, Volume 62, Issue 16, pp 2377–2397 | Cite as

New Approaches to Atrial Fibrillation Management

A Critical Review of a Rapidly Evolving Field
  • Stanley Nattel
  • Paul Khairy
  • Denis Roy
  • Bernard Thibault
  • Peter Guerra
  • Mario Talajic
  • Marc Dubuc
Review Article


Atrial fibrillation (AF) is the most common cardiac arrhythmia, the prevalence of which is increasing with the aging of the population. Because of its clinical importance and the lack of highly satisfactory management approaches, AF is the subject of active clinical and research efforts. This paper reviews recent and on-going developments in pharmacological and non-drug management of AF.

The ideal therapeutic goal for AF is the production and maintenance of sinus rhythm. Comparative studies suggest that available class I and III drugs have comparable and modest efficacy for sinus rhythm maintenance. Amiodarone, with actions of all antiarrhythmic classes, has recently been shown to have clearly superior efficacy compared with other available drugs. Newer agents are in development, but their advantages are as yet unclear and appear limited. A potentially interesting approach is the prescription of drugs upon the occurrence of an attack, rather than on a continuous basis. Recent insights into AF mechanisms may permit therapy to prevent development of the AF substrate.

An alternative to sinus rhythm maintenance is a rate control approach, with no attempt to prevent AF. Drugs to effect rate control include digitalis, β-blockers and calcium channel antagonists. Digitalis has limited value for control of exercise heart rate and for paroxysmal AF, but is particularly well suited for patients with concomitant AF and congestive heart failure. AV-nodal ablation and pacing is an effective alternative for rate control but leaves the patient pacemaker dependent. The relative merits of rate versus rhythm control are being evaluated in ongoing trials, preliminary results of which indicate no statistically significant differences in primary endpoints but highlight the risks of rhythm control therapy.

In patients requiring pacemakers, physiological pacing (dual chamber devices or atrial pacing) has an advantage over purely ventricular pacemakers in AF prevention. Newer pacing modalities that produce more synchronised atrial activation, as well as pacemakers that prevent excessive atrial rate swings, show promise in AF prevention and may soon see wider use. The usefulness of automatic atrial defibrillators is presently limited by discomfort during shocks.

Targeted destruction of pulmonary vein foci by radiofrequency catheter ablation suppresses paroxysmal AF. Efficacy in persistent AF is lower and still under study. Problems include potential recurrence in other veins and a small but non-trivial risk of pulmonary vein stenosis. Surgical division of the atria into zones with limited electrical connection, the MAZE procedure, is highly effective in AF prevention but is a major intervention that is not applicable to most patients.

In conclusion, significant advances are being made in the management of patients with AF but much more work remains to be done.


Atrial Fibrillation Amiodarone Pulmonary Vein Flecainide Propafenone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported by the Canadian Institutes of Health Research, the Quebec Heart and Stroke Foundation and the Mathematics of Information Technology and Complex Systems Network of Centers of Excellence. There are no relationships that would result in significant conflicts of interest.


  1. 1.
    Shapiro W, Klein G. Alterations in cardiac function immediately following electrical conversion of atrial fibrillation to normal sinus rhythm. Circulation 1968; 38: 1074–84PubMedCrossRefGoogle Scholar
  2. 2.
    Kannel WB, Abbott RD, Savage DD, et al. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med 1982; 306: 1018–22PubMedCrossRefGoogle Scholar
  3. 3.
    Nattel S. New ideas about atrial fibrillation 50 years on. Nature 2002; 415: 219–26PubMedCrossRefGoogle Scholar
  4. 4.
    Cairns JA, Connolly SJ. Nonrheumatic atrial fibrillation: risk of stroke and role of antithrombotic therapy. Circulation 1991; 84: 469–81PubMedCrossRefGoogle Scholar
  5. 5.
    Morris JJ, Entman M, North WC, et al. The changes in cardiac output with reversion of atrial fibrillation to sinus rhythm. Circulation 1965; 31: 670–8PubMedCrossRefGoogle Scholar
  6. 6.
    Hart RG, Halperin JL. Atrial fibrillation and stroke: concepts and controversies. Stroke 2001; 32: 803–8PubMedCrossRefGoogle Scholar
  7. 7.
    Dorian P, Jung W, Newman D, et al. The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J Am Coll Cardiol 2000; 36: 1303–9PubMedCrossRefGoogle Scholar
  8. 8.
    Dries DL, Exner DV, Gersh BJ, et al. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials: studies of left ventricular dysfunction. J Am Coll Cardiol 1998; 32: 695–703PubMedCrossRefGoogle Scholar
  9. 9.
    Allessie MA, Boyden PA, Camm AJ, et al. Pathophysiology and prevention of atrial fibrillation. Circulation 2001; 103: 769–77PubMedCrossRefGoogle Scholar
  10. 10.
    Nattel S, Hadjis T, Talajic M. The treatment of atrial fibrillation: an evaluation of drug therapy, electrical modalities and therapeutic considerations. Drugs 1994; 48: 345–71PubMedCrossRefGoogle Scholar
  11. 11.
    Channer KS. Current management of symptomatic atrial fibrillation. Drugs 2001; 61: 1425–3PubMedCrossRefGoogle Scholar
  12. 12.
    Lundstrom T, Ryden L. Chronic atrial fibrillation: long-term results of direct current conversion. Acta Med Scand 1988; 223: 53–9PubMedCrossRefGoogle Scholar
  13. 13.
    Vanderperren O, Roy D, Muller T, et al. Maintaining sinus rhythm after cardioversion of atrial fibrillation: role of sotalol versus digoxin [abstract]. Clin Invest Med 1990; 13: C98Google Scholar
  14. 14.
    Dethy M, Chassat C, Roy D, et al. Doppier echocardiographic predictors of recurrence of atrial fibrillation after cardioversion. Am J Cardiol 1988; 62: 723–6PubMedCrossRefGoogle Scholar
  15. 15.
    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: 913–20PubMedCrossRefGoogle Scholar
  16. 16.
    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: 1932–9PubMedCrossRefGoogle Scholar
  17. 17.
    Van Gelder IC, Crijns HJ, Van Gilst WH, et al. Prediction of uneventful cardioversion and maintenance of sinus rhythm from direct-current electrical cardioversion of chronic atrial fibrillation and flutter. Am J Cardiol 1991; 68: 41–6PubMedCrossRefGoogle Scholar
  18. 18.
    Dittrich HC, Erickson JS, Schneiderman T, et al. Echo-cardiographic and clinical predictors for outcome of elective cardioversion of atrial fibrillation. Am J Cardiol 1989; 63: 193–7PubMedCrossRefGoogle Scholar
  19. 19.
