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Aborted sudden death in a young male

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Q1: What is the ECG (fig 1; p 660) diagnosis? Why is it important to recognise this condition?

Figure 1

 Phases of the cardiac ventricular action potential; solid line shows normal ventricular action potential and dotted line shows Brugada-type action potential (schematic).

The ECG done on his arrival at the emergency room (see questions) shows (i) sinus tachycardia, (ii) a QRS complex that ends with a positive deflection (or prominent J wave) that is, a rsR′ pattern in V1 and V2, and (iii) an elevated downsloping ST segment ending in a small negative T-wave deflection. This ECG pattern in someone with a history of syncopy and documented ventricular fibrillation/aborted sudden death, is most consistent with the eponymous Brugada syndrome. Described first in 1992 by Brugada and Brugada, Brugada syndrome is an inherited arrhythmogenic disease, which may presage ventricular fibrillation and sudden cardiac death.1–5

The Gussak diagnostic criteria1 for Brugada syndrome are shown in box 1. One must be aware that ST elevation in the right praecordial ECG leads occurs in a variety of clinical conditions, as shown in box 2, and hence clinical correlation with diligent characterisation of the ECG is mandatory before a diagnosis of Brugada syndrome is made.

Box 1: Gussak’s criteria

  • Major criteria*:

    1. Presence of the ECG marker of Brugada syndrome in patients with structurally normal heart.

    2. Appearance of the ECG marker of Brugada syndrome after administration of sodium channel blocker.

  • Minor criteria*:

    1. Family history of sudden cardiac death.

    2. Syncopy of unknown origin.

    3. Documented episodes of ventricular tachycardia/ventricular fibrillation.

    4. Positive programmed electrocardiostimulation test on ventricular tachycardia/ventricular fibrillation.

    5. Genetic mutations of ion channels (yet to be fully defined).

Box 2: Causes of ST segment elevation in right praecordial ECG leads

  • Anterior myocardial infarction.

  • Right or left bundle branch block.

  • Right ventricular infarction.

  • Left ventricular aneurysm.

  • Exercise test induced.

  • Acute myocarditis.

  • Dissecting aortic aneurysm.

  • Acute pulmonary thromboembolism.

  • Right ventricular outflow tract obstruction (tumour, etc).

  • Various central and autonomic nervous system disorders.

  • Duchenne's muscular dystrophy.

  • Friedrich's ataxia.

  • Hypercalcaemia and hyperkalaemia.

  • Heterocyclic antidepressant overdose.

  • Cocaine intoxication.

  • Thiamine deficiency (beriberi).

Adapted from Gussak et al.2

Brugada syndrome is a recognised cause of sudden cardiac death, and hence the need for prompt recognition and treatment. Every year, in the United States alone, there are about 300 000 new cases of sudden death due to cardiac arrest. Altogether 3%–9% out-of-hospital cases of ventricular fibrillation, unrelated to myocardial infarction, occur in those with minimal or no structural heart disease.2 Such cases may include those with Brugada syndrome, congenital and acquired long QT syndromes, pre-excitation states such as Wolff-Parkinson-White syndrome, and cases where no ready cause is apparent (so called “idiopathic” ventricular fibrillation). Though seen worldwide, Brugada syndrome in endemic in Southeast Asia and Japan, where it is known as sudden unexplained death syndrome and sudden unexplained nocturnal death syndrome, and the incidence has been estimated to range between five and 66 events per 100 000 people.3 In some countries, the prevalence of Brugada-type ECG changes among those who were diagnosed with “idiopathic ventricular fibrillation”, has been estimated to be as high as 40%–60%.2 Studies quote an incidence of sudden cardiac death varying between 44%–62% in those with Brugada-type ECG and history of aborted sudden death/syncopy.3 Considerable variation exists in the clinical presentation, and several “forms” of Brugada syndrome have been described: manifest, concealed, asymptomatic, suspected, and simulated.4 Brugada syndrome affects males preferentially, and the mean age of those affected tends to be in the mid to late thirties. Clinical manifestation of Brugada syndrome are attributed exclusively to the malignant ventricular arrhythmias that occur in this condition. Tragically, sudden death may be the first and only clinical event. These arrhythmias often occur at rest, and in some at night-time. High sympathetic tone, anxiety, and alcohol consumption have all been proposed as possible provocative factors.2

Q2: What is the pathophysiological basis of this condition? What further diagnostic tests would you consider doing in this patient?

