Local impedance indicators in cardiac tissue treatment

Abstract

The therapeutic catheter is part of a system that includes a local impedance indicator displayed on a screen. The local impedance indicator displays relative changes in impedance to the user to quickly convey information that helps the user better understand where the catheter is positioned within the cardiac chamber.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority and benefit to U.S. Patent Application No. 63 / 493,713, filed on March 31, 2023, which is hereby incorporated by reference in its entirety.

Background Art

[0002] Therapeutic energy can be applied to the heart and vascular system for the treatment of various conditions, including atherosclerosis (particularly in the prevention of restenosis after angioplasty) and cardiac arrhythmias such as atrial fibrillation. Atrial fibrillation is the most common persistent cardiac arrhythmia and significantly increases the risk of death in affected patients, particularly by causing stroke. In this condition, the heart deviates from normal sinus rhythm due to the generation of errant electrical impulses. Atrial fibrillation is thought to originate in the myocardial sleeve of the pulmonary veins (PVs) because cells within the myocardial tissue of the PVs have automaticity. The pacemaker activity of these cells is thought to result in the formation of ectopic contractions that cause atrial fibrillation. Also, the PVs are thought to be important for maintaining atrial fibrillation because their disorganized structure and electrophysiological properties provide an environment in which atrial fibrillation can persist. Therefore, the goal is to destroy or remove these abnormal pacemaker cells within the myocardial sleeve of the PVs, and atrial fibrillation is often treated by delivering therapeutic energy to the pulmonary veins. However, reports of PV stenosis have led this approach to be conventionally modified to target the PV ostia in order to achieve a conduction block between the PVs and the left atrium. The PV ostia surround the ceiling and posterior wall of the left atrium in addition to the pulmonary veins and, in the case of the right PV ostium, also surround a portion of the atrial septum. In some instances, this technique provides a higher success rate and a lower complication rate compared to pulmonary vein isolation.

[0003] Thermal ablation therapy, particularly radiofrequency (RF) ablation, is now the “absolute standard” for treating atrial fibrillation symptoms caused by localized tissue necrosis. Typically, RF ablation is used to form a ring of ablation lesions around the outside of each of the four pulmonary veins. The RF current causes tissue drying by creating localized thermal areas, resulting in individualized coagulation necrosis. The necrotic tissue acts as a conduction block, thereby electrically insulating the veins.

[0004] Despite improvements in techniques for restoring sinus rhythm using available methods, both success rates and safety remain limited. RF ablation continues to present several limitations, some of which include the long procedure time required to isolate pulmonary veins using RF local catheters, potential gaps in ablation patterns due to point-to-point ablation techniques using conventional RF catheters, difficulty in forming and confirming transmural ablation lesions, carbonization and / or gas formation at the catheter tip-tissue interface due to high temperatures (which can lead to thrombosis or embolism during ablation), and thermal damage to collateral extracardial structures, including pulmonary vein stenosis, phrenic nerve injury, esophageal injury, atrial-esophageal fistula, periesophageal vagus nerve injury, perforation, thromboembolic events, vascular complications, and acute coronary artery occlusion. These limitations stem primarily from the ongoing debate faced by clinicians regarding balancing effective therapeutic doses with inadequate energy delivery to extracardiac tissues.

[0005] Therefore, while maintaining this technology in clinical practice, safer and more versatile methods for removing abnormal tissue are sought, including irreversible electroporation (IRE), a non-thermal therapy based on irreversible permeabilization of cell membranes caused by specific short pulses of high-voltage energy. IRE is known to be tissue-specific, induce apoptosis rather than necrosis, and be safe for structures adjacent to the myocardium. However, the success of these IRE methodologies has been uneven to date. In some cases, the delivery of IRE energy resulted in incomplete blocking of the abnormal electrical rhythm. This can be attributed to various factors such as irregularities in the procedure around the pulmonary veins, insufficient transmural delivery of energy, or other deficiencies in energy delivery. In any case, atrial fibrillation is either not adequately treated or recurs later. Therefore, improvement in the treatment of atrial fibrillation is desired. Such treatment should be safe, effective, and result in reduced complications. At least some of these objectives are achieved by the systems, devices, and methods described herein.

[0006] Reference All publications, patents, and patent applications described herein are incorporated herein by reference to the same extent as each individual publication, patent, or patent application is explicitly and individually referred to. [Overview of the project]

[0007] The therapeutic catheter is part of a system that includes a local impedance indicator displayed on a screen. The local impedance indicator displays relative changes in impedance to the user to quickly convey information that helps the user better understand where the catheter is positioned within the cardiac chamber.

[0008] In one embodiment, a system for delivering therapeutic energy during a tissue repair procedure is disclosed. The system includes at least one catheter and an energy delivery body configured with at least one catheter. The energy delivery body can be defined by a plurality of spline electrodes, each configured with at least one catheter. The system further includes at least one impedance sensor, each configured with at least one catheter, each impedance sensor being associated with at least one of the plurality of spline electrodes.

[0009] At least one processor is configured to process information associated with at least one impedance sensor by executing instructions stored in a processor-readable medium, and the display is configured to provide the information processed by at least one processor. At least one processor is further configured to (a) determine a reference impedance value, the reference impedance value being based on the impedance detected by at least one impedance sensor; (b) display on a display an impedance indicator consisting of a plurality of spokes, each spoke being associated with each electrode of a spline electrode, and each spoke being configured to represent the reference impedance value; (c) define a threshold impedance value; (d) detect by at least one impedance sensor a local impedance associated with at least one of the spline electrodes navigating around an organ via at least one catheter; (e) at least one processor determines the change in impedance from the reference impedance to the local impedance; (f) at least one processor modifies each of at least one spoke of the impedance indicator in response to the change in impedance to generate a modified impedance indicator; and (g) display on a display the modified impedance indicator, and the tissue modification device delivers therapeutic energy via an energy delivery body.

[0010] While the drawings are not necessarily drawn to scale, similar figures may illustrate similar components in different figures. Similar figures with different letter suffixes may represent different examples of similar components. The drawings schematically illustrate, but are not limiting, the various embodiments described herein. [Brief explanation of the drawing]

[0011] [Figure 1]An embodiment of the organizational restructuring system is shown. [Figure 2A] An embodiment of a therapeutic catheter configured to provide local therapy is shown. [Figure 2B] An embodiment of a therapeutic catheter configured to provide local therapy is shown. [Figure 3] A portion of the heart is illustrated, showing cross-sections of the right and left atria, with the therapeutic catheter positioned within them. [Figure 4] This demonstrates the repeated application of energy point by point around the left inferior pulmonary vein using a therapeutic catheter to form a circular treatment zone. [Figure 5] This shows an embodiment of the signal waveform defined by the energy delivery algorithm. [Figure 6] An exemplary waveform defined by the energy delivery algorithm is shown, which results in voltage imbalance. [Figure 7] Further examples of waveforms with uneven voltage are shown. [Figure 8] An example of a waveform with uneven pulse width is shown. [Figure 9] An exemplary waveform defined by a different energy delivery algorithm is shown, where the waveform is single-phase and illustrates a special case of imbalance where only the positive or negative portion of the waveform exists. [Figure 10] Further examples of waveforms with single-phase pulses are shown. [Figure 11] An example of a waveform that causes phase imbalance is shown. [Figure 12] An exemplary waveform defined by a different energy delivery algorithm is shown, where the pulse is sinusoidal rather than square. [Figure 13] This document illustrates an embodiment of a therapeutic catheter having an energy delivery body consisting of multiple splines. [Figure 14] Figure 13 provides a side view of an embodiment of a therapeutic catheter. [Figure 15] Figures 13 and 14 show the bottom view of the therapeutic catheter. [Figure 16]Provide another perspective view of the embodiment of FIG. 13. [Figure 17] Provide an enlarged view of the portion of the therapeutic catheter of FIG. 13 within the distal end of the shaft. [Figure 18A] Provide an enlarged view of the elements comprising the present embodiment of the therapeutic catheter of FIG. 13. [Figure 18B] Show the therapeutic catheter of FIG. 18A in a non-expanded state. [Figure 19A] It is a view of a therapeutic catheter according to another embodiment. [Figure 19B] It is a view of a therapeutic catheter according to another embodiment. [Figure 20A] It is a view of a therapeutic catheter in the form of a balloon catheter according to another embodiment. [Figure 20B] It is a view of a therapeutic catheter in the form of a balloon catheter according to another embodiment. [Figure 20C] It is a view of a therapeutic catheter in the form of a balloon catheter according to another embodiment. [Figure 21] Show the local impedance indicator at the reference value. [Figure 22] Show that as the detected local impedance value changes, the color, color tone, and shape of the local impedance indicator change. [Figure 23] It is a flowchart showing an exemplary method for calculating and displaying local impedance values. [Figure 24] Show a display with a direction arrow indicating the area of the energy delivery body of the therapeutic catheter that is in most contact with the tissue.

MODE FOR CARRYING OUT THE INVENTION

[0012] Devices, systems, and methods are provided for treating cardiac diseases, particularly the occurrence of arrhythmias, more specifically, to name a few, atrial fibrillation, atrial flutter, ventricular tachycardia, Wolff-Parkinson-White syndrome, and / or atrioventricular nodal reentrant tachycardia. The devices, systems, and methods deliver therapeutic energy to parts of the heart, particularly the entrances to the pulmonary veins, to provide tissue modification in the treatment of atrial fibrillation. Specific anatomical sites targeted include, to name a few, the superior vena cava, inferior vena cava, right pulmonary vein, left pulmonary vein, right atrium, right atrial appendage, left atrium, left atrial appendage, right ventricle, left ventricle, right ventricular outflow tract, left ventricular outflow tract, interventricular septum, left ventricular apex, myocardial scar region, myocardial infarction border zone, myocardial infarction channel, ventricular endocardium, ventricular epicardium, papillary muscle, and Purkinje system. Treatment is performed at isolated sites or as a series of treatments. Types of treatment include left atrial ceiling line formation, left atrial posterior / inferior line formation, posterior wall isolation, lateral mitral valve isthmus line formation, septal mitral valve isthmus line formation, left atrial appendage, right vena cava tricuspid isthmus (CTI), pulmonary vein isolation, superior vena cava isolation, Marshall's vein, lesion formation using complex schistoatrial potentials (CFAE), lesion formation using local impulse and rotor modulation (FIRM), and target ganglion ablation. Such tissue modification creates conduction blocks within the tissue to prevent the transmission of abnormal electrical signals. Devices, systems, and methods are typically used in electrophysiology laboratories or controlled operating rooms equipped with fluoroscopy and advanced ECG recording and monitoring capabilities. Typically, the electrophysiologist (EP) is the primary intended user of the system. The electrophysiologist is supported by trained nurses, technicians, and, if applicable, other electrophysiologist staff. Generally, tissue modification systems include specialized catheters, high-voltage waveform generators, and at least one unique energy delivery algorithm. Additional accessories and equipment may be available. Exemplary embodiments of specialized catheter designs are provided herein, including various delivery types, such as local delivery, "one-shot" delivery, and various possible combinations. For illustrative purposes, a simplified design is provided when describing the entire system. Such a simplified design provides unipolar local therapy. However, it can be understood that various other embodiments are also provided.

[0013] Figure 1 shows an embodiment of a tissue reshaping system 100, including a therapeutic catheter 102, a mapping catheter 104, a counter electrode 106, a waveform generator 108, and an external cardiac monitor 110. In this embodiment, the heart is accessed via the right femoral vein (FV) by an appropriate access procedure such as the Seldinger technique. Typically, the sheath 112 is inserted into the femoral vein FV, which serves as a conduit from which various catheters and / or tools, including the therapeutic catheter 102 and the mapping catheter 104, can advance. In some embodiments, it may be understood that the therapeutic catheter 102 and the mapping catheter 104 are combined within a single device. As shown in Figure 1, the distal ends of catheters 102 and 104 advance through the inferior vena cava, through the right atrium, and by transseptal puncture to the left atrium, thereby accessing the entrance to the pulmonary vein. The mapping catheter 104 is used to perform cardiac mapping, which refers to the process of identifying the temporal and spatial distribution of myocardial potentials during a particular rhythm. Cardiac mapping during abnormal heart rhythms aims to elucidate the mechanisms of the rhythm, describe the propagation of activation from initiation to completion within the region of interest, and identify the origin or key conduction sites to function as therapeutic targets. Once the desired treatment site is identified, catheter 102 is used to deliver therapeutic energy.

[0014] In this embodiment, the proximal end of the therapeutic catheter 102 is electrically connected to a waveform generator 108, which is software-controlled and produces short bursts of energy at high frequency delivered to the catheter 102 through a regulated energy output. In various embodiments, it may be understood that the output may be controlled or modified to achieve a desired voltage, current, or combination thereof. In this embodiment, the proximal end of the mapping catheter 104 is also electrically connected to the waveform generator 108, and the electronics for performing the mapping procedure are included in the generator 108. However, it may be understood that the mapping catheter 104 may instead be connected to a separate external device capable of providing a mapping procedure, such as an electroanatomical mapping (EAM) system (e.g., the CARTO® system by Biosense Webster / Johnson & Johnson, the EnSite® system by St. Jude Medical / Abbott, the KODEX-EPD system by Philips, or the Rhythmia HDX® system by Boston Scientific). Similarly, in some embodiments, a separate mapping catheter 104 is not used, and the mapping features are incorporated into the catheter 102.

[0015] In this embodiment, the generator 108 is connected to an external cardiac monitor 110, enabling energy delivery coordinated with cardiac signals detected from patient P. The generator synchronizes its energy output with the patient's cardiac rhythm. When the cardiac monitor detects the R wave of the patient's cardiac cycle, it provides a trigger signal to the generator 108. This trigger signal, along with the generator's algorithm, ensures that energy delivery is reliably synchronized with the patient's cardiac cycle, reducing the possibility of arrhythmias caused by energy delivery. Typically, a foot switch allows the user to initiate and control the delivery of energy output. The generator user interface (UI) provides the user with both audio and visual information regarding energy delivery and the operating status of the generator.