    Brodsky MA, Allen BJ, Capparelli EV, et al. Factors determining maintenance of sinus rhythm after chronic atrial fibrillation with left atrial dilatation. Am J Cardiol 1989; 63: 1065–8PubMedCrossRefGoogle Scholar
  20. 20.
    Nattel S. Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs. Cardiovasc Res 1998; 37: 567–77PubMedCrossRefGoogle Scholar
  21. 21.
    Lown B, Perlroth MG, Kaidbey S, et al. “Cardioversion” of atrial fibrillation: a report on the treatment of 65 episodes in 50 patients. N Engl J Med 1963; 269: 325–31PubMedCrossRefGoogle Scholar
  22. 22.
    Elhendy A, Gentile F, Khandheria BK, et al. Predictors of unsuccessful electrical cardioversion in atrial fibrillation. Am J Cardiol 2002; 89: 83–6PubMedCrossRefGoogle Scholar
  23. 23.
    Levy S, Lauribe P, Dolla E, et al. A randomized comparison of external and internal cardioversion of chronic atrial fibrillation. Circulation 1992; 86: 1415–20PubMedCrossRefGoogle Scholar
  24. 24.
    Oral H, Souza JJ, Michaud GF, et al. Facilitating transthoracic cardioversion of atrial fibrillation with ibutilide pretreatment. N Engl J Med 1999; 340: 1849–54PubMedCrossRefGoogle Scholar
  25. 25.
    Benditt DG, Samniah N, Iskos D, et al. Biphasic waveform cardioversion as an alternative to internal cardioversion for atrial fibrillation refractory to conventional monophasic waveform transthoracic shock. Am J Cardiol 2001; 88: 1426–8PubMedCrossRefGoogle Scholar
  26. 26.
    Bianconi L, Mennuni M, Lukic V, et al. Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study. J Am Coll Cardiol 1996; 28: 700–6PubMedCrossRefGoogle Scholar
  27. 27.
    Tse HF, Lau CP, Ayers GM. Incidence and modes of onset of early reinitiation of atrial fibrillation after successful internal cardioversion, and its prevention by intravenous sotalol. Heart 1999; 82: 319–24PubMedGoogle Scholar
  28. 28.
    Slavik RS, Tisdale JE, Borzak S. Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence. Prog Cardiovasc Dis 2001; 44: 121–52PubMedCrossRefGoogle Scholar
  29. 29.
    Azpitarte J, Alvarez M, Baun O, et al. Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation: results of a randomized, double-blind, controlled study. Eur Heart J 1997; 18: 1649–54PubMedCrossRefGoogle Scholar
  30. 30.
    Naccarelli GV, Dorian P, Hohnloser SH, et al. Prospective comparison of flecainide versus quinidine for the treatment of paroxysmal atrial fibrillation/flutter: the Flecainide Multicenter Atrial Fibrillation Study Group. Am J Cardiol 1996; 77: 53A–9APubMedCrossRefGoogle Scholar
  31. 31.
    Lee SH, Chen SA, Chiang CE, et al. Comparisons of oral propafenone and quinidine as an initial treatment option in patients with symptomatic paroxysmal atrial fibrillation: a double-blind, randomized trial. J Intern Med 1996; 239: 253–60PubMedCrossRefGoogle Scholar
  32. 32.
    Reimold SC, Cantillon CO, Friedman PL, et al. Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Am J Cardiol 1993; 71: 558–63PubMedCrossRefGoogle Scholar
  33. 33.
    Lee SH, Chen SA, Tai CT, et al. Comparisons of oral propafenone and sotalol as an initial treatment in patients with symptomatic paroxysmal atrial fibrillation. Am J Cardiol 1997; 79: 905–8PubMedCrossRefGoogle Scholar
  34. 34.
    Bellandi F, Dabizzi RP, Niccoli L, et al. Propafenone and sotalol: long-term efficacy and tolerability in the prevention of paroxysmal atrial fibrillation: a placebo-controlled double-blind study. G Ital Cardiol 1996; 26: 379–90PubMedGoogle Scholar
  35. 35.
    de Paola AA, Veloso HH. Efficacy and safety of sotalol versus quinidine for the maintenance of sinus rhythm after conversion of atrial fibrillation. SOCESP Investigators. The Cardiology Society of Sao Paulo. Am J Cardiol 1999; 84: 1033–7Google Scholar
  36. 36.
    Li D, Benardeau A, Nattel S. Contrasting efficacy of dofetilide in differing experimental models of atrial fibrillation. Circulation 2000; 102: 104–12PubMedCrossRefGoogle Scholar
  37. 37.
    Middlekauff HR, Wiener I, Stevenson WG. Low-dose amio-darone for atrial fibrillation. Am J Cardiol 1993; 72: 75F–8 1FPubMedCrossRefGoogle Scholar
  38. 38.
    Brodsky MA, Allen BJ, Walker CJ, et al. Amiodarone for maintenance of sinus rhythm after conversion of atrial fibrillation in the setting of a dilated left atrium. Am J Cardiol 1987; 60: 572–5PubMedCrossRefGoogle Scholar
  39. 39.
    Feld GK, Nademanee K, Stevenson W, et al. Clinical and electrophysiologic effects of amiodarone in patients with atrial fibrillation complicating the Wolff-Parkinson-White syndrome. Am Heart J 1988; 115: 102–7PubMedCrossRefGoogle Scholar
  40. 40.
    Gold RL, Haffajee CI, Charos G, et al. Amiodarone for refractory atrial fibrillation. Am J Cardiol 1986; 57: 124–7PubMedCrossRefGoogle Scholar
  41. 41.
    Graboys TB, Podrid PJ, Lown B. Efficacy of amiodarone for refractory supraventricular tachyarrhythmias. Am Heart J 1983; 106: 870–6PubMedCrossRefGoogle Scholar
  42. 42.
    Horowitz LN, Spielman SR, Greenspan AM, et al. Use of amiodarone in the treatment of persistent and paroxysmal atrial fibrillation resistant to quinidine therapy. J Am Coll Cardiol 1985; 6: 1402–7PubMedCrossRefGoogle Scholar
  43. 43.
    Blevins RD, Kerin NZ, Benaderet D, et al. Amiodarone in the management of refractory atrial fibrillation. Arch Intern Med 1987; 147: 1401–4PubMedCrossRefGoogle Scholar
  44. 44.
    Chun SH, Sager PT, Stevenson WG, et al. 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: 47–50PubMedCrossRefGoogle Scholar
  45. 45.
