Should all individuals with non

diagnostic Brugada-like ECG

abnormalities undergo sodium

channel blocker challenge?

A. Zorzi, F.Migliore, A, Marinelli, E.Marras*, A. Baritussio, G.

Allocca*, L Leoni, G. Buja, S. Iliceto, P. Delise*, D. Corrado

Inherited Arrhythmogenic Cardiomyopathy Unit,

Department of Cardiac, Thoracic and Vascular Sciences, University of Padova

* Division of Cardiology, Civil Hospital, Conegliano, Italy

• Arrhythmogenic disease

• ECG pattern of ST-segment elevation in right precordial leads

• Increased risk of sudden death due to VF

• Structurally normal heart

• SCN5A mutation in 18-30% of cases

BACKGROUND (1)

Brugada Syndrome

Brugada P. Brugada Syndrome: Up-date 2009. Hellenic J Cardiol 2009;50:352-72

ECG repolarization pattern

BACKGROUND (2)

BACKGROUND (3)

Sodium channel blocker challenge (SCB)

In familiar BrS with a positive SCN5A gene mutation: test sensitivity ~ 70-80%

test specificity ~ 90%

In the general population: test accurancy unknow

May a positive test reflect an individual non pathologic response to the Na+ channel blockers ?

BACKGROUND (4)

Risk stratification

Priori et al. Circulation. 2002;105:1342-1347 Eckardt et al. Circulation. 2005;111:257-263

OBJECTIVE

The aim of this study was to assess whether

systematic SCB test of individuals with non

diagnostic Brugada type 2/3 ECG test impacts

clinical management and outcome.

METHODS (1)

Study population

153 consecutive subjects referred to 2 institutions of the Veneto Region of Italy;

Enrollment criteria

Demostration of non diagnostic Brugada ECG, either type 2 or 3;

No previous spontaneous diagnostic Brugada ECG type 1;

No structural heart disease and others conditions mimicking Brugada Syndrome

METHODS (2)

Source of non diagnostic Brugada ECG abnormalities:

Routine ECG screening in 64 (42%).

Study of asymptomatic family members of patients with BrS or SD in 48 (31%);

Investigation of syncope of unknown origin in 36 (24%) patients;

Investigation of sudden cardiac arrest in 5 (3%);

METHODS (3) SCB test : All subjects underwent a SCB test (flecainide 2mg/Kg iv in 10 min

or ajmaline 1 mg/Kg iv in 5 min).The test was considered positive if a type 1 ECG

was induced;

Electrophysiological study (EPS): 2 different pacing cycle lenghts (600, 400

msc) with up to 3 extra stimuli ( two ventricular sites, RV apex and RVOT);

ICD implantation: proposed to all the patients with a positive SCB test and

previous sudden cardiac arrest, syncope or a postitive EPS

Follow-up (FU): serial outpatients evaluations

Adverse events: definied as: - appropriate ICD intervention

- SD

- sudden cardiac arrest (VF)

- unexplained syncope

Statistics: Event-free survival stratified by results of SCB test, family history and

previous symptoms

Clinical Characteristics of the overall study population (n=153)

Male 128 (83%)

Age, y 41.7 ± 14

Type 2 ECG pattern 91 (60%)

Type 3 ECG pattern 62 (40%)

Family history of BrS and/or SD 66 (37%)

History of syncope 36 (24%)

Hystory of cardiac arrest 5 (3%)

Fortuitous cases (asymptomatic non-family cases) 64 (41%)

RESULTS (1)

RESULTS (2)

Clinical Characteristics of the study population according to SCB test results

Negative SCB

test (n= 77)

Positive SCB

test (n= 76) P value

Age, years 40 ± 14 43 ± 14 0.546

Male gender 65 (84) 63 (83) 0.799

Personal history:

Syncope

Aborted sudden cardiac death

No symptoms

21 (27)

2 (3)

54 (70)

15 (20)

3 (4)

58 (76)

0.291

0.684

0.388

Family history of BrS 12 (16) 22 (29) 0.047

Family history of sudden death 14 (18) 22 (29) 0.117

Type Drug (Ajmaline) 42 32 0.230

Type 2 ECG 37 (48) 44 (58) 0.243

RESULTS (3)

7 patients (4.6%) experienced an adverse event (mean event rate = 1.1%/yr)

• SD in one (0.7%)

• Appropriate ICD intervention on VF in 2/15 (1.3%)

• Unexplained syncope in 4 (2.6%)

Follow-up (54±31 months)

