**2. Study population and risk factors**

pattern. Endocardial biopsy showed a correlation between functional and ultrastructural alterations. Endocardial RFA can eliminate the BrS phenotype and inducibility during pro-

**Keywords:** Brugada syndrome, radiofrequency catheter ablation, electrocardiography,

Since the original publication in 1992 [1], many researchers have tried to explain the mechanisms and substrate that causes an abnormal electrocardiographic (ECG) pattern and ventricular arrhythmias in Brugada syndrome (BrS) and few therapeutic options have been found. Initially three hypotheses were proposed for explain the mechanism and arrhythmias in BrS, the abnormal repolarization theory [2], the abnormal depolarization theory [3] and the abnor-

BrS is characterized by an elevated ST segment in the right precordial leads (V1–3) on the ECG and risk of sudden cardiac death (SCD) [1, 5]. The ECG 1 pattern is frequently intermittent and can be unmasked by the administration of a sodium channel blocker (**Figure 1**). The incidence of SCD in subjects with Brugada type 1 ECG pattern and no previous cardiac arrest

At present, there are just two therapeutic strategies, which include implantable cardioverterdefibrillator (ICD) and/or chronic quinidine therapy [6, 7]. However, quinidine is not effective

**Figure 1.** Characteristic BrS ECG. A. In the N°3 patient the ECG at baseline show spontaneous and intermittent type 1

mal expression of neural crest cells during cardiac development [4].

grammed ventricular stimulation (PVS).

mapping, biopsy

is 2 per 1000 patients per year [6, 7].

ECG BrS pattern. B. After flecainide test (400 mg, orally) [19].

**1. Introduction**

122 Cardiac Arrhythmias

The arrhythmic events occur in patients who presented spontaneous type 1 ECG BrS pattern and syncope of presumed arrhythmic origin, so both are considered high-risk factors [6]. The risk of SCD in patients without ICD is 2 per 1000 patients per year [6, 7]. But unfortunately, the possibility of survival out of hospital is low if the first symptom is the SCD.

We in a prospective single-center study consecutively included 13 caucasian patients when they presented all three high-risk criteria: (1) documented spontaneous type 1 BrS ECG pattern, (2) syncope of probable arrhythmic cause (syncope was defined as a no traumatic and reversible loss of consciousness, and was considered of arrhythmic origin in the absence of a prodrome or triggering circumstances), (3) inducible VF with PVS [19]. These were associated with at least one of the following conditions: family history of SCD at age < 45 years, type 1 BrS ECG pattern in family members, early repolarization pattern, and/or nocturnal agonal respiration [6, 9]. Structural heart disease, systemic diseases and phenocopies was ruled out in each case on the basis of clinical history and extensive evaluation with 2D Echocardiography, tilt test, brain computed tomography, 24-hour ambulatory ECG monitoring, HIV test, coxsackie and parvovirus B19 test, Chagas disease test, myocardial perfusion and cardiac nuclear magnetic resonance. All patients had 5 points according to the risk score model currently proposed by Sieira et al. [20] (spontaneous type 1 ECG pattern =1 point, inducible VF =2 points and syncope =2 points). None had a history of SCD or documented spontaneous VT/VF and did not receive antiarrhythmic drugs. Patients were submitted to endocardial bipolar and 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), alternating T and J-wave and changes of the ST segment elevation were found (**Figure 2**).

BrS is eight times more prevalent in males, probably for higher testosterone levels and a more prominent transient outward current (Ito). Males are at increased risk for developing a spontaneous type 1 ECG BrS pattern and VF during PVS. Nevertheless, because the majority of the asymptomatic patients are also male the gender is not an independent predictor of arrhythmic events [9, 24]. It is striking that eight of our patients (61.5%) were females. Five of these had between 38 and 58 years of age and menopausal symptoms, so we might suspect that lack

Endocardial Approach for Substrate Ablation in Brugada Syndrome

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

125

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

of estrogens could induce the expression of phenotype [19].

**functional substrate**

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

asymptomatic, as was previously reported for the epicardial RFA [17, 18].

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 and without arrhythmias in the ICD interrogation [19].

**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 (red arrows) [19].

BrS is eight times more prevalent in males, probably for higher testosterone levels and a more prominent transient outward current (Ito). Males are at increased risk for developing a spontaneous type 1 ECG BrS pattern and VF during PVS. Nevertheless, because the majority of the asymptomatic patients are also male the gender is not an independent predictor of arrhythmic events [9, 24]. It is striking that eight of our patients (61.5%) were females. Five of these had between 38 and 58 years of age and menopausal symptoms, so we might suspect that lack of estrogens could induce the expression of phenotype [19].