    Gosselink AT, Crijns HJ, Van GI, et al. Low-dose amiodarone for maintenance of sinus rhythm after cardioversion of atrial fibrillation or flutter. JAMA 1992; 267: 3289–93PubMedCrossRefGoogle Scholar
  46. 46.
    Martin A, Benbow LJ, Leach C, et al. Comparison of amiodarone and disopyramide in the control of paroxysmal atrial fibrillation and atrial flutter (interim report). Br J Clin Pract Suppl 1986; 44: 52–60PubMedGoogle Scholar
  47. 47.
    Vitolo E, Tronci M, Larovere MT, et al. Amiodarone versus quinidine in the prophylaxis of atrial fibrillation. Acta Cardiol 1981; 36: 431–44PubMedGoogle Scholar
  48. 48.
    Zarembski DG, Nolan PEJ, Slack MK, et al. Treatment of resistant atrial fibrillation: a meta-analysis comparing amio-darone and flecainide. Arch Intern Med 1995; 155: 1885–91PubMedCrossRefGoogle Scholar
  49. 49.
    Kochiadakis GE, Igoumenidis NE, Marketou ME, et al. Low-dose amiodarone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Am J Cardiol 1998; 81: 995–8PubMedCrossRefGoogle Scholar
  50. 50.
    Roy D, Talajic M, Thibault B, et al. Pilot study and protocol of the Canadian Trial of Atrial Fibrillation (CTAF). Am J Cardiol 1997; 80: 464–8PubMedCrossRefGoogle Scholar
  51. 51.
    Kochiadakis GE, Igoumenidis NE, Marketou ME, et al. Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study. Heart 2000; 84: 251–7PubMedCrossRefGoogle Scholar
  52. 52.
    Carmeliet E. Voltage-and time-dependent block of the delayed K+ current in cardiac myocytes by dofetilide. J Pharmacol Exp Ther 1992; 262: 809–17PubMedGoogle Scholar
  53. 53.
    Kiehn J. Differential effects of the new class III agent dofetilide on potassium currents in guinea pig cardiomyocytes. J Cardiovasc Pharmacol 1994; 24: 566–72PubMedCrossRefGoogle Scholar
  54. 54.
    Gwilt M. Dofetilide, a new class III antiarrhythmic agent, reduces pacing induced heterogeneity of repolarisation in vivo. Cardiovasc Res 1992; 26: 1102–8PubMedCrossRefGoogle Scholar
  55. 55.
    McClellan KJ, Markham A. Dofetilide: a review of its use in atrial fibrillation and atrial flutter. Drugs 1999; 58: 1043–59PubMedCrossRefGoogle Scholar
  56. 56.
    Falk RH, Pollak A, Singh SN, et al. Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators. J Am Coll Cardiol 1997; 29: 385–90CrossRefGoogle Scholar
  57. 57.
    Baskin EP, Serik CM, Wallace AA, et al. Effects of new and potent methanesulfonanilide class III antiarrhythmic agents on myocardial refractoriness and contractility in isolated cardiac muscle. J Cardiovasc Pharmacol 1991; 18: 406–14PubMedCrossRefGoogle Scholar
  58. 58.
    Tande PM, Bjornstad H, Yang T, et al. Rate-dependent class III antiarrhythmic action, negative chronotropy, and positive inotropy of a novel Ik blocking drug, UK-68,798: potent in guinea pig but no effect in rat myocardium. J Cardiovasc Pharmacol 1990; 16: 401–10PubMedCrossRefGoogle Scholar
  59. 59.
    DeCara JM, Pollak A, Dubrey S, et al. Positive atrial inotropic effect of dofetilide after cardioversion of atrial fibrillation or flutter. Am J Cardiol 2000; 86: 685–8PubMedCrossRefGoogle Scholar
  60. 60.
    Nattel S, Zeng FD. Frequency-dependent effects of antiarrhythmic drugs on action potential duration and refractoriness of canine cardiac Purkinje fibers. J Pharmacol Exp Ther 1984; 229: 283–91PubMedGoogle Scholar
  61. 61.
    Hondeghem LM. Development of class III antiarrhythmic agents. J Cardiovasc Pharmacol 1992; 20: S17–22PubMedCrossRefGoogle Scholar
  62. 62.
    Nattel S, Liu L, St Georges D. Effects of the novel antiarrhythmic agent azimilide on experimental atrial fibrillation and atrial electrophysiologic properties. Cardiovasc Res 1998; 37: 627–35PubMedCrossRefGoogle Scholar
  63. 63.
    Norgaard BL, Wachtell K, Christensen PD, et al. Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled trial. Danish Dofetilide in Atrial Fibrillation and Flutter Study Group. Am Heart J 1999; 137: 1062–9Google Scholar
  64. 64.
    Bianconi L, Castro A, Dinelli M, et al. Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled study. Eur Heart J 2000; 21: 1265–73Google Scholar
  65. 65.
    Kobayashi Y, Atarashi H, Ino T, et al. Clinical and electrophysiologic effects of dofetilide in patients with supraventricular tachyarrhythmias. J Cardiovasc Pharmacol 1997; 30: 367–73PubMedCrossRefGoogle Scholar
  66. 66.
    Frost L, Mortensen PE, Tingleff J, et al. Efficacy and safety of dofetilide, a new class III antiarrhythmic agent, in acute termination of atrial fibrillation or flutter after coronary artery bypass surgery. Dofetilide Post-CABG Study Group. Int J Cardiol 1997; 58: 135–40Google Scholar
  67. 67.
    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: 2385–90PubMedCrossRefGoogle Scholar
  68. 68.
    Greenbaum RA, Campbell TJ, Channer KS. Conversion of atrial fibrillation and maintenance of sinus rhythm by dofetilide [abstract]. Circulation 1998; 98: 1–633CrossRefGoogle Scholar
  69. 69.
    Torp-Pedersen C, Möller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999; 341: 857–65Google Scholar
  70. 70.
    Kober L, Bloch Thomsen PE, Möller M, et al. Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial. Lancet 2000; 356: 2052–8PubMedCrossRefGoogle Scholar
  71. 71.
    Pedersen OD, Bagger H, Keller N, et al. Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (DIAMOND) sub-study. Circulation 2001; 104: 292–6PubMedCrossRefGoogle Scholar
  72. 72.
    Lehmann MH, Hardy S, Archibald D, et al. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation 1996; 94: 2535–41PubMedCrossRefGoogle Scholar
  73. 73.
    Han W, Chartier D, Li D, et al. Ionic remodeling of cardiac Purkinje cells by congestive heart failure. Circulation 2001; 104: 2095–100PubMedCrossRefGoogle Scholar
  74. 74.
