System and method for mapping electrophysiological landmarks in the heart

Abstract

To provide a system and method for mapping electrophysiological landmarks in the heart.SOLUTION: A system and method are disclosed for locating electrophysiological (EP) landmarks in real-time during electrophysiological (EP) mapping of the heart. The method includes tracking a location in the heart of a distal end of the catheter, recording a reference location of a fiducial marker in the heart, and determining a region of interest (ROI) for locating the searched EP marker relative to the fiducial marker. To the extent that the distal end is within the ROI, the IEGM signal measured from the distal end and the concurrent ECG signal are processed to determine whether the predetermined characterizing signal feature of the searched EP landmark is manifested within a predetermined time window portion of the IEGM signal relative to the reference timing provided by the ECG. If the characterizing signal feature is manifested, the location at which the IEGM signal was measured is identified as the location of the searched EP landmark.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates generally to electrophysiological (EP) mapping of the heart, and in particular to identifying, mapping, and visualizing EP landmarks such as the His bundle, the right and left bundles of His, the crista terminalis, and other EP landmarks. [Background technology]

[0002] It is known to use ablation catheters to cause tissue necrosis in cardiac tissue and correct cardiac arrhythmias (including, but not limited to, atrial fibrillation, atrial flutter, atrial tachycardia, and ventricular tachycardia). Arrhythmias can result in a variety of dangerous conditions, including irregular heart rate, loss of synchronized atrioventricular contractions, and congestion of blood flow, which can lead to a variety of morbidity and even death.

[0003] During cardiac ablation, one or more lesions are created in specific locations of a patient's cardiac tissue to prevent or suppress errant electrical signals that cause arrhythmias. However, the heart contains an electrical conduction system that includes certain electrophysiological (EP) landmarks, and ablation of these landmarks should be avoided because they play an important role in proper cardiac function. For example, the His bundle, also known as the His bundle, is a portion of the myocardium that originates near the opening of the coronary sinus (CS), which is responsible for transmitting electrical impulses from the atrioventricular (AV) node, located between the atria and ventricles, to the ventricles of the heart. Other such EP landmarks include, for example, the sinoatrial (SA) node, the atrioventricular (AV) node, and the crista terminalis.

[0004] The His bundle, for example, is located in a vulnerable location within the heart and, if incorrectly ablated, can cause harmful and undesirable effects on the heart's electrical conduction system. During conventional ablation procedures, physicians often manually tag the His bundle and possibly other EP landmarks to identify their location within the heart and avoid ablating them during the procedure. Such manual tagging is tedious, time-consuming, and can result in incorrect identification (e.g., due to false-positive readings of IEGM signals that may appear to be signals from tagged EP landmarks).

[0005] Conventional automated or partially automated techniques for identifying EP landmarks in real time during EP mapping are often error-prone and can result in false-positive identification. Indeed, non-real-time techniques for identifying EP landmarks based on post-processing of cardiac electrophysiological maps (e.g., local activation time (LAT) maps and / or bipolar / unipolar potential maps) already acquired via EP mapping procedures and / or other diagnostic procedures may be more reliable. However, the use of such techniques for EP landmark identification can be tedious and time-consuming, as they require extensive prior cardiac electrophysiological mapping procedures to be performed first (e.g., to facilitate ablation) before EP landmarks can be identified. There is a need for automated and reliable systems and methods for automatically detecting EP landmark(s) reliably and accurately in real time during cardiac EP mapping and / or ablation procedures. [Brief explanation of the drawings]

[0006] In order to better understand the subject matter disclosed herein, and to illustrate how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which: [Figure 1]1 is a schematic, pictorial illustration of a system for electrophysiological (EP) mapping, in accordance with an exemplary embodiment of the present invention; [Figure 2A] 2 is a schematic pictorial diagram of a heart showing several landmarks, including examples of EP landmarks that may be mapped by the system of FIG. 1, and landmarks that may be used for EP mapping, in accordance with an exemplary embodiment of the present invention. [Figure 2B] 2 is a graphical illustration of simultaneous intracardiac electrogram (IEGM) and electrocardiogram (ECG) signals processed by the system of FIG. 1 during EP mapping. [Figure 3A] 2 is a block diagram illustrating in greater detail the processor configuration of the system of FIG. 1 used for electrophysiological mapping in accordance with an embodiment of the present invention. [Figure 3B] 1 is a flow diagram that schematically illustrates a method for real-time mapping of landmarks, in accordance with an exemplary embodiment of the present invention; DETAILED DESCRIPTION OF THE INVENTION

[0007] Some electrophysiological (EP) disorders, such as cardiac arrhythmias, may manifest as episodes of irregular EP signals, such as irregular intracardiac electrograms (IEGMs). A mapping catheter having one or more electrodes at its distal end may be used for cardiac EP mapping of the heart. The mapping catheter is used to acquire IEGMs and thereby detect (e.g., locate) the cardiac tissue(s) (e.g., arrhythmogenic tissue(s)) causing the irregular IEGMs so that they can be ablated.

[0008] Mapping catheters are also used to detect and locate cardiac electrophysiological (EP) landmarks (e.g., those that are part of the heart's electrical conduction system), the ablation of which should typically be avoided so as not to interfere with the heart's proper operation. One such EP landmark is, for example, the bundle of His, which is part of the Purkinje fibers located between the heart chambers. Other EP landmarks whose ablation should typically be avoided may include the sinoatrial (SA) node, the atrioventricular (AV) node, and the bundle branches, namely the crista terminalis, left bundle bundle, and right bundle bundle. Therefore, prior to ablation, it is important to locate these EP landmarks and identify them on the cardiac map presented to the physician so that the physician can avoid ablation of these tissue regions.

[0009] However, some EP landmarks are difficult to reliably identify from IEGMs captured by a mapping catheter (e.g., because their characterizing signal features in the IEGM may be small or similar to IEGM signal features obtained from other tissue regions). For example, reliably identifying the His bundle may be difficult because its specific signal peak in the IEGM signal is weak. As a result, identifying the His bundle based primarily on such small signal features (peaks) alone is prone to many false positive results (because such small peaks may also be detected / sensed from other tissue locations and / or due to noise).

[0010] The embodiments of the present invention described below provide systems and methods for automatically detecting and locating one or more EP landmarks in real time during EP mapping. The techniques of the present invention utilize an EP mapping catheter having at least one IEGM electrode at its distal end, which can measure IEGM signals from nearby cardiac tissue. The EP mapping catheter may be equipped with a position sensor and / or associated with another positioning technology (e.g., ACL, as described below) so that the location(s) of the IEGM electrode(s) at its distal end can be tracked within the heart during the EP mapping procedure. To provide accurate detection and location of EP landmarks in real time, the techniques of the present invention utilize both spatial and temporal criteria to process IEGM signals acquired by the catheter at the searched EP landmarks whose locations are searched. Advantageously, utilizing both spatial and temporal criteria avoids most / all false positive identifications, thus enabling real-time detection of desired EP landmarks during mapping. Further advantageously, when utilizing the techniques of the present invention to identify / locate multiple EP landmarks in real time, the location(s) of any one or more first EP landmarks identified during mapping can be incorporated / added to the spatial reference used for EP landmark identification and / or their IEGM signal features can be used as a temporal reference, thereby further assisting in the efficient detection of the location(s) of other sought EP landmarks. Thus, implementations in which the techniques of the present invention are performed in real time during EP mapping can facilitate a reduction in the duration of the EP mapping procedure (e.g., compared to techniques in which EP landmarks are searched for only after EP mapping is completed, i.e., compared to non-real-time techniques) because EP mapping can be performed until all necessary EP landmarks and possibly other impaired tissue locations have been identified (e.g., without necessarily generating a complete electrophysiological map of the tissue region of interest, as required by conventional techniques that rely on post-processing of cardiac EP maps to identify EP landmarks).

[0011] To this end, as described above, the techniques of the present invention provide real-time detection of located EP landmarks, relying on both spatial and temporal criteria. With regard to spatial criteria, each EP landmark is generally known to be located in a particular region of the heart, which may be within a distance range of one or more other cardiac landmarks (anatomical or electrophysiological landmarks). During EP mapping, the location of the catheter is tracked, and landmarks it passes through are identified (automatically or via input from the physician). For example, during mapping, the physician can indicate when the catheter passes a particular anatomical landmark, such as the inferior vena cava (IVC) or the entrance to the atrium, or other landmark, and the location of such landmark can be registered as a spatial reference. Alternatively or additionally, anatomical reference landmarks may be automatically identified during mapping, e.g., using real-time imaging (e.g., ultrasound), and their locations may be included as reference landmarks. Furthermore, the locations of particular EP landmarks already located by the techniques of the present invention may be registered as spatial references used to identify and locate additional EP landmarks during mapping.

[0012] Furthermore, in some embodiments, the timing of characteristic IEGM signal features of an already identified EP landmark may also be registered as a time reference used to further identify additional EP landmarks during the mapping procedure (e.g., by comparing the timing IEGM signal features suspected to be provided by such additional, searched EP landmarks with the timing of characteristic IEGM signal features of the already identified EP landmarks to determine whether the suspected IEGM signal features of the additional landmarks are within an acceptable time interval relative to the timing of the characteristic features of the already identified EP landmarks) (note that in such embodiments, the acceptable time intervals between characteristic IEGM signal features of various EP landmarks may be provided in the reference data used by the system).

