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

Nagase et al, JACC 2010, 56

Correlation between RVOT position and exploring electrodes

60 patients

“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