IL281311A - Analyzing and mapping ecg signals and determining ablation points to eliminate brugada syndrome - Google Patents

Description

1117-1623.1 FIELD AND BACKGROUND OF THE INVENTION

Claims (12)

CLAIMS CLAIMED IS:

1. A computer implemented method for determining target ablation areas of a heart, comprising: ing, over time, electrical signals for a plurality of areas of the heart; and generating an epicardial potential duration map for display by: calculating, for each electrical signal, a plurality of heart beats based on a heart beat cycle length and a reference point in time of one of the heart beats; assigning, for each heart beat of an electrical signal, a window of st (WOI) equal to an amount of time comprising at least the heart beat cycle length; for each WOI: determining a start potential duration and an end ial duration; calculating a potential duration value as the ence between the start potential duration and the end potential duration; and selecting the potential duration based on the potential duration values, wherein, when a selected potential duration of an electrical signal is r than or equal to a potential duration threshold, the area of the heart corresponding to the electrical signal is targeted for ablation.

2. The method according to claim 1, wherein generating the epicardial potential duration map further comprises determining another reference point in time of a prior heart beat according to an amount of 32 1117-1623.1 time from the reference point in time equal to the heart beat cycle length; and the prior heart beat is ated based on the heart beat cycle length and the other reference point in time.

3. The method according to claim 1, further comprising: performing epicardial on on the areas of the heart targeted for ablation; after performing the epicardial on, preparing an updated epicardial ial duration map and determining whether the updated epicardial potential duration map includes a displayed abnormality; and when the d epicardial potential duration map includes the abnormality, performing another epicardial ablation on an area of the heart corresponding to the displayed abnormality.

4. The method ing to claim 1, wherein the potential duration threshold is 200 ms.

5. The method according to claim 1, further comprising determining the start potential duration and the end ial duration for the epicardial potential duration map by determining peaks in the WOI which are equal to or greater than a peak threshold and fying the start potential duration as the start of the slope before a first determined peak and identifying the end potential duration as a second determined peak having a distance greater than or equal to 120 ms from the first determined peak.

6. The method according to claim 1, further comprising: Performing epicardial ablation on the area of the heart targeted for ablation; and 33 1117-1623.1 after performing the epicardial ablation, ing an updated epicardial potential duration map, n the epicardial potential on map, and the updated epicardial potential duration map include displayed concentric areas having a plurality of different f intervals.

7. A system for determining target ablation areas in a heart, comprising: a catheter for acquiring electrical signals for a plurality of areas of the heart; one or more processors configured to: generate an epicardial potential duration map for display by: calculating, for each electrical signal, a plurality of heart beats based on a heart beat cycle length and a reference point in time of one of the heart beats; assigning, for each heart beat of an electrical signal, a window of interest (WOI) equal to an amount of time comprising at least the heart beat cycle length; for each WOI: determining a start potential duration and an end potential duration; ating a potential duration value as the difference between the start potential duration and the end potential duration; and selecting the potential duration based on the ial on values, wherein, when a selected potential duration of an electrical signal is greater than or equal to a potential duration threshold, the area of the heart corresponding to the electrical signal is targeted for ablation; and 34 1117-1623.1 a y device for displaying the epicardial ial duration map.

8. The system according to claim 7, the one or more processors are further configured to: generate the epicardial potential duration map; by determining another reference point in time of a prior heart beat according to an amount of time from the reference point in time equal to the heart beat cycle length; and the prior heart beat is calculated based on the heart beat cycle length and the other nce point in time.

9. The system according to claim 7, the one or more processors are further configured to: control the catheter to perform dial ablation on the areas of the heart targeted for ablation; after performing the epicardial ablation, e an updated epicardial potential duration map and determine whether the updated epicardial potential duration map includes a displayed abnormality; and when the updated dial potential duration map includes the displayed abnormality, perform another epicardial ablation on an area of the heart corresponding to the displayed abnormality.

