Hemolysis prediction based on ablation parameters

Abstract

Systems and methods to predict the PFHb level in a patient undergoing PFA are provided. The system is configured to analyze PFA settings and patient data collected during PFA and determine a risk of hemolysis. In accordance with the determined risk of hemolysis, the systems and methods adjust the delivery of energy during PFA to achieve high efficacy while maintaining a level of risk of hemolysis below a predetermined threshold.

Description

HEMOLYSIS PREDICTION BASED ON ABLATION PARAMETERSTECHNICAL FIELD

[0001] The present application is generally related to treatment of tissue using pulsed field ablation and more particularly related to predicting hemolysis during pulsed field ablation.BACKGROUND

[0002] Pulsed field ablation (PF A) is a promising method for ablation of cardiac tissue and the treatment of arrhythmia. When applying PFA the high electrical field around the electrodes may cause damage to the red blood cells and lead to hemolysis. Currently, the presence of hemolysis in a patient can only be determined based on parameters determined by an analysis of blood or urine collected during a procedure. In certain circumstances, 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.SUMMARY

[0003] The present disclosure provides systems and methods to predict the PFHb level in a patient based on the PFA settings and data collected from the patient undergoing PFA. In accordance with the predicted PFHb levels, the systems and methods adjust the delivery of energy during PFA to achieve high efficacy of the ablation while preserving the safety of the patient. Individual patient hemolysis level calculations based on PFA settings and patient data, may advantageously prevent kidney damage before it actually occurs.

[0004] The present disclosure also provides an algorithm that determines the individual patient hemolysis level based on PFA settings and patent data during a PFA procedure. With the input of the expected hemolyzed volume based on PFA settings, the catheter being used, the information about electrodes floating in blood pool and the specific patient data (e.g. blood volume, hematocrit) an individual hemolysis level for every PFA application can be calculated. If a first threshold is reached, the electronic control unit (ECU) may inform the physician to pay attention about the hydration of the patient, to dilute the free Hb and support the kidney. If a second threshold is reached the ECU may warn the physician about risk of damaging the kidneys. And if a third threshold is reached, the ECU may terminate ablation and require manual override to continue ablation.

[0005] In some aspects, the techniques described herein relate to a system for predicting 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 a plurality of pulsed field ablation (PF A) measurement cycles; and an electronic control unit (ECU) configured to: determine a plurality of parameters corresponding to a patient; during delivery of PFA to the patient, receive from the measurement unit a plurality of measured impedance values for at least a portion of the plurality of electrodes during delivery of PFA to the patient, calculate a current hemolysis level based on at least a portion of the plurality of parameters and at least a portion of the plurality of measured impedance values, calculate an aggregate hemolysis level based on the current hemolysis level and all prior calculated hemolysis levels; and determine a prediction of hemolysis when the aggregate hemolysis level exceeds a predetermined threshold value.

[0006] In some aspects, the techniques described herein relate to a system, wherein the ECU is further configured to update a graphical user interface to provide the aggregate hemolysis level each time the aggregate hemolysis level is calculated.

[0007] In some aspects, the techniques described herein relate to a system, wherein the ECU is further configured to update the graphical user interface to present a message regarding hydration of the patient when the aggregate hemolysis level exceeds a first predetermined threshold value, update the graphical user interface to present a warning regarding kidney damage to the patient when the aggregate hemolysis level exceeds a second predetermined threshold value, and terminate delivery of PFA when the aggregate hemolysis level exceeds a third predetermined threshold value.

[0008] In some aspects, the techniques described herein relate to a system, wherein the ECU is further configured to resume delivery of PFA after terminating delivery of PFA in response to receiving an override instruction via the graphical user interface.

[0009] In some aspects, the techniques described herein relate to a system, wherein the ECU is configured to determine at least a portion of the plurality of parameters by receiving one or more of the plurality of parameters via a graphical user interface.

[0010] In some aspects, the techniques described herein relate to a system, wherein the ECU is configured to calculate the current hemolysis level after each PFA pulse train.

[0011] In some aspects, the techniques described herein relate to a system, wherein the ECU is configured to calculate the current hemolysis level after a plurality of PFA pulse trains.

[0012] In some aspects, the techniques described herein relate to a system, wherein the plurality of PF A pulse trains corresponds to a PF A shot.

[0013] In some aspects, the techniques described herein relate to a system, wherein the plurality of PFA pulse trains corresponds to a measurement cycle. In alternative aspects, a measurement cycle can be a single pulse train, a plurality of pulse trains, a cardiac cycle, or a PFA shot. In one aspect, when a measurement cycle is a cardiac cycle, the PFA delivery is synchronized to the QRS complex.

