Hemolysis detection based on impedance values

Abstract

A system for treatment of patient tissue by delivery of high-voltage pulses comprising an ablation catheter, a measurement unit and an electronic control unit (ECU). The measurement unit is configured to perform measurements using an energy source, whereby the impedance and / or current measurement values are determined as response to an alternating voltage and / or at least one voltage pulse. The ECU is configured to receive and analyze said measurement values provided by the measurement unit and identify a presence of hemolysis based on a determined decrease in the measured impedance values over time.

Description

[0001] HEMOLYSIS DETECTION BASED ON IMPEDANCE VALUES

[0002] The present application claims priority to U.S. Provisional Application No. 63 / 565,896, filed March 15, 2024, entitled “HEMOLYSIS DETECTION BASED ON IMPEDANCE VALUES”, and is related to co-pending U.S. Patent Application No. 17 / 563,620, filed Dec. 28, 2021, which claims the benefit of U.S. Provisional Patent Application No. 63 / 270,666, filed Oct. 22, 2021, and European Patent Application No. EP 21172336.6, filed May 5, 2021, and U.S. Provisional Patent Application No. 63 / 140,390, filed Jan. 22, 2021, each of which is incorporated herein by reference in its entirety.

[0003] The present invention relates to embodiments of a system comprising an ablation catheter suitable for pulsed-field ablation (PF A), a method for assessment of positions and / or configuration of electrodes of such ablation catheter, a respective computer program product and a respective computer readable data carrier.

[0004] In particular, the present invention relates to embodiments of a system comprising a PFA catheter, a measurement unit and an electronic control unit, whereby the system may be used for safely performing cardiac ablation procedures, such as, but not limited to, pulmonary vein isolation (PVI), persistent atrial fibrillation ablation, ventricular tachycardiac ablation. The catheter comprises multiple electrodes and delivers pulsed-field energy to achieve irreversible electroporation of cardiac tissue.

[0005] It is known to use ablation catheters for PVI procedures in the therapy of atrial fibrillation (AF) patients. In such procedures, the pulmonary veins (PV) are electrically isolated from the left atrium by creating contiguous circumferential ablation lesions around the pulmonary vein ostium (PVO) or around their antrum. Thus, irregular atrial contractions can be avoided by hindering undesired perturbing electrical signals generated within the PV from propagating into the left atrium. Ablation catheters may be used to deliver therapy to other tissues, such as, but not limited to: ventricles, right atrium, the body of the left atrium, etc. Additionally, other organs may be treated via use of catheters: lungs, liver, kidneys, etc.

[0006] Several types of ablation catheters are available including single point tip electrode catheters, circular multi-electrode loop catheters, and balloon-based ablation catheters using different energy sources. They all lack the ability of producing the required ablations, which safely electrically isolate the arrhythmogenic triggers from the rest of the heart chamber, in a ‘one-shot’ modality, without further repositioning, rotating or moving of the catheter. It is one goal of ablation catheter development to provide catheters and systems which safely achieve a ‘moat’ of electrical isolation in one shot. The concept of a moat of electrical isolation is defined as region of cardiac tissue that surrounds the arrhythmogenic trigger and prevents its propagation to the rest of the heart chamber. For example, without limitation, referring to situations when the arrhythmogenic triggers reside inside a pulmonary vein, an ablation region which completely renders non-viable the tissue located at the vein ostium or antrum, securing transmurality, would represent said moat of electrical isolation. Pulsed-field ablation (PF A), if designed appropriately, may have the advantage of creating these conduction block / electrical isolation moats in one shot, safely without or with minimal collateral tissue damage.

[0007] An ablation catheter that is particularly well suited for PFA treatment of a patient's tissue, for example for a PVI procedure at a patient's heart tissue or vein tissue, comprises an elongated catheter shaft and an ablation portion being arranged at a distal end of the catheter shaft with a plurality of electrodes accommodated along the ablation portion, wherein the ablation portion comprises at least two loop sections forming a three-dimensional spiral or similar flexible structures that allow one electrodes to move relative to another. PFA uses high-intensity electrical fields. Under some circumstances of the treatment the distance of two electrodes may become so small that an electromagnetic field intensity is sufficiently high to ionize the medium between these electrodes. In such case, arcing develops, in particular, if bipolar PFA is used. This means that for catheters with open loops or flexible splines, some electrode pairs can approach such that the risk for arcing is increased. Arcing presents an increased level of danger to patients, as it results in unintended tissue damage.

[0008] Furthermore, the high temperatures of arcs may melt catheter materials, leaving foreign particles in the patient's blood stream.

[0009] Accordingly, determining the position and / or configuration of the electrodes is essential for catheters operated with bipolar PFA and where electrode distances between each other can change due to manipulation (especially if electrodes on different polarities come close).

[0010] Another important parameter for the success of the PFA treatment of a patient is an information about good or poor positions of the electrodes with regard to their contact with the patient tissue and therefore the quality of catheter position for the treatment. The fact that one or some ablation electrodes of the ablation portion do not have sufficient contact to the targeted tissue may impede the creation of the above-mentioned moat of electrical isolation in one shot. International Publication No. WO 2018 / 102376 discloses a method of detecting arcing in an electroporation system including a direct current (DC) energy source, a return electrode connected to the DC energy source and a catheter connected to the DC energy source. The known method includes monitoring a system impedance with the return electrode positioned near the target location and the catheter electrode positioned within the body, detecting a positive deflection in the system impedance, the positive deflection indicative of arcing, and generating an alert, based on the detection, the alert indicating that arcing has occurred. The known method does only derive some information about arcing for unipolar ablation though. For bipolar PFA which is the preferred method to produce a moat of electrical isolation in one shot the known method does not give any meaningful values and adding external impedances does not necessarily prohibit arcing.

[0011] Accordingly, it is an objective of the present invention to provide reliable information about arcing risk and / or electrode contact to the operating health care professional (HCP) with regard to a bipolar PFA system in an easily understandable, reliable and time -effective way.

[0012] The present disclosure is directed toward overcoming one or more of the above mentioned problems, though not necessarily limited to embodiments that do.

