should all individuals with non diagnostic brugada-like ecg
TRANSCRIPT
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)