Systems, apparatuses, and methods for protecting electronic components from high power noise caused by high voltage pulses

Abstract

Systems, devices, and methods for electroporation ablation therapy are disclosed with protection devices for isolating isolation electronic circuitry, devices, and / or other components from a set of electrodes during a cardiac ablation procedure. A system can include a first set of electrodes disposable proximate to cardiac tissue of a heart and a second set of electrodes disposable in contact with patient anatomy. The system can also include a signal generator configured to generate a pulsed waveform, where the signal generator is coupled to the first set of electrodes and configured to repeatedly deliver the pulsed waveform to the first set of electrodes. The system can also include a protection device configured to selectively couple and decouple electronic devices from the second set of electrodes.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefit of U.S. Patent Application No. 16 / 689967, filed November 20, 2019, and is a continuation in part of that application, the entire disclosure of which is incorporated herein by reference. Technical Field

[0003] The embodiments described herein generally relate to medical devices for therapeutic electrical energy delivery, and more specifically, to systems, apparatus, and methods for protecting electronic components (e.g., sensitive equipment or circuitry) during a pulsed electric field ablation procedure. Background Technology

[0004] Applying a brief, ultrashort high-voltage pulse to tissue can generate a high electric field within the tissue, thereby creating a localized area of ​​tissue ablation through the biophysical mechanism of irreversible electroporation. In applications involving cardiac ablation, the high-voltage pulse can be applied synchronously with the subject's cardiac cycle. For example, the high-voltage pulse can be applied at specific times of the cardiac cycle (e.g., the refractory period of the heart chambers) to avoid the risk of inducing arrhythmias such as ventricular fibrillation. In some applications, to ensure synchronization of the pulsed field ablation pulse with the cardiac cycle, a cardiac stimulator can be used to pace or stimulate the heart chambers with a regular cycle of periodic pacing signals with a well-defined time period, thereby establishing the periodicity of the heart's electrocardiographic (ECG) activity. Other devices, such as sensing and / or mapping systems, monitoring equipment, or devices, can also be used to monitor the subject's cardiac cycle or record detailed cardiac activity. Cardiac stimulators can also be used in clinical procedures where pacing functionality is required to maintain periodic and regular electrical activity within the heart chambers for at least a portion of the procedure. Cardiac stimulators and other devices can use intracardiac devices (e.g., catheters) that can be appropriately positioned within one or more cardiac chambers to deliver or receive signals to or from cardiac or external surface patches or leads for recording patient surface ECGs. However, when these devices are used during pulsed electric field ablation, they may be exposed to high voltages. This exposure can result in large common-mode voltages and / or large (overall unbalanced) currents induced in the electrodes or leads of the intracardiac catheter relative to ground. Large unbalanced currents and / or voltages can cross frequency bands and disrupt the operation of cardiac stimulators and / or other devices, thereby interrupting pacing, sensing, mapping, magnetic sensor operation, and / or pulsed field ablation functions. Interruptions may occur due to hardware responses to voltage and current, or due to the equipment actively monitoring for abnormal signals from the patient for safety reasons.

[0005] Therefore, systems, apparatus and methods for solving this problem may be needed. Summary of the Invention

[0006] Systems, devices, and methods for protecting electronic components (e.g., circuits, devices, and / or other components) from exposure to induced currents and high voltages during a pulsed electric field ablation procedure are described herein.

[0007] In some embodiments, the ablation devices used in these systems can be deployed epicardially or endocardially in a cardiac application. The pulsed waveforms delivered by the ablation devices can include predetermined parameters or can be automatically generated by the signal generator.

[0008] In some embodiments, the system can include a first set of electrodes and a second set of electrodes. Generally, the second set of electrodes can be disposed proximate to cardiac tissue of a heart, or they can be part of a surface patch or similar external recording or monitoring device. The signal generator can be configured to generate a pulsed waveform. The signal generator can be coupled to the first set of electrodes and, in some embodiments, can be configured to repeatedly deliver the pulsed waveform to the first set of electrodes in synchronization with a set of cardiac cycles of the heart. In other embodiments, the signal generator can be configured to repeatedly deliver the pulsed waveform to the first set of electrodes without establishing synchronization with the cardiac cycles. In the latter case, it can still be useful to protect other electronic components, such as a cardiac stimulator (typically used for pacing functions), a mapping system, a magnetic tracking device, an imaging device, and the like laboratory equipment. The first set of electrodes can be configured to generate a pulsed electric field in response to the delivery of the pulsed waveform to ablate cardiac tissue. A protection device can be configured to selectively couple and decouple the electronic device to and from the second set of electrodes. A control element (e.g., a processor, a switch, a control signal) can be coupled to the protection device and configured to control the protection device to decouple the electronic device from the second set of electrodes during a time interval that begins before and ends after each delivery of the pulsed waveform to the first set of electrodes.

[0009] In some embodiments, an apparatus can include a first set of electrodes disposable proximate to cardiac tissue of a heart. A signal generator can be coupled to the first set of electrodes and configured to generate a pulsed waveform. A switching component can be coupled to the signal generator. The switching component can be configured to switch between a conductive state in which an electronic device is coupled to a second set of electrodes and a non-conductive state in which the electronic device is decoupled from the second set of electrodes. The second set of electrodes can be disposed proximate to the first set of electrodes, or generally in the heart or an anatomical chamber, or can be disposed on or proximate to an external surface of a subject. A processor can be coupled to the switching component. The processor can be configured to receive a trigger signal, each trigger signal associated with a cardiac cycle of the heart or an ablation output from the signal generator. In response to receiving each trigger signal, the processor can be configured to set the switching component to the non-conductive state such that the electronic device is decoupled from the second set of electrodes. The processor can be configured to, after setting the switching component to the non-conductive state, deliver the pulsed waveform from the signal generator to the first set of electrodes such that the first set of electrodes generates a pulsed electric field. The processor can be configured to, after delivering the pulsed waveform, set the switching component to the conductive state such that the electronic device is coupled to the second set of electrodes. In some embodiments, a control signal coupled to the switching component can set the state of the switch to perform the above functions.

[0010] In some embodiments, a method can include delivering a pacing signal to a heart via a second set of electrodes positioned proximate to cardiac tissue of the heart. After each pacing signal is delivered to the heart, a switching component selectively couplable to an electronic device can be set to a non-conductive state such that the second set of electrodes is decoupled from the electronic device. After the switching component is set to the non-conductive state, a pulsed waveform can be delivered to a first set of electrodes positioned proximate to the cardiac tissue of the heart such that the first set of electrodes generates a pulsed electric field for ablating the cardiac tissue. After the pulsed waveform is delivered, the switching component can be set to a conductive state such that the second set of electrodes is coupled to the electronic device. BRIEF DESCRIPTION OF DRAWINGS

[0011] Figure 1 is a schematic diagram of components of a signal generator and a cardiac stimulator disposed in a heart according to an embodiment.

[0012] Figure 2 is a schematic diagram of components of a signal generator and a cardiac stimulator disposed in a heart according to an embodiment with passive filtering for protection of the cardiac stimulator.

[0013] Figure 3A is a schematic diagram of a system for protecting electronic components from high voltage signals according to an embodiment.

[0014] Figure 3Bis a schematic of a system for protecting electronic components from high voltage signals according to embodiments, including electrodes that can be connected to externally and / or internally disposed electrodes of various medical equipment, including but not limited to cardiac stimulators, ECG recording systems, ECG or other patient data monitoring systems, electroanatomical mapping systems, device navigation / tracking systems, other monitoring systems and devices and combinations thereof, and the like.

[0015] Figure 4 is a schematic of a signal generator and components of one or more pieces of medical electronic equipment connected to electrodes disposed in the heart / cardiac anatomy or on the surface of a patient, with a protection device for protecting the medical electronic equipment, according to embodiments.

[0016] Figure 5 is a circuit diagram of a protection device for protecting electronic components from high voltage signals, according to embodiments.

[0017] Figure 6A is shown a method of protecting electronic components from high voltage signals, according to embodiments.

[0018] Figure 6B is shown a method for protecting electronic components from high voltage signals delivered asynchronously for ablation, according to embodiments.

[0019] Figure 7A is shown a time sequence of cardiac pacing signals, energy delivery, and device isolation, according to embodiments. Figure 7B is shown a time sequence of cardiac pacing signals, cardiac activity, energy delivery, and device isolation, according to embodiments.

[0020] Figure 8 is a schematic of a system for protecting electrical components from high voltage signals, according to embodiments.

[0021] Figure 9 is shown a time sequence of cardiac pacing signals, cardiac activity, energy delivery, and device isolation, according to embodiments.

[0022] Figure 10A-10E is a block diagram of an alternative arrangement of a protection device and high voltage generator, according to embodiments.

[0023] Figure 11 is a schematic of a protection device for controlling connections between electronic components operating in a high voltage exposure area, according to embodiments.

[0024] Figure 12 is a schematic of a system for protecting electronic components from high voltage signals, according to embodiments.

[0025] Figure 13Time series of cardiac pacing signal, cardiac activity, energy delivery, and device isolation according to an embodiment are shown.

[0026] Figure 14 is a schematic diagram of a protection device for controlling connections between electronic components operating in a high-voltage exposed area according to an embodiment.

[0027] Figure 15 is a schematic diagram of a protection device for controlling connections between electronic components operating in a high-voltage exposed area according to an embodiment.

[0028] Figure 16 is a schematic diagram of a protection device for controlling connections between electronic components operating in a high-voltage exposed area according to an embodiment.

[0029] Figure 17A and Figure 17B Time series of cardiac pacing signal, cardiac activity, energy delivery, and device isolation according to an embodiment are shown.

[0030] Figure 18 is a schematic diagram of a protection device for controlling connections between electronic components operating in a high-voltage exposed area according to an embodiment.

[0031] Figure 19 is a schematic diagram of a system for protecting electrical components from high-voltage signals according to an embodiment.

[0032] Figure 20A Time series of signal connections and energy delivery according to an embodiment are shown.

[0033] Figure 20B Time series of signal connections and energy delivery according to an embodiment are shown.

[0034] Figure 20C Time series of signal connections and energy delivery according to an embodiment are shown. DETAILED DESCRIPTION

[0035] Systems, devices, and methods for protecting electrical circuits from high power noise caused during pulsed electric field ablation are described herein. Pulsed electric field ablation uses ultra-short high voltage pulses to generate large electric fields in a desired region of interest to generate a local region of ablated tissue via irreversible electroporation. In certain applications, including cardiac applications, it can be desirable to generate pulses for pulsed electric field ablation in synchronization with the cardiac cycle. Synchronizing ablation energy delivery with the cardiac cycle can reduce the risk of inducing arrhythmias, such as atrial and / or ventricular fibrillation. One method of synchronized pulse delivery can be to pace or stimulate one or more heart chambers with a periodic pacing signal having a predefined time period. For example, a cardiac stimulator can be used to deliver pacing pulses to one or more heart chambers such that the patient's heart rhythm is synchronized with the pacing pulses.

[0036] In some embodiments, the pacing pulses can be delivered to a heart chamber via an intracardiac catheter that is properly positioned in the chamber. For example, Figure 1 A cardiac stimulator (28) is depicted that is coupled to an intracardiac catheter (30) that is properly positioned in a chamber of a heart (2). The catheter (30) can have one or more electrodes (32, 34) that are used to conduct pacing signals into the heart. In one embodiment, a pair of electrodes on the catheter (30) (e.g., the distal-most electrode (32) and the electrode (34) immediately proximal to the distal-most electrode (32)) can be used as a bipolar pair to deliver pacing signals, providing a forward current and return current path for the pacing signals. The heart chamber responds to the pacing pulses by timing its ECG signal generation (e.g., QRS waveform) to synchronize with the pacing pulses (referred to herein as "pacing capture"). Thus, a periodicity of the heart ECG activity can be established. Once this periodicity is established and confirmed by a physician (e.g., from displayed ECG activity, which is obtained, for example, for various recording or sensing electrodes), the delivery of the pulse field ablation pulses can be timed to begin in synchronization with the pacing pulses, including any predetermined offset, and the delivery can be completed within an

[0037] In cardiac applications, the pulse field ablation energy can be delivered through a custom ablation catheter that includes multiple electrodes. For example, as Figure 1As shown, a signal generator (22) (e.g., a pulsed field ablation pulse generator) can be coupled to an ablation catheter (10) having an electrode (12) suitably disposed in the heart (2). Delivery of the pulsed field ablation voltage pulses can be synchronized (with a suitable offset) with delivery of the pacing signals, as shown at (60). Since the pacing catheter (30) can also be located in the cardiac environment (e.g., in the same or a nearby chamber of the heart (2)), the high voltage pulse waveforms applied to the cardiac tissue can be coupled to the pacing catheter (30) and induce currents in the pacing catheter (30) and the device (e.g., the cardiac stimulator (28)) with which it is coupled.

