INTRODUCTION

During the past decade, catheter ablation of atrial fibrillation (AF) has evolved rapidly from an investigational procedure to its current status as a commonly performed ablation procedure in many major hospitals throughout the world. Surgical ablation of AF, using either standard or minimally invasive techniques, is also performed in many major hospitals throughout the world.

In 2007, an initial Consensus Statement on Catheter and Surgical AF Ablation was developed as a joint effort of the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society.1 The 2007 document was also developed in collaboration with the Society of Thoracic Surgeons and the American College of Cardiology. Since the publication of the 2007 document, there has been much learned about AF ablation, and the indications for these procedures have changed. Therefore the purpose of this 2012 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a Task Force, convened by the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society and charged with defining the indications, techniques, and outcomes of this procedure. Included within this document are recommendations pertinent to the design of clinical trials in the field of AF ablation, including definitions relevant to this topic.

This statement summarizes the opinion of the Task Force members based on an extensive literature review as well as their own experience. It is directed to all health care professionals who are involved in the care of patients with AF, particularly those who are undergoing, or are being considered for, catheter or surgical ablation procedures for AF. This statement is not intended to recommend or promote catheter ablation of AF. Rather the ultimate judgment regarding care of a particular patient must be made by the health care provider and patient in light of all the circumstances presented by that patient.

In writing a “consensus” document, it is recognized that consensus does not mean that there was complete agreement among all Task Force members. Surveys of the entire Task Force were used to identify areas of consensus and also to develop recommendations concerning the indications for catheter and surgical AF ablation. The grading system for indication level of class of evidence was adapted based on that used by the American College of Cardiology and the American Heart Association.2 However, it is important to state that this document is not a guideline. The indications for catheter and surgical ablation of AF are presented with a class and grade of recommendation to be consistent with what the reader is used to seeing in guideline statements. A Class I recommendation means that the benefits of the AF ablation procedure markedly exceed the risks, and that AF ablation should be performed. A Class IIa recommendation means that the benefits of an AF ablation procedure exceed the risks, and that it is reasonable to perform AF ablation. A Class IIb recommendation means that the benefit of AF ablation is greater or equal to the risks, and that AF ablation may be considered. A Class III recommendation means that AF ablation is of no proven benefit and is not recommended.

The committee reviewed and ranked evidence supporting current recommendations with the weight of evidence ranked as Level A if the data were derived from multiple randomized clinical trials or meta-analyses (of selected studies) or selected meta-analyses. The committee ranked available evidence as Level B when data were derived from a single randomized trial or nonrandomized studies. Evidence was ranked as Level C when the primary source of the recommendation was consensus opinion, case studies, or standard of care. For certain conditions for which inadequate data are available, recommendations are based on expert consensus and clinical experience and ranked as Level C.

The main objective of this document is to improve patient care by providing a foundation of knowledge for those involved with catheter ablation of AF. It is recognized that this field continues to evolve rapidly. As this document was being prepared, further clinical trials of catheter and surgical ablation of AF were underway.

The Task Force writing group was composed of experts representing seven organizations: the American College of Cardiology (ACC), the American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), the European Cardiac Arrhythmia Society (ECAS), the European Heart Rhythm Association (EHRA), the Society of Thoracic Surgeons (STS), and the Heart Rhythm Society (HRS). All members of the Task Force, as well as peer reviewers of the document, were asked to provide disclosure statements for all relationships that might be perceived as real or potential conflicts of interest. These tables are shown at the end of this document. Despite a large number of authors, the participation of several societies and professional organizations, and the attempts of the group to reflect the current knowledge in the field adequately, this document is not intended as a guideline. Rather, the group would like to refer to the current guidelines on AF management3,4 for the purpose of guiding overall AF management strategies. This Consensus Document is specifically focused on catheter and surgical ablation of AF, which we recognize is relevant for only a small portion of the population affected by AF.

ATRIAL FIBRILLATION: DEFINITIONS, MECHANISMS, AND RATIONALE FOR ABLATION

Definitions

AF is a common supraventricular arrhythmia that is characterized by chaotic contraction of the atrium. An electrocardiogram (ECG) recording is necessary to diagnose AF. Any arrhythmia that has the ECG characteristics of AF and lasts sufficiently long for a 12-lead ECG to be recorded, or at least 30 seconds on a rhythm strip, should be considered an AF episode.1,3 The diagnosis requires an ECG or rhythm strip demonstrating: (1) “absolutely” irregular RR intervals (in the absence of complete AV block), (2) no distinct P waves on the surface ECG, and (3) an atrial cycle length (when visible) that is usually variable and less than 200 milliseconds.3 Although there are several classification systems for AF, for this consensus document, we have adopted in large part the classification system that was developed by the ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation and the ESC 2010 Guidelines for the Management of Atrial Fibrillation.2,3,5 We recommend that this classification system be used for future studies of catheter and surgical ablation of AF.

Every patient who presents with AF for the first time is considered to have first diagnosed AF, irrespective of the duration of the arrhythmia. Paroxysmal AF is defined as recurrent AF (≥two episodes) that terminates spontaneously within seven days (Table 1). Persistent AF is defined as recurrent AF that is sustained for > seven days. In addition, we recommend that patients with continuous AF who undergo cardioversion within seven days be classified as having paroxysmal AF if the cardioversion is performed within 48 hours of AF onset, and persistent AF if the cardioversion is performed more than 48 hours after AF onset. A third category of AF is “longstanding persistent AF” that is defined as continuous AF of greater than one year's duration. The term permanent AF is defined as AF in which the presence of the AF is accepted by the patient (and physician). Within the context of any rhythm control strategy, including catheter ablation, the term permanent AF is not meaningful. The term permanent AF represents a joint decision by the patient and a physician to cease further attempts to restore and/or maintain sinus rhythm at a particular point in time. It is important, therefore, to recognize that the term “permanent AF” represents a therapeutic attitude on the part of a patient and their physician rather than any inherent pathophysiological attribute of the AF. Such decisions may change as symptoms, the efficacy of therapeutic interventions, and patient and physician preferences evolve. If after reevaluation, a rhythm control strategy is recommended, the AF should be redesignated as paroxysmal, persistent, or longstanding persistent AF.2 Silent AF is defined as asymptomatic AF often diagnosed by an opportune ECG or rhythm strip. Any of the above mentioned types of AF may be silent (i.e. asymptomatic). It is recognized that a particular patient may have AF episodes that fall into one or more of these categories.2 It is recommended that patients be categorized by their most frequent pattern of AF during the six months prior to performance of an ablation procedure.

TABLE 1:

TYPES AND CLASSIFICATION OF ATRIAL FIBRILLATION**

Atrial Fibrillation Episode An atrial fibrillation episode is defined as AF which is documented by ECG monitoring and has a duration of at least 30 seconds, or if less than 30 seconds, is present continuously throughout the ECG monitoring tracing. The presence of subsequent episodes of AF requires that sinus rhythm be documented by ECG monitoring between AF episodes. 
Paroxysmal AF* Paroxysmal AF is defined as recurrent AF (≥two episodes) that terminates spontaneously within 7 days. Episodes of AF of ≤48 hours' duration that are terminated with electrical or pharmacologic cardioversion should also be classified as paroxysmal AF episodes. 
Persistent AF* Persistent AF is defined as continuous AF that is sustained beyond seven days. Episodes of AF in which a decision is made to electrically or pharmacologically cardiovert the patient after ≥48 hours of AF, but prior to 7 days, should also be classified as persistent AF episodes. 
Longstanding Persistent AF Longstanding persistent AF is defined as continuous AF of greater than 12 months' duration. 
Permanent AF The term permanent AF is not appropriate in the context of patients undergoing catheter or surgical ablation of AF, as it refers to a group of patients for which a decision has been made not to restore or maintain sinus rhythm by any means, including catheter or surgical ablation. If a patient previously classified as having permanent AF is to undergo catheter or surgical ablation, the AF should be reclassified. 
Atrial Fibrillation Episode An atrial fibrillation episode is defined as AF which is documented by ECG monitoring and has a duration of at least 30 seconds, or if less than 30 seconds, is present continuously throughout the ECG monitoring tracing. The presence of subsequent episodes of AF requires that sinus rhythm be documented by ECG monitoring between AF episodes. 
Paroxysmal AF* Paroxysmal AF is defined as recurrent AF (≥two episodes) that terminates spontaneously within 7 days. Episodes of AF of ≤48 hours' duration that are terminated with electrical or pharmacologic cardioversion should also be classified as paroxysmal AF episodes. 
Persistent AF* Persistent AF is defined as continuous AF that is sustained beyond seven days. Episodes of AF in which a decision is made to electrically or pharmacologically cardiovert the patient after ≥48 hours of AF, but prior to 7 days, should also be classified as persistent AF episodes. 
Longstanding Persistent AF Longstanding persistent AF is defined as continuous AF of greater than 12 months' duration. 
Permanent AF The term permanent AF is not appropriate in the context of patients undergoing catheter or surgical ablation of AF, as it refers to a group of patients for which a decision has been made not to restore or maintain sinus rhythm by any means, including catheter or surgical ablation. If a patient previously classified as having permanent AF is to undergo catheter or surgical ablation, the AF should be reclassified. 

* It is recognized that patients may have both paroxysmal and persistent AF. A patient's AF type should be defined as the most frequent type of AF experienced within six months of an ablation procedure. Continuous AF is AF that is documented to be present on all ECG monitoring performed during a defined period of time.

** We recommend that the term “chronic AF” not be used in the context of patients undergoing ablation of AF as it is ambiguous, and there is no standardized definition of this term.

It is recognized by the consensus Task Force that these definitions of AF are very broad, and that when describing a population of patients undergoing AF ablation, additional details should be provided. This is especially important when considering the category of persistent AF and longstanding persistent AF. Pathophysiologically oriented classifications of AF, such as recently proposed, and reporting of concomitant cardiovascular diseases will help in this regard.6 Investigators are urged to specify the duration of time patients have spent in continuous AF prior to an ablation procedure, and also to specify whether patients undergoing AF ablation have previously failed pharmacologic therapy, electrical cardioversion, and/or catheter ablation. Shown in Table 1 are a series of definitions for types of AF that can be used for future trials of AF ablation and also in the literature to help standardize reporting of patient populations and outcomes.

Mechanisms of Atrial Fibrillation

For many years, three major schools of thought competed to explain the mechanism(s) of AF: multiple random propagating wavelets, focal electrical discharges, and localized reentrant activity with fibrillatory conduction.7–11 Considerable progress has been made in defining the mechanisms of initiation and perpetuation of AF.12–14 Perhaps the most striking breakthrough was the recognition that, in a subset of patients, AF was triggered by a rapidly firing focus and could be “cured” with a localized catheter ablation procedure.12,13 This landmark observation compelled the arrhythmia community to refocus its attention on the pulmonary veins (PVs) and the posterior wall of the left atrium (LA), as well as the autonomic innervation in that region (Figure 1). It also reinforced the concept that the development of AF requires a “trigger” and an anatomic or functional substrate capable of both initiation and perpetuation of AF.

Figure 1

Structure and Mechanisms of Atrial Fibrillation. Shown in Figure 1A, is a schematic drawing of the left and right atria as viewed from the posterior. The extension of muscular fibers onto the PVs can be appreciated. Shown in yellow are the five major left atrial autonomic ganglionic plexi (GP) and axons (superior left GP, inferior left GP, anterior right GP, inferior right GP, and Ligament of Marshall). Shown in blue is the coronary sinus which is enveloped by muscular fibers which have connections to the atria. Also shown in blue is the vein and ligament of Marshall which travels from the coronary sinus to the region between the left superior PV and the left atrial appendage. Figure 1b, demonstrates the large and small reentrant wavelets that play a role in initiating and sustaining AF. Shown in Figure 1c, are the common locations of PV (red) and also the common sites of origin of non PV triggers (shown in green). Shown in Figure 1d, is a composite of the anatomic and arrhythmic mechanisms of AF. Adapted from Circulation,28 Am J Cardiol,733 Tex Heart Inst J.734

Figure 1

Structure and Mechanisms of Atrial Fibrillation. Shown in Figure 1A, is a schematic drawing of the left and right atria as viewed from the posterior. The extension of muscular fibers onto the PVs can be appreciated. Shown in yellow are the five major left atrial autonomic ganglionic plexi (GP) and axons (superior left GP, inferior left GP, anterior right GP, inferior right GP, and Ligament of Marshall). Shown in blue is the coronary sinus which is enveloped by muscular fibers which have connections to the atria. Also shown in blue is the vein and ligament of Marshall which travels from the coronary sinus to the region between the left superior PV and the left atrial appendage. Figure 1b, demonstrates the large and small reentrant wavelets that play a role in initiating and sustaining AF. Shown in Figure 1c, are the common locations of PV (red) and also the common sites of origin of non PV triggers (shown in green). Shown in Figure 1d, is a composite of the anatomic and arrhythmic mechanisms of AF. Adapted from Circulation,28 Am J Cardiol,733 Tex Heart Inst J.734

In this section of the document, a contemporary understanding of the mechanisms of AF is summarized. As illustrated in Figure 2, some authors15–17 have proposed that, in the presence of an appropriate heterogeneous AF substrate, a focal trigger can result in sustained high frequency reentrant AF drivers (rotors). The waves that emerge from the rotors undergo spatially distributed fragmentation and give rise to fibrillatory conduction.7,8,18–21 Evidence suggests that when high frequency atrial activation is maintained for at least 24 hours, ion channel remodeling changes the electrophysiologic substrate,8,19,21 promoting sustained reentry and increasing the activity of triggers, further contributing to AF permanence. Sustained high rates in the atrium and/or the presence of heart disease are associated with structural remodeling of the atria and alter the substrate even further21 and help to perpetuate AF. AF can also be the result of preexisting atrial disease. Although much has been learned about the mechanisms of AF, they remain incompletely understood. Because of this, it is not yet possible to precisely tailor an ablation strategy to a particular AF mechanism in the great majority of AF patients.

