System, apparatus and method for protecting electronic components from high power noise caused by high voltage pulses

Abstract

Systems, apparatus, and methods for protecting electronic components from high power noise caused by high voltage pulses are disclosed. In particular, systems, devices, and methods are disclosed for electroporation ablation therapy having a protection device for isolating an isolation electronic circuit, device, and / or other component from a set of electrodes during a cardiac ablation procedure. A system may include a first set of electrodes that may be disposed proximate to heart tissue of a heart and a second set of electrodes that may be disposed in contact with patient anatomy. The system may also include a signal generator configured to generate a pulse waveform, where the signal generator is coupled to the first set of electrodes and configured to repeatedly deliver the pulse waveform to the first set of electrodes. The system may also include a protection device configured to selectively couple and decouple the electronic device with the second set of electrodes.

Description

[0001] This application is a divisional application of patent application No. 202080094074.X, filed on November 20, 2020, entitled "System, Apparatus and Method for Protecting Electronic Components from High-Power Noise Caused by High-Voltage Pulses".

[0002] Cross-references to related applications

[0003] 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

[0004] 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

[0005] 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 utilize 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 the cardiac stimulator and / or these other devices, thereby interrupting pacing, sensing, mapping, magnetic sensor operation, and / or pulsed field ablation functionality. 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.

[0006] Therefore, systems, apparatus and methods for solving this problem may be needed. Summary of the Invention

[0007] This article describes 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 pulsed electric field ablation procedures.

[0008] In some embodiments, the ablation device used in these systems may be deployed on the epicardium or endocardium of the heart. The pulse waveform delivered by the ablation device may include predetermined parameters or may be automatically generated by a signal generator.

[0009] In some embodiments, the system may include a first set of electrodes and a second set of electrodes. Typically, the second set of electrodes may be positioned near cardiac tissue, or they may be part of a surface patch or similar external recording or monitoring device. A signal generator may be configured to generate pulsed waveforms. The signal generator may be coupled to the first set of electrodes and, in some embodiments, may be configured to repeatedly deliver pulsed waveforms to the first set of electrodes in synchronization with a set of cardiac cycles. In other embodiments, the signal generator may be configured to repeatedly deliver pulsed waveforms to the first set of electrodes without establishing synchronization with cardiac cycles. In the latter case, protecting other electronic components (e.g., cardiac stimulators (typically used for pacing), mapping systems, magnetic tracking devices, imaging equipment, and other laboratory equipment) remains useful. The first set of electrodes may be configured to generate pulsed electric fields in response to the delivery of pulsed waveforms to ablate cardiac tissue. Protective devices may be configured to selectively couple electronic equipment to and decouple it from the second set of electrodes. Control elements (e.g., processors, switches, control signals) can be coupled to the protection device and configured to control the protection device to decouple the electronic equipment from the second set of electrodes during a time interval that begins before and ends after each delivery of a pulse waveform to the first set of electrodes.

[0010] In some embodiments, the device may include a first set of electrodes that can be disposed near cardiac tissue of the heart. A signal generator may be coupled to the first set of electrodes and configured to generate pulsed waveforms. A switching element may be coupled to the signal generator. The switching element may be configured to switch between an on state in which the electronics are coupled to a second set of electrodes and a non-conductive state in which the electronics are decoupled from the second set of electrodes. The second set of electrodes may be disposed near the first set of electrodes, or typically in the heart or an anatomical chamber, or may be disposed on or near the outer surface of the subject. A processor may be coupled to the switching element. The processor may be configured to receive trigger signals, 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 may be configured to set the switching element to a non-conductive state, thereby decoupling the electronics from the second set of electrodes. The processor may be configured to, after setting the switching element to a non-conductive state, deliver pulsed waveforms from the signal generator to the first set of electrodes, causing the first set of electrodes to generate pulsed electric fields. The processor may be configured to, after delivering the pulsed waveforms, set the switching element to a conductive state, thereby coupling the electronics to the second set of electrodes. In some embodiments, the control signal coupled to the switching component can set the state of the switch to perform the functions described above.

[0011] In some embodiments, a method may include delivering pacing signals to the heart via a second set of electrodes located near cardiac tissue. After each pacing signal is delivered to the heart, a switching element selectively coupled to an electronic device may be set to a non-conductive state, decoupling the second set of electrodes from the electronic device. After the switching element is set to the non-conductive state, a pulse waveform may be delivered to the first set of electrodes located near cardiac tissue, causing the first set of electrodes to generate a pulsed electric field for ablating the cardiac tissue. After the pulse waveform is delivered, the switching element may be set to a conductive state, coupling the second set of electrodes to the electronic device. Attached Figure Description

[0012] Figure 1 This is a schematic diagram of components of a signal generator and a heart stimulator disposed in the heart according to an embodiment.

[0013] Figure 2 This is a schematic diagram of a signal generator and a heart stimulator component disposed in the heart, according to an embodiment, having a passive filter for protecting the heart stimulator.

[0014] Figure 3A This is a schematic diagram of a system for protecting electronic components from high-voltage signals according to an embodiment.

[0015] Figure 3B This is a schematic diagram of a system for protecting electronic components from high-voltage signals according to an embodiment, which includes electrodes that can be connected to externally and / or internally disposed in various medical devices, 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.

[0016] Figure 4 This is a schematic diagram of a signal generator and components of one or more medical electronic devices connected to electrodes disposed in the heart / cardiac anatomy or on the patient's surface, according to an embodiment, having protective devices for protecting the medical electronic devices.

[0017] Figure 5 This is a circuit diagram of a protection device for protecting electronic components from high-voltage signals, according to an embodiment.

[0018] Figure 6A A method for protecting electronic components from high-voltage signals according to an embodiment is shown.

[0019] Figure 6B A method for protecting electronic components from high-voltage signals delivered asynchronously via ablation is illustrated according to an embodiment.

[0020] Figure 7A The time series of cardiac pacing signals, energy delivery, and device isolation according to an embodiment is shown. Figure 7B The time series of cardiac pacing signals, cardiac activity, energy delivery, and device isolation according to an embodiment are shown.

[0021] Figure 8 This is a schematic diagram of a system for protecting electrical components from high-voltage signals according to an embodiment.

[0022] Figure 9 The time series of cardiac pacing signals, cardiac activity, energy delivery, and device isolation according to an embodiment are shown.

[0023] Figures 10A-10E This is a block diagram of an alternative arrangement of the protection device and the high-voltage generator according to an embodiment.

[0024] Figure 11 This is a schematic diagram of a protective device for controlling connections between electronic components operating in a high-voltage exposed area, according to an embodiment.

[0025] Figure 12 This is a schematic diagram of a system for protecting electronic components from high-voltage signals according to an embodiment.

[0026] Figure 13 The time series of cardiac pacing signals, cardiac activity, energy delivery, and device isolation according to an embodiment are shown.

[0027] Figure 14 This is a schematic diagram of a protective device for controlling connections between electronic components operating in a high-voltage exposed area, according to an embodiment.

[0028] Figure 15 This is a schematic diagram of a protective device for controlling connections between electronic components operating in a high-voltage exposed area, according to an embodiment.

[0029] Figure 16 This is a schematic diagram of a protective device for controlling connections between electronic components operating in a high-voltage exposed area, according to an embodiment.

[0030] Figure 17A and Figure 17B The time series of cardiac pacing signals, cardiac activity, energy delivery, and device isolation according to an embodiment are shown.

[0031] Figure 18 This is a schematic diagram of a protective device for controlling connections between electronic components operating in a high-voltage exposed area, according to an embodiment.

[0032] Figure 19This is a schematic diagram of a system for protecting electrical components from high-voltage signals according to an embodiment.

[0033] Figure 20A The time series of signal connection and energy delivery according to an embodiment is shown.

[0034] Figure 20B The time series of signal connection and energy delivery according to an embodiment is shown.

[0035] Figure 20C The time series of signal connection and energy delivery according to an embodiment is shown. Detailed Implementation

[0036] This article describes systems, apparatus, and methods for protecting circuitry from high-power noise induced during pulsed electric field ablation. Pulsed electric field ablation uses ultrashort, high-voltage pulses to generate a large electric field in a desired region of interest to create a localized area of ​​ablated tissue via irreversible electroporation. In some applications, including cardiac applications, it may be necessary to generate pulses for pulsed electric field ablation in sync 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 synchronizing pulse delivery can be to pace or stimulate one or more cardiac 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 cardiac chambers, synchronizing the patient's heart rhythm with the pacing pulses.

[0037] In some embodiments, pacing pulses can be delivered to the heart chamber via an intracardiac catheter appropriately positioned within the chamber. For example... Figure 1 A cardiac stimulator (28) is depicted, coupled to an intracardiac catheter (30) appropriately positioned within a chamber of the heart (2). The catheter (30) may have one or more electrodes (32, 34) used to conduct pacing signals into the heart. In one embodiment, a pair of electrodes on the catheter (30) (e.g., the distal electrode (32) and the electrode (34) immediately adjacent to the distal electrode (32)) may be used as a bipolar pair to deliver the pacing signal, thereby providing a positive current and a return current path for the pacing signal. The cardiac chamber responds to the pacing pulse (referred to herein as “pacing capture”) by timing its ECG signal generation (e.g., QRS waveform) to synchronize with the pacing pulse. Thus, periodicity of cardiac ECG activity can be established. Once this periodicity is established and confirmed by a physician (e.g., from the displayed ECG activity, which is, for example, directed at various recording or sensing electrodes), the delivery of pulse field ablation pulses can be timed to begin synchronously with the pacing pulses, including any predetermined offset, and the delivery can be completed within the refractory period window following the QRS waveform of the ECG signal.

[0038] In cardiac applications, pulsed field ablation energy can be delivered via a custom-designed ablation catheter comprising multiple electrodes. For example, as... Figure 1 As shown, a signal generator (22) (e.g., a pulse field ablation pulse generator) can be coupled to an ablation catheter (10) having electrodes (12) suitably positioned in the heart (2). The delivery of pulse field ablation voltage pulses can be synchronized with the delivery of pacing signals (with appropriate offset), as shown in (60). Since the pacing catheter (30) can also be located in the cardiac environment (e.g., in the same or nearby chamber of the heart (2), a high-voltage pulse waveform applied to the cardiac tissue can be coupled to the pacing catheter (30) and induce current in one or more pacing catheters (30) and the devices coupled thereto (e.g., cardiac stimulators (28)).

