CN116669643A

CN116669643A - Ablation catheter and method of operating the same

Info

Publication number: CN116669643A
Application number: CN202280008259.3A
Authority: CN
Inventors: D·帕内斯库; C·哈塔; A·德拉拉玛; H·埃伯特; S·霍尔津格
Original assignee: CRC EP Inc.
Current assignee: CRC EP Inc.
Priority date: 2021-01-22
Filing date: 2022-01-21
Publication date: 2023-08-29

Abstract

The invention relates to an ablation catheter (1, 2, 3) for treating tissue of a patient, for example for performing PVI procedures on the heart of a patient, the ablation catheter comprising an elongate catheter shaft (20, 30, 40) and an ablation portion (12, 22, 32) arranged at the distal end of the catheter shaft, a plurality of electrodes (120, 220, 320) being accommodated along the ablation portion, wherein the ablation portion comprises at least two ring segments (121, 122, 221, 222, 321, 322) forming a three-dimensional spiral. To improve the safety of the ablation treatment, avoiding affecting adjacent tissue (e.g. nerves, blood vessels, esophagus) and shortening the ablation time, the spacing or gap (s 1, s 2) between two adjacent ring segments is larger than the ionization threshold of the medium (e.g. blood or gas generated by electrolysis) surrounding the distal segment. The invention also relates to a method of operating such an ablation catheter.

Description

Ablation catheter and method of operating the same

Technical Field

The present invention relates to embodiments of ablation catheters suitable for Pulsed Field Ablation (PFA). More particularly, the present invention relates to embodiments of PFA catheters that may be used to safely perform cardiac ablation procedures such as, but not limited to, pulmonary Vein Isolation (PVI), continuous atrial fibrillation ablation, ventricular tachycardia ablation. The catheter includes a plurality of electrodes and delivers pulsed field energy to effect irreversible electroporation of cardiac tissue.

Background

It is well known to use ablation catheters in the treatment of Atrial Fibrillation (AF) patients for PVI procedures. In this procedure, the Pulmonary Vein (PV) is electrically isolated from the left atrium by forming a continuous annular ablative lesion around the Pulmonary Vein Ostium (PVO) or vestibule thereof. Thus, by preventing unwanted perturbed electrical signals generated within the PV from propagating into the left atrium, irregular atrial contractions can be avoided. Ablation catheters may be used to treat other tissues such as, but not limited to: ventricular, right atrium, left atrium. In addition, other organs can be treated by using catheters: lung, liver, kidney, etc.

There are a variety of ablation catheter alternatives including single point tip electrode catheters, circular multi-electrode ring catheters, and balloon-based ablation catheters that use different energy sources. They lack the ability to produce the desired ablation that safely electrically isolates the arrhythmogenic trigger site from the rest of the ventricle in a "one-time" manner without further repositioning, rotating or moving the catheter.

It is desirable to further improve ablation therapy by providing catheters and systems that safely achieve electrically isolated "moats" in a disposable manner. The concept of an electrically isolated moat is defined as a region of cardiac tissue that surrounds the arrhythmogenic trigger point and prevents it from propagating to the rest of the ventricle. For example, in the case of an arrhythmia trigger point located in a pulmonary vein, an ablation zone that completely deactivates tissue located at the ostium or vestibule, ensuring transmurality, represents the electrically isolated moat, but is not limited to. As long as the tissue within the moat is not viable, excitation from the trigger point within the corresponding pulmonary vein is not conducted to the rest of the left atrium. This arrhythmogenic excitation is blocked by the moat and does not trap the body of the left atrium. In the case of atrial fibrillation, if the conduction block moat is implemented, the trigger mechanism is eliminated or its frequency of occurrence is reduced. Currently available techniques achieve the conduction block or electrically isolating the moat by either a point-by-point manner (i.e., repositioning the conduit in successive steps), a rotational manner (i.e., rotating the conduit moving element to form the moat), or a repositioning manner (i.e., repositioning the conduit moving element to an adjacent position to form the moat). In other words, the prior art implements the conduction block moat by employing a "multiple pass". While it is possible to obtain the conduction block moat once by over-powering the target tissue, doing so can cause collateral organs (e.g., esophagus, lung, diaphragm, etc.) to be irreversibly damaged. In some cases, these adverse events may pose a serious risk to the patient. For example, when the prior art over-powers the structures of the left atrium, they may result in an atrial-esophageal fistula. If found too late, the fistula may be fatal. If properly designed, pulsed field ablation can have the advantage of safely creating these conduction blocks/electrically isolated moats in a one-time fashion and avoiding or minimizing collateral tissue damage.

Disclosure of Invention

The above-mentioned problem is solved by an ablation catheter having the features of claim 1 and a method of operating such an ablation catheter having the features of claim 9.

In particular, one embodiment of an ablation catheter for treating tissue of a patient (e.g., for PVI procedures performed at heart tissue or venous tissue of the patient) includes an elongate catheter shaft and an ablation portion disposed at a distal end of the catheter shaft, a plurality of electrodes being housed along the ablation portion, wherein the ablation portion includes at least two ring segments forming a three-dimensional spiral, wherein a spacing and/or gap of the two adjacent ring segments is greater than an ionization threshold. Catheters employing ring segments or ring segments include, but are not limited to, catheters having a continuous or sequential spiral. Pulsed field ablation uses high-intensity electric fields. If the catheter is improperly designed, the field strength may be high enough to ionize the medium between the electrodes. In this case, an arc may be generated. Arcing can increase the risk to the patient as it can lead to unintended tissue damage. Furthermore, the high temperature of the arc may melt the catheter material, leaving foreign particles in the patient's blood stream. Therefore, it is important to use a catheter designed to prevent ionization from occurring. This may be accomplished by a design element that holds the catheter electrode at a distance greater than a known or expected trigger ionization (i.e., ionization threshold).

Within the framework of the present application, the phrase "ionization threshold" is understood to be a field strength sufficient to ionize a medium between electrodes in such a way that an arc is generated.

Within the framework of the present application, the phrase "at least two ring segments forming a three-dimensional helix" is understood to include a structure of at least two ring segments arranged in such a way as to form a three-dimensional helix. The at least two ring segments may be arranged as a continuous or discontinuous spiral. The start and end points of each ring segment may be arranged in the same or different planes with respect to the central axis of the three-dimensional spiral. Furthermore, the at least two ring segments themselves may be arranged in the same or different planes with respect to the central axis of the three-dimensional spiral. Fig. 1 shows an example of at least two ring segments forming a continuous spiral, wherein the start and end points of each ring segment are arranged in different planes with respect to the central axis of the three-dimensional axis, and wherein the at least two rings are arranged in different planes with respect to the three-dimensional axis.

Within the framework of the application, the spacing of two adjacent ring segments (or ring/spiral arms in the case of a continuous ring/spiral) is defined as: the distance of the opposing outer surfaces of each of the two adjacent ring segments, wherein the distance is measured perpendicular to the local tangential direction of the respective segment between which the distance is measured. The spacing is determined in a stage of the catheter in which the three-dimensional form of the ablation portion comprising the at least two ring segments is not limited by any external forces.

Within the framework of the application, the gap of two adjacent ring segments is defined in the same way as the spacing measured in the stage of the catheter in which the three-dimensional form of the ablation portion comprising said at least two ring segments is flattened or nearly flattened by external forces, for example when the catheter is pressed against the tissue as shown in fig. 18 b. If the ablation portion is flattened by an external force, the at least two ring segments are in the same plane with respect to the central axis of the three-dimensional spiral.

According to one embodiment, the ablation catheter is configured to deliver Pulsed Field Ablation (PFA) energy to atrial or ventricular tissue via an ablation electrode. In other words, the ablation catheter may be configured to perform PFA. In particular, the ablation catheter may be used to provide cardiac catheter ablation to treat a variety of cardiac arrhythmias, including AF. For example, the ablation catheter may be configured to be connected to a multi-channel PF energy generator configured to deliver PF energy. The waveform of the PF energy generator can be conceived such that it, in combination with the catheter circuit design, can achieve the desired therapeutic effect while minimizing or minimizing the chance of ionization. The catheter of the present application may also be used for different types of tissue, such as veins, lungs, liver, kidneys. It can be used for Pulmonary Vein Isolation (PVI), continuous atrial fibrillation ablation, ventricular tachycardia ablation, and other ablation procedures.

