Controversia: impianto di defibrillatore in prevenzione primaria Caso clinico: Ripolarizzazione precoce. Sindrome di Brugada Non così innocente come si pensava Torino, 31 marzo 2017 Carla Giustetto Carla Giustetto Divisione di Cardiologia Divisione Università di Cardiologia Torino Ospedale S.Giovanni Battista -Università di Torino Ospedale Città della Salute e della Scienza
Brugada electrocardiographic pattern: diagnosis J point 2mm Coved-type ST segment elevation Negative T wave 1 right precordial lead Spontaneous or after sodium-channel blockers V1 V2 Only type 1 ECG is diagnostic Ø increased risk of ventricular arrhythmias which cause may syncope or sudden death, also as first manifestation Wilde, Circulation 2002;106;2514-2519; HRS/EHRA/APHRS expert consensus statement. Europace 2013; 15: 1389 1406
A 45 years old man: traumatic syncope, which occurred after awakening at 6.30 a.m, while he was in the bathroom, with doubtful prodromes 1st ECG: sinus rhythm, normal conduction, non-significant ST-T alterations
Head-up tilt test (HUTT) Tilt test was negative but ST segment in V1-V2 with a type 2 Brugada pattern was recorded V1 V2
Pt with traumatic syncope + suspect Brugada ECG (type 2) V1 V2 Which investigations are reasonable/recommended? ECG with V1-V2 at 2 nd and 3 rd intercostal space (ICS)
Correlation between RVOT position and exploring electrodes RVOT is the section of the myocardium where I to is more represented and this area in the chest is variable between the 2 nd and 4 th ICS ICS= intercostal space Nagase et al, JACC 2010, 56
ECG was recorded with V1-V2 at a higher intercostal space à in this case it remained doubtful, still not diagnostic ECG 4th ICS V1 2 ICS V2 2 ICS
Which investigations are reasonable/recommended? Pt with traumatic syncope + suspect Brugada ECG pattern (type 2) ECG with V1-V2 at 2 nd and 3 rd intercostal space type 2 Brugada ECG Drug challenge with sodium channel blockers
Pharmacological challenge with Na+-channel blockers was performed Basal ECG V1 V2 Ajmaline infusion (1mg/kg in 5 min) V1 V2 V3 V4 V1 - II space V2 - II space V1 - II space V2 - II space
mean f-up 48±48 months
Sacher F, et al, Heart Rhythm 2012; 9:1272 1279 57 pts with syncope (28%) group 1 (40%) arrhytmic syncope: absence of prodromes and fast return to consciousness 6 ICD shock for VF 5.5% per year group 2 (30%) neurocardiogenic syncope: prodromes (sweating, nausea, pallor) and longer time of unconsciousness f-up 65 months group 3 (30%) uncertain origin of syncope loop recorder 35% No arrhythmic events, but recurrence of syncope similar to the initial one
Results: arrhythmic events at follow-up Mean follow-up of 62±48 months Freedom from arrhythmic events 1 0,95 0,9 0,85 0,8 0,75 0,7 0,65 G1 vs G2, p=0.02 G1 vs Asympt, p=0.58 G2 vs Asympt, p <0.0001 neurally-mediated Group1 Group2 asymptomatic neurally-mediated unexplained 1% (0.2% person-year) 2% (0.3% person-year) 9% (1.8% person-year) 0,6 0 2 4 6 8 10 12 time (years) G1 118 97 78 64 50 39 33 28 23 22 18 G2 77 68 59 49 42 37 30 26 19 12 9 Asympt 608 573 518 425 361 286 192 152 129 110 70
Summary ü45 years old man üsyncope of uncertain origin üdrug induced type 1 Brugada ECG pattern Which is the appropriate treatment for this patient? What does literature report? What do guidelines recommend?
