편집자문위원 ( 가나다순 ) 고재곤 / 울산의대 곽충환 / 경상의대 김대경 / 인제의대 김대혁 / 인하의대 김성순 / 연세의대 김영훈 / 고려의대 김유호 / 울산의대 김윤년 / 계명의대 김종윤 / 연세의대 김준 / 울산의대 김준수 / 성균관의대 김진배 / 경희의대 남궁

Transcription

1 편집자문위원 ( 가나다순 ) 고재곤 / 울산의대 곽충환 / 경상의대 김대경 / 인제의대 김대혁 / 인하의대 김성순 / 연세의대 김영훈 / 고려의대 김유호 / 울산의대 김윤년 / 계명의대 김종윤 / 연세의대 김준 / 울산의대 김준수 / 성균관의대 김진배 / 경희의대 남궁준 / 인제의대 노태호 / 가톨릭의대 박경민 / 인제의대 박상원 / 고려의대 박형욱 / 전남의대 배은정 / 서울의대 성정훈 / 차의과학대 신동구 / 영남의대 오동진 / 한림의대 오용석 / 가톨릭의대 이경석 / 전북의대 이만영 / 가톨릭의대 이명용 / 단국의대 이문형 / 연세의대 임홍의 / 고려의대 장성원 / 가톨릭의대 정중화 / 조선의대 조용근 / 경북의대 조정관 / 전남의대 최기준 / 울산의대 최윤식 / 서울의대 최의근 / 서울의대 최인석 / 가천의대 최종일 / 고려의대 한상진 / 한림의대 허준 / 성균관의대 현명철 / 경북의대

2 The Official Journal of Korean Heart Rhythm Society 목적과개요 부정맥 은 부정맥과관련된새로운임상연구, 진료지침, 증례등을소개하여부정맥연구회회원및개원의의지속적인의학교육에이바지하고자발행되는학술지입니다. 부정맥 은부정맥의진단과치료, 임상연구와관련된원저, 종설, 논평, 증례보고등의원고를공모하며, 제출된원고는편집위원회의검토를거쳐게재됩니다. 발행사 발행일 엠엠케이커뮤니케이션즈 대표 : 이영화편집 : 양관재, 김지현디자인 : 박선진서울시강남구논현로 523 노바빌딩 3 층 Tel Fax inquiry@mmk.co.kr 2014 년 12 월 23 일 부정맥은대한심장학회부정맥연구회가주관하며엠엠케이커뮤니케이션즈에서발행하고있습니다. 본지와관련된문의사항이나건의사항이있으시면발행사인엠엠케이커뮤니케이션즈로연락하여주시기바랍니다.

3 The Official Journal of Korean Heart Rhythm Society Contents Vol 15. No. 4 통권 51 호 December 2014 Cover: LAO view of 3-dimensional electroanatomical mapping (Page 42) 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 심방세동의약물치료 김남호 14 심방세동환자에서의항응고제치료 온영근 21 전극도자절제술과변화된국내보험규정 오세일 27 Article Review 심방세동환자에서전기적동율동전환시에 Warfarin 과새로운항응고제의비교연구 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 자율학습문제 54

4 ORIGINAL ARTICLE Electrocardiographic Features of Therapeutic Hypothermia 울산대학교의과대학내과학교실이우석, 남기병, 조욱, 최진희, 권창희, 김유리, 최기준, 김유호 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 ABSTRACT Background & Objectives: It has been known that therapeutic hypothermia (TH) can induce electrocardiographic 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 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 Introduction Received: September 4, 2014 Revision Received: December 3, 2014 Accepted: December 15, 2014 Correspondence: 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, Korea Tel: , Fax: gbnam@amc.seoul.kr Therapeutic hypothermia (TH) has emerged as an important adjunctive therapy of cardiac arrest victims recommended by the international resuscitation guidelines. 1,2 The positive effects on improvement in neurologic function and survival 4 The Official Journal of Korean Heart Rhythm Society

5 A During therapeutic hypothermia (32.9 ) ORIGINAL ARTICLE B After recovery from therapeutic hypothermia C During therapeutic hypothermia (33.0 ) D After recovery from therapeutic hypothermia 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. VOL.15 NO.4 5

6 ORIGINAL ARTICLE 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± ± ± Male 42 (61.8%) 28 (70.0%) 14 (50.0%) Temperature ( ) during hypothermia Heart rate(beats/min) 33.3± ± ± Pre hypothermia 101.7± ± ± During hypothermia 86.0± ± ± ECG characteristics Pre hypothermia PR interval (ms) 158.8± ± ± QRS duration (ms) 94.3± ± ± QT interval (ms) 371.1± ± ± QTc interval (ms) 468.0± ± ± During hypothermia PR interval (ms) 166.0± ± ± QRS duration (ms) 104.4± ± ± QT interval (ms) 439.8± ± ± QTc interval (ms) 512.7± ± ± have been proved in two recent trials. 3,4 Characteristic electrocardiographic (ECG) changes occur in patients with hypothermia. The J wave, also known as the Osborn wave, is the most characteristic ECG feature in hypothermia. 5 The J wave is also noted in certain non-hypothermic conditions such as Brugada syndrome and early repolarization syndromes (ERS). The presence of J waves in such syndromes is related to the occurrence of ventricular fibrillation (VF), leading to sudden death. However, whether hypothermic patients with J waves are susceptible to fatal ventricular arrhythmia remains undetermined. Previous reports have shown that the incidence of ventricular arrhythmia is unexpectedly low in hypothermic patients with J waves, varying from 0% to 2%. 6-8 In the present study, we investigated electrocardiographic changes induced by TH and the possible arrhythmogenic potential of the TH-induced J waves. Methods Study Design During the study period from August 2010 to August 2013, 68 patients underwent TH after return of spontaneous circulation. The patients medical records were reviewed to evaluate clinical characteristics such as age, sex, vital signs, cause of arrest, initial rhythm, and ECG findings on admission. To achieve the assigned temperature as rapidly as possible, ice-cold fluids and surface temperature-management devices (ARCTIC SUN 6 The Official Journal of Korean Heart Rhythm Society

7 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%) ORIGINAL ARTICLE Temperature Management System, BARD Medical, CO) were utilized. The following recommendations were made: cool unconscious patients to 33 within 12 hours post-restoration of spontaneous circulation; achieve the desired patient temperature as rapidly as possible; maintain the target temperature for 24 hours; rewarm gradually to 36.5 in hourly increments of /h; and maintain normothermia of ~37.5 after rewarming. We compared the clinical characteristics and basic ECG parameters of patients with and without J waves. The study protocol was reviewed and approved by the Ethics Committee of the College of Medicine, Ulsan University. ECG Analysis The following ECG parameters were analyzed: heart rate, PR interval, duration of the QRS complex, and QT and QTc intervals. J wave was defined as notches or slurs in the terminal part of the QRS complex with an amplitude 0.1 mv above the isoelectric line in at least 2 contiguous leads. 9 The J-wave amplitude was measured as the difference between the top of the J wave and the isoelectric line using Cardio Calipers (On-Screen Electrocardiogram Measurement) from Iconico.com. For the comparison of the distribution of J wave, ECG lead areas were grouped as right precordial (V1-3), left precordial (V4-6), high lateral (I, avl), and inferior (II, III, and avf). Statistical Analysis All statistical analyses were performed with SPSS software (SPSS Inc., Chicago, IL). Categorical VOL.15 NO.4 7

8 ORIGINAL ARTICLE Table 3. Initial cardiac rhythm Cardiac Causes Ventricular fibrillation Number (%) (90.9%) P value Pulseless electrical activity/asystole Non-Cardiac Causes 1 (9.1%) 51 < Ventricular fibrillation 4 (7.8%) Pulseless electrical activity/asystole 47 (92.2%) Unknown 6 Ventricular fibrillation 3 (50.0%) N/A Pulseless electrical activity/asystole 3 (50.0%) variables were analyzed by the χ 2 test. Continuous ECG parameters. variables were analyzed by the t-test. A P value < 0.05 was regarded as significant. ECG Changes Observed during TH Results Clinical Characteristics A total of 68 patients (mean age, 59.8±1.7 years; 42 male) who underwent TH were analyzed. The mean body temperature on TH was 33.3±0.1. J waves were observed in 40 patients during TH. J waves were newly developed in 37 patients and preexisting J waves were augmented in three patients. Two patients with ERS and a patient with alcoholic ketoacidosis displayed preexisting J waves on 12 lead ECG prior to TH. Figure 1 displays representative examples of J waves recorded during TH. A patient with ERS had prominent J waves compared to a patient with non-cardiogenic arrest. Clinical and ECG characteristics are presented in Table 1. There were no significant differences between patients with and without J waves in terms of age, sex, temperature achieved during TH and ECG tracings were assessed for the presence of TH-induced electrocardiographic changes. A consistent reduction in heart rate from 102±29 to 86±23 beats/min (15.4% reduction, p<0.0001) was observed. QRS duration showed a significant (10.7%) increase from 94.3±17.5 ms before TH to 104.4±25.4 ms during TH (p=0.001). The QT and QTc intervals displayed significant 18.5% and 8.7% increases, respectively (371.1±63.3 ms before TH to 439±86.9 ms during TH, p<0.0001, and 468.0±44.2 ms before TH to 512.7±74.6 ms during TH, p<0.0001). Causes of Cardiac Arrest and Initial Rhythm The causes of cardiac arrests were highly variable. Cardiac causes were responsible in 16.2% of the study subjects, while non-cardiac etiology was present in 75.0% of the patients (Table 2). In cardiac 8 The Official Journal of Korean Heart Rhythm Society

