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Atrial Fibrillation (Part 2) - Catheter Ablation

Abstract

More than 20 years since its initial use, catheter ablation has become a routinely performed procedure for the treatment of patients with atrial fibrillation (AF). Initially based on the electrical isolation of pulmonary veins in patients with paroxysmal AF, subsequent advances in the understanding of pathophysiology led to additional techniques not only to achieve better results, but also to treat patients with persistent forms of arrhythmia, as well as patients with structural heart disease and heart failure.

Arrhythmias Cardiac; Fibrilation Atrial; Catheter Ablation/methods; Echocardiography/methods

Resumo

Após mais de 20 anos desde sua utilização inicial, a ablação por cateter se tornou um procedimento rotineiramente realizado para tratamento de pacientes com fibrilação atrial (FA). Fundamentado inicialmente no isolamento elétrico das veias pulmonares em pacientes com FA paroxística, subsequentes avanços no entendimento da fisiopatologia levaram a técnicas adicionais não só para obter melhores resultados, mas também para tratar pacientes com formas persistentes de arritmia, assim como pacientes com cardiopatia estrutural e insuficiência cardíaca.

Arritmias Cardíacas; Fibrilação Atrial/terapia; Ablação por Cateter/métodos; Ecocardiografia/métodos

Significant technological advances, especially in 3D electroanatomic mapping, intracardiac echocardiography use and how energy is delivered to the tissue (cryoablation and tissue contact force with radiofrequency) have allowed a significant reduction in the rate of complications and in the use of ionizing radiation.

Currently, ablation is the most efficient treatment for patients with AF, and an excellent alternative to the use of antiarrhythmic drugs, whose development has been insignificant in recent decades.

With the pioneering observations made by Haissaguerre et al.,11. Haissaguerre M, Jais P, Shah DC, Hocini M, Quiniou G, Garrigue S, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998; 339(10): 659-66. the pivotal role of arrhythmogenic foci located in the pulmonary veins (PV) in the pathophysiology of the initiation and maintenance of AF episodes was shown. The concept of focal AF was then established, where atrial arrhythmia that diffusely affects both atria have a well-determined origin, and is therefore susceptible to therapeutic interventions. Techniques using catheter ablation were developed and improved to eliminate AF-generating foci through circumferential ablation around the PVs,22. Kanagaratnam L, Tomassoni G, Schweikert R, Pavia S, Bash D, Beheiry S, et al. Empirical pulmonary vein isolation in patients with chronic atrial fibrillation using a three-dimensional nonfluoroscopic mapping system: long-term follow-up. Pacing Clin Electrophysiol. 2001; 24(12): 1774-9.

3. Kanj MH, Wazni OM, Natale A. How to do circular mapping catheter-guided pulmonary vein antrum isolation: the Cleveland Clinic approach. Heart Rhythm. 2006; 3(7): 866-9.
-44. Verma A, Marrouche NF, Natale A. Pulmonary vein antrum isolation: intracardiac echocardiography-guided technique. J Cardiovasc Electrophysio.l 2004; 15(11): 1335-40. with higher success and performance rates compared to the best pharmacological therapy.55. Mark DB, Anstrom KJ, Sheng S, Piccini JP, Baloch KN, Monahan KH, et al. Effect of Catheter Ablation vs Medical Therapy on Quality of Life Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019; 321(13): 1275-85.

6. Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, 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 Cardio.l 2013; 61(16): 1713-23.

7. Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, PooleJE, et al. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019; 321(13): 1261-74.

8. Reynolds MR, Walczak J, White SA, Cohen DJ, Wilber DJ. Improvements in symptoms and quality of life in patients with paroxysmal atrial fibrillation treated with radiofrequency catheter ablation versus antiarrhythmic drugs. Circ Cardiovasc Qual Outcomes. 2010;3(6): 615-23.

9. Wilber DJ, Pappone C, Neuzil P, Paola A, Marchlinski F, Natale A, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010; 303(4): 333-40.
-1010. Saad EB, Tayar DO, Ribeiro RA, Junqueira SM, Jr., Andrade P, d’Avila A. Healthcare Utilization and Costs Reduction after Radiofrequency Ablation For Atrial Fibrillation in the Brazilian Private Healthcare System. Arq Bras Cardiol. 2019; 113(2): 252-7.

The aim of this article is to review the advances in catheter ablation for AF and describe to the clinical cardiologist state-of-the-art indications, techniques, results and complications.

Ablation Strategies

Over the last 20 years, several ablation strategies have been used to control AF. In common, there is a current consensus that the isolation of all PVs is fundamental in all groups of patients (paroxysmal, persistent or long-standing persistent AF).1111. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017;14(10): e275-e444.

12. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland Jr JC, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019; 140(2):e125-e51.

13. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016; 37(38): 2893-962.

14. Magalhaes LP, Figueiredo MJO, Cintra FD, Saad EB, Kuniyoshi RR, Lorga Filho AM, et al. Executive Summary of the II Brazilian Guidelines for Atrial Fibrillation. Arq Bras Cardiol 2016; 107(6): 501-8.
-1515. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020. Isolation must be electrically proven by circular mapping inside the PVs (Figures 1 and 2), as this step is paramount for the success of the procedure. Recent studies have shown that the procedure should be performed on uninterrupted oral anticoagulation, a strategy proven to reduce thrombotic and hemorrhagic complications.1616. Silva MA, Futuro GMC, Mercon ES, Vasconcelos D, Agrizzi RS, Elias Neto J, et al. Safety of Catheter Ablation of Atrial Fibrillation Under Uninterrupted Rivaroxaban Use. Arq Bras Cardiol. 2020; 114(3): 435-42.

17. Saad EB, Costa IP, Costa RE, Inacio Jr LA, Slater C, Camiletti A, et al. Safety of ablation for atrial fibrillation with therapeutic INR: comparison with transition to low-molecular-weight heparin. Arq Bras Cardiol. 2011; 97(4): 289-96.
-1818. Calkins H, Willems S, Gerstenfeld EP, Verma A, Schilling R, Hohnloser SH, et al. Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation. N Engl J Med. 2017; 376(17):1627-36.

In patients with paroxysmal AF, PV isolation is usually all that is needed, targeting additional sites only in specific situations (e.g., triggering foci mapped outside the PVs). Some centers routinely perform isolation of the superior vena cava1919. Arruda M, Mlcochova H, Prasad SK, Kilicaslan F, Saliba W, Patel D, et al. Electrical isolation of the superior vena cava: an adjunctive strategy to pulmonary vein antrum isolation improving the outcome of AF ablation. J Cardiovasc Electrophysiol. 2007; 18(12):1261-6.,2020. Gianni C, Sanchez JE, Mohanty S, Trivedi C, Rocca DG, Al-Ahmad A, et al. Isolation of the superior vena cava from the right atrial posterior wall: a novel ablation approach. Europace. 2018; 20(9): e124-e32.since it can also be, albeit rarely, a triggering AF-inducing source. Most publications show favorable results, with success rates above 70%.66. Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, 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 Cardio.l 2013; 61(16): 1713-23.

