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Electrophysiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation

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Abstract

Aims

Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post–repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium.

Methods

In 12 patients with persistent AF (11 male, 58 ± 5 yrs, 27 ± 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined.

Results

Both drugs prolonged APD90 during AF (flecainide from 109 ± 7 ms to 137 ± 10 ms, sotalol from 108 ± 6 ms to 131 ± 8 ms, both p < 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 ± 8 ms to 139 ± 8 ms, p < 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 ± 9 ms to 197 ± 28 ms, p < 0.05 vs. baseline and vs. sotalol).

Conclusions

Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.

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Abbreviations

AF:

Atrial Fibrillation

APD:

Action Potential Duration

ERP:

Effective Refractory Period

MAP:

Monophasic Action Potential

PRR:

Post–Repolarization Refractoriness

References

  1. AFFIRM Investigators (2002) A comparison of rate control and rhythm control in patients with atrial .brillation. N Engl J Med 347:1825–1833

    Google Scholar 

  2. Bode F, Kilborn M, Karasik P, Franz MR (2001) The repolarization-excitability relationship in the human right atrium is unaffected by cycle length, recording site and prior arrhythmias. J Am Coll Cardiol 37:920–925

    Google Scholar 

  3. Bosch RF, Scherer CR, Rüb N, Wöhrl S, Steinmeyer K, Haase H, Busch AE, Seipel L, Kuhlkamp V (2003) Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces I(Ca,L) and I(to) in rapid atrial pacing in rabbits. J Am Coll Cardiol 41:858–869

    Google Scholar 

  4. Dobrev D, Ravens U (2003) Remodeling of cardiomyocyte ion channels in human atrial fibrillation. Basic Res Cardiol 98:137–148

    PubMed  Google Scholar 

  5. Fabritz L, Kirchhof P, Franz MR, Eckardt L, Mönnig G, Milberg P, Breithardt G, Haverkamp W (2003) Prolonged action potential durations, increased dispersion of repolarization, and polymorphic ventricular tachycardia in a mouse model of proarrhythmia. Basic Res Cardiol 98:25–32

    Google Scholar 

  6. Fetsch T, Bauer P, Engberding R, Koch HP, Lukl J, Meinertz T, Oeff M, Seipel L, Trappe HJ, Treese N, Breithardt G (2004) Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial. Eur Heart J 25:1385–1394

    Article  Google Scholar 

  7. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG (2001) ACC/AHA/ESC guidelines 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 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. Eur Heart J 22:1852–1923

    Article  CAS  PubMed  Google Scholar 

  8. Hobbs WJ, Fynn S, Todd DM, Wolfson P, Galloway M, Garratt CJ (2000) Reversal of atrial electrical remodeling after cardioversion of persistent atrial fibrillation in humans. Circulation 101:1145–1151

    Google Scholar 

  9. Kirchhof P, Degen H, Franz M, Eckardt L, Fabritz L, Milberg P, Laer S, Neumann J, Breithardt G, Haverkamp W (2003) Amiodarone-induced post-repolarization refractoriness suppresses induction of ventricular fibrillation. J Pharmacol Exp Ther 305:257–263

    Google Scholar 

  10. Kirchhof P, Eckardt L, Franz MR, Mönnig G, Loh P, Wedekind H, Schulze-Bahr E, Breithardt G, Haverkamp W (2003) Prolonged atrial action potential durations and polymorphic atrial tachyarrhythmias in patients with long QT syndrome. J Cardiovasc Electrophysiol 14:1027–1033

    Google Scholar 

  11. Kirchhof P, Eckardt L, Loh P, Weber K, Fischer RJ, Seidl KH, Böcker D, Breithardt G, Haverkamp W, Borggrefe M (2002) Anterior-posterior versus anterior-lateral electrode positions for external cardioversion of atrial fibrillation: a randomised trial. Lancet 360:1275–1279

    Google Scholar 

  12. Kirchhof P, Fabritz L, Franz MR (1998) Post-repolarization refractoriness versus conduction slowing caused by class I antiarrhythmic drugs – antiarrhythmic and proarrhythmic effects. Circulation 97:2567–2574

    Google Scholar 

  13. Koller BS, Karasik PE, Solomon AJ, Franz MR (1995) Relation between repolarization and refractoriness during programmed electrical stimulation in the human right ventricle. Implications for ventricular tachycardia induction. Circulation 91:2378–2384

    Google Scholar 

  14. Madrid AH, Moro C, Marin Huerta E, Mestre JL, Novo L, Costa A (1993) Comparison of flecainide and procainamide in cardioversion of atrial fibrillation. Eur Heart J 14:1127–1131

    Google Scholar 

  15. Maltsev VA, Sabbah HN, Undrovinas AI (2001) Late sodium current is a novel target for amiodarone: studies in failing human myocardium. J Mol Cell Cardiol 33:923–932

    Google Scholar 

  16. Mandapati R, Skanes A, Chen J, Berenfeld O, Jalife J (2000) Stable microreentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. Circulation 101:194–199

    Google Scholar 

  17. Manios EG, Kanoupakis EM, Chlouverakis GI, Kaleboubas MD, Mavrakis HE, Vardas PE (2000) Changes in atrial electrical properties following cardioversion of chronic atrial fibrillation: relation with recurrence. Cardiovasc Res 47:244–253

    Article  Google Scholar 

  18. Martin CL, Palomo MA, McMahon EG (1996) Comparison of bidisomide, flecainide and dofetilide on action potential duration in isolated canine atria: effect of isoproterenol. J Pharmacol Exp Ther 278:154–162