[0039] During normal delivery of pacing pulses, the forward and return currents at the electrodes (32, 34) of the pacing catheter (30) are balanced (e.g., equal in magnitude and opposite in direction). However, the electrical coupling of high-voltage ablation energy to the pacing catheter (30) can cause large and generally unbalanced currents and / or common-mode voltages in the leads of the pacing catheter (30). These large unbalanced currents and / or voltages can span frequency bands and can disrupt the operation of the pacing system or the cardiac stimulator (28) or other electronic devices coupled thereto. For example, large voltage exposure of the pacing catheter (30) may exceed the common-mode inhibition of the cardiac stimulator (28) and lead to system failure and / or stimulator reset (which may be for pacing to synchronize ablation delivery or for pacing the cardiac chambers for other medical reasons). The high voltage and current levels associated with induced noise imply high power levels of noise and can potentially have adverse effects.

[0040] Such high-power induced noise can be difficult to suppress, and therefore, systems, apparatus, and methods for suppressing induced currents in auxiliary equipment may be needed in pulsed electric field ablation energy delivery applications. In some embodiments, the current induced by electric field ablation can be suppressed by implementing passive filtering systems, apparatus, and methods, as described in U.S. Application Serial No. 62 / 667887, filed May 7, 2018, entitled “SYSTEMS, APPARATUSES, AND METHODS FOR FILTERING HIGH VOLTAGE NOISE INDUCEDBY PULSED ELECTRIC FIELD ABLATION”, the entire contents of which are incorporated herein by reference. Figure 2An example of a system including passive filtering is depicted. A cardiac stimulator (28') may be coupled to a pacing catheter (30') including multiple electrodes (32', 34'). A signal generator (22') may be coupled to an ablation catheter (10') including multiple electrodes (12'). The electrodes (32', 34') of the pacing catheter (30') may be positioned in the heart (2') together with the electrodes (12') of the ablation catheter (10'). A filter element (50') may be coupled between the cardiac stimulator (28') and the pacing catheter (30'). The filter element (50') may passively filter signals from the pacing catheter (30') before the cardiac stimulator (28') receives signals, thereby suppressing certain induced currents. For example, at point A, a long lead may pick up a high voltage, while at point B, after passive filtering, residual voltage and current may be transmitted to the cardiac stimulator (28').

[0041] However, in some cases, passive filtering techniques may struggle to suppress coupling noise with large amplitudes (e.g., large voltage spikes), and therefore, equipment failure and / or reset, including cardiac stimulators, can still occur. Commercial stimulators may also incorporate different design parameters, making a level of protection sufficient for one type of stimulator but insufficient for a second.

[0042] The systems, apparatus, and methods disclosed herein utilize actively driven rapid switching of signal paths to provide protection for sensitive electronic and auxiliary devices in pulsed electric field ablation applications. In some embodiments, the protection device may be coupled to a pacing device to actively and selectively electrically isolate the pacing device from other electronic components of the ablation system. Specifically, the pacing device may be electrically isolated from the system during predetermined time periods corresponding to the delivery of pulse waveforms to tissue. The electrical connection can be re-established to enable the pacing device to operate between cycles of high-voltage energy delivery. In some embodiments, the protection device may 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 the currents induced in the pacing device by the high-voltage pulse waveforms applied by the ablation device. Additionally or alternatively, the protection device may further provide passive circuit protection.

[0043] In some embodiments, sensitive circuitry or auxiliary equipment artifacts (e.g., cardiac stimulators, electroanatomical mapping systems, ECG recording or monitoring systems, etc.) can be protected from high-voltage pulsed-field ablation signals present within the subject's body by electrically isolating such circuitry or equipment. Electrical isolation can be manually implemented by disconnecting conductors between circuitry or equipment, but in some cases, manual methods may not be feasible. For example, for certain types of equipment with repetitive functions, such as cardiac stimulators designed 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 cases, electronic components may be needed to achieve the physical disconnection. For example, electronic components may be used to provide bidirectional open-circuit isolation between the main body and the protected auxiliary equipment during specific time intervals where high voltage is present, and to re-establish the connection during other time intervals to allow the equipment to function as intended.

[0044] As used in this article, "electroporation" refers to applying an electric field to the cell membrane to alter its permeability to the extracellular environment. "Reversible electroporation" refers to applying an electric field to the cell membrane to temporarily alter its permeability. For example, cells undergoing reversible electroporation may exhibit temporary and / or intermittent formation of one or more pores in their cell membrane, which close upon removal of the electric field. "Irreversible electroporation" refers to applying an electric field to the cell membrane to permanently alter its permeability to the extracellular environment. For example, cells undergoing irreversible electroporation may exhibit the formation of one or more pores in their cell membrane, which persist even after the electric field is removed.

[0045] The pulse waveforms for electroporation energy delivery disclosed herein can enhance the safety, efficiency, and effectiveness of energy delivery to tissues by reducing the electric field threshold associated with irreversible electroporation, thereby producing more effective ablation lesions while reducing the total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein may be hierarchical and have a nested structure. For example, the pulse waveforms may include hierarchical groupings of pulses with associated time scales. In some embodiments, the methods, systems, and apparatuses disclosed herein may include one or more methods, systems, and apparatuses described in International Application Serial No. PCT / US2019 / 014226, filed January 18, 2019, which was published on July 25, 2019, entitled “SYSTEMS, DEVICES AND METHODS FOR FOCAL ABLATION”, International Publication No. WO / 2019 / 143960, the entire contents of which are incorporated herein by reference.

[0046] Systems and equipment

[0047] This document discloses systems and devices for suppressing induced currents associated with tissue ablation. Typically, the systems described herein for ablating tissue using high-voltage pulse waveforms may 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 the delivery of the 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 a high-voltage pulse waveform can be performed asynchronously (i.e., not synchronized with cardiac stimulation). In these embodiments, it is generally desirable to also protect other electronic devices, such as cardiac stimulators, electroanatomical mapping systems, device navigation / tracking systems, ECG recording or monitoring systems, etc., which can be connected to the patient via device electrodes placed inside or outside the patient, or attached to the patient surface (e.g., needle electrodes, pacing leads, etc.). Therefore, the systems, methods, and implementations described herein are suitable for asynchronous ablation delivery. Furthermore, as described herein, systems and devices can be deployed on the epicardium and / or endocardium to treat atrial fibrillation. Voltage can be applied to a selected subset of electrodes, where the independent subset selection is specific to the selection of anodic and cathodic electrodes.

[0048] Figure 3A An example system (1700) including an integrated protective element (1750) is shown. The protective element (1750) may be located between the electrical component (1730) and the target area (TA) (e.g., the patient's heart). The protective element (1750) may be configured with a rated voltage corresponding to the expected exposure voltage on the patient side of the pulsed electric field ablation procedure, which may be several kilovolts. The protective element (1750) may serve as an isolation component, configured to switch to an open-circuit configuration and return to a closed-circuit configuration based on a control signal. The protective element (1750) is configured to respond quickly (e.g., to switch rapidly between its open and closed configurations) to reduce the open-circuit duty cycle, such that the protective element (1750) can electrically isolate certain electrical components (1730) (e.g., monitoring equipment or devices, cardiac stimulators, etc.) during the duration of high-voltage exposure, but otherwise connect these electrical components to the target area (TA).

[0049] 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 may be less suitable for isolation component implementations because they operate more slowly than other types of protection devices and are prone to damage / contact meltdown if switched during exposure to high current. When a system (1700) is used with a protection element (1750) implemented as a reed relay, the coordination and timing of the system (1700) need to be adjusted to accommodate the slower response time of such relays. A preferred embodiment of the protection element (1750) is the use of two back-to-back MOSETs with a common source terminal, as referenced below. Figure 5 Further description.

[0050] Figure 3B An example system (1800) including an integrated protective element (1805) is shown. The protective element (1805) may be located between the electrical components (1801) and the patient's anatomy (1808). The protective element (1805) may be configured with a rated voltage corresponding to the expected exposure voltage on the patient side during a pulsed electric field ablation procedure, which may be several kilovolts. This high-voltage exposure may occur via an internally placed (relative to the patient) device electrode or sensor (1819) or an externally placed / mounted (on the patient's surface) electrode or sensor (1821). Such electrodes or sensors can typically be connected to a variety of medical electronic devices, including but not limited to electroanatomical mapping systems, device navigation / tracking systems, ECG recording / monitoring systems and combinations thereof, and similar devices commonly used in clinical laboratories or operating rooms. In the embodiments described herein, the sensor may be a general-purpose sensor, including a dedicated electromagnetic sensor, an electrode for receiving a voltage signal generated by a position tracking system, an electrode for monitoring natural cardiac electrical activity, and more generally a sensor for sensing various types of electrical signals. The protective element (1805) can be used as an isolation component, which is configured to switch to an open-circuit configuration and return to a closed-circuit configuration based on a control signal (1812). The protective element (1805) is configured to respond quickly (e.g., to switch rapidly between its open and closed configurations) to reduce the open-circuit duty cycle, so that the protective element (1805) can electrically isolate electrical components such as those described above (1801) during the duration of high-voltage exposure, but otherwise connect these electrical components to the patient's anatomy (1808).

[0051] 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 may be less suitable for isolation component implementations because they operate more slowly than other types of protection devices and are prone to damage / contact meltdown if switched during exposure to high current. When a system (1800) is used with a protection element (1805) implemented as a reed relay, the coordination and timing of the system (1800) need to be adjusted to accommodate the slower response time of such relays. In some embodiments, the protection element (1805) may comprise two back-to-back MOSFETs with a common source terminal, as referenced below. Figure 5 Further description.

