may be electrically actuated in a sequential manner to deliver a pulsed waveform at each anode-cathode pairing. In some embodiments, the electrodes may be electrically wired together within the spline, while in alternative embodiments, the electrodes may be wired together within the handle of the device, resulting in These electrodes will be at the same potential during ablation. In other embodiments, the size, shape, and spacing of the electrodes (3640) may vary as well. 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) can generate any number of splines, e.g., 2, 3, 4, 5, 6, 7, 8, 9, including all values and subranges in between. , 10, 12, 14, 16, 18, 20, or more splines. In some embodiments, the ablation device (3600) may include 3-20 splines. For example, ablation device (3600) may include 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, electrode (3640) may have an atraumatic shape, including a curved, flat, curved, and/or blunted portion configured to contact endocardial tissue. . In some embodiments, electrode (3640) may be located along any portion of spline (3630) distal to first catheter (3610). The electrodes (3640) may be the same or different in size, shape, and/or location along their respective splines.

In this manner, the electrode in the second configuration may be held close to or placed against a portion of the atrial wall of the left atrium, as described herein, to provide for any A lesion can be created directly thereon by actuating the appropriate electrodes using a suitable polarity combination. For example, the set of splines (3630) may be placed in contact with the atrial wall (3654) of the atrium (3652) adjacent to the pulmonary vein (3650) (e.g., ostium or sinus ostium) and/or the posterior wall. good.

37A-37B are perspective views of the ablation catheter (3730) and left atrium (3700). Figure 37A is a perspective view of an ablation catheter (3730) disposed in the left atrium (3700). The left atrium (3700) includes a set of pulmonary veins (3720) and a posterior wall (3710). The ablation device (3730), which may be structurally and/or functionally similar to the ablation devices (3500, 3600) described herein, is advanced into the left atrium (3700); The left atrium (3700) may be positioned proximate and/or in contact with the posterior wall (3710) of the left atrium (3700) without penetrating and/or causing trauma to the sensitive tissue of the posterior wall (3710). . For example, the set of splines may include flexible, non-invasive splines that are adjacent to or in contact with the rear wall (3710) without any other portion of the device (3730) contacting the rear wall (3710). The spline may extend distally relative to the distal end of the catheter coupled to the spline to obtain the spline. In embodiments where the distal-most portion of the device (3700) includes only a set of splines in the second configuration (e.g., having a flower shape), the deployed device is at risk of trauma from the ablation device (3700). can engage thin tissue structures, such as the heart wall, with minimal turbulence. A set of pulse waveforms may be applied by an electrode of an ablation device (3700) having a flower shape to ablate tissue within the ablation zone (3740).

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

In some embodiments, the electrodes or subsets of electrodes may be independently addressable so that the electrodes can be used at any time using any pulse waveform sufficient to ablate tissue by irreversible electroporation. It can be energized in this sequence. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver sufficient energy to electrically isolate one or more pulmonary veins. In some embodiments, alternate electrodes may be at the same potential, and so can all other alternate electrodes. Thus, in some embodiments, ablation may be delivered rapidly with all electrodes activated simultaneously. A variety of such electrode pair options exist and may be implemented based on their convenience.

27A and 27B are side views of an embodiment of an ablation device (2700) that includes a catheter shaft (2710) at the proximal end of the device (2700) and a distal end of the device (2700). a set of splines (2720) coupled distally to catheter shaft (2710). Ablation device (2700) may be configured to deliver a pulse waveform to tissue during use through one or more splines of set of splines (2720). Each spline (2720) of ablation device (2700) includes one or more optionally independently addressable electrodes (2730) formed on a surface (e.g., a distal end) of spline (2720). But that's fine. Each electrode (2730) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 2000V across its thickness without breakdown. Each spline of the set of splines (2720) may include an insulated lead for each electrode (2730) formed in the body of the spline (2720) (eg, within the lumen of the spline (2720)). In some embodiments, electrodes (2730) may be formed at the distal ends of their respective splines (2720).

A set of splines (2720) may form a delivery assembly at a distal portion of ablation device (2700) and may be configured to transition between a first configuration and a second configuration. The set of splines (2720) in the first configuration may be generally parallel to the longitudinal axis of the ablation device (2700) and closely spaced together. A set of splines (2720) in a second configuration is depicted in FIGS. 27A and 27B, where the set of splines (2720) extends out from the distal end of catheter shaft (2710) and Biased (eg, curved) away from the longitudinal axis of ablation device (2700) and other splines (2720). In this way, spline (2720) may more easily match the geometry of the endocardial cavity. The delivery assembly may be disposed in a first configuration prior to delivering a pulse waveform and transitioned to a second configuration into a portion of heart tissue, such as the posterior wall of the left atrium, or into a ventricle. Such devices that deliver irreversible electroporation pulse waveforms can generate large lesions for focal ablation.

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

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

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

In some of these embodiments, a handle (not shown) may be coupled to a set of splines. The handle may be configured to effect a transition between a first configuration and a second configuration of the set of splines. In some embodiments, the 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, such as in the handle. In this case, the electrodes (2730) may be electrically wired together within the handle of the device (2700) such 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 (2730) set of electrodes may include a non-invasive configuration to reduce trauma to tissue. For example, electrode (2730) may have an atraumatic shape, including a curved, flat, curved, and/or blunted portion configured to contact endocardial tissue. . In some embodiments, electrode (2730) may be located along any portion of spline (2720) distal to catheter shaft (2710). The electrodes (2730) may be the same or different in size, shape, and/or location along their respective splines.

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

27A and 27B are side views of an embodiment of an ablation device (2700) that includes a catheter shaft (2710) at a proximal end of the device (2700) and a catheter shaft (2710) at a distal end of the device (2700). It includes a set of splines (2720) coupled to the catheter shaft (2710) at the ends. Ablation device (2700) may be configured to deliver a pulse waveform to tissue during use through one or more splines of set of splines (2720). Each spline (2720) of ablation device (2700) includes one or more optionally independently addressable electrodes (2730) formed on a surface (e.g., a distal end) of spline (2720). But that's fine. Each electrode (2730) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 2000V across its thickness without breakdown. Each spline of the set of splines (2720) may include an insulated lead for each electrode (2730) formed in the body of the spline (2720) (eg, within the lumen of the spline (2720)). In some embodiments, electrodes (2730) may be formed at the distal ends of their respective splines (2720).

A set of splines (2720) may form a delivery assembly at a distal portion of ablation device (2700) and may be configured to transition between a first configuration and a second configuration. The set of splines (2720) in the first configuration may be generally parallel to the longitudinal axis of the ablation device (2700) and closely spaced together. A set of splines (2720) in a second configuration is depicted in FIGS. 27A and 27B, where the set of splines (2720) extends out from the distal end of catheter shaft (2710) and Biased (eg, curved) away from the longitudinal axis of ablation device (2700) and other splines (2720). In this way, spline (2720) may more easily match the geometry of the endocardial cavity. The delivery assembly may be disposed in a first configuration prior to delivering a pulse waveform and transitioned to a second configuration into a portion of heart tissue, such as the posterior wall of the left atrium, or into a ventricle. Such devices that deliver irreversible electroporation pulse waveforms can generate large lesions for focal ablation.

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

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

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

In some of these embodiments, a handle (not shown) may be coupled to a set of splines. The handle may be configured to effect a transition between a first configuration and a second configuration of the set of splines. In some embodiments, the 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, such as in the handle. In this case, the electrodes (2730) may be electrically wired together within the handle of the device (2700) such 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 (2730) set of electrodes may include a non-invasive configuration to reduce trauma to tissue. For example, electrode (2730) may have an atraumatic shape, including a curved, flat, curved, and/or blunted portion configured to contact endocardial tissue. . In some embodiments, electrode (2730) may be located along any portion of spline (2720) distal to catheter shaft (2710). The electrodes (2730) may be the same or different in size, shape, and/or location along their respective splines.

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

In FIGS. 27A-27B, one electrode (2730) is formed on the surface of each spline (2720) such that each spline (2720) includes one insulated conductor. This reduces the diameter of the lumen of spline (2720) and may make spline (2720) thicker and more mechanically robust. As a result, the reliability and lifetime of each spline (2720) and ablation device (2700) may be improved by further reducing dielectric breakdown. Additionally, in some embodiments, the radius of curvature of the spline may vary over the length of the spline. For example, the radius of curvature may increase monotonically. Such a variable radius of curvature may assist in positioning the electrode (2730) at several locations in the endocardial tissue. Splines (2720) may be the same or different in material, thickness, and/or radius of curvature. For example, the thickness of each spline may decrease distally.

In this way, the electrode in the second configuration can be pressed against the posterior wall of the left atrium, for example, and localized thereon by actuating the appropriate electrode using any suitable polarity combination. Or localized lesions can be generated directly. For example, adjacent electrodes (2730) may be configured with opposite polarity.

Since the electrodes or subsets of electrodes can be independently addressable, the electrodes can be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms), as discussed in further detail herein. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver transmural lesions over a relatively large area of endocardial tissue. In some embodiments, alternate electrodes may be at the same potential, and so can all other alternate electrodes. Therefore, 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, unless otherwise indicated, components with reference numbers similar to those of FIGS. 27A-27B (e.g., electrode (2730) of FIGS. 27A-27B and electrode (2730' of FIG. 27C) ) are understood to be structurally and/or functionally similar. Figure 27C shows a set of splines (2720') where each spline (2720') includes a pair of electrodes (2730', 2740).

The ablation device (2700') includes a catheter shaft (2710') at the proximal end of the device (2700') and a spline (2720') coupled to the catheter shaft (2710') at the distal end of the device (2700'). ). Ablation device (2700') may be configured to deliver a pulse waveform to tissue during use via one or more splines of the set of splines (2720'). Each spline (2720') of 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 conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 2000V across its thickness without breakdown. Each spline of the set of splines (2720') includes an insulated lead for each electrode (2730', 2740) formed in the body of the spline (2720') (e.g., within the lumen of the spline (2720')). But that's fine. Each electrode (2730', 2740) of spline (2720') may be approximately the same in size and shape. Furthermore, each electrode (2730', 2740) of a spline (2720') may be substantially the same in size, shape, and spacing as an electrode (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') have a cross-sectional dimension of about 0.5 mm to about 5.0 mm in length, including all values and subranges therebetween. (eg, diameter) from about 0.5 mm to about 4.0 mm. The spline wires (2720') in the second configuration are at the distal ends of the ablation device (2700') from about 5.0 mm to about 20.0 mm (including all values and subranges therebetween) from each other. may extend outwardly to a degree Sd and extend from the distal end of catheter shaft (2710') a length Sl of about 8.0 mm to about 20.0 mm, including all values and subranges therebetween. You can. In some embodiments, ablation device (2700') may include 4 splines, 5 splines, or 6 splines. In some embodiments, each spline may independently include one electrode, two electrodes, or three or more electrodes.

A set of splines (2720') may form a delivery assembly at a distal portion of ablation device (2700') and may be configured to transition between a first configuration and a second configuration. good. The set of splines (2720') in the first configuration may be generally parallel to the longitudinal axis of the ablation device (2700) and closely spaced together. A set of splines (2720') in a second configuration is depicted in FIG. 27C, where the set of splines (2720') extends out from the distal end of catheter shaft (2710'). , biased (e.g., curved) away from the longitudinal axis of ablation device (2700') and other splines (2720'). In this way, spline (2720') can more easily conform to the geometry of the endocardial cavity. The delivery assembly is disposed in a first configuration prior to delivering a pulse waveform and transitions to a second configuration to contact a region of endocardial tissue and irreversibly as disclosed herein. Large, localized lesions may be created when delivering pulse waveforms for targeted electroporation. In some embodiments, the electrode (2730') in the second configuration depicted in FIG. 27C (sometimes referred to as a "distal electrode") contacts and is pressed against endocardial tissue. However, the electrode (2740) in the second configuration (sometimes referred to as the "proximal electrode") may not contact endocardial tissue. In this way, focal ablation of tissue is obtained due to the electric field generated by the electrodes due to conduction between the proximal and distal electrodes through the blood pool.

In some embodiments, the proximal end of the set of splines (2720') may be slidably coupled to the distal end of the catheter shaft (2710'). As the set of splines (2720') extends further out of the catheter shaft (2710'), the distal ends of the set of splines (2720') are further spaced from each other and from the longitudinal axis of the catheter shaft (2710'). It may also be energized. The set of splines (2720') may be slidably advanced out of the catheter shaft (2710') independently or in groups of one or more. For example, a set of splines (2720') may be disposed within catheter shaft (2710') in a first configuration. Spline (2720') may then advance out of catheter shaft (2710') and transition to the second configuration. The splines (2720') may all advance together, or a set of splines (2720') corresponding to the anode electrode (2730) may advance a set of splines (2720') corresponding to the cathode electrodes (2730', 2740). It may be advanced, as may be advanced separately from the set. In some embodiments, splines (2710') may be independently advanced through each lumen (eg, sheath) of catheter shaft (2710'). In a second configuration, electrodes (2730', 2740) are biased away from catheter shaft (2710') longitudinally and/or laterally with respect to the longitudinal axis of the distal end of catheter shaft (2710'). Ru. This may assist in delivery and positioning of the electrodes (2730', 2740) relative to the endocardial surface. In some embodiments, each set of splines (2720') may extend up to about 5 cm from the distal end of catheter shaft (2710').

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

In some of these embodiments, a handle (not shown) may be coupled to a set of splines. The handle may be configured to effect a transition between a first configuration and a second configuration of the set of splines. In some embodiments, the 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, such as in the handle. In some embodiments, the electrodes (2730', 2740) are electrically wired together within the handle of the device (2700') such that the electrodes (2730', 2740) are at the same potential during ablation. obtain.

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

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

The ablation device (2700') can generate any number of splines, e.g., 3, 4, 5, 6, 7, 8, 9, 10, including all values and subranges in between. The splines may include 1, 12, 14, 16, 18, 20, or more splines. In some embodiments, ablation device (2700') may include 3-20 splines. For example, ablation device (2700') may include 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') includes two insulated conductors. The thickness of each spline may vary based on the number of electrodes formed on each spline (2720'), which may correspond to the number of insulated conductors on the spline (2720'). Splines (2720') may be the same or different in material, thickness, and/or radius of curvature. For example, the thickness of each spline (2720') may decrease distally.

