Skip to main content
Log in

Atrial Fibrillation: Basic Mechanisms, Remodeling and Triggers

  • State of the Art Review
  • Published:
Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Khairy P, Nattel S. New insights into the mechanisms and management of atrial fibrillation. Can Med Assoc J 2002;167:1012–1020.

    Google Scholar 

  2. Van den Berg MP, van Gelder IC, van Veldhuisen DJ. Impact of atrial fibrillation on mortality in patients with chronic heart failure. Eur J Heart Fail 2002;4:571–575.

    Article  PubMed  Google Scholar 

  3. Nattel S. New ideas about atrial fibrillation 50 years on. Nature 2002;415:219–226.

    Google Scholar 

  4. Garrey WE. Auricular fibrillation. Physiol Rev 1924;4:215–250.

    Google Scholar 

  5. Moe GK, Rheinboldt WC, Abildskov JA. A computer model of atrial fibrillation. Am Heart 1964;67:200–220.

    Article  Google Scholar 

  6. Allessie MA, Lammers WJEP, Bonke FIM, Hollen J. Experimental evaluation of Moe's multiple wavelet hypothesis of atrial fibrillation. In:Zipes DP, Jalife J, eds. Cardiac Arrhythmias . New York:Grune & Stratton 1985:265–276.

    Google Scholar 

  7. Li D, Fareh S, Leung TK, Nattel S. Promotion of atrial fibrillation by heart failure in dogs. Atrial remodeling of a different sort. Circulation 1999;100:87–95.

    PubMed  Google Scholar 

  8. Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Metayer P, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins. N Eng J Med 1998;339:659–666.

    Google Scholar 

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

    PubMed  Google Scholar 

  10. Morillo CA, Klein GJ, Jones DL, Guiraudon CM. Chronic rapid atrial pacing. Structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. Nature 1995;91:1588–1595.

    Google Scholar 

  11. Elvan A, Wylie K, Zipes DP. Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling. Circulation 1996;94:2953–2960.

    PubMed  Google Scholar 

  12. Gaspo R, Bosch RF, Talajic M, Nattel S. Functional mechanisms underlying tachycardia-induced sustained atrial fibrillation in a chronic dog model. Circulation 1997;96:4027–4035.

    PubMed  Google Scholar 

  13. Ausma J, Dispersyn GD, Duimel H, Thone F, Ver Donck L, Allessie MA, Borgers M. Changes in ultrastructural calcium distribution in goat atria during atrial fibrillation. J Moll Cell Cardio 2000;32:355–364.

    Article  Google Scholar 

  14. Yue L, Melnyk P, Gaspo R, Wang Z, Nattel S. Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation. Circ Res 1999;84:776–784.

    PubMed  Google Scholar 

  15. Yue L, Feng J, Gaspo R, Li GR, Wang Z, Nattel S. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. Circ Res 1997;81:512–525.

    PubMed  Google Scholar 

  16. Gaspo R, Bosch RF, Bou-Abbound E, Nattel S. Tachycardia-induced changes in Na current in a chronic dog model of atrial fibrillation. Circ Res 1997;81:1045–1052.

    PubMed  Google Scholar 

  17. Fareh S, Villemaire C, Nattel S. Importance of refractoriness heterogeneity in the enhanced vulnerability to atrial fibrillation induction caused by tachycardia-induced atrial electrical remodeling. Circulation 1998;98:2202–2209.

    PubMed  Google Scholar 

  18. Moe GK. On the multiple wavelet hypothesis of atrial fibrillation. Arch Int Pharmacodyn Ther 1962;140:183–188.

    Google Scholar 

  19. van der Velden HM, van Kempen MJ, Wijffels MC, van Zijverden M, Groenewegen WA, Allessie MA, Jongsma HJ. Altered pattern of connexin40 distribution in the goat. J Cardiovasc Electrophysio 1998;9:596–607.

    Google Scholar 

  20. van der Velden HM, Ausma J, Rook MB, Hellemons AJ, van Veen TA, Allessie MA, Jongsma HJ. Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. Cardiovasc Res 2000;46:476–486.

