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Current Cardiology Reports

, 16:509 | Cite as

Rotors as Drivers of Atrial Fibrillation and Targets for Ablation

  • Amir A. Schricker
  • Gautam G. Lalani
  • David E. Krummen
  • Sanjiv M. Narayan
Invasive Electrophysiology and Pacing (EK Heist, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Invasive Electrophysiology and Pacing

Abstract

Atrial fibrillation (AF) is the most common arrhythmia targeted by catheter ablation. Despite significant advances in our understanding of AF, ablation outcomes remain suboptimal, and this is due in large part to an incomplete understanding of the underlying sustaining mechanisms of AF. Recent developments of patient-tailored and physiology-based computational mapping systems have identified localized electrical spiral waves, or rotors, and focal sources as mechanisms that may represent novel targets for therapy. This report provides an overview of Focal Impulse and Rotor Modulation (FIRM) mapping, which reveals that human AF is often not actually driven by disorganized activity but instead that disorganization is secondary to organized rotors or focal sources. Targeted ablation of such sources alone can eliminate AF and, when added to pulmonary vein isolation, improves long-term outcome compared with conventional ablation alone. Translating mechanistic insights from such patient-tailored mapping is likely to be crucial in achieving the next major advances in personalized medicine for AF.

Keywords

Atrial fibrillation Ablation Focal sources Rotors Substrate Trigger 

Notes

Acknowledgments

This work was supported by grants to S. Narayan from the NIH (HL70529, HL83359, HL103800) and the Doris Duke Charitable Foundation.

Compliance with Ethics Guidelines

Conflict of Interest

Amir A. Schricker and Gautam G. Lalani declare that they have no conflict of interest.

