098青沼班GL念校0507.indd

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2 2011 Brugada QT Brugada Brugada 20 QT 70 1,2) 2007 Brugada ICD 5 2

3 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 syndromelqts T QT torsade de pointestdpventricular tachycardiavt ventricular fibrillationvf QT Romano-Ward Jervell and Lange-Nielsen 3-5) QT Jervell and Lange-Nielsen 3,6) 3

4 2011 Romano- Ward QT QT 7) QT T U Andersen Tawil 8-10) QT Bazett QT QTc 11) QTc 450 msec 460 msec Schwartz QT 11) 3.5 QT TdP 4

5 QT Brugada QTc 12,13) QT LQT1 3 QT ) Jervell and Lange-Nielsen 3,6) 2 compound mutations LQT ) 8.4 compound mutations QTc Jervell and Lange-Nielsen 1 QT 16-19) QT 550 msec TdP 600 msec T T wave alternans QT ) QTc 500 msec LQT1LQT2 LQT3 QTc 500 msec LQT3QTc 500 msec LQT1LQT2 LQT3 QTc 500 msec LQT1LQT2 12) QT QT TdP QT silent mutation carrier QT TdP TdP ,22) QT QT 1 / ) QT QT TdP 24,25) QT QT K Mg K QT 26) QT QTU T 26) msec QT 3 24 TdP 27) QT K + IK 28,29) IK QT TdP QT TdP QT 5

6 2011 QT QT K + QT 7,25,30-36) QT QT QT TdP QT III QT Romano-Ward ,38) K + LQT Na + LQT Ca 2+ LQT48 1/2 40 6

7 QT Brugada 2012 action potential duration APD QT QT QT TdP monophasic action potentialmap 39-43) MAP 44) MAP 0 Vmax 2 3 MAP APD QT QT T TdP 45-47) Epi APD mid-myocardialm EndoPurkinje QT LQT1LQT2 LQT3 broad-basedt low-amplitudenotchedt ST late-appearingt 48) QT T 45-47) MAP QT 45 46) MAP MAPD 39,40) early after depolarizationead hump 40,41) TdP 1 EAD 7

8 ) MAPD spatial dispersion of repolarizationsdr TdP SDR 40 QT QT TdP 45-47) LQT1LQT2LQT3 2 TdP AB TdP APD TdP 45,46) CTdP QRS M Purkinje EAD QT M APD transmural dispersion of repolarizationtdrtdp 2 SDR TDR QT QT TdP QT Vaughan Williams Ia III K + IK IKr K QT LQT1 LQT2LQT ) IKr QT T QT TdP IK IKs K + IKr QT 49) IKs Chromanol 293BQT TDR IKr E-4031 APD M APD QT TDR QT TdP T EAD TdP 49) QT QT T APD TdP TdP 1 EAD TdP 2 8

9 QT Brugada 2012 Brugada 12 V1V3 coved saddleback ST 50) Na + SCN5A 2) L Ca Brugada J 0.2 mv coved ST ) saddleback ST mv ST ) 14.2 / ) Brugada / coved 51,52,54,56) Brugada ) 5 65,66) Brugada K + Ito 1 SCN5A 67) IKsIKrIKl K + K + L Ca 2+ Brugada BMI 68) Brugada 69) 70) BezzinaShimizu SCN5A 3 6 B SCN5A 71) Brugada Brugada 72,73) 45 Brugada ) ,66) Priori 20 61) Brugada L Ca 2+ ST K + ItoST Brugada 74) 9

10 ) 75) 2 SCN5A 76) atrial fibrillationaf 1530 SCN5A 77) Brugada ,79) Heart Rhythm V1V3 ST 3 J 0.2 mv coved T 1ST 0.1 mv saddleback 2 ST 0.1 mv saddleback coved 3 74) 1 Brugada 2 3 Brugada Na Ca K ST Na + Ca 2+ K + ST 74) Junttila Brugada 80) Brugada Na + Brugada saddleback ST coved Brugada Brugada J 2 mm coved ST ) 74) 2001 J-IVFS Brugada 65,66) 2010 FINGER 64) FINGER 1 2 3J 1 mm 2 mm coved saddleback ST / 66) B msecbrugada 59-63) 10

