Dear Sir,
Brugada syndrome is an inherited arrhythmogenic disease characterized by a typical electrocardiographic pattern consisting of ST-segment elevation in the right precordial leads, and is known to carry a predisposition to sudden cardiac death.Reference Antzelevitch, Brugada and Borggrefe1–Reference Brugada and Brugada3 Its prevalence is 1–5 per 10,000 inhabitants worldwide. It is responsible for one-fifth of sudden deaths in patients with structurally normal hearts, with a mean age at death of 40 years.Reference Antzelevitch, Brugada and Borggrefe1 Prevalence of the syndrome in children is much lower than in adults,Reference Oe, Takagi and Tanaka4, Reference Yamakawa, Ishikawa and Uchino5 but Brugada syndrome is known to cause sudden infant death syndrome, and also to be responsible for sudden cardiac death during childhood.Reference Priori, Napolitano, Giordano, Collisani and Memmi6–Reference Probst, Denjoy and Meregalli9
To date, implantation of an automatic cardioverter-defibrillator is the only recommended treatment for patients with the syndrome who are considered to be at high risk.Reference Epstein, DiMarco and Ellenbogen10 Implantation of such devices in young children is challenging, and implies replacements of the devices over a lifetime, together with the likelihood of numerous complications.Reference Eicken, Kolb and Lange11 How to manage children with Brugada syndrome, therefore, remains a matter of debate,Reference Viskin12 with no safe alternatives between the options of administering no medication, courting the risk of sudden cardiac death occurring mostly in adulthood,Reference Antzelevitch, Brugada and Borggrefe1 or implanting a cardioverter-defibrillator.
Lifestyle measures are part of the programme to prevent sudden cardiac death, and include such features as prompt treatment of febrile illnesses with antipyretics, since fever represents the most important precipitating factor for arrhythmic events in children with Brugada syndrome.Reference Probst, Denjoy and Meregalli9 A pharmacological alternative is desirable, but class IA and IC antiarrhythmic drugs are contra-indicated, while amiodarone and beta-blockers are ineffective.Reference Antzelevitch, Brugada and Borggrefe1 One current theory to explain arrhythmogenesis in Brugada syndrome is based on an imbalance between depolarizing and repolarizing currents during the early repolarization phase of the action potential, mainly in epicardial cells of the right ventricle, which express a strong potassium transient outward current Ito supporting phase 2 reentrant activity.Reference Chen and Priori13, Reference Antzelevitch14 Quinidine, a specific class IA anti-arrhythmic agent with Ito blocking properties,Reference Antzelevitch15 has therefore been suggested as being useful in Brugada syndrome.
The clinical relevance of this suggestion has been proved by reports of quinidine-induced electrocardiographic normalization in patients with the syndrome.Reference Alings, Dekker, Sadée and Wilde16 Some clinical trials have shown quinidine to be safe in preventing both inducible and spontaneous ventricular fibrillation in adults with the syndrome known to be at high risk, when given at both high and low doses.Reference Belhassen, Glick and Viskin17–Reference Mizusawa, Sakurada, Nishizaki and Hiraoka19 In these trials, quinidine prevented ventricular fibrillation induction in up to nine-tenths of asymptomatic patients with an inducible arrhythmia, as well as reducing the recurrence of ventricular arrythmias in symptomatic patients.Reference Belhassen, Glick and Viskin17, Reference Hermida, Denjoy and Clerc18 Oral quinidine is also used to treat electrical storms in adults with Brugada syndrome.Reference Zipes, Camm and Borggrefe20
The dosage of quinidine for children is 30–60 mg/kg/day, given in 4 divided doses.Reference Ramesh Iyer21 Children with Brugada have been successfully treated in this fashion.Reference Suzuki, Torigoe, Numata and Yazaki8, Reference Probst, Denjoy and Meregalli9, Reference Probst, Evain and Gournay22 Suzuki et al, for example, reported an event-free period of 5 months following treatment of a symptomatic infant by combined oral therapy including quinidine and prophylactic implantation of a cardioverter-defibrillator placement after an electrical storm.Reference Suzuki, Torigoe, Numata and Yazaki8 We reported a period of follow-up of 16 months after treating a 3-year-old child exclusively with oral hydroquinidine after a first episode of ventricular tachycardia.Reference Probst, Evain and Gournay22 In the largest affected population of children published to date, 4 of the 30 children, aged 4 months to 10 years, including our 3-year-old boy, safely received oral quinidine, with a mean follow-up of 28 months.Reference Probst, Denjoy and Meregalli9
Challenging high-risk affected children with the syndrome remains a key issue. No clinical trial has assessed the safety of quinidine when used in children. It may be interesting to test this pharmacological treatment in the following situations. First, in symptomatic children with multiple appropriate shocks delivered from implantable cardioverter-defibrillators. Second, in high-risk asymptomatic children with inducible ventricular arrhythmias. Treatment should be guided by electrophysiological studies in such patients. Should the arrhythmias still be inducible despite treatment with quinidine, implantation of a cardioverter defibrillator must be recommended.
Further studies are needed to determine the right place of treatment with quinidine. At this stage, nonetheless, it appears to be a promising alternative to implantation of cardioverter-defibrillators in young children with the syndrome who are known to be at high risk, not only because of its safety, but also because of its excellent long-term tolerability at low doses.Reference Mizusawa, Sakurada, Nishizaki and Hiraoka19 As previously proposed, it could constitute a bridge to implantation of cardioverter-defibrillators in children known to be at high risk.Reference Belhassen, Viskin and Antzelevitch23
