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2011 Brugada QT 2005 2006 2007 Brugada Brugada 20 QT 70 2007 Brugada ICD ICD 5 2

QT Brugada 2012 QT QT QT Brugada Brugada 5 AHA/ACC ESC I II III A B C I II IIa IIb III A B C QT long QT syndrome LQTS QT torsade de pointes TdP ventricular tachycardia VT ventricular fibrillation VF QT QT Romano-Ward Jervell and Lange-Nielsen QT 3

2011 QT Romano-Ward 50 QT 60 70 Romano-Ward 13 LQT1 LQT13 90 LQT1 LQT3 QT 0. 9 2. 6 / QTc 500 msec LQT1 LQT2 LQT3 LQT1 LQT2 LQT3 20 LQT1 15 LQT1 LQT 2 5 14 QT QT TdP QT QT QT TdP 2. 0 8. 8 QT QT SNP QT KCNQ1 KCNH2 HERGSCN5A 4

QT Brugada 2012 QT QT RR QT TdP QT QT TdP QT TdP QT Romano-Ward 8 13 K + LQT1 2 5 6 7 11 13 Na + LQT3 9 10 12 Ca 2+ LQT4 8 action potential duration APD QT monophasic action potential MAP QT MAP MAPD early afterdepolarization EAD hump TdP 1 EAD MAPD spacial dispersion of repolarization SDR TdP SDR QT QT TdP LQT1 LQT2 LQT3 2 TdP TdP APD Epi TdP TdP QRS mid-myocardial MEndo Purkinje EAD QT M APD transmural dispersion of repolarization TDR TdP 2 SDR TDR 1 QT QT TdP 5

2011 Miyasaka 40 0. 1 mv ST 0.70 2. 14 Atarashi 0. 1 mv coved ST 0. 16 0. 1 mv coved ST 0. 01 Yamakawa 0. 1 mv coved saddleback ST 6 15 0. 054 91 72 76 45 22 55 50 70 94 16 Brugada 20 8 66 51 atrial fibrillation AF 29 12 20 Na 60 90 ST T T wave alternans ST 6

QT Brugada 2012 60 80 2 3 50 80 71 vs 52 17. 4 / 6. 2 / 0.6 3. 7 / 0. 5 1 Brugada / 5 / ST 7 / 14 Priori 1 ST 1 SCN5A 1 Brugada 16 Brugada 1998 Na + SCN5A SCN5A Brugada 18 30 SCN5A Na + Na + Na + trafficking defect Na + loss of function Na + loss of function Brugada Antzelevitch Brugada APD 1 1 K + ItoIto 0 Na + L Ca 2+ Ito K + K + IkATP K + Na + Ca 2+ ST a Na + loss of functionito ST J APD APD saddleback ST b ST T c Brugada coved ST 7

2011 Ca 2+ loss of dome dphase 2 reentry e QT Schwartz QTc torsade de pointes TdPT wave alternans notched T QT QT 3.5 8

QT Brugada 2012 1.5 3 1 3.5 Schwartz QT QT QT QT QT TdP QT 1 QT 5000 10000 1 QT Schwartz 4 1 1200 1 QT QT Schwartz QTc TdP T wave alternans 3 notched T TdP T wave alternans TdP notched T LQT2 HERG heterogeneity QT QT QT dispersion T 24 QT QT RR Bazett QT / RR 1/2 QT Bazett Fridericia QT / RR 1/3 QTc 9

2011 QRS QT TdP TdP T 1 T wave alternans T wave alternans QT bifid T T T T T 3 notched T Romano-Ward 3 2:1 QT QT T Moss LQT1 3 T Schwartz notched T bifid T LQT2 HERG heterogeneity QT dispersion QTd T T peak-t end Tp-Te transmural dispersion QT QT LQT1 QTc T Tp-TeLQT2 4 QTc 445 msec LQT1 LQT2 LQT1 QTc 460 msec LQT2 LQT1 LQT2 QTQT QT 410 msec QTc 490 msec QT QT 0 10 10

QT Brugada 2012 QT 75 g 30 60 120 180 QT QT QT dispersion QT QT QT 440 460 msec 12 Holter QT T Holter QT dispersion Tp-Te QT QT TdP LQT1 LQT2 Holter RR TdP QT T T wave alternans T wave alternans QT T wave alternans T wave alternans QT TdP MAP QT MAP EAD short-long-short EAD QT 11

