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1 Guidelines for Drug Treatment of Arrhythmias (JCS 2004) a 1Sicilian Gambit 2J-GAMBIT Circulation Journal Vol. 68, Suppl. IV,
2 CAST Na Vaughan Williams Sicilian Gambit Sicilian Gambit 1997 Sicilian Gambit CD-ROM CD-ROM J-GAMBIT J-RHYTHM ICD ICD QOL upstream upstream 1Sicilian Gambit CD-ROM CD-ROM Circulation Journal Vol. 68, Suppl. IV, 2004
3 Sicilian Gambit Cardiac Arrhythmia Suppression TrialCAST Sicilian Gambit Sicilian Gambit Sicilian Gambit Sicilian Gambit Sicilian Gambit CD-ROM 1 Sicilian Gambit 3 CD-ROM J-GAMBIT Sicilian Gambit 2 Vaughan Williams Singh Vaughan Williams Ia Ib Ic 1 Circulation Journal Vol. 68, Suppl. IV,
4 Na Purkinje 0 APD Singh a b 3 APD c APD K Na APD Purkinje Ia c c Na Na Na-Ca Ca Na 1 camp Ca ItoIKICl APD Na APD APD K K K IKr QT torsade de pointes, TdP K TdP APD QT TdP Ca Ca Ca 984 Circulation Journal Vol. 68, Suppl. IV, 2004
5 L Ca T Ca 3 Vaughan Williams APD c K 4 Sicilian Gambit Sicilian Gambit 2 Vaughan Williams ATP 2 1 Na Fast Med Slow A A A I A A A A A Ca K If M 2 A 1 Na-K ATPase PR QRS JT AI Circulation Journal Vol. 68, Suppl. IV,
6 Vaughan Williams Sicilian Gambit PQQRSQT Na Na fastintermediateslow Ca K If Vaughan Williams NaK 3 Na fast intermediateslow Ca K CAST Sicilian Gambit Na Na CAST Na Sicilian Gambit Na 1 Sicilian Gambit K 4 K K K K QT torsade de pointestdp K K IKr 1994 SWORD IKr d- K 5 K K K IKs IKr K Na Na 986 Circulation Journal Vol. 68, Suppl. IV, 2004
7 3 4 downstream upstream 6 ACE A Sicilian Gambit Vaughan Williams Na fast drugs slow drugs K K IKACh ATP K IKATP Na IKATP IKs K Vaughan Williams a K IKACh M2 K 7 Sicilian Gambit J-GAMBIT J- RHYTHM CD-ROM 1 Japanese Guideline for Arrhythmia Management By Individual TherapyJ-GAMBIT 2 Sicilian Gambit CD- ROM Circulation Journal Vol. 68, Suppl. IV,
8 PAF PVC CD-ROM CD-ROM PAF PVC CD-ROM PAF 274 PVC PAF PVC PAF PVC % 100 PAF PVC Circulation Journal Vol. 68, Suppl. IV, 2004
9 PAF 60 PVC 70 4 CD-ROM PAF % CD-ROM % CD-ROM % % % 16 6 % PVC % % % % % 9 4 % 5 PAF 5 PVC % % % % % % % 58.6 % % % % % % % % % % % % % % 69.7 % % % 5 The Sicilian Gambit Guideline on CD 1 CD-ROM PAF 79 %PVC 71 % CD-ROM PAF 6 PVC 5 CD-ROM Sicilian Gambit PAF PAF CD-ROM PVC RBBBLAD LBBBRAD QRS PVC PVC Circulation Journal Vol. 68, Suppl. IV,
10 PAF CD-ROM 3 1 slow kinetics Na 2 fast kinetics Na K K K 2 3 Ca Na Ca K 7 LVEF 4050 % CTR 5060 % NYHA LVEF 40 % CTR 60 % NYHA ACE ACE K 7 % QRS QRS 6040 QT QRS SLE 70 QT QRS 8020 QT QRS Cinchonism QRS QRS QT 80 QRS 70 QT QRS 85 QRS QRS 50 QT QT QT 5050 QT - ATP 990 Circulation Journal Vol. 68, Suppl. IV, 2004
