1. 5652Taiwan Heart Rhythm Society April 2012iVOL. 005 Shih-A ChenShih-Ann Chen -Ann(Taiwan Heart Rhythm Society) t )1004150222610041502226886-2-23821530886-2-23821528www.thrs.org.twI S S N 2 2 2 3 - 0 1 3 0 Yenn-JiangYenn-Jiang LinJin-LongJin-Long Huang / Yung-HsinYung-Hsin Yeh 30%(Dyssynchrony)(CardiacPo-ChingPo-Ching ChiWei-HuaWei-Hua Tangresynchronization therapy)(CRT)Jan-YowJan-Yow ChenShuenn-NanShuenn-Nan ChiuShih-ChungShih-Chung Huang Bien-Hsien HuangBien-HsienWen-ChinWen-Chin Tsai Shih-TsungShih-Tsung Cheng (Coronary vein)Tze-Tze- Fan Chao Hung-YuHung-Yu Chang(Left ventricular lead)() (Re-synchrony)Wide QRSduration1 - P1 (Electrical dyssynchrony)2 QRSdurationCRT(ICD) - P2(New York Heart Association (NYHA), functional class3 III-IV)(Left ventricular ejectionDabigatran - P4 fraction (LVEF) 35%, mean 21~30%)wideQRS duration(150 milliseconds (ms)4 Brugada Syndrome - P5120 ms, mean 155~209 ms)CRT5 CPVT - P7(NYHA functional class)COMPANION6 - - P9 trialCARE-HF studyCRTcombined endpoints7 ECG of the month - P9 CARE-HF study8 - P10CRT(Secondary endpoint)(Meta-analysis)CRT9 - P11ACC/AHA/HRS 2008 guideline for10 - P14 Device-Based Therapy of Cardiac Rhythm AbnormalitiesLVEF 35%QRS duration120 ms11 - P16 NYHA functional class

2. 2 THRS Taiwan Heart Rhythm Society1014VOL. 005III or IVCRTClass I CRTrecommendationNYHA functional class I or II(REVERSE studyVentricular pacingIIa MADIT-CRT study)REVERSE studyCRT-onCRTgroupCRT-off group(2009/7/1)Guideline(NYHA functional class I or II)12CLBBB(:QRS duration 140 ms120 ms6 1824) MADIT-CRT studyCRT+ICDICDMechanicalNYHA functional class I or IIdyssynchrony()2.412Electrical dyssynchronyQRS duration 120 ms30%MechanicalMechanical dyssynchronyQRS duration80DabigatranRE-LY (RandomizedaPTTEvaluation of Long-Term Anticoagulation Therapy)Dabigatran41811371. PRADAXAP- P-gpRifampinDabigatranDabigatran 110mg 150mg Quinidine/KetoconazoleWarfarinINR2-32 Dabigatran P-P-gpVerapamil20%AspirinAmiodaroneQuinidineClarithromycinWarfarin/110mg Dabigatran P-P-gpWarfarin/150mg Dabigatran1.69%41.53%p0.011.69%1.11%p0.0113.36%2.71%p=0.033.36%3.11%Dabigatran 30-50 mL/minp=0.31Dabigatran (0.12%0.10%) P-warfarin0.38%2Acetylsalicylic acidDabigatran etexilate 3 NSAIDDabigatran 4Clopidogrelthrombin, brinogenbrin5Dabigatran 4 . Dabigatranthrombin DabigatranDabigatran Dabigatran 752-3 60% RE-LY Warfarin Dabigatran etexilate 0.64% (warfarin) FEIBA 0.82% (Dabigatran etexilate 110 ) 0.81%VIIa IIIX X (Dabigatran etexilate 150 )4dabigatran etexilate 4,7. < Dabigatran Acute coronary30 mL/minDabigatran events 8 5. VOL. 005Taiwan Heart Rhythm Society1014 THRS5 4. Dabigatren5. Bovio JA, Smith SM, Gums JG. Dabigatran etexilate: a novel oral thrombin inhibitor for thromboembolic disease.Ann Pharmacother 2011;45:603-614. 6. Harper P, Young L, Merriman E. Bleeding risk with Dab-1. Fuster V, Rydn LE, Cannom DS , et al. ACC/AHA/ESC igatran in the frail elderly. N Engl J Med 2012;366:864-866. 2006 Guidelines for the Management of Patients with 7. Hohnloser SH, Oldgren J, Yang S, et al. Myocardial Isch- Atrial Fibrillation. Circulation 2006;114:e257-e354emic Events in Patients With Atrial Fibrillation Treated2. Connolly SJ, Ezekowitz MD, Yusuf S, et al. DabigatranWith Dabigatran or Warfarin in the RE-LY (Randomized versus warfarin in patients with atrial brillation. N Engl JEvaluation of Long-Term Anticoagulation Therapy) trial. Med 2009;361:1139-1151.Circulation 2012;125:669-76.3. Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N.In- 8. Uchino K, Hernandez AV. Dabigatran Association With vitro prole and ex-vivo anticoagulant activity of the directHigher Risk of Acute Coronary Events: Meta-analysis of thrombin inhibitor dabigatran and its orally active prodrug, Noninferiority Randomized Controlled Trials. Arch Intern dabigatran etexilate. Thromb Haemost 2007;98:155-162.Med 2012;12:397-402. Brugada Syndrome / ICD(Electrical storm)447 Brugada syndromeBrugada type 12ECGBrugada type 1 pattern (3A)pattern1 CCU(Implantable cardioverter 24Electrical stormdefribrillator[ICD]) 3 50 BPMMonomorphic premature ventricularICD19beat(Ventricular Fibrillation [VF])ICDCCUIsoproterenol1.0 g/minVFQuinidine 200mg qidQuinidineECGV1-V3 STQTc531ms(3B)Quinidine 200mg bidECGQTc443ms3CECGV1-V3VT/VF 6. 6 THRSTaiwan Heart Rhythm Society1014VOL. 005 Transmural gardient (Heterogenicity) Phase 2 (Refractoriness) (Phase 2 reentry) Brugada syndromeVT/VF Electrical storm (VT/VF)ICD24 3Electrical shock Brugada syndrome 5% 45% Brugada syndromeElectrical storm Brugada syndormeElectrical storm Brugada syndrome ()Brugada syndrome(Class Ia)Brugada syndorme(Syncope)(Seizure)(Cardiac arrest)VT/VFAmiodaroneLidocaineMexiletineBeta-blockerElectrical40 stormIsoproterelolinfusion (Class I Recommendation)BrugadasyndromeVagal tone enhancement(Polymorphic Ventricular Tachycardia [VT])(Ventricular Fibrillation Sympathomimetic agentsSympathetic[VF])(ICD)tone(Continuous infusion of 0.15-2.0 g/min)Brugada syndromeIsoproterololICa(L)(Phase 0)(Depolarization)Brugada syndromeItoloss of domeI Na(3VT/VF(Cardiac sodium channel gene, SCN5A) IsoproterelolECG V1~V3)(Decreased inward ST elevationPremature beatVT/VFsodium current)Phase 0 QuinidineI to (600~3200mg QD) (Class I Recommendation)QuinidineI to(Transient outward current)Quinidineanti-cholinergic effectvagalPhase 0 toneQuinidinePhase 1Brugada syndrome VT/VF80%Phase 1 QuinidineECGI Ca(L) V1~3 STPremature beat VT/VFQuinidinePhase 2(Phase 2 Plateau) (Loss of action potential dome) (Right ventricular outflowtract) (Cinchonism)(Epicardium) QT(Endocardium)Vagolytic effectAV nodeTransmural(Gradient)Cilostazol (Class IIb Recommendation)(Heterogenicity)ECGBrugada ItoOrciprenaline (Beta-syndrome V1-V3 ST (ST segment elevation) adrenergic receptor agonist )(Right Bundle Branch Block)(Class IIa Recommendation)Brugada syndromeVT/VF 7. VOL. 005Taiwan Heart Rhythm Society1014THRS7CPVT / Catecholaminergic polymorphic ventricular tachycardia(CPVT) QTcQRSBrugada19701990 (Sinus bradycardia)U3Ryanodine receptorisoform 2 (RYR2)Cardiac calsequestrin (CASQ2) (Action pontential)1-3Ventricular tachycardia (VT)Ventricular(Ca2+)(Second messen-brillation (VF) ger)Excitation-contraction coupling 4,530% Ryanodine receptor7-8 4,662% Sarcoplasmic reticulum (SR) (Sudden cardiac death, SCD)7CPVT Calcium-induced calcium release (CICR) (Bidirectional VT100 nM600~1000 nM1) Troponin CSR Ca 2+ATPase (SERCA)Sarcolem-mal sodium-calcium exchanger(NCX)Sarcolemmal Ca 2+ATPaseMitochondral Ca 2+uniport (2)Ryanodine receptorCalmodulin ()FK-506 bindingprotein (FKBP 12.61Bidirectional ventricular tachycardia in a patient with CPVTRyanodine receptor)Protein kinaseAPhosphatasesSorcinCASQ2TriadinJunctinPriori, et al.2000RYR230~50%RYR2 5 (autosomaldominant)Lahat, et al.2001CASQ2(autosomal recessive)SRSRSRStoreoverload induced Ca2+ release2CSQcalsequestrinNCXsodium-calcium exchangerRYRryanodine receptorSERCAsarcoplasmic reticulum calcium ATPase SRsarcoplasmic reticulum (SOICR) 2 SOICR 8. 