Patent Description:
Various techniques for ablating heart tissue by applying irreversible electroporation (IRE) pulses are known in the art.

For example, <CIT> describes a method for ablating tissue by applying at least one pulse train of pulsed-field energy. The method includes delivering a pulse train of energy having a predetermined frequency to cardiac tissue.

<CIT> describes a system including a pulse waveform generator and an ablation device coupled to the pulse waveform generator. The ablation device includes at least one electrode configured for ablation pulse delivery to tissue during use. The pulse waveform generator is configured to deliver voltage pulses to the ablation device in the form of a pulsed waveform.

<CIT> describes systems for electroporation ablation therapy including a pulse wafeform signal generator for medical ablation therapy, and an endocardial ablation device including at least one electrode for ablation pulse delivery to tissue. The signal generator may deliver voltage pulses to the ablation device in the form of a pulse waveform. The system may include a cardiac stimulator for generation of pacing signals and for sequenced delivery of pulse waveforms in synchrony with the pacing signal.

<CIT> describes a system for mapping tissue and produsing lesions for the treatment of cardiac arrythmias in a non-thermal and optimal manner, minimizing the amount of energy required to selectively stun or ablate the target tissues. Energy may be delivered only at the moment (s) of best device position and proximity of an electrode to target tissue and only during a time in the cardiac cycle determined to the optimal for reversible or irreversible effects.

Any methods of therapy and surgery herein are not claimed and exemplary only.

Irreversible electroporation (IRE) may be used, for example, for treating arrhythmia by ablating tissue cells using high voltage applied pulses. Cellular destruction occurs when the transmembrane potential exceeds a threshold, leading to cell death and formation of a lesion. In IRE-based ablation procedures, high-voltage bipolar electrical pulses are applied, for example, to a pair of electrodes in contact with tissue to be ablated, so as to form a lesion between the electrodes, and thereby to treat arrhythmia in a patient heart.

The rhythm of patient heart is determined, inter alia, by electrical activation pulses initiated by a sinus node of the heart. Thus, applying IRE pulses and activation pulses at the same time may interfere with the heart rhythm and therefore, be hazardous to the patient.

Embodiments of the present invention that are described hereinbelow provide improved systems for applying one or more IRE pulses during a refractory period between electrical activation pulses of the sinus node.

In some embodiments, a physician inserts an ablation catheter into an ablation site having tissue intended to be ablated in a patient heart. The ablation catheter comprises at least a pair of electrodes, which are in contact with heart tissue at the ablation site.

The pair of electrodes (also referred to herein as first electrodes) are configured to acquire intra-cardiac (IC) electrocardiogram (ECG) signals at the ablation site of the patient heart, and also, to apply bipolar IRE pulses to the heart tissue located between the two electrodes of the pair.

A second set of multiple electrodes are coupled, for example, to the patient skin, so as to acquire body-surface (BS) ECG signals from the patient heart.

A processor is configured to receive both the IC and BS ECG signals, and to check whether one or more of the acquired ECG signals is in the rhythm of the sinus node. In response to identifying one or more IC and/or BS ECG signals in the rhythm of the sinus node, the processor is configured to detect a refractory period of the patient heart, and to control an IRE pulse generator (IPG) to apply one or more IRE pulse (via at least a pair of the first electrodes) to the ablation site during the detected refractory period. Note that the entire process described above is carried out automatically, e.g., without intervention of the physician, however, the physician may have the means to intervene, and if needed, to adjust or abort the IRE ablation procedure.

The disclosed techniques improve the quality and safety of tissue ablation, by preventing events of applying IRE pulses to tissue at the same time when the sinus node applies the activation pulses, and by ensuring that IRE pulses are applied to tissue of the ablation site during refractory periods. Moreover, the disclosed techniques take away from the physician some of the burden associated with performing the IRE procedure, and allow him/her to monitor the quality of the IRE procedure.

<FIG> is a schematic, pictorial illustration of a catheter-based position-tracking and irreversible electroporation (IRE) ablation system <NUM>, in accordance with an embodiment of the present invention.

Reference is now made to an inset <NUM>. In some embodiments, system <NUM> comprises a deflectable tip section <NUM> that is fitted at a distal end 22a of a shaft <NUM> of a catheter <NUM> with deflectable tip section <NUM> comprising multiple electrodes <NUM>.

