Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs....
-
Upload
colombina-manfredi -
Category
Documents
-
view
216 -
download
3
Transcript of Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs....
![Page 1: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/1.jpg)
Why Present Brugada?1. Lots of us missed it.
2. A new discovery- first described in 1992.
3. Drs. Josep, Pedro and Ramon Brugada.
![Page 2: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/2.jpg)
![Page 3: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/3.jpg)
![Page 4: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/4.jpg)
Sindrome di Brugada
Pattern ECG tipo 1 spontaneo o dopo farmaci AA del I gruppo in associazione ad una delle seguenti condizioni:
• FV o TV polimorfa documentate• Storia familiare di MI (età<45 anni)• Presenza di ECG di tipo 1 in membri della
famiglia• Inducibilità di aritmie ventricolari con la SEP• Sincopi o respiro agonico notturno
![Page 5: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/5.jpg)
RELAZIONI TRA ECG E POTENZIALE D’AZIONE CELLULARE
![Page 6: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/6.jpg)
SCN5A gene• Codes for cardiac sodium channel that opens during phase 2 of the action
potential. In Brugada, it opens poorly in RV epicardial cells. • Autosomal dominant inheritance• 20-30% of cases have anbl SCN5A gene.• 80+ mutations, differing prognosis.
Priori, S. G. et al. Circulation 1999;99:674-681
1
12
3
4
0
4
4
0mVolts
-85mVolts
![Page 7: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/7.jpg)
GENESI DELLE ALTERAZIONI ELETTRICHE NELLA S. di Br.
![Page 8: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/8.jpg)
![Page 9: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/9.jpg)
![Page 10: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/10.jpg)
Mutazioni geniche nella S di Br.
• Mutazione SCN5Acodifica la subunità del canale per il Na (15% probandi )
• Mutazione GPD 1Lcodifica l’enzima glicerolo 3 fosfato deidrogenasi 1
• Mutazione CACNA 1ccodifica la subunità del canale per il Ca
• Mutazione CACNB 2bcodifica la subunità del canale per il Ca
(28% dei probandi)
![Page 11: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/11.jpg)
Pattern ECG di Brugada indotto da farmaci• Farmaci antiaritmici: bloccanti i canali del Na bloccanti i canali del Ca betabloccanti• Farmaci antianginosi: calcioantagonisti
nitrati farmaci che aprono il canale del K• Psicotropi: antidepressivi triciclici fenotiazine inibitori reuptake serotonina litio• Altri farmaci: intossicazione da cocaina intossicazione da alcohol• Anestetici locali: bupivacaina(per via epidurale)
![Page 12: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/12.jpg)
Quadri ECG che simulano quello di BrBBdx atipico Ipertrofia ventricolare sinistraRipolarizzazione precocePericardite acutaIschemia miocardica acuta e infarto miocardico acutoEmbolia polmonareVarii tipi di anormalità del sistema nervoso centrale e autonomoIperkaliemia,ipercalcemiaARVD/C Pectus excavatumIpotermia Compressione meccanica del RVOTCardioversione elettrica(transitoriamente)Deficienza di tiaminaDistrofia muscolare di DuchenneAneurisma aortico dissecante…
![Page 13: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/13.jpg)
Caratteristiche differenziali Rip. precoce, S Br.,ARVD/CRIP.PRECOCE S BRUGADA ARVD/C
Cardiopatia strutturale
NO NO (forme occulte ARVD)
SI
TV NO TV Poli./FV TV tipo BBS
Catecol./sforzo Riduce pattern ECG
Riduce pattern ECG ed aritmogenicità
Aumenta aritmogenicità
ECG durante RS STV4-V6 STV!-V3 (T)BBdx o J wave
T V1-V4,BBdx, waves,QRS >110 ms in V1-V3
Mutazioni geniche
30% dei casi (SCN5A,GPD1L, CACNA1c, CACNB2b)
50% dei casi (DSP, PKP2, DSG2-68% )
Test all’ajmalina Pattern tipo 1 nel 100% dei casi
Pattern tipo1 nel 16% dei casi (Peters et al.2004)
SAECG-PT
RMN (infiltrazione adiposa)
20% (Papavassiliu et al.2004)
![Page 14: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/14.jpg)
Genesi del pattern ECG di Brugada
1. Anomalia elettrica primaria (famiglia Brugada, Antzelevitch et al.)
2. Anormalità strutturale del Vdx forma occulta di ARVD/C (Scuola di Padova,Papavassiliu et al. 2004, Tada et al. 1998 )
3. Teoria ibrida:difetto elettrico primario che porta allo sviluppo di un difetto strutturale (Takkie et al.2004, Antzelevitch et al.2002). Parallelismo con rimodellamento elettrico atriale in corso di FA, miocardio ibernato.