N Sex Age HistoryECG

type

Test

ResultEPS ICD Event

1 M 37Fam Brugada,

cardiac arrest 3 Pos Pos Yes Shock on FV

2 M 48 Syncope 2 Neg No No Syncope

3 M 26 Syncope 3 Pos No No Syncope

4 M 36 Cardiac arrest 2 Pos No Yes Shock on FV

5 M 46 Syncope 3 Pos No No Sudden death

6 M 38 Fam. Brugada 2 Pos Neg No Syncope

7 M 44 Negative 2 Pos No No Syncope

RESULTS (4)

Clinical Characteristics of patients who experienced an adverse event during follow-up

Case Report

Baseline ECG ECG after SCB test

RESULTS (5)

Kaplan-Mayer analysis according to SCB test result in the overall study population

•mean event rate: SCB + subgroup 1.9 %/yr

SCB – subgroup 0.3 %/yr

RESULTS (6)

Overall

(n.153)

Positive

FU

(n.7)

Negative

FU

(n.146)

Univariate

analysis

Logrank

Multivariate

analysis

p

Sex (male) 128 (84%) 7 (100%) 121 (83%) 0.229 0.984

Age > 40 y 76 (50%) 3 (43%) 73 (50%) 0.531 0.404

Positive SCB

test

76 (50%) 6 (86%) 70 (48%) 0.043 0.057

1.3 [30.9-0.9]

Type 2 pre test

ECG

91 (60%) 4 (57%) 87 (60%) 0.491 0.465

Positive EPS 9/49 (18%) 1/2 (50%) 8/47 (17%) 0.275 -

Cardiac arrest/

Syncope

41 (27%) 5 (71%) 36 (25%) 0.023 0.039

5.7 [20.3-2.1]

Family history 56 (37%) 2 (29%) 54 (37%) 0.505 0.484

Predictors of adverse events during FU

RESULTS (7)Kaplan-Mayer subanalysis of SCB test results according to previous symptoms and positive

family history

Symptomatic

individuals

Asymptomatic

positive family Hx Asymptomatic

negative family Hx

6.5 %/yr

0.9 %/yr 0.8 %/yr

CONCLUSIONS

Although in individuals with a non diagnostic type 2 or 3

Brugada ECG, a positive SCB test was a significant

predictors of life-threatening events during FU, clinical

background significantly influenced the outcome.

In patients with a history of cardiac arrest or unexplained

syncope the induction of a diagnostic coved-type ST-

segment elevation by SCB test significantly predicted an

adverse outcome, while in asymptomatic individuals it did

not (regardless of family history and results of EPS).

Thus, in the presence of non-diagnostic Brugada-like

ECG abnormalities, systematic SCB test is not justified in

asymptomatic individuals because it does not provide

additional value for clinical management and prevention of

sudden cardiac death.

Instead, SCB test may contribute to arrhythmic risk

stratification and treatment of patients with a positive clinical

history.

• Mean follow-up

Population Test + Test- p

Overall 48,5 +/- 29,2 49,5 +/- 32,2 0,852

Symptomatic 51,8 +/- 29,9 60,0 +/- 29,6 0,388

Asymp. Family members

Asymp. No Family members

52,5 +/- 32,4

43,8 +/- 26,3

50,8 +/- 31,1

40,7 +/- 31,9

0,855

0,677

RESULTS (10)

Outcome of asymptomatic patients

- SCB test + 0.8%/yr

- SCB test - 0%/yr

RESULTS (11)

History Test result Present Study Evain et al. Mean

FU

Cumulative

aSD/syncope SCB test + 4/18 (5.4 %/yr) 1/12 (2.7 %/yr) 3.7 yr 5/30 (4.5 %/yr)

SCB test - 1/23 (1.1 %/yr) 2/23 (2.8 %/yr) 3.6 yr 3/46 (1.8 %/yr)

No SD/Syncope SCB test+ 2/58 (0.8 %/yr) 2/81 (0.8 %/yr) 3.5 yr 4/139 (0.8 %/yr)

SCB test - 0/54 (0.0 %/yr) 0/42 (0.0 %/yr) 3.6 yr 0/96 (0.0 %/yr)

Overall SCB test + 6/76 (1.9 %/yr) 3/93 (1.0 %/yr) 3.5 yr 9/169 (1.5 %/yr)

SCB test - 1/77 (0.3 %/yr) 2/65 (1.0 %/yr) 3.6 yr 3/142 (0.6 %/yr)