편집자문위원 (가나다순) -...

편집자문위원 (가나다순)

고재곤 / 울산의대 곽충환 / 경상의대 김대경 / 인제의대 김대혁 / 인하의대

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남궁준 / 인제의대 노태호 / 가톨릭의대 박경민 / 인제의대 박상원 / 고려의대

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최윤식 / 서울의대 최의근 / 서울의대 최인석 / 가천의대 최종일 / 고려의대

한상진 / 한림의대 허준 / 성균관의대 현명철 / 경북의대

부정맥은 대한심장학회 부정맥연구회가 주관하며 엠엠케이커뮤니케이션즈에서 발행하고 있습니다.

본지와 관련된 문의사항이나 건의사항이 있으시면 발행사인 엠엠케이커뮤니케이션즈로 연락하여 주시기 바랍니다.

발행사 엠엠케이커뮤니케이션즈㈜

대 표 : 이영화

편 집 : 양관재, 김지현

디자인 : 박선진

서울시 강남구 논현로 523 노바빌딩 3층

Tel 02-2007-5400 Fax 02-2179-8431 http://www.mmk.co.kr E-mail: [email protected]

발행일 2014년 12월 23일

The Official Journal of Korean

Heart Rhythm Society

목적과개요

‘부정맥’은부정맥과 관련된 새로운 임상 연구, 진료지침, 증례 등을 소개하여

부정맥연구회 회원 및 개원의의 지속적인 의학교육에 이바지하고자

발행되는 학술지입니다.

‘부정맥’은 부정맥의 진단과 치료, 임상 연구와 관련된 원저, 종설,

논평, 증례 보고 등의 원고를 공모하며, 제출된 원고는

편집위원회의 검토를 거쳐 게재됩니다.

Original Article

Electrocardiographic Features of Therapeutic Hypothermia

····················· 이우석, 남기병, 조욱, 최진희, 권창희, 김유리, 최기준, 김유호 ········· 04

Main Topic Reviews Atrial Fibrillation Based on European & 2014 ACC/AHA Guideline

심방세동의 약물 치료 ································· 김남호 ········· 14

심방세동 환자에서의 항응고제 치료 ························· 온영근 ········· 21

전극도자 절제술과 변화된 국내 보험 규정 ······················ 오세일 ········ 27

Article Review

심방세동 환자에서 전기적 동율동 전환 시에 Warfarin과 새로운 항응고제의 비교 연구 · 온영근 ········· 35

ECG & EP Cases

Atrial Tachycardia in a Patient with Extracardiac Conduit Fontan Circulation ··················

··························· 엄재선, 김남균, 박진규, 정보영, 박희남, 이문형 ········· 37

Warfarin-associated Extensive Spontaneous Spinal Epidural Hematoma

Mimicking Stroke ··································· 이기홍 ········· 45

Successful Use of a New Oral Anti-coagulant in a Stroke Patient with Poor ···············

Prothrombin Time Control Even After Warfarin Treatment ·············· 박환철 ········· 49

자율 학습 문제 ·················································· 54

The Official Journal of Korean Heart Rhythm Society

Vol 15. No. 4 ●통권51호●December 2014

Contents

Cover: LAO view of 3-dimensional electroanatomical mapping (Page 42)

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4 The Official Journal of Korean Heart Rhythm Society

Introduction

Therapeutichypothermia(TH)hasemergedasan

importantadjunctive therapyof cardiacarrest

victims recommended by the international

resuscitationguidelines.1,2Thepositiveeffectson

improvement inneurologic functionandsurvival

Received: September 4, 2014Revision Received: December 3, 2014Accepted: December 15, 2014Correspondence: Gi-Byoung Nam, MD, Heart Institute, Asan Medical Center, Department of Internal Medicine, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, KoreaTel: 82-2-3010-3150, Fax: 82-2-487-5918E-mail: [email protected]

울산대학교 의과대학 내과학교실 이 우 석, 남 기 병, 조 욱, 최 진 희, 권 창 희, 김 유 리, 최 기 준, 김 유 호

Woo Seok Lee, MD; Gi-Byoung Nam, MD; Uk Jo, MD; Jin Hee Choi, MD; Chang Hee Kwon, MD; YooRi Kim, MD; Kee-Joon Choi, MD; You-Ho Kim, MD.Heart Institute, Asan Medical Center, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea

Electrocardiographic Features of Therapeutic Hypothermia

ABSTRACT

Background & Objectives: It has been known that therapeutic hypothermia (TH) can induce electrocardio-

graphic J waves. However, electrocardiographic features, clinical significance, and arrhythmogenic potentials

of the J waves during TH remain unknown.

Subjects and Methods: We analyzed electrocardiograms from 68 patients, who underwent TH between

August 2010 and August 2013. The frequency, amplitudes, distribution of the J waves, and the development

of malignant arrhythmia (e.g. ventricular fibrillation [VF]) were analyzed.

Results: The average body temperature was 33.3±0.1 during hypothermia. 40 patients (58.8%) displayed J

wave primarily in leads II, III, aVF, and leads V4-6. J waves were newly developed in 37 patients and preexisting

J waves were augmented in three patients. The average amplitude of J waves was 0.20±0.01 mV. There were

two events of VF during TH. These events occurred in patients finally diagnosed with Brugada syndrome and

early repolarization syndrome (ERS). The maximum augmentation of the J waves in patients without electrical

arrhythmic disorders was 0.35 mV. In two patients with ERS, J waves were markedly augmented during TH

(mean 0.43±0.09 mV).

Conclusions: J waves are noted most frequently in the inferior or lateral precordial leads during TH. Two of

68 patients displayed life-threatening arrhythmias associated with J wave occurrence. Proarrhythmic potential

of hypothermia in patients with preexisting ERS or Brugada pattern on the electrocardiogram requires further

evaluation in future studies.

Key Words: ■ therapeutic hypothermia ■ J wave

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Figure 1. Twelve-lead electrocardiograms (ECGs) showing the augmented and newly developed J wave during therapeutic hypothermia (TH). (A) shows J waves appeared in inferolateral leads during TH in patient with non-cardiogenic arrest (due to asphyxia). (C) and (D) show J waves II, III, aVF present before TH augmented markedly in the inferior leads (II, III and aVF) while J wave appeared newly in left precordial leads (V5 and V6) during TH in patient diagnosed with early repolarization syndrome. After recovery, the J wave in inferior leads decreased to existing amplitude and the J wave in left precordial leads disappeared.

A During therapeutic hypothermia (32.9℃)

B After recovery from therapeutic hypothermia

C During therapeutic hypothermia (33.0℃)

D After recovery from therapeutic hypothermia

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have been proved in two recent trials.3,4

Characteristicelectrocardiographic (ECG)changes

occurinpatientswithhypothermia.TheJwave,also

known as the Osborn wave, is the most

characteristicECGfeatureinhypothermia.5TheJ

wave isalsonoted incertainnon-hypothermic

conditionssuchasBrugadasyndromeandearly

repolarizationsyndromes(ERS).ThepresenceofJ

wavesinsuchsyndromesisrelatedtotheoccurrence

ofventricularfibrillation(VF), leadingtosudden

death.However,whetherhypothermicpatientswith

J waves are susceptible to fatal ventricular

arrhythmiaremainsundetermined.Previousreports

have shown that the incidence of ventricular

arrhythmia isunexpectedly low inhypothermic

patientswithJwaves,varyingfrom0%to2%.6-8

In the present study, we investigated

electrocardiographicchangesinducedbyTHandthe

possible arrhythmogenic potential of the

TH-inducedJwaves.

Methods

StudyDesign

During thestudyperiod fromAugust2010 to

August2013,68patientsunderwentTHafterreturn

ofspontaneouscirculation.Thepatients’medical

records were reviewed to evaluate clinical

characteristicssuchasage,sex,vitalsigns,causeof

arrest, initial rhythm, and ECG findings on

admission.Toachievetheassignedtemperatureas

rapidlyaspossible, ice-cold fluidsandsurface

temperature-managementdevices(ARCTICSUN®

Table 1. Clinical and electrocardiogram (ECG) characteristics of the study patients

All (n=68) J wave (n=40) No J wave (n=28) P value

Age (years) 59.3±15.5 58.4±15.3 60.5±16.0 0.581

Male 42 (61.8%) 28 (70.0%) 14 (50.0%) 0.095

Temperature (℃)during hypothermia

33.3±0.80 33.3±0.7 33.3±0.8 0.825

Heart rate(beats/min)

Pre hypothermia 101.7±29.0 106.2±29.6 95.2±27.4 0.161

During hypothermia 86.0±22.5 83.0±20.0 92.2±23.3 0.089

ECG characteristics

Pre hypothermia

PR interval (ms) 158.8±38.6 153.8±27.0 167.0±46.4 0.226

QRS duration (ms) 94.3±17.5 93.5±16.0 95.3±19.8 0.710

QT interval (ms) 371.1±63.3 360.0±55.8 387.1±70.8 0.115

QTc interval (ms) 468.0±44.2 465.4±46.2 471.7±41.8 0.608

During hypothermia

PR interval (ms) 166.0±33.1 170.9±32.3 161.7±27.6 0.273

QRS duration (ms) 104.4±25.4 108.5±25.3 98.5±20.7 0.091

QT interval (ms) 439.8±86.9 450.2±71.5 424.1±103.3 0.229

QTc interval (ms) 512.7±74.6 517.4±57.0 511.5±89.6 0.745

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TemperatureManagementSystem,BARDMedical,

CO)wereutilized.Thefollowingrecommendations

weremade:coolunconsciouspatientsto33℃within

12hourspost-restorationofspontaneouscirculation;

achievethedesiredpatienttemperatureasrapidlyas

possible;maintainthetargettemperaturefor24

hours; rewarm gradually to 36.5℃ in hourly

increments of 0.1-0.25℃/h; and maintain

normothermiaof~37.5℃after rewarming.We

comparedtheclinicalcharacteristicsandbasicECG

parametersofpatientswithandwithoutJwaves.

Thestudyprotocolwasreviewedandapprovedby

theEthicsCommitteeoftheCollegeofMedicine,

UlsanUniversity.

ECGAnalysis

ThefollowingECGparameterswereanalyzed:

heart rate, PR interval, duration of theQRS

complex,andQTandQTcintervals.Jwavewas

definedasnotchesorslursintheterminalpartof

theQRScomplexwithanamplitude≥0.1mVabove

theisoelectric lineinat least2contiguousleads.9

The J-wave amplitudewasmeasured as the

differencebetweenthetopoftheJwaveandthe

isoelectric lineusingCardioCalipers (On-Screen

ElectrocardiogramMeasurement)fromIconico.com.

ForthecomparisonofthedistributionofJwave,

ECGleadareasweregroupedasrightprecordial(V1-3),

leftprecordial(V4-6),highlateral(I,aVL),andinferior

(II,III,andaVF).

StatisticalAnalysis

AllstatisticalanalyseswereperformedwithSPSS

software (SPSS Inc.,Chicago, IL).Categorical

Table 2. Causes of cardiac arrest

Number (%)

Cardiac Causes (number) 11 (16.2%)

Acute myocardial infarction 4

Variant angina 3

Idiopathic ventricular fibrillation 1

Early repolarization syndrome 1

Brugada syndrome 1

Dilated cardiomyopathy (pump failure) 1

Non-cardiac Causes (number) 51 (75.0%)

Respiratory causes 13

Accident 17

Metabolic causes 5

Septic shock 6

Pulmonary thromboembolism 3

Hypovolemic shock 2

Others 5

Unknown 6 (8.8%)

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variableswereanalyzedbytheχ2test.Continuous

variableswereanalyzedbythet-test.APvalue

<0.05wasregardedassignificant.

Results

ClinicalCharacteristics

Atotalof68patients(meanage,59.8±1.7years;

42male)whounderwentTHwereanalyzed.The

meanbodytemperatureonTHwas33.3±0.1℃.J

waveswereobservedin40patientsduringTH.J

waveswerenewlydeveloped in37patientsand

preexisting Jwaveswere augmented in three

patients.TwopatientswithERSandapatientwith

alcoholicketoacidosisdisplayedpreexistingJwaves

on 12 leadECGprior toTH.Figure 1displays

representativeexamplesofJwavesrecordedduring

TH.ApatientwithERShadprominentJwaves

comparedtoapatientwithnon-cardiogenicarrest.

ClinicalandECGcharacteristicsarepresentedin

Table 1.Therewereno significant differences

betweenpatientswithandwithoutJwavesinterms

ofage,sex,temperatureachievedduringTHand

ECGparameters.

ECGChangesObservedduringTH

ECGtracingswereassessedforthepresenceof

TH-induced electrocardiographic changes. A

consistentreductioninheartratefrom102±29to

86±23beats/min(15.4%reduction,p<0.0001)was

observed.QRSdurationshowedasignificant(10.7%)

increase from 94.3±17.5 ms before TH to

104.4±25.4msduringTH(p=0.001).TheQTand

QTcintervalsdisplayedsignificant18.5%and8.7%

increases,respectively(371.1±63.3msbeforeTHto

439±86.9 ms during TH, p<0.0001, and

468.0±44.2msbeforeTHto512.7±74.6msduring

TH,p<0.0001).

CausesofCardiacArrestandInitialRhythm

Thecausesofcardiacarrestswerehighlyvariable.

Cardiaccauseswereresponsible in16.2%of the

study subjects,whilenon-cardiac etiologywas

presentin75.0%ofthepatients(Table2).Incardiac

Table 3. Initial cardiac rhythm

Number (%) P value

Cardiac Causes

Ventricular fibrillation

Pulseless electrical activity/asystole

11

10 (90.9%)

1 (9.1%)

<0.0001

Non-Cardiac Causes



51

4 (7.8%)

47 (92.2%)

Unknown



6

3 (50.0%)

3 (50.0%)

N/A

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etiology, acutemyocardial ischemia causedby

myocardial infarctionor coronaryarteryspasm

predominated.

Initial rhythm determined by ECGs at the

emergency room is shown inTable3.VFwas

present in10/11(90.1%)ofpatients,andpulseless

electricalactivity/asystolewasrecordedin1/11(9.1%)

of the patients in the cardiac etiology group.

However,VFwaspresentinonly4/47(7.8%)ofthe

non-cardiaccausepatients.

DistributionandMeanAmplitudeofJWave

duringTH

AsshowninTable4,Jwaveswerecommoninthe

inferiorand leftprecordial leads,followedbythe

highlateralandrightprecordialleads.Althoughthe

frequencyofJwaveswaslowintherightprecordial

leads, themeanamplitudes of Jwaves (when

observable)werehigherintherightprecordialleads

thaninotherECGleads.Thisresultedinprominent

rightprecordialJwaveaugmentationintwopatients

with primary arrhythmic disorders. In these

patients,Jwavesweremarkedlyaugmentedduring

THcomparedwiththeremainder(0.450±0.095vs.

0.173±0.012mV).

PatientswhoDevelopedVFduringTH

VFoccurredintwopatientsduringTH.Thetwo

patients were later diagnosed with Brugada

syndromeandERS,respectively.A56-year-old

malepatientwhowasdiagnosedwithBrugada

syndromedisplayednewlydevelopedJwaveinthe

leftprecordialleadsduringTH(at32.8℃).However,

theJ-STsegmentelevationinV1andV2became

diminishedduringTH.Jwavesintheleftprecordial

leadsoccurredimmediatelypostDCcardioversionfor

VF(Figure2).A70-year-oldmalepatient,whowas

diagnosedwithERS,hadmarkedaugmentationofJ

waveintheleftprecordialleads(V3-4)duringTH(at

33.2℃)(Figure3).ProminentJwaveswereobserved

afterDCcardioversionforVF.Thetwopatients

underwentcardioverter/defibrillator implantation

priortodischarge.

Table 4. Distribution and mean amplitude of J wave during therapeutic hypothermia

ECG leadNumber of patients with

J waves (number)Mean amplitude of

J wave (mV)

I 15 0.163±0.017

aVL 12 0.113±0.013

II 26 0.205±0.018

III 22 0.161±0.019

aVF 26 0.165±0.018

V1 1 0.300±0.000

V2 7 0.450±0.165

V3 9 0.294±0.095

V4 18 0.231±0.040

V5 28 0.188±0.018

V6 27 0.211±0.015

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Discussion

Themainfindingsofthisstudyareasfollows:(1)

Jwaveswereinducedoraugmentedin58.8%ofthe

patientsundergoingmildTH(targettemperature

33℃);(2)Jwavesappearedmorecommonlyinthe

inferiorandlateralleadsthanintherightprecordial

leads;and(3)itwashypothesizedthatpatientswith

primaryarrhythmicdisordersdisplayedahigher

prevalenceandamplitudeofJwavesandweremore

vulnerable todevelopVFduringTHthanthose

withoutprimaryarrhythmicdisorders.

Recentpopulation-basedstudieshaveestablished

anassociationbetween theearly repolarization

patternandVF,whether idiopathic innatureor

secondary to ischemia.10-12 The tendency for

hypothermiatoinducesimilarelectrocardiographic

changesiswellestablished.5,13Consequently,THpost

cardiacarrestcanprovideanopportunitytoexamine

the impactofJwave-associatedhypothermiaon

malignantarrhythmicpotential.14Thisretrospective

cohort studyassessed the impactofTHon the

prevalence,distribution,andmagnitudeofJwaves,

andtheirassociationwithmalignantarrhythmia.

