Ablation catheter and method of performing the procedure

Abstract

The present invention is an ablation catheter for treating patient tissue, for example, for PVI (Pulse Vibration Invasion) procedures on a patient's heart. [Solution] The ablation catheter comprises an elongated catheter shaft and an ablation portion 12 located at the distal end of the catheter shaft, wherein a plurality of electrodes 120 are housed along the ablation portion, and the ablation portion comprises at least two loop sections 121, 122 that form a three-dimensional helix. To enhance the safety of ablation treatment, avoid damaging adjacent tissues (e.g., nerves, blood vessels, esophagus), and shorten the ablation time, the pitch or clearance between two adjacent loop sections is greater than the ionization threshold of the surrounding medium (e.g., blood or gas produced by electrolysis) of the distal portion. The present invention further relates to a method for operating such an ablation catheter.

Description

Technical Field

[0001] The present invention relates to an embodiment of an ablation catheter suitable for pulsed field ablation (PFA). In particular, the present invention relates to an embodiment of a PFA catheter that can be used to safely perform cardiac ablation procedures including, but not limited to, pulmonary vein isolation (PVI), persistent atrial fibrillation ablation, ventricular tachycardia ablation, etc. The catheter includes a plurality of electrodes and delivers pulsed field energy to achieve irreversible electroporation of cardiac tissue.

Background Art

[0002] It is known to use an ablation catheter in a PVI procedure for the treatment of patients with atrial fibrillation (AF). In such a procedure, the pulmonary veins (PVs) are electrically isolated from the left atrium by creating a continuous circumferential ablation lesion around the pulmonary vein ostium (PVO) or around the pulmonary vein antrum. Thus, irregular atrial contractions can be avoided by preventing unwanted perturbing electrical signals generated within the PVs from propagating to the left atrium. The ablation catheter can be used to deliver treatment to the ventricles, right atrium, left atrial body, and other tissues not limited thereto. Also, other organs such as the lungs, liver, and kidneys can be treated via the catheter.

Summary of the Invention

Problems to be Solved by the Invention

[0003] Several types of ablation catheters are available, such as single-point tip electrode catheters, circular multi-electrode loop catheters, and balloon-based ablation catheters using various energy sources. All of these lack the ability to create the necessary ablation to safely electrically isolate arrhythmogenic foci from the rest of the cardiac chamber in a "one-shot" manner without further repositioning, rotation, or movement of the catheter.

[0004] It is desirable to further improve ablation therapy by providing catheters and systems that safely achieve an electrical isolation "moat" in a single shot. The concept of an electrical isolation moat is defined as an area of ​​cardiac tissue that surrounds the arrhythmia trigger and prevents its propagation to the rest of the cardiac chamber. For example, but not limited to, referring to a situation where the arrhythmia trigger is located within the pulmonary vein, an ablation area that completely renders the tissue located at the venous orifice or venous sinus inviolable and ensures transmurality would represent the electrical isolation moat. If the tissue within the moat is inviolable, the excitation arising from the trigger in the corresponding pulmonary vein will not be conducted to the rest of the left atrium. Such arrhythmogenic excitation is blocked by the moat and cannot capture the left atrium itself. In the case of atrial fibrillation, when the conduction blocking moat is achieved, the triggering mechanism will be eliminated or its incidence will be reduced. Currently available techniques achieve conduction blockage or electrical isolation trenches by point-to-point (i.e., repositioning the catheter in a series of steps), rotation (i.e., rotating the active element of the catheter to complete the trench), or repositioning (i.e., repositioning the active element of the catheter to an adjacent location to complete the trench). In other words, conventional techniques achieve the conduction blockage trench by using "multiple shots." While it may be possible to achieve the conduction blockage trench in a single shot by supplying excessive power to the target tissue, doing so would result in irreversible damage to collateral organs (e.g., esophagus, lungs, diaphragm, etc.). In some cases, these adverse events can pose a significant risk to the patient. For example, supplying excessive power to the left atrium structure using conventional techniques can cause an atrial-esophageal fistula. If detected too late, the fistula can be fatal. Pulsed-field ablation, if properly designed, may have the advantage of being able to create these conduction blockage / electrical isolation trenches safely in a single shot with little to no collateral tissue damage. [Means for solving the problem]

[0005] The above problems are solved by an ablation catheter having the configuration of claim 1, and a method for operating such an ablation catheter having the configuration of claim 9.

[0006] In particular, one embodiment of an ablation catheter for treating patient tissue (e.g., for PVI procedures in the patient's cardiac or venous tissue) comprises an elongated catheter shaft and an ablation portion located at the distal end of the catheter shaft, wherein multiple electrodes are housed along the ablation portion, and the ablation portion comprises at least two loop sections forming a three-dimensional helix, the pitch and / or clearance between two adjacent loop sections being greater than the ionization threshold. Catheters using loop sections or loop segments include, but are not limited to, catheters with continuous or adjacent helices. In pulsed-field ablation, a high-intensity electric field is used. If the catheter is not properly designed, the electric field intensity can become sufficiently high, potentially ionizing the medium between the electrodes. In such situations, an arc discharge occurs. Arc discharge increases the level of danger to the patient because it can cause unintended tissue damage. Furthermore, the high temperature of the arc can melt the catheter material, potentially leaving foreign matter in the patient's bloodstream. Therefore, it is important to use a catheter designed to prevent ionization. This can be achieved by design elements that keep the catheter electrode at a greater distance than the amount known or expected to cause ionization (i.e., the ionization threshold).

[0007] Within the framework of this application, the term "ionization threshold" is understood as the electric field strength sufficient to ionize the medium between electrodes so that an arc discharge occurs.

[0008] Within the framework of this application, the expression "at least two loop sections forming a three-dimensional helix" is understood to mean a structure comprising at least two loop sections arranged to form a three-dimensional helix. The at least two loop sections may be arranged as a continuous or discontinuous helix. The beginning and end of each loop section may be located in either the same plane or different planes with respect to the central axis of the three-dimensional helix. Furthermore, the at least two loop sections themselves may be located in either the same plane or different planes with respect to the central axis of the three-dimensional helix. An example of at least two loop sections forming a continuous helix is ​​shown in Figure 1, where the beginning and end of each loop section are located in different planes with respect to the central axis of the three-dimensional helix, and thus the at least two loops are located in different planes with respect to the three-dimensional axis.

[0009] Within the framework of this application, the pitch between two adjacent loop sections (or loop / spiral arms in the case of a continuous loop / spiral) is defined as the distance between the opposing outer surfaces of each of the two adjacent loop sections, and the distance is measured perpendicular to the direction of the local tangency to each section between which the distance is measured. The pitch is determined at the catheter stage, and the three-dimensional shape of the ablation portion, which includes at least two loop sections, is not limited by any external force.

[0010] Within the framework of this application, the clearance between two adjacent loop sections is defined in the same manner as the pitch measured at the catheter stage, and the three-dimensional shape of the ablation portion, including at least two loop sections, is flattened or substantially flattened by an external force when the catheter is compressed against the tissue, as shown, for example, in Figure 18B. When the ablation portion is flattened by an external force, at least two loop sections are coplanar with respect to the central axis of the three-dimensional helix.

[0011] According to one embodiment, an ablation catheter is configured to deliver pulsed-field ablation (PFA) energy to atrial or ventricular tissue via an ablation electrode. In other words, an ablation catheter can be configured to perform PFA. In particular, an ablation catheter can be used to provide cardiac catheter ablation for the treatment of various cardiac arrhythmias, including AF. For example, an ablation catheter can be configured to be connected to a multi-channel PF energy generator configured to deliver PF energy. The waveform of the PF energy generator, in conjunction with the catheter loop design, is designed to achieve the intended therapeutic effect while minimizing or reducing the possibility of ionization. The catheter of the present invention can also be used in different types of tissues (e.g., veins, lungs, liver, kidneys). It may be used for pulmonary vein isolation (PVI), sustained atrial fibrillation ablation, ventricular tachycardia ablation, and other ablation procedures.

[0012] The catheter shaft may have a handle at its proximal end. Each electrode in the ablation section is electrically connected to a power source and a pulse generator located at the proximal end of the catheter shaft via a single electrode lead wire. Furthermore, the catheter may include an electronic control unit (ECU) for controlling the ablation procedure and / or processing measurement data. In another embodiment, two electrode lead wires are provided at the proximal end and intermediate section of the catheter shaft. To reduce the diameter of the catheter shaft, at the proximal end, the first electrode lead wire is connected to the first electrode group, and the second electrode lead wire is connected to the second electrode group. The electrodes can have a length of 1 mm to 10 mm, preferably 3 mm to 5 mm, along each loop section. The size of the catheter shaft may be compatible with sheaths with an inner diameter of 7F to 14F, preferably 8.5F. The width between adjacent electrodes along each loop section can be selected from 1 mm to 10 mm, preferably 3 to 6 mm, to provide a continuous ablation area in the patient's tissue.

