Catheter Ablation for Atrial Fibrillation

Background

Atrial fibrillation (AF) is the most commonly occurring tachyarrhythmia addressed by United States physicians, with a prevalence that is anticipated to increase over the next several decades.1 Approaches to symptomatic AF include rhythm control, either with pharmacological agents or, increasingly, with catheter ablation.2 Ablative therapy for AF has evolved rapidly over the last 25 years. Early ablative strategies focused on compartmentalizing atrial tissue with long, linear right- and left-sided lesions. The seminal observation that triggering of AF arises from ectopic foci typically located in the pulmonary veins led to a fundamental shift in strategy, and pulmonary vein isolation (PVI) has been the mainstay of AF ablation, both for paroxysmal and persistent AF, for well over a decade.3

Unfortunately, single-procedure success rates for PVI as a treatment for paroxysmal and especially persistent AF remain suboptimal. A number of adjunctive or alternative ablative strategies to PVI have been investigated over the last several years, including targeting of complex fractionated atrial electrograms (CFAEs),4 ganglionated plexi (GPs),5 non-PV trigger sites,6 and AF-sustaining rotors.7-11 Rotor ablation has been the subject of particularly impassioned debate12,13 over the last several years, and may represent a paradigm shift in the field of AF ablation similar to that seen with the recognized importance of PV triggers. Data about the effectiveness of rotor ablation, though, is decidedly mixed.

For Rotor Ablation

Rotor activity perpetuating cardiac arrhythmias is not a new concept. Jalife and colleagues have described rotor activity in optical mapping studies in a variety of models, including tissue monolayers, whole-organ models, and humans.14 A significant step forward in the development of rotor elimination as a therapeutic strategy for AF was in the work of Narayan and colleagues, who postulated that rotor activity in the atria: (1) was critical in maintenance of ongoing fibrillatory activity, and (2) could be identified and eliminated during an ablative procedure. Central to that identification of rotor activity was the development of novel mapping approaches (now commercially available; Topera Solution, Abbott, Chicago) allowing for the identification and localization of rotor cores. The concept of triggering beats initiating a sustained arrhythmia is obviously familiar to electrophysiologists; extension of that concept, with focus on elimination of the sustaining circuit rather than targeting of the triggering beats (i.e. targeting an accessory pathway, rather than the PACs that trigger orthodromic reciprocating tachycardia), makes rotor ablation an appealing and familiar concept.

Early clinical investigations of rotor elimination were remarkably promising.7,9 A series of single-center and multi-center trials demonstrated increased freedom from recurrent AF in patients treated with PVI and rotor ablation compared to PVI alone. In the CONFIRM (Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer) trial, for instance, freedom from AF at intermediate follow-up (average 273 days) was 82.4% in patients treated with PVI and focal impulse and rotor modulation (FIRM)-guided rotor ablation, versus 44.9% in PVI-only patients.7

Long-term follow-up of the same cohort showed durable results.8 Indeed, retrospective analysis of rotor sites in patients treated with PVI suggest that success of that procedure may in fact be due to fortuitous elimination of rotors, rather than PV isolation per se.15 These results have been promising enough that private industry has embraced the strategy.

Against Rotor Ablation

Rotor elimination as a central aspect of AF ablation has not been uniformly embraced; however, both at the mechanistic and clinical levels. Allessie and colleague have mapped atrial fibrillatory activity in a number of models, and have not seen AF-sustaining rotors of the sort described by Jalife, calling into question the basic physiology being targeted by rotor elimination.16 Instead of focal or meandering rotors, Allessie has observed by direct mapping of fibrillatory tissue a longitudinal dissociation of propagating wavefronts between epi- and endocardial atrial layers – a very different physiology than that described by Jalife and Narayan.

Equally significant, a number of recent clinical investigations have reported poor results in patients undergoing rotor ablation either as a stand-alone strategy or in conjunction with PVI. Natale and colleagues reported on premature termination of a study comparing rotor elimination as stand-alone therapy to PVI + FIRM ablation, and to PVI + trigger ablation.11 The FIRM-only group had low rates of acute success (termination of AF or organization into AT; 41%) and low rates of arrhythmia-free survival (17%). Similarly, poor results were reported by Shivkumar and colleagues, who reported 18 month follow-up in 43 patients undergoing FIRM-guided ablation.10 Long-term freedom from atrial arrhythmias without anti-arrhythmic therapy was 21%. The give-and-take between the proponents and detractors of rotor identification and ablation has been fascinating to watch, but certainly leaves an air of uncertainty for clinicians facing patients with symptomatic, persistent AF, for whom PVI is an imperfect solution.

