REVIEW ARTICLES Arrhythmia 2015;16(3): doi: 이식형심장사건기록기의임상적역할 박승정 성균관대학교의과대학내과학교실 Clinical Useful

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REVIEW ARTICLES doi: http://dx.doi.org/10.18501/arrhythmia.2015.

1 REVIEW ARTICLES doi: 박승정 성균관대학교의과대학내과학교실 Clinical Usefulness of Implantable Loop Recorder Seung-Jung Park, MD, PhD Division of Cardiology, Department of Internal Medicine, Heart Vascular and Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Received: January 19, 2015 Revision Received: September 8, 2015 Accepted: September 25, 2015 Correspondence: Seung-Jung Park, MD, PhD, Division of Cardiology, Department of Internal Medicine, Heart Vascular and Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, , Korea Tel: , Fax: Copyright 2015 The Official Journal of Korean Heart Rhythm Society Editorial Board & MMK Co., Ltd. ABSTRACT Initially, an implantable loop recorder (ILR) was introduced to find the cause of unexplained syncope, palpitation, and dizziness. It is now considered as a test of choice when repeated Holter recordings, more-prolonged external event loop recordings, head-up tilt test, or electrophysiological study fails to reveal the cause of recurrent syncope. However, with the help of technical advancement such as automated QRS morphology analysis, auto-adjusting sensing threshold, improved noise rejection, increased battery longevity, and remote monitoring function, the ILR has begun to play an important role in the diagnosis of life-threatening ventricular tachyarrhythmias as well. In addition, ILR monitoring shows clear usefulness in detecting atrial fibrillations after cryptogenic stroke, in differentiating true syncope from epilepsy, and in assessing the recurrence rate of atrial fibrillation after radiofrequency ablation. Overall, a smarter ILR will make possible earlier diagnosis, enhance diagnostic accuracy, and improve quality of life of patients with unexplained syncope, palpitation, non-syncopal transient loss of consciousness, and stroke. Key Words: Syncope Atrial Fibrillation Ventricular Tachycardia Stroke 서론 실신은매우흔한질환임에도불구하고정확한원인을진단하는것이쉽지않다. 기립경사테이블검사, 심장초음파및관상동맥조영술, 심장전기생리학검사, 뇌영상및뇌파검사등의신경과적인검사를포함한종합적인평가를 하더라도실신의원인이밝혀지지않는경우가약 1/3 정도나되는것으로알려져있다. 1,2 그런데원인불명의실신을경험한환자는실신을경험하지않은환자에비해예후가나쁜것으로알려져있어, 원인을정확하게진단하여바른치료를제공하는것이매우중요한과제이다. 3 이러한원인불명의실신이나일시적의식소실환자에서 147

Table 1. Several types of implantable loop recorder Medtronic Reveal DX Medtronic Reveal XT St. Jude Confirm Size 62 x 19 x 8 mm 62 x 19 x 8 mm 56.3 x 18.5 x 8 mm 9 ml 9 ml 6.

years 3 years 3 years Event storage 49.5 minutes 49.