Duringthecoolingphase,58.8%ofourstudy

populationdisplayedJwaveabove0.1mV.Itiswell

documentedthattheprevalenceofJwavevaries

withcoretemperature.15,16Reportsonpatientswith

accidentalhypothermiasuggestthattheprevalence

of J wave would be minimal during mild

hypothermia (temperature 33℃).15-17However,

Rolfastetalreporteda30%prevalenceofJwaves

duringTH18andthemostrecentstudybyWilliams

etaldiscoveredaprevalenceofJwave (51.2%)

similartoourstudyfindings.19Accordingtothese

resultsandourobservations,theprevalenceofJ

waveduringTHappearshigher thanpreviously

reported.

Similartoresultsofpreviousreports,theJwave

wasmostfrequentlyrecordedintheleadsfacingthe

Figure 2. Newly developed J wave during therapeutic hypothermia in patient with Brugada syndrome. (A) Brugada pattern ECG. No J wave in lateral leads (V4-6). (B) Ventricular fibrillation during therapeutic hypothermia. (C) J wave in lateral leads after DC cardioversion.

A CB

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leftventricleandintheinferiorlimbleads.20Recent

data show that the inferolateral J wave is

occasionallymalignant and therefore strongly

associatedwithsuddencardiacdeath.10,21Inaddition,

the inferolateralJwave inBrugadasyndromeis

significantlyassociatedwithapoorprognosis.22-25In

thisstudy,VFoccurredintwopatientswithprimary

arrhythmiadisorder(BrugadasyndromeandERS).

Thesmallnumberofsubjectsinthisstudymadeit

difficulttoestimatetheincidenceofVFduringTH.

Fromourresultsalone,wecannotdeterminethe

relationshipbetweenthepresenceofJwavesand

the incidenceofVF in thegeneralpopulation.

Nontheless,consideringthetemporalrelationship

betweentheJwaveandVFoccurrence,THmay

serveasa trigger forVF incertainsusceptible

patients.IncidenceofVFinpatientswithprimary

arrhythmicdisorderincomparisonwiththegeneral

population needs to be determined in future

prospectivestudies.Recently,aTargetTemperature

Managementtrial26showedthathypothermia,ata

targeted temperatureof33℃,didnot confera

benefitascomparedwithatargetedtemperatureof

36℃.Afterconsiderationofthisfinding,atargeted

temperatureof36℃maybeasafealternativeto

avoidpotentialTHcomplicationswhile treating

abnormalpatientgroups(e.g.,primaryarrhythmia

disorderpatients).

Figure 3. Twelve-lead ECGs showing the augmented and newly developed J wave during TH in patient 2 developed VF. (A). During therapeutic hypothermia, the J wave was marked augmented, especially in V3-4. (B) After recovery from TH, the J wave remained in V3-4.

A During therapeutic hypothermia (33.2℃)

B After recovery from therapeutic hypothermia

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Conclusion

Jwaveswerepresentinthemajorityofpatients

undergoingTHaftercardiacarrest.TH-relatedJ

wavesweremostfrequentlyrecordedintheinferior

andlateralprecordialleads.VFwasrarelyobserved

(2.7%)andwasconfinedtopatientswithBrugada

syndromeorERS.Althoughthisstudycannotprove

causalitybetweentheVFandtheJwaveduringTH,

it illustrates a temporal relationship between

hypothermiaandincreasedfrequencyofmalignant

arrhythmias inpatientswithprimaryarrhythmic

disorders.ApplicationofTHmayrequirecareful

attentioninthissusceptible,high-riskpopulation.

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Roy L, Pasquie JL, Nogami A, Babuty D, Yli-Mayry S, De Chillou C, Scanu P, Mabo P, Matsuo S, Probst V, Le Scouarnec S, Defaye P, Schlaepfer J, Rostock T, Lacroix D, Lamaison D, Lavergne T, Aizawa Y, Englund A, Anselme F, O'Neill M, Hocini M, Lim KT, Knecht S, Veenhuyzen GD, Bordachar P, Chauvin M, Jais P, Coureau G, Chene G, Klein GJ and Clementy J. Sudden cardiac arrest associated with early repolarization. N Engl J Med. 2008;358:2016-2023.

11. Patel RB, Ng J, Reddy V, Chokshi M, Parikh K, Subacius H, Alsheikh-Ali AA, Nguyen T, Link MS, Goldberger JJ, Ilkhanoff L and Kadish AH. Early repolarization associated with ventricular arrhythmias in patients with chronic coronary artery disease. Circ Arrhythm Electrophysiol. 2010;3:489-495.

12. Rosso R, Kogan E, Belhassen B, Rozovski U, Scheinman MM, Zeltser D, Halkin A, Steinvil A, Heller K, Glikson M, Katz A and Viskin S. J-point elevation in survivors of primary ventricular fibrillation and matched control subjects: incidence and clinical significance. J Am Coll Cardiol. 2008;52:1231-1238.

13. Emslie-Smith D, Sladden GE and Stirling GR. The significance of changes in the electrocardiogram in hypothermia. Br Heart J. 1959;21:343-351.

14. Bastiaenen R, Hedley PL, Christiansen M and Behr ER. Therapeutic hypothermia and ventricular fibrillation storm in early repolarization syndrome. Heart rhythm. 2010;7:832-834.

15. Vassallo SU, Delaney KA, Hoffman RS, Slater W and Goldfrank LR. A prospective evaluation of the electrocardiographic manifestations of hypothermia. Acad Emerg Med. 1999;6:1121-1126.

16. Higuchi S, Takahashi T, Kabeya Y, Hasegawa T, Nakagawa S and Mitamura H. J waves in accidental hypothermia. Circ J. 2013;78:128-134.

17. Mattu A, Brady WJ and Perron AD. Electrocardiographic manifestations of hypothermia. Am J Emerg Med. 2002;20:314-326.

18. Rolfast CL, Lust EJ and de Cock CC. Electrocardiographic changes in therapeutic hypothermia. Crit Care. 2012;16:R100.

19. Williams SE, Sabir I, Nimmo C, Linton N, Sebag FA, Harrison JL, Wright M, Barrett NA, Shankar-Hari M and O'Neill MD. Quantitative assessment of the effects of therapeutic hypothermia on early repolarization in idiopathic ventricular fibrillation survivors: a 7-year cohort study. Circ Arrhythm Electrophysiol. 2014;7:120-126.

20. Gussak I, Bjerregaard P, Egan TM and Chaitman BR. ECG phenomenon called the J wave. History, pathophysiology, and clinical significance. J Electrocardiol. 1995;28:49-58.

21. Haissaguerre M, Sacher F, Nogami A, Komiya N, Bernard A, Probst V, Yli-Mayry S, Defaye P, Aizawa Y, Frank R, Mantovan R, Cappato R, Wolpert C, Leenhardt A, de Roy L, Heidbuchel H, Deisenhofer I, Arentz T, Pasquie JL, Weerasooriya R, Hocini M,

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Jais P, Derval N, Bordachar P and Clementy J. Characteristics of recurrent ventricular fibrillation associated with inferolateral early repolarization role of drug therapy. J Am Coll Cardiol. 2009;53:612-619.

22. Kamakura S, Ohe T, Nakazawa K, Aizawa Y, Shimizu A, Horie M, Ogawa S, Okumura K, Tsuchihashi K, Sugi K, Makita N, Hagiwara N, Inoue H, Atarashi H, Aihara N, Shimizu W, Kurita T, Suyama K, Noda T, Satomi K, Okamura H, Tomoike H and Brugada Syndrome Investigators in J. Long-term prognosis of probands with Brugada-pattern ST-elevation in leads V1-V3. Circ Arrhythm Electrophysiol. 2009;2:495-503.

23. Kawata H, Morita H, Yamada Y, Noda T, Satomi K, Aiba T, Isobe M, Nagase S, Nakamura K, Fukushima Kusano K, Ito H, Kamakura S and Shimizu W. Prognostic significance of early repolarization in inferolateral leads in Brugada patients with documented ventricular fibrillation: a novel risk factor for Brugada syndrome with ventricular fibrillation. Heart rhythm. 2013;10:1161-1168.

24. Sarkozy A, Chierchia GB, Paparella G, Boussy T, De Asmundis C, Roos M, Henkens S, Kaufman L, Buyl R, Brugada R, Brugada J and Brugada P. Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome. Circ Arrhythm Electrophysiol. 2009;2:154-161.

25. Takagi M, Aonuma K, Sekiguchi Y, Yokoyama Y, Aihara N, Hiraoka M and Japan Idiopathic Ventricular Fibrillation Study I. The prognostic value of early repolarization (J wave) and ST-segment morphology after J wave in Brugada syndrome: multicenter study in Japan. Heart rhythm. 2013;10:533-539.

26. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H and Investigators TTMT. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369:2197-2206.

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원광대학교 의과대학 내과학교실 김 남 호

Nam-Ho Kim, MDDepartment of Internal Medicine, Wonkwang University Medical School, Iksan, Korea

서론

심방세동의약물치료는정상동율동을유지하는

율동치료(rhythmcontrol)및적절한심실박동수를

유지하는심박수조절치료(rate control)가있다.

환자의상황에따라서이중한가지방법을선택하게

되는데,어떠한방법을선택하더라도혈전색전증

(thromboembolism)을예방하기위한치료를병행해야

한다.본논문에서는2014년미국심장학회(AHA/

ACC/HRS)에서 발표한 내용을 기초로 하여

심방세동의약물치료를정리하였다.1

심박수조절치료(RateControl)

심박수조절은심방세동의약물치료에서중요한

치료전략으로삶의질향상,이환율감소,그리고

빈맥-유발성심근증의발생을감소시키는역할을

한다.주로beta-blockers,non-dihydropyridine

calciumchannelantagonists,digoxin,amiodarone,

sotalol같은약물을사용한다.이중어떠한약물들을

선택할것인가는환자의증상정도,혈역학적상태,

심부전의유무,심방세동의발생요인등을고려한다.

또한빠르게심박수를조절하기위해서는주사제를

사용하거나전기적율동전환등을고려한다(Table1,

Figure1).

심방세동의 약물 치료

Received: September 18, 2014Revision Received: November 20, 2014Accepted: December 15, 2014Corresponding author: Nam-Ho Kim, MD, Division of Cardiology, Department of Internal Medicine, Wonkwang University Medical School, 344-2 Shinyong-dong, Iksan, Jeonbuk 570-711, KoreaTel: +82-63-859-2523, Fax: +82-63-855-2025E-mail: [email protected]

ABSTRACT

Management of AF patients is aimed at reducing symptoms and at preventing severe complications associated

with AF. Prevention of AF-related complications relies on antithrombotic therapy, control of ventricular rate,

and adequate therapy of concomitant cardiac diseases. These therapies may already alleviate symptoms, but

symptom relief may require additional rhythm control therapy by cardioversion, antiarrhythmic drug therapy, or

ablation therapy. In this paper, I would like to introduce the 2014 AHA ACC HRS guideline focuses on medical

treatment of atrial fribrillation.

Key Words: ■ atrial fibrillation ■ anti-arrhythmic agents ■ guideline

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Table 1. Common medication dosage for rate control of atrial fibrillation

약물 정주 경구 상용 용량

Beta-blockers

Metoprolol tartrate 2분에 걸쳐 2.5-5.0 mg 투여, 3회까지 25-100 mg BID

Metoprolol XL (succinate) 없음 50-400 mg QD

Atenolol 없음 25-100 mg QD

Esmolol 1분에 걸쳐 500 μg/kg, 이후에 50-300 μg/kg/min 없음

Propranolol 1분에 걸쳐 1 mg, 2분 간격으로 3회까지 10-40 mg TID 또는 QID

Nadolol 없음 10-240 mg QD

Carvedilol 없음 3.125-25 mg BID

Bisoprolol 없음 2.5-10 mg QD

Non-dihydropyridine calcium channel antagonists

Verapamil 2분에 걸쳐 0.075-0.15 mg/kg 투여, 반응이 없으면 30분 후 10.0 mg 추가 투여, 그리고 0.005 mg/kg/min 투여

서방형: 180-480 mg QD

Diltiazem 2분에 걸쳐서 0.25 mg/kg 투여, 이후에 5-15 mg/h 서방형: 120-360 mg QD

Digitalis glycosides

Digoxin 0.25 mg 투여, 반복하여 24시간에 최대 1.5 mg까지 투여 0.125-0.25 mg QD

Others

Amiodarone1시간에 걸쳐서 300 mg, 이후에 24시간에 걸쳐서 10-50 mg/h

100-200 mg QD

BID, twice daily; QD, once daily; QID, four times a day; TID, three times a day.

Figure 1. Approach to selecting drug therapy for ventricular rate control

・ Beta blockers should be instituted following stabilization of patients with decompensated HF. The choice of beta blocker (cardio- selective, etc.) depends on the patient’s clinical condition.・ Digoxin is not usually first-line therapy. It may be combined with a beta blocker and/or a non-dihydropyridine calcium channel blocker

when ventricular rate control is insufficient and may be useful in patients with HF.・ In part because of concern over its side-effect profile, use of amiodarone for chronic control of ventricular rate should be reserved for patients who do not respond to or are intolerant of beta blockers or non-dihydropyridine calcium antagonists.

심방세동의 약물 치료

심혈관질환

없음

Beta-blocker

Diltiazem

Verapamil

고혈압 또는 좌심실

기능이 보존된 심부전

Beta-blocker

Diltiazem

Verapamil

Amiodarone

좌심실 기능 부전

또는 심부전

Beta-blocker

Digoxin

만성 폐쇄성

호흡기 질환

Beta-blocker

Diltiazem

Verapamil

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심박수조절에대한권장사항

ClassI

1.발작성, 지속성, 영구형 심방세동 환자에서

심박수조절을위해beta-blocker또는non-

dihydropyridinecalciumchannelantagonist

사용을권장한다(levelofevidence:B).

2.조기 흥분이 없는 심방세동 환자에서 급히

심박수조절을위해서는beta-blocker또는

non-dihydropyridinecalciumchannelblocker

의 주사제 사용을 권장한다. 혈역학적으로

불안정한 환자에서는 전기적 율동 전환을

시도한다(levelofevidence:B).

3.활동 시 심방세동과 관련된 증상이 있는

환자에서는 생리적인 범위 내의 심박수를

유지하도록필요한약물치료를통하여적절한

심박수조절을평가해야한다(levelofevidence:

C).

Table 2. Recommended drug doses for pharmacological cardioversion of atrial fibrillation

약물 투여 경로 용량 부작용

Amiodarone

경구하루에 600-800 mg을 나누어서 총 10 g까지 투여, 이후에 200 mg QD 유지

정맥염, 저혈압, 서맥, QT 간격 연장, torsades de pointes (드뭄), 위장 장애, 변비, INR 증가정주

150 mg을 10분에 걸쳐, 이후에 1 mg/min을 6시간, 0.5 mg/min을 18시간 또는 경구 용량

Dofetilide 경구

CrCl (mL/min)

>60

40-60

20-40

<20

용량(μg BID)

500

250

125

권장되지 않음

QT 간격 연장, torsades de pointes; 신장 기능, 체격, 연령에 따라 용량 조절

Flecainide 경구 200-300 mg × 1*

저혈압, 1:1 전도되는 심방조동, proarrhythmia;관상동맥질환과 중요한 구조적 심장질환이 있는 환자에서 금기

Ibutilide 정주1 mg을 10분에 걸쳐 투여, 충분한 반응이 나올 때까지 1 mg 반복(60 kg 미만-0.01 mg/kg)

QT 간격 연장, torsades de pointes, 저혈압

Propafenone 경구 450-600 mg × 1*

저혈압, 1:1 전도되는 심방조동, proarrhythmia;관상동맥질환과 중요한 구조적 심장질환이 있는 환자에서 금기

* Recommended given in conjunction with a beta blocker or non-dihydropyridine calcium channel antagonist administered ≥30 minutes before administering the Vaughan Williams Class IC agent.

BID, twice daily; QD, once daily

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Table 3. Dosage and safety considerations for maintenance of sinus rhythm in atrial fibrillation

약물 용량 금기 및 사용 시 주의 약물 상호 작용

Vaughan Williams class IA

Disopyramide ・ 속효성: 100-200 mg을

6시간 간격

・ 서방형: 200-400 mg을

12시간 간격

・심부전

・증가된 QT 간격

・칼륨, 녹내장

・QT 간격을 연장시키는 약물

・ CYP3A4에 의해 대사: 억제제(verapamil,

diltiazem, ketoconazole, macrolide anti-

biotics, protease inhibitors, 포도

주스)와 유도제(rifampin, phenobarbital,

phenytoin) 사용 주의

Quinidine ・ 324-648 mg을 8시간 간격 ・증가된 QT 간격

・설사

・ CYP2D6 억제: tricyclic antidepressants,

metoprolol, antipsychotics 농도 증가

・ P-glycoprotein 억제: digoxin 농도 증가

Vaughan Williams class IC

Flecainide ・�50-200 mg을 12시간 간격 ・동결절 또는 방실결절 장애・심부전・관상동맥질환・심방조동・방실결절 하방 전도 장애・브루가다 증후군・신장 또는 간질환

・�CYP2D6에 의해 대사: 억제제(quinidine, fluoxetine, tricyclics); 유전적으로 7-10% 인구에서는 없다.