No syncope, nor type 1 Circulation 2002;105:1342 Italian Registry 200 pts Asymptomatic spontaneous type 1 Syncope + induced type 1 Syncope + spontaneous type 1 HR 6.4 for risk of cardiac arrest
Circulation 2010;121: 635 Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events 1029 pz - median f-up 32 months HR=11 for SD (p<0.001) and HR=3.4 for syncope (p=0.002) HR=2.1 (p=0.01)
12-lead 24-hour Holter monitoring showed presence of intermittent spontaneous type 1 Brugada pattern V1 - II space h. 4:12 pm h. 11:44 pm h. 6:33 am h. 8:20 am h. 1:08 pm V2 - II space V1 standard V2 standard V5 V6
Brugada Piedmont Registry 684 patients 12 Lead - 24 hour Holter 251 patients 180 160 80% 70% 30% 140 120 100 80 Persistent type 1 Intermittent type 1 No type 1 spontaneous type 1 at basal ECG (group 1) drug-induced type 1 (group 2) 60 40 20 0 12% 57% 31% group 1 20% group 2 Cerrato, Giustetto et al. Am J Cardiol 2015; 115: 52-56
Circadian fluctuations of Brugada ECG pattern N of 12L-Holter with type 1 BrECG 100 80 60 40 20 p<0.001 12 midnight-6 am 6 am-12 noon 12 noon-6 pm 6 pm-12 midnight Cerrato, Giustetto et al. Am J Cardiol 2015; 115: 52-56
12 lead Holter monitoring: ü allows to identify, in group 2, at least 20% of subjects with spontaneous type 1, who would have been considered at low risk, based only on periodic 12-lead ECGs ü might be the first screening test, in alternative to pharmacological test, particularly in children, in presence of a borderline-diagnostic basal ECG and in the evaluation of family members Am J Cardiol 2015; 115: 52-56
Summary ü45 years old man üsyncope of uncertain origin üdrug induced type 1 Brugada ECG pattern and ü spontaneous type 1 documented at f-up Which is the appropriate treatment for this patient? What do guidelines recommend? What does literature report?
2015 ESC GUIDELINES DIFFERENT OPINIONS
Eventi aritmici al follow-up in relazione al risultato dello studio elettrofisiologico 135 pazienti 0/ 89 7/ 46 (15%) 135 patients Follow-up: 30±21 mesi
Results Role of of EP-study study in in Brugada Brugada pts pts (overall (overall population) P = 0.05 Probst et al, FINGER Registry, Circulation 2010;121: 635
Role of EP-study in Brugada patients with syncope 1029 pts median f-up 32 months Probst et al, FINGER Registry, Circulation 2010;121: 635
Role of electrophysiological study in pts with UNEXPLAINED SYNCOPE Mean f-up of 62±48 months 0 events 27% 5.2% per year Giustetto et al. Intern J Cardiol 2017, in press
Spontaneous type 1 ECG N= 97 Events 7 (7%) 1.4 per 100 person-year Unexplained syncope N= 51 Events 6 (12%) 2.3 per 100 person-year EPS done N= 39 (76%) EPS not done N= 12 (24%) ICD + N= 7 Events 0 ICD - N= 5 Events 0 EPS + N= 21 (53%) EPS - N= 18 (47%) ICD + N= 21 ICD - N= 0 ICD + N= 5 ICD - N= 13 Events 6 (29%) Events - Events 0 Events 0 Giustetto et al. Intern J Cardiol 2017
Syncope of uncertain origin + Brugada ECG Electrophysiologic study (EPS) pos neg ICD in primary prevention follow-up with implantable loop recorder
In our patient Electrophysiologic study (EPS) resulted in induction of VF Considering the syncope of uncertain origin, spontaneous type 1 ECG and positive EPS, an ICD was implanted
One year after The patient experienced the first episode of VF which was recognised and interrupted by ICD shock. He experienced other 3 episodes of VF in 2 years of follow-up 4 3 FV ICD Hydroquinidine 2 1 0
Conclusions 1. Spontaneous and drug-induced type 1 have different prognosis 2. >20% of drug-induced become spontaneous type 1 during followup (serial ECG and 12-lead 24-hour Holter monitoring) 3. Brugada patients with syncope of uncertain origin have a high risk of arrhythmic events at follow-up. 4. EP-study has a predominant role in this group to identify the patients with indication to ICD implant in primary prevention
Probably non-arrhythmicsyncope : Good prognosis, similar to asymptomatic subjects Spontaneous type 1 ECG EPS + EPS - + hydroquinidine loop recorder follow-up