Smart matrix-return electrode for minimizing muscle twitching during pulsed field ablation

Abstract

A method for pulsed field ablation, PFA, comprises providing at least one electrical ablation by a PFA catheter and balancing charges by a configurable return electrode system comprising a plurality of return electrodes, wherein a subset of the plurality of return electrodes may be reproducibly activated and / or deactivated, independently from at least one electrode of the plurality of return electrodes not comprised by the subset.

Description

[0001] Attorney Docket No. 132922-0015W0Q1

[0002] SMART MATRIX-RETURN ELECTRODE FOR MINIMIZING MUSCLE TWITCHING DURING PULSED FIELD ABLATION

[0003] TECHNICAL FIELD

[0004] The invention generally relates to (unipolar) pulsed field ablation (PF A) catheters and return electrodes thereof, as well as to corresponding methods, systems, and computer programs.

[0005] BACKGROUND

[0006] PFA is a procedure to treat and / or remove tissue, typically near the heart where said tissue may cause cardiac arrhythmias such as, e.g., atrial fibrillation, atrial flutter, and Wolff- Parkinson-White syndrome. Such arrhythmias may increase the risk of ventricular fibrillation, stroke, and sudden cardiac arrest.

[0007] For PFA, one or more flexible catheters may be advanced, e.g., into a patient’s blood vessels (e.g., the femoral vein, internal jugular vein, or subclavian vein). The one or more catheters may then typically be advanced towards the heart and / or to the position of the tissue to be treated. Electrical impulses are then used to treat the arrhythmia: cardiac tissue targeted by PFA is rendered electrically inactive while collateral tissues may be spared, e.g., through a process called irreversible electroporation.

[0008] Often, such procedure is performed under general anesthesia, which has a high procedure risk for the patient. General anesthesia needs to be administered by anesthesiologists, which increases costs of the procedure. Also, anesthesiologists are typically a bottleneck for planning a procedure. Alternatively, when no anaesthesia or mild sedation is employed, one must consider that the patient is aware of the steps performed in preparation during PFA.

[0009] While the cell death mechanism of PFA, i.e. irreversible electroporation, is superior over treating via heating and / or cooling in terms of selectivity such that less healthy tissue is damaged by the procedure, there are certain disadvantages of PFA: Providing (e.g.,

[0010] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1 electrical) ablation, i.e. delivering pulses of high electrical fields, to the patient body may, besides ablating tissue, also unwantedly stimulate muscles and / or nerves of the patient’s body via electrical stimulation. The resulting muscle twitching may not only be uncomfortable for the patient but also bears the risk of hurting the patient and / or damaging the equipment used for the procedure. Moreover, movement of the patient may lengthen the procedure as this may cause shifts on an electro-anatomical mapping system which is typically used in such procedures.

[0011] The current between the catheter and a return electrode may be tailored to avoid such unwanted side effects by accurate positioning of the return electrode. However, the known approaches in that regard are not always optimal. A repositioning of the return electrode may, for example, be cumbersome and time-consuming. It may also bother the patient as it feels like trial and error. This problem is in particular relevant when general anesthesia is not used for the reasons given above.

[0012] Therefore, there is still a need to further improve devices, systems, methods, and computer programs associated with such procedures.

[0013] SUMMARY

[0014] The various aspects described herein meet the above need at least in part.

[0015] According to a first aspect of the invention, a method for PFA is provided. Said method comprises providing at least one electrical ablation by a PFA catheter and a configurable return electrode system comprising a plurality of return electrodes, wherein a subset of the plurality of return electrodes may be reproducibly activated and / or deactivated, independently from at least one return electrode of the plurality of return electrodes not comprised by the subset.

[0016] Electrical ablation may be understood as providing pulsed field energy, whether or not the provided pulsed field energy is sufficient to cause irreversible electroporation.

[0017] - 2 -

[0018] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1

[0019] This method allows for PFA via the configurable return electrode system. In detail, the plurality of return electrodes may be reproducibly activated and / or deactivated which allows PFA without the need of physical repositioning of the return electrodes. This may beneficially increase the accuracy and / or reproducibility of this procedure while reducing the time required to test and / or realize return electrode configurations, i.e., configurations of the configurable electrode system. Further, potential errors due to human mistakes may be reduced. Thereby, the procedure may overall be more efficient and less unpleasant for the patient receiving the PFA treatment. Changing the virtual positioning of the return electrodes, by activating and deactivating one or more return electrodes at different locations, may allow optimizing the return electrode configuration such as to minimize the triggering of muscle twitching as the electrical field strength can be lowered at sensitive regions within the patient’s body. The planned PFA treatment may therefore be performed with minimal muscle twitching during PFA.

