Empiric Quinidine for Asymptomatic Brugada Syndrome—Preliminary Results of an International Registry

Abstract

<h3>Background</h3> Common practice for asymptomatic Brugada syndrome (BrS) has included risk stratification with electrophysiologic studies (EPS) and defibrillator implantation when the latter are positive. However, several multicenter studies show that EPS has limited value for predicting spontaneous ventricular fibrillation. Therefore, in 2008 we started this Prospective International Registry. <h3>Methods</h3> Patients with a type 1 Brugada ECG, who have no arrhythmia-related symptoms and no heart disease, are included in the Registry. They receive quinidine therapy or no therapy depending on physician's/patient's preference. EPS are not recommended. <h3>Results</h3> In total, 132 patients from the Netherlands (51), Italy (41), Israel (20), Germany (13), and Japan (7) have been recruited; 93 (70%) are male. Age at presentation is 43 ± 12 (11–79) years. Symptoms include palpitations (20%), chest pain (10%) and vagal syncope (20%); 54 patients have a family history of BrS or sudden death before age 50. The reason for index ECG was medical screening in 41 (31%), cardiac symptoms in 34 (26%), noncardiac symptoms (eg, fever) in 18 (14%), and screening for familial history of sudden death or BrS in 39 (30%). The type 1 ECG pattern was spontaneous in 45 patients (including spontaneous on "high leads" in 7 and fever-induced in 8) and drug-induced in 87. Disease-causing mutations were found in 23% and genetic variants of unknown significance in 5%. Nineteen patients received empiric quinidine therapy. Of them, 4 had presented with syncope (believed to be vasovagal) and 4 were asymptomatic but had familial history of sudden death or BrS. Nine patients had a spontaneous type 1 ECG pattern. Five (26%) patients discontinued quinidine because of asymptomatic QT prolongation (2 patients), diarrhea, asymptomatic abnormal liver function tests, and patient's preference (1 patient each). Follow-up >4 months (1.8 ± 0.9 years) is available for 59 patients. The only serious adverse event was syncope (leading to defibrillator implantation) in 1 untreated patient. <h3>Conclusions</h3> In our Prospective Registry of asymptomatic patients with BrS, most physicians and patients opt for no therapy. Long-term quinidine therapy is well tolerated by 74%. The risk of an arrhythmic event proved to be low.