[0052] Figure 4 This is a schematic diagram of an electroporation system disposed in the heart (202) of a patient (200). The electroporation system may include an ablation device (210), a signal generator (222), electrical components (e.g., medical electronic devices or equipment) (228), a catheter device (230), and protective devices (e.g., protective circuitry) (250). In some embodiments, the electrical component (228) may be implemented as a cardiac pacing system. The signal generator (222) may 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) may be configured to generate an ablation pulse waveform delivered to the tissue by the electrodes (212) of the ablation device (210). In some embodiments, the catheter device (230), implemented as a pacing device (230), may be configured to pace the heart and measure cardiac activity using respective pacing electrodes (232) and signal electrodes (234). In some embodiments, the electrical component (228) may be implemented as a monitoring device or apparatus that may be coupled to one or more sensors (e.g., electrodes) (232, 234, 271) for measuring the patient's physiological data. In some embodiments, the sensors (e.g., electrodes (271)) may be placed externally on the patient's surface. A protective device (250) may be coupled between the electrical component (228) and the electrodes (232, 234) or electrodes (271) of the catheter device (230). In some embodiments, the protective 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).

[0053] In some embodiments, a distal portion of the ablation device (210) may be introduced into the endocardial space (e.g., the left atrium) of the heart (202), for example, via a transseptal puncture through the interatrial septum. The distal end of the ablation device (210) may 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) may be placed near the internal radial surface of an inner lumen (e.g., one or more pulmonary vein orifices) (not shown) to deliver a pulsed waveform to the ablated tissue. In some embodiments, the electrodes (212) of the ablation device (216) may be a set of independently addressable electrodes. Each electrode may include an insulated lead configured to maintain a voltage potential of at least about 700 V without dielectric breakdown of its corresponding insulation layer. In some embodiments, the insulation on each lead may maintain a potential difference of about 200 V to about 3000 V over its thickness without dielectric breakdown. In some embodiments, the set of electrodes may include multiple electrodes. Multiple electrodes can be grouped into one or more anode-cathode subsets, such as a subset comprising one anode and one cathode, a subset comprising two anodes and two cathodes, a subset comprising two anodes and one cathode, a subset comprising one anode and two cathodes, a subset comprising three anodes and one cathode, a subset comprising three anodes and two cathodes, and / or similar cases.

[0054] The signal generator (222) can be configured to generate ablation pulse waveforms for irreversible electroporation of tissues such as, for example, pulmonary vein orifices. For example, the signal generator (222) can be a voltage pulse waveform generator and deliver the pulse waveforms to the ablation device (210).

[0055] In some embodiments, the signal generator (222) is configured to generate an ablation pulse waveform (e.g., within a common refractory period window) in sync with an indication of a pacing signal. For example, in some embodiments, the common refractory period window may begin immediately after a ventricular pacing signal (or after a very small delay) and continue thereafter for a duration of approximately 250 milliseconds (ms) or less. In such embodiments, the entire pulse waveform may be delivered within this duration.

[0056] A protection device (250) may be coupled between the electrical component (228) and the catheter device (230). As described in more detail herein, a control signal (also referred to herein as a protection signal) may be generated to synchronize the operation of the protection device (250) with the generation of a pulse waveform by a signal generator (222). The protection device (250) may be configured to receive the control signal to control the state of the electrical connection between the catheter device (230) and the electrical component (228). For example, the protection device (250) may be configured to form an open circuit between the electrical component (228) and the catheter device (230) at least during the delivery of ablation energy by the ablation device (210). Alternatively, the protection device (250) may be configured to electrically couple the pacing device (230) to the electrical component (228). In some embodiments, the protection device (250) may be configured to provide bidirectional open-circuit isolation during high-energy ablation energy delivery. In some embodiments, the protection device (250) may be formed separately from the electrical components (228) and / or the catheter device (230), and in other embodiments, the protection device (250) may be integrated into one or more electrical components (228) and / or the catheter device (230). In some embodiments, the protection device (250) may include one or more of an internal power supply (e.g., a battery) and a power connector coupled to an external power supply (e.g., a medical-grade power supply, a wall socket). The internal power supply may reduce ground noise injection.

[0057] In some embodiments, the electrical components (228), protection devices (250), and / or signal generators (220) may communicate with each other, for example, to coordinate the timing of pulse waveform delivery, pacing signal delivery, and / or protection device control signal delivery. In some embodiments, the protection devices (250) and / or signal generators (220) may communicate with each other, for example, to coordinate the timing of pulse waveform delivery, pacing signal delivery, and / or protection device control signal delivery. In some embodiments, the protection devices (250) may be integrated with the signal generators (222) in a single control console.

[0058] In some embodiments, electrical components (228), protection devices (250), and / or signal generators (220) may communicate with other devices (not shown) via, for example, one or more networks, each of which may be any type of network. A wireless network can refer to any type of digital network that is not connected by any type of cable. However, a wireless network may connect to a wired network 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, coaxial, 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 networks (CANs), global area networks (GANs) like the Internet, and virtual private networks (VPNs). In the following, a network refers to any combination of wireless, wired, public, and private data networks typically interconnected via the Internet to provide a unified network and information access solution. The system (100) may also include one or more output devices, such as displays, audio equipment, touchscreens, and combinations thereof.

[0059] Electrical components (228), protection devices (250), and / or signal generators (220) may include one or more processors, which may be any suitable processing device configured to run and / or execute a set of instructions or code. The processor may be, for example, a general-purpose processor, a field-programmable gate array (FPGA), an application-specific integrated circuit (ASIC), a digital signal processor (DSP), etc. The processor may be configured to run and / or execute application processes and / or other modules, processes, and / or functions associated with the system and / or a network (not shown) associated with it. The underlying device technology may be provided in various component types, such as metal-oxide-semiconductor field-effect transistor (MOSFET) technology like complementary metal-oxide-semiconductor (CMOS), bipolar technology like emitter-coupled logic (ECL), polymer technologies (e.g., silicon conjugated polymers and metal conjugated polymer metal structures), hybrid analog and digital, and / or similar technologies.

[0060] The electrical components (228), protection devices (250), and / or signal generator (220) may include one or more memories or storage devices, such as random access memory (RAM), memory buffers, hard disk drives, erasable programmable read-only memory (EPROM), electrically erasable read-only memory (EEPROM), read-only memory (ROM), flash memory, etc. The memories may store instructions to cause the processor of any of the electrical components (228), protection devices (250), and / or signal generator (220) to execute modules, processes, and / or functions, such as pulse waveform generation, isolation / protection, and / or cardiac pacing.

[0061] Although Figure 4 A system comprising electrical components (228) separate from the signal generator (220) is depicted, but in some embodiments, one or more electrical components (228) may form part of and / or be integrated into the signal generator (222). In some embodiments, one or more electrodes (212, 232, 234) may be used as sensing electrodes.

[0062] Figure 5 This 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 circuitry (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) that can receive a control signal 352 (e.g., isolation / optical coupling). The protection device (300) can be configured to reduce high-voltage coupling to connected devices. For example, the protection device (300) can be configured to withstand voltages up to approximately 3000 V delivered by an ablation device. The protection device (300) can be configured to switch between a closed-circuit configuration and an open-circuit configuration based on a received protection signal (352) (e.g., a control signal), such that the protection device (300) is in an open-circuit configuration during the duration of high-voltage ablation energy delivery and in a closed-circuit configuration at other times, so as to be able to deliver pacing signals, for example.

[0063] The protective device described in this article can be a standalone piece of equipment, or it can be integrated into auxiliary equipment or a pulse field ablation stimulator. Figures 10A-10E It is a block diagram of a group of systems including protection devices that are both integrated with and separate from other system components. Figures 10A-10E In this context, the protection device may include any other protection device that is structurally and / or functionally similar to those 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 19The components of the protective device shown. Figure 10A A signal generator (800) (e.g., for pulsed electric field ablation) is shown, which includes a protection device (810) integrated therewith. For example, one or more of the signal generator (800), 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 housing (e.g., a housing, a signal generator console). This allows sensitive electronic circuitry to be protected from high-voltage noise within the same housing. 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 point of high-voltage exposure (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, allowing the protection device (810) to time its blanking intervals to coincide with the time of potential high-voltage exposure. Figure 10A In 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 required for the 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 inside and outside the signal generator (800), thereby providing coordinated and robust protection.

[0064] In some embodiments, a manually operated switch may be configured to protect the device from noise caused by ablation.

[0065] In some embodiments, the signal generator and protection device may be monolithic components (e.g., formed in separate housings). In such embodiments, control signals can be transmitted between the signal generator and 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 standalone protection devices, the protection device may be battery-powered or wall-powered, for example using medical-grade isolation, but battery-powered protection devices may require less grounding noise injected into the patient from isolated wall power. Figure 10B A signal generator (800) is shown that is 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 that is coupled to a protection device (810) via a wireless connection. For example, the protection device (810) may include a wireless transceiver (830) configured to receive control signals (e.g., transmitted from the signal generator (800)).

[0066] In embodiments where the protective device is implemented independently of the signal generator (e.g., a pulsed field ablation generator), the protective device requires a mechanism to synchronize with the delivery of the high-voltage pulse, enabling effective isolation of certain electronic components during such delivery. In some embodiments, based on one or more of a timed trigger pulse from the stimulator, stimulation pulse sensing (e.g., stimulation pulses for cardiac capture), measured cardiac activity (e.g., R-wave detection and / or high-voltage sensing (e.g., rapid application of isolation upon detection of a high-voltage spike on the patient side)), the protective signal can synchronize the electrical isolation of specific electronic components (e.g., the stimulator) with the delivery of ablation energy to the tissue. (Refer to below) Figure 12 To elaborate further. Figure 10D and Figure 10E Two configurations for implementing synchronization are shown. This configuration is similar to the reference. Figure 7A-9 The configurations described. 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 ablation energy delivery performed by the signal generator (800) and the electrical isolation performed by the protection device (810) by outputting corresponding 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 the 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 predetermined threshold (e.g., 5 V) can be set high enough to reduce the likelihood of false alarm sensing, which could undesirably increase the occurrence of isolation and disconnection of protected electrical components from the patient.

