Cardiac autonomic dysfunction in Brugada syndrome

Circulation. 2002 Feb 12;105(6):702-6. doi: 10.1161/hc0602.103677.


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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Iodobenzylguanidine / pharmacokinetics
  • Adult
  • Aged
  • Autonomic Nervous System / cytology
  • Autonomic Nervous System / drug effects
  • Autonomic Nervous System / metabolism
  • Autonomic Nervous System Diseases / complications
  • Autonomic Nervous System Diseases / diagnosis*
  • Autonomic Nervous System Diseases / physiopathology*
  • Bundle-Branch Block / complications
  • Bundle-Branch Block / physiopathology
  • Death, Sudden, Cardiac / etiology
  • Electrocardiography*
  • Female
  • Heart / innervation*
  • Heart / physiopathology*
  • Heart Ventricles / physiopathology
  • Humans
  • Iodine Radioisotopes
  • Male
  • Middle Aged
  • Neurons / metabolism
  • Norepinephrine / metabolism
  • Presynaptic Terminals / metabolism
  • Radiopharmaceuticals / pharmacokinetics
  • Syndrome
  • Tachycardia, Ventricular / complications
  • Tachycardia, Ventricular / physiopathology
  • Tomography, Emission-Computed, Single-Photon


  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • 3-Iodobenzylguanidine
  • Norepinephrine