11 QT Brugada FINGER 1 64) 45 66) 1 1 J-IVFS V2 r-j 90 msec V6 QRS 90 msec 65) Brugada SCN5A PQ HV PQQRS 77) Morita V1V3 QRS 8 fragmented QRS 81) ) 700 FINGER 64) J-IVFS 45 65,66) Makimoto STV1V30.5mm 82) ) Brugada 12 V1V3 ST 50) ST 11

12 2011 ST coved saddleback coved Brugada ST 3 84) Na coved ST 74) 45 coved ST 1 Brugada ST saddleback coved ST Brugada Brugada 1998 Na + SCN5A 2) SCN5A Brugada 1830 SCN5A 3 QT LQT3 Lev-Lenegre 85) ) Na + SCN1B GPD-1L GPD1-LL Ca 2+ CACNA1C CACNB2bIto Kv4.3 KCNE3 87) SCN5A Na + Na + Na + trafficking defect Na + loss of function 2,88,89) Na + loss of function Brugada Antzelevitch Brugada 89,90) APD 1 1 K + Ito Ito 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 Ca 2+ ST T c Brugada coved ST Ca 2+ loss of dome dphase 2 reentry e 12

13 QT Brugada ST 91) Na Ca ST 92,93) 68,94) ST Na 1 mg/kg 10 Ca 2+ ST 92) Ito ST 95,96) 75) Brugada Antzelevitch 97) Aiba 98) Antzelevitch AP phase 2 reentry Brugada ventricular late potential 99) 13

14 ) QRS HV SCN5A 3050 Brugada ST 101,102) Brugada 103) 0150 Hz QRS fragmented QRS 81) fragmented QRS 2011 Nademanee Brugada coved 104) Brugada 105,106) Brugada QT Schwartz 4 11,107) QTcTdP T wave alternansnotched T QT QT ,12, ) Schwartz QT 112) QT QT T QT QT QT Jervel and Lange- Nielsen ) Romano-Ward 1990 QT 14

15 QT Brugada ) QT 116) QT 117) QT TdP ) 2:1 Wenckebach 120) 2:1 QT 2 LQT2 LQT3 118,119,120a) LQT1 121) LQT1 3 LQT1 120a,121) 3rd trimester QT SCN5A ) sudden infant death syndrome SIDS 1994 QT 16,18,123) /1000 QT QTc 440 msec QTc QTc 1.53 QTc ) QT KCNQ1KCNH2SCN5A 18,123,124) caveolin-3 CAV3 125) Na + SCN3B SCN4B 126) 1-syntrophin SNTA1 127) QT ) LQT3 13 LQT1LQT2 2 LQT6LQT QT LQT3 2 digenic inheritance LQT2 LQT3 1 LQT ) QT 2 15) 1 2 compound mutation 2 digenic inheritance 129) 15

16 2011 QT ) QT QT QT 1 130) QT ) QT Schwartz ) QT ) p 0.05 p SchwartzQT4 4.5 QT QT 134) QT Schwartz 11) 4 QTc TdP T wave alternans 3 notched T TdP 135) T wave alternans TdP 136) notched T LQT2HERG 137) heterogeneity QT QT dispersion 138,139) T 48,140) ) QT QT dispersion T ) 132) ) ) QT 16

17 QT Brugada ,159) Schwartz 4 QT T QT RR 2 Bazett QT /RR 1/2 QT Bazett 160) 75 /min 80 / min QT QT 4 IaVFV1V6 QT notched T V2 V4 135) 75 /min QT notched T 161) International Conference HarmonizationICHE14 Fridericia QT /RR 1/3 162) Fridericia 1 QT 163) QT Fridericia 164) QT QTc 165) 163) 17