[0013] In this regard, it should be noted that the term anatomical landmark is used herein to designate anatomical structures having a recognizable shape / form that can be identified by a physician or system during mapping (e.g., based on imaging or based on catheter movements / maneuvers performed when passing nearby). The term EP landmark is used herein to designate portions of the cardiac electrical conduction system that do not necessarily have distinctive / recognizable shapes / forms, but whose locations can be determined from distinctive electrophysiological signal features that appear in IEGM measurements obtained from nearby locations.

[0014] This technique utilizes spatial reference data that indicates spatial relationships (e.g., the relative position / range of distance between each EP landmark located by the system and one or more reference landmarks). Thus, with the accumulation of one or more reference landmarks whose locations within the heart are identified during EP mapping, a region of interest (ROI) in which the located EP landmarks are expected to reside can be defined based on the locations of the reference landmarks and their spatial relationships to the located EP landmarks as indicated in the spatial reference data.

[0015] During EP mapping, the location of the distal end of the catheter (i.e., the IEGM electrode(s) thereon) is tracked to determine whether it is within the ROI in which one or more of the sought-after EP landmarks are expected to reside. For example, the distance / relative position of the catheter's IEGM electrode(s) with respect to particular reference landmark(s) traversed by the catheter's IEGM electrode(s) may be monitored / processed (i.e., based on the spatial relationship shown above) to determine when it is within the ROI. The IEGM signal acquired by the catheter from the ROI is then processed utilizing the time-reference ECG signal to determine whether the IEGM signal acquired from the ROI manifests signal features characterizing the sought-after EP landmarks at the appropriate time relative to the time reference. Thus, by utilizing spatial criteria to limit the search for temporal characterization signal features of the searched EP landmarks to only IEGM signals from within the respective ROIs of the searched EP landmarks, many false positive identifications of the searched EP landmarks are avoided, and the IEGM signals are determined based on their spatial relationship to the reference landmarks and the searched EP landmarks (e.g., IEGM signals that may resemble the characteristic signals of the searched EP landmark but originate from other regions are a priori overruled as originating from the searched EP landmark).

[0016] Thus, IEGM signals measured by electrode(s) at the distal tip of the catheter from locations within an ROI where the located EP landmark may reside (i.e., an ROI that satisfies a reference spatial relationship to the identified reference landmark(s)) are processed to determine whether they manifest signal features (signal peaks and / or troughs) that match the characterizing signal feature(s) expected to result from the located EP landmark. Predetermined data indicative of the characterizing signal feature(s) of the located EP landmark (also referred to interchangeably herein as reference signal feature(s)) may be, for example, a time interval ΔT i(e.g., relative to an ECG reference timing or relative to the timing of signal features of other EP landmarks), and optionally also the shape (e.g., height / width / spectral content) of the particular signal feature expected to appear in the IEGM signal measured from the EP landmark being sought. To this end, the timing of the signal feature appearing in the IEGM signal may be inferred based on / relative to the timing of particular features (e.g., P and / or QRST complexes) in the ECG signal that serve as a baseline time reference, and the time interval(s) ΔT of the corresponding characterizing signal feature of the sought EP landmark to determine their correspondence. i Optionally, the shape (e.g., height and / or width) of the specified signal features may also be considered to determine their match with the reference signal features.

[0017] Thus, according to the techniques of the present invention, the location of a located EP landmark is determined / identified when: (i) an IEGM signal is measured by the mapping catheter from a location within the ROI where the located EP landmark is expected to be present (i.e., from a location that satisfies a reference spatial relationship with other reference landmarks), and (ii) the timing(s) and optionally shape(s) also demonstrate signal feature(s) that match the characterizing signal feature(s) expected from the located EP landmark.

[0018] The techniques of the present invention facilitate real-time identification and marking / tagging of EP landmarks during an EP mapping procedure, e.g., before an EP map is fully constructed. This allows the EP mapping procedure to be performed interactively, e.g., by presenting already mapped EP landmarks to the physician on a display in real time during mapping and, optionally, by providing real-time guidance for directing the distal tip of the catheter to the ROI(s) where each EP landmark should be searched. This facilitates efficient, short, and accurate EP mapping procedures (e.g., the physician may not need to continue mapping regions of already identified EP landmarks, but may be guided to search for desired EP landmarks in specific ROI(s)). Furthermore, based on tracking the catheter location and using spatial and temporal criteria to accurately identify searched EP landmarks, the techniques reduce / eliminate false-positive identifications and also eliminate the need to identify these EP landmarks through post-processing of cardiac electrophysiological maps.

[0019] Figure 1 is a schematic diagram of a system 21 for electrophysiological (EP) mapping, in accordance with an exemplary embodiment of the present invention. Figure 1 shows a physician 27 using a catheter 29 connected to the system 21 to perform EP mapping of a chamber of a heart 23 (e.g., the left atrium (LA) and / or the right atrium (RA) and / or the left ventricle (LV) and / or the right ventricle (RV)) of a patient 25.

[0020] Catheter 29, also referred to herein as an EP mapping catheter, may be a therapeutic catheter with EP mapping capabilities and / or designated EP mapping catheter. Catheter 29 generally includes at least one mapping / IEGM electrode 22 at its distal end 50, which is adapted to acquire signals from nearby tissue of heart 23. In this non-limiting example, catheter 29 includes an electrode array 50 including one or more arms / splines 20, with a mapping / IEGM electrode 22 disposed along each of the arms 20. It should be understood that different / other types of mapping catheters (e.g., with or without splines and / or having a different number (i.e., at least one) of mapping electrodes 22) may be used in various embodiments.

[0021] System 21 is further connectable to or includes one or more ECG electrodes 24, typically external / surface ECG electrodes, adapted to be coupled to the body surface / skin of patient 25 and configured to acquire an electrocardiogram (ECG) of the patient. For example, three surface ECG electrodes 24 may be coupled to the patient's chest and another three surface ECG electrodes may be coupled to the patient's back (in this non-limiting example, only one surface ECG electrode 24 is shown in the figures for clarity).

[0022] System 21 includes a processor 28 adapted to determine the location of one or more located EP landmarks in real time during an EP mapping procedure. In the non-limiting example of FIG. 1 , processor 28 includes, for example, a data acquisition utility 33 (e.g., a signal processor) and an EP landmark location processing utility 31. Data collection utility 33 is configured and operable to receive and preprocess signals from mapping electrode(s), ECG electrode(s) 24, and signals indicative of the position of catheter 29, and may be adapted to perform various signal processing operations, such as A / D conversion and / or filtering, on the received signals and provide data indicative thereof for further processing by EP landmark location processing utility 31. EP landmark location processing utility 31 is adapted to process data indicative of the signals acquired / preprocessed by data collection utility 33 and determine the location of one or more located EP landmarks based on spatial and temporal reference data. The EP landmark location processing utility 31 may be implemented, for example, using a general-purpose computerized system 31 including data storage / memory capable of storing reference data and a processing unit adapted to execute computer-readable code for processing data / signals obtained from the data acquisition utility 33 to determine the location(s) of the EP landmarks. The processor 28 may be programmed with software (e.g., downloadable over a network and / or stored on a non-transitory tangible medium) to perform the functions described herein.

[0023] It should be understood that the configuration of processor 28 illustrated herein is provided for clarity only, and those skilled in the art will readily appreciate that the techniques of the present invention described below may be implemented by processor 28 implementing other processing configurations.

[0024] During an EP mapping procedure, the location of the distal end 50 of the catheter 29, and more specifically, the location of its mapping electrode(s), is tracked by the processor 28. Tracking may be performed by magnetic positioning techniques and / or by Advanced Current Location (ACL) tracking methods, as described below. For example, in embodiments in which magnetic positioning techniques are used to track the distal end 50 of the catheter 29, the catheter 29 may include a magnetic position sensor 20 embedded at or near its distal end. The position sensor 20 may include three magnetic coils for sensing the three-dimensional (3D) position and orientation of the distal end 50 of the catheter 29 relative to an external magnetic field provided by a location pad (not specifically shown in the figures). The location pad may be part of the system 21 and may include magnetic field generator(s) (e.g., coils) that generate a magnetic field within a predetermined workspace surrounding the patient 25, based on which the three-dimensional (3D) position of the distal end 50 of the catheter 29 may be sensed by the catheter's magnetic position sensor 20. Thus, the real-time position of the distal end 50 of the catheter 29 can be tracked based on the magnetic field sensed by the position sensor 20. Details of magnetic-based position sensing techniques are described, for example, in U.S. Patent Nos. 5,5391,199; 5,443,489; 5,558,091; 6,172,499; 6,239,724; 6,332,089; 6,484,118; 6,618,612; 6,690,963; 6,788,967; and 6,892,091, the disclosures of which are incorporated herein by reference. Alternatively or additionally, the location(s) of the IEGM mapping electrode(s) 22 within the patient's heart 23 may be tracked by the processor 28 by utilizing advanced current location (ACL) tracking techniques. According to this technique, the processor 28 measures the electrical impedance between each tracked mapping electrode 22 and an external electrode, such as an ECG electrode 24, and uses these impedances to find the coordinates of the location of the tracked mapping electrode 22.Advanced Current Position (ACL) tracking technology is described in more detail, for example, in U.S. Patent No. 8,456,182, the disclosure of which is incorporated herein by reference. An example of a system that can use sensed impedance between mapping electrodes 22 and body surface ECG electrodes 24 to track their location using ACL tracking technology and / or can use magnetic positioning technology to track the location and orientation of the catheter's distal end is the CARTO® 3 system (manufactured by Biosense Webster Inc., Irvine, CA). Alternatively or additionally, system 21 can incorporate / combine both tracking methods, for example, to accurately track the positioning of individual mapping electrodes (e.g., magnetic positioning technology can be used to accurately determine the position of the distal end of catheter 29, and ACL technology can facilitate accurate determination of the relative position of one or more mapping electrodes 22 with respect to the distal end of catheter 29, thus collectively providing the precise location(s) of mapping electrode(s) 22 within heart 23).