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

Since the electrodes can be independently addressable, the electrodes can be energized in any sequence using any pulse waveform sufficient to ablate tissue by irreversible electroporation. For example, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms), as discussed in further detail herein. It should be appreciated that the size, shape, and spacing of the electrodes on and between the splines may be configured to deliver continuous/transmural energy to electrically isolate one or more pulmonary veins. . In some embodiments, alternate electrodes may be at the same potential, and so can all other alternate electrodes. Therefore, 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 shows an ablation device (2800) including a catheter shaft (2810) at the proximal end of the device (2800), a distal cap (2812) of the device (2800), and a set of splines (2814) coupled thereto. FIG. 3 is a side view of yet another embodiment of the invention. In some embodiments, the ablation device (2800) is useful for creating lesions on endocardial surfaces via focal ablation, as described herein.

Distal cap (2812) has a non-invasive shape and one or more independently addressable electrodes (2816) (referred to as "distal electrodes"), as described in further detail herein. ) may also be included. The proximal end of the set of splines (2814) may be coupled to the distal end of the catheter shaft (2810), and the distal end of the set of splines (2814) may be coupled to the distal cap (2812) of the device (2800). ) may be moored. Each spline (2814) of the ablation device (2800) includes one or more independently addressable electrodes (2818) (referred to as "proximal electrodes") formed on the surface of the spline (2814). ) may also be included. Each electrode (2816, 2818) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 2000V, including all values and subranges therebetween, throughout the thickness therebetween without breakdown. . Each spline (2814) may include an insulated lead for each electrode (2818) formed in the body of the spline (2814) (eg, within the lumen of the spline (2814)). One or more of the splines (2818) may further include an insulated lead of the distal electrode (2816). In some embodiments, the size and/or shape of the electrodes (2816, 2818) may differ from each other.

The set of splines (2814) and the configuration of the proximal electrode (2818) may control the depth, shape, and/or diameter/size of the focal ablation lesion produced by the ablation device (2800). The ablation device (2800) has a first configuration in which the set of splines (2814) are arranged generally parallel to the longitudinal axis of the ablation device (2800); and a second configuration that deflects radially outwardly from the directional axis. It is understood that the set of splines (2814) may transition to any intermediate configuration between the first configuration and the second configuration, either continuously or in discrete steps.

Actuation of the electrodes using a predetermined configuration may result in targeted and precise focal ablation by controlling the size of the focal ablation spot based on the expansion of the spline (2814). For example, in some embodiments, the distal electrode (2816) may be configured with a first polarity, and the one or more proximal electrodes (2818) may be configured with a second polarity opposite the first polarity. It may also be configured with polarity. When the proximal electrode (2818) of the ablation device (2800) is in the first configuration, a high intensity electric field with a relatively small/more focused diameter causes A focal ablation lesion on the intimal surface is obtained. When the proximal electrode (2818) of the ablation device (2800) is in the second configuration, a relatively more dispersed electric field is generated, which results in a relatively wider, more shallow, A focal ablation lesion on the endocardial surface is obtained. In this manner, by varying the degree of expansion of spline (2814), the depth, shape, and/or size of the lesion can be controlled without replacing the ablation device (2800). Such embodiments are useful for creating multiple lesions of varying size and/or depth using the same ablation device.

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

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

The first plane (2822) depicted in FIG. 28 may refer to a plane perpendicular to the longitudinal axis of the catheter shaft (2810). The distal cap (2812) is pressed against an endocardial surface in the first plane (2812), such as the luminal wall of a pulmonary vein, and is configured using any suitable polarity combination. A focal ablation lesion may be created directly thereon by activating the electrode. For example, a distal electrode (2816) may be pressed against an endocardial surface and used to form a focal ablation lesion (eg, a spot lesion). In some embodiments, one or more proximal electrodes (2818) may be configured with a polarity opposite that of the distal electrode (2816). Conversely, one or more of the proximal electrodes (2818) may be configured with the same polarity as the distal electrode (2816). In some embodiments, 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) has a length of about 0.5 mm to about 7.0 mm, including all values and subranges therebetween, and a cross-sectional dimension (e.g. , diameter) from about 0.5 mm to about 4.0 mm. In some embodiments, the proximal electrode (2818) is about 0.5 mm to about 5.0 mm in length and about 0.5 mm to about 2.0 mm in diameter, including all values and subranges in between. It may be 5 mm. Distal electrode (2816) may be separated from proximal electrode (2818) by a length of about 3.0 mm to about 12.0 mm, including all values and subranges therebetween. The distal electrode (2816) disposed on the distal cap (2812) is approximately 1.0 mm to about 4.0 mm from the distal end of the distal cap (2812), including all values and subranges therebetween. They may be located 0 mm apart. In some embodiments, the distal end of distal cap (2812) may include a distal electrode (2816). The one or more focal ablation zones may be formed to include a diameter of about 1.0 cm to about 2.0 cm, including all values and subranges therebetween.

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

In some embodiments, the ablation device (2900) is useful for creating lesions on endocardial surfaces via focal ablation, as described herein. The distal ends of catheters (2910, 2920) and/or electrodes (2916, 2922) may include atraumatic features to reduce trauma to tissue. For example, the distal ends of catheters (2910, 2920) and/or electrodes (2916, 2922) may be curved, flat, curved, and/or blunted, configured to contact endocardial tissue. It may have a non-invasive shape, including a portion that has been shaped.

Each electrode (2916, 2926) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 2000V, including all values and subranges therebetween, throughout the thickness therebetween without breakdown. . Each catheter (2910, 2920) may include an insulated 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 lead that leads to a handle (not shown) coupled to the proximal portion of the catheter (2910, 2920). In some embodiments, the size, shape, and/or location of electrodes (2916, 2926) may differ from each other.

In some embodiments, the configuration of the catheter (2910, 2920) and electrode (2916, 2926) controls the depth, shape, and/or diameter/size of the focal ablation lesion produced by the ablation device (2900). obtain. The first and second catheters (2910, 2920) may be configured to transition along the longitudinal axis of the outer catheter (2902). In some embodiments, the ablation device (2900) has a set of catheters (2910, 2920) arranged generally parallel to the longitudinal axis of the outer catheter (2902), and a distal portion of the catheter (2910, 2920) A first configuration (e.g., FIG. 29A) disposed within outer catheter (2902) and electrodes (2916, 2926) exiting from and extending from the distal end (2903) of outer catheter lumen (2902). a second configuration in which the distal portion of each catheter (2910, 2920) is advanced any suitable distance away from its corresponding hinge relative to the proximal portion of its corresponding catheter (2910, 2920); (2918, 2928), or may be configured to transition between third configurations (eg, FIGS. 29B-29D) that may be twisted or bent. For example, as best shown in FIGS. 29B-29C, first catheter (2910) is configured to position distal portion (2914) in multiple positions relative to proximal portion (2912). The distal portion (2914) may include a distal portion (2914) rotatable about a first hinge (2918). Catheters (2910, 2912) in the second and third configurations may be angled away from each other such that they are biased away from the longitudinal axis of outer catheter (2902). The distal ends of proximal portions (2912, 2922) may form an angle along the longitudinal axis of about 5 degrees to about 75 degrees (eg, FIG. 29D). It is understood that the ablation device (2900) may transition to any intermediate configuration between the first configuration, the second configuration, and the third configuration, either sequentially or in discrete steps.

In some embodiments, conduction between the electrodes through the blood pool and/or endocardial tissue results in generation of an electric field and application of the electric field as ablation energy to the endocardial surface. The electrodes are held in close physical proximity to or placed in physical contact with a portion of the atrial wall of the left atrium, and one of the electrodes is placed in physical contact with a portion of the atrial wall of the left atrium using any suitable polarity combination. A diseased area can be created thereon by actuating one or more. In this way, activating the electrodes using a predetermined configuration can adjust the focal ablation spot size by adjusting the position and orientation of the electrodes (2916, 2926) relative to the proximal portion (2912, 2922) of the catheter (2910, 2920). Targeted and precise focal ablation can be achieved by controlling based on . For example, in some embodiments, the first electrode (2916) may be configured with a first polarity and the second electrode (2926) may be configured with a second polarity opposite the first polarity. may be configured. When the electrodes (2916, 2926) are rotated such that they become relatively close to each other (e.g., when proximal portion (2912) and distal portion (2914) form an acute angle (2950)), the comparison A relatively high intensity electric field with a smaller/more focused diameter results in a focal ablation lesion on the endocardial surface with a smaller diameter and better depth. Merely for non-limiting example purposes, the acute angle formed at the articulated hinge may range from about 15 degrees to about 70 degrees. In some embodiments, the electric field strength within the focal ablation zone may be about 200 V/cm or greater. When the electrodes (2916, 2926) rotate about their corresponding hinges (2918, 2928) such that they become relatively apart from each other (e.g., proximal portion (2912) and distal portion (2914) forms a larger angle), a relatively dispersed and lower strength electric field is generated, which results in a relatively wider and shallower focal ablation lesion on the endocardial surface. In this manner, by varying the degree of rotation of the electrodes (2916, 2926) relative to the proximal portion (2912, 2922) of the catheter (2910, 2920), the depth, shape, and/or size of the lesion can be changed by ablation. It can be controlled without replacing the device (2900). Such embodiments are useful for creating multiple lesions of varying size, shape, and/or depth using the same ablation device. For example, the diameter of the affected area may be about 2 mm to about 3 cm, and the depth of the affected area may be about 2 mm to about 12 mm. Although the electrodes (2916, 2926) may be positioned to contact endocardial tissue, it is understood that the electrodes (2916, 2926) need not contact endocardial tissue.

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

29B-29C depict a first catheter (2910) having an articulated distal portion (2914). The first catheter (2910) may include a proximal portion (2912) hingedly (2918) coupled to a distal portion (2914). Distal portion (2914) may include an electrode (2916), as described herein. In some embodiments, hinge (2918) may include a rotating wheel. In other embodiments, the hinge (2918) has a reduced cross-sectional area compared to the first catheter (2910), the proximal portion (2912) or the distal portion is more flexible than other portions of the catheter. It may also include a portion (2914). In still other embodiments, the hinge (2918) may include a joint, a rotary wheel, a ball and socket joint, a condylar joint, a saddle joint, a pivot, a track, or the like.

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

FIG. 29D depicts an embodiment of the ablation device (2900) in a third configuration, where the distal portions of the first and second catheters (2910, 2920) are connected to the outer catheter or sheath (2902). ) and rotated into a desired (eg, fully rotated, fully flexed) position relative to the proximal portion (2912, 2922) of the catheter (2910, 2920). In some embodiments, the wires (2912, 2922) of each catheter (2910, 2920) may be coupled together at the handle such that actuation of the control mechanism causes the wires (2912, 2922) to Controlled together, the distal portions (2914, 2924) of each of the catheters (2910, 2920) may rotate simultaneously about their respective hinges (2918, 2928). In the second and third configurations, the first and second catheters (2910, 2920) may be biased away from the longitudinal axis of the outer catheter (2902).

As the first and second catheters (2910, 2920) extend out of the outer catheter (2902), one or more portions of the catheters (2910, 2920) are shaped in their natural (e.g. , unconstrained) shape(s). Catheters (2910, 2920) may be advanced out of outer catheter (2902) together or independently. In some embodiments, the proximal portions (2912, 2922) of the catheters (2910, 2920) include a flexible It may also include curvature. The minimum radius of curvature of the catheter (2910, 2920) may be in the range of about 1 cm or more. For example, proximal portions (2912, 2922) may have a radius of curvature of about 1 cm or more. In some embodiments, the distal portion (2914, 2924) may have a radius of curvature of about 1 cm or more.

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

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

Each electrode (3022, 3032, 3042, 3052) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 2000V, including all values and subranges therebetween, throughout the thickness therebetween without breakdown. . Each catheter (3020, 3030, 3040, 3050) has respective electrodes formed in the body of the catheter (3020, 3030, 3040, 3050) (e.g., within the lumen of the catheter (3020, 3030, 3040, 3050)). (3022, 3032, 3042, 3052) insulated conductive wires may be included. Each of the electrodes (3022, 3032, 3042, 3052) may be connected to a corresponding insulated lead that leads to a handle (not shown) coupled to the proximal portion of the catheter. In some embodiments, the size, shape, and/or location of the electrodes (3022, 3032, 3042, 3052) may differ from each other.

In some embodiments, the configuration of the catheters (3020, 3030, 3040, 3050) and electrodes (3022, 3032, 3042, 3052) affect the depth, shape, and shape of the focal ablation lesion produced by the ablation device (3000). /or diameter/size may be controlled. The set of catheters (3020, 3030, 3040, 3050) may be configured to translate along the longitudinal axis to transition between the first configuration, the second configuration, and the third configuration. good. In some embodiments, the ablation device (3000) includes a set of catheters (3020, 3030, 3040, 3050) arranged generally parallel to the longitudinal axis of the outer catheter or sheath (3010), , 3040, 3050) are disposed within the outer catheter (3010) and the electrodes (3022, 3032, 3042, 3052) are disposed at the distal end of the outer catheter (3010) lumen. (3011) and advance any suitable distance therefrom, and the distal portion of each catheter (3020, 3030, 3040, 3050) extends from its corresponding catheter (3020, 3030). , 3040, 3050) about its corresponding hinge (3021, 3031, 3041, 3051) or can be twisted or bent relative to the proximal portion of the third configuration (e.g. (Fig. 30). For example, first catheter (3020) is configured to position distal portion (3024) in multiple positions relative to proximal portion (3023), as discussed above with respect to FIGS. 29A-29D. The distal portion (3024) may include a distal portion (3024) rotatable about a first hinge (3021). It is understood that the ablation device (3000) may transition to any intermediate configuration between the first configuration, the second configuration, and the third configuration, either sequentially or in discrete steps. In a second configuration, the set of catheters 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 and cathode set. For example, adjacent or substantially diametrically opposed pairs of electrodes may operate together as an anode-cathode set. In FIG. 30, a first electrode (3022) is configured as an anode and may be mated with a second electrode (3032) configured as a cathode. The third electrode (3042) is configured as an anode and may mate with a fourth electrode (3052) configured as a cathode. The first and second pair of electrodes (3022, 3032) are used to generate a first pulse waveform and then a second pulse waveform in succession using a third and fourth pair of electrodes (3042, 3052). may be applied. In another embodiment, the pulse waveform may be applied to each of the electrodes simultaneously, where the second and third electrodes (3032, 3042) may be configured as anodes, and the first and fourth electrodes (3032, 3042) may be configured as anodes. The electrodes (3022, 3052) may be configured as cathodes. It is to be understood that any of the pulse waveforms disclosed herein can be applied to the anode-cathode electrode sequence progressively or sequentially. Some embodiments of ablation device (3000) may have the same dimensions as described above for ablation device (2900).

