Main Topic Reviews 허혈성심근증환자에서심실빈맥 경희대학교의과대학내과학교실김진배 Jin-Bae Kim, MD, PhD Cardiology Division, Department of Internal Medicine, Kyung Hee University Co

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1 허혈성심근증환자에서심실빈맥 경희대학교의과대학내과학교실김진배 Jin-Bae Kim, MD, PhD Cardiology Division, Department of Internal Medicine, Kyung Hee University College of Medicine, #1, Hoegi-dong, Dongdaemun-gu, Seoul, Korea Ventricular tachycardia in ischemic cardiomyopathy Abstract Despite the decreased incidence of coronary artery disease, several studies showed that the ischemic ventricular tachycardia (VT) are most common type of ventricular tachycardia. Ischemic VTs have been known to arise in the ventricular scar or border zone, consisting of the reentry circuit. Therefore, reentry has been accepted as the principal mechanism of ischemic VT. However, recent studies showed a different background of the mechanism. In treatment, antiarrhythmic agents and implantable cardioverter defibrillator (ICD) are the first line of therapy. However, some cases require a more invasive approach, such as catheter ablation or cardiac surgery. The techniques of these treatments have evolved for several decades, showing better clinical outcome than before. Therefore, the management for ischemic VT should be tailored in patients with broadspectrum disease. Key words: cardiomyopathy ischemic ventricular tachycardia 서론 심장질환에서대표적인심근경색은심장에반흔 (scar) 을형성하여이와관련한심실부정맥을유발한다. 이러 Received: May 27, 2013 Accepted: September 28, 2013 Correspondence: Jin-Bae Kim, MD, PhD, Cardiology Division, Department of Internal Medicine, Kyung Hee University College of Medicine, #1, Hoegi-dong, Dongdaemun-gu, Seoul, Korea Tel: , Fax: jinbbai@khu.ac.kr 한심근경색후발생하는심실빈맥 (post-infarct ventricular tachycardia) 은발생시기에따라급성기와만성기로나눠볼수있는데, 심근경색의급성기에는심실세동 (ventricular fibrillation) 으로이어지는다형성심실빈맥 (polymorphic ventricular tachycardia) 이흔하다. 경색후수주가지나면서경색부위에구조적인변화가발생하는데, 경색후발생되는섬유화는전도차단을일으키고경색주위의경계부위 (border zone) 에서는전도속도가느려지는현상이일어나면서이로인한회귀성경로가형성되는것으로알려져있다 1. 최근심근경색에대한치료가발전하면서이에따라심근경색이후발생하는심실빈맥의빈도가감소하게되었는데, 경색초 16 The Official Journal of Korean Heart Rhythm Society