[0025] 2A is a schematic diagram of a portion of heart 23 with certain landmarks that may be explored / traversed by a catheter during an EP mapping procedure. This diagram illustrates, in part, several prominent cardiac landmarks, including the right and left atria RA and LA, the right and left ventricles RV and LV, and, in this non-limiting example, the superior vena cava SVC, the inferior vena cava IVC, the sinoatrial node SA, the atrioventricular node AV, and the bundle of His 41. Typically, some of the landmarks shown, such as the bundle of His 41, may be EP landmarks explored during a typical EP mapping procedure, while others may serve as fiducial landmarks whose locations may be used by system 21 as spatial references to assist in accurate, real-time identification of EP landmarks explored during the EP mapping procedure. During an EP mapping procedure, physician 27 typically inserts a catheter into the desired chamber (e.g., atrium / ventricle) of the heart by following a predetermined path through heart 23. For example, catheter 29 may be inserted into heart 23 via the inferior vena cava IVC and advanced along a path within the right atrium RA, and optionally, if necessary, to map EP landmarks in the right atrium such as the sinoatrial node SA and / or atrioventricular node AV, typically further through the valves to the right ventricle RV, where EP landmarks such as the bundle of His and the crista terminalis are mapped.

[0026] 1 , the location of the distal end of catheter 29, and more specifically, the location(s) of one or more of its mapping electrode(s) 22, is tracked (e.g., by magnetic positioning and / or ACL techniques described above). In addition, the locations of landmarks identified along the path traversed by distal end 50 of catheter 29 (e.g., anatomical landmarks determined automatically based on imaging / ultrasound and / or based on input data from physician 27, and / or EP landmarks previously identified by the techniques of the present invention) may be tagged / recorded as fiducial landmarks.

[0027] The reference landmarks are processed by system 21 based on predetermined spatial reference data to determine respective regions of interest (ROI(s)) in which system 21 should search for the located EP landmark(s). More specifically, the spatial reference data used by processor 28 includes predetermined data indicating the spatial relationship (relative distance / location) between one or more of the reference landmarks and the located EP landmark. Processor 28 therefore utilizes these reference spatial relationships to define the ROI(s) in which each located EP landmark is expected to be located based on the locations of reference landmarks already located by the system or identified by a physician. The spatial relationships in the reference data may include, for example, for each located EP landmark, a range of distances or relative locations within which the located EP landmark is expected to be relative to one or more of the reference landmarks. For example, the relative location, provided in polar coordinates, of the location of the located EP landmark relative to one of the fiducial landmarks may be provided by a relative polar vector (Δr, Δθ, Δφ) defining an individual reference ROI in the form of a spherical sector in which the located EP landmark is expected to reside relative to the fiducial landmark (it will be appreciated that the relative vector location may be provided in other coordinates, such as Cartesian coordinates, and / or may be a scalar quantity defining a range of distances Δr and / or an angular range, e.g., Δθ and / or Δφ). With the accumulation of information about the locations of additional fiducial landmarks, relative locations are provided in the reference data for each located EP landmark, and processor 28 can further narrow the actual ROI for searching the located EP landmark by taking overlaps / sections of the individual reference ROIs associated with each located fiducial landmark relative to the located EP. Thus, as additional fiducial landmarks are identified / located during the procedure, the ROI for searching the located EP landmark is estimated with improved accuracy.

[0028] To this end, during an EP mapping procedure, physician 27 typically positions catheter 29 at one or more locations to enable electrode(s) 22 at distal end 50 to acquire IEGM signals, such as atrial electrograms, from nearby cardiac tissue. The signals captured by mapping electrode(s) 22, as well as signals indicative of the location of electrode(s) 22 at distal end 50 (e.g., signals from magnetic position sensor 20 at distal end 50 and / or ACL signals), are transmitted to processor 28. Based on these signals, processor 28 can link / associate each respective acquired IEGM signal with the location in the heart where the signal was acquired. Using reference landmarks (e.g., EP landmarks or anatomical landmarks previously tagged / identified along the path of catheter 29), processor 28 determines in real time whether the location in the heart where each IEGM signal was acquired is within a region of interest (ROI) where any one of the searched EP landmarks may reside. In some embodiments, the ROI is determined as a region whose location is identified within a predetermined distance range(s) relative to one or more spatial reference landmarks already identified in the procedure (the distance range(s) are part of the spatial reference data linking the expected location of the located EP landmark to one or more reference landmarks). In other embodiments, the spatial reference data further includes data indicating the relative positions (e.g., distance range and directional / angular range) between the located EP landmark and one or more reference landmarks, and the ROI of the located EP landmark may be determined accordingly based on the relative positions.

[0029] Therefore, if processor 28 determines that the acquired IEGM signal originates from within a ROI associated with at least one of the located EP landmarks, the processor further applies temporal processing to the acquired IEGM signal to determine whether the acquired IEGM signal has signal features with appropriate timing characteristic of the located EP landmarks.

[0030] The following description describes / illustrates one example of temporal processing performed by system 21 by utilizing predetermined time reference data indicative of time intervals and, optionally, shapes or other identifiers (e.g., frequency content / amplitude levels) of characterizing signal features expected to appear in IEGM signals from located EP landmarks. Nevertheless, as will be appreciated by those skilled in the art, similar temporal processing can also be implemented in system 21 by an appropriately trained machine learning processor / module.

[0031] FIG. 2B shows a graph of an intracardiac electrogram (IEGM) signal 301 and an ECG signal 300 used in the temporal processing. The IEGM signal 301 was obtained during the EP mapping process from a searched EP landmark ROI. In this example, the searched EP landmark is the His bundle 41. The His bundle ROI was determined to be within a predetermined distance from where the catheter 29 entered the atrium (e.g., typically the IVC). The IEGM signal 301 illustrates the IEGM signal measured by the mapping electrodes 22 of the catheter 29 from within that ROI. An electrocardiogram (ECG) signal 300 is simultaneously acquired by one or more of the ECG electrodes 24 of the system 21. The ECG signal 300 provides a temporal baseline and is used to determine a reference timing 306 relative to which the timing of signal features in the acquired IEGM signal(s) can be evaluated. For example, the timing of the P and / or QRST complexes of the ECG signal, and / or portions thereof, such as the timing of the R peak in this example, may be used as the reference timing 306. Note that the ECG features providing the reference timing 306 generally repeat with each cardiac cycle and can therefore be used as a time baseline against which the timing of signal features in IEGM signals acquired in different cardiac cycles, and possibly from different cardiac locations / EP landmarks, can be compared. Once the location of the catheter distal end 50 falls within the ROI of the His bundle 41, the processor 28 processes the acquired IEGM signal(s) 301 (or at least relevant time portions thereof) to determine whether the acquired IEGM 301 exhibits a characterizing signal feature of the sought EP landmark (His bundle). In this process, processor 28 utilizes ECG signals 300 acquired simultaneously by ECG electrode(s) 24 to determine reference timing(s) 306 (e.g., for the cardiac cycle appearing in signals 300 and 301) against which the timing of signal features appearing in the concurrent IEGM signals within the cardiac cycle is measured.To achieve this and facilitate the use of the ECG signal 301 as a time reference, a synchronization process can optionally first be performed to time synchronize the ECG signal 300 and the simultaneous IEGM signal 301 (i.e., to establish / determine the time alignment between them and, in some cases, compensate for any time delays / misalignments in the propagation of those signals from the electrodes 22 / 24 that sense them). The reference timing 306 is determined by identification of a predetermined feature (the R peak in this example) within the ECG signal 300. In this particular, non-limiting example, the reference timing 306 is based on the timing of the R peak in the ECG, although it should be understood that, in general, other suitable ECG features, such as, for example, the P and / or Q of a PQRST-ECG complex, can be used as a timing reference. The time reference data can then be used to determine a time window ΔT relative to the reference timing 306 during which at least one characterizing signal feature of the sought-after EP landmark should appear in the IEGM signal 301.

[0032] In this regard, the time interval(s) ΔT of the characteristic signal features of the searched EP landmarks provided in the time reference data i is a number of time interval(s) ΔT related to the expected timing of the characteristic signal feature of the located EP landmark relative to a reference timing 306 in the ECG signal and / or relative to the characteristic signal features of other EP landmarks. i Note that the time interval(s) ΔT relative to the reference ECG timing 306 may optionally be included. i and the time interval(s) ΔT relative to other previously identified EP landmarks. i and may be intersected to determine a time window ΔT in which the characterizing signal feature of the located EP landmark is expected to appear. More specifically, for example, a reference time interval ΔT related to the expected timing of the characteristic signal feature relative to the reference ECG timing 306. iThe section / segment of the IEGM signal 301 corresponding to may be determined directly relative to a reference timing 306 in the ECG signal. A reference time interval ΔT related to the expected timing of a characteristic signal feature relative to another previously identified characteristic signal feature of the EP landmark. i The sections / segments of the IEGM signal 301 corresponding to the reference time interval ΔT i can be determined by summing the timing of a characteristic signal feature of another already identified EP landmark relative to the reference ECG timing in the cardiac cycle in which it was identified, thus determining the corresponding section / segment in the current IEGM signal 301. Thus, the sections / segments, which may be determined based on the reference data and optionally also based on the timing of the already identified landmarks, may be intersected / overlapped to determine the time window ΔT within which the characterizing signal feature of the currently searched EP landmark should be searched.