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

31A-31B are perspective views of yet another embodiment of an ablation device (3100) that includes an outer catheter or sheath (3110) defining a longitudinal axis and an outer catheter or sheath (3110) within the outer catheter lumen. and a catheter (3160) that is slidable in the catheter. A catheter (3160) may extend from the distal end of the lumen. The catheter (3160) may include a proximal portion (3160), a plurality of distal portions (3122, 3132, 3142, 3152), and a joint (3162) coupling the proximal portion to each of the plurality of distal portions. good. For example, joints (3162) may include hinges, joints, rotating wheels, ball and socket joints, condylar joints, saddle joints, pivots, tracks, and the like. The distal portions (3122, 3132, 3142, 3152) are folded back within the outer catheter (3110), and internal springs (not shown) connecting each portion ) is in a compressed configuration when it is collapsed. When the distal portions (3122, 3132, 3142, 3152) are unconstrained (i.e., when the inner catheter (3160) is deployed or pushed far enough away from the outer catheter (3110)), the springs are in their original position. or an uncompressed configuration to cause folding of the joint (3162), which causes the distal portions (3122, 3132, 3142, 3152) to fold outwardly and generally align with the longitudinal axis of the catheter. Takes a vertical configuration. As shown in FIG. 31B, the distal end of catheter (3160) may be coupled to a set of electrodes (3120, 3130, 3140, 3150) via articulation (3162). In some embodiments, the joint (3162) includes a first distal portion (3122), a second distal portion (3132), a third distal portion (3142), and a fourth distal portion (3152). Electrodes (3120, 3130, 3140, 3150) may be disposed on the surface of each distal portion (3122, 3132, 3142, 3152). As catheter (3160) is advanced out of outer catheter (3110), distal portions (3120, 3130, 3140, 3150) align their natural positions so that they are approximately perpendicular to the longitudinal axis of catheter (3160). (e.g., unconstrained).

Electrodes (3120, 3130, 3140, 3150) may include non-invasive shapes (eg, curved, flat, curved, and/or blunted portions) to reduce trauma to tissue. Each electrode (3120, 3130, 3140, 3150) may include an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 2000V, including all values and subranges therebetween, throughout the thickness therebetween without breakdown. . Catheter (3160) may include an insulated lead for each electrode (3120, 3130, 3140, 3150) formed in the body (eg, lumen) of catheter (3160). Each of the electrodes (3120, 3130, 3140, 3150) may be connected to a corresponding insulated lead that leads to a handle (not shown) coupled to the proximal portion of the catheter (3160). In some embodiments, the size, shape, and/or location of the electrodes (3120, 3130, 3140, 3150) may be different from each other.

Catheter (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) includes a set of electrodes (3120, 3130, 3140, 3150) arranged within the outer catheter (3110) generally parallel to the longitudinal axis of the outer catheter (3110). the first configuration (e.g., FIG. 31A) and the set of electrodes (3120, 3130, 3140, 3150) are advanced out of the distal end (3111) of the outer catheter lumen any suitable distance. , a second configuration (not shown in FIG. 31A) and the electrodes (3120, 3130, 3140, 3150) rotate about their corresponding joints (3162) relative to the proximal portion of the catheter (3160). It may be configured to transition between a third configuration (eg, FIG. 31B), which can be twisted, twisted, or bent. Transitioning from the first configuration to the second and third configurations is accomplished by advancing catheter (3160) and electrodes (3120, 3130, 3140, 3150) out of the distal end of outer catheter (3110). It's okay to be hurt. It is understood that the ablation device (3100) may transition to any intermediate configuration between the first configuration, the second configuration, and the third configuration, either sequentially or in discrete steps.

FIG. 31B shows 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 and cathode set. For example, adjacent or substantially diametrically opposed pairs of electrodes may operate together as an anode-cathode set. In FIG. 31B, a first electrode (3120) is configured as an anode and may be mated with a third electrode (3140) configured as a cathode. The second electrode (3130) is configured as an anode and may mate with a fourth electrode (3150) configured as a cathode. The first and third electrode pairs (3120, 3140) are used to generate a first pulse waveform and then a second pulse waveform in succession using a second and fourth electrode pair (3130, 3150). may be applied. In another embodiment, the pulse waveform may be applied to each of the electrodes simultaneously, where the first and second electrodes (3120, 3130) may be configured as anodes, and the third and fourth electrodes (3120, 3130) may be configured as anodes. The electrodes (3140, 3150) may be configured as cathodes. It is to be understood that any of the pulse waveforms disclosed herein can be applied to the anode-cathode electrode sequence progressively or sequentially.

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

FIG. 32 is a cross-sectional schematic illustration of a high intensity electric field generated by an ablation device (3200) for ablation of tissue, such as tissue in a ventricular cavity. For example, ablation device (3200) may be disposed in the endocardial cavity of the left ventricle of the heart. The ablation device (3200) depicted in FIG. 32 may be similar to the ablation devices (3000, 3100) described with respect to FIGS. 30 and 31A-31B. In some embodiments, the electrodes (3210, 3220, 3230, 3240) may be apposed to the tissue wall when in the third configuration. In some embodiments, the electrodes (3210, 3220, 3230, 3240) of FIG. 32 may have a width of about 1 mm to about 3 mm and a length of about 3 mm to about 9 mm. For example, the electrodes (3210, 3220, 3230, 3240) may be approximately 2 mm wide and approximately 6 mm 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 and second electrodes (3210, 3230) may have a potential difference of up to about 1500V. By activating one or more of the electrodes (3210, 3220, 3230, 3240) of the one or more catheters, one or more ablation zones may be created along a portion of the wall of the ventricular cavity. The iso-field lines (3350) are iso-field lines that correspond to the ablation zone (3350) having a field strength threshold of approximately 460 V/cm when the first and third electrodes (3220, 3240) are activated. In some embodiments, the ablation zone (3350) may be up to about 12 mm wide and up to about 20 mm long. Alternatively, the ablation device may be placed adjacent to or against a portion of the posterior wall of the left atrium, and actuation of one or more electrodes creates an appropriate pulse waveform for irreversible electroporation energy delivery. may be delivered to ablate tissue.

FIG. 33A shows an outer shaft (3310) extending to the proximal end of the device (3300), an inner shaft (3320) extending from the distal end of the shaft lumen (3312) of the outer shaft (3310), and FIG. 12 is a perspective view of another embodiment of an ablation device/apparatus (3300) in the form of a catheter, including a set of coupled splines (3330). Inner shaft (3320) may be coupled to a handle (not shown) at a proximal end and disposed at a distal portion (eg, at the distal end) relative to cap electrode (3322). The inner shaft (3320) and set of splines (3330) may be translatable along the longitudinal axis (3324) of the ablation device (3300). In some embodiments, the inner shaft (3320) and set of splines (3330) may move together or may translate independently. Inner shaft (3320) may be configured to slide within lumen (3312) of outer shaft (3310). Cap electrode (3322) may include an atraumatic shape to reduce trauma to tissue. For example, cap electrode (3322) may have a flat, circular shape and/or a curved, blunted profile. The distal end of each spline in the set of splines (3330) may be anchored 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). In use, the ablation device (3300) applies a pulse waveform to the tissue via electrodes (3332, 3334) on the spline (3330) and the distal cap electrode (3322), as disclosed in FIGS. 21-25, for example. may be configured to deliver.

Each spline of the set of splines (3330) may include a set of electrodes (3332, 3334) on a surface of the spline. 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) compared to other electrodes in its corresponding set of electrodes on the same spline (eg, the set of proximal electrodes (3334)). Further, in some embodiments, the distal electrode (3332) may have only an exposed portion facing outward, i.e., a portion not facing the inner space/volume defined by the set of splines. good. For example, if the distal electrode (3332) is constructed from metal rings, a portion of each ring may be insulated such that only the exposed portion or "window" facing outward is exposed for delivery of ablation energy. You can leave it there. The cap electrode (3322) and each distal electrode (3332) of the set of distal electrodes may jointly have the same polarity during use. This combination of closely placed distal electrodes with outward facing windows and cap electrodes allows the distal end of the ablation device (3300) to generate and fire a stronger electric field, thereby Compared to either one of the electrodes alone, focal ablation lesions of tissue can be created more effectively at a desired depth.

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

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

In some embodiments, inner shaft (3320) is retracted a predetermined amount into outer catheter lumen (3312) to transition ablation device (3300) from the first configuration to the second configuration. You can. It is understood that the set of splines (3330) may transition to any intermediate configuration between the first configuration and the second configuration, either continuously or in discrete steps. The set of splines (3330) forms a shape that is generally parallel to the longitudinal axis (3324) of the inner shaft (3320) when undeployed, with the distal end of the set of splines (3330) extending toward the longitudinal axis (3324). ) may form a basket-like or bulb-like shape when deflected radially outwardly from the base.

33A, 33B, and 33E show a set of splines (3330), where each spline of the set of splines (3330) is connected to a distal electrode (3332) in size, shape, number, and spacing. one or more different proximal electrodes (3334). For example, FIG. 33A shows one distal electrode (3332) and two proximal electrodes (3334) for each spline in 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, ie, around the entire thickness of the spline. In some embodiments, each distal electrode (3332) may be formed on the surface of a portion of the spline's circumference. That is, as shown in FIGS. 33C and 33D, distal electrode (3332) may lie partially on the outer circumference of its corresponding spline and may not cover the entire circumference of its spline (3330). For example, distal electrode (3332) may be partially covered by an insulating layer surrounding the perimeter of its corresponding spline and exposing only a portion (eg, a window) of distal electrode (3332). In some embodiments, one or more electrodes may be completely covered by a thin insulating layer for two-step operation. In some embodiments, the set of distal electrodes (3332) of the set of splines (3330) has a diameter of about 30,000 around the center of its corresponding spline (3330), including all values and subranges therebetween. It may form an angle (3333) of from 300 degrees to about 300 degrees. For example, a set of distal electrodes (3332) of a set of splines (3330) may be at an angle (3333) of about 60 degrees to about 120 degrees about the center of its corresponding spline (3330). In this way, a significant proportion of the electric field generated by the set of distal electrodes (3332) in the second configuration is directed forward, toward the target, rather than away from the target tissue and into the blood. It may be fired into tissue to assist in focal ablation.

In this manner, distal electrode (3332) may be configured to point in a particular direction. For example, in FIGS. 33A and 33E, the set of distal electrodes (3332) and the cap electrode (3322) are connected to a second The distal end of the device (3300) is shown facing generally forward in the configuration. Additionally, distal electrode (3332) is disposed at the distal end of the set of splines (3330) such that distal electrode (3332) of the set of splines (3332) is disposed proximate cap electrode (3322). Good too.

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

In some embodiments, the cap electrode (3322) and the set of electrodes (3332, 3334) may be configured as an anode-cathode set. For example, each distal electrode of the set of cap electrode (3322) and distal electrode (3332) may be configured together as an anode, and all proximal electrodes (3334) may be configured together 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 set of distal electrodes (3332) and proximal electrodes (3334) for a given spline may have opposite polarities. The cap electrode (3322) and distal electrode (3332) set may have the same polarity. As discussed herein, the set of distal electrodes (3332) and the cap electrode (3322) may be wired together. In some embodiments, one or more sets of spline electrodes (3332, 3334) of the cap electrode and spline (3330) set operate together to create a pulse waveform for irreversible electroporation. May be delivered. In other embodiments, the delivery of the pulse waveform may be repeated sequentially across a predetermined subset of the set of electrodes (3332, 3334).

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

The ablation device (3300) described herein is disposed in a first configuration prior to delivering a pulse waveform and transitions to a second configuration to remove a tissue surface (e.g., the left atrium or ventricle). internal walls, and/or the like). In some of these embodiments, a handle (not shown) may be coupled to the catheter (3300) and the set of splines (3330), the handle being coupled to the first configuration of the set of splines (3330). and a second configuration. For example, the handle may be configured to translate inner shaft (3320) relative to outer shaft (3310). For example, by retracting the inner shaft (3320) into the lumen (3312) of the outer shaft (3310), the set of splines (3330) can be deployed into the bulbous shape shown herein. can. In some embodiments, activating a knob, wheel, or other control mechanism within the device handle may translate inner shaft (3324) and deploy the set of splines (3330). In some embodiments, the leads of at least two electrodes of the set of electrodes (3322, 3332, 3334) are electrically coupled at or near a proximal portion of the ablation device (3300), such as in the handle. Good too.

Additionally, the catheter handle (not shown) may include a mechanism for deflecting or guiding the distal portion of catheter device (3300). For example, a pull wire may extend from the catheter handle to one end of the distal portion of the device (3300) at or near the distal end of the outer shaft (3310), where tension in the pull wire causes the distal end of the device (3300) to The position part is deflected. Deflection of device (3300) may assist a user in positioning device (3300) in a preferred anatomical location in a controlled manner. In some embodiments, the distal cap electrode (3322) may be electrically wired separately from the distal spline electrode (3332). In this way, intracardiac ECG signals can be recorded only from the distal cap electrode (3322). In some embodiments, one or more distal spline electrodes (3332) may be electrically wired separately to monitor intracardiac ECG signals from each such electrode (3332). good. In some embodiments, some distal spline electrodes (3332) may be used for ECG monitoring, while other distal spline electrodes (3332) are used for delivering ablation energy. Good too. It should be appreciated that any of the ablation devices described herein may be used with separately electrically wired electrodes to monitor intracardiac ECG signals from each such electrode. In some embodiments, some electrodes of one or more splines of the set of splines may be used for ECG monitoring, while other electrodes are used for delivery of ablation energy. Good too.