Figure 2

Focal Triggers Leading to Initiation of Reentry. Figure 2 is a schematic drawing that illustrates the manner in which focal triggers lead to initiation of reentry (rotors). Eventually, atrial remodeling leads to additional focal triggers and perpetuation of reentry.

Figure 2

Focal Triggers Leading to Initiation of Reentry. Figure 2 is a schematic drawing that illustrates the manner in which focal triggers lead to initiation of reentry (rotors). Eventually, atrial remodeling leads to additional focal triggers and perpetuation of reentry.

Multiple Wavelet Hypothesis

Until the mid to late 1980s, the multiple wavelet hypothesis for AF was widely accepted as the dominant AF mechanism.22 This hypothesis was developed by Moe and colleagues and subsequently confirmed by experimental work.23 According to this hypothesis, AF results from the presence of multiple independent wavelets occurring simultaneously and propagating randomly throughout the left and right atria. This model suggests that the number of wavelets at any point in time depends on the atrial conduction velocity, refractory period, and excitable mass. Perpetuation of AF requires the presence of a minimum number of co-existing wavelets and is favored by slowed conduction, shortened refractory periods, and increased atrial mass. Enhanced spatial dispersion of refractoriness promotes perpetuation by heterogeneous conduction delay and block. It is notable that the development of the surgical Maze procedure was predicated on this model of AF and the concept that maintenance of AF needs a critical number of circulating wavelets, each of which requires a critical excitable mass of atrial tissue.24 However, experimental and clinical results suggest that, while AF maintenance by randomly propagating wavelets may occur in some cases, atrial refractory periods and cycle lengths do not seem to distribute randomly. Rather, as demonstrated in the atria of the dog, atrial fibrillation cycle length (AFCL) is significantly shorter in the LA compared with the right atrium, and an area in the posterior LA is consistently found to have the shorter AFCL.25

Focal Triggers

Haissaguerre and colleagues are credited with making the landmark observation that AF is often triggered by a focal source, and that ablation of that focal trigger can eliminate AF.12–14 This observation was reported in a series of three manuscripts. An initial series of three patients who underwent successful catheter ablation of AF was published in 1994.12 In each of these patients, AF was determined to arise from a “focal source.” The successful treatment of these three patients with catheter ablation suggested that in some patients, AF may result from a focal trigger and that ablation of this trigger could eliminate AF. It is notable that prior research in an animal model had demonstrated that AF could be induced by local administration of aconitine that triggered a rapid focal atrial tachycardia (AT).26 This type of “focal AF” also was shown to be cured by isolation of the site of the aconitine-induced focal AT from the remainder of the atria. In a subsequent report on 45 patients with frequent drug-refractory episodes of AF, Haissaguerre and colleagues found that a purely right-sided linear ablation approach resulted in an extremely low long-term success rate.27 These investigators also found that linear lesions were often arrhythmogenic due to gaps in the ablation lines, and that many patients were ultimately cured with ablation of a single rapidly firing ectopic focus. These ectopic foci were found at the orifices of the left or right superior PVs or near the superior vena cava (SVC). The latter observation led these investigators to systematically attempt cure of paroxysmal AF by mapping and ablating individual foci of ectopic activity.12–14 Many of these foci were found well into the PVs, outside of the cardiac silhouette, where myocardial sleeves are known to extend.14 These observations of the importance of a focal trigger in the development of AF have been confirmed by others. Thus, it is now well established that the PVs appear to be a crucial source of triggers that initiate AF.

Electrophysiology of the Pulmonary Veins

Nathan and Eliakim are credited with first drawing attention to the presence of sleeves of cardiac tissue that extend onto the PVs (Figure 1).28 However, investigation of the anatomic and electrophysiologic properties of the PVs remained limited, until the importance of PV triggers in the development of AF was appreciated. There is now general agreement that myocardial muscle fibers extend from the LA into all the PVs for 1 to 3 cm; the thickness of the muscular sleeve is highest at the proximal ends (1–1.5 mm), and then gradually decreases distally.11,29,30

PV focal firing may trigger AF or act as a rapid driver to maintain the arrhythmia. The mechanisms of this focal firing are incompletely understood. The location of the precursors of the conduction system is defined, during embryological development of the heart, by the looping process of the heart tube.31,32 Cell markers common to precursors of specialized conduction tissue derived from the heart tube have been found within myocardial sleeves.33 The presence of P cells, transitional cells, and Purkinje cells has been demonstrated in human PVs.34,35 PV-sleeve cardiomyocytes have discrete ion channel and action potential properties that predispose them to arrhythmogenesis.34,35 They have small background IK1, which could favor spontaneous automaticity,34 as could their reduced coupling to atrial tissue, a property common to pacemaking structures.36 Other work shows susceptibility to Ca2+-dependent arrhythmia mechanisms,37 possibly due to cells of melanocyte origin.38 Isolated cardiomyocytes from rabbit and canine PVs show abnormal automaticity and triggered activity during manipulations that enhance Ca2+-loading.37–39 These properties may explain the electrical activity within the PVs that is commonly observed after electrical disconnection of the PVs from the atrium.40

Other studies have provided evidence to suggest that the PVs and the posterior LA are also preferred sites for reentrant arrhythmias.16,41 One important factor may be the shorter action potential duration of the PVs versus atrium34 due to larger delayed-rectifier K+-currents and smaller inward Ca2+-currents in PV.39,42 In addition, PVs demonstrate conduction abnormalities that promote reentry due to abrupt changes in fiber orientation as well as Na+-channel inactivation by reduced resting potentials due to small IK1.34,41 Yet another study examined the impact of increasing atrial pressure on PV activation, finding that as LA pressure was increased above 10 cm H2O, the LA–PV junction became the source of dominant rotors.43 These observations help explain the clinical link between AF and increased atrial pressure. Several clinical studies have reported shorter refractory periods inside PVs compared to the LA, decremental conduction inside PVs, and easy induction of PV reentry with premature stimulation from the PVs. Accordingly, rapid reentrant activity with entrainment phenomenon have been described inside PVs after successful pulmonary vein isolation (PVI).44,45 Electrophysiologic evaluation of the PVs using a multielectrode basket catheter has revealed effective refractory period heterogeneity and anisotropic conduction properties within the PV and at the PV–LA junction which can provide a substrate for reentry.46 The response of PV activity to adenosine administration in patients with paroxysmal AF is more consistent with a reentrant than a focal ectopic type of mechanism.47,48 In addition, dominant-frequency analysis points to an evolution of mechanisms in AF-patients, with PV sources becoming less predominant as AF becomes more persistent and atrial remodeling progresses.44 There is considerable evidence for a role of autonomic regulation in AF occurrence, and the location of autonomic ganglia close to the PVs suggest a contribution of their specific innervation to PV arrhythmogenesis and the beneficial effects of PV ablation procedures.49,50

Frequency Gradients in Atrial Fibrillation Organization

A number of experimental and clinical studies have appeared over the last several years demonstrating the importance of the local atrial activation rate (cycle length) in the maintenance of AF,47,49,51–54 the role of atrial remodeling in the perpetuation of AF,19–21 the importance of wavebreak and reentry in the posterior LA,53,55 and the existence of a hierarchical organization and left-to-right gradients of the electrical excitation frequency.47,48,51,52,54 In addition, optical mapping studies in animals have confirmed that the turbulent electrical activity seen by electrogram (EGM) recordings of the atria during AF may in some cases be explained by fibrillatory conduction from a single or a small number of rapidly spinning sources in the LA.16,56 At the subcellular level, the high density of autonomic plexi and nerves on the posterior wall of the LA and its greater density of inward rectifier potassium channels57 provide a reasonable explanation for the shorter refractory periods in that region and for the hierarchical distribution of dominant frequency gradients that characterize AF. It was recently demonstrated that in sinus rhythm there are intra-atrial heterogeneities in the repolarizing currents. Chronic AF decreases ITo1 and IKur differentially in each atrium and increases IKs in both atria, an effect that further promotes reentry and likely contributes to the perpetuation of the arrhythmia.

The above studies offer mechanistic rationale for the empiric observation by clinical electrophysiologists that the LA is the region that seems to harbor the AF sources in the majority of patients. They also afford an explanation for the need for circumferential and linear ablation, as well as other anatomic approaches that not only include the PVs but also a large portion of the LA. Inclusion of the atrial myocardium in ablation strategies is particularly important in patients with persistent AF, who in fact represent the vast majority of patients presenting with this arrhythmia. Recent data in persistent AF patients provide compelling evidence that the sources are in fact reentrant and located outside of the PVs. Other studies in patients have used power spectral analysis and mapping to localize dominant frequency sites of activation.48 They demonstrated that in paroxysmal AF patients, the PV ostial region does harbor the highest frequency sites, and AF can be terminated successfully by targeting radiofrequency (RF) ablation to those sites in up to 87% of patients.48,58 However, in longstanding persistent AF patients, it is rare to find dominant frequency sites at the PV region, and this agrees well with the relatively poor success rate of RF ablation in such patients. The data suggest that in patients with longstanding persistent AF, atrial remodeling somehow augments the number of AF drivers and shifts their location away from the PV/ostial region.

Cardiac Autonomic Nervous System and Triggered Spontaneous Pulmonary Vein Firing

Autonomic input to the atria arises from both the central autonomic nervous system (pre-ganglionic) and the intrinsic cardiac autonomic nervous system (ANS).59,60 The intrinsic cardiac ANS includes clusters of ganglia, known as autonomic ganglionated plexi (GP), located in specific epicardial fat pads and within the ligament of Marshall. The GP receive input from the central (extrinsic) ANS and contain afferent neurons, post-ganglionic efferent parasympathetic and sympathetic neurons, and numerous interconnecting neurons that provide communication within and between the GP. In animal models, stimulating the vagosympathetic trunk (“vagus nerve”) allows AF to sustain but requires pacing or other stimuli to initiate AF.61,62 In contrast, stimulating the GP produces repetitive short bursts of rapid, irregular firing in the adjacent PV, initiating sustained AF.63 The focal firing in the PVs has a pause-dependent initiation pattern and produces EGMs that are very similar to the pattern of firing recorded in the PVs of patients with paroxysmal AF.64 Focal firing in the PVs by GP stimulation requires both sympathetic and parasympathetic activity.65–67 Parasympathetic stimulation shortens the action potential duration (and effective refractory period) in atrial and PV myocytes, and sympathetic stimulation increases calcium loading and automaticity. Combined, they cause pause-induced early after depolarizations (EADs) and triggered activity in PV and atrial myocytes. The mechanism of triggered firing may relate to the combination of a very short action potential duration and increased calcium release during systole, leading to high intracellular calcium during and after repolarization. These observations suggest that the high calcium concentration may activate the sodium/calcium exchanger, leading to a net inward current, EADs, and triggered firing.62,65,68 Compared to atrial myocytes, PV myocytes have a shorter action potential duration and greater sensitivity to autonomic stimulation, which may explain the predominance of focal firing in PVs in patients with paroxysmal AF and the interruption of focal firing by ablation of the autonomic GP.69 Interruption of nerves from the GP to the PVs may explain, at least in part, the frequent elimination of focal firing within the PVs produced by PVI procedures.70,71 These findings suggest that interruption of nerves from the GP may have a role in the success of PVI procedures and may explain the success of early ablation studies targeting only the GP in patients with paroxysmal AF.70,71 Regeneration of those axons may contribute to late recurrence of AF after PVI.72,73 Ablation of the nerve cell bodies, by targeting the GP, may permanently denervate the PVs. The addition of GP ablation to PVI appears to be synergistic, because each of these procedures is currently incomplete: all GP tissue cannot be localized for ablation by the current endocardial stimulation techniques; and PVI procedures are frequently associated with late reconnection to the atrium.74,75

A relationship has been observed between autonomic GP activity and complex fractionated atrial EGMs (CFAEs). The location of the GP can be identified as sites associated with transient AV block during high frequency electrical stimulation (HFS, 20 Hz).76,77 The GP are consistently located within areas of CFAEs.78 Stimulating the GP by HFS or the injection of acetylcholine into a fat pad containing a GP produces CFAEs in the same area as recorded during AF.76,78–80 Sequential ablation of multiple (four or more) GP in animal models and in patients with paroxysmal or persistent AF reduces or eliminates all CFAE, and decreases or eliminates the inducibility of AF.79–81 AF persisting after GP ablation typically shows more organized atrial EGMs with longer cycle lengths.80 These changes in EGM patterns with sequential ablation of GP are similar to the progressive slowing and organization of EGMs during the stepwise ablation technique performed in patients with longstanding persistent AF.81–84 The relationship between CFAE and GP activity may also explain the varied success reported for CFAE ablation. Studies describing high success with CFAE ablation show ablation sites concentrated in areas close to the GP,82 while studies describing poor success generally show a widespread pattern of ablation sites.84 The latter studies may have inadvertently targeted the peripheral CFAE sites, leaving the GP largely intact.

