The ajmaline challenge in Brugada syndrome

A useful tool or misleading information?

J Brugadaa,*, P Brugadab and R Brugadac

a Arrhythmia Section, Cardiovascular Institute, Hospital Clínic, University of Barcelona, Barcelona, Spain
b Cardiovascular Research and Teaching Institute, OLV Hospital, Aalst, Belgium
c Masonic Medical Research Laboratory, NY Utica, USA

* Corresponding author: Josep Brugada, MD, Arrhythmia Section, Cardiovascular Institute, Hospital Clínic, Villarroel 170, 08036, Barcelona, Spain. Tel. +34-93-22275551; fax. +34-93-4513045
E-mail address: jbrugada{at}clinic.ub.es

Received 3 April 2003; accepted 4 April 2003

See doi:10.1016/S1095-668X(03)00195-7for the article to which this editorial refers

Ajmaline is a class I antiarrhythmic drug with potent sodium channel blocking effects and a very short half-life which makes it a very useful drug for acute intravenous treatments. The drug has been very popular in some countries for the treatment of atrial fibrillation in patients with the Wolff–Parkinson–White syndrome and in well tolerated monomorphic ventricular tachycardias. It has also been used for many years as a drug to challenge the conduction system of the heart in cases of bundle branch block and syncope. In these cases, abnormal prolongation of the HV interval has been taken as a proof for infrahisian conduction defects tributary for permanent pacemaker implantation.

Some years ago, thanks to the work by Miyazaki et al.,1ajmaline and other class I antiarrhythmic drugs were used to unmask the electrocardiographic abnormalities diagnostic of the Brugada syndrome. In about 40% of the patients with the classical electrocardiographic pattern, transient normalization of the electrocardiogram occurred at some time during follow-up. Class I antiarrhythmic drugs administration were able to resume the electrocardiographic abnormalities.2

Some years later, the genetic nature of the disease was documented, and mutations in the cardiac sodium channel gene were described as responsible for the syndrome.3It was also reported that due to the incomplete penetrance, some patients carriers of the mutation had a basal normal electrocardiogram and thus, the disease was left undiagnosed in them unless a genetic testing was available.

The next step was to test if the use of ajmaline could unmask the electrocardiographic abnormalities in these mutation carriers with a basal normal electrocardiogram. The first report correlating genetic testing and ajmaline challenge showed a 100% specificity and sensitivity of the test.4Other reports have shown that some false positive tests might occur.5

In the present issue of the Journal, Rolff et al.6report the results of the ajmaline test in 158 patients. A positive test was found in 23% of the patients. Of notice, the test was positive in about 50% of patients with a suspicious pattern on the basal electrocardiogram. Also, 45% of patients without demonstrable structural heart disease and recovered from sudden cardiac death had a positive test. These data suggest that the test is highly effective in diagnosing the electrocardiographic abnormalities in a group of patients with the strong suspicion of having a primary electrical disease.

However, the main concern relates to the possibility of having a positive test in individuals not having the disease, for instance after a syncopal episode. In their series, Rolf et al. report that 9 out of 63 patients with syncope had a positive test, the majority having a family history of unexplained sudden death and a basal suspicious electrocardiogram. Only 2 out of 94 patients with a normal electrocardiogram and a history of syncope had a positive test. Whether these patients have the disease or are false-positive results can only be demonstrated be the genetic diagnosis available. Due to the impact that a positive test might have in the management of these patients, it is absolutely necessary to have more information in larger groups of patients with a genetically demonstrated disease to clarify the value of the test.

Very few reports have shown that the ajmaline challenge might result in some proarrhythmic effects. In this regard, the paper by Rolf et al. clarifies this subject. In their series, two patients presented with ventricular arrhythmias during the test. In both cases a very positive result of the test was noticed. The proarrhythmic effect occurred because despite a clearly positive electrocardiogram, the authors continued to administer the drug until the 1mg/kg dose was completed. In view of these two accidents, the authors changed the protocol and terminated the drug administration if a positive result was obtained, independently of the dose used. Since then, no new proarrhythmic events occurred.

Unfortunately, the very low price of the drug and the limited number of indications have led to a withdrawal of ajmaline from the market in the majority of countries. Other drugs might have a similar effect, like flecainide or procainamide. However, initial experience show that procainamide might be less useful and flecainide needs longer monitoring of the patients due to a prolonged effect. Once more, physicians have not been consulted and decisions affecting our daily practice are taken without looking at medical needs.

References

  1. Miyazaki T, Mitamura H, Miyoshi S et al. Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol. 1996;27:1061–1070.[CrossRef][Medline]
  2. Brugada J, Brugada R, Brugada P. Right bundle branch block and ST segment elevation in leads V1 through V3. A marker for sudden death in patients without demonstrable structural heart disease. Circulation. 1998;97:457–460.[Abstract/Free Full Text]
  3. Chen Q, Kirsch GE, Zhang D et al. Genetic basis and molecular mechanisms for idiopathic ventricular fibrillation. Nature. 1998;392:293–296.[CrossRef][Medline]
  4. Brugada R, Brugada J, Antzelevitch C 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;101:510–515.[Abstract/Free Full Text]
  5. Priori SG, Napolitano C, Gasparini M et al. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome. A prospective evaluation of 52 families. Circulation. 2000;102:2509–2515.[Abstract/Free Full Text]
  6. Rolf S, Bruns HJ, Wichter T et al. The ajmaline challenge in Brugada syndrome: Diagnostic impact, safety, and recommended protocol. Eur Heart J. 2003;24:1104–1112.[Abstract/Free Full Text]

Related articles in EHJ:

The ajmaline challenge in Brugada syndrome: Diagnostic impact, safety, and recommended protocol
Sascha Rolf, Hans-Jürgen Bruns, Thomas Wichter, Paulus Kirchhof, Michael Ribbing, Kristina Wasmer, Matthias Paul, Günter Breithardt, Wilhelm Haverkamp, and Lars Eckardt
EHJ 2003 24: 1104-1112. [Abstract] [Full Text]  




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