[0013] In one embodiment, the pitch between two adjacent loop sections is even smaller than the therapeutic threshold of each tissue. The therapeutic threshold of each tissue is understood as the distance at which a continuous trench is known or expected to be achieved.

[0014] The pitch and / or clearance of a first set of two adjacent loop sections may be different from or equal to the pitch and / or clearance of a second set of two adjacent loop sections. Again, the description and disclosure apply equally to catheter designs employing continuous or adjacent loop or helical structures.

[0015] The ablation catheter of the present invention, using PFA, is intended to render tissue unviable by irreversible electroporation (IRE). During IRE, the electric field provided by electrodes housed in adjacent loop sections creates pores in the cell membranes of the heart. If the number and size of the pores are sufficiently large, IRE occurs, and the cells themselves are programmed to die. Thus, the adjacent loop sections of the ablation portion form a so-called ablation region. To provide adequate treatment that induces IRE within the ablation region, the pitch and / or clearance of two adjacent loop sections must be greater than the ionization threshold to avoid ionization and the resulting scarring. Furthermore, if the pitch and / or clearance are selected to be below the treatment threshold, the generated electric field will reliably form pores. An additional advantage of matching the pitch of the loop sections to the aforementioned threshold is that the safety of the PFA treatment is improved, and the normal pumping performance of the heart is not affected because adjacent tissues (e.g., nerves, blood vessels, esophagus) are not damaged. Conduction blockage can be achieved in a single shot if the loop sections or helical arms are of appropriate size to deploy to the target region. As a result, the ablation time is shortened.

[0016] In one embodiment, the ionization threshold is 2 mm, particularly with respect to body fluids (e.g., blood), blood vessels, and / or atrial tissue. In a further embodiment, again particularly with respect to blood vessels and / or atrial tissue, the treatment threshold is 8 mm, preferably 4-6 mm. The ionization threshold and the treatment threshold are directly related to the distance between two electrodes having different polarities. In this embodiment, a pitch and / or clearance of at least 2 mm ensures that arc discharge and potential scarring are avoided. The same applies to the treatment threshold. A pitch and / or clearance of up to 8 mm, preferably 4-6 mm, ensures that continuous trenches are achieved.

[0017] In one embodiment, the pitch and / or clearance are selected to be greater than the median between the ionization threshold and the treatment threshold. Since the ablation area may be slightly compressed during ablation, the pitch and / or clearance selected within a region greater than half the distance between the ionization threshold and the treatment threshold ensures that the ablation area is a favorable size with respect to IRE, even when slightly compressed.

[0018] In one embodiment, the diameters of two adjacent loop sections increase toward the distal end of the ablation portion forming a plunger-type ablation catheter. A plunger-type ablation catheter can be used for ablation of the ventricular or posterior left atrium atrial region. Alternatively, the diameters of two adjacent loop sections decrease toward the distal end of the ablation portion forming a corkscrew-type ablation catheter. A corkscrew-type ablation catheter can be used for ablation in the atrial end region of the PV. The diameter of the loop sections can be, for example, 10 mm to 40 mm. More specifically, when used in the left atrium, the diameter of the widest loop section can be 20 to 35 mm, preferably 25 to 32 mm. The minimum diameter can be 12 to 22 mm, preferably 15 to 20 mm. The diameter is measured from both inner surfaces of the opposite loop sections. For both regions, the shape of the ablation portion is adapted to the specific shape of each region being ablated.

[0019] It is also within the scope of the present invention that the ablation portion may comprise multiple separate mapping electrodes, which are configured to receive electrical signals (e.g., electrical or biopotential) from blood vessels or atrial tissue. Alternatively, electrodes used for ablation in ablation mode may be used for mapping (i.e., receiving bioelectrical signals (e.g., acquiring electrical or biopotential) from blood vessels or atrial tissue). During ablation, these electrodes enter ablation mode. This not only enables mapping and ablation of PVI with a single ablation catheter, but may also enable ablation of some non-PV triggers in AF patients.

[0020] For example, in one embodiment, an additional loop section among the multiple loop sections may represent multiple mapping electrodes. Additionally or alternatively, in addition to the ablation electrodes, mapping electrodes may also be placed in one or both of two adjacent loop sections. Multiple mapping electrodes may also be incorporated distal to the multiple ablation electrodes or inside two ablation electrodes, for example, between two ablation electrodes (along each loop section). Furthermore, a third loop section may include ablation electrodes in addition to, or instead of, the mapping electrodes.

[0021] As suitable materials, the ablation electrode may include, for example, at least one of gold and platinum / iridium alloys.

[0022] To achieve this without adding too many ablation electrodes (which may make it more difficult to create continuous damage), relatively long ablation electrodes may be used. For example, the length of the ablation electrode can be in the range of 1 to 10 mm, preferably 3 to 5 mm. In one embodiment, the ablation electrode can be sleeve-shaped or tubular. For example, the diameter of such a sleeve-shaped or tubular ablation electrode can be in the range of 2 to 2.5 mm. Furthermore, as mentioned above, the length of the sleeve-shaped or tubular ablation electrode can be in the range of 1 to 10 mm, preferably 3 to 5 mm. Alternatively, a split electrode design may be used. In this embodiment, two electrodes in the form of a half-shell separated by a gap are placed on the inside (facing the body cavity) and outside (facing the tissue) of the catheter. The width of the gap can be 0.2 to 1 mm, preferably 0.5 mm. One such embodiment is shown in Figure 18C. Alternatively, the electrode may be solid, but the inside facing the blood (body cavity) may be coated with an insulating material. Parylene, polyimide, or Teflon® are examples of suitable coatings. The coating material must be an electrical insulator with a high dielectric strength of over 200 kV / mm.

[0023] In one embodiment, the ablation portion, particularly the loop section, may include a shape memory material. Preferably, the shape memory material is a superelastic material (e.g., a superelastic alloy), that is, the material is highly elastic and has shape memory properties. For example, nitinol is a biocompatible superelastic alloy suitable for this purpose. In one variant, the ablation portion, particularly the loop section, may comprise an internal support element (e.g., an internal support wire) having shape memory or superelastic properties. The shape memory support wire can have different stiffnesses and cross-sectional shapes in different sections. The internal support structure maintains the integrity of the structure and design of the ablation portion and extends along at least one section of the ablation portion. The internal support structure can be realized as a nitinol wire (e.g., a variable cross-section or tapered circular, rectangular, square wire). Also, this support structure includes those insulated with materials such as parylene, polyimide, Teflon® on the outer surface of the wire. Further, the wires of the ablation portion may have sections with different diameters or cross-sectional shapes to provide different stiffnesses.

[0024] In one embodiment, the ablation catheter may further comprise a manipulable delivery sheath. Thus, during operation, the position of the ablation portion can be easily adjusted in the target visceral tissue until contact of each ablation electrode is satisfied.

[0025] In one embodiment, two adjacent electrodes among the plurality of electrodes in the ablation portion are alternately arranged along a distance greater than the ionization threshold. This means that the electrodes can be alternately arranged so as to describe a helix within the axis of the loop. Therefore, in one embodiment, the distance between the opposing outer surfaces of each of the two adjacent loop sections in a direction perpendicular or inclined to the loop axis can also be selected to be greater than the ionization threshold. As a result, even when the loop is displaced left and right due to the anatomical structure of the heart, the possibility of the electrodes colliding is reduced. Also, even when they are not colliding, since the relative distance between the electrodes exceeds the ionization threshold, the electrodes are less likely to cause an arc discharge.

[0026] In one embodiment, each of the electrodes is connected to an electronic control unit (ECU), and this connection is provided via a pulse generator so as to pair each two of at least two electrodes in a predetermined manner. When there are three or more electrodes (for example, 16 electrodes), for example, each two electrodes accommodated adjacent to each other along the loop section can be paired (mode along the loop section), or each two electrodes accommodated adjacent to each other across two adjacent loop sections (mode across the loop section) can be paired to operate in a bipolar configuration. Therefore, eight pairs can be formed from 16 electrodes in both modes. The pairing can be switched between the two modes. Further, the pairing can be switched to another electrode pair, for example, along the loop section. For pairing, the electrodes may be connected to a switch unit, and the switch unit is connected to and controlled by the electronic control unit. The ECU may further be adapted to switch each electrode to the ablation mode and the mapping mode described above, respectively. The switch unit realizes the pairing along the loop section and, if applicable, the switching between the modes according to the control signal of the electronic control unit. The electronic control unit can include a microprocessor or a computer, etc.

