Cardiovascular Drugs and Therapy

, Volume 18, Issue 5, pp 377–386 | Cite as

Analysis of the Surface Electrocardiogram for Monitoring and Predicting Antiarrhythmic Drug Effects in Atrial Fibrillation

  • Daniela Husser
  • Martin Stridh
  • Leif Sornmo
  • Pyotr Platonov
  • S. Bertil Olsson
  • Andreas Bollmann


Specific antiarrhythmic therapy with class I and III drugs for atrial fibrillation (AF) conversion and prevention of its recurrence is frequently utilized in clinical practice. Besides being only moderate effective, the utilization of antiarrhythmic drugs may be associated with serious side effects. In the clinical setting it is difficult to directly evaluate the effects of antiarrhythmic drugs on the individual patient’s atrial electrophysiology, thereby predicting their efficacy in restoring and maintaining sinus rhythm.

Analysis of the surface electrocardiogram in terms of P-wave signal averaged ECG during sinus rhythm and spectral characterization of fibrillatory waves during AF for evaluation of atrial antiarrhythmic drug effects is a new field of investigation. Both techniques provide reproducible parameters for characterizing atrial electrical abnormalities and seem to contain prognostic information regarding antiarrhythmic drug efficacy. Further research is needed which elucidates the most challenging clinical questions in AF management whom to place on antiarrhythmic drug treatment and what antiarrhythmic drug to prescribe. Analysis of the surface ECG might have the potential to answer these questions.

Key Words

atrial fibrillation ECG electrical remodeling antiarrhythmic drugs drug monitoring 