・�신장 배설

Propafenone ・�속효성: 150-300 mg을 8시간 간격

・�서방형: 225-425 mg을 12시간 간격

・동결절 또는 방실결절 장애・심부전・관상동맥질환・심방조동・방실결절 하방 전도 장애・브루가다 증후군・간질환・천식

・�CYP2D6에 의해 대사: 억제제(quinidine, fluoxetine, tricyclics); 유전적으로 7-10% 인구에서는 없다. Poor metabolizer는 베타 차단 작용을 증가시킨다.

・�P-glycoprotein 억제: digoxin 농도 증가・�CYP2C9 억제: warfarin 농도 증가(INR

25% 상승)

Vaughan Williams class III

Amiodarone ・�경구: 2-4주간 하루 400-600 mg을 분복; 이후 하루에 1번 100-200 mg 유지

・�주사: 150 mg을 10분 이상 투여; 그리고 6시간 동안 1 mg/min; 이후 18시간은 0.5 mg/min 투여하거나 경구 제제로 변경; 24시간 이후 0.25 mg/min 감량 고려

・동결절 또는 방실결절 장애・방실결절 하방 전도 장애・간질환・증가된 QT 간격

・�대부분의 CYP 억제: warfarin (INR 0-200% 상승), statin, 그리고 많은 다른 약물들의 농도 증가

・�P-glycoprotein 억제: digoxin 농도 증가

Dofetilide ・�125-500 μg을 12시간 간격 ・증가된 QT 간격・신장질환・저칼륨혈증・이뇨제 사용・QT 간격을 연장시키는 약물

・�CYP3A에 의해 대사: 금기(verapamil, hydrochlorothiazide, cimetidine, ketoconazole, trimethoprim, prochlorperazine, megestrol); amiodarone은 약물 투여 최소 3개월 전 중지

Dronedarone ・400 mg을 12시간 간격 ・서맥・심부전・long-standing AF/flutter・간질환・증가된 QT 간격

・�CYP3A에 의해 대사: 억제제(verapamil, diltiazem, ketoconazole, macrolide antibiotics, protease inhibitors, 포도 주스)와 유도제(rifampin, phenobarbital, phenytoin) 사용 주의

・�CYP3A, CYP2D6, P-glycoprotein 억제: 일부 statins, sirolimus, tacrolimus, beta-blockers, digoxin 농도 증가

Sotalol ・40-160 mg을 12시간 간격 ・증가된 QT 간격・신장질환・저칼륨혈증・이뇨제 사용・QT 간격을 연장시키는 약물・동결절 또는 방실결절 장애・심부전・천식

・없음(신장 배설)

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ClassIIa

1.심박수 조절(안정 시 심박수 <80회/분)은

심방세동의증상관리를위해타당하다(levelof

evidence:B).

2.정주용amiodarone은조기흥분이없는중환자의

심박수조절에유용할수있다(levelofevidence:

B).

3.방실결절절제술및영구적인방실조율은약물

치료가불충분하고율동치료가안되는경우에

심박수조절을위해사용할수있다(level of

evidence:B).

ClassIIb

1.증상이없으면서좌심실수축기기능이보존되어

있는경우에는심박수조절(안정시심박수<110

회/분)을느슨하게하는것도타당성이있을것

같다(levelofevidence:B).

2.경구용amiodarone은다른방법들이실패하거나

금기일때심박수조절을위해사용할수있을것

같다(levelofevidence:C).

ClassIII

1.방실결절절제술및영구적인방실조율은약물

치료에 의해 심박수 조절을 시도하지 않은

상태에서는시행하지않는다(levelofevidence:

C).

2.Non-dihydropyridine calcium channel

antagonist는혈류역학적손상을초래할수

있으므로비대상성심부전(decompensatedheart

failure)환자에서는사용해서는안된다(levelof

evidence:C).

3.조기흥분이있는심방세동환자에서는digoxin,

Figure 2. Strategies for rhythm control in patients with paroxysmal and persistent AF

・ Catheter ablation is only recommended as first-line therapy (dotted line) for patients with paroxysmal AF (Class IIa recommendation). Depending on patient preference when performed in experienced centers.・ Dofetilide, flecainide, propafenone, sotalol are not recommended with severe LVH (wall thickness >1.5 cm).・ Defetilide, sotalol should be used with caution in patients at risk for torsades de pointes ventricular tachycardia.・ Flecainide, propafenone should be combined with AV nodal blocking agents.

구조적 심장질환 없음

Dofetilide

Dronedarone

Flecainide

Propafenone

Sotalol

전극도자

절제술

Amiodarone

구조적 심장질환

Amiodarone

Dofeilide

Dronedarone

Sotalol

Amiodarone

Dofetilide

전극도자

절제술

관상동맥질환 심부전

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non-dihydropyridine calcium channel

antagonist,정주용amiodarone을사용해서는안

된다.이약제들은심박수를증가시켜심실세동을

유발할수있다(levelofevidence:B).

4.Dronedarone은영구형심방세동환자에서심박수

조절을 위해 사용해서는 안 된다. 뇌졸중,

심근경색증, 전신성 혈전증, 심혈관 사망의

위험성을증가시킨다(levelofevidence:B).

율동치료(RhythmControl)

많은환자에서심박수조절치료가선행되나증상이

조절되지않는경우,적절한심박수조절이어려운

경우,젊은환자,빈맥-유발성심근증,첫번째인경우,

환자가원하는경우등에는율동치료를고려한다.율동

치료는전기적율동전환,항부정맥제,그리고전극도자

절제술을고려할수있다.여기서는약물에의한동율동

전환및유지에대해서만언급하기로한다(Table2,3,

Figure2).

약물에의한동율동전환시권장사항

ClassI

1.Flecainide, dofetilide, propafenone,정주용

ibutilide가선택된약물에대한금기사항이없다면

심방세동및심방조동의약물적인동율동전환에

유용하다(levelofevidence:A).

ClassIIa

1.경구용amiodarone투여가심방세동의약물학적

동율동 전환에 합리적인 선택이다(level of

evidence:A).

2.Beta-blocker 또는 non-dihydropyridine

calcium channel antagonist에 추가한

propafenone또는flecainide (“pill-in-the-

pocket”)는선택한환자의모니터링환경에서

안전하게사용했던적이있다면병원밖에서

심방세동을종료하기위한방법으로사용할수

있다(levelofevidence:B).

ClassIII

1.Dofetilide는과도한QT간격의연장을유도하여

torsadesdepointes를일으킬위험성이있기

때문에병원밖에서치료를시작해서는안된다

(levelofevidence:B).

동율동유지를위한항부정맥제에대한권장사항

ClassI

1.항부정맥 치료를 시작하기 전에 심방세동의

가역적인원인및 유발 요인에대한 치료가

이루어져야한다(levelofevidence:A).

2.심방세동환자에서다음과같은항부정맥제를

기저심장질환및동반된질환에따라동율동을

유지하기위해사용한다(levelofevidence:A).

a.Amiodarone

b.Dofetilide

c.Dronedarone

d.Flecainide

e.Propafenone

f.Sotalol

3.항부정맥제를사용하기전에각각항부정맥제의

부작용(특히proarrhythmia)을고려해야한다

(levelofevidence:C).

4.Amiodarone을사용할때에는amiodarone의

독성에의한위험성을고려해야하고,다른약물로

치료에 실패하거나 다른 약물이 금기일 때

사용해야한다(levelofevidence:C).

ClassIIa

1.심방세동환자에서빈맥-유발성심근증의치료에

항부정맥제를이용한율동치료는유용하다(level

ofevidence:C).

ClassIIb

1.항부정맥제에 의해 심방세동의 빈도수 또는

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증상이감소했을때,심방세동의재발이빈번하지

않고 증상이 심하지 않더라도 현 상태의

항부정맥제를지속하는것은타당할것같다(level

ofevidence:C).

ClassIII

1.심방세동이영구형으로진행되면율동치료를

위한항부정맥제(특히 dronedarone) 사용은

중지해야한다(levelofevidence:B).

2.Dronedarone은심부전(NYHA[NewYorkHeart

Association]classIII,IV)이있거나지난4주이내에

비대상성심부전이있었던경우심방세동의치료를

위해사용해서는안된다(levelofevidence:B).

결론

이번2014년미국심장학회의심방세동치료에대한

권장사항중혈전색전증예방을위한위험도평가및약

물사용에있어서는큰변화가관찰되나,약물을사용한

심박수조절및율동조절에대해서는크게바뀐것은없

는것같다.하지만항부정맥제사용시그효과와부작

용에대한심도있는고려가필요함을강조하고있다.그

래서환자의임상상태및심방세동발생요인등을종합

적으로평가하여적절한치료전략을수립하고환자에게

접근하는것이좋겠다.

Reference

1. January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC Jr, Cigarroa JE, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 [Epub ahead of print]

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VOL.15 NO.4

성균관대학교 의과대학 내과학교실 온 영 근

Young Keun On, MD, PhD, FHRSDivision of Cardiology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine

서론

심방세동은 심장 부정맥 중에서 가장 흔한

부정맥으로심방세동환자의경우혈전색전증에의한

뇌졸중의빈도가약5배증가하는것으로되어있고,

매년심방세동환자의약5%에서뇌졸중이발생하는

것으로알려져있다.혈전색전증에의한뇌졸중의

원인을분석해보면약 20%가 심방세동에의한

뇌졸중으로보고하고있다.특히심방세동에의한

혈전색전뇌졸중이발생하는경우다른원인에의한

경우보다뇌손상의범위가크고신경학적장애가

심하여사망이나중증장애로이어질위험이높아

항응고제치료를통한혈전색전증의예방이매우

중요하다.비판막성심방세동환자에서의항응고제

치료는뇌졸중위험도와항응고제사용에따른출혈

위험도를평가하여환자개개인별로적합한결정을

해야한다.이에2012년ESC(EuropeanSocietyof

Cardiology)심방세동치료권고안및2014년AHA/

ACC/HRS(AmericanHeartAssociation/American

College of Cardiology/HeartRhythmSociety)

심방세동 치료 권고안1-3을 중점으로 심방세동

환자에서의항응고제치료에대해기술하고자한다.Received: August 28, 2014Accepted: December 15, 2014Correspondence: Young Keun On, MD, PhD, FHRS, Division of Cardiology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine #81 Irwon-ro Gangnam-gu, Seoul, Korea, 135-710 +82-2-3410-3420, Fax: +82-2-3410-3849E-mail: [email protected], [email protected]

심방세동 환자에서의 항응고제 치료

ABSTRACT

Atrial fibrillation (AF), whether paroxysmal, persistent, or permanent, and whether symptomatic or silent,

significantly increases the risk of thromboembolic ischemic stroke. Non-valvular AF increases the risk of stroke

5 times and AF in the setting of mitral stenosis increases the risk of stroke 20 times over patients in sinus

rhythm. Thromboembolism occurring with AF is associated with a greater risk of recurrent stroke, more severe

disability, and mortality. The CHA2DS2-VASc score is recommended for thromboembolic risk evaluation in non-

valvular AF. HAS-BLED score is recommended for bleeding risk evaluation. Careful consideration is required to

balance the benefits and the risks of bleeding of anticoagulation in each individual patient.

Key Words: ■ atrial fibrillation ■ anticoagulation ■ warfarin ■ new oral anticoagulant

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비판막성 심방세동 환자에서의 뇌졸중

위험도평가

비판막성심방세동환자의뇌졸중위험도평가에

있어기존에심부전(Congestiveheartfailure),고혈압

(Hypertension), 연령(Age: 75세 이상), 당뇨병

(Diabetesmellitus),뇌졸중(Stroke)등을고려한

CHADS2점수(CHADS2score)가주로사용되어왔다.

그러나나이를세분화하고(75세이상2점,65-74세1

점),성별(여성1점)및혈관질환(Vasculardisease)

등의변수를더추가한CHA2DS2-VASc점수(Table1)

를 사용한 경우 예측력이 좀 더 우수한 것으로

알려짐에따라2010년ESC권고안부터는CHA2DS2-

VASc점수를권고하기시작하였고,2014년AHA/

ACC/HRS권고안에서도CHA2DS2-VASc점수를

뇌졸중위험도평가를위해추천하고있다.

비판막성심방세동환자에서의항응고제

치료에따른출혈위험도평가

항응고제사용에따른출혈위험도를임상에쉽게

평가하기위해HAS-BLED출혈위험점수(HAS-

BLEDbleedingriskscore)의사용을추천하고있다

(Table2).이는고혈압(Hypertension),신장혹은간

기능이상(Abnormalrenal/liver function),뇌졸중

(Stroke),출혈의병력이나성향(Bleedinghistoryor

predisposition), 불안정한 INR (Labile INR

[internationalnormalizedratio]),고령(Elderly,65세

이상)및출혈성향을증가시키는약제나과량의술

(Drug/alcohol)등의복용을출혈위험인자로고려한

점수로중증출혈의빈도가0-1점이면약1%,5점이면

12.5%정도로알려져있고,3점이상이면중증출혈의

빈도가3.74%정도나되어항응고제치료에따른

손익을신중히고려해야한다.그러므로항응고제치료

시 교정이 가능한 출혈 위험인자는 적극적으로

교정해야한다.

항응고제사용

2012년ESC권고안에서는CHA2DS2-VASc점수에

따라2군으로나누어1점및그이상인경우새로운

경구 항응고제의 사용을 1차 약제로 권장하고,

대안으로warfarin을사용할수있으며,0점인경우

항응고치료를하지않는다.단,여성환자로다른

뇌졸중위험변수가없는경우에는CHA2DS2-VASc

점수가1점이라도항응고제치료를권장하지않는다.

Table 1. CHA2DS2-VASc score

Letter Risk factor Score

C Congestive heart failure/LV dysfunction 1

H Hypertension 1

A2 Age ≥75 2

D Diabetes mellitus 1

S2 Stroke/TIA/thromboembolism 2

V Vascular disease* 1

A Age 65-74 1

S Sex category (i.e. female sex) 1

Maximum score 9

* Prior myocardial infarction, peripheral artery disease, aortic plaque LV, left ventricular; TIA, transient ischemic attack.

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VOL.15 NO.4

한편2014년AHA/ACC/HRS권고안에서는비판막성

심방세동에서CHA2DS2-VASc점수2점이상인경우

항응고제의 사용을 권장하며, warfarin 또는

dabigatran,4 rivaroxaban,5또는apixaban6과같은

새로운경구항응고제를사용할수있다.CHA2DS2-

VASc점수2점이상이면서말기신부전(CrCl<15mL/

min)환자에서는항응고제로warfarin을사용한다.

CHA2DS2-VASc점수1점인경우항응고제치료를하지

않거나,항응고제(새로운경구항응고제또는warfarin)

혹은aspirin을고려할수있다.0점인경우항응고

치료를권장하지않는다.

인공기계판막이있는심방세동환자의경우에는

warfarin의사용을권고하고,인공판막의종류와

위치에따라 INR범위(2.0-3.0또는 2.5-3.5)를

결정한다.

Warfarin을사용하는경우치료시작시기에는매주

INR을검사하고,INR이안정된이후에는1개월에한번

INR검사를시행해야한다.

인공판막이있는심방세동환자에서warfarin을

중단해야하는시술또는수술을받는경우에는heparin

또는저분자량 heparin (low molecular weight

heparin,LMWH)을warfarin중단기간에사용할것을

권장하고, 인공판막이 아닌 심방세동 환자에서의

heparin또는LMWH사용여부는환자의뇌졸중

위험도와출혈위험도및항응고중단기간을고려하여

결정한다.

항혈소판제

심방세동환자의뇌졸중발생에서일차예방을위한

aspirin의효과에대한연구결과들을메타분석해보면

약19%의상대적뇌졸중발생예방효과가있어매년

절대값으로0.8%의뇌졸중을예방하는것으로알려져

있다.한편일과성허혈발작(transient ischemic

attack,TIA)또는뇌졸중환자를대상으로한이차예방

효과에서는 aspirin이 절대값으로 매년 2.5%의

뇌졸중을예방하는것으로보고되고있다.

Aspirin과clopidogrel복합요법은aspirin단독요법에

비해28%의상대적뇌졸중발생예방효과가있으나

warfarin에비해서는열등하여warfarin이aspirin과

clopidogrel복합요법에비해40%의상대적뇌졸중발생

예방효과가있는것으로알려져있다.

Table 2. HAS-BLED bleeding risk score

Letter Risk factor Score

H Hypertension 1

A Abnormal renal and liver function (1 points each) 1 or 2

S Stroke 1

B Bleeding 1

L Labile INRs 1

E Elderly (e.g. age >65 years) 1

D Drugs or alcohol (1 point each) 1 or 2

Maximum score 9

* 'Hypertension' is defined as >systolic blood pressure 160 mmHg, ‘Abnormal kidney function’ is defined as the presence of chronic dialysis or renal transplantation or serum creatinine ≥200 mmol/L. ‘Abnormal liver function’ is defined as chronic hepatic disease (cirrhosis) or biochemical evidence of significant hepatic derangement (bilirubin >2 x upper limit of normal, in association with aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase >3 x upper limit normal, etc.). ‘Bleeding’ refers to pre-vious bleeding history and/or predisposition to bleeding, e.g. bleeding diathesis, anemia, etc. ‘Labile INRs’ refers to unstable/high INRs or poor time in therapeutic range (<60%). Drugs/alcohol use refers to concomitant use of drugs, such as antiplatelet agents, non-steroidal anti-inflammatory drugs, or alcohol abuse, etc.