David E. Krummen has received fellowship support from Biosense-Webster, Biotronik, Medtronic, and St. Jude Medical and consultant’s fees from Boston Scientific. Sanjiv Narayan is co-author of intellectual property owned by the University of California Regents and licensed to Topera Inc. Topera does not sponsor any research, including that presented here. S. Narayan holds equity in Topera; has received honoraria and fellowship support from Biotronik, Medtronic, and St. Jude Medical; has received consultant’s fees from the American College of Cardiology and Elsevier; and has received royalties from UpToDate.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Van Gelder IC, Groenveld HF, Crijns HJ, et al. Lenient vs strict rate control in patients with atrial fibrillation. N Engl J Med. 2010;362:1363–73.PubMedCrossRefGoogle Scholar
  2. 2.
    Roy D, Talajic M, Nattel S, et al. Rhythm control vs rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358:2667–77.PubMedCrossRefGoogle Scholar
  3. 3.•
    Saksena S, Slee A, Waldo AL, et al. Cardiovascular outcomes in the AFFIRM Trial (Atrial Fibrillation Follow-Up Investigation of Rhythm Management). An assessment of individual antiarrhythmic drug therapies compared with rate control with propensity score-matched analyses. J Am Coll Cardiol. 2011;58:1975–85. This study emphasizes the side-effects from pharmacologic approaches to maintain sinus rhythm, including an increase in hospitalization and mortality compared with ventricular rate control.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.•
    Wilber DJ, Pappone C, Neuzil P, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010;303:333–40. This landmark multicenter randomized clinical trial shows that catheter ablation for AF, while more effective than anti-arrhythmic drug therapy, yields a 70% multiprocedure efficacy with a lower single procedure efficacy in this study of patients with early paroxysmal AF.PubMedCrossRefGoogle Scholar
  5. 5.•
    Packer DL, Kowal RC, Wheelan KR, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial. J Am Coll Cardiol. 2013;61:1713–23. This multicenter trial confirms that PV isolation using a different energy source (cryoballoon ablation) produces a single-procedure 1 year freedom from AF of ≈58%.PubMedCrossRefGoogle Scholar
  6. 6.
    Oral H, Pappone C, Chugh A, et al. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. N Engl J Med. 2006;354:934–41.PubMedCrossRefGoogle Scholar
  7. 7.
    Morillo C, Verma A, Kuck KH, et al. Radiofrequency Ablation vs Antiarrhythmic Drugs as First-Line Therapy of Atrial Fibrillation (RAAFT 2) trial (abstract). Heart Rhythm. 2012; [Abstract].Google Scholar
  8. 8.
    Nielsen JC, Johannessen A, Raatikainen P, et al. Radiofrequency Ablation as Initial Therapy in Paroxysmal Atrial Fibrillation. N Engl J Med. 2012;367:1587–95.CrossRefGoogle Scholar
  9. 9.
    Calkins CH. 2012 HRS/EHRA/ECAS Expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Heart Rhythm. 2012;9:632–96.PubMedCrossRefGoogle Scholar
  10. 10.
    Parkash R, Tang AS, Sapp JL, Wells G. Approach to the catheter ablation technique of paroxysmal and persistent atrial fibrillation: a meta-analysis of the randomized controlled trials. J Cardiovasc Electrophysiol. 2011;22:729–38.PubMedCrossRefGoogle Scholar
  11. 11.
    Nattel S. New ideas about atrial fibrillation 50 years on. Nature. 2002;415:219–26.PubMedCrossRefGoogle Scholar
  12. 12.
    Allessie MA, Bonke FI, Schopman FJ. 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 anatomical obstacle. Circ Res. 1977;41:9–18.PubMedCrossRefGoogle Scholar
  13. 13.
    Schuessler RB, Grayson TM, Bromberg BI, Cox JL, Boineau JP. Cholinergically mediated tachyarrhythmias induced by a single extrastimulus in the isolated canine right atrium. Circ Res. 1992;71:1254–67.PubMedCrossRefGoogle Scholar
  14. 14.•
    Pandit SV, Jalife J. Rotors and the dynamics of cardiac fibrillation. Circ Res. 2013;112:849–62. This is a contemporary review on the basic science and history of rotors, from the laboratory that has pioneered studies to define their role.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Narayan SM, Krummen DE, Kahn AM, Karasik PL, Franz MR. Evaluating fluctuations in human atrial fibrillatory cycle length using monophasic action potentials. Pacing Clin Electrophysiol. 2006;29:1209–18.PubMedCrossRefGoogle Scholar
  16. 16.
    Narayan SM, Krummen DE, Rappel WJ. Clinical mapping approach to diagnose electrical rotors and focal impulse sources for human atrial fibrillation. J Cardiovasc Electrophysiol. 2012;23:447–54.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Rappel WJ, Narayan SM. Theoretical considerations for mapping activation in human cardiac fibrillation. Chaos. 2013;23:023113.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Narayan SM, Bode F, Karasik PL, Franz MR. Alternans of atrial action potentials as a precursor of atrial fibrillation. Circulation. 2002;106:1968–73.PubMedCrossRefGoogle Scholar
  19. 19.
    Narayan SM, Franz MR, Clopton P, Pruvot EJ, Krummen DE. Repolarization alternans reveals vulnerability to human atrial fibrillation. Circulation. 2011;123:2922–30.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Lalani G, Schricker A, Gibson M, Rostamanian A, Krummen DE, Narayan SM. Atrial conduction slows immediately before the onset of human atrial fibrillation: a bi-atrial contact mapping study of transitions to atrial fibrillation. J Am Coll Cardiol. 2012;59:595–606.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Narayan SM, Krummen DE, Donsky A, Swarup V, Miller JM. Precise Rotor Elimination without Concomitant pulmonary vein Isolation for the Successful Elimination of Paroxysmal Atrial Fibrillation. PRECISE-PAF. Heart Rhythm. 2013;10:LBCT4.Google Scholar
  22. 22.••
    Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel W-J, Miller J. Treatment of atrial fibrillation by the ablation of localized sources: the Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation: CONFIRM Trial. J Am Coll Cardiol. 2012;60:628–36. This study provides the first identification of electrical rotors as sustaining mechanisms for human AF, demonstrating rotors in 97% of patients with paroxysmal, persistent and longstanding persistent AF, where directed ablation (Focal Impulse and Rotor Modulation) improved long-term AF-freedom vs conventional ablation alone on rigorous follow-up.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Lazar S, Dixit S, Marchlinski FE, Callans DJ, Gerstenfeld EP. Presence of left-to-right atrial frequency gradient in paroxysmal but not persistent atrial fibrillation in humans. Circulation. 2004;110:3181–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Gerstenfeld EP, Sahakian AV, Swiryn S. Evidence for transient linking of atrial excitation during atrial fibrillation in humans. Circulation. 1992;86:375–82.PubMedCrossRefGoogle Scholar
  25. 25.
    Wu T-J, Doshi RN, Huang H-LA, et al. Simultaneous bi-atrial computerized mapping during permanent atrial fibrillation in patients with organic heart disease. J Cardiovasc Electrophysiol. 2002;13:571–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Sahadevan J, Ryu K, Peltz L, et al. Epicardial mapping of chronic atrial fibrillation in patients: preliminary observations. Circulation. 2004;110:3293–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Lee G, Kumar S, Teh A, et al. Epicardial wave mapping in human long-lasting persistent atrial fibrillation: transient rotational circuits, complex wavefronts, and disorganized activity. Eur Heart J. 2013;35:86–97.Google Scholar
  28. 28.
    Cox JL, Canavan TE, Schuessler RB, et al. 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. 1991;101:406–26.PubMedGoogle Scholar
  29. 29.
    Davidenko JM, Pertsov AV, Salomonsz R, Baxter W, Jalife J. Stationary and drifting spiral waves of excitation in isolated cardiac muscle. Nature. 1992;355:349–51.PubMedCrossRefGoogle Scholar
  30. 30.•
    Chou CC, Chang PC, Wen MS, et al. Epicardial ablation of rotors suppresses inducibility of acetylcholine-induced atrial fibrillation in left pulmonary vein-left atrium preparations in a beagle heart failure model. J Am Coll Cardiol. 2011;58:158–66. This study reports on mapping rotors in a canine model of AF, with interventions to ablate rotors causing AF suppression.PubMedCrossRefGoogle Scholar
  31. 31.
    Herweg B, Kowalski M, Steinberg JS. Termination of persistent atrial fibrillation resistant to cardioversion by a single radiofrequency application. Pacing Clin Electrophysiol. 2003;26:1420–3.PubMedCrossRefGoogle Scholar
  32. 32.
    Tzou WS, Saghy L, Lin D. Termination of persistent atrial fibrillation during left atrial mapping. J Cardiovasc Electrophysiol. 2011;22:1171–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Haissaguerre M, Hocini M, Shah AJ, et al. Noninvasive panoramic mapping of human atrial fibrillation mechanisms: a feasibility report. J Cardiovasc Electrophysiol. 2012;24:711–717.Google Scholar
  34. 34.
    Sanders P, Berenfeld O, Hocini M, et al. Spectral analysis identifies sites of high-frequency activity maintaining atrial fibrillation in humans. Circulation. 2005;112:789–97.PubMedCrossRefGoogle Scholar
  35. 35.
    Gerstenfeld E, Sahakian A, Swiryn S. Evidence for transient linking of atrial excitation during atrial fibrillation in humans. Circulation. 1992;86:375–82.PubMedCrossRefGoogle Scholar
  36. 36.
    Moe GK, Rheinboldt WC, Abildskov JA. A computer model of atrial fibrillation. Am Heart J. 1964;67:200–20.PubMedCrossRefGoogle Scholar
  37. 37.
    Jadidi AS, Cochet H, Shah AJ, et al. Inverse relationship between fractionated electrograms and atrial fibrosis in persistent atrial fibrillation - a combined MRI and high density mapping. J Am Coll Cardiol. 2013.Google Scholar
  38. 38.
    Konings KT, Kirchhof CJ, Smeets JR, Wellens HJ, Penn OC, Allessie MA. High-density mapping of electrically induced atrial fibrillation in humans. Circulation. 1994;89:1665–80.PubMedCrossRefGoogle Scholar
  39. 39.
    de Groot NM, Houben RP, Smeets JL, et al. Electropathological substrate of longstanding persistent atrial fibrillation in patients with structural heart disease: epicardial breakthrough. Circulation. 2010;122:1674–82.PubMedCrossRefGoogle Scholar
  40. 40.••
    Shivkumar K, Ellenbogen KA, Hummel JD, Miller JM, Steinberg JS. Acute termination of human atrial fibrillation by identification and catheter ablation of localized rotors and sources: first multicenter experience of Focal Impulse and Rotor Modulation (FIRM) ablation. J Cardiovasc Electrophysiol. 2012;23:1277–85. This study reports the acute results of the first multicenter validation of FIRM mapping to identify rotors and focal sources in human AF.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Lin YJ, Lo MT, Lin C, et al. Prevalence, characteristics, mapping, and catheter ablation of potential rotors in nonparoxysmal atrial fibrillation. Circ Arrhythm Electrophysiol. 2013;6:851–8.PubMedCrossRefGoogle Scholar
  42. 42.•
    Ghoraani B, Dalvi R, Gizurarson S, et al. Localized rotational activation in the left atrium during human atrial fibrillation: relationship to complex fractionated atrial electrograms and low-voltage zones. Heart Rhythm. 2013;10:1830–8. This study reports the acute results of the first multicenter validation of FIRM mapping to identify rotors and focal sources in human AF. PubMedCrossRefGoogle Scholar
  43. 43.•
    Narayan SM, Wright M, Derval N, et al. Classifying fractionated electrograms in human atrial fibrillation using monophasic action potentials and activation mapping: evidence for localized drivers, rate acceleration, and nonlocal signal etiologies. Heart Rhythm. 2011;8:244–53. This study uses detailed monophasic action potential recordings to demonstrate how clinically recorded AF bipolar signals often do not indicate local activation in AF.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Kadish A, Hauck J, Pederson B, Beatty G, Gornick C. Mapping of atrial activation with a noncontact, multi-electrode catheter in dogs. Circulation. 1999;99:1906–13.PubMedCrossRefGoogle Scholar
  45. 45.•
    Vaquero M, Calvo D, Jalife J. Cardiac fibrillation: from ion channels to rotors in the human heart. Heart Rhythm. 2008;5:872–9. This study uses detailed monophasic action potential recordings to demonstrate how clinically recorded AF bipolar signals often do not indicate local activation in AF.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Catheter Ablation of Supraventricular Arrhythmias. Cardiac Electrophysiology from Cell to Bedside: Chapter 107. In: Zipes DP, Jalife J, editors. Philadelphia: Saunders; 2009. p. 1083–1092.Google Scholar
  47. 47.
    Franz MR, Chin MC, Sharkey HR, Griffin JC, Scheinman MM. A new single catheter technique for simultaneous measurement of action potential duration and refractory period in vivo. J Am Coll Cardiol. 1990;16:878–86.PubMedCrossRefGoogle Scholar