[0033] The IEGM signal 301 is processed (e.g., utilizing signal feature identification techniques) to identify whether characteristic signal features of the currently searched EP landmark appear within the specified time window ΔT as determined above. If so, the system 21 may determine that the IEGM signal 301 does indeed originate from the searched EP landmark and mark / register the location where it was obtained as the location of the searched EP landmark. In some implementations, reduced processing load is achieved by processing only relevant portions / segments of the IEGM signal(s) within the specified time window ΔT.

[0034] It should be noted that, although the above description describes the temporal processing performed by system 21 as utilizing explicit processing (e.g., signal processing) of the IEGM and ECG signals based on time reference data, the present invention is not limited to this type of processing and may alternatively or additionally use trained machine learning modules / processors for processing the IEGM signals 301 and ECG signals 300 to determine whether the former manifest signal features expected from the located EP landmarks at the appropriate timing relative to the timing established by the latter. Accordingly, it should be understood that references made herein to temporal processing of signals based on time reference data may generally refer to signal processing using explicit time reference data and / or processing using trained machine learning modules in which such / similar time reference data was implicitly embedded during prior training. More specifically, a machine learning module trained based on appropriate training data (e.g., by supervised training) can implicitly incorporate (e.g., learn) the characteristics of the time reference data described above and can perform the above-described determination of whether an IEGM signal represents a signal feature characterizing a located EP landmark without explicitly using the time reference data (i.e., because the time reference data can be “learned” during training). For example, appropriate training data for such a machine learning module can include pairs of simultaneous ECG and IEGM signals originating from samples of the located EP landmark and from other locations, along with an indication of whether each IEGM signal originates from the located EP landmark (whereby the latter can be used to supervise training). After learning about the present invention, those skilled in the art will readily recognize various techniques by which such a machine learning module can be trained to identify whether an IEGM signal originates from a particular located EP landmark based on the IEGM signal and / or relevant portions thereof and the simultaneous ECG signal provided as input to the machine learning module.

[0035] In this example, the characterizing signal feature of the His bundle 41 in the time reference data is a small, narrow peak 303 signal feature 303 that is expected to be located within a predetermined time window ΔT after the reference timing 306. In another example, the reference data may indicate that activity within this time window ΔT that is above a defined amplitude / intensity threshold, or that has a predefined frequency content or shape, may be sufficient to identify the sought-after EP landmark / His 41. In this example, the shape of the peak 303 (e.g., its characteristic width and / or amplitude and / or spectral characteristics) and the predetermined time interval ΔT within which it should be located relative to the reference timing (in this example, the R peak in the ECG) may be sufficient to identify the His bundle 41. i Data representing both and were included as part of the time reference data used to determine whether the identified peaks in the IEGM signal obtained from the ROI were in fact peaks representing His41.

[0036] Thus, upon determining that the catheter's distal end 50 is spatially located within an ROI in which one of the searched EP landmarks may be present, the processor 28 processes the IEGM signal(s) 301 acquired therefrom by the electrode(s) 22 to determine whether they contain signal features that match signal feature(s) characterizing the searched EP landmark and whose timing is within a reference time window ΔT relative to the ECG's reference timing 306. The processor 28 can process only the relevant portion(s) of the IEGM signal(s) 301 that fall within the time window ΔT, thereby reducing processing load / complexity and facilitating agile, real-time identification of the searched EP landmark. If the acquired IEGM signal(s) contain such features within the reference time window ΔT, the processor 28 can determine that the IEGM signal(s) was obtained from the searched EP landmark and can mark / tag or otherwise register the location from which the IEGM signal was acquired (e.g., the distal end of the catheter or the location of that particular electrode 22) as the location of the searched EP landmark.

[0037] As described above, if a particular EP landmark, such as the His bundle 41, has already been identified, and the system 21 continues to search for additional EP landmarks, the system 21 can utilize the identified timing of the characterizing signal feature(s) of the already identified landmark as an additional time reference, thereby narrowing the search for signal features of the additional landmarks. For example, the timing(s) of the characterizing feature(s) of the already identified landmark (e.g., the timing of the discovered peak 303 of the His bundle 41 relative to the ECG signal 300—see FIG. 2B ) may be used as a time reference for identifying the additional / other searched EP landmark(s). More specifically, for example, once a His 41 is identified, the time difference 308 between that characterizing His feature 303 and the ECG reference timing 306 can be recorded, and the time difference 308 can be used to estimate the timing of the characterizing His feature 303 in any further cardiac cycle, even if the catheter has not measured an IEGM from that His (in such further cardiac cycle, the estimated timing is the ECG reference timing 306 obtained for the further cardiac cycle plus the time difference 308 between it and the characterizing His feature 303 recorded when the His was identified). Thus, in general, the timing of signal features of already identified EP landmarks can be further utilized in the techniques of the present invention as a time reference to aid in the efficient and accurate identification of additional EP landmarks that have been explored. The time reference data used by the system 21 can be used to estimate the reference time interval ΔT of the expected relative timing between the characterizing signal feature of a first EP landmark and the characterizing signal feature of a second EP landmark. iIf the timing of the characterizing signal feature of the first EP landmark indicates a time window ΔT within which to search for the characterizing signal feature of the second EP landmark with improved precision (i.e., search within a narrower time window ΔT), this can be utilized, along with the measured timing of the characterizing signal feature of the first EP landmark, to determine a time window ΔT within which to search for the characterizing signal feature of the second EP landmark with improved precision (i.e., search within a narrower time window ΔT). Thus, by accumulating EP landmarks identified during the EP mapping process, data (e.g., 308) acquired around the timing of those characterizing signal features (e.g., relative to a reference ECG timing 306) can be used by the system 21 to determine a narrower time window ΔT within which to search for the signal features of other searched EP landmarks. Furthermore, in this case, because the time window ΔT within which the characterizing signal features of the further searched EP landmarks are searched is specifically set with respect to signal features measured from the cardiac electrical conduction system of a particular patient, this further individualizes the EP mapping procedure to the particular patient being examined.

[0038] 1 , upon identifying and locating a searched EP landmark, a tag 48 or other indicator may be added by processor 28 to map 40 of heart 23 presented to physician 27 on display 26 in real time during the mapping procedure. Thus, physician 27, informed that a searched EP landmark has been located, may discontinue searching for that EP landmark and continue with EP mapping, perhaps to search for other EP landmarks and / or map EP characteristics of other cardiac tissues of interest. To this end, as described above, once a searched EP landmark has been located, its location may be added to a list of reference landmarks whose locations are known by the system and, therefore, may be further used as a spatial reference if system 21 / physician 27 proceeds to search for and locate additional EP landmark(s).

[0039] 3A is a block diagram illustrating in more detail the configuration of processor 28 of system 21. Processor 28 includes data acquisition utility 33 and electrophysiological landmark localization utility 31.

[0040] In some exemplary embodiments, the data acquisition utilities 33 include an IEGM signal provider / preprocessor 33.1, an ECG provider / preprocessor 33.2, and a catheter location tracker 33.3.

[0041] In this example, the IEGM signal provider / preprocessor 33.1 is connectable to one or more mapping electrodes 22 on the catheter 29 and is adapted to acquire and, optionally, preprocess (e.g., digitize / filter) as needed IEGM signals measured from the location of the distal end 50 of the catheter 29 within the patient's heart 23. The electrocardiogram provider / preprocessor 33.2 is connectable to one or more ECG electrodes 24 and is adapted to acquire and, optionally, preprocess (e.g., digitize / filter) as needed ECG signals measured from the patient's body. The catheter location tracker 33.3 is adapted to acquire a signal POS indicating the location of the catheter's distal end 50, more specifically the location of its particular mapping electrode(s), and process the POS signal to determine / estimate the location(s) of the electrode(s) 22. In some implementations, the catheter 29 includes a magnetic positioning sensor 20 optionally mounted at its distal end 50, and the catheter location tracker 33.3 is connectable to the sensor 20 and adapted to process signals POS obtained therefrom and determine the location of the catheter's distal end 50 according to the magnetic positioning techniques described above. Alternatively or additionally, in some implementations, the catheter location tracker 33.3 is connectable to one or more of the catheter's mapping electrode(s) 22 and one or more of the body surface ECG electrodes 24 and / or other body surface electrode(s), and adapted to obtain signals POS indicative of impedance between the mapping electrode(s) 22 and the body surface electrode(s) (e.g., 24), and to determine the location of the catheter's distal end 50 or the mapping electrode(s) thereat based on the ACL techniques described above. Further alternatively or additionally, in some embodiments, the catheter location tracker 33.3 is adapted to implement a combination of both magnetic positioning and ACL techniques to thereby determine the location of the catheter's distal end 50 and / or the mapping electrode(s) thereon with improved accuracy. To this end, the catheter location tracker 33.3 operates during an EP mapping procedure to track locations within the heart 23 through which the catheter's distal end 50 passes during mapping.

[0042] The electrophysiological landmark localization utility 31 is adapted to implement the method 100, described in more detail below, and to locate one or more located EP landmarks in real time during EP mapping, according to some exemplary embodiments of the present invention. In the non-limiting exemplary embodiment as shown in the figure, the electrophysiological landmark localization utility 31 includes a reference location data provider 210, a spatial relationship processor 220, a temporal relationship processor 230, and an EP space mapper 240.