The catheter shaft may include a handle at its proximal end. Each electrode at the ablation portion is electrically connected to a power source and a pulse generator disposed at the proximal end of the catheter shaft by an electrode lead. Furthermore, the catheter may comprise an Electronic Control Unit (ECU) for controlling the ablation procedure and/or processing the measurement data. In another embodiment, two electrode wires are provided at the proximal end and intermediate section of the catheter shaft. At the proximal end, a first electrode lead is connected to the first set of electrodes and a second electrode lead is connected to the second set of electrodes to reduce the diameter of the catheter shaft. The electrodes may have a length along the respective ring segments of 1 to 10 mm, preferably 3 to 5 mm. The catheter shaft is sized to be compatible with an outer sheath having an inner diameter of 7F to 14F, preferably 8.5F. The width between adjacent electrodes along the respective ring segments may be selected to be 1 to 10 mm, preferably 3 to 6 mm, to provide a continuous ablation zone at the patient tissue.

In one embodiment, the spacing of the two adjacent ring segments is also less than the treatment threshold for the respective tissue. The treatment threshold of the respective tissue is understood to be the known or expected distance at which the successive trenches are realized.

The spacing and/or gap of the first set of two adjacent ring segments may be different from or equal to the spacing and/or gap of the second set of two adjacent ring segments. The present specification and disclosure are equally applicable to catheter designs employing continuous or sequential loop or spiral configurations.

The ablation catheter of the invention using PFA is intended to render tissue non-viable by irreversible electroporation (IRE). During IRE, the electric field provided by the electrodes housed at adjacent ring segments creates a hole in the heart's cell membrane. IRE occurs when the number and size of the pores is large enough and the cells die themselves. Thus, adjacent ring segments of the ablation portion form a so-called ablation zone. To provide proper treatment to cause IRE at the ablation zone, the spacing and/or gap between two adjacent ring segments needs to be greater than the ionization threshold to avoid ionization and thereby scar. Furthermore, if the spacing and/or gap is selected to be less than the treatment threshold, the resulting electric field may reliably result in the formation of holes. An additional benefit of adapting the spacing of the ring segments to the above-described threshold is that the safety of the PFA treatment is improved and adjacent tissues (e.g., nerves, blood vessels, esophagus) are not affected so that the normal pumping performance of the heart is not affected. The conduction-blocking moat may be formed once if the ring segments or spiral arms are sized for deployment at the target region. As a result, the ablation time can be shortened.

In one embodiment, the ionization threshold is 2 millimeters, particularly for body fluids (e.g., blood), blood vessels, and/or atrial tissue. In another embodiment, especially for vascular 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 spacing and/or gap of at least 2 millimeters can ensure that any arcing and potential scarring are avoided. The same applies to the treatment threshold. A maximum spacing and/or clearance of 8 mm, preferably 4 to 6 mm, ensures that a continuous moat is obtained.

In one embodiment, the spacing and/or gap is selected to be greater than a center value between the ionization threshold and the treatment threshold. Since the ablation portion may be slightly compressed during ablation, the spacing and/or gap selected in the majority of the area between the ionization threshold and the treatment threshold reliably ensures that the ablation area has advantageous dimensions even in a slightly compressed state.

In one embodiment, the diameters of two adjacent ring segments increase in the direction of the distal end of the ablation portion, thereby forming a plunger-type ablation catheter. A plunger type ablation catheter may be used to ablate in the ventricular or posterior atrial region of the left atrium. Alternatively, the diameters of two adjacent ring segments decrease in the direction of the distal end of the ablation portion, thereby forming an open-corkscrew ablation catheter. An open-corkscrew ablation catheter may be used to ablate in the atrial end region of the pulmonary vein. The diameter of the ring segments may be, for example, 10 mm to 40 mm. More specifically, if used in the left atrium, the widest ring segment may have a diameter of 20 to 35 millimeters, preferably 25 to 32 millimeters. The minimum diameter may be 12 to 22 mm, preferably 15 to 20 mm. The diameter is measured from the two inner surfaces of the opposing ring segments. For both regions, the form of the ablation portion is adapted to the specific form of the respective region to be ablated.

It is within the scope of the invention that the ablation portion may include a plurality of separate mapping electrodes configured to receive electrical signals, such as electrical potentials or biopotential, from the blood vessel or atrial tissue. Alternatively, the electrodes used for ablation in the ablation mode may be used for mapping, i.e. receiving electrical biological signals from blood vessels or atrial tissue, e.g. acquiring electrical or biological potentials. During ablation, the electrodes are in an ablation mode. This may enable mapping and ablation for Pulmonary Vein Isolation (PVI) using a single ablation catheter, and ablating certain non-pulmonary vein trigger points for Atrial Fibrillation (AF) patients.

For example, in one embodiment, additional ring segments of the plurality of ring segments may present a plurality of mapping electrodes. Alternatively or additionally, mapping electrodes may be arranged on one or both of the two adjacent ring segments in addition to ablation electrodes. Multiple mapping electrodes may also be incorporated distal to the multiple ablation electrodes or intermediate to the two ablation electrodes (e.g., between the two ablation electrodes (along respective ring segments)). Further, in addition to or instead of the mapping electrode, the third ring segment may comprise an ablation electrode.

As a suitable material, the ablation electrode may comprise at least one of gold and a platinum/iridium alloy, for example.

To achieve this without adding too many ablation electrodes (which may make it more difficult to create sequential lesions), longer ablation electrodes may be used. For example, the length of the ablation electrode may be in the range of 1 to 10 millimeters, preferably 3 to 5 millimeters. In one embodiment, the ablation electrode may be cannulated or tubular. For example, the diameter of such a sleeve-shaped or tubular ablation electrode may be in the range of 2 to 2.5 millimeters. Furthermore, as mentioned above, the length of the sleeve-shaped or tubular ablation electrode may 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 half-shells separated by a gap are arranged on the inside (body cavity facing) and outside (tissue facing) of the catheter. The gap may be 0.2 to 1 mm wide, preferably 0.5 mm wide. Such an embodiment is shown in fig. 18 c. Alternatively, the electrodes may be solid, but coated with an insulating material on the inside facing the blood (body cavity). Parylene, polyimide or teflon are examples of suitable coatings. The coating material should be an electrical insulator with a high dielectric strength of over 200 kv/mm.

In one embodiment, the ablation portion (particularly the ring segment) may comprise a shape memory material. Preferably, the shape memory material is a superelastic material (e.g., a superelastic alloy), i.e., the material is elastic and has shape memory properties. For example, nitinol is a biocompatible superelastic alloy suitable for the present invention. In one variation, the ablation portion (particularly the ring segment) may include an internal support element, such as an internal support wire, having shape memory or superelastic properties. The shape memory support wire may have different stiffness and cross-sectional shape in different segments. The internal support structure maintains the structural and design integrity of the ablation portion and extends along at least a segment of the ablation portion. The internal support structure may be implemented as nickel titanium alloy wire (e.g., round, rectangular, or square wire with a variable cross-section or gradual change). In addition, the support structure includes an insulating material, such as parylene, polyimide, teflon, on the outer surface of the wire. Furthermore, the wire of the ablation portion may be divided into segments having different diameters or cross-sectional shapes to provide different stiffness.

In one embodiment, the ablation catheter may further comprise a steerable delivery sheath. Thus, in operation, the position of the ablation portion is easily adjusted at the targeted visceral tissue until contact of each ablation electrode is satisfied.

In one embodiment, two adjacent electrodes of the plurality of electrodes of the ablation portion are staggered along a distance greater than the ionization threshold. This means that the electrodes can be arranged staggered, as it is convoluted within the axis of the ring. Thus, in one embodiment, the distance of the outer opposing surface of each of the two adjacent ring segments in a direction perpendicular or oblique to the axis of the ring may also be selected to be greater than the ionization threshold. As a result, if the ring moves from side to side due to the heart anatomy, the electrodes are less likely to collide. Furthermore, even without collision, the electrodes are less likely to strike an arc because their relative spacing exceeds the ionization threshold.