[0067] 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 This is a block diagram of a system (910) coupled to a patient (900). One or more devices of the system (910) (e.g., pacing devices, catheters, needles, probes, electrodes, etc.) may be coupled to the patient (900) and may be susceptible to induced currents from high-voltage ablation energy delivery. Each device of the system (910) may be coupled to a protection device (920), which is configured to selectively electrically isolate electrical components located downstream of the protection device (920) from those parts of the device located in the heart and exposed to high voltage. The protection device (920) may include any other protection device structurally and / or functionally similar to those described herein (e.g., Figure 3A , Figure 3B , Figure 4 , Figure 5 , Figure 8 , Figures 10A-10E , Figure 12 , Figure 14-16 , Figure 18 and Figure 19 The components of the protection device shown. In some embodiments, a single protection signal (924) may be configured to control the protection device (920) and simultaneously provide electrical isolation for multiple electronic components, for example by protection elements implemented as multiple switches (922). In some embodiments, one or more switches (922) may include electromechanical relays (e.g., reed relays), solid-state relays, and / or MOSFET devices. For example, one or more switches (922) may include two back-to-back MOSFETs having a common source terminal, such as Figure 5 As shown.

[0068] In some embodiments, such as when the protection device is implemented as a stand-alone system and no signal is transmitted from the high-voltage pulse generator (e.g., for pulse field ablation), the operation of the protection device may be synchronized based on stimulation pulse sensing, trigger pulses from a cardiac stimulator, R-wave sensing, or high-voltage sensing. Figure 12 This is a schematic diagram of an electroporation system disposed in the heart (1002) of a patient (1000), comprising 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) may be coupled to the ablation device (1010). The signal generator (1022) may be configured to generate pulse waveforms of electrodes (1012) delivered to the ablation device (1010) to generate a pulsed electric field for ablation. The pacing device (1030) may be configured to pace the heart (1002) using pacing electrodes (1032, 1034) and / or measure cardiac activity (e.g., electrocardiogram) of the heart (1002) using one or more electrodes (e.g., electrodes (1032, 1034) or other electrodes (not shown)). A protective device (1050) may be coupled between the cardiac stimulator (1028) and the pacing device (1030). The protective device (1050) may include any other protective device structurally and / or functionally similar to those described herein (e.g., Figure 3A , Figure 3B , Figure 4 , Figure 5 , Figure 8 , Figures 10A-10E , Figure 11 , Figure 14-16 , Figure 18 and Figure 19 Components of the protective device shown.

[0069] In some embodiments, the protection device (1050) may 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) may be synchronized based on the same signal or combination of signals as the signal generator (1022), or independently based on one or more of the following: a stimulation signal (1060) from the cardiac stimulator (1028) (which may also be sent to the signal generator (1022)), measurement data (e.g., a stimulation pulse detection signal (1070), an R-wave detection signal (1090), and a high-voltage detection signal (1092)), and a signal generator signal (1080). In alternative embodiments, the protection device (1050) and the signal generator (1022) may be activated based on different signals or different combinations of signals. For example, the protection device (1050) may be controlled based on a cardiac pacing signal (1060), and the pulse waveform delivery may be based on a detected R-wave signal (1090). In embodiments using stimulation pulse sensing, sensing can be implemented with a predetermined threshold (e.g., about 5 V) to reduce false alarms that could increase the number of disconnections between the cardiac stimulator (1028) and / or other protected electronics and the patient (1000). To provide an additional layer of safety, protective devices for any external electronics can be configured to provide a low-impedance connection between the protected electronics and the patient when not powered. Figure 14 This 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, cardiac stimulators, any of those described herein) may be coupled to the patient (1220) and may be susceptible to induced currents from high-voltage ablation energy delivery. Each of the electrical components (1210) may be coupled to the protection device (1200) to selectively electrically isolate those components from devices located in the heart of the patient (1220). The protection device (1200) may include any other protection device structurally and / or functionally similar to those described herein (e.g., Figure 3A , Figure 3B , Figure 4 , Figure 5 , Figure 8 , Figures 10A-10E , Figure 11 , Figure 12 , Figure 15 , Figure 16 , Figure 18 and Figure 19 Components of the protective device shown.

[0070] The protection device (1200) can be configured such that when the protection device (1200) is not powered, the electrical component (1210) is electrically coupled to the patient (1220) (e.g., via a low-impedance connection). This safety feature allows the patient to connect by default and allows the electrical component (1210) to operate even when the protection device (1200) is de-energized. For example, when the protection device (1200) is de-energized, a cardiac stimulator (e.g., cardiac stimulator (28)) included in the electrical component (1210) can provide pacing to the patient (1220).

[0071] A first signal (1202) (e.g., a control signal) may be configured to control the protection device (1200) and provide electrical isolation via a first switch (1206) described herein. A second signal (1204) (e.g., a power signal) may be configured to control the protection device (1200) via a second switch (1208). In some embodiments, the second switch (1208) may include a relay (e.g., a reed switch or a solid-state switch) configured to be connected in parallel with the first switch (1206) for isolation / blanking and configured to disconnect when the protection device (1200) is energized. In some embodiments, the first switch (1206) may include an electromechanical relay (e.g., a reed relay), a solid-state relay, and / or a MOSFET device. For example, the first switch (1206) may include two back-to-back MOSFETs having a common source terminal, such as... Figure 5 As shown. The second path provided via the second switch (1208) can typically be set to a closed state to provide a low-impedance connection between the electrical component (1210) and the patient (1220).

[0072] Figure 15 Another example embodiment of a system including a protection device (1300) is provided. Specifically, Figure 15 This 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 stimulator) may be coupled to the patient (1320) via the protection device (1300), which is configured to selectively isolate those electrical components (1310) from devices disposed in the heart of the patient (1320), for example via a first signal (1302). The protection device (1300) may include any other protection device structurally and / or functionally similar to those described herein (e.g., Figure 3A , Figure 3B , Figure 4 , Figure 5 , Figure 8 , Figures 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 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 METHODSFOR FILTERING HIGH VOLTAGE NOISE INDUCED BY PULSED ELECTRIC FIELD ABLATION,” the entire contents of which are incorporated herein by reference.

[0073] In some cardiac stimulators (e.g., electrophysiology laboratory stimulator systems), a high impedance of 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 16This is a block diagram of electrical components (1410) coupled to a patient (1420). One or more electrical components (1410) (e.g., monitoring equipment, cardiac stimulator) may be coupled to the patient (1420) via a protective device (1400) configured to selectively electrically isolate these components from devices disposed in the heart of the patient (1420) via a signal (1402). The protective device (1400) may include any other protective device structurally and / or functionally similar to those described herein (e.g., Figure 3A , Figure 3B , Figure 4 , Figure 5 , Figure 8 , Figures 10A-10E , Figure 11 , Figure 12 , Figure 14 , Figure 15 , Figure 18 and Figure 19 Components of the protective device shown.

[0074] A cardiac stimulator included in the electrical components (1410) can continuously monitor the electrical connection with the patient (1420) and generate a disconnection signal (e.g., an alarm signal to the user) upon detecting a disconnection (e.g., high impedance). In some embodiments, to suppress the generation of a disconnection signal by the system (1410) during a protection interval of the protection device (1400), the protection device (1400) can provide the cardiac stimulator with a predetermined impedance (1440) (e.g., between about 100 ohms and about 10 kiloohms), which is within the range where the stimulator is expected to correspond to normal operation. For example, the protection device (1400) operating during the protection interval can send a signal to close a switch connected in series with a resistor (1440), which can then provide a fixed impedance value. The rapid transition between “patient connection” and “open circuit of fixed resistor load” can be fast enough to prevent the cardiac stimulator from issuing any warnings or alarms. In some embodiments, it may be useful to first connect the load to the electrical components within a short time interval (e.g., about 1 μs to 100 μs) before disconnecting the patient connection. If this is done, the electrical components will have an open circuit for a considerable period of time. The patient connection can then be connected before the resistive load is disconnected (e.g., immediately before). Another implementation optimization is to provide "load resistors" on both sides (including the patient side) to achieve symmetry in the implementation and to allow for the insertion of protective devices in any manner.

[0075] In some cases, use such Figure 16 The protective devices implemented in the system may introduce switching artifacts and short voltage spikes in patients. Figure 17A and Figure 17BThis is a schematic diagram of the time series of the cardiac stimulation (1510), electrocardiogram (1520), pulse field ablation delivery (1530), and protection interval (1540) channels, where a switching artifact may occur when the protection interval ends (1526). Figure 17A A single cardiac cycle is shown, and Figure 17B Multiple cardiac cycles are illustrated, as described in more detail herein. The stimulation or pacing signal (1510) may be periodic and may comprise rectangular pulses with a width between about 0.1 ms and about 100 ms. In some embodiments, any pacing device described herein (e.g., pacing devices (230, 630, 1030)) may be used to deliver the pacing pulse (1512). The pacing pulse (1512) may correspond to one or more of ventricular and atrial cardiac pacing. In response to the pacing pulse (1512), the cardiac cycle may be synchronized with the pacing pulse (1512). For example, Figure 17A and Figure 17B The QRS waveform (1522) in the pulse is synchronized with the pacing pulse (1512).

[0076] In some embodiments, the pulse waveform (1532) and the guard interval (1542) may 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 embodiments above. For example, the pulse waveform (1532) may have a first length, and the guard interval (1542) may have a second length at least as long as the first length. The pulse waveform (1532) may be delivered after a first delay (1534) following the trailing edge (1514) of the cardiac pacing pulse (1512). The first delay (1534) may be a predetermined value. For example, the first delay (1534) may be between about 1 ms and about 20 ms. Similarly, the guard interval (1542) may be synchronized with the cardiac pacing pulse (1512) after a second delay (1544). In this way, the cardiac pacing signal (1512) may be configured to trigger the pulse waveform (1532) and the guard interval (1542).

[0077] Including, such as Figure 16 In embodiments of the protective device implemented in the study, switching artifacts (1526) (e.g., voltage spikes) may be introduced into the patient and picked up in an electrocardiogram (1520) (e.g., via an electrocardiogram recording system), which may interfere with the analysis of cardiac activity. For example, the protective artifact (1526) may coincide with the trailing edge (1528) of the protective interval (1542). Figure 17BAn embodiment is shown in which a protection interval (1542) is provided for each heartbeat and an artifact (1526) can be generated, for example, for each protection interval / heartbeat. In some embodiments where less coordinated control of the protection device is available, one or more protection intervals (1542) may be provided without a corresponding pulse waveform (1532). For example, this may occur in embodiments where the pulse waveform (1530) and the protection signal (1540) are independently synchronized using different signals.