[0027] In one embodiment, the catheter shaft includes at least two lumens separated by a material having a dielectric strength greater than a dielectric constant threshold suitable for withstanding high-voltage PF pulses (e.g., high-voltage PF pulses with amplitudes greater than 1 kV, greater than 2.5 kV, or between 2.5 kV and 3.5 kV) used with the catheter described above and below. Such a material can be, for example, a polymer film, a polyimide film (e.g., Kapton® film) provided in the form of a tube, or a layer received by immersion. Its dielectric strength is 160 kV / mm. The thickness of the polymer film (polyimide layer) can be selected, for example, in the range of 0.012 mm to 0.125 mm. In this embodiment, a first lumen of the at least two lumens is configured to hold at least two electrode lead wires connected to an electrode providing the same first polarity, and a second lumen of the at least two lumens, different from the first lumen, is configured to hold at least two electrode lead wires connected to an electrode providing the same second polarity but different from the first polarity. This embodiment eliminates the need for insulation of each electrode lead wire, allowing for a smaller catheter shaft diameter while simultaneously providing the necessary safety against flashover. When an electrode embodiment such as that shown in Figure 18C is used, the lumen structure is adapted accordingly to accommodate the increased number of connecting wires. The same dielectric strength principle applies.

[0028] In one embodiment, the catheter shaft may have a total length of more than 1 m from the handle to the distal tip of the ablation portion.

[0029] In one embodiment, at least two of the multiple electrodes in the ablation portion are adapted to deliver high-voltage unipolar PF energy, bipolar PF energy, or a combination of unipolar and bipolar PF energy, as described later. Several examples of applicable waveforms are shown in Figures 15A and 15B. Such waveforms, when combined with the loop structure described above, ensure that an electric field low enough to produce a therapeutic effect that can create a conduction blockage trench, and low enough to avoid arc discharge, is applied in a single shot. The PFA pulse may be delivered gated by a QRS complex of the cardiac cycle. Alternatively, if the ablation targets a region away from the ventricle, the PFA pulse may be delivered asynchronously without QRS gate control. The electronic control unit is adapted to switch between unipolar PF energy delivery mode and bipolar PF energy delivery mode.

[0030] In another embodiment, the distal end of the ablation portion is connected to a steering wire or central wire that can be operated from a handle element located at the proximal end of the catheter shaft. Thus, the central wire can be connected to an operating mechanism within the handle element. The central wire extends along the ablation portion substantially along the longitudinal axis of the catheter shaft. A steering plate, steering ring, or other known steering structure can be located at the distal end of the catheter shaft connected to the distal helical or multi-loop ablation section. The central wire is connected to the steering structure. The central wire can be operated so that, depending on therapeutic needs, the longitudinal length of the ablation portion (i.e., its length along the longitudinal axis of the three-dimensional helical / multi-loop structure) or the loop section can be steered toward a tissue target.

[0031] In one embodiment, the electrodes are distributed along at least two loops such that the angular separation between the most distal electrode and the most proximal electrode is at least 360°. The angular separation is determined by the angle between the most distal electrode, the catheter axis, and the most proximal electrode.

[0032] In one embodiment, the catheter comprises at least one irrigation lumen configured to apply an irrigation solution to the treatment site. The at least one irrigation lumen may be connected to at least one individual irrigation opening in the ablation section. In one embodiment, individual electrodes may have individual irrigation openings between electrodes, or proximal and / or distal to the nearest electrode and the most distal electrode in the ablation section.

[0033] The irrigation lumen can be connected to a source of irrigation fluid at the proximal end of the catheter. The irrigation fluid may be a sterile fluid, preferably distilled water, or a low-salinity (preferably 0.1% or less) saline solution. Using distilled water or a low-salinity saline solution further reduces the risk of arc discharge because it lowers the salinity at the treatment site.

[0034] Another aspect of the present invention relates to a method for manipulating an ablation catheter for treating patient tissue, for example, for PVI procedures in the patient's cardiac or venous tissue. Such a method involves manipulating an elongated catheter shaft and an ablation portion located at the distal end of the catheter shaft. The ablation portion comprises a plurality of electrodes housed along the ablation portion. It also comprises at least two loop sections forming a three-dimensional helix, and the plurality of electrodes are energized with pulsed electric field energy delivered in a unipolar configuration, a bipolar configuration, or a combination of a unipolar and a bipolar configuration, and the pulsed electric field energy is delivered in a charge-balancing manner.

[0035] The charge balancing function has potential benefits in minimizing foaming, arcing, and skeletal muscle stimulation (directly or indirectly via motor nerves) (by reducing the possibility of electrolysis of the blood).

[0036] Within the framework of this application, delivering pulsed electric field energy in a charge-balanced manner is understood as charge balancing using pulses having positive and negative pulse peaks and corresponding pulse widths, such that a net charge as close to 0 μC as reasonably possible is delivered to the tissue. One method of delivering charge-balanced pulsed electric field energy is to use a two-phase pulse containing positive and negative pulse sections. The pulse width is the width of the positive section (or negative section). The peaks (amplitude) and widths of the positive and negative sections are designed to balance each other. As a result, the two-phase pulse itself is charge-balanced. Another method of delivering charge-balanced pulsed electric field energy is to use several pulses from a pulse train, thereby designing the peaks and widths of the individual pulses in the pulse train to balance each other.

[0037] In one embodiment, two adjacent electrodes along a loop section, or two adjacent electrodes in different loop sections, are energized in a bipolar configuration with pulsed electric field energy. By doing so, the electric field vector can be manipulated to generate a more complete trench of conduction blockage / electrical isolation.

[0038] In another embodiment, the voltage amplitude of the pulsed electric field is greater than 1kV, greater than 2.5kV, or between 2.5kV and 3.5kV. Depending on the selected electrode configuration, the overall current amplitude can be in the range of 5 to 150A.

[0039] In another embodiment, the pulse duration (positive or negative pulse width) is greater than 0.5 μs, preferably less than 30 μs. Preferably, the pulse is biphase, comprising a positive section containing a positive pulse peak and a negative section containing a negative pulse peak. The pulse width is the width of the positive section (or negative section). While not essential, it is preferable that the positive and negative-phase composite be charge-equalized so that the net charge delivered to the tissue approaches 0 μC as reasonably as possible. Alternatively, the charge-equalization function may be achieved over the duration of the pulse train. In this case, the net charge of the above train will approach 0 μC as reasonably as possible. The charge-equalization function has the potential benefits of minimizing foaming (by reducing the possibility of blood electrolysis), arc discharge (caused by ionization of gases resulting from blood or electrolysis), and skeletal muscle stimulation (direct or indirect via motor nerves). A biphase pulse beginning with a positive or negative section is understood as a positive or negative (biphase) pulse.

[0040] According to one embodiment, positive and negative pulses are separated by an interphase delay. The advantage of the pulse width according to the present invention is that the electric field acts on the cell for a sufficiently long time, so that pores are generated by the electric field. The interphase delay can be selected in the range of 1 μs to 100 μs so that the inverse phase does not immediately cancel out the effect of the positive phase, and the interphase delay does not become too long. If the interphase delay is too long, charge equilibrium will not function. The inverse and positive phases may be provided with the same amplitude or different amplitudes, as long as a charge equilibrium pulse train is achieved.

[0041] In one embodiment using two-phase pulses, the interphase delay is determined between two consecutive two-phase pulses, where a two-phase pulse is followed by an inverse two-phase pulse (e.g., a negative two-phase pulse following a positive two-phase pulse). The time between the start of the first two-phase pulse and the start of the next inverse two-phase pulse is the interphase delay, and is similarly in the range of 1 μs to 100 μs.