9 Table 4. Distribution and mean amplitude of J wave during therapeutic hypothermia ECG lead Number of patients with J waves (number) Mean amplitude of J wave (mv) I ±0.017 avl ±0.013 II ±0.018 III ±0.019 avf ±0.018 V ±0.000 V ±0.165 V ±0.095 V ±0.040 V ±0.018 V ±0.015 ORIGINAL ARTICLE etiology, acute myocardial ischemia caused by myocardial infarction or coronary artery spasm predominated. Initial rhythm determined by ECGs at the emergency room is shown in Table 3. VF was present in 10/11 (90.1%) of patients, and pulseless electrical activity/asystole was recorded in 1/11 (9.1%) of the patients in the cardiac etiology group. However, VF was present in only 4/47 (7.8%) of the non-cardiac cause patients. Distribution and Mean Amplitude of J Wave during TH As shown in Table 4, J waves were common in the inferior and left precordial leads, followed by the high lateral and right precordial leads. Although the frequency of J waves was low in the right precordial leads, the mean amplitudes of J waves (when observable) were higher in the right precordial leads than in other ECG leads. This resulted in prominent right precordial J wave augmentation in two patients with primary arrhythmic disorders. In these patients, J waves were markedly augmented during TH compared with the remainder (0.450±0.095 vs ±0.012 mv). Patients who Developed VF during TH VF occurred in two patients during TH. The two patients were later diagnosed with Brugada syndrome and ERS, respectively. A 56-year-old male patient who was diagnosed with Brugada syndrome displayed newly developed J wave in the left precordial leads during TH (at 32.8 ). However, the J-ST segment elevation in V1 and V2 became diminished during TH. J waves in the left precordial leads occurred immediately post DC cardioversion for VF (Figure 2). A 70-year-old male patient, who was diagnosed with ERS, had marked augmentation of J wave in the left precordial leads (V3-4) during TH (at 33.2 ) (Figure 3). Prominent J waves were observed after DC cardioversion for VF. The two patients underwent cardioverter/defibrillator implantation prior to discharge. VOL.15 NO.4 9

10 ORIGINAL ARTICLE A B C 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. Discussion The main findings of this study are as follows: (1) J waves were induced or augmented in 58.8% of the patients undergoing mild TH (target temperature 33 ); (2) J waves appeared more commonly in the inferior and lateral leads than in the right precordial leads; and (3) it was hypothesized that patients with primary arrhythmic disorders displayed a higher prevalence and amplitude of J waves and were more vulnerable to develop VF during TH than those without primary arrhythmic disorders. Recent population-based studies have established an association between the early repolarization pattern and VF, whether idiopathic in nature or secondary to ischemia The tendency for hypothermia to induce similar electrocardiographic changes is well established. 5,13 Consequently, TH post cardiac arrest can provide an opportunity to examine the impact of J wave-associated hypothermia on malignant arrhythmic potential. 14 This retrospective cohort study assessed the impact of TH on the prevalence, distribution, and magnitude of J waves, and their association with malignant arrhythmia. During the cooling phase, 58.8% of our study population displayed J wave above 0.1 mv. It is well documented that the prevalence of J wave varies with core temperature. 15,16 Reports on patients with accidental hypothermia suggest that the prevalence of J wave would be minimal during mild hypothermia (temperature 33 ) However, Rolfast et al reported a 30% prevalence of J waves during TH 18 and the most recent study by Williams et al discovered a prevalence of J wave (51.2%) similar to our study findings. 19 According to these results and our observations, the prevalence of J wave during TH appears higher than previously reported. Similar to results of previous reports, the J wave was most frequently recorded in the leads facing the 10 The Official Journal of Korean Heart Rhythm Society

11 A During therapeutic hypothermia (33.2 ) ORIGINAL ARTICLE B After recovery from therapeutic hypothermia 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. left ventricle and in the inferior limb leads. 20 Recent data show that the inferolateral J wave is occasionally malignant and therefore strongly associated with sudden cardiac death. 10,21 In addition, the inferolateral J wave in Brugada syndrome is significantly associated with a poor prognosis In this study, VF occurred in two patients with primary arrhythmia disorder (Brugada syndrome and ERS). The small number of subjects in this study made it difficult to estimate the incidence of VF during TH. From our results alone, we cannot determine the relationship between the presence of J waves and the incidence of VF in the general population. Nontheless, considering the temporal relationship between the J wave and VF occurrence, TH may serve as a trigger for VF in certain susceptible patients. Incidence of VF in patients with primary arrhythmic disorder in comparison with the general population needs to be determined in future prospective studies. Recently, a Target Temperature Management trial 26 showed that hypothermia, at a targeted temperature of 33, did not confer a benefit as compared with a targeted temperature of 36. After consideration of this finding, a targeted temperature of 36 may be a safe alternative to avoid potential TH complications while treating abnormal patient groups (e.g., primary arrhythmia disorder patients). VOL.15 NO.4 11

12 ORIGINAL ARTICLE Conclusion J waves were present in the majority of patients undergoing TH after cardiac arrest. TH-related J waves were most frequently recorded in the inferior and lateral precordial leads. VF was rarely observed (2.7%) and was confined to patients with Brugada syndrome or ERS. Although this study cannot prove causality between the VF and the J wave during TH, it illustrates a temporal relationship between hypothermia and increased frequency of malignant arrhythmias in patients with primary arrhythmic disorders. Application of TH may require careful attention in this susceptible, high-risk population. References 1. Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, Gabrielli A, Silvers SM, Zaritsky AL, Merchant R, Vanden Hoek TL, Kronick SL and American Heart A. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S Deakin CD, Nolan JP, Soar J, Sunde K, Koster RW, Smith GB and Perkins GD. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation. 2010;81: Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G and Smith K. Treatment of comatose survivors of out-ofhospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346: Hypothermia after Cardiac Arrest Study G. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346: Osborn JJ. Experimental hypothermia; respiratory and blood ph changes in relation to cardiac function. Am J Physiol. 1953;175: Delaney KA, Vassallo SU, Larkin GL and Goldfrank LR. Rewarming rates in urban patients with hypothermia: prediction of underlying infection. Acad Emerg Med. 2006;13: Rankin AC and Rae AP. Cardiac arrhythmias during rewarming of patients with accidental hypothermia. Br Med J (Clin Res Ed). 1984;289: Vassal T, Benoit-Gonin B, Carrat F, Guidet B, Maury E and Offenstadt G. Severe accidental hypothermia treated in an ICU: prognosis and outcome. Chest. 2001;120: Antzelevitch C. Genetic, molecular and cellular mechanisms underlying the J wave syndromes. Circ J. 2012;76: Haissaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de 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: 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: 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: Emslie-Smith D, Sladden GE and Stirling GR. The significance of changes in the electrocardiogram in hypothermia. Br Heart J. 1959;21: Bastiaenen R, Hedley PL, Christiansen M and Behr ER. Therapeutic hypothermia and ventricular fibrillation storm in early repolarization syndrome. Heart rhythm. 2010;7: 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: Higuchi S, Takahashi T, Kabeya Y, Hasegawa T, Nakagawa S and Mitamura H. J waves in accidental hypothermia. Circ J. 2013;78: Mattu A, Brady WJ and Perron AD. Electrocardiographic manifestations of hypothermia. Am J Emerg Med. 2002;20: Rolfast CL, Lust EJ and de Cock CC. Electrocardiographic changes in therapeutic hypothermia. Crit Care. 2012;16:R 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: Gussak I, Bjerregaard P, Egan TM and Chaitman BR. ECG phenomenon called the J wave. History, pathophysiology, and clinical significance. J Electrocardiol. 1995;28: 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, 12 The Official Journal of Korean Heart Rhythm Society

13 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: 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: 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: 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: 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: 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: ORIGINAL ARTICLE VOL.15 NO.4 13

14 MAIN TOPIC REVIEWS 심방세동의약물치료 원광대학교의과대학내과학교실김남호 Nam-Ho Kim, MD Department of Internal Medicine, Wonkwang University Medical School, Iksan, Korea 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 서론 심박수조절치료 (Rate Control) 심방세동의약물치료는정상동율동을유지하는율동치료 (rhythm control) 및적절한심실박동수를유지하는심박수조절치료 (rate control) 가있다. 환자의상황에따라서이중한가지방법을선택하게되는데, 어떠한방법을선택하더라도혈전색전증 (thromboembolism) 을예방하기위한치료를병행해야한다. 본논문에서는 2014년미국심장학회 (AHA/ ACC/HRS) 에서발표한내용을기초로하여심방세동의약물치료를정리하였다. 1 심박수조절은심방세동의약물치료에서중요한치료전략으로삶의질향상, 이환율감소, 그리고빈맥-유발성심근증의발생을감소시키는역할을한다. 주로 beta-blockers, non-dihydropyridine calcium channel antagonists, digoxin, amiodarone, sotalol 같은약물을사용한다. 이중어떠한약물들을선택할것인가는환자의증상정도, 혈역학적상태, 심부전의유무, 심방세동의발생요인등을고려한다. 또한빠르게심박수를조절하기위해서는주사제를사용하거나전기적율동전환등을고려한다 (Table 1, Figure 1). Received: September 18, 2014 Revision Received: November 20, 2014 Accepted: December 15, 2014 Corresponding author: Nam-Ho Kim, MD, Division of Cardiology, Department of Internal Medicine, Wonkwang University Medical School, Shinyong-dong, Iksan, Jeonbuk , Korea Tel: , Fax: cardionh@wku.ac.kr 14 The Official Journal of Korean Heart Rhythm Society

15 Table 1. Common medication dosage for rate control of atrial fibrillation 약물 정주 경구상용용량 Beta-blockers Metoprolol tartrate 2분에걸쳐 mg 투여, 3회까지 mg BID Metoprolol XL (succinate) 없음 mg QD MAIN TOPIC REVIEWS Atenolol 없음 mg QD Esmolol 1분에걸쳐 500 μg/kg, 이후에 μg/kg/min 없음 Propranolol 1분에걸쳐 1 mg, 2분간격으로 3회까지 mg TID 또는 QID Nadolol 없음 mg QD Carvedilol 없음 mg BID Bisoprolol 없음 mg QD Non-dihydropyridine calcium channel antagonists Verapamil 2 분에걸쳐 mg/kg 투여, 반응이없으면 30 분후 10.0 mg 추가투여, 그리고 mg/kg/min 투여 서방형 : mg QD Diltiazem 2분에걸쳐서 0.25 mg/kg 투여, 이후에 5-15 mg/h 서방형 : mg QD Digitalis glycosides Digoxin 0.25 mg 투여, 반복하여 24시간에최대 1.5 mg까지투여 mg QD Others Amiodarone 1 시간에걸쳐서 300 mg, 이후에 24 시간에걸쳐서 mg/h mg QD BID, twice daily; QD, once daily; QID, four times a day; TID, three times a day. 심방세동의약물치료 심혈관질환없음 고혈압또는좌심실기능이보존된심부전 좌심실기능부전또는심부전 만성폐쇄성호흡기질환 Beta-blocker Diltiazem Verapamil Beta-blocker Diltiazem Verapamil Beta-blocker Digoxin Beta-blocker Diltiazem Verapamil Amiodarone 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 (cardioselective, 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. VOL.15 NO.4 15