[0078] When artifacts (1526) are large enough, they can lead to clinical misinterpretations of cardiac activity. Several options exist to mitigate this risk. First, the protection module can be integrated with the signal generator such that a protection interval (1542) is provided only when the corresponding pulse waveform (1532) is present, and not when no pulse waveform (1532) is being delivered. Thus, a protection interval (1542) is provided when it is necessary to electrically isolate the cardiac stimulator or other protected electrical components (e.g., monitoring equipment) from the high-voltage pulse waveform. With this implementation, unnecessary protection switching does not occur, and the high-voltage ablation energy delivered to the cardiac tissue saturates the heartbeat for artifacts (1526) generated by the pulse waveform, preventing the artifacts (1526) from causing problems.

[0079] Secondly, for independent protection devices that may have less coordinated control with the pulse field ablation device, switching artifacts (1526) can be reduced, for example, by placing low-value capacitors on the disconnector or between protected channels to absorb some of the high-frequency local switching energy in the protection device. See, for example, Figure 2 Alternatively, the previously described passive filtering component can be implemented to reduce artifacts (1526). Other options include temporarily shorting the signal pairs together using additional switches / MOSFETs before reconnection to the patient (e.g., stimulator + / - and patient + / -), temporarily turning on the resistive load on the patient side during the blanking interval, etc.

[0080] Figure 18 This is a block diagram of electrical components (1610) coupled to a patient (1620) via a protective device (1600) including one or more capacitors for reducing artifacts. One or more electrical components (1610) (e.g., monitoring equipment, cardiac stimulator) may be coupled to the patient (1620) via the protective device (1600), which is configured to selectively electrically isolate these components from devices disposed in the heart of the patient (1620). In some embodiments, the protective device (1600) may be configured to reduce the size of artifacts (e.g., artifact (1526)). The protective device (1600) may include any other protective device structurally and / or functionally similar to those described herein (e.g., Figure 3A , Figure 3B , Figure 4 , Figure 5 , Figure 8 , Figures 10A-10E , Figure 11 , Figure 12 , Figure 14-16 and Figure 19 Components of the protective device shown.

[0081] The protection device (1600) may include one or more series-connected protective switches (1602) and resistors (1606). The protection device (1600) may also include one or more capacitors (1604) configured in parallel with the respective switches (1602) and resistors (1606). The capacitors (1604) may be configured to receive a portion of any voltage spikes generated by the switching operation of the protection device (1600). Additionally or alternatively, the protection device (1600) may include... Figure 15 The circuit components described herein are configured to reduce switching artifacts (e.g., filter device (1330), common mode protection device (1340), differential / high voltage protection device (1350)).

[0082] The resistor (1606) can be arranged in series with a switch, which can be configured to close before the series protective switch (1602) is closed to reduce artifacts caused by the switching of the protective switch (1602). For example, the switch in series with the resistor (1606) can be configured to close before the series protective switch (1602) is closed to provide a temporary path for one or more electrical components (1610) and the patient (1620), thereby reducing the risk of artifacts from the series protective switch (1602) when the load is subsequently disconnected.

[0083] Figure 19 This is a schematic diagram of a system for ablation via irreversible electroporation, including a protective device (1900). The system may include a signal generator (1930), an ablation device (1932), and electronic components (1940). In some embodiments, the electronic components (1940) may be implemented as a signal detector, such as a monitoring device for monitoring physiological data of a patient (1920). The protective device (1900) may include other protective devices structurally and / or functionally similar to those described herein (e.g., Figure 3A , Figure 3B , Figure 4 , Figure 5 , Figure 8 , Figures 10A-10E , Figure 11 , Figure 12 , Figure 14-16 , Figure 18 and Figure 19Components of the protective device shown.

[0084] A signal generator (1930) can be configured to generate pulse waveforms delivered to tissue by electrodes (not shown) of an ablation device (1932). In some embodiments, the signal generator (1930) can be configured to generate high-voltage ablation pulse waveforms for irreversible electroporation of tissue, such as, for example, the pulmonary vein orifice. In some embodiments, a protective device (1900) can be electrically coupled to a patient (1920) via a set of patient connections (1924). For example, one or more electrodes and / or sensors can be placed externally and / or internally to the patient (1920), for example, to measure physiological data of the patient (1920). The protective device (1900) can be coupled between the patient (1920) and the electronic components (1940).

[0085] In some embodiments, the signal generator (1922) may be configured to generate a pulse waveform synchronously with and / or within a refractory period window in response to a pacing signal. For example, in some embodiments, the common refractory period window may begin substantially immediately after the pacing signal (or after a very small delay) and thereafter last for a duration of approximately 250 milliseconds (ms) or less. In such embodiments, the entire pulse waveform may be delivered within this duration.

[0086] In some embodiments, the electronic components (1940), the protection device (1900), and / or the signal generator (1930) can communicate with each other, for example, for coordinating the timing of pulse waveform delivery and / or the timing of protection device control signal delivery. For example, the signal generator (1930) can be operatively 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), for example, to synchronize the operation of one or more components of the protection device (1900) with the delivery of the ablation pulse waveform. In one embodiment, the signal generator (1930) can periodically deliver the synchronization signal (1912) to the protection device (1900), which indicates to the protection device (1900) the timing of pulse waveform delivery. 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 control console.

[0087] The protection device (1900) can be configured to form an open circuit between the electronic component (1940) and one or more patient connections (1924) (e.g., sensors or electrodes placed near the ablation site) at least during the delivery of ablation energy by the ablation device (1932). The patient connections (1924) can allow the electronic component (1940) to monitor physiological data of the patient (1920). As described herein, the delivery of pulse waveforms to the patient (1920) can induce high voltages and / or currents in the patient connections (1924). Therefore, by isolating these connections (1924) from the electronic component (1940), the protection device (1900) can reduce or prevent such induced voltages and / or currents from being transferred to the electronic component (1940), thereby reducing noise interference entering and / or damaging the component. When the pulse waveform is not delivered to the patient (1920), the protection device (1900) can be configured to electrically couple the electronic component (1940) to the patient connection (1924), for example, to allow the electronic component (1940) to continue monitoring the patient's (1920) physiological data.

[0088] The protective device (1900) may include a set of one or more switches (e.g., series components) (1902) configured to form an open circuit between the patient connection (1924) and the electronic components (1940). This set of switches (1902) may include one or more electromechanical relays (e.g., reed relays), solid-state relays, and / or MOSFET devices.

[0089] In some embodiments, a component may be introduced that can electrically connect the protected patient signal to a common node (1906). For example, the protection device (1900) may include channels extending from each input into the electronics (1940) and connecting them to the common node (1906). Each channel may 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 electronics (1940) to the common node (1906). The resistive element (1904) may be coupled between the input and the common node (1906). The resistive element (1904) may be configured to reduce or minimize impedance when connecting the input to the common node (1906). During pulse field ablation (e.g., delivery of a pulse waveform), in order to reduce noise present at the inputs of the electronics (1940) (e.g., monitoring equipment), the inputs may be shorted together to reduce the amplitude of any differential noise. The switch (1902) may be open, for example, to isolate the electronic component (1940) from the patient connection (1924), however, any residual noise transferred or picked up by the open-circuit serial component (e.g., switch (1902)) during pulse field ablation delivery may be tied to the common node (1908), and the signal amplitude detected at the electronic component (1940) (e.g., measured by monitoring equipment) may be reduced or diminished.

[0090] In some embodiments, a component that can connect the common node (1906) to ground (1909) (e.g., chassis or grounding) may be introduced, for example, to further reduce noise that may be picked up at the input to the electronic component (1940) during pulsed field ablation delivery. By coupling the input, which is electrically tied together (e.g., through the common node (1906)), to the ground connection, the protection device (1900) can reduce the amplitude of common-mode noise and prevent large DC voltages above ground from being transferred to the electronic component (1940) (e.g., the input amplifier of the monitoring device). Coupling the common node (1906) to ground (1909) can also reduce the chance of interference from pulsed field ablation delivery affecting the electronic component (1940).

[0091] In some embodiments, components that can filter high-frequency signals at the ground connection (e.g., earth ground connection) of the signal generator (1930) and / or protection device (1900) (or other protection circuitry) may be introduced. For example, the signal generator (1930) may be coupled to ground via an inductive filter (e.g., ferrite clamp, ferrite toroidal coil, or series inductor) (1914). Alternatively, the protection device (1900) may be coupled to ground via an inductive filter (e.g., ferrite) (1901). Noise generated by the signal generator (1930) during ablation delivery may be conducted through the patient to the patient connection (1902), but may also be emitted at the ground connection of the signal generator (1930). To reduce noise caused by the connection from the signal generator (1930) to ground, components such as ferrite clamps, ferrite toroidal coils, or series inductors (e.g., filters (1914)) can be used to filter high-frequency noise on these connections and reduce the amplitude measured at the ground connection of the electronic components (1940).

[0092] Figures 20A-20C This is a time-series diagram illustrating the establishment of connections between one or more inputs or signals to the electronic component (1940), the common node (1906), and ground (1909) during pulsed field ablation delivery. The time series (2012, 2014, 2016) represents the timing of connecting the input to the electronic component (1940) to the common node (1906), the time series (2022, 2024, 2026) represents the timing of connecting the common node (1906) to ground (1909), the time series (2032, 2034, 2036) represents the timing of forming an open circuit between the patient connection (1924) and the electronic component (1940) using a series component or switch (1902), and the time series (2042, 2044, 2046) represents the timing of pulse waveform delivery (e.g., via a signal generator (1930)).

[0093] Figure 20AA time series (2010) is shown for components used to operate a protective device (1900) that connects its inputs to an electronic component (1940) via a common node (1906) and simultaneously connects the common node (1906) to ground (1909), as shown in (2012, 2022). As illustrated, the time series (2010) allows the electronic component (1940) to continue seeing a low impedance load between its inputs (e.g., from the patient connection (1924)) throughout the ablation delivery process, ensuring a low common-mode DC level. The time series (2010) ensures that the inputs to the electronic component (e.g., from the patient connection (1924)) are not high impedance, which could undesirably allow for large noise pickup. After connecting and grounding the inputs to the electronic component (1940) (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 the open state), which isolates the electronic component (1940) from the patient (1920), as shown in (2032). After establishing the open circuit, a pulse waveform can be delivered to the ablated tissue, as shown in (2042). After the ablation process is complete and the pulse waveform is no longer delivered to the patient (1920), the series components can reconnect the patient (1920) to the electronic device (1940). Subsequently, the inputs to the electronic component (1940) can be released from their common node and ground connection (e.g., switch (1903) can be set to the open state), and the electronic component (1940) can be reconfigured to receive data (e.g., physiological data) from the patient connection (1924) without any pulse field ablation interference.