INR, international normalized ratio.

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새로운항응고제

심방세동환자의뇌졸중발생에서warfarin의효과에

대한연구결과들을메타분석해보면약64%의상대적

뇌졸중발생예방효과가있어매년절대값으로2.7%의

뇌졸중을예방하는것으로알려져있다.Warfarin사용

시에는뇌졸중예방및출혈위험방지를위해INR

2.0-3.0을유지하는것이필수적이고,따라서정기적인

혈액검사가필요하다.그렇지만실제임상상황에서는

이러한INR2.0-3.0을유지하는비율이절반이하인

것으로알려져있고, warfarin의약물상호작용,

음식물과의상호작용,정기적인혈액검사의불편함

등이 제시되어 새로운 항응고제의 필요성이

대두되었다.새로개발된항응고제로는dabigatran,

rivaroxaban,apixaban,edoxaban이있으며,대규모

임상연구결과에의하면뇌졸중예방면에서warfarin

과비슷한성적을보이고있고,뇌출혈위험도면에서는

오히려더우수한결과를보이고있다.

Dabigatran

Dabigatran은directthrombin억제제로개발되어

심방세동에서의뇌졸중예방효과를warfarin과비교한

RE-LY (RandomizedEvaluationofLong-term

anticoagulant therapY)연구가발표되어있다.4이

연구에서 1개 이상의 뇌졸중 위험인자를 동반한

심방세동환자를dabigatran과warfarin사용군으로

나누고, 평균 2년간 추적 관찰하여 뇌졸중 및

혈전색전증을비교한결과dabigatran110mg또는150

mgBID투여군에서warfarin군에비해뇌졸중및

혈전색전증 발생 예방 효과가 비열등하였다.

Dabigatran 150 mg BID투여군에서뇌졸중및

혈전색전증이1.11%발생하여warfarin군의1.69%에

비해 예방 효과 면에서 우월하였고(RR=0.66),

dabigatran110mgBID투여군에서는중증의출혈이

2.71%발생하여warfarin군의3.36%에비해중증

출혈의발생이적었다.

Rivaroxaban

Rivaroxaban은factorXa억제제로개발되어뇌졸중

위험인자를 동반한 심방세동 환자를 대상으로

rivaroxaban20mg복용군과warfarin군으로나누어

평균19개월동안의뇌졸중및혈전색전증의발생을

비교한ROCKET-AF(RivaroxabanOnce-dailyOral

DirectFactorXaInhibitionComparedwithVitamin

K Antagonism for Prevention of Stroke and

Embolism Trial in Atrial Fibrillation) 연구가

발표되었다.5뇌졸중및혈전색전증이rivaroxaban

군에서 1.71 events/100 patient-year 발생하여

warfarin군의2.16events/100patient-year에비해

우월하였다.중증출혈의발생은rivaroxaban군에서

3.60events/100patient-year발생하여warfarin군의

3.45events/100patient-year과비교하여차이가

없었다.출혈성합병증에서rivaroxaban군은warfarin

군에비해출혈성뇌졸중(0.26%versus0.44%;HR,

0.59;p=0.024),두개내출혈(0.7%versus0.5%;HR,

0.67;p=0.02)및중증출혈은유의하게적었으나(0.5%

versus0.2%;HR,0.50;p=0.003),위장관출혈은더

많았다(3.3%versus2.2%;p<0.001).

Apixaban

Apixaban은factorXa억제제로개발되어뇌졸중


apixaban5mgBID복용군과warfarin군으로나누어

평균1.8년동안의뇌졸중및혈전색전증의발생을

비교한ARISTOTLE (Apixaban forReduction in

StrokeandOtherThromboembolicEventsinAtrial

Fibrillation)연구가발표되었다.6CHADS2점수1점

이상인비판막성심방세동환자에서 apixaban은

warfarin에비해우월한뇌졸중및전신색전증예방

효과를보였으며,중증출혈(2.13%versus3.09%;HR,

0.69;p<0.001),출혈성뇌졸중(0.24%versus0.47%;

HR,0.51;p<0.001),두개내출혈(0.33%versus0.80%;

HR,0.42;p<0.001)등의발생은더낮았다.

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Edoxaban

Edoxaban은factorXa억제제로개발되어뇌졸중


edoxaban군과warfarin군으로나누어평균2.8년

동안의 뇌졸중 및 혈전색전증의 발생을 비교한

ENGAGEAF-TIMI48 (EffectiveAnticoagulation

With Factor Xa Next Generation in Atrial

Fibrillation) 연구가 발표되었다.7 뇌졸중 및

혈전색전증의연간발생률은warfarin군 1.50%,

고용량edoxaban군1.18%(HR,0.79;p<0.001for

non-inferiority),저용량edoxaban군1.61%(HR,

1.07;p<0.005 fornon-inferiority)로비열등성이

확인되었으며,중증출혈의연간발생률은warfarin군

3.43%에비하여고용량edoxaban군2.75% (HR,

0.80;p<0.001)및저용량edoxaban군1.61%(HR,

0.47;p<0.001)로edoxaban군각각이더적었다.

관상동맥중재술을시행하는심방세동환자

심방세동환자에게관상동맥중재술을시행하는경우

에는시술중에항응고제투여를중단하여혈관천자부

위의출혈위험성을줄이도록하고,BMS(baremetal

stent)를시술하여이중항혈소판제투여기간을최소

화하도록권고한다.관상동맥중재술또는수술이후에

는CHA2DS2-VASc점수2점이상인경우항응고제와

clopidogrel병합요법을추천한다.

결론

심방세동의치료전략에는혈전색전에의한뇌졸중예

방을위한항응고요법이매우중요하며,뇌졸중위험도

와항응고제사용에따른출혈위험도를평가하여환자

개인별로맞춤치료를해야한다.뇌졸중위험도평가를

위해CHA2DS2-VASc점수를,출혈위험도평가를위

해HAS-BLED출혈위험점수를권고한다.CHA2DS2-

VASc점수2점이상의뇌졸중고위험도인심방세동환

자에서는항응고제의사용을권고하며,warfarin의투여

및INR2-3유지또는새로운항응고제가추천되고있

다.기존의warfarin을대체할수있는새로운항응고제

로는dabigatran,rivaroxaban,apixaban,edoxaban이

있으며,대규모임상연구결과에의하면약제의종류,용

량및제제에따라뇌졸중예방효과에있어warfarin치

료에비하여우수하거나동등하였고,뇌출혈위험도면

에서오히려더안전한결과를보였다.

References

1. January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC, Jr., Cigarroa JE, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: A report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Heart Rhythm Society. Circulation. 2014:129:000-000.

2. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33:2719-2747.

3. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation: the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31:2369-2429.

4. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-1151.

5. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2012;365:883-891.

6. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med.

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2011;365:981-992.7. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD,

Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093-2104.

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서론

심방세동환자를대상으로하는새로운약제,새로운

치료법의개발로심방세동가이드라인이자주업데이트

되고있다.이에전극도자절제술부문은최근가이드라

인에서어떤면들이새롭게언급되고있으며,지난6월

에개정된국내건강보험요양급여인정기준은어떤지

에대해알아보고자한다.

ESC (European Society of Cardiology)

2012년가이드라인업데이트1

1.새로운증거들

동리듬유지측면에서항부정맥제보다는전극도자

절제술의우수성이추가적인연구들(MANTRA-PAF

[Medical ANtiarrhythmic Treatment or

RadiofrequencyAblation inParoxysmalAtrial

Fibrillation],2RAAFT-2[RadiofrequencyAblationvs

AntiarrhythmicDrugsasFirst-LineTreatmentof

ParoxysmalAtrialFibrillation]3)에서입증되어2010년

가이드라인의권고사항이공고해졌다.또한시술관련

합병증발생의가능성이낮은선택된발작성심방세동

환자들에서는리듬유지를위한일차치료로전극도자

서울대학교 의과대학 내과학교실 오 세 일

Seil Oh, MD, PhD, FHRS Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

전극도자 절제술과 변화된 국내 보험 규정

Received: September 8, 2014Accepted: December 15, 2014Corresponding Author: Seil Oh, MD, PhD, FHRS, Professor of Internal Medicine, Seoul National University, College of Medicine and Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, KoreaTel: +82-2-2072-2088, Fax: +82-2-762-9662E-mail: [email protected]

ABSTRACT

Update interval of guideline publish for atrial fibrillation (AF) is getting shorter than the past due to rapidly expanding knowledge and evidences on AF. According to the current guidelines, catheter ablation is recom-mended as an alternative to antiarrhythmic drugs for patients with symptomatic recurrent paroxysmal AF, pro-vided the procedure is performed by an experienced center/operator. Catheter ablation is reasonable as first-line therapy in selected patients with paroxysmal AF and no structural heart disease. Continuation of warfarin can be considered throughout the ablation procedure but robust data for NOACs are lacking. Ongoing clinical trials should provide new information for assessing whether catheter ablation is superior to pharmacological therapy for reducing total mortality. These will help us to address whether catheter ablation provides benefit beyond quality of life.

Key Words: ■ catheter ablation ■ atrial fibrillation ■ guideline

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A No or minimal structural heart disease

Paroxysmal Persistent

Patient choice

Catheter ablation

DronedaroneFlecainide

PropafenoneSotalol

Patient choice

Amiodarone

a

b

B Relevant structural heart disease

HFYes

Yes

No

No

Due to AF

AmiodaroneDronedaronec

Sotalold

Patient choice

Catheter ablationb

Figure 1. Rhythm control strategy for atrial fibrillation with normal heart (A) or structural heart disease (B) recommended in 2012 focused update of the ESC guidelines. aUsually pulmonary vein isolation is appropriate. bMore extensive left atrial ablation may be needed. cCaution with coronary heart disease. dNot recommended with left ventricular hypertrophy. Heart failure due to AF=tachycardiomyopathy.AF, atrial fibrillation; HF, heart failure.

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VOL.15 NO.4

절제술을선택할수있음이타당하다는사실을다시

한번피력하고있다(Figure1A).

비록전극도자절제술이항부정맥제보다우수한

치료법이지만재발률은상당히높다.경험이많은

센터에서적절한환자,심지어loneatrialfibrillation

(AF)환자일지라도후기에재발하는경우가흔하다.

하지만 재발의 가장 중요한 예측인자는 초기

재발이다.4-7즉,초기재발상태가유지되는것이

나중에재발하는경우보다훨씬중요하다는의미이다.

합병증은유럽기관을대상으로조사한결과에서

뇌졸중0.6%,심낭압전1.3%,말초혈관합병증1.3%,

심낭염2%로나와이전에보고되었던미국데이터및

전세계설문조사와유사한결과를보였다.2005-2008

년 사이에 첫 번째 절제술을 받았던 4,156명의

데이터베이스분석에따르면총합병증발생률은5%,

절제술후1년이내의모든원인에의한입원율은38.5%

였다.8 무증상의 뇌경색은 4-25%로 다양하게

보고되었는데,9-11이는절제술에사용된도구의차이에

기인하는것으로추정된다.비록무증상뇌경색의

임상적의미는분명하지않으나더안전한심방세동

절제술방법의개발이필요함은분명하다.

2.심부전환자에서의절제술

개정된가이드라인에서는심부전환자의리듬조절

방법에 동원할 수 있는 항부정맥제로 유일하게

amiodarone만을권고한다.심부전환자의심방세동

증상조절을위해숙련된센터에서전극도자절제술을

시행하는것은하나의치료전략이될수있다.물론

심부전환자에서는재발률과합병증발생률이높다는

사실은인지해야한다.또한심방세동의증상이심부전

증상과혼돈될수있으므로주의깊은병력청취가

필요하다.환자의증상이심방세동에의한것으로

추정된다면리듬조절을위해amiodarone과절제술중

선택할수있다(Figure1B).

3.절제술전후의항응고요법

절제술전후의항응고요법은뇌졸중예방치료가

평생필요한환자뿐만아니라뇌졸중위험인자가없는

환자모두에게도움이되는것으로인식되고있다.

최근에는시술직전에항응고요법을중지하지않고

계속유지하는방법이안전하다는보고가있었으며,12-15

HRS/EHRA/ECAS(HeartRhythmSociety/European

Heart Rhythm Association/European Cardiac

Arrhythmia Society)합의문에서도항응고요법을

중지하고heparin을사용하는방법대신항응고요법을

중지하지않고계속투여하는방법으로사용할수

있다고권고한바있다.16ESC도이번가이드라인에서는

항응고요법을중지하지않고,계속투여하는방법을

사용할수있다고권고하고있으며,절제술과정중INR

(internationalnormalizedratio)은2.0-2.5정도를

추천한다.또한,CHA2DS2-VASc점수가2점이상인

경우에는 시술 성공 여부와 상관없이 장기간의

항응고요법을권한다.새로운항응고제(new oral

anticoagulants, NOAC)에대해서는아직증거가

불충분한상태여서강하게권고하고있지는않다.

4.권고강도와증거수준의변화

2010년에는항부정맥제로리듬조절에실패한발작성

심방세동의절제술권고강도가classIIa였으나,이후

축적된임상연구결과들로인해2012년에는class I

으로격상되었다.또한증상이심하고위험도가낮은

환자의경우일차치료로전극도자절제술을고려해야

한다고권고하고있다(권고강도IIa,증거수준B).물론

이는(1)매우경험이풍부한센터/시술자가시행하는

경우,(2)적절하게환자가선정된경우,(3)다른치료

대안에대해서주의깊게평가한경우, (4)환자가

선호하는경우로한정한다.

지속성심방세동에대한권고안은2010년에비해

변환된것이없다.아직까지무증상의심방세동환자에게는

절제술을권할만한증거가없다.

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AHA/ACC/HRS(AmericanHeartAssociation/

American College of Cardiology/Heart

RhythmSociety)2014년가이드라인17

ESC가이드라인의주요업데이트후2년만에발표된

내용이어서 전극도자 절제술 부문에서는 유럽의

가이드라인과비교하여치료전략에큰차이가없다.

1.주요권고사항

I군또는 III군의항부정맥제투여에도불구하고

증상이있는심방세동환자에서유형별로다음과같이

전극도자절제술을권고하고있다:발작성(권고강도I;

증거수준A),발작성의일차치료(권고강도IIa;증거

수준B),지속성(권고강도IIa;증거수준A),지속성의

일차치료(권고강도IIb;증거수준C),장기지속성(

권고강도IIb;증거수준B)

아직까지절제술이사망률,뇌졸중,심부전등을

줄여줄수있는지는증거가부족한상황이다.이는현재

진행중인 CABANA (Catheter Ablation vs.

AntiarrhythmicDrugTherapyforAtrialFibrillation),

EAST (EarlyTreatmentofAtrialFibrillationfor

StrokePreventionTrial)연구등이증명해줄수있을

것으로기대한다.

2.환자의선정

적절한환자의선정을위해서는심방세동의유형,

증상의정도,구조적심장질환이있는지등을평가해야

한다.리듬유지요법에대한전략은ESC가이드라인과

유사하다(Figure2).

Figure 2. Rhythm control strategy for atrial fibrillation without and with structural heart disease recommended in 2014 AHA/ACC/HRS guidelines. aDepending on patient preference when performed in experienced centers. bNot recommended with severe LVH (wall thickness >1.5 cm). cShould be used with caution in patients at risk for torsades de pointes ventricular tachycardia. dShould be combined with AV nodal blocking agents. AF, atrial fibrillation; CAD, coronary artery disease; HF, heart failure; and LVH, left ventricular hypertrophy.

No Structural HeartDisease

Structural Heart Disease

Catheter ablation

a

a

Catheter ablation

Amiodarone Amiodarone

Dofetilideb,c

DronedaroneFlecainideb,d

Propafenoneb,d

Sotalolb,c

Dofeilideb,c

DronedaroneSotalolb,c

CAD HF

AmiodaroneDofetilideb,c

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Table 1. Complications of radiofrequency catheter ablation for atrial fibrillation

Complication Symptoms/Signs Treatment

Air embolismAcute ischemia, cardiac arrest, AV block, hypotension

Supplemental oxygen, fluids, CPR, or pacing if indicated

Atrial-esophageal fistula Usually 1–4 wk after ablation, dysphagia, unexplained fever, chills, sepsis, neurological events (septic emboli)

CT or MRI of esophagus, avoiding endoscopy, immediate surgical correction

Cardiac tamponade/perforation Abrupt or gradual fall in BP Pericardiocentesis, emergent surgical drainage if pericardiocentesis fails

Phrenic nerve injury resulting indiaphragmatic paralysis

Shortness of breath, Elevated hemidiaphragm

None, usually resolvesspontaneously

Iatrogenic atrial flutter Tachycardia Cardioversion, antiarrhythmicdrugs, or repeat ablation

Gastric motility disorderNausea, vomiting, bloating, abdominal pain

Depends on severity of symptoms

Mitral valve injury requiringsurgery

Entrapment of catheter Advance sheath with gentle catheter retraction, surgical removal

Myocardial infarction Chest pain, ST changes, hypotension Standard therapy

Pericarditis Chest pain, typical quality NSAIDs, colchicine, steroids

Pulmonary vein stenosis Shortness of breath, cough, hemoptysis PV dilation/stent or no therapy

Radiation injury Pain and reddening at radiation site, can present late

Treat as burn injury

Stroke or TIA Neurological deficit Consider lysis therapy

Vascular access complication

Femoral pseudo aneurysm Pain or pulsatile mass at groin Observation, compression, thrombin injection, possible surgery

Arteriovenous fistula Pain, bruit at groin site Observation, compression, possible surgery

Hematoma Pain, swelling Compression

Death N/A N/A

(modified from 2014 AHA/ACC/HRS guidelines17)

AV, atrioventricular; BP, blood pressure; CPR, cardiopulmonary resuscitation; CT, computed tomography; MRI, magnetic resonance imaging; N/A, not applicable; NSAIDs, non-steroidal anti-inflammatory drugs; PV, pulmonary valve; and TIA, transient ischemic attack.