In one embodiment, each electrode is connected to an Electronic Control Unit (ECU), wherein the connection is provided via a pulse generator pairing each two of the at least two electrodes in a predetermined manner. For example, if there are more than two electrodes (e.g., 16 electrodes), each two electrodes received adjacently along a ring segment may be paired (pattern along the ring segment), or each two electrodes received adjacently across two adjacent ring segments (pattern across the ring segment) may be paired to operate in a bipolar arrangement. Thus, in both modes, 8 pairs of electrodes can be formed from 16 electrodes. Pairing can be switched between two modes. Furthermore, the pairing may be switched to another pair of electrodes, for example along the ring segment. For pairing, the electrodes may be connected to a switching unit, wherein the switching unit is connected and controlled by an electronic control unit. The electronic control unit may be further adapted to switch to the ablation mode and mapping mode described above for each electrode separately. The switching unit effects pairing along the ring segments and, where applicable, switching between modes in accordance with control signals of the electronic control unit. The electronic control unit may comprise a microprocessor, a computer or the like.

In one embodiment, the catheter shaft includes at least two lumens separated by a material having a dielectric strength greater than a dielectric threshold, the material being adapted to withstand high voltage PF pulses used in conjunction with the catheters described above and below, such as high voltage PF pulses having an amplitude greater than 1 kv, greater than 2.5 kv, or from 2.5 kv to 3.5 kv. Such a material may be, for example, a polymer film, in particular a polyimide film provided in the form of a tube or a layer received by impregnation (e.gA film). The dielectric strength was 160 kv/mm. The thickness of the polymer film (polyimide layer) may 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 leads connected to electrodes providing the same first polarity, and wherein a second lumen of the at least two lumens, different from the first lumen, is configured toAt least two electrode leads connected to electrodes providing the same second polarity different from the first polarity are maintained. This embodiment allows for a reduced diameter of the catheter shaft without the need to isolate each electrode lead, and at the same time provides the necessary safety with respect to arcing. If an electrode embodiment as shown in fig. 18c is used, the lumen structure is correspondingly adapted to accommodate a greater number of connecting wires. The same dielectric strength principle applies.

In one embodiment, the catheter shaft may have an overall length from the handle to the distal end of the ablation portion of greater than 1 meter.

In one embodiment, at least two of the plurality of electrodes of the ablation portion are adapted to deliver high voltage monopolar PF energy or bipolar PF energy, or a combination of monopolar and bipolar PF energy, as described below. Fig. 15a and b show examples of some suitable waveforms. Such a waveform, in combination with the loop structure described above, ensures that an electric field high enough to produce a therapeutic effect capable of forming a conduction block moat is applied at a time but below the ionization threshold to avoid arcing. Delivery of the PFA pulse may be gated by the QRS complex of the cardiac cycle. Alternatively, PFA pulses may be delivered asynchronously without QRS gating when ablation is directed to a region distal to the ventricle. The electronic control unit is adapted to switch between monopolar PF energy and bipolar PF energy supply modes.

In another embodiment, the distal tip of the ablation portion is connected to a steering wire or centerline that may be steered from a handle element disposed at the proximal end of the catheter shaft. Thus, the centre line may be connected to an actuation mechanism within the handle element. Along the ablation portion, the centerline extends generally along a longitudinal axis of the catheter shaft. A steering plate, ring, or other known steering structure may be disposed at the distal end of the catheter shaft, with the distal end of the catheter shaft being connected to a distal spiral or multi-ring ablation segment. A centerline is connected to the steering structure. Depending on the treatment requirements, the centerline may be manipulated so that the longitudinal length of the ablation portion (i.e., the length along the longitudinal axis of the three-dimensional helical/multi-loop structure) or loop segment can be directed toward the tissue target.

In one embodiment, the electrodes are distributed along the at least two rings such that the angular separation between the furthest electrode and the closest 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.

In one embodiment, the catheter includes at least one irrigation lumen configured to apply irrigation fluid at a treatment site. The at least one irrigation lumen may be connected to at least one separate irrigation opening at the ablation segment. In one embodiment, separate irrigation openings may be provided at each electrode, between the electrodes, or proximal and/or distal to the most proximal and distal electrodes of the ablation portion.

The irrigation lumen may be connected to an irrigation fluid source at the proximal end of the catheter. The flushing fluid may be a sterile fluid, preferably distilled water or a physiological saline solution having a low salinity (preferably not more than 0.1%). The use of distilled water or a low salinity brine solution can reduce the salinity of the treatment site, thus further reducing the risk of arcing.

Another aspect of the invention relates to a method of operating an ablation catheter for treating tissue of a patient, for example for PVI procedures performed at cardiac tissue or venous tissue of the patient. The method includes manipulating an elongate catheter shaft and an ablation portion disposed at a distal end of the catheter shaft. The ablation portion includes a plurality of electrodes received along the ablation portion. It further comprises at least two ring segments forming a three-dimensional spiral, the plurality of electrodes being excited by pulsed electric field energy delivered in a monopolar arrangement or a bipolar arrangement or a combination of a monopolar arrangement and a bipolar arrangement, and wherein the pulsed electric field energy is delivered in a charge balanced manner.

The charge balance characteristics have the potential benefits of minimizing blistering (by reducing the chance of blood electrolysis), arcing, and skeletal muscle stimulation (by motor direct or indirect stimulation).

Within the framework of the application, delivering pulsed electric field energy in a charge balanced manner is understood to mean using pulses with positive and negative pulse peaks and corresponding pulse widths such that the net charge delivered to the tissue is as close to 0 μc as reasonably possible to achieve charge balance. One way to deliver charge balanced pulsed electric field energy is to use biphasic pulses comprising a positive pulse section and a negative pulse section. The pulse width is the width of the positive portion (or negative portion). The peak (amplitude) and width of the positive and negative portions are designed to balance each other. Thus, the biphasic pulse itself is charge balanced. Another way to deliver charge balanced pulsed electric field energy is to use multiple pulses of one pulse train, whereby the peak and width of the individual pulses of the pulse train are designed to balance each other.

In one embodiment, in a bipolar arrangement, two adjacent electrodes along a ring segment or two adjacent electrodes of different ring segments are excited by pulsed electric field energy. In this way, the electric field vector can be manipulated to produce a more complete conduction block/electrical isolation moat.

In another embodiment, the voltage amplitude of the pulsed electric field is greater than 1 kilovolt or greater than 2.5 kilovolts, or between 2.5 kilovolts and 3.5 kilovolts. The total current amplitude may be in the range of 5 to 150 amps depending on the electrode configuration selected.

In another embodiment, the pulse duration (pulse width of either the positive or negative phase) is greater than 0.5 microseconds, preferably less than 30 microseconds. Preferably, the pulse is biphasic, comprising a positive portion comprising a positive pulse peak and a negative portion comprising a negative pulse peak. The pulse width is the width of the positive portion (or negative portion). Preferably, but not necessarily, the positive and negative phase complexes are charge balanced so that the net charge delivered to the tissue is as close to 0 μC as reasonably possible. Alternatively, the charge balance characteristic may be achieved over the duration of the pulse train. In this case the net charge of the pulse train would be as close to 0 muc as reasonably possible. The charge balance feature has the potential benefit of minimizing foaming (by reducing the chance of blood electrolysis), arcing (caused by ionization of blood or gas produced by electrolysis), and skeletal muscle stimulation (by direct or indirect motor nerve stimulation). Biphasic pulses beginning with a positive or negative portion are understood to be positive or negative (biphasic) pulses.

According to one embodiment, the positive and negative pulses are separated by an inter-phase delay. The pulse width of the present invention has the advantage that the electric field acts on the cells long enough to create pores through the electric field. The phase-to-phase delay may be selected in the range of 1 microsecond to 100 microseconds, such that the negative phase does not cancel the effect of the positive phase too quickly and the phase-to-phase delay is not too long. If the inter-phase delay becomes too long, charge balance does not work. The negative and positive phases may have the same amplitude or different amplitudes, as long as a charge-balanced pulse train is obtained.