10. The system according to claim 7, wherein the potential on threshold is 200 ms.

11. The system according to claim 7, the one or more processors are further ured to, determine the start potential duration and the end potential duration for the epicardial potential duration map by determining peaks in the WOI which are equal to or greater than a peak threshold 35 1117-1623.1 and identifying the start ial duration as the start of the slope before a first determined peak and identifying the end potential on as a second determined peak having a ce greater than or equal to 120 ms from the first determined peak. 12. The system according to claim 7, wherein the one or more processors are further configured to: control the catheter to perform epicardial ablation on the area of the heart targeted for ablation; and after performing the epicardial ablation, prepare an updated epicardial ial duration map, wherein at least one of the epicardial potential duration map, and the updated dial potential duration map include displayed concentric areas having a plurality of different cut-off intervals. 13. A non-transitory computer readable storage medium comprising ctions for causing a computer to execute a method of determining target ablation areas of a heart, the instructions comprising: acquiring, over time, electrical signals for a plurality of areas of the heart; and generating an epicardial ial duration map for display by: calculating, for each electrical signal, a plurality of heart beats based on a heart beat cycle length and a reference point in time of one of the heart beats; assigning, for each heart beat of an electrical signal, a window of interest (WOI) equal to an amount of time sing at least the heart beat cycle length; for each WOI: 36 1117-1623.1 determining a start potential duration and an end potential duration; calculating a potential duration value as the difference between the start potential duration and the end ial on; and selecting the potential duration based on the potential duration values, wherein, when a selected potential duration of an electrical signal is greater than or equal to a potential duration threshold, the area of the heart corresponding to the electrical signal is ed for ablation. 14. The computer readable storage medium according to claim 13, the instructions further comprising: ting the epicardial potential on map by determining another nce point in time of a prior heart beat according to an amount of time from the reference point in time equal to the heart beat cycle length; and the prior heart beat is calculated based on the heart beat cycle length and the other reference point in time. 15. The computer readable storage medium according to claim 13, the instructions further comprising: performing epicardial ablation on the areas of the heart targeted for ablation; after performing the epicardial ablation, preparing an updated epicardial potential duration map and determining whether the updated epicardial potential on map includes a displayed abnormality; and when the updated epicardial potential on map includes the abnormality, performing another epicardial ablation on an area of the heart corresponding to the displayed abnormality. 37 1117-1623.1 16. The computer readable storage medium according to claim 13, the instructions r comprising determining the start potential duration and the end ial duration for the epicardial potential on map by determining peaks in the WOI which are equal to or greater than a peak threshold and identifying the start potential duration as the start of the slope before a first determined peak and identifying the end potential duration as a second determined peak having a distance r than or equal to 120 ms from the first determined peak. 17. The er readable storage medium according to claim 13, the instructions further comprising: performing epicardial ablation on the area of the heart targeted for ablation; and after performing the epicardial ablation, preparing an updated epicardial potential duration map, wherein the epicardial potential duration map, and the updated epicardial potential duration map include displayed concentric areas having a plurality of different cut-off intervals. 38 101 101 101 FIG. 1 Define WOI S201 S211 Peaks match NO Calculate previous heart beats END criteria? S202 Calculate Peaks YES For Each WOI: Create List S203 Obtain next Find PD peak with Define PD Start - check S212 minimum time from ing of WOI S204 Find start of slope S213 and mark as PD END S205 Peak match Criteria? NO PD = PD START - PD END S214 YES Set second peaks MARK as PD Select PD as heart beat as current peaks; S206 Start S207 S215 with minimum std dev obtain next peak S2 09 Peaks duration Define PD end - > 120ms? NO check from end S208 of WOI YES Mark start of PD end S210 FIG. 2 305 301 FIG. 3A 305 301 FIG. 3B 305 301 FIG. 3C 305 301 FIG. 4A 301 FIG. 4B 0.32 [mV] M MAP 1-2 MAP 3-4 1 | ' R F E N 15 0.58 v nt’ltl|““' . l- a; X. ’a I I \ " 'l ‘ III A a \ - ‘ll'l"‘ \\\ I _ I ‘ ‘III"! ; — s \ s \- ' a \ "5 a 'I lunch: 3 sec V6 -\ I . \ ‘ ...m1n... .....ullmlnulllI Iflll Start procedure Catheter Ablation of delimited areas S706 Endocardial bipolar/ S701 on RV mapping Repeat Ajmaline test S707 Epicardial bipolar/ S702 duration map BrS pattern reappearance? Y ES S708 Ajmaline infusion NO S703 S709 Epicardial duration remap Epicardial duration map S704 Abnormal er Ablation >200ms EGM YES YES of new abnormal areas NO identified? areas S711 S705 delimitation? S710 NO End procedure FIG. 7 'T' TDD' 'U' UOQ' UDD' UOD' UDQ' UDS' UDC' UDT' UOS' UOC' UOT' 1005 1007 15.00 SCI 226.00 V1 BASELINE 110.00 200.00 0.32 [mV] 1006 I Area ement M 210 MAP 1-2 Marked Area: 2.2 cm2 ( 1.2 x) II 0.33 [mV] 1002 Inverse Area Total Area: 172.8 cm3 MAP 3-4 III Perimeter: 6.6 cm 1.06 [mV] 1001 MAP 1 aVR 1004 aVL -50 0 sec 400 aVF V2 V1 II 0.32 [mV] 136 M V2 II L MAP 1-2 V1 III 0.32 [mV] V2 III 1003 MAP 3-4 V1 IV 1.46 [mV] MAP 1 V2 IV -50 0 sec 400 FIG. 10A 17.00 SCI 524.00 AJMALINE CHALLENGE V2 110.00 200.00 I Area Measurement 0.32 [mV] 200 M Marked Area: 21.5 cm2 (12.5%) II MAP 1-2 e Area 0.32 [mV] Total Area: 172.4 cm2 III Perimeter: 19.7 cm MAP 3-4 1001 1.00 [mV] aVR 1004 M AP 1 aVL 1002 -50 0 sec 400 aVF V2 V1 II 0.32 [mV] 219 V2 II M L MAP 1-2 V1 III 0.32 [mV] 1003 V2 III MAP 3-4 1.00 [mV] V1 IV MAP 1 V2 IV -50 0 sec 400 FIG. 10B 15.00 SCI 144.00 V1 POST ON 110.00 144.00 I 0.32 [mV] 27 M MAP 1-2 II 0.33 [mV] III MAP 3-4 1.48 [mV] aVR 1003 MAP 1 aVL -50 0 sec 400 aVF V2 V1 II 0.32 [mV] 36 V2 II M L MAP 1-2 V1 III 0.32 [mV] V2 III MAP 3-4 V1 IV 1.46 [mV] MAP 1 V2 IV 0 sec -50 400 FIG. 10C A B C 1101 1103 1101 1103 1103 1102 1102 1102 1101 v2 v2 v2 0.22 (wM) 320 0.22 (wM) 254 M) MAP 12 MAP 12 225 0.12 (wM) 0.22 (wM) MAP 14 MAP 14 0.32(wM) 1.00 (wM) 1.00 (wM) MAP 9 MAP 1 1.00 (wM) MAP 1 -50 404 -50 430 -60 400 FIG. 11 I 66.00 SCI 349.00 V1 V1 Area Measurement 0.32 [mV] 0.32 [mV] II Marked Area: 21.5/ cm2 110.00 200.00 M M III Inverse Area: rea: 175.1 cm2 1202 1201 0.33 [mV] 220 0.33 [mV] aVR Perimiter: 22.0 cm 12 02 220 aVL aVF MAP 1-2 MAP 1-2 V1 II V2 II V1 III 1.46 1.06 [mV] 1.06 [mV] V2 III V1 IV V2 IV AP PA LAO RAO -50 400 -50 400 FIG. 12 22.00 SCI 200.00 I II 140.00 200.00 III aVR 1301 aVL aVF 1302 V1 II 1303 V2 II V1 III R L V2 III 1.36 V1 IV V2 IV ABL prox ABL dist AP PA LAO RAO LL RL INF SUP RV apex 22.00 SCI 200.00 I 140.00 200.00 II III aVR aVL aVF 1303 V1 II V2 II R V1 III L V2 III 1.36 V1 IV V2 IV ABL prox ABL dist AP PA LAO RAO LL RL INF SUP RV apex FIG. 13 15.00 SCI 226.00 15.00 SCI 226.00 110.00 200.00 110.00 200.00 1401 L L V1 FIG. 14 V1 0.32 [mV] 210 M 0.32 [mV] M 210 MAP 1-2 M AP 1-2 0.33 [mV] MAP 3-4 0.33 [mV] M AP 3-4 1.06 [mV] 1.06 [mV] MAP 1 MAP 1 -50 0 s ec 400 -50 0 sec 400 '(.' '(/' '''' '(0' '''' 498 0 R BIO5743USCIP1 ANALYZING AND MAPPING ECG SIGNALS AND DETERMINING ABLATION POINTS TO ELIMINATE BRUGADA SYNDROME CROSS REFERENCE TO RELATED APPLICATION [0001] This application incorporates by reference as if fully set forth U.S. Patent Application Serial No. 15/854,492 filed on er 26, 2017 titled “A Method And System For ating A Broad Range Of Cardiac Conditions By Analyzing Intracardiac Signals, Providing A Detailed Map And ining Potential Ablation Points”. This application claims the benefit of U.S. Provisional Application No. 62/450,388, filed on January 25, 2017. This ation is a Continuation in Part of U.S. Patent Application No. 15/854,485, filed on December 26, 2017 which is incorporated by reference as if fully set forth. SUMMARY [0002] There is provided according to embodiments of a system and method that s improved analysis of electrocardiography (ECG) signals to eliminate Brugada syndrome. (BrS) The system and method can create a potential duration map (PDM) by automatically measuring duration of signals and annotating ventricular eletrogram (EGM) duration from onset to offset. [0003] The method of Brugada syndrome epicardial ablation may comprise ing an endocardial duration map, preparing a baseline epicardial duration map comprising at least one or more areas of delimination, and when some of the areas of delimination are greater than 200ms, performing dial ablation of the areas of delimination r than 200ms. The method may r comprise ing an updated epicardial duration map after performing epicardial ablation, and determining whether or not a BrS pattern appears in the updated epicardial duration map; and when the BrS pattern appears, performing epicardial ablation. The method may r -1- 5034572-1 BIO5743USCIP1 comprise preparing an updated dial duration map after