    Waldo AL, Camm AJ, deRuyter H, et al. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction: the SWORD Investigators, survival with oral d-sotalol. Lancet 1996; 348: 7–12PubMedCrossRefGoogle Scholar
  75. 75.
    Salata JJ, Brooks RR. Pharmacology of azimilide dihydrochlo-ride (NE-10064), a class III antiarrhythmic agent. Cardiovasc Drug Rev 1997; 15: 137–56CrossRefGoogle Scholar
  76. 76.
    Fermini B, Jurkiewicz NK, Jow B, et al. Use-dependent effects of the class III antiarrhythmic agent NE-10064 (azimilide) on cardiac repolarization: block of delayed rectifier potassium and L-type calcium currents. J Cardiovasc Pharmacol 1995; 26: 259–71PubMedCrossRefGoogle Scholar
  77. 77.
    Yao JA, Tseng GN. Azimilide (NE-10064) can prolong or shorten the action potential duration in canine ventricular myocytes: dependence on blockade of K, Ca, and Na channels. J Cardiovasc Electrophysiol 1997; 8: 184–98PubMedCrossRefGoogle Scholar
  78. 78.
    Jurkiewicz NK, Sanguinetti MC. Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent: specific block of rapidly activating delayed rectifier K+ current by dofetilide. Circ Res 1993; 72: 75–83PubMedCrossRefGoogle Scholar
  79. 79.
    Qi XQ, Newman D, Dorian P. The class III effect of azimilide is not associated with reverse use-dependence in open-chest dogs. J Cardiovasc Pharmacol 1999; 34: 898–903PubMedCrossRefGoogle Scholar
  80. 80.
    Anonymous. Azimilide. NE 10064, Stedicor. Drugs R D 1999; 1: 297-300Google Scholar
  81. 81.
    Pritchett EL, Page RL, Connolly SJ, et al. Antiarrhythmic effects of azimilide in atrial fibrillation: efficacy and dose-response. Azimilide Supraventricular Arrhythmia Program 3 (SVA-3) Investigators. J Am Coll Cardiol 2000; 36: 794–802Google Scholar
  82. 82.
    Camm AJ, Karam R, Pratt CM. The azimilide post-infarct survival evaluation (ALIVE) trial. Am J Cardiol 1998; 81: 35D–9DPubMedCrossRefGoogle Scholar
  83. 83.
    Doggrell SA. Tedisamil: master switch of nature? Expert Opin Investig Drugs 2001; 10: 129–38PubMedCrossRefGoogle Scholar
  84. 84.
    Sager PT. New advances in class III antiarrhythmic drug therapy. Curr Opin Cardiol 2000; 15: 41–53PubMedCrossRefGoogle Scholar
  85. 85.
    Sun W, Sarma JS, Singh BN. Electrophysiological effects of dronedarone (SR33589), a noniodinated benzofuran derivative, in the rabbit heart: comparison with amiodarone. Circulation 1999; 100: 2276–81PubMedCrossRefGoogle Scholar
  86. 86.
    Varro A, Takacs J, Nemeth M, et al. Electrophysiological effects of dronedarone (SR 33589), a noniodinated amiodarone derivative in the canine heart: comparison with amiodarone. Br J Pharmacol 2001; 133: 625–34PubMedCrossRefGoogle Scholar
  87. 87.
    Rahme MM, Cotter B, Leistad E, et al. Electrophysiological and antiarrhythmic effects of the atrial selective 5-HT(4) receptor antagonist RS-100302 in experimental atrial flutter and fibrillation. Circulation 1999; 100: 2010–7PubMedCrossRefGoogle Scholar
  88. 88.
    Nattel S. Effects of ionic remodeling on cardiac antiarrhythmic drug actions. J Cardiovasc Pharmacol 2001; 38: 809–11PubMedCrossRefGoogle Scholar
  89. 89.
    Capucci A, Villani GQ, Aschieri D, et al. Safety of oral propafenone in the conversion of recent onset atrial fibrillation to sinus rhythm: a prospective parallel placebo-controlled multicentre study. Int J Cardiol 1999; 68: 187–96PubMedCrossRefGoogle Scholar
  90. 90.
    Botto GL, Bonini W, Broffoni T, et al. Randomized, crossover, controlled comparison of oral loading versus intravenous infusion of propafenone in recent-onset atrial fibrillation. Pacing Clin Electrophysiol 1998; 21: 2480–4PubMedCrossRefGoogle Scholar
  91. 91.
    Boriani G, Biffi M, Capucci A, et al. Conversion of recent-onset atrial fibrillation to sinus rhythm: effects of different drug protocols. Pacing Clin Electrophysiol 1998; 21: 2470–4PubMedCrossRefGoogle Scholar
  92. 92.
    Boriani G, Biffi M, Capucci A, et al. Oral loading with propafenone: a placebo-controlled study in elderly and non-elderly patients with recent onset atrial fibrillation. Pacing Clin Electrophysiol 1998; 21: 2465–9PubMedCrossRefGoogle Scholar
  93. 93.
    Fresco C, Proclemer A. Clinical challenge: II. management of recent onset atrial fibrillation. PAFIT-2 Investigators. Eur Heart J 1996; 17 Suppl. C: 41–7PubMedCrossRefGoogle Scholar
  94. 94.
    Blanc JJ, Voinov C, Maarek M. Comparison of oral loading dose of propafenone and amiodarone for converting recent-onset atrial fibrillation. PARSIFAL Study Group. Am J Cardiol 1999;84: 1029–32PubMedCrossRefGoogle Scholar
  95. 95.
    Peuhkurinen K, Niemela M, Ylitalo A, et al. Effectiveness of amiodarone as a single oral dose for recent-onset atrial fibrillation. Am J Cardiol 2000; 85: 462–5PubMedCrossRefGoogle Scholar
  96. 96.
    Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation: a study in awake chronically instrumented goats. Circulation 1995; 92(7): 1954–68PubMedCrossRefGoogle Scholar
  97. 97.
    Yue L, Feng J, Gaspo R, et al. Ionic remodelling underlying action potential changes in a canine model of atrial fibrillation. Circ Res 1997; 81: 512–25PubMedCrossRefGoogle Scholar
  98. 98.
    Nattel S, Li D. Ionic remodeling in the heart: pathophysiological significance and new therapeutic opportunities for atrial fibrillation. Circ Res 2000; 87: 440–7PubMedCrossRefGoogle Scholar
  99. 99.
    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: 167–73PubMedCrossRefGoogle Scholar
  100. 100.