[0013] In some aspects, the techniques described herein relate to a system for detecting hemolysis, including: a measurement unit adapted to electrically connect to each of a plurality of electrodes positioned along a distal end of a catheter shaft, the measurement unit configured to periodically measure an impedance value at each of the plurality of electrodes during each of a plurality of measurement cycles in a pulsed field ablation (PFA) shot; and an electronic control unit (ECU) configured to: receive from the measurement unit a plurality of measured impedance values for at least a portion of the plurality of electrodes for each of the plurality of measurement cycles in the PFA shot, calculate an average impedance value for a plurality of PFA shots, analyze the average impedance values for the plurality of PFA shots to identify a decrease in the average impedance value for the plurality of PFA shots that exceeds a predetermined threshold value, and determine a presence of hemolysis based on said identified decrease in the average impedance value for the plurality of PFA shots that exceeds the predetermined threshold value.

[0014] In some aspects, the techniques described herein relate to a method for detecting hemolysis, including: measuring an impedance value at each of a plurality of electrodes positioned along a distal end of a catheter shaft during each of a plurality of measurement cycles including a pulsed field ablation (PFA) shot; analyzing the measured impedance values for each measurement cycle in the PFA shot to calculate an average impedance value for the PFA shot; calculating a an average impedance value for a plurlaity of PFA shots; comparing the average impedance value for each of the plurality of PFA shots to identify a first PFA shot having a highest average impedance value and a second PFA shot having a lowest average impedance value; and determining a presence of hemolysis when the difference between the average impedance value for the first PFA shot and the average impedance value for the second PFA shot exceeds a predetermined threshold amount.

[0015] In some aspects, the techniques described herein relate to a system for detecting hemolysis, including: a measurement unit adapted to electrically connect to each of a plurality of electrodes positioned along a distal end of a catheter shaft, the measurement unit configured to periodically measure an impedance value at each of the plurality of electrodes during each of a plurality of measurement cycles in a pulsed field ablation (PFA) shot; and an electronic control unit (ECU) configured to: receive from the measurement unit a plurality of measured impedance values for at least a portion of the plurality of electrodes for each of the plurality of measurement cycles in a plurality of PFA shots, calculate an average impedance value for each of the plurality of PFA shots, estimate an overall average catheter impedance value for each of the plurality of PFA shots by dividing the average impedance value for each respective PFA shot by a number of active electrode pairs in the plurality of electrodes, analyze the overal average catheter impedance values for the plurality of PFA shots to identify a decrease in the average impedance value for the plurality of PFA shots that exceeds a predetermined threshold value, and determine a presence of hemolysis based on said identified decrease in the average impedance value for the plurality of PFA shots that exceeds the predetermined threshold value.

[0016] In some aspects, the techniques described herein relate to a system for detecting hemolysis, including: a measurement unit adapted to electrically connect to each of a plurality of electrodes positioned along a distal end of a catheter shaft, the measurement unit configured to periodically measure a voltage applied to each of the plurality of electrodes during each of a plurality of measurement cycles in a pulsed field ablation (PFA) shot and periodically measure a current applied to each of the plurality of electrodes during each of the plurality of measurement cycles in the PFA shot; and an electronic control unit (ECU) configured to: receive from the measurement unit a measured voltage value and a measured current value for each of a plurality of PFA shots, calculate an overall average catheter impedance value for each of the plurality of PFA shots by dividing the measured voltage value by the measured current value for each of the plurality of PFA shots, analyze the overal average catheter impedance values for the plurality of PFA shots to identify a decrease in the average impedance value for the plurality of PFA shots that exceeds a predetermined threshold value, and determine a presence of hemolysis based on said identified decrease in the average impedance value for the plurality of PFA shots that exceeds the predetermined threshold value.

[0017] Other features and advantages of the present invention will become more readily apparent to those of ordinary skill in the art after reviewing the following detailed description and accompanying drawings.

[0018] The various features and advantages of the present invention may be more readily understood with reference to the following detailed description and the embodiments shown in the drawings. Herein schematically and exemplarily,

[0019] FIG. 1 depicts a distal end of a first embodiment of an ablation catheter in a perspective side view;

[0020] FIG. 2 illustrates a delivery path for an ablation catheter leading to a pulmonary vein ostium of a human heart;

[0021] FIGS. 3 and 3 A show part of the electric control of the electrode leads for the embodiment of the ablation catheter of FIG. 1 ;

[0022] FIG. 4 depicts the distal end of the ablation catheter of FIG. 1 with electrode numbering in a top view;

[0023] FIGS. 5 and 6 show matrices containing AR indexes for each electrode pair and the impedance values of the ablation catheter of FIG. 1 for a saline position of the ablation portion;

[0024] FIG. 7 shows the ablation portion of the ablation catheter of FIG. 1 pressed to chicken heart tissue in a top view;

[0025] FIGS. 8 and 9 show matrices containing AR indexes for each electrode pair and the CU value of the ablation catheter of FIG. 1 in the position shown in FIG. 7;

[0026] FIG. 10 shows another position of the ablation portion of the ablation catheter of FIG. 1 pressed to chicken heart tissue in a top view; FIGS. 11-12 show matrices containing AR indexes for each electrode pair and the CU value of the ablation catheter of FIG. 1 in the position shown in FIG. 10;

[0027] FIG. 13 depicts a schematic example of an applicable PFA waveform;

[0028] FIG. 14 shows another position of the ablation portion of the ablation catheter of FIG. 1 pressed to a chicken heart tissue in a top view;

[0029] FIG. 15 shows a matrix containing impedance values and an AR index (flagged) for the electrode pairs 1,2; 2,3; 2,9; 8,9; 9,10, respectively of the ablation catheter of FIG. 1 in the position shown in FIG. 14;

[0030] FIG. 16 shows another position of the ablation portion of the ablation catheter of FIG. 1 pressed to a chicken heart tissue in a top view;

[0031] FIG. 17 shows a matrix containing impedance values and an AR index (flagged) for the electrode pairs 1,2; 2,3; 2,9; 8,9; 9,10, respectively of the ablation catheter of FIG. 1 in the position shown in FIG. 16;

[0032] FIG. 18 shows another position of the ablation portion of the ablation catheter of FIG. 1 pressed to a chicken heart tissue in a top view;

[0033] FIG. 19 shows a matrix containing impedance values and an AR index (flagged) for the electrode pairs 1,2; 2,3; 2,9; 8,9; 9,10, respectively of the ablation catheter of FIG. 1 in the position shown in FIG. 18;

[0034] FIG. 20 shows another position of the ablation portion of the ablation catheter of FIG. 1 pressed to a chicken heart tissue in a top view;

[0035] FIG. 20A shows another position of the ablation portion of the ablation catheter of FIG. 1 pressed to a chicken heart tissue in a top view;