16 MAIN TOPIC REVIEWS Table 2. Recommended drug doses for pharmacological cardioversion of atrial fibrillation 약물투여경로용량부작용 Amiodarone 경구 정주 하루에 mg 을나누어서총 10 g 까지투여, 이후에 200 mg QD 유지 150 mg을 10분에걸쳐, 이후에 1 mg/min을 6시간, 0.5 mg/min을 18시간또는경구용량 정맥염, 저혈압, 서맥, QT 간격연장, torsades de pointes ( 드뭄 ), 위장장애, 변비, INR 증가 Dofetilide 경구 CrCl (ml/min) > <20 용량 (μg BID) 권장되지않음 QT 간격연장, torsades de pointes; 신장기능, 체격, 연령에따라용량조절 Flecainide 경구 mg 1* 저혈압, 1:1 전도되는심방조동, proarrhythmia; 관상동맥질환과중요한구조적심장질환이있는환자에서금기 Ibutilide 정주 1 mg 을 10 분에걸쳐투여, 충분한반응이나올때까지 1 mg 반복 (60 kg 미만 mg/kg) QT 간격연장, torsades de pointes, 저혈압 Propafenone 경구 mg 1* 저혈압, 1:1 전도되는심방조동, proarrhythmia; 관상동맥질환과중요한구조적심장질환이있는환자에서금기 * 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 심박수조절에대한권장사항 Class I 1. 발작성, 지속성, 영구형심방세동환자에서심박수조절을위해 beta-blocker 또는 nondihydropyridine calcium channel antagonist 사용을권장한다 (level of evidence: B). 2. 조기흥분이없는심방세동환자에서급히심박수조절을위해서는 beta-blocker 또는 non-dihydropyridine calcium channel blocker 의주사제사용을권장한다. 혈역학적으로불안정한환자에서는전기적율동전환을시도한다 (level of evidence: B). 3. 활동시심방세동과관련된증상이있는환자에서는생리적인범위내의심박수를유지하도록필요한약물치료를통하여적절한심박수조절을평가해야한다 (level of evidence: C). 16 The Official Journal of Korean Heart Rhythm Society

17 Table 3. Dosage and safety considerations for maintenance of sinus rhythm in atrial fibrillation 약물용량금기및사용시주의약물상호작용 Vaughan Williams class IA Disopyramide 속효성 : mg 을 6 시간간격 서방형 : mg 을 12 시간간격 심부전 증가된 QT 간격 칼륨, 녹내장 QT 간격을연장시키는약물 CYP3A4 에의해대사 : 억제제 (verapamil, diltiazem, ketoconazole, macrolide antibiotics, protease inhibitors, 포도주스 ) 와유도제 (rifampin, phenobarbital, phenytoin) 사용주의 MAIN TOPIC REVIEWS Quinidine mg을 8시간간격 증가된 QT 간격 설사 CYP2D6 억제 : tricyclic antidepressants, metoprolol, antipsychotics 농도증가 P-glycoprotein 억제 : digoxin 농도증가 Vaughan Williams class IC Flecainide mg을 12시간간격 동결절또는방실결절장애 심부전 관상동맥질환 심방조동 방실결절하방전도장애 브루가다증후군 신장또는간질환 CYP2D6 에의해대사 : 억제제 (quinidine, fluoxetine, tricyclics); 유전적으로 7-10% 인구에서는없다. 신장배설 Propafenone 속효성 : mg 을 8 시간간격 서방형 : mg 을 12 시간간격 동결절또는방실결절장애 심부전 관상동맥질환 심방조동 방실결절하방전도장애 브루가다증후군 간질환 천식 CYP2D6 에의해대사 : 억제제 (quinidine, fluoxetine, tricyclics); 유전적으로 7-10% 인구에서는없다. Poor metabolizer 는베타차단작용을증가시킨다. P-glycoprotein 억제 : digoxin 농도증가 CYP2C9 억제 : warfarin 농도증가 (INR 25% 상승 ) Vaughan Williams class III Amiodarone 경구 : 2-4 주간하루 mg 을분복 ; 이후하루에 1 번 mg 유지 주사 : 150 mg 을 10 분이상투여 ; 그리고 6 시간동안 1 mg/min; 이후 18 시간은 0.5 mg/min 투여하거나경구제제로변경 ; 24 시간이후 0.25 mg/min 감량고려 동결절또는방실결절장애 방실결절하방전도장애 간질환 증가된 QT 간격 대부분의 CYP 억제 : warfarin (INR 0-200% 상승 ), statin, 그리고많은다른약물들의농도증가 P-glycoprotein 억제 : digoxin 농도증가 Dofetilide μg 을 12시간간격 증가된 QT 간격 신장질환 저칼륨혈증 이뇨제사용 QT 간격을연장시키는약물 CYP3A 에의해대사 : 금기 (verapamil, hydrochlorothiazide, cimetidine, ketoconazole, trimethoprim, prochlorperazine, megestrol); amiodarone 은약물투여최소 3 개월전중지 Dronedarone 400 mg을 12시간간격 서맥 심부전 long-standing AF/flutter 간질환 증가된 QT 간격 CYP3A 에의해대사 : 억제제 (verapamil, diltiazem, ketoconazole, macrolide antibiotics, protease inhibitors, 포도주스 ) 와유도제 (rifampin, phenobarbital, phenytoin) 사용주의 CYP3A, CYP2D6, P-glycoprotein 억제 : 일부 statins, sirolimus, tacrolimus, beta-blockers, digoxin 농도증가 Sotalol mg을 12시간간격 증가된 QT 간격 신장질환 저칼륨혈증 이뇨제사용 QT 간격을연장시키는약물 동결절또는방실결절장애 심부전 천식 없음 ( 신장배설 ) VOL.15 NO.4 17

18 MAIN TOPIC REVIEWS 구조적심장질환없음 구조적심장질환 관상동맥질환 심부전 Dofetilide Dronedarone Flecainide Propafenone Sotalol 전극도자절제술 Dofeilide Dronedarone Sotalol 전극도자절제술 Amiodarone Dofetilide Amiodarone Amiodarone 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. Class IIa 1. 심박수조절 ( 안정시심박수 <80회 / 분 ) 은심방세동의증상관리를위해타당하다 (level of evidence: B). 2. 정주용 amiodarone은조기흥분이없는중환자의심박수조절에유용할수있다 (level of evidence: B). 3. 방실결절절제술및영구적인방실조율은약물치료가불충분하고율동치료가안되는경우에심박수조절을위해사용할수있다 (level of evidence: B). Class IIb 1. 증상이없으면서좌심실수축기기능이보존되어있는경우에는심박수조절 ( 안정시심박수 <110 회 / 분 ) 을느슨하게하는것도타당성이있을것 같다 (level of evidence: B). 2. 경구용 amiodarone은다른방법들이실패하거나금기일때심박수조절을위해사용할수있을것같다 (level of evidence: C). Class III 1. 방실결절절제술및영구적인방실조율은약물치료에의해심박수조절을시도하지않은상태에서는시행하지않는다 (level of evidence: C). 2. Non-dihydropyridine calcium channel antagonist는혈류역학적손상을초래할수있으므로비대상성심부전 (decompensated heart failure) 환자에서는사용해서는안된다 (level of evidence: C). 3. 조기흥분이있는심방세동환자에서는 digoxin, 18 The Official Journal of Korean Heart Rhythm Society

19 non-dihydropyridine calcium channel antagonist, 정주용 amiodarone을사용해서는안된다. 이약제들은심박수를증가시켜심실세동을유발할수있다 (level of evidence: B). 4. Dronedarone은영구형심방세동환자에서심박수조절을위해사용해서는안된다. 뇌졸중, 심근경색증, 전신성혈전증, 심혈관사망의위험성을증가시킨다 (level of evidence: B). 율동치료 (Rhythm Control) 많은환자에서심박수조절치료가선행되나증상이조절되지않는경우, 적절한심박수조절이어려운경우, 젊은환자, 빈맥-유발성심근증, 첫번째인경우, 환자가원하는경우등에는율동치료를고려한다. 율동치료는전기적율동전환, 항부정맥제, 그리고전극도자절제술을고려할수있다. 여기서는약물에의한동율동전환및유지에대해서만언급하기로한다 (Table 2, 3, Figure 2). 약물에의한동율동전환시권장사항 Class I 1. Flecainide, dofetilide, propafenone, 정주용 ibutilide가선택된약물에대한금기사항이없다면심방세동및심방조동의약물적인동율동전환에유용하다 (level of evidence: A). Class IIa 1. 경구용 amiodarone 투여가심방세동의약물학적동율동전환에합리적인선택이다 (level of evidence: A). 2. Beta-blocker 또는 non-dihydropyridine calcium channel antagonist에추가한 propafenone 또는 flecainide ( pill-in-thepocket ) 는선택한환자의모니터링환경에서안전하게사용했던적이있다면병원밖에서심방세동을종료하기위한방법으로사용할수 있다 (level of evidence: B). Class III 1. Dofetilide는과도한 QT 간격의연장을유도하여 torsades de pointes를일으킬위험성이있기때문에병원밖에서치료를시작해서는안된다 (level of evidence: B). 동율동유지를위한항부정맥제에대한권장사항 Class I 1. 항부정맥치료를시작하기전에심방세동의가역적인원인및유발요인에대한치료가이루어져야한다 (level of evidence: A). 2. 심방세동환자에서다음과같은항부정맥제를기저심장질환및동반된질환에따라동율동을유지하기위해사용한다 (level of evidence: A). a. Amiodarone b. Dofetilide c. Dronedarone d. Flecainide e. Propafenone f. Sotalol 3. 항부정맥제를사용하기전에각각항부정맥제의부작용 ( 특히 proarrhythmia) 을고려해야한다 (level of evidence: C). 4. Amiodarone을사용할때에는 amiodarone의독성에의한위험성을고려해야하고, 다른약물로치료에실패하거나다른약물이금기일때사용해야한다 (level of evidence: C). Class IIa 1. 심방세동환자에서빈맥-유발성심근증의치료에항부정맥제를이용한율동치료는유용하다 (level of evidence: C). Class IIb 1. 항부정맥제에의해심방세동의빈도수또는 MAIN TOPIC REVIEWS VOL.15 NO.4 19

