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Carla GiustettoCarla Giustetto
Divisione di Cardiologia Ospedale S.Giovanni Battista -Università di Torino
Ripolarizzazione precoce. Non così innocente come si pensava
Ripolarizzazione precoce. Non così innocente come si pensava
Carla GiustettoCarla GiustettoDivisione di Cardiologia
Università di Torino Ospedale“Città della Salute e della Scienza”
Divisione di Cardiologia Università di Torino
Ospedale“Città della Salute e della Scienza”
Sincope in pazienti con pattern ECG di Brugada Sincope in pazienti con pattern ECG di Brugada
S.Margherita, 8 aprile 2016S.Margherita, 8 aprile 2016
Ø increased risk of ventricular arrhythmias which cause syncope and/or sudden death, also as first manifestation
Arrhythmogenic genetic disease:Arrhythmogenic genetic disease:
Ø without structural heart disease
Brugada electrocardiographic pattern
Ø young subjects (mean age 30-50 years)
Ø A genetic mutation can be indentified in 10-30% of ptsBrS18 SCN10A
Brugada ECG: diagnostic patternBrugada ECG: diagnostic pattern
V1
V2
Type 1 ECG = diagnostic• J point ≥ 2mm• Coved-type ST
segment elevation• Negative T wave• ≥1 right precordial
lead
Wilde, Circulation 2002;106;2514-2519; HRS/EHRA/APHRS expert consensus statement. Europace 2013; 15: 1389–1406
Wilde, Circulation 2002;106;2514-2519; HRS/EHRA/APHRS expert consensus statement. Europace 2013; 15: 1389–1406
Peaked and high r�wave
Rounded r�>0.04s duration
G.Oreto, F.Gaita, C.Giustetto et al. G Ital Cardiol , Vol 11, Suppl 2, 2010
Incomplete RBBB Brugada patten
Brugada pattern
V1
V2
V6
Incomplete RBBB
Mismatch between QRS duration in right and left precordial leads
V1
V2
V6
0.11 s
0.11 s
QRS=0.12 s
QRS=0.08 s
QRS durationin V1-V2 >than in V6
G.Oreto, F.Gaita et al, G Ital Cardiol Vol 11, 2010
Increased sensitivity with higher electrodes (V1-V2) position
Increased sensitivity with higher electrodes (V1-V2) position
Standard leads: 4th intercostal
space
Additional leads: 3rd - 2nd intercostal
space
V1 V2
V4
V3V5
V64th IC
3rd IC
2nd IC
Antzelevitch C et al, Second Consensus Conference. Circulation 2005; 11: 659-670
“Suspicious” ECGs: saddle-back type
V1
V2
V3
Type 2
V1
V2
Type 3
V1
V2
Wilde, Circulation 2002;106;2514-2519; HRS/EHRA/APHRS expert consensus statement. Europace 2013; 15: 1389–1406
Wilde, Circulation 2002;106;2514-2519; HRS/EHRA/APHRS expert consensus statement. Europace 2013; 15: 1389–1406
Ajmaline infusion (1mg/kg in 5 min)
V1 - II space
V2 - II space
V1
V2
V1 - II space
V2 - II space
V1
V2
V3
V4
Basal ECG
Ajmaline-testSensitivity 80%Specificity 94%PPV 93%NPV 83%
Drug challenge with Na+ channel blockers(ajmaline 1 mg/kg IV over 5 min o flecainide 2 mg/kg IV over 10 min)
Drug challenge with Na+ channel blockers(ajmaline 1 mg/kg IV over 5 min o flecainide 2 mg/kg IV over 10 min)
Benito et al, J Am Coll Cardiol 2008;52:1567–73
3/112=3%events at f-
up
31/272=12%events at f-up
mean f-up 58 months
384 patients (M=71%, F=29%)
Incidence of arrhythmic events in males vs femalesIncidence of arrhythmic events in males vs femalesMen with BrS have a worse prognosis than females
Probability of Sudden Death or Ventricular Fibrillation During Follow-up
Brugada et al. Circulation 2003;108:3092-3096
547 pts, mean f-up: 24�32 months
Syncope is a predictor of arrhythmic eventsSyncope is a predictor of arrhythmic events
24/423 (5.6%)
21/124 (17%)
Multivariate analysis identified history of syncope as predictor of sudden death or ventricular fibrillation at f-up.Multivariate analysis identified history of syncope as predictor of sudden death or ventricular fibrillation at f-up.