2 Table 1. Several types of implantable loop recorder Medtronic Reveal DX Medtronic Reveal XT St. Jude Confirm Size 62 x 19 x 8 mm 62 x 19 x 8 mm 56.3 x 18.5 x 8 mm 9 ml 9 ml 6.5 ml Weight 15 g 15 g 12 g Arrhythmia Detection Asystole, bradyarrhythmia VT/fast VT Asystole, bradyarrhythmia VT/fast VT, AT/AF, AT/AF burden, HRV Asystole, bradyarrhythmia VT/fast VT Longevity 3 years 3 years 3 years Event storage 49.5 minutes 49.5 minutes 48 minutes MRI labeling MR conditional MR conditional MR conditional Availability (Korea) Yes No Yes AF, atrial fibrillation; AT, atrial tachyarrhythmia; MRI, magnetic resonance imaging; VT, ventricular tachyarrhythmia; HRV, heart rate variability A 부정맥으로인한원인을밝히는데에매우유용한진단방법이바로이식형심장사건기록기 (implantable loop recorder, ILR) 이다. 4 최근에는기술적인발전에힘입어 ILR 의수명이길어지고, 진단의정확도가높아지고있다. 따라서기존에주로사용되던원인불명의실신외에, 심방세동, 원인불명의뇌졸중 (cryptogenic stroke), 간질 (epilepsy) 과같은질환에서도응용범위가점차확대되고있다. B ILR 의종류, 기능, 이식 C D Figure 1. Several types of implantable loop recorder; Medtronic Reveal DX (A), Medtronic Reveal XT (B), St. Jude Confirm Implantable Cardiac Monitor (ICM, C), and Medtronic Reveal LINQ (D). ILR 은 USB 메모리 stick 과유사하게납작한직사각형의작은상자모양을하고있으며, single-lead 심전도를기록하고저장할수있는기능을갖고있다 (Figure 1). 일정한범위의서맥이나빈맥이발생하면자동으로심전도를저장하도록프로그래밍할수있고, 환자가증상을느낄때추가적으로심전도를기록하도록 ILR을활성화시킬수도있다. 현재일반적으로사용되고있는 ILR의제품별사양은 Table 1에정리하였다. ILR은일반적으로좌흉골연부위 (left parasternal region) 에세로로이식한다. 최근에는외래에서피하주사하듯이간단하게이식이가능할정도로매우작아진 injectable ILR (Medtronic Reveal LINQ ) 이개발되었으며, 조만간국내에도도입되어환자에게보다많은편의를제공할것으로기대되고있다 (Figure 1). 148

3 1.00 Rate of second syncope 0.75 P = Conventional ILR Days from randomization Figure 2. Time to second syncope recurrence. Implantable loop recorder patients achieved a longer time to second syncope, suggesting a more appropriate treatment. ILR, implantable loop recorder. 원인불명의실신에서 ILR 의유용성 ILR은기존의진단법에비해원인불명의실신이나의식소실의원인에대한진단율이높다. 홀터모니터링검사, 비이식형사건기록기 (external loop recorder), 전기생리학검사및신경과적영상기법등은대부분 20% 미만의낮은진단율을보이고있고, 기립경사테이블검사의진단율이상대적으로높게보고되기도하나일관되지못한성적을보이고있다 (19-61%). 1,2 이에반해 ILR의진단율은 50-80% 정도로높게보고되는경우가많다. 5,6 따라서 2009년에발표된 European Society of Cardiology (ESC) 임상지침에서는원인불명의실신이반복되는환자에게 ILR을조기에사용할것을 class I으로권고하고있다. 7 ILR로증명된실신의부정맥원인으로는동기능부전이나고도방실차단과같은서맥성부정맥이가장흔하다. 5,8 우리나라에서는 2006년부터 ILR이이식되기시작하여 2013 년까지 75명의환자가 ILR 이식술을받았으며, ILR을통해진단된원인중서맥성부정맥이약 2/3를차지하여외국과유사한경향을보여주었다. 또한심장돌연사를일으킬수있는심실빈맥이나심실세동으로진단된경우도 30% 정도로높게나타나심실빈맥의진단에있어서도 ILR 이유용할수 있음을시사하였다 (2014년대한순환기관련학회춘계통합학술대회 ). 또한영국에서원인불명의환자를대상으로진행된 EaSyAS (Eastbourne Syncope Assessment Study) 연구는기존진단법에근거한치료에비하여 ILR 진단에근거한치료결과실신의재발이현저하게감소함을보고하여 ILR이보다정확한치료방법을결정하는데에매우중요한역할을하였음을보여주었다 (Figure 2). 9 심방세동진단을위한 ILR ILR은심방세동이의심되는경우에오랜기간동안심전도모니터링을가능하게해주어심방세동진단에도움을줄수있다. 좌심실기능이저하된초기급성심근경색환자 300여명을대상으로 ILR을이식하고진행된 CARISMA (Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction) 임상연구결과 28% 의환자에서심방세동이새롭게발견되었다. 또한 ILR은심방세동전극도자절제술후에재발을평가하는방법으로사용되기도한다. 10 ILR 은재발유무외에심방세동의 burden도측정할수있다는장점이있다. 최근에 Mittal 등이발표한흥미로운연구결과에따르면심방세동이증명되지않고심방조동만있었던 149

Figure 3. Ventricular fibrillation recorded by using implantable loop recorder during sleep in a 27 year-old male patient with unexplained recurrent syncopal episodes.