[0036] FIG. 21 shows a matrix containing impedance values for the adjoining electrode pairs derived from a bipolar measurement and a CU value of the ablation catheter of FIG. 1 in the position shown in FIG. 20 calculated from these impedance values; FIG. 21A shows a matrix containing impedance values for the adjoining electrode pairs derived from a bipolar measurement and a CU value of the ablation catheter of FIG. 1 in the position shown in FIG. 20A calculated from these impedance values;

[0037] FIG. 22 shows a table containing impedance values derived from a quasi-unipolar measurement at 500 kHz and a CU value calculated from these impedance values of the ablation catheter of FIG. 1 in the position shown in FIG. 20;

[0038] FIG. 22A shows a table containing impedance values derived from a quasi-unipolar measurement at 500 kHz and a CU value calculated from these impedance values of the ablation catheter of FIG. 1 in the position shown in FIG. 20A;

[0039] FIGS. 23-25 visualize three different pulse shapes for current measurements at each individual electrode;

[0040] FIGS. 26-29 show four different positions of the ablation catheter of FIG. 1, partly with respect to a chicken heart tissue in saline;

[0041] FIG. 30 shows a bar diagram containing impedance values determined for the four positions of FIGS. 26 to 29 with respect to each electrode of the ablation portion of the ablation catheter of FIG. 1;

[0042] FIG. 31 visualizes a flowchart for the use of a PFA catheter including PFA precheck determining AR indexes and CU value in order to treat paroxysmal atrial fibrillation;

[0043] FIGS. 32-33 show examples of visualization of impedance values for electrodes of an ablation section of an ablation catheter similar to the one of FIG. 1 ;

[0044] FIG. 34A-34B are graph diagrams illustrating example impedance value graphs for a plurality of PFA shots indicating no hemolysis;

[0045] FIG. 35A-35B are graph diagrams illustrating example impedance value graphs for a plurality of PFA shots indicating hemolysis; FIG. 36A-36B are graph diagrams illustrating example impedance value graphs for two PFA shots indicating a decrease in average impedance values;

[0046] FIG. 37 is a flow diagram illustrating an example process for determining a presence of hemolysis; and

[0047] FIG. 38 is a flow diagram illustrating an example process for monitoring impedance values during pulsed field ablation to determine a presence of hemolysis.

[0048] Disclosed herein are systems and methods for detecting catheter movement in a patient based on impedance values from an ablation catheter.

[0049] After reading this description it will become apparent to one skilled in the art how to implement the invention in various alternative embodiments and alternative applications. However, although various embodiments of the present invention will be described herein, it is understood that these embodiments are presented by way of example only, and not limitation. As such, this detailed description of various alternative embodiments should not be construed to limit the scope or breadth of the present invention as set forth in the appended claims.

[0050] FIGS. 1 and 4 illustrate a distal portion of an ablation catheter 1 in accordance with a first embodiment. The ablation catheter may be used for PFA, when used with the PFA generator and accessories, and is indicated for use in cardiac electrophysiological mapping (stimulation and recording) and in high-voltage, pulsed-field cardiac ablation. Peak voltages are, for example, without limitation, + / -1 kV to 3 kV with a pulse width of up to 30 ps. Higher peak voltages (e.g. up to 10 kV) may be used provided the pulse duration is correspondingly shorter (e.g. 0.5 ps). The catheter 1 has an elongated circular catheter shaft 10, which may connect with a handle comprising a steering mechanism at a proximal end (not illustrated). As a result, the catheter may control deflections of the depicted distal section carrying the ablation electrodes.

[0051] At the illustrated distal end of the catheter shaft 10 an ablation portion 12 is arranged, which comprises a plurality of loop sections 121, 122. The concept of loop sections includes embodiments that use continuous loops or spirals configurations. The catheter shaft may have an effective length of approximately 115 cm from the distal tip of the ablation portion 12. Each of a first loop section 121 and a neighboring second loop section 122 exhibits ablation electrodes 120 (altogether, for example, 10, 12, 14, 16, or 32 electrodes), which are configured for delivering energy to tissue. Although two loops are illustrated in FIG. 1, more can be used. It is preferred that at least a partial third loop is used in order to provide sufficient overlap among resulting ablation zones. Said overlap would increase chances of achieving a conduction block moat without drops in lesion continuity, contiguity or transmurality. The distal section comprises at least 45° of overlap of a 3rdloop section with the previous two sections. In particular, the ablation catheter 1 may be configured for delivering an electrical high voltage PFA signal to tissue via the ablation electrodes 120. For example, the ablation electrodes 120 may consist of or comprise gold and / or a platinum / iridium alloy. Alternatively, electrodes 120 from different loop sections may be positioned so that electrodes of same polarity are aligned. However, dependent on the form of the patient's tissue and the position of the ablation portion 12, electrodes of opposite polarities may collide when the spiral catheter is compressed thereby causing arcing and / or the contact of the electrodes with the patient's tissue may not be uniform. In the exemplary embodiment illustrated in FIG. 1, the ablation electrodes 120 of the second loop section 122 are arranged partly in a staggered manner with respect to the ablation electrodes 120 of the first loop section 121.

[0052] In order to address measurement values to the different electrodes 120, the electrodes are consecutively numbered as shown in FIG. 4 (see numbers at the electrodes). The most distal electrode has the number 1, whereas the most proximal electrode is denoted with number 14. Different numbering is possible, as well.

[0053] The loop sections 121, 122 may further exhibit a plurality of mapping electrodes, which are configured for receiving electrical signals from tissue.

[0054] Together, the loop sections 121, 122 form a three-dimensional spiral, which form a corkscrewsimilar form where the diameter of the loops decrease toward the distal end. Alternatively, they may form a plunger-like configuration where the diameter of the loops increases toward the distal end or any other suitable 3 -dimensional configuration (not shown).

[0055] The loop sections 121, 122 may comprise a shape memory material, for example, in the form of an inner structural support wire (not illustrated), for example a Nitinol wire as described above. In particular, the loop sections 121, 122 may have super-elastic properties.

[0056] The ablation portion 12 may be constrained into an essentially elongate shape for the purpose of delivery to a target region in the human body by means of a (fixed or steerable) delivery sheath 15, which may also be referred to as an introducer sheath. At the target position, upon exiting a distal end of the delivery sheath 15, the ablation portion 12 may then recoil to its original (biased) shape. The length of each electrode 120 along the respective loop section 121, 122 is, for example, 4 mm. In general, the electrode length is in the range 1-10 mm, preferably 3-5 mm. The catheter shaft 10 size may be compatible with an 8.5 F ID sheath and may consist of radiopaque extrudable polymer and, if applicable, a polymer-reinforcing braid. In general, the size of the catheter shaft 10 may be compatible with a 7 F to 14 F ID sheath. The width between neighboring electrodes along the respective loop section may be chosen between 1 mm and 10 mm, preferably 3-6 mm, in order to provide a contiguous ablated area at the patient's tissue.

