br Clinical evidence to support that PES
Clinical evidence to support that PES predicts cardiac events in BS Brugada et al. were the first to propose that inducibility of sustained ventricular arrhythmias with PES is useful to identify patients who are at high risk of SCD . During follow-up of patients with spontaneous type 1 Brugada ECG, they found a significantly higher rate of cardiac events (17%) in patients with inducible ventricular arrhythmias than in those without inducible arrhythmias (2%) (P=0.007). Other series published by Brugada et al. showed that the number of cardiac events during follow-up was much higher (13.0%) in patients in whom ventricular arrhythmia could be induced than in those in whom it could not be induced (1.1%) . Subsequent data from Brugada et al. also indicated that, in patients without previous cardiac arrest, the incidence of arrhythmic events was significantly higher in patients in whom ventricular arrhythmia could be induced (13.9%) than in those in whom it could not be induced (1.1%) (P=0.008), and that the inducibility of ventricular arrhythmias on PES is an independent predictor for cardiac events (hazards ratio [HR], 8.33; 95% confidence interval [CI], 2.8–25; P=0.0001) . In 2008, Benito et al. from Brugada\'s group reported a prospective study that included 384 patients during a mean follow-up of 58 months . In this study, the incidence of cardiac events was significantly higher (74.1%) in inducible male patients than in noninducible male patients (27.6%) (P<0.001). Multivariate analysis revealed that the inducibility of ventricular arrhythmias on PES is an independent predictor for cardiac events (HR, 2.93; 95% CI, 1.14–7.55; P=0.02). Recently, Delise et al. reported a very interesting combined clinical and electrophysiologic approach to risk stratification in BS . PES was performed in 245 patients with type 1 Brugada ECG and no previous cardiac arrest. During a median follow-up adenyl cyclase of 40 months, major arrhythmic events (VF or SCD) occurred in 14% of inducible patients, 0% of noninducible patients, and 5.3% of patients who did not undergo PES (P<0.001). No single clinical risk factor, including positive PES, was able to identify the patients at highest risk. However, the patients at the highest risk were those with spontaneous type 1 Brugada ECG along with at least 2 of the following risk factors: syncope, family history of sudden death, and positive PES. The combination best able to predict major arrhythmic events was spontaneous type 1 Brugada ECG, history of syncope, family history of sudden death, and positive PES (C-statistic, 0.87; 95% CI, 0.82–0.90).
Evidence to deny the predictive value of PES for cardiac events In the same year that Brugada et al. reported the useful prognostic value of PES as a predictor for cardiac events, Priori et al. were unable to confirm the predictive value of PES and suggested that PES might lead to unnecessary overtreatment with ICD due to the high inducible rate . They performed PES in 86 patients with BS. VF or sustained polymorphic ventricular tachycardia (VT) was induced in 57 of 86 patients (66%). Overall, the sensitivity and specificity for the inducibility of VF or VT were 66% and 34%, respectively. Kaplan–Meier analysis of cumulative survival from cardiac arrest failed to show an association between inducibility of VF or VT and spontaneous occurrence of VF. Over the years, other large multicenter studies, except those by Brugada et al., failed to confirm the ability of VF or VT inducibility to identify high-risk patients [4–7,14]. Eckardt et al. performed PES in 188 patients with type 1 Brugada ECG. During a mean follow-up period of 40 months, 9 patients experienced an arrhythmic event. Five of the 9 patients were inducible (56%). Positive and negative predictive values were low (5.4 and 95.7%, and 6.6 and 96.4%, with up to 3 or 2 extrastimuli, respectively). Kaplan–Meier analysis showed that inducibility of VF or VT was not a predictor of outcome of cumulative survival from cardiac events . In the FINGER study, a large multicenter European study that included 1029 consecutive individuals, PES was performed in 638 individuals (62%). Sustained ventricular tachyarrhythmias were inducible in 262 patients (41%). The rate of inducible ventricular tachyarrhythmia was higher in previously symptomatic patients (125/269, 46%) than in asymptomatic individuals (137/369, 37%) (P=0.02), but was not statistically different among the cardiac arrest, syncope, and asymptomatic groups (44%, 47%, and 37%, respectively; P=0.06) (Table 1). In multivariate analysis during a median follow-up period of 31.9 months, inducibility of VF or VT did not show an independent predictive value for cardiac events (P=0.48) . Recent multicenter large-scale prospective studies from Japan also indicated that inducibility of VF or VT was not a predictor of cardiac events. In a study performed by Kamakura et al. in 330 consecutive individuals, PES was performed in 232 (70%). The inducibility rate of VF or polymorphic VT in all patients was significantly higher (77/109; 72%) in symptomatic than in asymptomatic probands (61/123; 50%, P<0.005). However, in 172 patients with type 1 Brugada ECG, the inducibility rates of VF or polymorphic VT in the VF, syncope, and asymptomatic groups were 27/41 (66%), 31/40 (78%), and 52/91 (57%), respectively, (not significant) (Table 1). In multivariate analysis, during a mean follow-up period of 48.6 months for patients with type 1 Brugada ECG, inducibility of VF or VT was not an independent predictor for cardiac events (P=0.54) . In our previous study in 2007, which included 188 patients, PES was performed in 146 patients (31 VF, 52 syncope, 63 asymptomatic). VF or polymorphic VT was induced in 23 (74%), 41 (79%), and 50 patients (79%) in the VF, syncope, and asymptomatic groups, respectively. There were no significant differences in the rates of inducibility among the 3 groups (P=0.23). Inducibility of VF or VT was not useful in predicting cardiac events during a mean follow-up period of 37 months (P=0.63) . In our most recent study, which included 460 patients, PES was performed in 334 patients (62 VF, 91 syncope, 181 asymptomatic). VF or polymorphic VT was induced in 37 (60%), 66 (73%), and 121 patients (67%) in the VF, syncope, and asymptomatic groups, respectively (P=0.25) (Table 1). Similarly, inducibility of VF or VT was not useful in predicting cardiac events during a mean follow-up period of 50 months (P=0.20 in all patients and P=0.66 in patients without documented VF) .