Summary
Background
Ajmaline challenge is commonly used for the diagnosis of Brugada syndrome. A slow infusion rate has been recommended in view of the proarrhythmic risk, but the diagnostic value of various infusion rates has not been investigated.
Aims
To compare rapid and slow ajmaline infusion rates and to assess the proarrhythmic risk.
Methods
The first part of this study prospectively compared rapid and slow infusion rates in terms of results and ventricular arrhythmias. Thirty-two patients (mean age 41 ± 12 years; 26 men) received the two ajmaline challenges on different days. According to randomization, ajmaline (1 mg/kg) was infused at 1 mg/sec or over 10 minutes. The second part of the study retrospectively assessed the prevalence of ventricular arrhythmia during 386 challenges performed at a rapid infusion rate.
Results
No differences were observed between rapid and slow tests. All patients diagnosed as positive or negative with one test obtained the same result with the other test. Ventricular premature beats were observed in five of 32 patients during the slow challenge and in four of 32 patients during the rapid challenge. No sustained ventricular arrhythmias were observed. Analysis of the 386 tests revealed four episodes of ventricular arrhythmia (two complex ventricular premature beats, one non-sustained ventricular tachycardia and one ventricular fibrillation).
Conclusion
Slow and rapid infusions of ajmaline have identical diagnostic performances on suspected Brugada electrocardiograms. Owing to the risk of severe proarrhythmia, a slow infusion rate, allowing early discontinuation, should be recommended.
Résumé
Background
Le test à l’ajmaline est couramment utilisé pour le diagnostic du syndrome de Brugada. Une administration lente de l’ajmaline est recommandée en raison du risque d’arythmie, mais sa valeur diagnostique n’a pas été évaluée.
Objectifs
Comparer la valeur diagnostique des vitesses rapide et lente d’administration de l’ajmaline et évaluer le risque proarythmogène.
Méthodes
La première partie de l’étude a consisté à comparer de façon prospective les résultats et le taux de survenue d’arythmie ventriculaire pour deux vitesses d’administration de l’ajmaline. Trente-deux patients (hommes = 26; moyenne d’âge 41 ± 12 ans) ont réalisé deux tests à l’ajmaline sur deux jours distincts. Selon la randomisation, l’ajmaline (1 mg/kg) a été administrée à la vitesse d’1 mg/s ou sur dix minutes. La seconde partie de l’étude a évalué de façon rétrospective la prévalence des arythmies ventriculaires de 386 tests réalisés avec un protocole rapide d’administration de l’ajmaline.
Résultats
Aucune différence n’a été observée entre le test rapide et le test long. Tous les patients ayant un test rapide positif (15/32 [47 %]), ont eu également un résultat positif pour le test long. Des extrasystoles ventriculaires isolées ont été observées chez cinq sur 32 patients durant le test long et chez quatre sur 32 patients lors du test rapide. Aucun épisode d’arythmie ventriculaire soutenue n’est survenu. L’analyse des 386 tests rapides a mis en évidence quatre épisodes d’arythmie ventriculaire (deux extrasystoles ventriculaires complexes, une tachycardie ventriculaire non soutenue, une fibrillation ventriculaire).
Conclusion
Les protocoles rapide et lent d’administration de l’ajmaline offrent les mêmes performances diagnostiques dans les suspicions d’ECG de Brugada. En raison du risque d’arythmie ventriculaire sévère, une administration plus lente, permettant l’arrêt précoce de l’injection, est préconisée.
Background
BS is associated with a risk of sudden death due to VF . ECG abnormalities include J point elevation by at least 0.2 mV and a coved pattern of the ST segment with a negative T wave in the right precordial leads. Right bundle branch block can also be associated with the syndrome . These signs are sometimes intermittent. In 1996, Miyasaki et al. showed that ST elevation can be revealed by the use of sodium channel blocking agents . Ajmaline and flecainide have been used in Europe, procainamide in the USA and pilsicainide in Japan. The various drugs have been compared, and ajmaline has the highest sensitivity for detection of BS . However, ajmaline may have proarrhythmic effects and different infusion rates have been recommended . Administration of 1 mg/kg at the rate of 10 mg/min was proposed at the first consensus conference . Ajmaline challenge stopping criteria were defined in 2003 in order to avoid proarrhythmic effects. Fractionated administration of a dose of 10 mg every 2 minutes to reach a total dose of 1 mg/kg was proposed . In 2005, the second consensus conference recommended a dose of 1 mg/kg over 5 minutes . Other teams have reported their experience with protocols used to study conduction disorders, i.e. 1 mg/kg at a rate of 1 mg/sec . Finally, other authors (such as Wolpert et al.) use 1 mg/kg over 10 minutes . No randomized study has compared the sensitivity/specificity and risks associated with the various ajmaline administration protocols. Ajmaline induces concentration-dependent, frequency-independent and voltage-dependent sodium channel blockade , and concentration-dependent and frequency-independent inhibition of the transient outward potassium current . The rate of administration of ajmaline, by modifying the peak plasma concentration, can alter potassium channel inactivation and reactivation kinetics and modulate the intensity and duration of sodium channel blockade. Furthermore, as the time to onset of action of ajmaline is 2 to 3 minutes, rapid injection of ajmaline (1 mg/sec for a dose of 1 mg/kg) induces higher cardiac concentrations than the same dose injected over 10 minutes. Rapid injection could accentuate J point elevation during the first minutes to the detriment of the specificity of the test. Inversely, the dose injected over 10 minutes could reduce the sensitivity of the test. The objective of this study was to compare the electrocardiographic effects of two rates of administration of ajmaline and to determine whether the diagnostic contribution is modified by the ajmaline administration rate. Retrospective evaluation of the prevalence of VA in a series of 386 tests performed with injection of 1 mg/sec was designed to estimate the proarrhythmic risk during rapid injection of ajmaline.