18 2011 QRS QT TdP 135) TdP 135) T 1 T wave alternans 166,167) T wave alternans QT bifid T T T T T 137) 3 notched T 168) 11) Romano- Ward 3 169) 2 Rijnbeek 170) 2 2:1 QT 120a,171,172) LQT2 LQT3 LQT1 120a) QTpT 2:1 174) QT T QT T QT 175) T QT Moss LQT13 T 48) Zhang Moss T LQT1 infantilebroad-basednormal-appearing late-onset normal-appearing 4 LQT2 obvious bifid T wavesubtle bifid T wave with second component on top of T wave in limb and left precordial leadssubtle bifid T wave with second component on downslope of T wavelow-amplitude bifid T wave with second component merged with U wave 4 LQT3 late-onset peaked/biphasic T wave asymmetrical peaked T wave 2 140) 142) Schwartz 4 notched T bifid T LQT2HERG 137) LQT7Andersen-Tawil U QT QU complex 176) 170) heterogeneity QT dispersionqtd 138,139) 18

19 QT Brugada ) QTd 12 QT QT T end 139) T T peak-t endtp-te transmural dispersion LQT2 LQT1 Tp-Te 177) principle component analysispca 2 / 1 PCA ratio 141,178) PCA ratio QT 179) LQT2 QTc msectp-te msec 147) 4 QTc 445 msec LQT1 LQT ) LQT1 QTc 460 msec LQT ,182) QT 2 10 / min QT QT LQT2 LQT1 QT 25 msec ) Shimizu 188) µg/kg 0.1 µg/kg/min , ) QT QT RR RR QTc 5030 msec QT 8947 msec 180) QT LQT1QTc msect Tp-Te msec 19

20 RR peak 3 5 steady state 188) Ackerman µg/kg/min 189) Shimizu LQT1LQT2LQT3 188) 0.05 µg/kg/min QT 30 msec 189) 35 msec 188) 0.01 µg/ kg/min 30 msec 155) QTc 65 msec 190) 0.4 µg/kg/min QTc 600 msec 191) LQT QT QT 192) QT 410 msec QTc 490 msec QT ) QT V4 V V5 QTmsec/ HRbpm QTc 450 msec QT QT 196) 75 g QT QT QT dispersion QT 1 2 QT ) QT Holter T wave alternans 12) QT QT msec 11) 12 Holter QT T ) Holter QT dispersion Tp-Te QT 151,204,206) Holter 188) T QT LQT1 20

21 QT Brugada 2012 LQT2 137, ) QT TdP LQT1 LQT2 Holter RR TdP 207,208) QT Holter QT T Holter 209) QT T wave alternans 12) T wave alternans 210) T wave alternans Holter 141, ) TdP Holter T wave alternans QT 209,215) T wave alternans QT T wave alternans 216,217) T wave alternans 217) ) QT TdP QT QT TdP 1 MPurkinjeEAD 2 APD M Purkinje 45,46) LQT1 IKs LQT2 IKr LQT3 late Na + INa ATX-II QT TdP TdP 45,221) MAP QT MAP EAD 40,43,222) short-long-short EAD 223) QT 2:1 TdP 222,224) APD RR short-long-short 225,226) QT MAP QT T EAD EAD 41,42,227) 21

22 2011 QT Romano-Ward 8 13 LQT1 LQT13 37,38) Jervell and Lange-Nielsen 2 JLN1 JLN2 37,38) QT QT LQT1 40 LQT2 40 LQT ) 3 KCNQ1KCNH2SCN5A PCR DNA 1 single strand conformation polymorphism SSCPconformation sensitive gel electrophoresiscsge dhplcdenaturing HPLC WAVE DNA 2011 QT Heart Rhythm SocietyHRS European Heart Rhythm Association EHRA Expert Consensus Statement 228) 12 QT QT 12 QTQTc 480 msec 500 msec I QT I 12 QTc 460 msec 480 msec IIb QT Romano-Ward Jervell and Lange-Nielsen loss of function gain of function APD 37,38) LQT1 LQT5 KCNQ1 KCNE1 LQT2 LQT6 KCNH2 KCNE2 K + IKIKs IKr IKs IKr LQT3 SCN5A Na + late Na + INaLQT4 Na-K ATPase Na + -Ca 2+ INa-CaIP3 Ca 2+ QT LQT7 Andersen-Tawil LQT8 LQT7 LQT8 22