[0016] In this embodiment, the therapeutic catheter 102 is designed to be unipolar, with the distal end of the catheter 102 having a delivery electrode 122, and the counter electrode plate 106 being positioned on the skin outside the body, typically on the thigh, waist, or back. Figure 2A shows an embodiment of the therapeutic catheter 102 configured to provide local therapy. In this embodiment, the catheter 102 includes an elongated shaft 120, which has a delivery electrode 122 near its distal end 124 and a handle 126 near its proximal end 128. The delivery electrode 122 is shown as a “solid tip” electrode having a cylindrical shape with a continuous distal surface. In some embodiments, the cylindrical shape has a diameter of about 2–3 mm across the entire distal surface and a length along the shaft 120 of about 1 mm, 2 mm, 1–2 mm, 3 mm, 4 mm, 3–4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, etc. Such electrodes are typically hollow, but may be understood to be called solid electrodes due to their appearance. In some embodiments, the catheter 102 has an overall length of 50–150 cm, preferably 100–125 cm, more preferably 110–115 cm. Similarly, in some embodiments, the device has an outer diameter of 7 Fr, and an outer diameter of 3–15 Fr, preferably 4–12 Fr, more preferably 7–8.5 Fr. In some embodiments, the shaft 120 has a deflectable end 121, which may optionally have a length of 50–105 mm and may result in a curve with a diameter in the range of about 15–55 mm. Deflection may be achieved by various mechanisms including a pull wire extending to a handle 126. Thus, the handle 126 is used to manipulate the catheter 102, in particular to maneuver the distal end 124 during delivery and treatment. Energy is supplied to the catheter 102 via a cable 130 that can be connected to the generator 108, and subsequently to the delivery electrode 122.

[0017] A pulsed electric field (PEF) is provided by a generator 108 and delivered to the tissue via a delivery electrode 122 positioned above or near the target tissue area. In some embodiments, it may be understood that the delivery electrode 122 is positioned in contact with a conductive material that also contacts the target tissue. Such a solution may include an isotonic or hypertonic solution. These solutions may further include chemotherapy or adjuncts such as calcium to further enhance the therapeutic effect on both the targeted tissue type local therapy and potential local infiltration areas. High-voltage, short-duration, two-phase electrical pulses are delivered via the electrode 122 near the target tissue. These electrical pulses are provided by at least one energy delivery algorithm 152. In some embodiments, each energy delivery algorithm 152 defines a signal having a waveform comprising a series of energy packets, each energy packet comprising a series of high-voltage pulses. In such embodiments, the algorithm 152 specifies signal parameters such as energy amplitude (e.g., voltage) and duration of applied energy, consisting, to give some examples, the number of packets, the number of pulses in the packets, and the fundamental frequency of the pulse sequence. Additional parameters may include the switch time between the polarities of the two-phase pulse, the dead time between the two-phase cycles, and the pause time between packets, which will be described in more detail in a later section. There may be a fixed pause time between packets, or packets may be gated in accordance with the cardiac cycle, and thus variable with the patient's heart rate. There may be an algorithm for intentionally changing pause periods, or there may be no pause period between packets. It may include a feedback loop based on sensor information and automatic stop specifications and / or similar information.

[0018] A pulsed electric field (PEF) is provided by a generator 108 and delivered to the tissue via a delivery electrode 122 placed on or near a target tissue area within the heart H. One or more energy delivery algorithms 152 specify an electrical signal that provides the PEF energy to be delivered to the cardiac tissue, inducing cell death through non-thermal effects (e.g., energy below the threshold for thermal ablation, energy below the threshold for inducing coagulative thermal damage, etc.), thereby reducing or avoiding inflammation, and / or preventing the denaturation of interstitial proteins in anatomical structures (e.g., preventing stenosis) in sensitive areas that are involved in the morbidity or mortality of the treatment, such as the phrenic nerve, esophagus, and vascular system. It can be understood that the non-thermal energy is also not cryogenic (i.e., above the threshold for thermal damage caused by freezing). Therefore, the temperature of the target tissue is maintained in a range between reference body temperature (e.g., 35°C to 37°C, although it may drop to 30°C) and the threshold for thermal ablation. Therefore, the target tissue temperature range includes 30–65°C, 30–60°C, 30–55°C, 30–50°C, 30–45°C, and 30–35°C. Thus, since the tissue temperature is maintained below the threshold for thermal ablation (e.g., 65°C), cardiac tissue lesions are not caused by burns. Furthermore, the tissue impedance is typically maintained below the threshold caused by thermal ablation. Burning or charring of tissue alters the conductivity of cardiac tissue. This increase in impedance / decrease in conductivity often indicates burns and reduces the tissue's ability to receive further energy. In some examples, the impedance of the system circuit from cathode to anode is maintained in the range of 25–250Ω, 50–200Ω, or 75–125Ω during PEF energy delivery. Generally, algorithm 152 is adjusted to affect tissue up to a given depth and / or volume, and / or target a specific type of cellular response to the delivered energy.

[0019] In various embodiments, the therapeutic catheter 102 may include various special features. For example, in some embodiments, the catheter 102 includes a mechanism for measuring in real time the contact force applied by the catheter tip to the patient's heart wall during the procedure. In some embodiments, this mechanism is contained in the shaft 120 and comprises a triaxial optical force sensor utilizing white light interferometry. By monitoring and correcting the force applied throughout the procedure, the user can better control the catheter 102 to produce more consistent and effective damage.

[0020] In some embodiments, the catheter 102 includes one or more additional electrodes 125 (e.g., ring electrodes) positioned along the shaft 120 proximal to the delivery electrode 122, as shown in Figure 2B. In some embodiments, some or all of the additional electrodes can be used for stimulation and recording (for electrophysiological mapping), so a separate cardiac mapping catheter is not required when using the catheter 102 for lesion formation or other purposes such as detection.

[0021] In some embodiments, the catheter 102 includes a thermocouple temperature sensor optionally embedded in the delivery electrode 122. Similarly, in some embodiments, the catheter 102 includes a lumen that can be used for irrigation and / or aspiration. Typically, the lumen is connected to one or more ports along the distal end of the catheter 102 for purposes such as injecting isotonic saline or removing microbubbles.

[0022] In some embodiments, the catheter 102 includes one or more sensors that can be used to determine, to some extent, temperature, impedance, resistance, capacitance, conductivity, dielectric constant, and / or conductance. In some embodiments, one or more of the electrodes function as one or more sensors. In other embodiments, one or more sensors are separate from the electrodes. Sensor data can be used to plan treatment, monitor treatment, and / or provide direct feedback using the processor 154, which can then modify the energy delivery algorithm 152. For example, impedance measurements can be used not only to determine the initial dose to be applied, but also to determine whether further treatment is necessary.

[0023] Referring again to Figure 1, in this embodiment, the generator 108 includes a user interface 150, one or more energy delivery algorithms 152, a processor 154, a data retrieval / retrieval unit 156 (memory and / or database, etc.), and an energy storage subsystem 158 that generates and stores the energy to be delivered. In some embodiments, one or more capacitors are used for energy storage / delivery, but any other suitable energy storage element may be used. Furthermore, one or more communication ports are included.

[0024] In some embodiments, the generator 108 includes three subsystems: 1) a high-energy storage system, 2) a high-voltage medium-wave switching amplifier, and 3) a system controller, firmware, and user interface. In this embodiment, the system controller includes a cardiac synchronization trigger monitor that enables the pulse energy output to be synchronized with the patient's cardiac rhythm. The generator takes in an alternating current (AC) trunk line and powers multiple direct current (DC) power sources. The generator's controller can cause the DC power sources to charge the high-energy capacitor storage bank before energy delivery begins. At the start of therapeutic energy delivery, the generator's controller, high-energy storage bank, and two-phase pulse amplifier can operate simultaneously to produce a high-voltage, medium-wave output.

[0025] It will be understood that multiple generator electrical architectures can be employed to implement energy delivery algorithms. In particular, in some embodiments, advanced switching systems are used that allow pulsed electric field circuits to be directed to energy delivery electrodes, separate from the same energy storage system and high-voltage delivery system. Furthermore, generators used in advanced energy delivery algorithms employing rapidly changing pulse parameters (e.g., voltage, frequency, etc.) or multiple energy delivery electrodes can utilize modular energy storage systems and / or high-voltage systems, facilitating a highly customizable waveform and geographical pulse delivery paradigm. It should be further understood that the electrical architectures described above herein are illustrative only, and systems for delivering pulsed electric fields may or may not include additional switching amplifier components.

[0026] The user interface 150 may include a touchscreen and / or more conventional buttons, which enable the operator to input patient data, select a treatment algorithm (e.g., energy delivery algorithm 152), initiate energy delivery, view records stored in the storage / retrieval system 156, and / or otherwise communicate with the generator 108.

[0027] In some embodiments, the user interface 150 is configured to receive operator-defined inputs. Operator-defined inputs may include the duration of energy delivery, one or more other timing modes of the energy delivery pulses, power, and / or operating modes, or a combination thereof. Exemplary operating modes include (but are not limited to) system startup and self-test, operator input, algorithm selection, pre-treatment system status and feedback, energy delivery, post-energy delivery display or feedback, treatment data review and / or download, software updates, or any combination or partial combination thereof.

[0028] As described above, in some embodiments, the system 100 also includes a mechanism for acquiring an electrocardiogram (ECG), such as an external cardiac monitor 110, in situations where cardiac synchronization is desired. Exemplary cardiac monitors are available from AccuSync Medical Research Corporation and Ivy Biomedical Systems, Inc. In some embodiments, the external cardiac monitor 110 is operably connected to the generator 108. The cardiac monitor 110 can be used to continuously acquire the ECG signal. An ECG may be acquired by applying an external electrode 172 to patient P. The generator 108 provides the ability to synchronize energy delivery with the cardiac cycle by analyzing one or more cardiac cycles and identifying the start of a period in which energy is safely delivered to patient P. In some embodiments, this period is within milliseconds of the R wave (of the ECG QRS complex) to avoid inducing arrhythmias that may occur if the energy pulse is delivered on the T wave. While such cardiac synchronization is typically utilized when using unipolar energy delivery, it will be understood that it may be utilized as part of other energy delivery methods.

[0029] In some embodiments, the processor 154 modifies and / or switches between energy delivery algorithms, monitors energy delivery and any sensor data, and responds to the monitored data via a feedback loop, among other activities. In some embodiments, the processor 154 is configured to execute one or more algorithms for initiating a feedback control loop based on one or more measured system parameters (e.g., current), one or more measured tissue parameters (e.g., impedance), and / or a combination thereof.

[0030] The data retrieval / retrieval unit 156 stores data such as that related to delivered treatments, which can optionally be downloaded by connecting a device (e.g., a laptop or thumb drive) to the communication port. In some embodiments, the device has local software used to instruct the download of information such as instructions stored in the data retrieval / retrieval unit 156 and executable by the processor 154. In some embodiments, a user interface 150 allows the operator to download data to the device and / or system. Such devices and / or systems include, but are not limited to, computer devices, tablets, mobile devices, servers, workstations, cloud computing equipment / systems, and / or similar. The communication port, which may enable wired and / or wireless connections, enables data downloads as described herein, but may also enable data uploads, such as uploading custom algorithms or providing software updates.

[0031] As described herein, various energy delivery algorithms 152 are programmable or pre-programmable within the generator 108, such as being stored in memory or in the data retrieval / retrieval unit 156. Alternatively, the energy delivery algorithms can be added to the data retrieval / retrieval unit executed by the processor 154. Each of these algorithms 152 may be executed by the processor 154.

[0032] In some embodiments, the system 100 may include an automated treatment delivery algorithm, which may be understood to dynamically respond to inputs such as temperature, impedance at various voltages or AC frequencies, treatment duration or other timing aspects of energy delivery pulses, treatment power, and / or system status, and adjust and / or terminate the treatment.

[0033] As described above, in some embodiments, the cardiac monitor provides a trigger signal to the generator 108 when it detects the R wave of the patient's cardiac cycle. This trigger signal, and the generator's algorithm, ensure that energy delivery is synchronized with the patient's cardiac cycle, reducing the likelihood of arrhythmias caused by energy delivery. This trigger is within milliseconds of the peak of the R wave (of the ECG QRS complex), thereby avoiding the induction of arrhythmias that may occur if the energy pulse is delivered on the T wave, and ensuring that energy delivery occurs in a consistent phase of myocardial contraction. While such cardiac synchronization is typically used when using unipolar energy delivery, it will be understood that it may also be used as part of other energy delivery methods.

[0034] In this embodiment, the generator 108 is connected to an external cardiac monitor 110, enabling energy delivery in coordination with cardiac signals detected from patient P.

[0035] In some embodiments, the generator 108 receives feedback from the cardiac monitor 110 and responds based on the received information. In some embodiments, the generator 108 receives information about the patient's heart rate and either stops or modifies energy delivery, for example, by selecting a different energy delivery algorithm 152. In some embodiments, the generator 108 stops energy delivery when the heart rate reaches or falls below a threshold (30 bpm (bpm: heartbeats per minute) or 20 bpm). Optionally, the generator may provide an indicator, such as a visual or auditory indicator, when the heart rate reaches or falls below a lower threshold. For example, a yellow light flashes when the heart rate reaches 30 bpm, and a red light flashes when the heart rate reaches 20 bpm. Such safety measures ensure that therapeutic energy is not delivered at inappropriate times if sporadic low heart rates may indicate inaccurate readings.

[0036] In some embodiments, the generator 108 modifies energy delivery based on information from the cardiac monitor 110. For example, in some embodiments, energy delivery is provided in a 1:1 ratio when the heart rate is within a predetermined range, such as 40 bpm to 120 bpm. This involves delivering PEF energy at appropriate intervals with each heartbeat. In some embodiments, the generator 108 modifies energy delivery when the heart rate exceeds this range, such as when the heart rate exceeds 120 bpm. In some embodiments, energy delivery is modified to a 2:1 ratio (two heartbeats:one delivery), and PEF energy is delivered at appropriate intervals with each heartbeat. It can be understood that various ratios of the form m:n (where m and n are integers), e.g., 3:1, 3:2, 4:1, 4:3, 5:1, etc., may be utilized. In some embodiments, it can also be understood that the heart rate may be paced to achieve a desired heart rate. Such pacing may be provided by a separate pacemaker or an integrated pacemaker. In some embodiments, such pacing is provided by a catheter positioned within the coronary sinus, which is used for recording during the procedure but is also available for pacing. Such pacing can be triggered by a generator 108 or a cardiac monitor 110.

[0037] In some embodiments, the generator 108 stops or modifies energy delivery based on information from other sources, such as from various sensors including temperature sensors, impedance sensors, contact sensors, or contact force sensors. In some embodiments, the generator 108 modifies energy delivery based on detected temperature (e.g., temperature on catheter 102, in nearby tissue, in nearby structure, etc.). In some embodiments, energy delivery is modified to a 2:1 ratio, and when the temperature reaches a predetermined threshold, PEF energy is delivered at appropriate intervals per heartbeat. Such modification reduces slight thermal effects, thereby lowering the detected temperature. It can be understood that various ratios such as 3:1, 3:2, 4:3, 4:1, 5:1, etc., may be used.