[0020] This method is in stark contrast to conventional approaches that may, e.g., rely on manual repositioning of the return electrode(s). Such manual repositioning is cumbersome and time consuming. It may also bother the patient as it feels like trial and error and / or cause them pain. Often, it is even necessary to administer general anesthesia to the patient to avoid patient discomfort. Through the present invention, such measures may not be needed anymore. The present invention may thus avoid at least some of the disadvantages of common PFA treatments.

[0021] The PFA catheter may, e.g., comprise an elongated and / or flexible shaft comprising various components. At a distal end, the PFA catheter may comprise one or more catheter electrodes (ablation electrodes) configured for tissue contact and different from the return electrodes. The one or more catheter electrodes may be capable of delivering electrical energy to the target tissue. The PFA catheter may, e.g., further be coupled to and / or comprise one or more of: an electrical energy source, a pulse generator, and / or a control unit. The electrical energy source may supply the necessary energy for the electrical ablation. The pulse generator may generate the desired pulsed electrical signals. The control unit may, e.g., regulate the pulse generator and / or facilitate the adjustment of ablation parameters, e.g., such as pulse duration, pulse frequency, and / or amplitude.

[0022] - 3 -

[0023] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1

[0024] The pulse generator and / or the control unit may be configured to provide high-voltage pulses suitable for PF A. PFA according to the present invention may be charge balanced or not. Charge balanced PFA may be achieved by the pulses of opposite polarity, where each individual pulse is followed by a pulse of the opposite polarity, and / or by biphasic pulses.

[0025] Charge balanced biphasic pulses may be generated by a generator comprising a pulseshaping output stage (POS) for coupling to the one or more catheter electrodes and the return electrode system. The generator may further comprise an internal pulse generator for applying a plurality of internal pulses to the pulse-shaping output stage. The pulse-shaping output stage may comprise a transformer and at least one capacitor, such that each internal pulse is transformed into a substantially charge-balanced pulse having an interphase period of zero seconds (e.g. a charge balanced biphasic pulse).

[0026] In operation, the PFA catheter may, e.g., be configured to be inserted into a body cavity and / or vessel, guided to the target tissue, and / or positioned in close proximity thereof. The optional control unit may, e.g., be used to set the desired ablation parameters, e.g., based on the specific therapeutic objective. The PFA catheter may deliver controlled pulses, in particular charge balanced pulses, of electrical energy through the catheter electrodes, creating an electric field in the target tissue. The pulsed electrical signals may induce various physiological responses in the tissue, such as, e.g., depolarization, repolarization, and / or alteration of cellular membrane potential. Such electrical ablation effects may beneficially be utilized for different therapeutic purposes. For instance, the PFA catheter may, via the delivered ablation, affect neural activity (e.g., by unwanted neural stimulation), pain sensation, and / or tissue regeneration.

[0027] In PFA, charge balancing may be an important aspect ensuring safe and / or effective delivery of electrical energy to the target tissue. Charge balancing may, e.g., involve the equalization of electrical charges preventing the accumulation of charge imbalances that can lead to tissue damage and / or discomfort during the PFA procedure. In PFA, electrical energy may be delivered to the target tissue through the one or more catheter electrodes, - 4 -

[0028] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1 e.g., of the PFA catheter, which are configured for delivering energy to the target tissue, e.g., by pulsed electrical signals. These catheter electrodes may thus create an electric field in the target tissue, which, in the one hand may induce the desired therapeutic effects and, on the other hand, needs to be accounted for in terms of charge balancing preventing the accumulation of charges in the patient’s body. To achieve said charge balance, one or more of the plurality of return electrodes may be utilized. Said return electrodes may serve as a path for the flow of electrical current back to the electrical energy source, completing an electrical circuit.

[0029] The return electrodes may be placed at a location separate from the catheter electrodes, ensuring that the returning current flow does not interfere with the intended treatment area and / or lead to undesired triggering of muscle activity. Being able to reproducibly activate and / or deactivate a subset of the plurality of return electrodes, independently from at least one return electrode of the plurality of return electrodes not comprised by the subset may, e.g., improve the accuracy and / or efficiency of said crucial return electrode positioning and thus increase also patient comfort. The effective variation of the positioning by activating / deactivating different return electrodes that may be located at different (but fixed) positions may improve how electric fields are tailored, how electrical energy is distributed and / or prevent the concentration of current in specific regions, which could lead to tissue damage. Altogether, this may decrease unwanted stimulation of the patient and / or the patient’s muscles. Using multiple (active) return electrodes may further improve charge balancing: These return electrodes may be strategically placed / activated to distribute the returning current more evenly. By employing multiple return electrodes, the risk of charge accumulation and associated complications can thus be further reduced.