performing epicardial ablation, and determining whether or not an abnormal EGM exists in the updated epicardial on map; and when the al EGM exists, performing epicardial ablation. The method may further comprise preparing an updated dial map comprising ining anatomical volume data and adding electroanatomical data. The method may further comprise the baseline epicardial duration map, and the updated epicardial map displaying concentric areas having cut-off intervals. The method may further comprise, in the step of ing a baseline epicardial duration map, defining a window of interest (WOI) comprising at least a cycle length, calculating previous heart beats based on the cycle length and nce annotation, assigning the heart beats within the cycle length of the WOI to the WOI, finding a start potential duration and an end potential duration, and selecting an ablation point based on a heart beat having a minimum standard deviation from the heart beats assigned to the WOI. [0004] The system for Brugada syndrome epicardial ablation in a heart may comprise a er for measuring ECG signals, a computer adapted to: prepare an endocardial duration map; prepare a baseline epicardial duration map comprising at least one or more areas of delimination; and when one or more of the areas of nation are greater than 200ms, performing epicardial ablation of the areas of delimination greater than 200ms; and a display device for displaying the endocardial duration map and the baseline epicardial map. The computer in the system may further be adapted to prepare an updated epicardial duration map after performing epicardial ablation, and determine whether or not a BrS pattern appears in the d epicardial duration map, and when the BrS pattern appears, perform epicardial on. The er in the system may further be adapted to prepare an updated epicardial duration map after performing epicardial ablation, and determine whether or not an abnormal EGM exists in the updated epicardial duration map, and when the abnormal EGM , -2- 5034572-1 3USCIP1 perform dial ablation. The system may further comprise a tool for ing ne into the heart. The computer in the system may further be adapted to prepare an updated epicardial map after performing dial ablation, sing maintaining anatomical volume data and adding electroanatomical data. The computer in the system may further be adapted to display concentric areas having cut-off intervals on the baseline epicardial duration map and the updated epicardial map. The er in the system may further be adapted to prepare the baseline epicardial duration map by performing steps of defining a WOI comprising at least a cycle length, calculating previous heart beats based on the cycle length and reference annotation, assigning the heart beats within the cycle length of the WOI to the WOI, finding a start potential duration and an end potential duration, and selecting an ablation point based on a heart beat having a minimum standard deviation from the heart beats assigned to the WOI. [0005] A computer program product for Brugada syndrome epicardial ablation is also presented. [0006] These and other objects, features and advantages of the present invention will be apparent from the following detailed description of illustrative embodiments f, which is to be read in connection with the accompanying gs. BRIEF DESCRIPTION OF THE DRAWINGS [0007] For a better understanding of the present invention, reference is made to the detailed description of the invention, by way of example, which is to be read in conjunction with the ing drawings, wherein like elements are given like reference numerals. [0008] FIG. 1 shows a Potential Duration Map (PDM). [0009] FIG. 2 is a flow diagram of an example method in an embodiment. -3- 5034572-1 BIO5743USCIP1 [0010] FIGs. 3A, 3B, 3C show Brugada syndrome concentric substrate distribution. [0011] FIGs. 4A, 4B show a PDM before and after radiofrequency ablation. [0012] FIG. 5 shows a ation of potential duration. [0013] FIG. 6 shows changes in BS ECG signal. [0014] FIG. 7 is a work flow diagram of a syndrome dial ablation in one embodiment. [0015] FIG. 8 shows an e g system for real-time mapping of cardiac ablation in ance with an embodiment, in which the inventive technique is used. [0016] Figure 9 is a block diagram illustrating example ents of a medical system in one embodiment. [0017] Figures 10A, 10B, 10C illustrate test results for one example patient. [0018] Figure 11 illustrates additional test results for one patient. [0019] Figure 12 shows a spontaneous type 1 Brugada pattern for one patient. [0020] Figure 13 shows RF ablation in spontaneous type 1 Brugada pattern for one patient. [0021] Figure 14 shows a PDM before and after RF ablation for an example patient. [0022] Figure 15 shows ECG changes for the example patient. [0023] Figure 16 shows a table of ablation results for the example patient. [0024] Figure 17 shows a table of electrophysiological characteristics of study population. DETAILED DESCRIPTION OF THE INVENTION [0025] Brugada syndrome (BrS) is an ECG abnormality with a high incidence of sudden death in patients with urally normal hearts. This syndrome or disorder is characterized by sudden death associated with one of several -4- 5034572-1 BIO5743USCIP1 ECG patterns characterized by incomplete right -branch block and ST- segment elevations in the anterior dial leads. [0026] BrS is a genetically determined disease predisposing to sudden c death due to ventricular malignant arrhythmias. A first aspect of the present system and method is treating Brugada syndrome by analyzing the EGM signals, determining the on points, and manually editing the calipers on the mapping catheter to set the duration. A second aspect of the present system is an example method, presented below, which enables ization of the abnormal substrate according to the EGMs’ duration found on the epicardial layer of BrS patients. [0027] Figure 1 shows a Potential Duration Map (PDM) (e.g., RV epicardial Map), in the center, a selected point viewer in the left column, and Paso viewer in the right column. The PDM uses a scale of Shortex x Interval (SCI) which ranges from 15.0 ms to 171.0 ms. The PDM is created using the present system to measure the Potential Duration for each point that the EGM automatically creates in accordance with the mapping method. The EGM shown in Figure 1, left side, includes MAP1-2 and MAP3-4, each having peaks 101 that indicate changes in direction of the gs of the mapping catheter. [0028] The example method is performed to visualize the al substrate according to the EGMs duration found on the epicardial layer of BrS patients. Using, for example, the Complex Fractionated Atrial Electrograms (CFAE) module of the CARTO®3 system (Biosense r), for each electroanatomical acquired point, two calipers are manually moved by g the first on the onset and the second on the offset of the EGM recorded. Note that CFAE performs calculations using the fragmentation in Bipolar EGM signal in the acquired point. The fragmentation is marked as -5- 5034572-1 BIO5743USCIP1 interval duration with left and right borders. The present method s in the exact ement of the ventricular EGM duration, enabling the creation of a PDM that may comprise a coded mapping, such as a color-coded map (color shown using different hatching patterns), g different degrees of prolongation. The appropriate characterization of the abnormal substrate along with the localization of such EGMs helps to establish the appropriate target for catheter ablation in order to achieve a successful procedure, and the PDM enables such characterization. [0029] As shown in Figure 1, the t system can be used to automatically annotate and measure EGM signals (as shown in the left panel) to create the PDM for a syndrome elimination by ablation. This system uses an annotation que to improve conventional software, such as CARTO®3, by automating the process of detecting where to ablate. [0030] Figure 2 is a flow diagram of an example method for automatically determining ablation points in Brugada syndrome. As shown in Figure 2, the method is performed as follows. [0031] In step S201, a Window Of Interest (WOI) is defined, the WOI being the interval in the EGM and/or ECG which is normally used to calculate the voltage amplitude (peak to peak mV) and the signal duration. An example EGM is shown in Figure 1. [0032] In step S202, at least two previous heart beats are calculated based on cycle length and reference annotation, and a WOI is assigned for two of the heart beats. Note that each oanatomical acquired point (e.g., point EGM) contains data to be used for coloring the Map according to Map Type, such as PDM, CFAE, LAT, Bipolar Voltage etc. Example maps are shown in Figures 10-14, (described hereinafter). In one acquired point, for example, a -6- 5034572-1 BIO5743USCIP1 window equal to 2500ms of ECG and EGM is recorded. For e, if the nce annotation for a heart beat lays at 2000ms, the first WOI [-50ms, 350ms] goes from 2000ms - 50ms (e.g., 1950ms) to 2000ms + 350ms (e.g., 2350ms). If the heart beat cycle length is 800ms, there is more than one heart beat in the 2500ms WOI. The previous heart beat reference lays at 1200ms (2000ms – 800ms [e.g., 1200ms]) and the WOI will be from 1200ms -50ms (e.g., 1150ms) to 1200ms + 350ms (e.g., 1550ms). It should be noted that the abovementioned time intervals have been used by way of example and should not be considered as limiting. [0033] Next, for each WOI of each heart beat, the Potential Duration is ated as shown in steps S203-211, as