    Google Scholar 

  19. Maruyama T, Richardson LC, Sun W, McCarthy JJ, Gettes LS (1995) Acute effects of amiodarone on membrane properties, refractoriness, and conduction in guinea pig papillary muscles. Heart Vessels 10:78–86

    Google Scholar 

  20. Mittal S, Ayati S, Stein KM, Schwartzman D, Cavlovich D, Tchou PJ, Markowitz SM, Slotwiner DJ, Scheiner MA, Lerman BB (2000) Transthoracic cardioversion of atrial fibrillation: comparison of rectilinear biphasic versus damped sine wave monophasic shocks. Circulation 101:1282–1287

    Google Scholar 

  21. Nagatomo T, January CT, Makielski JC (2000) Preferential block of late sodium current in the LQT3 DeltaKPQ mutant by the class I(C) antiarrhythmic flecainide. Mol Pharmacol 57:101–107

    Google Scholar 

  22. Nattel S (2002) New ideas about atrial fibrillation 50 years on. Nature 415:219–226

    Google Scholar 

  23. Osaka T, Yamazaki M, Yokoyama E, Ito A, Kodama I (2004) Sotalol reverses remodeled action potential in patients with chronic atrial fibrillation but does not prevent arrhythmia recurrence. J Cardiovasc Electrophysiol 15:877–884

    Google Scholar 

  24. Pandozi C, Bianconi L, Villani M, Castro A, Altamura G, Toscano S, Jesi AP, Gentilucci G, Ammirati F, Lo Bianco F, Santini M (1997) Local capture by atrial pacing in spontaneous chronic atrial fibrillation. Circulation 95:2416–2422

    Google Scholar 

  25. Reisinger J, Gatterer E, Lang W, Vanicek T, Eisserer G, Bachleitner T, Niemeth C, Aicher F, Grander W, Heinze G, Kuhn P, Siostrzonek P (2004) Flecainide versus ibutilide for immediate cardioversion of atrial fibrillation of recent onset atrial fibrillation. Eur Heart J 25:1318–1324

    Google Scholar 

  26. Schotten U, Greiser M, Benke D, Buerkel K, Ehrenteidt B, Stellbrink C, Vazquez-Jimenez JF, Schoendube F, Hanrath P, Allessie M (2002) Atrial fibrillationinduced atrial contractile dysfunction: a tachycardiomyopathy of a different sort. Cardiovasc Res 53:192–201

    Google Scholar 

  27. Schumacher B, Jung W, Lewalter T, Vahlhaus C, Wolpert C, Luderitz B (1999) Radiofrequency ablation of atrial flutter due to administration of class IC antiarrhythmic drugs for atrial fibrillation. Am J Cardiol 83:710–713

    Google Scholar 

  28. Stabile G, De Simone A, Turco P, La Rocca V, Nocerino P, Astarita C, Maresca F, De Matteis C, Di Napoli T, Stabile E, Vitale DF (2001) Response to flecainide infusion predicts long-term success of hybrid pharmacologic and ablation therapy in patients with atrial fibrillation. J Am Coll Cardiol 37:1639–1644

    Google Scholar 

  29. Stambler BS, Wood MA, Ellenbogen KA (1997) Antiarrhythmic actions of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation: electrophysiological determinants of enhanced conversion efficacy. Circulation 96:4298–4306

    Google Scholar 

  30. Van Gelder I, Hagens VE, Bosker HA, Kingma H, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermanns AJM, Tijssen JGP, Crijns HJ (2002) A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 347:1834–1840

    Article  PubMed  Google Scholar 

  31. Wang Z, Fermini B, Nattel S (1995) Effects of flecainide, quinidine, and 4-aminopyridine on transient outward and ultrarapid delayed rectifier currents in human atrial myocytes. J Pharmacol Exp Ther 272:184–196

    CAS  PubMed  Google Scholar 

  32. Wijffels MC, Dorland R, Mast F, Allessie MA (2000) Widening of the excitable gap during pharmacological cardioversion of atrial fibrillation in the goat: effects of cibenzoline, hydroquinidine, flecainide, and d-sotalol. Circulation 102:260–267

    Google Scholar 

  33. Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA (1995) Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation 92:1954–1968

    Google Scholar 

  34. Wijffels MC, Kirchhof CJ, Dorland R, Power J, Allessie MA (1997) 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 96:3710–3720

    Google Scholar 

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Author notes

  1. W. Haverkamp

    Present address: Department of Cardiology, Humboldt-University Campus Virchow, Berlin, Germany

Authors and Affiliations

  1. Medizinische Klinik und Poliklinik C Kardiologie und Angiologie, Universitätsklinikum Münster, 48129, Münster, Germany

    P. Kirchhof, M. Engelen, M. Ribbing, K. Wasmer, G. Breithardt, W. Haverkamp & L. Eckardt

  2. Departments of Pharmacology and Cardiology, Georgetown University and VA Medical Centers, Washington DC, USA

    M. R. Franz

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  1. P. Kirchhof
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  2. M. Engelen
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Correspondence to P. Kirchhof.

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Drs. Kirchhof, Engelen and Breithardt are Members of the Kompetenznetz Vorhofflimmern

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Kirchhof, ., Engelen, M., Franz, M.R. et al. Electrophysiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation. Basic Res Cardiol 100, 112–121 (2005). https://doi.org/10.1007/s00395-005-0513-4

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  • DOI: https://doi.org/10.1007/s00395-005-0513-4

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