[0030] Generally, an activated return electrode may contribute to charge balancing, e.g., in the sense that current may flow through it. Vice versa, a deactivated return electrode may not contribute to charge balancing, e.g., in the sense that it is disconnected from charge transport means and / or no current may flow through it. Thus, current may flow in a circuit comprising the positive (or negative) catheter electrodes within the patient and the activated one or more negative (or positive, respectively) return electrodes outside the patient. The deactivated return electrodes are deactivated in the sense that they are disconnected from

[0031] - 5 -

[0032] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1 said circuit and thus no current flows through them. Thus, an activation-deactivation-means may connect (i.e., activate) and / or disconnect (i.e., deactivate) one or more return electrodes to and / or from the circuit. The circuit may comprise, e.g., the power supply / voltage source of the PFA catheter, the catheter electrodes, and / or the activated (connected) return electrode(s). In this sense, selectively activating and / or deactivating one or more return electrodes corresponds to adapting said electrical circuit such as to tailor the electric field and / or current distribution through the patient’s body, wherein typically, at least one return electrode may be activated to allow current to flow through the circuit.

[0033] The activation-deactivation of the one or more return electrodes may influence the impedance of the electrical circuit comprising the generator, the catheter with the catheter electrode(s), the patient and the return electrodes. A change of the impedance of the electrical circuit may result in a change of the waveform of the charge balanced pulses. Therefore the generator may adapt (may be equipped to adapt) the internal impedance of the generator to keep the overall impedance of the electrical circuit and thereby the waveform of the charge balanced pulses constant. In particular the generator may modify the capacity of the at least one capacitor of the pulse-shaping output stage depending on the current activation-deactivation status of the one or more return electrodes, e.g. which and how much return electrodes are activated or deactivated.

[0034] The method may, for example, further comprise determining a patient response to the at least one electrical ablation; and determining a configuration of the return electrode system at least in part based on the patient response.

[0035] Determining a patient response, e.g., associated to muscle twitching as described herein, and / or associating it with a current configuration of the configurable return electrode system and / or the ablation provided, e.g., by the PFA catheter, may allow to determine a configuration of the return electrode system at least in part based on the patient response, wherein said determining of the configuration may be based on logical decisions. For example, the return electrode configuration may be determined for which the (numerically) lowest patient response is observed / determined (e.g., the least muscle twitching). This may improve the over-all efficiency, reproducibility, and / or accuracy of the method. Further, - 6 -

[0036] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1 this may, e.g., occur in a fully or at least partly automated way saving time and reducing the risk of human errors.

[0037] In some examples, the method may further comprise providing a first electrical ablation with the return electrode system in a first return electrode configuration, switching the return electrode system into a second return electrode configuration by activating and / or deactivating at least one of the plurality of return electrodes, and / or providing a second electrical ablation with the return system in the second return electrode configuration.

[0038] Such method may thus comprise providing an electrical ablation with the return electrode system in a plurality of return electrode configurations. Due to the switching the configurable return electrode system into a second return electrode configuration by activating and / or deactivating at least one of the plurality of return electrodes, the first and second return electrode configuration are at least partly different. This may allow to compare, e.g., a patient response and / or any other measure and / or observation associated with the respective return electrode configuration and / or electrical ablation and thus to compare the plurality of configurations of the configurable return electrode system. This may allow to find a suitable return electrode configuration for PFA therapy. An exemplary approach for this is explained in the following:

[0039] The method may, for example, further comprise determining a first patient response to the first electrical ablation, determining a second patient response to the second electrical ablation, and / or determining a configuration of the return electrode system at least in part based on the first and / or second patient response.

[0040] For example, the patient response may be related to muscle twitching induced by the electrical ablation and may be stronger the less ideal the current is guided between the source of the electrical ablation, e.g., a PFA catheter and the activated return electrode(s). Therefore, determining the (preferred) configuration of the return electrode system at least in part based on the first and / or second patient response may comprise finding the ablation / return electrode configuration for the preferred patient response, in this example out of two tested return electrode configurations, and choosing the respective return - 7 -

[0041] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1 electrode configuration. This concept may be extended to three or more different electrical ablations and / or return electrode configurations such that determining the (preferred) configuration of the return electrode system at least in part based on the first and / or second patient response may comprise finding the ablation / retum electrode configuration for the preferred patient response, in this example out of three or more tested return electrode configurations. In particular, the electrical ablation provided during the determination of the preferred configuration of the return electrode may not be sufficient to induce irreversible electroporation.