Several recent observations in animal models may have an influence on AF therapy in the future. GP activity may play a role in the electrical remodeling produced by rapid atrial pacing. Shortening of the refractory period in the atria and PVs and the inducibility of AF produced in short-term models of rapid atrial pacing are facilitated by GP stimulation and blocked by GP ablation.85,86

Another recent finding is the inhibition of GP activity and PV firing by low-level stimulation of the vagosympathetic trunk.87 A loss of responsiveness of the GP to central vagal stimulation in older patients may help to explain the striking increase in the prevalence of AF in elderly people. Therapeutic implications include the possibility that chronic low-level stimulation of the vagosympathetic trunk may help suppress AF in patients with paroxysmal AF. Although these data suggest a potentially important role of the autonomic nervous system in the development of AF, as well as a role of autonomic modulation in the treatment of AF, it is important to recognize that definitive proof is lacking, as it is not possible to ablate autonomic ganglia without also ablating atrial myocardium.

Electrophysiologic Basis for Catheter Ablation of Atrial Fibrillation

It is well accepted that the development of AF requires both a trigger and a susceptible substrate. The goals of AF ablation procedures are to prevent AF by either eliminating the trigger that initiates AF or by altering the arrhythmogenic substrate. The most commonly employed ablation strategy today, which involves the electrical isolation of the PVs by creation of circumferential lesions around the right and the left PV ostia, probably impacts both the trigger and substrate of AF (Figure 3).88–91 In particular, this approach seeks to electrically isolate the PVs, which are the most common site of triggers for AF. Other less common trigger sites for AF, including the vein and ligament of Marshall and the posterior LA wall, are also encompassed by this lesion set. The circumferential lesions may also alter the arrhythmogenic substrate by elimination of tissue located near the atrial–PV junction that provides a substrate for reentrant circuits that may generate or perpetuate AF, and/or by reduction of the mass of atrial tissue needed to sustain reentry. The circumferential lesion set may interrupt sympathetic and parasympathetic innervation from the autonomic ganglia that have been identified as potential triggers for AF (Figure 1).92 Extensive atrial remodeling poses a particular challenge for the ablation of longstanding persistent AF.93,94

Figure 3

Schematic of Common Lesion Sets Employed in AF Ablation. Figure 3A shows the circumferential ablation lesions that are created in a circumferential fashion around the right and the left PVs. The primary endpoint of this ablation strategy is the electrical isolation of the PV musculature. Figure 3B shows some of the most common sites of linear ablation lesions. These include a “roof line” connecting the lesions encircling the left and/or right PVs, a “mitral isthmus” line connecting the mitral valve and the lesion encircling the left PVs at the level of the left inferior PV, and an anterior linear lesion connecting either the “roof line” or the left or right circumferential lesion to the mitral annulus anteriorly. A linear lesion created at the cavotricuspid isthmus is also shown. This lesion is generally placed in patients who have experienced cavotricuspid isthmus-dependent atrial flutter clinically or have it induced during EP testing. Figure 3C is similar to 3B but also shows additional linear ablation lesions between the superior and inferior PVs resulting in a figure of 8 lesion set as well as a posterior inferior line allowing for electrical isolation of the posterior left atrial wall, An encircling lesion of the superior vena cava (SVC) directed at electrical isolation of the SVC is also shown. SVC isolation is performed if focal firing from the SVC can be demonstrated. A subset of operators empirically isolates the SVC. Figure 3D shows some of the most common sites of ablation lesions when complex fractionated electrograms are targeted (these sites are also close to the autonomic GP). Adapted from Circulation,28 Am J Cardiol,733 Tex Heart Inst J.734

Figure 3

Schematic of Common Lesion Sets Employed in AF Ablation. Figure 3A shows the circumferential ablation lesions that are created in a circumferential fashion around the right and the left PVs. The primary endpoint of this ablation strategy is the electrical isolation of the PV musculature. Figure 3B shows some of the most common sites of linear ablation lesions. These include a “roof line” connecting the lesions encircling the left and/or right PVs, a “mitral isthmus” line connecting the mitral valve and the lesion encircling the left PVs at the level of the left inferior PV, and an anterior linear lesion connecting either the “roof line” or the left or right circumferential lesion to the mitral annulus anteriorly. A linear lesion created at the cavotricuspid isthmus is also shown. This lesion is generally placed in patients who have experienced cavotricuspid isthmus-dependent atrial flutter clinically or have it induced during EP testing. Figure 3C is similar to 3B but also shows additional linear ablation lesions between the superior and inferior PVs resulting in a figure of 8 lesion set as well as a posterior inferior line allowing for electrical isolation of the posterior left atrial wall, An encircling lesion of the superior vena cava (SVC) directed at electrical isolation of the SVC is also shown. SVC isolation is performed if focal firing from the SVC can be demonstrated. A subset of operators empirically isolates the SVC. Figure 3D shows some of the most common sites of ablation lesions when complex fractionated electrograms are targeted (these sites are also close to the autonomic GP). Adapted from Circulation,28 Am J Cardiol,733 Tex Heart Inst J.734

Recurrences of all types of AF following an initially successful AF ablation procedure result from PV reconnection. It is extremely unusual to find no evidence of return of PV conduction at the time of repeat AF ablation procedures.95 CFAEs are widely targeted in attempts to suppress the AF-maintaining substrate, but clinical results have varied widely.96 Detailed mechanistic analyses of CFAE generation promise to develop new methods by which they can be used to identify AF drivers.74 There is increasing recognition of the importance of atrial autonomic ganglia in AF maintenance and the value of targeting them in AF ablation procedures.97 Atrial fibrotic remodeling plays an important role in AF pathophysiology; recent work suggests that noninvasive assessment of atrial fibrosis may be predictive of the outcome of AF ablation procedures.98

Rationale for Eliminating Atrial Fibrillation with Ablation

There are several hypothetical reasons to perform ablation procedures for treatment of AF. These include improvement in quality of life (QOL), decreased stroke risk, decreased heart failure risk, and improved survival. In this section of the document, these issues will be explored in more detail. However, it is important to recognize that the primary justification for an AF ablation procedure at this time is the presence of symptomatic AF, with a goal of improving a patient's quality of life. Although each of the other reasons to perform AF ablation identified above may be correct, they have not been systematically evaluated as part of a large randomized clinical trial and are therefore unproven.

Several epidemiologic studies have shown strong associations between AF and increased risk of cerebral thromboembolism, development of heart failure, and increased mortality.99–101 It is well known that AF causes hemodynamic abnormalities including a decrease in stroke volume, increased LA pressure and volume, shortened diastolic ventricular filling period, AV valvular regurgitation, and an irregular and often rapid ventricular rate.102 AF with a rapid ventricular response can also cause reversible left ventricular (LV) systolic dysfunction. Persistence of AF leads to anatomic and electrical remodeling of the LA that may facilitate persistence of AF. Most importantly, many patients, even those with good rate control, experience symptoms during AF.

There have been multiple randomized clinical trials performed that address the question of whether rhythm control is more beneficial than rate control for AF patients.103–105 These studies have not demonstrated that sinus rhythm restoration is associated with better survival. In all trials, antiarrhythmic drugs were used for rhythm control. The Pharmacological Intervention in AF (PIAF) trial first demonstrated that rate control was not inferior to rhythm control in the improvement of symptoms and quality of life.106 An additional study reported similar findings.104 The Strategies of Treatment of AF (STAF) trial showed no significant difference in the primary endpoints of death, systemic emboli, and cardiopulmonary resuscitation between the two strategies.103 Another recent study demonstrated an improvement in quality of life and exercise performance at 12 months' follow-up in a series of patients with persistent AF.107 In the AF Follow-up Investigation of Rhythm Management (AFFIRM) trial, in which 4,060 AF patients with high risk for stroke and death were randomized to either rhythm control or rate control, there were no significant differences in all-cause death between the two strategies.105 However, a post-hoc on-treatment analysis of the AFFIRM study revealed that the presence of sinus rhythm was associated with a significant reduction in mortality, whereas the use of antiarrhythmic drugs increased mortality by 49%,108 suggesting that the beneficial effect of sinus rhythm restoration on survival might be offset by the adverse effects of antiarrhythmic drugs. Previously, the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) study also showed the presence of sinus rhythm was associated with improved survival.109 It must be noted, however, that this was a retrospective analysis, and the improvement in survival may have resulted from factors other than the presence of sinus rhythm. In contrast, a recent study demonstrated that a rhythm control strategy, or the presence of sinus rhythm, is not associated with better outcomes in congestive heart failure patients with AF.110

These clinical trials clearly show that the strategy of using antiarrhythmic drugs to maintain sinus rhythm does not achieve the potential goals of sinus rhythm mentioned above. However, there are signals in these data to suggest that sinus rhythm may be preferred over rate control if it could be achieved by a method other than drug therapy. One study compared the efficacy and safety of circumferential PV ablation with antiarrhythmic drug treatment in a large number of patients with long-term follow-up and showed that ablation therapy significantly improved the morbidity and mortality of AF patients.90 Because this was a single-center study, without audit of the raw data, and not a prospective randomized study, these findings must be considered very preliminary. Several recent small randomized trials in patients with paroxysmal AF demonstrated that catheter ablation was superior to antiarrhythmic therapy in the prevention of recurrent AF.111–113 A limitation of these studies is that most patients had previously failed treatment with at least one antiarrhythmic medication. There are several published studies that have reported a low risk of stroke in patients who discontinue systemic anticoagulation several months or more following AF ablation.114–117 These findings need to be interpreted with caution, however, because AF can recur early or late after AF ablation and recurrences are more likely to be asymptomatic following, as compared with prior to, AF ablation. In addition, patients' stroke risk profile often increases as they age and pick up additional comorbidities such as hypertension. Thus there are some data to suggest that there are benefits to sinus rhythm obtained by ablation techniques over rate control. However, large prospective multicenter randomized clinical trials will be needed to definitively determine whether sinus rhythm achieved with ablation techniques lowers morbidity and mortality as compared with rate control alone or treatment with antiarrhythmic therapy. The ongoing Catheter Ablation vs. Antiarrhythmic Drug Therapy for AF (CABANA) study will provide important information as it investigates whether catheter ablation is superior to medical therapy in patients with AF who are at increased stroke risk.118

Mechanisms of Recurrence Following Catheter or Surgical AF Ablation

It is now well established that both catheter and surgical ablation of AF are associated with an important risk of late recurrence of AF.72,73,119–127 Although the highest risk of recurrence is during the first 6 to 12 months following ablation, there is no follow-up duration at which point patients are no longer at risk of a “new” late recurrence of AF. Although the precise mechanisms of these late recurrences have not been defined completely, electrical reconnection of one or more PVs is an almost universal finding among patients who return for a second AF ablation procedure following an initial catheter or surgical ablation procedure. Because of this observation, most of the EP community feels that the dominant mechanism of recurrence of AF is electrical reconnection of the PVs. Additional evidence supporting this mechanism is the extremely low rate of late AF following double lung transplantation in which permanent PVI is achieved.128 There are several other potential mechanisms of late recurrence of AF which should be considered. First, it is possible that some late recurrences of AF result from non-PV arrhythmogenic foci that were not identified and targeted during an initial ablation procedure. Second, it is possible that late recurrences of AF are a result of post-ablation modulation in autonomic innervations of the heart and PVs.62–77 And finally, it is possible that ongoing electrical and structural remodeling of the atria as a result of aging, heart failure, inflammation, and other comorbidities such as diabetes129–136 leads to progressive atrial electrical instability. Evidence to support the latter hypothesis is derived in part by the studies reporting that patients with comorbid conditions such as sleep apnea, hypertension (HTN), and hypercholesterolemia, as well as those with a history of persistent AF, are at highest risk of late recurrence.135,137–139

Demographic Profile of AF Patients and Risk Factors for Development of AF

There are multiple conditions known as "risk factors for AF" that play an etiologic role through diverse mechanisms.6 Some of them, like HTN,135,139 obesity,140–142 endurance sport training,143,144 obstructive sleep apnea,140–142 and alcohol consumption145 are modifiable and therefore, in theory, strictly controlling them may prevent arrhythmia or modify post-ablation evolution. On the other hand, factors such as genetic disorders,146,147 age,137,148,149 sex,137 or tall stature44,150 can be identified but not prevented or treated. To individualize treatment, it is important to establish the most likely contributors to AF in each patient. Atrial size, a relevant marker of risk for AF and for post ablation recurrences of the disease, is a common pathway for the action of most of the identified risk factors.