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  1. 1.
    Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Circulation 2001;104:2118–2150.PubMedGoogle Scholar
  2. 2.
    Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991;22:983–988.PubMedGoogle Scholar
  3. 3.
    Britton M, Gustafsson C. Non-rheumatic atrial fibrillation as a risk factor for stroke. Stroke 1985;16:182–188.PubMedGoogle Scholar
  4. 4.
    Kannel WB, Abbott RD, Savage DD, et al. Epidemiologic features of chronic atrial fibrillation: The Framingham study. N Engl J Med 1982;306:1018–1022.PubMedCrossRefGoogle Scholar
  5. 5.
    Gajewski J, Singer RB. Mortality in an insured population with atrial fibrillation. Jama 1981;245:1540–1544.PubMedGoogle Scholar
  6. 6.
    Benjamin EJ, Wolf PA, D’Agostino RB, et al. Impact of atrial fibrillation on the risk of death: The Framingham Heart study. Circulation 1998;98:946–952.PubMedGoogle Scholar
  7. 7.
    Stewart S, Murphy N, Walker A, et al. Cost of an emerging epidemic: An economic analysis of atrial fibrillation in the UK. Heart 2004;90:286–292.PubMedGoogle Scholar
  8. 8.
    Levy S, Maarek M, Coumel P, et al. Characterization of different subsets of atrial fibrillation in general practice in France: The ALFA study. The College of French Cardiologists. Circulation 1999;99:3028–3035.PubMedGoogle Scholar
  9. 9.
    Humphries KH, Kerr CR, Connolly SJ, et al. New-onset atrial fibrillation: Sex differences in presentation, treatment, and outcome. Circulation 2001;103:2365–2370.PubMedGoogle Scholar
  10. 10.
    Zimetbaum P, Ho KK, Olshansky B, et al. Variation in the utilization of antiarrhythmic drugs in patients with new-onset atrial fibrillation. Am J Cardiol 2003;91:81–83.PubMedGoogle Scholar
  11. 11.
    Capucci A, Lenzi T, Boriani G, et al. Effectiveness of loading oral flecainide for converting recent-onset atrial fibrillation to sinus rhythm in patients without organic heart disease or with only systemic hypertension. Am J Cardiol 1992;70:69–72.PubMedGoogle Scholar
  12. 12.
    Khan IA. Single oral loading dose of propafenone for pharmcological cardioversion of recent-onset atrial fibrillation. J Am Coll Cardiol 2001;37:542–547.PubMedGoogle Scholar
  13. 13.
    Stambler BS, Wood MA, Ellenbogen KA. Comparative efficacy of intravenous ibutilide versus procainamide for enhancing termination of atrial flutter by atrial overdrive pacing. Am J Cardiol 1996;77:960–966.PubMedGoogle Scholar
  14. 14.
    Singh S, Zoble RG, Yellen L, et al. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter. The symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation 2000;102:2385–2390.PubMedGoogle Scholar
  15. 15.
    Deedwania PC, Singh BN, Ellenbogen K, et al. Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients with heart failure and atrial fibrillation: Observations from the veterans affairs congestive heart failure survival trial of antiarrhythmic therapy (CHF-STAT). The Department of Veterans Affairs CHF-STAT Investigators. Circulation 1998;98:2574–2579.PubMedGoogle Scholar
  16. 16.
    Kuhlkamp V, Schirdewan A, Stangl K, et al. Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: A randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 2000;36:139–146.PubMedGoogle Scholar
  17. 17.
    Plewan A, Lehmann G, Ndrepepa G, et al. Maintenance of sinus rhythm after electrical cardioversion of persistent atrial fibrillation; sotalol vs bisoprolol. Eur Heart J 2001;22:1504–1510.PubMedGoogle Scholar
  18. 18.
    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.PubMedGoogle Scholar
  19. 19.
    AFFIRM First Antiarrhythmic Drug Substudy Investigators. Maintenance of sinus rhythm in patients with atrial fibrillation: An AFFIRM substudy of the first antiarrhythmic drug. J Am Coll Cardiol 2003;42:20–29.Google Scholar
  20. 20.
    Bollmann A. Quantification of electrical remodeling in human atrial fibrillation. Cardiovasc Res 2000;47:207–209.PubMedGoogle Scholar
  21. 21.
    Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation 1995;92:1954–1968.PubMedGoogle Scholar
  22. 22.
    Wijffels MC, Kirchhof CJ, Dorland R, et al. Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: Roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation. Circulation 1997;96:3710–3720.PubMedGoogle Scholar
  23. 23.
    Wang J, Bourne GW, Wang Z, et al. Comparative mechanisms of antiarrhythmic drug action in experimental atrial fibrillation. Importance of use-dependent effects on refractoriness. Circulation 1993;88:1030–1044.PubMedGoogle Scholar