[0042] The method may, e.g., further comprise, for each of the at least one electrical ablation, storing information on the configuration of the return electrode system used for applying the ablation and the patient response determined for the ablation, and optionally one or more ablation parameters of the electrical ablation.

[0043] The stored information may, e.g., beneficially pose a data base for choosing the best return electrode configuration in different scenarios. In some cases, it might even be possible to directly determine a best return electrode configuration for a given PFA ablation and a given patient without testing various ablations and / or return electrode configurations in a trial-and-error mode but make predictions from said data base.

[0044] Similarly, the method may comprise determining the preferred configuration of the one or more catheter electrodes (ablation electrodes). Thereby the catheter may comprise multiple catheter (ablation) electrodes which could be activated or deactivated (selected). The determination and / or storing of the preferred configuration of catheter electrodes may be done in the same way as described above.

[0045] In some examples, the determining the return electrode configuration may be based on the configuration whose associated patient response indicates the least muscle twitching.

[0046] Muscle twitching poses a suitable patient response that may be observed to assess if a currently chosen return electrode configuration poses a beneficial tailoring of the path of the current between the catheter and the one or more return electrodes to avoid unwanted

[0047] - 8 -

[0048] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1 side effects, e.g., like muscle twitching. As muscle twitching may be a major side effect that the attending health professional may want to avoid, it is expedient to use that side effect as a patient response assessed for determining a return electrode configuration that may be chosen for a (subsequent) PFA treatment of the patient.

[0049] The concept related to the patient response in general and / or the muscle twitching as a specific patient response may be quantified as follows: In some examples, the patient response comprises motion data from a motion sensor.

[0050] The motion sensor may comprise one or more sensor modules. The sensor modules may comprise at least one of: an accelerometer, a gyroscope, a magnetometer, a vibration sensor and / or an optical sensor. These sensors may, e.g., work in tandem to capture motion-related parameters and / or provide accurate motion tracking. The motion sensor may comprise a data processing unit, a memory unit, and / or wireless communication means. The data processing unit may, e.g., receives raw motion data from the one or more sensor modules and / or process said raw motion data to extract meaningful motion parameters. These raw motion data and / or processed motion parameters may comprise: an acceleration, an angular velocity, an orientation, a position, a gesture, and / or an environmental parameter.

[0051] Preferably, the motion sensor is mounted on the patient’s chest. It may transmit motion data (e.g., acceleration information) by communicating with the control unit and / or server in a wired or wireless way (e.g., Blue-tooth, WiFi, etc.). The motion sensor may, for example, be configured to provide acceleration in X, Y or Z directions, or the value of the overall acceleration vector (e.g., magnitude and / or direction). Both acceleration magnitude and / or direction are important in order to minimize chances of muscular ablation. For example, preclinical research shows that phrenic nerve capture while ablating the right superior pulmonary vein may lead to Phrenic nerve stimulation which in turn may lead to skeletal muscle capture. The system according to this invention may detect the direction of the acceleration vector and determine return electrodes that change the direction of the stimulating electric field away for the phrenic nerve location.

[0052] - 9 -

[0053] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1

[0054] The motion data recorded by the sensor may be stored in the memory unit, which can be non-volatile memory, such as, e.g., flash memory and / or other suitable storage mediums. The memory unit may allow for the accumulation and / or storage of motion data, e.g., over extended periods. The wireless communication means may, e.g., be based on Bluetooth, Wi-Fi, and / or cellular connectivity. This may enable the motion sensor to transmit recorded motion data to (external) devices, such as, e.g., smartphones, tablets, and / or computers, e.g., for further analysis, visualization, and / or integration into applications.

[0055] Altogether, employing a motion sensor as described herein for recording motion data may increase reproducibility and / or reliability of the method and / or reduce the risk of human errors and / or the time needed to quantify the patient response.

[0056] In some examples, the motion data may comprise at least one of the following: a linear acceleration, a circular acceleration, a vibration, and an inclination.

[0057] The sensor may be configured as described herein and yield the advantage to be able to record various kinds of motion data. Each kind of motion data may be particularly suitable for different PFA treatments. Some exemplary measurements may be performed as follows: The motion sensor may record a linear acceleration in three-dimensional space, capturing changes in velocity over time, e.g., in form of a vibration. The sensor may measure rotational speed or angular velocity around various axes, providing information about rotational motion. The motion sensor may determine the sensor inclination and / or orientation relative to a reference frame, such as, e.g., the earth's magnetic field or a predefined coordinate system. For example, by integrating acceleration data over time, the motion sensor may estimate the position or displacement of the device in three-dimensional space. For gesture recognition, the sensor modules, e.g., in combination with pattern recognition algorithms, may detect and / or classify specific body gestures. The motion sensor may comprise additional sensors to record environmental parameters such as, e.g., temperature, humidity, atmospheric pressure, and / or ambient light levels.