[0038] During normal delivery of pacing pulses, the forward and return currents of the electrodes (32, 34) of the pacing catheter (30) are balanced (e.g., equal in magnitude, opposite in direction). However, the electrical coupling of the high voltage ablation energy with the pacing catheter (30) can induce large and overall unbalanced currents and / or common mode voltages in the leads of the pacing catheter (30). These large unbalanced currents and / or voltages can span the frequency band and can disrupt the operation of the pacing system or the cardiac stimulator (28) or other electronic devices coupled therewith. For example, the large voltage exposure of the pacing catheter (30) can exceed the common mode rejection of the cardiac stimulator (28) and result in system malfunction and / or stimulator reset (which can be pacing for synchronized delivery of ablation or pacing of a cardiac chamber for other medical reasons). The high voltage levels and high currents associated with the induced noise mean large power levels of the noise and can result in adverse effects.

[0039] This high power induced noise can be difficult to suppress, and thus, systems, devices, and methods to suppress induced currents in ancillary devices in pulsed electric field ablation energy delivery applications can be needed. In some embodiments, the currents induced by electric field ablation can be suppressed by implementing passive filtering systems, devices, and methods, as described in U.S. Application Serial No. 62 / 667,887, filed May 7, 2018, and entitled “SYSTEMS, APPARATUSES, AND METHODS FOR FILTERING HIGH VOLTAGE NOISE INDUCED BY PULSED ELECTRIC FIELD ABLATION,” the entirety of which is incorporated by reference herein. Figure 2An example of a system including passive filtering is depicted. A cardiac stimulator (28') can be coupled to a pacing catheter (30') including a plurality of electrodes (32', 34'). A signal generator (22') can be coupled to an ablation catheter (10') including a plurality of electrodes (12'). The electrodes (32', 34') of the pacing catheter (30') can be disposed in the heart (2') along with the electrodes (12') of the ablation catheter (10'). A filter element (50') can be coupled between the cardiac stimulator (28') and the pacing catheter (30'). The filter element (50') can passively filter signals from the pacing catheter (30') before they are received at the cardiac stimulator (28'), thereby suppressing certain induced currents. For example, at A, a long lead can pick up high voltage, while at B, after passive filtering, residual voltage and current can pass to the cardiac stimulator (28').

[0040] However, in some cases, it can be difficult to suppress coupled noise having large amplitude (e.g., large voltage spikes) using passive filtering techniques, and thus, malfunction and / or reset of equipment including cardiac stimulators can still occur. Commercial stimulators can also include different design parameters such that one level of protection can be adequate for one type of stimulator, but not for a second type of stimulator.

[0041] The systems, devices, and methods disclosed herein use active driving fast switching of the signal path to provide protection for sensitive electronics and ancillary equipment in pulsed electric field ablation applications. In some embodiments, a protection device can be coupled to a pacing device to actively and selectively electrically isolate the pacing device from other electronic components of an ablation system. In particular, the pacing device can be electrically isolated from the system during a predetermined period of time corresponding to the delivery of a pulsed waveform to tissue. Electrical connection can be reestablished to enable the pacing device to operate between periods of high voltage energy delivery. In some embodiments, the protection device can include a high speed switch coupled between the ablation system and the pacing device. Thus, system components such as cardiac stimulators can be protected from currents induced in the pacing device that can be caused by high voltage pulsed waveforms applied by the ablation device. Additionally or alternatively, the protection device can further provide passive circuit protection.

[0042] In some embodiments, sensitive electrical circuits or ancillary equipment (e.g., cardiac stimulators, electroanatomical mapping systems, ECG recording or monitoring systems, etc.) can be protected from the high-voltage pulsed field ablation signals present in the subject’s body by electrically isolating such circuits or equipment. Electrical isolation can be implemented manually by disconnecting conductors between the circuits or equipment, but in certain situations, a manual approach can not be feasible. For example, for certain types of equipment having a repetitive function, e.g., a cardiac stimulator intended to provide continuous pacing of the subject’s heart during pulsed field ablation, the physical connection between the equipment and the subject must remain intact. In these situations, it can be desirable to use electronic components to effectuate the physical disconnection. For example, electronic components can be used to provide bidirectional open circuit isolation between the subject and the protected ancillary equipment during certain time intervals in which high voltages are present, and to reestablish the connection during other time intervals to allow for the intended function of the equipment.

[0043] The term “electroporation” as used herein refers to the application of an electric field to a cell membrane to change the permeability of the cell membrane to the extracellular environment. The term “reversible electroporation” as used herein refers to the application of an electric field to a cell membrane to temporarily change the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing reversible electroporation can be observed to have temporary and / or intermittent formation of one or more pores in its cell membrane that close upon removal of the electric field. The term “irreversible electroporation” as used herein refers to the application of an electric field to a cell membrane to permanently change the permeability of the cell membrane to the extracellular environment. For example, a cell undergoing irreversible electroporation can be observed to have formation of one or more pores in its cell membrane that continue to exist upon removal of the electric field.

[0044] The pulsed waveforms for electroporation energy delivery disclosed herein can enhance the safety, efficiency, and effectiveness of energy delivery to tissue by reducing the electric field threshold associated with irreversible electroporation, resulting in more effective ablation lesions with reduced total energy delivered. In some embodiments, the voltage pulsed waveforms disclosed herein can be hierarchical and have a nested structure. For example, the pulsed waveforms can include hierarchical groupings of pulses with associated time scales. In some embodiments, the methods, systems, and devices disclosed herein can include one or more of the methods, systems, and devices described in International Application Serial No. PCT / US2019 / 014226, filed January 18, 2019, published July 25, 2019, and entitled “SYSTEMS, DEVICES AND METHODS FOR FOCAL ABLATION” as International Publication No. WO / 2019 / 143960, the entirety of which is hereby incorporated by reference herein.

[0045] Systems and devices

[0046] Disclosed herein are systems and devices for suppressing induced current associated with tissue ablation. Generally, the systems described herein for ablating tissue with high voltage pulse waveforms can include a cardiac stimulator for generating a cardiac pacing signal delivered to the heart by a pacing device. The cardiac pacing signal is used to synchronize delivery of a pulse waveform generated by a signal generator, and the pulse waveform is delivered using an ablation device having one or more electrodes. In another embodiment, ablation under high voltage pulse waveforms can be performed asynchronously (i.e., not synchronized with the cardiac stimulation). In these embodiments, it is also generally desirable to protect other electronic equipment, such as a cardiac stimulator, an electroanatomical mapping system, a device navigation / tracking system, an ECG recording or monitoring system, etc., which can be connected to the patient via device electrodes that can be placed in the patient’s body or outside the patient’s body, or attached to the patient’s surface (e.g., needle electrodes, pacing leads, etc.). Accordingly, the systems, methods, and implementations described in this disclosure are applicable to asynchronous ablation delivery. Further, as described herein, the systems and devices can be deployed epicardially and / or endocardially to treat atrial fibrillation. Voltage can be applied to selected subsets of electrodes, with independent subset selection for anode and cathode electrode selection.

[0047] Figure 3A An example system (1700) is shown that includes an integrated protection element (1750). The protection element (1750) can be positioned between electrical components (1730) and a target area (TA) (e.g., a patient’s heart). The protection element (1750) can be configured with a rated voltage corresponding to an expected exposure voltage on the patient side of a pulsed electric field ablation procedure, which can be several kilovolts. The protection element (1750) can function as an isolation component that is configured to transition to an open circuit configuration and return to a closed circuit configuration based on a control signal. The protection element (1750) is configured to respond quickly (e.g., to switch quickly between its open and closed configurations) to reduce the open circuit duty cycle, such that the protection element (1750) can electrically isolate certain electrical components (1730) (e.g., monitoring equipment or devices, a cardiac stimulator, etc.) for the duration of a high voltage exposure, but otherwise connect those electrical components to the target area (TA).

[0048] Examples of suitable protection elements (1750) include electromechanical relays (e.g., reed relays), solid state relays, and / or high voltage metal oxide semiconductor field effect transistor (MOSFET) devices. Reed relays can be less suitable for use in isolation component implementations because the action speed of such relays is slower than other types of protection devices, and are susceptible to damage / contact burnout if switched during exposure to high current. When the system (1700) is used with a protection element (1750) implemented as a reed relay, the coordination and timing of the system (1700) needs to be adjusted to account for the slower reaction time of such relays. A preferred implementation of the protection element (1750) is to use two back-to-back MOSETs with a common source terminal, as described below with reference to FIG. 18. Figure 5 Further described.

[0049] Figure 3B An example system (1800) is shown that includes an integrated protection element (1805). The protection element (1805) can be positioned between electrical components (1801) and patient anatomy (1808). The protection element (1805) can be configured with a rated voltage that corresponds to the expected exposure voltage on the patient side of a pulsed electric field ablation procedure, which can be several kilovolts. Such high voltage exposure can occur via device electrodes or sensors (1819) that are internally placed (relative to the patient) or electrodes or sensors (1821) that are externally placed / mounted (on the surface of the patient). Such electrodes or sensors can typically be connected to various medical electronic equipment, including but not limited to electroanatomical mapping systems, device navigation / tracking systems, ECG recording / monitoring systems, and combinations thereof, and similar equipment that can typically be used in a clinical laboratory or operating room. In embodiments described herein, the sensors can be general purpose sensors, including specialized electromagnetic sensors, electrodes for receiving voltage signals generated by a position tracking system, electrodes for monitoring natural heart electrical activity, and more generally sensors for sensing various types of electrical signals. The protection element (1805) can be used as an isolation component that is configured to transition to an open circuit configuration and return to a closed circuit configuration based on a control signal (1812). The protection element (1805) is configured to respond quickly (e.g., to quickly switch between its open and closed configurations) to reduce the open circuit duty cycle, such that the protection element (1805) can electrically isolate electrical components (1801) such as those described above from the patient anatomy (1808) for the duration of the high voltage exposure, but otherwise connect these electrical components to the patient anatomy.

[0050] Examples of suitable protection elements (1805) include electromechanical relays (e.g., reed relays), solid state relays, and / or high voltage metal oxide semiconductor field effect transistor (MOSFET) devices. Reed relays can be less suitable for use in isolated component implementations because the action speed of such relays is slower than other types of protection devices, and are susceptible to damage / contact burnout if switched during exposure to high current. When the system (1800) is used with a protection element (1805) implemented as a reed relay, the coordination and timing of the system (1800) needs to be adjusted to account for the slower reaction time of such relays. In some embodiments, the protection element (1805) can include two back-to-back MOSFETs with a common source terminal, as described below with reference to FIG. 2. Figure 5 Further described.