20 MAIN TOPIC REVIEWS 증상이감소했을때, 심방세동의재발이빈번하지않고증상이심하지않더라도현상태의항부정맥제를지속하는것은타당할것같다 (level of evidence: C). Class III 1. 심방세동이영구형으로진행되면율동치료를위한항부정맥제 ( 특히 dronedarone) 사용은중지해야한다 (level of evidence: B). 2. Dronedarone 은심부전 (NYHA [New York Heart Association] class III, IV) 이있거나지난 4주이내에비대상성심부전이있었던경우심방세동의치료를위해사용해서는안된다 (level of evidence: B). 결론 이번 2014년미국심장학회의심방세동치료에대한권장사항중혈전색전증예방을위한위험도평가및약물사용에있어서는큰변화가관찰되나, 약물을사용한심박수조절및율동조절에대해서는크게바뀐것은없는것같다. 하지만항부정맥제사용시그효과와부작용에대한심도있는고려가필요함을강조하고있다. 그래서환자의임상상태및심방세동발생요인등을종합적으로평가하여적절한치료전략을수립하고환자에게접근하는것이좋겠다. 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 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 [Epub ahead of print] 20 The Official Journal of Korean Heart Rhythm Society

21 심방세동환자에서의항응고제치료 MAIN TOPIC REVIEWS 성균관대학교의과대학내과학교실온영근 Young Keun On, MD, PhD, FHRS Division of Cardiology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine 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 nonvalvular 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 서론 심방세동은심장부정맥중에서가장흔한부정맥으로심방세동환자의경우혈전색전증에의한뇌졸중의빈도가약 5배증가하는것으로되어있고, 매년심방세동환자의약 5% 에서뇌졸중이발생하는것으로알려져있다. 혈전색전증에의한뇌졸중의원인을분석해보면약 20% 가심방세동에의한뇌졸중으로보고하고있다. 특히심방세동에의한 Received: August 28, 2014 Accepted: December 15, 2014 Correspondence: Young Keun On, MD, PhD, FHRS, Division of Cardiology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine #81 Irwon-ro Gangnamgu, Seoul, Korea, , Fax: yk.on@samsung.com, oykmd123@gmail.com 혈전색전뇌졸중이발생하는경우다른원인에의한경우보다뇌손상의범위가크고신경학적장애가심하여사망이나중증장애로이어질위험이높아항응고제치료를통한혈전색전증의예방이매우중요하다. 비판막성심방세동환자에서의항응고제치료는뇌졸중위험도와항응고제사용에따른출혈위험도를평가하여환자개개인별로적합한결정을해야한다. 이에 2012년 ESC (European Society of Cardiology) 심방세동치료권고안및 2014년 AHA/ ACC/HRS (American Heart Association/American College of Cardiology/Heart Rhythm Society) 심방세동치료권고안 1-3 을중점으로심방세동환자에서의항응고제치료에대해기술하고자한다. VOL.15 NO.4 21

22 MAIN TOPIC REVIEWS 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 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. 비판막성심방세동환자에서의뇌졸중위험도평가 비판막성심방세동환자의뇌졸중위험도평가에 있어기존에심부전 (Congestive heart failure), 고혈압 (Hypertension), 연령 (Age: 75 세이상 ), 당뇨병 (Diabetes mellitus), 뇌졸중 (Stroke) 등을고려한 CHADS2 점수 (CHADS2 score) 가주로사용되어왔다. 그러나나이를세분화하고 (75 세이상 2 점, 세 1 점 ), 성별 ( 여성 1 점 ) 및혈관질환 (Vascular disease) 등의변수를더추가한 CHA2DS2-VASc 점수 (Table 1) 를사용한경우예측력이좀더우수한것으로 알려짐에따라 2010 년 ESC 권고안부터는 CHA2DS2- VASc 점수를권고하기시작하였고, 2014 년 AHA/ ACC/HRS 권고안에서도 CHA2DS2-VASc 점수를 뇌졸중위험도평가를위해추천하고있다. 비판막성심방세동환자에서의항응고제치료에따른출혈위험도평가 항응고제사용에따른출혈위험도를임상에쉽게 평가하기위해 HAS-BLED 출혈위험점수 (HAS- BLED bleeding risk score) 의사용을추천하고있다 (Table 2). 이는고혈압 (Hypertension), 신장혹은간기능이상 (Abnormal renal/liver function), 뇌졸중 (Stroke), 출혈의병력이나성향 (Bleeding history or predisposition), 불안정한 INR (Labile INR [international normalized ratio]), 고령 (Elderly, 65세이상 ) 및출혈성향을증가시키는약제나과량의술 (Drug/alcohol) 등의복용을출혈위험인자로고려한점수로중증출혈의빈도가 0-1점이면약 1%, 5점이면 12.5% 정도로알려져있고, 3점이상이면중증출혈의빈도가 3.74% 정도나되어항응고제치료에따른손익을신중히고려해야한다. 그러므로항응고제치료시교정이가능한출혈위험인자는적극적으로교정해야한다. 항응고제사용 2012년 ESC 권고안에서는 CHA2DS2-VASc 점수에따라 2군으로나누어 1점및그이상인경우새로운경구항응고제의사용을 1차약제로권장하고, 대안으로 warfarin을사용할수있으며, 0점인경우항응고치료를하지않는다. 단, 여성환자로다른뇌졸중위험변수가없는경우에는 CHA2DS2-VASc 점수가 1점이라도항응고제치료를권장하지않는다. 22 The Official Journal of Korean Heart Rhythm Society

23 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 MAIN TOPIC REVIEWS * '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 previous 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. 한편 2014년 AHA/ACC/HRS 권고안에서는비판막성심방세동에서 CHA2DS2-VASc 점수 2점이상인경우항응고제의사용을권장하며, warfarin 또는 dabigatran, 4 rivaroxaban, 5 또는 apixaban 6 과같은새로운경구항응고제를사용할수있다. CHA2DS2- VASc 점수 2점이상이면서말기신부전 (CrCl <15 ml/ min) 환자에서는항응고제로 warfarin을사용한다. CHA2DS2-VASc 점수 1점인경우항응고제치료를하지않거나, 항응고제 ( 새로운경구항응고제또는 warfarin) 혹은 aspirin을고려할수있다. 0점인경우항응고치료를권장하지않는다. 인공기계판막이있는심방세동환자의경우에는 warfarin의사용을권고하고, 인공판막의종류와위치에따라 INR 범위 ( 또는 ) 를결정한다. Warfarin을사용하는경우치료시작시기에는매주 INR을검사하고, INR이안정된이후에는 1개월에한번 INR 검사를시행해야한다. 인공판막이있는심방세동환자에서 warfarin을중단해야하는시술또는수술을받는경우에는 heparin 또는저분자량 heparin (low molecular weight heparin, LMWH) 을 warfarin 중단기간에사용할것을권장하고, 인공판막이아닌심방세동환자에서의 heparin 또는 LMWH 사용여부는환자의뇌졸중위험도와출혈위험도및항응고중단기간을고려하여결정한다. 항혈소판제 심방세동환자의뇌졸중발생에서일차예방을위한 aspirin의효과에대한연구결과들을메타분석해보면약 19% 의상대적뇌졸중발생예방효과가있어매년절대값으로 0.8% 의뇌졸중을예방하는것으로알려져있다. 한편일과성허혈발작 (transient ischemic attack, TIA) 또는뇌졸중환자를대상으로한이차예방효과에서는 aspirin이절대값으로매년 2.5% 의뇌졸중을예방하는것으로보고되고있다. Aspirin과 clopidogrel 복합요법은 aspirin 단독요법에비해 28% 의상대적뇌졸중발생예방효과가있으나 warfarin에비해서는열등하여 warfarin이 aspirin과 clopidogrel 복합요법에비해 40% 의상대적뇌졸중발생예방효과가있는것으로알려져있다. VOL.15 NO.4 23

24 MAIN TOPIC REVIEWS 새로운항응고제 심방세동환자의뇌졸중발생에서 warfarin의효과에대한연구결과들을메타분석해보면약 64% 의상대적뇌졸중발생예방효과가있어매년절대값으로 2.7% 의뇌졸중을예방하는것으로알려져있다. Warfarin 사용시에는뇌졸중예방및출혈위험방지를위해 INR 을유지하는것이필수적이고, 따라서정기적인혈액검사가필요하다. 그렇지만실제임상상황에서는이러한 INR 을유지하는비율이절반이하인것으로알려져있고, warfarin의약물상호작용, 음식물과의상호작용, 정기적인혈액검사의불편함등이제시되어새로운항응고제의필요성이대두되었다. 새로개발된항응고제로는 dabigatran, rivaroxaban, apixaban, edoxaban이있으며, 대규모임상연구결과에의하면뇌졸중예방면에서 warfarin 과비슷한성적을보이고있고, 뇌출혈위험도면에서는오히려더우수한결과를보이고있다. Dabigatran Dabigatran은 direct thrombin 억제제로개발되어심방세동에서의뇌졸중예방효과를 warfarin과비교한 RE-LY (Randomized Evaluation of Long-term anticoagulant therapy) 연구가발표되어있다. 4 이연구에서 1개이상의뇌졸중위험인자를동반한심방세동환자를 dabigatran과 warfarin 사용군으로나누고, 평균 2년간추적관찰하여뇌졸중및혈전색전증을비교한결과 dabigatran 110 mg 또는 150 mg BID 투여군에서 warfarin 군에비해뇌졸중및혈전색전증발생예방효과가비열등하였다. Dabigatran 150 mg BID 투여군에서뇌졸중및혈전색전증이 1.11% 발생하여 warfarin 군의 1.69% 에비해예방효과면에서우월하였고 (RR=0.66), dabigatran 110 mg BID 투여군에서는중증의출혈이 2.71% 발생하여 warfarin 군의 3.36% 에비해중증출혈의발생이적었다. Rivaroxaban Rivaroxaban은 factor Xa 억제제로개발되어뇌졸중위험인자를동반한심방세동환자를대상으로 rivaroxaban 20 mg 복용군과 warfarin 군으로나누어평균 19개월동안의뇌졸중및혈전색전증의발생을비교한 ROCKET-AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) 연구가발표되었다. 5 뇌졸중및혈전색전증이 rivaroxaban 군에서 1.71 events/100 patient-year 발생하여 warfarin 군의 2.16 events/100 patient-year에비해우월하였다. 중증출혈의발생은 rivaroxaban 군에서 3.60 events/100 patient-year 발생하여 warfarin 군의 3.45 events/100 patient-year과비교하여차이가없었다. 출혈성합병증에서 rivaroxaban 군은 warfarin 군에비해출혈성뇌졸중 (0.26% versus 0.44%; HR, 0.59; p=0.024), 두개내출혈 (0.7% versus 0.5%; HR, 0.67; p=0.02) 및중증출혈은유의하게적었으나 (0.5% versus 0.2%; HR, 0.50; p=0.003), 위장관출혈은더많았다 (3.3% versus 2.2%; p<0.001). Apixaban Apixaban은 factor Xa 억제제로개발되어뇌졸중위험인자를동반한심방세동환자를대상으로 apixaban 5 mg BID 복용군과 warfarin 군으로나누어평균 1.8년동안의뇌졸중및혈전색전증의발생을비교한 ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) 연구가발표되었다. 6 CHADS2 점수 1점이상인비판막성심방세동환자에서 apixaban은 warfarin에비해우월한뇌졸중및전신색전증예방효과를보였으며, 중증출혈 (2.13% versus 3.09%; HR, 0.69; p<0.001), 출혈성뇌졸중 (0.24% versus 0.47%; HR, 0.51; p<0.001), 두개내출혈 (0.33% versus 0.80%; HR, 0.42; p<0.001) 등의발생은더낮았다. 24 The Official Journal of Korean Heart Rhythm Society