[0038] As described above, one or more energy delivery algorithms 152 are programmable or pre-programmable within the generator 108 for delivery to patient P. One or more energy delivery algorithms 152 specify an electrical signal that provides energy delivered to cardiac tissue that is non-thermal (e.g., below the threshold for thermal ablation, below the threshold for inducing coagulative thermal damage) to reduce or avoid inflammation of the tissue and / or prevent denaturation of interstitial proteins in the lumen structure. It can be understood that non-thermal energy is also not cryogenic (i.e., above the threshold for thermal damage caused by freezing). Therefore, the temperature of the target tissue is maintained within a range between reference body temperature (e.g., 35°C to 37°C, but potentially down to 30°C) and the threshold for thermal ablation. Thus, the target range of tissue temperature includes 30 to 65°C, 30 to 60°C, 30 to 55°C, 30 to 50°C, 30 to 45°C, and 30 to 35°C. Therefore, since the tissue temperature is maintained below the threshold for thermal ablation (e.g., 65°C), lesions in cardiac tissue do not occur due to burns. Furthermore, the impedance of the tissue is typically maintained below the threshold that occurs due to thermal ablation. Burning or charring of tissue alters the conductivity of cardiac tissue. This increase in impedance / decrease in conductivity often indicates burns and reduces the tissue's ability to receive further energy. In some examples, the impedance of the system circuit from cathode to anode is maintained in the range of 25–250Ω or 50–200Ω during the delivery of PEF energy. Generally, algorithm 152 is adjusted to affect tissue to a given depth and / or volume, and / or to target a specific type of cellular response to the delivered energy. However, it can be understood that the pulsed electric field energy described herein may be more readily available than other types of energy, such as those that cause burns without adverse effects. For example, because the energy does not cause burns, tissue can be overtreated to ensure sufficient lesion formation. For example, in a tissue layer 2 mm thick, enough energy can be applied to the tissue to form a lesion with a depth of 6 mm, ensuring a transmural lesion.Normally, excess energy is dissipated away from nearby critical structures through transverse tissue surfaces. In particular, the pericardial fluid surrounding the heart plays a role in dissipating energy and protecting extracardiac structures such as the esophagus, phrenic nerve, coronary arteries, lungs, and bronchi from damage. This is not the case when delivering energy that causes burn-induced lesions. In those cases, if conductive thermal energy propagates beyond the target myocardial tissue, it can result in burns to non-target extracardiac structures. Excessive burns to the esophagus can result in esophageal ulcers that can break down into life-threatening atrial-esophageal fistulas. Burns to the phrenic nerve can result in permanent diaphragmatic paralysis, leading to persistent shortness of breath and fatigue. Burns to the coronary arteries can result in coronary artery spasms, which can cause temporary or even permanent chest tightness / pain. Furthermore, thermal lesions of the heart in the pulmonary vein region can result in pulmonary vein stenosis. Pulmonary vein stenosis is a known complication of radiofrequency ablation near the pulmonary veins in patients with atrial fibrillation. This pathological process is associated with burns to tissues that induce post-treatment fibrosis and scarring. Stenosis has been described in patients treated with various forms of thermal energy, including radiofrequency energy and cryoablation.

[0039] Since the PEF lesions described herein are not caused by burns, the rate of “false positive” confirmations of electrical conduction block is also reduced. Burns can result in acute myocardial edema (i.e., accumulation of tissue fluid and swelling). When examining electrical conductivity throughout the area of ​​thermally ablated tissue, the tissue may appear to be blocking electrical conduction, but such blockage may simply be a result of temporary edema. After a recovery period that allows the swelling to subside, this area of ​​treated tissue no longer exhibits permeable nonconductivity. Furthermore, acute edema due to burns also weakens the ability of the tissue area to be retreated. When an area of ​​tissue receives a certain amount of burn, the resulting edema alters the thermal resistance and thermal conductivity properties of the tissue. Therefore, it is difficult to obtain the same effect as the initial response of the tissue. Consequently, any attempted retreatment is less effective, both acutely and chronically. These problems are avoided by the energy delivery described herein.

[0040] Figure 3 illustrates a portion of the heart H and shows a cross-section of the right atrium (RA) and left atrium (LA) in the treatment of atrial fibrillation. The largest pulmonary veins are the four major pulmonary veins (superior right pulmonary vein (RSPV), right inferior pulmonary vein (RIPV), left superior pulmonary vein (LSPV), and left inferior pulmonary vein (LIPV)), two of which drain from each lung into the left atrium (LA) of the heart H. Each pulmonary vein is connected to the capillary network of the alveoli in each lung, carrying oxygenated blood to the left atrium (LA). The left atrial muscle extends from the left atrium (LA) and encloses the proximal pulmonary veins. The superior veins have a longer muscular sleeve and have been reported to be more arrhythmogenic than the inferior veins. Generally, the length of the pulmonary vein sleeve varies from 13 mm to 25 mm. The morphology of the pulmonary veins has been reported to influence arrhythmia development. Similarly, cellular electrophysiology and other aspects of the pulmonary veins are related to the development and propagation of arrhythmias.

[0041] Various methods, including anatomical landmarks and cardiac mapping, are used to determine which tissues will be targeted for treatment. Typically, the mapping catheter is selected to fit the pulmonary vein as desired, adapting to the size and anatomical morphology of the pulmonary vein. The mapping catheter allows for the recording of electrophoretic signals from both the opening of the pulmonary vein and from deep within the pulmonary vein. These electrophoretic signals are displayed and timed for the user. The therapeutic catheter 102 is initially placed deep within the pulmonary vein and gradually withdrawn to the opening proximal to the mapping catheter. Then, mapping and treatment are initiated.

[0042] The current understanding of pulmonary vein electrophysiology is that most of the pulmonary vein fibers are circular and do not conduct electricity within the veins. The electrical conduction pathway is the longitudinal fibers extending between the left atrium (LA) and the pulmonary veins. Isolation of the pulmonary veins is achieved by ablation of the longitudinal fibers connecting them. In the left pulmonary veins, pacing of the distal coronary sinus tends to increase the separation of atrial signals and pulmonary vein potentials, making them more electrically visible. Signals originating from within the pulmonary veins are evaluated. Individual signals consist of distant-field atrial signals, which are generally low amplitude, and sharp, localized pulmonary vein spikes. The earliest pulmonary vein spikes represent the junction between the pulmonary veins and the atria. When examining pulmonary vein spikes and atrial potentials, in some poles of the mapping catheter, these potentials are greatly separated, while in other areas, there is a fused potential of atrial and PV signals. The latter indicates the location of longitudinal fibers and potential treatment sites.

[0043] In some embodiments, as shown in Figure 3, the tissue surrounding the opening of the left inferior pulmonary vein (LIPV) is treated point by point using a therapeutic catheter 102 (with the assistance of mapping) to form a circular treatment zone around the left inferior pulmonary vein (LIPV). In some examples, specialized navigation software may be used to enable proper positioning of the therapeutic catheter 120. The delivery electrode 122 is positioned near or relative to the target tissue area, and energy is delivered to the delivery electrode 122 to form treatment area A. Because the energy is delivered to a local area (local delivery), the electrical energy is concentrated over a small surface area, resulting in a stronger effect of delivery than delivery via an electrode that extends circumferentially around the lumen or opening. It also forces the delivery of electrical energy in a stepwise local approach, mitigating the potential effects of preferential current paths through surrounding tissue. These preferential current paths are regions that have electrical properties that induce a localized increase in the flow of current through that current path rather than through adjacent regions. Such pathways can result in an irregular current distribution around the target lumen, thus distorting the electric field and potentially leading to an irregular increase in therapeutic effect in some areas and a decrease in therapeutic effect in others. This can be mitigated or avoided by using local therapies that stabilize the therapeutic effect around the target area. Therefore, by delivering energy to a specific area at once, the electrical energy is applied "forcibly" across different areas of the circumference, ensuring an improvement in the degree of circumferential regularity of the treated area. Figure 4 shows the repeated application of point-by-point energy around the left inferior pulmonary vein (LIPV) using a therapeutic catheter 102 to form a circular treatment zone. As illustrated, in this embodiment, each treatment area A overlaps with adjacent treatment areas A to form a continuous treatment zone. The size and depth of each treatment area A may depend on various factors such as parameter values, treatment time, and tissue characteristics. It can be understood that the number of treatment areas A may vary depending on various factors, in particular, the specific anatomical and electrophysiological conditions of each patient.In some embodiments, the number of treatment areas A includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, or more.

[0044] When all electrical connections between the atria and veins are treated, there is electrical silence within the pulmonary veins, and only distant-field atrial signals are recorded. Occasionally, spikes in electrical activity are observed within the pulmonary veins, which are not conducted to the rest of the atria. These clearly demonstrate the electrical discontinuity of the veins from the rest of the atrial muscle.

[0045] Depending on the clinical symptoms, additional therapeutic areas can be formed in other locations to treat arrhythmias in either the right or left atrium. Next, examinations are performed to ensure that each target pulmonary vein is effectively isolated from the left atrium itself.

[0046] Energy delivery algorithm It can be understood that various energy delivery algorithms 152 may be used. In some embodiments, algorithm 152 defines a signal having a waveform containing a series of energy packets, each energy packet containing a series of high-voltage pulses. In such embodiments, algorithm 152 specifies signal parameters such as energy amplitude (e.g., voltage) and duration of applied energy, consisting, to name a few, the number of packets, the number of pulses in each packet, and the fundamental frequency of the pulse sequence. Additional parameters may include the switch time between the polarities of the two-phase pulses, the dead time between the two-phase cycles, and the pause time between packets, which will be described in more detail in later sections. There may be a fixed pause time between packets, or the packets may be gated to match the cardiac cycle, and thus variable with the patient's heart rate. There may be an algorithm for intentionally changing pause periods, or there may be no pause period between packets. A feedback loop based on sensor information and automatic stop specifications and / or similar information may be included.

[0047] Figure 5 shows an embodiment of the signal waveform 400 defined by the energy delivery algorithm 152. Here, two packets (a first packet 402 and a second packet 404) are shown, separated by a pause period 406. In this embodiment, each packet 402, 404 consists of a first two-phase cycle (including a first positive pulse peak 408 and a first negative pulse peak 410) and a second two-phase cycle (including a second positive pulse peak 408' and a second negative pulse peak 410'). The first two-phase pulse and the second two-phase pulse are separated by a dead time 412 (i.e., pause) between each two-phase cycle. In this embodiment, the two-phase pulses are symmetrical such that the set voltage 416 is the same at the positive and negative peaks. Here, the two-phase symmetric wave is also a square wave such that the magnitude and time of the positive voltage wave are approximately equal to the magnitude and time of the negative voltage wave.

[0048] A. Voltage The voltage used and considered may be the peak of a square waveform, the peak of a sinusoidal or sawtooth waveform, or the RMS voltage of a sinusoidal or sawtooth waveform. In some embodiments, energy is delivered in a unipolar manner, and each high-voltage pulse or set voltage 416 is approximately 500V to 10,000V, specifically approximately 1000V to 2000V, 2000V to 3000V, 3000V to 3500V, 3500V to 4000V, 3500V to 5000V, and 3500V to 6000V, including all values ​​and partial ranges in between, such as approximately 1000V, 2000V, 2500V, 2800V, 3000V, 3300V, 3500V, 3700V, 4000V, 4500V, 5000V, 5500V, and 6000V.

[0049] It can be understood that the set voltage 416 may vary depending on whether the energy is delivered in a unipolar or bipolar manner. In hyperbolic delivery, a lower voltage may be used due to the smaller, more directional electric field. The bipolar voltage selected for use in treatment depends on the separation distance of the electrodes, but in unipolar electrode configurations using one or more distant dispersion pad electrodes, delivery may be made without considering the precise placement of the catheter electrode and dispersion electrode implanted in the body. In embodiments of unipolar electrodes, a higher voltage is typically used at an effective separation distance of about 10 cm to 100 cm due to the dispersion behavior of the delivered energy reaching the dispersion electrode through the body. Conversely, in bipolar electrode configurations, the active areas of the electrodes are relatively close, about 0.5 mm to 10 cm (including 1 mm to 1 cm), which has a significant impact on the concentration of electrical energy delivered to the tissue and the effective dose from the separation distance. For example, if the target voltage-to-distance ratio is 3000 V / cm to produce the desired clinical effect at an appropriate tissue depth (1.3 mm), then changing the separation distance from 1 mm to 1.2 mm would increase the treatment voltage from 300 V to approximately 360 V (a 20% change).

[0050] B.Frequency When a signal is continuous, it can be understood that the number of two-phase cycles per second is the frequency. In some embodiments, two-phase pulses are used to reduce undesirable muscle stimulation, particularly myocardial stimulation. In other embodiments, the pulse waveform is single-phase and has no distinct natural frequency. Instead, the fundamental frequency can be conceived by doubling the length of the single-phase pulse to derive the frequency. In some embodiments, the frequency of the signal is in the range of 50 kHz to 1 MHz, more specifically, in the range of 50 kHz to 1000 kHz. It can be understood that at some voltages, frequencies of 100 to 250 kHz or lower than 100 to 250 kHz may produce undesirable muscle stimulation. Therefore, in some embodiments, the signal has frequencies in the range of 300 to 800 kHz, 400 to 800 kHz, or 500 to 800 kHz, such as 300 kHz, 400 kHz, 450 kHz, 500 kHz, 550 kHz, 600 kHz, 650 kHz, 700 kHz, 750 kHz, 800 kHz, etc. Furthermore, cardiac synchronization is typically used to reduce or avoid undesirable myocardial stimulation during sensitive rhythmic periods. It can be understood that even higher frequencies may be used when components that minimize signal artifacts are employed.

[0051] C. Voltage and frequency balance The frequency of the delivered waveform may vary relative to the therapeutic voltage, which is synchronized to maintain the appropriate therapeutic effect. Such synergistic variations may include a decrease in voltage that produces a weaker effect and a decrease in frequency that produces a stronger effect. For example, in some cases, treatment may be performed using 3000V in a unipolar system with a waveform frequency of 600kHz, while in other cases, treatment may be performed using 2000V with a waveform frequency of 400kHz.