PV isolation can be performed using: 1) radiofrequency (RF) energy, through point-by-point focal applications (Figure 1 – A), ideally with catheters with contact force sensors at the tip (Figure 1 – B), or 2) freezing (cryoablation), using a balloon catheter positioned in the antrum of the PVs, capable of performing ablation simultaneously around the entire circumference in contact with the tissue (Figure 1 - D). A randomized study (Fire and ICE)2121. Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, et al. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2016; 374(23):2235-45. directly comparing the two strategies for the treatment of paroxysmal AF showed similar results. These findings were replicated in a second randomized study (CIRCA-DOSE)2222. Andrade JG, Champagne J, Dubuc M, Deyell MW, Verma A, Macle L, et al. Cryoballoon or Radiofrequency Ablation for Atrial Fibrillation Assessed by Continuous Monitoring: A Randomized Clinical Trial. Circulation. 2019; 140(22):1779-88. that compared two cryoablation regimens (4 min vs. 2 min freezings) to the use of contact force-guided RF to isolate the PVs in patients with paroxysmal AF; in this study, there was a >98% reduction in AF burden demonstrated through continuous electrocardiographic monitoring. It is important to note that the Cryo balloon catheter is not commonly used for ablation at sites other than around the PVs; when necessary, an RF catheter should be used for that (Figure 1 - C).

Figure 1
– Catheter ablation for the treatment of paroxysmal AF. A) Isolation of left VPs by circumferential ablation (RF point-by-point) guided by 3D electroanatomic mapping (NAVx system — Abbott), demonstrating the elimination of electrograms (*) recorded by a circular catheter inside the PVs. B) Isolation of the right PVs (CARTO system — Biosense Webster) with a contact force-sensing catheter (shown by the force vector and force quantification = 7 g); the circular mapping catheter is inside the right superior PV. C) Persistent AF ablation (NAVx system — Abbott) demonstrating the additional linear RF lesions to isolate the LA posterior wall (roof and inferior lines), leading to the elimination of electrograms (recorded by the circular mapping catheter). D) Fluoroscopic imaging during cryoablation for isolation of the left superior PV, demonstrating the balloon catheter (arrow) inflated and in contact with the vein ostium. Balloon ablation along the PV circumference is performed simultaneously, which is usually restricted to PV isolation — when additional ablation is required, an RF catheter should be used.

In persistent and long-standing persistent forms of AF, additional electrical conduction barriers are often created, as stand-alone PV isolation is usually insufficient and associated with high recurrence rates.2323. Oral H, Knight BP, Tada H, Ozaydin M, Chugh A, Hassan S, et al. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation. 2002;105(9):1077-81.

24. 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(7):729-38.
-2525. Wynn GJ, Das M, Bonnett LJ, Panikker S, Wong T, Gupta D. Efficacy of catheter ablation for persistent atrial fibrillation: a systematic review and meta-analysis of evidence from randomized and nonrandomized controlled trials. Circ Arrhythm Electrophysiol. 2014; 7(5):841-52. Several strategies have been studied,2626. Scott PA, Silberbauer J, Murgatroyd FD. The impact of adjunctive complex fractionated atrial electrogram ablation and linear lesions on outcomes in persistent atrial fibrillation: a meta-analysis. Europace. 2016; 18(3): 359-67.

27. Romero J, Gianni C, Natale A, Di Biase L. What Is the Appropriate Lesion Set for Ablation in Patients with Persistent Atrial Fibrillation? Curr Treat Options Cardiovasc. Med 2017; 19(5): 35.

28. Mohanty S, Mohanty P, Trivedi C, Gianni C, Rocca DG, Biasi L, et al. Long-Term Outcome of Pulmonary Vein Isolation With and Without Focal Impulse and Rotor Modulation Mapping: Insights From a Meta-Analysis. Circ Arrhythm Electrophysiol. 2018; 11(3): e005789.

29. Hung Y, Lo LW, Lin YJ, Chang SL, Hu YF, Chung FP, et al. Characteristics and long-term catheter ablation outcome in long-standing persistent atrial fibrillation patients with non-pulmonary vein triggers. Int J Cardiol. 2017; 241: 205-11.

30. Bai R, Di Biase L, Mohanty P, Trivedi C, Russo AD, Themistoclakis S, et al. Proven isolation of the pulmonary vein antrum with or without left atrial posterior wall isolation in patients with persistent atrial fibrillation. Heart Rhythm. 2016; 13(1): 132-40.

31. Pambrun T, Denis A, Duchateau J, Sacher F, Hocini M, Jais P, et al. MARSHALL bundles elimination, Pulmonary veins isolation and Lines completion for ANatomical ablation of persistent atrial fibrillation: MARSHALL-PLAN case series. J Cardiovasc Electrophysiol. 2019; 30(1): 7-15.

32. Santangeli P, Zado ES, Hutchinson MD, Riley MP, Lin D, Frankel DS, et al. Prevalence and distribution of focal triggers in persistent and long-standing persistent atrial fibrillation. Heart Rhythm. 2016; 13(2): 374-82.

33. Hayashi K, An Y, Nagashima M, Hiroshima K, Ohe M, Makihara Y, et al. Importance of nonpulmonary vein foci in catheter ablation for paroxysmal atrial fibrillation. Heart Rhythm. 2015; 12(9):1918-24.

34. Kottkamp H, Berg J, Bender R, Rieger A, Schreiber D. Box Isolation of Fibrotic Areas (BIFA): A Patient-Tailored Substrate Modification Approach for Ablation of Atrial Fibrillation. J Cardiovasc Electrophysiol. 2016; 27(1): 22-30.

35. Thiyagarajah A, Kadhim K, Lau DH, Emami M, Linz D, Khokhar K, et al. Feasibility, Safety, and Efficacy of Posterior Wall Isolation During Atrial Fibrillation Ablation: A Systematic Review and Meta-Analysis. Circ Arrhythm Electrophysiol. 2019; 12(8):e007005.

36. Di Biase L, Burkhardt JD, Mohanty P, Sanchez J, Mohanty S, Horton R, et al. Left atrial appendage: an underrecognized trigger site of atrial fibrillation. Circulation. 2010; 122(2):109-18.
-3737. Brooks S, Metzner A, Wohlmuth P, Lin T, Wissner E, Tilz R, et al. Insights into ablation of persistent atrial fibrillation: Lessons from 6-year clinical outcomes. J Cardiovasc Electrophysiol. 2018; 29(2): 257-63. the most frequently used being: ablation of triggers outside the PVs, linear lesions in the left atrium (LA) and extensive RF applications at sites depicting fractionated electrograms during AF (most commonly observed in the posterior LA wall, septum, LA roof, mitral annulus, base of the left atrial appendage (LAA) and inside the coronary sinus). During RF applications at these sites, AF conversion to regular atrial tachycardias or even to sinus rhythm may occur.