25 Edoxaban Edoxaban은 factor Xa 억제제로개발되어뇌졸중위험인자를동반한심방세동환자를대상으로 edoxaban 군과 warfarin 군으로나누어평균 2.8년동안의뇌졸중및혈전색전증의발생을비교한 ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation) 연구가발표되었다. 7 뇌졸중및혈전색전증의연간발생률은 warfarin 군 1.50%, 고용량 edoxaban 군 1.18% (HR, 0.79; p<0.001 for non-inferiority), 저용량 edoxaban 군 1.61% (HR, 1.07; p<0.005 for non-inferiority) 로비열등성이확인되었으며, 중증출혈의연간발생률은 warfarin 군 3.43% 에비하여고용량 edoxaban 군 2.75% (HR, 0.80; p<0.001) 및저용량 edoxaban 군 1.61% (HR, 0.47; p<0.001) 로 edoxaban 군각각이더적었다. 관상동맥중재술을시행하는심방세동환자 심방세동환자에게관상동맥중재술을시행하는경우에는시술중에항응고제투여를중단하여혈관천자부위의출혈위험성을줄이도록하고, BMS (bare metal stent) 를시술하여이중항혈소판제투여기간을최소화하도록권고한다. 관상동맥중재술또는수술이후에는 CHA2DS2-VASc 점수 2점이상인경우항응고제와 clopidogrel 병합요법을추천한다. 결론 심방세동의치료전략에는혈전색전에의한뇌졸중예방을위한항응고요법이매우중요하며, 뇌졸중위험도와항응고제사용에따른출혈위험도를평가하여환자개인별로맞춤치료를해야한다. 뇌졸중위험도평가를위해 CHA2DS2-VASc 점수를, 출혈위험도평가를위해 HAS-BLED 출혈위험점수를권고한다. CHA2DS2- VASc 점수 2점이상의뇌졸중고위험도인심방세동환자에서는항응고제의사용을권고하며, warfarin의투여 및 INR 2-3 유지또는새로운항응고제가추천되고있 다. 기존의 warfarin 을대체할수있는새로운항응고제 로는 dabigatran, rivaroxaban, apixaban, edoxaban 이 있으며, 대규모임상연구결과에의하면약제의종류, 용 량및제제에따라뇌졸중예방효과에있어 warfarin 치 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 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: Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P 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: 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: 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: 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: 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. MAIN TOPIC REVIEWS VOL.15 NO.4 25

26 MAIN TOPIC REVIEWS 2011;365: 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: The Official Journal of Korean Heart Rhythm Society

27 전극도자절제술과변화된국내보험규정 MAIN TOPIC REVIEWS 서울대학교의과대학내과학교실오세일 Seil Oh, MD, PhD, FHRS Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea 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 recommended as an alternative to antiarrhythmic drugs for patients with symptomatic recurrent paroxysmal AF, provided the procedure is performed by an experienced center/operator. Catheter ablation is reasonable as firstline 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 서론 심방세동환자를대상으로하는새로운약제, 새로운 치료법의개발로심방세동가이드라인이자주업데이트 되고있다. 이에전극도자절제술부문은최근가이드라 인에서어떤면들이새롭게언급되고있으며, 지난 6 월 에개정된국내건강보험요양급여인정기준은어떤지 에대해알아보고자한다. Received: September 8, 2014 Accepted: December 15, 2014 Corresponding 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, , Korea Tel: , Fax: seil@snu.ac.kr ESC (European Society of Cardiology) 2012 년가이드라인업데이트 1 1. 새로운증거들 동리듬유지측면에서항부정맥제보다는전극도자 절제술의우수성이추가적인연구들 (MANTRA-PAF [Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation], 2 RAAFT-2 [Radiofrequency Ablation vs Antiarrhythmic Drugs as First-Line Treatment of Paroxysmal Atrial Fibrillation] 3 ) 에서입증되어 2010 년 가이드라인의권고사항이공고해졌다. 또한시술관련 합병증발생의가능성이낮은선택된발작성심방세동 환자들에서는리듬유지를위한일차치료로전극도자 VOL.15 NO.4 27

28 MAIN TOPIC REVIEWS A No or minimal structural heart disease Paroxysmal Persistent Patient choice a Catheter ablation Dronedarone Flecainide Propafenone Sotalol b Patient choice Amiodarone B Relevant structural heart disease Yes HF No Yes Due to AF No Amiodarone Dronedarone c Sotalol d Patient choice Catheter ablation b 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. a Usually pulmonary vein isolation is appropriate. b More extensive left atrial ablation may be needed. c Caution with coronary heart disease. d Not recommended with left ventricular hypertrophy. Heart failure due to AF=tachycardiomyopathy. AF, atrial fibrillation; HF, heart failure. 28 The Official Journal of Korean Heart Rhythm Society

29 절제술을선택할수있음이타당하다는사실을다시한번피력하고있다 (Figure 1A). 비록전극도자절제술이항부정맥제보다우수한치료법이지만재발률은상당히높다. 경험이많은센터에서적절한환자, 심지어 lone atrial fibrillation (AF) 환자일지라도후기에재발하는경우가흔하다. 하지만재발의가장중요한예측인자는초기재발이다. 4-7 즉, 초기재발상태가유지되는것이나중에재발하는경우보다훨씬중요하다는의미이다. 합병증은유럽기관을대상으로조사한결과에서뇌졸중 0.6%, 심낭압전 1.3%, 말초혈관합병증 1.3%, 심낭염 2% 로나와이전에보고되었던미국데이터및전세계설문조사와유사한결과를보였다 년사이에첫번째절제술을받았던 4,156명의데이터베이스분석에따르면총합병증발생률은 5%, 절제술후 1년이내의모든원인에의한입원율은 38.5% 였다. 8 무증상의뇌경색은 4-25% 로다양하게보고되었는데, 9-11 이는절제술에사용된도구의차이에기인하는것으로추정된다. 비록무증상뇌경색의임상적의미는분명하지않으나더안전한심방세동절제술방법의개발이필요함은분명하다. 3. 절제술전후의항응고요법절제술전후의항응고요법은뇌졸중예방치료가평생필요한환자뿐만아니라뇌졸중위험인자가없는환자모두에게도움이되는것으로인식되고있다. 최근에는시술직전에항응고요법을중지하지않고계속유지하는방법이안전하다는보고가있었으며, HRS/EHRA/ECAS (Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society) 합의문에서도항응고요법을중지하고 heparin을사용하는방법대신항응고요법을중지하지않고계속투여하는방법으로사용할수있다고권고한바있다. 16 ESC도이번가이드라인에서는항응고요법을중지하지않고, 계속투여하는방법을사용할수있다고권고하고있으며, 절제술과정중 INR (international normalized ratio) 은 정도를추천한다. 또한, CHA2DS2-VASc 점수가 2점이상인경우에는시술성공여부와상관없이장기간의항응고요법을권한다. 새로운항응고제 (new oral anticoagulants, NOAC) 에대해서는아직증거가불충분한상태여서강하게권고하고있지는않다. MAIN TOPIC REVIEWS 2. 심부전환자에서의절제술 4. 권고강도와증거수준의변화 개정된가이드라인에서는심부전환자의리듬조절방법에동원할수있는항부정맥제로유일하게 amiodarone만을권고한다. 심부전환자의심방세동증상조절을위해숙련된센터에서전극도자절제술을시행하는것은하나의치료전략이될수있다. 물론심부전환자에서는재발률과합병증발생률이높다는사실은인지해야한다. 또한심방세동의증상이심부전증상과혼돈될수있으므로주의깊은병력청취가필요하다. 환자의증상이심방세동에의한것으로추정된다면리듬조절을위해 amiodarone과절제술중선택할수있다 (Figure 1B). 2010년에는항부정맥제로리듬조절에실패한발작성심방세동의절제술권고강도가 class IIa였으나, 이후축적된임상연구결과들로인해 2012년에는 class I 으로격상되었다. 또한증상이심하고위험도가낮은환자의경우일차치료로전극도자절제술을고려해야한다고권고하고있다 ( 권고강도 IIa, 증거수준 B). 물론이는 (1) 매우경험이풍부한센터 / 시술자가시행하는경우, (2) 적절하게환자가선정된경우, (3) 다른치료대안에대해서주의깊게평가한경우, (4) 환자가선호하는경우로한정한다. 지속성심방세동에대한권고안은 2010년에비해변환된것이없다. 아직까지무증상의심방세동환자에게는절제술을권할만한증거가없다. VOL.15 NO.4 29