Syncope is a predictor of arrhythmic eventsSyncope is a predictor of arrhythmic events
Eckardt et al. Circulation 2005;111:257-263 Eckardt et al. Circulation 2005;111:257-263
212 pts, 40 months f-up, 4% arrhythmic events (overall incidence)212 pts, 40 months f-up, 4% arrhythmic events (overall incidence)
1/123 (1%) asymptomatic
4/65 (6%) syncope
4/24 (17%) cardiac arrest
Clinical risk factors in individualswith Brugada ECG: a meta-analysisClinical risk factors in individuals
with Brugada ECG: a meta-analysis
Gehi AK et al. J Cardiovasc Electrophysiol 2006, 17:577-583
19 prospective studies1545 patients
19 prospective studies1545 patients
History of syncope or SD RR = 3.51Spontaneous type 1 ECG RR = 4.65 Men (vs women) RR = 3.47
Family history of SCD RR = 1.04SCN5A mutation RR = 0.60Inducible at EP study(except the study of Brugada et al, Circulation2003)
RR = 1.88
Syncope is a predictor of arrhythmic eventsSyncope is a predictor of arrhythmic events
Probst et al. FINGER Registry, Circulation 2010; 121:635-643 Probst et al. FINGER Registry, Circulation 2010; 121:635-643
1029 pts, 32 months f-up, 5% arrhythmic events (overall incidence) 1029 pts, 32 months f-up, 5% arrhythmic events (overall incidence)
%
10/654 (1.5%)p=0.002HR 3.4
0.5% per year
19/313 (6%)
asymptomatic
syncope
Cardiac arrest
1.9% per year
22/62 (35%) 7.7% per yearp=0.001HR 12.4
Syncope as a predictor of arrhythmic eventsSyncope as a predictor of arrhythmic events
PRELUDE Registry, J Am Coll Cardiol 2012; 59:37–45
308 pts, 34 months f-up, 4.5% arrhythmic events (overall incidence)
7/244 (2.9%)p=0.011
7/64 (10.9%)
asymptomatic
syncope
Syncope as a predictor of arrhythmic eventsSyncope as a predictor of arrhythmic events
PRELUDE Registry, J Am Coll Cardiol 2012; 59:37–45
308 pts, 34 months f-up, 4.5% arrhythmic events (overall incidence)
7/244 (2.9%)p=0.011
7/64 (10.9%)
asymptomatic
syncope
syncope +spont type 1
6/34 (18%)
8/274 (3%)
2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of suddencardiac death
2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of suddencardiac death
UnexplainedN=10(24%)
VFN=3
(3/41=7%)
UnexplainedN=20(47%)
VFN=10
(10/43=23%)
With prodromal symptomsN=41
Without prodromal symptomsN=43
p=0.044
f-up 48 months
Heart Rhythm 2012;9:752-759
Occurrence of cardiacarrest during follow-upOccurrence of cardiacarrest during follow-up
342 ptsmedian f-up 54 months342 ptsmedian f-up 54 months Suspected arrhythmic syncope
2.2% per yearSuspected arrhythmic syncope
2.2% per year
ACA 8.7% per year
ACA 8.7% per year
Suspected non-arrhythmic0-0.3% per year
Suspected non-arrhythmic0-0.3% per year
31 years-old man
- No family history of sudden death- Syncope with brief prodromes whatching TV- In the emergency room, syncope during ECG
monitoring, with evidence of VF - ECG: type 1 Brugada pattern- ICD implant
2 years later…
- 3 episodes of pre-syncope after meals
-Once, after a heavy meal, pre-syncope à ICD intervention
Benito, Brugada et al. Progress in Cardiovascular Diseases, 2008; 51
SEF SEF
Role of EP-study in Brugada patients with syncopeRole of EP-study in Brugada patients with syncope
0/ 89
7/ 46 (15%)
Giustetto, Gaita et al. Europace 2009; 11: 507-13
NO EVENTS IN PTS WITH
NEGATIVE EPS
135 pts undergoing EPSmean f-up =30 �21 months
Role of EP-study in Brugada patients with syncopeRole of EP-study in Brugada patients with syncope