follows. [0034] In step S203, the peaks are calculated based on a predetermined threshold in WOI and a list of peaks in WOI are created. The EGM signal values are measured in mV, and, in one example, a peak with mV value greater than 0.05mV is . However, it should be noted that the peak threshold may be set by the physician. [0035] In step S204, Potential Duration Start (PD-Start) is defined by checking from the ing of the WOI, as shown in steps S205-S207 as follows. [0036] In step S205, it is determined whether or not two consecutive peaks have the same sign and the same peaks absolute values are less than 2 * Min. [0037] In step S206, if S205=YES (two consecutive peaks have the same sign and the absolute value of the consecutive peaks is less than 2*Min), the current peak is set as the second peak, the next peak is obtained and the method returns to step S205. -7- 5034572-1 BIO5743USCIP1 [0038] In step S207, if S205 = NO (two consecutive peaks do not have the same sign and/or the absolute value of the consecutive peaks is greater than or equal to 2*Min), the start of the slope before the current peak is found and marked it as Start potential duration. [0039] In step S208, Potential Duration End (PD-END) is defined, checking from the ending of the WOI, as shown in steps S209-S210 as follows. [0040] In step S209, it is ined whether or not two consecutive peaks’ distance is r than 120ms. [0041] In step S210, if S209=YES (two consecutive peaks are greater than 120 ms), the start of PD-End portion is marked as the peak with minimum time of the two consecutive peaks and the method returns to step S209. [0042] In step S211, if S209=NO (two consecutive peaks do not have distance greater than 120 ms), then in step S211, it is determined whether two consecutive peaks have the same sign and the peaks’ absolute values are less than 2*Min Threshold, whether the time between two consecutive peaks is greater than 120ms or whether the time n two utive peaks is less than 25ms. [0043] Keeping in mind that the stability and reproducibility of the duration of the potential can be a crucial , in one embodiment, the present technique can consider another factor; the technique can verify, in the ce of a double or late potential, that the late activity is also present in all the beats included in the 2500 ms recording window. [0044] In step S212, if S211=YES (two consecutive peaks have the same sign and the peaks’ absolute values are less than 2*Min, the time between two -8- 5034572-1 BIO5743USCIP1 consecutive peaks is greater than 120ms or the time between two consecutive peaks is less than 25ms), the next peak is obtained with minimum time, and the method returns to step S211. [0045] In step S213, if S211=NO (two utive peaks do not have the same sign, the peaks absolute values are equal to or r than 2*Min or the time between two consecutive peaks is less than or equal to than 120ms or the time n two consecutive peaks is greater than or equal to 25ms), the start of the slope after the current peak is found and marked as End Potential on. [0046] In step S214, the Potential on value is calculated as the difference between potential duration Start and potential duration End in ms. [0047] In step S215, the selected point potential duration value is set as the heart beat which has the minimum standard deviation of the positions on each heart beat WOI. Note that the area ement between the BS ECG IS when inducing the BrS and the BS ECG IS after treating the BrS can provide the indication of when to stop the procedure. [0048] In accordance with the PDM and the analysis described above, any EGM showing a duration ≥ 200 ms may be ered abnormal, and thus represents a target for catheter ablation. Three different concentric areas are identified according to the degree of prolongation by setting different cut-off intervals, for example, ≥ 300 ms, ≥ 250 ms and ≥ 200 ms, respectively. The different cut-offs are necessary to guide the ablation procedure, starting from the small ”core” of the substrate (area showing EGM duration ≥ 300 ms) and subsequently moving to the larger s having potential duration ≥ 250 ms and ≥ 200 ms, respectively, as shown in Figures 3A, 3B and 3C, described in more detail below. -9- 5034572-1 BIO5743USCIP1 [0049] The inventive technique may enable the elimination of all delayed and ged EGM activities located in the abovementioned regions. Class IC drug nge is performed at the end of ablation in order to ensure successful abolition of all al potentials and stable BrS-ECG pattern ation. In cases of BrS-ECG pattern reappearance after drug challenge, the epicardial PDM is a remap of the epicardial using PDM to identify target locations with PDM bigger than 200ms for ablation. This is repeated to identify any residual or additional abnormal signals for further RF applications in order to completely normalize the ECG pattern. The final end­ point, e.g., ablation point, is obtained by the ation and the non- inducibility of the BrS ECG pattern proved by the Class IC drug test and the abolition, using RF catheter ablation, of any prolonged and fragmented potential identified during the mapping procedure. [0050] Figures 3A, 3B and 3C show Brugada Syndrome concentric substrate distribution, that is, each of these figures show an epicardial PDM after Class IC drug-challenge. The maps are reconstructed by collecting the duration of each bipolar EGM. The color-code (shown as different hatching patterns) ranges from red 301 to purple 305, where red 301 is showing regions exhibiting less than 110 ms on. Purple 305 is representing areas with longer EGM duration (≥ 300 ms in Figure 3A, ≥ 250 ms in Figure 3B and ≥ 200 ms in Figure 3C). Additional colors (not shown) represent areas >110 ms to 300 ms. According to the different cut-off applied, a concentric distribution is shown, where the longest potentials (≥ 300 ms duration) are d in the inner circle (Figure 3A), whilst the relatively shorter ones, but still ≥ 200 ms, are in the outer circle (Figure 3C). The regions g longer ial duration have different dimensions (≥ 300 area is 5.9 cm2, ≥ 250 area is 14.7 cm2 and ≥ 200 ms area is 27.6 cm2, respectively). Below each map in Figures 3A, 3B, 3C, an example of the EGM recorded in the purple 305 area when the -10- 5034572-1 BIO5743USCIP1 coved-type pattern occurs after ajmaline test is shown (EGMs of 322 ms, 255 ms and 230 ms duration in each panel of Figure 3A, 3B, 3C, respectively). [0051] The QRS complex is a name for the combination of three of the graphical deflections seen on a typical electrocardiogram, e.g., EGM or ECG. QRS is usually the central and most visually obvious part of the tracing. It corresponds to the depolarization of the right and left ventricles of the human heart. In adults, deflections normally last 0.06–0.10 s; in children and during physical activity, it may be shorter. The Q, R, and S waves occur in rapid succession, do not all appear in all leads, and reflect a single event, and thus are usually considered together. A Q wave is any downward tion after the P wave. An R wave follows as an upward deflection, and the S wave is any downward deflection after the R wave. The T wave follows the S wave, and in some cases an additional U wave follows the T wave. The late activity is ed after the QRS termination and it is characterized by a fragmented and discrete late component. QRS represents simultaneous activation of the right and left cle. [0052] In each EGM panel shown in the lower portion of Figures 3A, 3B and 3C, V1 ECG lead, , proximal bipolar and unipolar signals are shown at 200 mm/sec speed, from top to bottom, respectively. [0053] The technique described herein will improve the existing process of manual measurements for duration map construction. The physician will no longer need to manually move and e the two duration calipers for each point taken during duration map reconstruction. By using the present method to ate each acquired point potential duration, the system can automatically annotate the ventricular EGMs duration from the onset to its offset, and automatically measure signals duration to create the PDM for a syndrome substrate characterization. -11- 5034572-1 BIO5743USCIP1 [0054] Moreover, the process of prolonged EGMs detection and their quantification in terms of potential duration is enhanced by the present technique. This approach creates PDM with objective annotation, correctly identifying the adequate ablation target areas. The system automatically acquires r and ial duration information by an ablation and/or multielectrode mapping (MEM) catheter to speed up the procedure. The method can be performed on two heart beats on the 2.5 seconds of the mapping bipolar signal of the acquired point, and the potential duration on the heart beat with the best positions stability can be selected. This enables positions stability to be considered in calculating potential duration, which cannot be done manually. [0055] Figures 4A and 4B show a PDM before and after RF ablation. Figure 4A top shows the PDM before ablation, while Figure 4A bottom shows an e of prolonged and fragmented potential found in the purple area 305 (distal bipolar EGM 255 ms duration “DP-EMG”). After ablation, Figure 4B top shows the PDM with the disappearance of abnormally prolonged EGMs, highlighting that the late component ation after the QRS – peaks above 0.05mV where Potential duration is bigger than 200ms) has been abolished (EGMs duration of 143 ms; Figure 4B bottom). The asterisk in Figure 4B bottom indicates the earance of the late components that had