In embodiments using biphasic pulses, the inter-phase delay is determined between two consecutive biphasic pulses, wherein the biphasic pulse is followed by an anti-biphasic pulse (e.g., a positive biphasic pulse is followed by a negative biphasic pulse). The time between the start of the first biphasic pulse and the next anti-biphasic pulse is an inter-phase delay and is also in the range of 1 microsecond to 100 microseconds.

In another embodiment, a pulse train (pulse train) comprising at least one pulse with a pulse width of more than 0.5 microseconds, preferably less than 30 microseconds, is provided in a period of 5 to 100 milliseconds. The inter-pulse delay may be, for example, 0.1 to 100 milliseconds. Preferably, the inter-pulse delay is longer than 1 millisecond. In one embodiment, a pulse train of 10 pulses with a 3 kilovolt amplitude, a 10 microsecond pulse width, and a 1 millisecond inter-pulse delay is used. In an alternative embodiment, a pulse train of 30 pulses with an amplitude of 1.625 kilovolts, a pulse width of 15 microseconds, and a 5 millisecond inter-pulse delay is used. In another embodiment, one burst or a plurality of such bursts, e.g. up to 500 bursts, are provided for a period of at least 10 seconds, preferably for a period of less than 2 minutes. During this time, the pores do not heal, since it takes several seconds for the pores to recover, so that the cells die themselves, thereby resulting in IRE.

In one embodiment, a sterile flushing solution is applied to the treatment site, whereby distilled water or a physiological saline solution having a low salinity (preferably not more than 0.1%) is preferably used as the flushing solution. The use of distilled water or a low salinity brine solution can reduce the salinity of the treatment site, thus further reducing the risk of arcing. Irrigation fluid may be applied through at least one separate irrigation opening at the ablation portion. In one embodiment, separate irrigation openings may be provided at each electrode, between the electrodes, or proximal and/or distal to the most proximal and distal electrodes of the ablation portion.

In the case of achieving charge balance, as described above, the pulse shape of the biphasic pulse may be, for example, a sine wave, a square wave, a triangular wave, an exponentially decaying wave, or a saw tooth wave. The single pulse (positive or negative) is preferably a rectangular pulse.

In addition, the mapping electrodes described above may be used to obtain electrical or biopotential from surrounding vascular or atrial tissue. The mapping electrode may have a similar structure as the ablation electrode, but may have a slightly smaller size than the ablation electrode to provide higher electrical signal resolution. The wire may be attached to one electrode using soldering. In one embodiment, a smaller mapping electrode (e.g., 1 millimeter in length) may be disposed between two ablation electrodes. The detected voltage signals are transmitted to the electronic control unit via the corresponding electrode leads. Alternatively or additionally, the mapping electrode may be used to collect current. For example, mapping electrodes may also be used to measure local tissue impedance. This is useful for monitoring the extent of tissue contact or the progress of the PFA effect. During treatment of a patient, mapping may be performed before ablation and after one ablation step or after more than one ablation step to observe ablation results and ablation progress. For convenience and to improve the evaluation, standard mapping or navigation techniques may be used to visualize the mapping signals, e.g. potential signals, received by the mapping electrodes or electrodes operating in mapping mode. Thus, the local conduction characteristics of the surrounding tissue can be plotted.

In one embodiment, the impedance is measured using a plurality of electrodes of the ablation portion of two adjacent ring segments to determine the relative distance of adjacent ring segments from each other upon contact with the tissue of the patient. In particular, the impedance is measured between two electrodes of adjacent ring segments. If the measured impedance is below a predetermined impedance threshold, this is an indication that adjacent ring segments are too close, which should be avoided if the electrodes of adjacent segments have different polarities. Monopolar or bipolar impedance may also be determined to demonstrate a uniform distribution of electrodes to determine contact of the ablation portion with the patient's tissue along its entire outer surface.

In one embodiment, the impedance between the two electrodes is measured over a specific frequency range, preferably determining a frequency dependent impedance curve. The frequency range may be 10 kilohertz to 500 kilohertz. A flat impedance curve of low impedance value (e.g., up to 300 ohms) may indicate a contact or collision between two electrodes. Upon collision or electrical contact of the two electrodes, the bipolar impedance phase increases, becoming significantly positive. This is because the inductance of the electrode wire imparts an inductive characteristic to the equivalent bipolar circuit (assuming electrode collisions). A significant decay of the impedance curve of higher value (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 is understood to mean an impedance-frequency dependence in which the deviation of the impedance value measured at high frequencies from the impedance value measured at low frequencies is less than 20%, preferably less than 10%. A distinct impedance curve is understood to be an impedance-frequency dependence of the measured impedance value at high frequencies deviating more than 20% from the measured impedance value at low frequencies.

According to one aspect of the application, the method of operation as described above is used to operate an ablation catheter as described above.

Another aspect of the application relates to a system for implementing a heart block moat in human or animal tissue, the system comprising:

1. a catheter including a catheter shaft and an ablation portion disposed at a distal end of the catheter shaft, a plurality of electrodes being accommodated along the ablation portion,

2. a high voltage generator configured to deliver positive and negative high voltage pulses including pulse peaks and pulse widths,

3. a catheter adapted to be connected to the generator and deliver pulses to a plurality of electrodes housed along the ablation portion, wherein

4. The generator is adapted to deliver pulsed electric field energy to the electrode, whereby the pulse peak and the pulse width are configured to generate pulsed electric field energy between an ionization threshold and a treatment threshold.

An arc may be generated if the electric field is strong enough to ionize the medium between the electrodes. Arcing can increase the risk to the patient as it can lead to accidental tissue or air pressure injuries. Furthermore, the high temperature of the arc may melt the catheter material, leaving foreign particles in the patient's blood stream. It is therefore important to configure the peak value and pulse width such that the pulse electric field energy generated at the electrodes is below the ionization threshold. On the other hand, pulsed electric field energy needs to be large enough to ensure one-time application of the electric field. Thus, the pulse peaks and pulse widths are configured to produce a pulsed electric field energy above a therapeutic threshold to produce a therapeutic effect capable of forming a conduction block moat. Within the framework of the application, a (pulsed) peak is understood to be a peak of the voltage amplitude.

The system may comprise any catheter as described above.

The generator is configured to provide a charge balanced pulse having positive and negative pulse peaks and corresponding pulse widths that achieve charge balance with a net charge of zero. In one embodiment, a biphasic pulse is generated comprising a positive pulse section and a negative pulse section. The pulse width is the width of the positive portion (or negative portion). The peak (amplitude) and width of the positive and negative portions are designed to balance each other. Thus, the biphasic pulse itself is charge balanced. The generator may be configured to generate biphasic pulses in the shape of a sine wave, a square wave, a triangle wave, an exponentially decaying wave, or a sawtooth wave.

Another way to deliver charge balanced pulsed electric field energy is to use multiple pulses of one pulse train, whereby the peak and width of the individual pulses of the pulse train are designed to balance each other.

The generator may be configured to deliver pulses having a pulse width of 0.5 microseconds to 30 microseconds. The individual pulses may be separated by an inter-pulse delay of 0.1 to 100 milliseconds. The inter-phase delay may be in the range of 1 microsecond to 100 microseconds.

The generator may also be configured to generate a pulse train comprising at least one pulse, preferably at least two pulses. The pulse train may comprise biphasic pulses and/or monophasic pulses. The length of such a burst may be 5 milliseconds to 100 milliseconds. The generator may be configured to deliver up to 500 bursts over a period of at least 1 second. Preferably the bursts are delivered in less than 2 minutes.

The system may further comprise means for measuring an electrocardiogram and detecting characteristic peaks of QRS cycles, P-waves and/or T-waves. The means for measuring an electrocardiogram are configured to be connected to and/or in communication with a generator. The means for measuring an electrocardiogram is configured to provide a trigger signal corresponding to the detection of at least one of the following: QRS period, P-wave and/or T-wave. The generator is configured to initiate at least one pulse or pulse train in combination with a trigger signal.