2011 2:1 TdP APD RR short-long-short QT MAP QT T EAD EAD Romano-Ward 8 13 LQT1 LQT13 Jervell and Lange- Nielsen 2JLN1 JLN2 QT 50 70 QT 20 2008 4 1 4000 500 LQT1 40 LQT2 40 LQT3 10 3 90 3 KCNQ1 KCNH2 SCN5A 2011 QT Heart Rhythm Society: HRS European Heart Rhythm Association: EHRA Expert Consensus Statement 12 QT QT 12 QT QTc 480 msec 500msec I QT I 12 QTc 460 msec 480 msec IIb loss of function gain of function APDLQT1 LQT5 KCNQ1 KCNE1 LQT2 LQT6 KCNH2 KCNE2 K + IKIKs IKr IKs IKr LQT3 SCN5A Na + late Na + INa QT LQT1 40 LQT2 40 LQT3 10 T Td P ICD 12

QT Brugada 2012 QT QT torsade de Pointes TdP TdP TdP TdP TdP QT TdP QT TdP TdP K TdP QT LQT3 Ca LQT8 Timothy EAD QT IKs IKr K + K QT SCN5A LQT3 LQT3 QT QT TdP 13

2011 QT ICD QT ICD TdP TdP ICD 14

QT Brugada 2012 QT torsade de pointes TdPQT 4 QT K Bazett QT QTc 25 500 msec QT A 2 g 2 20 mg/min B 100 /min B 100 /min B 4. 5 5 mmol/l C 50 100 mg C QT QT TdP Na + -K + K + QT EAD TdP Vaughan Williams Ia III TdP QTc 550 msec TdP TdP T short-longshort EAD QT T 60 /min QT TdP 70 /min QT TdP 15

2011 ICD QT QT 4 K TdP QT 2 g 1992 Brugada P Brugada J 12 V1 V3 ST QT 8 Brugada Brugada Brugada ST coved saddleback ST Wilde 2002 V1 V3 J 2 mm ST 1 ST coved 2 3 saddleback ST 1 mm 1 mm 1 coved ST ST gradually descending 2005 3 ST covedsaddleback 2012 Luna V1 V3 QRS-T 1 coved ST 2 saddleback ST 2 Brugada 1 1 45 1 1 2 3 1 Brugada Brugada 18 16

QT Brugada 2012 Brugada V1 V3 ST-T A 1 coved ST J 0.2 mvb 2 3 saddleback ST J 0.2 mvc S coved ST 0.2 mv J 0.1 mv 3 Brugada A 1 Brugada J 0.2 mv R R 40 0.4 mv R R 40 R 80 B 2 3 J 0.2 mv J ST T ST C S 0.2 mv J 0.1 mv A R R R 40 0.04 mv R 40 R 80 0.04 mv Brugada Brugada signal-averaging electrocardiography SAECG QRS f-qrs QRS 40 msec 2 RMS40 QRS 40 V LAS40 3 Brugada RMS40 LAS40 2 3 1 Brugada Brugada Brugada Brugada Brugada Brugada T wave alternans T wave alternans Brugada QT Tp-Te Tp-Te dispersion Brugada QT dispersion 17

2011 ST ST Vaughan Williams Ia Ic Na ST coved ST J 0.2 mv 1 mg/kg 10 2 mg/kg 10 10 mg/kg 10 ST saddleback ST Brugada ST saddleback ST Brugada Brugada saddleback ST Brugada ST ST saddleback coved ST coved ST ST-T saddleback coved coved ST Brugada Brugada Heart Rhythm 1 2 3 Brugada Brugada Brugada K + Ito Brugada Brugada Brugada His-PurkinjeHV 55 msec 18

QT Brugada 2012 HV SCN5A HV HV Brugada 1998 Na + SCN5A 300 BrS1 6 BrS2 7 Na + membrane trafficking Na + loss-of-function 0 Na + 1 Ito SCN5A BrugadaBrS1 20 SCN5A 19

2011 Brugada Brugada SCN5A SCN5A PQ HV Na PQ QRS Brugada SCN5A V1 S SCN5A Brugada 0. 1 0. 2 Brugada Brugada Brugada SCN5A SCN5A gain-of-function 3 QT LQT3 progressive cardiac conduction defects PCCD SCN5A Na SCN5A 6 SNP 2 HapA HapBHapB 25 SCN5A Brugada HapB Brugada SCN5A 7 BrS1 7 2 BrS2 glycerol-3 phosphate dehydrogenase like GPD1L Na + QT Brugada Ca 2+ 1 CACNA1C 2 CACNB2b BrS5 SCN1B BrS6 KCNE3 BrS7 SCN3B Ca2+ 2 CACNA2D1 HCN4 Brugada MOG1 KATP Kir6.1 KCNJ8 Brugada J Brugada V1 V3 J I V4 V6 II III avf J Brugada Ca 2+ 1C CACNA1C2b CACNB2b2 CACN2D1Brugada SCN5A KCNJ8 S422L Brugada Brugada J 20

QT Brugada 2012 Brugada ICD Brugada ICD ICD 0. 01 g/kg/min C 1400 mg/day 300 600 mg/day C ICa Ito 200 mg/day Brugada ICD Brugada ICD ICD ICD Ca Ito K + 200 mg/ day 21