been recorded prior to ablation. The EGM showed in Figure 4B has been registered in the same region that was previously exhibiting the prolonged and fragmented potential, illustrated in Figure 4A. In each EGM panel, V1 II ICS ECG lead, distal, proximal r, and ar signals recorded are shown from top to bottom, respectively. Of note, in Figure 4A bottom, the V1 lead is showing a typical type pattern, whereas in Figure 4B bottom, the same ECG lead is trating that the BrS pattern has been modified, showing a horizontal and flat ST-segment elevation after ablation. -12- 5034572-1 BIO5743USCIP1 [0056] Figure 5 shows a calculation of Potential Duration which is marked by the two vertical lines or borders, R1 and R2. These borders indicate WOI[- 50,400] from 2000ms – 50ms (1950ms) to 2000ms + 400ms (2400ms). As shown, the Potential Duration is greater than 200ms. Around the dotted vertical line is the QRS; the late component appears in the right part of the Potential on marked with the two borders R1 and R2. [0057] Figure 6 shows changes in BS ECG signal, that is, the changes of the BS ECG Signals 601 when the BrS is induced, and the BS ECG Signals 602 after treating the BrS with ablation. Accordingly, ECG 602 refers to end of class IC drug injection and ECG 601 refers to end of RF ablation. [0058] Figure 7 is a work flow m of Brugada syndrome epicardial ablation. In step S701, endocardial bipolar/duration RV mapping is performed. In step S702, epicardial bipolar/duration g is performed, creating a baseline PDM as shown, for example, in Figure 1. In step S703, an ajmaline infusion is administered and an ajmaline test is performed. In step S704, an updated epicardial duration map, which maintains the FAM (anatomical volume) data and adds electro-anatomical data is produced. In step S705, it is determined whether or not there are areas of delimination, that is, areas in which the duration of potentials exceed a threshold amount, for example, a threshold greater than 200ms. If so YES), in step S806 catheter on of the ) of delimination is performed. In step S707, the ajmaline test is repeated; this test had been initially performed in step S703. [0059] In step S708, it is ined whether or not the BrS n reappears. If the BrS pattern does reappear (S708=YES), the procedure continues at step S704. If the BrS pattern does not ar (S708=NO), at -13- 5034572-1 BIO5743USCIP1 step S709, an updated epicardial duration re-map is created. In step S710, it is ined whether or not any abnormal EGMs are identified. If there are none (S710=NO), the ure ends. [0060] If one or more abnormal EGMs are identified (S710=YES), at step S711, catheter ablation of the new abnormal EGM areas is prepared and the process continues at step S709. [0061] If the areas of nation are less than or equal to 200ms (S705=NO), then the procedure ends. [0062] Figure 8 is an ration of an example medical system 800 that may be used to generate and display ation 52 (e.g., PDM and other maps and anatomical models of a portion of a patient and signal information). Tools, such as tool 22, can be any tool used for diagnostic or therapeutic treatment, such as for example, a catheter having a plurality of electrodes for g electrical potentials in a heart 26 of a patient 28. Alternatively, tools may be used, mutatis mutandis, for other therapeutic and/or diagnostic purposes of different portions of anatomy, such as in the heart, lungs or other body organs, such as the ear, nose, and throat (ENT). Tools may include, for example, probes, catheters, cutting tools and suction devices. [0063] An operator 30 may insert the tool 22 into a portion of patient anatomy, such as the vascular system of the patient 28 so that a tip 56 of the tool 22 enters a r of the heart 26. The control console 24 may use magnetic position sensing to determine 3-D position coordinates of the tool (e.g., coordinates of the tip 56) inside the heart 26. To determine the position coordinates, a driver circuit 34 in the control console 24 may drive, via connector, 44, field tors 36 to generate magnetic fields within the y of the patient 28. -14- 5034572-1 3USCIP1 [0064] The field generators 36 include one or more emitter coils (not shown in Figure 8), placed at known positions external to the patient 28, which are configured to generate magnetic fields in a predefined working volume that ns a portion of interest of the patient anatomy. Each of the emitting coils may be driven by a different frequency to emit a constant magnetic field. For example, in the e medical system 800 shown in Figure 8, one or more emitter coils can be placed below the torso of the patient 28 and each configured to generate magnetic fields in a predefined working volume that contains the heart 26 of the patient. [0065] As shown in Figure 8, a magnetic field location sensor 38 is disposed at the tip 56 of tool 22. The magnetic field location sensor 38 generates electrical s, based on the amplitude and phase of the ic , indicating the 3-D position coordinates of the tool (e.g., position coordinates of the tip 56). The electrical signals may be communicated to the control console 24 to determine the position coordinates of the tool. The electrical signals may be communicated to the control console 24 via wire 45. [0066] Alternatively, or in addition to wired communication, the electrical signals may be wirelessly icated to the control console 24, for example, via a wireless ication interface (not shown) at the tool 22 that may communicate with input/output (I/O) interface 42 in the control console 24. For example, U.S. Pat. No. 6,266,551, whose disclosure is incorporated herein by reference, describes, inter alia, a wireless catheter, which is not ally connected to signal sing and/or computing apparatus and is incorporated herein by reference. Rather, a transmitter/receiver is attached to the proximal end of the catheter. The transmitter/receiver communicates with a signal processing and/or computer apparatus using ss communication methods, such as IR, RF, Bluetooth, -15- 5034572-1 BIO5743USCIP1 or acoustic transmissions. The wireless digital interface and the I/O interface 42 may operate in accordance with any suitable wireless communication standard that is known in the art, such as for e, IR, RF, Bluetooth, one of the IEEE 802.11 family of standards (e.g., Wi-Fi), or the HiperLAN standard. [0067] Although Figure 8 shows a single magnetic field location sensor 38 disposed at the tip 56 of tool 22, tools may include one or more magnetic field location sensors each disposed at any tool portion. The magnetic field location sensor 38 may include one or more miniature coils (not shown). For e, a magnetic field location sensor may include multiple miniature coils oriented along different axes. Alternatively, the magnetic field location sensor may se either another type of magnetic sensor or position transducers of other types, such as impedance-based or ultrasonic location sensors. [0068] The signal processor 40 is configured to process the signals to determine the position coordinates of the tool 22, including both location and orientation coordinates. The method of position sensing described hereinabove is implemented in the CARTO™ mapping system produced by Biosense r Inc., of Diamond Bar, , and is bed in detail in the patents and the patent applications cited herein. [0069] The tool 22 may also include a force sensor 54 contained within the tip 56. The force sensor 54 may measure a force applied by the tool 22 (e.g., the tip 56 of the tool) to the endocardial tissue of the heart 26 and generate a signal that is sent to the control e 24. The force sensor 54 may include a magnetic field transmitter and a receiver connected by a spring in the tip 56, and may te an indication of the force based on measuring a deflection of the spring. Further details of this sort of probe and force sensor are bed in U.S. Patent ation Publications 093806 and 2009/0138007, whose disclosures are incorporated herein by reference. Alternatively, the tip 56 may include another type of force sensor that may use, for example, fiber optics or impedance measurements. -16- 5034572-1 3USCIP1 [0070] The tool 22 may also include an electrode 48 coupled to the tip 56 and configured to function as an impedance-based position transducer. Additionally or alternatively, the electrode 48 may be ured to measure a certain physiological property, for example the local e electrical potential (e.g., of cardiac tissue) at one or more locations. The electrode 48 may be configured to apply RF energy to ablate endocardial tissue in the heart 26. [0071] Although the example medical system 800 may be configured to measure the position of the tool 22 using magnetic-based sensors, other position tracking techniques may be used (e.g., impedance-based sensors). Magnetic position tracking ques are described, for example, in U.S. Pat. Nos. 5,391,199, 5,443,489, 6,788,967, 6,690,963, 091, 6,172,499 6,177,792, the disclosures of which are incorporated herein by reference. Impedance-based position tracking techniques are described, for example, in U.S. Pat. Nos. 5,983,126, 6,456,828 and 022, the disclosures of which are incorporated herein by reference. [0072] The I/O ace 42 may enable the control console 24 to interact with the tool 22, the body surface electrodes 46 and any other sensors (not shown). Based on the electrical impulses received from the body surface electrodes 46 and the electrical signals received from the tool 22 via the I/O interface 42 and other components of medical system 900, the signal