11 Ccr Ccr 50 mlmin Ccr 5020 mlmin Ccr 20 mlmin Ccr Scr 1.3 mgdl Ccr 50 mlmin Scr mgdl Ccr 2050 mlmin Scr 2.0 mgdl Ccr 20 mlmin 8 2 ASTALT Child 10 8 Child A 12 mgdl 23 Child B 23 mgdl Child C 3 mgdl 89 Circulation Journal Vol. 68, Suppl. IV,
12 mgdl mgdl 3 mgdl 23mgdl 1 2mgdl - ATP 3 FDA Circulation Journal Vol. 68, Suppl. IV, 2004
13 CAST Na slow drug slow drug intermediate drug 18 Sicilian Gambit CD-ROM Circulation Journal Vol. 68, Suppl. IV,
14 Na intermediate Na slow * * Na intermediate Na intermediate Na intermediate Na slow * * Na intermediate 2 1 P f RR Circulation Journal Vol. 68, Suppl. IV, 2004
15 3 3 3 QOL DC Ca K Na 4 Na K QT QT torsade de pointestdp Ca Ca Ca camp Ca M Circulation Journal Vol. 68, Suppl. IV,
16 WPW K * * * Ca Na intermediateslow * * Ca 4AHA class b a QOL AFFIRM AHA cm Circulation Journal Vol. 68, Suppl. IV, 2004
17 QOL PIAFRACE AFFIRMSTAF QOL 1921 J-RHYTHM INR % SPORTIF 4 DC AF48 AF48 3 AF 4 Circulation Journal Vol. 68, Suppl. IV,
18 AF48 AF48 Na slow AF Na intermediate AF Brugada DC DC 75 % R 1 6AHA class IIb class IIa 23 7 Na Na Na 998 Circulation Journal Vol. 68, Suppl. IV, 2004
19 Na 6 11 Brugada ST Na downregulation Na 3335 K 6 K CHF-STAT 36 K downregulation K K K K CTAF AFFIRM K Na Na Na slow drugs Na inter-mediate drugs K 7Na Na K J-RHYTHM M2 Na Brugada Na ACE A- Circulation Journal Vol. 68, Suppl. IV,
20 Na slow Na intermediate K Na intermediate Na intermediate P T P on T Type Type 2 44 Type 1 Type 1 cavotricuspid isthmus CTI 4547 CTI-dependent atrial flutter 8A 48 upper loop reentry 49 Type 2 incisional reentrant 1000 Circulation Journal Vol. 68, Suppl. IV, 2004
21 A 8 B SVC SVC IVC IVC A B tachycardia 274 8B I Ic % 50 CTI 4551 K Na intermediateslow drugs K 5253 Na 1028 % DC R 50 J 100 Circulation Journal Vol. 68, Suppl. IV,
22 DC DC / 99/ K * Na intermediate slow K Na intermediate slow DC 1002 Circulation Journal Vol. 68, Suppl. IV, 2004
23 10 WPW 99 DC K Na intermediateslow drug 11 DC K Na 8 Na 11 1 K Na intermediate slow WPW WPW Circulation Journal Vol. 68, Suppl. IV,
24 WPW CTI 90 % WPW WPW 11 WPW % DC 2.2 % % AVNRT WPW AVRT mmhg 3 90 % Ca WPW K Na DC Valsalva Valsalva 54 % 15 % 15 % 58 Ca 1004 Circulation Journal Vol. 68, Suppl. IV, 2004
25 12 1 a Valsalva DC a) ATP Na DC 13 1 P QRS WPW 14 Na intermediate Na intermediate ATP 9095 % CD-ROM ATP100 %94 % Circulation Journal Vol. 68, Suppl. IV,
26 P QRS WPW P QRS WPW K Na intermediateslow K Na intermediateslow Na % 60 Na DC CD-ROM Na 13CD-ROM Na WPW Ca K Na intermediate slow drugs WPW Ca K Na intermediateslow drugs P QRS 1006 Circulation Journal Vol. 68, Suppl. IV, 2004