2 기의연구에의하면약 5% 미만의심근경색생존자들에서심실빈맥이발생하는것으로나타났다 2. 일반적으로경색부위가넓고심기능저하가심한경우와경색후 6 주이내에심실빈맥의발생과급사의위험이높은것으로알려져있으며, 급성기이후에발생하는심실빈맥이전기적, 구조적재형성 (remodeling) 에의한것인지아니면또다른허혈손상 (ischemic insult) 에의한것인지는잘알려져있지않다. 다만이시기에발생하는심실빈맥은부정맥의기질 (substrate) 이형성되어있어회귀에의한기전으로발생하며, 약제로치료가어려운것으로알려져있다. 허혈성심실빈맥의기전 서론에서언급한대로허혈성심실빈맥 (ischemic ventricular tachycardia) 은심장의반흔과경색의경계부위의회귀기전에의해서발생하는것이가장중요한기전으로알려져왔다. 심근경색에따른반흔의형성에서정상심근과는달리정상적인혈액공급을받지못하는상태에놓인경계부위가혼재하면서, 서로다른성질의기질이함께존재해회귀기전은당연한것처럼평가되어왔다. 2010년 Indiana University 그룹의 Das 등은 9% 정도가국소성 (focal type) 이며대부분회귀기전으로발생한다고보고하였으나, 최근 2012년에발표된동물실험모델에기초한실험연구에의하면초기심실빈맥의유도및유지는 triggered activity에의한국소성기전에의해발생하다가오래지속되면서심실벽간회귀 (intramural reentry) 에의해다형성심실빈맥이나심실세동으로전환되는것으로밝혀졌다. 3,4 본실험은각심실박동을 3D mapping하여얻은자료를기초로한보고로초기심실빈맥의유발및유지는회귀가아닌국소성기전에의한것임을시사하며, 추후보다많은연구를통해인간에게도같은기전이존재하는지확인해야할것이다. 허혈성심실빈맥의치료 1. 항부정맥제와이식형제세동기회귀기전에결정적인역할을하는기질 (substrate) 에대한항부정맥효과와빈맥발생의방아쇠 (trigger) 를억제하는효과로인해항부정맥제가치료로흔히사용된다. 하지만약물치료 2년내 40% 이상의환자가재발을경험하게되고, 심실빈맥의재발은급사의위험도를증가시키게된다. 5 이런경우대안으로제시할수있는것이이식형제세동기 (implantable cardioverter defibrilator, ICD) 이다. 1997년과 2000년에발표된항부정맥제와 ICD의비교에대한연구들에서항부정맥제에비해 ICD가고위험군의생존기간을향상시킨것으로나타나이후 ICD가일차치료로인정받게되었고, 항부정맥제의부작용을줄이면서서맥에대한예방효과를보여주었다. 6-8 하지만 ICD가심실부정맥의발생을예방하지는못하고, 이미발생한부정맥에대한치료에있어국한된역할을함으로써항부정맥제의사용이필요하고, 환자에따라서잦은전기충격 (electrical shock) 으로인해삶의질문제를야기하기도한다. 또항부정맥제, 특히 amiodarone은심율동전환에너지의역치 (defibrillation threshold) 를증가시켜때로심율동전환을더어렵게하는것으로입증되었다. 따라서약물과의료기에의한치료가아닌전극도자절제술의필요성이부각되었다. 2. 전극도자절제술고주파절제술 (radiofrequency ablation) 은전술한것과같이자주재발되는심실빈맥에서부가적치료 (adjunctive therapy) 의의미가있으며, 항부정맥제를사용중임에도재발한허혈성심실빈맥의재발을 75% 이상감소시키는것으로알려졌다 허혈성심실빈맥은혈역학적으로안정된상태인경우 (hemodynamically stable state) 와그렇지못한경우로나눠볼수있다. 전자의경우는빈맥의지도화 (mapping of ventricular tachycardia) 및전극도자절제술 (radiofrequency catheter ablation) 이심실빈맥을유도한상태에서진행하기때문에보다정밀한지도화와절제술로치료가용이한 Vol.14 No.3 17

3 Outer loop Bystander 1 Entrance site Common pathway (scar tissue) Exit site Inner loop Bystander 2 Bystander 3 Figure 1. Illustration of the circuit of ischemic ventricular tachycardia Table 1. The points of differential diagnosis of variable sites of the reentrant circuit. Site Electrogram timing in VT Entrainment with concealed fusion Entrained stimulus- QRS (S-QRS) VTCL Post-pacing interval Sinus rhythm pacemap QRS vs VT Stimulus- QRS Common pathway diastolic present =Egm-QRS <0.7 =TCL Same =Egm-QRS Inner loop systolic present <Egm-QRS >0.7 =TCL Same =Egm-QRS Outer loop systolic absent <Egm-QRS >0.7 =TCL Different <Egm-QRS Entrance site early diastolic present* =Egm-QRS <0.7 =TCL Different <Egm-QRS Exit site late diastolic present >Egm-QRS >0.7 >TCL Same =Egm-QRS Bystander 1 mid-diastolic* present >Egm-QRS >0.7 >TCL Same >Egm-QRS Bystander 2 late diastolic* present >Egm-QRS >0.7 >TCL Same >Egm-QRS Bystander 3 early diastolic* present* >Egm-QRS >0.7 >TCL Same >Egm-QRS *variable depends on whether captured orthodromically or antidromically 18 The Official Journal of Korean Heart Rhythm Society

4 Figure 2. Voltage mapping of substrate with 3D electroanatomic mapping system (CARTO ) not published data) 반면, 혈역학적으로불안정한경우는빈맥에대한자세한지도화가불가능하기때문에빈맥의발생과유지에결정적역할을하는심실의기질에대한지도화및이에대한절제술이진행된다. 회귀기전에대한이해와반흔사이의잠재적회귀로를확인하는방법등이발전함에따라여러다른회귀로에의한심실빈맥이나불 안정형심실빈맥에대한전극도자절제술에의한치료가확대되기에이르렀다 (Figure 1, table 1). 9,10 특히삼차원입체전기해부학적지도화 (3D electroanatomical mapping) 는전기생리학적자료를 3차원으로구현된해부학적자료와결부함으로써, 경색으로인한반흔의부위와정상부위, 경계부위를시술자에게직관적으로 Vol.14 No.3 19