4 Figure 3. Ventricular fibrillation recorded by using implantable loop recorder during sleep in a 27 year-old male patient with unexplained recurrent syncopal episodes. 20명의환자를 cavotricuspid isthmus (CTI) 절제술후평균 1 년정도경과를관찰한결과 11명 (55%) 의환자에서심방세동이관찰되었다. 11 따라서심방조동만이관찰되어 CTI 절제술로정상동율동이잘유지되는것으로보이는환자들도 CHA 2 DS 2 -VASc 점수가높다면항응고치료를지속해야할지에대한추가적인연구가필요할것으로생각된다. 원인불명의뇌졸중환자와 ILR 여러가지자세한검사를해도원인이밝혀지지않은원인불명의뇌졸중은전체뇌경색환자의약 1/3을차지하는것으로알려져있다. 이러한경우에심전도모니터링을한달가까이연장해보면약 20-23% 의환자에서발작성심방세동이관찰되기때문에, 발작성심방세동은원인불명뇌경색의중요한원인으로주목받고있다. 12,13 따라서 ILR은원인불명뇌경색환자들에서원인규명, 즉심방세동발견에중요한역할을할것으로기대되고있다. 2013년 Etgen 등이발표한결과에따르면 393명의뇌경색환자중 16.5% 인 65 명이원인불명의뇌경색이었고, 이들중 22명에서 ILR 삽입술을시행할수있었으며, 이들을대상으로 1년간관찰한결과 27.3% 인 6명의환자에서심방세동을발견할수있었다. 14 ILR 의기술적발전과심실빈맥의발견 ILR 사용초기에는주로원인불명의실신환자에서서맥성부정맥을발견하기위해사용되었다. 앞에서도이미설명했듯이서맥성부정맥이원인불명의실신환자에서가장흔한심장맥박의이상소견이지만, 약 10% 에서는심실부정맥이발견된다는보고도있다. 15 ILR을이용한심전도분석은 single channel만이용가능하다는점, signal undersensing ( 특히 P-wave), T-wave oversensing, noise oversensing 등의여러가지단점이있다. 따라서심실빈맥을진단하는면에서 ILR의유용성이다소떨어질수있다는우려가있다. 하지만최근 automated QRS wave morphology analysis, auto-adjusting sensing threshold, RR interval regularity analysis, pattern of heart rate increase analysis 등의알고리즘이도입되어상심실성빈맥과심실성빈맥의감별정확도가높아지게되었다. ICD 삽입 (implantation) 당시함께 ILR을삽입하고, 심실빈맥이나심실세동을유발한한연구결과 ILR은심실부정맥을 95-99% 정도로정확하게진단하였다. 16 또한 Ergul Y 등은 12명의원인불명실신의소아환자들에게 ILR을이식하고, 평균 20개월을추적 150

Figure 4. Electrocardiograms recorded in implantable loop recorder during tonic-clonic seizure. (A) Continuous muscle artifacts can be seen, indicating tonus.