23 QT Brugada 2012 KCNJ2CACNA1C K + IKlL Ca 2+ ICa-LLQT9LQT10 LQT12 CAV3SCN4BSNTA1 INa LQT11 AKAP-9 IKs LQT13 KCNJ5 K + IKACh QT JLN1 JLN2 KCNQ1 KCNE1 KCNQ1 KCNE1 QT 37,38) Romano-Ward QT QT QT Romano-Ward 229) QT LQT1LQT2LQT3 KCNQ1KCNH2SCN5A 32) QT LQT1LQT2 LQT3 12,48,110) T TdP 37) LQT1LQT2LQT3 KCNQ1KCNH2SCN5A 109,111,114,115) 23

24 2011 QT QT torsade de pointestdp TdP 230) TdP TdP TdP QT TdP QT TdP TdP K TdP TdP QT QTc 500 msec 12,231) QT Jervell and Lange-Nielsen 230,232) 60 /min 231) LQT1 LQT2 LQT3 233) Moss ) QTc 12) Priori LQT1LQT2LQT3 QT QTc 12) QT 110) T 48) 230) QT LQT2 QT KCNH2 K897T QT 234) QT LQT1 C ) implantable cardioverter defibrillatoricd 230) 235) ICD 24

25 QT Brugada ICD ) ICD ICD 12) 230) TdP ICD 237,238) LQT3 TdP LQT1 LQT2 LQT3 230,239) TdP 240) LQT3 Na + QT 241) LQT2 K K K QT 242) QT LQT3 Brugada 243) 230) TdP TdP 3040 mg/kg mg/min QT TdP QT TdP QT TdP TdP K TdP 12) 244) 25

26 2011 LQT1, LQT2, LQT3, LQT7Andersen 110) QT QTc 500 msec TdP LQT1 LQT2 LQT3 230,239) QT TdP 233) LQT1 LQT2 LQT3 LQT1 LQT2 230) QT Vaughan Williams Ia III K Mg 230) LQT2 TdP 245) QT QT TdP TdP 230) 146,235,238, ) QT LQT3 41, ) Ca LQT8 Timothy 255) EAD 242,256) QT IKsIKr K + K QT LQT2 K 42,47,257,258) ) SCN5A LQT ) TdP 2 g 220 mg/kg 3 12 mg/kg

27 QT Brugada QT ICD 12,236) 238) 263) QT 263a) ICD 264) 12,238) TdP TdP ICD ICD TdP LQT1 230,263,265,266) 27

28 2011 QT QT QT QTQT QT K QT torsade de pointestdp QT TdP 222) TdP APD EAD ) TdP QT QT APD 271) QT 4 QT TdP QT QT QT 4 TdP 29,272,273) QT TdP 21,274) 21, ) TdP ,22) QT Vaughan Williams III 22,279,280) TdP K + IK IKr IK IKs IKr APD QT 22,279) QT TdP 11 4 TdP 22) 280) QT 281) IV IKs IKr QT QT TdP III 282) QT 23, ) QT 1 / ) QT IKr ) QT QT EAD 267, ) TdP QT TdP EAD hump MAP 39) QT SNP 29,31,286,291,292) QT 30,293) 28

29 QT Brugada 2012 QT QT 40 7) 35,291,294,295) QT RR QT TdP 24,39,222,296) QT QT TdP QT TdP TdP QT QT EAD 267,268,297) K + QT 298,299) QT K 300) QTc 550 msec 500 msec TdP TdP T shortlong-short 24,222,296) TdP QT 600 msec RR Vaughan Williams Ia III TdP 24,267) TdP QT 39) QT QT 301) QT QT QT QT QT 301) QT 29,285) QT 302,303) QT QT 304,305) QT 306) QT 4 QT TdP QT QT K Bazett QT QTc msec QT QT 4 12,29,272,291) 230) A 29