processor 40 may ine the location of the tool in a 3-D space and generate the display information 52, which may be shown on a display 50. [0073] The signal processor 40 may be included in a general-purpose computer, with a suitable front end and interface circuits for receiving signals from the tool 22 and lling the other components of the control console 24. The signal processor 40 may be programmed, using software, to perform the ons that are described herein. The software may be downloaded to the l console 24 in electronic form, over a network, for example, or it may be ed on non-transitory tangible media, such as optical, magnetic -17- 5034572-1 BIO5743USCIP1 or electronic memory media. Alternatively, some or all of the functions of the signal processor 40 may be performed by ted or programmable digital hardware components. [0074] In the example shown at Figure 8, the control console 24 is connected, via cable 44, to body surface electrodes 46, each of which are attached to patient 28 using patches (e.g., indicated in Figure 8 as circles around the odes 46) that adhere to the skin of the patient. Body surface electrodes 46 may include one or more wireless sensor nodes integrated on a flexible substrate. The one or more ss sensor nodes may include a wireless transmit/receive unit (WTRU) ng local digital signal processing, a radio link, and a urized rechargeable battery. In addition or alternative to the patches, body surface electrodes 46 may also be positioned on the patient using articles worn by patient 28 which include the body surface electrodes 46 and may also include one or more position sensors (not shown) indicating the location of the worn article. For example, body surface electrodes 46 can be embedded in a vest that is configured to be worn by the t 28. During operation, the body surface electrodes 46 assist in providing a location of the tool (e.g., er) in 3-D space by detecting ical impulses generated by the polarization and depolarization of cardiac tissue and transmitting information to the control console 24, via the cable 44. The body surface electrodes 46 can be equipped with magnetic location ng and can help identify and track the respiration cycle of the patient 28. In addition to or alternative to wired communication, the body surface electrodes 46 may communicate with the control console 24 and one another via a wireless interface (not shown). [0075] During the diagnostic ent, the signal processor 40 may present the display information 52 and may store data representing the information 52 in a memory 58. The memory 58 may include any suitable le and/or non-volatile memory, such as random access memory or a hard disk drive. The operator 30 may be able to late the display information 52 using -18- 5034572-1 BIO5743USCIP1 one or more input devices 59. Alternatively, the medical system 800 may include a second operator that manipulates the l console 24 while the operator 30 manipulates the tool 22. It should be noted that the configuration shown in Figure 8 is exemplary. Any suitable configuration of the l system 800 may be used and implemented. [0076] Figure 9 is a block diagram illustrating example ents of a medical system 900 in which features described herein can be implemented. As shown in Figure 9, the system 900 es catheter 902, processing device 904, display device 906 and memory 912. As shown in Figure 9, the processing device 904, display device 906 and memory 912 are a part of computing device 914. In some embodiments, the display device 906 may be separate from computing device 914. Computing device 914 may also include an I/O interface, such as I/O interface 42 shown in Figure 9. [0077] Catheter 902 includes a plurality of er electrodes 908 for detecting the ical activity of the heart over time. Catheter 902 also includes sensor(s) 916, which include, for example, sensors (e.g., a magnetic field location sensor) for providing location signals to indicate the location of the catheter 902 in a 3-D space as well as sensors (e.g., position sensors, pressure or force sensors, ature sensors, impedance s) for providing ablation parameter signals during the ablation of the heart tissue. The example system 900 also includes one or more additional s 910, separate from the catheter 902, used to provide location signals indicating the location of the catheter 902 in a 3D space. [0078] The system 902 shown in e system 900 also includes an RF generator 918, which supplies high-frequency electrical energy, via er 902, for ablating tissue at locations engaged by the catheter 902. ingly, catheter 902 may be used to acquire electrical activity for generating mapping of the heart as well ablating cardiac tissue. As described above, however, embodiments may include catheters used to acquire the electrical -19- 5034572-1 BIO5743USCIP1 ty for generating mapping of the heart while not used to ablate cardiac tissue. [0079] sing device 904 may include one or more processors each configured to process the ECG s, record ECG signals over time, filter ECG s, fractionate ECG signals into signal components (e.g., slopes, waves, xes) and generate and combine ECG signal information for displaying the plurality of electrical signals on display device 906. Processing device 904 may also generate and olate mapping information for displaying maps of the heart on display device 906. Processing device 904 may e one or more processors (e.g., signal processor 40) configured to s the location ation acquired from sensors (e.g., additional sensor(s) 910 and catheter sensor(s) 916) to determine location and orientation coordinates. [0080] Processing device 904 is also configured to drive display device 906 to display c maps (i.e., spatio-temporal maps) of the heart and the electrical activity of the heart using the mapping information and the ECG data. Display device 906 may include one or more displays each configured to display maps of the heart representing spatio-temporal stations of the electrical activity of the heart over time and display the ECG signals acquired from the heart over time. [0081] The catheter electrodes 908, catheter sensor(s) 916 and additional sensor(s) 910 may be in wired or wireless communication with processing device 904. Display device 906 may also be in wired or wireless communication with processing device 904. [0082] The methods provided can be implemented in a general purpose computer, a processor, or a processor core. Suitable processors include, by way of example, a general purpose processor, a special purpose processor, a conventional processor, a digital signal processor (DSP), a plurality of microprocessors, one or more microprocessors in association with a DSP core, a controller, a microcontroller, ation Specific Integrated Circuits -20- 5034572-1 BIO5743USCIP1 (ASICs), Field Programmable Gate Arrays (FPGAs) circuits, any other type of integrated circuit (IC), and/or a state machine. Such processors can be manufactured by configuring a manufacturing process using the s of processed hardware description ge (HDL) instructions and other intermediary data including netlists (such instructions capable of being stored on a computer readable media). The results of such processing can be maskworks that are then used in a nductor manufacturing process to manufacture a processor which implements features of the disclosure. [0083] The methods or flow charts provided herein can be implemented in a er program, software, or firmware incorporated in a non-transitory computer-readable storage medium for execution by a general purpose computer or a processor. Examples of ansitory computer-readable storage s include a read only memory (ROM), a random access memory (RAM), a register, cache memory, semiconductor memory devices, magnetic media such as internal hard disks and removable disks, o­ optical media, and optical media such as CD-ROM disks, and digital versatile disks (DVDs). [0084] An example study employing the present method is presented. In this e study, a patient population is obtained comprising consecutive selected symptomatic ts diagnosed with type 1 BrS-ECG pattern either spontaneously or after ajmaline administration; each patient also had an ICD implanted. Ajmaline administration (1 mg/Kg in 5 minutes) was considered positive if the typical coved-type ECG pattern appeared in more than one right precordial lead ). [0085] Patients underwent a ed epi-endocardial g procedure (examples of mapping shown in Figures 10-15, described below). Under general anesthesia, an invasive arterial pressure line was obtained through radial artery access. The ECG was continuously recorded during the procedure. After femoral venous access, a olar diagnostic catheter was positioned at the RV apex. The epicardial access was gained by a -21- 5034572-1 BIO5743USCIP1 percutaneous subxyphoid access to the pericardial space, as is known in the art. Three dimensional RV endocardial and epicardial mapping, using CARTO®3, was performed in all patients during stable sinus rhythm and presence of type 1 BrS-ECG pattern. Epicardial mapping was systematically performed after endocardial mapping, in order to have adequate delimination of the RV boundaries when mapping the epicardium. Epicardial RV mapping and ablation catheter lation were assisted by a steerable sheath, such as Agilis EPI, St. Jude l, St. Paul, Minnesota. BrS epicardial substrate identification consisted in mapping the entire RV epicardial surface under baseline ions and after ajmaline infusion g in 5 minutes). Three groups of RV epicardial ograms properties are obtained