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1 종설 Korean Circulation J 2003;33(7): 심방세동의약물치료와침습적치료 고려대학교의과대학안암병원순환기내과학교실 김영훈 Rhythm Control Versus Rate Control of Atrial Fibrillation: Pharmacologic and Non-Pharmacologic Therapy Young-Hoon Kim, MD Department of Internal Medicine, Korea University, Medicine College, Seoul, Korea ABSTRACT Considerable controversy exists as to whether rhythm or rate control is the more appropriate management for the patients with persistent atrial fibrillation (AF). Until recently, it was our belief that the initial approach to rhythm management should give primary consideration to the restoration and maintenance of the sinus rhythm (SR), which provides the potential benefits of reducing the risk of thromboembolism and the need for anticoagulants, and improved the hemodynamics and quality of life. However, there are negative aspects of rhythm control, including the poor efficacy of the antiarrhythmic drugs and the potential of adverse effects. Five recent clinical trials;affirm (The Atrial Fibrillation Follow-Up Investigation of Rhythm Management), RACE (Rate Control versus Electrical Cardioversion), PIAF (Pharmacological Intervention in Atrial Fibrillation), HOT CAFE (How to Treat patients with Chronic Atrial Fibrillation) and STAF (The Strategies of Treatment of Atrial Fibrillation), have looked specifically at the issue of the balance between the benefits and risks of restoration and maintenance of the SR, primarily with drug therapy. The conclusions of these trials were consistent, although the study subjects were heterogeneous;1) Rhythm control, with anti-arrhythmics, does not lead to an improvement in the symptom control, quality of life or a reduction in the short to median term clinical events, in fact, in the longer term the mortality may increase. 2) Maintenance of the SR remains poor, even with an aggressive strategy. Hence, long term anticoagulation is needed for most patients treated with rhythm control, even if the SR is restored in the short term. A number of non-pharmacological therapies have emerged, such as catheter ablation and pacing, for patients remaining highly symptomatic, despite the use of several anti-arrhythmics and serial electrical cardioversion. In conclusions, rate control should be considered as the initial strategy in the majority of the patients with persistent AF. For the minority that remain highly symptomatic, aggressive rhythm control, with invasive treatments, such as pulmonary vein isolation or rate control, with atrioventricular nodal ablation and ventricular pacing, should be considered. (Korean Circulation J 2003;33 (7): KEY WORDS:Atrial fibrillation;antiarrhythmia agents;catheter ablation. 