![Page 15: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/15.jpg)
![Page 16: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/16.jpg)
![Page 17: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/17.jpg)
![Page 18: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/18.jpg)
![Page 19: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/19.jpg)
![Page 20: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/20.jpg)
![Page 21: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/21.jpg)
![Page 22: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/22.jpg)
Pattern circadiano delle FV nella S BrMatsuo te al.: Eur Heart J 1999
![Page 23: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/23.jpg)
S Br: fluttuazioni circadiane del sopraslivellamento di ST
Miyazaki et al.: JACC 1996 Stimolazione dei recettotri beta adrenergici, isoproterenolo: ST
Litovsky,Antzelevitch et al.: Stimolazione muscarinica mediante Circ Res 1990 edrophonium evi: ST Acetilcolina: perdita del plateau del PA epi. Incremento ST Aumento della eterogeneità elettrofisiol.
![Page 24: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/24.jpg)
S Br: Fluttuazioni ECG con periodo ≥ 24h
Voltmann et al.: Eur Heart J 2006 43 pz, 310 ECG eseguiti nel corso di un FU mediano di 17.7 mesi
Gruppo A- ECG tipo 1 ECG non diagnostico 15/43 (35%) Gruppo B-ECG permanentemente di tipo 1 1/43 (2%) Gruppo C-ECG non diagnostico diagnostico 8/43 (19%) tempo mediano: 16gg, tempo massimo: 66gg. Gruppo D-ECG mai diagnostico 20/43 (47%)
![Page 25: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/25.jpg)
Tempo cumulativo per il primo ECG diagnostico
![Page 26: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/26.jpg)
S Br: fattori che possono influenzare il quadro ECG indipendentemente dalle fluttuazioni
spontanee
• Posizionamento degli elettrodi precordiali• Uso di farmaci• Temperatura corporea• Relazione con i pasti (“full stomach test”)
![Page 27: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/27.jpg)
Odds ratios per l’incidenza di TV/FV spontanee nel corso del FU dei pazienti con S di Br sottoposti a SEP (n.1036. - Paul et al.: Eur Heart J 2007)
Inducibilità TV sost
OR(95%CI) Valori di p
Tutti gli studi 1.495(0.05-4.06) 0.399
Brugada et al. 10.002(3.81-26.232). <0.0001
Tutti gli studi
eccetto Brugada
0.771(0.42-1.41) 0.364
![Page 28: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/28.jpg)
Valore prognostico della SEP nei pz con S di Br asintomatici
728 pz
182(25%) ind 546(75%) non ind
Eventi aritmici 14(7,7%) 9(1,6%)FU= 34±40 mesi tot 23(3%)
Sens=60% Sp=76% VPP=7% VPN=98%
Paul et al.:Eur Heart J 2007
![Page 29: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/29.jpg)
Possibili cause alla base della discrepanza di risultati tra la casistica di Brugada e tutte le altre
(Paul et al.:Eur Heart J 2007)
• Inclusione di pz con pattern ECG non di tipo 1 (~7.2%).
• Possibile ruolo di fattori genetici (non definito ).• Variazioni della bilancia simpato vagale (fattore
modulante).• Popolazione del registro di Brugada selezionata
sui casi più severi
![Page 30: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/30.jpg)
![Page 31: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/31.jpg)
Possibili indicazioni alla SEP nei pz con pattern ECG di Brugada
o Nei pz asintomatici per l’identificazione di quelli a rischio molto basso (≤1.6%)(?)
o Identificazione dei pz con aritmie SV sintomatiche.