Probst et al, FINGER Registry, Circulation 2010;121: 635
Role of EP-study in Brugada patients with syncopeRole of EP-study in Brugada patients with syncope
1029 pts
median f-up 32 months
p=NS
BrugadaPiedmontRegistry2001-2014BrugadaPiedmontRegistry2001-2014
825consecutiveBrugadapatients(meanage45�14years;78%males)
608asymptomatic(74%)
198syncope(24%)
11SD(1%)8aSD(1%)
BrugadaPiedmontRegistry2001-2014BrugadaPiedmontRegistry2001-2014
825consecutiveBrugadapatients(meanage45�14years;78%males)
608asymptomatic
8aSD11SD
neurally-mediatedsyncope118(60%)
76(38%)4(2%)
arrhythmicsyncope
unexplainedsyncope
198syncope
Group1n=118
Group2n=4
Group3n=76
G1vsG2
G1vsG3
G2vsG3
Prodromes(nausea/vomiting,diaphoresis,pallor,flushing,dizziness,blurredvision,palpitations)
91% 25% 40% 0.002 <0.001 0.94
Fever 14% 0 16% 0.97 0.82 0.89Standing/posturalchanges 63% 0 43% 0.03 0.03 0.38Afterstrongemotion/trauma 14% 0 7% 0.97 0.20 0.60
Aftermicturition,venipuncture,seeingblood,intensepain
40% 0 0 0.28 <0.001 0.48
Aftermeal/drink 13% 50% 22% 0.20 0.12 0.51Duringdriving 1% 0 13% 0.99 <0.001 0.66Incontinence 3% 0 8% 0.19 0.17 0.70Agonalrespiration 0 25% 4% 0.07 0.11 0.48Withtrauma 8% 0 24% 0.75 0.01 0.62
Results:syncopalfeaturesResults:syncopalfeaturesG1
G3 G2
Group1n=118
Group2n=4
Group3n=76
G1vsG2
G1vsG3
G2vsG3
Ageatdiagnosis(years) 45±13 50±17 44±14 0.46 0.61 0.41
Ageat1stsyncope 33±16 47±19 36±15 0.13 0.19 0.22Men 70% 75% 83 0.72 0.07 0.79Spontaneoustype1ECG 31% 100% 66% 0.02 <0.001 0.38Recurrentsyncope 54% 75% 21% 0.76 <0.001 0.07GenetictestSCN5A/SCN1Bmutation
36%36%
50%0
54%27%
0.950.78
0.020.53
0.720.99
PRinterval(ms) 185±30 150±14 169±29 0.02 <0.001 0.20Supraventriculararrhythmias 10% 25% 9% 0.90 0.98 0.86TilttestPositivetilttest
23%44%
0 13%10%
0.64-
0.140.12
0.99-
EPSPositiveEPS
60%34%
75%67%
74%45%
0.940.58
0.080.29
0.600.88
Hydroquinidine 10% 25% 13% 0.90 0.68 0.94Looprecorder 11% 0 18% 0.90 0.22 0.79ICD 19% 100% 57% <0.001 <0.001 0.23DocumentedNSVT 4% 0 16% 0.48 0.02 0.89Meanfollow-up(months) 58�46 106�15
167�42 0.07 0.17 0.14
Results:patients’featuresResults:patients’featuresG1
G3 G2
Results:follow-upResults:follow-up
Meanfollow-upof62�48months
11arrhythmicevents(6%,1per100person-year)
intheoverallpopulation,allinpatientswithICD
0,000,100,200,300,400,500,600,700,800,901,00
0 2 4 6 8 10
G1 G2 G3
Years
G2 4 4 2 2 2 1 1 1 1 1
G3 76 71 62 51 46 39 31 27 20 13
G1 118 107 87 68 51 40 34 29 26 25
Freedo
mfrom
arrhy
thmicevents
118neurally-mediated(G1)vs 4arrhythmic(G2)vs 76unexplained(G3)syncope
G1vsG2:p<0.0001G1vsG3:p=0.04G2vsG3:p<0.0001
75%(8%person-year)
8%(0.5%person-year)
2%(0.2%person-year)
62�48monthsf-up
Results:arrhythmiceventsatfollow-upResults:arrhythmiceventsatfollow-up
0,50
0,60
0,70
0,80
0,90
1,00
0 2 4 6 8 10 12
G1asymptomatic
Years
Freedo
mfrom
arrhy
thmicevents
Group1vs asymptomaticpatients
G1 118 107 87 68 51 40 34 29 26 25 18 13
p=0.61
Asympt 608 518 425 361 286 192 152 129 110 70 51 36
2%0.2%person-year
1%0.2%person-year
5yearsmeanf-up
Results:arrhythmiceventsatfollow-upResults:arrhythmiceventsatfollow-up
51 years-old man
- No family history of sudden death- History of recurrent syncope after meals- Spontaneous type 1 Brugada pattern at ECG- Positive carotid sinus massage- VF induced at EP study, ICD implant - After 4 months he had recurrence of syncope
after meal and the ICD documented VFinterrupted by shock.