The well-known and more prevalent risk factors are age, male sex, HTN, diabetes mellitus, hyperthyroidism, and structural heart disease. Aging is a key risk factor136–138 that probably acts through age-related fibrosis. HTN is associated with increased risk for AF even if apparently well controlled.138,139 Structural heart disease, regardless of cause, is also a major contributor to AF, and mitral valve disease and hypertrophic cardiomyopathy produce severe atrial disease. In addition, systolic or diastolic dysfunction and heart failure of any etiology predispose to AF, probably through volume and/or pressure overload of the atrium.151,152 Diabetes mellitus and hyperthyroidism are well recognized and independent risk factors for AF; even when well-controlled, AF may recur.141,153 AF risk factors have also been shown to be of value in predicting progression of paroxysmal to persistent AF. Risk factors that have been identified as independent predictors of AF recurrence include heart failure, age, previous transient ischemic attack or stroke, chronic obstructive pulmonary disease, and hypertension. Based on this analysis, the HATCH score was developed to help predict those at highest risk of AF progression.154

In recent years, new risk factors have been described that may contribute to the marked, increased prevalence of AF that is not fully explained by the aging of the population.141,143,147,150,155–167 Obesity has proven to be associated with a higher risk of AF in several population-based studies. Tall stature also is associated with an increased risk, and may explain the sex-based difference in AF prevalence: AF is more prevalent in men than in women. The prevalence of AF is also increased in individuals with a long history of endurance training, perhaps, as suggested in an animal model, through training-related hypertrophy, atrial dilatation, fibrosis, or perhaps by training induced alterations in autonomic tone. However, moderate exercise may decrease the prevalence, perhaps by controlling other risk factors such as HTN and obesity. Obstructive sleep apnea also has been associated with AF. Whether this represents an independent factor or acts through its association with obesity and HTN remains to be elucidated, but it seems to increase the risk of recurrences after AF ablation. Finally, in a small percentage of patients, AF is due to hereditary genetic causes as discussed in the following paragraph.

Genetics of AF: Relevance to AF

The descendants of individuals with AF are at increased risk of developing AF, even after considering established risk factors for AF.157,158,160,168,169 Recent studies suggest that lone AF may be a traditional monogenic syndrome with reduced penetrance, and multiple genetic loci have been described in families with Mendelian forms of AF. However, not all160 the responsible genes have been identified.170,171 Gain-of-function mutations in KCNE2172 and KCNJ2,173 encoding the inward rectifier potassium current (IK1), have been associated with familial AF in two Chinese families. Similar studies have associated familial AF with various other genes, including those genes coding the α subunit of the Kv1.5 channel responsible for IKur(KCNA5); the gap junctional protein Connexin40 (GJA5); SUR2A, the adenosine triphosphate (ATP) regulatory subunit of the cardiac KATP channel (ABCC9); and KCNE5 which co-associates with KCNQ1 to form the IKs channel.174–177 Rare forms of familial AF are caused by mutations in one or more subunits of potassium, sodium, and calcium ion channel genes, as well as in a nuclear pore178 anchoring protein and natriuretic peptide gene173,179–183 and also have been associated with inherited channelopathies such as Brugada, Long QT, Short QT syndromes, and cardiomyopathies.172,175,178–184

Genetic linkage analyses have identified AF loci on chromosomes 10q22-24,170 6q14-16,171 5p13,185 and 11p15.5.182 In the case of 11p15.5, the genetic defect involved heterozygous missense mutations in KCNQ1, resulting in gain-of function of the KCNQ1-KCNE1 and KCNQ1-KCNE2 ion channels conducting the slowly activating delayed rectifier current, IKs.186 Genetic predisposition to AF has gained notoriety also thanks to genomic wide association studies (GWAS)187–191 that have identified at least two genetic variants on chromosome 4q25 associated with AF, although the mechanism of action for these variants remains unknown. One of such variants is located near the developmental left–right asymmetry homeobox gene, Pitx2, which implicates this gene and its signaling pathways in prevention of atrial arrhythmias.191

It is reasonable to suggest that investigating in detail the underlying bases of these and other characteristics of the LA that differentiate it from the right atrium may greatly advance therapy by helping to explain the mechanisms of the genesis and perpetuation of chronic AF.

INDICATIONS FOR CATHETER AND SURGICAL ABLATION OF ATRIAL FIBRILLATION

The 2007 HRS/EHRA/ESC Expert Consensus Document on Catheter and Surgical Ablation of Atrial Fibrillation recommended that the primary indication for catheter AF ablation is the presence of symptomatic AF, refractory or intolerant to at least one Class 1 or 3 antiarrhythmic medication.1 The 2007 Task Force also recognized that in rare clinical situations, it may be appropriate to perform catheter ablation of AF as first line therapy. Since publication of this document five years ago, a large body of literature, including multiple prospective randomized clinical trials, has confirmed the safety and efficacy of catheter ablation of AF. The substantial body of literature defining the safety and efficacy of catheter ablation of AF is summarized in section 8 of this document. Similarly, the body of literature defining the safety and efficacy of surgical ablation of AF either performed in conjunction with another cardiac surgical procedure or when performed as a stand-alone procedure is summarized in section 11 of this document.

Shown in Table 2 of this document are the Consensus Indications for Catheter and Surgical Ablation of AF. As outlined in the introduction section of this document, these indications are stratified as Class I, Class IIa, Class IIb, and Class III indications. The evidence supporting these indications is graded as Level A through C. In making these recommendations, the Task Force considered the body of literature that has been published which has defined the safety and efficacy of catheter and surgical ablation of AF. Both the number of clinical trials and the quality of these trials were considered. In considering the class of indications recommended by this Task Force, it is important to keep several points in mind. First, these classes of indications only define the indications for catheter and surgical ablation of AF when performed by an electrophysiologist or surgeon who has received appropriate training and/or has a certain level of experience and is performing the procedure in an experienced center (see section 10). Catheter and surgical ablation of AF are highly complex procedures, and a careful assessment of benefit and risk must be considered for each patient. Second, these indications stratify patients only based on the type of AF and whether the procedure is being performed prior to or following a trial of one or more Class 1 or 3 antiarrhythmic medications. As detailed in section 8, there are many additional clinical and imaging based variables that can be used to further define the efficacy and risk of ablation in a given patient. Some of the variables that can be used to define patients in whom a lower success rate or a higher complication rate can be expected include the presence of concomitant heart disease, obesity/sleep apnea, left atrial size, and the duration of time a patient has been in continuous AF. Each of these variables needs to be considered when discussing the risks and benefits of AF ablation with a particular patient. Third, it is key to consider patient preference. Some patients are reluctant to consider a major procedure or operation and have a strong preference for a pharmacologic approach. In these patients, trials of additional antiarrhythmic agents and amiodarone may be preferred to catheter ablation. On the other hand, some patients prefer a nonpharmacologic approach. Fourth, it is also important to recognize that in some patients, AF is a slowly progressive condition and that patients early in the course of their AF disease may do well with only infrequent episodes for many years to come, and/or may be responsive to well-tolerated antiarrhythmic drug therapy. And finally, it is important to bear in mind that a decision to perform catheter or surgical AF ablation should only be performed after a patient carefully considers the risks, benefits, and alternatives to the procedure.

TABLE 2:

CONSENSUS INDICATIONS FOR CATHETER AND SURGICAL ABLATION of AF

 CLASS LEVEL 
INDICATIONS FOR CATHETER ABLATION of AF 
Symptomatic AF refractory or intolerant to at least one Class 1 or 3 antiarrhythmic medication   
Paroxysmal: Catheter ablation is recommended* 
Persistent: Catheter ablation is reasonable IIa 
Longstanding Persistent: Catheter ablation may be considered IIb 
Symptomatic AF prior to initiation of antiarrhythmic drug therapy with a Class 1 or 3 antiarrhythmic agent   
Paroxysmal: Catheter ablation is reasonable IIa 
Persistent: Catheter ablation may be considered IIb 
Longstanding Persistent: Catheter ablation may be considered IIb 
INDICATIONS FOR CONCOMITANT SURGICAL ABLATION of AF 
Symptomatic AF refractory or intolerant to at least one Class 1 or 3 antiarrhythmic medication   
Paroxysmal: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Persistent: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Longstanding Persistent: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Symptomatic AF prior to initiation of antiarrhythmic drug therapy with a Class 1 or 3 antiarrhythmic agent   
Paroxysmal: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Persistent: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Longstanding Persistent: Surgical ablation may be considered for patients undergoing surgery for other indications IIb 
INDICATIONS FOR STAND ALONE SURGICAL ABLATION of AF 
Symptomatic AF refractory or intolerant to at least one Class 1 or 3 antiarrhythmic medication   
Paroxysmal: Stand alone surgical ablation may be considered for patients who have not failed catheter ablation but prefer a surgical approach IIb 
Paroxysmal: Stand alone surgical ablation may be considered for patients who have failed one or more attempts at catheter ablation IIb 
Persistent: Stand alone surgical ablation may be considered for patients who have not failed catheter ablation but prefer a surgical approach IIb 
Persistent: Stand alone surgical ablation may be considered for patients who have failed one or more attempts at catheter ablation IIb 
Longstanding Persistent: Stand alone surgical ablation may be considered for patients who have not failed catheter ablation but prefer a surgical approach IIb 
Longstanding Persistent: Stand alone surgical ablation may be considered for patients who have failed one or more attempts at catheter ablation IIb 
Symptomatic AF prior to initiation of antiarrhythmic drug therapy with a Class 1 or 3 antiarrhythmic agent   
Paroxysmal: Stand alone surgical ablation is not recommended III 
Persistent: Stand alone surgical ablation is not recommended III 
Longstanding Persistent: Stand alone surgical ablation is not recommended III 
 CLASS LEVEL 
INDICATIONS FOR CATHETER ABLATION of AF 
Symptomatic AF refractory or intolerant to at least one Class 1 or 3 antiarrhythmic medication   
Paroxysmal: Catheter ablation is recommended* 
Persistent: Catheter ablation is reasonable IIa 
Longstanding Persistent: Catheter ablation may be considered IIb 
Symptomatic AF prior to initiation of antiarrhythmic drug therapy with a Class 1 or 3 antiarrhythmic agent   
Paroxysmal: Catheter ablation is reasonable IIa 
Persistent: Catheter ablation may be considered IIb 
Longstanding Persistent: Catheter ablation may be considered IIb 
INDICATIONS FOR CONCOMITANT SURGICAL ABLATION of AF 
Symptomatic AF refractory or intolerant to at least one Class 1 or 3 antiarrhythmic medication   
Paroxysmal: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Persistent: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Longstanding Persistent: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Symptomatic AF prior to initiation of antiarrhythmic drug therapy with a Class 1 or 3 antiarrhythmic agent   
Paroxysmal: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Persistent: Surgical ablation is reasonable for patients undergoing surgery for other indications IIa 
Longstanding Persistent: Surgical ablation may be considered for patients undergoing surgery for other indications IIb 
INDICATIONS FOR STAND ALONE SURGICAL ABLATION of AF 
Symptomatic AF refractory or intolerant to at least one Class 1 or 3 antiarrhythmic medication   
Paroxysmal: Stand alone surgical ablation may be considered for patients who have not failed catheter ablation but prefer a surgical approach IIb 
Paroxysmal: Stand alone surgical ablation may be considered for patients who have failed one or more attempts at catheter ablation IIb 
Persistent: Stand alone surgical ablation may be considered for patients who have not failed catheter ablation but prefer a surgical approach IIb 
Persistent: Stand alone surgical ablation may be considered for patients who have failed one or more attempts at catheter ablation IIb 
Longstanding Persistent: Stand alone surgical ablation may be considered for patients who have not failed catheter ablation but prefer a surgical approach IIb 
Longstanding Persistent: Stand alone surgical ablation may be considered for patients who have failed one or more attempts at catheter ablation IIb 
Symptomatic AF prior to initiation of antiarrhythmic drug therapy with a Class 1 or 3 antiarrhythmic agent   
Paroxysmal: Stand alone surgical ablation is not recommended III 
Persistent: Stand alone surgical ablation is not recommended III 
Longstanding Persistent: Stand alone surgical ablation is not recommended III 

*Catheter ablation of symptomatic paroxysmal AF is considered a Class 1 indication only when performed by an electrophysiologist who has received appropriate training and is performing the procedure in an experienced center.