    Article  PubMed  Google Scholar 

  21. Ausma J, van der Velden HM, Lenders MH, van Ankeren EP, Jongsma HJ, Ramaekers FC, Borgers M, Allessie MA. Reverse structural and gap-junctional remodeling after prolonged atrial fibrillation in the goat. Nature 2003;107:2051–2058.

    Google Scholar 

  22. Sun H, Gaspo R, Leblanc N, Nattel S. Cellular mechanisms of atrial contractile dysfunction caused by sustained atrial tachycardia. Circulation 1998;98:719–727.

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  24. Nattel S. Atrial electrophysiological remodeling caused by rapid atrial activation:Underlying mechanisms and clinical relevance to atrial fibrillation. Cardiovasc Res 1999;42:298–308.

    Article  PubMed  Google Scholar 

  25. van der Velden HMW, van der Zee L, Wijffels MC, van Leuven C, Dorland R, Vos MA, Jongsma HJ, Allessie MA. Atrial fibrillation in the goat induces changes in monophasic action potential and mRNA expression of ion channels involved in repolarization. J Cardiovasc Electrophysio 2000;11:1262–1269.

    Article  Google Scholar 

  26. Cha TJ, Ehrlich JR, Zhang L, Nattel S. Atrial ionic remodeling induced by atrial tachycardia in the presence of congestive heart failure. Circulation 2004;110:1520–1526.

    Article  PubMed  Google Scholar 

  27. Ehrlich JR, Cha TJ, Zhang L, Chartier D, Villeneuve L, Hebert TE, Nattel S. Characterization of a hyperpolarization-activated time-dependent potassium current in canine cardiomyocytes from pulmonary vein myocardial sleeves and left atrium. J Physiol 2004;557:583–597.

    Article  PubMed  Google Scholar 

  28. Yagi T, Pu J, Chandra P, Hara M, Danilo P Jr, Rosen MR, Boyden PA. Density and function of inward currents in right atrial cells from chronically fibrillating canine atria. Cardiovasc Re 2002;54:405–415.

    Article  Google Scholar 

  29. Van Wagoner DR, Pond AL, McCarthy PM, Trimmer JS, Nerbonne JM. Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ Res 1997;80:772–781.

    PubMed  Google Scholar 

  30. Bosch RF, Zeng X, Grammer JB, Popovic K, Mewis C, Kuhlkamp V. Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc Res 1999;44:121–131.

    Article  PubMed  Google Scholar 

  31. Van Wagoner DR, Pond AL, Lamorgese M, Rossie SS, McCarthy PM, Nerbonne JM. Atrial L-type Ca2+ currents and human atrial fibrillation. Circ Res 1999;85:428–436.

    PubMed  Google Scholar 

  32. Dobrev D, Graf E, Wettwer E, Himmel HM, Hala O, Doerfel C, Christ T, Schuler S, Ravens U. Molecular basis of downregulation of G-protein-coupled inward rectifying K(+) current (I(K,Ach) in chronic human atrial fibrillation:Decrease in GIRK4 mRNA correlates with reduced I(K,Ach) and muscarinic receptor-mediated shortening of action potentials. Circulation 2001;104:2551–2557.

    PubMed  Google Scholar 

  33. Sun H, Chartier D, Leblanc N, Nattel S. Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes. Cardiovasc Res 2001;49:751–761.

    Article  PubMed  Google Scholar 

  34. Ramirez RJ, Nattel S, Courtemanche M. Mathematical analysis of canine atrial action potentials:Rate, regional factors, and electrical remodeling. Am J Physiol Heart Circ Physiol 2000;279:H1767–H1785.

    PubMed  Google Scholar 

  35. Brundel BJ, Kampinga HH, Henning RH. Calpain inhibition prevents pacing-induced cellular remodeling in a HL-1 myocyte model for atrial fibrillation. Cardiovasc Res 2004;62:521–528.

    Article  PubMed  Google Scholar 

  36. Kepplinger KJ, Forstner G, Kahr H, Leitner K, Pammer P, Groschner K, Soldatov NM, Romanin C. Molecular determinant for run-down of L-type Ca2+ channels localized in the carboxyl terminus of the 1C subunit. J Physiol 2000;529:119–130.

