**5. Effects of RFA on the ECG BrS pattern and substrate**

Simultaneously, TDT and RDT were prolonged, because early depolarization of RVOT occurs. (2) When the substrate was located only in the anterior part (30.8%), or anterior-septal (15.4%) or exclusively in the septal region (15.4%) of RVOT, the HV interval measured to DI and V2 leads showed no increase in its duration (mean 42.6 ± 6 ms and 41 ± 6.5 ms, respectively) and the widening of QRS was only rightward (widening QRS rightward). Moreover, the endocardial EGM of RVIT and RVOT, and beginning of QRS complex in DI-V1-V2 lead they were activated simultaneously, indicating that there is no RDT delay, while TDT of RVOT was pro-

**Figure 5.** Location of substrate in transverse plane of RVOT. A. The N°4 patient displays a substrate located in the anterior-lateral zone of RVOT which corresponds to a widening of QRS complex to left and right. The HV interval to DI lead is longer (120 ms) that the HV interval to V2 lead (80 ms), while RDT and TDT are prolonged. B. The N°11 patient displays a substrate located in the septal zone of RVOT which correspond only to a widening of end QRS complex. The

Was report that 11% of patients with BrS have early repolarization pattern in the inferior-lateral leads and a more severe phenotype [32]. Interestingly, as shown in **Figure 6** we found in two patients who had a substrate of exclusively septal location, showed end-QRS notching or slurring pattern. When the substrate was located in the bottom-septal zone of RVOT (patient N°7) only end-QRS notch in aVL lead and slurred S-wave in DII, DIII and a VF leads was observed (**Figure 6-A**). Whereas, when the substrate was located in the top-septal zone of RVOT (patient N°11) an end-QRS slur in DI and aVL leads was observed (**Figure 6-B**). Our observations suggest that a location of substrate in septal region of RVOT, with beginning of the depolarization at the

longed of dynamic manner. We defined this as "end delay depolarization of RVOT".

HV interval to DI and V2 leads is equal (55 ms) and only TDT is prolonged [19].

132 Cardiac Arrhythmias

Endocardial and epicardial RFA has been proposed as a new strategy to prevent SCD and VT/VF in BrS patients of high risk. Nademanee et al. found what RFA on prolonged and fractionated late potentials in the anterior zone of epicardium of RVOT normalized the ECG BrS pattern and prevented VT/VF in all but one patient during a follow-up of 20 ± 6 months [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. RFA eliminated both ECG BrS pattern and inducibility, with a median follow-up of 5 months [18].

areas with late depolarization, diastolic electrical activity and abnormal systolic EGMs [19]; probably by substrate homogenization and transmural lesion of the thin wall of RVOT (mean 3 mm). In addition, as show **Figures 2** and **3** we found pre-systolic potentials as was previously reported by Haissaguerre et al. [15]. In our patients the endocardial RFA of these poten-

Endocardial Approach for Substrate Ablation in Brugada Syndrome

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Coronel et al. show in a heart explanted of a BrS patient, fibrosis with epicardial fat infiltration as well as conduction slow without transmural repolarization differences [35]. Furthermore, interstitial fibrosis, fat tissue and myocyte disorganization with reduced gap junction expression in the presence of fractionated and unfractionated low voltage systolic EGMs in the endocardium and epicardium of RVOT was reported with optical microscopy [36–38].

In two patients, before RFA and after right internal jugular venous access through a steerable sheath we advanced a bioptome to RVOT and connected to 3-dimensional (3D) mapping system [19]. Guiding by electroanatomic and voltage map two samples of endo-myocardial biopsies of the three previously defined zones of substrate was obtained. Samples were fixed in 4% glutaraldehyde and 0.1% sodium phosphate (pH 7.4) for transmission electron microscopy (TEM) study as was described previously [39]. As show **Figure 8** the ultrastructural substrate and functional substrate were correlated [19]. In the **Figure 8A**, the patient N°13 in (a), (d) and (g) shows electro-anatomic and voltage map (functional substrate) with a central area of

**Figure 8.** Correlation between functional and ultrastructural substrate. On the left side the electro-anatomic and voltage map (functional substrate) and bioptome connected to the navigation system is shown. On the right side the ultrastructural substrate is shown. Scale Barr: 3.33, 2.2 and 1.42 μm; mitochondria (mi); myofibrils (mf); Purkinje cell

(pc); myofibrillar rests (\*); lipofusin deposit (ld); intercalated disk (id); remains of erythrocytes (er) [19].

located in the intermediate-anterior zone of the RVOT and the bioptome

**6. Correlation between functional and ultrastructural substrate**

tials suppress PVCs and inducibility on PVS [19].

substrate of 25 mm2

In our study, the endocardial RFA in 13 patients resulted in normalization of the ECG BrS pattern, disappearance of end-QRS notching or slurring and suppression of inducibility in all patients during a mean follow-up of 47.7 ± 15.5 months (**Table 1**) [19]. About 30 days after RFA a flecainide testing did not develop ECG BrS pattern. Seven patients who entered to procedure with spontaneous type 1 ECG pattern showed ECG normalization at the end of the procedure. Immediately after RFA was applied, activity and varying degrees of changes in ST segment were observed. With following applications of RFA the ECG pattern progressively decreased (**Figure 7**). After RFA local abnormal diastolic EGMs completely disappear and systolic EGMs were replaced by residual very low voltage areas. The mean time of procedure and fluoroscopy were 112 ± 24.5 and 13.7 ± 5.5 minutes, respectively (Table I). Postprocedure, predischarge, and follow-up 12-lead ECG confirmed the absence of BrS ECG pattern (**Figure 6C**). The patients were asymptomatic and free of arrhythmic events in the 24-hour ambulatory ECG monitoring and in follow-up the ICD interrogation. Two patients (15%) had a near-syncope with prodrome at 24 of 46 months and at 18 of 36 months of follow-up respectively, without arrhythmias in ICD interrogation.

Sunsaneewitayakul et al. reported that endocardial RFA on the late depolarization zones modified the ECG BrS pattern in three patients and suppress the VF storm in four patients, during follow-up of 12–30 months [16]. Similarly, we obtained suppression of inducibility, normalization of BrS ECG pattern and early repolarization pattern with endocardial RFA of

**Figure 7. Effects of radiofrequency ablation on ECG.** In the N°3 patient during endocardial RFA, intense activity and varying degrees of ST segment changes are shown. The ECG pattern progressively decreases with the following applications (red arrows). After RFA the local abnormal diastolic EGMs completely disappeared and systolic EGMs were replaced by residual low voltage areas [19].

areas with late depolarization, diastolic electrical activity and abnormal systolic EGMs [19]; probably by substrate homogenization and transmural lesion of the thin wall of RVOT (mean 3 mm). In addition, as show **Figures 2** and **3** we found pre-systolic potentials as was previously reported by Haissaguerre et al. [15]. In our patients the endocardial RFA of these potentials suppress PVCs and inducibility on PVS [19].
