Systems, devices, and methods for detecting ectopic electrocardiogram signals

Abstract

Systems, devices, and methods for detecting ectopic electrocardiogram signals are described herein, wherein a processor is used to confirm pacing capture or detect ectopic beats. An apparatus includes a processor to: receive cardiac signal data captured by a set of electrodes; extracting a sliding window of the heart signal data; identifying a peak frequency over a sub-range of frequencies associated with the extracted sliding window; detecting ectopic activity based at least on a measure of peak frequencies over a sub-range of frequencies; in response to detecting ectopic activity, an indication of ectopic activity is sent to a signal generator configured to generate a pulsed waveform for cardiac ablation such that the signal generator is deactivated or turned off to not generate the pulsed waveform. An apparatus may also include a processor to confirm pacing capture of a set of pacing pulses based on the cardiac signal data.

Description

[0001] This application is a divisional application of the Chinese patent application with application number "202080065395.7", application date "September 17, 2020", and invention name "System, device and method for detecting ectopic electrocardiogram signals during pulsed electric field ablation".

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to and is a continuation of U.S. patent application serial number 16 / 877,705, filed on May 19, 2020, which is a continuation of U.S. patent application serial number 16 / 741,506, filed on January 13, 2020, now issued U.S. Patent No. 10,688,305, which is a continuation of U.S. patent application serial number 16 / 573,704, filed on September 17, 2019, now issued U.S. Patent No. 10,625,080. This application also claims priority to U.S. patent application serial number 16 / 741,506 and U.S. patent application serial number 16 / 573,704. The entire disclosure of each of the foregoing applications is incorporated herein by reference in its entirety. Background Art

[0004] Through the biophysical mechanism of irreversible electroporation, the application of brief ultrashort high-voltage pulses to tissue can generate high electric fields in the tissue to produce localized areas of ablated tissue.

[0005] However, in cardiac applications, high voltage pulses may lead to complications such as inducing arrhythmias (e.g., ventricular fibrillation) if they are delivered during specific periods of cardiac activity. Therefore, it would be desirable to deliver high voltage pulses for pulsed electric field ablation synchronously with the cardiac cycle to avoid the risk of such complications. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Figure 1 is a block diagram of a system according to an embodiment.

[0007] Figure 2 is a schematic cross-sectional illustration of an ablation catheter and a pacing catheter disposed in a heart according to an embodiment.

[0008] Figure 3A and Figure 3B is a schematic illustration of a time series of electrocardiogram and cardiac pacing signals according to an embodiment.

[0009] Figure 4 A device for generating pulsed electric field ablation according to an embodiment is schematically depicted.

[0010] Figure 5Components of an apparatus for detecting cardiac activity according to an embodiment are depicted.

[0011] Figure 6 A method for tissue ablation according to an embodiment is shown.

[0012] Figure 7 A method for detecting ectopic cardiac activity according to an embodiment is shown.

[0013] Figure 8 A method for tissue ablation according to an embodiment is shown.

[0014] Fig. 9 A method for detecting ectopic cardiac activity according to an embodiment is shown.

[0015] Fig.10 A method for detecting ectopic cardiac activity and confirming pacing capture according to an embodiment is shown. DETAILED DESCRIPTION

[0016] Systems, devices and methods for detecting ectopic cardiac activity associated with delivering ablative energy to tissue, such as pulsed electric field ablation, are described herein. Pulsed electric field ablation uses ultrashort high voltage pulses to generate a larger electric field at a desired region of interest to generate a localized region of ablated tissue by irreversible electroporation. In certain applications, including cardiac applications, it is desirable to generate pulses for pulsed electric field ablation synchronously with the cardiac cycle. Synchronizing ablative energy delivery with the cardiac cycle can reduce the risk of inducing arrhythmias, such as atrial and / or ventricular fibrillation. One method of synchronously delivering pulses can be to pace and stimulate one or more cardiac chambers using a periodic pacing signal with a predetermined time period. For example, a cardiac stimulator can be used to deliver pacing pulses to one or more cardiac chambers so that the patient's heart rhythm is synchronized with the pacing pulses. In some embodiments, the pacing pulses can be delivered to (multiple) cardiac chambers by an intracardiac catheter appropriately positioned in (multiple) chambers. The intracardiac catheter may include one or more electrodes for conducting the pacing signal into the heart. For example, the catheter can have a pair of electrodes (e.g., a distal-most electrode and an electrode adjacent to the distal electrode) that function as a bipolar pair for delivering pacing signals, wherein the two electrodes provide forward and reverse current paths for the pacing signal. The pacing pulses can cause the cardiac chambers to generate their electrocardiogram (ECG) pulses in synchronization with the pacing pulses, thereby controlling the timing of the cardiac cycle.

[0017] Once the periodicity of the cardiac cycle is established and confirmed by, for example, a physician, the delivery of high voltage ablation pulses can be timed to begin synchronously with the pacing signal. For example, the ablation pulses can be delivered with a predetermined offset relative to the pacing signal so that their delivery falls within a refractory window following the QRS waveform of the cardiac cycle. In some embodiments, the ablation pulses can be delivered to the cardiac chamber using an ablation catheter configured for pulsed electric field ablation.

[0018] However, while the cardiac chamber is being paced, local electrical activity (e.g., pre-ventricular contraction (PVC)) may trigger ectopic cardiac activity that generates additional local T waves (e.g., ectopic beats) that may overlap with the next pacing pulse. Ablation energy delivered during these local T waves may have a high risk of inducing fibrillation.

[0019] Therefore, it would be desirable to detect such localized or ectopic ECG activity that may occur between consecutive pacing pulses during ablation so that the ablation system can ensure that ablation is not delivered during these times. For example, the ablation device can be configured to disconnect from the signal generator when ectopic activity is detected. By disconnecting or shutting down the ablation device (e.g., using a suitable relay), the risk of inducing a fibrillation event can be reduced.

[0020] The systems, devices, and methods described herein can be configured to detect ectopic signals and control the operation of an ablation device based on such detection. For example, the systems described herein may include a cardiac stimulator and a pacing device for electrically pacing the heart and ensuring pacing capture to establish periodicity and predictability of the cardiac cycle. The pacing device can be configured to measure cardiac electrical activity (e.g., an electrocardiogram (ECG) signal) for confirming pacing capture and / or detecting ectopic cardiac activity. For example, a predetermined portion of the ECG signal can be analyzed for ectopic beats and synchronization between pacing pulses and the cardiac cycle. A cardiac activity state can be output to indicate the state of pacing capture and / or ectopic cardiac activity and used to control the delivery of ablation energy to tissue.

[0021] The system may also include a signal generator and a processor configured to apply one or more voltage pulse waveforms to a selected electrode group of the ablation device to deliver energy to a region of interest (e.g., ablation energy for a group of tissues in the ostium of a pulmonary vein). The pulse waveforms disclosed herein may facilitate therapeutic treatment of various arrhythmias (e.g., atrial fibrillation).