    Article  PubMed  Google Scholar 

  37. Belles B, Hescheler J, Trautwein W, Blomgren K, Karlsson JO. A possible physiological role of the Ca dependent protease calpain and its inhibitor calpastatin on the Ca current in guinea pig myocytes. Pflugers Arch 1988;412:554–556.

    Article  PubMed  Google Scholar 

  38. Moretti A, Weig HJ, Ott T, Seyfarth M, Holthoff HP, Grewe D, Gillitzer A, Bott-Flugel L, Schomig A, Ungerer M, Laugwitz KL. Essential myosin light chain as a target for caspase-3 in failing myocardium. Proc Natl Acad Sci USA 2002;99:11860–11865.

    Article  PubMed  Google Scholar 

  39. Communal C, Sumandea M, de Tombe P, Narula J, Solaro RJ, Hajjar RJ. Functional consequences of caspase activation in cardiac myocytes. Proc Natl Acad Sci USA 2002;99:6252–6256.

    Article  PubMed  Google Scholar 

  40. Brundel BJ, van Gelder IC, Henning RH, Tuinenburg AE, Deelman LE, Tieleman RG, Grandjean JG, van Gilst WH, Crijns HJ. Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation. Cardiovasc Res 1999;42:443–454.

    Article  PubMed  Google Scholar 

  41. Brundel BJ, Van Gelder IC, Henning RH, Tieleman RG, Tuinenburg AE, Wietses M, Grandjean JG, Van Gilst WH, Crijns HJ. Ion channel remodeling is related to intra-operative atrial refractory periods in patients with paroxysmal and persistent atrial fibrillation. Circulation 2001;103:684–690.

    PubMed  Google Scholar 

  42. Brundel BJ, Ausma J, van Gelder IC, Van der Want JJ, van Gilst WH, Crijns HJ, Henning RH. Activation of proteolysis by calpains and structural changes in human paroxysmal and persistent atrial fibrillation. Cardiovasc Res 2002;54:380–389.

    Article  PubMed  Google Scholar 

  43. Goette A, Arndt M, Rocken C, Staack T, Bechtloff R, Reinhold D, Huth C, Ansorge S, Klein HU, Lendeckel U. Calpains and cytokines in fibrillating human atria. Am J Physiol Heart Circ Physio 2002;283:H264–H272.

    Google Scholar 

  44. Ehrlich JR, Nattel S, Hohnloser SH. Atrial fibrillation and congestive heart failure:Specific considerations at the intersection of two common and important cardiac disease sets. J Cardiovasc Electrophysiol 2002;13:399–405.

    Article  PubMed  Google Scholar 

  45. Shinagawa K, Shi YF, Tardif JC, Leung TK, Nattel S. Dynamic nature of atrial fibrillation substrate during development and reversal of heart failure in dogs. Circulation 2002;105:2672–2678.

    Article  PubMed  Google Scholar 

  46. Cha TJ, Ehrlich JR, Zhang L, Shi YF, Tardif JC, Leung TK, Nattel S. Dissociation between ionic remodeling and ability to sustain atrial fibrillation during recovery from experimental congestive heart failure. Circulation 2004;109:412–418.

    Article  PubMed  Google Scholar 

  47. Nattel S, Li D, Yue L. Basic mechanisms of atrial fibrillation—very new insights into very old ideas. Annu Rev Physiol 2000;62:51–77.

    Article  PubMed  Google Scholar 

  48. Derakhchan K, Li D, Courtemanche M, Smith B, Brouillette J, Page PL, Nattel S. Method for simultaneous epicardial and endocardial mapping of in vivo canine heart:Application to atrial conduction properties and arrhythmia mechanisms. J Cardiovasc Electrophysiol 2001;12:548–555.

    Article  PubMed  Google Scholar 

  49. Stambler BS, Fenelon G, Shepard RK, Clemo HF, Guiraudon CM. Characterization of sustained atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure. J Cardiovasc Electrophysiol 2003;14:499–507.

    Article  PubMed  Google Scholar 

  50. Fenelon G, Shepard RK, Stambler BS. Focal origin of atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure. J Cardiovasc Electrophysiol 2003;14:1093–1102.