As demonstrated in a large number of published studies, the primary clinical benefit from catheter ablation of AF is an improvement in quality of life resulting from elimination of arrhythmia-related symptoms such as palpitations, fatigue, or effort intolerance (see section 8). Thus, the primary selection criterion for catheter ablation should be the presence of symptomatic AF. As noted above, there are many other considerations in patient selection other than type of AF alone. In clinical practice, many patients with AF may be asymptomatic but seek catheter ablation as an alternative to long-term anticoagulation with warfarin or other drugs with similar efficacy. Although retrospective studies have demonstrated that discontinuation of warfarin therapy after catheter ablation may be safe over medium-term follow-up in some subsets of patients, this has never been confirmed by a large prospective randomized clinical trial and therefore remains unproven.116,117,192 Furthermore, it is well recognized that symptomatic and/or asymptomatic AF may recur during long-term follow-up after an AF ablation procedure.72,73,119,122,124,126,127 It is for these reasons that this Task Force recommends that discontinuation of warfarin or equivalent therapies post-ablation is not recommended in patients who have a high stroke risk as determined by the CHADS2 or CHA2DS2VASc score.193 Either aspirin or warfarin is appropriate for patients who do not have a high stroke risk. If anticoagulation withdrawal is being considered, additional ECG monitoring may be required, and a detailed discussion of risk versus benefit should be entertained. A patient's desire to eliminate the need for long-term anticoagulation by itself should not be considered an appropriate selection criterion. In arriving at this recommendation, the Task Force recognizes that patients who have undergone catheter ablation of AF represent a new and previously unstudied population of patients. Clinical trials therefore are needed to define the stroke risk of this patient population and to determine whether the risk factors identified in the CHADS2 or CHA2DS2VASc or other scoring systems apply to these patients.

TECHNIQUES AND ENDPOINTS FOR ATRIAL FIBRILLATION ABLATION

Historical Considerations

Cox and colleagues are credited with developing and demonstrating the efficacy of surgical ablation of AF.24,194 Subsequent surgeons evaluated the efficacy of surgical approaches that limit the lesion set to PVI.195,196 The final iteration of the procedure developed by Cox, which is referred to as the Maze-III procedure, was based on a model of AF in which maintenance of the arrhythmia was shown to require maintenance of a critical number of circulating wavelets of reentry. The Maze-III procedure was designed to abort or block all possible anatomical reentrant circuits in both atria. The success of the Maze-III procedure in the early 1990s led some interventional cardiac electrophysiologists to attempt to reproduce the procedure with RF catheter lesions using a transvenous approach. Swartz and colleagues reported recreation of the Maze-I lesion set in a small series of patients using specially designed sheaths and standard RF catheters.197 Although the efficacy was modest, the complication rate was high, and the procedure and fluoroscopy times were long. This demonstration of a proof of concept led others to try to improve the catheter-based procedure. Although a large number of investigators attempted to replicate the surgical Maze procedure through the use of either three-dimensional (3D) mapping systems or the use of multipolar ablation electrode catheters, these clinical trials had limited success.27,198–203 Based on these observations and the rapid advances in ablation of AF targeting initiating focal triggers, electrophysiologists lost interest in catheter-based linear ablation for AF ablation.

Ablation Approaches Targeting the Pulmonary Veins

The identification of triggers that initiate AF within the PVs led to prevention of AF recurrence by catheter ablation at the site of origin of the trigger.12–14,204 Direct catheter ablation of the triggers was limited by the infrequency with which AF initiation could be reproducibly triggered and also by the difficulty of precise mapping within the 3D venous structures. To overcome these limitations, an ablation approach was introduced by Haissaguerre and colleagues204 that was designed to electrically isolate the PV myocardium. This segmental PVI technique involved the sequential identification and ablation of the PV ostium close to the earliest sites of activation of the PV musculature. An ablation strategy of encircling the PVs with RF lesions guided by 3D electroanatomical mapping was subsequently developed by Pappone and colleagues.203,205

The recognition of PV stenosis as a complication of RF delivery within a PV, as well as the recognition that sites of AF initiation and/or maintenance were frequently located within the PV antrum, resulted in a shift in ablation strategies to target the atrial tissue located in the antrum rather than the PV itself.88,206 Ablation at these sites was either performed segmentally, guided by a circular mapping catheter204,207 positioned close to the PV ostium, the so called “segmental PV ablation,” or by wider continuous circumferential ablation lesions created to surround the right or left PVs,203,205,208 the so called “wide area circumferential ablation” or WACA. The circumferential ablation/isolation line was either guided by 3D electroanatomical mapping,89,205,209 by fluoroscopy,210 or by intracardiac echocardiography (ICE).88,211 Although previous studies comparing these two different procedures reported contradictory data, 212,213 a randomized study showed that isolation of a large circumferential area around both ipsilateral PVs with verification of conduction block is a more effective treatment of AF than segmental isolation.214 The endpoint for this procedure was amplitude reduction within the ablated area,205,209 elimination (or dissociation) of the PV potentials recorded from either one or two circular mapping catheters or a basket catheter within the ipsilateral PVs,88,89,210,212,213,215 and/or exit block from the PV.216

Elimination (or dissociation) of the PV potentials recorded from a circular multipolar electrode catheter is the primary endpoint for PV ablation procedures targeting the PVs for 75% of Task Force members. In contrast, only 10% of Task Force members rely on exit block as an endpoint for the ablation procedure. In a recent randomized study, the use of a circular catheter to guide and to confirm PVI obtained better results than single-catheter mapping.217 Consistent with the results of this study, a single catheter approach to AF ablation, without employing a circular multipolar electrode catheter as an ablation endpoint, was used by less than 10% of Task Force members. Although some studies have reported that an ATP challenge can identify dormant PV conduction and that ablation based on this approach reduces AF recurrence after PVI,218–220 less than one fourth of the Task Force members employ this technique as a routine clinical tool.

Ablation Approaches Not Targeting the Pulmonary Veins

Linear Ablation

Circumferential isolation of PVs has become the standard therapy for paroxysmal AF. However, due to the high recurrence rate observed in patients with persistent and longstanding persistent AF with PVI alone, continued efforts are underway to identify additive strategies to improve outcome. One of these strategies is to create additional linear lesions in the LA similar to those advocated with the Cox-Maze-III, and others (Figure 3).221–224 The most common sites are the LA “roof” connecting the superior aspects of the left and right upper PVI lesions, the region of tissue between the mitral valve and the left inferior PV (the mitral isthmus), and anteriorly between the roof line near the left or right circumferential lesion and the mitral annulus (Figure 3).221 A prior randomized, prospective trial of catheter ablation of paroxysmal AF comparing segmental PVI versus circumferential PV ablation (CPVA) plus left atrial (LA) linear ablation (CPVA–LALA) at the LA roof and myocardial infarction showed that significantly more patients had LA flutter in the CPVA–LALA group,225 suggesting that additional ablation lines should not be performed in cases of paroxysmal AF. The role of additional lines in cases of persistent AF remains controversial.226 Routine isolation of the posterior wall does not seem to achieve better results in a prospective randomized study.227 On the other hand, it has been widely demonstrated that incomplete block across the ablation lines can be responsible for AT recurrence.228–230 Therefore, if additional linear lesions are applied, line completeness should be demonstrated by mapping or pacing maneuvers.

In patients with long-lasting persistent AF, the stepwise approach has been proposed.231 The strategy starts by pulmonary isolation, following by ablation of CFAE, looking for reversion to sinus rhythm or AT. If this endpoint is not achieved, additional linear lesions are deployed.82,231,232 However, other studies did not find any correlation between acute termination of AF and better long-term outcome.233 Ablation of the cavotricuspid isthmus is recommended by the Task Force, based on consensus opinion, in patients with a history of typical atrial flutter or inducible cavotricuspid isthmus dependent atrial flutter.234

Non Pulmonary Vein Triggers

Non-PV triggers initiating AF can be identified in up to one-third of unselected patients referred for catheter ablation for paroxysmal AF.14,45,235–238 Supraventricular tachycardias such as AV nodal reentry or accessory pathway-mediated atrioventricular reciprocating tachycardia may also be identified in up to 4% of unselected patients referred for AF ablation and may serve as a triggering mechanism for AF.239 Non-PV triggers can be provoked in patients with both paroxysmal and more persistent forms of AF.237 In selected patients, elimination of only the non-PV triggers has resulted in elimination of AF.45,239,240 The sites of origin for non-PV atrial triggers include the posterior wall of the LA, the SVC, the inferior vena cava, the crista terminalis, the fossa ovalis, the coronary sinus (CS), behind the Eustachian ridge, along the ligament of Marshall, and adjacent to the AV valve annuli (Figure 1).45,236–238,240,241 Furthermore, reentrant circuits maintaining AF may be located within the right and left atria.242 Provocative maneuvers such as the administration of isoproterenol in incremental doses of up to 20 mcg/minute and/or cardioversion of induced and spontaneous AF, can aid in the identification of PV and non-PV triggers.

Ablation of Complex Fractionated Atrial Electrograms

Areas with CFAEs have been reported to potentially represent AF substrate sites and became target sites for AF ablation.82,92,243,244 CFAEs are EGMs with highly fractionated potentials or with a very short cycle length (<120 milliseconds). CFAEs usually are low-voltage multiple potential signals between 0.06 and 0.25 mV. The primary endpoints during RF ablation of AF using this approach are either complete elimination of the areas with CFAEs, conversion of AF to sinus rhythm (either directly or first to an AT), and/or noninducibility of AF. For patients with paroxysmal AF, the endpoint of the ablation procedure using this approach is noninducibility of AF. For patients with persistent AF, the endpoint of ablation with this approach is AF termination. This endpoint was found to be associated with improved outcome.232 When the areas with CFAEs are completely eliminated, but the arrhythmias continue as organized atrial flutter or AT, the atrial tachyarrhythmias are mapped and ablated. In patients with longstanding persistent AF, a stepwise approach to ablation has been reported to successfully convert AF to either sinus rhythm or AT in greater than 80% of patients.231,245 An endpoint of noninducibility of AF has never been evaluated.246

One of the limitations of targeting CFAEs with ablation has been the extensive amount of ablation needed. As a result some strategies for differentiating “active” from “passive” have been described. These include pharmacologic interventions, the use of monophasic action potential, limiting ablation to areas of continuous electrical activity, and activation mapping of AF.247–250 It is important to recognize that improved outcomes with CFAE ablation in patients with persistent AF have not been uniformly reported and that the scientific basis of CFAE ablation is not universally accepted.

Fifty percent of Task Force members routinely employ CFAE- based ablation as part of an initial ablation procedure in patients with long standing persistent AF. Fifty percent of those that perform CFAE-based ablation use AF termination as the desired endpoint of their procedure.

Ablation of Ganglionated Plexi

Adding GP to other ablation targets may improve ablation success.70,74,91,92 The four major LA GP (superior left GP, inferior left GP, anterior right GP, and inferior right GP) are located in epicardial fat pads at the border of the PV antrum, and can be localized at the time of ablation using endocardial high frequency stimulation (HFS) (Figure 1). For ablation, RF current can be applied endocardially at each site of positive vagal response to HFS. HFS is repeated and additional RF applications can be applied until the vagal response to HFS is eliminated. When considering ablation of GP, it is important to recognize that it is currently not possible to selectively ablate GPs without ablating atrial myocardium.

Task Force Consensus

Shown in Table 3 are the areas of consensus on ablation techniques that were identified by the Task Force. The Task Force recommends that ablation strategies that target the PVs and/or PV antrum are the cornerstone for most AF ablation procedures and that complete electrical isolation of all PVs should be the goal. Please refer to Table 3 for a review of the consensus recommendations.

TABLE 3:

RECOMMENDATIONS REGARDING ABLATION TECHNIQUE

• Ablation strategies that target the PVs and/or PV antrum are the cornerstone for most AF ablation procedures. 
• If the PVs are targeted, electrical isolation should be the goal. 
• Achievement of electrical isolation requires, at a minimum, assessment and demonstration of entrance block into the PV. 
• Monitoring for PV reconduction for 20 minutes following initial PV isolation should be considered. 
• For surgical PV isolation, entrance and/or exit block should be demonstrated. 
• Careful identification of the PV ostia is mandatory to avoid ablation within the PVs. 
• If a focal trigger is identified outside a PV at the time of an AF ablation procedure, ablation of that focal trigger should be considered. 
• If additional linear lesions are applied, operators should consider using mapping and pacing maneuvers to assess for line completeness. 
• Ablation of the cavotricuspid isthmus is recommended in patients with a history of typical atrial flutter or inducible cavotricuspid isthmus dependent atrial flutter. 
• If patients with long standing persistent AF are approached, operators should consider more extensive ablation based on linear lesions or complex fractionated electrograms. 
• It is recommended that RF power be reduced when creating lesions along the posterior wall near the esophagus. 
• Ablation strategies that target the PVs and/or PV antrum are the cornerstone for most AF ablation procedures. 
• If the PVs are targeted, electrical isolation should be the goal. 
• Achievement of electrical isolation requires, at a minimum, assessment and demonstration of entrance block into the PV. 
• Monitoring for PV reconduction for 20 minutes following initial PV isolation should be considered. 
• For surgical PV isolation, entrance and/or exit block should be demonstrated. 
• Careful identification of the PV ostia is mandatory to avoid ablation within the PVs. 
• If a focal trigger is identified outside a PV at the time of an AF ablation procedure, ablation of that focal trigger should be considered. 
• If additional linear lesions are applied, operators should consider using mapping and pacing maneuvers to assess for line completeness. 
• Ablation of the cavotricuspid isthmus is recommended in patients with a history of typical atrial flutter or inducible cavotricuspid isthmus dependent atrial flutter. 
• If patients with long standing persistent AF are approached, operators should consider more extensive ablation based on linear lesions or complex fractionated electrograms. 
• It is recommended that RF power be reduced when creating lesions along the posterior wall near the esophagus. 

