선천성심장병수술후발생한심실빈맥의치료 경북의대소아과 현명철 서론 선천성심장병수술후조기에는여러종류의부정맥이발생할수있으나이에대한보고는많지않으며보고자에따라 15%-48%(1-3) 까지보고되고있다. 심폐우회술기술과심근보호법의발달, 수술기법의발달로현재수술후조기에발생하는부정맥의빈도는과거에비해많이감소했으리라생각된다. 그러나더욱중요한부정맥은선천성심장병수술후후기에발생하는부정맥이다. 선천성심장병에대한수술기술이수십년간엄청난발전을보여과거영아기에사망하였던많은환자들이청소년기, 성인기까지삶을영위하게되었다. 한편이와같이생존율의향상으로결국많은선천성심장병환자들이수술후후기후유증을경험하게되었고이들을잘관리치료하는것이아주중요한문제가되기시작하였으며, 후기후유증중의가장대표적인것이부정맥의발생이다 (Table 1). 부정맥중특히심실빈맥에대한보고는활로사징수술후후기에발생하는심실빈맥에대한보고가대부분이고, 이에대한기전및치료등이대다수를이루며, 심실빈맥치료를대표하므로이에대해알아보고자한다. 그러나대규모의연구는거의없어서객관적인치료지침을만들기에는부족하고, 자연경과및적절한처치및예방에대한이해도아직은불완전한상태이다. Table 1. Arrhythmias and commonly associated congenital heart defects Tachycardias Wolff-Parkinson-White -Ebstein`s anomaly
Syndrome Intraatrial reentrant Tachycardia - Corrected transposition -Postoperative Mustard -Postoperative Senning -Postoperative Fontan -Other Atrial fibrillation -Mitral valve disease -Aortic stenosis -Single ventricle Ventricular tachycardia -Tetralogy of Fallot -Other Bradycardias SA node dysfunction -Postoperative Mustard -Postoperative Senning -Postoperative Fontan -Other Congenital AV block -Endocardial cushion defects - Corrected transposition Acquired AV block -VSD closure -Tetralogy of Fallot repair -Other 본론 선천성심장병수술후조기에발생하는심실빈맥 선천성심장병수술후조기에는심폐우회술의사용, 심근보호법등을사용한심장병수술후심기능이상이회복되는시기이면서, 저산소증, 전해질불균형, catecholamine 등심장에자극적인약물의사용, 심근에자극적인봉합선과상처, 잔존하는혈역학적인이상, 고통, 걱정등이원인이되어부정맥이발생하게된다. 대혈관전위에서대혈관치환술후
2-7%(4, 5), Fontan 수술후 3-12%(6-8), Ebstein s anomaly 수술후 13% 에서 (9) 심실부정맥이발생하였다고한다. 최근 Delaney 등 (1) 의보고에의하면수술후조기에발생한의미있는부정맥 ( 부정맥에대한조치나치료가필요하였던경우를의미 ) 은약 15% 에서발생하였고 (28/189명), 접합부이소성빈맥 (16명, 8.5%), 완전방실차단 (7명, 3.7%), 심실빈맥 (4명, 2.1%) 의순으로많이발생했으며, 환자의나이가어릴수록, 심폐우회시간이길수록, ACC time이길수록잘발생하며, 방실중격결손수술시가장많이발생함을보고하였다 (Table-2)(Table-3).