In an alternative embodiment, the measured electrocardiogram is analyzed by a generator and at least one pulse or pulse train is initiated in combination with QRS cycles, P-waves and/or T-waves.

It will be apparent to those skilled in the art that various modifications and variations can be made to the examples and embodiments described in light of the above teachings. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternative embodiments may include some or all of the features disclosed herein. Accordingly, this disclosure is intended to cover all such modifications and alternative embodiments as may fall within the true scope of the invention.

Drawings

The various features and advantages of the present invention will be more readily understood by reference to the following detailed description and the embodiments shown in the drawings. Schematically and exemplarily shown in the drawings:

Fig. 1 shows a distal end of a first embodiment of an ablation catheter in a perspective side view.

Fig. 2 shows the delivery path of an ablation catheter leading to the pulmonary vein ostium of a human heart.

Fig. 3 and 4 show the distal end of the embodiment of fig. 1 in perspective front and side views.

Fig. 5-7 show the distal end of a second embodiment of an ablation catheter in side, front and perspective front views.

Fig. 8-11 show the distal end of a third embodiment of an ablation catheter in side and front views.

Fig. 12 shows the distal end of the embodiment of fig. 1 in a perspective side view and contains some noted dimensions.

Fig. 13 shows a part of an electrical control device of the electrode lead of the embodiment of fig. 1.

Fig. 14 shows the electric field vector distribution electronically steered to achieve a conduction block moat.

Fig. 15a-b show exemplary waveforms for charge balancing. The waveform in fig. 15a is exponentially decaying. The waveform in fig. 15b is rectangular.

Fig. 16a-c illustrate the concept of QRS gating. Fig. 16a shows QRS detection signal (top trace), PFA trigger signal (middle trace) and ECG (bottom trace) for multiple heartbeats. Fig. 16b shows details of a heartbeat. The PFA trigger signal (middle trace) falls within the refractory period of the cardiac cycle. Fig. 16c shows PFA impulse artifacts recorded during preclinical studies.

Fig. 17 shows the actual histological slide marking the conduction block (or electrical isolation) moat around the Right Superior Pulmonary Vein (RSPV).

Fig. 18a-c further illustrate possible electrode distributions on the helical distal section. Figure 18a shows the catheter of the present invention facing the PV. Figure 18b shows the catheter of the present invention deployed while pressed against the wall of a pulmonary vein. Note the gap between the spiral arms. FIG. 18c shows an alternative split tip electrode configuration.

Fig. 19 shows three schematic impedance curves measured with frequency between two electrodes.

Fig. 20a, 20b show two examples of measured impedance as a function of frequency.

Detailed Description

Fig. 1, 3, 4 and 12 schematically and exemplarily show a distal portion of an ablation catheter 1 of a first embodiment. When used with a PFA generator and accessory, the ablation catheter is useful for PFA and is suitable for cardiac electrophysiology mapping (stimulation and recording) and high voltage pulse field cardiac ablation. The peak voltage is, for example, but not limited to + -1 kilovolt to 3 kilovolts, with a pulse width of up to 30 microseconds. If the pulse duration is short (e.g., 0.5 microseconds), a higher peak voltage (e.g., up to 10 kilovolts) may be used. The catheter 1 has an elongated circular catheter shaft 10, which catheter shaft 10 may be connected to a handle comprising a steering mechanism (not shown) at the proximal end. Thus, the catheter can control the deflection of the distal section carrying the ablation electrode as shown.

At the distal end of the catheter shaft 10 shown is arranged an ablation portion 12, which ablation portion 12 comprises a plurality of ring segments 121, 122. The concept of ring segments includes embodiments using a continuous ring or spiral configuration. The catheter shaft may have an effective length of about 115 centimeters from the distal tip of the ablation portion 12. Each of the first ring segment 121 and the adjacent second ring segment 122 presents an ablation electrode 120 (e.g., 14 total electrodes) configured to deliver energy to tissue. Although two rings are shown in fig. 1, more rings may be used. At least part of the third ring is preferably used to achieve a sufficient overlap between the formed ablation zones. The overlap increases the chance of achieving a conduction block moat without reducing the continuity, adjacency, or transmurality of the lesion. See, for example, the catheter schematic in fig. 14. The distal segment includes at least a 45 ° overlapping portion of the third loop segment with the first two segments. In particular, the ablation catheter 1 may be configured to deliver a high voltage PFA signal to tissue via the ablation electrode 120. For example, ablation electrode 120 may be composed of or include gold and/or platinum/iridium alloys. Alternatively, the electrodes 120 of different ring segments may be arranged such that electrodes of the same polarity are aligned. The interleaving method or polarity-based method ensures that electrodes of opposite polarity do not collide when the helical catheter is compressed.

In the exemplary embodiment shown in fig. 1, the ablation electrodes 120 of the second ring segment 122 are arranged in a partially staggered manner relative to the ablation electrodes 120 of the first ring segment 121.

The ring segments 121, 122 may also present a plurality of mapping electrodes configured to receive electrical signals from tissue.

The ring segments 121, 122 together form a three-dimensional helix that forms a form similar to a corkscrew. Alternatively, they may be formed in a plunger-like configuration, as shown in FIGS. 5-7. It should be noted that the diameter of each of the ring segments 121, 122 is such that the inner diameter D1 (e.g. 30 mm, see fig. 12) of the first, closer ring segment 121 is larger than the inner diameter D2 (e.g. 24 mm) of the second, farther ring segment 122. At the furthest tip of ablation portion 12, inner diameter D3 is smaller (e.g., 18 millimeters). Typically, the diameter of the ring segments may be, for example, 10 to 40 millimeters. More specifically, if used in the left atrium, the widest ring segment may have a diameter of 20 to 35 millimeters, preferably 25 to 32 millimeters. The minimum diameter may be 12 to 22 mm, preferably 15 to 20 mm.

The ring segments 121, 122 may comprise a shape memory material, such as in the form of internal structural support wires (not shown), such as nickel titanium alloy wires as described above. In particular, the ring segments 121, 122 may have superelasticity.

The ablation portion 12 may be constrained to a substantially elongate shape for delivery to a target area within the body by a (fixed or steerable) delivery sheath 15, which delivery sheath 15 may also be referred to as an introducer sheath. At the target site, after exiting the distal end of delivery sheath 15, ablation portion 12 may rebound to its original (biased) shape.

Each electrode 120 is, for example, 4 mm along the length of the respective ring segment 121, 122. Typically, the electrode length is in the range of 1 to 10 mm, preferably 3 to 5 mm. The catheter shaft 10 may be sized to be compatible with a sheath having an inner diameter of 8.5F and may be constructed of a radiopaque extrudable polymer and, if applicable, a polymer reinforced braid. In general, the catheter shaft 10 may be sized to be compatible with sheaths having inner diameters of 7F to 14F. The width between adjacent electrodes along the respective ring segments may be selected to be 1 to 10 mm, preferably 3 to 6 mm, to provide a continuous ablation zone at the patient tissue.

Fig. 2 schematically and exemplarily shows a delivery path of an ablation catheter 1 leading to a Pulmonary Vein Ostium (PVO) of a human heart. For orientation purposes, the Inferior Vena Cava (IVC), right Atrium (RA), right Ventricle (RV), left Atrium (LA), left Ventricle (LV), and Pulmonary Vein (PV) are shown, each with PVO. The large black arrows indicate the delivery path through the IVC, RA and through the Septum Wall (SW) into the LA. Finally, the catheter 1 is guided to the PVO area using suitable deflection means. Here, ablation may be performed in the vestibular end region of the pulmonary vein adjacent to the PVO using an open-corkscrew ablation catheter. The form of the ablation portion 12 is configured to fit the size of the target PVO. Alternatively, ablation may be performed at an SVC or attachment, such as a left atrial attachment or a right atrial attachment (LAA or RAA), using an corkscrew catheter.