30 MAIN TOPIC REVIEWS No Structural Heart Disease Structural Heart Disease a CAD HF Dofetilide b,c Dronedarone Flecainide b,d Propafenone b,d Sotalol b,c Catheter ablation b,c Dofeilide Dronedarone Sotalol b,c a Catheter ablation Amiodarone Dofetilide b,c Amiodarone Amiodarone Figure 2. Rhythm control strategy for atrial fibrillation without and with structural heart disease recommended in 2014 AHA/ACC/HRS guidelines. a Depending on patient preference when performed in experienced centers. b Not recommended with severe LVH (wall thickness >1.5 cm). c Should be used with caution in patients at risk for torsades de pointes ventricular tachycardia. d Should be combined with AV nodal blocking agents. AF, atrial fibrillation; CAD, coronary artery disease; HF, heart failure; and LVH, left ventricular hypertrophy. AHA/ACC/HRS (American Heart Association/ American College of Cardiology/Heart Rhythm Society) 2014 년가이드라인 17 ESC 가이드라인의주요업데이트후 2 년만에발표된 내용이어서전극도자절제술부문에서는유럽의 가이드라인과비교하여치료전략에큰차이가없다. 1. 주요권고사항 I 군또는 III 군의항부정맥제투여에도불구하고 증상이있는심방세동환자에서유형별로다음과같이 전극도자절제술을권고하고있다 : 발작성 ( 권고강도 I; 증거수준 A), 발작성의일차치료 ( 권고강도 IIa; 증거 수준 B), 지속성 ( 권고강도 IIa; 증거수준 A), 지속성의 일차치료 ( 권고강도 IIb; 증거수준 C), 장기지속성 ( 권고강도 IIb; 증거수준 B) 아직까지절제술이사망률, 뇌졸중, 심부전등을줄여줄수있는지는증거가부족한상황이다. 이는현재진행중인 CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation), EAST (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) 연구등이증명해줄수있을것으로기대한다. 2. 환자의선정적절한환자의선정을위해서는심방세동의유형, 증상의정도, 구조적심장질환이있는지등을평가해야한다. 리듬유지요법에대한전략은 ESC 가이드라인과유사하다 (Figure 2). 30 The Official Journal of Korean Heart Rhythm Society

31 Table 1. Complications of radiofrequency catheter ablation for atrial fibrillation Complication Symptoms/Signs Treatment Air embolism Acute ischemia, cardiac arrest, AV block, hypotension Supplemental oxygen, fluids, CPR, or pacing if indicated MAIN TOPIC REVIEWS 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 in diaphragmatic paralysis Shortness of breath, Elevated hemidiaphragm None, usually resolves spontaneously Iatrogenic atrial flutter Tachycardia Cardioversion, antiarrhythmic drugs, or repeat ablation Gastric motility disorder Mitral valve injury requiring surgery Nausea, vomiting, bloating, abdominal pain Entrapment of catheter Depends on severity of symptoms 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 guidelines 17 ) 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. VOL.15 NO.4 31

32 MAIN TOPIC REVIEWS 3. 절제술전후의항응고요법 ESC 가이드라인과마찬가지로항응고요법중지후 heparin 사용의대안으로계속해서항응고요법을유지하는전략에대해언급을하고있다. 하지만주요권고사항에는포함되어있지않다. NOAC, 특히 dabigatran에대한언급이있으나역시권고사항에는들어가있지않다. 시술후장기간항응고요법에대한의견도 ESC 가이드라인과유사하다. 즉, 위험도가낮지않은군에대한항응고요법중지에대해서는신중한입장이다. 4. 심부전환자의절제술역시 ESC 가이드라인과유사한의견을피력하고있다. 환자를전체적으로잘파악해서진행한다면심한좌심실기능부전이있는환자에서도증상이있는심방세동을치료하는데절제술이유용할수있다는내용이다. 5. 합병증알려진합병증들에대한요약은 Table 1과같다. 조절되지않는심방세동으로약제투여전후심전도검사에서심방세동이증명된경우. 다만, 영구형 (permanent) 심방세동은인정하지아니함 (2) 항부정맥약제에대한부작용또는동결절기능부전을동반한빈맥-서맥증후군에서와같이약제유지가불가능한심방세동으로서심전도에의해확인된경우 (3) 재시술은이전시술후 3개월이경과된이후에실시하되심전도상심방세동또는심방빈맥의재발이증명된경우 (4) 심방세동고주파절제술시 CTI (cavotricuspid isthmus)-dependent 심방조동이유도된경우 2. 3차원매핑 3차원매핑도 2014년 6월부터요양급여가인정되고있다. 기준을요약하면 3차원빈맥지도화를이용한심방세동의고주파절제술은요양급여를인정하며, 3 차원빈맥지도화를위해실시한영상진단 (CT, MRI) 은별도요양급여를인정한다. 결론 합병증발생률과연관된인자들은고령, 여성, CHADS2 점수 2이다. 8,18,19 또한 ESC 업데이트가이드라인에도언급되었듯이좌심방의절제술은 MRI로발견할수있는무증상의작은뇌경색을유발시킬수있다. 하지만대부분은시간이경과하면서해결되거나사라지는것으로보인다. 국내보험규정 1. 전극도자절제술 심방세동전극도자절제술의국내건강보험요양급여는 2014년 6월부터다음과같은기준의적용을받고있다. (1) 항부정맥약제 (class Ⅰ 또는 class Ⅲ) 중 1가지이상을 6주이상충분한용량으로투여한이후에도증상이 최근가이드라인에서의주요이슈는 (1) 전극도자절제술의유용성이더욱입증되었으며, (2) 일부발작성심방세동환자에게는일차치료법으로절제술을선택하는것이가능하고, (3) 시술전후항응고요법을지속하는방법이대두되고있다는점등이다. 가이드라인으로채택되기위해증거가더확보되어야하는부문은 (1) 전극도자절제술이사망률과뇌졸중을줄일수있는치료법으로인정받을수있을것인가, (2) 새로운항응고제 (NOAC) 의시술전후사용지침, (3) 시술과관련된합병증을줄일수있는좀더안전한방법의개발등이될것이다. 국내에서도최근요양급여인정기준이개정되어심방세동환자들뿐만아니라임상의들의진료에도큰도움이되고있다. 빠르게발전하는치료법과가이드라인에발맞춰국내보험인정기준도계속해서국제적인수준으로업데이트될수있기를바란다. 32 The Official Journal of Korean Heart Rhythm Society

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Circulation. 2010;121: 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: 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: 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: 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: Hakalahti A, Uusimaa P, Ylitalo K and Raatikainen MJ. Catheter ablation of atrial fibrillation in patients with therapeutic oral anticoagulation treatment. Europace. 2011;13: 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? 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Europace. 2012;14: 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 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 Hoyt H, Bhonsale A, Chilukuri K, Alhumaid F, Needleman M, MAIN TOPIC REVIEWS VOL.15 NO.4 33

34 MAIN TOPIC REVIEWS 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: 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: The Official Journal of Korean Heart Rhythm Society

35 심방세동환자에서전기적동율동전환시에 Warfarin 과새로운항응고제의비교연구 ARTICLE REVIEW 성균관대학교의과대학내과학교실온영근 Young Keun On, MD, PhD Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine 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 Heuzey, 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 Investigators Eur Heart J Sep 2. [Epub ahead of print] 배경 심방세동환자에서동율동전환전후에혈전색전증이 약 5-7% 발생하고, warfarin 의사용시혈전색전증의 발생이 % 까지줄어드는것으로알려져있다. 현 재유럽및미국심장학회 / 부정맥학회지침에서는동율 동전환이전에최소 3 주간의항응고치료를시행하고, 동율동전환이후에도최소 4 주간의항응고치료를시행 할것을권고하고있다. 새로운항응고제가비판막성심 Received: September 18, 2014 Accepted: December 15, 2014 Correspondence: 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, Korea Tel: , Fax: yk.on@samsung.com 방세동환자의뇌졸중예방을위해 warfarin을대체할수있는것으로알려져있으나아직까지동율동전환시에새로운항응고제사용에대한전향적인연구는없는실정이다. X-VeRT 연구는심방세동환자에서전기적동율동전환시에새로운항응고제를사용한최초의전향적무작위대조연구이다. 방법및결과 1,504명의환자를 rivaroxaban 군과 warfarin 군에 2:1의비율로무작위배정하였고, 연구자가무작위배정이후 1-5일이내에조기동율동전환또는 3-8주사이에지연동율동전환전략을선택하였다. 1차효과결과 (efficacy outcome) 는뇌졸중, 일과성허혈, 말초혈관색전증, 심근경색, 심혈관사망의총합으로분석하였고, 1차안전결과 (safety outcome) 는주요출 VOL.15 NO.4 35

36 ARTICLE REVIEW 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( ) 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) Ischemic stroke 0 2 (0.41) 0 1 (0.36) 0 1 (0.47) TIA SE 0 1 (0.20) 0 1 (0.36) 0 0 MI 1 (0.10) 1 (0.20) 1 (0.18) (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( ) 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) (0.47) Hb decrease 2 g/dl 4 (0.40) 1 (0.20) 1 (0.17) 1 (0.35) 3 (0.73) 0 Transfusion 2 units RBCs 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 혈로정의하였다. 978명의 rivaroxaban 군에서 2건의뇌졸중을포함한 5건 (0.51%) 의 1차효과결과가발생하였고, 492명의 warfarin 군에서는 2건의뇌졸중을포함하여 5건 (1.02%) 의 1차효과결과가발생하였다 (risk ratio, 0.50; CI, ). Rivaroxaban 투여시조기동율동전환전략으로 4명 (0.71%) 에서, 지연동율동전환전략으로는 1명 (0.24%) 에서 1차효과결과가발생하였다. 한편 warfarin 투여시조기동율동전환전략으로 3명 (1.08%) 에서, 지연동율동전환전략으로는 2명 (0.93%) 에서 1 차효과결과가발생하였다. 지연동율동전환전략에서 rivaroxaban 군에서동율동전환까지기간이평균 22 일로 warfarin 군에서의평균 30일에비해의미있게짧았다. 주요출혈은 rivaroxaban 군에서 6명 (0.6%) 발생 하였고, warfarin 군에서는 4명 (0.8%) 발생하였다 (risk ratio, 0.76; CI, ). 결론 심방세동환자에서전기적동율동전환시에 rivaroxaban은효과적이고안전하게 warfarin을대체할수있는것으로보인다. 36 The Official Journal of Korean Heart Rhythm Society