Methods
Patients
The study was approved by the local ethics committee. Each subject signed an informed consent form. Between 2005 and 2008, 32 consecutive subjects with type 2 or 3 BS were prospectively included in the first phase of the study. In this population, ECG changes were disclosed after the onset of symptoms, incidentally or in the context of family screening. Exclusion criteria were contraindications to ajmaline (previous myocardial infarction, heart failure or impaired left ventricular ejection fraction, complete left bundle branch block, bifascicular block, second- or third-degree atrioventricular block, use of a class I antiarrhythmic agent, pregnancy or breastfeeding, children under the age of 15 years).
The second phase of the study consisted of retrospective evaluation of ajmaline challenges performed with the rapid injection protocol between January 2002 and July 2009. This phase comprised 386 subjects in whom the test was performed for family screening of BS or sudden death, unexplained syncope, discovery of type 2 or 3 ECG, or resuscitated cardiac arrest. ECG recordings were reviewed specifically for the analysis of VAs. Single VPBs, complex VPBs (frequent VPBs, polymorphic VPBs, bigeminy, couplets), NSVT and VF were notified.
Ajmaline challenges
Ajmaline challenges were conducted in the electrophysiology laboratory, in the presence of a cardiologist. Each patient underwent two ajmaline challenges, and the order was determined by randomization, with a crossover design. The two tests were performed on different days, < 1 month apart. All tests were performed at the same time of the day, in the late morning. Tests were preceded by echocardiography and β-human chorionic gonadotropin if necessary. The ajmaline injection was performed at a dose of 1 mg/kg, either at an infusion rate of 1 mg/sec or over 10 minutes.
Continuous 12-lead ECG monitoring, including leads V1 and V2 in the second intercostal space, was performed on a computerized electrophysiology system (EP Med Systems, NJ, USA). Measurements were performed with the software callipers, at a time-scale of 200 mm/sec at T0 (0 minutes), T3 (T0 + 3 minutes), T5 (T0 + 5 minutes) and T10 (T0 + 10 minutes) after the end of injection for the two protocols, and at T0, T3 and T5 after the beginning of injection for the slow test. ECGs were printed on paper at these different times and recorded continuously on optical disk. The presence of any arrhythmias was recorded. At the end of administration of ajmaline, the ECG recording continued until the reading returned to normal. The test results were evaluated by two independent, blinded observers. The test was considered positive if more than one lead exhibited coved type with a J point elevation > 0.2 mV .
Statistics
Variables are expressed as means and standard deviations. Comparisons between groups were performed by analysis of variance or by using the Wilcoxon test for paired samples. A paired Student’s t test was used to compare paired variables. Tests were considered to be significant for p < 0.05. Statistical analysis was performed with SPSS software Version 11 (SPSS Inc., Chicago, IL, USA).
Results
Part I
Study population
Subjects had a mean age of 40.9 ± 12 years (range 19–69); the sex ratio was 4.3 (81.2% men). Patients had a type 2 ECG in 22 (68.8%) cases and a type 3 ECG in 10 (31.2%) cases. Symptoms consisted of syncope ( n = 5), faintness ( n = 2) or palpitations ( n = 11). The other subjects were asymptomatic ( n = 14) and their ECG abnormality was found during a family screening ( n = 7) or fortuitously ( n = 7).
Test results
The concordance between rapid tests and slow tests was 100%. All patients diagnosed as positive or negative with one test obtained the same result with the other test. No difference in the results was observed between the two tests according to readings by the two observers ( Fig. 1 ). The positive ajmaline challenge rate was 46.9% (15/32). Ajmaline challenges were more often positive for type 2 ECGs than for type 3 ECGs ( p < 0.001). No significant difference in the VPB rate was observed according to the protocol used ( p = 0.51). VPBs occurred in three subjects during positive tests and in five subjects during negative tests. No runs of VPBs were observed during the 64 tests; ECG changes were identical for the two protocols ( Table 1 ) and for both positive and negative tests, except for the QTc interval ( Table 2 ). The maximum variation of the amplitude of J point was observed in lead V2 for the two tests, in 75 and 69% of cases, respectively. The peak changes in J point elevation, PR, RR, QRS and QTc interval were observed 3 minutes after injection, except in RR in the slow test ( Figs. 2 and 3 ).
| Variable | Rapid infusion ( n = 32) | Slow infusion ( n = 32) | p a | ||||
|---|---|---|---|---|---|---|---|
| Baseline | 3 minutes | Δ (%) | Baseline | 10 minutes | Δ (%) | ||
| PR (ms) | 167 ± 28 | 219 ± 3 6 | 32.5 | 166 ± 32 | 217 ± 33 | 32.8 | 0.8 |
| QRS (ms) | 103 ± 14 | 134 ± 18 | 31.7 | 100 ± 13 | 132 ± 17 | 33.6 | 0.8 |
| QTc (ms) | 425 ± 37 | 481 ± 32 | 13.7 | 403 ± 24 | 470 ± 39 | 16.7 | 0.2 |
| RR (ms) | 847 ± 78 | 740 ± 10 | –11.1 | 902 ± 133 | 754 ± 87 | –15.5 | 0.06 |
| J wave (mV) | 0.28 ± 0.1 | 0.51 ± 0.17 | 95.0 | 0.26 ± 0.1 | 0.51 ± 0.22 | 96.8 | 0.5 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