서 심방세동은임상에서접하는지속성빈맥중에서가 교신저자 : 김영훈, 서울성북구안암동 5 가 고려대학교의과대학안암병원순환기내과학교실전화 :(02) 전송 :(02) yhkmd@unitel.co.kr 론 장흔한것으로전체인구의약 0.5% 유병률을보이고있으며연령증가에따라유병률이현저히증가하여심방세동환자의 70% 이상은 65세와 85세사이의연령층에서발생된다. 1) 심방세동이임상적으로문제가되는이유는심부전과뇌졸중과밀접한연관이있기때문인데정상인에비해심방세동환자는약 2배이상높은심혈관계질환으로의이환률과사망률을보이며 50 세 553

2 이상이되면뇌졸중의위험률이매연령층마다 2~3 배올라가 50 대에는 1.5% 이던것이 80 대로가면 23.5% 로올라가게된다. 2) 따라서지속성심방세동환자를가능한한정상동조율로전환시키고유지할수있는치료법은가장이상적인것이라고할수있겠으나때로는얻는것보다잃는것이더많은경우가있어환자마다올바른치료방침을정하기가쉽지않을때가있다. 율동치료 (Rhythm Control) 와심실반응수조절 (Rate Control) 의비교 최근심방세동의치료방침을결정하는데에중요한자료가될만한연구결과가연이어보고되었다. 대규모환자를대상으로심실반응수의조절 (rate control) 법과율동치료요법 (rhythm control) 의효과를판정한 AFFIRM 3) 과 RACE 4) 연구가그것이며이보다규모가적은연구인 PIAF, 5) HOT CAFE 6) 및 STAF 7) 연구들도최근에발표된것이다. 이상의연구결과가보고되기이전에는정상율동으로의전환및유지요법이심실반응수의조절에비해분명히이로울것이라고판단되어온것이사실이다. 이는정상율동으로의유지가심박출량의증강, 생활의질적향상, 뇌졸중의위험감소및장기간항응고요법이필요없다는장점등이있기때문이었다. 그러나율동전환유지를위해항부정맥제를투여하고몇번에걸쳐전기충격요법에의한율동전환을시도한다고하여도 1년후에는 53%, 8) 5년후에는오직 25% 9) 의환자가정상율동의상태로유지되는결과를보이고모든항부정맥약제에서피할수없는다양한종류의부작용이있다는점등으로인해과연율동치료가심실반응수조절에비해환자에게실질적인도움을줄수있는가에대한논란이제기되기에이른것이다. 554 각연구의대상, 방법및결과 PIAF 5) 는이를전향적으로규명하기위한첫번째연구로서 1년미만의지속성심방세동 252 명을대상으로한것으로서 1년후양군간에증상의개선정도에는유의한차이가없었다. 오히려율동치료군에서입원률이높았고약제에의한부작용이흔한것으로나타났다. 이연구는증상이현저한젊은 ( 평균연령 :60 세 ) 연령 층의환자를대상으로한것이며비교적짧은 (1년 ) 추적관찰기간이제한점이다. HOT CAFE 6) 연구도 PIAF에서와같이평균 61세의 205 명의환자를약 1년간관찰한것으로결과도유사하였다. 1년후율동치료군에서운동능력의개선이있었던반면입원률은심실반응조절군에비해유의하게높았다. STAF 연구 7) 는위의 2 연구들에비해추적기간이 19.6 개월로길었으나대상환자는 200 명으로많지않은숫자이었으며이들의평균연령은 66세이었다. 양군간에사망률, 심폐소생술, 뇌졸중및색전증의빈도에역시차이를보이지않았다. 율동치료군에서 4번까지의전기적율동전환요법과 3~4 종류의다른항부정맥제를이용하여정상율동유지를시도하였으나 3년후에정상율동을보인환자는 23% 에불과하여율동치료의한계점을명확하게확인시켜준연구이었다. AFFIRM 3) 연구는 4,060 명의환자 ( 평균연령 :69.7 세 ) 를대상으로평균 3.5 년을추적관찰한것인반면 RACE 연구 4) 는 522 명 ( 평균연령 :68세 ) 을대상으로 2.3 년을관찰한것이었다. RACE 연구는동율동전환요법이요구되는지속성심방세동환자만을대상으로하였으나 AFFIRM 연구에서는발작성심방세동의환자도포함되어약 30% 의환자가심방세동의첫번째에피소드이후이었다. 이러한대상환자의차이가 AFFIRM 환자군 (5년후, 62.6 %) 에서 RACE(3년후, 39%) 에비해정상리듬으로유지되는빈도가높은결과의이유일것으로판단된다. RACE 연구에서사용된항부정맥제는임상적으로흔히쓰이는방식에의거, sotalol, class 1C 및 amiodarone 을순차적으로투여한반면 AFFIRM 에서는의사개개인의판단에맡겼으며대부분의환자에서 amiodarone(37.5%) 이일차약제로투여되었다. 양연구의대상환자는색전증의위험인자를적어도하나이상가지고있다는점이공통된것이었는데그외에는대상환자의특징이나연구방법이약간씩차이가있었다. 그러나연구결과는매우유사하여심실반응수의조절과율동치료군사이에전체사망률, 심인성사망, 뇌졸중, 또는출혈등의빈도등이유의한차이가없었다. AFFIRM 에서는오히려율동치료군에서통계적인유의성은없었으나심실반응조절군에비해전체사망률이증가되는경향을보였다. 또 AFFIRM 연구의율동치료군에서위의다른보고에서와같이율동전환치료 Korean Circulation J 2003;33(7):