[0051] Figure 4 is a schematic diagram of an electroporation system disposed in a heart (202) of a patient (200). The electroporation system can include an ablation device (210), a signal generator (222), an electrical component (e.g., medical electronic equipment or device) (228), a catheter device (230), and a protection device (e.g., protection circuit) (250). In some embodiments, the electrical component (228) can be implemented as a cardiac pacing system. The signal generator (222) can be coupled to the ablation device (210) and configured to receive a pacing / synchronization signal (260) generated by the cardiac pacing system. The signal generator (222) can be configured to generate an ablation pulse waveform delivered to tissue by electrodes (212) of the ablation device (210). In some embodiments, the catheter device (230), implemented as a pacing device (230), can be configured to pace the heart and measure heart activity using respective pacing electrodes (232) and signal electrodes (234). In some embodiments, the electrical component (228) can be implemented as a monitoring equipment or device, which can be coupled to one or more sensors (e.g., electrodes) (232, 234, 271) for measuring physiological data of the patient. In some embodiments, the sensors (e.g., electrodes (271)) can be placed externally on the surface of the patient. The protection device (250) can be coupled between the electrical component (228) and the electrodes (232, 234) or electrodes (271) of the catheter device (230). In some embodiments, the protection device (250) is configured to synchronize the electrical isolation of the pacing device (230) with the delivery of ablation energy by the ablation device (210).

[0052] In some embodiments, a distal portion of an ablation device (210) can be introduced into an endocardial space of a heart (202) (e.g., a left atrium), for example, via a transseptal puncture through an atrial septum. The distal end of the ablation device (210) can include a set of electrodes (212) configured to deliver ablation energy (e.g., pulsed electric field energy) to tissue. For example, the ablation device (210) can be placed proximate to an inner radial surface of a lumen (e.g., one or more pulmonary vein ostia) (not shown) to deliver a pulsed waveform to ablate tissue. In some embodiments, the electrodes (212) of the ablation device (216) can be a set of independently addressable electrodes. Each electrode can include an insulated electrical lead configured to maintain a voltage potential of at least about 700 V without dielectric breakdown of its respective insulating layer. In some embodiments, the insulation on each electrical lead can maintain a potential difference of between about 200 V and about 3000 V across its thickness without dielectric breakdown. In some embodiments, the set of electrodes can include a plurality of electrodes. The plurality of electrodes can be grouped into one or more anode-cathode subsets, 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, a subset including one anode and two cathodes, a subset including three anodes and one cathode, a subset including three anodes and two cathodes, and / or the like.

[0053] The signal generator (222) can be configured to generate an ablation pulsed waveform for irreversible electroporation of tissue, such as, for example, a pulmonary vein ostium. For example, the signal generator (222) can be a voltage pulsed waveform generator and deliver a pulsed waveform to the ablation device (210).

[0054] In some embodiments, the signal generator (222) is configured to generate an ablation pulsed waveform in synchronization with an indication of a pacing signal (e.g., within a common refractory period window). For example, in some embodiments, the common refractory period window can begin immediately after a ventricular pacing signal (or after a very small delay) and continue for a duration of about 250 milliseconds (ms) or less thereafter. In such embodiments, an entire pulsed waveform can be delivered within this duration.

[0055] A protection device (250) can be coupled between the electrical component (228) and the catheter device (230). As described in greater detail herein, a control signal (also referred to herein as a protection signal) can be generated to synchronize operation of the protection device (250) with generation of the pulse waveform by the signal generator (222). The protection device (250) can be configured to receive the control signal to control a state of an electrical connection between the catheter device (230) and the electrical component (228). For example, the protection device (250) can be configured to form an open circuit between the electrical component (228) and the catheter device (230) at least during delivery of ablation energy by the ablation device (210). In addition to this, the protection device (250) can be configured to electrically couple the pacing device (230) with the electrical component (228). In some embodiments, the protection device (250) can be configured to provide bidirectional open circuit isolation during high-energy ablation energy delivery. In some embodiments, the protection device (250) can be formed separately from the electrical component (228) and / or the catheter device (230), and in other embodiments, the protection device (250) can be integrated into one or more of the electrical component (228) and / or the catheter device (230). In some embodiments, the protection device (250) can include one or more of an internal power source (e.g., a battery) and a power connector coupled to an external power source (e.g., a medical grade power supply, a wall outlet). The internal power source can reduce ground noise injection.

[0056] In some embodiments, the electrical component (228), the protection device (250), and / or the signal generator (220) can be in communication with one another, e.g., for coordinating timing of pulse waveform delivery, pacing signal delivery, and / or protection device control signal delivery. In some embodiments, the protection device (250) and / or the signal generator (220) can be in communication with one another, e.g., for coordinating timing of pulse waveform delivery, pacing signal delivery, and / or protection device control signal delivery. In some embodiments, the protection device (250) can be integrated with the signal generator (222) in a single console.

[0057] In some embodiments, the electrical component (228), protection device (250), and / or signal generator (220) can communicate with other devices (not shown) via, for example, one or more networks, each of which can be any type of network. Wireless networks can refer to any type of digital network that is not connected by any type of wire. However, wireless networks can connect to wired networks in order to interface with the Internet, other carrier voice and data networks, business networks, and personal networks. Wired networks are typically carried over copper twisted pair wires, coaxial cables, or fiber optic cables. There are many different types of wired networks, including wide area networks (WANs), metropolitan area networks (MANs), local area networks (LANs), campus area networks (CANs), global area networks (GANs) like the Internet, and virtual private networks (VPNs). Hereinafter, networks refer to any combination of wireless, wired, public, and private data networks, typically interconnected over the Internet, to provide a unified network and information access solution. The system (100) can also include one or more output devices, such as a display, an audio device, a touchscreen, combinations thereof, and the like.

[0058] The electrical component (228), protection device (250), and / or signal generator (220) can include one or more processors, which can be any suitable processing device configured to run and / or execute instructions or code. The processors can be, for example, general- purpose processors, field programmable gate arrays (FPGAs), application specific integrated circuits (ASICs), digital signal processors (DSPs), and / or the like. The processors can be configured to run and / or execute application processes and / or other modules, processes, and / or functions associated with the system and / or with networks (not shown) related thereto. The underlying device technologies can be provided in a number of component types, e.g., metal-oxide-semiconductor field-effect transistor (MOSFET) technologies like complementary metal-oxide-semiconductor (CMOS), bipolar technologies like emitter coupled logic (ECL), polymer technologies (e.g., silicon-conjugated polymer and metal-conjugated polymer metal structures), mixed analog and digital, and / or the like.

[0059] The electrical component (228), protection device (250), and / or signal generator (220) can include one or more memories or storage devices, e.g., which can be random access memory (RAM), storage buffers, hard drives, erasable programmable read only memories (EPROMs), electrically erasable read only memories (EEPROMs), read only memories (ROM), flash memories, and / or the like. The memories can store instructions to cause the processors of any of the electrical component (228), protection device (250), and / or signal generator (220) to perform modules, processes, and / or functions, such as pulse waveform generation, isolation / protection, and / or cardiac pacing.

[0060] While Figure 4 While the system is depicted as including electrical components (228) separate from the signal generator (220), in some embodiments, one or more of the electrical components (228) can form part of and / or be integrated into the signal generator (222). In some embodiments, one or more of the electrodes (212, 232, 234) can be used as a sensing electrode.

[0061] Figure 5 is a circuit diagram of a protection device (300) including a first MOSFET (310) and a second MOSFET (320). The MOSFETs (310, 320) can be arranged as back-to-back MOSFETs with a common source terminal, such that the body diodes of the MOSFETs (310, 320) are in opposite directions. This arrangement can provide bidirectional isolation with precise timing control. The MOSFETs (310, 320) can be driven by isolated gate drive circuits (330, 340). Specifically, the first MOSFET (310) can be coupled to a first gate driver (330), and the second MOSFET (320) can be coupled to a second gate driver (340). The first and second gate drivers (330, 340) can be coupled to a coupling (350) (e.g., an isolation / opto-coupling) that can receive a control signal 352. The protection device (300) can be configured to reduce high voltage coupling of a connected device. For example, the protection device (300) can be configured to withstand voltages up to about 3000V delivered by an ablation device. The protection device (300) can be configured to transition between a closed circuit configuration and an open circuit configuration based on a received protection signal (352) (e.g., control signal), such that the protection device (300) is in the open circuit configuration for the duration of high voltage ablation energy delivery, and in the closed circuit configuration at other times, to, for example, enable delivery of pacing signals.

[0062] The protection devices described herein can be single piece equipment, or can be integrated into auxiliary equipment or a pulsed field ablation stimulator. Figure 10A-10E is a block diagram of a set of systems including a protection device that is both integrated with and separate from other system components. In Figure 10A-10E , the protection device can include any other protection device described herein (e.g., Figure 3A , Figure 3B , Figure 4 , Figure 5 , Figure 8 , Figure 11 , Figure 12 , Figure 14-16 , Figure 18 and Figure 19components of the protection device shown. Figure 10A A signal generator (800) (e.g., for pulsed electric field ablation) is shown that includes a protection device (810) integrated therewith. For example, one or more of the signal generator (800), the protection device (810), electrical components (e.g., electrical components (228) including, for example, monitoring equipment, cardiac stimulators, etc.), and signal analyzers (e.g., signal detectors (670)) can be integrated into a single enclosure (e.g., a housing, a signal generator console). This can protect sensitive electronic circuitry within the same enclosure from high voltage noise. External electrical components (e.g., auxiliary equipment) can be similarly protected by coupling such components to the protection device (810) at a point further downstream from the high voltage exposure point (e.g., the patient). For example, external equipment can be protected by routing signals received by the system through the protection device (810) before those signals reach the patient, such that the protection device (810) can blank its interval timing to coincide with times of potential high voltage exposure. With the integrated configuration shown, the signal generator (800) can provide a digital “blanking” signal (e.g., a control signal) to the protection device to indicate the time needed for isolation (e.g., protection) of sensitive electronic components. The “blanking” signal can be configured to control the protection device to electrically isolate a set of electronic components internal and external to the signal generator (800), thereby providing coordinated and robust protection. Figure 10A

[0063] In some embodiments, a manually operated switch can be configured as a protection device to protect electronic components or equipment from ablation-induced noise.

[0064] In some embodiments, the signal generator and the protection device can be a single piece of equipment (e.g., formed in different enclosures). In such embodiments, control signals can be communicated between the signal generator and the protection device via wired or wireless communication; however, wired control signals can be more robust and avoid the latency risks typically associated with wireless communication. For external or separate protection devices, the protection device can be battery powered or wall powered, for example, using medical grade isolation, but battery powered protection devices can be more desirable to reduce ground noise injected from the isolated wall power supply to the patient. Figure 10B A signal generator (800) is shown coupled to a protection device (810) via a wired connection (820) (e.g., a power / data cable). Figure 10C A signal generator (800) is shown coupled to a protection device (810) via a wireless connection. For example, the protection device (810) can include a wireless transceiver (830) configured to receive control signals (e.g., communicated from the signal generator (800)).

[0065] ​In embodiments where the protection device is implemented independent of the signal generator (e.g., a pulsed field ablation generator), the protection device needs a mechanism to synchronize with the delivery of high voltage pulses so that certain electronic components can be effectively isolated during such delivery. In some embodiments, based on one or more of a timing trigger pulse from the stimulator, a stimulation pulse sensing (e.g., for cardiac capture), a measured cardiac activity (e.g., R-wave detection and / or high voltage sensing (e.g., fast application of isolation upon detection of a high voltage spike on the patient side)), the protection signal can synchronize the electrical isolation of certain electronic components (e.g., the stimulator) with the delivery of ablation energy to tissue. Reference is made below to Figure 12 This is further described. Figure 10D and Figure 10E Two configurations are shown that implement synchronization. Such configurations are similar to those described with reference to Figure 7A-9 described with reference to Figure 10D A signal generator (800) and a protection device (810) are shown, both configured to receive signals from a cardiac stimulator (840). The cardiac stimulator (840) can be configured to synchronize the delivery of ablation energy by the signal generator (800) and the electrical isolation by the protection device (810) by outputting respective signals (e.g., trigger signals or control signals) to the signal generator (800) and the protection device (810). Figure 10E A signal generator (800) and a protection device (810) are shown, both coupled to a patient (850) and configured to operate synchronously with each other based on measured data (e.g., cardiac stimulation or pacing pulses, R-wave detection, high voltage detection). When synchronization is implemented based on stimulation pulse detection, a sufficiently high predetermined threshold (e.g., 5V) can be set to reduce the likelihood of false positive sensing that can undesirably lead to an increased occurrence of the protected electrical components being isolated and disconnected from the patient.