[0014] In some aspects, the techniques described herein relate to a system, wherein the ECU is configured to calculate the current hemolysis level after each PFA shot.

[0015] In some aspects, the techniques described herein relate to a system, wherein the ECU is configured to calculate the current hemolysis level after each measurement cycle.

[0016] In some aspects, the techniques described herein relate to a system, wherein the predetermined threshold value is 50 mg / dL, or 75 mg / dL, or 100 mg / dL, or 200 mg / dL, or 300 mg / dL.

[0017] In some aspects, the techniques described herein relate to a system, wherein the plurality of parameters corresponding to the patient comprise one or more of: volume of the hemolyzed blood based on PFA settings Vref, factor assessing electrodes in the blood pool EBP, hematocrit Hr, concentration of hemoglobin Hbc, total blood volume of the patient VBI, and a number of measurement cycles.

[0018] In some aspects, the techniques described herein relate to a method for detecting hemolysis, including: determining a plurality of parameters corresponding to a patient about to receive pulsed field ablation (PFA) treatment; delivering PFA to the patient, and during delivery of PFA, measuring an impedance value at each of a plurality of electrodes positioned along a distal end of a catheter shaft employed to deliver PFA; calculating a current hemolysis level based on at least a portion of the plurality of parameters and at least a portion of the plurality of measured impedance values, calculating an aggregate hemolysis level based on the current hemolysis level and all prior calculated hemolysis levels; and determining a prediction of hemolysis when the calculated aggregate hemolysis level exceeds a predetermined threshold value.

[0019] In some aspects, the techniques described herein relate to a method, wherein calculating an aggregate hemolysis level further includes updating a graphical user interface to provide the aggregate hemolysis level.

[0020] In some aspects, the techniques described herein relate to a method, further including updating the graphical user interface to present a message regarding hydration of the patient when the aggregate hemolysis level exceeds a first predetermined threshold value, updating the graphical user interface to present a warning regarding kidney damage to the patient when the aggregate hemolysis level exceeds a second predetermined threshold value, and terminating delivery of PFA when the aggregate hemolysis level exceeds a third predetermined threshold value.

[0021] In some aspects, the techniques described herein relate to a method, further including resuming delivery of PFA after terminating delivery of PFA in response to receiving an override instruction via the graphical user interface.

[0022] In some aspects, the techniques described herein relate to a method, wherein determining the plurality of parameters includes receiving one or more of the plurality of parameters via a graphical user interface.

[0023] In some aspects, the techniques described herein relate to a method, wherein calculating the current hemolysis level includes calculating the current hemolysis level after each PFA pulse train.

[0024] In some aspects, the techniques described herein relate to a method, wherein calculating the current hemolysis level includes calculating the current hemolysis level after a plurality of PFA pulse trains.

[0025] In some aspects, the techniques described herein relate to a method, wherein the plurality of PFA pulse trains corresponds to a PFA shot.

[0026] In some aspects, the techniques described herein relate to a method, wherein the plurality of PFA pulse trains corresponds to a measurement cycle.

[0027] In some aspects, the techniques described herein relate to a method, wherein calculating the current hemolysis level includes calculating the current hemolysis level after each PFA shot, wherein a PFA shot includes a plurality of measurement cycles.

[0028] In some aspects, the techniques described herein relate to a method, wherein calculating the current hemolysis level includes calculating the current hemolysis level after each measurement cycle.

[0029] In some aspects, the techniques described herein relate to a method, wherein the predetermined threshold value is 50 mg / dL, or 75 mg / dL, or 100 mg / dL, or 200 mg / dL, or 300 mg / dL.

[0030] In some aspects, the techniques described herein relate to a system for predicting 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 one or more values at each of the plurality of electrodes during each of a plurality of pulsed field ablation (PF A) measurement cycles; and an electronic control unit (ECU) configured to: determine a plurality of parameters corresponding to a patient; during delivery of PFA to the patient, receive from the measurement unit a plurality of measured values for at least a portion of the plurality of electrodes during delivery of PFA to the patient, calculate a current hemolysis level based on at least a portion of the plurality of parameters and at least a portion of the plurality of measured values, calculate an aggregate hemolysis level based on the current hemolysis level and all prior calculated hemolysis levels; and determine a prediction of hemolysis when the aggregate hemolysis level exceeds a predetermined threshold value.