The negative results of the randomized Star AF II3838. Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015;372(19):1812-22.study should be noted. The study compared the addition of linear lesions and ablation of fragmented potentials to PV isolation in patients with persistent AF. In this study, there was no difference in the rates of sinus rhythm maintenance at 18 months between the groups (59% for PVI only vs. 49% and 46% in the other groups, without statistical significance). Therefore, many centers still perform PV isolation only, even in patients with persistent AF.

A more aggressive strategy for eliminating AF triggers was also tested in a randomized controlled trial (BELIEF Trial),3939. Di Biase L, Burkhardt JD, Mohanty P, Mohanty S, Sanches JE, Trivedi C, et al. Left Atrial Appendage Isolation in Patients With Longstanding Persistent AF Undergoing Catheter Ablation: BELIEF Trial. J Am Coll Cardiol. 2016; 68(18):1929-40. by electrical isolation of the left atrial appendage (LAA). Isolation of this structure in addition to conventional ablation was associated with a 55% reduction in the relative risk of AF recurrence in patients with long-term persistent AF. LAA isolation is currently performed selectively as it requires extensive RF applications and its association with increased risk of embolic phenomena (due to the loss of LAA contraction leading to slow flow and thrombus formation). Patients with electrically isolated LAA should be permanently anticoagulated, regardless of the CHADSVASC score, and should undergo occlusion of this structure if anticoagulation is contraindicated.4040. Di Biase L, Mohanty S, Trivedi C, Romero J, Natale V, Briceno D, et al. Stroke Risk in Patients With Atrial Fibrillation Undergoing Electrical Isolation of the Left Atrial Appendage. J Am Coll Cardiol. 2019; 74(8): 1019-28.

Therefore, more persistent forms of AF with significant atrial remodeling require modification of the atrial substrate, implying a greater number, sites and extent of RF applications. There is no consensus in the literature on the best strategy to be used (Table 1). The evolution of AF to persistent forms represent progression of a pathological process (atrial myopathy)4141. Marrouche NF, Wilber D, Hindricks G, Jais P, Akoum N, Marchlinsk F, et al. Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. JAMA. 2014; 311(5):498-506.,4242. Goette A, Kalman JM, Aguinaga L, Akar J, Cabrera JA, Chen AS, et al. EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: Definition, characterization, and clinical implication. Heart Rhythm. 2017; 14(1): e3-e40. and should motivate earlier intervention, ideally when AF is still paroxysmal, and LA remodeling is not yet present. A large retrospective study with more than 4,500 patients analyzed the impact of time between the diagnosis of AF and ablation therapy.4343. Bunch TJ, May HT, Bair TL, Johnson DL, Weiss JP, Crandall BG, et al. Increasing time between first diagnosis of atrial fibrillation and catheter ablation adversely affects long-term outcomes. Heart Rhythm. 2013; 10(9): 1257-62. The results are striking, demonstrating that the earlier the ablation is performed the better the results – establishing the so called “oncological concept of AF”, that is, the best results are obtained when treatment is done in the early stages of the disease (PV isolation in paroxysmal AF). In more advanced diseases (persistent and long-standing persistent AF), treatment is usually much more extensive and associated with worse results. A message to cardiologists and clinicians caring for AF patients is that the sooner the better.

Table 1
– Atrial fibrillation Ablation Strategies

Technologies to guide ablation

Regardless of the strategy used, imaging-based mapping methods are often used in addition to traditional electrophysiological mapping. Two types of technology are appropriate in this setting:

a) Electroanatomic mapping – this form of 3D mapping allows to accurately define the anatomy of the atrial cavities and the PVs, depict the functional substrate by measuring tissue voltage, mark the RF lesions spots (figure 1) on the constructed map and color-code the electrical activation information obtained. It is also possible to navigate on images of the true anatomy obtained by computed tomography or magnetic resonance imaging. 3D mapping is especially useful to reduce exposure to fluoroscopy and to make easy to show electrical activation of the arrhythmia circuit or focus as well as the RF lesions performed to treat them. Two systems are currently available in Brazil: CARTO — Biosense Webster and NavX — Abbott.

b) Intracardiac echocardiogram (ICE) – through an ultrasound catheter initially positioned (but not limited to) in the right atrium, it is possible to obtain detailed real-time images of cardiac anatomy4444. Enriquez A, Saenz LC, Rosso R, Silvestry FE, Callans D, Marchlinski FE, et al. Use of Intracardiac Echocardiography in Interventional Cardiology: Working With the Anatomy Rather Than Fighting It. Circulation. 2018; 137(21): 2278-94.,4545. Saad EB, Costa IP, Camanho LE. Use of intracardiac echocardiography in the electrophysiology laboratory. Arq Bras Cardiol. 2011; 96(1): e11-7.and visualize precise and safe manipulation of catheters through the various cardiac structures (Figure 2). Its use also allows the safe performance of transeptal punctures under direct visualization and the early detection of acute complications (pericardial effusion, thrombi). A recent study with more than 100,000 patients undergoing AF ablation showed the importance of this imaging method in significantly reducing the risk of a severe complication: cardiac perforation.4646. Friedman DJ, Pokorney SD, Ghanem A, Marcello S, Kalsekar I, Yadalam S, et al. Predictors of Cardiac Perforation With Catheter Ablation of Atrial Fibrillation. JACC Clin Electrophysiol. 2020; 6(6): 636-45. In this contemporary series, failure to use ICE was the greatest risk factor for cardiac perforation (RR 4.85).

Figure 2
Use of intracardiac echo (ICE) during AF ablation. A) Schematic diagram showing the ICE catheter in the right atrial cavity with the ultrasound beam directed to guide the two transeptal punctures and positioning of circular mapping and ablation catheters in LA. B) ICE image demonstrating PV antral positioning and tissue contact during RF delivery around the left superior PV (VPSE). LA: left atrium; LAA: left atrial appendage; Map: mapping catheter; RF: ablation catheter.

These non-fluoroscopic imaging tools have been increasingly used in the EP laboratory over the years and can even guide the entire ablation procedures, completely avoiding the use of X-rays.4747. Heidbuchel H, Wittkampf FH, Vano E, Ernst S, Schilling R, Picano E, et al. Practical ways to reduce radiation dose for patients and staff during device implantations and electrophysiological procedures. Europace. 2014; 16(7): 946-64. Initially reported approximately 10 years ago, “Zero-Fluoro” techniques are increasingly used in the electrophysiological community because they have been shown as safe and effective as traditional methods guided by fluoroscopy.4848. Lerman BB, Markowitz SM, Liu CF, Thomas G, Ip JE, Cheung JW. Fluoroless catheter ablation of atrial fibrillation. Heart Rhythm. 2017; 14(6): 928-34.