[0022] The cardiac stimulator can synchronize the generation of the pulse waveform with the paced heartbeat to reduce unexpected tissue damage. For example, a time window within the refractory period of a periodic cardiac cycle can be selected for voltage pulse waveform delivery. Therefore, a voltage pulse waveform can be delivered during the refractory period of the cardiac cycle to avoid interruption of the sinus rhythm of the heart. The pulse waveform can be generated based on the confirmation of the cardiac activity state indicating the absence of ectopic beats and pacing capture. For example, the pulse waveform can be generated synchronously with the pacing signal of the heart to avoid interruption of the sinus rhythm of the heart, and can be delivered outside the period of detected ectopic activity. The pulse waveform can be delivered to one or more electrodes of one or more catheters, which are placed around the heart epicardially and / or endocardially so that these electrodes generate a pulsed electric field to ablate tissue. In some embodiments, the pulse waveform may include a graded waveform to help tissue ablation and reduce damage to healthy tissue.

[0023] In some embodiments, an apparatus includes a memory and a processor operably coupled to the memory. The processor may be configured to receive cardiac signal data captured by a set of electrodes; extract a sliding window of the cardiac signal data; identify a peak frequency within a sub-range of frequencies associated with the extracted sliding window; detect ectopic activity based at least on a measure of the peak frequency within the sub-range of frequencies; and in response to detecting the ectopic activity, send an indication of the ectopic activity to a signal generator configured to generate a pulsed waveform for cardiac ablation, so that the signal generator is deactivated or turned off to not generate the pulsed waveform.

[0024] In some embodiments, a device includes a memory and a processor operably coupled to the memory. The processor can be configured to receive cardiac signal data captured by a set of electrodes; receive an indication of delivering a set of pacing pulses to cardiac tissue; extract portions of the cardiac signal data after delivering a subset of consecutive pacing pulses in the set of pacing pulses; calculate a set of moments of a function associated with the extracted portion for each extracted portion; confirm pacing capture of the set of pacing pulses based at least on the set of moments calculated for each extracted portion; and in response to confirming pacing capture, send an indication of pacing capture to a signal generator configured to generate a pulsed waveform for cardiac ablation, so that the signal generator is activated for generating a pulsed waveform. In some embodiments, the processor is also configured to: analyze the local peak frequency of the cardiac signal data to detect ectopic activity; and in response to detecting the ectopic activity, send an indication of the ectopic activity to the signal generator, so that the signal generator is turned off and does not generate a pulse waveform.

[0025] In some embodiments, a system includes: a first controller configured to generate a pulsed waveform and deliver the pulsed waveform to an ablation device synchronously with a set of pacing pulses; and a second controller operably coupled to the first controller, the second controller configured to: generate a set of pacing pulses and deliver the set of pacing pulses to a pacing device; receive cardiac signal data captured by a set of electrodes; confirm pacing capture of the set of pacing pulses based on the cardiac signal data; and in response to confirming pacing capture, send an indication of pacing capture to the first controller to activate generation of the pulsed waveform. In some embodiments, the second controller is further configured to: monitor the cardiac signal data for ectopic activity; and when ectopic activity is present, send an indication of ectopic activity to the first controller to shut down generation of the pulsed waveform.

[0026] In some embodiments, a method includes: receiving cardiac signal data captured by a set of electrodes disposed proximate to cardiac tissue; extracting a sliding window of the cardiac signal data; identifying a peak frequency within a sub-range of frequencies associated with the extracted sliding window; detecting ectopic activity based at least on a measure of the peak frequency within the sub-range of frequencies; and in response to detecting the ectopic activity, sending an indication of the ectopic activity to a signal generator configured to generate a pulsed waveform for cardiac ablation, such that the signal generator is turned off to not generate a pulsed waveform. The method may also include confirming pacing capture of the set of pacing pulses based on the cardiac signal data.

[0027] The term "electroporation" as used herein refers to the application of an electric field to the cell membrane to change the permeability of the cell membrane to the extracellular environment. The term "reversible electroporation" as used herein refers to the application of an electric field to the cell membrane to temporarily change the permeability of the cell membrane to the extracellular environment. For example, cells undergoing reversible electroporation can observe temporary and / or intermittent formation of one or more holes in their cell membranes, which are closed when the electric field is removed. The term "irreversible electroporation" as used herein refers to the application of an electric field to the cell membrane to permanently change the permeability of the cell membrane to the extracellular environment. For example, cells undergoing irreversible electroporation can observe the formation of one or more holes in their cell membranes, which still exist after the electric field is removed.

[0028] 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 damage while reducing the total energy delivered. In some embodiments, the voltage pulse waveforms disclosed herein can be graded and have a nested structure. For example, the pulse waveform can include graded pulse groupings with associated time scales. In some embodiments, the methods, systems, and devices disclosed herein may include one or more of the methods, systems, and devices described in international application serial number PCT / US2019 / 014226, filed on January 18, 2019, disclosed on July 25, 2019 as international publication number WO2019 / 143960, and entitled “SYSTEMS, DEVICES AND METHODS FOR FOCALABLATION”, the contents of which are incorporated herein by reference in their entirety.

[0029] system

[0030] Disclosed herein are systems and devices configured to monitor ectopic cardiac activity associated with tissue ablation that produces irreversible electroporation with the selective and rapid application of voltage pulses. In general, the system for ablating tissue described herein may include a cardiac stimulator for generating a pacing signal delivered to the heart by a pacing device. The system also measures cardiac electrical activity for identifying ectopic beats and / or confirming pacing capture of the heart. The detected pacing signal and / or detected cardiac activity can be used to control the delivery of a pulse waveform generated by a signal generator to an ablation device having one or more electrodes. As described herein, the system and device can be deployed epicardially and / or endocardially to treat cardiac conditions, such as atrial fibrillation. Voltage can be applied to a selected subset of electrodes, with the subset selection being independent for anode and cathode electrode selection.

[0031] In general, the systems and devices described herein include one or more devices (eg, catheters) configured to ablate tissue in the left atrial chamber of the heart. Figure 1 A system (100) configured to deliver a voltage pulse waveform is shown. The system (100) may include an apparatus (120) including one or more processors or controllers (124) and a memory (126). The processor(s) (124) may function as, be integrated into, and / or control a signal generator (122) and / or a cardiac stimulator (128).

[0032] Each of the one or more processors (124) can be any suitable processing device configured to run and / or execute a set of instructions or codes. The processor can 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 can 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 associated therewith (not shown). The underlying device technology can be provided in various component types, for example, metal oxide semiconductor field effect transistor (MOSFET) technology like complementary metal oxide semiconductor (CMOS), bipolar technology like emitter coupled logic (ECL), polymer technology (e.g., silicon conjugated polymer and metal conjugated polymer-metal structure), hybrid analog and digital, etc.

[0033] The memory (126) may include a database (not shown) and may be, for example, a random access memory (RAM), a memory buffer, a hard drive, an erasable programmable read-only memory (EPROM), an electrically erasable read-only memory (EEPROM), a read-only memory (ROM), flash memory, etc. The memory (126) may store instructions to cause the processor (124) to execute modules, processes, and / or functions associated with the system (100), such as pulse waveform generation and / or cardiac pacing.

[0034] The device (120) can be coupled to an ablation device (110) and / or a pacemaker device (130). When coupled to the ablation device (110) and the pacemaker device (130), one or more components of the device (120) (e.g., a processor (124) functioning as a signal generator (122) and / or a cardiac stimulator (128)) can electrically communicate with the ablation device (110) and / or the pacemaker device (130) to control the delivery of pacing signals, ablation signals, etc. via the ablation device (110) and the pacemaker device (130), and / or receive data (e.g., sensed signals) from the ablation device (110) and the pacemaker device (130). If the device (120) includes multiple processors (124), one or more of the processors (124) can communicate with each other to control pacing and / or ablation. The device (120) may also include an input / output device (127) that enables the device (120) to interface with other devices (e.g., ablation device (110) and / or pacing device (130)) and / or a user. For example, the device (120) may include a user interface that can present output to a user and / or receive input from a user, such as a display, an audio device, etc.