[0057] FIG. 2 schematically and exemplarily illustrates a delivery path for an ablation catheter 1 leading to a pulmonary vein ostium (PVO) of a human heart. For orientation, the inferior vena cava (IVC), the right atrium (RA), the right ventricle (RV), the left atrium (LA), the left ventricle (LV), as well as pulmonary veins (PV), each with a PVO, are shown. The large black arrows indicate a delivery path passing through the IVC, the RA, transeptally through the septal wall (SW), and into the LA. Finally, using appropriate deflection means, catheter 1 is steered to PVO regions. There, the corkscrew type ablation catheter may be used for ablation in the area of the atrial end of the pulmonary vein close to PVO. The form of the ablation portion 12 is configured such that it fits to the dimensions of the targeted PVO. Alternatively, corkscrew-type catheters may be used to ablate at the SVC or at Appendages, such as the left or right atrial appendages (LAA or RAA).

[0058] Reliable full ablation along a whole circumference is achieved with the first embodiment of the ablation catheter shown in FIGS. 1 and 4 at their respective position within the heart or the vein to which the form is adapted. A small compression of the ablation portion 12 of the respective catheter 1 may be possible during ablation into the direction of the longitudinal axis of the spiral.

[0059] The ablation procedure using one of the ablation catheters 1 may start after the ablation portion 12 is in the correct position relative to the targeted tissue, for example at a PVO. The assessment of the position and / or configuration of the ablation electrodes 120 is provided prior and / or between two ablation steps (if applicable) and is explained in more detail below. The ablation electrodes 120 will provide pulsed electric field in a unipolar or bipolar arrangement. Peak voltages are, for example, without limitation, + / -1 kV to 3 kV with a pulse width of up to 30 ps. Higher peak voltages (e.g. up to 10 kV) may be used provided the pulse duration is correspondingly shorter (e.g. 0.5 ps). The pulse width may be 5 ps (between 0.5-30 ps) forming a pulse train comprising up to 500 pulses / train.

[0060] The electric field generation (in particular voltage, current and impedance) is monitored by an electronic control unit (ECU) 70 which is connected to the leads 61 of the electrodes 120 and produced by a waveform generator 50 (see FIG. 3). FIG. 3A also shows connectivity that can be used to generate unipolar or bipolar electric fields. ECUs in FIGS. 3 and 3A may control application of PFA fields. FIG. 3 A illustrates a catheter 1401 (such was the one with reference number 1 from FIGS. 1 and 4) with its electrodes driven by ECU 1403. ECU 1403 can be controlled to deliver field vectors 1402 that cover the tissue zone in between catheter 1401 spiral arms / loops. By doing so, the AR index may be determined. In order to provide quasi-unipolar measurements, the PFA generator may be connected to one of the electrodes as the reference electrode instead of to the grounding pad 1404.

[0061] In order to assess the positions and / or configuration of the electrodes 120 with regard to each other and the targeted tissue, the ablation catheter further comprises a measurement unit 68 which is connected to the ECU 70 and a switch unit 60 with the waveform generator 50. The measurement unit 68 is configured to measure peak current and peak voltage as well as impedance at the respective electrode lead 61 and transmit these data to the ECU for further analysis. Further, the measurement unit 68 provides the electrodes 120 at the respective lead(s) 61 with pre-defined measurement signals (current or voltage pulses) via the waveform generator 50 in order to measure the above-mentioned parameter.

[0062] In the bipolar arrangement neighboring (adjoining) electrodes 120 may be paired along the loop sections 121, 122, across two neighboring loop sections 121 and 122 or any other pre-defined pair combination, in particular for impedance determination for AR value and / or CU value. Further, the electrodes 120 may be used in a unipolar arrangement. In this case, a ground pad 1404 may be provided at the surface of the patient's body. Alternatively, one of the non-adjacent electrodes 120 may be used as reference electrode thereby forming a quasi-unipolar arrangement.

[0063] In order to switch between different bipolar arrangements or between unipolar and bipolar arrangement, the ablation catheter 1 may comprise a switch unit 60 connected to and controlled by the ECU 70. The switch unit 60 provides the respective phase of the pulsed electric field provided by the waveform generator 50 to the predefined electrode lead 61 and thereby to the predefined electrode 120 wherein each electrode lead 61 is electrically connected to one particular electrode 120 at the ablation portion 12. The switch unit 60 comprises a switch matrix and may realize any configuration of phase distribution, for example, such that two neighboring electrodes along the loop sections, across the loop sections and any other electrodes are paired. The switching signal and configuration information is provided by the ECU 70. ECU 70 further may provide data processing of electrical or biopotential data or impedance data acquired the electrodes of ablation catheter 1. As indicated above mapping electrodes located in the ablation portions 12 may comprise mapping electrodes for determining the electrical potential of the surrounding tissue in order to observe the ablation progress at pre-defined time points during ablation procedure. Alternatively, the ablation electrodes 120 may be switched into the mapping mode and back into the ablation mode.

[0064] As indicated in the general description, prior ablation treatment and / or between ablation treatment steps the AR value and CU value are determined in order to assess the positions of the electrodes 120 and / or their configuration with regard to each other and / or with regard to the tissue under treatment.

[0065] In the first example, the ablation catheter of FIGS. 1 and 4 is measured with regard to the impedance of all pairs of the 14 electrodes in saline (for comparison), a first position axially pressed to a chicken heart tissue (see FIG. 7) and in a second position axially pressed to a chicken heart tissue wherein black rubber bands keep the electrodes 4 and 12 close to each other (see FIG. 10). The matrices of FIGS. 5 and 6 belong to the saline configuration, the matrices of FIGS. 8 and 9 to the position shown in FIG. 7 and the matrices of FIGS. 11 and 12 to the position shown in FIG. 10.

[0066] For example, AC voltage signals with a frequency of 500 kHz with a peak voltage (amplitude) of 1 V are chosen. The matrices of FIGS. 5, 8 and 11 show the AR index calculated from the bipolar impedance measurement values Zx>yof the electrode pair x,y. The number of the electrodes of the particular electrode pair can be found in the respective header line and the first row. The value at the row-line-intersection contains the AR index of the respective electrode pair x,y determined from the impedance measurement values for 500 kHz. The AR index is calculated using the formula:

[0067] All AR index values are zero or close to zero for the saline configuration. No risk of arcing exists since all electrodes have a sufficient distance to each other.