TECHNOLOGIES AND TOOLS

In this section, we provide an update on a large number of technologies and tools that are employed for AF ablation procedures. It is important to recognize that this is not a comprehensive listing and that new technologies, tools, and approaches are being developed. It is also important to recognize that radiofrequency energy (RF) is by far the dominant energy source that has been used for catheter ablation of AF. Cryoablation has more recently been developed as a tool for AF ablation procedures. Other energy sources and tools are in various stages of development and/or clinical investigation.

Energy Sources – Radiofrequency Energy

The presumed basis of successful AF ablation is production of myocardial lesions that block the propagation of AF wave fronts from a rapidly firing triggering source or modification of the arrhythmogenic substrate responsible for reentry. Successful ablation depends upon achieving lesions that are reliably transmural.251,252 The conventional approach employed by cardiac electrophysiologists to reach the goal of AF ablation is RF energy delivery by way of a transvenous electrode catheter.

RF energy achieves myocardial ablation by the conduction of alternating electrical current through myocardial tissue, a resistive medium. The tissue resistivity results in dissipation of RF energy as heat, and the heat then conducts passively to deeper tissue layers. Most tissues exposed to temperatures of 50°C or higher for more than several seconds will show irreversible coagulation necrosis, and evolve into non-conducting myocardial scar.253 High power delivery and good electrode–tissue contact promote the formation of larger lesions and improve procedure efficacy. High power delivery can be achieved with large-tip or cooled-tip catheters.254,255 Optimal catheter–tissue contact is achieved by a combination of steerable catheter selection, guide sheath manipulation, and skill of the operator. Significant complications can occur during AF ablation if high RF power is administered in an uncontrolled fashion. The increased risk of AF ablation compared to ablation of other arrhythmias may be attributable to the great surface area of tissue ablated, the large cumulative energy delivery, the risk of systemic thromboembolism, and the close location of structures susceptible to collateral injury, such as phrenic nerve,256 PVs,257 and esophagus.258 Thrombus and char can be minimized by limiting power and/or target temperature,259 by monitoring the production of steam microbubbles at the catheter tip with ICE,260–262 and by cooling the electrode–tissue interface with saline irrigated tips.263 Intramural steam pops can be reduced by limiting power and the electrode–tissue contact pressure, which is greater when the catheter is oriented perpendicular to the atrial wall.

Early reports of catheter ablation of AF employed conventional 4-mm or 5-mm tip ablation catheters. Lesions were created with point-to-point application of RF energy or with continuous RF energy application while the catheter was dragged across the myocardium. The majority of the members of the Task Force now employ irrigated tip catheters. Comparative trials of irrigated tip and large tip RF technologies versus conventional RF electrodes have demonstrated increased efficacy and decreased procedure duration in the ablation of atrial flutter,264–266 but only limited trials of large tip and open irrigation catheters have been performed in patients undergoing AF ablation. Despite the widespread adoption of irrigated RF ablation catheters, there is no definitive proof that these catheters reduce complications or improve outcomes when used for ablation of AF. Increased efficacy is observed with higher power applications of RF energy.267

Various techniques have been proposed to minimize collateral injury. Temperature sensors at the electrode catheter tip can provide gross feedback of surface temperature, but because of passive convective cooling from circulating blood flow, or active cooling in a cooled tip catheter, the peak tissue temperatures are sometimes millimeters below the endocardial surface. Three-fourths of the Task Force routinely decrease RF power when ablating in the posterior LA. Limiting power will limit collateral injury but at the expense of reliably transmural lesions. ICE has been employed to monitor lesion formation. If the tissue shows evidence of increased echogenicity, or if small gas bubbles are observed, then power should be reduced or terminated.260–262 It is important to note, however, that the presence of gas bubbles cannot be used to monitor lesion formation when an open irrigated catheter is used for ablation. The time to steady-state tissue temperatures during RF catheter ablation is approximately 60–90 seconds.253 Therefore, limiting lesion duration may result in smaller ablative lesions.

Contact Force Sensing Catheters and Systems

A constant challenge in catheter ablation is optimizing electrode–tissue contact. With excellent contact, energy coupling to tissue is optimized and less energy is dissipated into the circulating blood pool. Thus, more predictable and reliable lesions can be created with excellent catheter contact to the endocardium. Attempts have been made to monitor catheter contact to the endocardium with imaging, predominantly intracardiac echocardiography. However, the technology now exists to directly measure the force exerted at the catheter tip or to estimate contact force based on local impedance.268–272 It is hypothesized that monitoring electrode–tissue contact will improve efficacy of transmural lesion formation and improve procedure success. It is also hypothesized that monitoring electrode–tissue contact will reduce the rate of complications, particularly cardiac tamponade.

Energy Sources – Cryoablation Energy

Cryothermal energy is an alternative energy source that has been used for decades by cardiac surgeons for treatment of cardiac arrhythmias. More recently, a number of point-by-point and balloon-based cryoablation systems have been developed for endocardial use.273–277 Endocardial cryoablation catheters were employed initially for treatment of supraventricular arrhythmias, especially those near the AV node, and subsequently were used for AF ablation using a segmental PV isolation strategy.273–275,277 Although this point-by-point cryoablation approach proved to be associated with a low complication rate, the procedures were lengthy, and the long-term efficacy was limited. This early work ultimately paved the way for the development of a cryoablation balloon ablation catheter.276

Cryoablation systems work by delivering liquid nitrous oxide under pressure through the catheter to its tip or within the balloon, where it changes to gas, resulting in cooling of surrounding tissue. This gas is then carried back through the reciprocating vacuum lumen. The mechanism of tissue injury results from tissue freezing with a creation of ice crystals within the cell that disrupts cell membranes and interrupts both cellular metabolism and any electrical activity in that cell. In addition, interruption of micro-vascular perfusion may interrupt blood flow, similarly producing cell death.

Achieving optimal cryoablation lesions is critically dependent upon regional blood flow around the tip of the catheter or balloon. As with RF energy, good tissue contact is important for generation of effective lesions. Continued flow counters the effect of cooling, thus reducing the chance to achieve a full-thickness lesion. Because of this, complete vein occlusion is required for the creation of circumferential PV lesions and electrical PVI using the cryoballoon ablation catheter.276,278,279 The clinical results of catheter ablation of AF will be discussed in section 8.

Ultrasound and Laser Ablation Systems

Although point-by-point RF energy and cryoballoon ablation are the two standard ablation systems used for catheter ablation of AF today, balloon-based ultrasound ablation,280–282 RF ablation,283 and laser based ablation systems284,285 also have been developed for AF ablation. A novel RF point-by-point ablation catheter that relies on visually guided ablation through a virtual saline electrode is also in development.286 The first of these balloon ablation systems to be approved for clinical use in Europe was the focused ultrasound ablation system.280–282 Although this balloon-based ablation system was demonstrated to be effective, it was removed from the market because of a high incidence of atrial esophageal fistulas, some of which resulted in patient death. Early data from Japan has demonstrated the safety and effectiveness of a hot balloon ablation system that relies on RF energy to heat a saline-filled balloon positioned in the PVs.283 A final balloon-based laser ablation system involves a compliant balloon ablation catheter through which arcs of laser energy are delivered under visual guidance. Initial results of small clinical trials have demonstrated the safety and effectiveness of this ablation system, which is now approved for use in Europe and is entering a pivotal randomized clinical trial in the United States.284,285

Multielectrode Circumferential Ablation Catheters

A number of circumferential multielectrode ablation catheters have been developed to facilitate AF ablation and have undergone clinical evaluation. The principle purpose of these multielectrode circular ablation catheter systems is to provide ablation and mapping on a single platform.287–293 One of these ablation systems relies on phased RF energy for ablation287,291–293 and the other uses standard RF energy delivered through a novel mesh electrode.288–290 One of the potential limitations of such catheters is that operators are easily drawn to a more ostial location rather than the wider area circumferential antral ablation that can be achieved with a point-by-point ablation tip catheter under 3D guidance. The clinical results achieved with these multielectrode circular ablation catheters have been roughly equivalent in safety and efficacy to those achieved by point-by-point tip ablation catheters.287–293 However, several recent studies have reported a higher incidence of silent microemboli following ablation with a multielectrode ablation catheter.294,295 (See section 9.5.2 silent micro-emboli.) The precise mechanisms for development of these silent microemboli are not fully understood and remain an area of active investigation. Very recently the results of the TTOP Trial have been released.296 This trial enrolled 210 patients with persistent or long-standing persistent AF with the Medtronic Cardiac Ablation System, which incorporates several multielectrode ablation catheters, to either ablation or antiarrhythmic drug therapy. At 6 months of follow-up, 55.8% of patients who underwent one or more ablation procedures had a >90% reduction in AF burden on a 48-hour Holter monitor as compared with 26.4% of patients treated with drug therapy. The rate of major complications was 12.3% including a 2.3% incidence of stroke.

Electroanatomic Mapping Systems

AF is a disease frequently progressing from paroxysmal to persistent AF. The mechanisms underlying the process of arrhythmia perpetuation are complex. Major contributions to the understanding of the initiating and perpetuating factors derive from mapping studies in both patients and animal models of AF. It is well known that mapping and ablation of AF require accurate navigation in the LA. This can be obtained using standard fluoroscopy or more commonly with electroanatomic mapping systems that combine anatomical and electrical information by a catheter point-by-point mapping, allowing an accurate anatomical reconstruction of a 3D shell of the targeted cardiac chamber.

There are two different electroanatomic mapping systems that are widely used in clinical practice. The current generation of the CARTO mapping system (CARTO-3) relies both on a magnet-based localization for visualization of the ablation catheter and an impedance-based system that allows for both tip and catheter curve visualization as well as simultaneous visualization of multiple electrodes.110,297,291 The second electroanatomic mapping system is an electrical impedance mapping system (NavX, St. Jude Medical Inc., Minneapolis, MN, USA) using voltage and impedance for localization.298 The use of these 3D mapping systems has been demonstrated to reduce fluoroscopy duration.298,299 To further improve anatomical accuracy of the maps, integration of 3D images by computed tomography (CT) or magnetic resonance imaging (MRI) and of images acquired with intracardiac ultrasound during the procedure (before transseptal puncture) has become available.300–302 Image integration is performed by defining landmark points on the CT or MRI reconstruction of the LA followed by merging the CT or MRI image with the anatomical map that has been constructed using the mapping catheter. Another approach involves use of 3D rotational angiography images, which can be merged with live 2D fluoroscopy.303 However, it should be stressed that CT or MRI images are not real-time images, and that the accuracy of image integration is dependent on the accuracy of the image fusion. Another limitation of electroanatomical mapping systems is that they are only capable of sequential and not simultaneous multielectrode mapping. Because of this limitation, they are not capable of activation mapping of atrial fibrillation and other unstable cardiac arrhythmias.

Several studies performed to define the clinical benefit of image integration as compared to ablation guided only with a standard electroanatomic mapping system have generated mixed results. Whereas some studies have reported that use of these mapping systems with or without image integration improves the safety and efficacy of AF ablation,304–306 other studies have reported contradictory findings.307,308 Among Task Force members 90% employ electroanatomic mapping systems routinely when performing AF ablation (excluding cases where a balloon-based ablation system is used).

Robotic and Magnetic Catheter Navigation

Catheter-based ablation of AF places significant demands on the skill and experience of the electrophysiologist. The objectives of developing new technologies are to improve the efficacy and safety of procedures while containing or reducing costs. The concept of remote catheter navigation is appealing for the operator because these systems may reduce radiation exposure and the risk to the physician of developing orthopedic problems related to prolonged use of protective lead aprons during protracted cases. They also may facilitate analysis of intracardiac EGMs and 3D images because the catheter navigation and analysis can be performed from a work station where the operator is seated. The two technologies developed to meet these objectives include the magnetic navigation system designed by Stereotaxis, Inc.309–311 and a robotic controlled catheter system manufactured by Hansen Medical.312,313 Both technologies have been used to ablate AF. No randomized multicenter studies have compared these technologies to ablation with a manual catheter to demonstrate whether either system shortens procedure time, reduces cost, improves outcomes of ablation, or improves the safety profile of these and other complex ablation procedures.