    Article  PubMed  Google Scholar 

  51. Li D, Melnyk P, Feng J, Wang Z, Petrecca K, Shrier A, Nattel S. Effects of experimental heart failure on atrial cellular and ionic electrophysiology. Circulation 2000;101:2631–2638.

    PubMed  Google Scholar 

  52. Li D, Shinagawa K, Pang L, Leung TK, Cardin S, Wang Z, Nattel S. 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;104:2608–2614.

    PubMed  Google Scholar 

  53. Cardin S, Li D, Thorin-Trescases N, Leung TK, Thorin E, Nattel S. Evolution of the atrial fibrillation substrate in experimental congestive heart failure:Angiotensin-dependent and -independent pathways. Cardiovasc Res 2003;60:315–325.

    Article  PubMed  Google Scholar 

  54. Kumagai K, Nakashima H, Urata H, Gondo N, Arakawa K, Saku K. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardio 2003;41:2197–2204.

    Article  Google Scholar 

  55. Hanna N, Cardin S, Leung TK, Nattel S. Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failure. Cardiovasc Res 2004;63:236–244.

    Article  PubMed  Google Scholar 

  56. Verheule S, Sato T, Everett T 4th, Engle SK, Otten D, Rubart-von der Lohe M, Nakajima HO, Nakajima H, Field LJ, Olgin JE. Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1. Circ Res 2004;94:1458–1465.

    Article  PubMed  Google Scholar 

  57. Boixel C, Fontaine V, Rucker-Martin C, Milliez P, Louedec L, Michel JB, Jacob MP, Hatem SN. Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat. J Am Coll Cardiol 2003;42:336–344.

    Article  PubMed  Google Scholar 

  58. Khan A, Moe GW, Nili N, Rezaei E, Eskandarian M, Butany J, Strauss BH. The cardiac atria are chambers of active remodeling and dynamic collagen turnover during evolving heart failure. J Am Coll Cardio 2004;43:68–76.

    Article  Google Scholar 

  59. Verheule S, Wilson E, Everett T 4th, Shanbhag S, Golden C, Olgin J. Alterations in atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation. Circulation 2003;107:2615–2622.

    PubMed  Google Scholar 

  60. Verheule S, Wilson E, Banthia S, Everett TH 4th, Shanbhag S, Sih HJ, Olgin J. Left atrial dilatation resulting from chronic mitral regurgitation decreases spatiotemporal organization of atrial fibrillation in left atrium. Am J Physiol Heart Circ Physiol 2004;286:H2452–H2460.

    Article  PubMed  Google Scholar 

  61. Neuberger HR, Schotten U, Verheule S, Eijsbouts S, Blaauw Y, van Hunnik A, Allessie M. Development of a substrate of atrial fibrillation during chronic atrioventricular block in the goat. Circulatio 2005;111:30–37.

    Article  Google Scholar 

  62. Skanes AC, Krahn AD, Yee R, Klein GJ, Connolly SJ, Kerr CR, Gent M, Thorpe KE, Roberts RS. Canadian Trial of Physiologic Pacing. Progression to chronic atrial fibrillation after pacing:The Canadian Trial of Physiologic Pacing. CTOPP Investigators. J Am Coll Cardiol 2001;38:167–172.

    Article  PubMed  Google Scholar 

  63. Deroubaix E, Folliguet T, Rucker-Martin C, Dinanian S, Boixel C, Validire P, Daniel P, Capderou A, Hatem SN. Moderate and chronic hemodynamic overload of sheep atria induces reversible cellular electrophysiologic abnormalities and atrial vulnerability. J Am Coll Cardiol 2004;44:1918–1926.

    Article  PubMed  Google Scholar 

  64. Nattel S. Basic electrophysiology of the pulmonary veins and their role in atrial fibrillation:Precipitators, perpetuators, and perplexers. J Cardiovasc Electrophysiol 2003;14:1372–1375.

    Article  PubMed  Google Scholar 

  65. Chen YJ, Chen SA, Chen YC, Yeh HI, Chang MS, Lin CI. Electrophysiology of single cardiomyocytes isolated from rabbit pulmonary veins:Implication in initiation of focal atrial fibrillation. Basic Res Cardiol 2002;97:26–34.

