Pathophysiological mechanisms of Brugada syndrome: Depolarization disorder, repolarization disorder, or more?

Paola G. Meregalli, A. A M Wilde, Hanno L. Tan

Research output: Contribution to journalArticlepeer-review


After its recognition as a distinct clinical entity, Brugada syndrome is increasingly recognized worldwide as an important cause of sudden cardiac death. Brugada syndrome exhibits autosomal dominant inheritance with SCN5A, which encodes the cardiac sodium channel, as the only gene with a proven involvement in 20-30% of patients. Its signature feature is ST segment elevation in right precordial ECG leads and predisposition to malignant ventricular tachyarrhythmias. The pathophysiological mechanism of ST elevation and ventricular tachyarrhythmia, two phenomena strongly related, is controversial. Here, we review clinical and experimental studies as they provide evidence to support or disprove the two hypotheses on the mechanism of Brugada syndrome that currently receive the widest support: (1) nonuniform abbreviation of right ventricular epicardial action potentials ("repolarization disorder"), (2) conduction delay in the right ventricular outflow tract (" depolarization disorder"). We also propose a schematic representation of the depolarization disorder hypothesis. Moreover, we review recent evidence to suggest that other derangements may also contribute to the pathophysiology of Brugada syndrome, in particular, right ventricular structural derangements. In reviewing these studies, we conclude that, similar to most diseases, it is likely that Brugada syndrome is not fully explained by one single mechanism. Rather than adhering to the notion that Brugada syndrome is a monofactorial disease, we should aim for clarification of the contribution of various pathophysiological mechanisms in individual Brugada syndrome patients and tailor therapy considering each of these mechanisms.

Original languageEnglish
Pages (from-to)367-378
Number of pages12
JournalCardiovascular Research
Issue number3
Publication statusPublished - Aug 15 2005


  • Arrhythmia
  • Conduction (block)
  • Ion channels
  • Sudden death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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