Brugada syndrome: More than 20 years of scientific excitement

In 1992 we reported on eight patients with a particular electrocardiograph (ECG) showing ST segment elevation in the right precordial leads. All patients had a structurally normal heart and had survived one or multiple episodes of near sudden death caused by ventricular fibrillation. We showed 6 years later that this disease, known nowadays as Brugada syndrome, was caused by mutations in the SCN5A gene which encodes for the cardiac sodium channel. Other genes where mutations result in the same ECG have been also identified, with at present more than 17 different genes published. These data show that Brugada syndrome is a genetically heterogeneous disease as is also the case in the long QT syndrome. In Brugada syndrome, the clue to the initial clinical diagnosis remains the abnormal ECG. However, it was evident from the beginning that the ECG of Brugada syndrome is variable and sensitive to many autonomic, drug, exercise, emotions and other external influences such as a meal, fever, changes in heart rate from any cause, and even body position. When followed intensively, all patients with a Brugada ECG will show a completely normal ECG at one or another moment in their lives. The spontaneous normalization of the ECG represents a major diagnostic challenge, because a patient with Brugada syndrome seen during normalization of the ECG may fail to get the correct diagnosis. In these more than 20 years great challenges have been overcome but some remain, mainly the approach to the asymptomatic individual with a diagnosis of Brugada syndrome. In 30-50% of individuals who die suddenly because of documented or suspected Brugada syndrome, sudden death is the first manifestation of the disease. Thus, these individuals were fully asymptomatic until the first fatal event.