3 를위해병원에입원한빈도가높았으며 torsades de pointes 의빈도가많았다. 양연구에서적절치못한항응고요법을받은환자에서색전증의위험률이증가되었으며 coumadin 복용후 INR 3 이상인환자에서는출혈의빈도가유의하게높았다. 임상적의의, 제한점및결론 AFFIRM 과 RACE 연구에서동일하게 INR 2 이하의부적절한항응고요법을하게되면색전증의빈도가증가된결과를보였다. 이는색전증의위험인자를가지고있는심방세동환자의치료후정상동조율로유지되더라도장기적이고도적절한항응고요법이반드시필요하다는것을나타내는소견이다. 심방세동환자에서정상리듬으로유지되는것으로간주되는환자중아무런증상없이도심방세동이빈번하게나타날수있다고알려져있는데이때적절치못한항응고요법을하거나조기에항응고요법을중단하게되면색전증의위험이증가될수있는것이다. 심방세동의에피소드진단을기존심전도모니터링에만의존할경우에는심방세동의출현양상을파악하는데에적지않은문제점이있다는것을염두에두어야한다. 양연구에서의대상환자의평균연령은각각 69세, 68세이었는데젊은연령층의심방세동환자, 특히구조적인심장질환이없는 lone AF환자들에게도이연구결과를그대로적용시켜치료방침을정하는데에는무리가많다고본다. 이러한젊은환자군에서정상율동으로의유지는생활의질을높여줄뿐만아니라색전증이나약제에대한중증부작용이적으므로보다적극적인율동전환및유지요법이필요할것이기때문이다. 그러므로기저심장질환이없고뇌졸중의위험이낮은젊은연령층의심방세동환자에서는각개인별적절한약물요법또는침습적인치료법을선택하는것이바람직하다고하겠다. 이상의 5개연구의결과를종합해보면다음과같다. 1) 현재상용되고있는항부정맥제에의한율동치료는심실반응수의조절에비해증상및생활의질개선과사망률등을감소시키는효과가우수하지못하였다. 2) 중장기추적관찰시전기충격에의한율동전환요법을여러번시도하는등적극적인방법을동원하여도정상율동이유지되는환자의비율이매우낮았다. 3) 율동치료로정상율동이유지된다고하여도항응고요법은장기간계속하는것이바람직하다. 그러므로심실반응수의조절요법은지속성심방세동의치료에가장우선적으로고려할수있는효과적인방법이라고하겠다. 약제에의한심실반응수의조절에실패한환자가심한증상을호소할때는다음단계로항부정맥제의투여를고려하고그래도증상이지속될경우에는약제뿐만아니라최근시도되고있는고주파에너지에의한폐정맥분리술또는개흉에의한 maze 수술또는심도자법에의한방실결절절제후심장박동보조기삽입술도다음단계의치료법으로고려해보아야한다. 반면증상이경미하거나없는환자에서는율동전환을위한약물또는침습적인치료가별로도움이되지않는다. 심방세동으로인한증상이거의없는 60~70 대연령층의환자가율동전환요법을강력히원하는경우에도이상에서언급한연구들의결과를토대로장기간의율동전환및유지요법이심실반응수의조절에비해결코나을것이없다는점을환자에게설명할필요가있겠다. 심실반응수의조절은대부분약제에의해가능하나 RACE 연구에서는심실반응조절군의 5% 환자가약제에듣지않아직류전기충격요법으로율동전환을시행받거나고주파에의해방실접합부의절제후영구심박동보조기삽입수술을시행받았다. 또 AFFIRM 연구에서는심실반응수조절군의 14% 환자에서약제의부작용으로인해약을중단하였고 20% 에서사망, 뇌졸중, 출혈, 또는심장정지등이합병되었었다. 이러한결과는현재이용되고있는심실반응수의조절요법도율동전환요법과마찬가지로앞으로개선되어야할부분이많다는것을나타낸다. 침습적치료 심박동기요법방실결절절제후심박동기삽입시술과약제에의한심실반응수의조절의비교방실결절절제후심박동기삽입시술 (ablate and pace) 은약물에의해서심실반응수가적절히조절되지않고증상이심한심방세동환자의증상과심실기 555

4 능을개선하는데에매우효과적인것으로알려지면서현재까지많이시행되고있는방법이다. 10)11) 최근에발표된 AIRCRAFT(The Australian Intervention Randomized Control of Rate in Atrial Fibrillation) 12) 는심방세동으로인한증상이비교적경미한환자만을대상으로위의두치료법을비교한것인데양군간에심장수축기기능이나운동능력에는별차이를유발하지않았으나방실결절절제후심박동기삽입군에서생활의질이유의하게개선된결과를보였다. 이는심방동기요법을영구적인심방세동환자에서보다폭넓게적용할수있음을보여주는결과이다. 심방세동억제기능을가진심박동기심한서맥후심방세동이흔히나타나는경우, 즉미주신경매개성심방세동과빈번한심방조기수축후심방세동이유발되는경우는심방 pacing 에의해조기수축자체를억제 (overdrive suppression) 하거나조기수축발생부위의반대편 1~2 곳에 pacing 함으로써심방세동을예방하는효과가있다고한다. 13) 또심방내전도차단 (intraatrial conduction block) 또는좌우심방간전도차단및지연이있을때특히박동기요법이심방세동의발생을억제하게된다. 14) 우심방내 2 곳을 pacing 하거나좌우심방 ( 우심방과관정맥동 ) 의생리적조율 (biatrial synchronous pacing) 에의해심방세동의재발뿐만아니라항부정맥제의복용량도줄일수있는것으로알려지고있다. 15)16) 심도자를이용한심방세동의절제 Maze 수술요법이심방세동을제거하는데효과적인것으로인정되면서심도자에의한 maze 요법이응용되기시작하였는데심방에고주파에너지를이용해여러개의차단선을만들어심방내다발성회귀가존재할수없도록만드는것이다. 시술시간이길며정확한해부학적인지표가없고병변의깊이나넓이의파악이쉽지않은점들로인해이시술이보편화되지는못했으며효과와안전성에대해서는앞으로체계적인연구를통해밝혀지리라본다. 