    Article  PubMed  Google Scholar 

  66. Chen YJ, Chen SA, Chen YC, Yeh HI, Chan P, Chang MS, Lin CI. Effects of rapid atrial pacing on the arrhythmogenic activity of single cardiomyocytes from pulmonary veins:Implication in initiation of atrial fibrillation. Circulation 2001;104:2849–2854.

    PubMed  Google Scholar 

  67. Chen YC, Chen SA, Chen YJ, Chang MS, Chan P, Lin CI. Effects of thyroid hormone on the arrhythmogenic activity of pulmonary vein cardiomyocytes. J Am Coll Cardiol 2002;39:366–372.

    Article  PubMed  Google Scholar 

  68. Hocini M, Ho SY, Kawara T, Linnenbank AC, Potse M, Shah D, Jais P, Janse MJ, Haissaguerre M, De Bakker JM. Electrical conduction in canine pulmonary veins:Electrophysiological and anatomic correlation. Circulation 2002;105:2442–2448.

    Article  PubMed  Google Scholar 

  69. Ehrlich JR, Cha TJ, Zhang L, Chartier D, Melnyk P, Hohnloser SH, Nattel S. Cellular electrophysiology of canine pulmonary vein cardiomyocytes:Action potential and ionic current properties. J Physio 2003;551:801–813.

    Article  Google Scholar 

  70. Wang TM, Chiang CE, Sheu JR, Tsou CH, Chang HM, Luk HN. Homogenous distribution of fast response action potentials in canine pulmonary vein sleeves:A contradictory report. Int J Cardio 2003;89:187–195.

    Google Scholar 

  71. Cha TJ, Ehrlich JR, Zhang L, Chartier D, Leung TK, Nattel S. Atrial tachycardia remodeling of pulmonary vein cardiomyocytes:Comparison with left atrium and potential relation to arrhythmogenesis. Circulation 2005;111:728–735.

    Article  PubMed  Google Scholar 

  72. Honjo H, Boyett MR, Niwa R, Inada S, Yamamoto M, Mitsui K, Horiuchi T, Shibata N, Kamiya K, Kodama I. Pacing-induced spontaneous activity in myocardial sleeves of pulmonary veins after treatment with ryanodine. Circulation 2003;107:1937–1943.

    Article  PubMed  Google Scholar 

  73. Hamabe A, Okuyama Y, Miyauchi Y, Zhou S, Pak HN, Karagueuzian HS, Fishbein MC, Chen PS. Correlation between anatomy and electrical activation in canine pulmonary veins. Circulatio 2003;107:1550–1555.

    Article  Google Scholar 

  74. Arora R, Verheule S, Scott L, Navarrete A, Katari V, Wilson E, Vaz D, Olgin JE. Arrhythmogenic substrate of the pulmonary veins assessed by high-resolution optical mapping. Circulatio 2003;107:1816–1821.

    Article  Google Scholar 

  75. Kalifa J, Jalife J, Zaitsev AV, Bagwe S, Warren M, Moreno J, Berenfeld O, Nattel S. Intra-atrial pressure increases rate and organization of waves emanating from the superior pulmonary veins during atrial fibrillation. Circulation 2003;108:668–671.

    Article  PubMed  Google Scholar 

  76. Kumagai K, Ogawa M, Noguchi H, Yasuda T, Nakashima H, Saku K. Electrophysiologic properties of pulmonary veins assessed using a multielectrode basket catheter. J Am Coll Cardiol 2004;43:2281–2289.

    Article  PubMed  Google Scholar 

  77. Okuyama Y, Miyauchi Y, Park AM, Hamabe A, Zhou S, Hayashi H, Miyauchi M, Omichi C, Pak HN, Brodsky LA, Mandel WJ, Fishbein MC, Karagueuzian HS, Chen PS. High resolution mapping of the pulmonary vein and the vein of Marshall during induced atrial fibrillation and atrial tachycardia in a canine model of pacing-induced congestive heart failure. J Am Coll Cardiol 2003;42:348–360.

    Article  PubMed  Google Scholar 

  78. Zhou S, Chang CM, Wu TJ, Miyauchi Y, Okuyama Y, Park AM, Hamabe A, Omichi C, Hayashi H, Brodsky LA, Mandel WJ, Ting CT, Fishbein MC, Karagueuzian HS, Chen PS. Nonreentrant focal activations in pulmonary veins in canine model of sustained atrial fibrillation. Am J Physiol Heart Circ Physio 2002;283:H1244–H1252.