선천성심장병수술후조기에발생하는심실빈맥의치료는보통심실빈맥의치료와같다. 먼저환자가혈역학적으로불안정하면동기성직류심율동전환을먼저시행한다. 환자의상태가혈역학적으로안정되어있거나혹은동기성직류심율동전환에듣지않는경우는약물치료를시행한다. 보통 lidocaine을먼저사용하며 (1mg/kg), procainamide를사용하거나, 안되면 amiodarone을사용해본다. 일부의사들은 lidocaine의 negative inotropic effect때문에 amiodarone을더선호하기도한다. 만약심실빈맥의형태가다형성심실빈맥 (Torsades de Pointes:TdP) 이면먼저 Magnesium sulphate 를 iv bolus 로 15-30mg/kg 로 slowly iv 후 15mg/kg/min로 infusion 하는것이효과가있다. 이때 lidocaine은 TdP의치료에사용될수있으나, procainamide나 amiodarone은 QT interval을증가시키므로사용하면안된다. 이런치료와동시에전해질이상교정, 여러부정맥의원인을교정, 부정맥을일으킬수있는약제들의사용을감량혹은중단의조치등을동시에시행해본다. 대개수술후조기에오는심실빈맥은일시적이며장기적인치료가필요없다. 그러나가능성있는원인을교정후에도심실빈맥이지속된다면, 잔존혈역학적이상, 현재혈역학적상태등을보기위해심도자검사및심장전기생리검사를시행한후장기치료를결정하는것이좋을것같다. 선천성심장병수술후후기에오는심실빈맥의치료 활로사징수술후후기에오는심실빈맥이선천성심장병수술후후기에오는심실성부정맥의본보기가되며, 활로사징수술후후기심실빈맥의치료원칙이선천성심장병수술후심실상처에의해오는심실빈맥에적용된다. 그러므로활로사징수술후후기에오는심실빈맥에대해서알아보도록한다. 선천성심장병의빈도는살아출생한신생아 1000명당 4-6명정도이며이중약 10% 가활로사징이다. 또한수술기법의발달로수술한활로사징환자의생존율은 30세에 90% 를넘는다 (10). 수술한활로사징의후기합병증인급사 (1.5-4.5명사망 /1000 patient years) 의가장중요한원인이심실성빈맥이다 (11). 그러므로이런급사의위험성이있는환자를
찾아내어올바른처치를해주는것이매우중요하다. 활로사징수술후후기에오는심실빈맥은거의한가지모양 (momorphic) 의심실빈맥이며, 재입기전에의해발생한다. 대개수술에의해생기는심실의상처 (ventroculotomy scar, VSD patch 등 ) 가 substrate 로작용하며, modulating factor로는심실확장 ( 상처를 stretch 시킴 ), 심실비대, 섬유화, 전해질불균형 ( 이뇨제사용 ), catecholamine level(exercise/stress level), 서맥성부정맥, proarrhythmic drug의사용등이작용한다. Triggering factor로는주로심실조기수축이관여하며, 가끔은심방조기수축이관여되기도한다 ( 그림-1). Ventricular scar by Op : Substrate VT S D V. dialtation(scar stretch) Hypertrophy, Fibrosis Electrolyte imbalance Catecholamine level (exercise/ stress) Bradyarrhythmia Proarrhythmic drug 사용 Triggers 1. 주로 PVC 2. 가끔 PAC Modulating Factors Fig-1. Triangular model of factors causing/influencing occurrence of VT and sudden death 즉수술로인한상처부위가섬유성-지방질로대치되어 substrate로작용하고, 심실확장으로상처부위의분극과재분극 (depolarization and repolarization) 의이상을초래하고, 심실조기수축등에의해재입심실빈맥을일으키는것으로생각된다. 따라서심실빈맥의발생의예방과치료는심실빈맥의 substrate를감소시키는방향으로, modulating factor를감소시키는방향으로, trigger를없애는방향으로나아가게된다. 