[0043] The reference location data provider 210 is typically associated with data storage / memory 212 that stores spatial reference data indicating spatial relationships (e.g., relative distances / locations between each of the EP landmarks located by the system 21 and one or more reference landmarks (which may be anatomical or EP landmarks)). To this end, for each EP landmark whose location is automatically identified by the system, the spatial reference data includes data indicating its spatial relationship to at least one other landmark that serves as a spatial reference for locating the located landmark. The spatial relationship may be a distance range (i.e., a scalar) and / or a relative location range (i.e., a vector) that indicates the area in which the located EP landmark is located relative to the location of the reference landmark.

[0044] The spatial relationship processor 220 is connectable / coupled to the catheter location tracker 33.3 and is adapted to obtain from the catheter location tracker 33.3 data indicative of the location(s) within the heart of the mapping electrode(s) 22 at the catheter's distal end 50 and, optionally, store the path of the catheter's distal end 50 and / or the electrode(s) 22 within the heart in a data storage device 222. The spatial relationship processor 220 is connectable / coupled to the reference location data provider 210 and is adapted to utilize the spatial reference data obtained from the reference location data provider 210 to determine, based on the spatial relationships in the spatial reference data, whether the electrode(s) 22 at the catheter's distal end 50 are located within a ROI in which one of the located EP landmarks may be present. In some embodiments, the spatial relationship processor 220 is associated with a reference landmark input 225, thereby receiving data indicative of the location of a particular reference landmark within the heart 23. The fiducial landmark input 225 may be connected, for example, to a user interface (not specifically shown), whereby the spatial relationship processor 220 may be adapted to receive input from the physician 27 regarding the location(s) of certain fiducial landmarks. For example, as the physician manipulates the distal end of the catheter into and through different regions of the heart during a mapping procedure, the physician may recognize a particular landmark (e.g., an anatomical structure) (e.g., the IVC) through which the catheter is passed and provide input data indicating that the current location of the distal end of the catheter is currently near that fiducial landmark. Alternatively or additionally, the fiducial landmark input 225 may be connected to an imaging utility, such as an ultrasound imaging utility, operable to image, and perhaps identify / recognize based on the image (e.g., using image processing / pattern recognition or manual input), the locations of certain fiducial landmarks within the heart, and provide data indicative thereof to the spatial relationship processor 220 via the fiducial landmark input 225.

[0045] The spatial relationship processor 220 may then store the locations of the reference landmarks received via input 225 in memory 222 (e.g., optionally form in memory a record of the catheter's path, or nearby reference landmarks it has passed). Accordingly, the spatial relationship processor 220 further utilizes one or more of these locations of the reference landmarks stored in memory 222 and the spatial relationships (spatial reference data) obtained from the reference location data provider 210 to determine whether the catheter's distal end 50 is located in a region of interest (ROI) in which one or more of the located landmarks may be present. If so, the temporal relationship processor 230 may operate to process IEGM signals obtained from the catheter's electrode(s) 22 (as described in more detail below) to determine whether the catheter's distal end 50 is located near the located EP landmarks. Optionally, in some embodiments, the spatial relationship processor 220 can further utilize the locations of the reference landmarks and the spatial reference data to determine regions within the general area of ​​the catheter's distal end 50 where one or more of the searched EP landmarks may be located, and provide guidance to the physician to move the catheter's distal end 50 toward these regions to help the physician find the searched EP landmarks. In such embodiments, the spatial relationship processor 220 can be further connected to the display 26 and / or other output user interface utilities (e.g., audio) and can be adapted to provide guidance marks to the physician to instruct the physician in real time to move the catheter's distal end toward those regions where the searched EP landmarks may be found.

[0046] The temporal relationship processor 230 is connectable to both the IEGM signal provider / preprocessor 33.1 and the ECG signal provider / preprocessor 33.2 and is adapted to receive therefrom simultaneous data regarding the IEGM and ECG signals measured by the electrodes 22 and 24, respectively. Once the spatial relationship processor 220 determines that the catheter's distal end 50 is located in a region of interest (ROI) in the heart where one of the located EP landmarks may be present, the temporal relationship processor 230 operates to process the IEGM and ECG signals obtained from the ROI to determine whether the IEGM signal manifests signal features indicative of being sensed from the located EP landmark. To that end, the ECG signal may serve to determine a reference timing of interest against which the timing of the signal features may be evaluated.

[0047] In certain embodiments, the temporal relationship processor 230 optionally includes an EP signal feature identification utility 232 associated with a time reference data repository 233 that stores time reference data, including reference signal feature(s) expected to appear in the IEGM signal resulting from each located EM landmark, and reference time interval(s) ΔT during which the reference signal feature(s) are expected. iThe reference time interval(s) may be specified relative to particular reference timing(s) to be determined from the ECG signal (e.g., the timing of a particular signal feature of the ECG signal) and / or, optionally, relative to timing characterizing signal features of other located EP landmarks. In such an embodiment, upon receiving an indication from the spatial relation processor 220 that a particular obtained IEGM signal is acquired from an ROI in which one of the located EP landmarks may reside, the EP signal feature identification utility 232 process operates to process the IEGM signal utilizing the time reference data and the simultaneously acquired ECG signal to determine whether the IEGM signal manifests characterizing signal features (peaks / troughs) associated with the located EP landmarks having timing relative to the reference timing that matches / is within the reference time interval(s) ΔT (e.g., as shown in FIG. 2B ) indicated for those reference features in the time reference data.

[0048] As mentioned above, in some implementations, the reference signal features further include data indicating the shape(s) of the characteristic signal feature(s) of the located EP landmark, and the EP signal feature identification utility 232 operates to determine their presence in the IEGM signal based on their shape in addition to their timing.

[0049] To this end, for each EP landmark to be located by system 21, time reference data repository 233 may store time reference data including signal features, such as peaks and / or troughs, expected to appear in the IEGM signal measured from the ROI of the located EP landmark, as well as data indicating the expected time window ΔT during which those peaks and / or troughs are expected to appear in the ECG relative to a reference timing. Additionally, in some implementations, the time reference data may further include data indicating the shape (e.g., spectral content, characteristic width, and / or characteristic amplitude) of some of the characterizing signal features. EP signal feature identification utility 232 may implement a signal feature detection algorithm (e.g., a peak / trough detection algorithm) that can be applied to the acquired IEGM signal to detect / identify signal features (peaks / troughs) of predetermined characteristics (e.g., amplitude / width / shape) therein and determine their timing. Any suitable peak / trough detection algorithm may be used for this purpose, including, for example, amplitude-based and gradient-based algorithms known in the art, as well as other algorithms, such as machine learning algorithms / pattern recognition algorithms trained for signal feature detection / identification. Peak / trough detection may be performed, for example, using smoothing and then fitting a known function (e.g., a polynomial function) to the waveform. Alternatively or additionally, processor 28 may match known features to the waveform. Further alternatively or additionally, peaks and / or troughs may be detected by finding zero crossings (i.e., local maxima) in the difference (slope sign change) between a point and its neighbors.

[0050] For example, referring to the characteristic peak 303 of the His bundle shown in FIG. 2B , because this peak 303 is relatively narrow, the processor 28 (EP signal feature identification utility 232) can distinguish the peak by passing the IEGM signal 301 through a high-pass filter to extract only narrow, sharp peaks from the IEGM signal that may indicate a His bundle peak. The processor 28 (EP signal feature identification utility 232) then determines whether the timing of any such extracted peak relative to a reference ECG timing 306 falls within a reference time window ΔT during which a His peak is expected. To this end, the reference timing 306 may be determined by the EP signal feature identification utility 232 (by the processor 28) using a feature detection algorithm similar to that described above for the reference ECG signal 300 to identify and determine the timing of that particular predetermined complex signal. For example, the timing of any of the so-called P and / or R peaks and / or QRST complexes in the ECG signal may serve as the reference timing 306. The EP signal feature identification utility 232 then calculates the time difference 308 between the identified feature / peak 303 in the IEGM signal 301 and the reference timing 306 of the reference ECG signal 300, and if it falls within a predetermined reference time interval ΔT within which a corresponding reference feature in the IEGM signal resulting from the located EP landmark is expected, the EP signal feature identification utility 232 can determine that the IEGM signal results from the located EP landmark (provided that the IEGM signal also results from a tissue location that satisfies the spatial conditions set forth above) and output an indication IDF(signal / data) indicating so. In the example of FIG. 2B , as shown, the peak 303 coincides with the characteristic feature of the His bundle and, indeed, also falls within the time window ΔT within which it is expected.

[0051] Alternatively or additionally, in certain embodiments, the temporal relationship processor 230 may optionally include a training machine learning utility 235 that receives as input the IEGM and ECG signal and is trained to identify whether the IEGM, at appropriate timing relative to the timing of the ECG signal, exhibits signal characteristics consistent with those expected from an IEGM signal resulting from the located EP landmark. To that end, the trained machine learning utility 235 may implement, for example, a neural network appropriately trained to determine, based on the input IEGM and ECG signal, whether the IEGM signal originates from the located EP landmark. As will be readily understood by those skilled in the art of machine learning and / or pattern recognition informed by the present invention, a trained machine learning utility such as the trained machine learning utility 235 may be implemented by supervised training of one or more neural networks based on training data including multiple simultaneous IEGMs arising from the located EP landmark and from other cardiac regions, along with simultaneously acquired ECG signals, and supervised data indicating whether the training IEGM signal originates from the located landmark. Through training, the neural network of machine learning utility 235 actually learns to identify whether the IEGM signal provided thereto as input, at the appropriate time relative to the ECG signal provided thereto, manifests signal characteristics consistent with those expected from the located EP landmarks, and generates output data indicative thereof. To this end, temporal relationship processor 230 processes the IEGM signal and ECG signal measured by electrodes 22 and 24, respectively, to determine whether the IEGM signal arises from the located EP landmarks, and outputs an indication IDF(signal / data) indicative thereof.