[0068] In contrast, with regard to the ablation portion position of FIG. 7 it is apparent that the AR index of the electrode pair 5, 14 is considerable higher than the other AR indexes. In FIG. 7 it appears, that these electrodes are the only ones which are close to each other — there is an arcing risk with regard to these electrodes and repositioning is needed.

[0069] The matrix of FIG. 11 contains the AR index values calculated in a similar way for the configuration of FIG. 10 and a frequency of 500 kHz . It is apparent that in particular the electrode pairs 3, 11 and 4, 12 show considerably higher AR index values than any other AR index value of this matrix. For these pairs a risk for arcing exists, if the electrodes of these pairs would be at different polarities.

[0070] In another representation shown in FIGS. 6, 9 and 12 the calculated AR indexes of the respective electrode pairs (electrode numbers are shown in the header line and in the first row, formula see above) are provided for all electrode pairs but the adjoining electrode pairs (marked in the diagonal) for the respective ablation portion position. In the diagonal line the impedances of the adjoining electrode pairs are provided. In the matrix of FIG. 9 the AR index of the electrode pair 5 and 14 is highlighted since it indicates a high arcing risk (AR index >0.25). With regard to the third position (FIG. 10), in particular, the electrode pair 2, 9 has a higher arcing risk. Just for clarification, in this position the AR index values for the electrode pairs 4, 12 and 5, 13 are neglected since these electrodes share the same polarity and therefore no risk for arcing exists.

[0071] Further, the diagrams of FIGS. 6, 9 and 12 contain the CU value for the respective position in the upper left comer calculated from the following formula (see explanation above) and the measured bipolar impedances of the adjoining electrodes:

[0072] It appears from the matrices in FIGS. 6, 9 and 12 that the contact uniformity of the position shown in FIG. 7 is better than of the position shown in FIG. 10 as the CU value is greater (0.92>0.86). The contact uniformity is best in the saline position (0.99) — if all electrodes without contact, i.e. all electrodes are floating in saline.

[0073] Further examples of ablation catheter positions pressed to a chicken heart are shown in the following FIGS. 14 to 19, wherein a profile shown in FIG. 13 is used as PFA protocol, wherein V=2.5 kV, P=3 ps, Ii=25 ps, and F=2 ms. Further, a pulse number PN=20 were chosen intentionally to provoke arcing.

[0074] FIG. 14 shows a position of the ablation portion of the ablation catheter of FIGS. 1 and 4 in which the electrodes 2, 9 are in close proximity (see encircled area). Accordingly, the AR index of these electrodes is 0.455 indicating the high arcing risk (see matrix shown in FIG. 15). The arcing threshold for the pulse parameters P, Ii, U and PN given above was determined as 0.9 kV confirming the calculated AR index. FIG. 16 shows a position of the ablation portion of the ablation catheter of FIGS. 1 and 4 where electrodes 2, 9 do not overlap (see marked area, so-called edge-edge position). Accordingly, the AR index shown in FIG. 17 is lower than the one of FIG. 15. The lowest AR index may be found for the position of these electrodes 2, 9 shown in FIG. 18 in which these electrodes are sufficiently far away thereby having a low arcing risk (see marked area). Accordingly, the AR index of this electrode pair 2, 9 is close to zero (see FIG. 19).

[0075] In another example, the CU value for two positions of the ablation catheter of FIGS. 1 and 4 is determined, in particular the CU value determined from bipolar impedance measurements of adjoining electrodes using formula (n=l . . . 13) is compared with the CU value determined from quasi-unipolar impedance measurement values. For determination of the CU value for the quasi-unipolar impedance measurement values Znin the above formula the parameter Zn,n+i is replaced by Znfor the standard deviation and the mean value. In this case n=l . . . 14. The quasi-unipolar impedance one electrode (e.g. electrode 1) is measured against all electrodes of opposing polarity (e.g. against all even electrodes, and electrode 2 against all odd electrodes).

[0076] FIG. 20 shows a position in which three electrodes (2, 9, 10) are floating in saline while the others are in contact with the heart tissue. The CU value (bipolar, see FIG. 21) is 0.89 and the CU value (quasi-unipolar) is determined as 0.86 (see FIG. 22) which is comparably low thereby indicating bad contact uniformity. In contrast the position shown in FIG. 20A has all electrodes in contact with the chicken heart's tissue. Accordingly, CU value (bipolar, see FIG. 21 A) is 0.92 and the CU value (quasi-unipolar) is determined as 0.91 (see FIG. 22A).

[0077] FIGS. 23 and 24 show the current measurements using a single pulse for each of the electrodes in order to determine CU, namely a rectangular pulse. FIG. 23 represents a rectangular current waveform as response to the rectangular voltage pulse. The tooth shaped waveform shown in FIG. 24 represents the measured current in the case of a short circuit. Even in this case a current measurement and thereby impedance measurement is possible. Current measurements (total current as well as current flow through each electrode) have been performed with a current transformer (Magnelab CT-CO.5) while a 500 V rectangular biphasic pulse (4 ps pulse length, 25 ps interphase delay) was applied. The impedances determined from the peak current measurement values are displayed as bars for each electrode (electrode number at x-axis) and impedance (in Q at y-axis) in FIG. 30. The first bars refer to the position shown in FIG. 26 (ablation portion in saline), the second bars refer to the position shown in FIG. 27, the third bars refer to the position shown in FIG. 28, and the fourth bars refer to the position shown in FIG. 29.

[0078] The impedance values shown for the saline configuration are low because of the higher conductivity of saline (~0.7 S / m, which is matched to human blood in this experiment) compared to the chicken heart tissue. For the position shown in FIG. 27 the electrodes 2 to 5 and 11 to 13 have lesser contact, whereas the other electrodes have better contact. Regarding the position shown in FIG. 28 the electrodes 6 and 15 are short circuited and the position of the ablation portion needs to be corrected (impedance close to zero). The position shown in FIG. 29 provides impedance values similar to the position of FIG. 27.