0,50
0,60
0,70
0,80
0,90
1,00
0 2 4 6 8 10 12
sponttype1
drug-inducedtype1
Years
Freedo
mfrom
arrhy
thmicevents
spont type1 100 92 77 65 60 52 46 40 33 28 23 17
drug-induced 98 90 75 58 41 30 22 18 15 12 6 4
Spontaneousvs drug-inducedtype1ECG
p=0.005
7yearsmeanf-up
Results:arrhythmiceventsatfollow-upResults:arrhythmiceventsatfollow-up
9%1.5%person-year
0events
0,50
0,60
0,70
0,80
0,90
1,00
0 2 4 6 8 10 12
sponttype1
drug-inducedtype1
Years
Freedo
mfrom
arrhy
thmicevents
spont type1 100 92 77 65 60 52 46 40 33 28 23 17
drug-induced 98 90 75 58 41 30 22 18 15 12 6 4
Spontaneousvs drug-inducedtype1ECG
7yearsmeanf-up
Results:arrhythmiceventsatfollow-upResults:arrhythmiceventsatfollow-up
9%1.5%person-year
2%0.5%person-year
p=0.09
0,50
0,60
0,70
0,80
0,90
1,00
0 2 4 6 8 10
posEPSnegEPS
Positivevs negativeEP-study
Years
pos EPS 51 45 43 40 35 30 29 24 21 18 12
neg EPS 79 72 57 44 39 35 28 23 20 17 14
Freedo
mfrom
arrhy
thmicevents
p=0.003
0events
20%2.8%person-year
7yearsmeanf-up
Results:electrophysiological(EP)studyResults:electrophysiological(EP)study
0,50
0,60
0,70
0,80
0,90
1,00
-3 2 7 12
posEPS
negEPS
Group1(neurally-mediated)
Years
Freedo
mfrom
arrhy
thmicevents
pos 24
23
22
19
16
15
15
11
10
10
5
neg 47
43
34
26
23
20
16
15
14
13
12
p=0.07
Results:electrophysiological(EP)studyResults:electrophysiological(EP)study
Positivevs negativeEP-study
0,50
0,60
0,70
0,80
0,90
1,00
0 5 10
posEPSnegEPS
Years
p=0.02
0events
24%3.6%person-year
7yearsmeanf-up7yearsmeanf-up
8%1.2%person-year
0events
pos 25 22 21 20 18 15 14 13 11 8
neg 31 29 23 17 16 15 10 8 6 4
Group3(unexplained)
Group 2N=4 F-up= 106events 3 (75%)
8per100person-year
Group 1N= 46 F-up= 71
Events 1 (2%)0.4per100person-year
Group 3N= 50 F-up= 70Events 5 (10%)
2 per100person-year
EPS doneN= 39 (85%)
EPS +N= 14 (36%)
F-up= 80
EPS -N= 25 (64%)
F-up= 73
EPS doneN= 38 (76%)
ICD+N=11
ICD -N= 3
Events 1 (7%)*
ICD +N= 3
ICD -N= 22
Events 0
Events 0
Events 0
EPS +N= 20 (53%)
F-up= 83
EPS -N= 18 (47%)
F-up= 63
ICD +N= 20
ICD -N= 0
Events 5 (25%)*
ICD +N= 5
ICD -N= 13
Events 0
Events 0
EPS not doneN= 7 (15%) F-up= 30
EPS not doneN= 12 (24%)
F-up= 59
ICD +N= 7
Events0
Events-
ICD -N= 5
Events0
ICD +N= 0
Events0
Spontaneous type 1 ECGN= 100 F-up= 72 months
Events 9 (9%)0.8 per100person-year
EPS doneN= 3 (75%)
EPS +N= 2 (67%)
f-up= 35
Events2
EPS -N= 1 (33%)F-up = 331
Events0
EPS not doneN= 1 (25%) F-up= 22
ICD +N= 1
Events1
ICD +N= 2
ICD +N= 1
*G1vsG3:p=0.55
Group 3N= 50 F-up= 70Events 5 (10%)
2 per100person-year
EPS doneN= 38 (76%)
EPS +N= 20 (53%)
F-up= 83
EPS -N= 18 (47%)
F-up= 63
ICD +N= 20
ICD -N= 0
Events 5 (25%)*
ICD +N= 5
ICD -N= 13
Events 0
Events 0
EPS not doneN= 12 (24%)
F-up= 59
ICD +N= 7
Events0
Events-
ICD -N= 5
Events0
Spontaneous type 1 ECGN= 100 F-up= 72 months
Events 9 (9%)0.8 per100person-year
Theassociationbestpredictingtheoccurrenceof
ventriculareventsatfollow-up
TherapeuticmanagementandconclusionsTherapeuticmanagementandconclusions
Probablynon-arrhythmic syncope:Goodprognosis, similar toasymptomaticsubjects
looprecorder
EPS+ EPS-
follow-up
Spontaneoustype 1 ECG
Unexplained syncope:positiveEPSisthemainpredictor
ofarrhythmicevents
EPS+ EPS-
looprecorder
+hydroquinidine