49. Razminia M, Willoughby MC, Demo H, Keshmiri H, Wang T, D’Silva O, et al. Fluoroless Catheter Ablation of Cardiac Arrhythmias: A 5-Year Experience. Pacing Clin Electrophysiol. 2017; 40(4): 425-33.
-5050. Saad EB, Slater C, Inacio LAO, Jr., Santos GVD, Dias LC, Camanho LEM. Catheter Ablation for Treatment of Atrial Fibrillation and Supraventricular Arrhythmias Without Fluoroscopy Use: Acute Efficacy and Safety. Arq Bras Cardiol. 2020; 114(6): 1015-26.

Recurrences

Two main factors justify AF recurrences after ablation:

1. Reconnection or recurrent conduction in the PVs – for circumferential lesions to provide permanent PV isolation, contiguous fibrous tissue formation should form usually four to eight weeks after the acute injury (energy-induced tissue edema). If the lesion is not deep enough in the atrial wall, there may be remaining viable tissue after edema resorption. It only takes a small recovered segment to restore electrical PV-LA connection.

2. Occurrence of ectopic foci outside the PVs (non-PV triggers) – these occur more commonly (but not only) in persistent forms of AF or in patients with significant atrial remodeling.

PV reconnection is easily solved with new RF applications in conduction gaps. Reintervention is usually quick, easy and safe. In paroxysmal AF, it increases the control rates of AF in approximately 95% of cases. With the use of catheters with contact-force sensors, it has become an increasingly rare phenomenon5151. Natale A, Reddy VY, Monir G, Wilber DJ, Lindsay BD, McElderry HT, et al. Paroxysmal AF catheter ablation with a contact force sensing catheter: results of the prospective, multicenter SMART-AF trial. J Am Coll Cardiol. 2014; 64(7): 647-56.

52. Reddy VY, Dukkipati SR, Neuzil P, Natale A, Albenque AP, Kautzner J, et al. Randomized, Controlled Trial of the Safety and Effectiveness of a Contact Force-Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial Fibrillation: Results of the TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) Study. Circulation. 2015; 132(10): 907-15.
-5353. De Pooter J, Strisciuglio T, El Haddad M, Wolf M, Phlips T, Vandekerckhove Y, et al. Pulmonary Vein Reconnection No Longer Occurs in the Majority of Patients After a Single Pulmonary Vein Isolation Procedure. JACC Clin Electrophysiol. 2019; 5(3): 295-305.as RF lesions tend to be deeper and permanent.5454. Gokoglan Y, Mohanty S, Gunes MF, Trivedi C, Santangeli P, Gianni C, et al. Pulmonary Vein Antrum Isolation in Patients With Paroxysmal Atrial Fibrillation: More Than a Decade of Follow-Up. Circ Arrhythm Electrophysiol. 2016; 9(5)e003660.

Non-PV triggers represent a more diffuse atrial substrate; their recognition and extensive ablation are necessary to improve outcomes, without which arrhythmia control is usually not possible.3333. Hayashi K, An Y, Nagashima M, Hiroshima K, Ohe M, Makihara Y, et al. Importance of nonpulmonary vein foci in catheter ablation for paroxysmal atrial fibrillation. Heart Rhythm. 2015; 12(9):1918-24.,5454. Gokoglan Y, Mohanty S, Gunes MF, Trivedi C, Santangeli P, Gianni C, et al. Pulmonary Vein Antrum Isolation in Patients With Paroxysmal Atrial Fibrillation: More Than a Decade of Follow-Up. Circ Arrhythm Electrophysiol. 2016; 9(5)e003660.,5555. Della Rocca DG, Mohanty S, Trivedi C, Di Biase L, Natale A. Percutaneous Treatment of Non-paroxysmal Atrial Fibrillation: A Paradigm Shift from Pulmonary Vein to Non-pulmonary Vein Trigger Ablation? Arrhythm Electrophysiol Rev. 2018; 7(4): 256-60. They are most commonly located at the LA posterior wall, LAA and coronary sinus3232. Santangeli P, Zado ES, Hutchinson MD, Riley MP, Lin D, Frankel DS, et al. Prevalence and distribution of focal triggers in persistent and long-standing persistent atrial fibrillation. Heart Rhythm. 2016; 13(2): 374-82.,5454. Gokoglan Y, Mohanty S, Gunes MF, Trivedi C, Santangeli P, Gianni C, et al. Pulmonary Vein Antrum Isolation in Patients With Paroxysmal Atrial Fibrillation: More Than a Decade of Follow-Up. Circ Arrhythm Electrophysiol. 2016; 9(5)e003660. — structures that can also be isolated by RF applications. It is certainly possible to maintain sinus rhythm in the long term, even if more than one intervention if necessary.

Patient Selection and Results

The selection of patients for catheter ablation of AF is currently mainly based on the failure of medical therapy (Table 2). According to the last HRS/EHRA/ECAS/APHRS/SOLAECE consensus of experts in 2017,1111. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017;14(10): e275-e444. the primary indication for AF ablation is the presence of symptomatic paroxysmal or persistent AF, refractory or intolerant to at least one class I or III antiarrhythmic drug. There is solid evidence for improved quality-of-life parameters in these patients.55. Mark DB, Anstrom KJ, Sheng S, Piccini JP, Baloch KN, Monahan KH, et al. Effect of Catheter Ablation vs Medical Therapy on Quality of Life Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019; 321(13): 1275-85.,5656. Blomstrom-Lundqvist C, Gizurarson S, Schwieler J, Jensen SM, Bergfeldt L, Kenneback G, et al. Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation: The CAPTAF Randomized Clinical Trial. JAMA. 2019; 321(11): 1059-68.

Table 2
– Indications for atrial fibrillation ablation

AF ablation can be performed in patients with various types of heart disease (coronary artery disease, left ventricular hypertrophy, heart failure) and clinical presentations of AF (paroxysmal, persistent or long-lasting persistent), but the best results are obtained for patients with structurally normal hearts. In the largest randomized study that compared ablation with pharmacological therapy (CABANA),77. Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, PooleJE, et al. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019; 321(13): 1261-74. survival free of recurrent AF is significantly better (HR 0.53) in ablated patients compared to those who remained on multiple antiarrhythmic drugs. Nevertheless, in this study, there was no reduction in a combined hard endpoint (death, stroke, severe bleeding or cardiac arrest) in the “intention-to-treat” analysis, although there were problems with large crossover rates for the ablation group (27%). In this study, the subgroups that benefited the most were the youngest (<65 years) and patients with congestive heart failure.