The second embodiment of the ablation catheter 2 shown in fig. 5-7 is adapted for ablation in an atrial region surrounding PVO or left atrial LA located between PVOs (e.g. LA posterior wall). Alternatively, catheter 2 may be well suited for ablation on the ventricular (RV or LV) wall or in RA (e.g., free RA wall, tricuspid annulus, etc.). The ablation portion 22 comprises two ring segments 221 and 222 with a plurality of ablation electrodes 220 (and mapping electrodes where applicable), similar to the first embodiment. However, the form of the ablation portion 22 resembles a three-dimensional spiral having the form of a plunger, with the nearer first ring segment 221 having a smaller diameter than the farther second ring segment 222.

The third embodiment shown in fig. 8 to 11 is similar to the first embodiment. The elements of this embodiment (e.g., centerline 31 for helical expansion or compression) may be used in conjunction with other types of helical catheters, but are not limited thereto. In addition to the configuration of the first embodiment, the third embodiment of the ablation catheter 3 further comprises a centerline 31 for facilitating expansion or compression of the distal section. The centerline 31 is connected to the distal tip of the ablation portion 32. Ablation portion 32 carries ablation electrodes 320. The centerline 31 extends generally along the longitudinal axis of the helix formed by the ablation portion and its two ring segments 321, 322. A centerline 31 enters the catheter shaft 30 and extends therein. At the proximal end of the catheter, the centerline 31 is connected to an actuating element associated with or integrated into the catheter handle. The centerline 31 may be manipulated such that 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) and the diameters of the respective ring segments 321, 322 may vary and be tailored to the therapeutic needs and local conditions. In the view of fig. 8, the longitudinal length of the ablation portion is greatest compared to the views of fig. 9 and 10, as the centerline pushes the distal tip of ablation portion 32 in a distal direction. Thus, the diameter of the ring segments 321, 322 is minimal. Fig. 10 shows the shortest longitudinal length of the ablation portion 32 of the ablation catheter 3. This is achieved by pulling on the centre line 31. The ablation catheter 3 shown in fig. 9 has a nominal longitudinal length of the ablation portion 32, which is between the lengths of fig. 8 and 10. Thus, the diameters of the ring segments 321, 322 are greatest in fig. 10 and smallest in fig. 8.

With the first and second embodiments arranged at corresponding positions in the heart or in the vein adapted to the form thereof, a reliable complete ablation along the entire circumference is achieved. During ablation in the direction of the longitudinal axis of the helix, a slight compression of the ablation portion 12, 22 of the respective catheter 1, 2 is possible, but the distance of the ring segments 121, 122 or 221, 222 is still within the area limited by the treatment threshold and the ionization threshold.

To induce IRE, not affect adjacent tissue and shorten ablation time, the spacing of adjacent ring segments is selected between ionization threshold and treatment threshold, as detailed above. Referring to the first embodiment shown in fig. 12, the first spacing or gap s1 between the first ring segment 121 and the second ring segment 122 is about 5 mm, and the second spacing or gap s2 between the second ring segment 122 and the distal-most end of the ablation portion 12 is also about 5 mm. In general, the spacing or gap should be between the ionization threshold (2 millimeters) and the treatment threshold (8 millimeters maximum). As mentioned above, it is important that the angular offset between the most distal and most proximal electrodes on any of the catheters #1, #2 or #3 is in excess of 2 x 360 °, preferably 2 x 360 ° +45° (i.e. 1/8 of two complete rings plus the third ring).

An ablation procedure using one of the ablation catheters 1, 2, 3 may be initiated after the ablation portion 12, 22 or 32 is in the correct position (e.g., at the PVO) with respect to the target tissue. The ablation electrodes 120, 220, 320 may provide a pulsed radio frequency electric field in a monopolar or bipolar arrangement. The peak voltage is, for example, but not limited to + -1 kilovolt to 3 kilovolts, with a pulse width of up to 30 microseconds. If the pulse duration is short (e.g., 0.5 microseconds), a higher peak voltage (e.g., up to 10 kilovolts) may be used. The pulse width may be 12 microseconds (between 0.5 and 30 microseconds) forming a pulse train comprising up to 500 pulses/train. Any of the waveforms shown in fig. 15 may be used.

For example, the waveforms in fig. 15a illustrate biphasic exponentially decaying voltage pulses suitable for PFA treatment, but are not limited thereto. Throughout the waveform complex, the exponential decay achieves the goal of charge balance, which is required to minimize the chance of blistering, arcing, or unwanted tissue irritation. Such waveforms may be implemented using a high voltage output stage that is ac coupled to the ablation electrode 120, 220, or 320. The two biphasic pulses shown in fig. 15a form a pulse train that can be repeated N times. The biphasic pulse consists of a positive part PP and a negative part PN. As shown in fig. 15a, the positive biphasic pulse is followed by an inverted negative biphasic pulse. Phase-to-phase delay I ₁ Is the time between the end of the negative part PN of the first biphasic pulse and the start of the positive part of the next pulse. As defined above, if a biphasic pulse is used, the pulse width P corresponds to the length of the positive/negative part PP/PN. The next burst is delayed by the inter-pulse delay I ₂ And then starts.

Similarly, fig. 15b shows an example of a suitable PFA waveform having a rectangular shape. The rectangular pulse shown in fig. 15b is characterized by a voltage peak V and a pulse width P. After a positive rectangular pulse, an inter-phase delay I is passed ₁ Followed by a negative rectangular pulse. The two pulses shown in fig. 15b form a pulse train that is repeated N times. The next burst is delayed by the inter-pulse delay I ₂ And then starts. These waveforms are also charge balanced. Such charge balanced rectangular waveforms can be achieved by using a dc-coupled high voltage output stage with reasonably accurate control of positive and negative phase amplitude and duration. Thus, the net charge (current magnitude versus pulse width) can be controlled to achieve a net balance.

Fig. 16 shows a QRS gating output waveform. A typical lead I ECG waveform 1601a is shown in fig. 16 a. The output of the QRS detector is shown as signal 1602a. The trigger signal for the PFA waveform is shown as signal 1603a. Fig. 16b provides an enlarged view of fig. 16 a. The ECG waveform 1601b represents one cardiac cycle. Its R wave 1604 is detected by QRS detector output 1602 b. After a programmed delay 1605, the PFA waveform flip-flop 1603b is turned on. In this embodiment, delay 1605 is shown as about 70 milliseconds. Depending on the heart rate, delay 1605 may be 20 to 150 milliseconds. It is important to ensure that the PFA pulse is applied during the refractory period of the heart. As shown in fig. 16b, in this particular example, the pulse train ends before the T-wave 1606 begins. Fig. 16c shows an example of PFA pulse artifact recorded using a standard cardiac recording system. The R wave 1604c is followed by an artifact 1607 caused by the delivery of PFA pulses. The artifact 1607 ends safely before the T wave 1606c begins. The above procedure delivers a train of pulses over a cardiac cycle. In the above example, 10 pulses/train were delivered using waveform 1501 of fig. 15 a. Those skilled in the art can modify the above method by using other known parameters without departing from the spirit of the invention. For example, up to 500 bursts may be provided. However, it is preferable to select several strings such that the PFA application time remains greater than 1 second (to allow cell membrane perforation) but less than 2 minutes (to avoid lengthy surgery), although this is not required. The inter-phase delay may be 1 to 100 microseconds. The inter-pulse delay may be 0.1 milliseconds or 100 milliseconds.

The electric field generation, in particular voltage, current and impedance, is monitored by an Electronic Control Unit (ECU) 70 connected to the wires 61 of the electrodes 120, 220, 320 and generated by the waveform generator 50 (see fig. 13). Fig. 14 also shows connections that can be used to generate monopolar or bipolar electric fields. The ECU in fig. 13 and 14 can control the application of the PFA field with the purpose of achieving broad coverage of the tissue space between the catheter ring or spiral. Fig. 14 shows a catheter 1401 (e.g., #1, #2, or #3 in fig. 1 to 10), the electrodes of which catheter 1401 are driven by an ECU 1403. ECU 1403 may be controlled to deliver a field vector 1402 covering the tissue region between the spiral arms/rings of catheter 1401. In this way, it is more likely to achieve a conduction block/electrically isolating moat.

In a bipolar arrangement, adjacent (neighboring) electrodes 120, 220, 320 may be along ring segments 121, 122, 212, 222, 321, 322 or across two neighboring ring segments 121 and 122;221 and 222;321 and 322. Furthermore, the electrodes 120, 220, 320 may be used in a monopolar arrangement. In this case, a ground pad 1404 may be provided on the patient's body surface. Alternatively, a reference electrode associated with the catheter shaft may be used.

To switch between different bipolar arrangements or between monopolar and bipolar arrangements, the ablation catheter 1, 2, 3 may comprise a switching unit 60 connected to the ECU 70 and controlled by the ECU 70. The switching unit 60 supplies the respective phases of the pulsed electric field supplied by the waveform generator 50 to the predefined electrode leads 61 and thus to the predefined electrodes 120, 220, 320, wherein each electrode lead 61 is electrically connected to one specific electrode 120, 220, 320 at the ablation portion 12, 22, 32. The switching element 60 comprises a switching matrix and any configuration of phase distribution may be implemented, for example such that two adjacent electrodes along or across a loop segment are paired to achieve the aforementioned uniform conduction block moat. Any other configuration is possible. The switching signals and configuration information are provided by the ECU 70. The ECU 70 may also enable data processing of electrical potential or biopotential data or impedance data obtained by mapping the electrodes of the ablation catheter 1, 2, 3. As described above, the mapping electrodes located in the ablation portions 12, 22, 32 may include mapping electrodes for determining the electrical potential of surrounding tissue to observe the progress of ablation at predetermined points in time during an ablation procedure. Alternatively, the ablation electrodes 120, 220, 320 may be switched to the mapping mode and may return to the ablation mode. Furthermore, the impedance between adjacent electrodes or between two different adjacent ring segments may be determined prior to delivery of PFA energy. Thus, the impedance (monopolar or bipolar) is monitored to determine if adjacent ring segments and the electrodes of those segments, respectively, are located sufficiently far from the other ring segment or electrode. By monitoring the impedance, the ECU 70 or 1403 can alert the user when any two electrodes are too close, indicating that the corresponding inter-electrode distance is below the ionization threshold. Conversely, the user may be alerted when the impedance measurement indicates that the inter-electrode distance exceeds the treatment threshold.

As described above, the catheter shafts 10, 20, 30 may comprise a dielectric strongMaterials having a degree greater than the insulation threshold of the high voltage PFA pulse (e.g) Two lumens separated. The first lumen may hold, for example, 7 electrode wires 61 providing a first polarity and the second lumen may hold, for example, 7 electrode wires 61 providing a second polarity, thereby reducing the overall diameter of the catheter shaft.

The above-described embodiments of the ablation catheter achieve IRE to prevent electrical signals that cause arrhythmias from propagating along the adjoining area (i.e., to achieve conduction block) while improving safety because it does not affect adjacent tissue (e.g., nerves, blood vessels, esophagus) and ablation times are shorter. Fig. 17 shows such a conduction block or electrically isolated moat. The right superior pulmonary vein 1701 can be seen in the center of the picture. After applying the PFA pulses according to the present invention (total cumulative PFA application time is about 90 seconds/PV), continuous, contiguous and transmural lesions are achieved. The lesion perimeter 1402 is shown. The conduction block or electrical isolation moat 1403 completely covers the region of cardiac tissue between RSPV 1401 and lesion boundary 1402. Electroanatomical mapping confirmed long-term chronic isolation of pulmonary veins.

Figure 18a shows the catheter of the present invention facing the vestibule of a pulmonary vein. Figure 18b shows the catheter of the present invention deployed while pressed against the wall of a pulmonary vein. As shown by lines c1 and c2, the angular separation between the most distant electrode 1802 and the most proximate electrode 1801 exceeds 2 x 360 ° or 720 °. Fig. 18c shows another split tip electrode configuration in which the inner electrode faces blood and the outer electrode faces tissue.

Fig. 19 shows three schematic impedance curves measured with frequency between two electrodes. The impedance may be from a low frequency current f of 10 khz _{Low and low} The measurement is started until a frequency f of 500 khz is reached _{High height} . As at Z ₁ To Z ₄ The significant impedance curve of the topmost curve in the range of (c) indicates good tissue contact between the two electrodes. At Z ₃ To Z ₅ The flat lowest impedance curve in the lower range of (2) indicates the contact between the two electrodes. At Z ₂ To Z ₄ The middle flat impedance curve in the range of (2) indicates twoPoor tissue contact between the individual electrodes. For example, the following thresholds may be used, but are not limited thereto:

1. good tissue contact-at f _{Low and low} (e.g. 10 kHz), Z ₁ In the range of 100 to 500 ohms, depending on the electrode size and tissue characteristics. At f _{High height} (e.g. 500 KHz), Z ₄ Ratio Z ₁ At least 20% lower (S curve).

2. Poor contact-at f _{Low and low} (e.g. 10 kHz), Z ₂ In the range of 80 to 400 ohms, depending on the electrode size and blood characteristics. At f _{High height} (e.g., 500 kilohertz), Z ₄ At most ratio Z ₂ 20% lower, typically only 10% lower or less (flat curve). As shown in fig. 20a, the bipolar impedance decreases from about 113 ohms at 10 khz to about 110 ohms at 500 khz under poor electrical contact conditions. The phase change is small, increasing from about-4 ° to 2 °.

3. Electrode contact-at f _{Low and low} (e.g. 10 kHz), Z ₃ In the range of 0 to 300 ohms, depending on the amount of contact, electrode size, blood characteristics. At f _{High height} (e.g. 500 KHz), Z ₅ At most ratio Z ₃ 20% lower, typically only 10% lower or less (flat curve). As shown in FIG. 20b, when the electrodes collide and make good electrical contact, Z ₅ Lower, between 4 and 9 ohms, while the phase increases with frequency. At 500 khz the phase is about 66 °, which indicates the predominantly inductive electrical characteristic given by the electrode wire.

In view of all the foregoing disclosure, the present invention also provides the following consecutively numbered embodiments:

1. an ablation catheter (1, 2, 3) for treating tissue of a patient by delivering high voltage pulses, comprising a catheter shaft (20, 30, 40) and an ablation portion (12, 22, 32) arranged at a distal end of the catheter shaft, along which ablation portion a plurality of electrodes (120, 220, 320) are accommodated, wherein the ablation portion comprises at least two ring segments (121, 122, 221, 222, 321, 322) forming a three-dimensional spiral, wherein a spacing and/or a gap (s 1, s 2) of two adjacent ring segments is larger than an ionization threshold of a respective medium (e.g. blood or gas resulting from electrolysis) surrounding the electrodes.

2. The catheter of embodiment 1, wherein the spacing and/or gap of two adjacent ring segments (121, 122, 221, 222, 321, 322) is also less than a treatment threshold of the respective tissue.

3. The catheter of any of the foregoing embodiments, wherein the diameters of two adjacent ring segments (221, 222) increase in the direction of the distal end of the ablation portion (22) or the diameters (D1, D2, D3) of two adjacent ring segments (121, 122, 321, 322) decrease in the direction of the distal end of the ablation portion (12, 32).

4. The catheter of any of the foregoing embodiments, wherein at least two of the plurality of electrodes (120, 220, 320) of the ablation portion are adapted to deliver high-voltage monopolar Pulse Field Ablation (PFA) energy or bipolar PFA energy, or a combination of monopolar and bipolar PFA energy, to tissue.

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

6. The catheter of any of the foregoing embodiments, wherein the catheter shaft (10, 20, 30) comprises at least two lumens separated by a material having a dielectric strength greater than a threshold required to withstand a high pressure pulse.

7. The catheter of any of the foregoing embodiments, wherein a first lumen of the at least two lumens is configured to hold at least two electrode leads connected to electrodes providing the same first polarity, and wherein a second lumen of the at least two lumens, different from the first lumen, is configured to hold at least two electrode leads connected to electrodes providing the same second polarity, different from the first polarity.