[0031] 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.DESCRIPTION OF THE DRAWINGS

[0032] 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,

[0033] FIG. 1 illustrates an example distal end of an example ablation catheter in a perspective side view;

[0034] FIG. 2 illustrates an example distal end of the example ablation catheter of FIG. 1 with electrode numbering in a top view;

[0035] FIG. 3 illustrates an example delivery path for an example ablation catheter leading to a pulmonary vein ostium of a human heart;

[0036] FIG. 4 illustrates an example part of the electric control of the electrode leads for the example ablation catheter of FIG. 1;

[0037] FIG. 5 illustrates an example part of the electric control of the electrode leads for the example ablation catheter of FIG. 1;

[0038] FIG. 6 is a flow diagram illustrating an example process for predicting hemolysis during pulsed field ablation;

[0039] FIG. 7 is a flow diagram illustrating an example process for predicting hemolysis during pulsed field ablation; and

[0040] FIG. 8 is a flow diagram illustrating an alternative example process for predicting hemolysis during pulsed field ablation.DETAILED DESCRIPTION

[0041] Disclosed herein are systems and methods for predicting hemolysis in a patient based on patient related parameters, information related to pulsed field ablation, and information obtained from an ablation catheter during pulsed field ablation.

[0042] 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.

[0043] FIG. 1 illustrates a distal portion 100 of an ablation catheter 1 in accordance with a first embodiment. The ablation catheter 1 may be used for PF A, when used with a 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 shown). As a result, theablation catheter 1 may control deflections of the depicted distal portion 100 carrying the ablation electrodes.

[0044] 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 3rd loop 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.

[0045] In one aspect, to attribute measurement values to the different electrodes 120, the electrodes are consecutively numbered El - E14 as shown, e.g., in FIG. 2 (see numbers at the electrodes). The most distal electrode has the number El, whereas the most proximal electrode is denoted with number E14. Different numbering is possible, as well.

[0046] The loop sections 121, 122 may further exhibit a plurality of mapping electrodes, which are configured for receiving electrical signals from tissue.

[0047] Together, the loop sections 121, 122 form a three-dimensional spiral, which form a corkscrew-similar form where the diameter of each loop decreases 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).

[0048] 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.

[0049] 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.

[0050] 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 l4 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.

[0051] FIG. 3 schematically and exemplarily illustrates a delivery path 300 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).

[0052] Reliable full ablation along a whole circumference is achieved with the first embodiment of the ablation catheter shown in FIGS. 1 and 2 at their respective position within the heart or the vein to which the form is adapted. A small compression of the ablation portion12 of the respective catheter 1 may be possible during ablation into the direction of the longitudinal axis of the spiral.

[0053] 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.

[0054] FIG. 4 illustrates an example part 400 of the electric control of the electrode leads for the example ablation catheter of FIG. 1. 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.

[0055] FIG. 5 illustrates an example part 500 of the electric control of the electrode leads for the example ablation catheter of FIG. 1. FIG. 5 also shows connectivity that can be used to generate unipolar or bipolar electric fields. ECUs in FIG. 4 and FIG. 5 may control application of PFA fields. FIG. 5 illustrates a catheter 1401 (similar to the catheter with reference number 1 from FIGS. 1 and 2) 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 arcing risk (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.

[0056] Turning back to FIG. 4, 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.

[0057] 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 predefined pair combination, in particular for impedance determination for AR value and / or contact uniformity (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.

[0058] 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.

[0059] Advantageously, prior to 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.

[0060] In one aspect, the AR value is calculated using the formula:7ARx = 1_ t^y mln^y,y+l)

[0061] In one aspect, the calculated AR values are zero or close to zero when the ablation portion of the catheter is uncompressed and measured in saline. No risk of arcing exists since all electrodes have a sufficient distance between each other. In contrast, when electrodes ofopposite polarities are close to each other there is an arcing risk with regard to these electrodes and repositioning is needed.

[0062] In one aspect, the CU value is calculated using the below formula and the measured bipolar impedances of the adjoining electrodes:

[0063] The calculated contact uniformity value is best in the saline configuration (e.g., 0.99) because all electrodes are without contact, i.e. all electrodes are floating in saline. In practice, when the electrodes of the catheter are in good and uniform contact with the target tissue in the PVO, the CU value is high, i.e., approaching 1. On the other hand, the CU value decreases when the tissue contact becomes non-uniform, i.e., when some electrodes are in good contact, while others are in poor contact or are entirely in the blood pool. In one aspect, displaying the CU value on the GUI and periodically updating the displayed value (e.g., per second, per PFA shot, per measurement cycle, etc.) may help the physician to decide whether to reposition the catheter in an easily understandable, reliable and time-effective way.