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3.절제술전후의항응고요법

ESC가이드라인과마찬가지로항응고요법중지후

heparin사용의대안으로계속해서항응고요법을

유지하는전략에대해언급을하고있다.하지만주요

권고사항에는포함되어 있지 않다. NOAC, 특히

dabigatran에대한언급이있으나역시권고사항에는

들어가있지않다.시술후장기간항응고요법에대한

의견도ESC가이드라인과유사하다.즉,위험도가낮지

않은군에대한항응고요법중지에대해서는신중한

입장이다.

4.심부전환자의절제술

역시ESC가이드라인과유사한의견을피력하고

있다.환자를전체적으로잘파악해서진행한다면심한

좌심실기능부전이있는환자에서도증상이있는

심방세동을치료하는데절제술이유용할수있다는

내용이다.

5.합병증

알려진합병증들에대한요약은Table 1과같다.

합병증발생률과연관된인자들은고령,여성,CHADS2

점수≥2이다.8,18,19또한ESC업데이트가이드라인에도

언급되었듯이좌심방의절제술은MRI로발견할수

있는무증상의작은뇌경색을유발시킬수있다.하지만

대부분은시간이경과하면서해결되거나사라지는

것으로보인다.

국내보험규정

1.전극도자절제술

심방세동 전극도자 절제술의 국내 건강보험

요양급여는2014년6월부터다음과같은기준의적용을

받고있다.

(1)항부정맥약제(classⅠ또는classⅢ)중1가지이상을

6주이상충분한용량으로투여한이후에도증상이

조절되지않는심방세동으로약제투여전후

심전도검사에서심방세동이증명된경우.다만,

영구형(permanent)심방세동은인정하지아니함

(2)항부정맥 약제에 대한 부작용 또는 동결절

기능부전을동반한빈맥-서맥증후군에서와같이

약제유지가불가능한심방세동으로서심전도에

의해확인된경우

(3)재시술은이전시술후3개월이경과된이후에

실시하되심전도상심방세동또는심방빈맥의

재발이증명된경우

(4)심방세동고주파절제술시CTI (cavotricuspid

isthmus)-dependent심방조동이유도된경우

2.3차원매핑

3차원매핑도2014년6월부터요양급여가인정되고

있다.기준을요약하면3차원빈맥지도화를이용한

심방세동의고주파절제술은요양급여를인정하며,3

차원빈맥지도화를위해실시한영상진단(CT,MRI)은

별도요양급여를인정한다.

결론

최근가이드라인에서의주요이슈는(1)전극도자

절제술의유용성이더욱입증되었으며,(2)일부발작성

심방세동 환자에게는 일차 치료법으로 절제술을

선택하는것이가능하고,(3)시술전후항응고요법을

지속하는방법이대두되고있다는점등이다.

가이드라인으로채택되기위해증거가더확보되어야

하는부문은(1)전극도자절제술이사망률과뇌졸중을

줄일수있는치료법으로인정받을수있을것인가,(2)

새로운항응고제(NOAC)의시술전후사용지침,(3)

시술과관련된합병증을줄일수있는좀더안전한

방법의개발등이될것이다.

국내에서도최근요양급여인정기준이개정되어

심방세동환자들뿐만아니라임상의들의진료에도큰

도움이 되고 있다. 빠르게 발전하는 치료법과

가이드라인에발맞춰국내보험인정기준도계속해서

국제적인수준으로업데이트될수있기를바란다.

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References

1. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P and Guidelines ESCCfP. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33:2719-2747.

2. Cosedis Nielsen J, Johannessen A, Raatikainen P, Hindricks G, Walfridsson H, Kongstad O, Pehrson S, Englund A, Hartikainen J, Mortensen LS and Hansen PS. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med. 2012;367:1587-1595.

3. Morillo CA, Verma A, Connolly SJ, Kuck KH, Nair GM, Champagne J, Sterns LD, Beresh H, Healey JS, Natale A and Investigators R-. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. JAMA. 2014;311:692-700.

4. Arya A, Hindricks G, Sommer P, Huo Y, Bollmann A, Gaspar T, Bode K, Husser D, Kottkamp H and Piorkowski C. Long-term results and the predictors of outcome of catheter ablation of atrial fibrillation using steerable sheath catheter navigation after single procedure in 674 patients. Europace. 2010;12:173-180.

5. Lellouche N, Jais P, Nault I, Wright M, Bevilacqua M, Knecht S, Matsuo S, Lim KT, Sacher F, Deplagne A, Bordachar P, Hocini M and Haissaguerre M. Early recurrences after atrial fibrillation ablation: prognostic value and effect of early reablation. J Cardiovasc Electrophysiol. 2008;19:599-605.

6. Oral H, Knight BP, Ozaydin M, Tada H, Chugh A, Hassan S, Scharf C, Lai SW, Greenstein R, Pelosi F, Jr., Strickberger SA and Morady F. Clinical significance of early recurrences of atrial fibrillation after pulmonary vein isolation. J Am Coll Cardiol. 2002;40:100-104.

7. Pokushalov E, Romanov A, Corbucci G, Bairamova S, Losik D, Turov A, Shirokova N, Karaskov A, Mittal S and Steinberg JS. Does atrial fibrillation burden measured by continuous monitoring during the blanking period predict the response to ablation at 12-month follow-up? Heart Rhythm. 2012;9:1375-1379.

8. Shah RU, Freeman JV, Shilane D, Wang PJ, Go AS and Hlatky MA. Procedural complications, rehospitalizations, and repeat procedures after catheter ablation for atrial fibrillation. J Am Coll Cardiol. 2012;59:143-149.

9. Di Biase L, Burkhardt JD, Mohanty P, Sanchez J, Horton R, Gallinghouse GJ, Lakkireddy D, Verma A, Khaykin Y, Hongo R, Hao S, Beheiry S, Pelargonio G, Dello Russo A, Casella M, Santarelli P, Santangeli P, Wang P, Al-Ahmad A, Patel D, Themistoclakis S, Bonso A, Rossillo A, Corrado A, Raviele A, Cummings JE, Schweikert RA, Lewis WR and Natale A. Periprocedural stroke and management of major bleeding complications in patients undergoing catheter ablation of atrial fibrillation: the impact of periprocedural therapeutic international normalized ratio. Circulation. 2010;121:2550-2556.

10. Gaita F, Leclercq JF, Schumacher B, Scaglione M, Toso E, Halimi F, Schade A, Froehner S, Ziegler V, Sergi D, Cesarani F and Blandino A. Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electrophysiol. 2011;22:961-968.

11. Herrera Siklody C, Deneke T, Hocini M, Lehrmann H, Shin DI, Miyazaki S, Henschke S, Fluegel P, Schiebeling-Romer J, Bansmann PM, Bourdias T, Dousset V, Haissaguerre M and Arentz T. Incidence of asymptomatic intracranial embolic events after pulmonary vein isolation: comparison of different atrial fibrillation ablation technologies in a multicenter study. J Am Coll Cardiol. 2011;58:681-688.

12. Gautam S, John RM, Stevenson WG, Jain R, Epstein LM, Tedrow U, Koplan BA, McClennen S and Michaud GF. Effect of therapeutic INR on activated clotting times, heparin dosage, and bleeding risk during ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2011;22:248-254.

13. Gopinath D, Lewis WR, Di Biase L and Natale A. Pulmonary vein antrum isolation for atrial fibrillation on therapeutic coumadin: special considerations. J Cardiovasc Electrophysiol. 2011;22:236-239.

14. Hakalahti A, Uusimaa P, Ylitalo K and Raatikainen MJ. Catheter ablation of atrial fibrillation in patients with therapeutic oral anticoagulation treatment. Europace. 2011;13:640-645.

15. Page SP, Siddiqui MS, Finlay M, Hunter RJ, Abrams DJ, Dhinoja M, Earley MJ, Sporton SC and Schilling RJ. Catheter ablation for atrial fibrillation on uninterrupted warfarin: can it be done without echo guidance? J Cardiovasc Electrophysiol. 2011;22:265-270.

16. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ, Jr., Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Shemin RJ, Tsao HM and Wilber D. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace. 2012;14:528-606.

17. January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC, Jr., Cigarroa JE, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM and Yancy CW. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Heart Rhythm Society. Circulation. 2014.

18. Hoyt H, Bhonsale A, Chilukuri K, Alhumaid F, Needleman M,

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Edwards D, Govil A, Nazarian S, Cheng A, Henrikson CA, Sinha S, Marine JE, Berger R, Calkins H and Spragg DD. Complications arising from catheter ablation of atrial fibrillation: temporal trends and predictors. Heart Rhythm. 2011;8:1869-1874.

19. Piccini JP, Sinner MF, Greiner MA, Hammill BG, Fontes JD, Daubert JP, Ellinor PT, Hernandez AF, Walkey AJ, Heckbert SR, Benjamin EJ and Curtis LH. Outcomes of Medicare beneficiaries undergoing catheter ablation for atrial fibrillation. Circulation. 2012;126:2200-2207.

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VOL.15 NO.4

성균관대학교 의과대학 내과학교실 온 영 근

Young Keun On, MD, PhDDivision of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine

배경

심방세동환자에서동율동전환전후에혈전색전증이

약5-7%발생하고,warfarin의사용시혈전색전증의

발생이0.5-1.6%까지줄어드는것으로알려져있다.현

재유럽및미국심장학회/부정맥학회지침에서는동율

동전환이전에최소3주간의항응고치료를시행하고,

동율동전환이후에도최소4주간의항응고치료를시행

할것을권고하고있다.새로운항응고제가비판막성심

방세동환자의뇌졸중예방을위해warfarin을대체할

수있는것으로알려져있으나아직까지동율동전환시

에새로운항응고제사용에대한전향적인연구는없는

실정이다.X-VeRT연구는심방세동환자에서전기적

동율동전환시에새로운항응고제를사용한최초의전

향적무작위대조연구이다.

방법및결과

1,504명의환자를rivaroxaban군과warfarin군에

2:1의비율로무작위배정하였고,연구자가무작위배정

이후1-5일이내에조기동율동전환또는3-8주사이

에지연동율동전환전략을선택하였다.

1차효과결과(efficacyoutcome)는뇌졸중,일과성허

혈,말초혈관색전증,심근경색,심혈관사망의총합으로

분석하였고,1차안전결과(safetyoutcome)는주요출

심방세동 환자에서 전기적 동율동 전환 시에 Warfarin과 새로운 항응고제의 비교 연구

Received: September 18, 2014Accepted: December 15, 2014Correspondence: Young Keun On, MD, PhD, Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, KoreaTel: +82-2-3410-3420, Fax: +82-2-3410-3849 E-mail: [email protected]

Rivaroxaban vs vitamin K antagonists for cardioversion in atrial fibrillation

Riccardo Cappato, Michael D. Ezekowitz, Allan L. Klein, A. John Camm, Chang-Sheng Ma, Jean-Yves Le Heu-

zey, Mario Talajic, Maurício Scanavacca, Panos E. Vardas, Paulus Kirchhof, Melanie Hemmrich, Vivian Lanius,

Isabelle Ling Meng, Peter Wildgoose, Martin van Eickels, Stefan H. Hohnloser on behalf of the X-VeRT Inves-

tigators

Eur Heart J. 2014 Sep 2. [Epub ahead of print]

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혈로정의하였다.

978명의 rivaroxaban군에서2건의뇌졸중을포함

한5건(0.51%)의 1차효과결과가발생하였고, 492명

의warfarin군에서는 2건의뇌졸중을포함하여 5건

(1.02%)의1차효과결과가발생하였다(riskratio,0.50;

CI,0.15-1.73).Rivaroxaban투여시조기동율동전

환전략으로4명(0.71%)에서,지연동율동전환전략으

로는1명(0.24%)에서1차효과결과가발생하였다.한편

warfarin투여시조기동율동전환전략으로3명(1.08%)

에서,지연동율동전환전략으로는2명(0.93%)에서1

차효과결과가발생하였다.지연동율동전환전략에

서rivaroxaban군에서동율동전환까지기간이평균22

일로warfarin군에서의평균30일에비해의미있게짧

았다.주요출혈은rivaroxaban군에서6명(0.6%)발생

하였고,warfarin군에서는4명(0.8%)발생하였다(risk

ratio,0.76;CI,0.21-2.67).

결론

심방세동환자에서전기적동율동전환시에rivar-

oxaban은효과적이고안전하게warfarin을대체할수

있는것으로보인다.

Table 1. Primary efficacy and safety outcomes

Total by treatment Early Delayed

Rivaroxaban VKA RR (95% CI) Rivaroxaban VKA Rivaroxaban VKA

Efficacy, n (%) n=978 n=492 n=567 n=277 n=411 n=215

Primary end-point 5 (0.51) 5 (1.02) 0.50(0.15-1.73) 4 (0.71) 3 (1.08) 1 (0.24) 2 (0.93)

Stroke 2 (0.20) 2 (0.41) 2 (0.35) 1 (0.36) 0 1 (0.47)

Hemorrhagic stroke 2 (0.20) 0 2 (0.35) 0 0 0

Ischemic stroke 0 2 (0.41) 0 1 (0.36) 0 1 (0.47)

TIA 0 0 0 0 0 0

SE 0 1 (0.20) 0 1 (0.36) 0 0

MI 1 (0.10) 1 (0.20) 1 (0.18) 0 0 1 (0.47)

Cardiovascular death 4 (0.41) 2 (0.41) 3 (0.53) 2 (0.72) 1 (0.24) 0

All-cause death 5 (0.51) 3 (0.61) 3 (0.53) 3 (1.08) 2 (0.49) 0

Safety, n (%) n=988 n=499 n=575 n=284 n=413 n=215

Major bleeding 6 (0.61) 4 (0.80) 0.76(0.21-2.67) 3 (0.52) 3 (1.06) 3 (0.73) 1 (0.47)

Fatal 1 (0.10) 2 (0.40) 1 (0.17) 2 (0.70) 0 0

Critical site 2 (0.20) 3 (0.60) 2 (0.35) 2 (0.70) 0 1 (0.47)

ICH 2 (0.20) 1 (0.20) 2 (0.35) 0 0 1 (0.47)

Hb decrease ≥2 g/dL 4 (0.40) 1 (0.20) 1 (0.17) 1 (0.35) 3 (0.73) 0

Transfusion ≥2 unitsRBCs or whole blood

3 (0.30) 1 (0.20) 1 (0.17) 1 (0.35) 2 (0.48) 0

CI, confidence interval; CV, cardiovascular; Hb, hemoglobin; ICH, intracranial hemorrhage; MI, myocardial infarction; RBCs, red blood cells; RR, risk ratio; SE, systemic embolism; TIA, transient ischemic attack; VKA, vitamin K antagonist

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Introduction

Thesurvivalrateofpatientswithcomplexcon-

genitalheartdiseasehasrecentlyimproved,most

likely due to the development of new surgical

techniques and improved perioperative medical

management.1Asthenumberofadultpatients

withcongenitalheartdiseasehasincreased,ar-

rhythmiasandheartfailurearebecominggrow-

ingissuesinthesepatients.1Thus,itisnotsur-

prising that the demand for electrophysiologic

(EP) studiesand radiofrequency catheterabla-

tion(RFCA)isincreasing.EPstudiesandRFCA

arechallenginginpatientswhohaveundergone

extracardiac conduitFontanprocedures for the

palliativetreatmentofcongenitalheartdisease,

becausethesystemicvenousbloodisnotdrained

intotheheartinthesetechniques.Here,were-

portacaseoffocalatrialtachycardia,whichwas

ablatedviaatrans-conduitpunctureinapatient

whohadundergoneanextracardiacconduitFon-

tanprocedure.