The selection of patients with persistent and long-standing persistent forms of AF follows the same reasoning, but the decision should be individualized according to parameters of remodeling such as LA size or volume5757. Njoku A, Kannabhiran M, Arora R, Reddy P, Gopinathannair R, Lakkireddy D, et al. Left atrial volume predicts atrial fibrillation recurrence after radiofrequency ablation: a meta-analysis. Europace. 2018; 20(1): 33-42.(which is an important predictor of recurrence) and AF duration. Persistent AF is a heterogeneous disease, with different degrees of atrial fibrosis and with influence of the autonomic nervous system and other pathophysiological processes still poorly understood, which explains the heterogeneous results observed with different ablation strategies. Targeting this type of AF requires an individualized definition of the substrate and mechanisms involved.5858. Mohanty S, Mohanty P, Di Biase L, Trivedi C, Morris EH, Gianni C, et al. Long-term follow-up of patients with paroxysmal atrial fibrillation and severe left atrial scarring: comparison between pulmonary vein antrum isolation only or pulmonary vein isolation combined with either scar homogenization or trigger ablation. Europace. 2017; 19(11): 1790-7.,5959. Fochler F, Yamaguchi T, Kheirkahan M, Kholmovski EG, Morris AK, Marrouche NF. Late Gadolinium Enhancement Magnetic Resonance Imaging Guided Treatment of Post-Atrial Fibrillation Ablation Recurrent Arrhythmia. Circ Arrhythm Electrophysiol. 2019; 12(8): e007174.

It is important to note that even with the strategy of extensive RF applications described above, higher recurrences rates and need for reinterventions are observed. In the experience of Natale et. al., 60% of patients maintained sinus rhythm without drugs after the first procedure.5454. Gokoglan Y, Mohanty S, Gunes MF, Trivedi C, Santangeli P, Gianni C, et al. Pulmonary Vein Antrum Isolation in Patients With Paroxysmal Atrial Fibrillation: More Than a Decade of Follow-Up. Circ Arrhythm Electrophysiol. 2016; 9(5)e003660. In those undergoing a second intervention, 80% maintained sinus rhythm. Table 3 summarizes some of the main published studies.

Table 3
– Trials in atrial fibrillation ablation

Catheter ablation is less effective in certain subgroups of patients,6060. Al-Khatib SM, Benjamin EJ, Buxton AE, Calkins H, Chung MK, Curtis AB, et al. Research Needs and Priorities for Catheter Ablation of Atrial Fibrillation: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop. Circulation. 2020; 141(6): 482-92. where advances in pathophysiological knowledge are still needed: dilated and fibrous atria, persistent or long-standing AF, hypertrophic cardiomyopathy, amyloid infiltrate, obesity and sleep apnea.

Long-term follow-up of patients undergoing catheter ablation shows the occurrence of late recurrences,6161. Steinberg JS, Palekar R, Sichrovsky T, Arshad A, Preminger M, Musat D, et al. Very long-term outcome after initially successful catheter ablation of atrial fibrillation. Heart Rhythm. 2014; 11(5): 771-6.

62. Takigawa M, Takahashi A, Kuwahara T, Okubo K, Takahashi Y, Watari Y, et al. Long-term follow-up after catheter ablation of paroxysmal atrial fibrillation: the incidence of recurrence and progression of atrial fibrillation. Circ Arrhythm Electrophysiol. 2014; 7(2): 267-73.
-6363. Tilz RR, Heeger CH, Wick A, Saguner AM, Metzner A, Rillig A, et al. Ten-Year Clinical Outcome After Circumferential Pulmonary Vein Isolation Utilizing the Hamburg Approach in Patients With Symptomatic Drug-Refractory Paroxysmal Atrial Fibrillation. Circ Arrhythm Electrophysiol. 2018; 11(2): e005250. around 7% per year in the first 5 years. It should be noted that the estimation of the actual success of ablation is hampered by inconsistencies and heterogeneities in the definitions of success and recurrences in the different published studies. As an example, most studies consider as a recurrence any atrial arrhythmia lasting more than 30 seconds, a definition with clearly little clinical significance. In this scenario, the AF burden should be more valued and clinically meaningful in future research.

As new technologies and experiences tend to promote permanent PV isolation, recurrence is currently more frequently observed due to the appearance of non-PV triggers, which should be identified and addressed3232. Santangeli P, Zado ES, Hutchinson MD, Riley MP, Lin D, Frankel DS, et al. Prevalence and distribution of focal triggers in persistent and long-standing persistent atrial fibrillation. Heart Rhythm. 2016; 13(2): 374-82.,3333. Hayashi K, An Y, Nagashima M, Hiroshima K, Ohe M, Makihara Y, et al. Importance of nonpulmonary vein foci in catheter ablation for paroxysmal atrial fibrillation. Heart Rhythm. 2015; 12(9):1918-24.,5454. Gokoglan Y, Mohanty S, Gunes MF, Trivedi C, Santangeli P, Gianni C, et al. Pulmonary Vein Antrum Isolation in Patients With Paroxysmal Atrial Fibrillation: More Than a Decade of Follow-Up. Circ Arrhythm Electrophysiol. 2016; 9(5)e003660.,6464. Lin D, Santangeli P, Zado ES, Bala R, Hutchinson MD, Riley MP, et al. Electrophysiologic findings and long-term outcomes in patients undergoing third or more catheter ablation procedures for atrial fibrillation. J Cardiovasc Electrophysiol. 2015; 26(4): 371-7.. Therefore, it is important to maintain periodic monitoring of patients and it is prudent to maintain anticoagulant therapy in patients at higher risk who do not have contraindications.

Table 4 summarizes adjuvant care to maximize the safety and efficacy of the ablation procedure.

Table 4
– Adjunctive Strategies for atrial fibrillation ablation

Special Situations

International guidelines published in 2016 and 2017 and updated in 2019 and 2020 by different international societies (SBC/HRS/EHRA/ECAS/APHRS/ACC/AHA/ESC/EHRA)1111. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017;14(10): e275-e444.

12. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland Jr JC, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019; 140(2):e125-e51.
-1313. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016; 37(38): 2893-962.,1515. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020. almost consensually recommend ablative treatment in special situations (Table 2):

1) Ablation as first-choice therapy:

Increasing safety and efficacy allow ablation to be offered as first-line therapy for treatment (even before the use of antiarrhythmic drugs) in some special situations (athletes, young people, normal hearts).6565. Morillo CA, Verma A, Connolly SJ, Kuck KH, Nair GM, Champagne J, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. JAMA. 2014; 311(7): 692-700.,6666. Walfridsson H, Walfridsson U, Nielsen JC, Johannessen A, Raatikainen P, Janzon M, et al. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial. Europace. 2015; 17(2): 215-21. It is a Class IIa indication for patients with symptomatic paroxysmal or persistent AF. Other appropriate situations for this strategy are patients with symptomatic pauses upon arrhythmia interruption (brady-tachy syndrome)6767. Khaykin Y, Marrouche NF, Martin DO, Saliba W, Schweikert R, Wexman M, et al. Pulmonary vein isolation for atrial fibrillation in patients with symptomatic sinus bradycardia or pauses. J Cardiovasc Electrophysiol. 2004; 15(7): 784-9. or in competitive athletes, who may have contraindications to antiarrhythmic drug use.