27 WPW Ca % Ca % 3 63 Ca % % mg 70% 90270mg 60% 80160mg 60% 1,0002,000mg 60% mg 65% mg 75% Sicilian Gambit QRS QOL QRS Ca Ca Ca Ca Ca Circulation Journal Vol. 68, Suppl. IV,
28 RBBB LAD LBBB RAD Ca Na slow Na intermediatefast Ca Na slow Na intermediatefast Na slow Na intermediatefast Na DAD DAD Ca Ca Na ab Na Circulation Journal Vol. 68, Suppl. IV, 2004
29 16 1 Lown 1 Lown 25 Na fast Na intermediate Lown Grade 1 Grade 2-5 Na Na ATP K CAST 7072 slow kinetic Na ICD fastintermediate kinetic Na K Fast kinetic drug Circulation Journal Vol. 68, Suppl. IV,
30 Na slow Na fastintermediate a aca K Na fastintermediate a Na fastintermediate a Na slow Na fastintermediate Na fast Na intermediate Na ACE A- ICD ACE A- Na 7374 MADIT- ICD ACE A wide QRS 1010 Circulation Journal Vol. 68, Suppl. IV, 2004
31 2 75 Ca DC 18 QRS 1 RBBBLAD Ca Ca 18 1 DC RBBB LAD LBBB RAD ATP Na a DC a Circulation Journal Vol. 68, Suppl. IV,
32 Ca 2 Na LBBBRAD ATP Na Na slow kinetic Na 8081 DC 19 1 ACE A- ICD VT CAST slow drugs ACE A- EPS ICD 1012 Circulation Journal Vol. 68, Suppl. IV, 2004
33 75 ICD ICD ICD fastintermediate kinetic Na K 86 ICD 83 ICD ICD ICD ICD 69 ICD QT QT 2 94 QRS QRS QT 95 QT torsade de pointestdp Circulation Journal Vol. 68, Suppl. IV,
34 IA III K Mg Ca 4. 5., HIV QT QT 11 Jervell, Lange-Nielsen Romano-Ward Romano-Ward LQT1 LQT QT Brugada Brugada ST DC 99 3 DC ACLS 100 DC DC DC 3 DC ACLS QT DC DC QT Mg QT QT 1014 Circulation Journal Vol. 68, Suppl. IV, 2004
35 21 QT QT ICD IDC QT QT Brugada QT ICD ICD ICD ICD QT QT QT Mg 101 QT 102 QT 96 QT QT ICD 86 ICD QT QT QT 96 ICD QT Brugada Brugada ICD ICD ICD Circulation Journal Vol. 68, Suppl. IV,
36 Wenckebach a b a b Class I 1 Class IIa 1 2 Class IIb 1 Class III 1 Class I Class IIa Class IIb Class III 1016 Circulation Journal Vol. 68, Suppl. IV, 2004
37 Rubenstein mg RR mgkg mg mg gkg mg mg 34 A1 K A cyclic-amp mg RR VVIR mg RR Class I 1 Class IIa 1 Class III 1 Class IIII12 Circulation Journal Vol. 68, Suppl. IV,
38 Class I Class IIa 1 3 His His 2 1 His His Class IIb Class III Wenckebach 2 3 Class IIII a b a b DDDR VDDR Circulation Journal Vol. 68, Suppl. IV, 2004
39 24 DC ATP* Na DC AVNRTAVRT WPW , 3 24 Ice bag ATP Ca Na 25 WPW Na Ca Circulation Journal Vol. 68, Suppl. IV,
40 Na intermediateslow Ca Na intermediateslow Ca ATP* Na intermediateslow K Ca 122 WPW Ca Na DC Jkg Ca ATP ATP 5 % Ca ATP Na K Ca 127 ATP 1020 Circulation Journal Vol. 68, Suppl. IV, 2004
41 QT torsade de pointestdp QRS LBBBRAD DAD RBBBLAD 2 a b 200 c 200 d 3 27 RBBBLAD Ca Na LBBBRAD Ca Na Na 28 Ca Na Na 27 RBBBLAD LBBBRAD Ca Na intermediateslow Ca Na intermediateslow Na fast Circulation Journal Vol. 68, Suppl. IV,