30 g 2 20 mg/min B 100 /min B 100 /min B mmol/l C mg C QT QT TdP 24,39,297) Na + -K + K QT EAD TdP 267,268, ) QT TdP 24) Vaughan Williams Ia III TdP 267,268,301) QTc 550 msec TdP TdPT short-long-short 24,268) 268,307) EAD QT T QT 60 /min QT TdP 70 /min 24) QT TdP ICD QT QT 4 K QT ) QT QT msec msec 309) 30 QT QTc 440 msec 310) QT 2 QT 12 QT 309) 32 QTc 450 msec 24 QTc 450 msec 311) QT Ito IKl 312) 30

31 QT Brugada 2012 QT TdP 313,314) 315) 316,317) QT 1 IDDM QT 318,319) QT 2 NIDDM TdP 320) QT 321) K QT T 322) K QT TdP 323) QT QT 324) QT U T 325) 27) 326) QT TdP msec QT TdP 27) TdP QT 2g 1992 Brugada PBrugada J 50) 12 V1V3 ST QT 8 Brugada Brugada Brugada ICD Brugada Na 31

32 2011 SCN5A Brugada Brugada 50) ST V1V3 ST 327) ST R coved saddleback Brugada ST coved saddleback ST Wilde 84) 2002 V1V3 J 2mm ST 1 ST coved 2 3 saddleback ST 1mm 1mm 1 coved ST ST gradually descending 84) ST coved saddleback 74) 2012 Luna V1V3 QRS-T 1 coved ST 2 saddleback ST 2 328) Brugada ,329) 2, 3 1 Brugada Brugada 330) 23 1 V1V3 1 Brugada Brugada 331) Brugada 332) Brugada ST ST coved ST J 1mm 51,52,54,333,334) J 1mm coved ST Brugada V1 V3 ST-T A = 1coved ST J 0.2 mvb = 23saddleback ST J 0.2 mvc = Scoved ST 0.2 mv J 0.1 mv 3 329,335) Brugada A = 1 Brugada J 0.2 mv R R mv R R40 R80 B = 23 J 0.2 mv J ST T ST C = S 0.2 mv J 0.1 mv A R R R mvr40 R mv Brugada 335,336) 32

33 QT Brugada 2012 coved saddleback 50) Brugada 52,54,336) ST ST Vaughan Williams Ia Ic Na ST coved ST J 0.2 mv 1 mg/kg 10 2 mg/kg mg/kg 10 74,84,92, ) ST saddleback ST Brugada ICD 74,84,341) Brugada ST saddleback ST Brugada 74,341) Brugada saddleback ST Brugada 62,64-66,345) ST coved saddleback 92) ST ST ST saddleback coved 94,346) ST coved ST ST-T saddleback coved 346,347) coved ST 348) 12 ST coved 331,338,349) Brugada 350,351) Brugada signal-averaging electrocardiographysaecg 69,99,352,353) 33

34 2011 QRS f-qrs QRS 40 msec 2 RMS40 QRS 40 V LAS40 3 Brugada RMS40 LAS ,354) ,356) 81,354,357,358) ) 81,100) Brugada 362) 363) Brugada 338,364) Brugada 94,348, ) Brugada 351) Brugada 346,357,370) T wave alternans T wave alternans Brugada Brugada T wave alternans 94,339) T wave alternans Brugada 99,371) QT Tp-Te Tp-Te dispersion Brugada ) QT dispersion 99) Brugada ST Antzelevitch 89) 360) 100) 104) phase 2 reentry Brugada Brugada Heart Rhythm ) Brugada Brugada 34

35 QT Brugada 2012 Brugada 62,375) 376) 91,103,377) 352) K + Ito 95,96) Brugada Brugada 60) 61,62,378) Brugada His-PurkinjeHV 55 msec 69) HV SCN5A HV HV 379) 380) Brugada Brugada ST ST K + Ito 2 381) 1998 Na + SCN5A 300 BrS1 6 BrS27 2,382) Na membrane trafficking Na + loss-of-function 0 35