Fortunately, more data should be soon forthcoming. The REAFFIRM (Randomized Evaluation of Atrial Fibrillation Treatment With Focal Impulse and Rotor Modulation Guided Procedures) trial is an industry-sponsored, prospective, randomized, multicenter investigation comparing the efficacy of PVI + FIRM ablation to PVI only [ClinicalTrials.gov; NCT02274857]. The study is estimated to finish in 2018, and should provide independent, multicenter data on whether FIRM-guided ablation improves outcomes in AF ablation for persistent AF. A second trial, not yet underway, is planned to examine FIRM-guided ablation in repeat ablative procedures for recurrent AF.

Should FIRM-Guided Ablation Be Adopted Aggressively in 2016?

What, then, is a practitioner to do with persistent AF patients undergoing ablation for AF in late 2016? Certainly, PVI seems to remain a reasonable and central aspect to the procedure, and indeed, the STAR AF (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial - Star AF II Study) ,which admittedly, did not investigate rotor elimination, suggests that PVI alone is a best first step.17 Other adjunctive approaches to AF ablation, including testing for, and ablating macro-reentrant flutter(s) and non-PV trigger sites, can be done safely, easily, and with minimal additional infrastructural costs and minimal risk to the patient. For investigators grappling with whether to invest in novel mapping and ablative systems, fortunately there are trials forthcoming that should help make that decision easier.

References

  1. Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:119-25.
  2. Calkins H, Kuck KH, Cappato R, et al. 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.
  3. Haissaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659-66.
  4. 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.
  5. Katritsis DG, Giazitzoglou E, Zografos T, et al. Rapid pulmonary vein isolation combined with autonomic ganglia modification: a randomized study. Heart Rhythm 2011;8:672-8.
  6. Dixit S, Marchlinski FE, Lin D, et al. Randomized ablation strategies for the treatment of persistent atrial fibrillation: RASTA study. Circ Arrhythm Electrophysiol 2012;5:287-94.
  7. Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ, Miller JM. 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 2012;60:628-36.
  8. Narayan SM, Baykaner T, Clopton P, et al. Ablation of rotor and focal sources reduces late recurrence of atrial fibrillation compared with trigger ablation alone extended follow-pp of the CONFIRM trial (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation. J Am Coll Cardiol 2014;63:1761-8.
  9. Miller JM, Kowal RC, Swarup V, et al. Initial independent outcomes from focal impulse and rotor modulation ablation for atrial fibrillation: multicenter FIRM registry. J Cardiovasc Electrophysiol 2014;25:921-9.
  10. Buch E, Share M, Tung R, et al. Long-term clinical outcomes of focal impulse and rotor modulation for treatment of atrial fibrillation: A multicenter experience. Heart Rhythm 2016; 13:636-41.
  11. Gianni C, Mohanty S, DiBiase L, et al. Acute and early outcomes of focal impulse and rotor modulation (FIRM)-guided rotors-only ablation in patients with nonparoxysmal atrial fibrillation. Heart Rhythm 2016;13:830-5.
  12. Jalife J, Filgueiras Rama D, Berenfeld O. Letter by Jalife et al regarding article, "Quantitative analysis of localized sources identified by focal impulse and rotor modulation mapping in atrial fibrillation". Circ Arrhythm Electrophysiol 2015;8:1296-8.
  13. Buch E, Benharash P, Frank P, et al. Response to Letter by Jalife et al Regarding Article, "Quantitative Analysis of Localized Sources Identified by Focal Impulse and Rotor Mapping in Atrial Fibrillation". Circ Arrhythm Electrophysiol 2015;8:1299-300.
  14. Narayan S, Jalife J. CrossTalk proposal: Rotors have been demonstrated to drive human atrial fibrillation. J Physiol 2014;592:3163-6.
  15. 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 trial (Conventional ablation for AF with or without focal impulse and rotor modulation). J Am Coll Cardiol 2013;62:138-47.
  16. Allessie M, de Groot N. CrossTalk opposing view: Rotors have not been demonstrated to be the drivers of atrial fibrillation. J Physiol 2014;592:3167-70.
  17. Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015;372:1812-2.

Clinical Topics: Arrhythmias and Clinical EP, Cardio-Oncology, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anti-Arrhythmia Agents, Atrial Fibrillation, Catheter Ablation, Colonoscopy, Colorectal Neoplasms, Electrophysiologic Techniques, Cardiac, Heart Atria, Heart Conduction System, Pulmonary Veins, Tachycardia, Tachycardia, Reciprocating


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