In the embodiment described herein, electrodes <NUM> are configured to sense intra-cardiac (IC) electrocardiogram (ECG) signals, and may additionally be used for IRE ablation of tissue of left atrium of a heart <NUM>, such as IRE ablation of an ostium <NUM> of a pulmonary vein (PV) in heart <NUM>. Note that the techniques disclosed herein are applicable, mutatis mutandis, to other sections (e.g., atrium or ventricle) of heart <NUM>, and to other organs of a patient <NUM>.

Reference is now made back to the general view of <FIG>. In some embodiments, the proximal end of catheter <NUM> is connected to a control console <NUM> (also referred to herein as a console <NUM>, for brevity) comprising an ablative power source, in the present example an IRE pulse generator (IPG) <NUM>, which is configured to deliver peak power in the range of tens of kilowatts (kWs). Console <NUM> comprises a switching box <NUM>, which is configured to switch the power applied by IPG <NUM> to one or more selected pairs of electrodes <NUM>. A sequenced IRE ablation protocol may be stored in a memory <NUM> of console <NUM>.

In some embodiments, a physician <NUM> inserts distal end 22a of shaft <NUM> through a sheath <NUM> into heart <NUM> of patient <NUM> lying on a table <NUM>. Physician <NUM> navigates distal end 22a of shaft <NUM> to a target location in heart <NUM> by manipulating shaft <NUM> using a manipulator <NUM> positioned near the proximal end of catheter <NUM>. During the insertion of distal end 22a, deflectable tip section <NUM> is maintained in a straightened configuration by sheath <NUM>. By containing tip section <NUM> in a straightened configuration, sheath <NUM> also serves to minimize vascular trauma when physician <NUM> moves catheter <NUM>, through the vasculature of patient <NUM>, to the target location, such as an ablation site, in heart <NUM>.

Once distal end 22a of shaft <NUM> has reached the ablation site, physician <NUM> retracts sheath <NUM> and deflects tip section <NUM>, and further manipulates shaft <NUM> to place electrodes <NUM> disposed over tip section <NUM> in contact with ostium <NUM> at the ablation site. In the present example, the ablation site comprises one or more PVs of heart <NUM>, but in other embodiments, physician <NUM> may select any other suitable ablation site.

In some embodiments, electrodes <NUM> are connected by wires running through shaft <NUM> to a processor <NUM>, which is configured to control switching box <NUM> using interface circuits <NUM> of console <NUM>.

As further shown in inset <NUM>, distal end 22a comprises a position sensor <NUM> of a position tracking system, which is coupled to distal end 22a, e.g., at tip section <NUM>. In the present example, position sensor <NUM> comprises a magnetic position sensor, but in other embodiments, any other suitable type of position sensor (e.g., other than magnetic based) may be used. During navigation of distal end 22a in heart <NUM>, processor <NUM> receives signals from magnetic position sensor <NUM> in response to magnetic fields from external field generators <NUM>, for example, for the purpose of measuring the position of tip section <NUM> in heart <NUM> and, optionally, for displaying the tracked position overlaid on the image of heart <NUM>, on a display <NUM> of console <NUM>. Magnetic field generators <NUM> are placed at known positions external to patient <NUM>, e.g., below table <NUM>. Console <NUM> also comprises a driver circuit <NUM>, configured to drive magnetic field generators <NUM>.

The method of position sensing using external magnetic fields is implemented in various medical applications, for example, in the CARTO™ system, produced by Biosense Webster Inc. (Irvine, Calif. ) and is described in detail in <CIT>, <CIT>,<CIT>,<CIT>, <CIT> and<CIT>, in <CIT>, and in <CIT>, <CIT> and <CIT>.

Typically, processor <NUM> of console <NUM> comprises a general-purpose processor of a general-purpose computer, with suitable front end and interface circuits <NUM> for receiving signals from catheter <NUM>, as well as for applying ablation energy via catheter <NUM> in a left atrium of heart <NUM> and for controlling the other components of system <NUM>. Processor <NUM> typically comprises a software in memory <NUM> of system <NUM>, which is programmed to carry out the functions described herein. The software may be downloaded to the computer in electronic form, over a network, for example, or it may, alternatively or additionally, be provided and/or stored on non-transitory tangible media, such as magnetic, optical, or electronic memory.