using a CARTO®3 g system: 1) bipolar/unipolar voltage map, 2) local activation time map (LAT), and 3) potential duration map (PDM) in which abnormal long-duration r electrograms were defined as low-frequency (up to 100 Hz) ged duration (>200ms) bipolar signals with delayed activity extending beyond the end of the QRS complex. Figures 10-12, which are described below, rate this. The bipolar electrograms were filtered from 16Hz to 500Hz, displayed at a speed of 200 ms and were recorded between the distal electrode pair. Electrograms were excluded if their cal quality was insufficient or if catheter-induced extrasystoles occurred. [0086] Voltage mapping, in this example study is bed as follows. Color- coded electroanatomical voltage (not shown), activation (not shown) and duration maps (shown in Figure 10A, 10B, 10C using various hash patterns to indicate various colors) were performed and mposed to cardiac anatomy. Red color 1003 tes low-voltage dense scar that arbitrarily was defined as bipolar signal amplitude <0.5mV, while purple color 1001 indicates voltage areas >1.5mV. Areas of low voltage were identified using standard voltage cut-off values for dense scar (<0.5mV) and border zone (BZ) (<1.5mV). Electrograms below the 0.05mV threshold were not considered. -22- 5034572-1 BIO5743USCIP1 [0087] LAT mapping in this example study is described as follows. To study activation, the local activation time was assessed, d as the interval (in milliseconds) from a peak of QRS in lead II to the st negative change in voltage over time (dV/dt) of the intrinsic deflection in the r electrogram. Activation-duration was defined as the interval (in milliseconds) between the earliest activation time of any electrogram ation-start) and the latest tion time of any electrogram (activation-end). [0088] Potential Duration Mapping (PDM) in this example study is described as s. The maximum electrogram duration was the longest electrogram with continuous deflections t an intervening ctric line as recorded with a 0.45sec window of interest (WOI). Fractionation of electrograms was defined as the presence of more than two intrinsic deflections and expressed as number of intrinsic deflections per ogram. Electrogram duration was measured before and after ajmaline in the bipolar signal as the interval between the onset of the first and the offset of the last component of the electrogram, measured at the time scale of 200mm/sec, and expressed as mean bipolar electrogram duration (in milliseconds). A cut-off range from 100ms to 200ms, 250ms and 280ms was used for defining color- coded duration maps. As a result, a color-code map was obtained showing the regions ying the shortest (<110ms cut-off, red 1003) and the longest on (>200 ms cut-off, purple 1001), respectively. The degree of on of the potentials was displayed from the longest (purple 1001) to the shortest potential (red 1003) using different duration cut-off values (illustrated in Figures 10-14). According to the selected cut-offs, three different concentric circles were drawn around purple areas as shown in Figure 11. The PDM was med by collecting the duration of each bipolar electrogram using the CARTO®3 system. [0089] Substrate-based ablation in this example study is described as follows. Epicardial ablation was performed during sinus rhythm using a stepwise strategy in a descending order of abnormal potential duration as displayed on -23- 5034572-1 3USCIP1 the map and beginning from the longest ials. The t-duration potential area was displayed in purple by setting the color-bar upper limit (300ms) in the three-dimensional on map, as created simultaneously during voltage and LAT mapping. Afterwards, RF ablation was performed sequentially by gradually moving at substrate sites towards areas with less prolonged late (250ms and 200ms) potentials according to the stepwise gy. RF was delivered with an externally irrigated 3.5mm tip ablation catheter. A power control mode having from 35W up to 45W was used. The irrigation rate was in for RF on, which was delivered by a dragging strategy, up to complete elimination of all long-duration, delayed ty. [0090] Figure 15 shows BrS-ECG pattern changes during epicardial RF ablation that were analyzed by continuous ECG monitoring. The ST-segment cations were evaluated using a correlation software, such as PASO in CARTO®3. Immediate on endpoint was the elimination of all abnormally prolonged late activity with normalization of BrS-ECG pattern, as shown in Figure 15. [0091] Ajmaline was systematically re-infused after RF ablation to ensure abolition of all abnormal ventricular ials while confirming the BrS- ECG pattern elimination. In patients in whom the BrS-ECG pattern reappeared during infusion, epicardial duration maps were repeated to identify any residual or additional abnormal signals for further RF applications in order to definitively normalize the ECG pattern. Once a stable BrS-ECG pattern elimination was obtained, VT/VF inducibility was assessed. Intrapericardial liquid was permanently withdrawn through the deflectable sheet during the ure to avoid serum accumulation. [0092] The end-point of the example study was elimination of all abnormal electrical ventricular potentials before and after ajmaline, leading to ECG normalization and non-inducibility of ventricular tachycardia (VT) with respect to ventricular fibrillation (VF), e.g., VT/VF. -24- 5034572-1 BIO5743USCIP1 [0093] BrS was diagnosed in the presence of a coved-type ST elevation of >2mm as documented in more than one lead from V1 to V3 positioned in the second, third, or fourth ostal space. Because of the variable nature of the BrS-ECG pattern, BrS patients were classified according to their ECG at the time of the presentation and defined as spontaneous ECG pattern. Three BrS patient groups (BrS-1 to BrS-3) were d as coved-type (BrS-1), back ST configuration (BrS-2), and either type 1 or type 2 but with <2mm of ST segment elevation (BrS-3). BrS ts with typical BrS- related symptoms included those with documented VF or polymorphic VT at the time of symptoms. BrS patients without typical BrS-related symptoms were considered as patients with different symptoms (from dizziness to palpitations) without ECG documentation at the time of events but all with inducible VT/VF. Patients with the worst clinical presentation were defined as those who experienced cardiac arrest or syncope due to documented ventricular fibrillation. A proband was d as the first patient sed with Brugada syndrome in a family on the basis of a type 1 Brugada ECG pattern. Major complications were defined as those that required prolonged hospitalization. [0094] Procedural data in the example study e the following. The median procedure, fluoroscopy and RF application times were 169 minutes (Inter-quartil (IQR) 160-214, min-max 105-266), 8 minutes (IQR 7-9, min­ max 6-14) and 18 minutes (IQR 17-21, min-max 12-31), respectively. During the procedure, the tion, voltage and duration maps were successfully acquired during sinus rhythm and after ne-induced type 1 BrS-ECG pattern in all patients. At baseline, epicardial activation started in the lower septum/apex and subsequently diverged toward the tricuspid annulus and RVOT. As shown in Figures 10-14, for example, the red areas indicate short activation times while blue areas indicate longer activation times. No apparent tion block was observed in any patient. After ajmaline infusion, the epicardial tion time was ly longer without change in -25- 5034572-1 BIO5743USCIP1 the sequence activation pattern, but this difference was not statistically significant, as shown in the table in Figure 16. Overall, electro-anatomical voltage maps showed very small low-voltage areas in RVOT, which were larger in Group 1, ularly in patients with the worst clinical presentation than in Group 2 (P<0.001 as shown in Figure 16). Before and after ne, 3D epicardial duration maps displayed large areas of variable size with abnormally prolonged potentials in the RVOT, which contrasted with normal signals in the surrounding areas. [0095] Electrophysiological substrate characteristics according to spontaneous ECG pattern in the example study are as follows. Baseline al and ECG characteristics did not differ between the two groups including patients with the worst clinical presentation; spontaneous type 1 BrS-ECG pattern was less frequently found regardless of clinical presentation, as shown in the table in Figure 17. CARTO®3 maps fied epicardial areas of abnormal prolonged electrical signals over the RVOT (>75%) extending after ajmaline to RV free wall (see Figures 10-14). The area of electrical substrate significantly sed in size after ajmaline in both groups as shown in the table in Figure 16. Before and after ajmaline, Group 1 showed wider area and more prolonged and abnormal potentials than Group 2, although the increase in Group 2 was three times higher as compared with baseline values shown in the table in Figure 16. Of note, regardless of clinical presentation, before and after ajmaline the epicardial electrical substrate was larger in men than women. Areas with the longest abnormal potentials (>280 ms) in different RV regions appeared on color-coded maps to be smaller, ying a characteristic onion-like substrate of concentric circles showing in the center of the area with the widest electrograms (see Figure 11). [0096] Electrophysiological substrate teristics according to spontaneous ECG n in the example study are described as follows. There was no difference in clinical teristics between patients with and without