5 Figure 4. Electrocardiograms recorded in implantable loop recorder during tonic-clonic seizure. (A) Continuous muscle artifacts can be seen, indicating tonus. (B) Discrete muscle artifacts of the clonus. (C) The clonic artifacts attenuated and the electrocardiographic complexes becoming visible again as the seizure began to fade. 검사한결과 5명 (42%) 의환자에서 Torsade de pointes, 심실세동, 심실빈맥이관찰되어 17 ILR이치명적인심실부정맥을조기에발견하는데도움이될수있음을시사하였다. Figure 3는원인불명실신의원인이심실세동이었음이 ILR 로잘증명된국내증례이다. 18 반복되는실신과급성심장사의가족력 ( 부친 ) 을주소로입원한 27세남성환자로심장초음파, 기립경사테이블검사, 심장전기생리학검사및뇌파검사에서는특이소견이없었다. ILR 시술후 5 개월째밤에자다가갑자기경련성실신이발생하였고, 당시 ILR 기록상심실빈맥및심실세동이 90초간기록되어 ILR을제거하고삽입형심실제세동기를시술하였다. 유용하게쓰일수있다 (Figure 4) 년 Europace에발표된전향적연구인 REVISE (Reveal in the Investigation of Syncope and Epilepsy) 연구결과에따르면기존에간질의진단이다소불분명했던 103 명의환자에게 ILR 을이식하고, 평균 2.4 년을경과관찰하였을때 21% 인 22 명의환자에서경련움직임 (convulsive movement) 을동반한심한서맥 (bradyarrhythmia or asystole) 이관찰되어진단명이바뀌게되었다. 이들은간질약을끊고인공심장박동기이식을한후에증상이더이상발생하지않았다. 21 결론 간질과 ILR 실신이사지의이상한움직임을동반할때 (convulsive reflex syncope) 간질과의감별이어려울수있다. 기존의연구에따르면간질환자의 13-42% 가오진인것으로밝혀졌고, 이중대부분이실신이원인이었다. 19,20 이러한경우 ILR은실신당시심장박동의변화뿐아니라 tonic-seizure에동반되는근전위 (myopotential [muscle artifacts]) 를보여줄수있기때문에이두가지를보다정확히감별하는데에매우 ILR은원인불명의실신환자에서서맥성부정맥을조기에발견하는데에최선의검사일뿐만아니라기술적인발전에힘입어치명적인심실성부정맥의발견에도도움이되고있다. 최근에는점차그사용영역이확대되고있어원인불명의심계항진, 심방세동및심방조동치료후에심방세동의발생의추적관찰, 원인불명의뇌경색환자에서원인질환규명, 간질과실신의감별등에도유용하게사용되고있다. 특히무선통신기술도입으로인한 remote 모니터링기능이추가되어향후조기진단, 조기예방, 조기 151