    Tieleman RG, De Langen C, Van Gelder IC. Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation 1997; 95: 1945–53PubMedCrossRefGoogle Scholar
  101. 101.
    De Simone A, Stabile G, Vitale DF, et al. Pretreatment with verapamil in patients with persistent or chronic atrial fibrillation who underwent electrical cardioversion. J Am Coll Cardiol 1999; 34: 810–4PubMedCrossRefGoogle Scholar
  102. 102.
    Van Noord T, Van Gelder IC, Tieleman RG, et al. VERDICT: the Verapamil versus Digoxin Cardioversion Trial: a randomized study on the role of calcium lowering for maintenance of sinus rhythm after cardioversion of persistent atrial fibrillation. J Cardiovasc Electrophysiol 2001; 12: 766–9PubMedCrossRefGoogle Scholar
  103. 103.
    Lee SH, Yu WC, Cheng JJ, et al. Effect of verapamil on long-term tachycardia-induced atrial electrical remodeling. Circulation 2000; 101: 200–6PubMedCrossRefGoogle Scholar
  104. 104.
    Fareh S, Bénardeau A, Nattel S. Differential efficacy of L-and T-type calcium channel blockers in preventing tachycardia-induced atrial remodeling in dogs. Cardiovasc Res 2001; 49: 762–70PubMedCrossRefGoogle Scholar
  105. 105.
    Li D, Fareh S, Leung TK, et al. Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort. Circulation 1999; 100: 87–95PubMedCrossRefGoogle Scholar
  106. 106.
    Li D, Shinagawa K, Pang L, et al. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation 2001; 104: 2608–14PubMedCrossRefGoogle Scholar
  107. 107.
    Pedersen OD, Bagger H, Kober L, et al. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 1999; 100: 376–8PubMedCrossRefGoogle Scholar
  108. 108.
    Farshi R, Kistner D, Sarma JSM, et al. Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens. J Am Coll Cardiol 1999; 33: 304–10PubMedCrossRefGoogle Scholar
  109. 109.
    Shinbane JS, Wood M, Jensen DN, et al. Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies. J Am Coll Cardiol 1997; 29: 709–15PubMedCrossRefGoogle Scholar
  110. 110.
    Wyse DG. Overview of atrial fibrillation trials. Cardiac Electrophysiol Rev 2000; 4: 149–55CrossRefGoogle Scholar
  111. 111.
    Hohnloser SH, Kuck KH, Lilienthal J, et al. Rhythm or rate control in atrial fibrillation: pharmacological intervention in atrial fibrillation (PIAF): a randomised trial. Lancet 2000; 356: 1789–94PubMedCrossRefGoogle Scholar
  112. 112.
    Redfors A. Plasma digoxin concentration: its relation to digoxin and clinical effects in patients with atrial fibrillation. Br Heart J 1972; 34: 383–91PubMedCrossRefGoogle Scholar
  113. 113.
    David D, Segni ED, Klein HO, et al. Inefficacy of digitalis in the control of heart rate in patients with chronic atrial fibril-lation: beneficial effect of an added beta adrenergic blocking agent. Am J Cardiol 1979; 44: 1378–82PubMedCrossRefGoogle Scholar
  114. 114.
    Beasley R, Smith DA, McHaffie DJ. Exercise heart rates at different serum digoxin concentrations in patients with atrial fibrillation. Br Med J 1985; 290: 9–11CrossRefGoogle Scholar
  115. 115.
    Rawles JM, Metcalfe MJ, Jennings K. Time of occurrence, duration, and ventricular rate of paroxysmal atrial fibrillation: the effect of digoxin. Br Heart J 1990; 63: 225–7PubMedCrossRefGoogle Scholar
  116. 116.
    Prystowsky EN, Benson Jr DW, Fuster V, et al. Management of patients with atrial fibrillation: a statement for healthcare professionals, from the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association. Circulation 1996; 93: 1262–77PubMedCrossRefGoogle Scholar
  117. 117.
    DiBianco R, Morganroth J, Freitag RJ, et al. Effects of nadolol on the spontaneous and exercise-provoked heart rate in patients with chronic atrial fibrillation receiving stable doses of digoxin. Am Heart J 1984; 108: 1121–7PubMedCrossRefGoogle Scholar
  118. 118.
    Channer KS, James MA, MacConnell T, et al. Beta-adrenoceptor blockers in atrial fibrillation: the importance of partial agonist activity. Br J Clin Pharmacol 1994; 37: 53–7PubMedCrossRefGoogle Scholar
  119. 119.
    Packer M, Bristow MR, Cohn JN, et al. for the US Carvedilol Heart Failure Study Group. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996; 334: 1349–55Google Scholar
  120. 120.
    MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: MEtoprolol CR/XL Randomised Intervention Trial in congestive Heart Failure (MERIT-HF). Lancet 1999; 353: 2001–7CrossRefGoogle Scholar
  121. 121.
    CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol study II (CIBIS-II): a randomized trial. Lancet 1999; 353: 9–13CrossRefGoogle Scholar
  122. 122.
    Lundstrom T, Ryden L. Ventricular rate control and exercise performance in chronic atrial fibrillation: effects of diltiazem and verapamil. J Am Coll Cardiol 1990; 16: 86–90PubMedCrossRefGoogle Scholar
  123. 123.
    Goldstein RE, Boccuzzi SJ, Cruess D, et al. the Adverse Experience Committee and the Multicenter Diltiazem Postinfarction Research Group. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. Circulation 1991; 83: 52–60Google Scholar
  124. 124.
    Deedwania PC, Singh BN, Ellenbogen K, et al., for the Department of Veterans Affairs CHF-STAT Investigators. 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). Circulation 1998; 98: 2574–9PubMedCrossRefGoogle Scholar
  125. 125.
    Scheinman MM, Morady F, Hess DS, et al. Catheter-induced ablation of the atrioventricular junction to control refractory supraventricular arrhythmias. JAMA 1982; 248: 851–5PubMedCrossRefGoogle Scholar
  126. 126.
    Gallagher JJ, Svenson RH, Kasell JH, et al. Catheter technique for closed-chest ablation of the atrioventricular conduction system: a therapeutic alternative for the treatment of refractory supraventricular tachycardia. N Engl J Med 1982; 306: 194–200PubMedCrossRefGoogle Scholar
  127. 127.
    Evans Jr GT, Scheinman MM, Zipes DP, et al. The Percutaneous Cardiac Mapping and Ablation Registry: summary of results. Pacing Clin Electrophysiol 1987; 10: 1395–9PubMedCrossRefGoogle Scholar
  128. 128.
