심방세동 환자에서 주요 항부정맥제의 전기생리 작용의 차이

Differing Electrophysiological Effects of Various Antiarrhythmic Drugs on the Cardiac Chamber in Atrial Fibrillation

  • 장수영 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 조정관 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 정형기 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 기원주 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 이경진 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 고점석 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 이민구 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 박근호 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 심두선 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 윤남식 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 윤현주 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 홍영준 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 박형욱 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 김주한 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 안영근 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 정명호 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 박종춘 (전남대학교 의과대학 전남대학교병원 심장센터) ;
  • 강정채 (전남대학교 의과대학 전남대학교병원 심장센터)
  • Jang, Su-Young (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Cho, Jeong-Gwan (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Jung, Hyung-Ki (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Ki, Won-Ju (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Lee, Kyoung-Jin (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Ko, Jum-Suk (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Lee, Min-Goo (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Park, Keun-Ho (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Sim, Doo-Sun (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Yoon, Nam-Sik (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Yoon, Hyun-Ju (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Hong, Young-Joon (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Park, Hyung-Wook (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Kim, Ju-Han (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Ahn, Young-Keun (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Jeong, Myung-Ho (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Park, Jong-Chun (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Kang, Jung-Chaee (The Heart Center of Chonnam National University Hospital, Chonnam National University Medical School)
  • 발행 : 2011.06.01

초록

목적: 장기적인 항부정맥 약물요법은 주로 심방세동에서 시행되고 있으며 심방세동을 억제하고 동율동을 유지하는 것이 그 목적이다. 심방세동의 항부정맥 약물요법에 흔히 사용되는 amiodarone, flecainide, propafenone 등의 심방과 심실에 대한 전기생리 작용의 차이를 파악하고자 하였다. 방법: 2006년 1월부터 2009년 12월까지 전남대학교병원에 내원한 심방세동으로 amiodarone, flecainide, propafenone 중 한 가지 약제를 6개월 이상 복용하고 있으며, 동율동이 유지되고 있는 134명(60.4 ${\pm}$ 12.5세, 남:여 = 1.14:1)을 대상으로 하였으며 발작성 심방세동으로 약물을 투여하지 않고 동율동이 유지되고 있는 환자(28명)을 약물 투여군과 비교하였다. 표준 12유도 심전도를 사용하여, P파 간격과 분산, QRS 간격과 분산, QT 간격과 분산을 측정하여 분석하였다. 결과: P파와 QRS파의 폭과 분산은 amiodarone 복용 군에서 가장 작았으며 P파와 QRS파 최대 폭의 비는($P_{max}/QRS_{max}$) amiodarone 복용 군에서 가장 컸다(amiodarone군 1.2, flecainide군 0.9, propafenone군 1.0, p < 0.001). QT 간격은(amiodarone군 454 ${\pm}$ 34, flecainide군 428 ${\pm}$ 52, propafenone군 434 ${\pm}$ 25, p = 0.006) amiodarone 복용 군에서 가장 길었고 QT 분산과 (amiodarone군 28 ${\pm}$ 13, flecainide군 38 ${\pm}$ 16, propafenone군 35 ${\pm}$ 13, p = 0.002) QTpe 분산은(amiodarone군 13.3 ${\pm}$ 11.2, flecainide군 30.7 ${\pm}$ 24.9, propafenone군 31.8 ${\pm}$ 21.6, p < 0.001) amiodarone 복용 군에서 가장 작았다. 결론: Amiodarone은 flecainide나 propafenone에 비하여 심방과 심실의 전도 억제작용이 약하나 심방에 대한 선택성이 더 크며, 심실의 재분극 억제 작용이 강하지만 비교적 균일하게 작용함을 알 수 있었다. 이러한 전기생리학적 특성으로 인하여 심방세동의 치료에 flecainide 혹은 propafenone보다 amiodarone이 더 우월한 것으로 생각되었다.