37 Atrial Tachycardia in a Patient with Extracardiac Conduit Fontan Circulation ECG & EP CASES 연세대학교의과대학내과학교실엄재선, 김남균, 박진규, 정보영, 박희남, 이문형 Jae-Sun Uhm, MD 1 ; Nam Kyun Kim, MD 2 ; Jin-Kyu Park, MD 1 ; Boyoung Joung, MD 1 ; Hui-Nam Pak 1 ; Moon-Hyoung Lee 1 Departments of Cardiology 1 and Pediatric Cardiology 2, Arrhythmia Center, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea 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 Introduction The survival rate of patients with complex congenital heart disease has recently improved, most likely due to the development of new surgical techniques and improved perioperative medical management. 1 As the number of adult patients Received: May 28, 2014 Accepted: December 15, 2014 Correspondence: Jae-Sun Uhm, MD, Department of Cardiology, Severance Cardiovascular Hospital, 50 Yonsei-ro Seodaemun-gu, Seoul, Korea, Tel: , Fax: jason@yuhs.ac.krm-suk Ko, MD, PhD, Division of Cardiology with congenital heart disease has increased, arrhythmias and heart failure are becoming growing issues in these patients. 1 Thus, it is not surprising that the demand for electrophysiologic (EP) studies and radiofrequency catheter ablation (RFCA) is increasing. EP studies and RFCA are challenging in patients who have undergone extracardiac conduit Fontan procedures for the palliative treatment of congenital heart disease, because the systemic venous blood is not drained into the heart in these techniques. Here, we report a case of focal atrial tachycardia, which was ablated via a trans-conduit puncture in a patient who had undergone an extracardiac conduit Fontan procedure. Case A 14-year-old male patient visited the emergency room complaining of palpitations for 3 VOL.15 NO.4 37

38 ECG & EP CASES A B Figure 1. (A) electrocardiogram during palpitation shows regular narrow QRS tachycardia with short RP interval. (B) electrocardiogram during sinus rhythm. 38 The Official Journal of Korean Heart Rhythm Society

39 A B C ECG & EP CASES Ao RA RA V V c rv PA c LA LA rv Figure 2. Cardiac CT shows findings compatible with complete transposition of the great arteries, double-inlet left ventricle, large ventricular 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. A LPA B C ICE HV IVC Needle Snare Sheath C Needle D Needle RA Snare Sheath 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. VOL.15 NO.4 39

40 ECG & EP CASES A B Figure 4. Positioning of the EP catheters during basic EP study (A) and during tachycardia mapping (B). hours. He had experienced several episodes of palpitations during the past year. His blood pressure was 82/49 mmhg. The electrocardiogram (ECG) showed regular, narrow QRS tachycardia with a rate of 160 beats/min and a short RP interval (Figure 1A). In the emergency room, the tachycardia spontaneously converted into sinus rhythm (Figure 1B). The QRS morphology of the tachycardia was similar to that in sinus rhythm. When he was 10 days old, he was diagnosed with double-inlet left ventricle (DILV), complete transposition of the great arteries (TGA), and large ventricular septal defect (VSD). When he was 5 months old, the bidirectional cavopulmonary shunt and interatrial septectomy were performed for palliation. At the age of 1 year, an extracardiac conduit Fontan procedure was performed with the autologous pericardium. We decided to perform the EP study for diagnosis and treatment of the tachycardia. Cardiac computed tomography (CT) was performed for assessment of the heart anatomy, showing findings compatible with TGA, DILV, large VSD, functional single ventricle, and extracardiac Fontan conduit (Figure 2). Both femoral veins were punctured. Conduit angiography was performed with a Bermantype angiography catheter (Arrow International, Reading, PA, USA) (Figure 3A). Two SR-0 Swartz transseptal introducer sheath (St Jude Medical, St Paul, MN, USA), a snare catheter (PFM Medical, Nonnweiler, Germany), and an intracardiac echocardiography catheter (AcuNav, Siemens, Mountain View, CA, USA) were inserted into the Fontan conduit via the femoral veins. A BRK-1 Brockenbrough transseptal needle (St Jude Medical) was inserted into the Swartz sheath, and the dilator tip of the Swartz sheath was held with the snare catheter to prevent it from sliding up along the conduit wall (Figure 3B and D). We punctured the wall between the conduit and the right atrium with the Brockenbrough transseptal needle under intracardiac echocardiography guidance (Figure 3C). Right and left atriography was performed with the pigtail catheter via the trans-conduit puncture. A deflectable decapolar catheter (St 40 The Official Journal of Korean Heart Rhythm Society

41 A ECG & EP CASES I avf V1 HAp HAd ABLd ABLp Vd Vp Stim Carto B I avf V1 HAp HAd Vd Vp Stim Carto 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. VOL.15 NO.4 41

42 ECG & EP CASES A B RSPV LSPV RA LA LAA LAA His 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. Jude Medical) was placed in the high left atrium via the Swartz sheath and a decapolar catheter (St Jude Medical) was placed in the ventricle via the aorta (Figure 4A). The initial rhythm was normal sinus rhythm. During ventricular pacing and single ventricular extrastimuli, the atrial electrogram showed one-to-one ventriculoatrial conduction with decremental properties. During the atrial pacing of 240 ms and infusion of isoproterenol at a rate of 2 μg/min, tachycardia with a 290 ms cycle length was induced. Tachycardia was maintained despite the presence of a premature ventricular complex and atrioventricular block (Figure 5A and B). Therefore, atrioventricular reentrant tachycardia could be excluded. During tachycardia, the atrioventricular or ventriculoatrial interval varied (Figure 5B). It was not compatible with atrioventricular nodal reentrant tachycardia. The tachycardia was not entrainable by ventricular pacing. The decapolar catheter was moved to the right atrium (RA) side in the Fontan conduit, and an irrigated ablation catheter (Thermocool, Biosense Webster, Diamond Bar, CA, USA) was inserted into the atrium via the conduit puncture for tachycardia mapping (Figure 4B). During tachycardia, 3-dimensional electroanatomical mapping was performed with CARTO (Biosense Webster, Diamond Bar, CA, USA). The tachycardia was originating from the mid portion of the remnant interatrial septum (Figure 6). The tachycardia was compatible with focal atrial tachycardia originating from the interatrial septum. During sinus rhythm, we mapped the His bundle potentials. The His bundle area was located in the lower posterior potion of the interatrial septum. The origin of the tachycardia was away from the His bundle area by 13.6 mm (Figure 6B). We performed RFCA of the origin of the atrial tachycardia by delivering 30 watts of RF energy for 90 s with the irrigated ablation catheter during sinus rhythm. The procedure ended after we confirmed that the tachycardia was not induced 42 The Official Journal of Korean Heart Rhythm Society

43 by the programmed electric stimulation and isoproterenol infusion. The patient had no symptom and maintained sinus rhythm for 6 months after RFCA. Discussion The case was focal atrial tachycardia originating from the septum in a patient who had undergone an extracardiac conduit Fontan procedure. We performed an EP study and RFCA of the origin of the focal atrial tachycardia successfully via the trans-conduit puncture. The lifelong prevalence of atrial tachycardia in patients with extracardiac Fontan circulation is approximately 50%, 2-4 and it is considerably higher than in the normal population. In patients with extracardiac conduit Fontan circulation, it is difficult to perform an EP study, because the heart is completely excluded from the systemic venous system. There were previous case reports of EP studies and RFCA via various routes in patients with Fontan circulation, including via a trans-thoracic puncture, sternotomy approach, trans-apical access and trans-conduit puncture. 5-8 The EP catheters can be transvascularly placed via 2 pathways: the trans-conduit puncture and retrograde transaortic approach. The approach via the trans-conduit puncture is suitable for gaining access to the atrium and the retrograde transaortic approach is suitable for gaining access to the ventricle. It is challenging to puncture the Fontan conduit because fibrosis forms around the conduit. In addition, the conduit wall is vertical unlike the interatrial septum and the transseptal needle tends to slide up along the conduit wall instead of puncturing it. The use of a Brockenbrough transseptal needle while holding the dilator tip of the Swartz sheath with a snare catheter is a useful method for puncturing the Fontan conduit. 9 A large-curve BRK-1 transseptal needle is superior to a smallcurve BRK needle. Moreover, the radiofrequency transseptal needle can be a good option for puncturing the fibrotic Fontan conduit. In patients with congenital heart disease, the EP study and RFCA are very challenging because of the unusual anatomy of the heart. In addition, it is common for patients to have vascular anomalies including a persistent left superior vena cava and inferior vena cava interruption. It is important that the operator be completely aware of the anatomy of heart and vessels of each patient. Every patient has a unique heart structure, even though this patient group has the same diagnosis of congenital heart disease. The operator needs to review and understand the previous cardiac surgery and intervention. The operator should make a meticulous plan for the procedure, taking into consideration the types of EP catheters to be used for each chamber, pathways to be used for positioning of the EP catheters, and appropriate angles for the X-ray beam to improve visualization. The operator needs to discuss the current hemodynamics and long-term prognosis of the patient with the pediatric cardiologists. Given the complex heart anatomy, cardiac CT and a 3-dimensional electroanatomic mapping system are necessary for guiding the procedure. Intracardiac echocardiography can be helpful for real-time visualization of the anatomy and EP catheters. The activated coagulation time should be maintained at ms by heparin infusion during the EP study in patients with a single ventricle, as the catheters are placed in the systemic chambers. In the present case, the remnant interatrial septum might become arrhythmogenic after septectomy due to degenerative changes of the interatrial septum. This patient is likely to develop ECG & EP CASES VOL.15 NO.4 43

44 ECG & EP CASES atrial tachyarrhythmia originating from other parts of the atrium. In addition, an advanced atrioventricular block can occur in the future, although the peri-procedural ECG showed first degree atrioventricular block. Thus, the patient will require long-term follow-up. Conclusion EP studies and RFCA are feasible via a transconduit puncture in patients with extracardiac conduit Fontan circulation. 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: Gelatt M, Hamilton RM, McCrindle BW, Gow RM, Williams WG, Trusler GA, Freedom RM. Risk factors for atrial tachyarrhythmias after the Fontal operation. J Am Coll Cardiol. 1994;24: 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: Lasa JJ, Glatz AC, Daga A, Shah M: Prevalence of arrhythmias late after the Fontan operation. Am J Cardiol. 2014;133: Nehgme R, Carboni MP, Care J, Murphy JD. Transthoracic percutaneous access for electroanatomic mapping and catheter ablation of atrial tachycardia in patients with a lateral tunnel Fontan. Heart Rhythm. 2006;3: 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: 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 Interv. 2009;74: 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: Aoki H, Nakamura Y, Takeno S, Takemura T. A new procedure for a transconduit 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 doi: /j.hrthm [Epub ahead of print]. 44 The Official Journal of Korean Heart Rhythm Society