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

Each of the splines in the set of splines (3300) may include a respective electrode (3332, 3334) having a non-invasive, generally curved shape to reduce trauma to tissue. In this manner, the distal electrode in the second configuration is held close to or placed against a portion of the atrial wall of the left atrium, as described herein, and A lesion may be created thereon by actuating the appropriate electrodes using any suitable polarity combination. For example, the cap electrode (3322) and distal electrode (3332) of the set of splines (3330) may be oriented generally perpendicular or generally oblique to the tissue wall (3350), as shown in FIG. 33E. ) may be placed in contact with or in close proximity to. This configuration of distal electrodes (3322, 3332) allows the ablation device (3300) in the deployed configuration to abut the tissue wall (3350) at an angle (e.g., obliquely) as desired. It is possible to generate a localized affected area at a depth of .

In some embodiments, the ablation device (3300) shown in FIGS. 33A-33E may be configured for focal ablation and may include a distal cap (3322) that does not include a distal electrode. This distal cap (3322) without electrodes may be generally non-invasive and may have the same size, shape, and dimensions as the distal cap electrode.

FIG. 38A shows an outer shaft (3810) (e.g., first shaft) extending to a proximal end of a device (3800), a shaft lumen (3812) of outer shaft (3810) extending from a distal end. FIG. 12 is a perspective view of another embodiment of an ablation device/apparatus (3800) in the form of a catheter, including an inner shaft (3820) (e.g., a second shaft) and a set of splines (3830) coupled thereto. . Ablation device/apparatus (3800) may include similar components and/or functionality as ablation device/apparatus (3300), but ablation device/apparatus (3800) does not include a cap electrode. Inner shaft (3820) is coupled at a proximal end to a handle (not shown) and has a distal end disposed near or adjacent distal portion (3822) (e.g., distal end). It is possible. For example, distal portion (3822) may be coupled to the distal end of inner shaft (3820). A proximal end of the set of splines (3830) may be coupled to a distal end of catheter shaft (3810). The inner shaft (3820) and set of splines (3830) may be translatable along the longitudinal axis (3824) of the ablation device (3800). In some embodiments, the inner shaft (3820) and set of splines (3830) may move together. Splines can be flexible. The spline may transition between configurations (eg, deployed, undeployed) as the inner shaft translates relative to the outer shaft (3810). Inner shaft (3820) may be configured to slide within lumen (3812) of outer shaft (3810). Distal portion (3822) may include an atraumatic shape to reduce trauma to tissue. For example, distal portion (3822) may have a flat, circular shape and/or a curved, blunted profile. In some embodiments, distal portion (3822) may include a cap. In Figures 38A-38D, the distal portion (3822) does not include electrodes. This allows the shape, profile, and size of distal portion (3822) to be configurable and/or reduced. The distal end of each spline in the set of splines (3830) may be anchored and/or coupled to a distal portion of the inner shaft (3820). A proximal portion of the set of splines (3830) may be attached to and/or coupled to the outer shaft (3810). The ablation device (3800) is configured to deliver a pulse waveform to the tissue during use, such as as disclosed in FIGS. 21-25, through electrodes (3832, 3834) on the spline (3830). Good too.

The ablation device/apparatus may include a plurality of electrodes configured to generate an electric field to ablate tissue. Each spline of the set of splines (3830) may include a set of electrodes (3832, 3834) from a plurality of electrodes formed on the surface of the spline. Each set of electrodes may include a distal electrode (3832) such that the set of splines includes a set of distal electrodes (3832). Each of the distal electrodes (3832) is closest to the distal portion (3822) compared to other electrodes of a corresponding set of electrodes on the same spline (eg, the set of proximal electrodes (3834)). Each set of electrodes may include a proximal electrode, such that the set of splines includes a set of proximal electrodes (3834). In some embodiments, each set of electrodes (3832, 3834) may extend around the outer circumference of its spline. For example, the distal electrode (3832) may be constructed from a metal ring surrounding its splined perimeter. In some embodiments, each distal electrode (3832) of the set of distal electrodes may jointly have the same polarity during use. This combination of closely placed distal electrodes causes the distal end of the ablation device (3800) to generate and fire a stronger electric field compared to either one of these electrodes alone. This makes it possible to more effectively create a focal ablation area of tissue at a desired depth. In other embodiments, at least two distal electrodes may have the same electrical polarity for ablation delivery.

Each spline (3830) of the ablation device (3800) can include at least one set of independently addressable electrodes (3832, 3834) on a surface of that spline (3830). Each electrode (3832, 3834) may be coupled to an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 3000V across its thickness without breakdown. Each spline (3830) may include an insulated lead for each electrode (3832, 3834) within the body of the spline (3830) (eg, within the lumen of the spline (3830)). In some embodiments, inner shaft (3820) may include insulated leads for one or more of distal electrodes (3832). In other embodiments, a subset of electrodes (3832, 3834) may be wired together. For example, the proximal electrodes (3834) of each spline in the set of splines (3830) may be wired together. As another example, all distal electrodes (3832) may be wired together.

In some embodiments, the set of splines (3830) is aligned with the first set of splines (3830) shown in FIG. configuration and a second configuration shown in FIG. 38B (e.g., expanded configuration, basket configuration, deployed configuration). That is, the distal portion (3804) of the spline (3830) forms a bend relative to the proximal portion (3802) of the spline (3830), as described in more detail with respect to FIGS. 38B and 38C. In some embodiments, inner shaft (3820) may be pulled toward outer shaft (3810) to deploy device (3800) in the second configuration (e.g., outer shaft (3810) (may be moved proximal to). The set of splines (3830) in the second configuration may define a space between them, where the space is larger in the expanded configuration of the set of splines than in the first configuration.

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

In some embodiments, the dot product of unit vectors u ₁ and u ₂ is equal to the cosine of angle (3848). In some embodiments, the dot product of each unit tangent vector is negative. That is, the angle (3848) between the distal electrode (3832) and the proximal electrode (3834) is between 90 degrees and 180 degrees.

In this manner, the set of distal electrodes (3832) may be shaped/oriented to form the second configuration shown in FIGS. 38B, 38C, and 38D. Distal portion (3822) may be separated from each distal electrode of the set of distal electrodes (3832) by, for example, up to about 6 mm, including all values and subranges therebetween. For example, distal portion (3822) may be separated from each distal electrode of the set of distal electrodes (3832) by about 0.5 mm to about 3 mm. In the second configuration, the distal portion of each spline in the set of splines (3830) is between about 90 degrees and about 180 degrees relative to the proximal portion (3802), including all values and subranges therebetween. An angle (3836) may be added. Distal portion (3804) may be generally linear in the second configuration, depending in part on the length and stiffness of the set of distal electrodes (3832). For example, in the second configuration, the distal portion (3822) and the set of distal electrodes (3832) extend along the longitudinal axis (3822) in a manner similar to the front view of the device/apparatus (3300) shown in FIG. 33B. ) may take the shape of a "plus" sign (eg, an "X" or a cross) when projected onto a plane perpendicular to ).

In some embodiments, inner shaft (3820) is retracted a predetermined amount into outer catheter lumen (3812) to transition ablation device (3800) from the first configuration to the second configuration. You can. It is understood that the set of splines (3830) may transition to any intermediate configuration between the first configuration and the second configuration, either continuously or in discrete steps. The set of splines (3830) forms a shape that is generally parallel to the longitudinal axis (3824) of the inner shaft (3820) when undeployed, with a distal portion of the set of splines (3830) extending along the longitudinal axis (3824). ) and may form a basket-like or pyramid-like shape when angled radially outwardly from the spline proximal portion (3802).

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

The set of distal electrodes (3832) may be configured to face in a particular direction. For example, FIGS. 38B, 38C, and 38D show the device (3800) in a second configuration when the distal portion (3822) of the set of splines (3830) deflects radially outwardly from the longitudinal axis (3824). ) shows a set of distal electrodes (3832) and a distal portion (3822) facing generally forward at the distal end of the FIG. Additionally, distal electrode (3832) is distal of the set of splines (3830) such that distal electrode (3832) of the set of splines (3830) is disposed proximate distal portion (3822) of device (3800). It may also be placed at the end.

In some embodiments, each spline of the set of splines (3830) has approximately the same size, shape, number, and spacing of electrodes (3832, 3834) as the corresponding electrodes (3832, 3834) of an adjacent spline. May include sets. The thickness of each spline (3830) may vary based on the number of electrodes (3832, 3834) formed on each spline (3830), which may correspond to the number of insulated conductors in the spline (3830). . Splines (3830) may be the same or different in material, thickness, and/or length.

In some embodiments, the set of electrodes (3832, 3834) may consist of an anode-cathode set. For example, each distal electrode of the set of distal electrodes (3832) may be collectively configured as an anode, and the set of proximal electrodes (3834) may be collectively configured as a cathode (or (The reverse is also true). In some embodiments, the set of distal electrodes (3832) and the set of proximal electrodes (3834) may have opposite polarities. For example, the set of distal electrodes (3832) and proximal electrodes (3834) for a given spline may have opposite polarities. The set of distal electrodes (3832) may have the same polarity. As discussed herein, the set of distal electrodes (3832) may be wired together. In some embodiments, one or more of the sets of spline electrodes (3832, 3834) of the set of splines (3830) may operate together to deliver a pulse waveform for irreversible electroporation. good. In other embodiments, the delivery of the pulse waveform may be repeated sequentially across a predetermined subset of the set of electrodes (3832, 3834). For example, a particular actuation sequence may include activating the distal electrodes (3432) of half of the splines (3830) (e.g., two of the four splines (3830) depicted in FIGS. 38A-38D); (3830) (eg, two of the four splines (3830) depicted in FIGS. 38A-38D). Depending on the direction of the electric field generated by the electrodes (3832, 3834) desired, the actuating distal electrode (3832) and proximal electrode (3834) may be offset from each other (e.g., the distal electrode (3832) 3832) may be on an adjacent spline (3830) from the proximal electrode (3834), or the distal electrode (3832) may be at an angle (e.g., 90 degrees) from the proximal electrode (3834). ).

In some embodiments, the set of distal electrodes (3832) may be separated from the distal portion (3822) by up to 6 mm from the distal end of each spline (3830). In some embodiments, the set of distal electrodes (3832) may be separated from the set of proximal electrodes (3834) by about 1 mm to about 20 mm. In some embodiments, each electrode of the set of electrodes (3832, 3834) may have a diameter of about 0.5 mm to about 3 mm. In some embodiments, distal portion (3822) may have a cross-sectional diameter of about 1 mm to about 5 mm. In some embodiments, each electrode in the set of electrodes (3832, 3834) may be about 0.5 mm to about 5 mm in length. In some embodiments, the set of splines (3830) in the second configuration has an expanded cross-sectional diameter (i.e., an effective diameter in the expanded or second configuration in a plane corresponding to its largest portion) of about It may be from 6 mm to about 24 mm. In some embodiments, the set of splines (3800) may extend from about 6 mm to about 24 mm from the distal end (3812) of outer shaft (3810). In some embodiments, outer shaft (3810) may have an outer diameter of about 1.5 mm to about 6.0 mm.

The ablation device (3800) described herein is disposed in a first configuration prior to delivering a pulse waveform and transitions to a second configuration to remove the tissue surface (e.g., the left atrium or ventricle). internal walls, and/or the like). In some of these embodiments, a handle (not shown) may be coupled to the catheter (3800) and the set of splines (3830), where the handle is coupled to the first configuration of the set of splines (3830). and a second configuration. For example, the handle may be configured to translate inner shaft (3820) relative to outer shaft (3810). For example, by retracting the inner shaft (3820) into the lumen (3812) of the outer shaft (3810), the set of splines (3830) is deployed into the basket or pyramid-like shape shown herein. be able to. In some embodiments, activating a knob, wheel, or other control mechanism within the device handle may translate the inner shaft (3824) and deploy the set of splines (3830). In some embodiments, the leads of at least two electrodes of the set of electrodes (3832, 3834) may be electrically coupled at or near a proximal portion of the ablation device (3800), such as in the handle. .

Additionally, the catheter handle (not shown) may include a mechanism for deflecting or guiding the distal portion (3804) of the catheter device (3800). For example, a pull wire may extend from the catheter handle to one end of the distal portion (3804) of the device (3800) at or near the distal end of the outer shaft (3810), where tension in the pull wire causes the device (3800 ) is deflected. Deflection of device (3800) may assist a user in positioning device (3800) in a preferred anatomical location in a controlled manner. In some embodiments, one or more distal spline electrodes (3832) may be electrically wired separately to monitor intracardiac ECG signals from each such electrode (3832). good. In some embodiments, some distal spline electrodes (3832) may be used for ECG monitoring, while other distal spline electrodes (3832) are used for delivering ablation energy. Good too. In some embodiments, several proximal spline electrodes (3834) may be wired separately for intracardiac ECG monitoring. It should be appreciated that any of the ablation devices described herein may be used with separately electrically wired electrodes to monitor intracardiac ECG signals from each such electrode. In some embodiments, some electrodes of one or more splines of the set of splines may be used for ECG monitoring, while other electrodes are used for delivery of ablation energy. Good too.

The ablation device (3800) can generate any number of splines, e.g., 2, 3, 4, 5, 6, 7, 8, 9, including all values and subranges in between. , 10, 12, 14, 16, 17, 20, or more splines. In some embodiments, the ablation device (3800) may include 3-20 splines. For example, ablation device (3800) may include 4 to 12 splines.

Each of the splines in the set of splines (3800) may include a respective electrode (3832, 3834) having a non-invasive, generally curved shape to reduce trauma to tissue. In this way, the distal electrode in the second configuration approaches a portion of the atrial wall of the left atrium, or more generally any atrial or ventricular cavity, as described herein. and a lesion can be created thereon by actuating appropriate electrodes using any suitable polarity combination. For example, the distal portion (3822) of the set of splines (3830) and/or the distal electrode (3832) may be arranged in a substantially perpendicular or generally oblique orientation relative to the tissue wall, as shown in FIG. 38D. It may be placed in contact with or in close proximity to the wall (3850). This distal electrode (3832) configuration allows the desired depth to be reached even when the ablation device (3800) in the deployed configuration abuts the tissue wall (3850) at an angle (e.g., diagonally). This makes it possible to generate localized affected areas.