[0052] EP space mapper 240 is configured / operable to obtain indication(s) IDF for the identified EP landmark(s) in real time from temporal relationship processor 230 and is also adapted to receive data indicative of the location of the catheter's distal end 50 where each IEGM signal was acquired from catheter location tracker 33.3. Upon receiving an indication IDF for an IEGM signal emanating from a particular located EP landmark, EP space mapper 240 obtains the catheter location where the IEGM signal was acquired and accordingly marks / places a sign / tag 48 indicative of the located EP landmark in an appropriate location on a map of heart 23, or a portion thereof, that is or would be displayed on display 26. For example, EP space mapper 240 may tag the discovered EP landmark with a tag 48 on the heart / EP map 40 displayed on the display (e.g., "H" illustrated in FIG. 1 designates His) and / or color-code that region of map 40 with a color coding indicative of the type of identified landmark. Thus, system 21 provides physician 27 with real-time indication of EP landmarks identified along the path of the catheter within heart 27 during the EP mapping procedure.

[0053] 3B is a flow diagram illustrating, in a self-explanatory manner, a method 100 for locating electrophysiological landmark(s) in the heart in real time, according to one embodiment of the present invention. Method 100 may be implemented by processor 28 of system 21 described above. In operation 110, spatial reference data is provided that indicates the spatial relationship between one or more reference locations in the heart and one or more located EP landmarks that are to be placed during the mapping procedure. As shown in operation 120, the location of catheter distal end 50 is tracked during the EP mapping procedure.

[0054] Operation 130 is performed during an EP mapping procedure to acquire / receive data indicative of the locations of (electrophysiological and / or anatomical) fiducial landmarks within the patient's heart. The locations of some fiducial landmarks may be identified, for example, based on input from a physician and / or by additional systems such as an imaging utility, and / or may include the locations of EP landmarks already identified by method 100 along the path of catheter 29. Alternatively or additionally, the locations of certain particular landmarks, such as the entrances to the atria from the superior vena cava (SVC) and / or inferior vena cava (IVC), may be assessed by system 21 by monitoring IEGM signals acquired by the catheter as it passes from particular blood vessels (e.g., SVC / IVC) to the heart chambers. Considering that IEGM signals are generally not acquired from within blood vessels such as the SVC / IVC, and given predetermined data regarding the blood vessel (e.g., the IVC) into which the catheter is inserted into the heart during the mapping procedure, the system 21 can monitor sensed IEGM signals, and upon detecting that an IEGM signal is sensed by the catheter, determine that the distal end 50 of the catheter is located just at the entrance from that blood vessel to the ventricle / atrium it connects to, and therefore can automatically identify this location as the spatial reference location.

[0055] Thus, in operation 130, which may be performed throughout the mapping procedure, data regarding fiducial landmark locations is accumulated based on one or more sources of information, for example, based on input from a physician and / or input from an imaging utility, and / or based on IEGM monitoring aided by predetermined / input data regarding the path / vessel(s) through which the catheter is inserted into the heart.

[0056] Based on the location of the identified fiducial landmark, operation 140 is performed to utilize spatial reference data to determine a region of interest (ROI) in which at least one of the EP landmarks located in the EP mapping procedure should be located. Operation 150 is performed during the procedure to determine, based on the location of the distal end 50 being tracked (see 120 above), whether the distal end is within the ROI of the located EP landmark determined in operation 140. If not, optional operation 155 may be performed to provide guidance (such as a guide mark, e.g., an arrow on the display 26) to the physician 27 to guide the physician 27 toward the ROI, and operation 150 is repeated. Conversely, if the distal end of the catheter is within the ROI in which one of the located EP landmarks should be located, the method proceeds to operations 160-190 to identify the location of the located EP landmark within the ROI based on signal features of one or more IEGM signals acquired from one or more locations within the ROI. In operation 160, at least one IEGM signal measured by catheter 29 from one or more consecutive locations within the ROI is obtained. In addition, in operation 170, an ECG signal measured substantially simultaneously from the patient's body / skin is also obtained. The obtained IEGM signal and ECG signal are then processed in operation 180 to determine whether the IEGM signal arises from the located EP landmark. This processing accounts for the temporal relationship(s) between signal features of the IEGM signal relative to the ECG signal (e.g., relative to its particular features, such as the Q and / or PQRST complexes) and / or relative to the timing of particular signal feature(s) in the IEGM signal(s) of other located EP landmarks in IEGM signals already identified by the system. The temporal processing determines whether the IEGM signal has features whose timing relative to a reference timing represented by the ECG signal or the IEGM signal of the already identified EP landmark matches the expected timing of those signal features for the IEGM signal obtained from the located EP landmark. The temporal relationship may be one or more time intervals ΔT that relate the timing of signal features in the IEGM of the located EP landmark to the timing of one or more signal features in the ECG signal and / or IEGM signal of other EP landmarks.i Given the ECG signal and optionally the IEGM signals of the previously identified EP landmarks, processor 28 may calculate these time intervals ΔT i and intersect them to generate a time window ΔT that specifies the portion of the IEGM signal within which the characterizing signal features of the located EP landmark should be searched. Accordingly, processor 28 then processes the IEGM signal (or at least that portion / segment of the IEGM signal within the time window ΔT) to search for signal features therein that match the characterizing signal features of the located EP landmark. To this end, as described above, the processing load associated with determining a match between features in the IEGM signal and the characterizing signal features of the located EP landmark is typically reduced by processing only the relevant portion / section of the IEGM signal that is within the time window ΔT.

[0057] As shown in optional operations 182 and 184, respectively, operation 180 may include calculating an expected time interval ΔT during which a characterizing signal feature of the located EP landmark should occur relative to signal feature(s) in the ECG or IEGM from other EP landmarks. iThis may be done explicitly, utilizing predetermined time reference data indicative of the IEGM signal, and / or utilizing a neural network / machine learning model trained to recognize the timing of those features. Optionally, the shape(s) of the signal features in the IEGM signal are also considered to determine their match with expected signal features from the IEGM signal, as described above. As shown in operation 185, operations 160 through 180 may be repeated until a match is determined in operation 180. Then, once the IEGM signal is determined to originate from the located EP landmark, in operation 190, the location in the heart where it was acquired by the catheter (which may be determined based on tracking 120) is identified / set as the location of the located EP landmark, and an indication (e.g., a sign / tag) marking may be presented on the cardiac map on display 26. If additional EP landmarks are to be searched for in the EP mapping procedure, the method may proceed to optional operations 192 and 194, where the locations of the EP landmarks may be added to the list of reference landmarks (obtained in operation 130), and the method may continue to identify the locations of additional searched EP landmarks by repeating operations 120 through 190.

[0058] Although exemplary embodiments of the present invention are described above with particular reference to elements of system 21 for purposes of specificity and clarity, the principles of the present invention may likewise be applied to other EP mapping systems having appropriate sensing capabilities, and all such alternative embodiments are considered to be within the scope of the present invention. [Example]

[0059] Example 1. A method of locating electrophysiological (EP) landmarks in a patient's heart in real time during catheter-based electrophysiological mapping of the heart, comprising: (a) Tracking the location within the heart through which the distal tip of the catheter passes during electrophysiological mapping; (b) recording a reference location of at least a first spatial reference landmark within the heart; (c) determining a region of interest (ROI) for locating the searched EP landmark based on a predetermined distance range relative to at least the first spatial reference landmark; (d) As long as at least one electrode at the distal end is within the ROI: i) acquiring data indicative of an IEGM measured by at least one electrode synchronously with data indicative of an ECG signal; ii) identifying reference timing based on the ECG signal; iii) identifying the portion of the IEGM signal that is within a predetermined time window relative to a reference timing; iv) determining whether predetermined characterizing signal features of the sought EP landmark appear within the portion of the IEGM; and v) identifying the location of at least one electrode as the location of the sought EP landmark upon determining that the characterization signal feature appears within the time window; (e) marking the locations of the located EP landmarks on a map of the heart rendered on the display.

[0060] Example 2. The method of Example 1, wherein the reference timing is identified as the timing of a predetermined feature in the PQRST complex of the ECG signal.

[0061] Example 3. The method of example 1 or 2, further comprising determining a predetermined time window based on predetermined time reference data indicating at least one time interval during which the characterization signal feature should appear in the IEGM signal obtained from the located EP landmark.

[0062] Example 4. The method of example 3, wherein the predefined time reference data further includes data indicative of at least one of a shape, a frequency content, and an amplitude of the characterizing signal feature. Thus, determining whether the characterizing signal feature is manifested within the time window includes processing a portion of the IEGM signal to determine whether it includes a signal feature having at least one of a shape, a frequency content, and an amplitude that matches the time reference data.

[0063] Example 5. A method according to any one of Examples 1-4, utilizing a machine learning (ML) processor / model trained to determine whether an IEGM signal arises from a sought EP landmark.