8 THRS Taiwan Heart Rhythm Society1014VOL. 005NCX Dantrolene-malignant hyperthermia13 Ca 2+ sparkCPVTCPVT(S406L-RYR2)Delay afterdepolarization (DAD) Induced pluripotent stem cells (iPSCs)Early afterdepolarization (EAD)RYR2SRCardiomyocytesCaffeineSOICRSR Isoproterenolflou-4Ca 2+ spark 2RYR2SOICR Patch clampDantroleneCalsequestrinRyanodine receptorCalcium spark frequencyTriggered activitiesCalsequestrinGyorke, et al.CalsequestrinSR CPVT RYR2Knollmann, et al. 60%RYR2CASQ2CSQ2 knock-out mice cardiomyocytesBidirectional VTVFCatecholamineCalsequestrin -adrenergic blockersRyanodine receptor CatecholamineRyanodine receptor CPVTFlecainideR-propafenone KN-93DantroleneCPVTCPVT Calcium releaseTriggered activitiesCPVT Heart failure-adrenergic blockersLeenhardt, et al.Ventricular outflow tract tachycardia nadalol 6 (Implantable cadioverter- FlecainidePropafenonedebrillator, ICD)3KN-93OxidativeCPVTclass IA stressVFCPVTSOICRGalimberti, et al.2011Journal of Molecular and Cellular CardiologyR-propafenoneflecainideCa2+ wave propagation (IC50 ~ 10M)CASQ2 -/- 1. Wilde AA, Bhuiyan ZA, Crotti L, et al. Left cardiac sym-Sopanin (40g/ml) Permeabilized car- pathetic denervation for catecholaminergic polymorphicdiomyocytes (ventricular tachycardia. N Engl J Med 2008;358:2024-)flou-4Confocal mi-2029.croscopeR-propafenoneFlecainide2. Priori SG, Chen SR. Inherited dysfunction of sarcoplasmicCa2+ wave propagationCa2+ spark frequencyreticulum ca2+ handling and arrhythmogenesis. Circula-amplitudespeedTetracaineCa 2+ tion research 2011;108:871-883.wave frequencyR-propafenoneFlecainide3. Liu N, Colombi B, Raytcheva-Buono EV, Bloise R, PrioriCa2+ wave amplitudeCa2+SG. Catecholaminergic polymorphic ventricular tachycar-wave propagationFlecainideR- dia. Herz 2007;32:212-217.propafenone4. Priori SG, Napolitano C, Memmi M, et al. Clinical andmolecular characterization of patients with catecholamin-Liu N, et al.2011Journal of Molecular and ergic polymorphic ventricular tachycardia. CirculationCellular CardiologyCalmodulin kinase 2002;106:69-74.II (CaMKII) CPVT5. Sy RW, Gollob MH, Klein GJ, et al. Arrhythmia char-RyR2R4496C+/- knock-in miceCPVTacterization and long-term outcomes in catecholaminer-epinephrinecaffeinein vivogic polymorphic ventricular tachycardia. Heart RhythmKN-93 (a specific CaMKII inhibitor) 2011;8:864-871.CPVT 6. Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, Cou-EpinephrineCaffeinemel P. Catecholaminergic polymorphic ventricular tachy-Autocamtide-2 related inhibitory peptide (AIP)cardia in children. A 7-year follow-up of 21 patients. Cir-Triggered activitiesculation 1995;91:1512-1519.7. Cerrone M, Colombi B, Bloise R, et al. Clinical and molec-Fura-2Ca2+ waveIsoproterenol ular characterization of a large cohort of patients affectedAIPCaMKII by catecholaminergic polymorphic ventricular tachycardia.CPVT Circulation 2004;110:552-553.Jung, et al.2011EMBO Molecular Medicine 9. VOL. 005 Taiwan Heart Rhythm Society1014 THRS9 -(Sick sinus syndrome)( 40)3 10%(Sinus bradycardia) (7)(SA nodal block)(Sinusarrest)(Bradycardia- tachycardia syndrome)7023% -- ()EKG Case of the Month / 711512QRS99ST-TP(notched)PV1V3~V6IIIIIaVFaVRaVLPR interval136 ms 1,2 P (AtrialTachycardia, AT) V1P() aVLATV1P 1. Kistler PM, Fynn SP, Haqqani H, et al. Focal atrial tachy-()aVLATcardia from the ostium of the coronary sinus: electrocar-ATdiographic and electrophysiological characterization and rPPV1aVLadiofrequency ablation. J Am Coll Cardiol 2005;45:1488-aVRIIIIIaVF 1493.