**3. Electrophysiological study and mapping: identification of functional substrate**

electroanatomic mapping and RFA. One month before of mapping and RFA, 10 patients accepted the implant of an ICD with class IIa indication [9]. **Table 1** shows the clinical characteristics of the study patients. About 13 patients with spontaneous type 1 ECG BrS pattern, symptomatic by syncope without prodromes, and VF induced during programed ventricular stimulation (PVS) were enrolled and completed the study protocol. Five males (38.5%) and eight females (61.5%), with an average age of 38.7 ± 12.3 years (range 19–58 years) were enrolled. Most patients (54%) had a family history of SCD and all patients experienced previous syncopal episodes without prodromes. In four patients (31%) nocturnal agonal respiration and family history of ECG 1 BrS pattern were evident. All patients had a VRP ≤ 200 m (180 ± 13.6 ms). A QRS complex duration >120 ms in V1 or V2 leads (129.6 ± 27 ms) in six patients (46%) and a R wave with an amplitude ≥3 mm in aVR lead during flecainide testing (3 ± 1.4 mm) in seven patients (54%) was found. In five patients (38.5%) a HV interval to DI lead >55 ms (53.4 ± 21 ms), in three patients a QRS fragmentation (23%) and in two patients a J wave (15.4%) were present. Interestingly, during bipolar mapping after premature ventricular contractions (PVCs), alter-

nating T and J-wave and changes of the ST segment elevation were found (**Figure 2**).

and without arrhythmias in the ICD interrogation [19].

(red arrows) [19].

124 Cardiac Arrhythmias

Syncope constitutes an important diagnostic and therapeutic challenge in BrS. Approximately one-third of BrS patients present syncope. Some cases of syncope may be related to VF that terminates spontaneously. Vagal syncope is probably the most frequent cause of syncope in the BrS [21] and vagal hypertony may facilitate the onset of spontaneous VF in BrS [22]. Also symptoms suggesting of vagal syncope may also be observed in syncope of cardiac origin [23]. In our study, two patients (15%) after RFA had near-syncope with vaso-vagal prodrome

**Figure 2.** Endocardial mapping. A. The N° 3 patient in the peripheral zone of substrate show middle diastolic, presystolic and continuous EGMs. The split pre-systolic potential (red arrows) triggers PVC (red star). B. After PVCs (red star), alternating T and J wave are shown (electric turbulence). Also displays spontaneous ST segment elevation changes Nademanee et al., found prolonged and fractionated late potentials in the anterior zone of epicardium of RVOT [17]. Recently, Brugada et al. in 14 inducible patients reported abnormal EGMs only in epicardium of the anterior free wall of right ventricle and in RVOT [18]. However, consistently we find a substrate in the endocardium of RVOT and RFA eliminates abnormal EGMs, ECG BrS pattern and inducibility during a median follow-up of 44.7 ± 15.5 months in 13 patients. We saw the substrate not only in the anterior zone of RVOT but also in septal and lateral regions, but never in the posterior region [19]. Sunsaneewitayakul et al. reported late depolarization zones on the endocardial of RVOT. Endocardial RFA about these zones modified the ECG BrS pattern and suppress the VF storm [16]. Similarly, we reported areas with late depolarization, diastolic electrical activity and abnormal systolic EGMs. In our study high-density detailed endocardial electroanatomical and bipolar voltage mapping of right ventricle and RVOT was performed, using 3-dimensional (3D) mapping system En Site NavXTM under local anesthesia and sedation, during stable sinus rhythm [19]. AH and HV interval to DI and V2 lead and ventricular refractory period (VRP) were measured. Bipolar EGMs were filtered from 10 to 400 Hz and displayed at 100–200 mm/s speeds. Systolic EGMs with an amplitude ≤1.5 Mv, split or fractionated whit a duration >80 ms and delayed components extending beyond the end of QRS complex and accompanied by late potentials (LPs) were defined as abnormal. The EGMs found in the diastole were referred as "diastolic electrical activity". The number of diastolic EGMs (separated by isoelectric line) in two successive sinus cycles was counted. PVS of RVOT with 3 cycle lengths (600, 500 and 400 ms) and up to two premature extrastimuli was performed. Premature extrastimuli was decreased in 20 ms step until a coupling interval of 200 ms or the VRP was reached or VF lasting >10 seconds was induced. The induction with PVS up to two premature beats is independent predictors of poor prognosis with a high negative predictive value and was associated with increased risk, but has a controversial prognostic value. The lack of induction does not necessarily portend a low risk and hence clinical factors are the most important determinants [6, 20, 25, 26]. VF inducibility rate is highest in patients with BrS and syncope of unknown origin (80%), the lowest in asymptomatic patients (61.5%), and intermediate in patients with vasovagal syncope (70.5%) [26–29]. However, it is important to note that these observations correspond to the pre-ablation era of BrS and therefore, the PVS could be a good predictor of outcome after RFA [18]. In our patients the endocardial RFA of diastolic electrical activity and abnormal systolic EGMs suppressed the type 1 ECG BrS pattern and inducibility with PVS, making the patients asymptomatic, as was previously reported for the epicardial RFA [17, 18].