    Langberg JJ, Chin MC, Rosenqvist M, et al. Catheter ablation of the atrioventricular junction with radiofrequency energy. Circulation 1989; 80: 1527–35PubMedCrossRefGoogle Scholar
  129. 129.
    Dubuc M, Khairy P, Rodriguez-Santiago A, et al. Catheter cryoablation of the atrioventricular node in patients with atrial fibrillation: a novel technology for ablation of cardiac arrhythmias. J Cardiovasc Electrophysiol 2001; 12: 439–44PubMedCrossRefGoogle Scholar
  130. 130.
    Touboul P. Atrioventricular nodal ablation and pacemaker implantation in patients with atrial fibrillation. Am J Cardiol 1999; 83: 241D–5DPubMedCrossRefGoogle Scholar
  131. 131.
    Brignole M, Menozzi C. Control of rapid heart rate in patients with atrial fibrillation: drugs or ablation? Pacing Clin Electrophysiol 1996; 19: 348–56PubMedCrossRefGoogle Scholar
  132. 132.
    Brignole M. Ablate and pace: a pragmatic approach to paroxysmal atrial fibrillation not controlled by antiarrhythmic drugs. Heart 1998; 79: 531–3PubMedGoogle Scholar
  133. 133.
    Brignole M, Menozzi C, Gianfranchi L, et al. Assessment of atrioventricular junction ablation and WIR pacemaker versus pharmacological treatment in patients with heart failure and chronic atrial fibrillation: a randomized, controlled study. Circulation 1998; 98: 953–60PubMedCrossRefGoogle Scholar
  134. 134.
    Fitzpatrick AP, Kourouyan HD, Siu A, et al. Quality of life and outcomes after radiofrequency His bundle catheter ablation and permanent pacemaker implantation: impact of treatment in paroxysmal and established atrial fibrillation. Am Heart J 1996; 131: 499–507PubMedCrossRefGoogle Scholar
  135. 135.
    Brignole M, Gianfranchi L, Menozzi C, et al. Assessment of atrioventricular junction ablation and DDDR mode-switching pacemaker versus pharmacological treatment in patients with severely symptomatic paroxysmal atrial fibrillation: a randomized controlled study. Circulation 1997; 96: 2617–24PubMedCrossRefGoogle Scholar
  136. 136.
    Lee SH, Chen SA, Tai CT, et al. Comparisons of quality of life and cardiac performance after complete atrioventricular junction ablation and atrioventricular junction modification in patients with medically refractory atrial fibrillation. J Am Coll Cardiol 1998; 31: 637–44PubMedCrossRefGoogle Scholar
  137. 137.
    Kay GN, Ellenbogen KA, Giudici M, et al. The Ablate and Pace Trial: a prospective study of catheter ablation of the AV conduction system and permanent pacemaker implantation for treatment of atrial fibrillation. J Interv Card Electrophysiol 1998; 2: 121–35PubMedCrossRefGoogle Scholar
  138. 138.
    Marshall HJ, Harris ZI, Griffith MJ, et al. Atrioventricular nodal ablation and implantation of mode switching dual chamber pacemakers: effective treatment for drug refractory paroxysmal atrial fibrillation. Heart 1998; 79: 543–7PubMedGoogle Scholar
  139. 139.
    De Lima G, Talajic M, Dubuc M, et al. Malignant ventricular arrhythmias after atrioventricular nodal ablation: a long-term follow-up study [abstract]. Circulation 1996; 94 Suppl. I: I–666Google Scholar
  140. 140.
    Ozcan C, Jahangir A, Friedman PA, et al. Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation. N Engl J Med 2001; 344: 1043–51PubMedCrossRefGoogle Scholar
  141. 141.
    Gianfranchi L, Brignole M, Menozzi C, et al. Progression of permanent atrial fibrillation after atrioventricular junction ablation and dual-chamber pacemaker implantation in patients with paroxysmal atrial tachyarrhythmias. Am J Cardiol 1998; 81: 351–4PubMedCrossRefGoogle Scholar
  142. 142.
    Williamson BD, Man KC, Daoud E, et al. Frequency catheter modification of atrioventricular conduction to control the ventricular rate during atrial fibrillation. N Engl J Med 1994; 331: 910–7PubMedCrossRefGoogle Scholar
  143. 143.
    Twidale N, McDonald T, Nave K, et al. Comparison of the effects of AV nodal ablation versus AV nodal modification in patients with congestive heart failure and uncontrolled atrial fibrillation. Pacing Clin Electrophysiol 1998; 21: 641–51PubMedCrossRefGoogle Scholar
  144. 144.
    Rosenqyist M, Brandt J, Schuller H. Long term pacing in sinus node disease: effect of stimulation mode on cardiovascular mortality and morbidity. Am Heart J 1988; 116: 16–22CrossRefGoogle Scholar
  145. 145.
    Hesselson AB, Parsonet V, Bernstein AD, et al. Deleterious effects of long-term single chamber ventricular pacing in patients with sick sinus syndrome: the hidden benefits of dual chamber pacing. J Am Coll Cardiol 1992; 19: 1542–9PubMedCrossRefGoogle Scholar
  146. 146.
    Sgarbossa EB, Pinski SL, Maloney JD, et al. Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome: relevance of clinical characteristics and pacing modalities. Circulation 1993; 88: 1045–53PubMedCrossRefGoogle Scholar
  147. 147.
    Anderson HR, Thuessen L, Bagger JP, et al. Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome. Lancet 1994; 344: 1523–8CrossRefGoogle Scholar
  148. 148.
    Anderson HR, Nielson JC, Thomsen PE, et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 1997; 350: 1210–6CrossRefGoogle Scholar
  149. 149.
    Mattioli AV, Vivoli D, Mattioli G. Influence of pacing modalities on the incidence of atrial fibrillation in patients without prior atrial fibrillation: a prospective study. Eur Heart J 1998; 19: 282–6PubMedCrossRefGoogle Scholar
  150. 150.
    Connolly SJ, Kerr CR, Gent M, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med 2000; 342: 1385–91PubMedCrossRefGoogle Scholar
  151. 151.
    Skanes AC, Krahn AD, Yee R, et al. Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing. CTOPP Investigators. J Am Coll Cardiol 2001; 38: 167–72PubMedCrossRefGoogle Scholar
  152. 152.
    Tang AS, Roberts RS, Kerr C, et al. Relationship between pacemaker dependency and the effect of pacing mode on cardiovascular outcomes. Circulation 2001; 103: 3081–5PubMedCrossRefGoogle Scholar
  153. 153.