[0052] D. Packet As previously mentioned, algorithm 152 typically defines a signal having a waveform containing a series of energy packets, each energy packet containing a series of high-voltage pulses. The cycle count 420 is half the number of pulses in each two-phase packet. Referring to Figure 5, the cycle count 420 for the first packet 402 is 2 (i.e., four two-phase pulses). In some embodiments, the cycle count 420 is set to 2 to 1000 per packet, including all values ​​and partial ranges in between. In some embodiments, the number of cycles 420 is 5 to 1000 per packet, 2 to 10 per packet, 2 to 20 per packet, 2 to 25 per packet, 10 to 20 per packet, 20 per packet, 20 to 30 per packet, 25 per packet, 20 to 40 per packet, 30 per packet, 20 to 50 per packet, 30 to 60 per packet, up to 60 per packet, up to 80 per packet, up to 100 per packet, up to 1,000 per packet, or up to 2,000 per packet, and includes all values ​​and partial ranges between them.

[0053] Packet duration is determined by the number of cycles, among other factors. For matching pulse durations (or sequences of positive and negative pulse durations for a two-phase waveform), a higher number of cycles results in a longer packet duration and a greater amount of energy delivered. In some embodiments, packet durations are in the range of approximately 50 to 1000 microseconds, some examples being 50 μs, 60 μs, 70 μs, 80 μs, 90 μs, 100 μs, 125 μs, 150 μs, 175 μs, 200 μs, 250 μs, 100 to 250 μs, 150 to 250 μs, 200 to 250 μs, 500 to 1000 μs, etc. In other embodiments, packet durations are in the range of approximately 100 to 1000 microseconds, such as 150 μs, 200 μs, 250 μs, 500 μs, or 1000 μs.

[0054] The number of packets delivered during treatment, or the packet count, typically includes 1 to 250 packets, encompassing all values ​​and partial ranges within that range. In some embodiments, the number of packets delivered during treatment includes 10, 15, 20, 25, 30, or more than 30 packets.

[0055] E. Break time In some embodiments, the time between packets, called the pause period 406, is set to approximately 0.001 seconds to approximately 5 seconds, including all values ​​and partial ranges within that range. In other embodiments, the pause period 406 is in the range of approximately 0.01 to 0.1 seconds, including all values ​​and partial ranges within that range. In some embodiments, the pause period 406 is, to give a few examples, approximately 0.5 ms to 500 ms, 1 ms to 250 ms, or 10 ms to 100 ms.

[0056] F. Batch In some embodiments, the signal is synchronized with the heart rhythm so that each packet is delivered synchronously with the heartbeat within a specified period relative to the heartbeat, and the rest period coincides with the heartbeat. It can be understood that the packets delivered within each specified period relative to the heartbeat can be considered as batches or bundles. Thus, each batch has a desired number of packets so that a desired total number of packets are delivered at the end of the treatment period. Each batch may have the same number of packets, but in some embodiments, batches may have varying numbers of packets.

[0057] In some embodiments, only one packet is delivered between heartbeats. In such examples, the pause period can be considered the same as the period between batches. However, when two or more packets are delivered between batches, the pause time is usually different from the period between batches. In such examples, the pause time is usually much shorter than the period between batches. In some embodiments, each batch contains, to give a few examples, 1-10 packets, 1-5 packets, 1-4 packets, 1-3 packets, 2-3 packets, 2 packets, 3 packets, 4 packets, 5 packets, or 5-10 packets. In some embodiments, each batch has a period of, to give a few examples, 0.5ms-1 second, 1ms-1 second, 10ms-1 second, or 10ms-100ms. In some embodiments, the period between batches is variable depending on the patient's heart rate. In some examples, the period between batches is 0.25-5 seconds.

[0058] Treatment of a tissue area continues until the desired number of batches are delivered to the tissue area. In some embodiments, 2 to 50 batches are delivered per treatment, and the treatment is considered to be for a specific tissue area. In other embodiments, treatments include 5 to 40 batches, 5 to 30 batches, 5 to 20 batches, 5 to 10 batches, 5 batches, 6 batches, 7 batches, 8 batches, 9 batches, 10 batches, 10 to 15 batches, and so on.

[0059] G. Switch time and dead time As shown in Figure 5, the switch time is the delay in energy delivery or the period of no energy between the positive and negative peaks of a two-phase pulse. In some embodiments, the switch time is in the range of about 0 to about 1 microsecond, including all values ​​and partial ranges within that range. In other embodiments, the switch time is in the range of 1 to 20 microseconds, including all values ​​and partial ranges within that range. In other embodiments, the switch time is in the range of about 2 to about 8 microseconds, including all values ​​and partial ranges within that range.

[0060] Furthermore, delays can be inserted between each two-phase cycle, and are called "dead time." Dead time occurs within a packet, but between two-phase pulses. This is in contrast to pauses that occur between packets. In other embodiments, the dead time 412 is in the range of about 0 to 0.5 microseconds, 0 to 10 microseconds, 2 to 5 microseconds, 0 to 20 microseconds, about 0 to about 100 microseconds, or about 0 to about 100 milliseconds, including all values ​​and partial ranges within that range. In some embodiments, the dead time 412 is in the range of 0.2 to 0.3 microseconds. Dead time can also be used to define the period between separate single-phase pulses within a packet.

[0061] Delays such as switch time or dead time are introduced into packets to reduce the effects of biphasic cancellation in the waveform. In some examples, both switch time and dead time are increased together to enhance the effect. In other examples, only the switch time or only the dead time is increased to induce this effect.

[0062] G. Waveform Figure 5 shows an embodiment of a waveform 400 having symmetrical pulses such that the voltage and duration of a pulse in one direction (i.e., positive or negative) are equal to the voltage and duration of a pulse in the other direction. Figure 6 shows an exemplary waveform 400 defined by another energy delivery algorithm 152, in which waveform 400 results in voltage imbalance. Here, two packets (a first packet 402 and a second packet 404) are shown, separated by a pause period 406. In this embodiment, each packet 402, 404 consists of a first two-phase cycle (including a first positive pulse peak 408 having a first voltage V1 and a first negative pulse peak 410 having a second voltage V2) and a second two-phase cycle (including a second positive pulse peak 408' having a first voltage V1 and a second negative pulse peak 410' having a second voltage V2), where the first voltage V1 is greater than the second voltage V2. The first two-phase cycle and the second two-phase cycle are separated by a dead time 412 between each pulse. Therefore, the voltage in one direction (i.e., positive or negative) is greater than the voltage in the other direction. As a result, the area under the positive portion of the curve is not equal to the area under the negative portion of the curve. This unbalanced waveform may result in a more pronounced therapeutic effect because the dominant positive or negative amplitude prolongs the duration of the potential of the charge cell membrane. In this embodiment, the first positive peak 408 has a set voltage 416(V1) that is greater than the set voltage 416'(V2) of the first negative peak 410. Figure 7 shows further examples of waveforms with uneven voltages. Here, four different types of packets are shown in a single figure for simplified illustration. The first packet 402 consists of pulses with equal pulse widths but uneven voltages, and has no switch time and dead time. Therefore, the first packet 402 consists of four two-phase pulses, each pulse containing a positive peak 408 with a first voltage V1 and a negative peak 410 with a second voltage V2, where the first voltage V1 is greater than the second voltage V2. The second packet 404 consists of pulses that are voltage-uneven (like the first pulse 402) but pulse-width symmetrical, with a switch time equal to the dead time.The third packet 405 consists of pulses with uneven voltage but symmetrical pulse width (like the first pulse 402), with a switch time shorter than the dead time. The fourth packet 407 consists of pulses with uneven voltage but symmetrical pulse width (like the first pulse 402), with a switch time longer than the dead time. In some embodiments, the positive and negative phases of the two-phase waveform are not identical but are balanced, and the voltage in one direction (i.e., positive or negative) is greater than the voltage in the other direction, but the pulse lengths are calculated such that the area under the positive-phase curve is equal to the area under the negative-phase curve.

[0063] In some embodiments, the imbalance includes pulses with pulse widths having uneven durations. In some embodiments, the two-phase waveform is unbalanced so that the voltage in one direction is equal to the voltage in the other direction, but the duration in one direction (i.e., positive or negative) is longer than the duration in the other direction, so the area under the curve of the positive portion of the waveform is not equal to the area under the negative portion of the waveform.

[0064] Figure 8 shows further examples of waveforms with uneven pulse widths. Here, four different types of packets are shown in a single figure for simplified illustration. The first packet 402 consists of pulses with equal voltage but uneven pulse widths, with no switch time and no dead time. Thus, the first packet 402 consists of four two-phase pulses, each pulse containing a positive peak 408 with a first pulse width PW1 and a negative peak 410 with a second pulse width PW2. Here, the first pulse width PW1 is greater than the second pulse width PW2. The second packet 404 consists of pulses with uneven voltage but uneven pulse widths (like the first pulse 402), with a switch time equal to the dead time. The third packet 405 consists of pulses with equal voltage but uneven pulse widths (like the first pulse 402), with a switch time shorter than the dead time. The fourth packet 407 consists of pulses with equal voltage but uneven pulse width (like the first pulse 402), and the switch time is longer than the dead time.

[0065] Figure 9 shows an exemplary waveform 400 defined by another energy delivery algorithm 152, where the waveform 400 is monophase, thereby representing a special case of imbalance where only the positive portion of the waveform or only the negative portion of the waveform exists. Here, two packets (a first packet 402 and a second packet 404) are shown, separated by a pause period 406. In this embodiment, each packet 402, 404 consists of a first monophase pulse 430 and a second monophase pulse 432. The first monophase cycle 430 and the second monophase cycle 432 are separated by a dead time 412 between each pulse. This monophase waveform may yield a more desirable therapeutic effect because the same charged cell membrane potential is maintained for a longer duration. However, adjacent muscle groups are stimulated more by the monophase waveform compared to the biphase waveform.

[0066] Figure 10 shows further examples of waveforms with single-phase pulses. Here, four different types of packets are shown in a single figure for simplified illustration. The first packet 402 consists of pulses having the same voltage and pulse width, with no switch time (because the pulses are single-phase), and the dead time is equal to the active time. In some cases, the duration of the dead time may be shorter than the active time of a given pulse. Thus, the first packet 402 consists of three single-phase pulses 430, each containing a positive peak. When the dead time is equal to the active time, the waveform may be considered unbalanced at the fundamental frequency where there is no dead time, representing a cycle period twice the active time. The second packet 404 consists of single-phase pulses 430 with the same voltage and pulse width (like the first pulse 402), but with a longer dead time. The third packet 405 consists of single-phase pulses 430 with the same voltage and pulse width (like the first pulse 402), but with an even longer dead time. The fourth packet 407 consists of a single-phase pulse 430 with the same voltage and pulse width (like the first pulse 402), and the dead time is even longer.

[0067] In some embodiments, an unbalanced waveform is achieved by delivering two or more pulses of one polarity before inverting them into an uneven number of pulses of opposite polarity. Figure 11 shows further examples of waveforms with such phase imbalance. Here, four different types of packets are shown in a single figure for simplified illustration. The first packet 402 consists of four cycles with equal voltage and pulse width, but with pulses of opposite polarity mixed with single-phase pulses. Thus, the first cycle includes a positive peak 408 and a negative peak 410. The second cycle is single-phase and includes a single positive pulse without a subsequent negative pulse 430. This is then repeated. The second packet 404 consists of mixed two-phase and single-phase cycles (like the first packet 402), but the pulses have uneven voltages. The third packet 405 consists of mixed two-phase and single-phase cycles (like the first packet 402), but the pulses have uneven pulse widths. The fourth packet 407 consists of mixed two-phase and single-phase pulses (like the first packet 402), but the pulses have uneven pulse widths and uneven voltages. Therefore, multiple combinations and permutations are possible.

[0068] H.Wave shape Figure 12 shows an exemplary waveform 400 defined by another energy delivery algorithm 152, where the pulse is sinusoidal rather than square. In this case as well, two packets (a first packet 402 and a second packet 404) are shown, separated by a pause period 406. In this embodiment, each packet 402, 404 consists of three two-phase pulses 440, 442, 444. These pulses 440, 442, 444 are sinusoidal rather than square waves. One advantage of the sinusoidal shape is that, by being balanced or symmetrical, the shape of each phase is equal. Balancing can help reduce undesirable muscle stimulation. In other embodiments, it may be understood that the pulse has a decayed waveform.

[0069] Energy delivery can be activated by various mechanisms, such as using a button on the catheter 102 or a footswitch operably connected to the generator 104. Such activation typically delivers a single energy dose. The energy dose is defined by the number of packets delivered and the voltage of the packets. Each energy dose delivered to the tissue maintains the tissue temperature or the temperature within the tissue below the threshold for thermal ablation. Furthermore, the dose may be titrated or mitigated over time to further reduce or eliminate heat buildup during the treatment procedure. Instead of inducing thermal damage defined as protein coagulation at the critical site of treatment, the energy dose delivers a level of energy that treats the disease without damaging sensitive tissue.

[0070] Another embodiment includes selecting energy delivery based on determining factors that determine optimal delivery through a particular electrode. Based on which electrode meets the criteria for optimal delivery, the energy dose can be scaled or otherwise divided to deliver an equivalent amount of energy.

[0071] Design of therapeutic catheters The systems and devices described herein may be used with various types and styles of therapeutic catheters 102. In some embodiments, the therapeutic catheter 102 is designed to provide local therapy, and in other embodiments, the therapeutic catheter 102 is designed to provide "one-shot" therapy. Local therapy is considered therapy in which energy is delivered continuously, such as by repeatedly applying energy point by point, as shown in Figure 4 above, or by forming a circular therapeutic zone around the pulmonary veins along a line, curve, etc. One-shot therapy is considered therapy in which energy is delivered all around the entrance of the pulmonary veins via an energy delivery body or delivery electrode(s). However, such deliveries may be repeated as needed. This may optionally include rotation of the energy delivery body or electrode(s) 122 between "shots".

[0072] Figures 13-17 and 18A-18B show embodiments of a therapeutic catheter 1502 configured for local delivery. Here, the therapeutic catheter 1502 includes a shaft 1504 having a distal end 1506 (Figure 14) and an energy delivery body 1522 positioned near the distal end 1506. Here, the energy delivery body 1522 includes a plurality of conductive splines 1524 that form a convex distal surface. Furthermore, in this embodiment, the energy delivery body 1522 is equipped with a distal tip electrode 1526. Here, the distal tip electrode 1526 is positioned along the center of the convex distal surface. This provides additional energy delivery to the tissue to which the convex distal surface is positioned. This helps to avoid any potential deficiency or missing areas of energy delivery, such as causing a donut-shaped lesion within the tissue, thus resulting in a continuous circular lesion.