[0064] Turning now to FIGS. 6, 7 and 8, example methods for predicting hemolysis during pulsed field ablation will be described. Initially, when preparing a patient for PFA, the physician will select certain parameters for the PFA treatment. For example, such parameters may include the pulse protocol (e.g., number of pulses, pulse width, and pulse separation), applied pulse voltage, the number of pulses in each PFA shot, catheter dimensions (e.g., number of electrodes, electrode positions, and electrode spacings), which electrodes to use when delivering energy to tissue, and patient information (e.g., height and weight, hematocrit value, glomerular filtration rate (GFR), and blood volume). Once the initial parameters are set, the physician inserts the catheter into the patient and positions the catheter at a first location. Certain initial measurements such as electrode impedance may be taken at the first location to ensure proper placement of the catheter. For example, the AR and the CU may be calculated from the measured electrode impedance to ensure that the risk of arcing is low and that each of the electrodes are in contact with tissue. Once the initial measurements are taken, the physician may proceed with the PFA treatment by interacting with a graphical user interface to instruct the ECU to carry out the PFA treatment. In one aspect, the PFA treatment includes delivery of energy to tissue in a number of PFA pulse trains. In one aspect, a measurement cycle may be a single PFA pulse train or a plurality of PFA pulse trains. In one aspect, a measurement cyclemay be a PF A shot. In one aspect, for example when delivery of PF A is synchronized with the QRS complex, a measurement cycle may be a cardiac cycle. In one aspect, when PFA is delivered synchronously with the QRS cycle of the patient, each PFA shot comprises delivery of energy to tissue for a predetermined number of cardiac cycles. Alternatively, PFA may be delivered asynchronously such that the PFA delivery measurement cycles are determined by the number of PFA pulse trains. Once the desired number of PFA pulse trains (synchronous or asynchronous) have been completed at the first location, the physician may reposition the catheter to a second location where the process repeats and certain parameters are selected and certain initial measurements are taken before delivering energy to tissue at the second location. The PFA treatment may include a plurality of PFA pulse trains at a plurality of locations, delivered synchronously or asynchronously.

[0065] FIG. 6 is a flow diagram illustrating an example process 600 for predicting hemolysis during pulsed field ablation. Initially, at 610 certain key parameters and initial measurements are determined by the ECU. For example, certain key parameters such as the pulse protocol (e.g., number of pulses, pulse width, and pulse separation), applied pulse voltage, the number of pulses in each PFA pulse train, catheter dimensions (e.g., number of electrodes, electrode positions, and electrode spacings), and which electrodes to use when delivering energy to tissue, and patient information (e.g., height and weight, hematocrit value, GFR, and blood volume) may be received by the ECU via a user interface. Additionally, certain measurements such as the impedance values at each electrode may be taken to calculate the arcing risk and the contact uniformity for the electrodes that will be activated during delivery of energy to tissue. Certain parameters may also be calculated or obtained from a memory where standard values are stored or received via a user interface. Such parameters may include the ablation volume of blood (Vref), patient’s hematocrit (Hr), the concentration of hemoglobin in the patient’s red blood cells (Hbc), the patient’s blood volume (VBI), and the position of the electrodes in the blood pool (EBP), which is a factor related to the electrodes position with respect to tissue contact.

[0066] Next, at 615, the ECU applies the first PFA pulse train at the first location by delivering energy to tissue via one or more electrodes.

[0067] Next, at 620, the ECU calculates the hemolysis level (HL) value for the patient at the end of the first PFA pulse train. In one aspect, the HL is expressed as a concentration of plasma free hemoglobin (PFHb) and is expressed in units of mg / dL. The HL value can be determined using the following equation:

[0068] An alternative equation may also be used that includes an optional variable Cc that accounts for catheter compression:

[0069] In the HL equations,

[0070] Vref = ablation volume of blood, which is dependent on PFA generator parameter settings

[0071] EBP = position of electrodes in blood pool

[0072] Hr = patient’s hematocrit value

[0073] VBI = patient’s total blood volume

[0074] Hbc = fixed value representing the concentration of Hb in red blood cells

[0075] ccs = number of measurement cycles, and

[0076] Cc = catheter compression value (optional parameter).

[0077] In one aspect, Vref can be determined experimentally for each pulse protocol and each catheter. In order to calculate the HL value for a new pulse protocol or a new catheter, the HL value can be determined experimentally or finite element method (FEM) simulations may be carried out and the HL value extrapolated from the previously acquired experimental values. Moreover, if only a subset of electrodes is energized during PFA treatment, Vref can be modified according to the subset of electrodes that is energized during PFA treatment. This may also be done experimentally or by carrying out FEM simulations.

