CLINICAL STUDIES
The Brugada syndrome: clinical, electrophysiologic and genetic aspects
Ihor Gussak, MD, PhD*,
Charles Antzelevitch, PhD, FACC ,
Preben Bjerregaard, MD, DMSc, FACC*,
Jeffrey A. Towbin, MD, FACC and
Bernard R. Chaitman, MD, FACC*
* St. Louis University Health Science Center, St. Louis, Missouri, USA
Masonic Medical Research Laboratory, Utica, New York, USA
Baylor College of Medicine, Houston, Texas, USA
Manuscript received January 8, 1998;
revised manuscript received August 12, 1998,
accepted September 15, 1998.
Address for correspondence: Dr. Ihor Gussak, St. Louis University Health Science Center, Internal Medicine, Division of Cardiology, 1034 Brentwood Blvd., Suite 1550, St. Louis, Missouri 63117
ibgussak{at}ecglab.org
This review deals with the clinical, basic and genetic aspects of a recently highlighted form of idiopathic ventricular fibrillation known as the Brugada syndrome. Our primary objective in this review is to identify the full scope of the syndrome and attempt to correlate the electrocardiographic manifestations of the Brugada syndrome with cellular and ionic heterogeneity known to exist within the heart under normal and pathophysiologic conditions so as to identify the cellular basis and thus potential diagnostic and therapeutic approaches. The available data suggest that the Brugada syndrome is a primary electrical disease resulting in abnormal electrophysiologic activity in right ventricular epicardium. Recent genetic data linking the Brugada syndrome to an ion channel gene mutation (SCN5A) provides further support for the hypothesis. The electrocardiographic manifestations of the Brugada syndrome show transient normalization in many patients, but can be unmasked using sodium channel blockers such as flecainide, ajmaline or procainamide, thus identifying patients at risk. The available data suggest that loss of the action potential dome in right ventricular epicardium but not endocardium underlies the ST segment elevation seen in the Brugada syndrome and that electrical heterogeneity within right ventricular epicardium leads to the development of closely coupled premature ventricular contractions via a phase 2 reentrant mechanism that then precipitates ventricular tachycardia/ventricular fibrillation (VT/VF). Currently, implantable cardiac defibrillator implantation is the only proven effective therapy in preventing sudden death in patients with the Brugada syndrome and is indicated in symptomatic patients and should be considered in asymptomatic patients in whom VT/VF is inducible at time of electrophysiologic study.
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Abbreviations and Acronyms
| | ARVD | = arrhythmogenic right ventricular dysplasia | | ECG | = electrocardiographic | | ERS | = early repolarization syndrome | | ICa | = calcium current | | ICD | = implantable cardiac defibrillator | | IK-ATP | = adenosine triphosphate–sensitive potassium current | | INa | = sodium current | | Ito | = transient outward current | | RBBB | = right bundle branch block | | SUDS | = sudden and unexplained death syndrome | | TdP | = Torsade de Pointes | | VF | = ventricular fibrillation | | VT | = ventricular tachycardia |
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