[0066] The protection devices described herein can be configured to isolate multiple electrical components (e.g., sensitive circuits or equipment) from high voltage and induced current. Figure 11 A block diagram of a system (910) coupled to a patient (900) is shown. One or more devices of the system (910) (e.g., pacing devices, catheters, needles, probes, electrodes, etc.) can be coupled to the patient (900) and can be susceptible to induced current from high voltage ablation energy delivery. Each device of the system (910) can be coupled to a protection device (920) configured to selectively electrically isolate electrical components disposed downstream of the protection device (920) from those portions of the devices disposed in the heart and exposed to high voltage. The protection device (920) can include any other protection device described herein (e.g., Figure 3A , Figure 3B ,Figure 4 、 Figure 5 、 Figure 8 、 Figure 10A-10E 、 Figure 12 、 Figure 14-16 、 Figure 18 and Figure 19 The protection device (920) can be configured to provide electrical isolation for one or more electronic components (e.g., the components of the ablation device (910), the components of the signal generator (922), the components of the cardiac stimulator (928), the components of the pacing device (930), and / or the components of the protection device (920) as shown in the protection devices shown in Figure 5 .

[0067] In some embodiments, for example, where the protection device is implemented as a stand-alone system without signals being communicated from a high-voltage pulse generator (e.g., for use in pulse field ablation), the operation of the protection device can be synchronized based on stimulation pulse sensing, trigger pulses from a cardiac stimulator, R-wave sensing, or high-voltage sensing. Figure 12 is a schematic diagram of an electroporation system disposed in a heart (1002) of a patient (1000) including an ablation device (1010), a signal generator (1022), a cardiac stimulator (1028), a pacing device (1030), and a protection device (1050). The signal generator (1022) can be coupled to the ablation device (1010). The signal generator (1022) can be configured to generate a pulse waveform delivered to electrodes (1012) of the ablation device (1010) to generate a pulsed electric field for ablation. The pacing device (1030) can be configured to pace the heart (1002) using pacing electrodes (1032, 1034) and / or measure cardiac activity (e.g., an electrocardiogram) of the heart (1002) using one or more electrodes (e.g., electrodes (1032, 1034) or other electrodes (not shown)). The protection device (1050) can be coupled between the cardiac stimulator (1028) and the pacing device (1030). The protection device (1050) can include components similar in structure and / or function to the components of any other protection device described herein (e.g., the protection devices shown in Figure 3A 、 Figure 3B 、 Figure 4 、 Figure 5 、 Figure 8 、 Figure 10A-10E 、 Figure 11 、 Figure 14-16 、 Figure 18 and Figure 19 The protection device (920) can be configured to provide electrical isolation for one or more electronic components (e.g., the components of the ablation device (910), the components of the signal generator (922), the components of the cardiac stimulator (928), the components of the pacing device (930), and / or the components of the protection device (920) as shown in the protection devices shown in

[0068] In some embodiments, the protection device (1050) can be configured to synchronize the electrical isolation of the cardiac stimulator (1028) with the pulse waveform delivery of the ablation device (1010) based on one or more signals. The protection device (1050) can be synchronized based on the same signal or signal combination as the signal generator (1022), or independently based on one or more of the stimulation signals (1060) from the cardiac stimulator (1028) (which can also be sent to the signal generator (1022)), the measurement data (e.g., stimulation pulse detection signal (1070), R-wave detection signal (1090), and high voltage detection signal (1092)), and the signal generator signals (1080). In alternative embodiments, the protection device (1050) and the signal generator (1022) can be activated based on different signals or different signal combinations. For example, the protection device (1050) can be controlled based on the cardiac pacing signals (1060), and the pulse waveform delivery can be based on a detected R-wave signal (1090). In embodiments using stimulation pulse sensing, the sensing can be implemented with a predetermined threshold (e.g., about 5 V) in order to reduce false positives that can increase the number of disconnections between the cardiac stimulator (1028) and / or other protected electronic components and the patient (1000). To provide another layer of safety, the protection device for any external electronic components can be configured to provide a low impedance connection between the protected electronic components and the patient when not powered. Figure 14 is a block diagram of electrical components (1210) (e.g., including sensitive equipment or circuitry) coupled to a patient (1220) via a protection device (1200). One or more electrical components (1210) (e.g., monitoring equipment, a cardiac stimulator, any of those described herein) can be coupled to the patient (1220) and can be susceptible to induced current from high voltage ablation energy delivery. Each of the electrical components (1210) can be coupled to the protection device (1200) to selectively electrically isolate those components from devices disposed in the heart of the patient (1220). The protection device (1200) can include components similar in structure and / or function to any other protection device described herein (e.g., the protection device of Figure 3A 、 Figure 3B 、 Figure 4 、 Figure 5 、 Figure 8 、 Figure 10A-10E 、 Figure 11 、 Figure 12 、 Figure 15 、 Figure 16 、 Figure 18 and Figure 19 .

[0069] The protection device (1200) can be configured such that when the protection device (1200) is not powered on, the electrical components (1210) are electrically coupled (e.g., through a low impedance connection) to the patient (1220). This safety feature allows the patient connection by default and allows the electrical components (1210) to operate even when the protection device (1200) is powered off. For example, a cardiac stimulator (e.g., cardiac stimulator (28)) included in the electrical components (1210) can provide pacing to the patient (1220) when the protection device (1200) is powered off.

[0070] The first signal (1202) (e.g., a control signal) can be configured to control the protection device (1200) and provide electrical isolation through the first switch (1206) described herein. The second signal (1204) (e.g., a power signal) can be configured to control the protection device (1200) through the second switch (1208). In some embodiments, the second switch (1208) can include a relay (e.g., a reed switch or a solid state type switch) configured to be in parallel with the first switch (1206) for isolation / blanking and configured to be open when the protection device (1200) is powered on. In some embodiments, the first switch (1206) can include an electromechanical relay (e.g., a reed relay), a solid state relay, and / or a MOSFET device. For example, the first switch (1206) can include two back-to-back MOSFETs with a common source terminal as shown in Figure 5 The second path provided via the second switch (1208) can generally be set to a closed state to provide a low impedance connection between the electrical components (1210) and the patient (1220).

[0071] Figure 15 Another example embodiment of a system including a protection device (1300) is provided. Specifically, Figure 15 is a block diagram of electrical components (1310) coupled to a patient (1320) via a protection device (1300). One or more electrical components (1310) (e.g., monitoring equipment, cardiac stimulators) can be coupled to the patient (1320) via the protection device (1300) configured to selectively electrically isolate those electrical components (1310) from devices disposed in the heart of the patient (1320), e.g., via a first signal (1302). The protection device (1300) can include any other protection device described herein that is structurally and / or functionally similar (e.g., Figure 3A 、 Figure 3B 、 Figure 4 、 Figure 5 、 Figure 8 、 Figure 10A-10E 、 Figure 11 、 Figure 12 ,Figure 14 , Figure 16 , Figure 18 and Figure 19 Components of the protective device shown. To be consistent with... Figure 14 In a similar manner, when the protection device (1300) is not energized, the electrical component (1310) can be electrically coupled to the patient (1320) via a normally closed switch configured in parallel with the blanking / protection component. When power is supplied to the protection device (1300), a signal (1304) corresponding to the power supply can open the normally closed switch. In some embodiments, the protection device (1300) may include additional circuit protection and filtering functions configured to reduce the peak-to-peak voltage of high slew rate and / or high voltage signals even when the protection device (1300) is not energized and / or the electrical component (1310) is not isolated from the patient (1320). The protection device (1300) may include a passive filtering device (1330) (as referenced above). Figure 2 The methods, systems, and apparatus disclosed herein may include one or more of the following: common-mode protection device (1340) and differential / high-voltage protection device (1350) (which may include one or more common-mode and differential-mode chokes using ferrite / magnetic materials), inductor- and capacitor-based filters, and differential high-voltage and differential clamping components (which include one or more of transient voltage suppression (TVS) diodes / transient diodes, gas discharge tubes, and thyristors). In some embodiments, the methods, systems, and apparatus disclosed herein may include one or more of the methods, systems, and apparatus described in U.S. Application Serial No. 62 / 667887, filed May 7, 2018, entitled “SYSTEMS, APPARATUSES, AND METHODS FORFILTERING HIGH VOLTAGE NOISE INDUCED BY PULSED ELECTRIC FIELD ABLATION,” the entire contents of which are incorporated herein by reference.

[0072] In some cardiac stimulators (e.g., electrophysiology laboratory stimulator systems), a high impedance in the patient connection can be monitored to alert the user to disconnect. To prevent unwanted warnings during the use of protective devices (e.g., during blanking intervals), a fixed, known impedance can be supplied to the stimulator connection (e.g., through a fixed resistor with a value within the stimulator's expected range, such as, for example, 1 kiloohm). Figure 16is a block diagram of electrical components (1410) coupled to a patient (1420). One or more electrical components (1410) (e.g., monitoring equipment, cardiac stimulator) can be coupled to a patient (1420) via a protection device (1400) configured to selectively electrically isolate these components from devices disposed in the heart of the patient (1420) via a signal (1402). The protection device (1400) can include components similar in structure and / or function to those of any other protection device described herein (e.g., Figure 3A 、 Figure 3B 、 Figure 4 、 Figure 5 、 Figure 8 、 Figure 10A-10E 、 Figure 11 、 Figure 12 、 Figure 14 、 Figure 15 、 Figure 18 and Figure 19 .

[0073] A cardiac stimulator included in the electrical components (1410) can continuously monitor the electrical connection to the patient (1420) and generate a disconnection signal (e.g., alert the user) upon detecting a disconnection (e.g., high impedance). In some embodiments, to suppress the system (1410) from generating a disconnection signal during the protection interval of the protection device (1400), the protection device (1400) can provide a predetermined impedance (1440) (e.g., between about 100 ohms to about 10 kilo-ohms) to the cardiac stimulator, which is within a range that the stimulator expects to correspond to normal operation. For example, the protection device (1400) operating during the protection interval can send a signal to close a switch in series with a resistor (1440), which can then provide a fixed impedance value. The fast transition between the “patient connection” and the “open circuit with fixed resistor load” can be fast enough to prevent the cardiac stimulator from issuing any warnings or alarms. In some embodiments, it can be useful to first connect a load to the electrical component for a short interval of time (e.g., about 1 us to 100 us) before disconnecting the patient connection. If this is done, the electrical component will have a non-trivial amount of time to appear open circuit. Then, the patient connection can be connected before (e.g., immediately before) the resistive load is disconnected. Another implementation optimization is to provide a “load resistor” on both sides (the patient side as well) so as to have symmetry in the implementation, and it can be inserted into the protection device in any way.

[0074] In some cases, using a protection device as implemented in Figure 16 may introduce switching artifacts and short voltage spikes on the patient. Figure 17A and Figure 17Bis a schematic of a time series of cardiac stimulation (1510), electrocardiogram (1520), pulse field ablation delivery (1530), and protection interval (1540) channels, where a switch artifact (1526) can occur when the protection interval ends. Figure 17A A single cardiac cycle is shown, and Figure 17B A plurality of cardiac cycles is shown, as described in more detail herein. The stimulation or pacing signal (1510) can be periodic and can include a rectangular pulse with a width between about 0.1 ms to about 100 ms. In some embodiments, the pacing pulse (1512) can be delivered using any of the pacing devices described herein (e.g., pacing devices (230, 630, 1030)). The pacing pulse (1512) can correspond to one or more of ventricular and atrial cardiac pacing. In response to the pacing pulse (1512), the cardiac cycle of the heart can be synchronized with the pacing pulse (1512). For example, Figure 17A and Figure 17B the QRS waveform (1522) in

[0075] In some embodiments, the pulse waveform (1532) and the protection interval (1542) can be synchronized with one or more of the pacing signal (1512) and the cardiac cycle (e.g., via R-wave detection), as described in the above embodiments. For example, the pulse waveform (1532) can have a first length, and the protection interval (1542) can have a second length that is at least as long as the first length. The pulse waveform (1532) can be delivered after a first delay (1534) from a trailing edge (1514) of the cardiac pacing pulse (1512). The first delay (1534) can be a predetermined value. For example, the first delay (1534) can be between about 1 ms and about 20 ms. Likewise, the protection interval (1542) can be synchronized with the cardiac pacing pulse (1512) after a second delay (1544). In this way, the cardiac pacing signal (1512) can be configured to trigger the pulse waveform (1532) and the protection interval (1542).