[0079] In the following the usage of an inventive catheter as described with regard to FIGS. 1 and 4 is explained in detail referring to the flowchart of FIG. 31. In the first step 201, the catheter 1 is manipulated to targeted PV antrum in the usual way. During advancement of the catheter the ablation portion 12 is covered by the delivery sheath 15 until the distal end of the catheter reaches the targeted region. In the next step 202, the catheter provides quality EGMs to confirm placement near PV and to assess pre-PFA amplitudes and / or an electro-anatomical mapping system displays the 3 -dimensional shape and location of the catheter 1. Then, in the next step 203, and after release of the ablation portion 12 from the delivery sheath 15 by retracting the delivery sheath into proximal direction, the AR index and / or CU value measurement is started, e.g., by short pressing a foot pedal of the generator 50 or pressing a button of the generator 50. Then, in step 204, accurate current or impedance measurements between electrodes 120 of the catheter are provided as explained above in detail by the measurement unit 68, the waveform generator 50 and the ECU 70. In one embodiment, the measurement may be provided to all electrodes 120 of the ablation portion 12 or, alternatively, electrodes at positions at risk are measured. Afterwards, the current or impedance measurement values are processed by the ECU 70 and the impedance values for all ablation electrodes, AR indexes of electrode pairs and / or the CU value for all ablation electrodes of the ablation portion 12 are determined in the following step 205. In step 206, the GUI connected with the ECU 70 colors catheter electrodes or a respective bar diagram at risk of arcing in easy-to-see colors as shown in FIGS. 32 and 33. FIG. 32 depicts the ablation portion 12 with 16 numbered electrodes 120 and a respective bar diagram 230, wherein the height of a bar shown with reference to the electrode number represents the impedance value. The bar diagram shows a low impedance for electrodes number 7 and 10. Electrodes 3 and 4 are configured as mapping electrodes and therefore do not measure impedance during pulse delivery. FIG. 32 may also display the measured impedance values directly at the electrode location of electrodes 7 and 10 at the ablation portion 12 with different colors, wherein each color represents the deviation from the target impedance value. For example, the illustrated electrode number 10 visualizes a greater deviation from the target impedance value than the illustrated electrode number 7.

[0080] If a risk of arcing is identified and visualized by the GUI (step 207), the electrodes are grouped such that the critical electrodes are split into separate energy-delivery groups (step 208). Now, in step 209, the GUI displays impedances, AR indexes and / or CU value of electrodes that are in an acceptable range. If there is no risk of arcing identified step 209 can be directly reached from step 206. Then, in step 210, a PFA treatment is initiated by, e.g. a foot pedal of the ablation generator is continued to be pressed (e.g., for some number of seconds) by the HCP to the patient if an acceptable positioning of the ablation catheter is shown. Then, in step 211, the procedure continues with step 204 if there was no PFA precheck measurement, with step 212 if the PFA precheck measurement is OK, and with step 213 if the PFA precheck measurement failed. Step 213 contains a repositioning of the catheter, in particular of its ablation portion 12 with respect to the targeted PV antrum. After step 213 the procedure continues with step 202 (see above).

[0081] Then, if PFA delivery is aborted by the user in step 212, the procedure continues with step 213 (see explanation of step 213 above). If the PFA delivery is not aborted during treatment, the procedure continues with step 214 the PFA generator provides accurate delivery of ablation energy according to pulse protocol to the user by the electrodes 120 of the ablation portion 12.

[0082] According to above procedure, the PFA arcing risk and / or contact uniformity is checked prior PFA ablation in order to guarantee the catheter position with the highest contact uniformity and lowest arcing risk for all electrodes taking part in the PFA. Accordingly, dangerous arcing can be avoided and the electrodes have a uniform contact to the targeted tissue in order to provide high-quality PFA realizing a moat of electrical isolation in one shot.

[0083] FIG. 34A-34B are graph diagrams illustrating example impedance value graphs 340 and 345 for a plurality of PFA shots indicating no hemolysis. In FIG. 34A, the Y axis represents an overall catheter impedance value and the X axis represents the pulsed field ablation shot. The overall catheter impedance value can be estimated by dividing the average impedance value of the electrodes by the number of active electrode pairs. Alternatively, the overall catheter impedance value can be measured by measuring the voltage applied to the catheter and measuring the current applied to the catheter and dividing the measured voltage by the measured current to determine the overall catheter impedance value. In FIG. 34B, the Y axis represents an average impedance value of the electrodes. As shown in both FIG. 34A and 34B, the average impedance value decreases as the number of shots increase. In one aspect, to determine a presence of hemolysis, in FIG. 34A, the lowest average impedance value 3415 is subtracted from the highest average impedance value 3410. In the illustrated embodiment, the difference between the highest average impedance value 3410 and the lowest average impedance value 3415 is below a predetermined threshold and accordingly no hemolysis is identified. Similarly, to determine a presence of hemolysis, in FIG. 34B, the lowest average impedance value 3435 is subtracted from the highest average impedance value 3430. In the illustrated embodiment, the difference between the highest average impedance value 3430 and the lowest average impedance value 3435 is below a predetermined threshold and accordingly no hemolysis is identified. An alternative way to determine the presence of hemolysis is to subtract the average of the impedance values across all PFA shots from the maximum impedance value of all PFA shots and compare the resulting value to the predetermined threshold. This technique may be used with any of the methods to measure or estimate the average impedance value for a PFA shot.

[0084] FIG. 35A-35B are graph diagrams illustrating example impedance value graphs 350 and 355 for a plurality of PFA shots indicating hemolysis. In FIG. 35 A, the Y axis represents an overall catheter impedance value and the X axis represents the pulsed field ablation shot. The overall catheter impedance value can be estimated by dividing the average impedance value of the electrodes by the number of active electrode pairs. Alternatively, the overall catheter impedance value can be measured by measuring the voltage applied to the catheter and measuring the current applied to the catheter and dividing the measured voltage by the measured current to determine the overall catheter impedance value.

[0085] In FIG. 34B, the Y axis represents an average impedance value of the electrodes. As shown in both FIG. 35A and FIG. 35B, the average impedance value decreases as the number of shots increase. In one aspect, to determine a presence of hemolysis, in FIG. 35 A, the lowest average impedance value 3515 is subtracted from the highest average impedance value 3510. In the illustrated embodiment, the difference between the highest average impedance value 3510 and the lowest average impedance value 3515 is above a predetermined threshold and accordingly hemolysis is identified. Similarly, to determine a presence of hemolysis, in FIG. 35B, the lowest average impedance value 3535 is subtracted from the highest average impedance value 3530. In the illustrated embodiment, the difference between the highest average impedance value 3530 and the lowest average impedance value 3535 is above a predetermined threshold and accordingly hemolysis is identified. An alternative way to determine the presence of hemolysis is to subtract the average of the impedance values across all PFA shots from the maximum impedance value of all PFA shots and compare the resulting value to the predetermined threshold. This technique may be used with any of the methods to measure or estimate the average impedance value for a PFA shot.