2) AF in patients with Heart Failure (HF):

HF may predispose to AF occurrence through various mechanisms, such as increased left ventricular filling pressures or LA dilatation and fibrosis, leading to atrial structural and electrical remodeling. AF can increase mortality in patients with left ventricular dysfunction.6868. Swedberg K, Olsson LG, Charlesworth A, Cleland J, Hanrath P, Komajda M, et al. Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET. Eur Heart J. 2005; 26(13): 1303-8. Treatment of AF in this subset of patients is of critical importance6969. Di Biase L, Mohanty P, Mohanty S, Santangeli P, Trivedi C, LakkiReddy D, et al. Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Multicenter Randomized Trial. Circulation. 2016; 133(17): 1637-44.

70. Hunter RJ, Berriman TJ, Diab I, Kamdar R, Richmond L, Baker V, et al. A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial). Circ Arrhythm Electrophysiol. 2014; 7(1): 31-8.

71. Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008; 358(25): 2667-77.

72. Lobo TJ, Pachon CT, Pachon JC, Pachon EI, Pachon MZ, Pachon JC, et al. Atrial fibrillation ablation in systolic dysfunction: clinical and echocardiographic outcomes. Arq Bras Cardiol. 2015; 104(1): 45-52.
-7373. Scanavacca M, Bocchi EA. Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure. Arq Bras Cardiol. 2018; 110(4): 300-2.given the limitations of Amiodarone, the only antiarrhythmic drug available for this subgroup. In the most recent European guidelines published in 2020, AF ablation in patients with HF received a Class Ia1515. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020. indication based on comparative studies with Amiodarone (AATAC)6969. Di Biase L, Mohanty P, Mohanty S, Santangeli P, Trivedi C, LakkiReddy D, et al. Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Multicenter Randomized Trial. Circulation. 2016; 133(17): 1637-44. and the publication of randomized studies such as AMICA7474. Kuck KH, Merkely B, Zahn R, Arentz T, Seidl K, Schluter M, et al. Catheter Ablation Versus Best Medical Therapy in Patients With Persistent Atrial Fibrillation and Congestive Heart Failure: The Randomized AMICA Trial. Circ Arrhythm Electrophysiol. 2019; 12(12): e007731. and CASTLE-AF,7575. Marrouche NF, Brachmann J, Andresen D, Siebels J, Boersma L, Jordaens L, et al. Catheter Ablation for Atrial Fibrillation with Heart Failure. N Engl J Med. 2018; 378(5): 417-27. the latter performed in patients with severe HF (mean EF 32%), demonstrating a significant reduction in mortality or hospitalization for HF (38%) and cardiovascular mortality (51%). These unprecedented findings confirm the negative prognosis of AF in this population and open a new frontier of indications for ablation in centers with adequate experience and infrastructure. Recent positive results are encouraging, with demonstration of improvement in ventricular function and reversal of atrial remodeling.7676. Sugumar H, Prabhu S, Voskoboinik A, Young S, Gutman SJ, Wong JR, et al. Atrial Remodeling Following Catheter Ablation for Atrial Fibrillation-Mediated Cardiomyopathy: Long-Term Follow-Up of CAMERA-MRI Study. JACC Clin Electrophysiol. 2019; 5(6): 681-8.

3) AF in the elderly:

There are studies that have focused on reporting the results of AF ablation in older individuals. The age limit for the definition of elderly ranged from ≥70, 75 or 80 years. However, the number of elderlies in these studies was relatively small, with five of the seven studies enrolling less than 100 patients and the largest series reporting on 261 patients. Overall, the results of these studies provide evidence that ablation meets safety and efficacy criteria in this population,7777. Nademanee K, Amnueypol M, Lee F, Drew CM, Suwannasri W, Schwab MC, et al. Benefits and risks of catheter ablation in elderly patients with atrial fibrillation. Heart Rhythm. 2015; 12(1): 44-51.,7878. Santangeli P, Di Biase L, Mohanty P, Burkhardt JD, Horton R, Bai R, et al. Catheter ablation of atrial fibrillation in octogenarians: safety and outcomes. J Cardiovasc Electrophysiol. 2012; 23(7): 687-93. despite a reduction in AF-free survival rates with every decade of age (Class IIa).

4) AF in asymptomatic patients and reduced risk of stroke:

Ablation of AF (paroxysmal or persistent) in truly asymptomatic patients can be considered7979. Kalman JM, Sanders P, Rosso R, Calkins H. Should We Perform Catheter Ablation for Asymptomatic Atrial Fibrillation? Circulation. 2017; 136(5): 490-9. despite the lack of definitive evidence of significant changes in hard outcomes – particularly in the risk of thromboembolic phenomena/stroke. It should be performed by experienced operators and after a detailed discussion of the risks and benefits (Class IIb). There is solid evidence of reduction of hospitalizations8080. Guo J, Nayak HM, Besser SA, Beaser A, Aziz Z, Broman M, et al. Impact of Atrial Fibrillation Ablation on Recurrent Hospitalization: A Nationwide Cohort Study. JACC Clin Electrophysiol. 2019; 5(3): 330-9.and resource utilization, with favorable cost-effectiveness.1010. Saad EB, Tayar DO, Ribeiro RA, Junqueira SM, Jr., Andrade P, d’Avila A. Healthcare Utilization and Costs Reduction after Radiofrequency Ablation For Atrial Fibrillation in the Brazilian Private Healthcare System. Arq Bras Cardiol. 2019; 113(2): 252-7. In this scenario, patients with a higher probability of success should be prioritized (young people, paroxysmal AF, without significant atrial remodeling).

Several retrospective observational studies point to a significant reduction in thromboembolic risks in patients with CHADVASC score ≤3 undergoing successful AF ablation,8181. Saad EB, d’Avila A, Costa IP, Aryana A, Slater C, Costa RE, et al. Very low risk of thromboembolic events in patients undergoing successful catheter ablation of atrial fibrillation with a CHADS2 score ≤3: a long-term outcome study. Circ Arrhythm Electrophysiol. 2011; 4(5): 615-21.

82. Proietti R, AlTurki A, Di Biase L, China P, Forleo G, Corrado A, et al. Anticoagulation after catheter ablation of atrial fibrillation: An unnecessary evil? A systematic review and meta-analysis. J Cardiovasc Electrophysiol. 2019; 30(4): 468-78.

83. Themistoclakis S, Corrado A, Marchlinski FE, Jais P, Zado E, Rossillo A, et al. The risk of thromboembolism and need for oral anticoagulation after successful atrial fibrillation ablation. J Am Coll Cardiol. 2010; 55(8): 735-43.