활로사징수술후후기에심실빈맥발생의위험인자는과거에는수술후잔존우심실유출로협착이있는경우 ( 우심실수축기압 > 60mmHg, 우심실-폐동맥압력차 > 40mmHg) 에위험성이높다고생각했으나현재는그렇게큰관련은없는것으로알려져있으며, 심한폐동맥역류의유무가가장중요한위험인자로알려져있다 (12, 13). 심전도상소견으로심실빈맥발생의위험인자는 QRS 간격이 180ms 이상시지속성심실빈맥에 100% sensitivity, 180ms 미만시에는 100% negative predictive value를보였다 (14). QRS 간격의연장은폐동맥역류와우심실확장과관련이있으며 (15), QRS
간격이매년평균 3.5ms 이상확장될때도급사와심실빈맥의위험성이증가하였다 (16). 재분극의이상으로는 QRS 간격 180ms 이상및 QT dispersion 60ms 이상혹은 JT dispersion 60ms 이상시심실빈맥예견에 98% sensitivity, 100% specificity를보였다 (17). 그러나이런소견은성인에서만나타나고소아에서는분극, 재분극의이상소견을보이지않았다 (18). Holter검사상심실조기수축과비지속성심실빈맥은흔히보는소견이며, 이런부정맥은시간이지날수록안정되고나빠지지않는다 (19, 20). 그러므로심실빈맥의예견에는사용되지않고, 심계항진등의증상이있으나심실빈맥이확인되지않은환자에서진단목적으로사용된다. 신호평균화심전도 (SAECG, signal averaged ECG) 소견으로는활로사징교정술환자에서증상이있는심실빈맥이있는경우나심실세동이있었던경우마지막 40ms 동안 root mean square voltage가낮고, terminal filtered QRS complex의 low amplitude signal duration이더길다고하였으나 (21), SAECG는 Holter검사상비지속성혹은지속성심실빈맥이있는경우와정상인경우를구별하지못하는것같다 (22). 최근 Giulia Russo 등 (23) 의연구에서는 filter QRS가 170ms 이상시에심실빈맥의발생을예견하였다는보고도있으나아직심실빈맥의발생을예견하는지표로서효용성에대해서는의문이많다. Heart rate variability의감소는, QRS 간격연장, 우심실확장및폐동맥역류등과관련이있고우심실기능과는관계가없다는보고가있다 (24). 폐동맥역류가심할수록 heart rate variability의감소가심하다는보고 (25) 도있으나, 이것이후기급사를예견할수있나에대해서는더연구가필요하다. 운동부하검사중약 25% 에서부정맥이발견된다. 특히수술시나이가많을수록, 수술후추적관찰기간이길수록 (26), 우심실수축기압력이높을수록 ( > 60mmHg) 운동유발성부정맥이더잘생긴다 (27). 수술을시행하지않은활로사징환자에서는누두부 (pulmonary infundibulum) 의섬유화때문에, 수술한경우는우심실절개부위상처때문에심실부정맥이생기리라생각된다. 전기생리검사에서도위의두위치모두에서회로가발견되고, 약물에듣지않는경우전극도자절제술의성공을보고하였다 (28). 그러나전기생리검사자체는위양성, 위음성결과가많아서급사를예견하기는어렵다 (29). 실신등의증상이있으나심실빈맥이입증되지않은경우에전기생리검사를시행해본다. 만약검사에서한가지모양의심실빈맥이생긴다면이것은증상과일치하는것으로보고적극적으로치료를시작한다. 그러나심실빈맥이유발되지않았다고해서심실빈맥이아니라고는말할수없다. 실제로심실빈맥이없고의심할만한증상도없는환자에서심실빈맥이유발되어도실제이환자에서심실빈맥발생의위험성이확실하다는것은아니다. 후기급사와관련된혈역학적이상은 1) 우심실수축기압력 > 60mmHg 2) 폐동맥유출로압력차 > 40mmHg 3) 우심실용적과부하 4) 우심실기능이상등이있다 (30). 이런혈역학적이상은다음의 2가지기전으로급사의위험성을증가시키리라생각된다. 1)