    Leon AR, Marinchak R, Yee R, et al. Incidence of atrial fibrillation in patients with sinus node dysfunction treated with ventricular pacing as compared with dual chamber pacing [abstract]. Circulation 2001; 104 Suppl. II: 11–382Google Scholar
  154. 154.
    Gillis AM, Wyse DG, Connolly SJ, et al. Atrial pacing periablation for prevention of paroxysmal atrial fibrillation. Circulation 1999; 99: 2553–8PubMedCrossRefGoogle Scholar
  155. 155.
    Gillis AM, Connolly SJ, Lacombe P, et al. Randomized crossover comparison of DDDR versus VDD pacing after atrioventricular junction ablation for prevention of atrial fibrillation: the atrial pacing peri-ablation for paroxysmal atrial fibrillation (PA(3)) study investigators. Circulation 2000; 102: 736–41PubMedCrossRefGoogle Scholar
  156. 156.
    Becker R, Klinkott R, Bauer A, et al. Multisite pacing for prevention of atrial tachyarrhythmias: potential mechanisms. J Am Coll Cardiol 2000; 35: 1939–46PubMedCrossRefGoogle Scholar
  157. 157.
    Yu WC, Tsai CF, Hsieh MH, et al. Prevention of the initiation of atrial fibrillation: mechanism and efficacy of different atrial pacing modes. PACE 2000; 23: 373–9PubMedCrossRefGoogle Scholar
  158. 158.
    Papageorgiou P, Anselme F, Kirchhof CJHJ, et al. Coronary sinus pacing prevents induction of atrial fibrillation. Circulation 1997; 96: 1893–8PubMedCrossRefGoogle Scholar
  159. 159.
    Padeletti L, Porciani MC, Michelucci A, et al. Interatrial septum pacing: a new approach to prevent recurrent atrial fibrillation. J Interv Card Electrophysiol 1999; 3: 35–43PubMedCrossRefGoogle Scholar
  160. 160.
    Bailin SJ, Adler S, Giudici M. Prevention of chronic atrial fibrillation by pacing in the region of Bachmann’s bundle: results of a multicenter randomized trial. J Cardiovasc Electrophysiol 2001; 12: 912–7PubMedCrossRefGoogle Scholar
  161. 161.
    Daubert C, Gras D, Leclercq C, et al. Biatrial synchronous pacing: a new therapeutic approach to prevent refractory atrial tachyarrhythmias [abstract]. J Am Coll Cardiol 1995; 25: 230ACrossRefGoogle Scholar
  162. 162.
    Devault D’Allones G, Pavin D, Leclercq C, et al. Long-term effects of biatrial synchronous pacing to prevent drug-refractory atrial tachyarrhythmia: a nine-year experience. J Cardiovasc Electrophysiol 2000; 11: 1081–91CrossRefGoogle Scholar
  163. 163.
    Default P, Saksena S, Prakash A, et al. Long-term outcome of patients with drug-refractory atrial flutter and fibrillation after single-and dual-site right atrial pacing for arrhythmia prevention. J Am Coll Cardiol 1998; 32: 1900–8CrossRefGoogle Scholar
  164. 164.
    Lau CP, Tse HF, Yu CM, et al. New Indication for Preventing Pacing in Atrial Fibrillation (NIPP-AF) Investigators: dual-site atrial pacing for atrial fibrillation in patients without bradycardia. Am J Cardiol 2001; 88: 371–5PubMedCrossRefGoogle Scholar
  165. 165.
    Saksena S, Prakash A, Fitts S, et al. Dual site Atrial Pacing for Prevention of Atrial Fibrillation (DAPPAF) Trial: substudy on device-based detection of recurrent atrial fibrillation [abstract]. PACE 2001; 24: 616CrossRefGoogle Scholar
  166. 166.
    Leclercq JF, De Sisti A, Fiorello P, et al. Is dual site better than single site atrial pacing in the prevention of atrial fibrillation? Pacing Clin Electrophysiol 2000; 23: 2101–7PubMedCrossRefGoogle Scholar
  167. 167.
    Funck RC, Adamec R, Lurje L, et al., on behalf of the PROVE Study Group. Atrial overdriving is beneficial in patients with atrial arrhythmias: first results of the PROVE study. Pacing Clin Electrophysiol 2000; 23: 1891–3PubMedGoogle Scholar
  168. 168.
    Israel CW, Lawo T, Lemke B, et al. Atrial pacing in the prevention of paroxysmal atrial fibrillation: first results of a new combined algorithm. Pacing Clin Electrophysiol 2000; 23: 1888–90PubMedCrossRefGoogle Scholar
  169. 169.
    Friedman PA, Dijkman B, Warman EN, et al. Atrial therapies reduce atrial arrhythmia burden in defibrillator patients. Circulation 2001; 104: 1023–8PubMedCrossRefGoogle Scholar
  170. 170.
    Wellens HJ, Lau CP, Luderitz B, et al. Atrioverter: an implantable device for the treatment of atrial fibrillation. Circulation 1998; 98: 1651–6PubMedCrossRefGoogle Scholar
  171. 171.
    Adler II SW, Wolpert C, Warman EN, et al., for the Worldwide Jewel AF0 Investigators. Efficacy of pacing therapies for treating atrial tachyarrhythmias in patients with ventricular arrhythmias receiving a dual-chamber implantable cardioverter defibrillator. Circulation 2001; 104: 887–92PubMedCrossRefGoogle Scholar
  172. 172.
    Tse HF, Lau CP, Yu CM, et al. Effect of the implantable atrial defibrillator on the natural history of atrial fibrillation. J Cardiovasc Electrophysiol 1999; 10: 1200–9PubMedCrossRefGoogle Scholar
  173. 173.
    Keane D, Zou L, Ruskin J. Nonpharmacologic therapies for atrial fibrillation. Am J Cardiol 1998; 81: 41C–5CPubMedCrossRefGoogle Scholar
  174. 174.
    Cox JL, Schuessler RB, D’Agostino HJ, et al. The surgical treatment of atrial fibrillation: III. development of a definitive surgical procedure. J Thorac Cardiovasc Surg 1991; 101: 569–83PubMedGoogle Scholar
  175. 175.
    Cox JL, Schuessler RB, Lappas DG, et al. An 8 1/2-year clinical experience with surgery for atrial fibrillation. Ann Surg 1996; 224: 267–73PubMedCrossRefGoogle Scholar
  176. 176.
    Mitchell MA, McRury ID, Haines DE. Linear atrial ablations in a canine model of chronic atrial fibrillation: morphological and electrophysiological observations. Circulation 1998; 97: 1176–85PubMedCrossRefGoogle Scholar
  177. 177.