[0073] Each spline 1524 can function as an electrode, and it can be understood that the splines are energized independently or in groups simultaneously. Therefore, in some embodiments, energy is delivered simultaneously from all or a subset of multiple splines 1524, and as a result, the energy delivery body 1522 delivers energy in a unipolar manner using at least one remote counter electrode plate. Similarly, the distal tip electrode 1526 can be further energized simultaneously with the splines 1524 to deliver energy simultaneously in a unipolar manner. In other embodiments, energy is delivered between selected splines or selected groups of splines so that energy is delivered in a bipolar manner. Similarly, a combination of one or more splines 1524 and distal tip electrodes 1526 can be energized to deliver energy in a bipolar manner. Furthermore, energy may be delivered only from the tip electrode 1526 without delivering energy from one or more splines 1524, and similarly, energy may be delivered from one or more splines 1524 and not from the tip electrode 1526. It can be understood that the splines 1524 may be wires, flat wires, struts, planks, strips, etc. In this embodiment, the splines 1524 are made of a shape memory material such as a nitinol flat wire. In this embodiment, the nitinol flat wire has a platinum core to improve visualization under fluorescence fluoroscopy. In this embodiment, the multiple splines 1524 are partially covered by an insulating material 1528. Here, the insulating material 1528 is located proximal to the energy delivery body 1522, and as a result, the energy conducted to the multiple splines 1524 resists delivery through the insulating material 1528, and the energy is directed to the non-insulated portions of the multiple splines 1524 facing distally. As a result, the energy supplied to the energy delivery unit 1522 is concentrated distally. Since the distal convex surface can be positioned relative to the target tissue area, the energy is efficiently directed toward the target tissue area without energy loss from the proximal side of the energy delivery unit 1522. This conserves energy and reduces energy sinking into surrounding blood, etc.

[0074] In this embodiment, the distal tip electrode 1526 is made of platinum-iridium and has a ball shape. Other suitable materials may be used, and it can be understood that other shapes such as flat, oval, or pointed shapes may be used, to give some examples. In some embodiments, the distal tip electrode 1526 facilitates directing the therapeutic catheter 1502 to a target tissue area. This is achieved by using the distal tip electrode 1526 to detect areas of active cardiac tissue that still need to be treated. Thus, by reading the electrophoresis, the next placement of the catheter can be determined. In some embodiments, the distal tip electrode 1526 is used to record data, as described in a later section.

[0075] The energy delivery body 1522 is transitionable between a folded configuration and an extended configuration. Figure 13 shows the energy delivery body 1522 in the extended configuration. To fold the energy delivery body 1522, the sheath or delivery tube is advanceable distally on the shaft 1504. As the sheath advances on the energy delivery body 1522, the flexibility of the spline 1524 allows the spline 1524 to be straightened, thereby flattening the shape of the energy delivery body 1522 and fitting it into the sheath. Furthermore, it can be understood that straightening the spline 1524 in this way increases the distance between the distal tip electrode 1526 and the distal end 1506 of the shaft 1504. For this reason, the tip electrode wire 1530 that conducts energy through the shaft 1504 to the distal tip electrode 1526 is loose when the energy delivery body 1522 is in the extended configuration, as shown in Figure 13. Such slack allows the device to become longer when in a folded configuration.

[0076] It can be understood that when the catheter 1504 is delivered to a targeted therapeutic area in the body, the energy delivery body 1522 is folded and held within a sheath, sleeve, or delivery device. Upon desired positioning in the body, the energy delivery body 1522 is advanced from the sheath (or the sheath is retracted) so that the energy delivery body 1522 is exposed. Such exposure allows the energy delivery body 1522 to self-expand into an expanded configuration. In other embodiments, it can be understood that the energy delivery body 1522 may be expanded by other mechanisms, such as by the retraction of a plunger connected to a distal tip electrode 1526, or by the expansion of a flexible expandable member (e.g., a balloon) within the energy delivery body 1522. However, the embodiment in Figure 13 provides an energy delivery body 1522 without a central shaft forming a hollow circular cage. This allows for additional flexibility of the energy delivery body 1522. For example, pressing the convex distal surface against target tissue may cause the additional force to bend multiple splines 1524 outward, increasing the diameter of the convex distal surface. Similarly, moving the shaft 1504 while keeping the convex distal surface stationary may increase the force applied to the tissue in the direction of movement by causing the splines 1524 to bend. For example, moving the shaft 1504 to the right may increase the engagement of the splines 1524 on the right side of the convex distal surface, allowing more force to be applied to this area of ​​tissue. Furthermore, such increased flexibility may allow the energy delivery body 1522 to be more easily manipulated, such as by bending it more freely using a pull wire.

[0077] Figure 14 provides a side view of an embodiment of the therapeutic catheter 1502 of Figure 13. In this embodiment as well, the splines 1524 are shown in an extended configuration in which the energy delivery body 1522 forms a ball-shaped cage having a convex distal surface. In this embodiment, the splines 1524 are separated around the shaft plug 1532 in the shaft 1504 and assemble in an equally spaced circumferential arrangement. In this embodiment, each of the splines 1524 is connected to a conductive wire extending through the shaft 1504 for connection to an energy generator. In this embodiment, the splines 1524 terminate around the distal tip electrode 1526 by curving and bending inward to attach to the tip interior 1534, as can be seen again by referring to Figure 13. Thus, in this embodiment, the splines 1524 are arranged equally spaced in a circumferential arrangement around the tip interior 1534. By curving and bending inward around the distal tip electrode 1526, a smooth distal surface is formed for positioning relative to the target tissue.

[0078] In this embodiment, the energy delivery body 1522 includes a sensing electrode 1540 positioned within the energy delivery body 1522 to avoid contact with target tissue. In this embodiment, the sensing electrode 1540 is positioned proximal to the distal tip electrode 1526 (i.e., behind the distal tip electrode 1526) within a circular cage of multiple splines 1524. Here, the sensing electrode 1540 comprises a ring electrode, such as a single 0.030-inch ring electrode extending around the tip interior 1534. In this embodiment, additional electrodes 1542, 1544 are positioned proximal to the energy delivery body 1522 along the shaft 1504, such as two 0.070-inch ring electrodes. In this embodiment, the electrodes 1540, 1542, 1544 are made of platinum-iridium and also function as marker bands for visualization under fluorescence fluoroscopy.

[0079] The sensing electrode 1540 and the additional electrodes 1542, 1544 are typically used to detect ECG signals and also to provide information to an electroanatomical mapping system. For example, when detecting an ECG signal, the user can verify or confirm the location of the therapeutic catheter 1502 within the heart based on the detected ECG signal. When approaching the ventricle, the user can verify such approach by confirming an increase in the amplitude of the ventricular signal. Similarly, in some examples, impedance measurements are tracked by the sensing electrode 1540 and / or the additional electrodes 1542, 1544. The electroanatomical mapping system uses such impedance measurements to visualize the location of these electrodes 1540, 1542, 1544, and thus the location of the therapeutic catheter 1502, within the heart.

[0080] Referring to Figure 14, this embodiment also includes a steering mechanism. In this embodiment, the steering mechanism comprises a pull ring 1560 positioned along the shaft 1504. The pull ring 1560 is connected to one or more pull wires. In this embodiment, the pull ring 1560 is connected to a first pull wire 1562a and a second pull wire 1562b, and the pull wires 1562a and 1562b are attached to the pull ring 1560 on opposite sides. The pull wires 1562a and 1562b extend toward the proximal end of the shaft 1504 so that the distal end 1506 can be remotely operated. When the first pull wire 1562a is pulled, the distal end 1506, and consequently the energy delivery body 1522, bends in the direction of the first pull wire 1562a (for example, to the left), and when the second pull wire 1562b is pulled, the distal end 1506, and consequently the energy body 1522, bends in the direction of the second pull wire 1562b (for example, to the right). It can be understood that any appropriate number of pull wires may be present to steer in various directions. Similarly, other steering mechanisms may be used instead of, or in addition to, the steering mechanisms described herein.

[0081] Figure 15 shows a bottom view of the therapeutic catheter 1502 of Figures 13-14, facing the convex distal surface of the energy delivery body 1522. As shown, in this embodiment, the energy delivery body 1522 includes 10 splines 1524, but any suitable number of splines 1524 may be present, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 or more. Here, the distal portion of each spline 1524 extends radially outward from the distal tip electrode 1526 and then curves back proximal, forming a ball, sphere, or circular cage shape. Thus, each of these spline surfaces is not insulated and delivers energy to the tissue. In this embodiment, an angle θ is formed between each spline 1524, and therefore each angle θ is 36 degrees. It can be understood that the angle θ changes depending on the number of splines 1524, but such angles θ are typically in the range of 10 to 45 degrees, such as 10 to 20 degrees, 20 to 30 degrees, or 30 to 45 degrees. When the number of splines 1524 decreases, such angles θ can increase to, to some examples, 50 degrees, 60 degrees, 70 degrees, 80 degrees, or 90 degrees.

[0082] Figure 16 provides another perspective view of the embodiment shown in Figure 13. In this figure, the irrigation port 1570 is seen along the distal surface of the shaft plug 1532. The irrigation port 1570 is positioned to deliver irrigation fluid to the proximal end of the energy delivery body 1522, allowing flow toward the distal end of the energy delivery body 1522 (i.e., toward the tip interior 1534 and the distal tip electrode 1526). Such irrigation helps reduce the formation of any potential blood clots along the energy delivery body 1522. In some examples, blood clots may be more likely to occur between elements such as splines 1524 that are closely separated and positioned in blood-filled areas. As shown in Figure 16, the distance between the splines 1524 tapers toward the proximal end of the energy delivery body 1522 and toward the distal end of the energy delivery body 1522. Such areas are more likely to develop blood clots because of the increased stagnation of blood in these areas. Stagnant blood can clot, posing a risk to the patient. Using a flow of saline solution or similar irrigation fluid within and around spline 1524 reduces the likelihood of blood clot formation.

[0083] It can be understood that the desired flow of irrigation fluid will be sufficient to reach all or most of the potentially stagnant blood-filled area around the spline 1524. In some embodiments, this is achieved by using multiple irrigation ports 1570 configured to create turbulence within the hollow cage of the energy delivery body 1522. A single irrigation lumen may provide a fluid flow output large enough to reach the proximal end of the energy delivery body 1522, but the flow rate may not be strong enough to reach the distal end of the energy delivery body 1522. However, with a single irrigation lumen, as the fluid passes through multiple irrigation ports 1570, turbulence is created in the flow at the proximal end of the energy delivery body 1522, and this turbulence continues as a fan-shaped fluid flow that extends to the distal end of the energy delivery body 1522. The spreading fan-shaped flow also occupies the area covering the energy delivery body 1522 when the energy delivery body 1522 is bent laterally or moving during positioning or operation. It can also be understood that such turbulence can be achieved using multiple irrigation lumens. Typically, the number of irrigation lumens is less than the number of irrigation ports to deliver an appropriate flow rate while generating turbulence. Figure 17 provides an enlarged view of a portion of the therapeutic catheter 1502 within the distal end 1506 of the shaft 1504. Here, when the shaft 1504 is removed, a shaft plug 1532 is revealed, with splines 1524 arranged around it. Conduction wires 1525 are shown connected to each spline 1525. The conduction wires 1525 extend proximal along the shaft 1504 to connect to the generator 108 to deliver energy to the splines 1525. The embodiment in Figure 17 includes two irrigation lumens 1580 that deliver fluid to irrigation ports 1570. Here, five irrigation ports 1570 are present. It can be understood that various irrigation lumens 1580 can exist, including 1, 2, 3, 4, 5, 6, or 7 or more. Similarly, various irrigation ports 1570 can exist, including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 or more. However, in the case of turbulence, the number of irrigation ports 1570 usually exceeds the number of irrigation lumens 1580.

[0084] Figures 18A and 18B provide additional illustrations of the embodiment of Figure 13. Figure 18A provides an enlarged view of the elements comprising this embodiment of the therapeutic catheter 1502. As shown, this embodiment may include a distal tip electrode 1526, a tip interior 1534, a tip electrode wire 1530, an energy delivery body 1522 including a plurality of splines 1524 at least partially covered by insulating material 1528, a retaining band 1590, a shaft plug 1532, a soldering board 1592, adhesive potting 1594, a pull ring 1560, an irrigation lumen 1580, a shaft 1504 with electrodes 1542, 1544, and a shaft tip section 1596. Figure 18B shows the therapeutic catheter 1502 of Figure 39A in an unextended state.

[0085] As described above, the therapeutic catheter 1502 is described as a local therapeutic device designed to form a lesion that is larger than the footprint of a therapeutic catheter with a solid tip, but smaller than the footprint of a one-shot device, as shown in Figures 2A and 2B. In some embodiments, the shaft 1504 of the therapeutic catheter 1502 is 8 French (2.67 mm) and is delivered using an 8.5 French (2.83 mm) sheath. In such embodiments, the energy delivery body 1522 is configured to fit within the 8.5 French sheath in its folded configuration and therefore has an outer diameter of less than 2.83 mm. When the energy delivery body 1522 is released into its expanded state, its outer diameter expands to 8 to 15 mm, which is typically 3 to 6 times the diameter of the shaft 1504. The footprint of such devices may vary within this size range, which includes 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 8-10mm, 9-10mm, 9-15mm, 10-15mm, 12-15mm, etc.

[0086] Sensor and irrigation The tissue modification system 100 described herein delivers a series of PEF batches or bundles described herein over a period of time such as several seconds. This accumulation of energy delivery results in a small amount of Joule heating inherent in all PEF therapies, as it is a byproduct of energy delivery. However, acute, subacute, mid-term, and long-term histological data all indicate no substantial indicators of thermal damage to tissue using the systems, devices, and methods described herein. Thus, it is clear that no thermal damage (denaturation of extracellular proteins) occurs in cardiac tissue, and the likelihood of adverse events such as pulmonary vein stenosis and anatomical defects resulting from the treatment is reduced. This eliminates the generation of surface carbonization or burns that would hinder energy delivery to underlying tissues, and reduces the ability to generate transmural lesions.

