Published Online
on December 31, 2001

A more recent version of this article appeared on February 12, 2002

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Submitted on June 6, 2001
Revised on November 20, 2001
Accepted on December 14, 2001

Cardiac Autonomic Dysfunction in Brugada Syndrome

Thomas Wichter MD, FESC^*, Peter Matheja MD, Lars Eckardt MD, Peter Kies MD, Klaus Schäfers PhD, Eric Schulze-Bahr MD, Wilhelm Haverkamp MD, Martin Borggrefe MD, FESC, Otmar Schober MD, PhD, FESC, Günter Breithardt MD, FESC, and Michael Schäfers MD

From the Hospital of the Westfälische Wilhelms-University, Department of Cardiology and Angiology (T.W., L.E., E.S.-B., W.H., M.B., G.B.), the Institute for Arteriosclerosis Research (T.W., P.K., W.H., G.B.), and the Department of Nuclear Medicine (P.M., P.K., K.S., O.S., M.S.), Münster, Germany.

^* To whom correspondence should be addressed. E-mail: wichtet{at}uni-muenster.de.

Background—Patients with Brugada syndrome present with characteristic ECG abnormalities (atypical right bundle-branch block and ST-segment elevation) and life-threatening ventricular tachyarrhythmias despite structurally normal hearts. Involvement of the autonomic nervous system is suggested by the occurrence of ventricular tachyarrhythmias and sudden death at rest or during sleep and by changes of typical ECG signs under pharmacological modulation of the myocardial autonomic tone.

Methods and Results—This study investigated the presynaptic cardiac neuronal reuptake of norepinephrine (uptake 1) in 17 patients with Brugada syndrome and 10 age-matched control subjects with the use of the norepinephrine analogue [¹²³I]m-iodobenzylguanidine (¹²³I-MIBG), single-photon emission CT (SPECT), and quantitative 33-segment bull's-eye analysis. Regionally reduced ¹²³I-MIBG uptake was present in 8 (47%) of 17 patients with Brugada syndrome but in none of the control subjects. Quantitative analysis showed segmental reduction of ¹²³I-MIBG uptake in the inferior and septal left ventricular wall in patients with Brugada syndrome compared with control subjects (P<0.05). No correlation was found between the findings of ¹²³I-MIBG-SPECT and clinical characteristics of the study patients.

Conclusions—The present study demonstrated an abnormal ¹²³I-MIBG uptake in patients with Brugada syndrome, indicating presynaptic sympathetic dysfunction of the heart. These findings may have potential impact on the pathophysiology and arrhythmogenesis in patients with Brugada syndrome. Future quantitative investigations of the presynaptic and postsynaptic sympathetic and parasympathetic branches of the cardiac autonomic nervous system may clarify whether these observations represent a primary adrenergic dysfunction or an imbalance between sympathetic and parasympathetic innervation of the heart.

Key words: Brugada syndrome • death, sudden • nervous system, autonomic • tomography • norepinephrine

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