[0035] The signal generator (122) can be configured to generate an ablation pulse waveform for irreversible electroporation of tissue (e.g., pulmonary vein ostia). For example, the signal generator (122) can be a voltage pulse waveform generator and deliver the pulse waveform to the ablation device (110). The processor (124) can combine data received from the memory (126), the cardiac stimulator (128), and the pacing device (130) to determine parameters (e.g., timing, amplitude, width, duty cycle, etc.) of the pulse waveform to be generated by the signal generator (122). The memory (126) can also store instructions to cause the signal generator (122) to execute modules, processes, and / or functions associated with the system (100), such as ectopic cardiac activity detection, pulse waveform generation, and / or cardiac pacing synchronization. For example, the memory (126) can be configured to store one or more of cardiac activity data, pulse waveforms, and cardiac pacing data.

[0036] A pacing device (130) disposed within a patient's body may be configured to receive a cardiac pacing signal generated by a cardiac stimulator (128) of an apparatus (120) for cardiac stimulation. An indication of the pacing signal may be transmitted by the cardiac stimulator (128) to a signal generator (122). Based on the pacing signal, an indication of a voltage pulse waveform may be selected, calculated, and / or otherwise identified by a processor (124) and generated by the signal generator (122). In some embodiments, the signal generator (122) is configured to generate a pulse waveform based on a cardiac activity state, wherein the pulse waveform is synchronized with the indication of the pacing signal (e.g., within a common refractory period window). For example, in some embodiments, the common refractory period window may begin substantially immediately after the 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.

[0037] In some embodiments, one or more intracardiac electrodes, such as a pacing device (130) and / or an ablation device (110), may be configured to sense signals within the heart and deliver the signals to one or more of processor(s) 124. Processor(s) 124 may analyze the sensed signals for ectopic activity and control the operation of signal generator (122) based on such analysis, as described further below.

[0038] The system (100) can communicate with other devices (not shown) via, for example, one or more networks, each of which can 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 can be connected 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 by copper twisted pairs, coaxial cables, or fiber optic cables. There are many different types of wired networks, including wide area networks (WANs), metropolitan area networks (MANs), local area networks (LANs), campus area networks (CANs), global area networks (GANs), such as the Internet and virtual private networks (VPNs). Hereinafter, a network refers to any combination of wireless, wired, public, and private data networks that are typically interconnected by the Internet to provide a unified networking and information access solution. The system (100) may also include one or more output devices, such as displays, audio devices, touch screens, combinations thereof, and the like.

[0039] Figure 2 is a schematic illustration of a heart (200) according to an embodiment described herein, for example as viewed from the front side (e.g., the front of a subject) including an ablation device (220) and a pacing device (210) disposed therein. The pacing device (210) can be configured to measure cardiac activity and / or deliver pacing signals to the heart (200), and the ablation device (220) can be configured to receive pulse waveforms and / or deliver pulse waveforms to cardiac tissue. As shown, in Figure 2 In the front cross-section of the heart (200) depicted in , the dashed lines (201) schematically approximate the boundaries of four heart chambers including the right ventricle RV (202) and the left atrium LA (204). A pacing device (210) can be introduced into the right ventricle (202) and positioned so that it can stimulate the right ventricle (202) and obtain pacing capture. The pacing device (210) can include a first electrode (212), a second electrode (214), a third electrode (216), and a fourth electrode (218). The first electrode (212) and the second electrode (214) can be configured as a bipolar pacing electrode pair to pace the right ventricle (202). The pacing electrodes (212, 214) can be coupled to a cardiac stimulator (e.g., cardiac stimulator (128)). The third electrode (216) and the fourth electrode (218) can be configured as sensor elements to measure intracardiac activity (e.g., ECG signals) of the heart (200). Although the pacing device (210) is described as being positioned in the right ventricle (202), it is understood that the pacing device (210) may be positioned in other suitable locations. For example, the pacing device (210) may be placed in the coronary sinus, and a suitable electrode pair (e.g., electrodes (212, 214)) may be used to pace the ventricle.

[0040] The ablation device (220) can be introduced into the endocardial space of the left atrium (204) through a transseptal puncture through the atrial septum. The distal portion of the ablation device (220) may include a set of electrodes (222, 224) configured to deliver ablative energy (e.g., pulsed electric field energy) to the tissue. In some embodiments, the electrodes (222, 224) of the ablation device (220) can be a set of independently addressable electrodes. Each electrode may include an insulated electrical lead configured to maintain a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulating portion. In some embodiments, the insulating portion on each of the electrical leads can maintain a potential difference between about 200V and about 2500V over its thickness without dielectric breakdown. In some embodiments, the set of electrodes may include a plurality of electrodes. The plurality of electrodes may be grouped into one or more anode-cathode subsets, such as a subset including one anode and one cathode, a subset including two anodes and two cathodes, a subset including two anodes and one cathode, a subset including one anode and two cathodes, a subset including three anodes and one cathode, a subset including three anodes and two cathodes, etc. Although two electrodes (222, 224) are depicted, it will be appreciated that the ablation device (220) may include one or more additional electrodes, wherein one or more groups of electrodes may be configured to have opposite polarities to deliver a pulsed electric field to ablate tissue.

[0041] The operation of systems and devices for detecting pacemaker signals and / or ectopic activity can be referenced Figure 3A and Figure 3B To understand, Figure 3A and Figure 3B A time sequence of periodic pacing pulses accompanying cardiac activity according to embodiments described herein is schematically illustrated.

[0042] Figure 3A is a schematic diagram of a time series of an electrocardiogram (300) and a cardiac pacing signal (310). The pacing signal (310) may include a set of periodic pacing pulses (312). For example, the pacing pulses (312) may include rectangular pulses having a width between about 1 ms and about 5 ms. In some embodiments, the pacing pulses (312) may be delivered using any pacing device described herein (e.g., pacing device (130, 210)). For example, the pacing pulses (312) may be delivered via pacing electrodes (212, 214) of a pacing catheter (210). In response to the pacing pulses (312), the cardiac cycle of the heart may be synchronized with the pacing pulses (312). For example, Figure 3AThe QRS waveform (302) in the pacing pulse (312) is synchronized with the corresponding pacing pulse (312). The T wave (304) following the QRS waveform (302) corresponds to the beginning of repolarization occurring in the cardiomyocyte. Thus, starting to deliver the ablation pulse waveform after the T wave may lead to complications (e.g., atrial and / or ventricular fibrillation) and should therefore be avoided. The time period (330) starting from the beginning of the pacing pulse (312) and ending before the T wave (304) represents a safe time window during which the ablation pulsed electric field can be delivered to the heart. In some embodiments, the ablation pulse waveform is delivered within the refractory period (320) of the cardiac cycle following the pacing pulse (312). In some embodiments, more than one cardiac chamber can be paced (e.g., simultaneous pacing of the atria and ventricles) to establish a common refractory period for more than one cardiac chamber. In such an embodiment, the pacing pulse (312) can be delivered during a common refractory period or overlapped in a refractory period associated with each cardiac chamber.