[0058] - 10 -

[0059] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1

[0060] In some examples, the determining the configuration may be at least in part based on the motion data, preferably based on a parameter of the motion data parametrizing muscle twitching.

[0061] The parameters utilized for characterizing and quantifying muscle twitching may, e.g., comprise one or more of the following: a frequency, an amplitude, a duration, an intertwitch interval, a recruitment pattern, a spatial distribution, and / or a coherence. These exemplary parameters are described in further detail in the following: The frequency parameter may represent a number of muscle twitches occurring within a specific time interval, typically measured in twitches per minute (TPM) or hertz (Hz). The amplitude parameter may quantify the intensity and / or magnitude of muscle twitches. It may express the extent of movement and / or force and / or acceleration generated during a twitch may be measured in units such as millimeters, newtons, millimeter per second squared and / or percentage of maximal voluntary contraction. The duration parameter may measure the time taken for each individual muscle twitch, typically recorded in milliseconds (ms) or seconds (s). The inter-twitch interval parameter may measure the time gap between consecutive muscle twitches. It may thus quantify the temporal spacing between twitch events and is typically measured in milliseconds (ms) or seconds (s). The recruitment pattern parameter may describe the order and timing of muscle fiber activation during muscle twitching. It may, e.g., provide information about the motor unit recruitment pattern. The spatial distribution parameter may characterize the distribution and location of muscle twitches within a specific muscle or muscle group. It can be assessed using techniques such as ultrasound imaging or spatial mapping of muscle activity. The coherence parameter may measure the degree of synchronization or coordination between muscle twitches within a muscle and / or across different muscles. It can be quantified using techniques such as cross-correlation analysis or coherence analysis of electromyography signals. One or more of these exemplary parameters can be recorded using various measurement techniques, including surface electromyography, force transducers, motion sensors as described herein, and / or imaging modalities. The recorded data can be processed and analyzed using signal processing algorithms, statistical methods, and / or machine learning techniques to derive meaningful insights about muscle twitching patterns.

[0062] - 11 -

[0063] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1

[0064] This may offer several advantages in the field of muscle twitching analysis. By providing standardized parameters, it enables consistent and objective quantification of muscle twitching events across different individuals, conditions, or studies. This facilitates accurate comparisons, assessment of treatment efficacy for the purpose of determining a return electrode configuration for PF A.

[0065] In some examples, the method may further comprise adjusting at least one ablation parameter of the electrical ablation based on a patient response.

[0066] This may, e.g., be an advantageous step in situations in which no satisfying return electrode configuration and / or catheter electrode configuration can be found for the chosen PF A treatment. For example, in such a situation the intensity of the PFA treatment and / or any other parameter described herein may be reduced, increased and / or otherwise adjusted. For the changed PFA treatment it may then be possible to find a satisfying return electrode configuration as described herein.

[0067] In some examples, the method may further comprise temporarily attaching the configurable return electrode system to a patient’s body.

[0068] For example, the return electrodes may be attached individually in an arrangement that may be adapted to the specific needs during a planned PFA treatment. Alternatively, the return electrodes may be positioned in a predetermined mutual arrangement on a common path which may be attached to the patient’s body saving time and increasing reproducibility. Such predetermined arrangement may be in any form that proved beneficial in such treatments.

[0069] Temporarily attaching the configurable return electrode system to a patient’s body may especially comprise attaching the configurable return electrode system to the patient’s skin, preferably the patient’s chest, back, and / or limbs. One or more such configurable return electrode systems may be attached to different parts of the patient’s body at the same time or one after another.

[0070] - 12 -

[0071] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1

[0072] According to a further aspect, a configurable return electrode system for a pulsed field ablation PFA catheter is provided. Said configurable return electrode system comprises a plurality of return electrodes, wherein a subset of the return electrodes is adapted for being reproducibly activated and / or deactivated, independently from at least one return electrode of the plurality of return electrodes not comprised by the subset.

[0073] This configurable return electrode system may, e.g., be attached to the patient’s body and / or yields the advantages as described herein in reference to the according method.

[0074] According to a third aspect, a control unit is provided which is configured to reproducibly activate and / or deactivate a subset of the return electrodes of the configurable return electrode system described herein. Said control unit may further be configured to control at least one parameter for providing the electrical ablation via the PFA catheter and / or receive motion data from a motion sensor to determine a configuration of the configurable return electrode system, based at least in part on the motion data. In some examples, it may additionally or alternatively be configured to control a pulse generator providing the electrical ablation energy via the PFA catheter.