[0086] FIG. 36A-36B are graph diagrams illustrating example impedance value graphs for two PFA shots indicating a decrease in average impedance values. In the illustrated embodiment, the Y axis represents the measured impedance value and the X axis represents the cardiac cycle during the pulsed field ablation shot. In the illustrated graphs, the average impedance values 3620 (first shot - FIG. 36A) and 3630 (second shot - FIG. 36B) are collected for each cardiac cycle and an average impedance value is determined for the first shot based on the individual cardiac cycle impedance values 3620 and an average impedance value is determined for the second shot based on the individual cardiac cycle impedance values 3630. Although the average impedance value 3610 for the first shot is higher than the average impedance value for the second shot, the difference is not above a predetermined threshold so hemolysis is not identified based on these two PFA shots.

[0087] FIG. 37 is a flow diagram illustrating an example process 370 for determining a presence of hemolysis. In one aspect, the process of FIG. 37 may be carried out by one or more of the previously described systems. Initially, at 3710, the system measures an average impedance value across all active electrodes for each cardiac cycle in a PFA shot. In one aspect, there may be 60 cardiac cycles in a PFA shot. Next, at 3715, the system determines an average impedance value for a plurality of PFA shots. In one aspect, the average impedance value for a PFA shot is an average of the average impedance values for each cardiac cycle in the PFA shot and the average impedance value for a cardiac cycle is the average of the impedance values of all active electrodes during that cardiac cycle.

[0088] Next, at 3720, the system compares the average impedance values for each PFA shot in the plurality of PFA shots to identify a highest average impedance value and a lowest average impedance value in the plurality of PFA shots. Once the highest and lowest average impedance values are identified, the difference between them is calculated.

[0089] Next, at 3725, the system determines if the different between the highest and lowest average impedance values in the plurality of PFA shots exceeds a predetermined threshold. If the different does exceed the predetermined threshold, at 3730, the system determines the presence of hemolysis. In one aspect, the predetermined threshold amount ranges between 5% and 15% of the highest average impedance value. In one aspect, the predetermined threshold amount is 10%. In one aspect, predetermined threshold amount is 30% of the highest average impedance value. In one aspect, when the presence of hemolysis is determined, the system is configured to provide an alert to an operator / physician and / or terminate pulsed field ablation to promote the safety of the patient.

[0090] FIG. 38 is a flow diagram illustrating an example process 380 for monitoring impedance values during pulsed field ablation to determine a presence of hemolysis. In one aspect, the process of FIG. 38 may be carried out by one or more of the previously described systems. Initially, at 3810, the ECU collects and evaluates impedance values as previously described with respect to FIG. 37. When the system determines that the average impedance value has decreased, at 3815 the identified decrease in the average impedance value is analyzed to determine if the decrease exceeds a first predetermined threshold. If the decrease does not exceed the first predetermined threshold, the system returns to monitoring the impedance values at 3810. However, the decrease does exceed the first predetermined threshold, at 3820 the identified decrease in the average impedance value is analyzed to determine if the decrease also exceeds a second predetermined threshold, which is greater than the first predetermined threshold. If the decrease only exceeds the first predetermined threshold, at 3825 the system automatically generates an alert. For example, the ECU may update a graphical user interface with a visual alert when the identified decrease in the average impedance value exceeds the first predetermined threshold or the ECU may play an audio alert or the ECU may issue both a visual alert and an audio alert. If the decrease exceeds both the first predetermined threshold and the second predetermined threshold, at 3830 the system automatically terminates pulsed field ablation to increase safety for the patient.

[0091] Example Embodiment

[0092] In an example embodiment, determining the risk of hemolysis is essential for PFA treatment because hemolysis may result in high values of plasma free hemoglobin (PFHb) which is toxic for the kidneys. If the amount of PFHb is too high, the patient may experience acute kidney failure, which may be life threatening for the patient. Presently, the presence of hemolysis created by PFA treatment can only be determined from a blood or urine analysis that takes place after the PFA treatment.

[0093] In this example embodiment, impedance values are measured at one or more electrodes during PFA treatment. The PFA treatment includes a plurality of pulse trains and the impedance value measurements may be taken during delivery of the pulse trains and / or in between delivery of the pulse trains. The impedance value measurements may also be taken at each electrode on the ablation catheter or at select electrodes, for example, only the active electrodes. The ECU is configured to receive the measured impedance values and determine one or more average impedance values. For example, the ECU may determine an overall average impedance value across all electrodes on the ablation catheter and the ECU may determine an individual average impedance value for a particular electrode during a particular cardiac cycle. The ECU may also determine an average impedance value for each cardiac cycle during PFA treatment.

[0094] Advantageously, during PFA treatment, the ECU continuously receives measured impedance values and calculates average impedance values and compares measured impedance values for each electrode during a first cardiac cycle to the average impedance value for the first cardiac cycle. The ECU may also compare the average impedance value for a current cardiac cycle to the overall average impedance value for the PFA treatment session.

[0095] When performing the comparisons, the ECU is determining whether the measured impedance value for a particular electrode in a first cardiac cycle is less than the average impedance value for the first cardiac cycle. The ECU is also determining whether the average impedance value for the current cardiac cycle is less than the overall average impedance value for the PFA treatment session.

[0096] If the measured impedance value for a particular electrode in a first cardiac cycle is less than the average impedance value for the first cardiac cycle and the difference exceeds a predetermined threshold value, the ECU identifies a presence of hemolysis. If the difference exceeds a first predetermined threshold value, the ECU is configured to automatically issue an alert to the operator / physician regarding the risk of hemolysis. If the difference exceeds a second predetermined threshold value, the ECU is configured to automatically terminate PFA.

[0097] Similarly, if the average impedance value for the current cardiac cycle is less than the overall average impedance value for the PFA treatment session and the difference exceeds a predetermined threshold value, the ECU identifies a presence of hemolysis. If the difference exceeds a first predetermined threshold value, the ECU is configured to automatically issue an alert to the operator / physician regarding the risk of hemolysis. If the difference exceeds a second predetermined threshold value, the ECU is configured to automatically terminate PFA.