84. Bunch TJ, May HT, Bair TL, Weiss JP, Crandall BG, Osborn JS, et al. Atrial fibrillation ablation patients have long-term stroke rates similar to patients without atrial fibrillation regardless of CHADS2 score. Heart Rhythm. 2013; 10(9): 1272-7.

85. Bunch TJ, Crandall BG, Weiss JP, May HT, Bair TL, Osborn JS, et al. Patients treated with catheter ablation for atrial fibrillation have long-term rates of death, stroke, and dementia similar to patients without atrial fibrillation. J Cardiovasc Electrophysiol. 2011; 22(8): 839-45.

86. Kalbfleisch SJ. Atrial fibrillation ablation, stroke, and mortality: Evaluating the effects of therapy in the era of big data. Heart Rhythm. 2017; 14(5): 643-4.
-8787. Saliba W, Schliamser JE, Lavi I, Barnett-Griness O, Gronich N, Rennert G. Catheter ablation of atrial fibrillation is associated with reduced risk of stroke and mortality: A propensity score-matched analysis. Heart Rhythm. 2017; 14(5): 635-42. many of them reporting favorable outcomes even in patients who discontinued anticoagulant therapy. Data from the KP-RHYTHM8888. Go AS, Reynolds K, Yang J, Gupta N, Lenane J, Sung SH, et al. Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study. JAMA Cardiol. 2018; 3(7): 601-8.study, proving that the risk of stroke is proportional to the burden of AF in paroxysmal patients, regardless of CHADVASC score, and a metanalysis from randomized studies8989. Asad ZUA, Yousif A, Khan MS, Al-Khatib SM, Stavrakis S. Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Circ Arrhythm Electrophysiol. 2019; 12(9): e007414. suggesting reduced mortality and hospitalizations, are compatible with the hypothesis of risk reduction after a successful ablation.

It should be emphasized, however, that there is no direct evidence from randomized studies specifically designed for this purpose; the CABANA77. Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, PooleJE, et al. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019; 321(13): 1261-74. trial did not show any reduction in a combined endpoint in a heterogeneous population (paroxysmal and persistent AF) comparing ablation versus drug treatment. The recently published EAST-AFNET 49090. Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020 Oct 1;383(14):1305-1316. demonstrated a significant benefit in cardiovascular outcomes with a strategy of early rhythm control compared to heart rate control, but in this important randomized study, only 20% of patients were treated with ablation.

All current guidelines recommend that ablative treatment should not aim at discontinuation of anticoagulant therapy,1111. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017;14(10): e275-e444.

12. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland Jr JC, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019; 140(2):e125-e51.

13. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016; 37(38): 2893-962.
-1414. Magalhaes LP, Figueiredo MJO, Cintra FD, Saad EB, Kuniyoshi RR, Lorga Filho AM, et al. Executive Summary of the II Brazilian Guidelines for Atrial Fibrillation. Arq Bras Cardiol 2016; 107(6): 501-8. which should have its indication based on the baseline risk of the patient (usually indicated in patients with CHADSVASC score ≥ 2). All patients undergoing ablation should use anticoagulants for a minimum period of 2 months regardless of risk factors, and its continuation should be individualized by the risk score.

The ongoing OCEAN9191. Verma A, Ha ACT, Kirchhof P, Hindricks G, Healey JF, Hill MD, et al. The Optimal Anti-Coagulation for Enhanced-Risk Patients Post-Catheter Ablation for Atrial Fibrillation (OCEAN) trial. Am Heart J. 2018; 197: 124-32. study compares the maintenance of anticoagulation therapy (Rivaroxaban) with Aspirin in patients at moderate to severe risk undergoing ablation and maintaining sinus rhythm for at least 1 year after the procedure. The results should help refine indications of long-term anticoagulation after ablation.

Complications

The ablation procedure is associated with low complication rates in centers of excellence with high volume and experience, with major complications individually lower than 1% in highly experienced centers.1111. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017;14(10): e275-e444.Table 5 summarizes the main complications and their incidences as reported in the literature.

Table 5
– Complications Related to AF Ablation

It is important to be aware of a late complication (in the first weeks) related to esophageal injury due to its proximity to the LA posterior wall. During energy application in this region, power and/or time should be reduced, in addition to monitoring the luminal esophageal temperature (Table 4). An available alternative consists of different methods of mechanical esophageal deviation to increase its distance from the site of energy delivery.9292. Mateos JC, Mateos EI, Pena TG, Lobo TJ, Mateos JC, Vargas RN, et al. Simplified method for esophagus protection during radiofrequency catheter ablation of atrial fibrillation--prospective study of 704 cases. Rev Bras Cir Cardiovasc. 2015; 30(2): 139-47.

93. Bhardwaj R, Naniwadekar A, Whang W, Mittnacht AJ, Palaniswamy C, Koruth JS, et al. Esophageal Deviation During Atrial Fibrillation Ablation: Clinical Experience With a Dedicated Esophageal Balloon Retractor. JACC Clin Electrophysiol. 2018; 4(8): 1020-30.

94. Iwasawa J, Koruth JS, Mittnacht AJ, Tran VN, Palaniswamy C, Sharma D, et al. The impact of mechanical oesophageal deviation on posterior wall pulmonary vein reconnection. Europace. 2020; 22(2): 232-9.
-9595. Palaniswamy C, Koruth JS, Mittnacht AJ, Miller MA, Choudry S, Bhardwaj R, et al. The Extent of Mechanical Esophageal Deviation to Avoid Esophageal Heating During Catheter Ablation of Atrial Fibrillation. JACC Clin Electrophysiol. 2017; 3(10): 1146-54. There are reports of atrio-esophageal fistulas, with a high mortality rate.9696. Vasconcelos JT, Filho S, Atie J, Maciel W, Souza OF, Saad EB, et al. Atrial-oesophageal fistula following percutaneous radiofrequency catheter ablation of atrial fibrillation: the risk still persists. Europace. 2017; 19(2): 250-8.

97. Calkins H, Natale A, Gomez T, Etlin A, Bishara M. Comparing rates of atrioesophageal fistula with contact force-sensing and non-contact force-sensing catheters: analysis of post-market safety surveillance data. J Interv Card Electrophysiol. 2019.

98. Gunes MF, Gokoglan Y, Biase L, Gianni C, Mohanty S, Horton R, et al. Ablating the Posterior Heart: Cardioesophageal Fistula Complicating Radiofrequency Ablation in the Coronary Sinus. J Cardiovasc Electrophysiol. 2015; 26(12): 1376-8.