    Google Scholar 

  79. Park AM, Chou CC, Drury PC, Okuyama Y, Peter A, Hamabe A, Miyauchi Y, Kass RM, Karagueuzian HS, Fishbein MC, Lin SF, Chen PS. Thoracic vein ablation terminates chronic atrial fibrillation in dogs. Am J Physiol Heart Circ Physiol 2004;286:H2072–H2077.

    Article  PubMed  Google Scholar 

  80. Tieleman RG, De Langen C, Van Gelder IC, de Kam PJ, Grandjean J, Bel KJ, Wijffels MC, Allessie MA, Crijns HJ. Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulatio 1997;95:1945–1953.

    Google Scholar 

  81. 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;49:762–770.

    Article  PubMed  Google Scholar 

  82. Lee SH, Yu WC, Cheng JJ, Hung CR, Ding YA, Chang MS, Chen SA. Effect of verapamil on long-term tachycardia-induced atrial electrical remodeling. Circulation 2000;101:200–206.

    PubMed  Google Scholar 

  83. Shinagawa K, Derakhchan K, Nattel S. Pharmacological prevention of atrial tachycardia induced atrial remodeling as a potential therapeutic strategy. Pacing Clin Electrophysiol 2003;6:752–764.

    Article  Google Scholar 

  84. Jayachandran JV, Zipes DP, Weksler J, Olgin JE. Role of the Na+/H+ exchanger in short-term atrial electrophysiological remodeling. Circulation 2000;101:1861–1866.

    PubMed  Google Scholar 

  85. Nakashima H, Kumagai K, Urata H, Gondo N, Ideishi M, Arakawa K. Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation 2000;101:2612–2617.

    PubMed  Google Scholar 

  86. Shinagawa K, Mitamura H, Ogawa S, Nattel S. Effects of inhibiting Na+/H+-exchange or angiotensin converting enzyme on atrial tachycardia-induced remodeling. Cardiovasc Res 2002;54:438-446.

    Article  PubMed  Google Scholar 

  87. Blaauw Y, Beier N, van der Voort P, van Hunnik A, Schotten U, Allessie MA. Inhibitors of the Na+/H+ exchanger cannot prevent atrial electrical remodeling in the goat. J Cardiovasc Electrophysio 2004;15:440–446.

    Article  Google Scholar 

  88. Fareh S, Benardeau A, Thibault B, Nattel S. The T-type Ca2+ channel blocker mibefradil prevents the development of a substrate for atrial fibrillation by tachycardia-induced atrial remodeling in dogs. Circulation 1999;100:2191–2197.

    PubMed  Google Scholar 

  89. Shinagawa K, Shiroshita-Takeshita A, Schram G, Nattel S. Effects of antiarrhythmic drugs on fibrillation in the remodeled atrium. Insight into the mechanisms of the superior efficacy of amiodarone. Circulation 2003;107:1440–1446.

    Article  PubMed  Google Scholar 

  90. Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, Kus T, Lambert J, Dubuc M, Gagne P, Nattel S, Thibault B. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med 2000;342:913–920.

    Article  PubMed  Google Scholar 

  91. Mihm MJ, Yu F, Carnes CA, Reiser PJ, McCarthy PM, Van Wagoner DR, Bauer JA. Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 2001;104:174–180.

    PubMed  Google Scholar 

  92. Carnes CA, Chung MK, Nakayama T, Nakayama H, Baliga RS, Piao S, Kanderian A, Pavia S, Hamlin RL, McCarthy PM, Bauer JA, Van Wagoner DR. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Re 2001;89:e32–38.

    Google Scholar 

  93. Shiroshita-Takeshita A, Schram G, Lavoie J, Nattel S. Effect of simvastatin and antioxidant viamins on atrial fibrillation promotion by atrial-tachycardia remodeling in dogs. Circulatio 2004;110:2313–2319.