[0043] Figure 3B is a schematic diagram of the time series of an electrocardiogram (340) and a cardiac pacing signal (350). Figure 3A , each pacing pulse (352) may include a rectangular pulse having a width between about 1 ms and about 5 ms and may be delivered using any of the pacing devices described herein (e.g., pacing devices (130, 210)). For example, the pacing pulse (352) may be delivered via a pacing electrode (212, 214) of a pacing catheter (210). In response to the pacing pulse (352), the heart's natural pacing function may be synchronized with the QRS waveform (342). The T wave (344) following the QRS waveform (342) corresponds to the onset of repolarization in the cardiomyocytes. In the absence of ectopic activity, a time period (370) starting from the beginning of the pacing pulse (352) and ending before the T wave (344) represents a safe time window during which an ablation pulsed electric field may be delivered to the heart. The electrocardiogram (340) includes a refractory period (360) during which ablation may be delivered. In the presence of ectopic activity, such as represented by ectopic pulses (380) in the electrocardiogram (340), delivering pulsed electric field ablation during time period (370) may induce fibrillation. Figure 3BAs depicted, an ectopic pulse or composite pulse (380) may precede a QRS waveform (342) that is synchronized with a pacing pulse (352). The ectopic pulse (380) may generate an ectopic T wave (382) that precedes a T wave (344) of the QRS waveform (342). If a pulse waveform is delivered during a period (328) after the ectopic pulse (380), the pulse waveform may overlap with the ectopic T wave (382) and thereby cause complications, such as by inducing fibrillation. Therefore, it may be desirable to detect the occurrence of an ectopic composite pulse such as an ectopic pulse (380) during an ablation procedure (e.g., in real time) and, when detected, interrupt the delivery of a pulsed electric field ablation pulse. As described in more detail herein, the systems, devices, and methods described herein are capable of detecting ectopic beats in real time (e.g., during a pacing and / or ablation procedure) and, in response thereto, controlling the delivery of ablation energy to tissue (e.g., interrupting the delivery of the pulse waveform pulse). For example, such systems, devices, and methods can be configured for automatic detection of ectopic ECG activity such that if an ectopic beat is detected, subsequent ablation delivery can be terminated, e.g., until the user has repositioned the device, adjusted pacing parameters, or made other clinical adjustments to obtain an ECG waveform synchronized with pacing pulses that do not include ectopic activity.

[0044] Figure 4 An example apparatus (903) for generating pulsed electric field energy for tissue ablation is schematically depicted. The apparatus (903) may include a device structurally and / or functionally similar to that described above with reference to Figure 1 The apparatus (903) may be configured to generate a waveform for pulsed electric field ablation via an ablation output (911) connected to an energy delivery device, such as an ablation catheter (e.g., ablation device (110)).

[0045] The controller (908) can be configured to generate a pacing stimulus and send the pacing stimulus to an intracardiac pacing catheter or similar medical device (e.g., pacing device (130)) via a pacing output (920). The controller (908) can also send an indication (915) of the pacing stimulus to the controller (907) so that the delivery of the pulsed electric field energy can be synchronized with cardiac pacing. The controllers (907, 908) can be operably coupled to each other, for example, via a communication bus (917). As described above, by synchronizing the delivery of pulsed electric field ablation energy with the pacing stimulus, the device (903) can ensure that the pulsed electric field energy is delivered to sensitive anatomical structures (e.g., cardiac chambers) during the refractory period, thereby avoiding the risk of inducing arrhythmias (such as fibrillation events).

[0046] In some cases, ectopic beats can be generated by autonomous generation from the ventricular cavity. As described above, pulsed electric field ablation delivered during the period of ectopic activity may increase the risk of inducing arrhythmias. Therefore, it is desirable to detect such ectopic activity. In order to detect such activity, a cardiac signal (e.g., an ECG record) from an intracardiac electrode pair can be sent to a controller (908) as a sensing signal (922). The controller (908) can be configured to analyze the cardiac signal to obtain ectopic beats. When the controller (908) detects an ectopic beat, the controller (908) can be configured to communicate, for example, via a communication bus (917) with a controller (907) responsible for generating an ablation waveform to stop the delivery of pulsed electric field energy. For example, in response to detecting ectopic activity, the controller (908) can send a signal to the controller (907) to stop or interrupt ablation.

[0047] In some embodiments, the device (903) may be configured to confirm pacing capture prior to delivering pulsed electric field energy. For example, the device (903), via the controller (908), may analyze the sensed cardiac signal (922) and communicate with the controller (907) to deliver ablation when pacing capture is confirmed. In some embodiments, the device (903) may be provided with a user interface for confirming pacing capture, such as by manual input (927) by a user. For example, the device (903) may include a display that displays pacing signals and cardiac signals to allow the user to confirm pacing capture and indicate such confirmation to the device (903) (e.g., by pressing a button on the user interface). In some embodiments, the device (903) may analyze the sensed cardiac activity and, if such cardiac activity is found to be out of sync with the pacing stimulus, not perform ablation delivery and / or notify the user that pacing capture does not exist (e.g., via a user interface or message). The user and / or the device (903) may then modify the pacing conditions, such as by attempting pacing capture at a different rate, or by moving the pacing catheter to a position or location with better anatomical engagement.

[0048] Figure 5 Schematically depicts a signal (eg, an ECG signal) passing through a controller (eg, Figure 48)). As depicted, an incoming signal (1003) (e.g., a raw simulated cardiac activity signal captured using intracardiac electrodes) can be received at an amplifier (1007). The amplifier (1007) can be configured to amplify the signal (1003) for digitization by an analog-to-digital converter (ADC) (1009). The ADC (1009) can output processed cardiac data as a digitized data stream. The digitized data can be stored or buffered in a memory (1011) as cardiac activity data. A processor (1013) can analyze and / or process the cardiac data buffered in segments of a predetermined size (e.g., windowed data) for ectopic cardiac activity.

[0049] In some embodiments, the analysis can be based on comparing the data to one or more thresholds, which are, for example, predetermined and preprogrammed into the processor (1013) and / or provided by the user via user input (1017) to a user interface (e.g., a touch screen monitor or other type of monitor, etc.). Based on the analysis, the processor (1013) can be configured to output the cardiac activity state to a controller or pulse generator controller (e.g., signal generator (122) or controller (907)) for generating ablation waveforms.

[0050] The signal (1015) may indicate one or more of a pacing capture state (e.g., an ECG signal that is synchronized / asynchronous with a pacing pulse) and an ectopic cardiac activity state. For example, if pacing capture is not detected, the processor (1013) may send a corresponding status signal (1015) to the pulse generator controller indicating the lack of pacing capture. The processor (1013) and / or the pulse generator controller may then warn the user, for example, via a user interface, that pacing capture is not present and ablation cannot be performed. The user may then take appropriate action, such as stopping the ablation procedure and / or reconfiguring the system. For example, the user may reposition one or more of the ablation device (e.g., ablation device (110)) and / or the pacing device (e.g., pacing device (130)), and / or adjust other system parameters. If pacing capture is confirmed by the processor (1013), a different signal (1015) indicating that ablation is ready may be sent to the pulse generator controller, whereby the pulse generator controller may be configured to initiate ablation when requested by the user. In some embodiments, the systems and devices described herein can measure cardiac activity before, during, and after ablative energy delivery.