  24. 24.
    Shinagawa K, Mitamura H, Takeshita A, et al. Determination of refractory periods and conduction velocity during atrial fibrillation using atrial capture in dogs: Direct assessment of the wavelength and its modulation by a sodium channel blocker, pilsicainide. J Am Coll Cardiol 2000;35:246–253.PubMedGoogle Scholar
  25. 25.
    Asano Y, Saito J, Matsumoto K, et al. On the mechanism of termination and perpetuation of atrial fibrillation. Am J Cardiol 1992;69:1033–1038.PubMedGoogle Scholar
  26. 26.
    Wijffels MC, Dorland R, Mast F, et al. Widening of the excitable gap during pharmacological cardioversion of atrial fibrillation in the goat: Effects of cibenzoline, hydroquinidine, flecainide, and d-sotalol. Circulation 2000;102:260–267.PubMedGoogle Scholar
  27. 27.
    Holm M, Pehrson S, Ingemansson M, et al. Non-invasive assessment of the atrial cycle length during atrial fibrillation in man: Introducing, validating and illustrating a new ECG method. Cardiovasc Res 1998;38:69–81.PubMedGoogle Scholar
  28. 28.
    Bollmann A, Kanuru NK, McTeague KK, et al. Frequency analysis of human atrial fibrillation using the surface electrocardiogram and its response to ibutilide. Am J Cardiol 1998;81:1439–1445.PubMedGoogle Scholar
  29. 29.
    Bollmann A, Binias KH, Toepffer I, et al. Importance of left atrial diameter and atrial fibrillatory frequency for conversion of persistent atrial fibrillation with oral flecainide. Am J Cardiol 2002;90:1011–1014.PubMedGoogle Scholar
  30. 30.
    Bollmann A, Husser D, Stridh M, et al. Frequency measures obtained from the surface electrocardiogram in atrial fibrillation research and clinical decision-making. J Cardiovasc Electrophysiol 2003;14:S154–S161.PubMedGoogle Scholar
  31. 31.
    Bollmann A, Husser D, Steinert R, et al. Echo- and electrocardiographic predictors for atrial fibrillation recurrence following cardioversion. J Cardiovasc Electrophysiol 2003;14:S162–S165.PubMedGoogle Scholar
  32. 32.
    Bollmann A, Sonne K, Esperer HD, et al. Non-invasive assessment of fibrillatory activity in patients with paroxysmal and persistent atrial fibrillation using the Holter ECG. Cardiovasc Res 1999;44:60–66.PubMedGoogle Scholar
  33. 33.
    Bollmann A, Sonne K, Esperer HD, et al. Circadian variations in atrial fibrillatory frequency in persistent human atrial fibrillation. Pacing Clin Electrophysiol 2000;23:1867–1871.PubMedGoogle Scholar
  34. 34.
    Meurling CJ, Waktare JE, Holmqvist F, et al. Diurnal variations of the dominant cycle length of chronic atrial fibrillation. Am J Physiol Heart Circ Physiol 2001;280:H401–H406.PubMedGoogle Scholar
  35. 35.
    Xi Q, Sahakian AV, Swiryn S. The effect of QRS cancellation on atrial fibrillatory wave signal characteristics in the surface electrocardiogram. J Electrocardiol 2003;36:243–249.PubMedGoogle Scholar
  36. 36.
    Fujiki A, Sakabe M, Nishida K, et al. Role of fibrillation cycle length in spontaneous and drug-indcued termination of human atrial fibrillation—spectral analysis of fibrillation waves from surface electrocardiogram. Circ J 2003;67:391–395.PubMedGoogle Scholar
  37. 37.
    Fujiki A, Tsuneda T, Sugao M, et al. Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm. Am J Cardiol 2003;92:472–475.PubMedGoogle Scholar
  38. 38.
    Stridh M, Sornmo L. Spatiotemporal QRST cancellation techniques for analysis of atrial fibrillation. IEEE Trans Biomed Eng 2001;48:105–111.PubMedGoogle Scholar
  39. 39.
    Stridh M, Sornmo L, Meurling CJ, et al. Characterization of atrial fibrillation using the surface ECG: Time-dependent spectral properties. IEEE Trans Biomed Eng 2001;48:19–27.PubMedGoogle Scholar
  40. 40.
    Stridh M, Sornmo L, Meurling CJ, et al. Sequential characterization of atrial tachyarrhythmias based on ECG time-frequency analysis. IEEE Trans Biomed Eng 2004;51:100–114.PubMedGoogle Scholar
  41. 41.
    Bollmann A, Husser D, Olsson SB. Atrial fibrillatory frequency, atrial fibrillatory rate or atrial cycle length—does it matter? Am J Cardiol 2004;94:147.PubMedGoogle Scholar
  42. 42.
    Husser D, Stridh M, Sornmo L, et al. Frequency analysis of atrial fibrillation from the surface electrocardiogram. Indian Pacing Electrophysiol J 2004;4:122–136.PubMedGoogle Scholar
  43. 43.