Irreversible electroporation (IRE), also referred to as Pulsed Field Ablation (PFA), may be used as a minimally invasive therapeutic modality to kill tissue cells at the ablation site by applying high-voltage pulses to the tissue. In the present example, IRE pulses may be used for killing myocardium tissue cells in order to treat cardiac arrhythmia in heart <NUM>. Cellular destruction occurs when the transmembrane potential exceeds a threshold, leading to cell death and thus the development of a tissue lesion. Therefore, of particular interest is the use of high-voltage bipolar electrical pulses, e.g., using a pair of electrodes <NUM> in contact with tissue at the ablation site, to generate high electric fields (e.g., above a certain threshold) to kill tissue cells located between the electrodes.

In the context of this disclosure, "bipolar" voltage pulse means a voltage pulse applied between two electrodes <NUM> of catheter <NUM> (as opposed, for example, to unipolar pulses that are applied, e.g., during a radio-frequency ablation, by a catheter electrode relative to some common ground electrode not located on the catheter).

To implement IRE ablation over a relatively large tissue region of heart <NUM>, such as a circumference of an ostium of a pulmonary vein (PV) or any other suitable organ, it is necessary to use multiple pairs of electrodes <NUM> of catheter <NUM> having multi electrodes <NUM> in deflectable tip section <NUM>. To make the generated electric field as spatially uniform as possible over a large tissue region it is best to have pairs of electrodes <NUM> selected with overlapping fields, or at least fields adjacent to each other. However, there is a Joule heating component that occurs with the IRE generated fields, and this heating may damage the electrodes when multiple pairs of electrodes <NUM> are continuously used for delivering a sequence of IRE pulses.

In an embodiment, system <NUM> comprises surface electrodes <NUM>, shown in the example of <FIG>, as attached by wires running through a cable <NUM> to the chest and shoulder of patient <NUM>. In some embodiments, surface electrodes <NUM> are configured to sense body-surface (BS) ECG signals in response to beats of heart <NUM>. Acquisition of BS ECG signals may be carried out using conductive pads attached to the body surface or any other suitable technique. Any pair of electrodes <NUM> can measure the electrical potential difference between the two corresponding locations of attachment. Such a pair forms a lead. However, "leads" can also be formed between a physical electrode and a virtual electrode, known as the Wilson's central terminal. For example, ten electrodes <NUM> attached to the body are used to form <NUM> ECG leads, with each lead measuring a specific electrical potential difference in heart <NUM>. As shown in <FIG>, surface electrodes <NUM> are attached to the chest and shoulder of patient <NUM>, however, additional surface electrodes <NUM> may be attached to other organs of patient <NUM>, such as limbs. In the context of the present disclosure and in the claims, the electrical potential difference measured between surface electrodes <NUM> are referred to herein as body-surface (BS) ECG signals.

In heart <NUM>, a sinus rhythm is any cardiac rhythm in which depolarization of the cardiac muscle begins at the sinus node. The sinus rhythm is characterized by the presence of correctly oriented P waves on the ECG. Sinus rhythm is necessary, but not sufficient, for normal electrical activity within the heart. After an action potential initiates (e.g., by the sinus node), a cardiac cell of heart <NUM> is unable to initiate another action potential for some duration of time. This period of time is referred to herein as a refractory period, which is about <NUM> in duration and helps to protect the heart.

In some embodiments, electrodes <NUM> are configured to sense the aforementioned IC ECG signals, and (e.g., at the same time) surface electrodes <NUM> are sensing the BS ECG signals.

In some embodiments, processor <NUM> is configured to receive the body-surface (BS) ECG signals from surface electrodes <NUM>, and the intra-cardiac (IC) ECG signals from electrodes <NUM>. Processor <NUM> is further configured to check whether either the IC ECG signals, or the BS ECG signals are in the rhythm of the sinus node.

In some embodiments, in case none of the acquired ECG signals is in the rhythm of the sinus node, processor <NUM> continues to receive and analyze additional IC and BS ECG signals over time.

In some embodiments, based on the acquired BS and IC ECG signals, and in response to ECG signals that are in the rhythm of the sinus node, processor <NUM> is configured to detect the refractory period of heart <NUM>. Note that for safety reasons, applying IRE pulses is allowed during the refractory period and not during the initiation of action potential.

In some embodiments, processor <NUM> is configured to control IPG <NUM> to apply one or more IRE pulses to tissue at the ablation site of heart <NUM>, via one or more pairs of electrodes <NUM> selected by switching box <NUM>. For example, physician <NUM> may send a command to processor <NUM> to activate IPG <NUM> (or may directly activate a controller of IPG <NUM>), e.g., by pressing a foot pedal. Processor <NUM> is configured to receive the IC and BS ECG signals from electrodes <NUM> and <NUM>, respectively, and to control IPG <NUM> to apply the IRE pulses at the detected refractory period when at least one of the IC and/or BS ECG signals indicates a sinus rhythm. In other words, when detecting the refractory period of heart <NUM>, processor <NUM> controls IPG <NUM> to apply the IRE pulses to tissue of the ablation site of heart <NUM>.