[0051] Additionally or alternatively, the processor (1013) can detect ectopic beats. For example, if pacing capture is confirmed but an ectopic beat is detected, the processor (1013) can be configured to send a signal (1015) to the pulse generator controller so that the pulse generator controller does not generate a pulse waveform for ablation. The processor (1013) and / or the pulse generator controller can notify the user, for example, via a user interface, of the presence of an ectopic beat and that ablation cannot be performed. The processor (1013) can also continue to monitor the sensed ECG signal for ectopic beats that may occur during ablation. If such an ectopic beat is detected, the processor (1013) can send a signal (1015) to the pulse generator controller indicating that ablation should be paused or interrupted. In response to receiving the signal (1015), the pulse generator controller can then stop further ablation delivery, for example, until the user adjusts the system and / or no ectopic beat activity is detected.

[0052] method

[0053] Also described herein are methods for detecting ectopic cardiac activity during a tissue ablation procedure performed in a cardiac chamber using the above-described systems and devices. The cardiac chamber may be a left atrial chamber and include its associated pulmonary veins. In general, the methods described herein include introducing and setting a pacing device (e.g., a pacing device (130), a pacing device (210)) in contact with one or more cardiac chambers. The pacing device may use a cardiac stimulator or other processor (e.g., a cardiac stimulator (128), a controller (908), a processor (1013)) to measure cardiac activity and deliver pacing signals to the heart. The measured signals may be processed and analyzed to detect pacing capture and / or ectopic cardiac activity that may interfere with tissue ablation, for example, by such processors and controllers as described herein. An ablation device (e.g., an ablation device (110), an ablation device (220)) may be introduced and set in contact with one or more pulmonary vein ostia or sinus regions. A pulse waveform may be delivered by one or more electrodes (e.g., electrodes (112), electrodes (222, 224)) of the ablation device to ablate tissue. In some embodiments, detection of autonomously generated ectopic cardiac activity can prompt rapid interruption of ablation energy delivery, thereby reducing the risk of inducing arrhythmias (e.g., fibrillation). In addition, cardiac pacing signals (e.g., delivered by a pacing device (e.g., pacing device (130), pacing device (210))) can synchronize the delivered pulse waveform with the cardiac cycle. By synchronizing the delivery of ablation energy with the pacing stimulation (e.g., during a refractory period), the risk of inducing arrhythmias (such as fibrillation) can be further reduced.

[0054] Additionally or alternatively, the pulse waveform can include multiple levels of a hierarchical structure to reduce the total energy delivery, for example, as described in international application serial number PCT / US2019 / 031135 filed on May 7, 2019 and entitled “SYSTEMS, APPARATUSES AND METHODS FORDELIVERY OF ABLATIVE ENERGY TO TISSUE,” the contents of which are incorporated herein by reference in their entirety. Tissue ablation performed in this manner can be delivered in the absence of ectopic cardiac activity and in synchronization with a paced heartbeat to reduce the risk of atrial and / or ventricular fibrillation and damage to healthy tissue. It should be understood that any of the ablation devices described herein (e.g., ablation device (110), ablation device (220)) can appropriately use the methods discussed below to ablate tissue.

[0055] In some embodiments, the ablation devices described herein (e.g., ablation device (110), ablation device (220)) can be used for epicardial and / or endocardial ablation. Examples of suitable ablation catheters are described in International Application Serial No. PCT / US2019 / 014226.

[0056] Figure 6 is an example method (400) for tissue ablation. In some embodiments, the voltage pulse waveform described herein can be applied during a refractory period of the cardiac cycle to avoid interruption of the heart's sinus rhythm. The method (400) includes introducing a pacing device (e.g., a pacing device (130, 210)) into an endocardial space, such as a right ventricle, at (402). At (404), the pacing device can be advanced to be placed in contact with cardiac tissue. For example, a sensor electrode configured for cardiac activity measurement (e.g., an ECG signal) and a pacing electrode configured for delivering a pacing signal can be placed in contact with an inner surface of the right ventricle. At (406), an ablation device (e.g., an ablation device (110, 220)) can be introduced into an endocardial space, such as a left atrium. At (408), the ablation device can be advanced to be placed in contact with a pulmonary vein ostium. In some embodiments, at (410), a pacing signal may be generated by a cardiac stimulator (e.g., cardiac stimulator (128)) for cardiac stimulation of the heart. The pacing signal may then be applied to the heart using pacing electrodes of a pacing device at (412). For example, the heart may be electrically paced using the pacing signal to ensure pacing capture, thereby establishing periodicity and predictability of the cardiac cycle. One or more of atrial pacing and ventricular pacing may be applied. Reference is made herein to Figure 3A and Figure 3BExamples of applied pacing signals related to patient cardiac activity are described in greater detail. At (414), one or more electrodes of the pacing device and / or ablation device may further measure cardiac activity (e.g., ECG signals) corresponding to electrical cardiac activity of the heart. In some embodiments, cardiac activity may be measured before, during, and / or after cardiac stimulation and tissue ablation.

[0057] The device (e.g., device (120, 903)) can process and / or analyze cardiac signals sensed by one or more electrodes. Based on the analysis of the cardiac data, a status signal can be generated at (416). The status signal can indicate the status of one or more of pacing capture and / or ectopic cardiac activity. For example, Figure 7 , Fig. 9 and Fig.10 A more detailed example of detecting ectopic cardiac activity is provided. At (418), a status signal may be output to a signal generator (e.g., signal generator (122)) or one or more of any processors associated with the ablation device (110, 220), and / or output to a user interface. Based on the status signal, at (420), the signal generator may or may not generate a pulse waveform, for example, based on predetermined criteria described herein. For example, when the status signal indicates that one or more of ectopic cardiac activity (e.g., ectopic beats) is not present in the cardiac data and pacing capture (e.g., synchronization between the pacing signal and the cardiac cycle) is confirmed, the pulse waveform may be generated synchronously with the pacing signal (e.g., during a refractory period). For example, when pacing capture is observed in the absence of ectopic cardiac activity for several heartbeats, the signal generator may generate a pulse waveform when activated by a user (e.g., an operator). Conversely, the signal generator may be configured to inhibit pulse waveform generation and / or output an alert to a user when the cardiac activity state indicates one or more of ectopic cardiac activity (e.g., ectopic beats) in the cardiac data and / or an absence of pacing capture.

[0058] In some embodiments, pacing capture can be automatically confirmed by a device described herein (e.g., device (120, 903)) based on received cardiac data. Additionally or alternatively, pacing capture can be confirmed by a user, for example, after viewing the output of pacing signals and cardiac signal data. For example, a user can confirm pacing capture based on the cardiac activity output on a display using a user interface (e.g., an input / output device such as a touch screen monitor or other type of monitor). If the signal generator and / or processor or a user viewing the displayed cardiac activity output determines that there is one or more of ectopic cardiac activity and no pacing capture, pulse waveform generation can be prohibited and the user can be prompted to adjust system parameters by, for example, repositioning the pacing device to improve tissue engagement and / or modify pacing signal parameters (e.g., pulse width, pulse amplitude, pulse frequency, etc.).