5 제공하여시술이더욱용이하게되었다 (Figure 2). 최근 Michigan 그룹에서발표한 24명의심근경색환자를대상으로하는후향적연구에의하면반흔사이의채널이모두심실빈맥과관련되어있지않고, late potential 과함께존재하는채널이심실빈맥과연결된결정적경로 (critical pathway) 임을확인하였다. 13 이보고는기존의구조적질환과동반된심실빈맥의전극도자절제술의연구와일관된결과를보여주고있다. 예를들면부정맥유발형우심실이형성증 (arrhythmogenic right ventricular dysplasia) 이나브루가다증후군에서도비슷한결과를보여주고있다 또하나심내막뿐아니라심외막에서도심실빈맥의유발이가능하기에동시에두부위에접근할필요가있는경우도고려해야한다. 최근증례보고에서심장이식수술을받은심실빈맥환자의전극도자절제술후심장병리소견을보면 lesion size를증폭시키는 irrigation tip catheter를사용했음에도 transmural lesion을얻지못하였음을알수있다. 이는심실빈맥치료시심내막으로의접근으로심외막에서유래하는심실빈맥이나심외막을결정적경로로이용하는심실빈맥을치료할수없음을반증하며, 반드시심외막에대한접근도고려해야함을시사한다. 17 또한 2013년 UCLA의 Tung 등이발표한자료를보면비허혈성심실빈맥환자에비해허혈성심실빈맥의경우심내막, 심외막양쪽으로모두전극도자절제술을시행한환자군에서심실빈맥의재발이의미있게적었음을알수있었다. 이는허혈성심실빈맥의전극도자절제술을시행하는경우반드시심내막과더불어심외막으로접근하는것도함께고려해야함을뒷받침한다 심실빈맥의수술치료심근경색후발생하는심근의재형성과심실류 (ventricular aneurysm) 와관련하여발생하는심실부정맥의치료목적으로수술적교정 (surgical correction or left ventricular aneurysmectomy) 이시도되었다. 1970~1980년대초기성적은항부정맥제치료성적에비해좋았으나수술후조기사망률이문제가되었고, 1990년대 Dor 등이수술법을변형한 subtotal endocardiectomy를 시행하여좋은결과를얻었으며, 이후 cryoablation이도입되면서수술후심기능향상및심실부정맥을줄이는결과를얻을수있었다 하지만수술적응증에해당하지않는환자들에게는도움이되지않고, 수술경험이많은기관과적은기관의성적차이가커치료법이확대되지는못하였다. 현재에는관상동맥질환에심한심근재형성이동반되어수술치료를고려할때부가적인치료로받아들여지고있는실정이다. 결론 허혈성심실빈맥은관상동맥치료가발전함에따라그발생빈도가줄었지만, 아직도가장많은형태의심실빈맥이며예후가좋지않아적극적인치료가필요하다. 현재 ICD의보편화로허혈성심실빈맥으로인한사망률은줄었으나이로인해더많은부정맥이발견되고 ICD shock으로인해환자불편감이증가한경우전극도자절제술이부가적인의미로중요한치료법이될수있다. 현재시행되고있는전극도자절제술에대한이론적발전과기술의발전으로인하여시술에대한성적이향상되고있고, 아직도많은부분에서발전할여지가있기에보다더좋은결과가나올것으로예상된다. 또한카테터를이용한치료외에도국한된환자군에서는수술적치료도고려해야할것이다. References 1. Wit A, Janse MJ. The ventricular arrhythmia of ischemia and infarc tion: Electrophysiological mechanisms. Mount Kisco, NY: Futura; Andresen D, Steinbeck G, Brüggemann T, Müller D, Haberl R, Behrens S, Hoffmann E, Wegscheider K, Dissmann R, Ehlers HC. Risk stratification following myocardial infarction in the thrombolytic era. J Am Coll Cardiol.1999;33: Das MK, Scott LR, Miller JM. Focal mechanism of ventricular tachy cardia in coronary artery disease. Heart Rhythm. 2010;7: Johnson CM, Pogwizd SM. Focal initiation of sustained and nonsustained ventricular tachycardia in a canine model of ischemic cardiomyopathy. J Cardiovasc Electrophysiol. 2012;23: The Official Journal of Korean Heart Rhythm Society