36 2011 Na + 1 Ito SCN5A Brugada BrS ) SCN5A Brugada 383) Brugada SCN5A SCN5A PQ HV Na PQ QRS 384) Brugada SCN5A 77) V1 S SCN5A 61,74) Brugada Brugada Brugada Brugada SCN5A SCN5A gain-of-function 3 QT LQT3 progressive cardiac conduction defectspccd SCN5A Na SCN5A 6 SNP 2 HapAHapB 385) HapB 25 SCN5A Brugada HapB Brugada SCN5A 7 BrS17 2 BrS2 glycerol-3 phosphate dehydrogenase likegpd1l 386) Na + 387) QT Brugada Ca 2+ 1 CACNA1C2 CACNB2b 388) BrS5 SCN1B 389) BrS6KCNE3 390) BrS7SCN3B 391) Ca 2+ 2 CACNA2D1 392) HCN4 393) Brugada MOG1 394) KATP Kir6.1 KCNJ8 395) Brugada QRS-ST Osborn 36

37 QT Brugada 2012 Haïssaguerre idiopathic ventricular fibrillationivf mv QRS-ST J 396) J early repolarization syndromeers KATP Kir6.1 KCNJ8 395,397) Kir6.1 S422L Brugada J 398) Brugada V1V3 J IV4V6IIIIIaVF J Brugada Ca 2+ 1CCACNA1C2bCACNB2b2 CACN2D1Brugada SCN5A 399) KCNJ8 S422L Brugada 395) Brugada J Brugada ICD ,66,341,400,401) ICD ) Brugada ICD Brugada ICD ICD QOL Brugada K + Ito Na + Ca 2+ ATP K + IKsIKr ST phase 2 reentry ICD Brugada ICD ICD ICD 37

38 ) ) 1998 Brugada ) 2002 Brugada / 59) / 341) Priori Eckardt 61,62) Priori 200 Brugada ) Eckardt ) Brugada ) / / / / / / 29 / Priori Eckardt 59 Brugada 1 ST 59,375) 61) 74) SCN5A Na 1 ST 406) 351,354) fragmented QRS 81) 62 coved ST 23 38

39 QT Brugada ) ST 1 ST 12 Na S 407) Brugada 59,375) ,401,408) Priori PRELUDE 378) 409) Priori 1 61) msec 3.9 fragmented QRS4.9 J ) fragmented QRS 2006 ACC/AHA Gehi 402,408) ICD 66) Brugada ICD Brugada ICD ICD 0.01 g/kg/min 92,230) C 12 g 0.15 g/min g/kg/min 410,411) 1400 mg/day 66 39

40 mg/day 95,96,230,412) C ICa Ito 200 mg/day 413) Ca Ito K mg/ day 414) SCN5A 100 mg/day 415) 416) 417) 411) Brugada ICD 2005 HRS/EHRA 1 ST ICD I IIa 74) 2008 ACC/AHA/HRS Brugada IIa 263a) 2001 I 2006 IIa 403,418) ACC/AHA Brugada Brugada Brugada ICD 1 ST 2 IIa 2 + IIb 3 IIa Brugada ICD Brugada ICD ICD Brugada 2.6 ICD ) ICD 59-62,74,84,420) ICD 104, ) 104) 40

41 QT Brugada Schwartz PJ, Priori SG. Long QT syndrome: genotype-phenotype correlations. In: Zipes DP, Jalife J, editors. Cardiac Electrophysiology: From Cell to Bedside, 4th ed. WB Saunders Co, 2004: Chen Q, Kirsch GE, Zhang D, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998; 392: Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J 1957; 54: Romano C, Gemme G, Pongiglione R. Rare cardiac arrhythmias of the pediatric age II. Syncopal attacks due to paroxysmal ventricular fibrillation. (Presentation of 1st case in Italian pediatric literature). Clin Pediatr (Bologna) 1963; 45: (in Italian). 5. Ward OC. A new familial cardiac syndrome in children. J Ir Med Assoc 1964; 54: Schwartz PJ, Spazzolini C, Crotti L, et al. The Jervell and Lange- Nielsen syndrome: natural history, molecular basis, and clinical outcome. 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