반면나이가젊고기저심장질환이없으면서심방조기수축이나심방빈맥이선행한후심방세동으로빈번히전환되는발작성심방세동은이때까지알려져왔었던다발성회귀파형에의한심방세동이아니라국 556 소, 특히폐정맥의개구부또는폐정맥과좌심방의연결부위약 1~2 cm 이내에서매우빠르고불규칙적인자극이형성되는국소성심방세동으로분류되고있다. 빈번히심방조기수축이선행되고이로인해심방세동이쉽게유발될때폐정맥내원인병소만을국소적으로절제한후에는중장기추적결과재발이많은것으로알려져있는데이는동일한폐정맥내다른병소에의해서심방세동이촉발될수있기때문이다. 따라서원인폐정맥의좌심방과의연결부위 (ostium) 를좌심방과완전분리하는것이보다효과적인치료법으로인정되고있다 ) 이때심방세동원인폐정맥만을분리하느냐아니면 4개의폐정맥전체를각각좌심방으로부터분리할것이냐에대해서는아직은논란이있는상태이다. 나이가젊고기질적인심질환이없으면서동일한폐정맥에서유래된심방조기수축에의한심방세동이일관되게유발될때는원인폐정맥만을완전분리해도심방세동을근치시킬수있으리라예상되나이를규명하기위해서는향후많은환자를대상으로전향적인연구가있어야할것이다. 심도자법에의한심방세동의치료성공률은대개 40~85% 정도로알려지고있다 ) 심방세동을촉발하는심방조기수축의발생부위가 2~4 개로다발성일경우성공률이현저히감소된다. 또시술당시심방세동의원인이되는심방조기수축이충분히나타나지않을때는처음부터 4개의폐정맥과좌심방의접합부위를분리시키는방법을쓰게되는데이때폐정맥과관계없는다른부위에원인이숨어있는경우가있으면심방세동의완전제거에실패하게된다. 따라서 Isoproterenol(3~10 ug/min) 의주입후출현한심방조기수축과이로인해촉발된심방세동을분석함으로써원인부위색출을시도하는데비교적효과적인것으로알려져있다. 좌심방과폐정맥을효과적으로분리시키기위해폐정맥개구부의전기적양상과폐정맥전위 (pulmonary vein potential) 를기록할수있는 ring형태의전극도자 (Lasso, Spiral) 17-19) 가널리이용되고있으며최근에는 3차원고해상시스템 (CARTO, 24-26) EnSite 28-30) 을이용한좌심방-폐정맥분리술이효과적인방법으로다양하게시도되고있다. 폐정맥분리술의가장큰제한점은폐정맥협착등의합병증인데폐정맥내고주파에너지를투여할때는 50, Korean Circulation J 2003;33(7):

5 30 watt 이하, 폐정맥개구부위나좌심방-폐정맥접합부에는 55, 40 watt 정도의제한된에너지를선택하면폐정맥협착의빈도를현저히줄일수있는것으로알려져있다. 장기적인추적관찰결과가나오면보다확립된에너지양이나방법등이제시될수있을것이다. 심방세동의수술적치료현재까지심방세동의수술적요법은변형된 maze 수술 (Maze Ⅲ) 과좌심방분리술이가장효과적인방법으로알려져있다. 심방세동에서수술적치료는 1) 심방세동의제거 2) 동결절기능의보전 3) 방실전도의유지및 4) 심방기능의회복등을목표로한다. Maze 수술은좌우심방을마치미로와같이여러구획으로나누어한부위에라도심방세동의유지에필요한파형이존재하지못하도록하는시술이다. 성공율은 80~95% 정도이다. 좌우심방의기능회복에는 2~3개월이소요되므로수술후적어도 3~6 개월간은항응고요법을하는것이좋다. 좌심방분리술은판막질환등으로개흉술을시행할때추가로좌심방, 특히폐정맥부위를절개하여분리하는방법으로서성공율이 85~90% 정도이고추적관찰시동율동으로의유지율도높은것으로알려져있으나심방세동만을가진환자를위해개흉술을통한수술요법은국내에서아직보편화되어있지않다. 결 현재까지심방세동의가장적절한치료법이무엇인가에대한정답은없는것이사실이다. 색전증의위험이높은심방세동환자에서심실반응수의조절요법은율동유지요법과비슷한정도로효과가있으나양치료법에는개선되어야할여지가많은것이사실이다. 보다효과적인항부정맥제의개발과보다간편하고안전하게심방세동근치를가능케할심도자법등의개발은이분야에서절실한연구과제가되고있다. 론 중심단어 : 심방세동 ; 항부정맥제 ; 도자절제술. REFERENCES 1) Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, Hart RG. Prevalence, age distribution, and gender of patients with atrial fibrillation: analysis and implications. Arch Intern Med 1995;155: ) Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke. Stroke 1991;22: ) Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347: ) van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermans AJ, Tijssen JG, Crijns HJ. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347: ) Hohnloser SH, Kuck H-H, Lilienthal J. Rhythm or ratecontrol in atrial fibrillation: a randomized trial. Lancet 2000; 356: ) Opolski C, Torbicki A, Kosior D, Szulc M, Wretowski D, Zawadzka M. Rate control in patients with non valvular clironic atrial fibrillation. Eur Heart J 2002;4(suppl):486. 