[0087] However, in some embodiments, it may be understood that the system 100 includes temperature sensing and / or control means for various purposes. In some embodiments, the temperature is sensed and controlled to ensure that the temperature is maintained within the ranges of 30-65°C, 30-60°C, 30-55°C, 30-50°C, 30-45°C, and 30-35°C. Thus, the tissue temperature is maintained below the threshold for thermal ablation, and the lesion does not result in burns. In some embodiments, one or more temperature sensors are used to measure the temperature of the electrode and / or tissue during treatment to ensure that the energy delivered to the tissue does not result in any clinically significant tissue heating. For example, in some embodiments, the temperature sensors monitor the temperature of the tissue and / or electrode, and if it exceeds a predetermined threshold temperature (e.g., 65°C), the generator modifies its algorithm to automatically stop energy delivery or to reduce the temperature below a preset threshold. For example, in some embodiments, if the temperature exceeds 65°C, the generator attempts to lower the temperature by reducing the pulse width or increasing the time between pulses and / or packets (e.g., delivering energy every heartbeat, every three heartbeats, etc.). This can occur as a percentage of parameters in a predetermined stepwise approach, or in other ways. It can be understood that the temperature sensor may be positioned on the electrode, adjacent to the electrode, or at any suitable position along the distal end of the catheter. Alternatively or additionally, the sensor may be positioned on one or more separate devices.

[0088] In other embodiments, temperature is detected to assess lesion formation. This can be particularly useful when generating lesions in anatomical structures with target tissue areas of varying thickness. A rapid rise in temperature indicates that the lesion is penetrating deeper into the tissue and is nearing completion. Detecting such temperature changes can be particularly useful when generating lesions in thicker tissue or tissue at unknown depths.

[0089] In some embodiments, the therapeutic catheter includes irrigation to assist in controlling the temperature of the delivery electrode or surrounding tissue. In some examples, irrigation cools the delivery electrode, allowing for more PEF delivery per dose without increasing any potential heat-mediated damage. In some examples, irrigation also reduces or prevents coagulation near the tip of the catheter. It can be understood that irrigation may be activated, increased, decreased, or stopped based on information from one or more sensors, particularly one or more temperature sensors.

[0090] Such cooling is achieved by delivering a fluid, such as isotonic saline, through the catheter lumen, exiting through one or more irrigation ports along the distal end of the catheter. The fluid may be a cooling fluid, a room temperature fluid, or a warming fluid. The fluid flow can be driven by various mechanisms, including gravity-driven infusions, peristaltic pumps, centrifugal pumps, etc. In some embodiments, the irrigation flow rate is 0.1 to 10 ml / min, including 1 ml / min, 2 ml / min, 3 ml / min, 4 ml / min, 5 ml / min, or 6 ml / min or more. In some embodiments, the flow rate is detected by an electrical or mechanical flow detection mechanism. In some embodiments, the temperature of the fluid is measured, and in other embodiments, the temperature of the fluid is modified (heated or cooled, etc.) when the fluid is pumped into the therapeutic catheter based on the measured temperature, etc. In some embodiments, the fluid flow rate is determined based on the measured temperature of the tissue being treated.

[0091] In some embodiments, the pump communicates with a generator 108, and the fluid flow rate is modified by the generator 108 based on the state of energy delivery to the therapeutic catheter 102. For example, in some embodiments, the fluid flow rate increases during energy delivery. Similarly, in some embodiments, the fluid flow rate increases for a predetermined time before energy delivery and / or for a predetermined time(s) during energy delivery. Alternatively or additionally, the flow rate may be controlled by the user as needed. It can be understood that the pump communicates with the generator 108 and may operate at different speeds based on various aspects of the energy delivery algorithm 152. In some embodiments, the flow rate is detected and, using communication with the generator 108, energy delivery is prevented if irrigation has not been initiated. In other embodiments, a fluid flow rate suitable for the energy delivery algorithm 152 is then selected by the selection of the energy delivery algorithm 152. In some embodiments, at least one irrigation port is located along the electrode, and / or optionally, at least one irrigation port is located along the shaft.

[0092] It can be understood that any of the catheter designs described herein may include one or more sensors (e.g., microsensors) such as impedance sensors, contact sensors, contact force sensors, and electroanatomical mapping sensors. Such sensors may be positioned on the electrodes, adjacent to the electrodes, or at any suitable location along the distal portion of the catheter. For example, microsensors may be positioned along one or more loops of the delivery electrodes or along a support structure near the delivery electrodes. Alternatively or additionally, sensors may be positioned in one or more separate devices.

[0093] While various delivery electrodes are described as conductive wires from which energy can be delivered, it should be understood that such designs may also utilize individual electrodes (e.g., microelectrodes) separated along a non-conductive wire. Optionally, such electrodes may be separated along a conductive wire when the conductive wire is insulated from the electrode to which the electrodes are attached.

[0094] Figures 19A and 19B show a therapeutic catheter 1600 according to another embodiment. The therapeutic catheter 1600 shares similarities with the therapeutic catheter 1500, and therefore similar elements are numbered similarly. Specifically, the therapeutic catheter 1600 includes an energy delivery body 1522 that is at least partially defined by a plurality of conductive splines 1524. In this embodiment, there is no distal tip electrode 1526, nor is there a tip electrode wire 1530 that is located inside the spherical arrangement of splines 1524 and extends. Thus, the sphere of the therapeutic catheter 1600 is defined by the expanded plurality of splines 1524.

[0095] Instead, at the base of the sphere is a NAV (navigation) sensor 1610, which is in the form of a projection extending from the distal end of the shaft 1540 to the lower (proximal) part of the sphere. As shown, the NAV sensor 1610 is coaxial with the tip interior 1534 but is separated and spaced apart from the tip interior 1534. Since the NAV sensor 1610 replaces the sensing electrode 1540 which is coupled to the tip interior 1534 at the upper (distal) part of the sphere, there is no tip electrode wire 1530 extending through the interior of the sphere.

[0096] As is known, the NAV sensor 1610 can be any number of commercially available NAV sensors, each designed to provide improved navigation of the therapeutic catheter 1600. For example, the NAV sensor 1610 may be in the form of a magnetic navigation sensor that provides precise catheter positioning.

[0097] The embodiments shown in Figures 19A and 19B utilize a NAV sensor 1610, in contrast to the distal tip electrode 1526 shown in Figure 13. However, like the distal tip electrode 1526, it will be understood that the NAV sensor 1610 functions as a central electrode located inside the basket. As previously mentioned, the NAV sensor 1610 is located more proximal to the distal tip electrode 1526. However, in both embodiments (i.e., embodiments of the distal tip electrode 1526 and the NAV sensor 1610), contact is determined by applying a weak current from the central electrode (NAV sensor 1610) (center of the basket) to one or more of the electrodes on the sphere (spline electrodes). Alternatively, in both configurations, the current can be applied from one electrode on the sphere (spline) (one spline electrode) to another electrode (another spline electrode). Both approaches provide contact information to the user, but the sensitivity differs between spline electrodes and between a reference electrode or central electrode and a spline electrode.

[0098] Balloon therapy catheter Referring here to Figures 20A to 20C, another therapeutic catheter 1700 according to a different embodiment is shown. Unlike other catheters described and illustrated herein, the therapeutic catheter 1700 includes a balloon catheter.

[0099] Therapeutic catheter 1700 is similar to that disclosed in jointly owned U.S. Patent Application Publication No. 2022 / 0323143, which is expressly incorporated herein by reference in whole. More specifically, the therapeutic catheter 1700 can be used for energy delivery, and an exemplary method for ablating target tissue includes (a) delivering the therapeutic catheter 1700 to target tissue, wherein the therapeutic catheter 1700 includes a flexible balloon 1701, a visualization device 1710, and an electrode array 1720 visible to the visualization device 1710, each electrode configured to deliver ablation energy, and the electrode array 1720 being independently movable relative to the flexible balloon 1701; (b) isolating the target tissue so that at least one electrode of the electrode array is in contact with the target tissue; and (c) using the visualization device 1710 to deliver ablation energy to the electrodes of the electrode array 1720 which are confirmed to be in contact with the target tissue.

[0100] As with other embodiments disclosed herein, the therapeutic catheter 1700 is part of or integrated with one or more computer implementation systems, which may consist of one or more processors (e.g., processor 154), memory, controllers, and displays for processing data received from connected devices into visual information. The visualization device 1710 is preferably in the form of an endoscope, preferably located within the therapeutic catheter 1700, and may consist of a lens, an image sensor, and memory for capturing and recording both live and still images. The position of the endoscope will be further described herein. The processor(s) may be configured to process various types of information and information from various sources, including live visual data and data provided via one or more of the ablation sensors, instrument controllers, and displays(s), for example, by executing instructions stored in a non-temporary processor-readable medium.

[0101] In one or more embodiments, one or more processors may be configured to execute instructions, for example, provided by a set of software and / or hardware modules, to interpret, manipulate, and record visual information received from the treatment site. Furthermore, the processors may be configured to manipulate and provide exemplary and graphic overlays and to generate composite or hybrid visual data on a display device. The ablation system may further include haptic technology that provides vibrational or other feedback in response to information processed by one or more processors. For example, as described herein, the display provides a graphic representation of an impedance indicator as a sum of electrode inputs. In addition to visual graphic representations, the ablation system may include a catheter configured to provide haptic feedback corresponding to a visual impedance representation. Thus, the ablation system may include providing multiple pieces of information, including visual and physical feedback, and substantially in real time.

[0102] The ablation system, including the therapeutic catheter 1700, may further comprise a user interface operably coupled to a processor(s) and / or controller. For example, the controller may be configured to control the output of the energy source, the illumination and excitation sources of the energy transmitter, and (as further described below) to process information to determine the distance and movement of the energy transmitter to the tissue at the ablation site. Also, as can be understood from the description below, the endoscope is preferably supported by the therapeutic catheter 1700, and the captured images may be processed by the processor(s), including determining whether sufficient ablation energy delivery was directed to a specific area of ​​the treatment site. As described herein, the data acquired from the endoscope may include video and still images of the treatment site captured substantially in real time and as viewable from the ablation instrument. The video and still images may be stored in memory for later use.

[0103] The therapeutic catheter 1700 includes a main catheter shaft 1703 having a distal end. It should also be understood that the therapeutic catheter 1700 may include two or more shafts, often including an internal catheter shaft and an external catheter shaft, or otherwise including multiple concentric structures. An inflatable balloon 1701 is included and is coupled to the main catheter shaft 1703, with the distal end of the inflatable balloon 1701 close to the distal end of the main catheter shaft 1703, and the proximal end of the inflatable balloon 1701 spaced apart from its distal end. Thus, the inflatable balloon 1701 surrounds the main catheter shaft 1703. Figure 20B shows the balloon 1701 partially disassembled to show its internal components, and Figure 20C shows the balloon 1701 inflated.

[0104] The therapeutic catheter 1700 may include an internal shaft together with an endoscope (visualization device 1710). The endoscope extends along the outside of the internal shaft and is typically positioned at one end of the balloon, facing forward relative to the other end of the balloon.

[0105] The endoscope is positioned within the flexible balloon 1701. The endoscope allows the operator of the therapeutic catheter 1700 to visualize the treatment site and the progression of lesion formation. Such systems are described in Melsky et al. (U.S. Patent No. 9,421,066) and Melsky et al. (U.S. Patent No. 9,033,961), each of which is incorporated by reference in whole. Thus, the endoscope is positioned proximal to the location where energy is delivered to the tissue, allowing the user to visualize the energy delivery and the resulting tissue lesion(s). The endoscope is one of the endoscopes described herein and may also be described in any of the documents incorporated by reference herein.

[0106] The endoscope is forward-facing and is typically positioned adjacent to one of the catheter shafts, such as a central tube formed from a transparent polymer material. As used herein, the term forward-facing refers to the field of view of the endoscope distal to the catheter body. Similarly, the term lateral refers to the field of view of the endoscope radially outward from the side of the catheter body. The endoscope may be a fiber optic endoscope inserted through the lumen of the catheter and positioned within the proximal region of the inflatable balloon. In another embodiment, the therapeutic catheter 1700 includes first and second imaging devices to provide direct visualization of the area to be treated, the first imaging device being fixed to the catheter body. The first and second imaging devices may be in the form of first and second imaging chip endoscopes. Details of the first and second imaging chip endoscopes are described in jointly owned U.S. Patent Application No. 17 / 524,472, which is incorporated herein by reference in whole.

[0107] In one or more embodiments, the therapeutic catheter 1700 includes an expandable basket 1705, which surrounds an inflatable balloon 1701 and is configured to expand when the inflatable balloon is inflated, and similarly to contract when the inflatable balloon is deflated and deflated. The expandable basket 1705 may have a first collar (first ring) at a first (proximal) end and a second collar (second ring) at a second (distal) end. The first and second collars may have an annular shape and, consequently, a continuous ring shape. The sizes of the two collars may differ from each other, and in the illustrated embodiment, the first collar is larger than the second collar. The two collars are sized and configured to securely connect the expandable basket 1705 to the main catheter shaft (or one or more other catheter shafts), and the inflatable balloon 1701 is positioned between the two collars. Therefore, the first collar is preferably positioned proximal to the inflatable balloon 1701, while the second collar is positioned distal to the inflatable balloon.

[0108] The expandable basket 1705 includes a plurality of splines 1715, one end of which is attached to a first collar and the other end to a second collar. The plurality of splines extend longitudinally along the length of the inflatable balloon. The plurality of splines 1715 are offset from each other circumferentially using the open space formed between adjacent splines 1715. The splines 1715 are constructed to expand and contract under the action of the inflatable balloon 1701 below. In particular, when the inflatable balloon 1701 expands under inflation, the splines 1715 expand outward, and conversely, when the inflatable balloon 1701 contracts under deflation, the splines 1715 contract inward. Thus, the splines 1715 conform to the shape of the inflatable balloon 1701.

[0109] Each spline 1715 supports one or more electrodes 1730. For example, each spline 1715 may include multiple electrodes 1730 that can be configured as an electrode array. In the illustrated embodiment, there are three electrodes 1730 arranged along the length of the spline 1715. The electrodes 1730 are separated longitudinally (in series) along the spline. Thus, the electrodes 1730 are spaced apart from each other by a predetermined set distance. The position of the spline 1715 is selected so that the electrodes 1730 are centered relative to the inflatable balloon 1701. This is because, when the inflatable balloon 1701 inflates, the electrodes 1730 are implanted in the target tissue to be ablated using pulsed-field ablation (PFA) technique, as described herein.

[0110] The electrodes 1730 defining the electrode array may or may not be of the same electrode type. For example, the shape and size of electrodes 1730 may be the same as those shown. The material of the expandable basket is not elastic in that the splines do not stretch elastically in the longitudinal direction, but can be expanded and contracted by the inflatable balloon underneath. Therefore, the longitudinal spacing between electrodes does not change as the expandable basket moves between the expanded and contracted positions. Instead, it is important that the distance is fixed, and this information is used during the visualization and ablation process to form the desired lesion, as described herein.