중등도이상의혈역학적이상이있는환자는빠른심실빈맥을견디지못한다. 2) 우심실과폐동맥판막의기능이상은 mechano-electrical interaction을통해위험성을더증가시킨다 (14). 특히우심실유출로에패치를댄후발생한심한폐동맥역류환자에서높은위험성을보인다. 활로사징수술후후기에발생한심한폐동맥역류 ( 폐동맥판막치환술 ) 와우심실유출로협착을교정한후 QRS 간격이안정되고 ( 수술안하면점점더길어짐 )(31), 심실빈맥의빈도를감소시킨다 (32, 33). 방사선핵종심실혈관촬영 ( Radionuclide ventricular angiography, RNA) 으로우심실용적, 기능등을볼수있다. 폐동맥역류가증가하면우심실용적이증가하여우심실이확장되고 QRS 기간연장을일으키고심실부정맥을일으킨다. 흉골연장축상단면도 M-형심에코도상우심실크기의증가 (34), 심초음파상우심실과좌심실의장축비교 (14), 심초음파상우심실과좌심실의최대단축직경의비교 (35), biplane Simpson 방법으로확장기말우심실용적측정등이심실빈맥과급사와관련이있다는보고가있으나 (22) 일관된결과를보여주지못하였고, 우심실의 3차원적인복잡한모양때문에경흉부심초음파로우심실의크기와기능을측정하는것은한계가있다. 폐동맥역류가심하면심실빈맥과급사의위험성이커진다고알려져있으나심초음파로폐동맥역류를측정하는것은반정량적이기때문에역시한계가있다. 자기공명영상 (Magnetic resonance imaging, MRI) 으로우심실의기능과폐동맥역류정도를측정할수있다. velocity mapping MRI 로제한성우심실, 폐동맥역류의정도, 우심실용적의변화등을알수있다 (36). 그러나 MRI 자체만으로심실빈맥을예견하는역할은아직은하지못하고있다. 수술후후기에초래되는심실빈맥은대개한가지모양이고큰재입빈맥의회로를형성하고, 상처난우심실유출로혹은누두부중격주위에보호받는전도복도 (protected conduction corridor) 를형성한다. 심실빈맥이빠르면전형적인증상으로실신이나심정지를일으키기도하며, 일부에서는심실빈맥의주기가길어서혈역학적으로안정되어심계항진등의증상만나타나기도한다. 그러나수술한활로사징환자에서심실성빈맥도흔하므로이와의감별진단도필요하다. 활로사징교정술후다수에서완전우각차단이발생하여넓은 QRS를보일수있어서상실성빈맥이발생시심실빈맥과감별진단이어렵다. 빈맥중에방실해리를보이면심실빈맥이며, 만약심실과심방이 1:1로뛰면 adenosine을투여하여심방과심실의해리가생기면심실빈맥혹은편도전위된방실접합부빈맥이라할수있다. 만약 adenosine에의해빈맥이종료되면빈맥은방실재입빈맥혹은방실결절재입빈맥이다. 그러나혈역학적으로불안정한넓은 QRS 빈맥은일단심실빈맥으로보고치료하는것이바람직하다. 심실빈맥의치료는혈역학적으로불안정한경우는동기성직류심율동전환 (1-2 J/kg의에너지 ) 으로치료하는것이일차치료이다. 혈역학적으로안정된경우는약물사용도시도해볼수있다. 전통적인방법으로는 lidocaine이나 procainamide를사용한다. 최근에는불응의심실빈맥이나혹은심실기능이떨어져있는경우는 1차약제로 amiodarone 정맥주사를사용한다 (37). 재발
방지를위한치료로는환자의심실빈맥위험에대해확신이없을때에는가끔경험적으로베타차단제혹은 class IB 약제를사용해보기도하였고, 최근에는 class III 약제인 amiodarone, sotalol, calss IC 약제을많이사용하는것같다. 어떤약물이가장효과가있는가에대해서는아직잘모른다 (Table-4). 그러나지속성심실빈맥이있거나심정지가발생하였던경우는약물치료만하는것은좋지않다. 현재선천성심장병환자에서심실빈맥의치료는환자의상태및심실빈맥의심각성에따라 1) 약물치료 2) 전극도자절제술 3) 수술적절제술 + 잔존이상교정 4) ICD(implantable cardioverterdefibrillator) 4가지중한가지혹은복합해서사용한다. 심실빈맥의치료에대해최종결정을내리기위해서는보통우측및좌측심도자검사를모두시행하고심장전기생리검사까지모두시행한다. 