FIG. 39A shows an outer shaft (3910) extending to the proximal end of the device (3900), a first inner shaft (3920) extending from the distal end of the shaft lumen (3912) of the outer shaft (3910). FIG. 7 is a perspective view of another embodiment of an ablation device/apparatus (3900) in the form of a catheter, including a second inner shaft (3921), a set of splines (3930), and an expandable member (3950). . Ablation device (3900) may have functionally and/or structurally similar components to other ablation devices described herein, such as ablation device (3800). A second inner shaft (3921) extends from the distal end of the first inner shaft (3920) and may be coupled to a set of splines (3930). Ablation device/apparatus (3900) may include similar components and/or functionality as ablation device/apparatus (3300, 3800). In some embodiments, ablation device/apparatus (3900) does not include a cap electrode formed on distal portion (3922). The first inner shaft (3920), the second inner shaft (3921), and the outer shaft (3910) may be coupled at their respective proximal ends to a catheter handle (not shown). The distal end of the second inner shaft (3921) may be coupled to the distal portion (3922). A proximal portion of expandable member (3950) (eg, expandable member, balloon) may be coupled to a distal portion of first inner shaft (3920). For example, expandable member (3950) may be disposed distal to the distal end of outer shaft (3910) and within the space between the sets of splines (3930).

Optionally, the distal portion of the expandable member (3950) may be coupled to one or more of the distal portion (3922) and the distal portion of the second inner shaft (3921). A proximal portion of each spline in the set of splines (3930) may be coupled to a distal portion of the outer shaft (3910). The distal portion of each spline of the set of splines (3930) may be coupled to one or more of the distal portion (3922) and the distal portion of the second inner shaft (3921). Expandable member (3950) may be disposed in the space between the sets of splines (3930) such that it is surrounded by the sets of splines (3930). In some embodiments, expandable member (3950) may be translatable independently of the set of splines (3930), e.g., expandable member (3950) may be translatable independently of the set of splines (3930). It may be movable. In such embodiments, expandable member (3950) can be moved into a particular predetermined position relative to the set of splines (3930). In some embodiments, the expandable member (3950) has a different shaft or other May be attached to a structure. For example, expandable member (3950) may be coupled to a third inner shaft (not shown). In some embodiments, the expandable member may define a lumen and the second inner shaft (3921) may extend through the lumen of the expandable member.

The first inner shaft (3920), the second inner shaft (3921), and the set of splines (3930) may be translatable along the longitudinal axis (3924) of the ablation device (3900). For example, the set of splines (3930) may be configured to transition to an expanded configuration in response to movement of the second inner shaft (3921) relative to the first inner shaft (3920). As another example, the set of splines (3930) may be configured to transition to an expanded configuration in response to movement of the second inner shaft (3921) relative to the longitudinal axis (3924). In some embodiments, the first inner shaft (3920), the second inner shaft (3921), and the set of splines (3930) may move together. Spline (3930) may be flexible. The spline may transition between configurations (e.g., a deployed configuration, an undeployed configuration) when the first and second inner shafts (3920, 3921) translate relative to the outer shaft (3910). . First inner shaft (3920) and second inner shaft (3921) may be configured to slide within lumen (3912) of outer shaft (3910). The set of splines (3930) may be translated by moving the second inner shaft (3921) relative to the outer shaft (3910) using, for example, an activation mechanism in the handle.

Distal portion (3922) may include an atraumatic shape to reduce trauma to tissue. For example, distal portion (3922) may have a flat, circular shape and/or a curved, blunted profile. In some embodiments, distal portion (3922) may include a cap. In Figures 39A-39D, the distal portion (3922) does not include electrodes. This allows the shape, profile, and size of distal portion (3922) to be configurable and/or reduced. The distal end of each spline of the set of splines (3930) may be anchored and/or coupled to a distal portion of the second inner shaft (3921). A proximal portion of the set of splines (3930) may be attached to and/or coupled to the outer shaft (3910). Ablation device (3900) is configured to deliver pulse waveforms to tissue during use, such as as disclosed in FIGS. 21-25, through electrodes (3932, 3934) on splines (3930). Good too.

The ablation device/apparatus may include a plurality of electrodes configured to generate an electric field to ablate tissue. Each spline of the set of splines (3930) may include a set of electrodes (3932, 3934) from a plurality of electrodes formed on the surface of the spline. Each set of electrodes may include a distal electrode (3932) such that the set of splines includes a set of distal electrodes (3932). Each of the distal electrodes (3932) is closest to the cap electrode (3922) compared to other electrodes of a corresponding set of electrodes on the same spline (eg, the set of proximal electrodes (3934)). Each set of electrodes may include a proximal electrode, such that the set of splines includes a set of proximal electrodes (3934). In some embodiments, each set of electrodes (3932, 3934) may extend around the outer circumference of its splines. For example, the distal electrode (3932) may be constructed from a metal ring surrounding its splined perimeter. In some embodiments, each distal electrode (3932) of the set of distal electrodes may jointly have the same polarity during use. This combination of closely placed distal electrodes causes the distal end of the ablation device (3900) to generate and fire a stronger electric field compared to either one of these electrodes alone. As a result, focal ablation of the tissue can be more effectively created at a desired depth. In other embodiments, at least two distal electrodes may have the same electrical polarity for ablation delivery.

Each spline (3930) of the ablation device (3900) can include at least one set of independently addressable electrodes (3932, 3934) on a surface of that spline (3930). Each electrode (3932, 3934) may be coupled to an insulated conductive wire configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. In other embodiments, the insulation of each of the conductive wires may maintain a potential difference of about 200V to about 3000V across its thickness without breakdown. Each spline (3930) may include an insulated lead for each electrode (3932, 3934) within the body of the spline (3930) (eg, within the lumen of the spline (3930)). In some embodiments, inner shaft (3920) may include insulated leads for one or more of distal electrodes (3932). In other embodiments, a subset of electrodes (3932, 3934) may be wired together. For example, the proximal electrodes (3934) of each spline in the set of splines (3930) may be wired together. As another example, all distal electrodes (3932) may be wired together.

In some embodiments, the set of splines (3930) is arranged in the first set shown in FIG. 39C, where the set of splines (3930) is arranged generally parallel to the longitudinal axis (3924) of the ablation device (3900) configuration and a second configuration shown in FIGS. 39A, 39B, and 39D, in which the distal portion (3904) of each spline of the set of splines (3930) deflects radially outwardly from the longitudinal axis (3924) (e.g. , expanded configuration, basket configuration, deployed configuration). That is, the distal portion (3904) of the spline (3930) forms a bend relative to the proximal portion (3902) of the spline (3930), as described in more detail with respect to FIG. 39D. In some embodiments, the first and second inner shafts (3920, 3921) may be pulled toward the outer shaft (3910) to deploy the device (3900) in the second configuration. (eg, may be moved proximally relative to outer shaft (3910)). The set of splines (3930) in the second configuration may have a basket or pyramid-like shape. As shown in FIG. 39C, when the set of splines (3930) is in the first configuration, the expandable member (3950) is in the contracted configuration. The set of splines (3930) in the second configuration may define a space between them, the space being larger in the expanded configuration of the set of splines than in the first configuration.

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

In some embodiments, the dot product of unit vectors u ₁ and u ₂ is equal to the cosine of angle (3948). In some embodiments, the dot product of each unit tangent vector is negative. That is, the first angle (3948) between the distal electrode (3932) and the proximal electrode (3934) is between about 90 degrees and about 180 degrees. As shown in FIG. 39D, in a second configuration (e.g., an expanded configuration), a second Angle (3960) is at least about 70 degrees.

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

Distal portion (3904) may be generally linear in the second configuration, depending in part on the length and stiffness of the set of distal electrodes (3932). For example, in the second configuration, the distal portion (3922) and the set of distal electrodes (3932) extend along the longitudinal axis (3922) in a manner similar to the front view of the device/apparatus (3300) shown in FIG. 33B. ) may take the shape of a "plus" sign (eg, an "X" or a cross) when projected onto a plane perpendicular to ).

In some embodiments, second inner shaft (3921) is retracted a predetermined amount into outer catheter lumen (3912) to move ablation device (3900) from the first configuration to the second configuration. You may also move to It is understood that the set of splines (3930) may transition to any intermediate configuration between the first configuration and the second configuration, either continuously or in discrete steps. The set of splines (3930) forms a shape generally parallel to the longitudinal axis (3924) when undeployed, with a distal portion of the set of splines (3930) radially outwardly from the longitudinal axis (3924). When deflected and forming an angle with respect to the proximal portion of the spline (3902), it may form a basket-like or pyramid-like shape.

In some embodiments, the expandable member (3950) is arranged as shown in FIGS. 39C, and the outer surface of the expandable member (3950) deflects radially outwardly from the longitudinal axis (3924) when the set of splines is in the expanded configuration, as shown in FIGS. 39A and 39D. and an expanded configuration. In some embodiments, the set of splines (3930) is configured to transition to the expanded configuration in response to transitioning the expandable member to the expanded configuration. In an expanded configuration in which the expandable member (3950) is disposed distal to the distal end of the outer shaft (3910) and within the space between the sets of splines (3930), the expandable member (3950) The electric field generated by the plurality of electrodes is configured to be driven from the space between the sets of splines so that the electric field can create a larger lesion within the tissue. In some embodiments, the expandable member (3950) in the expanded configuration substantially fills the space between the sets of splines in the expanded configuration. The set of splines (3930) can be in a first configuration (FIG. 39C) or a second configuration (FIG. 39B) when the expandable member (3950) is in the deflated configuration.

In some embodiments, the expandable member in the expanded configuration has an asymmetric shape (e.g., FIG. 39A , 39D).

In some embodiments, pulling the first and second inner shafts (3920, 3921) toward the outer shaft (3910) (e.g., moving them proximally relative to the outer shaft (3910)); The set of splines (3930) in the second configuration can be deployed and/or the inflatable member (3950) transitioned to the expanded expanded configuration. In some embodiments, a fluid source in fluid communication with the expandable member (3950) can be used to transition the expandable member (3950) from its deflated configuration to its expanded configuration. For example, first inner shaft (3920) may be configured to couple (e.g., in fluid communication) with a fluid source (not shown), thereby directing fluid to first inner shaft (3920). ) to the expandable member (3950) to transition the expandable member (3950) to the expanded configuration. In some embodiments, the expandable member (3950) in the expanded configuration may conform to the shape formed by the set of splines (3930) in the second configuration. That is, the expanded or expanded expandable member (3950) may form a bulbous, basket, or pyramid-like shape. In some embodiments, expandable member (3950) may be expanded such that an outer surface of expandable member (3950) engages a region of the set of splines (3930). It is understood that the inflatable member (3950) may transition to any intermediate configuration between the deflated and expanded configurations, either continuously or in discrete steps. In some embodiments, transitioning the expandable member (3950) from the contracted configuration to the expanded configuration applies a force to the set of splines (3930), causing the set of splines to change from the first configuration to the second configuration. to be transferred to For example, expandable member (3950) can be expanded to engage an area of the set of splines (3930) to apply an outward force to the set of splines (3930), thereby causing the splines to (3930) causes the configuration to change from its first configuration (i.e., the unexpanded configuration shown in FIG. 39C) to its second configuration (i.e., the expanded configuration shown in FIG. 39D) .

In some embodiments, the expandable members described herein can have an expandable structure and include polyvinyl chloride (PVC), polyethylene (PE), crosslinked polyethylene, polyolefins, polyolefin copolymers. Various insulation or It can be constructed of any of the dielectric materials. Preferred embodiments may be constructed from polyurethane or silicone. In some embodiments, one or more portions of the expandable member may include a radiopaque portion. In some embodiments, fluid flows through the expandable member (3950), for example, through the lumen of the first inner shaft (3920) or another shaft or structure coupled to the expandable member (3950). ) can be expanded. For example, the expandable member (3950) can be expanded through a fluid port attached to the catheter handle where a fluid such as distilled or deionized water can be injected under pressure.

With the use of a fluid (e.g., distilled or deionized water, saline, air, or other liquid and/or gas) to inflate the inflatable member, the inflatable member can be It acts as an effective insulator during delivery, driving an electric field to the outside of the inflatable member or balloon and to the region surrounding the balloon. This combination of an expandable member and a set of splines allows the distal end of the ablation device (3900) to fire or deliver a stronger electric field at a greater distance from the ablation device (3900), thereby allowing the set of splines only to It becomes possible to more effectively generate a focal ablation lesion of tissue at a desired depth compared to the conventional method. Thus, the device (3900) in the second and expanded configurations (FIGS. 39A and 39D) moves away from the expandable member (3950) and second inner shaft (3921) toward the tissue to be ablated. , by redirecting the electric field generated by the set of electrodes (3932, 3934), lesions may be efficiently formed in tissue with less power. In some embodiments, when the set of splines (3930) is in the expanded configuration, at least one electrode from the set of distal electrodes (3932) contacts the tissue surface from about 0.5 cm to about 2.5 cm. It is configured to create a focal ablation lesion on the tissue surface having a diameter of 5 cm.

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

The set of distal electrodes (3932) may be configured to face in a particular direction. For example, FIGS. 39B, 39C, and 39D show the device (3900) in a second configuration when the distal portion (3904) of the set of splines (3930) deflects radially outward from the longitudinal axis (3924). ) shows a set of distal electrodes (3932) and a distal portion (3922) facing generally forward at the distal end of the FIG. Further, distal electrode (3932) is distal of the splines (3930) such that the distal electrode (3932) of the set of splines (3930) is disposed proximate the distal portion (3922) of the device (3900). It may also be placed at the end.

In some embodiments, the set of electrodes (3932, 3934) of each spline of the set of splines (3930) is approximately the same size, shape, number, and spacing as the corresponding electrodes (3932, 3934) of an adjacent spline. may have. The thickness of each spline (3930) may vary based on the number of electrodes (3932, 3934) formed on each spline (3930), which may correspond to the number of insulated conductors in the spline (3930). . Splines (3930) may be the same or different in material, thickness, and/or length.

The set of electrodes (3932, 3934) can be suitably polarized to deliver high voltage pulses corresponding to pulsed electric field (PEF) ablation energy that can be applied to tissue to cause cell death by irreversible electroporation. . In some embodiments, at least one distal electrode from the set of distal electrodes may be configured to operate at a first polarity, and at least one proximal electrode from the set of proximal electrodes may be configured to operate at a first polarity. may be configured to operate at a second polarity opposite to the first polarity to collectively generate an electric field. For example, a subset of distal electrodes (3932) may have one electrical polarity, while a subset of proximal electrodes (3934) may have opposite electrical polarity, thereby providing for delivery of PEF ablation energy. A bipolar pair of electrodes may be defined. Generally, similar bipolar sequences may be defined for PEF ablation delivery. As another example, all distal electrodes (3932) may have one electrical polarity, while all proximal electrodes (3934) may have the opposite electrical polarity.