[0075] The control unit may be coupled with the configurable return electrode system, e.g., to reproducibly activate and / or deactivate a subset of the return electrodes of the configurable return electrode system described herein. For example, the control unit may additionally control the pulse generator when it is configured to control at least one parameter for providing the electrical ablation via the PFA catheter and / or be configured to receive motion data from a motion sensor to determine a configuration of the configurable return electrode system, based at least in part on the motion data.

[0076] Said control unit may act as an intersection between the configurable return electrode system and at least one of the PFA catheter and the motion sensor. Said control unit may, e.g., be distributed across multiple devices, e.g., there may pe separate control devices for the configurable return electrode system, the PFA catheter, and / or the motion sensor which collectively pose the control unit. Further, the control unit may outsource one or more functionalities to external devices and / or servers, e.g., a cloud-based server.

[0077] - 13 -

[0078] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1

[0079] According to a fourth aspect, a system comprises a configurable return electrode system as described herein, and at least one of the following: a control unit as described herein, a pulse generator, a PFA catheter, and a motion sensor.

[0080] Such system yields the advantages described in reference to the respective method executed by such system and / or the respective components.

[0081] According to a fifth aspect, a computer program comprises instructions for providing at least one electrical ablation by a PFA catheter, activating and / or deactivating a subset of a plurality of return electrodes of a configurable return electrode system.

[0082] Such computer program yields the advantages described herein in reference to the according method.

[0083] Any steps of the method described herein may also be implemented as means of the corresponding device, e.g., the configurable return electrode system, the control unit and / or the system comprising any of those, functionalities thereof, and / or instructions of a computer program and vice versa.

[0084] DESCRIPTION OF THE DRAWINGS

[0085] Fig. 1 shows an exemplary system comprising a PFA catheter, a control unit, a configurable return electrode system controlled by a activation-deactivation-means, and a motion sensor;

[0086] Fig. 2 shows an exemplary arrangement of four equally shaped return electrodes of a configurable return electrode system;

[0087] Fig. 3 shows an exemplary arrangement of nine return electrodes of a configurable return electrode system placed on a common patch;

[0088] - 14 -

[0089] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1

[0090] Fig. 4 shows an exemplary workflow for testing all possible configurations of the configurable return electrode system of Fig. 2.

[0091] DETAILED DESCRIPTION

[0092] Fig. 1 shows an exemplary system 100 comprising a PF A catheter 110, a central control unit 120, a configurable return electrode system 140 controlled by an activation- deactivation-means 130, such as a switch, and a motion sensor 150. In said system 100 the control unit 120 is the central element connecting the PFA catheter 110, the configurable return electrode system 140, and the patient muscular activity sensor (motion sensor) 150.

[0093] First, the control unit 120 may be configured to control the ablation provided by the PFA catheter 110 as described herein. At the same time, it may receive patient muscular activity data recorded by the motion sensor 150, e.g., associated with motions induced by the PFA treatment delivered by the PFA catheter 110.

[0094] Further, the control unit 120 is coupled to the activation-deactivation-means 130 for reproducibly activating and / or deactivating a subset of the plurality of return electrodes 140a, 140b, 140c, 140d of the configurable return electrode system 140. Said subset may comprise only one or up to all return electrodes 140a, 140b, 140c, 140d of the configurable return electrode system 140. The return electrodes 140a, 140b, 140c, 140d of the configurable return electrode system 140 may be placed on the patient’s body as described herein.

[0095] In an exemplary operation, wherein the control unit 120 also comprises a pulse generator as described above inducing the ablation via the catheter 110, the control unit 120 may select (activate and / or deactivate) appropriate return electrodes. In response, the impedance seen at its output may change. In order to keep the PFA waveform profile and parameters the same from one application to the next, the control unit 120 may be adapted to adjust its internal impedance, in particular the internal impedance of the pulse generator. For example, in order to keep the PFA waveform charge balanced and to use similar amount of

[0096] - 15 -

[0097] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1 charge levels at various locations, the control unit may modify the capacity of the at least one capacitor of the pulse-shaping output stage of the pulse generator, in particular its output series capacitance of the pulse-shaping output stage as a function of which return electrode 140a, 140b, 140c, 140d is used or the number of selected return electrodes 140a, 140b, 140c, 140d used.

[0098] Fig. 2 shows an exemplary arrangement of four equally shaped return electrodes 240a, 240b, 240c, 240d of a configurable return electrode system 240 controlled by an activation- deactivation-means 230 (which in turn may be controlled by a control unit, e.g., as described in reference to Fig. 1).