We identified three zones of substrate according to amplitude of the systolic EGMs: central very low voltage zone <0.5 mV, peripheral low voltage zone of 0.5–1.5 mV (border) and normal voltage zone >1.5 mV [19]. The central zone of substrate using filling scaling was measured in mm2 and located in the RVOT. Areas showing low-amplitude signals were mapped with greater point density. Abnormal endocardial electroanatomic voltage maps, characterized by very low-voltage EGMs with clean diastoles in the central area of substrate were found. Only three patients (23%) during bipolar mapping showed fragmented systolic EGMs of low-voltage (≤ 1.5 mV) with duration greater of 80 ms between central and peripheral zone (border zone) of voltage mapping. As shown in **Figure 3**, only in the peripheral zone of substrate the endocardial diastolic EGMs (mean 6.7 ± 1.4 EGMs in two successive sinus cycles) were present. Overall, the median baseline very low voltage or central area of substrate (≤ 0.5 mV) was 14.2 mm2 (SD = 10.5) (**Table 1**).

It is important to note, that epicardial mapping may not recognized a substrate located in the septal zone of RVOT. In addition, during epicardial mapping the interposition of fat tissue between the epicardium and the exploratory catheter could decrease the amplitude of the potentials recorded, giving false areas of low voltage. Our study only inclusion 13 patients and may be considered a small size sample [19]. However, our results are consistent allowing us to reach reliable conclusions. We not performed genetic studies. However, it is unlikely that this could affect our observations because mutations have been described in over 24 genes and BrS-susceptibility genes can only partially explain the clinically diagnosed cases.

**Figure 3.** Endocardial electroanatomic maps and location of abnormal EGMs. Double systolic EGMs, late potentials, middle diastolic potentials and continuous diastolic activity in peripheral zone that triggers PVCs is displays. Prolonged and fragmented systolic EGMs of low voltage in border zone in three patients can be observed. In the central zone of substrate observe clean diastole with very low-voltage systolic potentials. The N°3 patient displays single and split presystolic potentials in peripheral zone of substrate which triggers PVCs [19].

**Patient**

Age

Sex

Spontaneous type 1 ECG pattern

Syncope without prodromes

Nocturnal agonal respiration

Palpitations Family history SCD

Family history BrS

VRP ≤ 200 ms QRS duration in V2 lead (> 120

R wave in aVR lead (≥ 3

QRS fragmentation

J wave HV interval to DI lead (>55

HV interval to V2 lead (>55

Follow-up (months)

CDI implant

Biopsy Very low-voltage AREA(≤ 0.5

N° endocardial diastolic EGMs IN 2

successive cycles sinus (≥4 EGMs)

Procedure time (min)

Fluoroscopy time (min)

M = male, F =

Source: Ref. [19].

**Table 1.**

Basal characteristic and risk factors.

female, SD =

standard deviation, (#)

 =

during flecainide test, VRP

 =

ventricular refractory period.