Background/Aims: Long-term antiarrhythmic drug therapy remains the principal approach for suppressing atrial fibrillation (AF) and maintaining sinus rhythm. In this study, we examined the differing electrophysiological effects of various antiarrhythmic drugs on the cardiac chamber and atrial selectivity in patients with AF. Methods: We analyzed 134 patients (60.4 ${\pm}$ 12.5 years, M:F = 1.14:1) who were administered a single antiarrhythmic agent for AF over 6 months: amiodarone (group A), flecainide (group F), or propafenone (group P). The P wave, QRS complex duration and dispersion, and QT interval and its dispersion were evaluated using a standard 12-lead electrocardiogram. Results: There was no significant difference in age, gender ratio, or associated diseases among the three groups. In group A, $P_{max}$, $P_{min}$, P dispersion, $QRS_{max},\;QRS_{min}$, and QRS dispersion were shorter than in groups F and P, whereas $P_{max}/QRS_{max}$ was the highest in group A (A = 1.2, F = 0.9, P = 1.0; p < 0.01). $QTc_{max}$ and $QTc_{min}$ were longer in group A, whereas QTc dispersion and the QT peak to end (A = 13.3 ${\pm}$ 11.2, F = 30.7 ${\pm}$ 24.9, P = 31.8 ${\pm}$ 21.6; p < 0.01) were shorter in group A than in the other groups. Conclusions: Amiodarone had a weaker, but more selective, inhibitory effect on intra-atrial conduction, and inhibited ventricular repolarization more effectively and homogenously than flecainide or propafenone. These differing electrophysiological effects may contribute to the superior effectiveness and safety of amiodarone over flecainide or propafenone.