o Studio delle sincopi a genesi non chiara
![Page 32: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/32.jpg)
Markers prognostici non invasivi
Pesenza di PT al SAECG
Sens 89% Spec 50% Ikeda et al.: JACC 2001
QTc >460 ms in V2
Tp-e ≥100 ms
Tp-e disp.> 20 ms
Sens 78% Spec 70%
Sens 67% Spec 90%Hevia et al.: JACC 2006
aVR sign R≥3 mm
R/q≥0.75
Sens 83% Spec 85%
Sens 81% Spec 84%
Bigi et al.: Heart Rhythm 2007
V2 QRS≥120 ms Sens 52% Spec 70% Junttila et al.: J Cardiovasc Electrophisiol 2008
![Page 33: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/33.jpg)
Incidenza di aritmie atriali spontanee: 6%38% Inducibilità di aritmie atriali: 3%100%
Fattori favorenti: 1) aumento del tempo di conduzione inter -intratriale (Morita et al.:JACC 2002) 2) dispersione dei PR atriali (preminenza corrente Ito. Francis JACC.:2008) 3) prevalenza notturnaincremento attività vagale (Kusana.:JACC 2008)Prognosi: Stadio più avanzato della malattia. FA spontanea predittrice di FV (Kusano et all.: JACC 2008)
Terapia: FA principale causa di shock inappropriati nei portatori di ICD.(14-41% vs 7-17% di shock appropriati). impatto favorevole con l’impiego di farmaci che aumentano la corrente del Ca (isoproterenolo, cilostazolo) o che inibiscono la corrente Ito.
Sindrome di Brugada ed aritmie atriali-FA
![Page 34: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/34.jpg)
Relazioni tra S di Br, sincope neuromediata e mutazione SCN5A
• Parecchi case reports suggeriscono una associazione tra S di Br e sincope neuromediata.
• Uno studio clinico ha mostrato che il tilt test era positivo in 35 % dei pazienti con pattern ECG di Brugada.
• Disfunzione dei gangli simpatici presinaptici del cuore (Wichter et al 2002)
• Espressione di SCN5A nei neuroni intracardiaci del cane (Scornik 2006)
![Page 35: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/35.jpg)
![Page 36: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/36.jpg)
Farmaci antiaritmici nella S di Br I
• Chinidina: blocca la corrente Ito; elimina i rientri in fase 2; effetto vagolitico
Belhassen 2004: chinidina 1500 mg/die;
Hermida 2004: chinidina 600-900 mg/die; Mitzurawo 2006: chinidina 300-600 mg/die; prevenzione inducibiltà rispettivamente nel 88%,76%, 44%.
• Procainamide: proaritmia.
• Disopiramide: blocca i canali K+ ed anche Ito;effetto vagolitico.
• Farmaci AA classe 1C: proaritmia
• Farmaci AA classe 2: betabloccanti.Non prevengono la MI
![Page 37: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/37.jpg)
Farmaci antiaritmici nella S di Br II
Classe 3-farmaci che bloccano la corrente Ik• Amiodarone: riduce la dispersione transmurale dei PR
(Sicouri 1997); sopprime il rientro in fase 2; riduce Ito (Yan 1996); antagonizza T3 ed il suo effetto sui canali del K+ (Guo 1997)
• Sotalolo: possibile inibizione di Ito; elimina il rientro in fase 2 (Glatter 2004).
Classe 4-calcioantagonisti: proaritmia
![Page 38: Why Present Brugada? 1. Lots of us missed it. 2. A new discovery- first described in 1992. 3. Drs. Josep, Pedro and Ramon Brugada.](https://reader035.fdocuments.us/reader035/viewer/2022081518/5542eb4e497959361e8bc881/html5/thumbnails/38.jpg)
Farmaci sperimentali con effetto antiaritmico nella S di Br
• Tedisamil: blocca la corrente ik. Allunga il QT, possibili TP.• Cilostazol: inibisce la PDE III.Sopprime Ito per aumento della FC e/o
aumenta la ICa.Risultati contrastanti.• Bepridil: Ca antagonista, blocca anche INa (cinetica rapida). Inibisce
molti tipi di Ik, incluso Ito.• Dimetil litospermato B: rallenta l’inattivazione di Ina.
• AVE 0118: somministrabile solo per via ev
Altri farmaci/presidi utili• Isoproterenolo: normalizza l’ECG del Brugada. Aumenta
Ica.Utilizzato in corso di arrhythmicstorm.• Overdreive pacing: le alte frequenze inibiscono Ito.Utilizzato in
corso di arrhythmicstorm.