Flecainide Test in Brugada Syndrome: A Reproducible but Risky Tool

Abstract

The flecainide test is widely used in Brugada syndrome. However, its reproducibility and safety remain ill-defined. This study included 22 patients (18 men, mean age 34 years). Mutations in the SCN5A gene were found in eight patients. Two patients had aborted sudden cardiac death, 8 had syncope/presyncope, and 12 were asymptomatic. The ECG was diagnostic in 19 patients and suggestive in 3. At baseline, 21 of 22 patients underwent a flecainide test (2 mg/kg IV bolus over 10 minutes). In 21 of 21 patients the test was diagnostic or amplified the typical ECG pattern. At the end of drug infusion, sustained VT lasting 7-10 minutes developed in two patients. A second flecainide test was performed within 2 months in 20 patients. The test was not repeated in the two patients with prior development of VT. The flecainide test was diagnostic in 20 of 20 patients. Sustained VT occurred in one patient and recurrent VF in another. The reproducibility of the flecainide test was 100%. In 4 (18%) of 22 patients major VAs were documented after the end of flecainide infusion. VA occurred in 3 (43%) of 7 patients with, versus 1 (7%) 15 without SCN5A gene mutation (P < 0.05). No diagnostic ECG changes or arrhythmias developed in 25 control patients without structural heart disease who underwent the same study protocol. This study shows a high flecainide reproducibility, supporting its diagnostic value in Brugada syndrome. However, the occurrence of major VA, significantly higher in patients with documented SCN5A gene mutation, including in asymptomatic patients, mandates the performance under appropriate medical supervision. Whether a slower rate of drug infusion can lower the risk of VA induction, while maintaining the sensitivity of the test should be explored.

Two Cases of Pilsicainide Intoxication showing the Brugada-type Electrocardiographic Findings and Incessant Wide QRS Tachycardia

“…The challenge test with the administration of a class IC drug could induce lethal ventricular arrhythmias. 2,10) Incessant and monomorphic VT is well known as a proarrhythmia induced by a strong slowing effect of intraventricular conduction due to class IC antiarrhythmic agents. 11) Although we could not identify their wide QRS tachyacardia as ventricular in origin, we speculate that their incessant tachyacardia may be VT as a proarrhythmic effect due to intoxication of IC drugs.…”

Epicardial Substrate Ablation in Brugada Syndrome

“…The use of the class 1c drugs flecainide and pilsicainide in BrS patients has been reported to elicit major ventricular arrhythmias in 15% to 20% of the patients. 16, 17 The occurrence of major ventricular arrhythmias was found to be significantly higher in symptomatic patients 16 and in patients with documented SCN5A mutations. 17 As stated earlier, the patients in this study by Brugada et al were not an overtly high-risk subset; it is logical to speculate that the incidence could be much higher in BrS patients with frequent ICD discharges because of recurrent VT/VF episodes, who have a clear indication for an ablative procedure for substrate elimination.…”

“…16, 17 The occurrence of major ventricular arrhythmias was found to be significantly higher in symptomatic patients 16 and in patients with documented SCN5A mutations. 17 As stated earlier, the patients in this study by Brugada et al were not an overtly high-risk subset; it is logical to speculate that the incidence could be much higher in BrS patients with frequent ICD discharges because of recurrent VT/VF episodes, who have a clear indication for an ablative procedure for substrate elimination. The risks of precipitating refractory VT/VF in the electrophysiology laboratory during flecainide infusion should indeed be greatly considered before recommending that the drug be used routinely for unmasking the BrS arrhythmogenic substrates or for seeking better alternative sodium channel blockers (ie, ajmaline or procainamide) for this purpose.…”

Pharmacogenetic Considerations in Diseases of Cardiac Ion Channels

“…This disorder manifests as J-point and ST segment elevation in the right precordial leads of the ECG, without significant prolongation of the QT interval. Patients with the Brugada syndrome may be susceptible to ventricular arrhythmias after treatment with drugs that block I Na , specifically class I antiarrhythmic agents such as flecainide, which is used to accentuate the ECG abnormalities of suspected Brugada patients to aid diagnosis (Gasparini et al, 2003). SCN5A mutations are capable of producing a wide range of clinical symptoms; whereas LQT and Brugada syndrome sufferers experience life-threatening arrhythmias, other SCN5A mutations can cause cardiac-conduction disease, light-headedness, or syncope.…”