[0059] At (422), the generated pulse waveform can be delivered to the tissue. In some embodiments, the voltage pulse waveform can be applied within a common refractory period associated with the atrial pacing signal and the ventricular pacing signal. Based on the captured cardiac data and / or other parameters associated with ablation delivery, a pulse waveform with a time offset can be generated relative to the indication of the pacing signal. For example, the refractory period can be offset from the pacing signal by a predetermined time period, and the ablation device can be configured to deliver pulses during the refractory period offset from the pacing signal. In some embodiments, (multiple) voltage pulse waveforms can be applied over a series of heartbeats in corresponding refractory periods (e.g., a common refractory period).

[0060] In some embodiments, a pulse waveform can be delivered to a pulmonary vein ostium of a patient's heart via one or more splines in a set of splines of an ablation device (e.g., ablation device (110, 220)). In other embodiments, a voltage pulse waveform as described herein can be selectively delivered to a subset of electrodes, such as an anode-cathode subset for ablation and isolation of the pulmonary veins. For example, a first electrode in an electrode group can be configured as an anode and a second electrode in an electrode group can be configured as a cathode. These steps can be repeated for a desired number of pulmonary vein ostia or sinus areas to be ablated (e.g., 1, 2, 3, or 4 sinus ostia). Suitable examples of ablation devices and methods are described in International Application No. PCT / US2019 / 014226.

[0061] Figure 7An example method (500) for detecting ectopic cardiac activity is provided. In some embodiments, one or more steps of method (500) may be performed by any of the devices described herein (e.g., devices (120, 903)) or any suitable processor associated with the devices and methods described herein. Method (500) includes receiving a cardiac activity signal corresponding to electrical cardiac activity of a heart (e.g., an ECG waveform) at (502). For example, the cardiac activity signal may include analog data continuously received from a set of electrodes (e.g., electrodes (216, 218)) of a pacing device (e.g., pacing device (210)) in contact with a chamber of the heart (e.g., the right ventricle). In some embodiments, a processor (e.g., controller (908), processor (1013)) or other processor associated with an ablation device may receive the cardiac activity signal and perform ectopic cardiac activity detection. The raw cardiac activity signal may be received and processed at (504) to generate processed cardiac activity data. For example, signal processing may include signal conditioning (e.g., filtering), amplification, and digitization (e.g., using an analog-to-digital converter (ADC)) to generate processed cardiac activity data. For example, the cardiac activity signal may be sampled at a frequency in the range of approximately 1 kHz or at a sampling time interval of approximately 1 ms and stored at a predetermined resolution (e.g., a discrete time series of 16-bit signed integer data). The sampling time interval of 1 ms corresponds to a Nyquist frequency of 500 Hz. At (506), the processed cardiac activity data is stored in a memory, such as a buffer. In some embodiments, the buffer clears the stored cardiac data based on the received pacing signal. For example, the buffer deletes previously stored cardiac data upon receiving the next pacing pulse. In some embodiments, the pacing signal may include a predetermined pacing frequency.

[0062] At (508), the processed cardiac activity data can be analyzed for one or more of ectopic cardiac activity and pacing capture. For example, the processed cardiac activity data can be analyzed by extracting sliding windows of data, and each sliding window can be evaluated for ectopic cardiac activity, for example using a discrete Fourier transform method. Fig. 9 and Fig.10 Specific implementations of such analysis are described further below. Optionally, in some embodiments, at (512), the processed cardiac activity data may be analyzed to confirm pacing capture.

[0063] In some embodiments, the ectopic cardiac activity detection at (510) may be performed in parallel with the pacing capture detection at (512). In other embodiments, the pacing capture detection at (512) may be performed before the ectopic cardiac activity detection at (510).

[0064] Based on the results of the detected ectopic cardiac activity and / or pacing capture, a status signal may be generated at (514). In some embodiments, the status signal may be output to one or more components of an ablation device (e.g., device (120)), including, for example, a signal or pulse generator (e.g., signal generator (122)) and / or another computing device. For example, a user interface of a tissue ablation system (e.g., a user interface such as a display, included in device (120)) may be configured to display an indication confirming pacing capture (e.g., "pacing capture confirmed") and display an "ablation" icon configured to allow a user to initiate delivery of ablative energy to tissue. In some embodiments, if pacing capture is confirmed and no ectopic beats are detected, there is no need to output the cardiac activity status to the user. Conversely, an indication (e.g., an audio and / or visual alarm) may be made when pacing capture cannot be confirmed or an ectopic beat is detected.

[0065] Fig. 9 and Fig.10 is a flow chart depicting an example method for detecting ectopic cardiac activity and / or confirming pacing capture. One or more steps of the method may be performed by any of the apparatuses (120, 903) described herein or any suitable processor associated with the apparatus and methods described herein. Fig. 9 As shown, a method for detecting ectopic cardiac activity includes receiving an ECG input at (702). The ECG input may be, for example, ECG signal data received from a set of electrodes of a pacing device (e.g., electrodes (216, 218) of a pacing device (210)). The ECG signal may be an analog signal. At (704), the ECG input may be processed, for example, by conditioning (e.g., filtering) and / or amplifying the signal. At (706), the ECG signal may be converted from analog to digital, for example, using an ADC. In some embodiments, the data may be sampled at a frequency that achieves sufficient resolution, for example, at a frequency of approximately 1 kHz or a sampling time interval of approximately 1 ms, and stored as bit-based integer data (e.g., 16-bit signed integer data, 32-bit signed integer data, etc.). At (708), the digitized or sampled data may be stored in a memory (e.g., memory (126, 1011)). For example, data may be buffered starting from each pacing signal so that each set of buffered data is associated with a single heartbeat or cardiac cycle. At (737), the pacing signal data may be provided, for example, by a pacing device (e.g., pacing device (130, 210)) and / or a processor associated with the pacing device (e.g., processor (124, 908, 1013)). When a subsequent set of data associated with the second pacing signal is received, the existing buffer may be cleared and this new data associated with the second pacing signal may be stored in the buffer.

[0066] At (710), the buffered data may be analyzed by extracting sliding windows of a predetermined length. For example, starting at a time interval equal to the pacing pulse width after the leading edge of the pacing pulse, the buffered data may be extracted in a sliding window of a predetermined length (e.g., a window of 220 data points), which corresponds to a frequency resolution of approximately 4.54 Hz. The sliding window may start after the pacing pulse (i.e., after a time interval equal to the pulse width) and advance in discrete steps, for example, where the step size is equal to a preset number of sampling time intervals (such as 10 sampling time intervals). The number of sliding windows extracted from the buffered data for each cardiac cycle may depend on one or more parameters, such as the length between pacing pulses, the window length, and / or the step size, each of which may be a predetermined parameter.

[0067] At (712), a discrete Fourier transform (e.g., a fast Fourier transform) can be performed on each sliding window. At (714), the results of the Fourier transform (e.g., amplitude) can be filtered (e.g., by a smoothing filter) to output a function f corresponding to a local average over a set of neighboring values ​​around each data point. Local peaks in the function f can be identified within a sub-range of the data for each sliding window. For example, if the sliding window has a length of 220 data points, a sub-range ranging from about 12 to about 100 (the 12th data point to the 100th data point) can be used, which corresponds to a frequency band from about 54 Hz to about 454 Hz. Although these particular sliding window lengths and frequency bands are provided as examples, it will be appreciated that other sliding window lengths and frequency bands can be used, e.g., depending on desired parameters, processing capabilities, etc. At (720), analysis of peaks within the frequency band can be used to determine whether ectopic cardiac activity is present.