7) Carlsson J, Miketic S, Windeler J, Cuneo A, Haun S, Micus S, Walter S, Tebbe U. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation. J Am Coll Cardiol 2003;41: ) Bertaglia E, D Este D, Zerbo F, Zoppo F, Delise P, Pascotto P. Success of serial external electrical cardioversion of persistent atrial fibrillation in maintaining sinus rhythm; a randomized study. Eur Heart J 2002;23: ) van Gelder IC, Crijns HJ, Tieleman RG, Brugemann J, de Kam PJ, Gosselink AT, Verheugt FW, Lie KI. Chronic atrial fibrillation: success of serial cardioversion therapy and safety of oral anticoagulation. Arch Intern Med 1996;156: ) Brignole M, Menozzi C, Gianfranchi L, Musso G, Mureddu R, Bottoni N, Lolli G. Assessment of atrioventricular junction ablation and VVIR pacemaker versus pharmacologic treatment in patients with heart failure and chronic atrial fibrillation: a randomized, controlled study. Circulation 1998; 98: ) Ueng KC, Tsai TP, Tsai CF, Wu DJ, Lin CS, Lee SH, Chen SA. Acute and long-term effects of atrioventricular junction ablation and VVIR pacemaker in symptomatic patients with chronic lone atrial fibrillation and normal ventricular response. J Cardiovasc Electrophysiol 2001;12: ) Weerasooriya R, Davis M, Powell A, Szili-Torok T, Shah C, Whalley D, Kanagaratnam L, Heddle W, Leitch J, Perks A, Ferguson L, Bulsara M. The Australian Intervention Randomized Control of Rate in Atrial Fibrillation Trial. J Am Coll Cardiol 2003;41: ) Lee MA, Weachter R, Pollak S, Kremers MS, Naik AM, Silverman R, Tuzi J, Wang W, Johnson LJ, Euler DE. The effect of atrial pacing therapies on atrial tachyarrhythmia burden and frequency: results of a randomized trial in patients with bradycardia and atrial tachyarrhythmias. J Am Coll Cardiol 2003;41: ) Savelieva I, Camm AJ. The results of pacing trials for the prevention and termination of atrial tachyarrhythmias: is there any evidence of therapeutic breakthrough? J Interv Card Electrophysiol 2003;8: ) Saksena S, Prakash A, Ziegler P, Hummel JD, Friedman P, Plumb VJ, Wyse DG, Johnson E, Fitts S, Mehra R. Improved suppression of recurrent atrial fibrillation with dual-site right atrial pacing and antiarrhythmic drug therapy. J Am 557

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13.ÀÇÇÐ°�ÁÂb61è¿µÈÆ837~845’ J KMA Continuing Education Column Catheter Ablation of Atrial Fibrillation Young Hoon Kim, MD Division of Cardiology, Korea University College of Medicine E mail : yhkmd@unitel.co.kr J Korean Med Assoc