In some embodiments, processor <NUM> is configured to carry out the IRE ablation procedure automatically. In such embodiments, processor <NUM> is configured to control: (i) the number and quality of IC and BS ECG signals acquired from heart <NUM>, (ii) the timing for applying the IRE pulses to tissue 9during one or more refractory periods), and (iii) at least some parameters of the applied IRE pulses. Note that after positioning at least a pair of electrodes <NUM> in contact with tissue at the ablation site, physician <NUM> may command processor <NUM> to control the acquisition of the ECG signal and the applying of the IRE pulses, automatically. However, if required (e.g., in case of emergency), physician <NUM> may intervene in the IRE procedure, e.g., by adjusting and/or aborting the process carried out by processor <NUM>.

<FIG> is a flow chart that schematically illustrates a method for automatically performing IRE ablation during a refractory period of heart <NUM>.

The method begins at a catheter insertion step <NUM>, with physician inserting catheter <NUM>, and using the position tracking system for positioning one or more pairs of electrodes <NUM> attached to the ablation site of heart <NUM>, as described in <FIG> above.

At an ECG signal acquisition step <NUM>, processor <NUM> is configured to receive intra-cardiac (IC) and body-surface (BS) ECG signals from electrodes <NUM> and <NUM>, respectively, as described in <FIG> above.

At a sinus rhythm detection step <NUM>, processor <NUM> is configured to check whether one or more IC ECG signals and/or BS ECG signals are in the rhythm of the sinus node. In case no ECG signals found in the rhythm of the sinus node, the method loops back to step <NUM> and processor <NUM> continues to check additional IC and BS ECG signals acquired, respectively, by electrodes <NUM> and <NUM>. In case processor identifies IC and/or BS ECG signals, which are in the rhythm of the sinus node, the method continues to an IRE ablation step <NUM>, which terminates the method.

At IRE ablation step <NUM>, based on the IC and/or BS ECG signals that are in the rhythm of the sinus node, processor <NUM> is configured to: (i) detect a refractory period of the patient heart, and (ii) control IPG <NUM> to apply IRE pulses for ablating tissue at an ablation site of heart <NUM>, during the detected refractory period. Note that the IRE pulses are applied to the tissue via one or more pairs of electrodes <NUM> selected by switching box <NUM> or using any other suitable selection mechanism.

Note that the method described in <FIG> is carried out automatically, e.g., without intervention of physician <NUM>, however, physician <NUM> may have the means to intervene, and if needed, to adjust or abort the automatic IRE ablation procedure described above.

Although the embodiments described herein mainly address IRE ablation of cardiac tissue, the methods and systems described herein can also be used in other applications, such as in ablating other organs of humans or other mammals.

Claim 1:
A system for performing irreversible electroporation during heart refractory period, the system comprising:
an ablation catheter (<NUM>);
a first plurality of electrodes (<NUM>) fitted on the catheter (<NUM>) and configured to sense intra-cardiac (IC) ECG signals at an ablation site;
a second plurality of electrodes configured to be coupled to a surface of the patient and configured to sense body-surface (BS) ECG signals of the patient heart;
an interface, which is configured to receive multiple electrocardiogram (ECG) signals of the patient heart, wherein the interface is configured to receive (i) the IC ECG signals, and (ii) the BS ECG signals;
an irreversible electroporation (IRE) pulse generator (<NUM>) configured to apply one or more bipolar IRE pulses between a pair of the first plurality of electrodes (<NUM>); and
a processor (<NUM>), which is configured, based on the received ECG signals, to
check whether one or more of the IC ECG signals and/or the BS ECG signals are indicative of a sinus rhythm pulse, wherein when none of the ECG signals are indicative of a sinus rhythm pulse, the processor (<NUM>) is configured to continue to check whether additional IC and BS ECG signals acquired are indicative of a sinus rhythm pulse, and wherein when one or more of the ECG signals are indicative of a sinus rhythm pulse the processor (<NUM>) is configured to:
detect a refractory period of the patient heart by indicating a sinus rhythm in at least one of the received ECG signals, and
control the irreversible electroporation pulse generator (<NUM>) to apply IRE pulses to tissue at the ablation site during the detected refractory period.