In some embodiments, the set of electrodes (3932, 3934) may consist of an anode-cathode set. For example, each distal electrode of the set of distal electrodes (3932) may be collectively configured as an anode, and the set of proximal electrodes (3934) may be collectively configured as a cathode (or (The reverse is also true). In some embodiments, the set of distal electrodes (3932) and the set of proximal electrodes (3934) may have opposite polarities. For example, the set of distal electrodes (3932) and proximal electrodes (3934) for a given spline may have opposite polarities. The set of distal electrodes (3932) may have the same polarity. As discussed herein, the set of distal electrodes (3932) may be wired together. In some embodiments, one or more of the sets of spline electrodes (3932, 3934) of the set of splines (3930) may operate together to deliver a pulse waveform for irreversible electroporation. good. In other embodiments, the delivery of the pulse waveform may be repeated sequentially across a predetermined subset of the set of electrodes (3932, 3934). For example, a particular actuation sequence may include actuating the distal electrodes (3932) of half of the splines (3930) (e.g., two of the four splines (3930) depicted in FIGS. 39A-39D); (3930) (eg, two of the four splines (3930) depicted in FIGS. 39A-39D). Depending on the desired electric field generated by the electrodes (3932, 3934), the actuated distal electrode (3932) and proximal electrode (3934) may be offset from each other (e.g., the distal electrode (3932) may be on an adjacent spline (3930) from the proximal electrode (3934), or the distal electrode (3932) may be offset at an angle (e.g., 90 degrees) from the proximal electrode (3934). ).

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

The ablation device (3900) described herein can be disposed in a first configuration prior to delivering a pulse waveform and transitioned to a second configuration to remove the tissue surface (e.g., the left atrium or ventricle). internal walls, and/or the like). In some of these embodiments, a handle (not shown) may be coupled to the catheter (3900) and the set of splines (3930), the handle being coupled to the first configuration of the set of splines (3930). and a second configuration. For example, the handle may be configured to translate the first inner shaft (3920) and the second inner shaft (3921) relative to the outer shaft (3910). For example, by retracting the first and second inner shafts (3920, 3921) into the lumen (3912) of the outer shaft (3910), the set of splines (3930) can be inserted into the basket shown herein. Or it can be expanded into a pyramid-like shape. In some embodiments, actuation of a knob, wheel, or other control mechanism within the device handle translates the first and second inner shafts (3920, 3921) and causes the set of splines (3930) to May be expanded. In some embodiments, the leads of at least two electrodes of the set of electrodes (3932, 3934) may be electrically coupled at or near a proximal portion of the ablation device (3900), such as in the handle. .

Additionally, the catheter handle (not shown) may include a mechanism for deflecting or guiding the distal portion (3904) of the catheter device (3900). For example, a pull wire may extend from the catheter handle to one end of the distal portion (3904) of the device (3900) at or near the distal end of the outer shaft (3910), where tension in the pull wire causes the device (3900 to ) is deflected. Deflection of device (3900) may assist the user in positioning device (3900) in a preferred anatomical location in a controlled manner. For example, device (3900) may be slidably disposed within a moveable sheath (not shown) that is used to deliver device (3900) to a desired location, such as a ventricular cavity. Once within the cavity, device (3900) may be further deflected or guided to access the desired site and deliver ablation energy.

In some embodiments, one or more distal spline electrodes (3932) are separately configured to receive and/or monitor intracardiac electrocardiogram (ECG) signals from each such electrode (3932). It may be electrically wired. For example, an electrode configured for ablation and another electrode configured to receive an ECG signal can be coupled to separate insulated leads. In some embodiments, some distal spline electrodes (3932) may be used for ECG monitoring while other distal spline electrodes (3932) are used for delivering ablation energy. Good too. In some embodiments, several proximal spline electrodes (3934) may be wired separately for intracardiac ECG monitoring. It should be appreciated that any of the ablation devices described herein may be used with separately electrically wired electrodes to monitor intracardiac ECG signals from each such electrode. In some embodiments, some electrodes of one or more splines of the set of splines may be used for ECG monitoring, while other electrodes are used for delivery of ablation energy. In other embodiments, only some electrodes may be used for ECG monitoring, while all electrodes may be used for delivering ablation energy.

An exemplary method of using an ablation device (3900) that includes an expandable member (3950) may include disposing the ablation device (3900) within a ventricular cavity of a subject's heart. The set of splines (3930) can be transitioned to an expanded configuration in which a distal portion of each spline in the set of splines deflects radially outwardly from the longitudinal axis (3924). Transitioning the set of splines (3930) to the expanded configuration includes retracting a distal portion of the second shaft relative to the first shaft. Retracting the distal portion of the second shaft relative to the first shaft may include using a handle coupled to at least one of the second shaft or the first shaft.

Inflatable member (3950) may transition to an expanded configuration. delivering an ablation pulse waveform to a plurality of electrodes (3932, 3934) disposed on the set of splines (3930) such that the set of splines (3930) generates an electric field to ablate tissue in the ventricular cavity; The expandable member (3950) directs the electric field toward the tissue.

In some embodiments, the electric field is configured to create a focal ablation lesion on the surface of the tissue having a diameter of about 0.5 cm to about 2.5 cm. A first electrode from the set of at least one splined electrode can be configured as an anode. A second electrode from the set of at least one splined electrode can be configured as a cathode. An ablation pulse waveform can be delivered to the first electrode and the second electrode.

At least one set of electrodes may be configured for ablation and at least one set of electrodes may be configured for receiving electrophysiology data. Electrophysiology data may be recorded from the heart using at least one set of electrodes. The electrophysiology data may include at least one pulmonary vein intracardiac electrocardiogram (ECG) signal data.

The tissue may include the endocardial surface of the ventricular cavity. In some applications, the ventricular cavity is the ventricle, and in other applications, the ventricular cavity can be the atrium. In some embodiments, a pacing device may be advanced into the right ventricle of the heart or other heart regions. A pacing signal for cardiac stimulation of the heart may be generated. A pacing device can be used to apply a pacing signal to the heart, and an ablation pulse waveform is generated in synchronization with the pacing signal. The ablation pulse waveform may include a time offset with respect to the pacing signal. The radiopaque portion of the ablation device may be visualized under fluoroscopy during one or more steps.

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

The expandable member may include multiple expandable sections. Each expandable portion from the plurality of expandable portions may be independently expandable from other expandable portions of the plurality of expandable portions.

In some variations, transitioning the set of splines to an expanded configuration comprises converting the set of splines into an expanded configuration in which the distal portion of each spline from the set of splines is angled at more than 70 degrees relative to the longitudinal axis. may include migrating. In some embodiments, transitioning the set of splines to the expanded configuration is responsive to transitioning the expandable member to the expanded configuration.

The ablation device (3900) can generate any number of splines, e.g., 2, 3, 4, 5, 6, 7, 8, 9, including all values and subranges in between. , 10, 12, 14, 16, 17, 20, or more splines. In some embodiments, the ablation device (3900) may include 3-20 splines. For example, ablation device (3900) may include 4 to 12 splines.

Each of the splines in the set of splines (3900) may include a respective electrode (3932, 3934) having a non-invasive, generally curved shape to reduce trauma to tissue. In this manner, the distal electrode (3932) in the second configuration can be attached to a portion of the atrial wall of the left ventricle, or more generally to any atrium or ventricular cavity, as described herein. A lesion may be created thereon by activating appropriate electrodes, held close to or placed against the electrode, using any suitable polarity combination. For example, the distal portion (3922) of the set of splines (3930) and/or the distal electrode (3932) may be oriented generally perpendicular or generally oblique to the tissue wall, similar to that shown in FIG. 38D. , may be placed in contact with or in close proximity to the tissue wall (3950). This distal electrode (3932) configuration allows the desired depth to be reached even when the ablation device (3900) in the deployed configuration abuts the tissue wall (3950) at an angle (e.g., diagonally). This makes it possible to generate localized affected areas.

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

In some embodiments, an ablation device (eg, 2900, 3000, 3100, 3200) may include 2 to 6 catheters. The ablation device (eg, 2900, 3000, 3100, 3200) may include any number of catheters, such as 2, 3, 4, 5, 6, or more catheters. For example, in some embodiments, an ablation device (eg, 2900, 3000, 3100, 3200) may include 3 to 6 catheters. In some embodiments, the catheter of the ablation device (eg, 2900, 3000, 3100, 3200) may include 2 to 6 distal portions. The catheter may include any number of distal portions, such as two, three, four, five, six, or more distal portions. For example, in some embodiments, the catheter may include 2 to 4 distal portions. Additionally, in some embodiments, the shape (eg, curvature, length, size) of the catheter may be asymmetrical to assist in controlling the depth, shape, and/or size of the 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, a subset of electrodes may be independently addressable, and the electrodes may be selectively activated using any pulse waveform sufficient to ablate tissue by irreversible electroporation. The power may be applied in sequence. For example, different sets of electrodes may deliver different sets of pulses (eg, hierarchical pulse waveforms).

In all of the embodiments described above, and without limitation, the ablation catheter may itself be configured to control deflection by suitable mechanisms in the catheter handle, as is known to those skilled in the art. It may also be a mobile device with a pull wire.

Balloons In some embodiments, an ablation device may include one or more balloons to deliver 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 cavity (1000) of a heart. There is. The ablation device (1010) may include a first balloon (1012) and a second balloon (1014) that may be configured to be disposed at the ostium (1002) of a pulmonary vein (1004). The first balloon (1012) in the expanded (eg, inflated) configuration may be larger in diameter than the second balloon (1014) in the expanded configuration. This allows the second balloon (1014) to be advanced and placed further into the pulmonary vein (1014) while the first balloon (1012) is inserted into the ostium (1002) of the pulmonary vein (1004) and/or It can be placed near it. The inflated second balloon functions to stabilize the positioning of the first balloon at the ostium of the pulmonary vein. In some embodiments, the first balloon (1012) and the second balloon (1014) may be filled with any suitable conducting fluid, such as saline. The first balloon (1012) and the second balloon (1014) may be electrically isolated from each other. For example, each balloon (1012, 1014) may be associated with an insulated conductor, each conductor having sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness without dielectric breakdown. has. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 2500V, including all values and subranges therebetween, throughout the thickness therebetween without breakdown. . For example, the leads of the second balloon (1014) may be insulated as they extend through the first balloon (1012).

In some embodiments, the first and second balloons (1012, 1014) may form an anode-cathode pair. For example, in one embodiment, the first and second balloons may carry electrically separate saline fluids, the first balloon (1012) may be configured as a cathode, and the second balloon (1012) may be configured as a cathode. The balloon (1014) may be configured as an anode, and vice versa, where electrical energy may be capacitively coupled across the balloon or saline-filled electrode. Device (1010) may receive pulse waveforms that are delivered to tissue (1002). For example, one or more of the biphasic signals may be transmitted such that tissue may be ablated between the first balloon (1012) and the second balloon (1014) at a desired location in the pulmonary vein (1004). may be applied. The first and second balloons (1012, 1014) substantially reduce the electric field and the damage to tissue remote from the ostium (1002) of the pulmonary vein (1004). 1012) and the second balloon (1014). In another embodiment, one or both of electrodes (1018) and (1019) disposed proximally and distally of the first balloon, respectively, may be used as one polarized electrode; The fluid in the first balloon may act as an electrode of opposite polarity. A biphasic pulse waveform may then be delivered between these electrodes of opposite polarity by capacitive coupling across the balloon to create a zone of irreversible electroporation ablation in a region around the first balloon. . In some embodiments, one or more of the balloons (1012, 1014) may include wire mesh.

FIG. 11 shows a balloon ablation device (1110) (e.g., structurally and/or functionally similar to ablation device (1010)) disposed in a left atrial cavity (1100) and a right atrial cavity (1104) of a heart. ) is a cross-sectional view of another embodiment of the invention. Ablation device (1110) may include a balloon (1112) that may be configured to be advanced and disposed within right atrial cavity (1104). For example, balloon (1112) may be placed in contact with the septum (1106) of the heart. Balloon (1112) may be filled with saline. Device (1110) may further include an electrode (1120) that may be advanced from the right atrial cavity (1104) through the balloon (1112) and septum (1106) and into the left atrial cavity (1100). For example, electrode (1120) may extend from balloon (1112), puncture septum (1106), and be advanced into left atrial cavity (1100). As electrode (1120) is advanced into left atrial cavity (1100), the distal portion of electrode (1120) may deform to form a predetermined shape. For example, the distal portion of electrode (1120) may include a non-linear shape, such as a circle, an ellipsoid, or any other geometry. In FIG. 11, the distal portion of the electrode (1120) forms a loop that may surround one or more ostia of the pulmonary vein (1102) in the left atrial cavity (1100). In other embodiments, the distal portion of electrode (1120) may be approximately the same in diameter as the ostium of pulmonary vein (1102).

Balloon (1112) and electrode (1120) may be electrically isolated from each other. For example, balloon (1112) and electrode (1120) may each include a respective insulated conductor (1114, 1122), each conductor (1114, 1122) having a voltage of at least 700 V across its thickness without dielectric breakdown. It has sufficient electrical insulation to maintain a potential difference of . In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 2000V, including all values and subranges therebetween, throughout the thickness therebetween without breakdown. . The conductor (1122) of the electrode (1120) may be insulated through the balloon (1112). In some embodiments, the saline in balloon (1112) and electrode (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. Device (1110) may receive a pulse waveform delivered to the ostium of pulmonary vein (1102). For example, a biphasic waveform may be applied to ablate tissue. The pulse waveform creates a strong electric field around the electrode (1120) and current is applied to the balloon (1112) via capacitive coupling to complete the circuit. In some embodiments, electrode (1120) may include high gauge wire and balloon (1112) may include wire mesh.

In another embodiment, electrode (1120) is advanced through pulmonary vein (1102) without advancing through balloon (1112) and/or septum (1106) to form one of the pulmonary vein ostia. One or more may be provided. Balloon (1112) and electrode (1120) may be configured as a cathode-anode pair and receive pulse waveforms in the same manner as discussed above.