[0099] The four return electrodes 240a, 240b, 240c, 240d have essentially the same shape and size: They have a rectangular shape but in other examples, the return electrodes 240a, 240b, 240c, 240d might have different shapes and / or differ in shape (e.g., circular and / or any polygon) and / or size relative to one another.

[0100] Further, in Fig. 2, return electrodes 240a, 240b, 240c, 240d are positioned in a 2 x 2 matrix. The two return electrodes 240a, 240b at the top are spaced as far apart from the two return electrodes 240c, 240d as the two return electrodes 240a, 240c on the left are spaced apart from the two return electrodes 240b, 240d on the right. Also, the distances between return electrodes 240a, 240b, 240c, 240d might vary in other embodiments. The return electrodes 240a, 240b, 240c, 240d of Fig. 2 may be positioned independently from one another, e.g., by means of an adherent layer on one side of the return electrodes 240a, 240b, 240c, 240d. Said adherent layer allows, e.g., to attach the return electrodes 240a, 240b, 240c, 240d to a patient’s body during a PF A treatment.

[0101] Fig. 3 shows an exemplary arrangement of nine essentially rectangular return electrodes 340a, 340b, 340c, 340d, 340e, 340f, 340g, 340h, 340i of a configurable return electrode system 340 placed on a common patch 341. The return electrodes 340a, 340b, 340c, 340d, 340e, 340f, 340g, 340h, 340i are positioned in a 3 x 3 matrix on the patch, wherein neighboring electrodes are separated by a distance dv vertically and by a distance dh horizontally. The return electrodes 340a, 340c, 340g, 340i in the corners of the 3 x 3 matrix - 16 -

[0102] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1 have the same essentially rectangular shape with the smallest area. The central top and central bottom return electrodes 340b, 340h are slightly longer in the horizontal direction but have the same height. The central right and central left electrodes are vertically wider than the return electrodes 340a, 340c, 340g, 340i in the comers and the central electrode 340e has the largest area.

[0103] The patch 341 may, e.g., be attached to the patient’s body by attaching the return electrodes 340a, 340b, 340c, 340d, 340e, 340f, 340g, 340h, 340i in a predetermined arrangement relative to one another on the patient’s body.

[0104] Fig. 4 shows an exemplary workflow 400 for testing all possible configurations of the configurable return electrode system comprising four electrodes in a 2 x 2 matrix as shown, e.g., in Fig. 2. Each row 410, 420, 430, 440, 450 corresponds to testing a certain number of activated return electrodes (black) vs. deactivated electrodes (white).

[0105] First, a configuration is tested wherein all four return electrodes are activated 410. Second, four configurations in which three out of the four return electrodes are active are tested 420. Third, all six configurations in which two out of the four return electrodes are active are tested 430. Fourth, all configurations in which only one out of the four return electrodes are active are tested 440. Last, the configuration in which no return electrode is activated is tested 450. In another embodiment steps two to four may be reversed.

[0106] Thereby, all possible configurations for the configurable return electrode system with a 2 x 2 return electrode matrix may be tested. Testing may, e.g., comprise recording a patient response as described herein for a certain time for each electrode configuration and saving the recorded motion data while providing PFA ablation to the patient. Based thereon, the preferred return electrode configuration out of the 16 tested possibilities may be determined for executing the subsequent PFA treatment.

[0107] The concept may be transferred to any other number, shape, and / or arrangement etc. of electrodes. Not all possible combinations must be tested. One might, e.g., terminate a process as the one illustrated in Fig. 4 as soon as one electrode configuration is found, for

[0108] - 17 -

[0109] 132922-0015W001 / 9995321 1 Attorney Docket No. 132922-0015W0Q1 which the patient response and / or at least one parameter of the motion data is below a predetermined threshold, e.g., indicating that the patient response is sufficiently moderate.

[0110] Algorithms may be used to minimize the number of required arrangements. These algorithms may compare the movement / acceleration results of different arrangements. Example for algorithm to find the return electrode or a combination of return electrodes to minimize muscle twitching: Compare acceleration a when all return electrodes are active versus only one return electrode active. If a all < a_i determine the minimum acceleration by checking (in case of 4 return electrodes) all combinations of 3 electrodes, if a all > a_i determine the minimum acceleration by checking all combinations of 2 electrodes. If one a_i value is particularly lower than other acceleration values this could be used to directly stop further test pulses or only use return electrode pairs containing return electrode i which has the lowest acceleration value. Stop when a certain threshold is achieved or when the change in acceleration is lower than a predefined threshold.