[0111] Accordingly, the embodiments shown in Figures 20A to 20C utilize a visualization device for guidance, which can be used in combination with the local impedance indicator disclosed herein to provide the user with information regarding the progression and state of the lesion.

[0112] The therapeutic catheter 1700 allows for the measurement of local impedance between electrodes around the diameter of the balloon. Alternatively, the system can measure impedance from the balloon electrodes to a reference electrode positioned on the catheter shaft or on the distal end of the balloon, similar to the embodiments described herein. Thus, using a reference electrode with the therapeutic catheter 1700 functions similarly to a central electrode (e.g., distal end electrode 1526), ​​in that local impedance can be measured between one spline electrode and this reference electrode.

[0113] display As described above, generally, a tissue correction system may include a specialized therapeutic catheter, a high-voltage waveform generator, and at least one processor configured to apply a unique energy delivery algorithm. Additional accessories and equipment, including electroanatomical mapping (EAM) systems, are also available. The EAM system allows the operator to record intracardiac electrical activation with respect to specific anatomical locations within the heart by generating the anatomical shape of the heart and capturing measured electrical signal metrics (intensity, delay of signal arrival from remote stimulation, etc.). Thus, EAM technology enables a person to accurately determine the location of the source of arrhythmia, define the shape of the ventricle in three dimensions, depict the anatomical area of ​​interest, and manipulate and position the catheter without fluoroscopic guidance. Furthermore, the devices, systems, and methods described herein provide information on the effectiveness of treatment during the procedure so as to produce an electrical blockage within the heart that maintains its persistence and effectiveness over the long term. In one or more embodiments, the information from EAM technology is generated using a mapping catheter, while in other examples, this is achieved by technology incorporated into the specialized therapeutic catheter. One or more embodiments include EAM technology combined with a special therapeutic catheter, but other configurations including mapping catheters and therapeutic catheters are supported and assumed herein.

[0114] EAM systems are available in various forms, including CARTO®, ENSITE®, KODEX-EPD, ACQMAP, and RHYTHMIA HDX®. The CARTO mapping system, for example, utilizes low-level magnetic fields delivered from three separate coils within a locator pad beneath the patient. The strength of the magnetic field from each coil is detected by a position sensor implanted near the tip of a specialized therapeutic catheter. The magnetic field strength of each coil, as measured by the position sensor, is inversely proportional to the distance between the sensor and the coil. Therefore, the position sensor (and thus the catheter tip position) can be triangulated in space by integrating the magnetic field strength of each coil and converting this measurement into distance. Specialized therapeutic catheters typically include a pair of proximal and distal electrodes and a tip electrode capable of delivering therapeutic energy. The catheter can be moved along the surface of the heart to record local endocardial activation times for arrhythmia mapping, while simultaneously recording position points to generate a three-dimensional (3D) ventricular shape. It can provide an accurate representation of the ventricular shape and the ability to generate isochronous activation maps and reproducible propagation maps. Furthermore, the location of important anatomical landmarks (e.g., bundle of His), electrical scar areas (e.g., for forming voltage / scar maps), and blood vessels (e.g., coronary sinuses, pulmonary veins) can be recorded. In addition, EAM systems such as CARTO mapping systems can record the location of ablation lesions, thereby facilitating the formation of ablation lines.

[0115] Prior to arrhythmia mapping, a stable positional reference can be established, for example, by placing a positional magnet (e.g., a triangular device containing three magnetic coils) under the patient and the table. The position of this magnet can be aligned at any point within the circumference defined at the start of the procedure. Furthermore, a reference patch can be attached to the patient's back, roughly positioned above the target ventricle. If the positional reference magnet or patch becomes displaced during the procedure, its original position is recorded to allow for proper repositioning. This enables accurate tracking of the mapping catheter's position, consistency in the location of anatomical landmarks and ablation lesions, and accurate reconstruction of the ventricular morphology.

[0116] Once the positional reference is stably established, an appropriate timing reference and window are selected. The timing reference is a selected recording, such as an intracardiac electrogram (EGM) or surface ECG lead, that represents the ventricular activation of the arrhythmia origin. Intracardiac EGMs are often chosen as timing references because they are generally more visually consistent, have more accurate timing, and are consequently more reliable than surface ECG recordings. Any component of the electrogram can be selected as a timing reference, including maximum (positive peak) deflection, minimum (negative peak) deflection, maximum upward slope (dV / dT), or maximum downward slope. In addition to using electrical signal metrics based on timing within the incoming signal, the time delay for the electrical signal itself to reach the target location from the spontaneous or induced propagation event can also be measured.

[0117] In addition to facilitating activation mapping, the EAM system provides a location mapping capability that allows recording of anatomically relevant sites, areas of low endocardial voltage representing scarring, and areas of ablation. Ablation induces a range of cellular responses, from stun to necrotizing and death, as will be described in more detail herein. Cardiomyocytes at each of these stages conduct little to no electricity immediately after ablation. Stunned cardiomyocytes recover and regain their ability to conduct electricity, a process that takes several minutes to several hours or more. Dead or necrotizing cardiomyocytes will cease to conduct electricity in the long term. Over a period of 1–4 weeks post-ablation, dead cells are removed from the body and replaced with scar tissue, and the accumulated necrotic zone is used to create permanent conduction blockage. Specific anatomical locations that can be targeted include, to name a few, the superior vena cava, inferior vena cava, right pulmonary vein, left pulmonary vein, right atrium, right atrial appendage, left atrium, left atrial appendage, right ventricle, left ventricle, right ventricular outflow tract, left ventricular outflow tract, interventricular septum, left ventricular apex, myocardial scar area, myocardial infarction border zone, myocardial infarction channel, ventricular endocardium, ventricular epicardium, papillary muscle, and Purkinje system. Treatment is performed at isolated sites or as a series of treatments. Types of treatment include formation of the left atrial ceiling line, formation of the left atrial posterior / inferior line, posterior wall isolation, formation of the lateral mitral isthmus line, formation of the septal mitral isthmus line, left atrial appendage, right vena cava tricuspid isthmus (CTI), pulmonary vein isolation, superior vena cava isolation, Marshall's vein, lesion formation targeting complex schizoid atrial potentials (CFAE), lesion formation targeting local impulse and rotor modulation (FIRM), and target ganglion ablation. Such tissue modifications create conduction blocks within the tissue to prevent the transmission of abnormal electrical signals.

[0118] In one or more embodiments, tissue modification is achieved by treating the tissue point by point using the therapeutic catheter 102. As previously described, the entire system described herein may include a display of the EAM system while treating cardiac tissue of the heart point by point using the therapeutic catheter 102 (with the assistance of mapping) to form treatment zones for overlapping lesions. The lesions can be displayed as spheres in 3D space.

[0119] The display may also provide a local impedance indicator in the lower right corner of the display. Described in more detail below and shown in Figures 21-22 using the reference letter 2000, the local impedance indicator displays relative changes in impedance to the user to quickly convey information that helps the user to better understand where the catheter is positioned within the cardiac chamber. In this embodiment, the local impedance indicator 2000 has a shape that correlates with the end effector of the therapeutic catheter, particularly the end effector diagram shown in Figure 15. Figure 15 shows a bottom view of the therapeutic catheter 1502 of Figures 13-14, facing the convex distal surface of the energy delivery body 1522. Here, the energy delivery body 1522 includes 10 splines 1524. Thus, in this embodiment, the local impedance indicator 2000 has a wheel shape with 10 spokes, each spoke of the wheel representing a spline and terminating with a circle representing an electrode. There are 10 spokes corresponding to 10 splines. It can be understood that the number of spokes on the local impedance indicator 2000 may vary to match the number of splines. Alternatively, certain spokes may be visually reduced, such as being grayed out, if they do not correlate with splines on the catheter.

[0120] Figure 21 provides a magnified view of the local impedance indicator 2000. During operation, the spokes of the local impedance indicator 2000 can change properties such as color, color intensity, hue, saturation, lightness, or other color characteristics as the local impedance changes during the procedure. For illustrative purposes, in the figure, the gradient of the stippling reflects the change in color and / or intensity. A higher density of stippling indicates a higher impedance value (ohms). The local impedance is measured between each spline electrode 1524 and the central (distal) electrode 1526. In Figures 21 and 22, the individual electrodes are numbered sequentially for reference purposes, and the measured impedance values ​​are listed (in ohms) for each individual electrode. Therefore, the impedance values ​​in Figure 21 are reference values.

[0121] When the user first inserts the therapeutic catheter into the heart chamber, the catheter is guided to the center of the blood pool, and the program is set to "zero". This causes all spokes / electrodes of the local impedance indicator 2000 to display the baseline color, or an intermediate color such as gray (shown as colorless (white) in Figure 21 for illustrative purposes). This state of the local impedance indicator 2000 is shown in Figure 21. Each electrode also has a baseline value associated with it at this point.

[0122] Referring to Figure 22, the local impedance indicator 2000 changes color and / or shape as the detected local impedance value changes, providing the user with rapid graphical feedback. The local impedance indicator 2000 is associated with a threshold value at which the detected local impedance changes from a reference value to a certain value. In this case as well, the numbers indicated within or next to each spline electrode are the impedance values ​​measured in real time. When the detected local impedance exceeds the threshold, the local impedance indicator 2000 changes color along the corresponding spoke, such as from gray to green. As the detected local impedance increases, the spokes extend or "increase" away from the center to provide a visual representation of the increase in impedance strength. The local impedance indicator 2000 is also associated with one or more range values, and when the detected local impedance exceeds one or more range values, the color intensity changes along the surface to various shades from light green to dark green, etc., along with the extension of the corresponding spoke, which reaches its maximum extension in dark green. As the end effector of the therapeutic catheter moves around the cardiac chamber, the local impedance indicator 2000 indicates the change in sensing impedance corresponding to the splines of the end effector by changing the intensity of the color of the corresponding spoke (e.g., changing to green for increased intensity) and also by changing the length of the spoke. Thus, good solid tissue contact can be quickly and easily detected on the display by finding darker and / or longer spokes.

[0123] Figure 23 is a flowchart of exemplary step 2300 associated with preprocessing according to an exemplary embodiment of the present disclosure. It should be understood that some of the logical operations described herein are implemented as (1) a sequence of actions or program modules performed by a computer running on a communication device, and / or (2) interconnected mechanical logic circuits or circuit modules within the communication device. The embodiments are choices that depend on the requirements of the device (e.g., size, energy, consumption, performance, etc.). Therefore, the logical operations described herein are variously referred to as operations, structural devices, actions, or modules. Some of these operations, structural devices, actions, and modules can be implemented in software, firmware, special-purpose digital logic, and any combination thereof. It should also be understood that more or fewer operations may be performed than those shown in the figures and described herein. These operations may also be performed in a different order than those described herein. More specifically, in another embodiment, a graphic gradient scale can be used in which changes in impedance values ​​from a reference value transition from red (indicating no change, and therefore no contact) to different shades of green indicating different levels of satisfactory contact. For example, darker shades of green indicate strong contact.

[0124] In the exemplary steps shown in Figure 23, in step 2302, the process begins and impedance information is received from, for example, an electrode (e.g., electrode 1 of 10 electrodes arranged in a spline). Using the impedance information received in step 2302, a reference impedance value can be determined (step 2304). For example, electrode 1 is set to "zero" and the reference value is 50 ohms. In step 2306, the display indicator 2000 is displayed and the display indicator is formatted according to the reference value (e.g., neutral gray color, all spokes are of equal length). Then, in step 2308, the threshold impedance value and the maximum range value are set to, for example, 10 ohms, and the maximum range value is set to, for example, 30 ohms. As the electrode comes into contact with tissue, the detected local impedance changes (i.e., increases). Information associated with the local impedance, such as a value representing the local impedance when electrode 1 is in contact with tissue, is received (step 2310). In step 2312, a determination is made as to whether the local impedance exceeds a threshold (e.g., exceeds the neutral value) and whether the local impedance exceeds the maximum range value. If the determination is positive (yes), the process branches to step 2314, and the impedance indicator is updated and displayed. For example, when the impedance of electrode 1 increases to 60 ohms (+10 ohms from the reference value), the corresponding electrode on the local impedance indicator 2000 changes to display light green, and the spoke length increases (e.g., the bar extends beyond the circle representing the electrode). The color continues to darken to a darker green, and the bar continues to extend as the detected local impedance increases. When the local impedance of electrode 1 is 80 ohms (+30 ohms from the reference value), the corresponding electrode on the local impedance indicator 2000 is the darkest shade of green, and the bar extends fully.

[0125] Continuing to refer to Figure 23, if the decision in step 2312 is negative (no), the process proceeds to step 2316 to determine whether additional local impedance information has been received, thereby requiring further updates to the impedance indicator 2000. Similarly, the process continues from step 2314 to step 2316. If the decision in step 2316 is positive (yes), the process loops back to step 2312 to make a further decision on whether the local impedance value exceeds a threshold. Alternatively, if the decision in step 2316 is negative (no), the process branches to step 2318 and terminates. For example, therapeutic energy is delivered to the site.

[0126] The disclosed system may include additional features, such as the following, that can be implemented. The system can be configured to receive and process measurements from a combination of electrodes to confirm contact between the region of the energy delivery body and the tissue. More specifically, the system can determine whether the electrode readings (received from each individual spline electrode) are reliable using a weighted evaluation that focuses on each electrode plus adjacent electrodes (spline electrodes). For example, if the electrode in question (spline electrode) shows contact, but measurements from the two adjacent electrodes (spline electrodes) do not show contact, the system will determine that each individual electrode is not in contact either. In other words, the system will determine that the readings (local impedance measurements) from each individual electrode are false positives. Instead, if all three adjacent electrodes (spline electrodes) show contact, and the electrode opposite the tip (i.e., the opposite side of the three adjacent electrodes) also shows contact, the system will calculate that perfect contact exists.

[0127] In one embodiment, weighted evaluation may be based on a comparison of ratios or thresholds. For example, if the local impedance value of an adjacent electrode is 50% or more of the impedance value of each individual electrode, contact with tissue is assumed. For example, if the impedance value of each individual electrode is 100 ohms, then if the adjacent electrode has an impedance value of 50 ohms or more, complete contact is considered to exist. Conversely, if the impedance value of the adjacent electrode is less than 50 ohms, it is considered that the individual electrodes are not in complete contact.

