Is Quinidine the Ideal Drug for Brugada Syndrome?

Abstract

Brugada syndrome (BrS) is a cardiac disease caused by an inherited ion channelopathy that is associated with a propensity to develop ventricular fibrillation (VF). Patients with BrS and a history of cardiac arrest are considered to be at the highest risk for recurrent arrhythmic events and should be treated with an implantable cardioverter-defibrillator (ICD). However, the beneficial effects of an ICD are solely the result of VF termination by the device, whereas the device does not affect VF occurrence. For the past 3 decades, our group at the Tel-Aviv Medical Center has developed an alternative therapeutic approach to ICD use in BrS patients based on the high efficacy (90%) of quinidine bisulfate at a mean dose of 1.5 g daily to prevent inducibility of VF. This approach has been associated with both excellent reproducibility of electrophysiologic (EP) results and clinical efficacy during the long term as attested by the fact that none of our drug-responder and drug-tolerant patients has yet exhibited a recurrent arrhythmic event. Hermida et al obtained similar results using another slowrelease quinidine preparation (quinidine hydrochloride 600– 900 mg daily). We have been using the latter medication for the past 5 years because of AstraZeneca’s decision to stop production of quinidine bisulfate. Electric storms of VF represent the more malignant form of ventricular arrhythmias in patients with BrS, accounting for up to 10% of the untreated patient population and up to 38% of arrhythmic events in ICD patients. The arrhythmic storms may reveal the disease or occur after ICD implantation, and they are frequently, but not always, triggered by fever. They may lead to multiple DC shocks or ICD discharges with multiple consequences, such as psychologic disorders, proarrhythmia, deleterious effect on cardiac function, electromechanical dissociation, and death. Heart transplantation has even been used as the last resort in a patient with intractable VF (see references in Belhassen et al). Isoproterenol infusion has been shown to be very effective for the acute management of arrhythmic storms in the setting of BrS. However, it can be administered only during a short period of time, and the arrhythmia frequently recurs