키워드

참고문헌

  1. Alpert JS, Petersen P, Godtfredsen J. Atrial fibrillation: natural history, complications, and management. Annu Rev Med 1988; 39:41-52. https://doi.org/10.1146/annurev.me.39.020188.000353
  2. Krahn AD, Manfreda J, Tate RB, Mathewson FA, Cuddy TE. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study. Am J Med 1995; 98:476-484. https://doi.org/10.1016/S0002-9343(99)80348-9
  3. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham Study. N Engl J Med 1982;306:1018-1022. https://doi.org/10.1056/NEJM198204293061703
  4. Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005;293: 2634-2640. https://doi.org/10.1001/jama.293.21.2634
  5. Jais P, Cauchemez B, Macle L, et al. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation: the A4 Study. Circulation 2008;118:2498-2505. https://doi.org/10.1161/CIRCULATIONAHA.108.772582
  6. Bonanno C, Paccanaro M, La Vecchia L, Ometto R, Fontanelli A. Efficacy and safety of catheter ablation versus antiarrhythmic drugs for atrial fibrillation: a meta-analysis of randomized trials. J Cardiovasc Med (Hagerstown) 2010;11:408-418. https://doi.org/10.2459/JCM.0b013e328332e926
  7. Burashnikov A, Antzelevitch C. Atrial-selective sodium channel blockers: do they exist? J Cardiovasc Pharmacol 2008;52:121-128. https://doi.org/10.1097/FJC.0b013e31817618eb
  8. Deal KK, England SK, Tamkun MM. Molecular physiology of cardiac potassium channels. Physiol Rev 1996;76:49-67. https://doi.org/10.1152/physrev.1996.76.1.49
  9. Burashnikov A, Antzelevitch C. Can inhibition of IKur promote atrial fibrillation? Heart Rhythm 2008;5:1304-1309. https://doi.org/10.1016/j.hrthm.2008.05.020
  10. Schram G, Zhang L, Derakhchan K, Ehrlich JR, Belardinelli L, Nattel S. Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects. Br J Pharmacol 2004;142:1300-1308. https://doi.org/10.1038/sj.bjp.0705879
  11. Antzelevitch C, Belardinelli L, Zygmunt AC, et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 2004;110:904-910. https://doi.org/10.1161/01.CIR.0000139333.83620.5D
  12. Suttorp MJ, Kingma JH, Jessurun ER, Lie-A-Huen L, van Hemel NM, Lie KI. The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. J Am Coll Cardiol 1990;16:1722-1727. https://doi.org/10.1016/0735-1097(90)90326-K
  13. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation 2004;110:227-239. https://doi.org/10.1161/01.CIR.0000133317.49796.0E
  14. American Diabetes Association. Standards of medical care in diabetes: 2009. Diabetes Care 2009;32(Suppl 1):S13-S61. https://doi.org/10.2337/dc09-S013
  15. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440-1463. https://doi.org/10.1016/j.echo.2005.10.005
  16. Bazett H. An analysis of the time relationships of the heart. Heart Rhythm 1920;7:353-370.
  17. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines 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 European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). J Am Coll Cardiol 2006;48:854-906. https://doi.org/10.1016/j.jacc.2006.07.009
  18. Vassallo P, Trohman RG. Prescribing amiodarone: an evidencebased review of clinical indications. JAMA 2007;298:1312-1322. https://doi.org/10.1001/jama.298.11.1312
  19. Roy D, Talajic M, Dorian P, et al. Amiodarone to prevent recurrence of atrial fibrillation: Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med 2000;342:913-920. https://doi.org/10.1056/NEJM200003303421302
  20. Vaughan Williams EM. Classifying antiarrhythmic actions: by facts or speculation. J Clin Pharmacol 1992;32:964-977. https://doi.org/10.1002/j.1552-4604.1992.tb03797.x
  21. Chun SH, Sager PT, Stevenson WG, Nademanee K, Middlekauff HR, Singh BN. Long-term efficacy of amiodarone for the maintenance of normal sinus rhythm in patients with refractory atrial fibrillation or flutter. Am J Cardiol 1995;76:47-50. https://doi.org/10.1016/S0002-9149(99)80799-1
  22. Hohnloser SH, Meinertz T, Dammbacher T, et al. Electrocardiographic and antiarrhythmic effects of intravenous amiodarone: results of a prospective, placebo-controlled study. Am Heart J 1991;121:89-95. https://doi.org/10.1016/0002-8703(91)90960-P
  23. Punnam SR, Goyal SK, Kotaru VP, Pachika AR, Abela GS, Thakur RK. Amiodarone - a 'broad spectrum' antiarrhythmic drug. Cardiovasc Hematol Disord Drug Targets 2010;10:73-81. https://doi.org/10.2174/187152910790780032
  24. Juul-Moller S, Edvardsson N, Rehnqvist-Ahlberg N. Sotalol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation. Circulation 1990;82: 1932-1939. https://doi.org/10.1161/01.CIR.82.6.1932
  25. Burashnikov A, Di Diego JM, Zygmunt AC, Belardinelli L, Antzelevitch C. Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation 2007;116:1449-1457. https://doi.org/10.1161/CIRCULATIONAHA.107.704890
  26. Burashnikov A, Di Diego JM, Sicouri S, Ferreiro M, Carlsson L, Antzelevitch C. Atrial-selective effects of chronic amiodarone in the management of atrial fibrillation. Heart Rhythm 2008;5: 1735-1742. https://doi.org/10.1016/j.hrthm.2008.09.015
  27. Chaudry II, Qamar S, Spodick DH. QT interval effects of normal QRS variation. Am J Cardiol 1994;74:628-629. https://doi.org/10.1016/0002-9149(94)90761-7
  28. Sundqvist K, Sylven C. Cardiac repolarization properties during standardized exercise test as studied by QT, QT peak and terminated T-wave intervals. Clin Physiol 1989;9:419-425. https://doi.org/10.1111/j.1475-097X.1989.tb00996.x
  29. Merri M, Benhorin J, Alberti M, Locati E, Moss AJ. Electrocardiographic quantitation of ventricular repolarization. Circulation 1989;80:1301-1308. https://doi.org/10.1161/01.CIR.80.5.1301