8. Catheter according to any of the preceding embodiments, wherein the ablation portion (32) comprises an internal support structure and/or a centre line (31) connected to the distal tip of the ablation portion.

9. The catheter of any one of the foregoing embodiments, wherein the electrodes are distributed along the at least two rings such that an angular separation between a most distal electrode and a most proximal electrode is at least 2 x 360 °, or at least 720 °.

10. A method of operating an ablation catheter (1, 2, 3) for treating tissue of a patient, for example for PVI procedures on the heart of a patient, the ablation catheter comprising an elongate catheter shaft (20, 30, 40) and an ablation portion (12, 22, 32) arranged at the distal end of the catheter shaft, a plurality of electrodes (120, 220, 320) being accommodated along the ablation portion, wherein the ablation portion comprises at least two ring segments (121, 122, 221, 222, 321, 322) forming a three-dimensional spiral, wherein the plurality of electrodes are excited by a high voltage charge balancing pulsed electric field, the electric field being delivered in a monopolar arrangement or a bipolar arrangement or a combination of a monopolar arrangement and a bipolar arrangement.

11. The method of embodiment 10, wherein two adjacent electrodes (120, 220, 320) along a ring segment (121, 122, 221, 222, 321, 322) or two adjacent electrodes of different ring segments are excited in a bipolar arrangement by the pulsed electric field.

12. The method of any of embodiments 10-11, wherein the voltage amplitude of the pulse delivered to the catheter electrode is greater than 1 kv, preferably greater than 2.5 kv, more preferably between 2.5 kv and 3.5 kv.

13. The method of any of embodiments 10-12, wherein the pulse width is greater than 0.5 microseconds, preferably between 0.5 microseconds and 30 microseconds.

14. The method of any one of embodiments 10-13, wherein an electrode of the plurality of electrodes is used to measure an impedance of a medium surrounding the plurality of electrodes.

15. The method of any of embodiments 10-14, wherein biopotential is acquired from surrounding tissue using at least two mapping electrodes located on the ablation portion or a plurality of electrodes (120, 220, 320) for ablation used in a mapping mode.

16. The method of any one of embodiments 10-15, wherein impedance values are measured over a range of frequencies using the plurality of electrodes.

17. The method of any one of embodiments 10 to 16 for operating an ablation catheter as in any one of embodiments 1 to 9.

18. A system for implementing a cardiac conduction block moat in human or animal tissue, comprising:

an o-catheter comprising a catheter shaft and an ablation portion disposed at a distal end of the catheter shaft, a plurality of electrodes being accommodated along the ablation portion,

o a high voltage generator configured to deliver positive and negative high voltage pulses comprising a pulse peak and a pulse width,

the catheter is adapted to be connected to a generator and deliver pulses to a plurality of electrodes housed along the ablation portion, whereby the pulse peaks and pulse widths are configured to produce an electric field strength between an ionization threshold and a treatment threshold.

19. The system of embodiment 18 wherein the generator is configured to provide the charge balanced pulse having positive and negative pulse peaks and corresponding pulse widths.

20. The system of embodiment 19, wherein the generator is configured to provide biphasic pulses in the shape of a sine wave, a square wave, a triangle wave, an exponentially decaying wave, or a sawtooth wave.

21. The system of any of embodiments 19 or 20, wherein the generator is configured to generate a pulse train comprising at least one pulse, preferably at least two pulses.

22. The system of embodiment 21 wherein the pulses have a pulse width of 0.5 microsecond to 30 microsecond, an inter-pulse delay of 0.1 millisecond to 100 milliseconds, and an inter-phase delay in the range of 1 microsecond to 100 microseconds.

23. The system of any of embodiments 18 to 21, wherein the generator is configured to generate a pulse train comprising at least one pulse, preferably at least two pulses, wherein the pulse train may comprise biphasic pulses and/or monophasic pulses, and wherein the length of the pulse train is 5 milliseconds to 100 milliseconds.

24. The system of embodiment 23, wherein the generator is configured to deliver up to 500 bursts in a time period of at least 1 second, preferably less than 2 minutes.

25. A system as in any of embodiments 18-24, further comprising means for measuring an electrocardiogram and detecting characteristic peaks of QRS cycles, P-waves and/or T-waves.

26. The system of embodiment 25, wherein the device is configured to connect and/or communicate with a generator.

27. The system of embodiment 26, wherein the apparatus is configured to provide a trigger signal corresponding to detection of at least one of: QRS period, P-wave and/or T-wave.

28. The system of embodiment 27, wherein the generator is configured to initiate at least one pulse or pulse train in conjunction with a trigger signal.

29. The system of embodiment 26, wherein the generator is configured to analyze an electrocardiogram and initiate at least one pulse or pulse train in conjunction with QRS cycles, P-waves, and/or T-waves.

30. The system of any one of embodiments 18 to 29, comprising the catheter of any one of embodiments 1 to 9.

Claims

1. An ablation catheter (1, 2, 3) for treating tissue of a patient by delivering high voltage pulses, comprising a catheter shaft (20, 30, 40) and an ablation portion (12, 22, 32) arranged at a distal end of the catheter shaft, along which ablation portion a plurality of electrodes (120, 220, 320) are accommodated, wherein the ablation portion comprises at least two ring segments (121, 122, 221, 222, 321, 322) forming a three-dimensional spiral, wherein a spacing and/or a gap (s 1, s 2) of two adjacent ring segments is larger than an ionization threshold of a medium surrounding the respective electrode.

2. The catheter of claim 1, wherein the spacing and/or gap of two adjacent ring segments (121, 122, 221, 222, 321, 322) is also less than a treatment threshold of the respective tissue.

3. The catheter of any of the foregoing claims, wherein the diameters of two adjacent ring segments (221, 222) increase in the direction of the distal end of the ablation portion (22) or the diameters (D1, D2, D3) of two adjacent ring segments (121, 122, 321, 322) decrease in the direction of the distal end of the ablation portion (12, 32).

4. The catheter of any of the foregoing claims, wherein at least two of the plurality of electrodes (120, 220, 320) of the ablation portion are adapted to deliver a high voltage monopolar or bipolar pulse field or a combination of monopolar and bipolar high voltage fields.

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

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

7. The catheter of any one of the foregoing claims, wherein a first lumen of the at least two lumens is configured to hold at least two electrode leads connected to electrodes providing the same first polarity, and wherein a second lumen of the at least two lumens, different from the first lumen, is configured to hold at least two electrode leads connected to electrodes providing the same second polarity, different from the first polarity.

8. Catheter according to any of the preceding claims, wherein the ablation portion (32) comprises an internal support structure and/or a centre line (31) connected to a distal tip of the ablation portion.

9. A catheter according to any one of the preceding claims, wherein the electrodes are distributed along the at least two rings such that the angular separation between the furthest and closest electrodes is at least 2 x 360 °, or at least 720 °.

10. A method of operating an ablation catheter (1, 2, 3) for treating tissue of a patient, such as for PVI procedures on the heart of a patient, the ablation catheter comprising an elongated catheter shaft (20, 30, 40) and an ablation portion (12, 22, 32) arranged at the distal end of the catheter shaft, a plurality of electrodes (120, 220, 320) being accommodated along the ablation portion, wherein the ablation portion comprises at least two ring segments (121, 122, 221, 222, 321, 322) forming a three-dimensional spiral, wherein the plurality of electrodes are excited by a high voltage charge balance pulse electric field, the electric field being delivered in a monopolar arrangement or a bipolar arrangement or a combination of monopolar and bipolar arrangements.

11. The method of claim 10, wherein two adjacent electrodes (120, 220, 320) along a ring segment (121, 122, 221, 222, 321, 322) or two adjacent electrodes of different ring segments are excited in a bipolar arrangement by the pulsed electric field.

12. A method according to any one of claims 10 to 11, wherein the voltage amplitude of the pulses delivered to the catheter electrode is greater than 1 kv, preferably greater than 2.5 kv, more preferably between 2.5 kv and 3.5 kv.

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

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

15. The method of claim 14, wherein impedance values are measured over a range of frequencies using the plurality of electrodes.

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

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