42 RBBBLAD LBBBRAD Ca Na Na intermediateslow Na intermediateslow Ca Ca Na QRS RBBBLAD 1 RBBBLAD LBBBRAD DC Na QRS RBBBLAD Ca ATP Na Na Na DC 30 RBBBLAD Ca Na Circulation Journal Vol. 68, Suppl. IV, 2004
43 29 DC RBBBLAD Na fast LBBBRAD Ca Na intermediateslow ATP Na intermediateslow Na intermediateslow DC 30 RBBBLAD LBBBRAD Ca Na Ca Na Na Ca ICD Circulation Journal Vol. 68, Suppl. IV,
44 LBBBRAD Ca Na Ca K ICD Ca DC 2 Jkg 5 70 QTc0.46 QT Bazett QTc QTc K Na QT EAD torsade de pointestdp 2 QT QTc T QT 140 torsade de pointes QT K Ito K IKrIKs 1024 Circulation Journal Vol. 68, Suppl. IV, 2004
45 31 I to, I K, I K1 I K1 Ca 2 DAD DAD EAD I K EAD I to, I Na 32 K upstream approach downstream approach KIK1 K APD K EADDAD 31 upstream upstream ACE IIA-IIARB K Circulation Journal Vol. 68, Suppl. IV,
46 Atrial fibrillation begets atrial fibrillation L Ca ICa,L APD A-II upstream upstream downstreami downstream downstream 32 upstream downstream downstream upstream ms WPWWolff- Parkinson-White fast pathway slow pathway excitable gap entrainment excitable gap entrainment A inactive core wave length excitable gap gap junction 1026 Circulation Journal Vol. 68, Suppl. IV, 2004
47 A. 33 B. C. Planar wave Circular wave Spiral wave A ms inactive coreallessie MA, et al. Circ Res 41:9-18, 1977 Banisotropic reentry VT LADLL 8 Dillon SM, et al. Circ Res 63: , 1988 C planar wavecircular wave spiral wavewave length, WLSpiral wave qpertsov AM, et al. Circ Res 72: , 1993 Gap junction anisotropy 33B wave breakcurvature 33C planar wave circular wave wave frontwave tail wave length Circulation Journal Vol. 68, Suppl. IV,
48 meandering wave break curvature 3 Na 1 Na resting : R activated : Ainactivated : I RA I R Na Na INa Vmax 34 2 R Na use-dependent block use-dependent block diastolic interval 34 0 mv 80 Na 100 R I R I R A A A I R % 0 Vmax V/sec Circulation Journal Vol. 68, Suppl. IV, 2004
49 15 APD use-dependent block b c a fast I I intermediate I AI A A slow A A A A A I usedependent block use-dependent block fast drug intermediate drug slow drug 15 intermediate drug slow drug 2000 CD-ROM 3 fast drug Na intermediate drug slow drug use-dependent block QRS 4 Na 15 APD APD Na Na 4 K 0 Na 1 Ito ICa, L 2 KIKrIKs 3 3 K IK1 35 K IKur ATP ATP KIKATP APD KIKAChAPD Circulation Journal Vol. 68, Suppl. IV,