[0111] It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teaching. For example, the muscular activity sensor 150 may be optional. A skilled user could use the invention by adjusting the return electrode matrix manually, based on visual assessment of patient’s muscular activity in response to PF A pulse application. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention.

[0112] - 18 -

[0113] 132922-0015W001 / 9995321 1

Claims

Attorney Docket No. 132922-0015W0Q1CLAIMSWhat is claimed is1. A method for pulsed field ablation, PF A, comprising: providing at least one electrical ablation by a PFA catheter; and a configurable return electrode system comprising a plurality of return electrodes, wherein a subset of the plurality of return electrodes may be reproducibly activated and / or deactivated, independently from at least one electrode of the plurality of return electrodes not comprised by the subset.

2. The method of claim 1, further comprising: determining a patient response to the at least one electrical ablation; and determining a configuration of the return electrode system at least in part based on the patient response.

3. The method of claim 1 or 2, further comprising: providing a first electrical ablation with the return electrode system in a first configuration; switching the return electrode system into a second configuration by activating and / or deactivating at least one of the plurality of electrodes; and providing a second electrical ablation with the return system in the second configuration.

4. The method of claim 3, further comprising: determining a first patient response to the first electrical ablation; determining a second patient response to the second electrical ablation; and determining a configuration of the return electrode system at least in part based on the first and / or second patient response.

5. The method of claim 4, further comprising, for each of the at least one electrical ablation, storing information on the configuration of the return electrode system used- 19 -132922-0015W001 / 9995321 1Attorney Docket No. 132922-0015W0Q1 for applying the ablation and the patient response determined for the ablation, and optionally one or more ablation parameters of the electrical ablation.

6. The method of any of claims 2 - 5, wherein determining the configuration is based on the configuration whose associated patient response indicates the least muscle twitching.

7. The method of any of claims 2 - 6, wherein the patient response comprises motion data from a motion sensor.

8. The method of claim 7, wherein the motion data comprises at least one of the following: a linear acceleration, a circular acceleration, a vibration, and an inclination.

9. The method of any of claims 7 or 8, wherein the determining the configuration is at least in part based on the motion data, preferably based on a parameter of the motion data parametrizing muscle twitching.

10. The method of any of claims 1 - 9, further comprising adjusting at least one ablation parameter of the electrical ablation based on a patient response.

11. The method of any of claims 1 - 10, further comprising temporarily attaching the configurable return electrode system to a patient’s body.

12. A configurable return electrode system for a pulsed field ablation comprising: a plurality of return electrodes; wherein a subset of the return electrodes is adapted for being reproducibly activated and / or deactivated, independently from at least one electrode of the plurality of return electrodes not comprised by the subset.- 20 -132922-0015W001 / 9995321 1Attorney Docket No. 132922-0015W0Q113. A control unit configured to reproducibly activate and / or deactivate a subset of the return electrodes of the configurable return electrode system of claim 12, wherein the control unit is further configured to: control at least one parameter for providing the electrical ablation via the PFA catheter, in particular control a pulse generator providing the electrical ablation energy via the PFA catheter; and / or receive motion data from a motion sensor to determine a configuration of the configurable return electrode system, based at least in part on the motion data.

14. A system comprising the configurable return electrode system of 12, and at least one of the following: the control unit of claim 13; a pulse generator, a PFA catheter; and a motion sensor.

15. A computer program comprising instructions for: providing at least one electrical ablation by a pulsed field ablation catheter; activating and / or deactivating a subset of a plurality of return electrodes of a configurable return electrode system.

16. A configurable return electrode system for a pulsed field ablation comprising: a plurality of return electrodes; means for connecting the plurality of return electrodes to a control unit; wherein a subset of the return electrodes is adapted for being reproducibly activated and / or deactivated, independently from at least one electrode of the plurality of return electrodes not comprised by the subset.

17. The configurable reture electrode system of claim 16, wherein the control unit of claim is configured to reproducibly activate and / or deactivate a subset of the return electrodes of the configurable return electrode system, wherein the control unit being further configured to:- receive patient muscular activity data from a sensor to determine a configuration of the configurable return electrode system, based at least in part on said activity data;- 21 -132922-0015W001 / 9995321 1Attorney Docket No. 132922-0015WOQ1- control at least one parameter for providing electrical ablation energy to a catheter.

18. A computer program comprising instructions for: - driving a control unit to activate and / or deactivate a subset of a plurality of return electrodes of a configurable return electrode system in response to data from a patient’s activity sensor; and- deliver electrical ablation energy to a PFA catheter;- activating and / or deactivating a subset of the plurality of return electrodes of a configurable return electrode system.- 22 -132922-0015W001 / 9995321 1

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