[0042] In a further embodiment, a pulse train (pulse sequence) including at least one pulse having a pulse width greater than 0.5 μs (preferably less than 30 μs) is provided within a period of 5 to 100 ms. The inter-pulse delay can be, for example, 0.1 to 100 ms. Preferably, the inter-pulse delay is longer than 1 ms. In one embodiment, a pulse train of 10 pulses with amplitude 3 kV, pulse width 10 μs, and inter-pulse delay 1 ms is used. In another embodiment, a pulse train of 30 pulses with amplitude 1.625 kV, pulse width 15 μs, and inter-pulse delay 5 ms is used. In a further embodiment, one or more such pulse trains (e.g., up to 500 pulse trains) are provided within a period of at least 10 seconds (preferably less than 2 minutes). Within this time, the pores do not heal, as it takes several seconds for the pores to recover, and the cells themselves are programmed to die, causing IRE.

[0043] In one embodiment, a sterile cleaning solution is applied to the treatment site, preferably distilled water or a low-salinity (preferably 0.1% or less) saline solution. Using distilled water or a low-salinity saline solution further reduces the risk of arc discharge because it lowers the salinity of the treatment site. The cleaning solution can be applied through at least one individual cleaning opening in the ablation section. In one embodiment, individual cleaning openings may be present on individual electrodes, between electrodes, or proximal and / or distal to the nearest and farthest electrodes in the ablation section.

[0044] As described above, against the backdrop of achieving charge equilibrium, the pulse shape of the biphasic pulse can be, for example, a sine wave, a square wave, a triangular wave, an exponentially decaying wave, or a sawtooth wave. The single pulse (positive or negative pulse) is preferably a square pulse.

[0045] Furthermore, the mapping electrodes described above can be used to acquire electrical or biopotentials from surrounding blood vessels or atrial tissue. While mapping electrodes may have a similar structure to ablation electrodes, they may be slightly smaller in size to provide higher electrical signal resolution. Wires can be attached to one electrode using welding. In one embodiment, a smaller mapping electrode (e.g., having a length of 1 mm) can be placed between two ablation electrodes. The detected voltage signals are transmitted to an electronic control unit via the respective electrode leads. Additionally or alternatively, current may be acquired using the mapping electrodes. For example, local tissue impedance may be measured using the mapping electrodes. This can be useful for monitoring the degree of tissue contact or the progression of the PFA effect. During patient treatment, mapping can be performed before ablation, after one ablation step, or after multiple ablation steps to observe the outcome and progression of the ablation. To facilitate and improve evaluation, the received mapping signals (e.g., potential signals) from the mapping electrodes, or electrodes operating in mapping mode, can be visualized using standard mapping or navigation techniques. This allows for mapping the local conductivity characteristics of the surrounding tissue.

[0046] In one embodiment, impedance is measured using multiple electrodes on the ablation portions of two adjacent loop sections to determine the relative distance between adjacent loop sections when they are in contact with the patient's tissue. Specifically, the impedance is measured between two electrodes spanning the adjacent loop sections. If the measured impedance is lower than a predetermined impedance threshold, the adjacent loop sections are too close together, which must be avoided to prevent arc formation if the electrodes of the adjacent sections have different polarities. Furthermore, unipolar or bipolar impedance can be determined to demonstrate a uniform distribution of electrodes and thereby confirm that the ablation portion is in contact with the patient's tissue along its entire outer surface.

[0047] In one embodiment, the impedance between two electrodes is measured over a specific frequency range, and preferably, a frequency-dependent impedance curve is determined. The frequency range can be 10 kHz to 500 kHz. A flat impedance curve at low impedance values ​​(e.g., up to 300 ohms) may indicate contact or collision between the two electrodes. When the two electrodes collide or make electrical contact, the phase of the bipolar impedance increases and becomes significantly positive. This is because the inductance of the electrode wires gives the equivalent bipolar circuit (considering electrode collision) inductive properties. A significant attenuation of the impedance curve at higher values ​​(e.g., 100 ohms to 500 ohms) may indicate good tissue contact between the two electrodes. A flat impedance curve in the medium impedance range may indicate poor tissue contact between the two electrodes. A flat impedance curve should be understood as the impedance dependence from frequency, where the impedance value measured at high frequencies deviates by less than 20%, preferably less than 10%, from the impedance value measured at low frequencies. The prominent impedance curve should be understood as the frequency dependence of impedance, with impedance values ​​measured at high frequencies deviating by more than 20% from impedance values ​​measured at low frequencies.

[0048] According to one aspect of the present invention, the operating method disclosed above is used to operate the ablation catheter disclosed above.

[0049] Another aspect of the present invention is a system for realizing cardiac conduction blockage within human or animal tissue, 1. A catheter comprising a catheter shaft and an ablation portion located at the distal end of the catheter shaft, which houses multiple electrodes along the ablation portion, 2. A high-voltage generator configured to output positive and negative high-voltage pulses including pulse peak and pulse width, Equipped with, 3. The catheter is fitted to connect to a generator and deliver pulses to multiple electrodes housed along the ablation area. 4. The generator is configured to deliver pulsed electric field energy to electrodes, thereby configuring the pulse peak and pulse width to generate pulsed electric field energy between the ionization threshold and the therapeutic threshold, relating to the system.

[0050] Arc discharge can occur if the electric field strength is sufficient to ionize the medium between electrodes. Arc discharge increases the level of danger to the patient because it can cause unintended tissue damage or barotrauma. Furthermore, the high temperature of the arc can melt the catheter material, potentially leaving foreign matter in the patient's bloodstream. Therefore, in a sense, it is important to set the peak and pulse width so that the pulsed electric field energy generated at the electrodes is below the ionization threshold. On the other hand, the pulsed electric field energy must be sufficient to reliably apply the electric field in a single shot. Thus, the pulse peak and pulse width are configured to produce a therapeutic effect that can generate a pulsed electric field energy exceeding the therapeutic threshold, thereby creating a conduction-blocking trench. Within the framework of this application, the (pulse) peak is understood as the peak of the voltage amplitude.

[0051] This system can be equipped with any of the above-mentioned catheters.

[0052] This generator is configured to provide a charge-balanced pulse having charge balance of positive and negative pulse peaks and corresponding pulse widths, such that the net charge is zero in some sense. In one embodiment, a two-phase pulse is generated, comprising positive and negative pulse sections. The pulse width is the width of the positive section (or negative section). The peaks (amplitudes) and widths of the positive and negative sections are designed to be balanced with respect to each other. As a result, the two-phase pulse itself is charge-balanced. The generator can be configured to produce two-phase pulses in the shape of a sine wave, square wave, triangular wave, exponentially decaying wave, or sawtooth wave.

[0053] Another method for delivering charge-equalizing pulsed electric field energy is to use several pulses from a pulse train, thereby designing them so that the peaks and widths of the individual pulses in the pulse train are in equilibrium with each other.

[0054] The generator can be configured to emit pulses with pulse widths of 0.5 μs to 30 μs. Individual pulses can be separated by inter-pulse delays of 0.1 ms to 100 ms. The inter-phase delay can be in the range of 1 μs to 100 μs.

[0055] The generator can also be configured to produce a pulse train containing at least one pulse, preferably at least two pulses. The pulse train may include two-phase pulses and / or single-phase pulses. The length of such a pulse train can be 5 ms to 100 ms. The generator may be configured to deliver up to 500 pulse trains within a time frame of at least 1 second. Preferably, the pulse train is delivered in less than 2 minutes.

[0056] The system may further include a device for measuring an electrocardiogram and detecting characteristic peaks of the QRS period, P wave, and / or T wave. The device for measuring the electrocardiogram is configured to connect to and / or communicate with a generator. The device for measuring the electrocardiogram is configured to provide a trigger signal corresponding to the detection of at least one of the QRS period, P wave, and / or T wave. The generator is configured to initiate at least one pulse or pulse train in relation to the trigger signal.

[0057] In an alternative embodiment, the measured electrocardiogram is analyzed by a generator, and at least one pulse or pulse train is initiated in relation to the QRS period, P wave, and / or T wave.

[0058] In light of the above teachings, it will be apparent to those skilled in the art that the examples and embodiments described are subject to numerous modifications and variations. The disclosed examples and embodiments are presented for illustrative purposes only. Other alternative embodiments may include some or all of the configurations disclosed herein. It is therefore intended to cover all such modifications and alternative embodiments that may fall within the true scope of the invention.