[0068] The processed ECG data within each sliding window can be used to detect ectopic cardiac activity. In an embodiment, the peak value (a) of f over a predetermined interval (or sub-range or frequency band) can be used to detect ectopic cardiac activity. p ) and the maximum value of f up to the Nyquist frequency (a max ) is compared with a predetermined threshold value t to detect ectopic beats. In some embodiments, when the ratio a p / a maWhen t is greater than t, ectopic beats can be detected in the sliding window. Because ectopic beats increase the amount of certain frequencies in the ECG signal, detection can be accomplished by identifying situations in which frequencies greater than normal are present in the sampled cardiac data. In some embodiments, t can be between about 0.01 and about 0.25, between about 0.01 and about 0.2, between about 0.01 and about 0.15, including all subvalues ​​and ranges therebetween. In some embodiments, at (716), the user can enter t into a user interface of the tissue ablation system. The threshold t can represent the sensitivity of the system, that is, a system with a lower threshold t has a higher sensitivity than a system with a higher threshold t.

[0069] When no ectopic beats are detected in a particular sliding window (720: No), the process continues to the next sliding window. When ectopic beats are detected (720: Yes), a status signal may be generated at (724) that, for example, notifies a computing device and / or a user of ectopic activity, as described above with reference to Figure 7 As described in (514) in .

[0070] In some embodiments, the received ECG data can be used to confirm pacing capture. Fig.10 As depicted, an example method for detecting ectopic beats and confirming pacing capture is depicted. Fig. 9 In the method depicted in (802), an ECG input can be received. At (804), the ECG input can be processed, for example, by conditioning (e.g., filtering) and / or amplifying the signal. At (806), the ECG signal can be converted from analog to digital, for example using an ADC. At (808), the digitized data can be stored in a memory (e.g., memory (126)). For example, the digitized data can be buffered in the memory starting with each pacing signal, such that each set of buffered data is associated with a single heartbeat or cardiac cycle.

[0071] At (810), the buffered data may be analyzed by extracting sliding windows of data, each sliding window having a predetermined length and being advanced through the buffered data in discrete steps. The detection of ectopic beats at (812) (e.g., by discrete Fourier transform of the data), the filtering and analysis of the data at (814), and the detection of peaks in the Fourier transform data greater than a preset threshold at (820) may be similar to Fig. 9 In some embodiments, this detection may be based on user input (816).

[0072] Where ECG data is available, pacing capture may also be confirmed at (822). To confirm pacing capture, a subset of sampled data may be extracted from the ECG data at the start of the pacing signal, as indicated by (837). For example, ECG data associated with a predetermined time interval T (e.g., the duration of the pacing pulse) starting from the start of the pacing pulse may be extracted. For example, the time period may have a length between approximately 5 ms and approximately 50 ms. Thus, depending on the sampling frequency and the time interval T, the subset of sampled data may, for example, include the first ten to fifty data points. A function g(t) may be defined by the subset of sampled data over the time interval T. In some embodiments, g(t) may represent an ECG signal scaled relative to the maximum amplitude of the ECG signal over the time interval T. A set of moments (e.g., M0, M1, ..., M2) of this function over the time interval T may be expressed as follows: n ) can be calculated and can be tracked over a predetermined number of consecutive pacing periods (e.g., 1, 2, 3, 4, 5 consecutive pacing periods). The set of moments of the function can include, for example, the first three moments, which can be calculated in discretized form as averages, or as g(t), tg(t), and tg(t) over a time interval T. 2 Other suitable integral representations of g(t) (e.g., using the trapezoidal rule, Simpson's rule, or other integration metrics).

[0073] Using the calculated moments, the average value A of the nth moment over a set of i consecutive time periods n It can be given by the following formula: A n =(M n 1 +M n 2 +M n 3 +…+M n i ) / i. Therefore, for the first three moments of 5 consecutive pacing periods, the average value will be:

[0074] A0=(M0 1 +M0 2 +…M0 5 ) / 5

[0075] A1=(M1 1 +M1 2 +…M1 5 ) / 5

[0076] A2=(M2 1 +M2 2 +…M2 5 ) / 5

[0077] The average moment value A can be calculated nand the normalized difference between the moment values ​​for the i-th time period (e.g., for five time periods, i=1, 2, ..., 5) of a given moment n. For the first three moments (n=1, 2, 3), the following set of equations provides this normalized difference:

[0078] S i =|A0–M0 i | / A0

[0079] T i =|A1–M1 i | / A1

[0080] U i =|A2–M2 i | / A2

[0081] When the corresponding one of A0, A1 or A2 is zero, S i , T i and U i The value is set to zero.

[0082] Can be based on S i , T i and U i value to detect the confirmation of pace capture. For example, if for A n For each non-zero value of i , T i and U i If the value is less than a predetermined threshold or a set of thresholds, then the pacing capture within the i predetermined time period can be confirmed. For example, this threshold of the moment M0 can be in the range between 0 and 0.1. n i Small deviations from the corresponding mean values ​​indicate that the temporal behavior of the ECG signal (viewed as a function of time) is morphologically consistent over consecutive pacing periods, thereby demonstrating pacing capture. In some embodiments, this threshold may be user defined, for example, via input (816) provided by a user interface (e.g., of an input / output device (127)). If pacing capture is confirmed (822), this may be indicated, for example, on the user interface, by highlighting a "pacing capture confirmed" indicator.

[0083] As above reference Figure 7As described, if no ectopic beating activity is detected and pacing capture is confirmed, the ablation device and associated (multiple) processors (e.g., the pulse generation controller (907) and other devices described herein) can be configured to deliver pulsed electric field ablation. If ectopic beating activity is detected and / or pacing capture is not confirmed, the ablation device and / or associated (multiple) processors can be deactivated and / or not configured to deliver pulsed electric field ablation, for example, by activating an appropriate relay that disconnects the ablation device from the ablation generator. Specifically, if ectopic beating activity is detected, it is not desirable to deliver pulsed electric field ablation because it can cause fibrillation.

[0084] In some embodiments, graded voltage pulse waveforms having a hierarchical structure of nested structures and time intervals as described herein may be useful for irreversible electroporation, providing control and selectivity in different tissue types. Figure 8 Flowchart (600) is a flowchart of an embodiment of a tissue ablation process. The method (600) includes introducing a device (e.g., an ablation device (110, 220)) into an endocardial space, such as the left atrium, at (602). At (604), the ablation device can be advanced to be positioned in the ostium of a pulmonary vein. In embodiments in which the device can include a first and a second configuration (e.g., compact and expanded), the device can be introduced in the first configuration and converted to the second configuration at (606) to contact tissue at or near the pulmonary vein sinus or ostium, wherein further description of suitable ablation devices is provided in International Application No. PCT / US2019 / 014226. The ablation device can include electrodes and can be configured in an anode-cathode subset at (608), as discussed in detail above. For example, a subset of the electrodes of the device can be selected as anodes, and another subset of the electrodes of the device can be selected as cathodes, wherein a voltage pulse waveform is applied between the anode and the cathode.