spontaneous type 1 ECG pattern including age, sex, or family y of -26- 5034572-1 BIO5743USCIP1 sudden death of those less than 45 years old. Large abnormal areas and wider abnormal electrograms were found in patients with type 1 ECG pattern than in ts without. The localization of abnormal areas did not differ between patients with and without type 1 ECG pattern. Baseline ST segment elevation did not differ between Group 1 and Group 2, but after ne the increase was significantly higher in Group 1. Overall, after ajmaline the degree of type 1 ST-segment elevation correlated with the magnitude of the wider area (r=0.682, p<0.001). [0097] Substrate-based epicardial ablation in the example study can be described as follows. Once the areas targeted for ablation were established on the map of electrogram duration, RF started beginning on areas with the widest electrical potentials, which during ablation disappeared without significant change in voltage-amplitude after RF was turned off. Elimination of abnormal signals was med by remap and ajmaline reinfusion. Seventy-eight patients after ne reinfusion showed reappearance of suspicious coved ECG pattern ing further RF ablation to eliminate any residual abnormal potentials. Ablation at these sites eliminated the type 1 ECG pattern with successful ssion of VT/VF. Characteristically, during l delivery of RF energy on the t potential duration areas, the type 1 ECG pattern increased for some seconds, to progressively invert the ST segment slope from descending to ascending (see Figure 12), and the increase was higher in Group 1. Immediately after, there was a typical flat ST-segment elevation progressively ng ant in V1 and V2, which was not further modified by ajmaline and isoproterenol infusion. [0098] Figures 10-17 illustrate the example study. Note that different hatching patterns are used to show ent colors, e.g., color-coding, in Figures 10-15. Figures 10 and 11 illustrate a 39-year-old Brugada me (BrS) patient, presenting with a family history of BrS and syncope, who had -27- 5034572-1 BIO5743USCIP1 an ICD implantation. The t had positive ajmaline test and VT/VF inducibility during an electrophysiological study. [0099] Figure 10A shows baseline BrS-ECG pattern and epicardial color- coded duration CARTO® maps. A saddle-back pattern is evident in V2 (II intercostal space) with a corresponding small (2.2 cm2) purple area 1001 of abnormally prolonged potentials (210 ms in the example). The border-zone area (green/blue area 1002 greater than 110ms and less than 200ms) shows potentials with relatively r duration (136 ms). [00100] Figure 10B shows G pattern and color-coded duration maps after ne. After type 1 ne-induced ECG pattern, the abnormal purple area 1001 significantly increased to 21.5 cm2. es of abnormal and prolonged electrograms (EGMs) found in the purple area 1001 after ne test are shown beside the map (289ms and 219ms). [00101] Figure 10C shows BrS-ECG pattern and color-coded duration maps after RF ablation of epicardial substrate. After ajmaline re-challenge at the end of the procedure, the ECG showed a horizontal and ant ST- segment elevation, with minimal intraventricular conduction delay characterized by slight QRS broadening with a more pronounced S wave in leads I and II and qR morphology in a VR. Abnormally prolonged fragmented and delayed EGMs disappeared (87ms and 96ms, light-blue color 1004). [00102] The two examples of ventricular EGMs shown on the right side of Figures 10A, 10B and 10C (one above the other) were recorded from the previously abnormal area, and the red asterisks indicate disappearance of the late components. The two EGM panels in each of Figures 10A, 10B and 10C are from the CARTO®3 system and each ECG panel shows V2 ECG lead (top), distal (second from top), proximal bipolar (third from top) and ar -28- 5034572-1 BIO5743USCIP1 (bottom) signals at a speed of 200 ms. Of note, in Figure 10B, V2 lead shows a typical coved-type pattern, which after on was modified into a horizontal and flat ST-segment ion. [00103] Figure 11 shows a Potential Duration Map and Concentric ‘Onion-like’ ate. This is the same patient as in Figure 10. The epicardial map shows a concentric ‘onion-like’ substrate distribution after ajmaline. White lines delimitate multiple areas exhibiting electrograms (EGMs) with different duration (≥300 panel A, ≥250 panel B, and ≥200 ms panel C). Areas with the longest potential on (≥300 ms) are in the inner circle (panel A), while relatively shorter areas (≥250 and ≥200 ms) are in the outer circle (panels B and C). In Figure 11, red regions 1101 represent areas with EGM potential duration ≤110 ms. Below each map, there is an example of the EGM recorded in the purple area 1102 (320 ms duration in panel A, 264 in B and 225 in C, respectively). Each EGM panel from the CARTO® system shows V2 ECG lead (top), distal d from top), proximal bipolar (third from top) and unipolar (bottom) signals at speed of 200 ms speed. [00104] Figure 12 shows spontaneous type 1 Brugada pattern. The figure refers to a 32-year old patient with spontaneous type 1 Brugada pattern implanted with an ICD due to history of frank syncope without prodromes and an electrophysiological study (EPS) positive for VT/VF induction. In the left panel, the 12-lead ECG with precordial leads placed in V1 and V2 at higher intercostal spaces (II, III and IV ICS) shows typical type 1 a n particularly evident in V1 and V2 II ICS and in V1 III ICS. The middle panel of Figure 12, shows the epicardial PDM in which the purple area 1201 exhibits long duration potentials (≥200 ms; dimensions 21.5 cm2). The two right panels show two examples of electrograms (EGMs) found in the most nted and prolonged region (purple area 1201). Of note, typical EGM of wide duration with low voltage and fragmented delayed -29- 5034572-1 BIO5743USCIP1 components are shown in the distal bipolar (second line from top) signal, 320 and 280 ms duration, respectively). In each EGM panel, V1 and V2 II ICS ECG lead (top), distal (second from top), proximal bipolar (third from top) and unipolar (bottom) signals are shown at speed of 200 ms. [00105] Figure 13 shows RF ablation in spontaneous type 1 Brugada pattern, using the same patient as in Figure 12. The top left panel shows the PDM with white circles 1301 tating the areas exhibiting ials duration ≥300 ms (inner circle) and ≥200 ms (outer circle). RF ablation in the inner circle (red dots 1302) determined initial ascending and ntal ST- segment elevation in the high right precordial leads, shown in the top panel on the right, box 1303. In the left bottom panel, the complete set of lesions has been delivered in the whole area ≥200 ms ing in persistent horizontal and flat ST elevation in the right precordial leads, which are not showing the a type 1 pattern at the end of ablation (right bottom panel, red box 1303). [00106] Figure 14 shows a PDM before and after RF ablation, using the same patient as in Figure 12. The left-top panel shows the PDM before ablation. The left-bottom panel shows an example of a wide and nted potential discovered in the purple area 1401 (distal bipolar EGM 320 ms duration). After ablation, the PDM in the right-top panel shows the disappearance of ally prolonged EGMs, highlighting that the late component has been abolished by ablation (EGM duration 69 ms, right­ bottom panel, red asterisk). The EGM showed in the right-bottom panel has been recorded in the same region that had previously exhibited the prolonged and fragmented potential illustrated in the left-bottom panel. The on catheter shadow in both CARTO® maps indicates the location where such ials have been recorded. In each EGM panel, (bottom left and right) V2 II ICS ECG lead (top), distal (second from top), proximal bipolar (third from -30- 5034572-1 BIO5743USCIP1 top) and unipolar (bottom) signals are shown at speed of 200 ms. Of note, in the left-bottom panel, the V2 lead is showing typical coved-type n, whereas in the right-bottom panel, the same ECG lead is trating that the Brugada pattern has been modified, showing a horizontal and flat ST segment elevation after ablation. ] Figure 15 shows ECG changes immediately after ablation and en months following the procedure, using the same patient as in Figure

12. The top panel shows the acute disappearance of the type 1 pattern after RF ablation of the area showing fragmented and prolonged potentials. On the left, the baseline Brugada ECG is followed by the disappearance of the type 1 n immediately after ablation (top-middle , proved by the final ajmaline challenge ed at the end of the procedure (top-right panel). The high right precordial leads show horizontal and flat ment ion that ears during the follow-up (bottom panel). The bottom panel shows the persistent disappearance of Brugada type 1 pattern, proved by ajmaline challenge thirteen months after ablation. Ajmaline infusion determines PR interval prolongation with QRS broadening and slight ST segment horizontal elevation without the morphological characteristics of the coved-type ECG. From left to right, baseline 12-leads ECG, ECG with high right precordial leads at baseline and after ajmaline administration are shown. [00108] It will be appreciated by persons skilled in the art that the present teachings are not limited to what has been particularly shown and described herein. Instead, the scope of the present teachings include both combinations and sub-combinations of the various features described herein, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description. -31- 5034572-1