    Avitall B, Helms RW, Chiang W, et al. Nonlinear atrial radio-frequency lesions are arrhythmogenic: a study of skipped lesions in the normal atria [abstract]. Circulation 1995; 92: 1–265CrossRefGoogle Scholar
  178. 178.
    Haissaguerre M, Jais P, Shah DC, et al. Right and left atrial radiofrequency catheter ablation of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 1996; 7: 1132–44PubMedCrossRefGoogle Scholar
  179. 179.
    Jais P, Shah DC, Haissaguerre M, et al. Efficacy and safety of septal and left-atrial linear ablation for atrial fibrillation. Am J Cardiol 1999; 84: 139R–46RPubMedCrossRefGoogle Scholar
  180. 180.
    Schwartzman D, Michele JJ, Trankiem CT, et al. Electrogram-guided radiofrequency catheter ablation of atrial tissue comparison with thermometry-guide ablation: comparison with thermometry-guide ablation. J Interv Card Electrophysiol 2001; 5: 253–66PubMedCrossRefGoogle Scholar
  181. 181.
    Schwartzman D, Kuck KH. Anatomy-guided linear atrial lesions for radiofrequency catheter ablation of atrial fibrillation. Pacing Clin Electrophysiol 1998; 21: 1959–78PubMedCrossRefGoogle Scholar
  182. 182.
    Ernst S, Schluter M, Ouyang F, et al. Modification of the substrate for maintenance of idiopathic human atrial fibrillation: efficacy of radiofrequency ablation using nonfluoroscopic catheter guidance. Circulation 1999; 100: 2085–92PubMedCrossRefGoogle Scholar
  183. 183.
    Nathan H, Eliakim M. The junction between the left atrium and the pulmonary veins: an anatomic study of human hearts. Circulation 1966; 34: 412–22PubMedCrossRefGoogle Scholar
  184. 184.
    Jais P, Haissaguerre M, Shah DC, et al. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation 1997; 95: 572–6PubMedCrossRefGoogle Scholar
  185. 185.
    Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339: 659–66PubMedCrossRefGoogle Scholar
  186. 186.
    Gerstenfeld EP, Guerra P, Sparks PB, et al. Clinical outcome after radiofrequency catheter ablation of focal atrial fibrillation triggers. J Cardiovasc Electrophysiol 2001; 12: 900–8PubMedCrossRefGoogle Scholar
  187. 187.
    Haissaguerre M, Jais P, Shah DC, et al. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Circulation 2000; 101: 1409–17PubMedCrossRefGoogle Scholar
  188. 188.
    Sippensgroenewegen A, Mlynash MD, Roithinger FX, et al. Electrocardiographic analysis of ectopic atrial activity obscured by ventricular repolarization: P wave isolation using an automatic 62-lead QRST subtraction algorithm. J Cardiovasc Electrophysiol 2001; 12: 780–90PubMedCrossRefGoogle Scholar
  189. 189.
    Hsieh MH, Chen SA, Tai CT, et al. Double multielectrode mapping catheters facilitate radiofrequency catheter ablation of focal atrial fibrillation originating from pulmonary veins. J Cardiovasc Electrophysiol 1999; 10: 136–44PubMedCrossRefGoogle Scholar
  190. 190.
    Haissaguerre M, Shah DC, Jais P, et al. Electrophysiological breakthroughs from the left atrium to the pulmonary veins. Circulation 2000; 102: 2463–5PubMedCrossRefGoogle Scholar
  191. 191.
    Pappone C, Rosanio S, Oreto G, et al. Circumferential radiofrequency ablation of pulmonary vein Ostia: a new anatomic approach for curing atrial fibrillation. Circulation 2000; 102: 2619–28PubMedCrossRefGoogle Scholar
  192. 192.
    Pappone C, Oreto G, Rosanio S, et al. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation 2001; 104: 2539–44PubMedCrossRefGoogle Scholar
  193. 193.
    Natale A, Pisano E, Shewchik J, et al. First human experience with pulmonary vein isolation using a through-the-balloon circumferential ultrasound ablation system for recurrent atrial fibrillation. Circulation 2000; 102: 1879–82PubMedCrossRefGoogle Scholar
  194. 194.
    Tanaka K, Satake S, Saito S, et al. A new radiofrequency thermal balloon catheter for pulmonary vein isolation. J Am Coll Cardiol 2001; 38: 2079–86PubMedCrossRefGoogle Scholar
  195. 195.
    Robbins IM, Colvin EV, Doyle TP, et al. Pulmonary vein stenosis after catheter ablation of atrial fibrillation. Circulation 1998; 98: 1769–75PubMedCrossRefGoogle Scholar
  196. 196.
    Sohn RH, Schiller NB. Left upper pulmonary vein stenosis 2 months after radiofrequency catheter ablation of atrial fibrillation. Circulation 2000; 101: E154–5PubMedCrossRefGoogle Scholar
  197. 197.
    Scanavacca MI, Kajita LJ, Vieira M, et al. Pulmonary vein stenosis complicating catheter ablation of focal atrial fibrillation. J Cardiovasc Electrophysiol 2000; 11: 677–81PubMedCrossRefGoogle Scholar
  198. 198.
    Moak JP, Moore HJ, Lee SW, et al. Case report: pulmonary vein stenosis following RF ablation of paroxysmal atrial fibrillation: successful treatment with balloon dilation. J Interv Card Electrophysiol 2000; 4: 621–31PubMedCrossRefGoogle Scholar
  199. 199.
    Murgatroyd FD. “Pills and pulses”: hybrid therapy for atrial fibrillation. J Cardiovasc Electrophysiol. 2002; 13 (1 Suppl.): 40S–6SGoogle Scholar
  200. 200.
    Defauw JJ, Guiraudon GM, Van Hemel NM, et al. Surgical therapy of paroxysmal atrial fibrillation with the “corridor” operation. Ann Thorac Surg 1992; 53: 564–70PubMedCrossRefGoogle Scholar
  201. 201.
    Cox JL, Ad N. New surgical and catheter-based modifications of the Maze procedure. Semin Thorac Cardiovasc Surg 2000; 12: 68–73PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Stanley Nattel
    • 1
    • 2
  • Paul Khairy
    • 1
  • Denis Roy
    • 1
  • Bernard Thibault
    • 1
  • Peter Guerra
    • 1
  • Mario Talajic
    • 1
  • Marc Dubuc
    • 1
  1. 1.Department of Medicine and Research CenterMontreal Heart Institute and University of MontrealMontrealCanada
  2. 2.Department of PharmacologyMcGill UniversityMontrealCanada

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