[0059] The various configurations and advantages of the present invention can be more readily understood by referring to the embodiments shown in the following detailed description and drawings, which are described here in a general and illustrative manner. [Brief explanation of the drawing]

[0060] [Figure 1] The distal end of the first embodiment of the ablation catheter is shown in a lateral perspective view. [Figure 2] This shows the delivery route of the ablation catheter to the pulmonary vein opening of the human heart. [Figure 3] The distal end of the embodiment shown in Figure 1 is shown in a front perspective view. [Figure 4] The distal end of the embodiment shown in Figure 1 is shown in a side view. [Figure 5]The distal end of the second embodiment of the ablation catheter is shown in a side view. [Figure 6] The distal end of the second embodiment of the ablation catheter is shown in a front view. [Figure 7] The distal end of the second embodiment of the ablation catheter is shown in a front perspective view. [Figure 8] The distal end of the third embodiment of the ablation catheter is shown in a side view. [Figure 9] The distal end of the third embodiment of the ablation catheter is shown in a side view. [Figure 10] The distal end of the third embodiment of the ablation catheter is shown in a side view. [Figure 11] The distal end of the third embodiment of the ablation catheter is shown in a front view. [Figure 12] The distal end of the embodiment shown in Figure 1 is shown in a side perspective view, along with several dimensions indicated by reference numerals. [Figure 13] This shows a part of the electrical control of the electrode lead wires for the embodiment shown in Figure 1. [Figure 14] The electronically manipulated electric field vector distribution is shown to achieve conduction blocking. [Figure 15A] The image shows an example of a charge-equalized waveform, which is an exponential decay type waveform. [Figure 15B] An example waveform with balanced charge is shown, which is a rectangular waveform. [Figure 16A] This illustrates the concept of QRS gate control, showing the QRS detector signal (upper trace), PFA trigger signal (center trace), and ECG (lower trace) over several heartbeats. [Figure 16B] This illustrates the concept of a QRS gate, showing the details of a single heartbeat. The PFA trigger signal (center trace) is within the refractory period of the cardiac cycle. [Figure 16C] This illustrates the concept of QRS gating and shows PFA pulse artifacts recorded during preclinical studies. [Figure 17]This image shows an actual histological slide identifying a trench of conduction blockage (or electrical isolation) around the right superior pulmonary vein (RSPV). [Figure 18A] Further illustrating possible electrode distributions on the spiral distal section, the catheter of the present invention facing the PV is shown. [Figure 18B] Further illustrating possible electrode distributions on the helical distal section, the catheter of the present invention is shown unfolded when pressed against a PV wall (note the gaps between the helical arms). [Figure 18C] Further examples of possible electrode distributions on the helical distal section are provided, and alternative segmented tip electrode structures are shown. [Figure 19] Three schematic impedance curves measured across the frequency between the two electrodes are shown. [Figure 20A] An example of impedance measured over frequency is shown. [Figure 20B] An example of impedance measured over frequency is shown. [Modes for carrying out the invention]

[0061] Figures 1, 3, 4, and 12 schematically and illustratively show the distal portion of the ablation catheter 1 according to the first embodiment. The ablation catheter can be used for PFA when used with a PFA generator and accessories, and its use in cardiac electrophysiological mapping (stimulation and recording) and high-voltage pulsed-field cardiac ablation is shown. The peak voltage is, for example, ±1kV to 3kV with a pulse width of up to 30μs, but is not limited thereto. If the pulse duration is correspondingly shorter (e.g., 0.5μs), a higher peak voltage (e.g., up to 10kV) can be used. The catheter 1 has an elongated circular catheter shaft 10, which can be connected to a handle (not shown) with a steering mechanism at its proximal end. As a result, the catheter can control the deflection of the illustrated distal section that supports the ablation electrode.

[0062] The illustrated distal end of the catheter shaft 10 is located on an ablation section 12 comprising a plurality of loop sections 121, 122. The concept of loop sections includes embodiments using continuous loops or helical configurations. The catheter shaft may have an effective length of about 115 cm from the distal end of the ablation section 12. Each of the first loop section 121 and the adjacent second loop section 122 is shown to contain ablation electrodes 120 (e.g., 14 electrodes in total) configured to deliver energy to the tissue. Although two loops are shown in Figure 1, more loops may be used. It is preferable to use at least partially a third loop to provide sufficient overlap between the resulting ablation zones. The overlap will increase the likelihood of achieving conduction blockage without reducing the continuity, adjacency, or transmurality of the damage. See the catheter diagram in Figure 14 as an example. The distal section includes at least a 45-degree overlap between the third loop section and the two preceding sections. In particular, the ablation catheter 1 can be configured to deliver an electrical high-voltage PFA signal to the tissue via the ablation electrode 120. For example, the ablation electrode 120 may be made of or contain gold and / or a platinum / iridium alloy. Alternatively, electrodes 120 from different loop sections may be arranged so that electrodes of the same polarity are aligned. Either an alternating arrangement or a polarity-based approach ensures that electrodes of opposite polarity do not collide when the helical catheter is compressed.

[0063] In the exemplary embodiment shown in Figure 1, the ablation electrodes 120 of the second loop section 122 are partially alternating with respect to the ablation electrodes 120 of the first loop section 121.

[0064] Loop sections 121 and 122 may further show a plurality of mapping electrodes configured to receive electrical signals from tissue.

[0065] The loop sections 121 and 122 together form a three-dimensional helix, creating a corkscrew-like shape. Alternatively, they may form a plunger-like configuration, as shown in Figures 5 to 7. It should be noted that the diameters of the loop sections 121 and 122 are such that the first, more proximal loop section 121 has a larger inner diameter D1 (e.g., 30 mm, see Figure 12) than the second, more distal loop section 122 (inner diameter D2, e.g., 24 mm). At the farthest distal tip of the ablation portion 12, the inner diameter D3 is even smaller (e.g., 18 mm). Generally, the diameter of the loop sections can be, for example, 10 mm to 40 mm. More specifically, when used in the left atrium, the diameter of the widest loop section can be 20 to 35 mm, preferably 25 to 32 mm. The minimum diameter can be 12 to 22 mm, preferably 15 to 20 mm.

[0066] The loop sections 121 and 122 may include, for example, internal structural support wires (not shown), shape memory materials in the form of, for example, nitinol wires as described above. In particular, the loop sections 121 and 122 may have superelastic properties.

[0067] The ablation portion 12 may be constrained to an essentially elongated shape for the purpose of being delivered to a target area of ​​the human body by a delivery sheath 15 (which may also be called an introduction sheath) (which may be fixed or maneuverable). At the target location, once it exits the distal end of the delivery sheath 15, the ablation portion 12 may recoil to its original (biased) shape.

[0068] The length of each electrode 120 along each loop section 121, 122 is, for example, 4 mm. Generally, the length of the electrodes is in the range of 1 to 10 mm, preferably 3 to 5 mm. The size of the catheter shaft 10 can be compatible with a sheath with an inner diameter of 8.5 F and can be made of a radiopaque extrudeable polymer (polymer-reinforced braid, where applicable). Generally, the size of the catheter shaft 10 can be compatible with a sheath with an inner diameter of 7 to 14 F. The width between adjacent electrodes along each loop section can be selected from 1 mm to 10 mm, preferably 3 to 6 mm, to provide a continuous ablation area in the patient's tissue.

[0069] Figure 2 schematically and illustratively shows the delivery route for an ablation catheter 1 leading to the pulmonary vein orifice (PVO) of the human heart. Directions are shown from the inferior vena cava (IVC), right atrium (RA), right ventricle (RV), left atrium (LA), left ventricle (LV), and pulmonary veins (PV), each of which has a PVO. Large black arrows indicate the delivery route through the IVC and RA, across the septum (SW), to the LA. Finally, catheter 1 is guided to the PVO region using appropriate deflection means, where a corkscrew-shaped ablation catheter is used for ablation of the atrial end region of the pulmonary veins near the PVO. The shape of the ablation portion 12 is configured to fit the dimensions of the target PVO. Alternatively, a corkscrew-shaped catheter can also be used to perform ablation in the spondyloventricular cavity (SVC) or in accessory organs such as the left or right atrial appendage (LAA or RAA).

[0070] The second embodiment of the ablation catheter 2 shown in Figures 5-7 is adapted for use in ablation in the atrial region of the left atrium LA (e.g., the posterior wall of the LA) surrounding or located between the PVOs. Alternatively, catheter 2 may also be well suited for ablation of the ventricular (RV or LV) wall or RA (e.g., the free RA wall, tricuspid annulus, etc.). The ablation portion 22 comprises two loop sections 221 and 222, which also include a plurality of ablation electrodes 220 (and mapping electrodes, if applicable), similar to the first embodiment. However, the ablation portion 22 is formed like a three-dimensional helix having the form of a plunger, with the more proximal first loop section 221 having a smaller diameter than the more distal second loop section 222.

