Clinical, diagnostic and therapeutic aspects of Brugada syndrome in different age-related categories of patients: focus on children and the elderly

Abstract

Brugada syndrome (BrS) is an inherited primary arrhythmia syndrome
characterized by an increased risk of sudden death. The features and the
best therapeutic management of the syndrome in particular age-related
categories of patients remain unclear. This dissertation aimed to
investigate various aspects of the syndrome with a particular focus on the
paediatric and elderly patients. First, the clinical presentation, prognosis
and specific management of the syndrome was assessed in these two
categories of patients. Therefore, we investigated specific diagnostic
aspects of the syndrome and their influence on prognosis. Finally, the
therapeutic management of BrS concerning implantable-cardioverter
defibrillator therapy and ablation of atrial fibrillation was analyzed.
According to our data, BrS in children presents with clinical features similar
to those of adult patients. It is commonly associated with male gender,
sustained atrial arrhythmias and sinus node dysfunction. Life-threatening
arrhythmias during ajmaline challenge occur in 1.8% of patients with BrS.
Children are a category of patients at higher risk of experiencing sustained
ventricular arrhythmias during ajmaline challenge. Moreover, repeating
ajmaline challenge after puberty is valuable and can unmask BrS in 23% of
family members with previously negative drug test. Thirty percent of these
newly positive patients develop symptoms and 10% spontaneous
ventricular fibrillation. The existence of an evolution of the phenotype from
childhood to adult age of previously asymptomatic family members with
normal ECGs is worrisome and support the need for continuous monitoring
of patients and family members, including those initially considered at low
risk before puberty. The clinical features and the benign prognosis of
elderly patients with BrS identify a lower risk category of patients as
compared to younger individuals. Brugada syndrome in the elderly is
commonly associated with baseline atrioventricular (AV) conduction
disturbances. Ajmaline challenge in the elderly is a safe procedure to
unmask AV conduction disease and can lead to unexpected diagnoses of
BrS. Diagnosis of BrS in this setting is important mainly because of the
clinical impact on the younger family members. Implantable cardioverterdefibrillator
(ICD) therapy is effective in BrS, treating ventricular
arrhythmias in 17% of patients during a long-term follow-up. In children
with ICD, the rate of device-related problems and inappropriate shocks is
considerable and even higher than appropriate interventions. The
treatment of atrial fibrillation by the means of ablation procedures is an
effective and safe approach, especially for young patients with
inappropriate ICD interventions.

Date of Award	24 Mar 2015
Original language	English
Awarding Institution	Vrije Universiteit Brussel
Supervisor	Pedro Brugada (Promotor), Carlo De Asmundis (Co-promotor), Pierre Van Den Brande (Jury), Steven Droogmans (Jury), Jan Poelaert (Promotor), Angelo Auricchio (Jury), D. Corrado (Jury) & M. Duytschaever (Jury)