Fibrosis and Conduction Abnormalities as Basis for Overlap of Brugada Syndrome and Early Repolarization Syndrome

Figures

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  Figure 1. Abnormal conduction in the right ventricular outflow tract (RVOT) as explanation for the Brugada syndrome. (A). The structural abnormalities (yellow) in the RVOT separate activation fronts causing fractionated unipolar electrograms. (B). The abnormalities may also set the stage for current-to-load mismatch leaving part of the myocardium unexcited. This myocardium acts as a current sink during systole and receives current from adjacent—excited—tissue causing unipolar electrograms with ST segment elevation (J-point). (C) Current-to-load mismatch may also generate unidirectional block and the onset of reentry. The lighter shade of purple in the RVOT indicates a lower conduction reserve resulting from a distinct embryonic origin [28]. RVOT, right ventricular outflow tract; RV, right ventricle; Endo, endocardium; Epi, epicardium.

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  Figure 2. Local J-wave and excitation failure in relation to the early repolarization syndrome. (A). Simulated activation maps and extracellular potentials during sodium channel reduction (30%) in the absence (upper) and presence (lower) of structural abnormalities. Propagation and extracellular potential were simulated using a similar approach as published previously [12]. In brief, propagating action potentials (AP) were simulated with a monodomain reaction-diffusion equation, using software that has been described previously [40]. Ionic currents were computed with the Ten Tusscher-Noble-Noble-Panfilov model for the human ventricular myocyte [41], which distinguishes subendocardial, mid-myocardial, and subepicardial cell types. Computation of extracellular potentials (electrograms) from the simulated membrane potentials was based on the bidomain model for cardiac tissue [42]. Delayed activation in location a resulted in a pronounced J-wave in the corresponding local electrograms. In the presence of structural abnormalities excitation failure occurred and the local J-wave disappeared. Panel (B) shows the epicardial activation pattern at the right inferior wall measured during open chest…

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  Figure 3. Inferolateral J waves and their attenuation by sodium channel blockers. The effects of reduced Na current, reduced coupling, and increased transient outward current on inferolateral J waves were evaluated with computer simulations using a detailed model of the human heart and torso [44]. Propagating action potentials were simulated with a monodomain reaction-diffusion model. At 1-ms intervals the simulated transmembrane currents were inserted in a torso model and a static bidomain problem was solved to obtain the electrocardiogram (ECG). Global reduction in Na-channel conductivity deformed and prolonged the QRS complex, masking the inferolateral J-waves. Subtraction of the ECGs with and without local intervention showed that the ECG change associated with the local reduction in Na current was not reduced, but was only hidden by the expanding QRS complex.

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  Figure 4. The definition of structural heart disease is based on the ability to detect structural abnormalities. An increased spatial resolution of the detection technique will lead to a leftward shift of the red zone. ERP, early repolarization pattern; BrS, Brugada syndrome; ARVC, arrhythmogenic right ventricular cardiomyopathy; Uhl’s, Uhl’s disease; MRI, magnetic resonance imaging; Echo, echocardiography. This figure was used with permission from [54].