[0078] In one aspect, EBP is determined by both experimental data and FEM simulations. Experimentally, it can be determined if an electrode has good contact to the cardiac tissue, is close to / barely touching the tissue or is fully in the blood pool and not touching / close to any tissue. Each of the three situations above have a different implication on hemolysis as the volume of blood which exceeds the electric field threshold for hemolysis changes. Therefore, FEM simulations can also be carried out to determine the increase in HL that is caused by poor contact between the electrodes and tissue.

[0079] In one aspect, EBP is determined by measuring the impedance value (Z) at each electrode on the catheter and calculating EBP using the below equation:

[0080] Where #E is the number of electrodes with a particular measured impedance value (Z) of, for example, less than 140Q, between 140Q and 170Q, and greater than 170Q. The impedance value Z is good (e.g., > 170Q) when the electrodes are in strong contact with the tissue and this results in the best EBP value. The impedance value is average (e.g., between 140Q and 170Q) when the electrodes are in close proximity to tissue and the impedance value is worst (e.g., less than 140Q) when the electrodes are floating in the blood pool not close to tissue.

[0081] In one aspect, Hr and VBI are patient specific parameters that are gathered in a preprocedure physical exam and / or blood test. If these patient specific parameters are not obtained in a pre-procedure examination, then average values may be used. For example, an Hr value of 45% can be used for male patients and an Hr value of 42% can be used for female patients. If the patient’s sex is unknown, an average Hr value of 43.5% of can be used. Similarly, an average VBI value of 5.5L can be used for male patients and an average VBI value of 4.5L can be used for female patients. If the patient’s sex is unknown, an average VBI value of 5.0L of can be used. In one aspect, VBI can be calculated using the Nadler Equation when the height, weight, and sex of the patient is known. For example, the below Nadler Equations may be used to calculate VBI in liters for men and women where the height (H) is in meters and the weight (W) is in kilograms:Men: (0.3669 ■ #3) + (0.03219 ■ W) + 0.6041Women: (0.3561 ■ #3) + (0.03308 ■ W) + 0.1833

[0082] In one aspect, the Hbc value represents the mean corpuscular hemoglobin concentration in a patient’s red blood cells. In one aspect, the Hbc value is a patient specific parameter that can be gathered in a pre-procedure physical exam, for example using a blood test. If the Hbc value is not obtained during a pre-procedure physical exam, then an average value may be used for the Hbc value. For example, in one aspect, and average Hbc value is 330 mg / mL.

[0083] In one aspect, the ccs value is provided to the ECU via the graphical user interface. In one aspect, when the HL value is calculated after each PFA pulse train as illustrated in FIG. 6, the ccs value is 1. In one aspect, the number of measurement cycles per shot is 35.Alternatively, the number of measurement cycles per shot is 60. Various other values for the number of measurement cycles per PFA shot may also be employed. In one aspect, a measurement cycle is represented by a cardiac cycle when measurements are synchronized with the QRS complex of the patient.

[0084] In one aspect, the optional Cc value, can be included in the HL equation if localization of catheter electrodes is available. For example, if the catheter is compressed, then the E-field is more localized. However, it should be noted that precise calculation of correction factors may not be straightforward as torque and compression of the catheter also may lead to an increase of the E-field.

[0085] Next, at 625, the ECU determines the aggregate HL value and updates a graphical user interface to reflect the aggregate HL value. In one aspect, the aggregate HL value is presented on the user interface as a bar graph that increases in length as the aggregate HL value increase. Additionally, the color of the graphical representation of the aggregate HL value may change as the value approaches and / or exceeds certain threshold values. For example, when the aggregate HL value is below a first predetermined threshold, the graphical representation of the aggregate HL value may be green, and when the aggregate HL value is above the first predetermined threshold but below a second predetermined threshold, the graphical representation of the aggregate HL value may be yellow and present a message regarding hydration of the patient, and when the aggregate HL value is above the second predetermined threshold, the graphical representation of the aggregate HL value may be red and present a warning regarding kidney damage to the patient. In one aspect, various values may be used for the predetermined thresholds. For example, 50 mg / dL, 75 mg / dL, 100 mg / dL, 125 mg / dL, 150 mg / dL, 175 mg / dL, 200 mg / dL, 225 mg / dL, 250 mg / dL, 275 mg / dL, and 300 mg / dL, may all be used as predetermined threshold values. In one aspect, the first predetermined threshold value is 75mg / dL and the second predetermined threshold value is 150 mg / dL. In one aspect, if the aggregate HL value exceeds a third predetermined threshold, e.g., 200 mg / dL, the GUI is also updated to indicate that PFA has been (or will be) terminated and the GUI is also updated to provide the physician with an ability to override the termination of PFA. In one aspect, the predetermined threshold values may be patient specific and determined prior to beginning the PFA treatment.