Case

A14-year-oldmalepatientvisitedtheemer-

gency room complaining of palpitations for 3

Received: May 28, 2014Accepted: December 15, 2014Correspondence: Jae-Sun Uhm, MD, Department of Cardiology, Severance Cardiovascular Hospital, 50 Yonsei-ro Seodaemun-gu, Seoul, Korea, 120-752Tel: +82-2-2228-8441, Fax: +82-2-2227-7732 E-mail: [email protected] Ko, MD, PhD, Division of Cardiology

ABSTRACT

Electrophysiology (EP) studies and radiofrequency catheter ablation (RFCA) are challenging in patients who have undergone extracardiac conduit Fontan procedures, because of the difficult vascular access. Here, we report on a 14-year-old male patient who underwent extracardiac conduit Fontan procedure for a double-inlet left ventricle, complete transposition of the great arteries, and large ventricular septal defect. The EP study was performed via a trans-conduit puncture. Focal atrial tachycardia originating from the mid portion of the interatrial septum was induced. RFCA of the origin of atrial tachycardia was successfully performed. EP studies and RFCA are feasible via a trans-conduit puncture in patients with extracardiac conduit Fontan circulation.

Key words: ■ atrial tachycardia ■ congenital heart disease ■ Fontan procedure

연세대학교 의과대학 내과학교실 엄 재 선, 김 남 균, 박 진 규, 정 보 영, 박 희 남, 이 문 형

Jae-Sun Uhm, MD1; Nam Kyun Kim, MD2; Jin-Kyu Park, MD1; Boyoung Joung, MD1; Hui-Nam Pak1; Moon-Hyoung Lee1

Departments of Cardiology1 and Pediatric Cardiology2, Arrhythmia Center, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea

Atrial Tachycardia in a Patient with Extracardiac Conduit Fontan Circulation

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Figure 1. (A) electrocardiogram during palpitation shows regular narrow QRS tachycardia with short RP interval. (B) electrocardio-gram during sinus rhythm.

A

B

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Figure 2. Cardiac CT shows findings compatible with complete transposition of the great arteries, double-inlet left ventricle, large ven-tricular septal defect and extracardiac Fontan conduit. Ao, aorta; C, Fontan conduit; LA, left atrium; PA, pulmonary artery; RA, right atrium; rV, rudimentary ventricle; V, ventricle.

Figure 3. (A) Fontan conduit angiography (B) Fluoroscopic image of performing trans-conduit puncture (C) Intracardiac echocardiography of the trans-conduit puncture (D) The Brockenbrough transseptal needle and the Swartz transseptal introducer sheath with holding the dilator tip of the Swartz sheath with the snare catheter to prevent it from sliding up along the conduit wall. C, Fontan conduit; HV, hepatic vein; ICE, intracardiac echocardiography; IVC, inferior vena cava; LPA, left pulmonary artery; RA, right atrium.

A B C

Ao RA RAV

rV rVLA LA

V

PA c c

A B

C D

LPA

C

HVIVC

ICE

Needle

Snare

Needle

Snare

Sheath

Sheath

Needle

RA

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hours. He had experienced several episodes of

palpitationsduringthepastyear.Hisbloodpres-

sure was 82/49mmHg. The electrocardiogram

(ECG)showedregular,narrowQRStachycardia

witharateof160beats/minandashortRPin-

terval(Figure1A).Intheemergencyroom,the

tachycardia spontaneously converted into sinus

rhythm(Figure1B).TheQRSmorphologyofthe

tachycardiawassimilartothatinsinusrhythm.

When he was 10 days old, he was diagnosed

withdouble-inletleftventricle(DILV),complete

transposition of the great arteries (TGA), and

large ventricular septal defect (VSD).Whenhe

was5monthsold,thebidirectionalcavopulmo-

naryshuntandinteratrialseptectomywereper-

formedforpalliation.At theageof1year,an

extracardiacconduitFontanprocedurewasper-

formedwiththeautologouspericardium.Wede-

cidedtoperformtheEPstudyfordiagnosisand

treatmentofthetachycardia.Cardiaccomputed

tomography(CT)wasperformedforassessment

oftheheartanatomy,showingfindingscompat-

iblewithTGA,DILV,largeVSD,functionalsingle

ventricle,andextracardiacFontanconduit(Fig-

ure2).

Both femoral veins were punctured. Conduit

angiography was performed with a Berman-

typeangiographycatheter(ArrowInternational,

Reading,PA,USA)(Figure3A).TwoSR-0Swartz

transseptalintroducersheath(StJudeMedical,St

Paul,MN,USA),asnarecatheter(PFMMedi-

cal,Nonnweiler,Germany),andanintracardiac

echocardiography catheter (AcuNav, Siemens,

MountainView,CA,USA)wereinsertedintothe

Fontanconduitviathefemoralveins.ABRK-1

Brockenbroughtransseptalneedle(StJudeMedi-

cal)wasinsertedintotheSwartzsheath,andthe

dilatortipoftheSwartzsheathwasheldwiththe

snarecathetertopreventitfromslidingupalong

theconduitwall(Figure3BandD).Wepunctured

thewallbetweentheconduitandtherightatrium

withtheBrockenbroughtransseptalneedleunder

intracardiac echocardiography guidance (Figure

3C).Right and left atriographywas performed

with thepigtail catheter via the trans-conduit

puncture. A deflectable decapolar catheter (St

Figure 4. Positioning of the EP catheters during basic EP study (A) and during tachycardia mapping (B).

A B

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VOL.15 NO.4

Figure 5. Intracardiac electrogram of induction (A) and maintenance (B) of tachycardia. The tachycardia was maintained in spite of premature ventricular complex (red box in A) and atrioventricular block (red box in B). The atrioventricular or ventriculoatrial interval was varying.

A

B

I

aVF

V1

HAp

HAd

ABLd

ABLp

Vd

Vp

Stim

Carto

I

aVF

V1

HAp

HAd

Vd

Vp

Stim

Carto

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A B

JudeMedical)wasplacedinthehighleftatrium

viatheSwartzsheathandadecapolarcatheter

(StJudeMedical)wasplacedintheventriclevia

the aorta (Figure 4A). The initial rhythmwas

normal sinus rhythm.During ventricular pac-

ingandsingleventricularextrastimuli,theatrial

electrogramshowedone-to-oneventriculoatrial

conductionwithdecrementalproperties.During

theatrialpacingof240msandinfusionofiso-

proterenolatarateof2μg/min,tachycardiawith

a290mscyclelengthwasinduced.Tachycardia

wasmaintaineddespitethepresenceofapre-

matureventricularcomplexandatrioventricular

block (Figure 5A and B). Therefore, atrioven-

tricularreentranttachycardiacouldbeexcluded.

Duringtachycardia,theatrioventricularorven-

triculoatrialintervalvaried(Figure5B).Itwasnot

compatiblewithatrioventricularnodalreentrant

tachycardia.Thetachycardiawasnotentrainable

byventricularpacing.Thedecapolarcatheterwas

movedtotherightatrium(RA)sideintheFontan

conduit,andanirrigatedablationcatheter(Ther-

mocool, Biosense Webster, Diamond Bar, CA,

USA)wasinsertedintotheatriumviathecon-

duit puncture for tachycardiamapping (Figure

4B).Duringtachycardia,3-dimensionalelectro-

anatomicalmappingwasperformedwithCARTO

(BiosenseWebster,DiamondBar,CA,USA).The

tachycardiawasoriginatingfromthemidpor-

tionoftheremnantinteratrialseptum(Figure6).

Thetachycardiawascompatiblewithfocalatrial

tachycardiaoriginatingfromtheinteratrialsep-

tum.Duringsinusrhythm,wemappedtheHis

bundlepotentials.TheHisbundleareawaslocat-

edinthelowerposteriorpotionoftheinteratrial

septum.Theoriginofthetachycardiawasaway

fromtheHisbundleareaby13.6mm(Figure6B).

WeperformedRFCAof theoriginof theatrial

tachycardiabydelivering30wattsofRFenergy

for90swiththeirrigatedablationcatheterdur-

ingsinusrhythm.Theprocedureendedafterwe

confirmedthatthetachycardiawasnotinduced

Figure 6. LAO view of 3-dimensional electroanatomical mapping shows the origin (black arrow) of focal atrial tachycardia originating from the mid portion of the septum. His, His bundle area; LA, left atrium; LAA, left atrial appendage; LAO, left anterior oblique view; LSPV, left superior pulmonary vein; RA, right atrium; RSPV, right superior pulmonary vein.

RA

RSPVLSPV

LAA LAA

His

LA

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VOL.15 NO.4

bytheprogrammedelectricstimulationandiso-

proterenolinfusion.Thepatienthadnosymptom

andmaintainedsinusrhythmfor6monthsafter

RFCA.

Discussion

Thecasewasfocalatrialtachycardiaoriginat-

ingfromtheseptuminapatientwhohadunder-

goneanextracardiacconduitFontanprocedure.

WeperformedanEPstudyandRFCAoftheori-

ginofthefocalatrialtachycardiasuccessfullyvia

thetrans-conduitpuncture.

The lifelong prevalence of atrial tachycardia

inpatientswithextracardiacFontancirculation

is approximately 50%,2-4 and it is considerably

higherthaninthenormalpopulation.Inpatients

withextracardiacconduitFontancirculation, it

isdifficulttoperformanEPstudy,becausethe

heart iscompletelyexcluded fromthesystemic

venous system. There were previous case re-

portsofEPstudiesandRFCAviavariousroutes

in patients with Fontan circulation, including

viaatrans-thoracicpuncture,sternotomyap-

proach, trans-apical access and trans-conduit

puncture.5-8TheEPcatheterscanbetransvas-

cularlyplacedvia2pathways:thetrans-conduit

puncture and retrograde transaortic approach.

Theapproachviathetrans-conduitpunctureis

suitableforgainingaccesstotheatriumandthe

retrograde transaortic approach is suitable for

gainingaccesstotheventricle.Itischallenging

topuncturetheFontanconduitbecausefibrosis

formsaroundtheconduit.Inaddition,thecon-

duitwallisvertical—unliketheinteratrialsep-

tum—andthetransseptalneedletendstoslideup

alongtheconduitwallinsteadofpuncturingit.

TheuseofaBrockenbroughtransseptalneedle

whileholdingthedilatortipoftheSwartzsheath

with a snare catheter is a useful method for

puncturing theFontanconduit.9A large-curve

BRK-1transseptalneedleissuperiortoasmall-

curveBRKneedle.Moreover,theradiofrequency

transseptalneedlecanbeagoodoptionforpunc-

turingthefibroticFontanconduit.

Inpatientswithcongenitalheartdisease,the

EPstudyandRFCAareverychallengingbecause

oftheunusualanatomyoftheheart.Inaddition,

itiscommonforpatientstohavevascularanom-

aliesincludingapersistentleftsuperiorvenacava

andinferiorvenacavainterruption.Itisimpor-

tantthattheoperatorbecompletelyawareofthe

anatomy of heart and vessels of each patient.

Everypatienthasauniqueheartstructure,even

thoughthispatientgrouphasthesamediagnosis

ofcongenitalheartdisease.Theoperatorneeds

to review and understand the previous cardiac

surgery and intervention. The operator should

makeameticulousplanfortheprocedure,taking

intoconsiderationthetypesofEPcatheterstobe

usedforeachchamber,pathwaystobeusedfor

positioningoftheEPcatheters,andappropriate

anglesfortheX-raybeamtoimprovevisualiza-

tion.Theoperatorneedstodiscussthecurrent

hemodynamicsand long-termprognosisof the

patientwiththepediatriccardiologists.Giventhe

complexheartanatomy,cardiacCTanda3-di-

mensional electroanatomicmapping systemare

necessaryforguidingtheprocedure.Intracardiac

echocardiography can be helpful for real-time

visualizationof theanatomyandEPcatheters.

Theactivatedcoagulationtimeshouldbemain-

tainedat350–400msbyheparininfusionduring

theEPstudyinpatientswithasingleventricle,

asthecathetersareplacedinthesystemiccham-

bers.

In the present case, the remnant interatrial

septummightbecomearrhythmogenicaftersep-

tectomyduetodegenerativechangesofthein-

teratrialseptum.Thispatientislikelytodevelop

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atrial tachyarrhythmia originating from other

parts of the atrium. In addition, an advanced

atrioventricular block can occur in the future,

althoughtheperi-proceduralECGshowedfirst

degreeatrioventricularblock.Thus,thepatient

willrequirelong-termfollow-up.

Conclusion

EPstudiesandRFCAarefeasibleviaatrans-

conduit puncture in patients with extracardiac

conduitFontancirculation.

References

1. Mackie AS, Ionescu-Ittu R, Therrien J, Pilote L, Abrahamowicz M, Marelli AJ. Children and adults with congenital heart disease lost to follow-up; who and when? Circulation. 2009;120:302-309.

2. Gelatt M, Hamilton RM, McCrindle BW, Gow RM, Williams WG, Trusler GA, Freedom RM. Risk factors for atrial tachyarrhythmias after the Fon-tal operation. J Am Coll Cardiol. 1994;24:1735-1741.

3. Weipert J, Noebauer C, Schreiber C, Kostolny M, Zrenner B, Wacker A, Hess J, Lange R. Occurrence and management of atrial arrhythmia after long-term Fontan circulation. J Thorac Cardiovasc Surg. 2004;127:457-464.

4. Lasa JJ, Glatz AC, Daga A, Shah M: Prevalence of arrhythmias late after the Fontan operation. Am J Cardiol. 2014;133:1184-1188.

5. Nehgme R, Carboni MP, Care J, Murphy JD. Transthoracic percutane-ous access for electroanatomic mapping and catheter ablation of atrial tachycardia in patients with a lateral tunnel Fontan. Heart Rhythm. 2006;3:37-43.

6. Khairy P, Fournier A, Ruest P, Vobecky SJ. Transcatheter ablation via a sternotomy approach as a hybrid procedure in a univentricular heart. Pacing Clin Electrophysiol. 2008;31:639-640.

7. Brown SC, Boshoff DE, Rega F, Eyskens B, Budts W, Heidbuechel H, Meyns B, Gewillig M. Transapical left ventricular access for difficult to reach interventional targets in the left heart. Catheter Cardiovasc In-terv. 2009;74:137-142.

8. Dave AS, Aboulhosn J, Child JS, Shivkumar K. Transconduit puncture for catheter ablation of atrial tachycardia in a patient with extracardiac Fontan palliation. Heart Rhythm. 2010;7:413-416.

9. Aoki H, Nakamura Y, Takeno S, Takemura T. A new procedure for a trans-conduit puncture by grasping the dilator tip with a snare catheter: an alternative access method during catheter ablation of supraventricular tachycardias after an extracardiac Fontan operation. Heart Rhythm. 2013. doi: 10.1016/j.hrthm.2013.10.036 [Epub ahead of print] .

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VOL.15 NO.4

Warfarin-associated Extensive Spontaneous Spinal Epidural Hematoma Mimicking Stroke

전남대학교 의과대학 내과학교실 이 기 홍

Ki Hong Lee, MD, PhDThe Heart Research Center of Chonnam National University Hospital, Cardiovascular Research Institute of Chonnam National University, Gwangju, Korea

Introduction

Oralanticoagulation(OAC)therapyisstrongly

recommendedtopreventthromboembolicstroke

inpatientswithatrialfibrillation(AF).1However,

strictcontrolisneededtoachieveoptimalthera-

peuticlevelwhenusingwarfarinastheantico-

agulant.Cliniciansusuallysuspectacutestroke

whenpatientswithAFpresentwithneurologic

symptoms.2IreportanAFpatientonwarfarin

therapycomplainingofacute-onsetrighthemi-

plegia,whichwasdiagnosedasextensivespinal

epiduralhematomaratherthanstroke.

Case

A 70-year-old female patient presented to

theemergencydepartmentcomplainingofchest

discomfortandmotorweaknessintherightarm

andleg.Shehadbeenonwarfarinfor6years

afteradiagnosisofparoxysmalAF.Thepatient

reportedahistoryofhypertensionanddyslipi-

Received: August 21, 2014Revision Received: November 28, 2014Accepted: December 15, 2014Correspondence: Ki Hong Lee, MD, PhD, The Heart Center of Chonnam National University Hospital, 42 Jaebongro, Dong-gu, Gwangju 501-757, South KoreaTel: +82-62-220-6246, Fax: +82-62-223-3105E-mail: [email protected], MD, PhD, Division of Cardiology

ABSTRACT

Clinicians usually suspect acute stroke when patients with atrial fibrillation (AF) present with neurologic symp-toms. I report such a patient on warfarin therapy complaining of acute-onset right hemiplegia, which was diagnosed as extensive spinal epidural hematoma rather than stroke. International normalized ratio (INR) was within therapeutic range, with no recent dosage change. Brain MRI revealed no acute stroke. Further neurolog-ic examination demonstrated reduced pain and temperature sensations below T2 level. Subsequently, cervical MRI was performed and revealed a massive spinal epidural hematoma in the posterior and right posterolateral regions of the spinal canal from C1 to T2. The patient underwent emergency right cervical decompressive laminectomy 24 hours after symptom onset. After 2 weeks of rehabilitation, the patient made a near-complete recovery of motor and sensory function. Spinal epidural hematoma should be the first differential diagnosis considered during acute stroke work-up in patients on warfarin medication.

Key Words: ■ spinal epidural hematoma ■ warfarin

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demia.Therehadbeennorecentchangesinwar-

farin dosage, and her international normalized

ratio (INR)hadbeen2.0at lastmeasurement,

withinthe therapeuticrange.Promptmagnetic

resonanceimaging(MRI)ofthebrainwasper-

formedtoevaluateacutestrokeevents.However,

itrevealednoevidenceofcerebralinfarctionor

hemorrhage. Detailed neurological examination

showeddecreasedmotorstrengthinrightupper

andlowerextremities,reducedpainandtemper-

aturesensationsbelowT2,andhyperreflexiain

the lowerextremities.Nocognitivedysfunction

ordysarthriawasnoted.Cranialnerveexami-

nationwasnormal.Takentogether,thesefind-

ingssuggestedcervicalspinalcordcompression.