왜냐하면수술로교정할수있는병변 ( 예 : 잔존하는심실중격결손, 폐동맥역류, 폐동맥분지협착등 ) 이있는지심도자검사로찾아보고, 전기생리검사로빈맥의기전이심실빈맥인지확인하고, 어느부분이 critical isthmus로작용하는지알아내어, 만약수술로잔존병변을교정시에는빈맥에대한절제술을같이할때절제위치를정하는데도움을주며, 어떤경우는환자의증상을일으키는부정맥이심실빈맥인지혹은심방내재입빈맥인지구분을할수있으며, 심실빈맥의치료에가장잘듣는약물을찾기위해전기생리검사를시행하기도한다. ICD를넣는환자에서심실빈맥이 overdrive pacing에중단되는지를보아서 ICD programming에도움을주기도한다. 만일다른교정할병변이없으면서심실빈맥이유도되고느리면서혈역학적으로안정시에는지도화 (mapping) 후바로전극도자절제술을시도할수도있다. 전극도자절제술의급성성공률은높으나 (28, 38) 재발율에대해서는아직잘모르고확신이없다. 최근 3차원의지도화이용한 CARTO를사용하여 fluoroscope 없이전극도자절제술을보고한경우도있으며 (39), 전극도자절제술과 class III약제를같이사용하여좋은효과를보았다는보고도있다 (40). 그러나대개의선천성심장병수술후발생하는심실빈맥에서급사의위험성이크므로 ICD를넣는경우가많다. ICD는대개정맥을통해넣으나이것이불가능한단심실이거나의미있는심장내단락이있는경우에는색전증의위험때문에심외막으로유도를넣는다. ICD를넣더라도전극도자절제술을같이시행하거나약물치료를같이시행해서 ICD에서의 discharge를줄이려고노력한다.
Table. 4 Medical thrapy in ventricular tachycardia after repair of congenital heart disease. Progress In Pediatric cardiology 1995;4:229-236 236 Table 5. Pathophysiology of chronic Pulmonary regurgitation Substrate Post-repair of tetralogy of Fallot Post-valvotomy for pulmonary stenosis (balloon or surgical) Absent pulmonary valve syndrome(rare) Isolated congenital PR(rare) Co-variable/s Peripheral pulmonary artery stenosis(-) Pulmonary hypertension(-) RVOT aneurysm/akinesia(-) RV restrictive diastolic physiology (+ in the older patient)
Clinical progression RV dilatation (there is usually a long compensatory phase while RV systolic function is maintained) QRS Prolongation (associated with increased risk of sustained ventricular tachycardia and SCD) Onset of tricuspid regurgitation RV systolic dysfunction Overt symptoms ensue (-/+) indicates negative or positive effect on PR and/or RV function. 폐동맥역류와후기심실빈맥폐동맥역류는심장에여러가지나쁜영향을미치고 (Table 5), 또한심실빈맥발생의위험성과상당히긴밀한관계가있어, 폐동맥역류를적절한시기에수술하면심실빈맥의발생도막고우심실의기능도보전할수있다. Bove 등 (41) 은처음으로폐동맥판막치환술후우심실확장의감소와우심실박출계수의호전을관찰하여, 비교적조기에수술시우심실기능이상이회복될수있음과운동수행능력이향상됨을보고하였다. d Udekam 등 (42) 은우심실크기의감소와기능적인등급 (functional class) 이향상됨을보고하였고, Conte 등 (43) 은심초음파를이용한연구에서증상이없더라도운동수행능력, 우심실혈역학적기능에는상당한이상을보이므로, 증상단독만으로폐동맥판막치환술의시기를판단하면안된다고하였다. Therrien 등 (44) 은폐동맥판막치환술전우심실박출계수가 40% 이상이었던환자 10명중 5명 (50%) 에서폐동맥판막치환술후에우심실박출계수가 40% 이상이었고, 폐동맥판막치환술전우심실박출계수가 40% 미만이었던환자 15명중 2명 (13%) 에서폐동맥판막치환술후에우심실박출계수가 40% 이상임을보였고, 폐동맥판막치환술후 QRS 간격이안정되고, 냉동절제술을같이시행한경우이미존재하던심방및심실빈맥의빈도를감소시켰다고하였다. 