6 치료가더욱활발해지고, 따라서환자의삶의질을크게향상시킬것으로기대되고있다. References 1) Kang GH, Oh JH, Kim JS, On YK, Song HG, Jo IJ, Kim SJ, Bae SJ, Shin TG. Diagnostic patterns in the evaluation of patients presenting with syncope at the emergency or outpatient department. Yonsei Med J. 2012;53: ) Pires LA, Ganji JR, Jarandila R, Steele R. Diagnostic patterns and temporal trends in the evaluation of adult patients hospitalized with syncope. Arch Intern Med. 2001;161: ) Soteriades ES, Evans JC, Larson MG, Chen MH, Chen L, Benjamin EJ, Levy D. Incidence and prognosis of syncope. N Engl J Med. 2002;347: ) Edvardsson N, Frykman V, van Mechelen R, Mitro P, Mohii- Oskarsson A, Pasquie JL, Ramanna H, Schwertfeger F, Ventura R, Voulgaraki D, Garutti C, Stolt P, Linker NJ; PICTURE Study Investigators. Use of an implantable loop recorder to increase the diagnostic yield in unexplained syncope: results from the PICTURE registry. Europace. 2011;13: ) Kang GH, Oh JH, Chun WJ, Park YH, Song BG, Kim JS, On YK, Park SJ, Huh J. Usefulness of an implantable loop recorder in patients with syncope of an unknown cause. Yonsei Med J. 2013;54: ) Furukawa T, Maggi R, Bertolone C, Fontana D, Brignole M. Additional diagnostic value of very prolonged observation by implantable loop recorder in patients with unexplained syncope. J Cardiovasc Electrophysiol. 2012;23: ) Task Force for the Diagnosis and Management of Syncope; European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA); Heart Failure Association (HFA); Heart Rhythm Society (HRS), Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB, Deharo JC, Gajek J, Gjesdal K, Krahn A, Massin M, Pepi M, Pezawas T, Ruiz Granell R, Sarasin F, Ungar A, van Dijk JG, Walma EP, Wieling W. Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009;30: ) Boersma L, Mont L, Sionis A, Garcia E, Brugada J. Value of the implantable loop recorder for the management of patients with unexplained syncope. Europace. 2004;6: ) Farwell DJ, Freemantle N, Sulke N. The clinical impact of implantable loop recorders in patients with syncope. Eur Heart J. 2006;27: ) Verma A, Champagne J, Sapp J, Essebag V, Novak P, Skanes A, Morillo CA, Khaykin Y, Birnie D. Discerning the incidence of symptomatic and asymptomatic episodes of atrial fibrillation before and after catheter ablation (DISCERN AF): a prospective, multicenter study. JAMA Intern Med. 2013;173: ) Mittal S, Pokushalov E, Romanov A, Ferrara M, Arshad A, Musat D, Preminger M, Sichrovsky T, Steinberg JS. Long-term ECG monitoring using an implantable loop recorder for the detection of atrial fibrillation after cavotricuspid isthmus ablation in patients with atrial flutter. Heart Rhythm. 2013;10: ) Elijovich L, Josephson SA, Fung GL, Smith WS. Intermittent atrial fibrillation may account for a large proportion of otherwise cryptogenic stroke: a study of 30-day cardiac event monitors. J Stroke Cerebrovasc Dis. 2009;18: ) Tayal AH, Tian M, Kelly KM, Jones SC, Wright DG, Singh D, Jarouse J, Brillman J, Murali S, Gupta R. Atrial fibrillation detected by mobile cardiac outpatient telemetry in cryptogenic TIA or stroke. Neurology. 2008;71: ) Etgen T, Hochreiter M, Mundel M, Freudenberger T. Insertable cardiac event recorder in detection of atrial fibrillation after cryptogenic stroke: an audit report. Stroke. 2013;44: ) Nierop PR, van Mechelen R, van Elsacker A, Luijten RH, Elhendy A. Heart rhythm during syncope and presyncope: results of implantable loop recorders. Pacing Clin Electrophysiol. 2000;23: ) Volosin K, Stadler RW, Wyszynski R, Kirchhof P. Tachycardia detection performance of implantable loop recorders: results from a large 'real-life' patient cohort and patients with induced ventricular arrhythmias. Europace. 2013;15: ) Ergul Y, Tanidir IC, Ozyilmaz I, Akdeniz C, Tuzcu V. Evaluation Rhythm Problems in Unexplained Syncope Etiology with Implantable Loop Recorder. Pediatr Int. 2015;57: ) Shin DH, Kim JS, Park JW, Yim HR, Kim JH, Lee SM, Kim KS, Lee CH, Jung DC, On YK, Kim DK, Lee SH, Hong KP, Park JE. The Use of an Implantable Loop Recorder in Patients with Syncope of Unknown Origin. Korean Circ J. 2008;38: ) Zaidi A, Clough P, Cooper P, Scheepers B, Fitzpatrick A. Misdiagnosis of epilepsy: many seizure like attacks have a cardiovascular cause. J Am Coll Cardiol. 2000;36:

7 20) Josephson CB, Rahey S, Sadler RM. Neurocardiogenic syncope: frequency and consequences of its misdiagnosis as epilepsy. Can J Neurol Sci. 2007;34: ) Petkar S, Hamid T, Iddon P, Clifford A, Rice N, Claire R, McKee D, Curtis N, Cooper PN, Fitzpatrick AP. Prolonged implantable electrocardiographic monitoring indicates a high rate of misdiagnosis of epilepsy-revise study. Europace. 2012;14:

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ºÎÁ¤¸ÆÃÖÁ¾ MAIN TOPIC REVIEWS Young-Keun On, MD, PhD Division of Cardiology, Department of Medicine Cardiac & Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Catheter