Brugada Syndrome and Brugada ECG Pattern: Unusual Causes of ST Elevation

S Ley, A Cameron

Brugada Syndrome is a channelopathy that leads to ST elevation or right bundle branch block pattern in the right ventricular leads on ECG analysis and predisposes to ventricular tachyarrhythmias and sudden death [1]. The ECG pattern can also be drug induced with several agents [2,3]. This case describes a patient who presented after a mixed overdose of amitriptyline, olanzapine and alimemazine with ST elevation and T wave inversion on his ECG that were initially thought to be due to an Acute Coronary Syndrome.

Case Report

A 40 year old bricklayer with a background of anxiety and psychotic depression was found by his mother shaking and groaning after ingesting 1.2g of amitriptyline, and unknown quantities of olanzapine and alimemazine (a first generation anti-histamine). Further questioning revealed that he had taken 800mg of amitriptyline two days previously and had been regularly taking higher than prescribed doses as he felt his symptoms were not being adequately controlled. He complained of some abdominal discomfort but had no other symptoms. He had no past medical history or family history of note, specifically no history of cardiac disease, syncope, palpitations or sudden death in the family.

Assessment in the emergency department revealed an agitated patient with a GCS of 15 and normal observations apart from a mild tachycardia (104/min). Examination of the chest revealed normal heart sounds with vesicular breathing throughout both lungs with mild bibasal inspiratory crepitations. There was some epigastric tenderness but no signs of peritonism. Central nervous system examination revealed bilateral nystagmus, intention tremor and past pointing but no other abnormalities.

Routine bloods were unremarkable with a blood glucose of 5.5 and undetectable paracetamol and salicylate levels. Blood gas analysis was normal and chest x-ray showed some atelectesis at the right base but no signs of cardiac failure.

His 12 lead ECG showed a narrow complex sinus tachycardia (rate of approximately 100) with left axis deviation (present on previous admission) with ST elevation and inverted T waves in V1-V3. Acute Coronary Syndrome was initially considered, however the absence of typical cardiac chest pain and an absence of an elevation in serum Troponin T, an alternative diagnosis of type 1 Brugada ECG pattern secondary to mixed overdose was made.

The patient was admitted to the medical receiving unit and monitored via telemetry. His ECG was repeated during the night and the next morning by which time the ST elevation and T wave inversion had resolved (fig 1) and the patient was well and was discharged after psychiatric review.

The amitriptyline levels as measured in the national reference centre subsequently showed that although the Brugada pattern had resolved on his ECG, the serum TCA levels had actually climbed during this period, making amitriptyline an unlikely sole cause of the ECG abnormalities. Olanzapine is not known to cause Brugada pattern changes on ECG. The main clinical findings were tachycardia and cerebellar signs which are more in keeping with alimemazine overdose. Since this is a first generation antihistamine, this gives a plausible explanation for the ECG changes as first generation antihistamines are known to be responsible for producing a Brugada pattern ECG [4].

Figure 1 Leads V1-3 from ECGs taken before, during and after admission showing different degrees of ST elevation and T wave inversion, with corresponding amitriptyline levels.

Previous admission ECG and Amitriptyline Levels on Presentation in ED ECG and Amitriptyline Levels 15 hours post presentation
  Amitriptyline 440μgrams/L Amitriptyline 740 μgrams/L
  Nortriptyline 250 μgrams/L Nortriptyline 200 μgrams/L

Lab Ranges - In therapy serum amitriptyline plus nortriptyline concentrations are usually less than 300 ug/L. Concentrations greater than 1000ug/L are often associated with serious toxicity.

 

Discussion

Brugada Syndrome is a channelopathy characterised by right bundle branch block and ST elevation in the anterior chest leads and is a cause of sudden cardiac death due to ventricular tachyarrhythmias [1]. It is either inherited in an autosomal dominant pattern or caused by new genetic mutation causing errors in the coding for ion channels in cardiac myocytes. The most commonly documented mutation is that of the SCN5A gene, which codes for voltage gated sodium channels [5].

The net effect is a reduction of the sodium current through phase 0 and 1 of the cardiac action potential, with the greatest effect in the right ventricle. The reduced sodium current leads to early repolarisation of the epicardial cells compared to endocardial cells resulting in a voltage gradient and elevation of the ST segment in the right ventricular leads. This uncoordinated repolarisation can predispose to re-entry arrhythmias leading to ventricular tachycardia and fibrillation [6].

Brugada syndrome has a number of subtypes based on ECG characteristics (fig 2).
Type 1 has an elevated coved ST segment elevation with an inverted T wave and is pathognomonic of Brugada Syndrome. Type 2 has ST elevation in a “saddle back” appearance that remains at least 1mm above the isoelectric line followed by a T wave that is positive or biphasic. Type 3 is similar to Type 2, however the ST segment elevation may drop within 1mm of the isoelectric line [7].

Figure 2 ECG characteristics of the different types of Brugada Syndrome. Re-produced with permission from: A Wilde, A, Antzelevitch, Borggrefe, M, J et al. Proposed Diagnostic Criteria for the Brugada Syndrome. Circulation 2002;106:2514. Copyright © American Heart Association

Diagnosis of Brugada Syndrome when a type 2or 3 pattern is present is by challenge with a class I (sodium channel blocker) anti-arrhythmic drug e.g. flecainide or procainamide to induce the type 1 ECG changes [7]. Pharmacological management has been tried, the preferred long term management of Brugada Syndrome in by insertion of an implantable cardiac defibrillator [8].

Although Brugada Syndrome is a genetic condition, there are an increasing number of drugs not related to class I anti-arrhythmics that have been reported to cause a temporary Brugada ECG pattern in patients who do not have the characteristic genetic mutations. These include tricyclic antidepressants, fluoxetine, lithium, trifluoperazine, antihistamines, and cocaine. Whilst the exact mechanism is unclear, it has been hypothesised that exposure to these drugs unmasks a latent ion channel dysfunction leading to the Brugada pattern ECG [9]. It is unclear whether these ECG changes predispose to the ventricular tachyarrhythmias that affect people with Brugada Syndrome; however, many of the drugs had well known and well documented cardiac side effects of their own.

Conclusion

In this case, our patient had taken excessive quantities of two drugs known to cause a Brugada pattern ECG, amitriptyline and alimemazine. There was nothing in his family history to suggest inherited disease and no prior Brugada pattern on previous ECGs.

The resolution of the ECG changes with the concurrent rise in amitriptyline levels suggests that maybe the ECG changes in this scenario were due to the action of the significant amount of alimemazine ingested. Other cases of Brugada ECG pattern related to antihistamines include a patient taking 4 different oral antihistamines (all first or second generation) and a patient receiving an IV infusion of dimenhydrinate, a first generation antihistamine [10]. In both these cases the ECG reverted to normal with cessation of the drug. This story is similar to our patient.

Brugada Syndrome and Brugada pattern ECG changes are important differentials to consider when looking at an ECG that shows ST elevation in the anterior chest leads. Doctors should be aware there are a variety of drugs, both prescribed and illicit that can cause an ECG appearance similar to that of a ST elevation myocardial infarction and the differing aetiologies should be recognised to avoid potentially dangerous procedures such as thrombolysis or percutaneous coronary intervention. Doctors should also be aware of the Brugada Syndrome itself which, untreated, can lead to sudden cardiac death.

References

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