99. Mohanty S, Santangeli P, Mohanty P, Biase L, Trivedi C, Bai R, et al. Outcomes of atrioesophageal fistula following catheter ablation of atrial fibrillation treated with surgical repair versus esophageal stenting. J Cardiovasc Electrophysiol. 2014; 25(6): 579-84.
-100100. Han HC, Ha FJ, Sanders P, Spencer R, Teh AW, O’Donnell D, et al. Atrioesophageal Fistula: Clinical Presentation, Procedural Characteristics, Diagnostic Investigations, and Treatment Outcomes. Circ Arrhythm Electrophysiol. 2017; 10(11). Fortunately, this is a rare complication, with an estimated incidence of approximately 0.04%. Its early recognition is critical to avoid a fatal outcome.9999. Mohanty S, Santangeli P, Mohanty P, Biase L, Trivedi C, Bai R, et al. Outcomes of atrioesophageal fistula following catheter ablation of atrial fibrillation treated with surgical repair versus esophageal stenting. J Cardiovasc Electrophysiol. 2014; 25(6): 579-84.,101101. Wu TC, Pisani C, Scanavacca MI. Approaches to the Diagnosis and Management of Atrial-Esophageal Fistula After Catheter Ablation for Atrial Arrhythmias. Curr Cardiovasc Risk Rep. 2019; 13.

102. Pappone C, Vicedomini G, Santinelli V. Atrio-Esophageal Fistula After AF Ablation: Pathophysiology, Prevention &Treatment. J Atr Fibrillation. 2013; 6(3): 860.
-103103. Kim YG, Shim J, Lee KN, Lim JY, Chung JH, Jung JS, et al. Management of Atrio-esophageal Fistula Induced by Radiofrequency Catheter Ablation in Atrial Fibrillation Patients: a Case Series. Sci Rep. 2020; 10(1): 8202.

Future Perspectives

The use of high-power RF with short duration has been advocated to produce better quality tissue lesions,104104. Bhaskaran A, Chik W, Pouliopoulos J, Nalliah C, Qian P, Barry T, et al. Five seconds of 50-60 W radio frequency atrial ablations were transmural and safe: an in vitro mechanistic assessment and force-controlled in vivo validation. Europace. 2017; 19(5): 874-80.,105105. Leshem E, Zilberman I, Tschabrunn CM, Barkagan M, Contreras-Valdes FM, Govari A, et al. High-Power and Short-Duration Ablation for Pulmonary Vein Isolation: Biophysical Characterization. JACC Clin Electrophysiol. 2018; 4(4): 467-79. besides causing wider and shallower lesions and therefore less risk of collateral damage (especially to the esophagus). This technique was associated with shorter RF application and LA instrumentation times and low complication rates,106106. Winkle RA, Moskovitz R, Hardwin Mead R, Engel G, Kong MH, Fleming W, et al. Atrial fibrillation ablation using very short duration 50 W ablations and contact force sensing catheters. J Interv Card Electrophysiol. 2018; 52(1): 1-8.,107107. Winkle RA, Mohanty S, Patrawala RA, Mead RH, Kong MH, Engel G, et al. Low complication rates using high power (45-50 W) for short duration for atrial fibrillation ablations. Heart Rhythm. 2019; 16(2): 165-9. boosting further investigations of catheters that can cause more permanent lesions within seconds of energy delivery.108108. Reddy VY, Grimaldi M, De Potter T, Vijgen JM, Bulava A, Duytschaever MF, et al. Pulmonary Vein Isolation With Very High Power, Short Duration, Temperature-Controlled Lesions: The QDOT-FAST Trial. JACC Clin Electrophysiol. 2019; 5(7): 778-86.

There are great expectations for the development of a new energy source for ablation: “electroporation”. Unlike thermal energies (RF, cryotherapy, laser, ultrasound and microwave), which damages all tissues indiscriminately, pulsed field ablation (PFA) or “electroporation,” which is a non-thermal ablation modality in which ultrafast electric fields (<1 s) are applied to target tissue selectively, destabilizing cell membranes and culminating in cell death. This is possible because tissues have different thresholds for necrosis. This technology is already in use to treat unresectable solid tumors in close proximity to blood vessels or nerves, given their different resistance to pulsed electric fields.109109. Rubinsky B, Onik G, Mikus P. Irreversible electroporation: a new ablation modality--clinical implications. Technol Cancer Res Treat. 2007; 6(1): 37-48.,110110. Davalos RV, Mir IL, Rubinsky B. Tissue ablation with irreversible electroporation. Ann Biomed Eng. 2005; 33(2): 223-31. Cardiomyocytes have one of the lowest tissue injury thresholds, and PFA can therefore be applied during catheter ablation, limiting collateral damage to nearby structures such as the esophagus111111. Koruth JS, Kuroki K, Kawamura I, Brose R, Viswanathan R, Buck ED, et al. Pulsed Field Ablation vs Radiofrequency Ablation: Esophageal Injury in a Novel Porcine Model. Circ Arrhythm Electrophysiol. 2020 Mar;13(3):e008303.and phrenic nerve.112112. Koruth JS, Kuroki K, Iwasawa J, Viswanathan R, Brose R, Buck ED, et al. Endocardial ventricular pulsed field ablation: a proof-of-concept preclinical evaluation. Europace. 2020 Mar 1;22(3):434-9

Initial experience in patients undergoing ultra-fast PV isolation is very promising, with permanent isolation rates never reported before (100%).113113. Reddy VY, Neuzil P, Koruth JS, Petru J, Funosako M, Cochet H, et al. Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial Fibrillation. J Am Coll Cardiol. 2019; 74(3): 315-26. This technology has great potential to replace RF and other thermal energies for catheter treatment of AF.

The recently published ERADICATE-AF114114. Steinberg JS, Shabanov V, Ponomarev D, Losik D, Ivanickiy E, Kropotkin E, et al. Effect of Renal Denervation and Catheter Ablation vs Catheter Ablation Alone on Atrial Fibrillation Recurrence Among Patients With Paroxysmal Atrial Fibrillation and Hypertension: The ERADICATE-AF Randomized Clinical Trial. JAMA. 2020; 323(3): 248-55. study evaluated the additional effect of catheter renal denervation in 302 hypertensive patients undergoing AF ablation, randomized to simply PV isolation or combined with renal artery ablation. The addition of denervation resulted in better AF-free survival at 12 months (72% vs. 56%). These findings certainly need to be replicated in a blinded model of renal denervation, but modulation of the autonomic nervous system is an important pathophysiological mechanism that should be further explored.

Conclusions

Catheter ablation is the most effective method for rhythm control in patients with AF, associated with significant improvement in symptoms, AF burden, quality of life and hospital admissions. It is associated with low complication rates when performed in experienced centers. Its role in reducing thromboembolic events and mortality still needs definitive proof in future randomized studies.

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  • Study Association
    This study is not associated with any thesis or dissertation work.
  • Sources of Funding.There were no external funding sources for this study.

Publication Dates

  • Publication in this collection
    01 Mar 2021
  • Date of issue
    Feb 2021

History

  • Received
    30 May 2020
  • Reviewed
    05 Sept 2020
  • Accepted
    22 Oct 2020
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