Long-term efficacy of low doses of quinidine on malignant arrhythmias in Brugada syndrome with an implantable cardioverter-defibrillator: A case series and literature review☆
Introduction
The only evidence-based option to prevent sudden cardiac death (SCD) in symptomatic Brugada syndrome (BrS) is an implantable cardioverter-defibrillator (ICD). 1 In order to prevent the recurrence of ventricular arrhythmias (VA) with oral drugs, only quinidine has been consistently reported to have a beneficial effect.2, 3, 4, 5, 6, 7, 8 The dose of quinidine that was found to effectively prevent arrhythmic events in patients with BrS (1.0–1.5 g/d) has been derived from electrophysiological (EP) studies with drug testing. 9 Also, experimental studies suggest that high doses of quinidine (≥1 g/d) must be prescribed in order to obtain transient outward potassium current (Ito) block and to prevent torsades de pointes secondary to inhibition of the rapidly activating delayed rectifier current. 10 In contrast, the suggested efficacy of low doses of quinidine (<600 mg/d) is based on the beneficial results of such doses in abolishing arrhythmic storms.11, 12 The purpose of this article is to describe the experience of 2 referral centers regarding the use of low doses of quinidine as long-term therapy in patients who experienced appropriate shocks after implantation of an ICD. Results were compared with those reported in the literature.
Section snippets
Methods
From the medical records databases of the National Institute of Cardiology Ignacio Chavez and the Pitié-Salpêtrière Hospital, 6 patients diagnosed with BrS who underwent ICD implantation and who met the following inclusion criteria were chosen for analysis: a clinical diagnosis of BrS based on a history of syncope; VA defined as sustained recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) or aborted SCD in conjunction with a type 1 electrocardiogram (ECG) pattern of BrS,
Case series
Table 1 lists the cases of men from the National Institute of Cardiology (n = 3) and the Pitié-Salpêtrière Hospital (n = 3) that were analyzed and the formulation and doses of quinidine that were used in each case. Two cases have been previously reported.13, 14 The age range was 30–50 years (median value 40 years). All cases had a type I BrS pattern, spontaneously in 5 (3 in standard right precordial leads and 2 in high precordial leads) and 1 after ajmaline challenge. Time from ICD
Literature review
Inclusion criteria were found in 6 case reports and 4 case series in the literature.4, 11, 12, 16, 17, 18, 19, 20, 21, 22 The 3 infant cases were excluded from analysis because quinidine doses were adjusted there to the weight of the children.16, 19, 22 Table 2 summarizes the data from the present series and the 14 adult patients reported in the literature treated with doses of quinidine≤600 mg/d after VA for a total of 20 subjects. In 2004, Hermida et al 4 reported on 4 male subjects with an
Discussion
Patients with symptomatic BrS are considered at high risk of SCD, and therefore an ICD is recommended. 1 In the case of recurrence of symptoms, VA, and/or appropriate ICD shocks, pharmacological strategies are needed. The only drug that has been utilized with some success is quinidine; unfortunately, long-term treatment is associated with a large percentage of treatment suspension during follow-up because of undesirable side effects. 3
In a pool analysis of the literature and the 6 patients
Conclusions
In subjects with symptomatic BrS and appropriate ICD shocks, doses of quinidine or hydroquinidine≤600 mg/d were effective and well tolerated to prevent long-term arrhythmic events. These beneficial results of quinidine confirm the efficacy of this medication in this patient population.
Acknowledgments
The authors are indebted to Ms Corine Tachtiris for editing the manuscript for English usage.
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This work was supported by Instituto Nacional de Cardiología “Ignacio Chávez,” Mexico City, Mexico and Pitié-Salpêtrière Hospital, Paris, France.