[0128] The system can also be configured to process electrode measurements to determine a proportional generator output (electrode and variable energy for a given electrode or electrode group (i.e., spline electrodes)). In one embodiment, the system is configured to deliver 33A to the entire tip (energy delivery body including spline electrodes) regardless of the number of electrodes in contact with the tissue (as determined by local impedance values, visualization, and / or other techniques). In one embodiment, the system includes 10 electrodes (10 splines), and the system can be configured so that the number of electrodes is proportional to the contact area of ​​the tip. Thus, by using fewer electrodes as part of the system, the system can increase the ablation energy to ensure that the current density is the same during energy delivery in any contact scenario. If there are too few electrodes, the system will not be able to deliver ablation energy.

[0129] For example, if fewer than a threshold number of electrodes are in contact with the tissue, it is decided that the dose will be adjusted to provide a dose that achieves the same target depth of the desired lesion (e.g., 6-8 mm). For example, if the system is of the type that delivers 33 amperes when solid contact is established (e.g., when all spline electrodes are in contact), and it is determined that less than 50% of the electrodes are in contact, the dose (amperes) can be increased to ensure that the target lesion depth is achieved. For example, considering that complete contact is not obtained between the electrodes and the tissue, the dose may be increased to 45-50 amperes.

[0130] Another feature is that the system can determine contact stability using a time analysis of electrode measurements. This feature ensures that there is no intermittent contact between the electrode and the target tissue. For example, by looking at a first electrode and a second electrode (e.g., spline electrodes #1 and #2) and comparing the sequence of impedance measurements over time from these electrodes, the system can determine whether there is stable contact. This would involve examining the stability of impedance measurements at a single electrode and comparing its stability assessment with that of adjacent electrodes.

[0131] For example, regarding anatomical locations, there may be threshold stability calculations to determine whether electrode contact is stable. For instance, stability is established when the measured impedance value remains within a given range over a specified period. For example, within the left side of the heart, stability might be an impedance value of 10 ohms ± 3 ohms, meaning that stability is recorded if the measured impedance remains within the range of 7 ohms to 13 ohms over a specified period (e.g., 500 milliseconds). For the right side of the heart, different magnitudes are measured, and therefore, stability might be a measured impedance value of 60 ohms ± 10 ohms, meaning that stability is recorded if the measured impedance remains within the range of 50 ohms to 70 ohms over a specified period.

[0132] In other embodiments, the impedance indicators described and illustrated herein may have different configurations. In particular, the impedance indicator may be the sum of all electrode inputs (i.e., the sum of all impedance values ​​from all electrodes (all electrode splines)) and be represented as a vector. In contrast, the spoke / spider orientations shown in Figures 21-22 can provide a directional vector when the electrode spline comprises one leg of the spoke structure, indicating the maximum contact area of ​​the energy delivery body, as described below.

[0133] Figure 24 shows the direction vector (DA), which indicates the direction of the region of the energy delivery body that is in the greatest contact with the tissue (based on the measured local impedance values ​​described above). It will be understood that other graphic information can be provided, such as the electrode reference number and, if a visualization device is used, images from that device. The direction vector is a real-time representation, and as the therapeutic catheter moves, the direction vector moves on the display, and the graphic information provided therein, such as the degree of contact, also changes. Furthermore, as with Figures 21-22, the intensity / magnitude of the impedance value can be graphically represented by color and / or hue. In this case, as with Figures 21-22, a higher density of dots indicates a higher impedance value (ohms). If all electrode splines are in solid contact with the tissue, instead of using the direction area, circular graphics can be displayed around the spokes (in the spline representation), and similarly, the intensity / magnitude of the impedance can be graphically represented by the color and / or hue of the circles.

[0134] In another embodiment, the system is configured so that vectors are transmitted and displayed on the mapping system as 3D vectors on graphics of the working catheter (shown in Figure 18B, etc.). In other words, the vectors are displayed on a display where the tip of the catheter is being observed (e.g., using a visualization device), making them easily visible and providing guidance to the user. In yet another embodiment, an algorithm executed by a processor is used to determine the total impedance vector / direction by principal component analysis or similar statistical analysis of time-varying data. This enables a running display that will show the statistical characteristics of the contact, such as variability, statistical deviation, range, etc. In yet another embodiment, the size of the display is integrated with tactile feedback within the catheter. This feature provides the customer with feedback that gives a slight vibration or pulse to a handle that the user can touch, thereby providing confirmation that sufficient contact has been made to initiate ablation.

[0135] For example, haptic feedback provided to indicate that sufficient contact has been established and that the user should continue energy delivery may be based on different criteria. These criteria may include the determination that a threshold number of electrodes are in contact with the tissue, when the measured impedance exceeds a threshold, and / or based on time analysis calculations as described herein.

[0136] The above detailed description includes references to accompanying drawings that form part of the detailed description. The drawings illustrate specific embodiments that can put the invention into practice. These embodiments are also referred to herein as “Examples.” Such Examples may include elements in addition to the elements shown or described. However, the inventors have also conceived of embodiments in which only the elements shown or described are provided. Furthermore, the inventors have also conceived of embodiments that use any combination or permutation of the elements shown or described (or one or more embodiments thereof) with respect to a particular embodiment (or one or more aspects thereof) or with respect to other embodiments (or one or more aspects thereof) shown or described herein.

[0137] In the event of any inconsistency in usage between this document and any document that references it in this manner, the usage described in this document shall prevail.

[0138] In this text, the terms “a” or “an” are used to include one or more, as is common in patent documents, and are not related to any other examples or uses of “at least one” or “one or more.” In this text, the term “or” is used to mean non-exclusively, or unless otherwise indicated, “A or B” is used to include “A but not B,” “B but not A,” and “A and B.” In this text, the terms “including” and “in which” are used as easily understandable English equivalents of the terms “comprising” and “wherein.” Furthermore, in the following claims, the terms “including” and “comprising” are not restricted. That is, a system, device, article, composition, formulation, or process comprising elements added to the elements described after such terms in a claim is considered to be further included within the scope of that claim. Furthermore, in the following claims, terms such as “first,” “second,” and “third” are used solely for identification purposes and are not intended to impose any numerical requirements on the subject matter.

[0139] The above description is illustrative and not limiting. For example, the above examples (or one or more of them) may be used in combination with each other. Other embodiments may be used by those skilled in the art when considering the above description. The abstract is provided in accordance with 37 CFR §1.72(b) so that readers may quickly grasp the essence of the technical disclosure. It is presented with the understanding that it is not to be used to interpret or limit the scope or meaning of the claims. Also, in the modes for carrying out the above invention, various features may be grouped together to streamline the disclosure. This should not be interpreted as meaning that any disclosed features not claimed are essential to any claim. Rather, the subject matter of the invention may lie in features less than all of the features of the particular embodiments disclosed. Accordingly, the following claims are invoked as examples or embodiments in modes for carrying out the invention, and it is conceivable that each claim stands alone as a separate embodiment, and such embodiments may be combined with each other in various combinations or permutations. The scope of the present invention should be determined with respect to the appended claims, together with the entire scope of equivalents to which such claims grant rights.

Claims

1. A system for delivering therapeutic energy during tissue repair procedures, At least one catheter, An energy delivery body comprising at least one catheter, A plurality of spline electrodes, each consisting of at least one catheter, An at least one impedance sensor comprising the at least one catheter, wherein each of the at least one impedance sensor is associated with at least one of the plurality of spline electrodes, A processor configured to process information associated with the at least one impedance sensor by executing instructions stored on a processor-readable medium, A display configured to provide information processed by the at least one processor, The aforementioned at least one processor further, Determining a reference impedance value, wherein the reference impedance value is based on the impedance detected by the at least one impedance sensor, Displaying an impedance indicator composed of multiple spokes on the display, wherein each spoke is associated with each electrode of the spline electrode, and each spoke is configured to represent the reference impedance value, and the display is as described above. Defining the threshold impedance value, The at least one impedance sensor detects a local impedance associated with at least one of the spline electrodes that navigate around an organ via the at least one catheter, The at least one processor determines the change in impedance from the reference impedance to the local impedance, The at least one processor modifies each of at least one spoke of the impedance indicator in response to the change in the impedance to generate a modified impedance indicator. The system is configured to display the modified impedance indicator on the display, The tissue modification device is a system that delivers the therapeutic energy via the energy delivery body.

2. Each of the spokes is configured to have a single length representing the reference value, The system according to claim 1, further comprising the processor being configured to modify each of the at least one spokes by extending the length of each of the at least one spokes.

3. The aforementioned at least one processor further, Defining the threshold impedance value, Each of the spokes is composed of a color representing the reference value, The system according to claim 1, further comprising the processor being configured to change the at least one spoke by changing the color of each of the at least one spoke when the detected local impedance exceeds the threshold.

4. The aforementioned at least one processor further, Defining multiple threshold impedance values, When the detected local impedance exceeds each of the plurality of thresholds, the at least one spoke is modified by changing the changed color of each of the at least one spokes, The system according to claim 3, configured to perform the following:

5. The system according to claim 4, wherein the at least one processor is further configured to modify the changed color by changing at least one of the intensity, hue, color tone, saturation, and lightness of the changed color.

6. The system according to claim 1, wherein the at least one catheter further includes a central electrode.

7. The system according to claim 6, wherein the detected local impedance is based on the impedance detected by at least one impedance sensor associated with at least one of the plurality of spline electrodes and at least one impedance sensor associated with the central electrode.

8. The system according to claim 1, wherein the at least one catheter includes a therapeutic catheter and a mapping catheter.

9. The aforementioned at least one computing device further includes, The system according to claim 1, comprising determining contact stability by analyzing electrode measurements as a function of time.

10. The system according to claim 1, wherein the impedance indicator represents the sum of all electrode inputs in vector form.

11. The system further comprises a mapping component, and the at least one processor is further configured to transmit the vector to the mapping component. Furthermore, the system according to claim 10, wherein the mapping component displays the vector as a three-dimensional vector on the graphics of the moving catheter.

12. The aforementioned processor further, The system according to claim 1, configured to determine the total impedance vector / direction by principal component analysis or statistical analysis using time-varying data.

13. The processor further comprises a tactile sensation composed of at least one catheter, The system according to claim 1, configured to provide haptic-based feedback associated with the state of the impedance indicator.

14. A method for delivering therapeutic energy during tissue repair procedures, Determining a reference impedance value by a tissue correction device including at least one catheter, an energy delivery body, at least one impedance sensor, at least one processor, and a display, wherein the at least one catheter includes a plurality of spline electrodes, Displaying an impedance indicator composed of multiple spokes on the display, wherein each spoke is associated with each electrode of the spline electrode, and each spoke is configured to represent the reference impedance value, and the display is as described above. The above-mentioned at least one processor defines a threshold impedance value, The at least one impedance sensor detects a local impedance associated with at least one of the spline electrodes that navigate around an organ via the at least one catheter, The at least one processor determines the change in impedance from the reference impedance to the local impedance, The at least one processor modifies each of at least one spoke of the impedance indicator in response to the change in the impedance to generate a modified impedance indicator. The modified impedance indicator is displayed on the aforementioned display, The aforementioned tissue modification device delivers therapeutic energy, The method, including the method described above.

15. Each of the spokes is configured to have a length representing the reference value, Furthermore, the method according to claim 14, wherein modifying the at least one spoke includes extending the length of each of the at least one spokes.

16. The above-mentioned at least one processor defines a threshold impedance value, Each of the spokes is composed of a color representing the reference value, Furthermore, the method according to claim 14, wherein changing the at least one spoke includes changing the color of the at least one spoke when the detected local impedance exceeds the threshold.

17. The above-mentioned processor further includes defining a plurality of threshold impedance values, Furthermore, the system according to claim 3, wherein changing the at least one spoke includes changing the altered color of each of the at least one spoke when the detected local impedance exceeds each of the plurality of thresholds.

18. Changing the aforementioned color means The method according to claim 17, comprising changing at least one of the intensity, hue, tone, saturation, and lightness of the changed color.

19. The method according to claim 14, wherein the at least one catheter further includes a central electrode.

20. The method according to claim 14, wherein the at least one catheter includes a therapeutic catheter and a mapping catheter.

21. The method according to claim 14, wherein the reference impedance value is determined by measuring the impedance in the blood.

22. A system for delivering therapeutic ablation energy to tissue, At least one catheter, An energy delivery body comprising at least one catheter, wherein the energy delivery body includes a plurality of spline electrodes arranged circumferentially to form a basket structure, A reference electrode, disposed within the basket structure and configured to function as an impedance sensor, To process information associated with the impedance sensor, at least one processor is configured to execute instructions stored on a processor-readable medium, A display configured to provide information processed by the at least one processor, The aforementioned at least one processor further, The calculation involves determining an initial reference impedance value for each of the plurality of spline electrodes, wherein the reference impedance value for each spline electrode is based on the impedance detected by the impedance sensor. The display is configured to show an impedance indicator for each spline electrode, indicating the change in impedance from the reference impedance value to the current impedance value measured in real time by the impedance sensor for each spline electrode. The tissue modification device is a system that delivers the therapeutic energy via the energy delivery body.

23. The system according to claim 22, wherein the reference electrode is positioned at the distal end of the basket.

24. The system according to claim 22, wherein the reference electrode is positioned at the proximal end of the basket.

25. The system according to claim 24, wherein the reference impedance value and the current impedance value of each spline electrode are based on an impedance calculation between the reference electrode and each of the spline electrodes.

26. The system according to claim 22, wherein the proximal end region of each spline electrode has an insulating material, the reference electrode is positioned distal to the insulating material in the distal end region of the basket, and the length of the spline electrode distal to the insulating material includes an exposed metal electrode.

27. The system according to claim 22, wherein the processor is further configured to calculate a contact stability value for each spline electrode and to compare the contact stability value with a threshold contact stability value to determine whether the contact of each electrode with the tissue is stable over a predetermined period of time.

28. The system according to claim 22, wherein the processor is further configured to provide tactile feedback to the user by generating vibration or pulses in the handle of the at least one catheter, the vibration or pulses providing confirmation that a threshold of at least degree of contact between the energy delivery body and the tissue has been achieved and that delivery of therapeutic energy can be initiated.

29. The system according to claim 22, wherein the processor is configured to determine the integrity of the current impedance value of each spline electrode by comparing the current impedance value of each spline electrode with the current impedance value of an adjacent spline electrode.

30. The system according to claim 29, wherein if the difference in measured impedance values ​​between each of the spline electrodes and each of the adjacent spline electrodes exceeds a predetermined threshold, the processor flags the impedance value of each of the spline electrodes as unreliable.

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