[0085] At (610), a pulse waveform may be generated by a signal generator (e.g., signal generator (122)) and may include multiple levels in a hierarchical structure. As disclosed herein, various hierarchical waveforms may be generated using a signal generator. For example, a pulse waveform may include a first level of a hierarchical structure of pulse waveforms including a first group of pulses. Each pulse has a pulse duration and a first time interval separating consecutive pulses. A second level of the hierarchical structure of pulse waveforms may include multiple first groups of pulses as a second group of pulses. A second time interval may separate consecutive first groups of pulses. The second time interval may be at least three times the duration of the first time interval. A third level of the hierarchical structure of pulse waveforms may include multiple second groups of pulses as a third group of pulses. A third time interval may separate consecutive second groups of pulses. The third time interval may be at least thirty times the duration of the second level time interval. At (612), a pulse waveform generated by a signal generator may be delivered to tissue using an ablation device. As described herein, if ectopic beating activity is detected or pacing capture is not confirmed, the delivery of the pulse waveform activity may be interrupted, for example at (608) or (610). Examples of pulse waveforms that may be used with the ablation devices described herein are provided in International Application No. PCT / US2016 / 57664, filed on October 19, 2016, and entitled “Systems, apparatuses and methods for delivery of ablative energy to tissue,” the entire contents of which are incorporated herein by reference.

[0086] It should be understood that although the examples herein identify separate monophasic and biphasic waveforms, it should be understood that combined waveforms can also be generated in which some portions of the waveform hierarchy are monophasic and other portions are biphasic. Voltage pulse waveforms having a hierarchy can be applied to different anode-cathode subsets (optionally with time delays). As discussed above, one or more of the waveforms applied to the anode-cathode subsets can be applied during the refractory period of the cardiac cycle. The pulse waveform can be delivered to the tissue. It should be understood that the steps described in certain figures can be appropriately combined and modified.

[0087] It should be understood that the examples and illustrations in the present disclosure are for exemplary purposes, and deviations and variations, such as the number of splines, the number of electrodes, etc., can be constructed and deployed according to the teachings herein without departing from the scope of the present invention. Although specific parameters such as sampling frequency, time interval, etc. are given in the description herein for exemplary purposes only, it should be understood that other values ​​of various parameters can be conveniently used by those skilled in the art for applications based on the teachings presented in the present disclosure.

[0088] As used herein, the terms "about" and / or "approximately" when used in conjunction with numerical values ​​and / or ranges generally refer to those numerical values ​​and / or ranges that are close to the stated numerical values ​​and / or ranges. In some cases, the terms "about" and "approximately" can mean within ±10% of the stated value. For example, in some cases, "about 100 [units]" may mean within ±10% of 100 (e.g., from 90 to 110). The terms "about" and "approximately" can be used interchangeably.

[0089] Some embodiments described herein relate to computer storage products with non-transitory computer-readable media (also referred to as non-transitory processor-readable media) having thereon instructions or computer codes for performing various computer-implemented operations. Computer-readable media (or processor-readable media) are non-transitory in the sense that they do not include transient propagating signals themselves (e.g., propagating electromagnetic waves that carry information on a transmission medium such as space or cables). The media and computer codes (also referred to as codes or algorithms) may be those designed and constructed for one or more specific 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 compact disks / digital video disks (CD / DVD), compact disk read-only memories (CD-ROMs), and holographic devices; magneto-optical storage media such as optical disks; carrier signal processing modules; and hardware devices specially configured to store and execute program codes, such as application specific integrated circuits (ASICs), programmable logic devices (PLDs), read-only memories (ROMs), and random access memory (RAM) devices. Other embodiments described herein relate to computer program products, which may include, for example, the instructions and / or computer codes disclosed herein.

[0090] The systems, devices and / or methods described herein may be implemented by software (implemented on hardware), hardware or a combination thereof. Hardware modules may include, for example, a general purpose processor (or microprocessor or microcontroller), a field programmable gate array (FPGA) and / or an application specific integrated circuit (ASIC). Software modules (implemented on hardware) may be expressed in various software languages ​​(e.g., computer code), including C, C++, Ruby, Visual and / or other object-oriented, procedural or other programming languages ​​and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, machine instructions such as those produced by a compiler, code for generating network services, and files containing high-level instructions executed by a computer using an interpreter. Additional examples of computer code include, but are not limited to, control signals, encrypted code, and compressed code.

[0091] The specific examples and descriptions herein are exemplary in nature and one skilled in the art may develop embodiments based on the teachings herein without departing from the scope of the present invention.

Claims

1. A system comprising: a first controller configured to generate a pulsed waveform and deliver the pulsed waveform to an ablation device in synchronization with a set of pacing pulses; as well as A second controller, wherein the second controller is configured to: generating the set of pacing pulses and delivering the set of pacing pulses to a pacing device for cardiac stimulation of the heart; receiving cardiac signal data of the heart; confirming pacing capture of the heart based on the cardiac signal data; monitoring ectopic activity of the heart by analyzing frequency components associated with the cardiac signal data; as well as A set of signals is generated based on the confirming and the monitoring and sent to the first controller.

2. The system of claim 1, wherein the second controller is configured to monitor ectopic activity by: extracting a sliding window of the cardiac signal data after delivering each pacing pulse in the set of pacing pulses; performing a discrete Fourier transform of the sliding window to obtain frequency components of the sliding window; Identifying a peak frequency over a sub-range of frequencies in the frequency components of the sliding window; as well as The presence or absence of ectopic activity is determined based on analyzing the peak frequency.

3. The system of claim 2, wherein the second controller is configured to determine, for each sliding window, whether there is an ectopic activity by: Calculating a ratio of the amplitude of the peak frequency of the sliding window to the maximum amplitude of frequencies up to the Nyquist frequency of the frequency components of the sliding window; and It is determined whether the ratio is greater than a threshold.

4. The system of claim 1 , wherein the second controller is configured to confirm pacing capture by: extracting portions of the cardiac signal data after delivering a subset of consecutive pacing pulses from the set of pacing pulses; calculating, for each extracted portion, a set of moments of a function associated with the extracted portion; and Pacing capture of the set of pacing pulses is confirmed based at least on the set of moments calculated for each extracted portion.

5. The system of claim 4, wherein each extracted portion of the cardiac signal data comprises cardiac signal data within a predetermined time interval after the start of a pacing pulse from the subset of consecutive pacing pulses.

6. The system of claim 1 further comprising the pacing device comprising a first set of electrodes for cardiac stimulation of a heart and a second set of electrodes for capturing the cardiac signal data.

7. The system of claim 1 further comprising the ablation device comprising a set of electrodes for generating a pulsed electric field to ablate cardiac tissue in response to receiving the pulsed waveform.

8. The system of claim 1, wherein the set of signals includes a signal indicative of pace capture, The second controller is configured to generate and transmit a signal indicative of pace capture in response to confirming pace capture.

9. The system of claim 8, wherein the set of signals includes a signal indicative of ectopic activity, The second controller is configured to generate and transmit a signal indicative of the ectopic activity in response to detecting the ectopic activity based on the monitoring.

10. An apparatus comprising: Memory; as well as a processor operably coupled to the memory, the processor being configured to: extracting portions of cardiac signal data after delivering a set of continuous pacing pulses to the heart; calculating, for each extracted portion, a set of moments of a function associated with the extracted portion; confirming paced capture of the heart based at least on the set of moments calculated for each extracted portion; as well as In response to confirming paced capture, a signal indicative of paced capture is generated and sent to a signal generator configured to generate a pulsed waveform for cardiac ablation, such that the signal generator is activated to generate the pulsed waveform in response to receiving the signal.

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