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  • Review Article
  • Published:

Pathogenesis and management of Brugada syndrome

Nature Reviews Cardiology volume 13, pages 744–756 (2016)Cite this article

Subjects

Key Points

  • Brugada syndrome is an inherited disease responsible for a large number of sudden deaths in young people without structural heart anomalies

  • The pathophysiology of Brugada syndrome is unclear; repolarization–depolarization abnormalities underlying this disease can present with different features in different patients

  • A common electrocardiogram (ECG) phenotype seen in patients with Brugada syndrome might be the result of different pathophysiological mechanisms

  • Symptom-type, a spontaneous type 1 ECG pattern, the presence of sinus node dysfunction, and inducible ventricular arrhythmias during programmed stimulation of the heart might help to stratify patients by risk

  • Implantable cardioverter–defibrillator therapy is the most accepted treatment strategy for at-risk patients

  • Electrophysiological-guided therapy with quinidine and radiofrequency substrate ablation might also have a role in the management of these patients

Abstract

Brugada syndrome is an inherited disease characterized by an increased risk of sudden cardiac death owing to ventricular arrhythmias in the absence of structural heart disease. Since the first description of the syndrome >20 years ago, considerable advances have been made in our understanding of the underlying mechanisms involved and the strategies to stratify at-risk patients. The development of repolarization–depolarization abnormalities in patients with Brugada syndrome can involve genetic alterations, abnormal neural crest cell migration, improper gap junctional communication, or connexome abnormalities. A common phenotype observed on the electrocardiogram of patients with Brugada syndrome might be the result of different pathophysiological mechanisms. Furthermore, risk stratification of this patient cohort is critical, and although some risk factors for Brugada syndrome have been frequently reported, several others remain unconfirmed. Current clinical guidelines offer recommendations for patients at high risk of developing sudden cardiac death, but the management of those at low risk has not yet been defined. In this Review, we discuss the proposed mechanisms that underlie the development of Brugada syndrome and the current risk stratification and therapeutic options available for these patients.

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Figure 1: The repolarization theory of Brugada syndrome.
Figure 2: The depolarization theory of Brugada syndrome.
Figure 3: Neural crest cell migration.
Figure 4: Electrocardiogram patterns associated with Brugada syndrome.

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Authors and Affiliations

  1. Heart Rhythm Management Centre, UZ Brussel-VUB, Brussels, Laarbeeklaan 101, 1090, Brussels, Belgium

    Juan Sieira, Gregory Dendramis & Pedro Brugada

  2. Cardiology Department, University Hospital Erasme, Route de Lennik 808, 1070, Brussels, Belgium

    Juan Sieira

  3. Cardiovascular Division, University Hospital “Paolo Giaccone”, Via Del Vespro 127., 90127, Palermo, Italy

    Gregory Dendramis

Authors
  1. Juan Sieira
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  2. Gregory Dendramis
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  3. Pedro Brugada
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Contributions

J.S. and G.D. contributed equally to this work. All the authors researched data for the article, substantially contributed to discussion of content, and wrote, reviewed, and edited the manuscript before submission.

Corresponding author

Correspondence to Pedro Brugada.

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Competing interests

P.B. has received institutional grants from Biotronik, Medtronic, and St. Jude Medical. The other authors declare no competing interests.

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Sieira, J., Dendramis, G. & Brugada, P. Pathogenesis and management of Brugada syndrome. Nat Rev Cardiol 13, 744–756 (2016). https://doi.org/10.1038/nrcardio.2016.143

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