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

For example, one or more return electrodes may be disposed on the skin of the patient (1200). In one embodiment, eight return electrodes (1230) may be positioned on the patient's back surrounding 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 appreciated that any of the ablation devices described herein can be used with one or more return electrodes (1230). In Figures 12A-12B, electrodes (1220) are disposed around the four ports (1210).

FIG. 12B shows an energized electrode (1220) creating an electric field (1240) around the ostium of a pulmonary vein (1210). Return electrode (1230) then receives the monophasic and/or biphasic waveform delivered by 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 electrode (eg, ablation electrode, return electrode) may include a biocompatible metal such as titanium, palladium, silver, platinum or a platinum alloy. For example, the electrode may preferably include platinum or a platinum alloy. Each electrode may include a conductive wire having sufficient electrical insulation to maintain a potential difference of at least 700V across its thickness without dielectric breakdown. In other embodiments, the insulation of each of the conductors may maintain a potential difference of about 200V to about 2500V throughout the thickness therebetween without breakdown, including all values and subranges therebetween. . The insulated lead runs to the proximal handle portion of the catheter, from where it can be connected to a suitable electrical connector. The catheter shaft may be made of a flexible polymeric material such as Teflon, nylon, Pebax, etc.

Methods Also described herein are methods for ablating tissue in a cardiac cavity using the systems and devices described above. The heart cavity may be the left atrial cavity and may include its associated pulmonary veins. Generally, the methods described herein include introducing a device and placing it in contact with one or more pulmonary vein ostium or cavity regions. A pulse waveform may be delivered to 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 include multiple levels of hierarchy to reduce total energy delivery. Tissue ablation performed in this manner may be delivered in synchronization with paced heartbeats and with less energy delivery to reduce damage to healthy tissue. It should be appreciated that any of the ablation devices described herein can be used to optionally ablate tissue using the methods discussed below.

In some embodiments, the ablation devices described herein may be used for focal ablation of cardiac features/structures identified as being responsible for an arrhythmia. For example, a cardiac electrophysiology diagnostic catheter (e.g., a mapping catheter) may be used to map cardiac structures, such as the rotor, that may later be ablated by focal ablation using any of the ablation devices described herein. Good too. Focal ablation may, for example, create a spot lesion that disables the rotor while protecting surrounding tissue. In some embodiments, one or more focal ablation lesions may be formed in combination with one or more box-shaped or linear lesions to treat cardiac arrhythmias. As a non-limiting example, in some embodiments, the system includes one or more mapping catheters, one or more ablation catheters useful for creating lesions by focal ablation (e.g., FIGS. 9D, 9E, 27A-27C). , 28, 29, 30, 31, 32) and one or more catheters useful for creating box-shaped and/or linear lesions (e.g., FIGS. 3-8, 9A-9C, 10-12). , 26A-26B).

FIG. 13 is a method (1300) for one embodiment of a tissue ablation process. In some embodiments, the voltage pulse waveforms described herein may be applied during the refractory period of the cardiac cycle to avoid disruption of the heart's sinus rhythm. The method (1300) includes the steps of: using a device (e.g., ablation device (110) and/or ablation device (200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, 2900, 3000, 3100); (1302) into the endocardial cavity of the left atrium. The device may be advanced and placed in contact with the pulmonary vein ostium (1304). For example, the electrodes of the ablation device may form a generally circular array of electrodes disposed in contact with the inner radial surface at the pulmonary vein ostium. In some embodiments, a pacing signal for cardiac stimulation of the heart may be generated (1306). A pacing signal may then be applied to the heart (1308). For example, the heart may be electrically paced by a cardiac stimulator to ensure pacing capture and establish periodicity and predictability of the cardiac cycle. One or more of atrial pacing and ventricular pacing may be applied. An indication of the pacing signal may be sent to the signal generator (1310). Thereafter, a time window during the refractory period of the cardiac cycle may be defined within which one or more voltage pulse waveforms may be delivered. In some embodiments, the refractory time window may follow the pacing signal. For example, a common refractory time window may be between an atrial refractory time window and a ventricular refractory time window.

A pulse waveform may be generated synchronously with the pacing signal (1312). For example, voltage pulse waveforms may be applied with a common refractory time window. In some embodiments, the pulse waveform may be generated with a time offset with respect to the display of the pacing signal. For example, the start of the refractory time window may be offset from the pacing signal by a time offset. The voltage pulse waveform(s) may be applied over a series of heartbeats over a corresponding common refractory 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 ostia of the patient's heart via one or more splines of the 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 isolation and ablation of pulmonary veins. For example, a first electrode of the group of electrodes may be configured as an anode and a second electrode of the group of electrodes may be configured as a cathode. These steps may be repeated for the desired number of ablated pulmonary vein ostia or cavity regions (eg, one, two, three, or four ostia).

In some embodiments, hierarchical voltage pulse waveforms with nested structures and time interval hierarchies described herein are useful for irreversible electroporation, providing control and selectivity in different tissue types. . FIG. 14 is a flowchart (1400) of another embodiment of a tissue ablation process. The method (1400) includes 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)). including introducing into the endocardial cavity of the left atrium (1402). The device may be advanced and placed in the pulmonary vein ostium (1404). In embodiments where the device may include first and second configurations (e.g., compact and expanded), the device is introduced in the first configuration and transitions to the second configuration to provide a The tissue may be contacted (1406) in the vicinity of the tissue. The device may include electrodes and may be configured in an anode-cathode subset (1408), as discussed in detail above. For example, a subset of the device's electrodes may be selected as anodes, while another subset of the device's electrodes may be selected as cathodes, and a voltage pulse waveform is applied between the anode and the cathode.

The pulse waveform may be generated by a signal generator (eg, signal generator 122) and may include multiple levels in a hierarchy (1410). A variety of hierarchical waveforms may be generated using the signal generators disclosed herein. For example, the pulse waveform may include a first level of a hierarchy of pulse waveforms that includes a first set of pulses. Each pulse has a pulse duration and a first time interval separating successive pulses. A second level of the hierarchy of pulse waveforms may include a first set of pulses as a second set of pulses. A second time interval may separate the first set of consecutive pulses. The second time interval may be at least three times the duration of the first time interval. A third level of the hierarchy of pulse waveforms may include a second set of pulses as a third set of pulses. A third time interval may separate the second set of consecutive pulses. The third time interval may be at least 30 times the duration of the second level time interval.

Although the examples herein identify separate monophasic and biphasic waveforms, it should be understood that combination waveforms can also be generated in which some portions of the waveform hierarchy are monophasic and other portions are biphasic. A voltage pulse waveform with a hierarchical structure may be applied across different anode-cathode subsets (optionally with a time delay). As discussed above, one or more of the waveforms applied across 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 FIGS. 13 and 14 may be combined and modified as desired.

15-18 illustrate implementation of a method for ablating tissue in the left atrial cavity of a heart as described above using an ablation device described herein (e.g., FIGS. 2-5). It depicts the form. FIG. 15 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial cavity of a heart using an ablation device (1500) that corresponds to the ablation device (210) depicted in FIG. It is. A left atrial cavity (1502) is depicted having four pulmonary veins (1504), and an ablation device (1500) sequentially ablates tissue to electrolyte one or more of the pulmonary veins (1504). It can be used for electrical insulation. As shown in FIG. 15, the ablation device (1500) is inserted into the left atrium using a transseptal approach (e.g., extending from the right atrial cavity through the septum to the left atrial cavity (1502)). It may be introduced into an endocardial cavity, such as cavity (1502). Ablation device (1500) may include a catheter (1510) and a guidewire (1520) slidable within the lumen of catheter (1510). The distal portion of catheter (1510) may include a set of electrodes (1512). The distal portion (1522) of the guidewire (1520) may be advanced into the left atrial cavity (1502) so as to be disposed near the ostium of the pulmonary vein (1504). Catheter (1510) may then be advanced over guidewire (1520) to position electrode (1512) near the ostium of pulmonary vein (1504). When electrode (1512) contacts the ostium of pulmonary vein (1504), electrode (1512) may be configured in an anode-cathode subset. The voltage pulse waveform generated by a signal generator (not shown) may be delivered to the tissue using electrodes (1512) in synchronization with the paced heartbeat and/or may include a waveform hierarchy. . After tissue ablation is completed in one of the pulmonary veins (1504), the catheter (1510) and guidewire (1520) are repositioned in another pulmonary vein (1504) to remove the remaining pulmonary vein (1504). Tissue may be ablated in one or more of the.

FIG. 16 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial cavity of a heart using an ablation device (1600) that corresponds to the ablation device (310) depicted in FIG. It is. A left atrial cavity (1602) is depicted having four pulmonary veins (1604), and an ablation device (1600) sequentially ablates tissue to electrically connect one or more of the pulmonary veins (1604). It can be used for electrical insulation. As shown in FIG. 16, an ablation device (1600) may be introduced into an endocardial cavity, such as a left atrial cavity (1602), using a transseptal approach. Ablation device (1600) may include a sheath (1610) and a catheter (1620) slidable within the lumen of sheath (1610). Distal portion (1622) of catheter (1620) may include a set of electrodes. The distal portion (1622) of the catheter (1620) may be advanced into the left atrial cavity (1602) so that the electrode is disposed near the ostium of the pulmonary vein (1604). When the electrode contacts the ostium of the pulmonary vein (1604), the electrode may be configured in an anode-cathode subset. The voltage pulse waveform generated by a signal generator (not shown) may be delivered to tissue using electrodes in synchronization with a paced heartbeat and/or may include a waveform hierarchy. After completing the tissue ablation in the pulmonary vein (1604), the catheter (1620) is repositioned in another pulmonary vein (1604) to ablate tissue in one or more of the remaining pulmonary veins (1604). You can.

FIG. 17 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial cavity of a heart using an ablation device corresponding to the ablation device (410) depicted in FIG. A left atrial cavity (1702) is depicted having four pulmonary veins (1704), and an ablation device (1700) ablate tissue to electrically isolate one or more of the pulmonary veins (1704). can be used to As shown in FIG. 17, an ablation device (1700) may be introduced into an endocardial cavity, such as a left atrial cavity (1702), using a transseptal approach. Ablation device (1700) may include a sheath (1710) and a plurality of catheters (1720, 1721) slidable within the lumen of sheath (1710). Each of the catheters (1720, 1721) may include a respective guidewire (1722, 1723) slidable within the catheter (1720, 1721). A distal portion of the guidewire (1722, 1723) may include an electrode configured to deliver a voltage pulse waveform. Each of the catheters (1720, 1721) and corresponding guidewires (1722, 1723) are advanced into the left atrial cavity (1702) so as to be disposed near the respective ostium of the pulmonary vein (1704). You can. When the guidewire electrodes (1722, 1723) contact the ostium of the pulmonary vein (1704), the electrodes may be configured in an anode-cathode subset. For example, the first guidewire (1722) may be configured as an anode and the second guidewire (1723) may be configured as a cathode. In this configuration, a voltage pulse waveform generated by a signal generator (not shown) may be delivered for ablation and simultaneous isolation of a pair of pulmonary veins (1704). Additionally or alternatively, the voltage pulse waveform may be delivered to tissue using electrodes in synchronization with a paced heartbeat and/or may include a waveform hierarchy. After completing tissue ablation in two of the pulmonary veins (1704), the catheter (1720, 1721) may be repositioned to ablate tissue in the remaining two pulmonary veins (1704). In some embodiments, sheath (1710) may include three or four catheters disposed in pulmonary veins (1704).

FIG. 18 is a cross-sectional view of an embodiment of a method for ablating tissue disposed in the left atrial cavity of a heart using an ablation device (1800) corresponding to the ablation device (500) depicted in FIG. It is. A left atrial cavity (1802) is depicted having four pulmonary veins (1804), and an ablation device (1800) sequentially ablates tissue to electrolyte one or more of the pulmonary veins (1804). can be used for electrical insulation. As shown in FIG. 18, an ablation device may be introduced into an endocardial cavity, such as the left atrial cavity (1802), using a transseptal approach. The ablation device may include a sheath (1820) and a catheter (1810) slidable within the lumen of the sheath (1820). The distal portion (1812) of the catheter (1810) may be flower-shaped, as discussed in detail with respect to FIG. A distal portion (1812) of catheter (1810) may be advanced into the left atrial cavity (1802) in a compact first configuration and disposed near the ostium of a pulmonary vein (1804). Distal portion (1812) of catheter (1810) then transitions to an expanded second configuration such that distal portion (1812) of catheter (1810) is positioned near the ostium of pulmonary vein (1804). As shown in FIG. 18, the distal portion may be formed into a flower shape as shown in FIG. When the electrode contacts the ostium of the pulmonary vein (1804), the electrode may be configured in an anode-cathode subset. The voltage pulse waveform generated by a signal generator (not shown) may be delivered to tissue using electrodes in synchronization with a paced heartbeat and/or may include a waveform hierarchy. After completing the tissue ablation in the pulmonary vein (1804), the catheter (1810) is repositioned in another pulmonary vein (1804) to ablate tissue in one or more of the remaining pulmonary veins (1804). You can.

Any of the methods described herein (e.g., FIGS. 13-18) may include a return electrode (e.g., FIGS. 12A and 18) configured to safely remove current from the patient during application of the voltage pulse waveform. The method may further include coupling one or more return electrodes (1230) (depicted in 12B) to the patient's back.

19A-20B depict embodiments of electrodes placed in contact with and electric fields generated therefrom around the ostium of a pulmonary vein. FIG. 19A is a schematic representation (1900) of an embodiment of a set of electrodes (1910) disposed at the ostium of a pulmonary vein (1904). The left atrial cavity (1902) may contain a blood pool (1906) and the pulmonary vein (1904) may contain a blood pool (1908). The left atrial cavity (1902) and pulmonary vein (1904) may each have a wall thickness of up to about 4 mm.