[0064] Example 6. The method of example 5, wherein the ML processor is adapted to perform at least a portion of operation (d) (shown in example 1).

[0065] Example 7. The method of any one of Examples 1-6, further comprising recording at least one additional reference location of at least one additional spatial reference landmark within the heart, the method including determining an ROI based on at least a predetermined distance range relative to the first reference location and the at least one additional reference location.

[0066] Example 8. The method of any one of Examples 1-7, further comprising locating at least one additional located EP landmark by further performing operation (d) so long as the at least one electrode is within a second region of interest (ROI) determined based on at least one second predetermined distance range relative to at least one of the reference location and another reference location.

[0067] Example 9. The method of Example 8, wherein the location of the located EP landmark serves as another reference location relative to which a second ROI is determined for locating at least one additional located EP landmark.

[0068] Example 10. The method of example 8 or 9, wherein performing operation (d) to identify the location of the additional located EP landmark further includes determining a second predetermined time window during which a second characterizing signal feature of the additional located EP landmark should appear in a second IEGM signal obtained from the additional located EP landmark. The second predetermined time window is determined by the intersection of one or more time intervals based on predetermined time reference data indicating one or more time intervals during which the second characterizing signal feature should appear in the second IEGM signal.

[0069] Example 11. The method of Example 10, wherein the one or more time intervals include at least one of: a time interval relative to a reference timing; and a time interval relative to the timing of a characterizing signal feature of the searched EP landmark that has already been identified.

[0070] Example 12. The method of any one of Examples 1-11, wherein the EP landmark located is at least one of the bundle of His, right bundle, left bundle, crista terminalis, SA node, and AV node.

[0071] Example 13. A method according to any one of Examples 1-12, adapted to operate in real time during an intracardiac electrogram mapping procedure having a predetermined mapping path that traverses near one or more of at least a first spatial reference landmark within the heart.

[0072] Example 14. The method of Example 13, wherein the predetermined mapping path continues from the inferior vena cava (IVC) to the right atrium, identifying the His bundle, and then subsequently identifying the right and left bundles and the crista terminalis.

[0073] Example 15. The method of any one of Examples 1-14, wherein the EP mapping is performed using a catheter having one or more electrodes at its distal end capable of measuring IEGM signals.

[0074] Example 16. A method according to any one of Examples 1 to 15, further comprising providing a guide mark for directing the catheter to the ROI of the located EP landmark upon determining that at least one electrode is not within the ROI of the located EP landmark.

[0075] Example 17. A system for locating electrophysiological (EP) landmarks within the heart in real time during catheter-based electrophysiological mapping of a patient's heart. The system includes: (a) Tracking the location within the heart through which the distal tip of the catheter passes during electrophysiological mapping; (b) recording a reference location of at least a first spatial reference landmark within the heart; (c) determining a region of interest (ROI) for locating the searched EP landmark based on a predetermined distance range relative to at least a first spatial reference landmark; (d) As long as at least one electrode at the distal end is within the ROI: i) acquiring data indicative of an IEGM measured by at least one electrode synchronously with data indicative of an ECG signal; ii) determining a reference timing based on the ECG signal; iii) identifying a portion of the IEGM signal that is within a predetermined time window relative to a reference timing; iv) determining whether predetermined characterizing signal features of the sought EP landmark appear within the portion of the IEGM; v) identifying the location of at least one electrode as the location of the sought EP landmark upon determining that the characterization signal feature is present; and (e) one or more processors configured and operable to mark the locations of the located EP landmarks on a map of the heart rendered on the display.

[0076] Example 18. One or more processors perform the following steps to determine whether an IEGM signal results from a searched EP landmark: - determining a predetermined time window based on predetermined time reference data indicative of the characterizing signal feature, the predetermined time window having at least one time interval during which the characterizing signal feature should appear in the IEGM signal obtained from the located EP landmark, and processing a portion of the IEGM signal to determine whether the IEGM signal originates from the located EP landmark based on the occurrence of the predetermined characterizing signal feature within the portion; and -using a trained machine learning (ML) model to determine whether the IEGM signal originates from the searched EP landmark.

[0077] Example 19. One or more processors include: - determining at least one second region of interest (ROI) based on one or more second predetermined distance ranges within which additional searched EP landmarks are expected to exist relative to at least one of the reference location and another reference location; and - A system as described in Example 17 or Example 18, adapted to determine the location of at least one additional located EP landmark by performing operation (d) for determining the location of the additional located EP landmark (an operation similar to the operation shown in Example 17), as long as at least one electrode is within the second ROI.

[0078] Example 20. The location of the detected EP landmark serves as another reference location from which a second ROI for locating at least one additional detected EP landmark is determined; and 19. The system of claim 18, wherein, in performing operation (d) to identify the location of the additional located EP landmark, the one or more processors determine a second predetermined time window during which the second characterizing signal feature of the additional located EP landmark should appear in a second IEGM signal obtained from the additional located EP landmark. The second predetermined time window is determined based on one or more predetermined time intervals indicating an expected timing of the second characterizing signal feature relative to at least one of the reference timing and the timing of the previously identified characterizing signal feature of the located EP landmark.

[0079] Example 21. A system according to any one of Examples 17-20 adapted to carry out the method according to any one of Examples 1-16.

[0080] The above-described embodiments are cited by way of example, and it will be understood that the present invention is not limited to what has been particularly shown and described above. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described in the above specification, as well as variations and modifications thereof not disclosed in the prior art that would occur to one skilled in the art upon reading the foregoing description. Documents incorporated by reference into this patent application are to be considered an integral part of this application, provided that, to the extent that any term in these incorporated documents is defined in a manner that contradicts a definition expressly or implicitly made herein, only the definition herein shall be considered.

[0081] [Embodiment] (1) A method for locating electrophysiological (EP) landmarks in a patient's heart in real time during catheter-based electrophysiological mapping of the heart, comprising: (a) tracking locations within the heart through which the distal end of the catheter passes during the electrophysiological mapping; (b) recording a reference location of at least a first spatial reference landmark within the heart; (c) determining a region of interest (ROI) for locating the located EP landmark based on a predetermined distance range relative to the at least first spatial reference landmark; (d) so long as at least one electrode at the distal end is within the ROI; i) acquiring data indicative of an IEGM measured by the at least one electrode synchronously with data indicative of an ECG signal; ii) determining a reference timing based on the ECG signal; and iii) identifying a portion of the IEGM signal that is within a predetermined time window relative to the reference timing; and iv) determining whether predetermined characterizing signal features of the located EP landmark appear within the portion of the IEGM; v) identifying the location of the at least one electrode as the location of the located EP landmark upon determining that the characterizing signal feature appears within the time window; (e) marking the locations of the located EP landmarks on the map of the heart rendered on a display. (2) The method of embodiment 1, wherein the reference timing is identified as the timing of a predetermined feature in the PQRST complex of the ECG signal. (3) The method of embodiment 1, further comprising determining the predetermined time window based on predetermined time reference data indicating at least one time interval in which the characterization signal feature should appear in the IEGM signal obtained from the searched EP landmark. (4) The method of embodiment 3, wherein the predetermined time reference data further includes data indicating at least one of a shape, a frequency content, and an amplitude of the characterizing signal feature, and wherein determining whether the characterizing signal feature appears within the time window includes processing the portion of the IEGM signal to determine whether the portion includes a signal feature having at least one of a shape, a frequency content, and an amplitude that matches the time reference data. (5) The method of embodiment 1, utilizing a machine learning (ML) processor trained to determine whether the IEGM signal originates from the searched EP landmark.

[0082] (6) The method of embodiment 5, wherein the ML processor is adapted to perform at least a portion of operation (d). (7) The method of embodiment 1, further comprising recording at least one additional reference location of at least one additional spatial reference landmark within the heart, wherein the method comprises determining the ROI based on a predetermined distance range for the at least first reference location and a predetermined distance range for the at least one additional reference location. (8) The method of embodiment 1, further comprising: locating at least one additional located EP landmark by further performing operation (d) so long as the at least one electrode is within a second region of interest (ROI) determined based on at least one second predetermined distance range relative to at least one of the reference location and another reference location. (9) The method described in embodiment 8, wherein the location of the searched EP landmark serves as another reference location from which the second ROI for identifying the location of the at least one additional searched EP landmark is determined. (10) The method of embodiment 8, wherein performing operation (d) to identify the location of the additional located EP landmark includes determining a second predetermined time window within which a second characterizing signal feature of the additional located EP landmark should appear within a second IEGM signal obtained from the additional located EP landmark, the second predetermined time window being determined by an intersection of the one or more time intervals based on predetermined time reference data indicating one or more time intervals within which the second characterizing signal feature should appear within the second IEGM signal.

[0083] (11) The method described in embodiment 10, wherein the one or more time intervals include at least one of a time interval relative to the reference timing and a time interval relative to the timing of a characterizing signal feature of the already identified searched EP landmark. (12) The method of embodiment 1, wherein the EP landmark searched for is at least one of the His bundle, the right bundle, the left bundle, the crista terminalis, the SA node, and the AV node. (13) The method of embodiment 1, adapted to operate in real time during an intracardiac electrogram mapping procedure having a predetermined mapping path that traverses near one or more of the at least first spatial reference landmarks within the heart. (14) The method described in embodiment 8, wherein the predetermined mapping path continues from the inferior vena cava (IVC) to the right atrium, identifies the His bundle, and then subsequently identifies the right and left bundles to identify the crista terminalis. (15) The method of embodiment 1, wherein the EP mapping is performed using a catheter having one or more electrodes at its distal end capable of measuring the IEGM signal.