[0094] Figure 20B Another time series (2020) of components used for operating the protective device (1900) is depicted. Figure 20B The time series (2020) is similar to Figure 20AThe time series (2010) shows that the connection from the common node (1906) to ground (1909) does not occur simultaneously with the connection from the input of the electronic component (1940) to the common node (1906). In some embodiments, the connection from the common node (1906) to ground (1909) (e.g., switch (1908) switches to the closed state) may occur when the series component of the protection device (1900) switches to an open configuration (e.g., switch (1902) switches to the open state), as shown in (2024, 2034). This ensures 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 switched to the open state. By preventing the patient (1920) from being temporarily grounded, any residual current in the system does not have a path from the patient (1920) to ground. Then, once the patient signal is open (e.g., switch (1902) is switched to the open state), energy (e.g., an ablation pulse waveform) can be delivered to the patient (1920), and after the energy delivery is complete, the patient signal can be reconnected (e.g., switch (1902) is switched back to the closed state), while the ground connection is released (e.g., switch (1908) is switched back to the open state). After these events, the input to the electronic component (1940) can be released from the common node (1906) to allow the electronic component (1940) to measure the patient signal again via the patient connection (1924) without interference or noise from the ablation energy delivery.

[0095] Figure 20C Another time series (2030) of the components used to operate the protective device (1900) is depicted. Figure 20C The time series (2030) is similar to Figure 20A and Figure 20BThe time series (2010, 2020) is such that no connection is formed between the common node and ground at any point during the sequence, allowing the common node (1906) to remain floating. This ensures that the ground (1909) input connection does not interfere with the input of the electronic component (1940). As mentioned above, during ablation, high-frequency signals can travel from the signal generator (1030) and / or other components of the system to ground (1909). Therefore, establishing a connection to ground (1909) could cause such signals to interfere with the operation of the electronic component (1940), for example, by generating noise. While the aforementioned inductive filters (1901, 1914) can be used to reduce some of these high-frequency signals, it may be necessary to adjust such inductive filters (1901, 1914) based on whether the individual components of the system are in an on or off state, and therefore may be imperfect in filtering high-frequency signals. Similar to the time series (2010, 2020), series components can be switched to an open state, and ablation energy can be delivered when series components are in an open state. After delivering ablation energy, the serial component can switch back to a closed-loop state, reconnect the patient connection (1924) to the electronic component (1940), and release the input to the electronic component (1940) from the common node (1906).

[0096] method

[0097] This document also describes methods for protecting electronic circuitry from induced currents and voltages during tissue ablation procedures performed in one or more cardiac chambers using the systems and devices described herein. In one embodiment, the cardiac chamber may be the left atrium and ventricle, and includes its associated pulmonary veins. Typically, the methods described herein involve introducing and positioning a pacing device (e.g., a pacing device (230)) in contact with one or more cardiac chambers. The pacing device may use a cardiac stimulator (e.g., cardiac stimulator (28, 28')) to deliver pacing signals to the heart and / or measure cardiac activity. An ablation device (e.g., ablation device (210)) may be introduced and configured to contact one or more pulmonary vein openings or sinus regions. A pulse waveform may be delivered to the ablated tissue by one or more electrodes of the ablation device (e.g., electrode (212)). In some embodiments, a protection device (e.g., protection device (250)) may be in an open-circuit configuration to isolate one or more sensitive electrical components (e.g., cardiac stimulator, monitoring equipment) during the delivery of the pulse waveform. Such electrical components may otherwise be electrically coupled to the pacing device and configured to deliver pacing signals to the heart and / or receive measurements of cardiac activity. In some embodiments, a control signal may be generated to control the open-circuit interval (e.g., protection interval) of the protection device. The control signal may be based on one or more of the cardiac pacing signal, pulse waveform signal (e.g., signal generator signal), measured cardiac activity (e.g., R-wave detection), and combinations thereof.

[0098] Additionally or alternatively, the pulse waveform may include multiple levels of hierarchy to reduce the total energy delivery, for example, as described in International Application Serial No. PCT / US2019 / 031135, filed May 7, 2019, entitled “SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OFABLATIVE ENERGY TO TISSUE”, which is incorporated herein by reference.

[0099] In some embodiments, the ablation device described herein (e.g., ablation device (210)) may 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 above by reference.

[0100] Figure 6AThis is an example method (400) of tissue ablation, wherein ablation energy is delivered synchronously with cardiac pacing. In some embodiments, the voltage pulse waveform described herein may be applied during the refractory period of the cardiac cycle to avoid interruption of the sinus rhythm of the heart. Method (400) includes introducing a pacing device (e.g., pacing device (230)) into an endocardial space, for example, the endocardial space of the right ventricle, at (402). At (404), the pacing device may be advanced to be positioned in contact with cardiac tissue. For example, sensor electrodes may be configured for measuring cardiac activity (e.g., ECG signals), and pacing electrodes may be configured to deliver pacing signals and may be positioned in contact with an inner endocardial surface, for example, in the right ventricle. At (406), an ablation device (e.g., ablation device (210)) may be introduced into an endocardial space, for example, the endocardial space of the left atrium. At (408), the ablation device may be advanced to be positioned in contact with the pulmonary vein orifice. In some embodiments, at (410), a pacing signal may be generated by a cardiac stimulator (e.g., 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 electrodes of the pacing device. For example, the pacing signal can be used to electrically pace the heart to ensure pacing capture, thereby establishing periodicity and predictability of the cardiac cycle. One or more of atrial and ventricular pacing may be applied. Examples of applied pacing signals related to a patient's cardiac activity are described in more detail herein, such as... Figure 7B .

[0101] In some embodiments, pacing capture may be automatically acknowledged by one or more of a signal generator (e.g., signal generator (222)), a cardiac stimulator, or other processors operatively coupled to one or more components of the system. In some embodiments, pacing capture may be acknowledged by a user. For example, a user may acknowledge pacing capture using a user interface (e.g., an input / output device, such as a touchscreen monitor or other type of monitor) based on measured cardiac activity signals. If the signal generator, processor, and / or the user viewing the displayed cardiac output determines that pacing capture is absent, pulse waveform generation may be disabled, and the user may be prompted (e.g., by 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.).

[0102] In some embodiments, at (414), the pacing device can measure cardiac activity (e.g., ECG signal) corresponding to the heart's electrical activity. For example, the measured cardiac activity may include measured cardiac pacing pulses, R waves, etc.

[0103] A control signal or protection signal may be generated based on one or more of the following: cardiac pacing signals, pulse waveform signals (e.g., signals received from a signal generator), measured cardiac activity (e.g., R-wave detection, predetermined voltage thresholds), and combinations thereof, and applied to the protection device at (418). For example, the protection signal may be generated based on cardiac pacing signals received from a cardiac stimulator (e.g., cardiac stimulator (28)) or ECG signals measured by a pacing device (e.g., pacing device (230)). As another example, the protection signal may be generated at least in part based on pulse waveform signals received from a signal generator (e.g., signal generator (222)). The protection signal may have a predetermined time period and length. At (418), in response to the protection signal, the cardiac stimulator and / or other electronic components may be electrically isolated throughout the protection interval. For example, a protection device coupled to a pacing device can electrically isolate the cardiac stimulator from a high-voltage pulse electric field ablation signal delivered by an ablation system (e.g., a signal generator (222), an ablation device (210), etc.) based on a received protection signal.

[0104] In some embodiments, a protective signal can synchronize the electrical isolation of the cardiac stimulator with the delivery of ablation energy to the tissue. For example, the protective signal can be generated based on one or more of cardiac pacing signals, measured cardiac activity, and signal generator signals, as described in detail herein. Additionally or alternatively, the protective device can generate a protective signal even when the cardiac stimulator is not actively delivering a pacing signal during pulsed electric field ablation. This may be useful, for example, in medical emergencies requiring rapid cardiac pacing. Such protection can also be used to isolate electronic components frequently found in clinical procedure rooms (e.g., medical electronic devices 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 after the delivery of a set of ablation pulses, the protective device is deactivated (424) to restore connectivity between the medical device electrodes and the corresponding electronic components (e.g., medical electronic devices, cardiac stimulator, electroanatomical mapping system, ECG recording or monitoring system, device navigation / tracking system, etc.).

[0105] At (420), a signal generator (e.g., signal generator (222) or any associated processor) can be configured to generate a pulse waveform synchronized with a protection interval, for example, based on a predetermined criterion. For example, the pulse waveform can be generated during a refractory period that begins after and ends before the protection interval. The refractory period can follow a pacing signal. For example, a common refractory period can occur between atrial and ventricular refractory period time windows. A voltage pulse waveform can be applied within the common refractory period. In some embodiments, a pulse waveform and / or protection signal with an indicated time offset relative to the pacing signal can be generated. For example, the start of the refractory period can be offset by a time offset from the pacing signal. A voltage pulse waveform can be applied over a series of heartbeats within the respective common refractory period. In some embodiments, the pulse waveform and protection signal can be generated based on the same or different signals or information (e.g., pacing signal, sensed R wave).

[0106] At (422), in response to receiving a pulse waveform, the ablation device can generate an electric field (e.g., a pulsed electric field) delivered to the tissue.

[0107] In some embodiments, a hierarchical voltage pulse waveform with a nested structure and time interval hierarchy as described herein can be used for irreversible electroporation to provide control and selectivity across different tissue types. For example, the pulse waveform can be generated by a signal generator (e.g., signal generator (222)) and can include multiple levels in the hierarchy. Various hierarchical waveforms can be generated using the signal generator disclosed herein. For example, the pulse waveform can include a first level of a pulse waveform hierarchy containing a first set of pulses. Each pulse has a pulse duration and a first time interval separating consecutive pulses. A second level of the pulse waveform hierarchy can include multiple first sets of pulses as a second set of pulses. A second time interval can separate consecutive first sets 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 multiple second sets of pulses as a third set of pulses. A third time interval can separate consecutive second sets of pulses. The third time interval can be at least thirty times the duration of the second level time interval.