Intracardiac Echocardiography

Intracardiac echocardiography, which allows for real-time imaging of cardiac anatomy, is used in many EP laboratories throughout the world to facilitate AF ablation procedures.91,314–317 Advocates of the use of ICE find it to be of value as it can (1) help identify anatomic structures relevant to ablation, including the PVs and esophagus, (2) facilitate transseptal access, (3) guide accurate placement of the multielectrode circular ablation catheter and/or balloon-based ablation system, (4) allow titration of delivered energy, (5) allow for recognition of thrombus formation on sheaths and catheters,318 and (6) allow early recognition of cardiac perforation and/or the development of a pericardial effusion. ICE does not replace TEE for screening for the presence of a LA thrombus. Fifty percent of Task Force members routinely use ICE to facilitate the transseptal procedure and/or to guide catheter ablation.

Pulmonary Vein Venography

PV venography is performed by many centers at the time of catheter ablation procedures.319,320 The purpose of PV venography is to help guide catheter manipulation, determine the size and location of the PV ostia, and also assess PV stenosis, particularly among patients undergoing repeat ablation procedures. Among Task Force members, 50% routinely use PV venography during their AF ablation procedures. There are three techniques that have been described for PV venography. The first technique involves selective delivery of contrast media into each of the PV ostia. This can be accomplished by positioning the transseptal sheath in the region of the right and left PV trunks and injecting contrast medium, or by selectively engaging each of the four PV ostia using a deflectable catheter or a multipurpose angiography catheter.320 A limitation of the selective PV venography approach is that noncatheterized PVs can be missed if a pre-acquired CT or MRI scan is not available to make sure that all PVs are identified. The second technique is performed by injection of contrast medium into the left and right pulmonary arteries or the pulmonary trunk. The location of the PVs can then be assessed during the venous phase of pulmonary arteriography. The third technique involves the injection of contrast media in the body of the LA or at the roof of the right or left superior PV ostium immediately after delivery of a bolus of adenosine to induce AV block. The contrast media will fill the LA body, PV antrum, and the proximal part of PV during the phase of ventricular asystole.

CT and/or MRI scans and Rotational Angiography to Define the Anatomy of the Atrium, PVs, and Antrum

The left atrial anatomy is complex. A detailed understanding of this anatomy is essential for a safe and effective AF ablation procedure. Left atrial imaging may facilitate AF ablation by (1) providing a detailed anatomical description of the PVs and LA pre-procedurally, and (2) assisting in the detection of post-procedural complications.

There is significant inter- and intra-patient variability in the number, size, and bifurcation of the PVs.321–327 Understanding these variations can be useful for the application of ablation lesions around or outside the PV ostia. One common variant is the existence of supernumerary right PVs. These have been shown to be present in 18% to 29% of the patients.321–326 Knowledge of the presence of a right middle or right top PV may help avoid placing ablation lesions over their ostia, which may result in PV occlusion. Another common variant is the presence of a common PV trunk. This is more frequently encountered on the left-sided PVs (>30%).328,329 The branching pattern of the PVs may also have procedural implications. A significantly longer distance between the PV ostium and first branch was demonstrated for the left versus right PVs.324 A pre-procedural knowledge of the bifurcation pattern may also be important during cryoballoon PVI, where wiring of different branches may be needed to ensure optimal occlusion.330

Pre-procedural CT and MR imaging can also be used for image integration. This technology helps facilitate AF ablation by providing detailed information about the anatomy.300,301 When using these systems, it is critical to confirm accurate registration.

Intraprocedural acquisition of LA volumes using rotational angiography has recently been introduced.303,331–337 After contrast medium injection in the right heart chambers, the fluoroscopy c-arm is rapidly rotated around the patient, and images are acquired throughout the rotation to generate 3D volumetric anatomical rendering of the LA–PVs. Such images can be superimposed onto the fluoroscopic projections of the heart or integrated into an electroanatomical mapping system. Recent studies have demonstrated that this modality can provide intra-procedural imaging with anatomical accuracy comparable to that of CT.333–335,337 This innovative technique might overcome the limitation of acquiring the images in a different time with respect to the ablation procedure, but the consistent iodinated contrast agent load and radiation dose are important limiting factors.338 Less than one-third of Task Force members employ rotational angiography as part of some or all of their AF ablation procedures.

Assessment of Left Atrial Volume

Left atrial volume can be assessed by a variety of techniques. Perhaps the most widely employed approach is measurement of the end-systolic LAD in the parasternal long axis view according to the American Society of Echocardiography guidelines.339 Although this parameter is widely used clinically to determine eligibility for AF ablation with LAD cutoffs of 5 or 5.5 cm, recent reports have demonstrated that this parameter correlates poorly with true left atrial volume, as assessed by CT imaging.340,341 Alternative methods to assess left atrial volume include 3D echo,342 CT imaging, MR imaging,343 left atrial angiography,344 3D electroanatomic mapping, 344 and TEE.341 Various approaches to calculating left atrial volume can be used with each of these approaches. Recent studies have demonstrated, for example, that calculation of left atrial volume based on three orthogonal left atrial dimensions obtained from CT, MR, or 3D echo imaging underestimates true left atrial volume as determined by the gold standard multiple-slice technique by 10–20%.342,343,345 In contrast, invasive techniques for determining LA volume such as angiography and point-by-point electroanatomic mapping result in an overestimation of LA size and left atrial volume.344 Recently, perhaps not surprisingly, a series of studies have demonstrated that LA volume is one of the strongest predictors of outcome following AF ablation.341,346–349

MR Imaging of Atrial Fibrosis and Ablation Lesions

Magnetic resonance imaging has been used to visualize myocardial inflammation and fibrous tissue by using delayed clearance of gadolinium from myocardial areas with high content of fibrous tissue, high volume of extracellular matrix, and high inflammatory activity. All of these result in enhanced extravasation of gadolinium and slower removal from cardiac tissue, which is then detectable as “delayed enhancement,” i.e. detectable deposition of gadolinium after the usual time needed to remove it from the tissue. This technique is well validated to visualize myocardial scars in the left ventricular myocardium.350,351 Delayed enhancement can also visualize lesions induced by radio frequency catheter ablation in atrial tissue.98,352,353 More recent studies from a single center have demonstrated that the extent of LA fibrosis prior to ablation can predict the outcomes of catheter ablation of AF.98,354 Further work is needed, however, to determine the reproducibility of MRI measurements of fibrosis by different centers and also to validate the predictive accuracy of MRI detected fibrosis in predicting outcomes of AF ablation. Based on this initial work, efforts are now underway to allow catheter ablation of AF to be performed under MRI guidance.355,356 Despite the promise of using these MRI techniques to improve the outcomes of AF ablation, it is important to recognize that technical aspects of magnetic resonance-based imaging of atrial fibrosis and ablation lesions make it difficult to adapt these techniques for clinical use today.

Approaches to Mapping Atrial Fibrillation Including CFAEs, Dominant Frequency, Nests, and Rotors

Over the past decade, several mapping studies in human AF have made the following important observations: (1) atrial EGMs during sustained AF have three distinct patterns: single potential, double potential, and CFAE;82,243,244 (2) the distribution of these atrial EGMs during AF has a proclivity to localize in specific areas of the atria;82,243,357 (3) CFAE areas are believed to reflect the AF substrate and to be important target sites for AF ablation by some investigators;82,92,243,244,358 (4) and high dominant frequency (DF) as assessed using Fast Fourier transformation (FFT) is thought to represent drivers of AF.16,48 Mapping of areas that harbor stable CFAE and/or high DF could identify sites that perpetuate AF and in turn be considered targets for AF ablation.

CFAEs are defined as low voltage (≤0.15 mV) multiple potential signals and have one or both of the following characteristics: (1) atrial EGMs that have fractionated EGMs composed of two deflections or more, and/or have a perturbation of the baseline with continuous deflection of a prolonged activation complex; (2) atrial EGMs with a very short cycle length ( ≤120 milliseconds), with or without multiple potential; however, when compared with the rest of the atria, this site has the shortest cycle length. The distribution of CFAEs in the right and left atria is vastly different from one area to the others. In spite of regional differences in the distribution, CFAEs are surprisingly stationary, exhibiting relative spatial and temporal stability.357,358 Thus, one can perform point-to-point mapping of these CFAE areas and incorporate into an electroanatomical map. Each of the currently available electroanatomic mapping systems has available software that allows for user defined, automated detection of CFAEs. Mapping is always performed during AF.358 Detailed mapping of the LA, CS, and occasionally the right atrium is performed. The primary target sites for AF substrate ablation are the CFAE areas that are stable that exhibit either very short cycle length (<100 milliseconds) or continuous activity. The primary endpoints during RF ablation targeting CFAE sites are either complete elimination of the areas with CFAE, conversion of AF to sinus rhythm (SR), and/or non-inducibility of AF. For patients with paroxysmal AF, the endpoint of the ablation procedure using this approach is non-inducibility of AF. For patients with persistent AF, the endpoint of ablation with this approach is AF termination. When the areas with CFAEs are completely eliminated, but the arrhythmias continue as organized atrial flutter or AT, the atrial tachyarrhythmias are mapped and ablated.

It is noteworthy to recognize the recent observation that occurrences of CFAE may involve the complex interplay of the intrinsic cardiac nervous system on atrial tissues.76,78–80,359 Hence, mapping CFAE areas may provide a surrogate for identification of the GPs. Please see the earlier section of this document for more details. It is also important to recognize that CFAEs may be generated by “fibrillatory conduction” or far field signals and thus are not always critical for AF maintenance.

The purpose of DF mapping is to identify sites of maximal DF during AF.48,360 There is evidence that ablation at such maximal DF sites results in slowing and termination in a significant proportion of paroxysmal AF patients, suggesting their role in AF maintenance.

Recently, a system for real-time spectral mapping using FFT in sinus rhythm was created to identify sites in which the unfiltered, bipolar atrial EGMs contain unusually high frequencies, namely fibrillar myocardium, or the so-called AF Nest.361–363 Most investigators use customized amplifiers and software for real-time spectral mapping. The system applies FFT to the unfiltered bipolar atrial EGMs from the distal pair of electrodes on the ablation catheter. The full spectrum of each EGM is then continuously displayed in 3D. Ablation of the aforementioned AF nest sites in conjunction with PVI may improve outcomes of AF ablation in patients with paroxysmal AF.361,362,364 All of the above techniques are based on, and suited to, sequential single catheter techniques with all their inherent limitations.

Strategies for Mapping and Ablation of Linear Ablation Lines Including Left Atrial Flutter

The development of a left AT or left atrial flutter (referred to as LAFL throughout this document) following AF ablation is common, occurring in between 1% and 50% of patients. LAFL is rarely observed in the context of paroxysmal AF ablation when the procedure is limited to PVI.212,223,225,365–368 The incidence of LAFL is relatively uncommon (<1%) when the cryoballoon is used for treatment of patients with paroxysmal AF.369 The likelihood of developing a LAFL increases markedly in patients with longstanding persistent AF, markedly dilated atria, and where linear ablation strategies are employed.223,225,231,366–368 There is debate as to whether the development of a LAFL following AF ablation should be considered a “proarrhythmic” complication of the procedure or whether it should be considered as partial success as evidenced by significant modification of the atrial electrophysiologic substrate as compared with prior to ablation. Because the outcomes of catheter ablation of LAFL are superior to those associated with catheter ablation of AF alone, some consider the development of a LAFL evidence of partial success, while others do not.370 It is important to recognize that many patients with LAFL are highly symptomatic and/or have a very difficult to control ventricular response, making the performance of another ablation procedure mandatory in many patients.

Diagnostic Mapping Strategies

Evaluation of the 12-lead ECG is of some value in the diagnosis of an LAFL. The presence of a positive or biphasic but dominantly positive deflection in V1 accompanied by deflections in other leads inconsistent with typical counter clockwise atrial flutter should suggest the presence of an LAFL.371–375 It is also important to note that the demonstration of P waves on the 12-lead ECG separated by long isoelectric intervals should not lead to exclusion of a re-entrant AT but rather may indicate microreentry involving slowly conducting isthmus often near one of the prior AF ablation lesions. Although the analysis of the surface ECG has been used to predict centrifugal vs. macro-reentrant arrhythmias and identify perimitral circuits, the use of the 12-lead ECG for localization of the LAFL may be limited by extensive LA ablation, disease and dilatation.

The most widely used strategy for mapping these flutters relies on 3D electro-anatomic mapping systems using signals obtained either by a point-by-point roving catheter or a multipolar catheter. In addition to standard activation mapping strategies, color entrainment maps can be constructed using the return cycle length values obtained during flutter entrainment from various sites.376 A rapid deductive approach that involves a sequence of activation and entrainment mapping has also been described.377 Conventional mapping is also an effective strategy to establish the diagnosis of LAFL.

