Should all individuals with A non diagnostic Brugada-Electrocardiogram undergo sodium channel blocker TEST?

SUPPLEMENTAL FILES

Supplemental Discussion

Diagnostic value of SCB test

The role of SCB agents in unmasking or worsening the typical electrical phenotype of BrS was first reported by Miyazaki et al1. Afterwards, experimental studies confirmed that class I anti-arrhythmic drugs may further reduce the sodium-current in the presence of a genetic ion channel defect and unmask a coved-type ECG2.

Brugada et al. reported a 100% diagnostic sensitivity of flecainide test in a group of patients who survived cardiac arrest and in their genetically-affected family members3. In 2004 the same authors showed the high accuracy of ajmaline test for identification of gene mutation carriers (sensitivity 80%, specificity 95%). Wolpert et al. compared the two drugs and found that the diagnostic accuracy of ajmaline is superior to that of flecainide4. Priori et al. reported a lower sensitivity of SCB test (~35%) compared with genotyping5-6. This finding was confirmed in another study on a large series of patients in which the SCB test demonstrated a very high positive (96%) but a low negative (36%) predictive value7.

The diagnostic accuracy of SCB test in the general population of individuals with a type 2/3 baseline ECG cannot be assessed due to the lack of a “gold standard” for diagnosis of BrS. Whether a positive SCB test always reflects a BrS or may represent an individual, non pathologic response to pharmacologic SCB remains to be established.

Supplemental References

  1. Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S. Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol 1996;27:1061-1070.
  2. Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 1999;100:1660-1666.
  3. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000;101:510-515.
  4. Wolpert C, Echternach C, Veltmann C, et al. Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome. Heart Rhythm 2005;2:254-260.
  5. Priori SG, Napolitano C, Gasparini M, et al. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation 2000;102:2509-2515.
  6. Gasparini M, Priori SG, Mantica M, et al. Flecainide test in Brugada syndrome:a reproducible but risky tool. Pacing Clin Electrophysiol 2003;26:338-341.
  7. Meregalli PG, Ruijter JM, Hofman N, Bezzina CR, Wilde AA, Tan HL. Diagnostic value of flecainide testing in unmasking SCN5A-related Brugada syndrome. J Cardiovasc Electrophysiol 2006;17:857-864.

Supplemental Table 1- Clinical characteristics according to sodium channel block drug used.

Negative SCB test / Positive SCB test
Flecainide
N=33 / Ajmaline
N=44 / P / Flecainide
N=41 / Ajmaline
N=35 / P
Age, years / 44 ± 15 / 38 ± 13 / 0.63 / 44 ± 12 / 41 ± 14 / 0.84
Male gender / 31 (94%) / 34 (77%) / 0.06 / 32 (78%) / 31 (89%) / 0.36
Personal history
Syncope
Cardiac arrest / 8 (24%)
1 (3%) / 13 (30%)
1 (2%) / 0.80
1.0 / 8 (20%)
1 (2%) / 7 (20%)
2 (6%) / 1.0
0.59
Asymptomatic / 24 (73%) / 30 (68%) / 0.80 / 32 (78%) / 26 (74%) / 0.79
Family history
Brugada syndrome
Sudden death / 5 (15%)
5 (15%) / 7 (16%)
9 (20%) / 1.0
0.77 / 14 (35%)
13 (32%) / 8 (23%)
9 (26%) / 0.32
0.62
Negative / 25 (76%) / 28 (64%) / 0.32 / 22 (54%) / 22 (63%) / 0.49
Type 2 ECG / 20 (61%) / 22 (50%) / 0.49 / 26 (63%) / 23 (66%) / 1.0

SCB=sodium channel blocker.

Supplemental Table 2 - Electrocardiographic characteristics before and after sodium channel blockers administration.

Negative SCB test / Positive SCB test / p
RR
Baseline (ms)
Post-test (ms) / 926 ± 214
911 ± 194 / 914 ± 193
907 ± 201 / 1.0
0.73
PR
Baseline (ms)
Post-test (ms) / 151 ± 20
163 ± 27 / 146 ± 18
160 ± 28 / 0.68
1.0
QRS
Baseline (ms)
Post-test (ms) / 98 ± 12
114 ± 15 / 100 ± 11
116 ± 14 / 0.74
1.0
QTc
Baseline (ms)
Post-test (ms) / 408 ± 34
413 ± 32 / 412 ± 32
416 ± 29 / 0.37
0.52
ST elevation
Baseline (mV)
Post-test (mV) / 3.1 ± 0.8
3.2 ± 0.9 / 3.4 ± 0.9
5.8 ± 1.8 / 0.43
0.001

Data are expressed as mean ± standard deviation; PR=PR interval; QRS=QRS interval; QTc=corrected QT interval using the Bazzet formula; RR=RR interval; ST=ST segment at J point