(Coronary Sinus Ostium) AT 2. Qian ZY, Hou XF, Xu DJ, et al. An algorithm to predict the site of origin of focal atrial tachycardia. Pacing Clin Electrophysiol 2011;34:414-421. 10. 10 THRSTaiwan Heart Rhythm Society1014 VOL. 005 Webmed.com March 8, 2012. http://www.webmd.com/rheumatoid-arthritis/ news/20120308/rheumatoid-arthritis-linked-irregular- heartbeat : Jesper Lindhardsen Jesper Lindhardsen Dabigatran MedPage Today March 26, 2012. XEN-D0103 http://www.medpagetoday.com/Cardiology/ Arrhythmias/31828 news-medial.net March 20, 2012. Dabigatran http://www.news-medical.net/news/20120320/Positive- Warfarin data-from-XENTIONs-XEN-D0103-phase-1-trial-on-AF. Dabigatran aspx?page=2 Xention XEN-Dhanunjaya Lakkireddy D0103 145 XEN-D0103 Dabigatran146 XEN-D0103 WarfarinDabigatran Kv1.5Acetyl-Odds ratio2.76 choline-activated potassium channel IKACh (Kir3.1/3.4) Dabigatran K1.5 Dhanunjaya Lakkireddy IKAChXEN-D0103 Xention XEN-D0103 Medicalxpress.com March 26. 2012 http://medicalxpress.com/news/2012-03-pacemaker-faint- Biomedical system ing-patient-population.html (Neurally mediated syncope, NMS) Medgadget.com March 22, 2012. http://medgadget.com/2012/03/long-term-ecg-monitoring- system-offers-advanced-arrhythmia-analysis.html Biomedical Systems (Maryland Heights, MO) NMS TruVue ECG systemBiomedical SystemsISSUE-3NMS 57% ISSUE -3 (Third International Study on Syncope of Biomedical System Uncertain Etiology) trialGenoa Ospedali Tigullio in LavagnaMichele Brignole 11. VOL. 005Taiwan Heart Rhythm Society1014 THRS11 ISSUE-3 51 darone 51140NMS ISSUE-3NMS FDACitalopram ( ) 57%CardiologyToday.com March 28, 2012. http://www.cardiologytoday.com/view.aspx?rid=96046 25%Michele Brignole Citalopram( Celexa, Forest, ) NMS Citalopram QT Torsade de pointesFDA 61Citalopram ( )1 DronedaroneCitolopram Arch Intern Med March 26, 2012. http://archinte.ama-assn.org/cgi/content/2 Long QT syndrome short/172/6/516?rss=1Citolopram FDALong QT syndrome Arch Intern MedDronedarone Citolopram Citolopram AmiodaroneBronchiolo-FDACitolopramLong QT syndrome tis obliternas with organizing pneumonia BOOP(contraindicated) Amiodarone(not recommended) Dronedarone3 6020 Dronedarone(mg) Amiodarone 4 QTc500msCitalo- DronedaroneAmio- pram (57.7% vs. 23.1%) Atrial Fibrillation NewsAnn Thorac Surg. 2012 March The Effect of a High Dose of Atorvastatin on theOccurrence of Atrial Fibrillation After CoronaryPLoS One. 2012 MarchArtery Bypass Grafting. (Karimi A, et al., Iran)Clinical Impact of Atrial Fibrillation in Patients (Statin) with Pulmonary Hypertension. (Rottlaender D, et statinal., Australia) 1,839225 atorvastatinNT-proBNP72531.1%statinstatin 40 mg/d 80 mg/dNYHA functional classNT- 65.1%30.2%Multivariate logistic regressionproBNP Statin-blockersAtorvastatinstatin 12. 12 THRSTaiwan Heart Rhythm Society1014VOL. 005(Dispersion) K(+) channelEuropace. 2012 March rare variantsAtrial arrhythmogenic substrateDaily Distribution of Atrial Arrhythmic Episodesin Sick Sinus Syndrome Patients: ImplicationsCirculation. 2012 Feb.for Atrial Arrhythmia Monitoring.(Capucci A, etCardiac Biomarkers are Associated with anal., Italy)Increased Risk of Stroke and Death in Patients with Atrial Fibrillation: A RELY Substudy. (Hijazi Z, et al., Sweden)Burden II Study250 BiomarkersBrady-tachy syndrome Troponin I NT-proBNP RELY trial6189CircadianTroponin I: