3167
J Physiol 592.15 (2014) pp 3167–3170
C R O S S TA L K
CrossTalk opposing view: Rotors have not been demonstrated to be the drivers of atrial fibrillation Maurits Allessie1 and Natasja de Groot2 Department of Physiology, University of Maastricht, The Netherlands 2 Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
1
mapped by two basket catheters, Narayan et al. (2012a,b,c, 2013) postulated that human AF is due to the presence of a stable rotor that serves as a ‘driver’ to sustain AF. Ablation of the centre of these rotors abruptly terminated or consistently slowed AF in the vast majority of cases, and substantially improved long-term freedom from AF compared to conventional ablation alone (Narayan et al. 2012b).
The Journal of Physiology
Email: [email protected]
Despite extensive research, it is still not clear how atrial fibrillation (AF) perpetuates itself. Experimental studies have shown that various mechanisms may sustain this ‘eternal’ arrhythmia (Lewis et al. 1921; Moe & Abildskov, 1959; Moe, 1962; Allessie et al. 1977, 1985; Konings et al. 1994; Mandapati et al. 2000; Jalife et al. 2002; Waldo, 2003). Roughly, they can be divided into focal (repetitive ectopic discharges) and reentrant mechanisms (mother-wave, rotor, multiple wavelets). Recently, we introduced a third mechanism, independent of focal or reentrant activity (the double layer hypothesis; Allessie et al. 2010; de Groot et al. 2010; Eckstein et al. 2011). Using high-resolution optical mapping in isolated sheep hearts subjected to high concentrations of acetylcholine, Jalife and co-workers clearly demonstrated that pacing-induced AF was due to the presence of a very rapid rotor (15–20 Hz) in the left atrium (Mandapati et al. 2000; Jalife et al. 2002). However, although it is unquestionable that under experimental conditions a single rapid rotor can serve as a ‘driver’ of AF, the question still remains whether this is also the operative mechanism in patients with longlasting persistent AF. Based on a series of clinical studies, in which the electrical activity of the atria was
High-density versus ‘panoramic’ mapping of AF High resolution mapping of AF has been performed in patients during open-chest surgery, by positioning a regular array of 128–256 electrodes (spatial resolution 10 min (equating to thousands of cycles)’ (Narayan et al. 2012b), in none of their studies do they actually show that the maps were reproducible over a prolonged period of time. No regular and monomorphic electrograms. Given the large size of the rotors
(in the latest two examples they occupied the whole posterior or anterior wall of the left atrium; Narayan et al. 2013), even in the case of some spatial precession, one would expect predominantly regular and monomorphic electrograms in the area of stable repetitive circular activation. However all recordings from the rotor area presented in the publications of Narayan et al. are highly irregular and polymorphic (Narayan et al. 2012a,b,c, 2013). Without electrograms a rotor is not a rotor. Only a few electrograms are given
Figure 1. Endo-epicardial breakthroughs recorded by high-resolution mapping of acutely induced human AF A flexible rectangular array of 8 × 16 electrodes was positioned consecutively on different parts of the atria (10 s recordings). Breakthroughs occurred at multiple sites distributed over the entire epicardial surface of the left and right atrium. The diagram at the bottom illustrates how endo-epicardial breakthrough sites may serve as sources of ‘new’ fibrillation waves (modified from de Groot et al. 2010).
to support the presence of a rotor and in no case were local activation times assigned to them. Many electrograms are of poor quality and represent either far-field or injury potentials (Fig. 1 of Narayan et al. 2012b). In the most recent publication, only two or three bipolar electrograms at the rotor path were given (Narayan et al. 2013). Magnification of these electrograms reveals that the two
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
CrossTalk
J Physiol 592.15
electrograms recorded from opposite limbs of a rotor in the anterior wall of the left atrium (LA) (their Fig. 2; A54 and H65) were not in anti-phase, whereas the three electrograms along a rotor in the posterior LA (their Fig. 3; D45, F45 and E12) did not bear any fixed time relationships. Thus, in none of the maps of the publications of Narayan et al. (2012a,b,c, 2013) are the pathways of repetitive circular activation documented by a sufficient number of electrograms recorded around the rotor path. Clinical efficacy of rotor ablation? In the absence of convincing evidence that human AF is driven by a single rotor, it is puzzling how we should interpret the CONFIRM study, in which ‘rotor ablation’ almost doubled the long-term success rate of AF-ablation (Narayan et al. 2012b). In itself, this observation does not prove that human AF is driven by a single rapid source, and the reported clinical success needs to be confirmed by other centres, especially in patients with longstanding persistent AF. It also remains to be seen to what extent body surface mapping might improve the long-term efficacy of AF-ablation (Haissaguerre et al. 2013).
Conclusion At present, the mechanisms responsible for perpetuation of human AF remain unclear. Low-resolution mapping studies claiming that a stable rotor is the main ‘driving force’ behind AF need to be validated by high-resolution mapping. On the other hand, the hypothesis that the substrate of AF is primarily based on endo-epicardial dissociation requires additional proof by simultaneous endo-epicardial mapping in patients with AF. Understanding the mechanisms operative in the perpetuation of human AF is essential for the development of more effective strategies to modify the substrate of AF in order to restore and maintain sinus rhythm (Allessie & de Groot, 2013). Call for comments Readers are invited to give their views on this and the accompanying CrossTalk articles in this issue by submitting a brief comment. Comments may be posted up to 6 weeks after publication of the article, at which point the discussion will close and authors will be invited to submit a ‘final word’. To submit a comment, go to
http://jp.physoc.org/letters/submit/jphysiol; 592/15/3167
References Allessie MA, Bonke FIM & Schopman FJG (1977). Circus movement in rabbit atrial muscle as a mechanism of tachycardia. III. The ‘leading circle’ concept: a new model of circus movement in cardiac tissue without the involvement of an anatomic obstacle. Circ Res 41, 9–18. Allessie MA & de Groot NMS (2013). Wave-mapping as a guide for ablation of atrial fibrillation: a daydream? Circ Arrhythm Electrophysiol 6, 1056–1058. Allessie MA & de Groot NMS (2014). Rotors during AF: drivers or bystanders? Eur Heart J 35, 63–65. Allessie MA, de Groot NMS, Houben RPM, Schotten U, Boersma E, Smeets JL & Crijns HJ (2010). Electropathological substrate of long-standing persistent atrial fibrillation in patients with structural heart disease: longitudinal dissociation. Circ Arrhythm Electrophysiol 3, 606–615. Allessie MA, Lammers WJEP, Bonke FIM & Hollen SJ (1985). Experimental evaluation of Moe’s multiple wavelet hypothesis of atrial fibrillation. In Cardiac Arrhythmias, 1st edn, ed. Zipes DP & Jalife J, pp 265–276. Grune & Stratton. Cox JL, Canavan TE, Schuessler RB, Cain ME, Lindsay BD, Stone C, Smith PK, Corr PB & Boineau JP (1991). The surgical treatment of atrial fibrillation. II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. J Thorac Cardiovasc Surg 101, 406–426. Cuculich PS, Wang Y, Lindsay BD, Faddis MN, Schuessler RB, Damiano RJ Jr, Li L & Rudy Y (2010). Noninvasive characterization of epicardial activation in humans with diverse atrial fibrillation patterns. Circulation 122, 1364–1372. de Groot NMS, Houben RPM, Smeets JL, Boersma E, Schotten U, Schalij MJ, Crijns H & Allessie MA (2010). Electropathological substrate of longstanding persistent atrial fibrillation in patients with structural heart disease: epicardial breakthrough. Circulation 122, 1674–1682. Eckstein J, Maesen B, Linz D, Zeemering S, van Hunnik A, Verheule S, Allessie M & Schotten U (2011). Time course and mechanisms of endo-epicardial electrical dissociation during atrial fibrillation in the goat. Cardiovasc Res 89, 816–824. Gerstenfeld EP, Sahakian AV & Swiryn S (1992). Evidence for transient linking of atrial excitation during atrial fibrillation in humans. Circulation 86, 375–382.
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
3169 Haissaguerre M, Hocini M, Shah AJ, Derval N, Sacher F, Jais P & Dubois R (2013). Noninvasive panoramic mapping of human atrial fibrillation mechanism: A feasibility report. J Cardiovasc Electrophysiol 24, 711–717. Harada A, Sasaki K, Fukushima T, Ikeshita M, Asano T, Yamauchi S, Tanaka S & Shoji T (1996). Atrial activation during chronic atrial fibrillation in patients with isolated mitral valve disease. Ann Thorac Surg 61, 104–111. Holm M, Johansson R, Brandt J, Luhrs C & Olsson SB (1997). Epicardial right atrial free wall mapping in chronic atrial fibrillation. Documentation of repetitive activation with a focal spread–a hitherto unrecognised phenomenon in man. Eur Heart J 18, 290–310. Jalife J, Berenfeld O & Mansour M (2002). Mother rotors and fibrillatory conduction: a mechanism of atrial fibrillation. Cardiovasc Res 54, 204–216. Kanagaratnam P, Cherian A, Stanbridge RD, Glenville B, Severs NJ & Peters NS (2004). Relationship between connexins and atrial activation during human atrial fibrillation. J Cardiovasc Electrophysiol 15, 206–216. Konings KT, Kirchhof CJ, Smeets JR, Wellens HJ, Penn OC & Allessie MA (1994). High-density mapping of electrically induced atrial fibrillation in humans. Circulation 89, 1665–1680. Lee G, Kumar S, Teh A, Madry A, Larobina M, Goldblatt J, Brown R, Atkinson V, Moten S, Morton JB, Sanders P, Kistler PM & Kalman J (2014). Epicardial wave mapping in human long-lasting persistent atrial fibrillation: transient rotational circuits, complex wave fronts and disorganized activity. Eur Heart J 35, 86–97. Lewis T, Drury AN & Iliescu CC (1921). A demonstration of circus movement in clinical fibrillation of the auricles. Heart 8, 361–379. Mandapati R, Skanes A, Chen J, Berenfeld O & Jalife J (2000). Stable micro-reentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. Circulation 101, 194–199. Moe GK (1962). On the multiple wavelet hypothesis of atrial fibrillation. Arch Int Pharmacodyn Ther 140, 183–188. Moe GK & Abildskov JA (1959). Atrial fibrillation as a self-sustaining arrhythmia independent of focal discharge. Am Heart J 58, 59–70. Narayan SM, Krummen DE & Rappel WJ (2012a). Clinical mapping approach to diagnose electrical rotors and focal impulse sources for human atrial fibrillation. J Cardiovasc Electrophysiol 23, 447–454.
3170 Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ & Miller JM (2012b). Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (conventional ablation for atrial fibrillation with or without focal impulse and rotor modulation) trial. J Am Coll Cardiol 60, 628–636. Narayan SM, Patel J, Mulpuru S & Krummen DE (2012c). Focal impulse and rotor modulation ablation of sustaining rotors abruptly terminates persistent atrial fibrillation to sinus rhythm with elimination on follow-up: a video case study. Heart Rhythm 9, 1436–1439. Narayan SM, Shivkumar K, Krummen DE, Miller JM & Rappel WJ (2013). Panoramic electrophysiological mapping but not electrogram morphology identifies stable sources for human atrial fibrillation. Stable atrial fibrillation rotors and focal sources relate poorly to fractionated electrograms. Circ Arrhythm Electrophysiol 6, 58–67.
CrossTalk Sahadevan J, Ryu K, Peltz L, Khrestian CM, Stewart RW, Markowitz AH & Waldo AL (2004). Epicardial mapping of chronic atrial fibrillation in patients: preliminary observations. Circulation 110, 3293–3299. Waldo AL (2003). Mechanisms of atrial fibrillation. J Cardiovasc Electrophysiol 14, S267–S274 Wu TJ, Doshi RN, Huang HLA, Blanche C, Kass RM, Trento A, Cheng W, Karagueuzian HS, Peter CT & Chen PS (2002). Simultaneous biatrial computerized mapping during permanent atrial fibrillation in patients with organic heart disease. J Cardiovasc Electrophysiol 13, 571–577.
J Physiol 592.15
Yaksh A, Kik C, Knops P, Roos-Hesselink JW, Bogers AJJC, Zijlstra F, Allessie MA, de Groot NMS. Atrial Fibrillation: to Map or Not to Map? Neth Heart J 2013; Oct 16 [Epub ahead of print; doi: 10.1007/s12471-013-0481-0].
Additional information
Competing interests None declared.
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
J Physiol 592.15 (2014) pp 3167–3170
C R O S S TA L K
CrossTalk opposing view: Rotors have not been demonstrated to be the drivers of atrial fibrillation Maurits Allessie1 and Natasja de Groot2 Department of Physiology, University of Maastricht, The Netherlands 2 Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
1
mapped by two basket catheters, Narayan et al. (2012a,b,c, 2013) postulated that human AF is due to the presence of a stable rotor that serves as a ‘driver’ to sustain AF. Ablation of the centre of these rotors abruptly terminated or consistently slowed AF in the vast majority of cases, and substantially improved long-term freedom from AF compared to conventional ablation alone (Narayan et al. 2012b).
The Journal of Physiology
Email: [email protected]
Despite extensive research, it is still not clear how atrial fibrillation (AF) perpetuates itself. Experimental studies have shown that various mechanisms may sustain this ‘eternal’ arrhythmia (Lewis et al. 1921; Moe & Abildskov, 1959; Moe, 1962; Allessie et al. 1977, 1985; Konings et al. 1994; Mandapati et al. 2000; Jalife et al. 2002; Waldo, 2003). Roughly, they can be divided into focal (repetitive ectopic discharges) and reentrant mechanisms (mother-wave, rotor, multiple wavelets). Recently, we introduced a third mechanism, independent of focal or reentrant activity (the double layer hypothesis; Allessie et al. 2010; de Groot et al. 2010; Eckstein et al. 2011). Using high-resolution optical mapping in isolated sheep hearts subjected to high concentrations of acetylcholine, Jalife and co-workers clearly demonstrated that pacing-induced AF was due to the presence of a very rapid rotor (15–20 Hz) in the left atrium (Mandapati et al. 2000; Jalife et al. 2002). However, although it is unquestionable that under experimental conditions a single rapid rotor can serve as a ‘driver’ of AF, the question still remains whether this is also the operative mechanism in patients with longlasting persistent AF. Based on a series of clinical studies, in which the electrical activity of the atria was
High-density versus ‘panoramic’ mapping of AF High resolution mapping of AF has been performed in patients during open-chest surgery, by positioning a regular array of 128–256 electrodes (spatial resolution 10 min (equating to thousands of cycles)’ (Narayan et al. 2012b), in none of their studies do they actually show that the maps were reproducible over a prolonged period of time. No regular and monomorphic electrograms. Given the large size of the rotors
(in the latest two examples they occupied the whole posterior or anterior wall of the left atrium; Narayan et al. 2013), even in the case of some spatial precession, one would expect predominantly regular and monomorphic electrograms in the area of stable repetitive circular activation. However all recordings from the rotor area presented in the publications of Narayan et al. are highly irregular and polymorphic (Narayan et al. 2012a,b,c, 2013). Without electrograms a rotor is not a rotor. Only a few electrograms are given
Figure 1. Endo-epicardial breakthroughs recorded by high-resolution mapping of acutely induced human AF A flexible rectangular array of 8 × 16 electrodes was positioned consecutively on different parts of the atria (10 s recordings). Breakthroughs occurred at multiple sites distributed over the entire epicardial surface of the left and right atrium. The diagram at the bottom illustrates how endo-epicardial breakthrough sites may serve as sources of ‘new’ fibrillation waves (modified from de Groot et al. 2010).
to support the presence of a rotor and in no case were local activation times assigned to them. Many electrograms are of poor quality and represent either far-field or injury potentials (Fig. 1 of Narayan et al. 2012b). In the most recent publication, only two or three bipolar electrograms at the rotor path were given (Narayan et al. 2013). Magnification of these electrograms reveals that the two
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
CrossTalk
J Physiol 592.15
electrograms recorded from opposite limbs of a rotor in the anterior wall of the left atrium (LA) (their Fig. 2; A54 and H65) were not in anti-phase, whereas the three electrograms along a rotor in the posterior LA (their Fig. 3; D45, F45 and E12) did not bear any fixed time relationships. Thus, in none of the maps of the publications of Narayan et al. (2012a,b,c, 2013) are the pathways of repetitive circular activation documented by a sufficient number of electrograms recorded around the rotor path. Clinical efficacy of rotor ablation? In the absence of convincing evidence that human AF is driven by a single rotor, it is puzzling how we should interpret the CONFIRM study, in which ‘rotor ablation’ almost doubled the long-term success rate of AF-ablation (Narayan et al. 2012b). In itself, this observation does not prove that human AF is driven by a single rapid source, and the reported clinical success needs to be confirmed by other centres, especially in patients with longstanding persistent AF. It also remains to be seen to what extent body surface mapping might improve the long-term efficacy of AF-ablation (Haissaguerre et al. 2013).
Conclusion At present, the mechanisms responsible for perpetuation of human AF remain unclear. Low-resolution mapping studies claiming that a stable rotor is the main ‘driving force’ behind AF need to be validated by high-resolution mapping. On the other hand, the hypothesis that the substrate of AF is primarily based on endo-epicardial dissociation requires additional proof by simultaneous endo-epicardial mapping in patients with AF. Understanding the mechanisms operative in the perpetuation of human AF is essential for the development of more effective strategies to modify the substrate of AF in order to restore and maintain sinus rhythm (Allessie & de Groot, 2013). Call for comments Readers are invited to give their views on this and the accompanying CrossTalk articles in this issue by submitting a brief comment. Comments may be posted up to 6 weeks after publication of the article, at which point the discussion will close and authors will be invited to submit a ‘final word’. To submit a comment, go to
http://jp.physoc.org/letters/submit/jphysiol; 592/15/3167
References Allessie MA, Bonke FIM & Schopman FJG (1977). Circus movement in rabbit atrial muscle as a mechanism of tachycardia. III. The ‘leading circle’ concept: a new model of circus movement in cardiac tissue without the involvement of an anatomic obstacle. Circ Res 41, 9–18. Allessie MA & de Groot NMS (2013). Wave-mapping as a guide for ablation of atrial fibrillation: a daydream? Circ Arrhythm Electrophysiol 6, 1056–1058. Allessie MA & de Groot NMS (2014). Rotors during AF: drivers or bystanders? Eur Heart J 35, 63–65. Allessie MA, de Groot NMS, Houben RPM, Schotten U, Boersma E, Smeets JL & Crijns HJ (2010). Electropathological substrate of long-standing persistent atrial fibrillation in patients with structural heart disease: longitudinal dissociation. Circ Arrhythm Electrophysiol 3, 606–615. Allessie MA, Lammers WJEP, Bonke FIM & Hollen SJ (1985). Experimental evaluation of Moe’s multiple wavelet hypothesis of atrial fibrillation. In Cardiac Arrhythmias, 1st edn, ed. Zipes DP & Jalife J, pp 265–276. Grune & Stratton. Cox JL, Canavan TE, Schuessler RB, Cain ME, Lindsay BD, Stone C, Smith PK, Corr PB & Boineau JP (1991). The surgical treatment of atrial fibrillation. II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. J Thorac Cardiovasc Surg 101, 406–426. Cuculich PS, Wang Y, Lindsay BD, Faddis MN, Schuessler RB, Damiano RJ Jr, Li L & Rudy Y (2010). Noninvasive characterization of epicardial activation in humans with diverse atrial fibrillation patterns. Circulation 122, 1364–1372. de Groot NMS, Houben RPM, Smeets JL, Boersma E, Schotten U, Schalij MJ, Crijns H & Allessie MA (2010). Electropathological substrate of longstanding persistent atrial fibrillation in patients with structural heart disease: epicardial breakthrough. Circulation 122, 1674–1682. Eckstein J, Maesen B, Linz D, Zeemering S, van Hunnik A, Verheule S, Allessie M & Schotten U (2011). Time course and mechanisms of endo-epicardial electrical dissociation during atrial fibrillation in the goat. Cardiovasc Res 89, 816–824. Gerstenfeld EP, Sahakian AV & Swiryn S (1992). Evidence for transient linking of atrial excitation during atrial fibrillation in humans. Circulation 86, 375–382.
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
3169 Haissaguerre M, Hocini M, Shah AJ, Derval N, Sacher F, Jais P & Dubois R (2013). Noninvasive panoramic mapping of human atrial fibrillation mechanism: A feasibility report. J Cardiovasc Electrophysiol 24, 711–717. Harada A, Sasaki K, Fukushima T, Ikeshita M, Asano T, Yamauchi S, Tanaka S & Shoji T (1996). Atrial activation during chronic atrial fibrillation in patients with isolated mitral valve disease. Ann Thorac Surg 61, 104–111. Holm M, Johansson R, Brandt J, Luhrs C & Olsson SB (1997). Epicardial right atrial free wall mapping in chronic atrial fibrillation. Documentation of repetitive activation with a focal spread–a hitherto unrecognised phenomenon in man. Eur Heart J 18, 290–310. Jalife J, Berenfeld O & Mansour M (2002). Mother rotors and fibrillatory conduction: a mechanism of atrial fibrillation. Cardiovasc Res 54, 204–216. Kanagaratnam P, Cherian A, Stanbridge RD, Glenville B, Severs NJ & Peters NS (2004). Relationship between connexins and atrial activation during human atrial fibrillation. J Cardiovasc Electrophysiol 15, 206–216. Konings KT, Kirchhof CJ, Smeets JR, Wellens HJ, Penn OC & Allessie MA (1994). High-density mapping of electrically induced atrial fibrillation in humans. Circulation 89, 1665–1680. Lee G, Kumar S, Teh A, Madry A, Larobina M, Goldblatt J, Brown R, Atkinson V, Moten S, Morton JB, Sanders P, Kistler PM & Kalman J (2014). Epicardial wave mapping in human long-lasting persistent atrial fibrillation: transient rotational circuits, complex wave fronts and disorganized activity. Eur Heart J 35, 86–97. Lewis T, Drury AN & Iliescu CC (1921). A demonstration of circus movement in clinical fibrillation of the auricles. Heart 8, 361–379. Mandapati R, Skanes A, Chen J, Berenfeld O & Jalife J (2000). Stable micro-reentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. Circulation 101, 194–199. Moe GK (1962). On the multiple wavelet hypothesis of atrial fibrillation. Arch Int Pharmacodyn Ther 140, 183–188. Moe GK & Abildskov JA (1959). Atrial fibrillation as a self-sustaining arrhythmia independent of focal discharge. Am Heart J 58, 59–70. Narayan SM, Krummen DE & Rappel WJ (2012a). Clinical mapping approach to diagnose electrical rotors and focal impulse sources for human atrial fibrillation. J Cardiovasc Electrophysiol 23, 447–454.
3170 Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ & Miller JM (2012b). Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (conventional ablation for atrial fibrillation with or without focal impulse and rotor modulation) trial. J Am Coll Cardiol 60, 628–636. Narayan SM, Patel J, Mulpuru S & Krummen DE (2012c). Focal impulse and rotor modulation ablation of sustaining rotors abruptly terminates persistent atrial fibrillation to sinus rhythm with elimination on follow-up: a video case study. Heart Rhythm 9, 1436–1439. Narayan SM, Shivkumar K, Krummen DE, Miller JM & Rappel WJ (2013). Panoramic electrophysiological mapping but not electrogram morphology identifies stable sources for human atrial fibrillation. Stable atrial fibrillation rotors and focal sources relate poorly to fractionated electrograms. Circ Arrhythm Electrophysiol 6, 58–67.
CrossTalk Sahadevan J, Ryu K, Peltz L, Khrestian CM, Stewart RW, Markowitz AH & Waldo AL (2004). Epicardial mapping of chronic atrial fibrillation in patients: preliminary observations. Circulation 110, 3293–3299. Waldo AL (2003). Mechanisms of atrial fibrillation. J Cardiovasc Electrophysiol 14, S267–S274 Wu TJ, Doshi RN, Huang HLA, Blanche C, Kass RM, Trento A, Cheng W, Karagueuzian HS, Peter CT & Chen PS (2002). Simultaneous biatrial computerized mapping during permanent atrial fibrillation in patients with organic heart disease. J Cardiovasc Electrophysiol 13, 571–577.
J Physiol 592.15
Yaksh A, Kik C, Knops P, Roos-Hesselink JW, Bogers AJJC, Zijlstra F, Allessie MA, de Groot NMS. Atrial Fibrillation: to Map or Not to Map? Neth Heart J 2013; Oct 16 [Epub ahead of print; doi: 10.1007/s12471-013-0481-0].
Additional information
Competing interests None declared.
C 2014 The Authors. The Journal of Physiology C 2014 The Physiological Society