Thereafter,cervicalMRIwasperformedandre-

Figure 1. 1. Spinal epidural hematoma (white arrow) at posterior and right posterolateral region of C1 to T2 level as low signal intensity in T1-weighted sagittal image (A) and high signal intensity in T2-weighted sagittal image (B). Spinal epidural hematoma compressed spinal cord (white arrow head) deviated to left side with compressive myelopathy at C6 to7 in T2-weighted axial image at C3 level (C) and C6 level (D).

A

C

B

D

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vealedamultiloculatedcysticmass(11×1.5×

1 cm) in the posterior and right posterolateral

regionsofthespinalcanalfromC1toT2,with

masseffectonthespinalcordandcompressive

myelopathyontherightsideatC6–7.Inaddi-

tion,therewasmoderateleftcentraldischernia-

tionatC6–7.Afterintravenousadministrationof

5mgofvitaminK,thepatientunderwentemer-

gencyrightcervicaldecompressivelaminectomy

24hoursaftersymptomonset.Amassivecervical

epiduralhematomaextendingfromC1toT1was

foundandremoved.Thepatientwashospitalized

forrehabilitationfor2weeksaftertheoperation.

Follow-upcervicalMRIshowedcompleteremoval

ofhematomafromthespinalcanal.Anticoag-

ulationwasstarted2daysafteroperationwith

intravenousunfractionatedheparin,whichwas

changedtooralwarfarin5daysafteroperation.

Athospitaldischarge,themotorpowerofthearm

hadbeencompletelyrecovered,and lower limb

strengthwasmostlyrestoredwithapowergrade

of4/5.

Discussion

OACshouldbeconsideredinAFpatientswith

highriskofthromboembolism.1However,ifwar-

farinisusedforthispurpose,thedosemustbe

strictlycontrolled toavoidseverecomplications

(embolic stroke if INR falls below therapeutic

rangeandhemorrhagicstrokeifitrisesabove).

Neurologicdeficitinpatientsonwarfarinmedi-

cationusually indicatesacutestroke.However,

thispatientdevelopedextensivespinalepidural

hematomaratherthanstroke.Spontaneousspi-

nalepiduralhematomaisararecondition,that

usuallyrequiresemergentsurgicalintervention;

3itsoccurrenceinpatientsonwarfarinwithan

INRwithinthetherapeuticrangehaspreviously

beenreportedbyotherauthors.4,5Inthecurrent

case,laboratorytestsfoundINRtobewithinthe

therapeuticrange,andthepatientdidnothave

anytraumaorunderlyingcoagulopathicdisease.

Thecombinationofhypertensionandcervicaldisc

herniationmayhaveledtotheepiduralbleeding.

Therefore,spinalepiduralhematomashouldbe

consideredinadditiontoacutestrokewhenfo-

calneurologicdeficitisfoundinpatientstaking

warfarin,anddetailedneurologicexaminationis

mandatorytodifferentiatespinalepiduralhema-

tomafromstroke.

Earlydiagnosisandemergencysurgicalinter-

vention are essential in spinal epidural hema-

tomatoenablerecoveryfromneurologicseque-

lae.6Surgicaltreatmentmorethan48hoursafter

manifestation is likely to result in permanent

neurologicimpairmentwithincompletedysfunc-

tionofthespinalcord.7Spinalepiduralhematoma

usuallymanifestsassudden,unexplainedcervical

orbackpain.8However,thepatientonlycom-

plainedofmildchestdiscomfort in thecurrent

case.Thisshowsthatspinalepiduralhematoma

canvaryinitsclinicalpresentation,andcareful

examinationisimportantinpatientswithneuro-

logicsymptoms,especiallyAFpatientsonwarfa-

rinmedication.

Spinalepiduralhematomashouldbethefirst

differential diagnosis considered in patients on

warfarinmedicationwhenneurologicsymptoms

suggest acute stroke, even without cervical or

backpain.Anydelay indiagnosisandsurgical

interventionmayresultinpermanentneurologic

impairment.

References

1. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P; ESC Committee for Practice Guidelines (CPG). 2012 focused update of the ESC Guidelines for the manage-ment of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special

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contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33:2719-2747.

2. McManus DD, Rienstra M, Benjamin EJ. An update on the prognosis of patients with atrial fibrillation. Circulation. 2012;126:e143-146.

3. Pullarkat VA, Kalapura T, Pincus M, Baskharoun R. Intraspinal hem-orrhage complicating oral anticoagulant therapy: an unusual case of cervical hematomyelia and a review of the literature. Arch Internal Med. 2000;160:237-240.

4. Kirazli Y, Akkoc Y, Kanyilmaz S. Spinal epidural hematoma associ-ated with oral anticoagulation therapy. Am J Phys Med Rehabil. 2004;83:220-223.

5. Lederle FA, Cundy KV, Farinha P, McCormick DP. Spinal epidural he-matoma associated with warfarin therapy. Am J Med. 1996;100:237-238.

6. Groen RJ, van Alphen HA. Operative treatment of spontaneous spinal epidural hematomas: a study of the factors determining postoperative outcome. Neurosurgery. 1996;39:494-508; discussion 508-509.

7. Groen RJ. Non-operative treatment of spontaneous spinal epidural he-matomas: a review of the literature and a comparison with operative cases. Acta Neurochir. 2004;146:103-110.

8. Horcajadas A, Katati M, Arráez MA, Ros B, Abdullah O, Castañeda M, de la Linde C. Spontaneous epidural spinal hematoma: report of 2 cases and review of the literature. Neurologia. 1998;13:401-404.

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Successful Use of a New Oral Anti-coagulant in a Stroke Patient with Poor Prothrombin Time Control Even After Warfarin Treatment

한양대학교 의과대학 내과학교실 박 환 철

Hwan-Cheol Park, MD, PhDCardiology Division, Department of Internal Medicine, Hanyang University Guri Hospital, Guri city, Republic of Korea

Introduction

For the lastseveraldecades,vitaminKan-

tagonists(VKAs)havebeentheprimarymedica-

tioninanti-coagulanttherapyforthepreven-

tionandtreatmentofthromboticevents.Dueto

theindividualvariationinprothrombintime(PT)

responses,individualizedadjustmentoftheVKA

dose is essential to manage the international

normalized ratio (INR);however, thisplacesa

significantpracticalburdenonboththephysi-

cianandpatient.AppropriateINRmanagement

is very difficult in some cases, which makes

theapplicationoftherapyinvolvingfixeddos-

esoforalanti-coagulantsanattractiveoption

forpracticalreasons.Neworalanti-coagulants

(NOACs)haverecentlybeendevelopedtopre-

ventembolicstrokeandtoreducetheincidence

ofmajorbleedingincomparisonwiththatas-

sociatedwithVKAuse.1,2Inthepresentreport,

theauthorpresentsacasewithpoorINRcontrol

withwarfarin treatment thatwas successfully

treatedwithaNOACtopreventembolicstroke

recurrence.

Received: September 12, 2014Revision Received: November 26, 2014Accepted: December 15, 2014Correspondence: Hwan-Cheol Park, MD, PhD, Cardiology Division, Department of Internal Medicine, Hanyang University Guri Hospital, Guri city, Republic of KoreaTel: +82-31-560-2655, Fax: +82-031-553-7369E-mail: [email protected], MD, PhD, Division of Cardiology

ABSTRACT

A 76-year-old woman presented to our hospital with right-side motor weakness. She was diagnosed with par-oxysmal atrial fibrillation in June 2010 and underwent treatment with warfarin and a class Ic anti-arrhythmic drug (flecainide). However, during the follow-up period, her international normalized ratio could not be con-trolled despite laborious adjustment of warfarin dose. Therefore, warfarin treatment was discontinued and dual antiplatelet agent therapy was initiated. Three months after stopping warfarin treatment, she presented to an emergency clinic with right-side motor weakness and was diagnosed with acute middle cerebral artery occlusion. However, as she did not wish to take warfarin, the author prescribed treatment with a new oral anti-coagulant (NOAC) in order to prevent the development of further stroke.

Key Words: ■ atrial fibrillation ■ stroke ■ new oral anti-coagulant

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Case

A76-year-oldwomanwasreferredtoourin-

stitutioninJune2010fortheevaluationofnewly

diagnosedatrialfibrillationthatoccurred3days

after an episode of transient right-sidemotor

weakness.Shehadbeendiagnosedwithessential

hypertension15yearspreviouslyandwastak-

ing losartan (50mg q.d.) and hydrochlorothi-

azide(12.5mgq.d.).Herbodytemperaturewas

36.7°C,herpulseratewas78beatsperminute,

andherbloodpressurewas126/78mmHg.Her

radialpulsewasirregular,andagradeIIIsystolic

murmurcouldbeheardinhermitralvalvearea.

Figure 1. The initial electrocardiogram shows atrial fibrillation. ST segment depression is noted in the anterolateral leads.

A B

Figure 2. The coronary angiogram shows significant atherosclerotic stenosis with ectatic formation (white arrows) in the middle segment of the left anterior descending artery on the right anterior cranial view (A) and the right anterior caudal view (B).

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Sheshowednoneurologicdeficitandwasmen-

tallyalert.

Aspreviouslystated,thepatienthadexperi-

encedtransientright-sidemotorweakness(for

approximately2hours)3dayspreviouslyandhad

been admitted to undergo evaluation of new-

ly diagnosed paroxysmal atrial fibrillation.Her

hemogram values, biochemical marker levels,

andthyroidhormonelevelswerewithinnormal

limits.Theinitialelectrocardiogram(ECG)con-

firmedthepresenceofatrialfibrillation(Figure

1).Transthoracicechocardiographyshowednor-

mal left ventricular systolic function (ejection

fraction,58%)andgradeIImitralregurgitation.

The leftatriumwasmildly enlarged (diameter,

42.4mm).BecausetheanterolateralECGleads

showed ST segment depression (Figure 1), she

underwent a coronary angiogram,which indi-

catedafixedatheroscleroticlesioninthemid-

dlesegmentoftheleftanteriordescendingartery

andshowed70%stenosis(Figure2).Percutane-

ouscoronaryinterventionwasnotperformedas

shedidnotexperienceanychestpainordiscom-

fort.Therefore,theauthordecidedtouseaclass

Icanti-arrhythmicdrug(flecainide)andwarfarin

topreventembolicstroke,basedonherCHADS2

scoreof4(1pointforhypertension,1pointfor

age≥75years,and2pointsforhistoryoftran-

sientischemicattack).

However,despitethefrequentbloodsampling

andvisitstotheoutpatientclinic(whichthepa-

Figure 4. A magnetic resonance image shows an acute cerebral infarction in the left middle and posterior cerebral artery territories (white arrows).

Figure 3. A follow-up electrocardiogram obtained in the outpatient clinic after 3 months shows normal sinus rhythm.

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tient complained about), her INR could not be

controlledduringthefollow-upperiod.After3

months,herECGshowednormalsinusrhythm

(Figure3),afterwhichsherefusedtotakewar-

farinregardlessofourrecommendations.Hence,

shewastreatedwithacombinationoftwoan-

ti-coagulants (aspirin and clopidogrel).After 3

months, shepresented toouremergency clinic

with right-side motor weakness and slurred

speech. Diffusion magnetic resonance images

(MRI) showed acute left middle and posterior

cerebral artery infarction (Figure 4). Follow-

ingrecovery,theauthorrecommendedthatthe

patientshouldcontinue treatmentwithwarfa-

rintopreventembolicstroke.Sheacceptedour

recommendationatthattimeandcontinuedwith

warfarin treatment after discharge. However,

despiteseveralwarfarindosetitrations,herPT/

INRcontrolwasfoundtobepoorateveryvisitto

theclinic(Figure5).Moreover,whentheINRin-

creasedtoabove3.5,shecomplainedaboutgum

bleeding.AstheINRwasconsistentlyoutsidethe

targetrangeof2.5–3.5,theauthordecidedto

switchthetreatmentfromwarfarintoaNOAC.

At present, the patient has not experienced

embolic strokeoranymajororminorbleeding

events.Inaddition,shereportedthatsheissat-

isfiedwiththeconvenienceofthenewregimen.

Discussion

NOACshavebeenintroducedworldwidetoim-

proveanti-coagulationtherapy.Inpatientswho

showpoorPT/INRcontrolwithwarfarin,NOACs

mayprovideaparticularlypromisingalternative.

Unlikewarfarin,whichhasanarrowtherapeutic

windowandrequiresindividualizeddosingbased

ontheINR,NOACshaveawidetherapeuticwin-

dow,therebyfacilitatingfixeddosingwithoutthe

needforlaboratorymonitoringordosetitration.

SeveralclinicalstudiesonNOACsarecurrent-

ly investigating protocols for dose adjustment,

managingbleedingevents,andothersuchfac-

tors.However,onlyafewstudieshavedescribed

patientadherencetoNOACs.Hence,theauthor

believesthatmoresustainablemethodsforim-

provingpatientadherencetoNOACsareneeded.

Patientsmaybemoremotivatedtotakeanti-

hypertensivemedicationiftheyperceiveatan-

gible benefit such as reduction of headache or

reducedchestflutters.However,intheabsence

of such benefits, the adherence may drop—in

particular,thisphenomenonmaybeobservedin

patients undergoing warfarin treatment (most

usersarechronicatrialfibrillationpatients),even

thoughtheyregularlyundergoinconvenientdose

monitoring.

AlthoughNOACsarecurrentlybeingprescribed

worldwide, it is uncertain whether accurate

dataoncomplicationsarebeingreported.Ma-

jorbleedingcomplicationshavebeennotedwith

NOACuse;however,itisnotpossibletomake

definitiveconclusionsduetothelackofdataon

comparisons with VKA use under real-world

Table 1. Medical laboratory examination results indicating the uncontrolled PT/INR values despite frequent warfarin dose titration.

2014.04.10 2014.03.11 2014.02.11 2014.01.28 2014.01.15 2013.12.27

PT (sec) 47.4 19.9 43.5 14.9 46.5 13.8

PT (INR) 3.96 1.68 3.62 1.27 3.87 1.18

Warfarin dose (mg)

4&4.5 every other day

4.25 4.5 4 5

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conditions. Patients in clinical trials ofNOACs

aregenerallyhighlymotivatedtocomplywiththe

requirementforregularvisitsandfollow-upcalls

and provided education regarding their disease

stateandtheimportanceofmedicationadher-

ence(monitoredviapillcounts).3However,given

thelackofarequirementforregularcoagulation

monitoring,thismaynotbeobservedforsome

patientswhoareprescribedNOACsinthereal-

worldsetting.4Thisisespeciallycriticalinchronic

atrialfibrillationpatients,mostofwhomhavenot

experiencedathromboticevent.Therequirement

forINRmonitoringinpatientsreceivingwarfarin

treatment effectively enables themonitoringof

adherence.Furthermore,thetwice-dailydosing

schedulesofsomeNOACsmaybemoredifficult

forsomepatientstoadheretoascomparedtoa

dailyregimen.Atpresent, inSouthKorea,the

markedlyhighercostsofNOACsshouldalsobe

carefullyconsidered.Evenforpatientswithin-

surance that covers NOACs, physicians should

ascertain how much the patients pay for the

treatmentwithNOACscomparedwithwarfarin.

Highdrugcostsmayresultinreducedmedication

adherence.

Inthepresentcase,thepatientwishedtodis-

continuebloodsamplingandcomplainedofminor

bleeding(gumbleeding).Sherequestedtoreceive

NOACtreatment,regardlessofthecost,andhas

adhered to hermedication thus far. Thus, the

authorrecommendsthatNOACsshouldbecon-

sideredforselectedpatientswhowishtoavoid

thelimitationsassociatedwithconventionalVKA

treatment.

References

1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xa-vier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wal-lentin L, Committee R-LS, Investigators. Dabigatran versus warfarin

in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-1151.

2. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Han-na M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mo-han P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L, Committees A, Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.

3. Bauer KA. Pros and cons of new oral anticoagulants. Hematology Am Soc Hematol Educ Program. 2013;2013:464-470.

4. Rodriguez RA, Carrier M, Wells PS. Non-adherence to new oral anticoagulants: A reason for concern during long-term anticoagu-lation? J Thromb Haemost. 2013;11:390-394.

자율 학습 문제

부정맥에서는매호자율학습문제를수록합니다.해당호에실린원고를바탕으로출제된문제로선생님들의

자기계발에도움이되시길바랍니다.많은참여부탁드립니다.모범답안은다음호에게재합니다.

1. 심방세동 환자에서 증상 관리를 위한 안정 시 심박수의 목표치는 분당 몇 회인가?

① 60회/분 ②70회/분

③80회/분 ④110회/분

2. 심부전 환자에서 발작성과 지속성 심방세동의 동율동 유지를 위해 사용할 수 있는 약제는 무엇인가?