Genetic studies have shown that Brugada syndrome and chromosome 3-linked long QT syndrome (LQT3) are allelic disorders of the cardiac channel gene (SCN5A, 3p21). The inheritance is autosomal dominant with variable penetrance. The SCN5A gene codes for the alpha subunit of the sodium channel. Mutations of this gene results in abnormalities of the sodium channel, with abnormal ion conductance patterns and can be demonstrated in up to 25% Brugada syndrome cases.2–35 Brugada-type downsloping ST segment is a normal feature of the ECG in some rodents, whereas in higher mammals, the ST segment is usually isoelectric in the normal state. Figure 1 (below) describes the various phases of the cardiac ventricular action potential. Failure of the plateau phase or “dome” to develop occurs when the transient outward currents, termed Ito (phases 1 and 3; fig 1) overwhelms the inward current, mainly the calcium current termed ICa (phase 2; fig 1). This results in a 40%–70% abbreviation of the action potential in some, but not all epicardial sites (schematically represented by the dotted line in fig 1), resulting in a marked dispersion of repolarisation within the ventricular muscle. This is manifest on the ECG as marked QT-dispersion. Propagation of the dome from sites where it is maintained to sites where it is abolished (termed phase 2 re-entry) can result in local re-excitation, producing closely coupled extrasystoles, which in turn may initiate circus movement re-entry.2 In those cases where the typical ECG changes are evanescent, programmed electrical stimulation (PES) with or without chemical challenge with certain drugs may unmask the ST segment elevation in V1–V3 and right bundle branch block-like pattern in many patients.1 Sodium channel blockers (SCB) such as procainamide, ajmaline and flecainide, β-blockers such as propranalol, α-adrenergic and muscarinic stimulation—all may bring out the typical ECG features, and indeed induce ventricular tachyarrhythmia and/or ventricular fibrillation in those with Brugada syndrome. While PES and SCB challenge may be useful in risk stratifying patients with Brugada syndrome, their ability to identify the symptomatic (cardiac arrest, syncopy) cases is at best modest (for PES, positive and negative predictive values and overall accuracy 50%, 46% and 49% respectively; for SCB challenge, positive predictive value 35%).1 A complete workup of a symptomatic patient with Brugada syndrome may also include echocardiography, coronary angiography, stress testing, magnetic resonance imaging, and rarely, myocardial biopsy.4 This patient underwent PES with procainamide challenge, which resulted in inducing the ventricular tachyarrhythmia. He underwent cardiac catheterisation, which revealed normal coronary artery anatomy and left ventricular function.

Q3: How is this condition treated? What is the prognosis?

For the symptomatic Brugada patients (syncopy, aborted sudden death) the treatment of choice is placement of an implantable cardioverter-defibrillator (ICD) device. The incidence of arrhythmic events is similar in patients receiving either an ICD device, β-blocker or amiodarone, but only the ICD device protects patients with Brugada syndrome from sudden death. To this date, there is no pharmacological agent that has been shown to confer a survival benefit to patients with Brugada syndrome.12

In some countries such as Japan, the incidence of asymptomatic Brugada syndrome cases is very high and far exceeds those with symptoms. In as much as the ICD device prevents death in symptomatic cases, many lives could be potentially saved if we could successfully identify the high risk, asymptomatic patients as well.3 There is some evidence that asymptomatic patients with Brugada syndrome who have a positive provocative test may benefit by placement of an ICD device. When followed up for over 33 months, 17% of inducible Brugada syndrome patients had an arrhythmia compared with a mere 2% among those who were not inducible.3 As to what constitutes optimal therapy for non-inducible cases of Brugada syndrome, is still unclear and more studies are required to address this question.5

Regardless of the presence or absence of symptoms, the prognosis of Brugada syndrome is poor, with a 10% per year mortality.5 While no correlation between right bundle branch block and SCD has yet been established in a population other than those with Brugada syndrome, the magnitude of ST segment elevation has been linked to the incidence of life threatening arrhythmias, especially in Brugada syndrome.2 Careful attention to the ECG is mandated in every case of aborted sudden cardiac death in order to recognise and treat the patient with the Brugada syndrome.

Final diagnosis

Brugada syndrome.

References

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Footnotes

  • * One major and one minor criterion together are needed for a diagnosis of Brugada syndrome.

  • Typically consists of rsR′ pattern with an elevated terminal portion of the QRS complex (prominent J-wave ) in V1–V3, non-injury related elevated descending ST segment and negative T-wave in the same leads. Adapted from Gussak et al.1

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