[0076] In embodiments including a protection device as implemented in Figure 16 In embodiments including a protection device as implemented in Figure 17BEmbodiments are shown in which a protection interval (1542) is provided for each heartbeat and artifacts (1526) can be generated, for example, for each protection interval / heartbeat. In some embodiments in which less coordinated control of the protection device is available, one or more protection intervals (1542) can be provided without a corresponding pulse waveform (1532). This can occur, for example, in embodiments in which the pulse waveform (1530) and the protection signal (1540) use different signal independent synchronization.

[0077] When the size of the artifacts (1526) is large enough, they can cause clinical misinterpretation of the heart activity. To reduce this risk, several options are available. First, the protection module can be integrated with the signal generator such that a protection interval (1542) is only provided when there is a corresponding pulse waveform (1532) and not when there is no pulse waveform (1532) delivered. Thus, the protection interval (1542) is provided when the cardiac stimulator or other electrical component (e.g., monitoring equipment) to be protected needs to be electrically isolated from the high voltage pulse waveform. With this implementation, no unnecessary protection switches occur and for the artifacts (1526) of the pulse waveform generation, the high voltage ablation energy delivered to the cardiac tissue saturates the heartbeat such that the artifacts (1526) do not cause a problem.

[0078] Second, for independent protection devices in which less coordinated control with the pulse field ablation device is possible, the switching artifacts (1526) can be reduced, for example, by placing low value capacitors on the isolation switches or between the protected channels to absorb some of the high frequency local switching energy in the protection device. See, for example, Figure 2 The previously described implementations of passive filtering components can also be implemented to reduce the artifacts (1526). Other options include temporarily shorting the signal pairs together (e.g., stimulator + / - and patient + / -) using additional switches / MOSFETs before reconnecting to the patient, temporarily turning on a resistive load on the patient side during the blanking interval, etc.

[0079] Figure 18 is a block diagram of an electrical component (1610) coupled to a patient (1620) via a protection device (1600) that includes one or more capacitors for reducing artifacts. One or more electrical components (1610) (e.g., monitoring equipment, cardiac stimulator) can be coupled to a patient (1620) via a protection device (1600) configured to selectively electrically isolate these components from a device disposed in the heart of the patient (1620). In some embodiments, the protection device (1600) can be configured to reduce the size of artifacts (e.g., artifacts (1526)). The protection device (1600) can include one or more of the protection devices described herein (e.g.,Figure 3A 、 Figure 3B 、 Figure 4 、 Figure 5 、 Figure 8 、 Figure 10A-10E 、 Figure 11 、 Figure 12 、 Figure 14-16 and Figure 19 .

[0080] The protection device (1600) can include one or more series protection switches (1602) and resistors (1606). The protection device (1600) can also include one or more capacitors (1604) configured in parallel with the respective switches (1602) and resistors (1606). The capacitors (1604) can be configured to receive a portion of any voltage spikes generated by the switch operation of the protection device (1600). Additionally or alternatively, the protection device (1600) can include one or more circuit components configured to reduce switch artifacts (e.g., the filter device (1330), the common mode protection device (1340), the differential / high voltage protection device (1350)) described in Figure 15

[0081] The resistors (1606) can be arranged in series with the switches, which can be configured to close prior to closing the series protection switches (1602) to reduce artifacts resulting from the switching of the protection switches (1602). For example, the switches in series with the resistors (1606) can be configured to close prior to the closing of the series protection switches (1602) in order to provide a temporary path for the one or more electrical components (1610) and the patient (1620), thereby reducing the risk of artifacts from the series protection switches (1602) upon subsequent disconnection of the load.

[0082] Figure 19 is a schematic diagram of a system for ablation via irreversible electroporation including a protection device (1900). The system can include a signal generator (1930), an ablation device (1932), and an electronic component (1940). In some embodiments, the electronic component (1940) can be implemented as a signal detector, for example, such as monitoring equipment for monitoring physiological data of a patient (1920). The protection device (1900) can include one or more of the protection devices described herein (e.g., Figure 3A 、 Figure 3B 、 Figure 4 、 Figure 5 、 Figure 8 、 Figure 10A-10E 、 Figure 11 、 Figure 12 、 Figure 14-16 、 Figure 18 and Figure 19 ​components of the protection device shown in FIG. 19.

[0083] The signal generator (1930) can be configured to generate a pulse waveform delivered by electrodes (not shown) of the ablation device (1932) to tissue. In some embodiments, the signal generator (1930) can be configured to generate a high-voltage ablation pulse waveform for irreversible electroporation of tissue, such as, for example, a pulmonary vein ostium. In some embodiments, the protection device (1900) can be electrically coupled to the patient (1920) via a set of patient connections (1924). For example, one or more electrodes and / or sensors can be placed on and / or inside the patient (1920), e.g., to measure physiological data of the patient (1920). The protection device (1900) can be coupled between the patient (1920) and the electronic components (1940).

[0084] In some embodiments, the signal generator (1922) can be configured to generate the pulse waveform in synchronization with an indication of the pacing signal and / or within a refractory period window. For example, in some embodiments, a common refractory period window can begin substantially immediately after the pacing signal (or after a very small delay) and continue for a duration of about 250 milliseconds (ms) or less thereafter. In such embodiments, the entire pulse waveform can be delivered within this duration.

[0085] In some embodiments, the electronic components (1940), the protection device (1900), and / or the signal generator (1930) can be in communication with one another, e.g., for coordinating timing of pulse waveform delivery and / or protection device control signal delivery. For example, the signal generator (1930) can be operably coupled to the protection device (1900) such that the signal generator (1930) can deliver a signal (e.g., a synchronization signal (1912)) to the protection device (1900), e.g., for synchronizing operation of one or more components of the protection device (1900) with delivery of the ablation pulse waveform. In one embodiment, the signal generator (1930) can periodically deliver a synchronization signal (1912) to the protection device (1900) that indicates to the protection device (1900) the timing of delivery of the pulse waveform. As Figure 19 As shown, the signal generator (1930) and the protection device (1900) can be separate devices. Alternatively, in some embodiments, the protection device (1900) can be integrated with the signal generator (1930) in a single console.

[0086] The protection device (1900) can be configured to form an open circuit between the electronic components (1940) and one or more patient connections (1924) (e.g., sensors or electrodes placed in proximity to the ablation site) at least during delivery of ablation energy by the ablation device (1932). The patient connections (1924) can allow the electronic components (1940) to monitor physiological data of the patient (1920). As described herein, delivery of the pulsed waveform to the patient (1920) can induce high voltages and / or currents in the patient connections (1924). Thus, by isolating these connections (1924) from the electronic components (1940), the protection device (1900) can reduce or prevent such induced voltages and / or currents from transferring to the electronic components (1940), thereby reducing noise interference into and / or damage to such components. When the pulsed waveform is not being delivered to the patient (1920), the protection device (1900) can be configured to electrically couple the electronic components (1940) with the patient connections (1924), e.g., to allow the electronic components (1940) to continue monitoring physiological data of the patient (1920).

[0087] The protection device (1900) can include a set of one or more switches (e.g., series components) (1902) configured to form an open circuit between the patient connections (1924) and the electronic components (1940). The set of switches (1902) can include one or more electromechanical relays (e.g., reed relays), solid state relays, and / or MOSFET devices.

[0088] In some embodiments, components can be introduced that can electrically connect the protected patient signals to a common node (1906). For example, the protection device (1900) can include channels that extend from each input into the electronic components (1940) and connect them to the common node (1906). Each channel can include a switch (1903) and a resistive element (1904) (e.g., a resistor). When the switch (1903) is closed, the channel can connect the input to the electronic components (1940) to the common node (1906). The resistive element (1904) can be coupled between the input and the common node (1906). The resistive element (1904) can be configured to reduce or minimize impedance when connecting the input to the common node (1906). During the delivery of pulsed field ablation (e.g., of a pulsed waveform), to reduce the noise present at the input of the electronic components (1940) (e.g., monitoring equipment), the inputs can be shorted together to reduce the amplitude of any differential noise. The switch (1902) can be open, for example, to isolate the electronic components (1940) from the patient connection (1924), but any residual noise picked up by the open circuit series components (e.g., the switch (1902)) during the pulsed field ablation delivery can be tied to the common node (1908), and the signal amplitude detected at the electronic components (1940) (e.g., measured by the monitoring equipment) can be reduced or diminished.

[0089] In some embodiments, components can be introduced that can connect the common node (1906) to ground (1909) (e.g., chassis or ground), for example, to further reduce the noise that can be picked up at the inputs to the electronic components (1940) during the pulsed field ablation delivery. By coupling the inputs that are electrically tied together (e.g., by the common node (1906)) to a ground connection, the protection device (1900) can reduce the amplitude of common mode noise and prevent large DC voltages above ground from being transferred into the electronic components (1940) (e.g., the input amplifiers of the monitoring equipment). Coupling the common node (1906) to ground (1909) can also reduce the chance of interference from the pulsed field ablation delivery affecting the electronic components (1940).

[0090] In some embodiments, components that filter high frequency signals on the ground connections (e.g., earth ground connections) at the signal generator (1930) and / or the protection device (1900) (or other protection circuitry) can be introduced. For example, the signal generator (1930) can be coupled to ground via an inductive filter (e.g., a ferrite clamp, a ferrite toroid, or a series inductor) (1914). Additionally or alternatively, the protection device (1900) can be coupled to ground via an inductive filter (e.g., a ferrite) (1901). Noise generated by the signal generator (1930) at the time of ablation delivery can be conducted through the patient to the patient connection (1902), but can also be emitted on the ground connections of the signal generator (1930). To reduce the noise caused by the signal generator (1930) connections to ground, components such as a ferrite clamp, a ferrite toroid, or a series inductor (e.g., filter (1914)) can be used to filter high frequency noise on these connections and reduce the amplitude measured at the ground connections of the electronic components (1940).

[0091] Figure 20A-20C is a time sequence diagram of the establishment of connections between one or more inputs or signals to the electronic components (1940), the common node (1906), and ground (1909) during the delivery of a pulse field ablation. Time sequence (2012, 2014, 2016) represents the timing of connecting the input to the electronic components (1940) to the common node (1906), time sequence (2022, 2024, 2026) represents the timing of connecting the common node (1906) to ground (1909), time sequence (2032, 2034, 2036) represents the timing of using a series component or switch (1902) to open a circuit between the patient connection (1924) and the electronic components (1940), and time sequence (2042, 2044, 2046) represents the timing of the delivery of a pulse waveform (e.g., by the signal generator (1930)).

[0092] Figure 20AA time sequence (2010) is shown for operating components of a protection device (1900) that ties input to an electronic component (1940) via a common node (1906) and simultaneously ties the common node (1906) to ground (1909), as shown in (2012, 2022). As shown, the time sequence (2010) allows the electronic component (1940) to continue to see a low impedance load between its input (e.g., from patient connection (1924)) throughout the ablation delivery process and ensures a low common mode DC level. The time sequence (2010) ensures that the input to the electronic component (e.g., from patient connection (1924)) is not high impedance, which can undesirably allow large noise pickup. After tying the input to the electronic component (1940) together and to ground (1909), the series components can form an open circuit between the patient connection (1924) and the electronic component (1940) (e.g., switch (1902) can be set to an open state), which isolates the electronic component (1940) from the patient (1920), as shown in (2032). After the open circuit is established, a pulsed waveform can be delivered to ablate tissue, as shown in (2042). After the ablation process is complete and the pulsed waveform is no longer being delivered to the patient (1920), the series components can reconnect the patient (1920) to the electronic equipment (1940). Subsequently, the input to the electronic component (1940) can be released from their common node and ground connection (e.g., switch (1903) can be set to an open state), and the electronic component (1940) can again be configured to receive data (e.g., physiological data) from the patient connection (1924) without any pulsed field ablation interference.

[0093] Figure 20B Another time sequence (2020) is depicted for operating components of a protection device (1900). Figure 20B The time sequence (2020) is similar to Figure 20Athe input to the electronic component (1940) from the common node (1906) does not occur at the same time. In some embodiments, the connection of the common node (1906) to ground (1909) (e.g., switch (1908) switching to a closed state) can occur when the series component of the protection device (1900) transitions to an open configuration (e.g., switch (1902) transitioning to an open state), as shown in (2024, 2034). This can ensure that the patient (1920) is not temporarily grounded (i.e., the patient connection (1924) is not coupled to ground (1909)) after the input to the electronic component (1940) is connected to the common node (1906) but the series component has not yet transitioned to an open state. By not having the patient (1920) temporarily grounded, any residual current within the system does not have a path to ground through the patient (1920). Then, once the patient signal is open (e.g., switch (1902) transitions to an open state), energy (e.g., an ablation pulse waveform) can be delivered to the patient (1920), and upon completion of the energy delivery, the patient signal can be reconnected (e.g., switch (1902) transitions back to a closed state) while releasing the large ground connection (e.g., switch (1908) switching back to an open state). After these events, the input to the electronic component (1940) from the common node (1906) can be released to allow the electronic component (1940) to again measure the patient signal via the patient connection (1924) without interference or noise from the ablation energy delivery.

[0094] Figure 20C Another time sequence (2030) is depicted for operating the components of the protection device (1900). Figure 20C The time sequence (2030) is similar to Figure 20A and Figure 20Btime series (2010, 2020), except that the connection between the common node and ground at any point during the sequence is not made, such that the common node (1906) remains floating. This can ensure that the ground (1909) input connection does not interfere with the input of the electronic component (1940). As described above, during ablation, high frequency signals can travel from the signal generator (1030) and / or other components of the system to the ground (1909). Thus, establishing a connection to the ground (1909) can cause such signals to interfere with the operation of the electronic component (1940), for example, by generating noise. While the above inductive filters (1901, 1914) can be used to reduce some of these high frequency signals, it can be necessary to adjust such inductive filters (1901, 1914) based on whether the various components of the system are in an open or closed state, and thus can be imperfect in filtering high frequency signals. Similar to the time series (2010, 2020), the series component can be switched to an open state, and ablation energy can be delivered while the series component is in the open state. After delivery of the ablation energy, the series component can be switched back to a closed state, reconnecting the patient connection (1924) to the electronic component (1940), and the input to the electronic component (1940) from the common node (1906) connection can be released.

[0095] Method

[0096] Methods of protecting electronic circuitry from induced current and voltage during performance of a tissue ablation procedure within one or more heart chambers using the systems and devices described herein are also described herein. In one embodiment, the heart chamber can be the left atrial chamber and include its associated pulmonary veins. Generally, the methods described herein include introducing and positioning a pacing device (e.g., pacing device (230)) in contact with one or more heart chambers. The pacing device can deliver pacing signals to the heart and / or measure heart activity using a cardiac stimulator (e.g., cardiac stimulator (28, 28’)). An ablation device (e.g., ablation device (210)) can be introduced and positioned in contact with one or more pulmonary vein openings or ostial regions. A pulse waveform can be delivered to the ablation tissue by one or more electrodes (e.g., electrodes (212)) of the ablation device. In some embodiments, a protection device (e.g., protection device (250)) can be in an open circuit configuration to isolate one or more sensitive electrical components (e.g., cardiac stimulator, monitoring equipment) during delivery of the pulse waveform. Such electrical components can otherwise be electrically coupled to the pacing device and configured to deliver pacing signals to the heart and / or receive heart activity measurements. In some embodiments, a control signal can be generated to control the open circuit interval (e.g., protection interval) of the protection device. The control signal can be based on one or more of a cardiac pacing signal, a pulse waveform signal (e.g., signal generator signal), a measured heart activity (e.g., R-wave detection), and combinations.

[0097] Additionally or alternatively, the pulse waveform can include multiple hierarchical levels to reduce total energy delivery, for example, as described in International Application Serial No. PCT / US2019 / 031135, filed May 7, 2019, and entitled “SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OF ABLATIVE ENERGY TO TISSUE,” and incorporated by reference herein.

[0098] In some embodiments, the ablation devices described herein (e.g., ablation device (210)) can be used for epicardial ablation and / or endocardial ablation. Examples of suitable ablation catheters are described in International Application Serial No. PCT / US2019 / 014226, which is incorporated by reference above.

[0099] Figure 6Ais an example method (400) of tissue ablation, in which ablation energy is delivered in synchronization with cardiac pacing. In some embodiments, the voltage pulse waveforms described herein can be applied during a refractory period of a cardiac cycle to avoid disruption of the sinus rhythm of the heart. The method (400) includes introducing a pacing device (e.g., the pacing device (230)) into an endocardial space, e.g., an endocardial space of the right ventricle, at (402). At (404), the pacing device can be advanced to be disposed in contact with cardiac tissue. For example, a sensor electrode can be configured for cardiac activity measurement (e.g., an ECG signal), and a pacing electrode can be configured for delivery of a pacing signal and can be disposed in contact with an endocardial surface, e.g., in the right ventricle. At (406), an ablation device (e.g., the ablation device (210)) can be introduced into an endocardial space, e.g., an endocardial space of the left atrium. At (408), the ablation device can be advanced to be disposed in contact with a pulmonary vein ostium. In some embodiments, at (410), a pacing signal can be generated by a cardiac stimulator (e.g., the cardiac stimulator (28, 28’)) for cardiac stimulation of the heart. Then, at (412), the pacing signal can be applied to the heart using the pacing electrode of the pacing device. For example, the heart can be electrically paced using the pacing signal to ensure pacing capture, thereby establishing periodicity and predictability of the cardiac cycle. One or more of atrial and ventricular pacing can be applied. Examples of the applied pacing signal in relation to patient cardiac activity are described in more detail herein, e.g., Figure 7B .

[0100] In some embodiments, pacing capture can be automatically confirmed by one or more of a signal generator (e.g., the signal generator (222)), a cardiac stimulator, or other processor operably coupled to one or more components of the system. In some embodiments, pacing capture can be confirmed by a user. For example, the user can confirm pacing capture using a user interface (e.g., an input / output device such as a touch screen monitor or other type of monitor) based on a measured cardiac activity signal. If the signal generator, processor, and / or user viewing the display determines that pacing capture is not present, then pulse waveform generation can be disabled, and the user can be prompted (by, e.g., repositioning the pacing device) to adjust system parameters to improve tissue engagement and / or modify pacing signal parameters (e.g., pulse width, pulse amplitude, pulse frequency, etc.).

[0101] In some embodiments, at (414), the pacing device can measure cardiac activity (e.g., an ECG signal) corresponding to cardiac electrical activity of the heart. For example, the measured cardiac activity can include a measured cardiac pacing pulse, an R-wave, etc.

[0102] The control signal or protection signal can be generated based on one or more of a cardiac pacing signal, a pulse waveform signal (e.g., a signal received from a signal generator), measured cardiac activity (e.g., R-wave detection, a predetermined voltage threshold), and combinations thereof, among others, and applied to the protection device at (418). For example, the protection signal can be generated based on a cardiac pacing signal received from a cardiac stimulator (e.g., cardiac stimulator (28)) or an ECG signal measured by a pacing device (e.g., pacing device (230)). As another example, the protection signal can be generated based at least in part on a pulse waveform signal received from a signal generator (e.g., signal generator (222)). The protection signal can have a predetermined time period and length. In response to the protection signal, the cardiac stimulator and / or other electronic components can be electrically isolated during the entire protection interval at (418). For example, the protection device coupled to the pacing device can electrically isolate the cardiac stimulator from high-voltage pulsed electric field ablation signals delivered by the ablation system (e.g., signal generator (222), ablation device (210), etc.) based on the received protection signal.

[0103] In some embodiments, the protection signal can synchronize the electrical isolation of the cardiac stimulator with the delivery of ablation energy to tissue. For example, the protection signal can be generated based on one or more of a cardiac pacing signal, measured cardiac activity, and a signal generator signal, as described in detail herein. Additionally or alternatively, the protection device can generate the protection signal even when the cardiac stimulator is not actively delivering pacing signals during a pulsed electric field ablation procedure. This can be useful, for example, in medical emergencies requiring rapid cardiac pacing. Such protection can also be used to isolate electronic components that are often present in a clinical procedure room (e.g., medical electronic equipment other than the ablation device, including but not limited to: ECG recording or monitoring equipment, electroanatomical mapping systems, device navigation / tracking systems, etc.). It is important to note that the protection device is deactivated (424) after a set of ablation pulses are delivered in order to restore connectivity between the medical device electrodes and the corresponding electronic components (e.g., medical electronic equipment, cardiac stimulator, electroanatomical mapping systems, ECG recording or monitoring systems, device navigation / tracking systems, etc.).

[0104] At (420), a signal generator (e.g., signal generator (222) or any processor associated therewith) can be configured to generate a pulse waveform synchronized to the protection interval, e.g., based on a predetermined criterion. For example, the pulse waveform can be generated during an refractory period that starts after the protection interval and ends before the protection interval. The refractory period can follow the pacing signal. For example, a common refractory period can be between atrial and ventricular refractory period time windows. The voltage pulse waveform can be applied within the common refractory period. In some embodiments, a pulse waveform and / or a protection signal can be generated with an indicated time offset relative to the pacing signal. For example, the start of the refractory period can be offset from the pacing signal by a time offset amount. The voltage pulse waveform can be applied over a series of heartbeats within the respective common refractory period. In some embodiments, the pulse waveform and the protection signal can be generated based on the same or different signals or information (e.g., the pacing signal, a sensed R-wave).

[0105] At (422), in response to receiving the pulse waveform, the ablation device can generate an electric field (e.g., a pulsed electric field) delivered to the tissue.

[0106] In some embodiments, a hierarchical voltage pulse waveform with nested structures and time interval hierarchy as described herein can be used for irreversible electroporation to provide control and selectivity in different tissue types. For example, a pulse waveform can be generated by a signal generator (e.g., signal generator (222)) and can include multiple levels in a hierarchy. A variety of hierarchical waveforms can be generated using the signal generators disclosed herein. For example, the pulse waveform can include a first level of a pulse waveform hierarchy that includes a first set of pulses. Each pulse has a pulse duration and a first time interval that separates consecutive pulses. A second level of the pulse waveform hierarchy can include the plurality of first set of pulses as a second set of pulses. A second time interval can separate consecutive first set of pulses. The second time interval can be at least three times the duration of the first time interval. A third level of the pulse waveform hierarchy can include the plurality of second set of pulses as a third set of pulses. A third time interval can separate consecutive second set of pulses. The third time interval can be at least thirty times the duration of the second level time interval.

[0107] In some embodiments, the pulse waveform can be delivered to a patient's pulmonary vein ostia via a set of tines of an ablation device, such as ablation device (210), or to a device placed anywhere in the cardiac anatomy or more generally in other parts of the patient's anatomy. In some embodiments, the voltage pulse waveform as described herein can be selectively delivered to a subset of electrodes, such as an anode-cathode subset for ablation and isolation of a pulmonary vein. For example, a first electrode of a set of electrodes can be configured as an anode and a second electrode of the set of electrodes can be configured as a cathode. These steps can be repeated to cause a desired number of pulmonary vein openings or sinus regions to have been ablated (e.g., 1, 2, 3, or 4 ostia). Suitable examples of ablation devices and methods are described in International Application No. PCT / US2019 / 014226, which is incorporated by reference above.