[0108] In some embodiments, the pulse waveform may be delivered to the pulmonary vein orifices of the patient via a set of splines of an ablation device (e.g., ablation device (210)), or to a device placed anywhere within the cardiac anatomy or more generally within other parts of the patient's anatomy. In some embodiments, the voltage pulse waveform as described herein may be selectively delivered to a subset of electrodes, such as an anode-cathode subset for ablation and isolation of the pulmonary veins. For example, a first electrode of a set of electrodes may be configured as an anode, and a second electrode of the set of electrodes may be configured as a cathode. These steps may be repeated so that a desired number of pulmonary vein orifices or sinus regions have been ablated (e.g., 1, 2, 3, or 4 orifices). Suitable examples of ablation devices and methods are described in International Application No. PCT / US2019 / 014226, which is incorporated herein by reference.

[0109] Figure 6B An example method of tissue ablation (1900) is described, in which ablation energy is delivered asynchronously (without cardiac pacing). At (1905), the ablation device is introduced into the patient's anatomy and positioned in the region of interest, such as the location in the cardiac anatomy where ablation is required. At (1909), the protective device can be activated, for example, by a suitable control signal that can be directly coupled to a hardware switching isolation circuit or a processor that controls the switching isolation circuit. As used herein, the control element can refer to one or more of the control signal, the processor, and the switching circuit (e.g., the switching isolation circuit). Thus, the electronic component or device to be protected is isolated from any ablation pulse that may be picked up during the isolation time interval. The pulse waveform is generated at (1913) and delivered to the tissue at (1917) during the isolation time interval. After the ablation pulse is delivered at (1917), the protective device is deactivated at (1920) to restore electrical connection between the electronic component or device and any relevant patient contact electrodes. Such protected electronic devices may include one or more cardiac stimulators, electroanatomical mapping systems, ECG recording / monitoring systems, device navigation / tracking systems, etc.

[0110] For example, in embodiments where a cardiac stimulator is used to pace the heart during a portion of a pulsed electric field ablation process, the patient connection between the cardiac stimulator and the heart needs to remain intact for the duration of the pacing or stimulation pulse. In such embodiments, a protective signal (e.g., a control signal for activating a protective device) can synchronize the electrical isolation of the cardiac stimulator with the delivery of ablation energy to the tissue. Figure 7A This is a schematic diagram of the time series of cardiac stimulation (510), pulsed electric field ablation delivery (530), and protective interval (540) channels (e.g., blanking or opening). Figure 7BThis is a schematic diagram of the time sequence of the cardiac stimulation (510), electrocardiogram (520), pulsed electric field ablation delivery (530), and protective interval (540) channels. The cardiac stimulation (510) may include a set of periodic pacing pulses (512). Each pacing pulse (512) may include a rectangular pulse with a width between about 0.1 ms and about 20 ms. The pacing pulses (512) may 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) may correspond to one or more of ventricular and atrial cardiac pacing. In response to the pacing pulses (512), the cardiac cycle may be synchronized with the pacing pulses (512). For example, Figure 7B The QRS waveform (522) is synchronized with the corresponding pacing pulse (512). The T wave (524) following the QRS waveform (522) corresponds to the onset of repolarization occurring in cardiomyocytes. In some embodiments, an electrocardiogram (520) can be measured using a pacing device.

[0111] In some embodiments, the high voltage application during the pulsed electric field ablation process can be synchronized with the cardiac cycle, such as... Figure 7A and Figure 7B As shown. Pacing can be synchronized with high voltage application in several ways. For example, atrial pacing, ventricular pacing, or multi-chamber pacing can be performed. Ventricular pacing may be desired because the ventricles are more susceptible to arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation) if stimulated during ventricular repolarization (e.g., T wave). When a stimulation pulse is applied, the high voltage output from pulsed electric field ablation can occur simultaneously with pacing or with a predetermined delay after the stimulation pulse.

[0112] In some embodiments, delivery of the pulse waveform (532) may begin with a first delay (534) (e.g., a time interval or cycle) after the trailing edge (514) of each pacing pulse (512). Each pulse waveform (532) may be applied during the interval (532). In some embodiments, the first delay (534) may be a predetermined value (e.g., input by a user). For example, the first delay (534) may be between about 1 ms and about 100 ms. A second pulse delay (536) may separate the end of the pulse waveform (532) from the beginning of the T wave. As mentioned above, it may be desirable to deliver the pulse waveform during the refractory period associated with the cardiac cycle. Therefore, the second pulse delay (536) represents a safety boundary between the pulse waveform (532) and the T wave (524).

[0113] The blanking interval or guard interval (542) can be configured to begin immediately or shortly after each pacing pulse (512). The guard interval (542) can be configured to encapsulate the duration for which the pulse waveform (532) is delivered. For example, the guard interval (542) can begin with a third delay (544) after the trailing edge (514) of the pacing pulse (512), wherein 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 not zero, such that the guard interval (542) (e.g., open-circuit state, blanking interval) does not overlap with the pacing pulse (512), because the stimulator and pacing device require a closed-circuit connection to deliver the pacing pulse (512). In some embodiments, the guard interval (542) is at least equal to and preferably greater than the first length of the pulse waveform (532), such that the guard interval (542) at least overlaps (e.g., encapsulates) the entire pulse waveform (532). Figure 7A and Figure 7B In the pulse waveform (532) and the leading and trailing edges (550) of the guard interval (542), the guard interval (542) is longer than the pulse waveform (532).

[0114] If the timing of the high-voltage application for pulsed electric field ablation is known (e.g., regarding the pacing or stimulation pulse of a cardiac stimulator), a protection interval (542) can be customized 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., a first delay (534)) between the stimulation pulse (e.g., a pacing pulse (512)) and the initiation of the high-voltage application on the patient (e.g., the leading edge (550) of the pulse waveform (532)). This delay can provide sufficient time for the protective element to transition to its isolated state (e.g., an open-circuit state or configuration) and begin the protection interval (542). The protection interval (542) is then maintained for a duration longer 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.

[0115] 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 with the cardiac cycle. For example, the patient's intrinsic R-wave can be sensed and used as a trigger for one or more of ablation energy delivery and electrical isolation. In some embodiments, this R-wave sensing can be used in place of cardiac pacing. In alternative embodiments, R-wave sensing can be used in conjunction with pacing. For example, pacing can be performed in the atrium or ventricle, and the captured R-wave response of the pulsation can be sensed and used for synchronization. Figure 8This is a schematic diagram of an electroporation system installed in the heart (602) of a patient (600). The electroporation system may include an ablation device (610), a signal generator (622) (e.g., a pulsed field ablation generator), a cardiac stimulator (628), a pacemaker (630), a protective device (650), and one or more signal detectors (670, 672). Although Figure 8 Two signal detectors (670, 672) are depicted in the paper, but it is understood that the methods described herein can be implemented using a single signal detector instead of two separate detectors.

[0116] A signal generator (622) may be coupled to the ablation device (610) and a signal detector (672). The signal generator (622) may be configured to generate pulse waveforms for delivery to the electrodes (612) of the ablation device (610), for example, for delivering ablation energy to the heart (602). A pacing device (630) may be configured to pace the heart using pacing electrodes (632) of the pacing device (630). One or more diagnostic devices (636) may be configured to measure cardiac activity (e.g., electrocardiogram) of the heart (600), for example, 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) may be used as sensing electrodes, which may be connected to a processor (e.g., a signal detector (670, 672)) to further detect and / or analyze components of the cardiac cycle.

[0117] A protective device (650) may be coupled between the cardiac stimulator (628) and the pacing device (630). In some embodiments, the protective device (650) may be configured to synchronize the electrical isolation of the cardiac stimulator (628) with the ablation energy delivery of the ablation device (610). One or more signal detectors (670, 672) may be coupled to one or more of the signal generator (622), the pacing device (630), the protective device (650), and the cardiac stimulator (628). Figure 8 As shown, a first signal detector (670) is coupled to a protection device (650), and a second signal detector (672) is coupled to a signal generator (622). However, in an alternative embodiment, a single signal detector may be coupled to both the protection device (650) and the signal generator (622).

[0118] Each signal detector (670, 672) may be coupled to a corresponding diagnostic device (636) coupled to a patient (600). Alternatively, the signal detectors (670, 672) may be integrated with one or more of a signal generator (622), a pacing device (630), a protection device (650), and a cardiac stimulator (628). The signal analyzer (670) may be configured to receive and analyze electrocardiogram signals to detect one or more R waves. In some embodiments, R waves may be detected using an R wave amplitude threshold and some exclusion criteria for noise. When an R wave is detected, the signal detectors (670, 672) may be configured to output signals to the protection device (650) and the signal generator (622). Specifically, the signal detector (672) coupled to the signal generator (622) may send a signal to the signal generator (622) upon detecting an R wave to indicate the timing of the R wave and thus notify the signal generator (622) when to deliver pulsed electric field ablation. When a signal detector (670) coupled to the protection device (650) detects an R-wave, it 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 notify the protection device (650) when to initiate protection or blanking intervals, as referenced. Figure 9 Further description.

[0119] Figure 9 This is a schematic diagram of the time series of the cardiac stimulation (710), electrocardiogram (720), pulse field ablation delivery (730), and protection interval (740) channels. Figure 9 The time series depicted can include similar to Figure 7B The time series aspects described in the text. Cardiac stimulation (710) (e.g., through, as...) Figure 8The illustrated cardiac stimulator (628) can provide optional and / or periodic stimulation pulses (712) to a patient (e.g., patient (600)). In one embodiment, the stimulation pulses may be periodic and may include rectangular pulses with a width between about 1 ms and about 5 ms. In some embodiments, any pacing device described herein (e.g., pacing device (630)) may be used to deliver the pacing pulses (712). The pacing pulses (712) may correspond to one or more of ventricular and atrial cardiac pacing. The electrocardiogram (720) may include one or more P waves (721), QRS waveforms (722), and T waves (724). The P wave (721) corresponds to atrial depolarization. The T wave (724) following the QRS waveform (722) corresponds to the onset of repolarization occurring in cardiomyocytes. In some embodiments, the delivery of the pulse waveform (732) may be synchronized with the detection of an R wave (726), for example, immediately after the detection of the R wave or after a first delay (734). In embodiments where a protective device (e.g., protective device (650)) is used to isolate certain electronic components from the patient during pulsed electric field ablation delivery, it may be desirable to implement a predetermined delay such that the protective device has sufficient time to isolate such electronic components after R-wave detection and before pulsed electric field ablation delivery. In some embodiments, the first delay (734) may be a predetermined value. For example, the first delay (734) may be between about 1 ms and about 5 ms. In some embodiments, the pulse waveform (732) may be separated from the T wave (724) by a second delay (736), for example, to provide a safety margin.