[0071] Similar to the first embodiment, there is a third embodiment shown in Figures 8 to 11. However, elements of this embodiment (e.g., the central wire 31 for helical expandability or compressibility) may be used with other types of helical catheters, although they are not limited to these. In addition to the structure of the first embodiment, the third embodiment of the ablation catheter 3 includes a central wire 31 used to facilitate expandability or compressibility of the distal section. The central wire 31 is connected to the distal end of the ablation portion 32. The ablation portion 32 includes an ablation electrode 320. The central wire 31 extends substantially along the longitudinal axis of the helix formed by the ablation portion and its two loop sections 321, 322. The central wire 31 enters the catheter shaft 30 and extends inside it. At the proximal end of the catheter, the central wire 31 is connected to an actuation element associated with or incorporated into the catheter handle. The central wire 31 can be manipulated to change the diameter of the loop sections 321, 322 by the longitudinal length of the ablation portion 32 (i.e., the length along the longitudinal axis of the three-dimensional helix of the ablation portion 32) in order to adapt to therapeutic needs and local conditions. In the drawing of Figure 8, the central wire pushes the distal tip of the ablation portion 32 distally, so the longitudinal length of the ablation portion is maximum compared to the drawings of Figures 9 and 10. Therefore, the diameter of the loop sections 321, 322 is minimum. Figure 10 shows the shortest longitudinal length of the ablation portion 32 of the ablation catheter 3. This is achieved by pulling the central wire 31. The ablation catheter 3 shown in Figure 9 has a nominal longitudinal length of the ablation portion 32 that is between that of Figures 8 and 10. Therefore, the diameter of the loop sections 321, 322 is maximum in Figure 10 and minimum in Figure 8.

[0072] Reliable and complete ablation along the entire circumference is achieved by the first and second embodiments at their respective locations within the heart or vein where the shape is adapted. The ablation portions 12, 22 of each catheter 1, 2 may be slightly compressible in the direction of the longitudinal axis of the helix during ablation, but the distance of the loop sections 121, 122 or 221, 222 remains within a region limited by the therapeutic threshold and the ionization threshold.

[0073] To avoid causing IRE, damaging adjacent tissue, and shortening the ablation time, the pitch of adjacent loop sections is selected between the ionization threshold and the therapeutic threshold, as detailed above. Referring to the first embodiment shown in Figure 12, the first pitch or clearance s1 of the first loop section 121 and the second loop section 122 is approximately 5 mm, and the second pitch or clearance s2 of the second loop section 122 and the furthest distal end of the ablation portion 12 is similarly approximately 5 mm. Generally, the pitch or clearance should be between the ionization threshold (2 mm) and the therapeutic threshold (up to 8 mm). As mentioned above, the angular offset between the furthest and nearest electrodes of any of catheters #1, #2, or #3 is preferably 2 × 360° + 45° (i.e., two complete loops + 1 / 8 of the third loop).

[0074] The ablation procedure using one of the ablation catheters 1, 2, or 3 can be initiated after the ablation portion 12, 22, or 32 is correctly positioned relative to the target tissue (e.g., PVO). The ablation electrodes 120, 220, and 320 provide a pulsed electrical RF field in a unipolar or bipolar configuration. The peak voltage is, for example, ±1kV to 3kV with a pulse width of up to 30μs, but is not limited thereto. Higher peak voltages (e.g., up to 10kV) can be used if the pulse duration is correspondingly shorter (e.g., 0.5μs). The pulse width is 12μs (0.5 to 30μs), forming a pulse train consisting of up to 500 pulses / strand. Either the waveform shown in Figure 15A or Figure 15B may be used.

[0075] As an example, though not limited to this, the waveform in Figure 15A shows a biphasic exponentially decaying voltage pulse suitable for PFA treatment. Throughout the composite waveform, the exponential decay achieves the goal of charge equilibrium necessary to minimize the possibility of bubbling, arcing, or undesirable tissue irritation. Such a waveform can be achieved by using a high-voltage output stage AC-coupled to ablation electrodes 120, 220, or 320. The two biphasic pulses shown in Figure 15A form a pulse train, which can be repeated N times. A biphasic pulse consists of a positive section PP and a negative section PN. As shown in Figure 15A, a positive biphasic pulse is followed by an inverse negative biphasic pulse. The interphase delay I1 is the time between the end of the negative section PN of the first biphasic pulse and the start of the positive section of the next pulse. When biphasic pulses are used as defined above, the pulse width P corresponds to the length of the positive / negative section PP / PN. The next pulse train begins after the inter-pulse delay I2.

[0076] Similarly, Figure 15B shows an example of a suitable PFA waveform with a rectangular shape. The rectangular pulse shown in Figure 15B is characterized by a voltage peak V and a pulse width P. A positive rectangular pulse is followed by a negative rectangular pulse after an inter-phase delay I1. The two pulses shown in Figure 15B form a pulse train that is repeated N times. The next pulse train begins after an inter-pulse delay I2. These waveforms are also charge-balanced. Such charge-balanced rectangular waveforms can be realized by using a DC-coupled high-voltage output stage that rationally and precisely controls the amplitude and duration of the positive and negative phases. As a result, net balance can be achieved by controlling the net charge (current amplitude × pulse width).

[0077] Figures 16A–16C show QRS gate-controlled output waveforms. A typical ECG waveform 1601a for lead I is shown in Figure 16A. The output of the QRS detector is shown as signal 1602a. The trigger for the PFA waveform is shown as signal 1603a. Figure 16B provides a magnified view of Figure 16A. The ECG waveform 1601b is represented over one cardiac cycle. Its R wave 1604 is detected by the QRS detector output 1602b. After a programmed delay 1605, the PFA waveform trigger 1603b is turned on. In this embodiment, the delay 1605 is shown to be approximately 70 ms. The delay 1605 can be 20–150 ms depending on the heart rate. It is important to ensure that the PFA pulse is applied within the cardiac refractory period. As shown in Figure 16B, in this particular example, the pulse train ends before the T wave 1606 begins. Figure 16C shows an example of a PFA pulse artifact recorded on a standard cardiac recording system. Following the R wave 1604c, artifact 1607 caused by the delivery of the PFA pulse can be observed. Artifact 1607 safely terminates before the start of the T wave 1606c. The process described above delivers one column of pulses within one cardiac cycle. In the example above, 10 pulses / column were delivered using waveform 1501 in Figure 15A. Those skilled in the art can modify the above approach using other known parameters without departing from the essence of the invention. For example, up to 500 pulse columns can be provided. However, although not essential, it is desirable to select the number of columns so that the PFA application time is greater than 1 second (to allow cell membrane perforation) but less than 2 minutes (to avoid a long procedure). The interphase delay can be 1 to 100 μs. The interpulse delay can be 0.1 ms or 100 ms.

[0078] The generation of the electric field (particularly voltage, current, and impedance) is monitored by an electronic control unit (ECU) 70 connected to the lead wires 61 of electrodes 120, 220, and 320, and is also generated by a waveform generator 50 (see Figure 13). Figure 14 also shows the connectivity which can be used to generate a unipolar or bipolar electric field. The ECUs in Figures 13 and 14 can control the application of a PFA field with the aim of achieving a wider range of tissue space between the catheter loop or helix. Figure 14 shows a catheter 1401 (such as #1, #2, or #3 in Figures 1-10) with electrodes driven by ECU 1403. ECU 1403 can be controlled to deliver a field vector 1402 that covers the tissue zone between the helical arms / loops of catheter 1401. Doing so increases the likelihood of achieving conduction blockage / electrical isolation moats.

[0079] In a bipolar configuration, adjacent electrodes 120, 220, and 320 may be paired along loop sections 121, 122, 212, 222, 321, and 322, or across two adjacent loop sections 121 and 122, 221 and 222, and 321 and 322. Furthermore, electrodes 120, 220, and 320 may be used in a unipolar configuration. In this case, a grounding pad 1404 can be placed on the surface of the patient's body. Alternatively, a reference electrode associated with the catheter shaft may be used.