① Dronedarone

②Amiodarone

③Propafenone

④Flecainide

3. 다음 중 HAS-BLED 출혈 위험 점수 계산에 포함되는 인자로 옳지 않은 것은 무엇인가?

① Chronicdialysis

②Timeintherapeuticrange65%

③Hypertensionhistorywithsystolic/diastolicBPof135/75mmHg

④Useofclopidogrel

4. 심방세동 환자의 고주파 전극도자 절제술 과정 중 적절한 INR은 얼마인가?

① 1.5-2.0

②2.0-2.5

③2.5-3.0

④3.0-3.5

Vol.15 No.3 |통권50호 |자율 학습 문제 [모범 답안]

1. 다음 중 영구형 심박동기의 적응증으로 적당하지 않은 것은?

① 증상을동반한동휴지가입증된경우

②증상을동반한심박수변동부전(chronotropicincompetence)이있는경우

③심실성부정맥을초래하는고도2도방실차단

④증상이없는심방세동에서3초이상의무수축심정지가증명된경우

☞ 정답 : ④ 증상이없는심방세동에서5초이상의무수축심정지가증명된경우

2. 영구형 인공 심박동기 삽입 시 적절한 심방의 조율 역치와 감지 신호의 크기가 맞는 조합은?

① 1.0V이하–5.0mV이상

②1.0V이하–2.0mV이상

③1.5V이하–5.0mV이상

④1.5V이하–2.0mV이상

☞ 정답 : ② 적절한심방의조율역치와감지신호의크기는각각1.5V이하,2.0mV이상이다.

3. 심박동기 시술 후 추적관찰 중에 갑자기 임피던스가 2,200 Ω 소견이 관찰되었다. 이 경우 의심할 수 있는 것은?

① 박동기이식site감염

②박동기이식한정맥의폐색

③전극선단락

④전극선절연피폭손상

☞ 정답 : ③ 2,000Ω이상인경우전극선단락을의심해야한다.

4. 인공 심박동기 감염의 위험인자가 아닌 것은?

① 말기신부전

②일시형심박동기삽입

③박동기교환

④혈종형성

☞ 정답 : ② 일시형심박동기삽입은감염의위험인자가아니다.

투고 및 윤리 규정

목적과개요

부정맥(TheOfficialJournalofKoreanHeartRhythmSociety)

은대한심장학회부정맥연구회의주관으로발행되며,부정맥과관

련된새로운임상연구,진료지침,증례등을소개하여부정맥연

구회회원및개원의의지속적인의학교육에이바지하고자발행

되는최신학술지이다.본지는부정맥의진단과치료,임상연구

와관련된원저,종설,논평,증례보고등을편집위원회에서검토

후게재한다.

연구및출판윤리규정

본규정은대한심장학회부정맥연구회회원들의학술활동중연

구윤리를확보하는데필요한역할과책임에관하여기본적인원

칙과방향을제시하기위하여제정되었으며,각회원은연구활동

중정직성,진실성,정확성이연구결과의신뢰성확보를위한필

수조건임을인식하고모든연구활동을수행함에있어이규정을

준수하도록한다.

1.저자들은UniformRequirementsforManuscripts

SubmittedtoBiomedicalJournals(http://www.icmje.

org/)에서규정한윤리규정을준수해야한다.

2.본학술지에투고하는원고의연구대상이사람인경우는헬

싱키선언(DeclarationofHelsinki[www.wma.net])의윤

리기준에일치해야하며,기관의윤리위원회또는임상시험심사

위원회(InstitutionalReviewBoard)의승인을받고,필요한경

우에연구대상자의동의서를받았음을명시해야한다.

3.동물실험연구는실험과정이연구기관의윤리위원회의규정

이나NIHGuide for theCareandUseofLaboratory

Animals의기준에합당해야한다.

4.간행위원회는필요시환자동의서및윤리위원회승인서의

제출을요구할수있다.

5.이해관계명시(Disclosureofconflictofinterest):연구에

소요된연구비수혜내용은감사의글에필히기입해야한다.

연구에관계된주식,자문료등이해관계가있는모든것은표지

하단에밝혀져야하며,이를모두명시했음을원고의저자전원

의자필서명이있어야한다.

6.원칙적으로타지에이미게재된같은내용의원고는게재

하지않으며,본지에게재된것은타지에게재할수없다.단,독

자층이다른타언어로된학술지에게재하기위한경우등의중

복출판은양측간행위원장의허락을받고,중복출판원고표지에

각주로표시하는등,다음문헌에서규정한요건을갖춘경우에만

가능하다(AnnInternMed1997;126:36-47).

7.윤리규정및표절/중복게재/연구부정행위등모든연구윤리와

연계되는사항에대한심사및처리절차는대한의학학술지편집

인협의회에서제정한'의학논문출판윤리가이드라인(http://

kamje.or.kr/publishing_ethics.html)'을따른다.

원고범위

1.원저(OriginalArticle)는인간을대상으로한연구(임상적조사

및보고서)와동물을이용한실험및생체외실험에대한연구(

기초과학보고서)로한다.

2.종설(ReviewArticle)은특정분야나주제에관해간결하고

포괄적으로평가한논문으로위촉된종설에한하여게재하는것

을원칙으로하나편집진의재량에따라위촉되지않은종설도게

재가능하다.

3.논평(Editorial)은타학술지에게재된논문에대한저자의

견해를기술한것으로,편집진의의뢰하에쓰여진다.

4.증례보고(CaseReport)의요건은국내첫증례또는희귀

증례로제한한다.

집필규정

1.원저와증례보고는영어,종설과논평은한글을사용하여맞춤법에

맞게작성하며모든학술용어는대한의사협회에서발간한의학용

어집의최신판에수록

된용어를사용한다.

2.한글로작성하는원고는원어의적당한한글용어가없는경우한

글뒤()안에원어는표기할수있다.부득이외국어를사용할때

는대소문자의구별을정확히해야한다(예：고유명사,지명,인

명은첫글자를대문자로하고그외에는소문자로기술함을원칙

으로한다).적절한번역어가없는의학용어,고유명사,약품명,단

위등은원어를그대로사용한다.

3.번역어가있으나의미전달이명확하지않은경우에는그용어

가최초로등장할때번역어다음소괄호속에원어로표기하고

그이후로는번역어만사용한다.

4.검사실검사수치의단위는SI단위(InternationalSystemof

Units)를사용하고,편집위원회의요구나필요에따라괄호안에

비SI단위수치를첨부할수있다.

5.약자는가능한한사용하지않는것이좋지만,본문에일정용어

가반복사용됨으로인해부득이약자를사용해야하는경우

에는그용어가처음나올때괄호안에약자를함께표기하고

다음부터약자를사용할수있다.

6.원고는컴퓨터문서작성프로그램(MS워드또는한글)을사용

하여작성한다.글자의크기는명조계통의10point,정렬은좌측

정렬을하며,줄간은한글의경우160%,워드의경우1줄간격

으로하며좌우및위아래여백은3cm로한다.원고면의번호

는제목쪽부터시작하여차례대로중앙하단에표시한다.

원고의형식

1. 원저(Original Article)

표지,초록과키워드,본문,감사문,참고문헌,도표,그림/사진

설명,그림및사진의순으로하며,제목쪽과초록및참고문

헌은각각분리된쪽으로작성한다.

1) 표지(Title Page)

①제목,소속,저자명,영문제목및영문소제목(빈칸을포함

하여50자이내),영문저자명,영문소속순으로하며,표지

하단에교신저자(correspondingauthor)의이름,주소,소속,

전화번호,팩스번호,E-mail주소등을명시해야한다.

②저자들의소속이다수인경우소속명을같은행에연이어

나열하며,아라비아숫자의어깨번호로소속과저자명을

일치시킨다.영문저자명뒤의MD나PhD등에는글자다

음에구두점을찍지않는다.

2) 초록과 키워드(Abstracts and Key Words)

모든원고에는영문초록을첨부해야하며,초록은250단어이

내로한다.BackgroundandObjectives,Subjects(Materials)

andMethods,Results,Conclusion의순으로구분하여소제

목에따라줄바꿈없이작성한다.증례보고인경우소제목없

이가능하며,초록은150단어이내로한다.단논평의경우초

록과keywords를첨부하지않는다.그리고각초록의말미에

Indexmedicus에등재된용어5개이내로영문keywords를

삽입한다.

3) 본문(Text)

서론,대상(재료)및방법,결과,고찰,요약,중심단어순으로

작성한다.

①서론에는연구와관련된간략한배경과연구의목적이언급

되어야한다.

②대상(재료)및방법은매우상세히기재해야하며결과의통

계적검증방법도밝혀야한다.

③고찰은연구결과와연관된새롭고중요한측면에대한내용

으로제한한다.

④요약은결과와고찰로부터유도되고,서론에서언급한연구

목적과부합되어야하며,결과의단순한요약은금한다.

요약의구성은배경및목적,방법,결과,결론의순으로구

분하여소제목에따라줄바꿔작성한다.그리고국문논문은

요약다음에한글중심단어를초록의영문중심단어와일치시

켜삽입한다.

4) 감사문(Acknowledgments)

감사문에는본연구의연구비지원기관,본연구를수행하는데

여러가지로도움을주었던분들에대한사항을기술한다.

5) 참고문헌(References)

①원저는30개이하,증례보고는20개이하로제한한다.종설

은참고문헌수를제한하지않는다.

②참고문헌은본문에나타난것만인용한다.본문에서는인용

순서에따라아라비아숫자로저자명뒤또는문장끝에어

깨번호로표시한다.참고문헌의배열도인용한순서대로작

성한다.동일저자의경우연도순으로나열하며,국내문헌도

영문표기를원칙으로한다.

③참고문헌의저자는모두기재한다.저자표기는lastname은

다쓰고,firstname과secondname은첫글자를대문자로

붙이고initial에마침표(.)는사용하지않는다.저자명사이

에는쉼표(,)로구분하고,마지막저자명뒤에는마침표(.)

를찍는다.

④잡지명은‘ListofJournalsIndexMedicus’에의거약어로

기재하며,인용학술지명뒤에는마침표를찍는다.인용논문

의제목중첫글자는대문자로하고,부제목이있는경우

쌍점(：)을붙인후소문자로기재하며제목뒤에는마침표

(.)로표시하며,연도를표시한후쌍반점(；)으로붙여서구

분후,권：시작쪽-끝쪽의전체페이지를기재하며,마지막

에마침표를찍는다.

예)SmithHJ,AllenS,YuW,FardS.Thisisthetitle.

Circulation.2004;104:276-308.

6) 표(Table)

①표는영문과아라비아숫자로기록하며표의제목을명료하게

절혹은구의형태로기술한다.문장의첫자를대문자로한다.

②분량은4줄이상의자료를포함하여1쪽을넘지않는다.

③본문에서인용되는순서대로번호를붙인다.

④약어를사용할때는해당표의하단에알파벳순으로풀어서

설명한다.

⑤기호를사용할때는*,†,‡,§,‖,¶,**,††,‡‡의

순으로하며이를하단각주에설명한다.

⑥표의내용은이해하기쉬워야하며,독자적기능을할수있

어야한다.

⑦표를본문에서인용할때는영문(Table1과같이)을사용한다.

7) 그림 및 사진(Figure)

①그림및사진은‘ppt’파일형식으로원문과별도의파일을만

들어서제출한다.

②동일번호에서2개이상의그림이필요한경우에는아라비아

숫자이후에알파벳글자를기입하여표시한다(예:Figure

1A,Figure1B).

③그림을본문에서인용할때에는한글(Figure1과같이)을사

용한다.

④최종통과시그림및사진은‘jpg’파일형식으로1장씩10메

가이내로파일을만들어서제출한다.

8) 그림 및 사진 설명(Figure Legends)

①본문에인용된순으로아라비아숫자로번호를붙인다.

②모든그림및사진은설명이있어야하며,별지에영문으로

구나절이아닌문장형태로기술한다.

③현미경사진의경우배율을기록한다.

2. 원저 이외의 원고

일반사항은원저에준한다.

1) 종설(Review Article)

종설은특정제목에초점을맞춘고찰로서편집위원회에서위촉

혹은투고에의하여게재한다.단,투고된원고는심사를거쳐게

재여부를결정한다.

2) 증례 보고(Case Report)

①전체분량이A4용지10매이내로작성한다.

②영문초록은항목구분없이150단어이내로한다.

③고찰은증례가강조하고있는특정부분에초점을맞추며

장황한문헌고찰은피한다.

④참고문헌의수는20개이내,그림은5장이내로한다.

⑤저자수는7명이내로한다.

3) 논평(Editorial)

학회지에출판된특정논문에대한논평을의뢰받아집필되는부

문으로학회의의견을반영하는것은아니다.원고는A4용지4

매이내로작성하고참고문헌은10개이내로제한한다.

기타사항

1.본학회지는연간4회(3,6,9,12월말일)발간한다.

2.필요할경우원문에영향을미치지않는범위내에서자구와

체제를편집방침에따라편집위원이수정할수있다.

3.원고의게재여부는원고심사후편집위원회에서결정하며

본규정에맞지않는원고는개정을권유하거나게재를보류할

수있다.

4.학회지의게재는원고의저작권이저자로부터학회지로이양

되는것을저자가승인한것으로인정한다.

5.원고제출처

•부정맥연구회온라인논문투고사이트

http://arrhythmia.medimedia.co.kr

•엠엠케이커뮤니케이션즈(주)

E-mail:[email protected]

주소:서울시강남구논현로523,노바빌딩3층

(135-909)

전화:82-2-2007-5435팩스:82-2-3452-5984

저자 점검표

•저자(소속): •논문제목:

다음은귀하가본부정맥(TheOfficialJournalofKoreanHeartRhythmSociety)에투고하는논문이투고규정에맞도록각항목별

로충실히작성되어있는지점검하는저자점검표입니다.논문투고시해당칸에표시하여논문과함께반드시제출하여주십시오.

일반사항

1.본논문의내용은다른학회지에게재되지않았고,게재예정도없다 ☐2.원고는A4용지10포인트크기로여백상,하,좌,우3.5,3,3,3cm,줄간격1기준으로작성하였다 ☐3.원저는표지,영문초록,서론,본론,결론,참고문헌,Table,Figure순서의양식으로구성하며,본론은소제목으로구분한다 ☐4.증례는표지,영문초록,서론,증례,고찰,참고문헌,Table,Figure순서의양식으로구성한다 ☐5.일련쪽수를하단에기재하였다 ☐

표지

1.논문제목 ☐2.저자소속,이름 ☐3.영문제목,영어저자명,영어소속 ☐4.요약제목(Runningtitle)-국문제목30자이상,영문제목12단어이상 ☐5.책임저자이름,주소,전화,Fax,전자우편주소 ☐6.연구비에대한사항을각주에적었다(해당되는경우) ☐

영문 초록

1.영문제목이한글제목과일치하도록작성,영문성명,영문소속의올바른기재 ☐2.원저는내용을Background,Objective,Method,Result,Conclusion으로규정된형식으로작성하였다 ☐3.증례는내용을한단락(paragraph)으로작성하였다 ☐4.KeyWords3-5개를MeSH에맞게작성하였다 ☐

본문

1.한글로사용가능한용어는한글로기재하였다 ☐2.본문중해당참고문헌의어깨번호를표시하였다 ☐

참고문헌

1.투고규정준수에맞게모두영문으로작성하여PubMed와KorMed에서확인하였다 ☐2.참고문헌의모든공저자를기재하였다 ☐3.학술지표기는IndexMedicus의공인된약어를사용하였다 ☐4.학술지를이탤릭체로표기하였다 ☐

Table과 Figure

1.Table과Figure는중복되지않도록작성하였다 ☐2.Table과Figure는투고규정에맞도록작성하였다 ☐3.제목및설명모두영문으로기재하였다 ☐4.제목에서약자를사용하지않으며,Table과Figure에사용된약자는하단에설명을기재하였다 ☐

본논문의저자(들)은부정맥(TheOfficialJournalofKoreanHeartRhythmSociety)의투고규정에따른

위의사항들을확인하였으며,논문게재를요청합니다.

20년월일

저자대표________________________(서명)

저작권 이양 동의서

논문 제목

•국 문

•영 문

본 논문의 저자(들)은 본 논문의 부정맥(The Official Journal of Korean Heart Rhythm Society) 게재를 바라며, 이에 다음 사

항들에 대하여 동의합니다.

1.본논문의저자(들)은본논문이창의적이며,다른논문의저작권침해,비방,혹은사적침해등내포하지않음을확인합니다.

2.본논문의저자(들)은본논문에실제적이고지적인공헌을하였으며,본논문의내용에대하여공적인책임을공유합니다.

3.본논문은과거에출판된적이없으며,현재다른학술지에게재를목적으로제출되었거나제출할계획이없습니다.

4.본논문의저자(들)은본논문이부정맥(TheOfficialJournalofKoreanHeartRhythmSociety)에게재될경우,저작권에

관한모든권리,이익및저작권에대한모든권한행사등을대한심장학회부정맥연구회에이양하기로동의합니다.이는저자(들)이

향후다른논문에본논문의자료를사용할경우대한심장학회부정맥연구회로부터서면허가를받아야하며,이경우자료가발표된

원논문을밝혀야하다는것을의미합니다.

년월일

저자 성명 서명 저자 성명 서명

책임저자 제5저자

제1저자 제6저자




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