[0108] Figure 6B is an example method of tissue ablation (1900) in which ablation energy is delivered asynchronously (without cardiac pacing). At (1905), an ablation device is introduced into a patient's anatomy and positioned in a region of interest, such as at a location in the cardiac anatomy where ablation is desired. At (1909), a protection device can be activated, such as by a suitable control signal that can be directly coupled to a hardware switch isolation circuit or a processor that controls the switch isolation circuit. As used herein, a control element can refer to one or more of a control signal, a processor, and a switch circuit (e.g., a switch isolation circuit). Thus, the electronic components or equipment to be protected are isolated from potentially picked-up ablation pulses for an isolation time interval. A pulse waveform is generated at (1913) and delivered to tissue at (1917) for the isolation time interval. After the ablation pulse is delivered at (1917), the protection device is deactivated at (1920) so as to restore electrical connections between the electronic components or equipment and any associated patient contact electrodes. Such protected electronic devices can include one or more cardiac stimulators, electroanatomical mapping systems, ECG recording / monitoring systems, device navigation / tracking systems, etc.

[0109] For example, in embodiments in which a cardiac stimulator is used to pace the heart for a portion of a pulsed electric field ablation procedure, patient connections between the cardiac stimulator and the heart need to remain intact for the duration of the pacing or stimulation pulses. In such embodiments, the protection signal (e.g., a control signal used to activate the protection device) can synchronize electrical isolation of the cardiac stimulator with delivery of ablation energy to tissue. Figure 7A is a schematic illustration of a time sequence of cardiac stimulation (510), pulsed electric field ablation delivery (530), and a protection interval (540) (e.g., a blanking or open circuit) channel. Figure 7Bis a schematic illustration of a time sequence of cardiac stimulation (510), electrocardiogram (520), pulsed electric field ablation delivery (530), and a protection interval (540) channel. The cardiac stimulation (510) can include a set of periodic pacing pulses (512). Each pacing pulse (512) can include a rectangular pulse with a width between about 0.1 ms to about 20 ms. The pacing pulses (512) can be generated by a stimulator (e.g., stimulator (28, 28’)) and delivered to cardiac tissue using a pacing device (e.g., pacing device (230)). The pacing pulses (512) can correspond to one or more of ventricular and atrial cardiac pacing. In response to the pacing pulses (512), a cardiac cycle of the heart can be synchronized with the pacing pulses (512). For example, Figure 7B QRS complex (522) in electrocardiogram (520) is synchronized with the corresponding pacing pulse (512). The T wave (524) following the QRS complex (522) corresponds to the onset of repolarization occurring in the myocardial cells. In some embodiments, the electrocardiogram (520) can be measured using the pacing device.

[0110] In some embodiments, the high voltage application of the pulsed electric field ablation procedure can be synchronized with the cardiac cycle, as shown in Figure 7A and Figure 7B Pacing can be synchronized with the high voltage application in a variety of ways. For example, atrial pacing, ventricular pacing, or multi-chamber pacing can be performed. It can be desirable to implement ventricular pacing because the ventricles are more susceptible to causing arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation) if stimulated during ventricular repolarization (e.g., T wave). The high voltage output of the pulsed electric field ablation can occur concurrently with the pacing, or a predetermined delay after the stimulation pulse when the stimulation pulse is applied.

[0111] In some embodiments, the delivery of the pulsed waveform (532) can begin a first delay (534) (e.g., a time interval or period) after the trailing edge (514) of each pacing pulse (512). Each pulsed waveform (532) can be applied during the interval (532). In some embodiments, the first delay (534) can be a predetermined value (e.g., input by a user). For example, the first delay (534) can be between about 1 ms to about 100 ms. A second pulse delay (536) can separate the end of the pulsed waveform (532) and the beginning of the T wave. As described above, it can be desirable to deliver the pulsed waveform during a refractory period associated with the cardiac cycle. Thus, this second pulse delay (536) represents a safety margin between the pulsed waveform (532) and the T wave (524).

[0112] The blanking interval or protection interval (542) can be configured to start immediately or soon after each pacing pulse (512). The protection interval (542) can be configured to encapsulate the duration that the pulse waveform (532) is delivered. For example, the protection interval (542) can start a third delay (544) after the trailing edge (514) of the pacing pulse (512), where the third delay (544) is less than the first delay (534) of the pulse waveform (532). For example, the third delay (544) can be less than about 5 ms. The third delay (544) can be close to zero but non-zero, such that the protection interval (542) (e.g., open circuit state, blanking interval) does not overlap with the pacing pulse (512), as the stimulator and pacing device requires a closed circuit to deliver the pacing pulse (512). In some embodiments, the protection interval (542) is at least equal to and preferably greater than the first length of the pulse waveform (532), such that the protection interval (542) at least overlaps (e.g., encapsulates) the entire pulse waveform (532). In Figure 7A and Figure 7B In some embodiments, the leading and trailing edges (550) of the pulse waveform (532) and the protection interval (542) are such that the protection interval (542) is longer than the pulse waveform (532).

[0113] If the timing of the high voltage application for the pulse field ablation is known (e.g., with respect to a pacing or stimulation pulse of a cardiac stimulator), the protection interval (542) can be tailored around the duration of the high voltage application to ensure that the isolation protection encapsulates the high voltage application interval. The signal generator for the high voltage application can be configured to have a predetermined amount of delay (e.g., the first delay (534)) between the stimulation pulse (e.g., the pacing pulse (512)) and the initiation of the high voltage application to the patient (e.g., the leading edge (550) of the pulse waveform (532)). This delay can provide sufficient time for the protection element to transition to its isolation state (e.g., open circuit state or configuration) and start the protection interval (542). The protection interval (542) then remains longer in duration than the high voltage application interval. The timing of the protection interval (542) and the pulse waveform (532) can be repeated for each cardiac cycle.

[0114] In some embodiments, cardiac sensing or monitoring (e.g., for R-waves) (e.g., ventricular depolarization / contraction) can be used to synchronize the delivery of ablation energy to the tissue to the cardiac cycle. For example, the patient’s intrinsic R-wave can be sensed and used as a trigger for one or more of the ablation energy delivery and the electrical isolation. In some embodiments, this R-wave sensing can be used in place of cardiac pacing. In alternative embodiments, the R-wave sensing can be used in conjunction with pacing. For example, pacing can be performed in the atrium or ventricle, and the R-wave response of the captured beat can be sensed and used for synchronization. Figure 8is a schematic illustration of an electroporation system disposed in a heart (602) of a patient (600). The electroporation system can include an ablation device (610), a signal generator (622) (e.g., a pulsed field ablation generator), a cardiac stimulator (628), a pacing device (630), a protection device (650), and one or more signal detectors (670, 672). While Figure 8 two signal detectors (670, 672) are depicted in FIG. 6, it is understood that a single signal detector can be used instead of two separate detectors to implement the methods described herein.

[0115] The signal generator (622) can be coupled to the ablation device (610) and the signal detector (672). The signal generator (622) can be configured to generate a pulsed waveform that is delivered to the electrodes (612) of the ablation device (610), e.g., for delivering ablation energy to the heart (602). The pacing device (630) can be configured to pace the heart using pacing electrodes (632) of the pacing device (630). One or more diagnostic devices (636) can be configured to measure cardiac activity of the heart (600) (e.g., an electrocardiogram), e.g., by using externally placed electrode pads or intracardiac electrodes (634). Alternatively, in some embodiments, one or more electrodes of the pacing device (630) and / or the ablation device (610) can be used as sensing electrodes, which can be connected to a processor (e.g., the signal detectors (670, 672)) to further detect and / or analyze components of the cardiac cycle.

[0116] The protection device (650) can be coupled between the cardiac stimulator (628) and the pacing device (630). In some embodiments, the protection device (650) can be configured to synchronize electrical isolation of the cardiac stimulator (628) with ablation energy delivery of the ablation device (610). One or more signal detectors (670, 672) can be coupled to one or more of the signal generator (622), the pacing device (630), the protection device (650), and the cardiac stimulator (628). As Figure 8 shown, the first signal detector (670) is coupled to the protection device (650), and the second signal detector (672) is coupled to the signal generator (622). However, in alternative embodiments, a single signal detector can be coupled to both the protection device (650) and the signal generator (622).

[0117] Each signal detector (670, 672) can be coupled to a respective diagnostic device (636) coupled to the patient (600). Alternatively, the signal detectors (670, 672) can be integrated with one or more of the signal generator (622), the pacing device (630), the protection device (650), and the cardiac stimulator (628). The signal analyzer (670) can be configured to receive and analyze electrocardiogram signals to detect one or more R-waves. In some embodiments, R-waves can be detected using an R-wave amplitude threshold and some exclusion criteria for noise. Upon detection of an R-wave, the signal detectors (670, 672) can be configured to output a signal to the protection device (650) and the signal generator (622). Specifically, the signal detector (672) coupled to the signal generator (622) upon detection of an R-wave can send a signal to the signal generator (622) to indicate the timing of the R-wave and thus inform the signal generator (622) when to deliver pulsed field ablation. The signal detector (670) coupled to the protection device (650) upon detection of an R-wave can send a signal (e.g., a control signal as described above) to the protection device (650) to indicate the timing of the R-wave and thus inform the protection device (650) when to initiate a protection or blanking interval, as referenced to Figure 9 Further aspects are described.

[0118] Figure 9 is a schematic diagram of a time sequence of cardiac stimulation (710), electrocardiogram (720), pulsed field ablation delivery (730), and protection interval (740) channels. Figure 9 The time sequence depicted in FIG. 7A can include aspects similar to Figure 7B The time sequence depicted in FIG. 7A. The cardiac stimulation (710) (e.g., by a pacing device (630) as described above with reference to FIG. 6) can be delivered to the patient (600) at a time t0. Figure 8The illustrated cardiac stimulator (628) can provide optional and / or periodic stimulation pulses (712) to the patient (e.g., patient (600)). In one embodiment, the stimulation pulses can be periodic and can include rectangular pulses with a width between about 1 ms and about 5 ms. In some embodiments, any of the pacing devices described herein (e.g., pacing device (630)) can be used to deliver the pacing pulses (712). The pacing pulses (712) can correspond to one or more of ventricular and atrial cardiac pacing. The electrocardiogram (720) can include one or more P-waves (721), QRS waveforms (722), and T-waves (724). The P-waves (721) correspond to atrial depolarization. The T-waves (724) following the QRS waveforms (722) correspond to the onset of repolarization occurring in the myocardial cells. In some embodiments, the delivery of the pulse waveform (732) can be synchronized with the R-wave (726) detection, e.g., immediately after the R-wave detection or after a first delay (734). In embodiments where a protection device (e.g., protection device (650)) is used to isolate certain electronic components from the patient during the delivery of the pulsed electric field ablation, it can be desirable to implement a predetermined delay so that the protection device has sufficient time to isolate such electronic components after the R-wave detection and before the pulsed electric field ablation delivery. In some embodiments, the first delay (734) can be a predetermined value. For example, the first delay (734) can be between about 1 ms and about 5 ms. In some embodiments, the pulse waveform (732) can be separated from the T-wave (724) by a second delay (736), e.g., to provide a safety margin.

