Cellular mechanism and arrhythmogenic potential of T-wave alternans in the Brugada syndrome

J Cardiovasc Electrophysiol. 2008 Mar;19(3):301-8. doi: 10.1111/j.1540-8167.2007.01025.x. Epub 2007 Nov 21.


Introduction: T-wave alternans (TWA) is characterized by beat to beat alteration in the amplitude, polarity and/or morphology of the electrocardiographic T wave. TWA has been reported in patients with the Brugada syndrome (BS) and is thought to be associated with an increased risk for development of VT/VF. The cellular mechanisms involved are not well-defined and are the subject of this investigation.

Methods: In an experimental model of BS composed of an arterially perfused canine right ventricular wedge preparation pretreated with verapamil (1-7 microM), an agent with sodium and calcium channel blocking activity, we simultaneously recorded transmembrane action potentials from two epicardial and one endocardial site, together with a pseudo-ECG. At select frequencies, verapamil induced alternans of both the T-wave amplitude and QT interval. The alternans resulted from either loss of the epicardial action potential dome on alternate beats or concealed phase 2 reentry within the epicardium on alternate beats. Loss of the epicardial action potential dome significantly increased transmural dispersion of repolarization (TDR) when compared with control (18.0 +/- 7.8 ms vs. 82.1 +/- 16.8 ms, P < 0.001, n = 8). During alternans, TDR was greater in beats displaying a more negative T wave (55.1 +/- 45.2 ms vs. 89.8 +/- 39.3 ms, P < 0.001, n = 22 data points from 8 preparations).

Conclusions: Our data indicate that TWA in an experimental model of the Brugada syndrome is due to alternating loss of the epicardial AP dome and/or concealed phase 2 reentry, both serving to increase TDR and create the substrate for the development VT/VF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / diagnosis
  • Arrhythmias, Cardiac / physiopathology*
  • Body Surface Potential Mapping*
  • Brugada Syndrome / diagnosis
  • Brugada Syndrome / physiopathology*
  • Cells, Cultured
  • Disease Models, Animal*
  • Dogs
  • Female
  • Heart Conduction System / physiopathology*
  • In Vitro Techniques
  • Male
  • Myocytes, Cardiac*