[0086] In one aspect the aggregate HL value is a simple sum of the HL values calculated at the end of each PF pulse train. In addition to updating a graphical user interface, the ECU may also play an audible sound to notify the physician about the aggregate HL value.

[0087] Next, at 630, the ECU determines if the aggregate HL value exceeds a predetermined threshold. In this case, the predetermined threshold is the highest threshold that represents a risk to the safety of the patient, for example, 300 mg / dL.

[0088] If the aggregate HL value does not exceed the predetermined threshold, then at 640 the ECU re-determines the key parameters and initial measurements as needed and proceeds back to 615 to apply the next PF A pulse train.

[0089] However, if the aggregate HL value does exceed the predetermined threshold, then at 645 the ECU terminates PFA to ensure safety of the patient. In an alternative aspect, the ECU timing of the termination may be adjusted with respect to the timing of a potential physician override such that the physician has an opportunity to override the termination and continue with PFA to avoid interruption in the PFA treatment.

[0090] Next, at 650 the ECU determines if the physician has provided a manual override of the termination of PFA. If no manual override has been received (e.g., via the GUI), the ECU proceeds with termination of PFA according to 645. However, if the ECU has received an instruction for a manual override, the ECU proceeds to 640 to re-determine the key parameters and initial measurements as needed and subsequently proceeds back to 615 to apply the next PFA shot.

[0091] FIG. 7 is a flow diagram illustrating an example process 700 for predicting hemolysis during pulsed field ablation. Initially, at 710 certain key parameters and initial measurements are determined by the ECU. For example, certain key parameters such as the pulse protocol (e.g., number of pulses, pulse width, and pulse separation), applied pulse voltage, the number of pulses in each PFA shot, catheter dimensions (e.g., number of electrodes, electrode positions, and electrode spacings), and which electrodes to use when delivering energy to tissue, and patient information (e.g., height and weight, hematocrit value, GFR, and blood volume) may be received by the ECU via a user interface. Additionally, certain measurements such as the impedance values at each electrode may be taken to calculated the arcing risk and the contact uniformity for the electrodes that will be activated during delivery of energy to tissue. Certain parameters may also be calculated or obtained from a memory where standard values are stored or received via a user interface. Such parameters may include the ablation volume of blood (Vref), patient’s hematocrit (Hr), the concentration of hemoglobin in the patient’s red blood cells (Hbc), the patient’s blood volume (VBI), and the position of the electrodes in the blood pool (EBP), which is a factor related to the electrodes position with respect to tissue contact.

[0092] Next, at 715, the ECU applies the first PF A shot at the first location by delivering energy to tissue via one or more electrodes.

[0093] Next, at 720, the ECU calculates the hemolysis level (HL) value for the patient at the end of the first PFA shot as described above.

[0094] Next, at 725, the ECU determines the aggregate HL value and updates a graphical user interface to reflect the aggregate HL value. In one aspect, the aggregate HL value is presented on the user interface as a bar graph that increases in length as the aggregate HL value increase. Additionally, the color of the graphical representation of the aggregate HL value may change as the value approaches and / or exceeds certain threshold values. For example, when the aggregate HL value is below a first predetermined threshold, the graphical representation of the aggregate HL value may be green, and when the aggregate HL value is above the first predetermined threshold but below a second predetermined threshold, the graphical representation of the aggregate HL value may be yellow and present a message regarding hydration of the patient, and when the aggregate HL value is above the second predetermined threshold, the graphical representation of the aggregate HL value may be red and present a warning regarding kidney damage to the patient. In one aspect, the first predetermined threshold value is 75 mg / dL and the second predetermined threshold value is 150 mg / dL. In one aspect, if the aggregate HL value exceeds a third predetermined threshold, e.g., 200 mg / dL, the GUI is also updated to indicate that PFA has been (or will be) terminated and the GUI is also updated to provide the physician with an ability to override the termination of PFA.

[0095] In one aspect the aggregate HL value is a simple sum of the HL values calculated at the end of each PF shot. In addition to updating a graphical user interface, the ECU may also play an audible sound to notify the physician about the aggregate HL value.