  48. 48.
    Rensma PL, Allessie MA, Lammers WJ, Bonke FI, Schalij MJ. Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs. Circ Res. 1988;62:395–410.PubMedCrossRefGoogle Scholar
  49. 49.
    Calvo D, Atienza F, Jalife J, et al. High-rate pacing-induced atrial fibrillation effectively reveals properties of spontaneously occurring paroxysmal atrial fibrillation in humans. Europace. 2012;14:1560–6.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Nademanee K, McKenzie J, Kosar E, et al. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol. 2004;43:2044–53.PubMedCrossRefGoogle Scholar
  51. 51.
    Narayan SM, Kazi D, Krummen DE, Rappel W-J. Repolarization and activation restitution near human pulmonary veins and atrial fibrillation initiation: a mechanism for the initiation of atrial fibrillation by premature beats. J Am Coll Cardiol. 2008;52:1222–30.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Krummen DE, Bayer JD, Ho J, et al. Mechanisms of human atrial fibrillation initiation: clinical and computational studies of repolarization restitution and activation latency. Circ Arrhythm Electrophysiol. 2012;5:1149–59.PubMedCrossRefGoogle Scholar
  53. 53.
    Klos M, Calvo D, Yamazaki M, et al. Atrial septopulmonary bundle of the posterior left atrium provides a substrate for atrial fibrillation initiation in a model of vagally mediated pulmonary vein tachycardia of the structurally normal heart. Circ Arrhythm Electrophysiol. 2008;1:175–83.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Lalani G, Gibson M, Schricker A, Rostamanian A, Krummen DE, Narayan SM. Dynamic conduction slowing precedes human atrial fibrillation initiation: insights from bi-atrial basket mapping during burst pacing. J Am Coll Cardiol. 2011b.Google Scholar
  55. 55.
    Ganesan AN, Kuklik P, Lau DH, et al. Bipolar electrogram shannon entropy at sites of rotational activation: implications for ablation of atrial fibrillation. Circ Arrhythm Electrophysiol. 2013;6:48–57.PubMedCrossRefGoogle Scholar
  56. 56.
    Narayan SM, Baykaner T, Clopton P, Schricker A, Lalani GG, Krummen DE, et al. Ablation of rotor and focal sources reduces late recurrence of atrial fibrillation compared with trigger ablation alone: extended follow-up of the CONFIRM trial (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation). J Am Coll Cardiol. 2014;63(17):1761–8.Google Scholar
  57. 57.
    Miller JM, Kowal RC, Swarup V, Daoud E, Day J, Ellenbogen K, et al. Initial Independent Outcomes from Focal Impulse and Rotor Modulation Ablation for Atrial Fibrillation: Multicenter FIRM Registry. J Cardiovascular Electrophysiology; 2014; in press.Google Scholar
  58. 58.•
    Narayan SM, Krummen DE, Clopton P, Shivkumar K, Miller JM. Direct or coincidental elimination of stable rotors or focal sources may explain successful atrial fibrillation ablation: on-treatment analysis of the CONFIRM (CONventional ablation for AF with or without Focal Impulse and Rotor Modulation) Trial. J Am Coll Cardiol. 2013;58–67. This study shows that rotor ablation – whether performed directly by FIRM or unintentionally during conventional anatomic ablation lesions—greatly improves outcomes compared with ablation that does not pass through rotors. Google Scholar
  59. 59.•
    Narayan SM, Shivkumar K, Krummen DE, Miller JM, Rappel W-J. Panoramic electrophysiological mapping but not individual electrogram morphology identifies sustaining sites for human atrial fibrillation (af rotors and focal sources relate poorly to fractionated electrograms). Circ Arrhythm Electrophysiol. 2013;6. This study shows that localized AF sources—where the rotor core or focal source demonstrates spatial precession—is not well correlated with bipolar electrogram amplitude or traditionally defined fractionation. Google Scholar
  60. 60.
    Narayan SM, Krummen DE, Enyeart MW, Rappel WJ. Computational mapping identifies localized mechanisms for ablation of atrial fibrillation. PLoS One. 2012;7:e46034.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Amir A. Schricker
    • 1
  • Gautam G. Lalani
    • 1
  • David E. Krummen
    • 1
  • Sanjiv M. Narayan
    • 1
  1. 1.Department of Medicine/CardiologyUniversity of California San Diego Medical CenterSan DiegoUSA

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