    Meurling CJ, Ingemansson MP, Roijer A, et al. Attenuation of electrical remodelling in chronic atrial fibrillation following oral treatment with verapamil. Europace 1999;1:234–241.PubMedGoogle Scholar
  44. 44.
    Holm M, Johansson R, Olsson SB, et al. A new method for analysis of atrial activation during chronic atrial fibrillation in man. IEEE Trans Biomed Eng 1996;43:198–210.PubMedGoogle Scholar
  45. 45.
    Schwartz RA, Langberg JJ. Atrial electrophysiological effects of ibutilide infusion in humans. Pacing Clin Electrophysiol 2000;23:832–836.PubMedGoogle Scholar
  46. 46.
    Ingemansson MP, Smideberg B, Olsson SB. Intravenous MgSO4 alone and in combination with glucose, insulin and potassium (GIK) prolongs the atrial cycle length in chronic atrial fibrillation. Europace 2000;2:106–114.PubMedGoogle Scholar
  47. 47.
    Stambler BS, Wood MA, Ellenbogen KA. Antiarrhythmic actions of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation: Electrophysiological determinants of enhanced conversion efficacy. Circulation 1997;96:4298–4306.PubMedGoogle Scholar
  48. 48.
    Fujiki A, Nagasawa H, Sakabe M, et al. Spectral characteristics of human atrial fibrillation waves of the right atrial free wall with respect to the duration of atrial fibrillation and effect of class I antiarrhythmic drugs. Jpn Circ J 2001;65:1047–1051.PubMedGoogle Scholar
  49. 49.
    Konings KT, Kirchhof CJ, Smeets JR, et al. High-density mapping of electrically induced atrial fibrillation in humans. Circulation 1994;89:1665–1680.PubMedGoogle Scholar
  50. 50.
    Tieleman RG, Van Gelder IC, Crijns HJ, et al. Early recurrences of atrial fibrillation after electrical cardioversion: A result of fibrillation-induced electrical remodeling of the atria? J Am Coll Cardiol 1998;31:167–173.PubMedGoogle Scholar
  51. 51.
    Lombardi F, Colombo A, Basilico B, et al. Heart rate variability and early recurrence of atrial fibrillation after electrical cardioversion. J Am Coll Cardiol 2001;37:157–162.PubMedGoogle Scholar
  52. 52.
    Everett TH 4th, Li H, Mangrum JM, et al. Electrical, morphological, and ultrastructural remodeling and reverse remodeling in a canine model of chronic atrial fibrillation. Circulation 2000;102:1454–1460.PubMedGoogle Scholar
  53. 53.
    Yu WC, Lee SH, Tai CT, et al. Reversal of atrial electrical remodeling following cardioversion of long-standing atrial fibrillation in man. Cardiovasc Res 1999;42:470–476.PubMedGoogle Scholar
  54. 54.
    Manios EG, Kanoupakis EM, Chlouverakis GI, et al. Changes in atrial electrical properties following cardioversion of chronic atrial fibrillation: Relation with recurrence. Cardiovasc Res 2000;47:244–253.PubMedGoogle Scholar
  55. 55.
    Sato T, Mitamura H, Kurita Y, et al. Recoevry of electrophysiological parameters after conversion of atrial fibrillation. Int J Cardiol 2001;79:183–189.PubMedGoogle Scholar
  56. 56.
    Tse HF, Lau CP, Ayers GM. Heterogeneous changes in electrophysiologic properties in the paroxysmal and chronically fibrillating human atrium. J Cardiovasc Electrophysiol 1999;10:125–135.PubMedGoogle Scholar
  57. 57.
    Liu Z, Hayano M, Hirata T, et al. Abnormalities of electrocardiographic P wave morphology and their relation to electrophysiological parameters of the atrium in patients with sick sinus syndrome. Pacing Clin Electrophysiol 1998;21:79–86.PubMedGoogle Scholar
  58. 58.
    Platonov PG, Carlson J, Ingemansson MP, et al. Detection of inter-atrial conduction defects with unfiltered signal-averaged P-wave ECG in patients with lone atrial fibrillation. Europace 2000;2:32–41.PubMedGoogle Scholar
  59. 59.
    Guidera SA, Steinberg JS. The signal-averaged P wave duration: A rapid and noninvasive marker of risk of atrial fibrillation. J Am Coll Cardiol 1993;21:1645–1651.CrossRefPubMedGoogle Scholar
  60. 60.
    Rosenheck S. Signal-averaged P wave in patients with paroxysmal atrial fibrillation. Pacing Clin Electrophysiol 1997;20:2577–2586.PubMedGoogle Scholar
  61. 61.
    Jordaens L, Tavernier R, Gorgov N, et al. Signal-averaged P wave: Predictor of atrial fibrillation. J Cardiovasc Electrophysiol 1998;9:S30–S34.PubMedGoogle Scholar
  62. 62.
    Wijffels MCEF, Crijns HJGM. Recent advances in drug therapy for atrial fibrillation. J Cardiovasc Electrophysiol 2003;14:S40–S47.PubMedGoogle Scholar
  63. 63.
    Derakhchana K, Villemaireb C, Talajic M, et al. The class III antiarrhythmic drugs dofetilide and sotalol prevent AF induction by atrial premature complexes at doses that fail to terminate AF. Cardiovasc Res 2001;50:75–84.Google Scholar