[0096] Next, at 730, the ECU determines if the aggregate HL value exceeds a predetermined threshold. In this case, the predetermined threshold is the highest threshold that represents a risk to the safety of the patient, for example, 300 mg / dL.

[0097] If the aggregate HL value does not exceed the predetermined threshold, then at 740 the ECU re-determines the key parameters and initial measurements as needed and proceeds back to 715 to apply the next PFA shot.

[0098] However, if the aggregate HL value does exceed the predetermined threshold, then at 745 the ECU terminates PFA to ensure safety of the patient. In an alternative aspect, the ECU timing of the termination may be adjusted with respect to the timing of a potential physicianoverride such that the physician has an opportunity to override the termination and continue with PFA to avoid interruption in the PFA treatment.

[0099] Next, at 750 the ECU determines if the physician has provided a manual override of the termination of PFA. If no manual override has been received (e.g., via the GUI), the ECU proceeds with termination of PFA according to 745. However, if the ECU has received an instruction for a manual override, the ECU proceeds to 740 to re-determine the key parameters and initial measurements as needed and subsequently proceeds back to 715 to apply the next PFA shot.

[0100] FIG. 8 is a flow diagram illustrating an alternative example process 800 for predicting hemolysis during pulsed field ablation. Initially, at 810 certain key parameters and initial measurements are determined by the ECU as discussed above.

[0101] Next, at 815, the ECU applies the first PFA shot at the first location by delivering energy to tissue via one or more electrodes as described above. Notably, a PFA shot typically comprises a plurality of measurement cycles as discussed above.

[0102] Next, at 820, the ECU calculates the hemolysis level (HL) value for the patient at the end of the first measurement cycle of the PFA shot. In one aspect, the HL is expressed as a concentration of plasma free hemoglobin (PFHb) and is expressed in units of mg / dL. The HL value can be determined using the equation discussed above, where the ccs value is 1.

[0103] Next, at 825, the ECU determines the aggregate HL value and updates the GUI as discussed above. If the aggregate HL value exceeds a predetermined threshold, as determined by the ECU at 830, the ECU terminates PFA at 845. Alternatively, the ECU may prepare to terminate PFA in the absence of a manual override from a physician, which is determined at 850. As discussed above, the timing of the automatic termination of PFA due to the aggregate HL value exceeding the predetermined threshold can be adjusted in connection with the potential manual override by the physician. However, if the aggregate HL value exceeds the predetermined threshold value and there is no physician override, the ECU automatically terminates PFA at 845.

[0104] If the physician does provide a manual override, then the PFA treatments proceeds and at 840 the ECU determines if the end of the PFA shot has been reached. If the PFA shot still has more measurement cycles, the ECU continues to deliver energy to tissue for the next measurement cycle and proceeds back to 820 to calculate the HL value for the next measurement cycle.

[0105] Next, at 840, if the ECU determines that the PFA shot has ended, the ECU proceeds to 855 to re-determine the key parameters and initial measurements as needed and subsequently proceeds back to 815 to apply the next PFA shot.

[0106] It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teachings of the disclosure. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention, which is to be given the full breadth thereof. Additionally, the disclosure of a range of values is a disclosure of every numerical value within that range, including the end points.

Claims

CLAIMSWhat is claimed is:

1. A system for predicting 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 a plurality of pulsed field ablation (PF A) measurement cycles; and an electronic control unit (ECU) configured to: determine a plurality of parameters corresponding to a patient; during delivery of PF A to the patient, receive from the measurement unit a plurality of measured impedance values for at least a portion of the plurality of electrodes during delivery of PF A to the patient, calculate a current hemolysis level based on at least a portion of the plurality of parameters and at least a portion of the plurality of measured impedance values, calculate an aggregate hemolysis level based on the current hemolysis level and all prior calculated hemolysis levels; and determine a prediction of hemolysis when the aggregate hemolysis level exceeds a predetermined threshold value.

2. The system of claim 1, wherein the ECU is further configured to update a graphical user interface to provide the aggregate hemolysis level each time the aggregate hemolysis level is calculated.

3. The system of claim 2, wherein the ECU is further configured to update the graphical user interface to present a message regarding hydration of the patient when the aggregate hemolysis level exceeds a first predetermined threshold value, update the graphical user interface to present a warning regarding kidney damage to the patient when the aggregate hemolysis level exceeds a second predetermined threshold value, and terminate delivery of PFA when the aggregate hemolysis level exceeds a third predetermined threshold value.