[0119] In some embodiments, a protection device (e.g., protection device (650)) implementing a protection interval (742) (e.g., an open circuit or blanking interval) can be synchronized using R-wave (726) detection. The protection device can start the protection interval (742) after a third delay (744) from the R-wave (726). The third delay (744) can be less than the first delay (734). The third delay (744) can be less than about 5 ms. When the protection device is used with cardiac stimulation, the protection interval (742) (e.g., open circuit state, blanking interval) can be configured to not overlap with the stimulation or pacing pulses (712). The protection interval (742) can be at least equal to, and preferably greater than, the length of the pulse waveform (732) such that the protection interval (742) at least overlaps (e.g., encapsulates) the entire pulse waveform (732). In some embodiments, the pulse waveform (732) and the protection interval (742) can be implemented independently (e.g., using separate R-wave detectors (670, 672)) or simultaneously (e.g., using a single R-wave detector (670)). By starting the protection interval (742) immediately or shortly after R-wave (726) detection, and continuing it for a longer time than the expected pulse field ablation delivery duration, the protection interval (742) can protect electronic components (e.g., sensitive equipment such as, for example, a cardiac stimulator) even when intracardiac pacing is not actively used during the pulse field ablation procedure. Protecting such electronic components such as a cardiac stimulator can be important in medical emergencies where rapid pacing or other types of pacing can be needed, even if such equipment is not actively used during the ablation procedure, and thus allow such electronic components to function, connect, and be available at all times throughout the procedure.

[0120] The protection or isolation of certain electronic components during the high voltage interval can be implemented using a fixed blanking interval of sufficient duration to cover the longest expected ablation interval, or an adjustable or settable blanking interval (e.g., a user or system can set it to a certain value based on the expected pulse field ablation time). Figure 13 is a schematic of a time sequence of a cardiac stimulation (1110), electrocardiogram (1120), pulse field ablation delivery (1130), and protection interval (1140) channels. The cardiac stimulation (1110) channel can optionally include pacing or stimulation signals (1112), which can be periodic, and can include rectangular pulses with a width between about 0.1 ms and about 100 ms. In some embodiments, any of the pacing devices described herein (e.g., pacing device (230, 630, 1030)) can be used to deliver the pacing pulses (1112). The pacing pulses (1112) can correspond to one or more of ventricular and atrial cardiac pacing. In response to the pacing pulses (1112), the cardiac cycle of the heart can be synchronized with the pacing pulses (1112). For example, Figure 13The P-wave (1121), QRS complex (1122), and T-wave (1124) in the electrocardiogram (ECG) signal (1120) can be synchronized with the pacing pulse (1112). The P-wave (1121) corresponds to atrial depolarization, and the T-wave (1124) following the QRS complex (1122) corresponds to the onset of repolarization occurring in the myocardial cells.

[0121] In some embodiments, the pulse waveform (1132) and the protection interval (1142) can be synchronized based on one or more of a pacing or stimulation pulse sense (1144) and an R-wave detection (1124). The pulse waveform (1132) can have a first length or duration (1134), and the protection interval (1142) can have a second length or duration (1148) that is at least as long as the duration of the pulse waveform (1132). The duration (1148) of the protection interval (1142) can be fixed or adjustable. The pulse waveform (1134) can be delivered after a first delay (1136) from a trailing edge (1114) of a cardiac pacing pulse (1112) (e.g., signaled by a cardiac stimulator or detected). The first delay (1136) can be a predetermined value. For example, the first delay (1136) can be between about 1 ms to about 5 ms. Likewise, the protection interval (1142) can be synchronized with the cardiac pacing pulse (1112) (e.g., signaled by a cardiac stimulator or detected) after a second delay (1144). In this way, the cardiac pacing signal (1112) can be configured to trigger the protection interval (1142). The protection interval (1142) (e.g., open circuit state, blanking interval) can overlap the entire pulse waveform (1132).

[0122] In some embodiments, the pulse waveform (1132) and the protection interval (1142) can be synchronized with the R-wave detection (1124), e.g., after respective third and fourth delays (1138) and (1146). In this way, the R-wave detection (1124) can be configured to trigger the protection interval (1142). The R-wave detection can be implemented using any of the systems described herein. The third delay (1138) can be a predetermined value. For example, the third delay (1138) can be between about 1 ms to about 20 ms. In some embodiments, the pulse waveform (1132) and the protection interval (1142) can begin substantially simultaneously with the R-wave detection (1124).

[0123] In some embodiments, one or both of the second delay (1144) and the fourth delay (1146) can be adjustable, such that the protection interval (1142) can have an adjustable duration (1148).

[0124] It should be understood that the examples and illustrations in the present disclosure are for exemplary purposes only and that departures can be made from the examples and illustrations in the number of electrodes, sensors, and devices, etc. that can be constructed and deployed in accordance with the teachings herein without departing from the scope of the present invention. In particular, the systems, devices, and methods disclosed herein can be configured to protect various medical electronic equipment, including but not limited to cardiac stimulators, electroanatomical mapping systems, ECG recording systems, ECG monitoring systems, device navigation or tracking systems, etc., whether the ablation energy with high voltage pulse waveform is delivered synchronously with cardiac pacing or asynchronously (e.g., without cardiac pacing). It should be understood that the protective device embodiments described herein can be implemented in a multi-channel format that can protect multiple device electrodes or groups of device electrodes that can be connected to such electronic equipment. For example, the protective device can contain 2, 4, 6, 8, 64, 256, or 512 protective channels. Further, the control signal for activating the protective device can be output to multiple such devices, providing a scalable protective device in which the number of protective channels can be scaled in a modular fashion.

[0125] As used herein, the terms“about” and / or“approximately” when used in conjunction with a numerical value and / or a range, generally mean a number and / or a range of numbers close to the stated numerical value and / or range. In certain instances, the terms“about” and“approximately” can mean within ±10% of the stated value. For example, in certain instances,“about 100 [units]” can mean within ±10% of 100 (e.g., from 90 to 110). The terms“about” and“approximately” can be used interchangeably.

[0126] Some embodiments described herein relate to computer storage products with a non-transitory computer readable medium (also can be referred to as non-transitory processor readable medium) having instructions or computer code thereon for performing various computer-implemented operations. The computer readable medium (or the processor-readable medium), in and of itself, can not be a transitory propagating signal per se (e.g., a propagating electromagnetic wave carrying information on a transmission medium, such as spatially or cable-based transmission of the propagating electromagnetic wave). The media and computer code (also can be referred to as code or algorithm) can be those designed and constructed for the specific purpose or purposes. Examples of non-transitory computer-readable media include, but are not limited to, magnetic storage media such as hard disks, floppy disks, and magnetic tape; optical storage media such as Compact Discs / Digital Video Discs (CD / DVDs), Compact Disc-Read Only Memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical disks; carrier wave signal processing modules; and hardware devices that are specially configured to store and execute program code, such as Application Specific Integrated Circuits (ASICs), Programmable Logic Devices (PLDs), Read-Only Memory (ROM) and Random-Access Memory (RAM) devices. Other embodiments described herein relate to computer program products, which can include, for example, the instructions and / or computer code disclosed herein.

[0127] The systems, devices, and / or methods described herein can be executed by software (executed on hardware), hardware, or combinations thereof. Hardware modules can include, for example, a general-purpose processor (or microprocessor or microcontroller), a field programmable gate array (FPGA), and / or an application specific integrated circuit (ASIC). Software modules (executed on hardware) can be expressed in a variety of software languages, including C, C++, Ruby, Visual Basic, Java, Fortran, Pascal, Eiffel, Smalltalk, Haskell, Objective-C, JavaScript, Python, Perl, Coldfusion, and / or other object-oriented, procedural, or other programming language and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, machine instructions, such as produced by a compiler, code used to produce a web service, and files containing higher-level instructions that are executed using an interpreter. Examples of computer code include, but are not limited to, microcode or microinstructions, machine instructions, such as produced by a compiler, code used to produce a web service, and files containing higher-level instructions that are executed using an interpreter.

[0128] The particular examples and descriptions given above are illustrative of the general principles of the present application and are not intended to limit the scope or application thereof. Embodiments can be implemented based on the description taught above with respect to the material within the scope of the claims.​

Claims

1. A system comprising: a first set of electrodes deployable proximate to cardiac tissue of a heart; a second set of electrodes configured to be in contact with patient anatomy; a signal generator configured to generate a pulsed waveform, the signal generator coupled to the first set of electrodes and configured to repeatedly deliver the pulsed waveform to the first set of electrodes, the first set of electrodes configured to generate a pulsed electric field in response to delivery of the pulsed waveform to ablate the cardiac tissue; a protection device configured to selectively couple and decouple an electronic device to and from the second set of electrodes, wherein the protection device comprises a first switching component and a second switching component, wherein the first switching component is configured to switch between a conductive state in which the electronic device is coupled to the second set of electrodes and a non-conductive state in which the electronic device is decoupled from the second set of electrodes, and wherein the second switching component is configured to be in a conductive state when the protection device is de-energized and in a non-conductive state when the protection device is energized, the second switching component being arranged in parallel with the first switching component such that the electronic device is coupled to the second set of electrodes when the protection device is de-energized; and a control element coupled to the protection device and configured to control the protection device to decouple the electronic device from the second set of electrodes during a time interval that begins before and ends after each delivery of the pulsed waveform to the first set of electrodes.

2. The system of claim 1, wherein, the electronic device is a cardiac stimulation device configured to generate pacing signals, the cardiac stimulation device configured to deliver the pacing signals to the heart via the second set of electrodes to control timing of a group of cardiac cycles.

3. The system of claim 2, wherein, the control element is further configured to: receive trigger signals from the cardiac stimulation device, each trigger signal indicating when a pacing signal was delivered to the heart, the control element configured to control the protection device to decouple the cardiac stimulation device from the second set of electrodes in response to receiving each trigger signal; and couple the cardiac stimulation device to the second set of electrodes after each delivery of the pulsed waveform to the first set of electrodes so that the cardiac stimulation device can deliver subsequent pacing signals to the heart.

4. The system of claim 2, wherein, the signal generator is configured to deliver the pulsed waveform to the first set of electrodes at a time delay from delivery of each pacing signal to the heart.

5. The system of claim 4, wherein, the time delay is a first time delay, the control element configured to control the protection device to decouple the cardiac stimulation device from the second set of electrodes after a second time delay from delivery of each pacing signal, the second time delay being less than the first time delay so that the cardiac stimulation device is decoupled from the second set of electrodes before each delivery of the pulsed waveform.

6. The system of claim 1, wherein, the electronic device comprises at least one of: an electroanatomical mapping system configured to generate a map of cardiac electrical activity; a device tracking and navigation system configured to generate an anatomical map of a chamber of the heart; or an electrocardiogram (ECG) system configured to monitor cardiac electrical activity.

7. The system of claim 1, further comprising a sensing device configured to detect, from a set of cardiac cycles, an R-wave associated with each cardiac cycle, the signal generator is configured to deliver the pulse waveform during each cardiac cycle from the set of cardiac cycles at a time delay from an R-wave of each cardiac cycle from the set of cardiac cycles, the time delay enabling the electronic device to be decoupled from the second set of electrodes prior to delivery of the pulse waveform.

8. The system of claim 7, wherein, the control element is further configured to: receive, from the sensing device, a trigger signal, each trigger signal indicating when an R-wave was detected, the control element configured to, in response to receiving each trigger signal, control the protection device to decouple the electronic device from the second set of electrodes; and after each delivery of the pulse waveform, couple the electronic device to the second set of electrodes.

9. The system of claim 1, wherein, the protection device is integrated into the signal generator, and wherein the control element is further configured to coordinate the delivery of the pulse waveform to the first set of electrodes with the decoupling of the electronic device from the second set of electrodes.

10. The system of claim 1, wherein, the switching component comprises a metal-oxide-semiconductor field-effect transistor (MOSFET) pair, the MOSFET pair has a common source terminal and gate terminals coupled to one or more isolated gate drive circuits configured to deliver control signals to the gate terminals to switch the MOSFET pair between the conductive state and the non-conductive state.

11. The system of claim 1, wherein, the protection device further comprises one or more of: a common-mode choke, a differential-mode choke, or a filter circuit.

12. The system of claim 1, wherein, the protection device further comprises at least (i) one or more capacitors, or (ii) an access resistor configured to absorb energy associated with a switching component that switches between the conductive state and the non-conductive state.

13. The system of claim 1, wherein, the protection device is configured to selectively couple and decouple a plurality of electronic devices with a plurality of second sets of electrodes, the plurality of electronic devices including the electronic device, and the plurality of second sets of electrodes including the second set of electrodes.

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