Elsevier

Heart Rhythm

Volume 9, Issue 12, December 2012, Pages 1995-2000
Heart Rhythm

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

https://doi.org/10.1016/j.hrthm.2012.08.027Get rights and content

BACKGROUND

To prevent the recurrence of ventricular arrhythmias (VA) in Brugada syndrome (BrS), only quinidine has been consistently reported to have a beneficial effect. Recommended doses are≥1 g/d. The efficacy of lower doses of quinidine has been suggested on the basis of a few isolated experiences.

OBJECTIVES

To describe the efficacy and safety of doses≤600 mg/d of quinidine after cardioverter-defibrillator implantation in BrS at 2 referral centers and to compare those results with a comprehensive review of the literature.

METHODS

In a retrospective analysis of medical records from the 2 centers, 6 men with BrS who received≤600 mg/d of quinidine sulfate or hydroquinidine after cardioverter-defibrillator implantation were identified. Quinidine was initiated after arrhythmic syncope or appropriate shocks, including arrhythmic storm in 4. A literature search was performed to find previous cases with symptomatic BrS reported as having received≤600 mg/d of quinidine.

RESULTS

Quinidine prevented recurrence of VA in all patients from our series without side effects during a median follow-up of 4 years (from 2 to 8 years). In the literature review, 14 additional adults were found. With the exception of 3, quinidine effectively suppressed arrhythmic events in all of them. Four subjects who discontinued the medication experienced VA recurrence, successfully treated by restarting quinidine.

CONCLUSIONS

Low doses of quinidine were well tolerated and effective to prevent the recurrence of VA, including arrhythmic storm, in subjects with BrS with an implantable cardioverter-defibrillator. Effectiveness of quinidine or hydroquinidine in doses≤600 mg/d is 85%.

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.

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