4. The system of claim 3, wherein the ECU is further configured to resume delivery of PFA after terminating delivery of PFA in response to receiving an override instruction via the graphical user interface.

5. The system of claim 1, wherein the ECU is configured to determine at least a portion of the plurality of parameters by receiving one or more of the plurality of parameters via a graphical user interface.

6. The system of claim 1, wherein the ECU is configured to calculate the current hemolysis level after each PFA pulse train.

7. The system of claim 1, wherein the ECU is configured to calculate the current hemolysis level after a plurality of PFA pulse trains.

8. The system of claim 7, wherein the plurality of PFA pulse trains corresponds to a PFA shot.

9. The system of claim 7, wherein the plurality of PFA pulse trains corresponds to a measurement cycle.

10. The system of claim 1, wherein the ECU is configured to calculate the current hemolysis level after each PFA shot.

11. The system of claim 1, wherein the ECU is configured to calculate the current hemolysis level after each measurement cycle.

12. The system of claim 1, wherein the predetermined threshold value is 75 mg / dL.

13. The system of claim 1, wherein the plurality of parameters corresponding to the patient comprise one or more of Vref, EBP, Hr, Hbc, VBI, and a number of measurement cycles.

14. A method for detecting hemolysis, comprising: determining a plurality of parameters corresponding to a patient about to receive pulsed field ablation (PFA) treatment; delivering PFA to the patient, and during delivery of PFA, measuring an impedance value at each of a plurality of electrodes positioned along a distal end of a catheter shaft employed to deliver PFA; calculating a current hemolysis level based on at least a portion of the plurality of parameters and at least a portion of the plurality of measured impedance values, calculating an aggregate hemolysis level based on the current hemolysis level and all prior calculated hemolysis levels; anddetermining a prediction of hemolysis when the calculated aggregate hemolysis level exceeds a predetermined threshold value.

15. The method of claim 14, wherein calculating an aggregate hemolysis level further comprises updating a graphical user interface to provide the aggregate hemolysis level.

16. The method of claim 15, further comprising updating the graphical user interface to present a message regarding hydration of the patient when the aggregate hemolysis level exceeds a first predetermined threshold value, updating the graphical user interface to present a warning regarding kidney damage to the patient when the aggregate hemolysis level exceeds a second predetermined threshold value, and terminating delivery of PF A when the aggregate hemolysis level exceeds a third predetermined threshold value.

17. The method of claim 16, further comprising resuming delivery of PF A after terminating delivery of PF A in response to receiving an override instruction via the graphical user interface.

18. The method of claim 14, wherein determining the plurality of parameters comprises receiving one or more of the plurality of parameters via a graphical user interface.

19. The method of claim 14, wherein calculating the current hemolysis level comprises calculating the current hemolysis level after each PFA pulse train.

20. The method of claim 14, wherein calculating the current hemolysis level comprises calculating the current hemolysis level after a plurality of PFA pulse trains.

21. The method of claim 20, wherein the plurality of PFA pulse trains corresponds to a PFA shot.

22. The method of claim 20, wherein the plurality of PFA pulse trains corresponds to a measurement cycle.

23. The method of claim 14, wherein calculating the current hemolysis level comprises calculating the current hemolysis level after each PFA shot, wherein a PFA shot comprises a plurality of measurement cycles.

24. The method of claim 14, wherein calculating the current hemolysis level comprises calculating the current hemolysis level after each measurement cycle.

25. The method of claim 14, wherein the predetermined threshold value is 75 mg / dL.

26. A system for predicting 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 one or more values at each of the plurality of electrodes during each of a plurality of pulsed field ablation (PF A) measurement cycles; and an electronic control unit (ECU) configured to: determine a plurality of parameters corresponding to a patient; during delivery of PF A to the patient, receive from the measurement unit a plurality of measured values for at least a portion of the plurality of electrodes during delivery of PF A to the patient, calculate a current hemolysis level based on at least a portion of the plurality of parameters and at least a portion of the plurality of measured values, calculate an aggregate hemolysis level based on the current hemolysis level and all prior calculated hemolysis levels; and determine a prediction of hemolysis when the aggregate hemolysis level exceeds a predetermined threshold value.

27. A system for predicting hemolysis, comprising: means to measure impedance values for at least a portion of a plurality of electrodes carried by a catheter that delivers PFA to a patient; means to estimate a hemolysis level based on at least a portion of the plurality of measured impedance values; and means to determine a prediction of hemolysis when the estimated hemolysis level exceeds a predetermined threshold value.

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