50 I to I K (I Kr,I Ks ) S2 S3 S4 S1 S5 S6 H5 M1 M2 H5 I K1 Ito I K (I Kur,I Kr,I Ks ) H5 S1 S2 S3 S4 S5 S6 M1 H5 M2 I K1 Ito Kv4.2/4.3 IKur Kv1.5 IKr HERG+MiRP1 IKs KvLQT1 + mink IK1 Kir2.1 IK.ACh Kir3.1/3.4 IK.ATP Kir6.2 + SUR2A 1990 K K K K 2 K K K K 16 K K K IKr IKr IKr HERG K IKr IKs IKr APD IKr APD torsade de pointestdp IKr IKs APD IKr IKs 16 IKr IKs IKur Ito IK1 IK.ACh IK.ATP Ia Ib Ic 1030 Circulation Journal Vol. 68, Suppl. IV, 2004
51 IKur K Ito APD K K IKACh 16 APD ATP K IKATP APD ATP K ATP K ATP K 5 1 QT LQTS Romano- WardRW Jervell, Lange- NielsenJNLJNL RW K QT QRS torsade de pointes TdP 1990 RW LQT1 LQT6 6 JNL JNL1JNL RW LQT1 11p15.5 KCNQ1KvLQT1 I Ks LQT2 7q35-36 KCNH2HERG I Kr LQT3 3p21-24 SCN5A I Na LQT4 4q25-27 ANK2ankyrin-B LQT5 21q22 KCNE1minK I Ks LQT6 21q22 KCNE2MiRP1 I Kr JLN JNL1 11p15.5 KCNQ1 KvLQT1 I Ks JNL2 21q22 KCNE1 mink I Ks LQT1KvLQT1 LQTS 6 subunit KvLQT1KCNQ1 1 subunit minkkcne1 K IKs IKs QT LQT1 IKs K L Ca ICaL APD EADTdP LQT2 K IKr subunit HERG KCNH2 LQT2 LQT2 TdP HERG K LQT2 K K LQT3 Na subunit SCN5A Na LQT3 Na APD LQT1 LQT2 EAD TdP LQT3 LQT1 LQT2 QT TdP Circulation Journal Vol. 68, Suppl. IV,
52 LQT4LQT5LQT6 2 QT Brugada 1992 V1-V3 ST Brugada 2030 % Na Brugada Na subunit SCN5A Na Na 3 SR Ca RyR catecholaminergic polymorphic ventricular tachycardia, CPVT familial polymorphic ventricular tachycardia, FPVT arrhythmogenic right ventricular dysplasia 2ARVD2 RyR FKBP SR Ca camp Na K HCN hyperpolarization-activated cyclic-nucleotide-gated cation channel 4 If 2 T Ca 4 ICaT ICaT T Ca 3 RyR camp ICaL Ca ITI Ca Ca 1032 Circulation Journal Vol. 68, Suppl. IV, 2004
53 4 Na-K ATPaseNa-K pump Na-H ph Na-H Na-Ca Ca Na-Ca 5 Na Na K Gd camp Ca Cl K 4 K Na K 6 upstream ACE A- ARB ETA mgkg mg mg mgcr mg % 18 % 63 % 11 % p Na K 1 39 % 69 % INa IKr Circulation Journal Vol. 68, Suppl. IV,
54 mg 2 % mg bidtid mg mg % % 47 %Ca 39 % 38 % 6 31 % % % % 14 % 56 % % 25 % 5 p ns TdP m % 23.8 % 0.8 % 0.6 % 34.6 % 21.3 % 0.2 % 0.1 % p % 1034 Circulation Journal Vol. 68, Suppl. IV, 2004
55 36 % 6 ICD 23 % 61 % AVID ICD VF 84 %VT 16 % 46 %73 % 10 % 3 4 ICD mg mg 600 mg mg1,2 200 mg 21 DC ICD 36.4 % 13.0 % 43.5 % 29.5 % 45.4 % 35.1 % ICD vs p vs ns ns 1 ICD % 1232 CABG 58 % PTCA 45 % MI>6mo 88 % EF 23 % AF 9 % QRS 0.12sec 50 % 3 76 ICD % ACEI 72 % 70 % ICD 14.2 % 19.9 % 19.8 % 14.9 % p ICD 1 Circulation Journal Vol. 68, Suppl. IV,
56 ICD backup pacing mgkg mgkg AMI AMI primary VF CCU 1996 ACCAHA AMI, VT VF VF Na APD Na K %75 % 71 % spectrotemporal Ia Ic 156 Na QT LQT3Na SCN5A QT K IKr HERG LQT LQT3 QT QT mg % 70 % Circulation Journal Vol. 68, Suppl. IV, 2004
57 mg % DC mg % mg 3060 % 7080 % mg 50 % % 1020 % QRS QT mg % mgkg 91 % 32 % mg % 10 %1 65 % 35 % mg % 10 % mg 50 % % 32 % 4 % 177 ICD CASH % % 1.4 % Na 179 IKrIK, ACh IKur mg Gottlieb Lown mgkg % mgkg mg mg mg mg 47 6 SMART Sinus Rhythm Maintenance in Atrial Fibrillation Randomized Trial INa IKrIKs IKAChIKATPICa M Circulation Journal Vol. 68, Suppl. IV,