[0120] 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 may begin the protection interval (742) after a third delay (744) from the R-wave (726). The third delay (744) may be less than the first delay (734). The third delay (744) may 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) may be configured not to overlap with the stimulation or pacing pulse (712). The protection interval (742) may 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 initiating the protection interval (742) immediately or shortly after R-wave (726) detection and allowing it to continue for a longer period 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 if intracardiac pacing is not actively used during the pulse field ablation procedure. In medical emergencies where rapid pacing or other types of pacing may be required, protecting such electronic components, such as cardiac stimulators, even if such equipment is not actively used during the ablation procedure, and thus allowing such electronic components to function, connect, and be readily available throughout the procedure.

[0121] A fixed blanking interval, which lasts long enough to cover the longest expected ablation interval, or an adjustable or configurable blanking interval (e.g., which the user or system can set to a value based on the expected pulse field ablation time), can be used to implement protective or isolation coverage of certain electronic components during the high-voltage interval. Figure 13 This is a schematic diagram of the time series of the cardiac stimulation (1110), electrocardiogram (1120), pulse field ablation delivery (1130), and protective interval (1140) channels. The cardiac stimulation (1110) channel may optionally include a pacing or stimulation signal (1112), which may be periodic and may include a rectangular pulse with a width between about 0.1 ms and about 100 ms. In some embodiments, any pacing device described herein (e.g., pacing devices (230, 630, 1030)) may be used to deliver the pacing pulse (1112). The pacing pulse (1112) may correspond to one or more of ventricular and atrial cardiac pacing. In response to the pacing pulse (1112), the cardiac cycle may be synchronized with the pacing pulse (1112). For example, Figure 13 The P wave (1121), QRS waveform (1122), and T wave (1124) can be synchronized with the pacing pulse (1112). The P wave (1121) corresponds to atrial depolarization, and the T wave (1124) following the QRS waveform (1122) corresponds to the onset of repolarization in cardiomyocytes.

[0122] In some embodiments, the pulse waveform (1132) and the guard interval (1142) may be based on synchronization of one or more of pacing or stimulation pulse sensing (1144) and R-wave detection (1124). The pulse waveform (1132) may have a first length or duration (1134), and the guard interval (1142) may have a second length or duration (1148) at least as long as the duration of the pulse waveform (1132). The duration (1148) of the guard interval (1142) may be fixed or adjustable. The pulse waveform (1134) may be delivered after a first delay (1136) from the trailing edge (1114) of a cardiac pacing pulse (1112), e.g., signaled or detected by a cardiac stimulator. The first delay (1136) may be a predetermined value. For example, the first delay (1136) may be between about 1 ms and about 5 ms. Similarly, the guard interval (1142) can be synchronized with the cardiac pacing pulse (1112) (e.g., signaled or detected by the cardiac stimulator) after the second delay (1144). In this way, the cardiac pacing signal (1112) can be configured to trigger the guard interval (1142). The guard interval (1142) (e.g., open circuit state, blanking interval) can overlap the entire pulse waveform (1132).

[0123] In some embodiments, the pulse waveform (1132) and the guard interval (1142) may be synchronized with the R-wave detection (1124), for example, after corresponding third delays (1138) and fourth delays (1146). In this way, the R-wave detection (1124) can be configured to trigger the guard interval (1142). R-wave detection can be implemented using any system described herein. The third delay (1138) may be a predetermined value. For example, the third delay (1138) may be between approximately 1 ms and approximately 20 ms. In some embodiments, the pulse waveform (1132) and the guard interval (1142) may begin substantially simultaneously with the R-wave detection (1124).

[0124] In some embodiments, one or both of the second delay (1144) and the fourth delay (1146) may be adjustable, such that the protection interval (1142) may have an adjustable duration (1148).

[0125] It should be understood that the examples and illustrations in this disclosure are for illustrative purposes, and deviations and variations in the number of electrodes, sensors, and devices, etc., constructed and deployed based on the teachings herein are possible without departing from the scope of the invention. In particular, regardless of whether the ablation energy with a high-voltage pulse waveform is delivered synchronously or asynchronously with cardiac pacing (e.g., without cardiac pacing), the systems, devices, and methods disclosed herein can be configured to protect a variety of medical electronic devices, including but not limited to cardiac stimulators, electroanatomical mapping systems, ECG recording systems, ECG monitoring systems, device navigation or tracking systems, etc. 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 multiple sets of device electrodes connectable to such electronic devices. For example, the protective device may include 2, 4, 6, 8, 64, 256, or 512 protective channels. Furthermore, control signals for activating the protective device can be output to multiple such devices, thereby providing scalable protective devices, wherein the number of protective channels can be expanded in a modular manner.

[0126] As used herein, the terms “approximately” and / or “approximately”, when used in conjunction with a numerical value and / or range, generally refer to a numerical value and / or range close to said numerical value and / or range. In some cases, the terms “approximately” and “approximately” may mean within ±10% of said value. For example, in some cases, “approximately 100 [units]” may mean within ±10% of 100 (e.g., from 90 to 110). The terms “approximately” and “approximately” are used interchangeably.

[0127] Some embodiments described herein relate to computer storage products having a non-transitory computer-readable medium (also referred to as a non-transitory processor-readable medium) having instructions or computer code thereon for performing various computer-implemented operations. A computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not itself include transiently propagating signals (e.g., propagating electromagnetic waves carrying information over a transmission medium such as space or cable). The medium and computer code (also referred to as code or algorithm) can be those designed and constructed for a particular purpose or multiple purposes. Examples of non-transitory computer-readable media include, but are not limited to, magnetic storage media such as hard disks, floppy disks, and magnetic tapes; optical storage media such as optical discs / digital video discs (CD / DVD), optical disc read-only memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical discs; carrier signal processing modules; and hardware devices specifically configured to store and execute program code, such as application-specific integrated circuits (ASICs), programmable logic devices (PLDs), read-only memories (ROMs), and random access memories (RAMs). Other embodiments described herein relate to computer program products that may include, for example, the instructions and / or computer code disclosed herein.

[0128] The systems, devices, and / or methods described herein can be implemented by software (executing on hardware), hardware, or a combination thereof. Hardware modules may include, for example, general-purpose processors (or microprocessors or microcontrollers), field-programmable gate arrays (FPGAs), and / or application-specific integrated circuits (ASICs). Software modules (executing on hardware) can be expressed in various software languages ​​(e.g., computer code), including C, C++, Java®, Ruby, Visual Basic®, and / or other object-oriented, procedural, or other programming languages ​​and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, machine instructions (such as those generated by a compiler), code for generating network services, and files containing higher-level instructions executed by a computer using an interpreter. Other examples of computer code include, but are not limited to, control signals, encryption code, and compression code.

[0129] The specific examples and descriptions herein are exemplary in nature, and those skilled in the art can develop embodiments based on the materials taught herein without departing from the scope of the invention.

Claims

1. A system comprising: The first set of electrodes can be placed near the heart tissue of the heart; The second set of electrodes is configured to contact the patient's anatomical structures. A signal generator configured to generate a pulse waveform, the signal generator being coupled to the first set of electrodes and configured to repeatedly deliver the pulse waveform to the first set of electrodes, the first set of electrodes being configured to generate a pulsed electric field in response to the delivery of the pulse waveform to ablate the cardiac tissue; A protection device configured to selectively couple electronic devices to and decouple them from the second set of electrodes; as well as 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 pulse waveform to the first set of electrodes.

2. The system according to claim 1, wherein, The control element includes at least one of the following: a circuit or a processor configured to be activated by a control signal.

3. The system according to any one of claims 1-2, wherein, The electronic device is a cardiac stimulation device configured to generate pacing signals, and the cardiac stimulation device is configured to deliver the pacing signals to the heart via the second set of electrodes to control the timing of the cardiac cycle group.

4. The system according to claim 3, wherein, The control element is also configured to: The control element is configured to receive trigger signals from the cardiac stimulation device, each trigger signal indicating when a pacing signal is delivered to the heart, and to control the protection device to decouple the cardiac stimulation device from the second set of electrodes in response to receiving each trigger signal. as well as After each delivery of the pulse waveform to the first set of electrodes, the cardiac stimulation device is coupled to the second set of electrodes, enabling the cardiac stimulation device to deliver subsequent pacing signals to the heart.

5. The system according to claim 3, wherein, The signal generator is configured to deliver the pulse waveform to the first set of electrodes with a time delay between each pacing signal being delivered to the heart.

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

7. The system according to claim 1, wherein, The electronic device includes at least one of the following: An electroanatomical mapping system configured to generate mapping maps of cardiac electrical activity; A device tracking and navigation system configured to generate anatomical maps of the heart chambers; or An electrocardiogram (ECG) system is configured to monitor the electrical activity of the heart.

8. The system according to any one of claims 1-2, further comprising a sensing device configured to detect an R wave associated with each cardiac cycle from a set of cardiac cycles. The signal generator is configured to deliver a pulse waveform during each cardiac cycle from the set of cardiac cycles, after detecting the R wave of that cardiac cycle.

9. The system according to claim 8, wherein, The signal generator is configured to deliver the pulse waveform with a time delay between the 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 the delivery of the pulse waveform.

10. The system according to claim 8, wherein, The control element is also configured to: The control element is configured to receive trigger signals from the sensing device, each trigger signal indicating when an R-wave is detected, and to control the protection device to decouple the electronic device from the second set of electrodes in response to receiving each trigger signal. as well as After each delivery of the pulse waveform, the electronic device is coupled to the second set of electrodes.

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