  64. 64.
    Allessie MA, Wijffels MC, Dorland R. Mechanisms of pharmacologic cardioversion of atrial fibrillation by Class I drugs. J Cardiovasc Electrophysiol 1998;9:S69–S77.PubMedGoogle Scholar
  65. 65.
    Yamada T, Fukunami M, Shimonagata T, et al. Dispersion of signal-averaged P wave duration on precordial body surface in patients with paroxysmal atrial fibrillation. Eur Heart J 1999;20:211–220.PubMedGoogle Scholar
  66. 66.
    Villani GQ, Piepoli M, Rosi A, et al. P-wave dispersion index: A marker of patients with paroxysmal atrial fibrillation. Int J Cardiol 1996;55:169–175.PubMedGoogle Scholar
  67. 67.
    Carlson J, Johansson R, Olsson SB. Classification of electrocardiographic P-wave morphology. IEEE Trans Biomed Eng 2001;48:401–405.PubMedGoogle Scholar
  68. 68.
    Stafford P, Denbigh P, Vincent R. Frequency analysis of the P wave: Comparative techniques. Pacing Clin Electrophysiol 1995;18:261–270.PubMedGoogle Scholar
  69. 69.
    Christiansen EH, Frost L, Pilegaard H, et al. Within- and between-patient variation of the signal-averaged P wave in coronary artery disease. Pacing Clin Electrophysiol 1996;19:72–81.PubMedGoogle Scholar
  70. 70.
    Ehlert FA, Zaman N, Steinberg JS. Immediate and short-term reproducibility of the P wave signal-averaged electrocardiogram. Pacing Clin Electrophysiol 1997;20:1636–1645.PubMedGoogle Scholar
  71. 71.
    Hofmann M, Goedel-Meinen L, Beckhoff A, et al. Analysis of the p wave in the signal-averaged electrocardiogram: Normal values and reproducibility. Pacing Clin Electrophysiol 1996;19:1928–1932.PubMedGoogle Scholar
  72. 72.
    Savelieva I, Aytemir K, Hnatkova K, et al. Short-, mid-, and long-term reproducibility of the atrial signal-averaged electrocardiogram in healthy subjects: Comparison with the conventional ventricular signal-averaged electrocardiogram. Pacing Clin Electrophysiol 2000;23:122–127.PubMedGoogle Scholar
  73. 73.
    Stafford PJ, Cooper J, Fothergill J, et al. Reproducibility of the signal averaged P wave: Time and frequency domain analysis. Heart 1997;77:412–416.PubMedGoogle Scholar
  74. 74.
    Cheema AN, Ahmed MW, Kadish AH, et al. Effects of autonomic stimulation and blockade on signal-averaged P wave duration. J Am Coll Cardiol 1995;26:497–502.PubMedGoogle Scholar
  75. 75.
    Tukek T, Akkaya V, Demirel S, et al. Effect of Valsalva maneuver on surface electrocardiographic P-wave dispersion in paroxysmal atrial fibrillation. Am J Cardiol 2000;85:896–899, A10.PubMedGoogle Scholar
  76. 76.
    Faggiano P, D’Aloia A, Zanelli E, et al. Contribution of left atrial pressure and dimension to signal-averaged P-wave duration in patients with chronic congestive heart failure. Am J Cardiol 1997;79:219–222.PubMedGoogle Scholar
  77. 77.
    Ehlert FA, Korenstein D, Steinberg JS. Evaluation of P wave signal-averaged electrocardiographic filtering and analysis methods. Am Heart J 1997;134:985–993.PubMedGoogle Scholar
  78. 78.
    Ehrlich JR, Zhang GQ, Israel CW, et al. P-Wellen Signalmittelungs-EKG: Normalwerte und Reproduzierbarkeit. Z Kardiol 2001;90:170–176.PubMedGoogle Scholar
  79. 79.
    Kubara I, Ikeda H, Hiraki T, et al. Dispersion of filtered P wave duration by P wave signal-averaged ECG mapping system: Its usefulness for determining efficacy of disopyramide on paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 1999;10:670–679.PubMedGoogle Scholar
  80. 80.
    Stafford PJ, Cooper J, de Bono DP, et al. Effect of low dose sotalol on sthe signal averaged P wave in patients with paroxysmal atrial fibrillation. Br Heart J 1995;74:636–640.PubMedGoogle Scholar
  81. 81.
    Banasiak W, Telichowski A, Anker SD, et al. Effects of amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease. Am J Cardiol 1999;83:112–114, A9.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2004

Authors and Affiliations

  • Daniela Husser
    • 1
    • 2
  • Martin Stridh
    • 3
  • Leif Sornmo
    • 3
  • Pyotr Platonov
    • 4
  • S. Bertil Olsson
    • 4
  • Andreas Bollmann
    • 1
    • 2
    • 4
  1. 1.Los Angeles Biomedical Research Institute at Harbor-UCLAGood Samaritan HospitalLos AngelesUSA
  2. 2.Department of CardiologyGood Samaritan HospitalLos AngelesUSA
  3. 3.Department of ElectroscienceLund UniversityLundSweden
  4. 4.Department of CardiologyLund UniversityLundSweden

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