Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome
Introduction
Brugada syndrome is characterized by an ECG pattern of right bundle branch block and ST-segment elevation in the right precordial leads (V1–V3).1 Intensive screening among patients with aborted sudden death or syncope has increased the number of patients since the first report by Brugada et al.2 Pharmacologic challenge with intravenous administration of sodium channel blockers has been suggested to unmask the ECG pattern in patients with Brugada syndrome.3, 4 A variety of drugs, such as flecainide, ajmaline, procainamide, and pilsicainide, reportedly provoke typical ST-segment elevation.5, 6, 7, 8, 9 However, comparative studies for ajmaline and flecainide are lacking. Therefore, in the present study the effects of intravenous flecainide and ajmaline were studied with respect to their ability to unmask the typical Brugada ECG and their effects on the 12-lead surface ECG. In addition, the effect of ajmaline and flecainide on the Ito current in canine ventricular epicardial cells was measured in in vitro experiments to determine the mechanisms for possible differences in the response to the two sodium channel blockers in patients diagnosed with Brugada syndrome.
Section snippets
Patients and methods
A total of 22 consecutive, unrelated patients with Brugada syndrome diagnosed between August 2000 and March 2003 were prospectively enrolled into the study. All patients gave informed consent to clinical investigation. Diagnostic work-up included full noninvasive and invasive testing, including echocardiography, exercise testing, pharmacologic challenge, right ventricular angiography, coronary angiography, and programmed stimulation. Up to three extrastimuli at three different basic driving
Results
A total of 22 patients diagnosed with Brugada syndrome underwent ajmaline and flecainide challenge. No ventricular tachyarrhythmias were observed during the pharmacologic challenge, except for isolated premature ventricular beats in three patients. No severe side effects occurred. One of 22 patients developed urticaria and flush during ajmaline infusion. At baseline immediately before drug testing, seven patients displayed a type I ECG in no more than one right precordial lead. The remaining
Discussion
In this prospective study, we investigated the response of the surface ECG to two different intravenously administered sodium channel blockers—ajmaline and flecainide. In 15 of 22 patients (68%) with Brugada syndrome, the study of intravenous drug challenge with flecainide and ajmaline revealed concordant results, whereas a discordant result was found in another seven patients (32%). In the seven patients, intravenous flecainide did not produce the typical ECG changes diagnostic of Brugada
References (22)
- et al.
Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report
J Am Coll Cardiol
(1992) - et al.
Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome
J Am Coll Cardiol
(1996) - et al.
Genotype-phenotype relationship in Brugada syndromeelectrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients
J Am Coll Cardiol
(2002) - et al.
The electrophysiologic mechanism of ST-segment elevation in Brugada syndrome
J Am Coll Cardiol
(2002) - et al.
Brugada syndrome: 1992–2002. A historical perspective
J Am Coll Cardiol
(2003) - et al.
Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3
Circulation
(2002) - et al.
Further characterization of the syndrome of right bundle branch block, ST segment elevation, and sudden cardiac death
J Cardiovasc Electrophysiol
(1997) - et al.
Natural history of Brugada syndromeinsights for risk stratification and management
Circulation
(2002) - et al.
Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts
Circulation
(2000) - et al.
The ajmaline challenge in Brugada syndromediagnostic impact, safety, and recommended protocol
Eur Heart J
(2003)
Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation
Circulation
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2019, Journal of ElectrocardiologyCitation Excerpt :Excessive QRS widening and frequent premature ventricular beats indicate high-risk of complications and encourage interruption of the challenge [33]. The used drugs have presented good reproducibility [38], but flecainide has been shown to present significantly lower sensitivity than ajmaline (77% against 100%, respectively) [39,40]. A negative result in the provocative test supports the diagnosis of Brugada phenocopy; nevertheless, it must not be overlooked that there may be up to 23% of false-negatives [39] when using flecainide, and cases of delayed diagnosis of Brugada syndrome have been reported [41].
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Supported by Grant HL47678 from the National Heart, Lung and Blood Institute to Dr. Antzelevitch and a grant from the American Heart Association to Dr. Antzelevitch.