[0084] (16) The method of embodiment 1, further comprising providing a guide mark for directing the catheter toward the ROI of the searched EP landmark when it is determined that the at least one electrode is not within the ROI of the searched EP landmark. (17) A system for locating electrophysiological (EP) landmarks in a patient's heart in real time during catheter-based electrophysiological mapping of the heart, comprising: (a) tracking locations within the heart through which the distal end of the catheter passes during the electrophysiological mapping; (b) recording a reference location of at least a first spatial reference landmark within the heart; (c) determining a region of interest (ROI) for locating the located EP landmark based on a predetermined distance range relative to the at least first spatial reference landmark; (d) so long as at least one electrode at the distal end is within the ROI; i) acquiring data indicative of an IEGM measured by the at least one electrode synchronously with data indicative of an ECG signal; ii) determining a reference timing based on the ECG signal; iii) identifying a portion of the IEGM signal that is within a predetermined time window relative to the reference timing; iv) determining whether predetermined characterizing signal features of the located EP landmark appear within the portion of the IEGM signal; v) upon determining that the characterizing signal feature is present, identifying the location of the at least one electrode as the location of the located EP landmark; (e) a system comprising one or more processors configured and operable to mark the locations of the located EP landmarks on a map of the heart rendered on a display. (18) The one or more processors, to determine whether the IEGM signal originates from the located EP landmark, - determining the predetermined time window based on predetermined time reference data indicative of the characterizing signal feature, the predetermined time window having at least one time interval during which the characterizing signal feature should appear in the IEGM signal obtained from the located EP landmark, and processing the portion of the IEGM signal to determine whether the IEGM signal originates from the located EP landmark based on the occurrence of the predetermined characterizing signal feature within the portion; and - Utilizing a trained machine learning (ML) model to determine whether the IEGM signal originates from the searched EP landmark. (19) The one or more processors are adapted to locate at least one additional located EP landmark, whereby, to locate the at least one additional located EP landmark, the one or more processors: - determining at least one second region of interest (ROI) based on one or more second predetermined distance ranges within which the additional located EP landmark is expected to be located relative to at least one of the reference location and another reference location; - The system described in embodiment 17, wherein operation (d) is performed to identify the location of the additional searched EP landmark as long as the at least one electrode is within the second ROI. (20) - The location of the located EP landmark serves as the another reference location from which the second ROI for locating the at least one additional located EP landmark is determined; and - When performing operation (d) to identify the location of the additional located EP landmark, the one or more processors determine a second predetermined time window within which a second characterizing signal feature of the additional located EP landmark should appear in a second IEGM signal obtained from the additional located EP landmark, the second predetermined time window being determined based on one or more predetermined time intervals indicating the expected timing of the second characterizing signal feature relative to at least one of the reference timing and the timing of the characterizing signal feature of the located EP landmark as already identified.

Claims

1. 1. A system for locating electrophysiological (EP) landmarks in a heart in real time during catheter-based electrophysiological mapping of a patient's heart, comprising: (a) tracking locations within the heart through which the distal end of the catheter passes during the electrophysiological mapping; (b) recording a reference location of at least a first spatial reference landmark within the heart; (c) determining a region of interest (ROI) for locating the located EP landmark based on a predetermined distance range relative to the at least first spatial reference landmark; (d) so long as at least one electrode at the distal end is within the ROI; i) acquiring data indicative of an IEGM measured by the at least one electrode synchronously with data indicative of an ECG signal; ii) determining a reference timing based on the ECG signal; iii) identifying a portion of the IEGM signal that is within a predetermined time window relative to the reference timing; iv) determining whether predetermined characterizing signal features of the located EP landmark appear within the portion of the IEGM signal; v) upon determining that the characterizing signal feature is present, identifying the location of the at least one electrode as the location of the located EP landmark; (e) a system comprising one or more processors configured and operable to mark the locations of the located EP landmarks on a map of the heart rendered on a display.

2. The one or more processors may: - determining the predetermined time window based on predetermined time reference data indicative of the characterizing signal feature, the predetermined time window having at least one time interval during which the characterizing signal feature should appear in the IEGM signal acquired from the located EP landmark, and processing the portion of the IEGM signal to determine whether the IEGM signal originates from the located EP landmark based on the occurrence of the predetermined characterizing signal feature within the portion; and - utilizing a trained machine learning (ML) model to determine whether the IEGM signal originates from the located EP landmark.

3. The one or more processors are adapted to locate at least one additional located EP landmark, whereby to locate the at least one additional located EP landmark, the one or more processors: determining at least one second region of interest (ROI) based on one or more second predetermined distance ranges within which the additional located EP landmarks are expected to be located relative to at least one of the reference location and another reference location; The system of claim 1 , further comprising: performing an operation (d) for locating the additional located EP landmarks to the extent that the at least one electrode is within the second ROI.

4. - the location of the located EP landmark serves as the further reference location from which the second ROI for locating the at least one additional located EP landmark is determined; and - when performing operation (d) to identify the location of the additional located EP landmark, the one or more processors determine a second predetermined time window within which a second characterizing signal feature of the additional located EP landmark should appear in a second IEGM signal obtained from the additional located EP landmark, wherein the second predetermined time window is determined based on one or more predetermined time intervals indicating the expected timing of the second characterizing signal feature relative to at least one of the reference timing and the timing of the characterizing signal feature of the located EP landmark as previously identified.

5. 1. A method for locating electrophysiological (EP) landmarks in a patient's heart in real time during catheter-based electrophysiological mapping of the heart, comprising: (a) tracking locations within the heart through which the distal end of the catheter passes during the electrophysiological mapping; (b) recording a reference location of at least a first spatial reference landmark within the heart; (c) determining a region of interest (ROI) for locating the located EP landmark based on a predetermined distance range relative to the at least first spatial reference landmark; (d) so long as at least one electrode at the distal end is within the ROI; i) acquiring data indicative of an IEGM measured by the at least one electrode synchronously with data indicative of an ECG signal; ii) determining a reference timing based on the ECG signal; and iii) identifying a portion of the IEGM signal that is within a predetermined time window relative to the reference timing; iv) determining whether predetermined characterizing signal features of the located EP landmark appear within the portion of the IEGM; v) identifying the location of the at least one electrode as the location of the located EP landmark upon determining that the characterizing signal feature appears within the time window; (e) marking the locations of the located EP landmarks on the map of the heart rendered on a display.

6. The method of claim 5 , wherein the reference timing is identified as the timing of a predetermined feature in a PQRST complex of the ECG signal.

7. 6. The method of claim 5, further comprising determining the predetermined time window based on predetermined time reference data indicating at least one time interval during which the characterizing signal feature should appear in the IEGM signal obtained from the located EP landmark.

8. 8. The method of claim 7, wherein the predetermined time reference data further includes data indicative of at least one of a shape, a frequency content, and an amplitude of the characterizing signal feature, and wherein determining whether the characterizing signal feature appears within the time window includes processing the portion of the IEGM signal to determine whether the portion includes a signal feature having at least one of a shape, a frequency content, and an amplitude that matches the time reference data.

9. The method of claim 5 , utilizing a machine learning (ML) processor trained to determine whether the IEGM signal arises from the located EP landmark.

10. The method of claim 9 , wherein the ML processor is adapted to perform at least a portion of operation (d).

11. 6. The method of claim 5, further comprising recording at least one additional reference location of at least one additional spatial reference landmark within the heart, the method comprising determining the ROI based on a predetermined distance range for the at least first reference location and a predetermined distance range for the at least one additional reference location.

12. 6. The method of claim 5, further comprising: locating at least one additional located EP landmark by further performing operation (d) so long as the at least one electrode is within a second region of interest (ROI) determined based on at least one second predetermined distance range relative to at least one of the reference location and another reference location.

13. 13. The method of claim 12, wherein the location of the located EP landmark serves as the another reference location from which the second ROI for locating the at least one additional located EP landmark is determined.

14. 13. The method of claim 12, wherein performing operation (d) to identify the location of the additional located EP landmark includes determining a second predetermined time window within which a second characterizing signal feature of the additional located EP landmark should appear within a second IEGM signal obtained from the additional located EP landmark, the second predetermined time window being determined by an intersection of the one or more time intervals based on predetermined time reference data indicating one or more time intervals within which the second characterizing signal feature should appear within the second IEGM signal.

15. 15. The method of claim 14, wherein the one or more time intervals include at least one of a time interval relative to the reference timing and a time interval relative to the timing of a characterizing signal feature of a previously identified located EP landmark.

16. 6. The method of claim 5, wherein the located EP landmark is at least one of the bundle of His, the right bundle, the left bundle, the crista terminalis, the SA node, and the AV node.

17. 6. The method of claim 5, adapted to operate in real time during an intracardiac electrogram mapping procedure having a predetermined mapping path that traverses near one or more of the at least first spatial reference landmarks within the heart.

18. 13. The method of claim 12, wherein the predetermined mapping path continues from the inferior vena cava (IVC) to the right atrium, identifies the His bundle, and further subsequently identifies the right and left bundles to identify the crista terminalis.

19. The method of claim 5 , wherein the EP mapping is performed using a catheter having one or more electrodes at its distal end capable of measuring the IEGM signals.

20. 6. The method of claim 5, further comprising providing a guide mark for directing the catheter to the ROI of the located EP landmark upon determining that the at least one electrode is not within the ROI of the located EP landmark.

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