6 5. The ESVEM investigators. Determinants of predicted efficacy of antiarrhythmic drugs in the electrophysiologic study versus electrocar diographic monitoring trial. Circulation. 1993;87: The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implanable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med. 1997;337: Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, Mitchell LB, Green MS, Klein GJ, O'Brien B. Canadian implantable defibrillator study (CIDS); a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation. 2000; 101: Kuck KH, Cappato R, Siebels J, Rüppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest. The cardiac arrest study Hamburg (CASH). Circulation. 2000;102: Marchlinski FE, Callans DJ, Gottlieb CD, Zado E. Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation. 2000;101: Soejima K, Suzuki M, Maisel WH, Brunckhorst CB, Delacretaz E, Blier L, Tung S, Khan H, Stevenson WG. Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping. Circulation. 2001;104: Stevenson WG, Friedman PL, Sweeney MO. Catheter ablation as an adjunct to ICD therapy. Circulation. 1997;96: Strickberger SA, Man KC, Daoud EG, Goyal R, Brinkman K, Hasse C, Bogun F, Knight BP, Weiss R, Bahu M, Morady F. A prospective evaluation of catheter ablation of ventricular tachycardia as adjuvant therapy in patients with coronary artery disease and implantable cardioverter-defibrillator. Circulation.1997;96: Mountantonakis SE, Park RE, Frankel DS, Hutchinson MD, Dixit S, Cooper J, Callans D, Marchlinski FE, Gerstenfeld EP. Relationship between voltage map "channels" and the location of critical isthmus sites in patients with post-infarction cardiomyopathy and ventricular tachycardia. J Am Coll Cardiol. 2013;61: Jaïs P, Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia R, Shah A, Derval N, Cochet H, Knecht S, Miyazaki S, Linton N, Rivard L, Wright M, Wilton SB, Scherr D, Pascale P, Roten L, Pederson M, Bordachar P, Laurent F, Kim SJ, Ritter P, Clementy J, Haïssaguerre M. Elimination of Local Abnormal Ventricular Activities : A New End Point for Substrate Modification in Patients With Scar-Related Ventricular Tachycardia. Circulation. 2012;125: Marcus FI, Abidov A. Arrhythmogenic right ventricular cardiomyopathy 2012: diagnostic challenges and treatment. J Cardiovasc Electrophysiol. 2012;23: Nademanee K, Veerakul G, Chandanamattha P, Chaothawee L, Ariyachaipanich A, Jirasirirojanakorn K, Likittanasombat K, Bhuripanyo K, Ngarmukos T. Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium. Circulation. 2011;123: Kelesidis I, Yang F, Maybaum S, Goldstein D, D'Alessandro DA, Ferrick K, Kim S, Palma E, Gross J, Fisher J, Krumerman A. Examination of explanted heart after radiofrequency ablation for intractable ventricular arrhythmia. Circ Arrhythm Electrophysiol.2012;5:e Tung R, Michowitz Y, Yu R, Mathuria N, Vaseghi M, Buch E, Bradfield J, Fujimura O, Gima J, Discepolo W, Mandapati R, Shivkumar K. Epicardial ablation of ventricular tachycardia: an institutional experience of safety and efficacy. Heart Rhythm. 2013;10: Guiraudon G, Fontaine G, Frank R, Escande G, Etievent P, Cabrol C. Encircling endocardial ventriculotomy: A new surgical treatment for life-threatening ventricular tachycardias resistant to medical treatment following myocardial infarction. Ann Thorac Surg. 1978; 26: Josephson, M. E., Harken, A. H., Horowitz, L. N. Endocardial excision: A new surgical technique for the treatment of recurrent ventricular tachycardia. Circulation. 1979;60: Cox JL, Gallagher JJ, Ungerleider RM. Encircling endocardial ventriculotomy for refractory ischemic ventricular tachycardia. Clinical indication, surgical technique, mechanism of action, and results. J Thorac Cardiovasc Surg. 1982; 83: Dor V, Sabatier M, Montiglio F, Rossi P, Toso A, Di Donato M. Results of nonguided subtotal endocardiectomy associated with left ventricular reconstruction in patients with ischemic ventricular arrhythmias. J Thorac Cardiovasc Surg. 1994;107: Vol.14 No.3 21

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