[0080] To switch between different bipolar configurations, or between unipolar and bipolar configurations, the ablation catheters 1, 2, and 3 may be equipped with a switch unit 60 connected to and controlled by an ECU 70. The switch unit 60 provides each phase of the pulsed electric field provided by the waveform generator 50 to predetermined electrodes 120, 220, and 320 via predetermined electrode leads 61, each electrode lead 61 electrically connected to one specific electrode 120, 220, and 320 in the ablation sections 12, 22, and 32. The switch unit 60 includes a switch matrix that can realize any configuration of the phase distribution, for example, two adjacent electrodes along or across a loop section paired together to achieve the aforementioned uniform conduction blockage trench. Any other configuration is also possible. Switching signals and configuration information are provided by the ECU 70. The ECU 70 may further provide data processing of electrical or biopotential data, or impedance data, obtained by mapping the electrodes of the ablation catheters 1, 2, and 3. As shown above, the mapping electrodes located in the ablation sections 12, 22, and 32 may be equipped with mapping electrodes for determining the potential of the surrounding tissue in order to observe the progress of ablation at a predetermined point in time during the ablation procedure. Alternatively, the ablation electrodes 120, 220, and 320 can be switched to mapping mode and then back to ablation mode. Furthermore, the impedance between adjacent electrodes or across two different adjacent loop segments can be determined before the delivery of PFA energy. This allows the impedance (unipolar or bipolar) to be monitored to determine whether the electrodes of adjacent loop segments, and therefore the electrodes of these segments, are each located at a sufficient distance from other loop segments or electrodes. By monitoring the impedance, the ECU 70 or 1403 can warn the user if any two electrodes are too close together and the distance between each electrode falls below the ionization threshold. Conversely, if the impedance measurement indicates that the distance between electrodes exceeds the therapeutic threshold, the user can also be warned.

[0081] As shown above, the catheter shafts 10, 20, and 30 may have two lumens separated by a material (e.g., Kapton®) having a dielectric strength higher than the insulation threshold of the high-voltage PFA pulse. The first lumen may, for example, hold seven electrode lead wires 61 that provide a first polarity, and the second lumen may, for example, hold seven electrode lead wires 61 that provide a second polarity, thereby reducing the overall diameter of the catheter shaft.

[0082] The ablation catheter embodiments described above achieve IRE to prevent the electrical signals causing arrhythmias from spreading to adjacent areas (i.e., achieving conduction blockade) by improving safety to ensure that adjacent tissues (e.g., nerves, blood vessels, esophagus) are not damaged, and by shortening the ablation time. Figure 17 shows a trench of such conduction blockade or electrical isolation. The right upper pulmonary vein 1701 is visible in the center of the photograph. After application of PFA pulses according to the present invention (total cumulative PFA application time is approximately 90 seconds / PV), continuous and adjacent transmural injury was achieved. The periphery of the injury 1402 is shown. The conduction blockade or electrical isolation trench 1403 completely covers the cardiac tissue zone between RSPV 1401 and the injury boundary 1402. Electroanatomical mapping confirmed that chronic isolation of the pulmonary vein continued.

[0083] Figure 18A shows the catheter of the present invention facing the pulmonary vein atrium. Figure 18B shows the catheter of the present invention deployed when pressed against the pulmonary vein wall. As indicated by lines c1 and c2, the angular separation between the most distal electrode 1802 and the most proximal electrode 1801 is greater than 2 × 360°, or 720°. Figure 18C shows an alternative split-tip electrode structure with an inner electrode facing blood and an outer electrode facing tissue.

[0084] Figure 19 shows three schematic impedance curves measured across frequency between the two electrodes. The impedance is measured at a low frequency of 10 kHz f low Starting from a frequency of 500kHz f highMeasurements were possible up to this point. The prominent impedance curve as the uppermost curve in the Z1-Z4 range indicates good tissue contact between the two electrodes. The flattest lowest impedance curve in the lower Z3-Z5 range indicates contact between the two electrodes. The flat impedance curve in the middle of the Z2-Z4 range indicates poor tissue contact between the two electrodes. For example, without being limited to these, the following thresholds can be used. 1. Good tissue contact - f LOW (For example, at 10 kHz), depending on the electrode size and tissue characteristics, Z1 is in the range of 100 to 500 ohms. HIGH (For example, at 500kHz), Z4 will be at least 20% lower than Z1 (S-shaped curve). 2.Poor contact-f LOW (For example, at 10 kHz), depending on the electrode size and blood characteristics, Z2 is in the range of 80 to 400 ohms. HIGH At (for example, 500 kHz), Z4 is up to 20% lower than Z2, and is usually only 10% or less lower (flat curve). As shown in Figure 20A, with poor electrical contact, the bipolar impedance decreases from approximately 113 ohms at 10 kHz to approximately 110 ohms at 500 kHz. The phase changes only slightly, increasing from approximately -4° to 2°. 3. Contact electrode-f LOW (For example, at 10 kHz), Z3 is in the range of 0 to 300 ohms depending on the contact amount, electrode size, and blood characteristics. HIGH At (for example, 500 kHz), Z5 is up to 20% lower than Z3, and is usually no lower than 10% (flat curve). As shown in Figure 20B, when the electrodes collide and form good electrical contact, Z5 drops to 4-9 ohms, and the phase increases with frequency. At 500 kHz, the phase is approximately 66°, exhibiting primarily inductive electrical properties given by the electrode wires.