    Article  Google Scholar 

  94. Shiroshita-Takeshita A, Shi YF, Beatch G, Ezrin A, Tardif J-C, Nattel S. Differential efficacy of drugs with antioxidant properties on atrial fibrillation promotion by atrial tachycardia remodeling in dogs. Circulation 2003;108:(suppl IV):IV–148 (abstr).

    Google Scholar 

  95. Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A, Carnes CA, Bauer JA, Tchou PJ, Niebauer MJ, Natale A, Van Wagoner DR. C-reactive protein elevation in patients with atrial arrhythmias. Inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001;104:2886–2891.

    PubMed  Google Scholar 

  96. Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA, Tracy RP, Van Wagoner DR, Psaty BM, Lauer MS, Chung MK. Inflammation as a risk factor for atrial fibrillation. Circulation 2003;108:3006–3010.

    Article  PubMed  Google Scholar 

  97. Shiroshita-Takeshita A, Nattel S. Pharmacological prevention of AF promotion by atrial tachycardia-inducedc remodeling in dogs. Circulation 2004;110(suppl III):III–163 (abstr).

    Article  Google Scholar 

  98. Dernellis J, Panaretou M. Relationship between C-reactive protein concentration during glucocorticoid therapy and recurrent atrial fibrillation. Eur Heart J 2004;25:1100–1107.

    Article  PubMed  Google Scholar 

  99. Siu CW, Lau CP, Tse HF. Prevention of atrial fibrillation recurrence by statin therapy in patients with lone atrial fibrillation after successful cardioversion. Am J Cardiol 2003;92:1343–1345.

    Article  PubMed  Google Scholar 

  100. Young-Xu Y, Jabbour S, Goldberg R, Blatt CM, Graboys T, Bilchik B, Ravid S. Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease. Am J Cardio 2003;92:1379–1383.

    Article  Google Scholar 

  101. Tveit A, Grundtvig M, Gundersen T, Vanberg P, Semb AG, Holt E, Gullestad L. Analysis of pravastatin to prevent recurrence of atrial fibrillation after electrical cardioversion. Am J Cardio 2004;93:780–782.

    Article  Google Scholar 

  102. Pedersen OD, Bagger H, Kober L, Torp-Pedersen C. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 1999;100:376–380.

    PubMed  Google Scholar 

  103. Vermes E, Tardif JC, Bourassa MG, Racine N, Levesque S, White M, Guerra PG, Ducharme A. Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction:Insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials. Circulation 2003;107:2926–2931.

    Article  PubMed  Google Scholar 

  104. L'Allier PL, Ducharme A, Keller PF, Yu H, Guertin MC, Tardif JC. Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurrence of atrial fibrillation. J Am Coll Cardiol 2004;44:159–164.

    Article  PubMed  Google Scholar 

  105. Wachtell K, Lehto M, Gerdts E, Olsen MH, Hornestam B, Dahlof B, Ibsen H, Julius S, Kjeldsen SE, Lindholm LH, Nieminen MS, Devereux RB. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol:The Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol 2005;45:712–719.

    Article  PubMed  Google Scholar 

  106. Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, Rodriguez A, Cano L, Cano JM, Cabeza P, Moro C. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation:A prospective and randomized study. Circulation 2002;106:331–336.

    Article  PubMed  Google Scholar 

  107. Ueng KC, Tsai TP, Yu WC, Tsai CF, Lin MC, Chan KC, Chen CY, Wu DJ, Lin CS, Chen SA. Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation. Results of a prospective and controlled study. Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation. Results of a prospective and controlled study. Eur Heart J 2003;24:2090–2098.

    Article  PubMed  Google Scholar 

  108. Viko EL, Marvin HM, White PD. A clinical report on the use of quinidine sulphate. Arch Int Me 1923;31:345–363.

    Google Scholar 

  109. Courtemanche M, Ramirez RJ, Nattel S. Ionic targets for drug therapy and atrial fibrillation-induced electrical remodeling:Insights from a mathematical model. Cardiovasc Res 1999;42:477–489.

    Article  PubMed  Google Scholar 

  110. Li D, Benardeau A, Nattel S. Contrasting efficacy of dofetilide in differing experimental models of atrial fibrillation. Circulation 2000;102:104–112.

