Assessment of the Arrhythmic Risk – the Most Important Clinical Problem in the Brugada Syndrome

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Assessment of the Arrhythmic Risk – the Most Important Clinical Problem in the Brugada Syndrome

The identification of BrS patients with high arrhythmic risk especially among those without previous history of arrhythmia-related symptoms is currently the most important and yet unresolved clinical problem in the BrS. In some aspects, this problem is similar to one of the main (also still not fully resolved) problems of modern cardiology – the identification of patients with ischaemic heart disease (IHD) at high risk of dying suddenly who need prophylactic implantable cardioverter-defibrillator (ICD).

In BrS patients with a previous history of arrhythmic syncope or aborted cardiac arrest the annual event rate of sustained VT or VF is relatively high – between 1.9 %⁶³ and 8.8 %⁶⁴ and between 7.7 %⁶² and 13.8 %⁶³, respectively. It is universally accepted that those with aborted cardiac arrest or documented spontaneous sustained VT (with or without syncope) should receive an ICD which is the single therapy with proven efficacy (Class I indication, “…is recommended”).⁶ There is also evidence that patients with spontaneous type 1 pattern and syncope judged to be of arrhythmic origin (“intermittent risk” group) also are indicated for ICD implantation (currently class IIa indication, “…can be useful.”), whereas asymptomatic patients with spontaneous type 1 pattern are currently considered to represent a “low risk” group (class IIb indication, “…may be considered” depending on the presence or absence of other, not yet fully established risk factors, see below).⁶ A very recently published Japanese multicentre study confirmed the difference in the level of risk between the latter two patient groups (2.2 % vs 0.5 % during a mean follow-up of 62 months).⁶⁵

However, the decision to offer an ICD even to a BrS patient with a syncope of presumably arrhythmic origin often is difficult because unlike IHD patients, most of them are relatively young, apparently healthy and without any previous awareness of cardiac problems. Most importantly, it is often very difficult to exclude non-arrhythmic cause of the syncope. In addition, the rate of ICD-related complications (20–30 % annually including inappropriate shocks) is higher than the rate of appropriate activation of the device (2.6–8 % annually).^66,67,68 This suggests that novel, better methods of risk-stratification could benefit even some symptomatic BrS patients (i.e. those with the current class IIa indications).⁶

The majority of BrS patients (64 % in the largest reported series of 1029 BrS patients, the France, Italy, Netherlands, Germany (FINGER) study⁶² and 63 % in the report of the Brugada syndrome investigators in Japan⁶⁹) have no symptoms at the time of establishment of the diagnosis. The annual rate of SCD or sustained VT in these patients is low – between 0 %^70,71 and 0.8⁷² (0.5 % in the FINGER study⁶² and the Japanese multicentre study,⁶⁶ 0.4–1 % in several Japanese studies^73,74,75) and cannot justify ICD implantation in all of them. On the other hand, the majority of the patients in this heterogeneous group have generally structurally normal hearts and are young or middle aged when diagnosed (median age 45 years in the FINGER study), and therefore the low annual risk can translate into a considerable cumulative arrhythmic risk for the next several decades of their life expectancy. In fact, the majority of victims of SCD in BrS come from this “low risk” (according to current standards) population. One study showed that among patients with the BrS who have died suddenly 68 % had no previous history of arrhythmia-related symptoms and therefore had not been protected by ICD.¹³ Currently, there are no firmly established reliable methods for the identification of these patients. Similarly, the largest absolute number of patients with IHD who die suddenly also comes from a large patient population considered to have generally low risk (i.e. post-myocardial infarction patients with relatively preserved left ventricular ejection fraction).⁷⁶

While some studies^77,78,79 reported increased occurrence of arrhythmic events in BrS patients with SCN5A mutations these findings have not been confirmed by other studies.⁸⁰ The genetic analysis is expensive, time-consuming and available only in specialised centres. The role of programmed ventricular stimulation (PVS) during EPS for induction of VT has been an object of controversy and debate since the 1990s. While some early studies supported its value for risk stratification mainly due to its high negative predictive value,^81,82 most recent studies failed to confirm its independent predictive value.^66,83,84 In the FINGER study,⁶² inducibility during EPS also did not predict arrhythmic events in multivariate analysis whereas in the multicentre PRELUDE study which tested uniform protocol of PVS during EPS in all 308 patients, the rate arrhythmic events during an average follow-up of three years was not significantly different between the 126 inducible (3.9 %) and the 182 non-inducible patients (4.9 %).⁸⁵ Currently its role of EPS for risk stratification is accepted only as a Class IIb (“may be considered”) indication.^7,86 The method is inherently limited by its invasive character and probably also by the labile nature of the underlying electrophysiologic substrate.⁸⁷