58 mg 52 % 29 % 22 % mg % AVRT8 3 AVNRT mg 75 % 33 % % 33 % Hoffman 8 % 33 % Vaughan Williams Ia Na Na slow kinetic drug 179 Ca K 200 M2 M % 52 % 71 % 60 % Na M Vaughan Williams Ic Na K mg 63 % 75 % 40 % 8188 % 100 % 3 mgkg 80 % % 7481 % 83 % % mg 3 59 % % 208 Ic Hybrid 209 Na SCN5A QT 1038 Circulation Journal Vol. 68, Suppl. IV, 2004
59 LQT3 QT 210 Brugada LQT3 Brugada mg %73 % mg mg 4 52 %12 86 % mgkg 89 % mg 6971 % mg Lown 35 %18 %13 % mgkg % 4 % 32 AH HV 217 QRS % Na Ca K, K IKurIKsIK1ItoIKAChIKATPIKNa QT IKur 6971 % ATP QTQTc 221 QT dispersionqt dispersion 222 QT dispersion % 48 % 50 % 3066 % QT TdP mg 8098 % DC 230 DC 231 Circulation Journal Vol. 68, Suppl. IV,
60 L Ca L Ca RBBBLAD QT L Ca EAD 142 L Ca mgmin 10 mg L Ca , DC mg 40 % mg6 52 % ESVEM 39 %EPS 36 % 41 % mg 2 13 % 38 % mg3 14 % 23 % mg 59 % 75 % mg 15 % 50 % 25 % 51 % 16 % 44 % RR QTc 3 % torsade 1040 Circulation Journal Vol. 68, Suppl. IV, 2004
61 de pointestdp 2 % TdP 2 % 4 % % 1 % 14 VTVF 2 VF % AVID 86 ICD ICD MADIT ICD 67 ICD 92 1 ICD %CTAF % % mg 5 80 % 1015 % 68 % 15 % 30 % 25 % 35 % ATMA 1 % % 16 % 12 % 9 % 3 % % 11 % 10 % 1 % 80 % IKr QT QT QT torsade de pointes TdP 270 VTVF VTVF mgkg mgkg QT VTVF 1 1 TdP VTVF Mg Circulation Journal Vol. 68, Suppl. IV,
62 VF 13 ICD VTVFelectrical storm 87 VT 2 50 % mg5 ml 1000 mg10 ml 50 mg100 mg 125 mg5 ml 50 mg100 mg R 150 mg 50 mg5 ml 100 mg150 mg 10 mg20 mg 100 mg10 ml 50 mg100 mg 70 mg5 ml 50 mg100 mg 50 mg100 mg 50 mg5ml 25 mg50 mg 50 mg5 ml 50 mg100 mg 40 mg 5 mg2 ml 30 mg60 mg R 100 mg200 mg 10 mg50 mg250 mg 40 mg80 mg 100 mg 50 mg 10 mg20 mg LA 60 mg 2 mg2 ml 98 % 0.5 mg1 ml) ATP 10 % 20 mg60 mg 10 mg20 mg40 mg Torsade des Pointes 2 g20 ml mg0.25 mg 125 mg250 mg 10 %1 ml2 ml 100 mg 1042 Circulation Journal Vol. 68, Suppl. IV, 2004
63 mg12 mgkg mg 4 mg mg mg23 mgkg mgkg 100 mg 1 3 R 150 mg mg mg 1 40 mg 60 mg % mlkg 1.52 mgkg 510 ml 100 mg mg 450 mg mgkg mg mg 200 mg mlkg12 mgkg mg mg mg mgkg 1 1 mgkg mg mg mg mg mg 320 mg mg200 mg mgkg mgkr 1 30 mg 90 mg mg mg mg mg g 1 4 mg 0.51 mg 0.5 mg mg mg50100 mg1 500 mg mg mg13 3 Circulation Journal Vol. 68, Suppl. IV,
64 mgkg mgkg 23 mgkg mgkg 515 mgkg mgkg mgkg mgkg 3 12 mgkg mgkg mgkg 5 36 mgkg 3 12 mgkg 8mgkg 2 10 mgkg mgkg 12 QT mgkg 13 mgkg mgkg ATP mgkg Torsade de pointes 1020 mgkg mgkg 0.04 mgkg 0.03 mgkg 0.01 mgkg mgkg 515 mgkg mgkg Circulation Journal Vol. 68, Suppl. IV, 2004
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