Aborted sudden death in a young male

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 rsR9 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. The Gussak diagnostic criteria 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. 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-ofhospital cases of ventricular fibrillation, unrelated to myocardial infarction, occur in those with minimal or no structural heart disease. 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. 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%. 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. Considerable variation exists in the clinical presentation, and several ‘‘forms’’ of Brugada syndrome have been described: manifest, concealed, asymptomatic, suspected, and simulated. 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. Q2: What is the pathophysiological basis of this condition? What further diagnostic tests would you consider doing in this patient?