[0085] In consideration of all the disclosures described above, the present invention also provides the following sequentially numbered embodiments. (Embodiment 1) Ablation catheters (1, 2, 3) for treating patient tissue by delivering high-voltage pulses, Catheter shafts (20, 30, 40) and The ablation portion (12, 22, 32) is located at the distal end of the catheter shaft, and multiple electrodes (120, 220, 320) are housed along the ablation portion. Equipped with, The ablation portion comprises at least two loop sections (121, 122, 221, 222, 321, 322) that form a three-dimensional helix. The pitch and / or clearance (s1, s2) of two adjacent loop sections of the ablation catheter (1, 2, 3) is greater than the ionization threshold of the respective medium around the electrode (e.g., blood or gases resulting from electrolysis). (Embodiment 2) The catheter according to Embodiment 1, wherein the pitch and / or clearance of two adjacent loop sections (121, 122, 221, 222, 321, 322) is even smaller than the therapeutic threshold of the respective tissues. (Embodiment 3) A catheter according to Embodiment 1 or 2, wherein the diameters of two adjacent loop sections (221, 222) increase toward the distal end of the ablation portion (22), or the diameters (D1, D2, D3) of two adjacent loop sections (121, 122, 321, 322) decrease toward the distal end of the ablation portion (12, 32). (Embodiment 4) A catheter according to any one of embodiments 1 to 3, wherein at least two of the multiple electrodes (120, 220, 320) in the ablation portion are adapted to deliver high-voltage unipolar pulsed-field ablation (PFA) energy or bipolar PFA energy, or a combination of unipolar and bipolar PFA energy, to the tissue. (Embodiment 5) A catheter according to any one of embodiments 1 to 4, wherein at least two of the electrodes (120, 220, 320) are controlled by an electronic control unit (70), the electronic control unit is adapted to connect at least two of the plurality of electrodes (120, 220, 320) to a high-voltage pulse generator (50) and to pair these at least two electrodes in a predetermined manner. (Embodiment 6) The catheter according to any one of embodiments 1 to 5, wherein the catheter shaft (10, 20, 30) comprises at least two lumens separated by a material having a dielectric strength greater than the threshold required to withstand high-voltage pulses. (Embodiment 7) A catheter according to any one of embodiments 1 to 6, wherein a first lumen of at least two lumens is configured to hold at least two electrode lead wires connected to an electrode providing the same first polarity, and a second lumen of at least two lumens, different from the first lumen, is configured to hold at least two electrode lead wires connected to an electrode providing the same second polarity different from the first polarity. (Embodiment 8) The catheter according to any one of embodiments 1 to 7, wherein the ablation portion (32) comprises an internal support structure and / or a central wire (31) connected to the distal tip of the ablation portion. (Embodiment 9) A catheter according to any one of embodiments 1 to 8, wherein the electrodes are distributed along at least two loops such that the angular separation between the most distal electrode and the most nearest electrode is at least 2 × 360° or at least 720°. (Embodiment 10) For example, a method of manipulating ablation catheters (1, 2, 3) to treat a patient's tissue, such as in a PVI procedure on the patient's heart, wherein the ablation catheters (1, 2, 3) are Long, slender catheter shafts (20, 30, 40) The ablation portion (12, 22, 32) is located at the distal end of the catheter shaft, and multiple electrodes (120, 220, 320) are housed along the ablation portion. Equipped with, The ablation portion comprises at least two loop sections (121, 122, 221, 222, 321, 322) that form a three-dimensional helix. A method in which multiple electrodes are energized by a high-voltage charge-balancing pulsed electric field delivered in a unipolar configuration, a bipolar configuration, or a combination of unipolar and bipolar configurations. (Embodiment 11) The method according to Embodiment 10, wherein two adjacent electrodes (120, 220, 320) along a loop section (121, 122, 221, 222, 321, 322), or two adjacent electrodes in different loop sections, are energized in a bipolar configuration by the pulsed electric field. (Embodiment 12) The method according to Embodiment 10 or 11, wherein the voltage amplitude of the pulse delivered to the catheter electrode is greater than 1 kV, preferably greater than 2.5 kV, and more preferably 2.5 kV to 3.5 kV. (Embodiment 13) The method according to any one of embodiments 10 to 12, wherein the pulse width is greater than 0.5 μs, preferably 0.5 μs to 30 μs. (Embodiment 14) The method according to any one of embodiments 10 to 13, wherein the impedance of the medium surrounding the plurality of electrodes is measured using electrodes from the plurality of electrodes. (Embodiment 15) The method according to any one of embodiments 10 to 14, wherein biopotentials are acquired from the surrounding tissue using at least two mapping electrodes located on the ablation area, or multiple electrodes (120, 220, 320) for ablation used in mapping mode. (Embodiment 16) The method according to any one of embodiments 10 to 15, wherein the impedance value is measured over a frequency range using the plurality of electrodes. (Embodiment 17) A method for operating an ablation catheter described in any one of Embodiments 1 to 9, according to any one of Embodiments 10 to 16. (Embodiment 18) A system for creating cardiac conduction blockage within human or animal tissue, A catheter comprising a catheter shaft and an ablation portion located at the distal end of the catheter shaft, which houses multiple electrodes along the ablation portion, A high-voltage generator configured to output positive and negative high-voltage pulses including pulse peak and pulse width, Equipped with, The system is configured such that the catheter is connected to a generator and adapted to deliver pulses to multiple electrodes housed along the ablation portion, thereby configuring the pulse peak and pulse width to generate an electric field intensity between the ionization threshold and the therapeutic threshold. (Embodiment 19) The system according to embodiment 18, wherein the generator is configured to provide charge-balancing pulses having positive and negative pulse peaks and corresponding pulse widths. (Embodiment 20) The system according to embodiment 19, wherein the generator is configured to provide two-phase pulses in the shape of a sine wave, square wave, triangular wave, exponentially decaying, or sawtooth wave. (Embodiment 21) The system according to embodiment 19 or 20, wherein the generator is configured to produce a pulse train comprising at least one pulse, preferably at least two pulses. (Embodiment 22) The system according to Embodiment 21, wherein the pulse has a pulse width of 0.5 μs to 30 μs, an inter-pulse delay of 0.1 ms to 100 ms, and an inter-phase delay in the range of 1 μs to 100 μs. (Embodiment 23) The generator is configured to produce a pulse train comprising at least one pulse, preferably at least two pulses, the pulse train may comprise two-phase pulses and / or single-phase pulses, and the length of the pulse train is 5 ms to 100 ms, according to any one of embodiments 18 to 21. (Embodiment 24) The system according to embodiment 23, wherein the generator is configured to send out a maximum of 500 pulse trains within a time frame of at least 1 second, preferably less than 2 minutes. (Embodiment 25) The system according to any one of embodiments 18 to 24, further comprising a device for measuring an electrocardiogram and detecting characteristic peaks of the QRS period, P wave, and / or T wave. (Embodiment 26) The system according to embodiment 25, wherein the device is configured to connect to and / or communicate with a generator. (Embodiment 27) The system according to embodiment 26, wherein the device is configured to provide a trigger signal corresponding to the detection of at least one of the QRS period, P wave, and / or T wave. (Embodiment 28) The system according to embodiment 27, wherein the generator is configured to initiate at least one pulse or pulse train in relation to a trigger signal. (Embodiment 29) The system according to embodiment 26, wherein the generator is configured to analyze an electrocardiogram and initiate at least one pulse or pulse train in relation to the QRS period, P wave, and / or T wave. (Embodiment 30) A system according to any one of embodiments 18 to 29, comprising a catheter according to any one of embodiments 1 to 9.

Claims

1. Ablation catheters (1, 2, 3) for treating patient tissue by delivering high-voltage pulses, Catheter shafts (20, 30, 40) and The ablation portion (12, 22, 32) is located at the distal end of the catheter shaft, and a plurality of electrodes (120, 220, 320) are housed along the ablation portion. Equipped with, The ablation portion comprises at least two loop sections (121, 122, 221, 222, 321, 322) that form a three-dimensional helix, The pitch and / or clearance (s1, s2) of two adjacent loop sections is greater than the ionization threshold of the medium around each electrode in the ablation catheter (1, 2, 3).

2. The catheter according to claim 1, wherein the pitch and / or clearance of two adjacent loop sections (121, 122, 221, 222, 321, 322) is even smaller than the therapeutic threshold of the respective tissues.

3. The catheter according to claim 1 or 2, wherein the diameters of two adjacent loop sections (221, 222) increase toward the distal end of the ablation portion (22), or the diameters (D1, D2, D3) of two adjacent loop sections (121, 122, 321, 322) decrease toward the distal end of the ablation portion (12, 32).

4. The catheter according to any one of claims 1 to 3, wherein at least two of the plurality of electrodes (120, 220, 320) in the ablation portion are adapted to deliver a high-voltage unipolar or bipolar pulsed field, or a combination of a unipolar and bipolar high-voltage field.

5. The catheter according to any one of claims 1 to 4, wherein at least two of the electrodes (120, 220, 320) are controlled by an electronic control unit (70), the electronic control unit is adapted to connect at least two of the plurality of electrodes (120, 220, 320) to a high-voltage pulse generator (50), and to pair these at least two electrodes in a predetermined manner.

6. The catheter according to any one of claims 1 to 5, wherein the catheter shaft (10, 20, 30) comprises at least two lumens separated by a material having dielectric strength greater than the threshold required to withstand high-voltage pulses.

7. A catheter according to any one of claims 1 to 6, wherein a first lumen of at least two lumens is configured to hold at least two electrode lead wires connected to an electrode providing the same first polarity, and a second lumen of at least two lumens, different from the first lumen, is configured to hold at least two electrode lead wires connected to an electrode providing the same second polarity different from the first polarity.

8. The catheter according to any one of claims 1 to 7, wherein the ablation portion (32) comprises an internal support structure and / or a central wire (31) connected to the distal tip of the ablation portion.

9. The catheter according to any one of claims 1 to 8, wherein the electrodes are distributed along the at least two loops such that the angular separation between the most distal electrode and the most nearest electrode is at least 2 × 360° or at least 720°.

10. For example, a method of manipulating an ablation catheter (1, 2, 3) to treat a patient's tissue, such as in a PVI procedure on the patient's heart. Long, slender catheter shafts (20, 30, 40) The ablation portion (12, 22, 32) is located at the distal end of the catheter shaft, and a plurality of electrodes (120, 220, 320) are housed along the ablation portion. Equipped with, The ablation portion comprises at least two loop sections (121, 122, 221, 222, 321, 322) that form a three-dimensional helix, A method wherein the plurality of electrodes are energized by a high-voltage charge-balancing pulsed electric field delivered in a unipolar configuration, a bipolar configuration, or a combination of a unipolar configuration and a bipolar configuration.

11. The method according to claim 10, wherein two adjacent electrodes (120, 220, 320) along a loop section (121, 122, 221, 222, 321, 322), or two adjacent electrodes in different loop sections, are energized in a bipolar configuration by the pulsed electric field.

12. The method according to claim 10 or 11, wherein the voltage amplitude of the pulse delivered to the catheter electrode is greater than 1 kV, preferably greater than 2.5 kV, and more preferably between 2.5 kV and 3.5 kV.

13. The method according to any one of claims 10 to 12, wherein the pulse width is greater than 0.5 μs, preferably 0.5 μs to 30 μs.

14. The method according to any one of claims 10 to 13, wherein the impedance of a medium surrounding the plurality of electrodes is measured using electrodes from the plurality of electrodes.

15. The method according to claim 14, wherein the impedance value is measured over a frequency range using the plurality of electrodes.

16. The method according to any one of claims 10 to 15, wherein biopotentials are acquired from the surrounding tissue using at least two mapping electrodes located on the ablation portion, or the plurality of electrodes (120, 220, 320) used for ablation in mapping mode.

17. The method according to any one of claims 10 to 16, comprising operating the ablation catheter according to any one of claims 1 to 9.

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