120 95

105 95

170

112 13.7

5.5

127

24.5

http://dx.doi.org/10.5772/intechopen.75932

mV) in (mm2

) 23 8

8

8

5

7

7

9

6

6

9

6

6

7

4

13

100%

19 42 5

4

8

25 4

13

100%

14.2 mm2 10.5

Endocardial Approach for Substrate Ablation in Brugada Syndrome

6.7

1.4

 ms)

 ms)

 mm) (#)

 ms)

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 13 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 13

No No No No Yes No Yes No Yes No No Yes No 4

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 13

No No Yes Yes Yes No No Yes Yes Yes Yes No No 7

No Yes No No No No No No Yes Yes Yes No No 4

3 No Yes No No No No No Yes No No No No Yes 3

No No No No No No Yes No No No Yes No No 2

60 57 40

No Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes No 10

No No No No No No No No No No Yes No Yes 2

4.5 2

2.5 1.5 1

4

4

1.5 6

3

4

1

7

54% 23%

15.4%

38.5%

7.7% 100%

77%

15%

53.4 ms 44.8 ms

44.7

15.5

11.5

21

3 mm

1.4

**1**

M

F

F

M

F

M

M

F

F

M

F

F

F

F = 8 M = 5 F =

61.5%-M = 38.5%

100%

100%

31%

100%

54%

31%

100%

46%

180 ms 129.6 ms 27

13.6

**2**

**3**

**4**

**5**

**6**

**7**

**8**

**9**

**Total**

**%**

**Mean**

38.7

12.3

**SD**


We identified three zones of substrate according to amplitude of the systolic EGMs: central very low voltage zone <0.5 mV, peripheral low voltage zone of 0.5–1.5 mV (border) and normal voltage zone >1.5 mV [19]. The central zone of substrate using filling scaling was measured

greater point density. Abnormal endocardial electroanatomic voltage maps, characterized by very low-voltage EGMs with clean diastoles in the central area of substrate were found. Only three patients (23%) during bipolar mapping showed fragmented systolic EGMs of low-volt

age (≤ 1.5 mV) with duration greater of 80 ms between central and peripheral zone (border zone) of voltage mapping. As shown in **Figure 3**, only in the peripheral zone of substrate the

ent. Overall, the median baseline very low voltage or central area of substrate (≤ 0.5 mV) was

It is important to note, that epicardial mapping may not recognized a substrate located in the septal zone of RVOT. In addition, during epicardial mapping the interposition of fat tissue between the epicardium and the exploratory catheter could decrease the amplitude of the potentials recorded, giving false areas of low voltage. Our study only inclusion 13 patients and may be considered a small size sample [19]. However, our results are consistent allowing us to reach reliable conclusions. We not performed genetic studies. However, it is unlikely that this could affect our observations because mutations have been described in over 24 genes and BrS-susceptibility genes can only partially explain the clinically diagnosed cases.

**Figure 3.** Endocardial electroanatomic maps and location of abnormal EGMs. Double systolic EGMs, late potentials, middle diastolic potentials and continuous diastolic activity in peripheral zone that triggers PVCs is displays. Prolonged and fragmented systolic EGMs of low voltage in border zone in three patients can be observed. In the central zone of substrate observe clean diastole with very low-voltage systolic potentials. The N°3 patient displays single and split pre-

systolic potentials in peripheral zone of substrate which triggers PVCs [19].

and located in the RVOT. Areas showing low-amplitude signals were mapped with

± 1.4 EGMs in two successive sinus cycles) were pres



in mm 2

126 Cardiac Arrhythmias

14.2 mm 2 (SD

endocardial diastolic EGMs (mean 6.7

= 10.5) (**Table 1**).

**Table 1.** Basal characteristic and risk factors.

Endocardial Approach for Substrate Ablation in Brugada Syndrome http://dx.doi.org/10.5772/intechopen.75932 127 Although the results of mapping and RFA were good, we do not perform epicardial mapping and do not ignore the possibility that a portion of the substrate can remain present after ablation.

In addition, we found pre-systolic potentials as was previously reported by Haissaguerre et al. [15]. We showed with TEM Purkinje fibers in RVOT (**Figures 2** and **3**) [19]. These could be involved in the origin of pre-systolic potentials and genesis of early-onset PVCs that can trigger VT or VF, by spontaneous depolarization or micro-reentry circuit in the Purkinje network [30].