Claims

Claims1. A system for detecting hemolysis, comprising: a measurement unit adapted to electrically connect to each of a plurality of electrodes positioned along a distal end of a catheter shaft, the measurement unit configured to periodically measure an impedance value at each of the plurality of electrodes during each of a plurality of measurement cycles in a pulsed field ablation (PF A) shot; and an electronic control unit (ECU) configured to: receive from the measurement unit a plurality of measured impedance values for at least a portion of the plurality of electrodes for each of the plurality of measurement cycles in the PFA shot, calculate an average impedance value for a plurality of PFA shots, analyze the average impedance values for the plurality of PFA shots to identify a decrease in the average impedance value for the plurality of PFA shots that exceeds a predetermined threshold value, and determine a presence of hemolysis based on said identified decrease in the average impedance value for the plurality of PFA shots that exceeds the predetermined threshold value.

2. The system of claim 1, wherein the ablation catheter comprises at least 10 electrodes.

3. The system of claim 1, wherein the ablation catheter comprises 14 electrodes.

4. The system of claim 1, wherein the ablation catheter comprises 16 electrodes.

5. The system of claim 1, wherein the ablation catheter comprises 32 electrodes.

6. The system of claim 1, wherein the plurality of measurement cycles comprises two or more measurement cycles during QRS-synchronized pulsed field ablation.

7. The system of claim 1, wherein the plurality of measurement cycles comprises at least a portion of the measurement cycles during asynchronous pulsed field ablation.

8. The system of claim 1, wherein the decrease in the average impedance value for the plurality of PFA shots is determined by subtracting a lowest average impedance value for the plurality of shots from a highest average impedance value for the plurality of shots.

9. The system of claim 1, wherein the decrease in the average impedance value for the plurality of PFA shots is determined by subtracting an average impedance value for the plurality of shots from a highest average impedance value for the plurality of shots.

10. The system of claim 1, wherein the ECU is further configured to update a graphical user interface with an alert when the identified decrease in the average impedance value for the plurality of PFA shots exceeds a first predetermined threshold.

11. The system of claim 1, wherein the ECU is further configured to automatically terminate delivery of pulse field ablation when the identified decrease in the average impedance value for the plurality of PFA shots exceeds a first predetermined threshold.

12. A method for detecting hemolysis, comprising: measuring an impedance value at each of a plurality of electrodes positioned along a distal end of a catheter shaft during each of a plurality of measurement cycles comprising a pulsed field ablation (PFA) shot; analyzing the measured impedance values for each measurement cycle in the PFA shot to calculate an average impedance value for the PFA shot; calculating a an average impedance value for a plurlaity of PFA shots; comparing the average impedance value for each of the plurality of PFA shots to identify a first PFA shot having a highest average impedance value and a second PFA shot having a lowest average impedance value; and determining a presence of hemolysis when the difference between the average impedance value for the first PFA shot and the average impedance value for the second PFA shot exceeds a predetermined threshold amount.

13. The method of claim 12, further comprising automatically updating a graphical user interface with an alert when the difference between the average impedance value for the first PFA shot and the average impedance value for the second PFA shot exceeds a first predetermined threshold amount.

14. The method of claim 12, further comprising automatically terminating delivery of pulse field ablation when the difference between the average impedance value for the first PFA shot and the average impedance value for the second PFA shot exceeds a first predetermined threshold amount.

15. The system of claim 1, wherein the decrease in the average impedance value for the plurality of PFA shots is determined by subtracting a lowest average impedance value for the plurality of shots from a highest average impedance value for the plurality of shots.

16. The system of claim 1, wherein the decrease in the average impedance value for the plurality of PFA shots is determined by subtracting an average impedance value for the plurality of shots from a highest average impedance value for the plurality of shots.

17. A system for detecting hemolysis, comprising: a measurement unit adapted to electrically connect to each of a plurality of electrodes positioned along a distal end of a catheter shaft, the measurement unit configured to periodically measure an impedance value at each of the plurality of electrodes during each of a plurality of measurement cycles in a pulsed field ablation (PFA) shot; and an electronic control unit (ECU) configured to: receive from the measurement unit a plurality of measured impedance values for at least a portion of the plurality of electrodes for each of the plurality of measurement cycles in a plurality of PFA shots, calculate an average impedance value for each of the plurality of PFA shots, estimate an overall average catheter impedance value for each of the plurality of PFA shots by dividing the average impedance value for each respective PFA shot by a number of active electrode pairs in the plurality of electrodes, analyze the overal average catheter impedance values for the plurality of PFA shots to identify a decrease in the average impedance value for the plurality of PFA shots that exceeds a predetermined threshold value, and determine a presence of hemolysis based on said identified decrease in the average impedance value for the plurality of PFA shots that exceeds the predetermined threshold value.

18. The system of claim 17, wherein the decrease in the overall average catheter impedance value for the plurality of PFA shots is determined by subtracting a lowest overall average catheter impedance value for the plurality of shots from a highest overall average catheter impedance value for the plurality of shots.

19. The system of claim 17, wherein the decrease in the overall average catheter impedance value for the plurality of PFA shots is determined by subtracting an average overall averagecatheter impedance value for the plurality of shots from a highest overall average catheter impedance value for the plurality of shots.

20. A system for detecting hemolysis, comprising: a measurement unit adapted to electrically connect to each of a plurality of electrodes positioned along a distal end of a catheter shaft, the measurement unit configured to periodically measure a voltage applied to each of the plurality of electrodes during each of a plurality of measurement cycles in a pulsed field ablation (PF A) shot and periodically measure a current applied to each of the plurality of electrodes during each of the plurality of measurement cycles in the PFA shot; and an electronic control unit (ECU) configured to: receive from the measurement unit a measured voltage value and a measured current value for each of a plurality of PFA shots, calculate an overall average catheter impedance value for each of the plurality of PFA shots by dividing the measured voltage value by the measured current value for each of the plurality of PFA shots, analyze the overal average catheter impedance values for the plurality of PFA shots to identify a decrease in the average impedance value for the plurality of PFA shots that exceeds a predetermined threshold value, and determine a presence of hemolysis based on said identified decrease in the average impedance value for the plurality of PFA shots that exceeds the predetermined threshold value.

21. The system of claim 20, wherein the decrease in the overall average catheter impedance value for the plurality of PFA shots is determined by subtracting a lowest overall average catheter impedance value for the plurality of shots from a highest overall average catheter impedance value for the plurality of shots.

22. The system of claim 20, wherein the decrease in the overall average catheter impedance value for the plurality of PFA shots is determined by subtracting an average overall average catheter impedance value for the plurality of shots from a highest overall average catheter impedance value for the plurality of shots.

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