    PubMed  Google Scholar 

  111. Blaauw Y, Gogelein H, Tieleman RG, van Hunnik A, Schotten U, Allessie MA. “Early” class III drugs for the treatment of atrial fibrillation:Efficacy and atrial selectivity of AVE0118 in remodeled atria of the goat. Circulation 2004;110:1717–1724.

    Article  PubMed  Google Scholar 

  112. Tieleman RG, Van Gelder IC, Bosker HA, Kingma T, Wilde AA, Kirchhof CJ, Bennekers JH, Bracke FA, Veeger NJ, Haaksma J, Allessie MA, Crijns HJ. Does flecainide regain its antiarrhythmic activity after electrical cardioversion of persistent atrial fibrillation? Heart Rhythm 2005;2:223–230.

    Article  PubMed  Google Scholar 

  113. Wolf L. Familial auricular fibrillation. N Engl J Med 1943;229:396–397.

    Google Scholar 

  114. Brugada R, Tapscott T, Czernuszewicz GZ, Marian AJ, Iglesias A, Mont L, Brugada J, Girona J, Domingo A, Bachinski LL, Roberts R. Identification of a genetic locus for familial atrial fibrillation. N Engl J Med 1997;336:905–911.

    Article  PubMed  Google Scholar 

  115. Chen YH, Xu SJ, Bendahhou S, Wang XL, Wang Y, Xu WY, Jin HW, Sun H, Su XY, Zhuang QN, Yang YQ, Li YB, Liu Y, Xu HJ, Li XF, Ma N, Mou CP, Chen Z, Barhanin J, Huang W. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 2003;299:251–254.

    Article  PubMed  MathSciNet  Google Scholar 

  116. Yang Y, Xia M, Jin Q, Bendahhou S, Shi J, Chen Y, Liang B, Lin J, Liu Y, Liu B, Zhou Q, Zhang D, Wang R, Ma N, Su X, Niu K, Pei Y, Xu W, Chen Z, Wan H, Cui J, Barhanin J, Chen Y. Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am J Hum Gene 2004;75:899–905.

    Article  Google Scholar 

  117. Brugada R, Hong K, Dumaine R, Cordeiro J, Gaita F, Borggrefe M, Menendez TM, Brugada J, Pollevick GD, Wolpert C, Burashnikov E, Matsuo K, Wu YS, Guerchicoff A, Bianchi F, Giustetto C, Schimpf R, Brugada P, Antzelevitch C. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 2004;109:30–35.

    Article  PubMed  Google Scholar 

  118. Fox CS, Parise H, D'Agostino RB Sr, Lloyd-Jones DM, Vasan RS, Wang TJ, Levy D, Wolf PA, Benjamin EJ. Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring. JAM 2004;291:2851–2855.

    Article  Google Scholar 

  119. Firouzi M, Ramanna H, Kok B, Jongsma HJ, Koeleman BP, Doevendans PA, Groenewegen WA, Hauer RN. Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation. Circ Res 2004;95:e29–e33.

    Article  PubMed  Google Scholar 

  120. Hagendorff A, Schumacher B, Kirchhoff S, Luderitz B, Willecke K. Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation. Circulation 1999;99:1508–1515.

    PubMed  Google Scholar 

  121. Lai LP, Su MJ, Yeh HM, Lin JL, Chiang FT, Hwang JJ, Hsu KL, Tseng CD, Lien WP, Tseng YZ, Huang SK. Association of the human minK gene 38G allele with atrial fibrillation:Evidence of possible genetic control on the pathogenesis of atrial fibrillation. Am Heart J 2002;144:485–490.

    Article  PubMed  Google Scholar 

  122. Ehrlich JR, Zicha S, Coutu P, Hébert TE, Nattel S. Effects of the atrial fibrillation-associated MinK38G/S polymorphism on co-expressed delayed rectifier current and membrane localization. Cardiovasc Res (in press).

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stanley Nattel MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shiroshita-Takeshita, A., Brundel, B.J.J.M. & Nattel, S. Atrial Fibrillation: Basic Mechanisms, Remodeling and Triggers. J Interv Card Electrophysiol 13, 181–193 (2005). https://doi.org/10.1007/s10840-005-2362-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10840-005-2362-y

Keywords

Navigation