수술한활로사징환자에서의미있는폐동맥역류가있고, 증상은없거나미미한경우는연속적인운동부하검사, 주기적인심초음파검사, 방사선핵종심실혈관촬영이나자기공명영상으로우심실기능을평가하여초기에우심실기능이상과악화를발견하여야한다. 다음과같은경우에폐동맥판막치환술을시행한다. 1) 증상이없더라도심한폐동맥역류가있고,
진행되는우심실확장과기능이상 ( 심초음파검사, 방사선핵종심실혈관찰영, 자기공명영상등으로검사 ) 이있거나, 진행되는운동능력저하가있을때 2) 우심실기능이상의동반과는상관없이, 장기간지속되는심한폐동맥역류와우심실확장이있으면서증상 ( 숨참등 ) 이있을때 3) 증등도이상의폐동맥역류가있고수술적교정이필요한혈역학적으로의미있는동반병변이있는무증상혹은증상이있는환자 4) 우심실기능이상의동반과는상관없이, 심한폐동맥역류와우심실확장과관련된심각한심실부정맥 ( 지속성심실빈맥 ) 이있는환자 ( 이경우에는폐동맥판막치환술과냉동절제술을같이하면가장효과적 ). 적기에폐동맥판막치환술을시행하면, 대개의환자 ( 본인이폐동맥판막치환술전에증상이없었다고생각하는사람도포함 ) 에서기능적등급 (functional class) 의호전을보이고, 우심실크기가감소하고, 우심실박출계수도호전된다. 그러므로우심실기능이상과우심실부전의증상이나타나기전에폐동맥판막치환술해야한다. 지속성심실빈맥이나급사의위험성이큰경우에는폐동맥판막치환술시절제술과함께 ICD를넣는것도반드시고려해야한다. 폐동맥역류만있는환자에서폐동맥역류에대한수술이불가능하거나아직수술시기가아니면약물치료도시도해본다. 1) 우심실심부전증상치료를위해이뇨제를사용한다. 2) 활로사징환자에서신경-호르몬의활성화 (neurohormonal activation) 와심장자율신경활동장애가있음이보고 (45) 되고있으므로 ACE 억제제와베타차단제사용으로예후를좋게하고, 폐동맥판막치환술의시기를늦출수있지않을까기대되어이에대한연구가더필요하다. 최근에는활로사징을고식적수술을하지않고영아기에완전교정술을해주므로박동성 (pulsatile) 폐동맥혈류를증가시켜폐동맥혈관의발달을유도하고, 폐동맥의왜곡 (distorsion) 을방지할수있어잔존폐동맥협착과폐동맥역류를줄일수있게되었다 (43, 46). 즉이미생긴폐동맥역류에대한수술을적절한시기에시행하면, 심실빈맥의발생과심실기능이상을방지할수있으며, 활로사징교정수술을조기에시행하면심실빈맥의발생을줄일수있으며, 심실을통한접근대신심방및폐동맥을통한접근으로심실의상처를줄이고, 폐동맥협착수술시 TAP 를피하고, 우심실유출로에작은 patch를대고, 가능한한폐동맥판막을살리려는노력으로폐동맥역류의발생을줄여, 심실빈맥및심실기능이상이생기지않도록노력하고있다. 일본에서최근에시행한여러센터의합동연구결과를보면서구에비해활로사징수술후심실빈맥의빈도가훨씬적었다. 일본은 1970년중반부터활로사징수술시심실기능을감소시킬수있는완전우각차단을방지하기위해우심실절개를작게하거나우심실절개를하지않고, 또한가능한한작은 transannular patch를이용한결과수술후우심실기능이유지되고, 폐동맥역류를방지할수있지않나추측하였고, 그결과서구의연구에비해 QRS가넓지도않고, 심실빈맥의기질 (substrate) 이적어심실빈맥이적지않을까생각된다고하였다 (47). 한국의논문에서도 (48) 수술후지속성심실빈맥이서양에서와같이많은것같지는않으나여러센터의합동연구가된것은아직없는실정이다.
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