45 Warfarin-associated Extensive Spontaneous Spinal Epidural Hematoma Mimicking Stroke ECG & EP CASES 전남대학교의과대학내과학교실이기홍 Ki Hong Lee, MD, PhD The Heart Research Center of Chonnam National University Hospital, Cardiovascular Research Institute of Chonnam National University, Gwangju, Korea ABSTRACT Clinicians usually suspect acute stroke when patients with atrial fibrillation (AF) present with neurologic symptoms. 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 neurologic 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 Introduction Oral anticoagulation (OAC) therapy is strongly recommended to prevent thromboembolic stroke in patients with atrial fibrillation (AF). 1 However, strict control is needed to achieve optimal therapeutic level when using warfarin as the anticoagulant. Clinicians usually suspect acute stroke when patients with AF present with neurologic symptoms. 2 I report an AF patient on warfarin therapy complaining of acute-onset right hemiplegia, which was diagnosed as extensive spinal epidural hematoma rather than stroke. Case Received: August 21, 2014 Revision Received: November 28, 2014 Accepted: December 15, 2014 Correspondence: Ki Hong Lee, MD, PhD, The Heart Center of Chonnam National University Hospital, 42 Jaebongro, Dong-gu, Gwangju , South Korea Tel: , Fax: drgood2@naver.comko, MD, PhD, Division of Cardiology A 70-year-old female patient presented to the emergency department complaining of chest discomfort and motor weakness in the right arm and leg. She had been on warfarin for 6 years after a diagnosis of paroxysmal AF. The patient reported a history of hypertension and dyslipi- VOL.15 NO.4 45

46 ECG & EP CASES A B C D Figure 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). demia. There had been no recent changes in warfarin dosage, and her international normalized ratio (INR) had been 2.0 at last measurement, within the therapeutic range. Prompt magnetic resonance imaging (MRI) of the brain was performed to evaluate acute stroke events. However, it revealed no evidence of cerebral infarction or hemorrhage. Detailed neurological examination showed decreased motor strength in right upper and lower extremities, reduced pain and temperature sensations below T2, and hyperreflexia in the lower extremities. No cognitive dysfunction or dysarthria was noted. Cranial nerve examination was normal. Taken together, these findings suggested cervical spinal cord compression. Thereafter, cervical MRI was performed and re- 46 The Official Journal of Korean Heart Rhythm Society

47 vealed a multiloculated cystic mass ( cm) in the posterior and right posterolateral regions of the spinal canal from C1 to T2, with mass effect on the spinal cord and compressive myelopathy on the right side at C6 7. In addition, there was moderate left central disc herniation at C6 7. After intravenous administration of 5 mg of vitamin K, the patient underwent emergency right cervical decompressive laminectomy 24 hours after symptom onset. A massive cervical epidural hematoma extending from C1 to T1 was found and removed. The patient was hospitalized for rehabilitation for 2 weeks after the operation. Follow-up cervical MRI showed complete removal of hematoma from the spinal canal. Anticoagulation was started 2 days after operation with intravenous unfractionated heparin, which was changed to oral warfarin 5 days after operation. At hospital discharge, the motor power of the arm had been completely recovered, and lower limb strength was mostly restored with a power grade of 4/5. Discussion OAC should be considered in AF patients with high risk of thromboembolism. 1 However, if warfarin is used for this purpose, the dose must be strictly controlled to avoid severe complications (embolic stroke if INR falls below therapeutic range and hemorrhagic stroke if it rises above). Neurologic deficit in patients on warfarin medication usually indicates acute stroke. However, this patient developed extensive spinal epidural hematoma rather than stroke. Spontaneous spinal epidural hematoma is a rare condition, that usually requires emergent surgical intervention; 3 its occurrence in patients on warfarin with an INR within the therapeutic range has previously been reported by other authors. 4,5 In the current case, laboratory tests found INR to be within the therapeutic range, and the patient did not have any trauma or underlying coagulopathic disease. The combination of hypertension and cervical disc herniation may have led to the epidural bleeding. Therefore, spinal epidural hematoma should be considered in addition to acute stroke when focal neurologic deficit is found in patients taking warfarin, and detailed neurologic examination is mandatory to differentiate spinal epidural hematoma from stroke. Early diagnosis and emergency surgical intervention are essential in spinal epidural hematoma to enable recovery from neurologic sequelae. 6 Surgical treatment more than 48 hours after manifestation is likely to result in permanent neurologic impairment with incomplete dysfunction of the spinal cord. 7 Spinal epidural hematoma usually manifests as sudden, unexplained cervical or back pain. 8 However, the patient only complained of mild chest discomfort in the current case. This shows that spinal epidural hematoma can vary in its clinical presentation, and careful examination is important in patients with neurologic symptoms, especially AF patients on warfarin medication. Spinal epidural hematoma should be the first differential diagnosis considered in patients on warfarin medication when neurologic symptoms suggest acute stroke, even without cervical or back pain. Any delay in diagnosis and surgical intervention may result in permanent neurologic 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) 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 ECG & EP CASES VOL.15 NO.4 47

48 ECG & EP CASES contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33: McManus DD, Rienstra M, Benjamin EJ. An update on the prognosis of patients with atrial fibrillation. Circulation. 2012;126:e Pullarkat VA, Kalapura T, Pincus M, Baskharoun R. Intraspinal hemorrhage complicating oral anticoagulant therapy: an unusual case of cervical hematomyelia and a review of the literature. Arch Internal Med. 2000;160: Kirazli Y, Akkoc Y, Kanyilmaz S. Spinal epidural hematoma associated with oral anticoagulation therapy. Am J Phys Med Rehabil. 2004;83: Lederle FA, Cundy KV, Farinha P, McCormick DP. Spinal epidural hematoma associated with warfarin therapy. Am J Med. 1996;100: Groen RJ, van Alphen HA. Operative treatment of spontaneous spinal epidural hematomas: a study of the factors determining postoperative outcome. Neurosurgery. 1996;39: ; discussion Groen RJ. Non-operative treatment of spontaneous spinal epidural hematomas: a review of the literature and a comparison with operative cases. Acta Neurochir. 2004;146: 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: The Official Journal of Korean Heart Rhythm Society

49 Successful Use of a New Oral Anti-coagulant in a Stroke Patient with Poor Prothrombin Time Control Even After Warfarin Treatment ECG & EP CASES 한양대학교의과대학내과학교실박환철 Hwan-Cheol Park, MD, PhD Cardiology Division, Department of Internal Medicine, Hanyang University Guri Hospital, Guri city, Republic of Korea ABSTRACT A 76-year-old woman presented to our hospital with right-side motor weakness. She was diagnosed with paroxysmal 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 controlled 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 Introduction For the last several decades, vitamin K antagonists (VKAs) have been the primary medication in anti-coagulant therapy for the prevention and treatment of thrombotic events. Due to the individual variation in prothrombin time (PT) responses, individualized adjustment of the VKA dose is essential to manage the international Received: September 12, 2014 Revision Received: November 26, 2014 Accepted: December 15, 2014 Correspondence: Hwan-Cheol Park, MD, PhD, Cardiology Division, Department of Internal Medicine, Hanyang University Guri Hospital, Guri city, Republic of Korea Tel: , Fax: pigpooh76@hanmail.netko, MD, PhD, Division of Cardiology normalized ratio (INR); however, this places a significant practical burden on both the physician and patient. Appropriate INR management is very difficult in some cases, which makes the application of therapy involving fixed doses of oral anti-coagulants an attractive option for practical reasons. New oral anti-coagulants (NOACs) have recently been developed to prevent embolic stroke and to reduce the incidence of major bleeding in comparison with that associated with VKA use. 1,2 In the present report, the author presents a case with poor INR control with warfarin treatment that was successfully treated with a NOAC to prevent embolic stroke recurrence. VOL.15 NO.4 49

50 ECG & EP CASES 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). Case A 76-year-old woman was referred to our institution in June 2010 for the evaluation of newly diagnosed atrial fibrillation that occurred 3 days after an episode of transient right-side motor weakness. She had been diagnosed with essential hypertension 15 years previously and was taking losartan (50 mg q.d.) and hydrochlorothiazide (12.5 mg q.d.). Her body temperature was 36.7 C, her pulse rate was 78 beats per minute, and her blood pressure was 126/78 mmhg. Her radial pulse was irregular, and a grade III systolic murmur could be heard in her mitral valve area. 50 The Official Journal of Korean Heart Rhythm Society

51 ECG & EP CASES Figure 3. A follow-up electrocardiogram obtained in the outpatient clinic after 3 months shows normal sinus rhythm. Figure 4. A magnetic resonance image shows an acute cerebral infarction in the left middle and posterior cerebral artery territories (white arrows). She showed no neurologic deficit and was mentally alert. As previously stated, the patient had experienced transient right-side motor weakness (for approximately 2 hours) 3 days previously and had been admitted to undergo evaluation of newly diagnosed paroxysmal atrial fibrillation. Her hemogram values, biochemical marker levels, and thyroid hormone levels were within normal limits. The initial electrocardiogram (ECG) confirmed the presence of atrial fibrillation (Figure 1). Transthoracic echocardiography showed normal left ventricular systolic function (ejection fraction, 58%) and grade II mitral regurgitation. The left atrium was mildly enlarged (diameter, 42.4 mm). Because the anterolateral ECG leads showed ST segment depression (Figure 1), she underwent a coronary angiogram, which indicated a fixed atherosclerotic lesion in the middle segment of the left anterior descending artery and showed 70% stenosis (Figure 2). Percutaneous coronary intervention was not performed as she did not experience any chest pain or discomfort. Therefore, the author decided to use a class Ic anti-arrhythmic drug (flecainide) and warfarin to prevent embolic stroke, based on her CHADS 2 score of 4 (1 point for hypertension, 1 point for age 75 years, and 2 points for history of transient ischemic attack). However, despite the frequent blood sampling and visits to the outpatient clinic (which the pa- VOL.15 NO.4 51