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

20A-20B are schematic representations (2000) of an embodiment of an electric field (2020) generated by a set of electrodes (2010) disposed at the ostium of a pulmonary vein (2002). FIG. 20A is a perspective view of the outer wall of the pulmonary vein (2002) and left atrial cavity (2004), while FIG. 20B is a cross-sectional view thereof. The shaded electric field (2020) indicates when the electric field (2020) exceeds the threshold when the adjacent electrode (2010) delivers energy (eg, voltage pulse waveform) to ablate tissue. For example, the electric field (2020) represents a potential difference of 1500V applied between adjacent electrodes (2010). Under this applied voltage, the electric field (2020) strength is at least above a threshold of 500 V/cm within the shaded capacitive electric field (2020) and may be sufficient to produce irreversible ablation in cardiac tissue. By aligning the pulse waveform across adjacent pairs of electrodes (2010) as detailed above, the pulmonary vein (2002) ostium is ablated to electrically direct the pulmonary vein (2002) from the left atrial cavity (2004). can be insulated.

Pulsed Waveforms Disclosed herein are methods, systems, and devices for selective and rapid application of pulsed electric fields/waveforms to achieve tissue ablation by irreversible electroporation. The pulse waveform(s) disclosed herein can be used in the systems (100) disclosed herein, in the devices (e.g., 200, 300, 400, 500, 600, 700, 800, 900, 1010, 1110, , 1500, 1600, 1700, 1800, 1910, 2010, 2900, 3000, 3100), and methods (e.g., 1300, 1400). Some embodiments are directed to pulsed high voltage waveforms with sequenced delivery schemes to deliver energy to tissue through a set of electrodes. In some embodiments, peak electric field values can be reduced and/or minimized while maintaining a sufficiently large electric field strength in the area where tissue ablation is desired. This also reduces the possibility of excessive tissue damage or electrical arcing and localized high temperatures. In some embodiments, a system useful for irreversible electroporation includes a signal generator and a processor that may be configured to apply a pulsed voltage waveform to a selected plurality of electrodes or a subset of electrodes of an ablation device. In some embodiments, the processor is configured to control the input such that a subset of anode-cathode pairs of the selected electrodes are sequentially triggered based on a predetermined sequence. In one embodiment, sequenced delivery can be triggered from a heart stimulator and/or pacing device. In some embodiments, the ablation pulse waveform is applied during the refractory period of the cardiac cycle to avoid disrupting the heart's sinus rhythm. One example method of doing this is to electrically pace the heart with a heart stimulator, ensure capture of the pacing to establish periodicity and predictability of the cardiac cycle, and then use this It is to define the time window within the refractory period within the periodic cycle.

In some embodiments, the pulsed voltage waveforms disclosed herein are hierarchical and have a nested structure. In some embodiments, the pulse waveform includes hierarchical groupings of pulses with different associated timescales. Additionally, the associated time scales and pulse widths, as well as the number of pulses and hierarchical groupings, may be selected to satisfy one or more of a set of Diophantine inequalities involving the frequency of cardiac pacing.

The pulse waveforms for electroporation energy delivery disclosed herein increase the safety, efficiency, and effectiveness of energy delivery by lowering the electric field threshold associated with irreversible electroporation and the delivered It can result in more effective ablation of the lesion with lower total energy. This may expand the field of clinical applications of electroporation, including therapeutic treatment of various cardiac arrhythmias.

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

FIG. 22 introduces a pulse waveform with a hierarchical structure of nested pulses. FIG. 22 shows pulses of pulse width/pulse duration w, such as pulses (2200), separated by a time interval (sometimes also referred to as a first time interval), such as duration t1 (2202), between successive pulses. shows a series of monophasic pulses, a number m1 of which are arranged to form a group of pulses (2210) (sometimes also referred to as a first set of pulses). Further, the waveform includes groups of such pulses (sometimes a second set of pulses) separated by a time interval (2212) (sometimes also referred to as a second time interval) of duration t2 between successive groups. ) has a number m2. A group of pulses, such as the m2 set marked by (2220) in FIG. 22, constitutes the next level of the hierarchy, which may be referred to as a third set of packets and/or pulses. Both the pulse width and the inter-pulse time interval t1 can range from microseconds to hundreds of microseconds, including all values and subranges in between. In some embodiments, time interval t2 may be at least three times greater than time interval t1. In some embodiments, the ratio t2/t1 can range from about 3 to about 300, including all values and subranges therebetween.

FIG. 23 further details the structure of the nested pulse hierarchy waveform. In this figure, a series of m1 pulses (individual pulses not shown) form a group of pulses (2300) (eg, a first set of pulses). A series of m2-like groups separated by an intergroup time interval (2310) of duration t2 (e.g., a second time interval) between one group and the next group are separated by a packet 132 (e.g., a pulse form a second set of A sequence of packets m3, such as packets separated by a time interval (2312) of duration t3 (e.g., a third time interval) between one packet and the next packet, is transferred to the next level in the hierarchy, in fig. (2320) forming a superpacket (e.g., the third set of pulses) labeled (2320). In some embodiments, time interval t3 may be at least about 30 times greater than time interval t2. In some embodiments, time interval t3 may be at least 50 times greater than time interval t2. In some embodiments, the ratio t3/t2 can range from about 30 to about 800, including all values and subranges therebetween. The amplitude of the individual voltage pulses within the pulse hierarchy can be anywhere 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 with a hierarchical structure. In the illustrated example, a biphasic pulse, such as (2400), has a positive voltage portion and a negative voltage portion to complete one cycle of the pulse. There is a time delay (2402) between adjacent cycles of duration t1 and n1 (e.g., a first time interval), and such cycles are associated with a group of pulses (2410) (e.g., a first set of pulses). ) to form. A series of n2 such groups separated by an inter-group time interval (2412) (e.g., a second time interval) of duration t2 between one group and the next is a packet (2420) (e.g. a second set of pulses). The figure also shows a second packet (2430) with a time delay (2432) (eg, a third time interval) of duration t3 between packets. As with monophasic pulses, higher level hierarchies can also be formed. The amplitude of each pulse or the voltage amplitude of a biphasic pulse may be anywhere from 500 volts to 7,000 volts or more, including all values and subranges therebetween. The pulse width/pulse duration may range from nanoseconds, or even sub-nanoseconds to tens of microseconds, and the delay t1 may range from zero to several microseconds. The inter-group time interval t2 may be at least 10 times larger than the pulse width. In some embodiments, time interval t3 may be at least about 20 times larger than time interval t2. In some embodiments, time interval t3 may be at least 50 times greater than time interval t2.

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

In some embodiments, hierarchical waveforms with nested structures and time interval hierarchies described herein are useful for irreversible electroporation ablation energy delivery and provide sufficient control and for application in different tissue types. Provides selectivity. A variety of hierarchical waveforms can be generated using a suitable pulse generator. Although the examples herein identify monophasic and biphasic waveforms separately for clarity, combination waveforms where some parts of the waveform hierarchy are monophasic and other parts biphasic are also possible. Please understand that it can be generated/implemented.

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

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

As used herein, the terms "about" and/or "approximately" when used in conjunction with a numerical value and/or range generally refer to the vicinity of the recited numerical value and/or range. or refer to a 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]" may mean within ±10% of 100 (eg, 90-110). The terms "about" and "approximately" may be used interchangeably.

Some embodiments described herein include non-transitory computer-readable media (also referred to as non-transitory processor-readable media) having instructions or computer code for performing various computer-implemented operations. related to computer storage products. A computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not itself contain transitory propagating signals (eg, propagating electromagnetic waves that carry information over a transmission medium such as space or a cable). Media and computer code (also referred to as code or algorithms) are designed and constructed for a specific purpose. Examples of non-transitory computer-readable media include hard disks, floppy disks, magnetic storage media such as magnetic tape, optical storage media such as compact discs/digital video discs (CD/DVD), and compact disc read-only memory (CD-DVD). ROM), holographic devices, magneto-optical storage media such as optical disks, carrier signal processing modules, application-specific integrated circuits (ASICs), programmable logic devices (PLDs), read-only memories (ROMs), and random access memories. hardware devices specifically configured to store and execute program code, such as (RAM) devices. Other embodiments described herein, for example, relate to computer program products that may include the instructions and/or computer code disclosed herein.

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

The specific examples and descriptions herein are exemplary in nature and embodiments may be made using the materials taught herein without departing from the scope of the invention, which is limited only by the appended claims. can be developed by a person skilled in the art based on the following.

Claims (34)

A device,
a first shaft defining a longitudinal axis and a lumen;
a second shaft disposed within the lumen and having a distal portion extending from a distal end of the first shaft;
a plurality of electrodes configured to generate an electric field to ablate tissue;
a set of splines, each spline of the set of splines comprising:
a set of electrodes from said plurality of electrodes formed on said spline, each set of electrodes comprising: (1) a distal electrode such that said set of splines includes a set of distal electrodes; ) a set of electrodes, including a proximal electrode, such that the set of splines includes a set of proximal electrodes;
a proximal end coupled to the distal end of the first shaft; and a distal end coupled to the distal end of the second shaft;
the set of splines is configured to transition to an expanded configuration, the set of splines defining a space therebetween, the space being larger in the expanded configuration of the set of splines; a set of splines,
an expandable member disposed distal to the distal end of the first shaft and within the space between the sets of splines, the member being expandable when the sets of splines are in the expanded configuration; an inflatable member configured to transition into a configuration. 2. The apparatus of claim 1 , wherein the expandable member in the expanded configuration substantially fills the space between the sets of splines in the expanded configuration. the expandable member from a collapsed configuration in which the outer surface of the expandable member is substantially parallel to the longitudinal axis; 2. The device of claim 1 , wherein the device is configured to transition to the expanded configuration in which it flexes. 2. The apparatus of claim 1 , wherein the set of splines is configured to transition to the expanded configuration in response to transitioning the expandable member to the expanded configuration. 2. A distal portion of each spline from the set of splines is angled at least about 70 degrees relative to the longitudinal axis when the set of splines is in the expanded configuration. equipment. 2. The expandable member in the expanded configuration forms an asymmetric shape with a distal portion of the expandable member having a larger outer diameter than a proximal portion of the expandable member. The device described. The device of claim 1 , wherein the expandable member in the expanded configuration defines a shape having an outer diameter at its greatest portion from about 6 mm to about 24 mm. When the set of splines is in the expanded configuration, at least one electrode from the set of distal electrodes contacts a tissue surface and forms a focal ablation lesion having a diameter of about 0.5 cm to about 2.5 cm. 7. The device of claim 1 , configured to form on the tissue surface. 2. The device of claim 1 , wherein at least a portion of the expandable member is formed from an insulating material. The device of claim 1 , wherein the expandable member includes a radiopaque portion. the first shaft is a first inner shaft, the second shaft is a second inner shaft, and the apparatus further comprises an outer shaft, the first inner shaft and the second inner shaft an inner shaft of the expandable member is configured to slide relative to the outer shaft, a proximal portion of the expandable member being coupled to a distal portion of the first inner shaft; The device of claim 1 , wherein a distal portion is coupled to a distal portion of the second inner shaft. The first inner shaft is configured to couple to a fluid source, thereby delivering fluid to the expandable member through the lumen of the first inner shaft to 12. The device of claim 11 , wherein the inflatable member is capable of transitioning into the expanded configuration. 12. The apparatus of claim 11 , wherein the set of splines is configured to transition to the expanded configuration in response to movement of the second inner shaft relative to the first inner shaft. 12. The device of claim 11 , wherein the expandable member defines a lumen and the second inner shaft extends through the lumen of the expandable member. the expandable member is configured in fluid communication with a fluid source, the fluid source delivering fluid to the expandable member to transition the expandable member to the expanded configuration; 2. The apparatus of claim 1 , wherein the apparatus is configured. The apparatus of claim 1 , wherein when the set of splines is in the expanded configuration, the set of splines extends outwardly from the distal end of the first shaft about 6 mm to about 24 mm. The apparatus of claim 1 , wherein the first shaft has an outer diameter of about 1.5 mm to about 6.0 mm. 2. The set of splines is configured to transition to the expanded configuration in response to movement of the second shaft relative to the first shaft along the longitudinal axis . The device described in . 2. The distal set of electrodes is angled from about 90 degrees to about 180 degrees relative to the proximal set of electrodes when the set of splines is in the expanded configuration. Device. 2. The device of claim 1, wherein the set of splines in the expanded configuration form an asymmetric shape with a distal portion having a larger outer diameter than that of the proximal portion. 2. The apparatus of claim 1 , wherein the distal end of the second shaft is up to about 6 mm away from each distal electrode from the set of distal electrodes. The device of claim 1 , wherein the distal end of the second shaft has a cross-sectional diameter of about 1 mm to about 5 mm. The device of claim 1 , wherein the distal portion of the device has an atraumatic shape. 2. The apparatus of claim 1 , wherein each electrode from the plurality of electrodes circumscribes a respective spline from the set of splines over which it is disposed. At least one distal electrode from the set of distal electrodes is configured to operate at a first polarity, and at least one proximal electrode from the set of proximal electrodes is configured to operate at a first polarity. 2. The apparatus of claim 1 , wherein are configured to operate with an opposite second polarity to collectively generate the electric field. The set of distal electrodes is configured to operate at a first polarity and the set of proximal electrodes is configured to operate at a second polarity opposite the first polarity. , the apparatus of claim 1 . The apparatus of claim 1 , wherein each electrode from the plurality of electrodes has a length of about 0.5 mm to about 5 mm. 2. The apparatus of claim 1 , wherein each electrode from the plurality of electrodes is independently addressable from other electrodes from the plurality of electrodes. Each spline from the set of splines includes a set of insulated conductors disposed therein, and each insulated conductor from the set of insulated conductors includes at least one insulated conductor from the set of electrodes formed on the spline. 2. The apparatus of claim 1, wherein the apparatus is electrically coupled to two electrodes and configured to maintain a potential of at least about 700V without breakdown of the corresponding insulation. The apparatus of claim 1 , wherein each electrode from the plurality of electrodes has a diameter of about 0.5 mm to about 3 mm. 2. The apparatus of claim 1 , wherein for each spline from the set of splines, the distal-most electrode is about 1 mm to about 40 mm away from the most proximal electrode. Each spline from the set of splines includes a plurality of proximal electrodes and at least one flexible member disposed between adjacent proximal electrodes from the plurality of proximal electrodes to increase flexibility of the spline. 2. The device of claim 1 , comprising: a flexible portion. The apparatus of claim 1 , wherein the set of proximal electrodes includes at least one coil electrode. the set of electrodes of each spline of the set of splines includes at least one electrode configured only for ablation and at least one electrode configured to receive an electrocardiogram (ECG) signal; The device according to claim 1 .