Quinidine therapy in children affected by Brugada syndrome: are we far from a safe alternative?

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. 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. Prevalence of the syndrome in children is much lower than in adults, but Brugada syndrome is known to cause sudden infant death syndrome, and also to be responsible for sudden cardiac death during childhood. 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. 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. How to manage children with Brugada syndrome, therefore, remains a matter of debate, with no safe alternatives between the options of administering no medication, courting the risk of sudden cardiac death occurring mostly in adulthood, 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. A pharmacological alternative is desirable, but class IA and IC antiarrhythmic drugs are contra-indicated, while amiodarone and beta-blockers are ineffective. 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. Quinidine, a specific class IA anti-arrhythmic agent with Ito blocking properties, 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. 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. 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. Oral quinidine is also used to treat electrical storms in adults with Brugada syndrome. The dosage of quinidine for children is 30–60 mg/kg/day, given in 4 divided doses. Children with Brugada have been successfully treated in this fashion. 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 cardioverterdefibrillator placement after an electrical storm. 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. In the largest affected population of Correspondence to: Dr Alban-Elouen Baruteau, Département de Cardiologie et Maladies Vasculaires, Hôpital Pontchaillou, CHU de Rennes, 2 rue Henri Le Guilloux, 35033 Rennes cedex, France. Tel: (00 33) 299282525; Fax: (00 33) 299282510; E-mail: [email protected]