Page 160 - YORAM RUDY BOOK FINAL

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Brugada Syndrome 320

Brugada syndrome (BrS) is a highly arrhythmogenic inherited cardiac disorder associated
with increased incidence of sudden death. It affects predominantly men in their forties 321,322 . It
presents on the ECG as an atypical right bundle branch block (RBBB) pattern and ST-segment

elevation (STE) in leads V1 through V3. BrS is considered a primary electrical disorder, because no
structural abnormalities are detected by conventional imaging. About 30% of BrS patients test
positive for mutations in SCN5A, causing loss of sodium channel function. AS in the LQT
syndrome, there has been extensive research of the genetic and molecular basis of BrS,

but the substrate in the intact human heart has not been fully defined. We applied ECGI in
25 BrS patients to map ventricular activation and repolarization, and to reconstruct epicardial
EGMs during sinus rhythm 320 . Figure 5.22 shows EGM characteristics and localization for
representative examples in 3 BrS patients (normal maps are provided for reference in the left

column). STE (examples in Figure 5.22A) was observed in the RV outflow tract (RVOT) of all 25
patients (2.21±0,67 mV vs 0 mV in control, p<0.005), but rarely detected outside the RVOT. 59% of
EGMs in RVOT had STE>1mV. EGM peak magnitude (Figure 5.22B) was lower in RVOT (0.47±0.16
vs 3.74±1.60 mV in control, p<0.005) than in other regions (>2.5 mV). 46% of EGMs in the RVOT had

voltage< 2mV. Fractionated EGMs (Figure 5.22C) were present in the RVOT (number of deflections
= 2.97±0.69 vs 0 in control, p<0.005). 27% of EGMs in RVOT had >2 deflections. Figure 5.22D shows
EGMs from locations marked by white dots in Figure 5.22C, representative of abnormal morphol-
ogy of RVOT EGMs. Red arrows indicate low voltage fractionated EGMs.

Figure 5.23A shows activation isochrones maps from these BrS patients, with a normal
control map provided for reference (left panel). The BrS patients had normal RV epicardial
breakthrough (asterisk) on the RV free wall (indicative of a normally functioning conduction

system) and normal activation of most of the RV, but delayed activation of the RVOT (blue), which
was last to activate (in normal hearts, latest activation is in the lateral LV base). The mean time
needed for activation of the RVOT was 36±16 ms, while the entire RV free wall took only 16±3 ms
to activate, and the entire RV (including the RVOT) took 40±14 ms, indicating that most of the RV

activation duration was taken by slow spread of excitation in the RVOT. Figure 5.23B and C show
representative maps of repolarization in the same three patients, together with normal
repolarization maps for reference (left panel). Figure 5.23B shows ARI maps that reflect local
repolarization (local APD), independent of the activation sequence. Figure 5.23C displays recovery

time (RT) maps that are determined by both, local repolarization and the sequence of activation.
The similarity of the ARI and RT maps indicates that local repolarization is the major determinant
of the repolarization pattern. ARI and RT are both prolonged in the RVOT region (ARI: 318 vs 241 ms
in control; RT: 381 vs 311 ms in control). The localized prolongation caused steep gradients of ARI

and RT at the RVOT-RV free wall or RVOT-LV free wall borders (red arrows in Figure 5.23B and C).