Catheter Ablation of Left Atrial Flutter

The macro-reentrant circuits that are dependent on the roof line or mitral isthmus line are easy to diagnose but may be difficult to ablate (see below). Drawing a roof line connecting both superior PVs is usually easier than the mitral isthmus line. Roof linear ablation is recommended at the roof of the LA rather than on the posterior left atrial wall because the latter is associated with an increased risk of atrial esophageal fistula. After restoration of sinus rhythm, demonstration of an ascending activation front in the posterior LA during pacing from the LA atrial roof or LAA ascertains complete linear roof block.222 The ablation of localized centrifugal arrhythmias can be accomplished with focal RF energy delivery. Non reentrant focal arrhythmias often originate at lesion edges.

Strategies, Tools, and Endpoints for Creation of Linear Ablation Lesions including Mitral Isthmus Block

Linear lesion is considered a double-edged sword because an incompletely blocked line can be as much associated with man-made AT as a completely blocked line can provide freedom from it.225 Linear lesions typically are created between two anatomical or electrical barriers. Completeness of the linear ablation lesion should be demonstrated with pacing and/or mapping maneuvers.

In the context of AF ablation, mitral isthmus linear lesion was first proposed in 2004.223 The ablation of mitral isthmus is the most challenging linear lesion in AF ablation. This may be due to anatomical difficulties, increased tissue thickness, and heat sink effect of the CS. Two distinct strategies have been reported. The original description of the most commonly used approach consists of delivering the ablation lesion below the base of the left atrial appendage, corresponding to a 3–4 o'clock position in the LAO view. Ablation in this location is challenging, possibly because of the heat sink effect of the blood flowing in the epicardially located CS. As a consequence, ablation from inside the CS is frequently needed to achieve a transmural lesion. However, lesion at this location will produce no local delay in sinus rhythm as it lies in the region where the anterior and inferior activation wavefronts collide. Mitral isthmus linear ablation recently has been proposed in an anterior or more superior location than usual. Although there is no randomized comparison with conventional site of ablation, achieving complete mitral isthmus block seems to be facilitated by anterosuperior location of the linear lesion. However, its major drawback is that it can significantly modify the activation pattern in sinus rhythm, especially that of the left atrial appendage. The latter is activated with a substantial delay; sometimes simultaneously with or after the QRS. This could impact left atrial function significantly more than the inferior approach.

The most commonly used approach consists of using a fixed curved left atrial sheath to facilitate ablation by dragging the catheter from the mitral annulus to the ostium of the left inferior PV. However, the achievement of a complete isthmus block remains difficult. The occlusion of the segment of CS with a balloon to prevent a heat sink has been shown to facilitate creation of a mitral isthmus block but is currently not widely employed in clinical practice.117,378 The roof line connecting both superior PVs is usually easier than the mitral isthmus line. The anatomy of the LA roof varies highly from being flat, concave, and even convex. Ablation is undertaken with the support of a sheath.

During ongoing AF, assessment of complete linear block is not possible. It is therefore recommended to assess linear block after the restoration of sinus rhythm. The endpoint of linear lesion is complete, bidirectional block across the linear lesion. The assessment of complete block is based on the concept of differential pacing that was initially demonstrated for cavotricuspid isthmus ablation. Briefly, pacing from a site close to the line of block generates an activation wavefront that is blocked in the direction toward the line. The wavefront, then, necessarily travels in the direction away from the line and courses all around the LA to eventually reach the other side of the line. The following criteria establish the diagnosis of complete, bidirectional block across mitral isthmus linear lesion: (1) pacing from the site immediately posterior to the ablation line (usually distal bipole (CS 1-2) of the catheter lying inside the CS) should be associated with a longer delay to the left atrial appendage as compared with pacing from a more proximal site (usually bipole CS 3-4); and (2) pacing from the base of the left atrial appendage, a site anterior to the line of block should result in a proximal to distal activation of the catheter lying in the CS with its distal bipole being the latest activated site as long as it is located below the ablation line. These criteria are robust and the only limitation is the presence of a very slowly conducting gap in the mitral isthmus line such that the activation through the gap would take longer than the activation around the mitral annulus. It is worth noting that it is easier to distinguish residual slow conduction from complete conduction block across a mitral ablation line as compared with a roof line, probably for anatomic reasons. In addition to these criteria, mapping the ablation line during pacing from a site adjacent to the line shows widely separated double potentials with no bridging activity. Any absolute value of perimitral conduction delay should not be considered a reliable indicator of block. Complete block has been observed with a delay as short as 100 milliseconds. On the other hand, more than 200 milliseconds of conduction delay may not be indicative of block.

The assessment of complete block across the roof can be undertaken during sinus rhythm or during pacing from the anterior LA. The concept is that during both rhythms, the posterior LA is activated downward from the anterior roof in the absence of block, while in the presence of complete block, the activation wave must proceed downward (after having arrived from right atrium over the Bachmann's bundle in sinus rhythm or from the pacing site) on the anterior wall and then upward on the posterior wall. Therefore, during both rhythms, the demonstration of block relies on an ascending activation front of the posterior LA. This is easily demonstrated by recording the local activation time high on the posterior wall, below the ablation line, and lower in the mid posterior LA. The former should be activated later in the presence of block. The comment on the absolute value of delay necessary to call it a blocked mitral line holds true for the roof line, too. Electro-anatomical systems can, of course, be used to easily demonstrate the activation front detour due to complete line of block during pacing after ablation.

OTHER TECHNICAL ASPECTS

Anticoagulation Strategies to Prevent Thromboembolism During and Following AF Ablation

AF patients are at increased risk of thromboembolism (TE) during, immediately following, and for several weeks to months after their ablation.379,380 This prothrombotic period results in a higher, but transient TE risk in AF patients who were identified as low-risk before ablation. Careful attention to anticoagulation of patients before, during, and after ablation for AF is critical to avoid the occurrence of a TE event. Consensus recommendations for anticoagulation prior to, during, and following ablation are summarized in Table 4. The ablation procedure leaves patients with substantial areas of damaged LA endothelium that may become a nidus for thrombus formation. Transseptal sheath placement and insertion of electrode catheters can precipitate thrombus formation on the catheter or on or within the sheath during the procedure.318,381–384 The atrial tissue may be stunned for several weeks or even months post procedure, leading to impairment of normal contraction.385 Anticoagulation, in turn, contributes to some of the most common complications of the procedure, including hemopericardium, pericardial tamponade, and vascular complications.386–388 Therefore, attention must be paid to achieving the optimal safe level of anticoagulation throughout the process.

TABLE 4:

ANTICOAGULATION STRATEGIES: PRE, DURING, AND POST ABLATION

Pre Ablation 
 • Anticoagulation guidelines that pertain to cardioversion of AF be adhered to in patients who present for an AF ablation in atrial fibrillation at the time of the procedure. In other words, if the patient has been in AF for 48 hours or longer or for an unknown duration, we require three weeks of systemic anticoagulation at a therapeutic level prior to the procedure, and if this is not the case, we advise that a TEE be performed to screen for thrombus. Furthermore, each of these patients will be anticoagulated systemically for two months post ablation. 
 • Prior to undergoing an AF ablation procedure a TEE should be performed in all patients with atrial fibrillation more than 48 hours in duration or of an unknown duration if adequate systemic anticoagulation has not been maintained for at least three weeks prior to the ablation procedure. 
 • Performance of a TEE in patients who are in sinus rhythm at the time of ablation or patients with AF who are in AF but have been in AF for 48 hours or less prior to AF ablation may be considered but is not mandatory. 
 • The presence of a left atrial thrombus is a contraindication to catheter ablation of AF. 
 • Performance of catheter ablation of AF on a patient who is therapeutically anticoagulated with warfarin should be considered. 
During Ablation 
 • Heparin should be administered prior to or immediately following transseptal puncture during AF ablation procedures and adjusted to achieve and maintain an activated clotting time (ACT) of 300 to 400 seconds. 
 • Performance of AF ablation in a patient systemically anticoagulated with warfarin does not alter the need for intravenous heparin to maintain a therapeutic ACT during the procedure. 
 • Administration of protamine following ablation to reverse heparin should be considered. 
Post Ablation 
 • In patients who are not therapeutically anticoagulated with warfarin at the time of AF ablation, low molecular weight heparin or intravenous heparin should be used as a bridge to resumption of systemic anticoagulation with warfarin following AF ablation. 
 • Initiation of a direct thrombin or Factor Xa inhibitor after ablation may be considered as an alternative post procedure anticoagulation strategy. 
 • Because of the increased risk of post procedure bleeding on full dose low molecular weight heparin (1 mg/kg bid) a reduction of the dose to 0.5 mg/kg should be considered. 
 • Systemic anticoagulation with warfarin or a direct thrombin or Factor Xa inhibitor is recommended for at least two months following an AF ablation procedure. 
 • Decisions regarding the continuation of systemic anticoagulation agents more than two months following ablation should be based on the patient's risk factors for stroke and not on the presence or type of AF. 
 • Discontinuation of systemic anticoagulation therapy post ablation is not recommended in patients who are at high risk of stroke as estimated by currently recommended schemes (CHADS2 or CHA2DS2VASc)3 
 • Patients in whom discontinuation of systemic anticoagulation is being considered should consider undergoing continuous ECG monitoring to screen for asymptomatic AF/AFL/ AT. 
Pre Ablation 
 • Anticoagulation guidelines that pertain to cardioversion of AF be adhered to in patients who present for an AF ablation in atrial fibrillation at the time of the procedure. In other words, if the patient has been in AF for 48 hours or longer or for an unknown duration, we require three weeks of systemic anticoagulation at a therapeutic level prior to the procedure, and if this is not the case, we advise that a TEE be performed to screen for thrombus. Furthermore, each of these patients will be anticoagulated systemically for two months post ablation. 
 • Prior to undergoing an AF ablation procedure a TEE should be performed in all patients with atrial fibrillation more than 48 hours in duration or of an unknown duration if adequate systemic anticoagulation has not been maintained for at least three weeks prior to the ablation procedure. 
 • Performance of a TEE in patients who are in sinus rhythm at the time of ablation or patients with AF who are in AF but have been in AF for 48 hours or less prior to AF ablation may be considered but is not mandatory. 
 • The presence of a left atrial thrombus is a contraindication to catheter ablation of AF. 
 • Performance of catheter ablation of AF on a patient who is therapeutically anticoagulated with warfarin should be considered. 
During Ablation 
 • Heparin should be administered prior to or immediately following transseptal puncture during AF ablation procedures and adjusted to achieve and maintain an activated clotting time (ACT) of 300 to 400 seconds. 
 • Performance of AF ablation in a patient systemically anticoagulated with warfarin does not alter the need for intravenous heparin to maintain a therapeutic ACT during the procedure. 
 • Administration of protamine following ablation to reverse heparin should be considered. 
Post Ablation 
 • In patients who are not therapeutically anticoagulated with warfarin at the time of AF ablation, low molecular weight heparin or intravenous heparin should be used as a bridge to resumption of systemic anticoagulation with warfarin following AF ablation. 
 • Initiation of a direct thrombin or Factor Xa inhibitor after ablation may be considered as an alternative post procedure anticoagulation strategy. 
 • Because of the increased risk of post procedure bleeding on full dose low molecular weight heparin (1 mg/kg bid) a reduction of the dose to 0.5 mg/kg should be considered. 
 • Systemic anticoagulation with warfarin or a direct thrombin or Factor Xa inhibitor is recommended for at least two months following an AF ablation procedure. 
 • Decisions regarding the continuation of systemic anticoagulation agents more than two months following ablation should be based on the patient's risk factors for stroke and not on the presence or type of AF. 
 • Discontinuation of systemic anticoagulation therapy post ablation is not recommended in patients who are at high risk of stroke as estimated by currently recommended schemes (CHADS2 or CHA2DS2VASc)3 
 • Patients in whom discontinuation of systemic anticoagulation is being considered should consider undergoing continuous ECG monitoring to screen for asymptomatic AF/AFL/ AT. 

Screening Transesophageal Echocardiography

The risk of a thromboembolic event at the time of an AF ablation procedure varies depending upon a number of factors including: (1) the type of AF, (2) the presence, absence, and duration of AF as the presenting rhythm, and (3) the patient's stroke risk profile including left atrial size and CHADS2 or CHA2DS2VASc score. The recommendations of this Consensus Writing Group are summarized in Table 4. Among these recommendations, several are of particular importance. First, we recommend that the anticoagulation guidelines that pertain to cardioversion of AF be adhered to in patients who present in AF for an AF ablation procedure. In other words, if the patient has been in AF for 48 hours or longer or for an unknown duration, we require three weeks of systemic anticoagulation at a therapeutic level prior to the procedure. If this is not the case, we advise that a TEE be performed to screen for thrombus. Furthermore, following the recommendations for cardioversion, we advise that patients are anticoagulated systemically for two months post ablation (Table 4).

Several studies have evaluated the incidence of LA thrombus on TEE among patients undergoing AF ablation who have been therapeutically anticoagulated.389–391 The results of these three studies have been remarkably consistent, demonstrating that 1.6% to 2.1% of patients will demonstrate a thrombus or “sludge” in the left atrial appendage. The probability of identifying a thrombus was directly related to the CHADS2 score in each of these studies. Other variables that were identified as risk factors were left atrial size and persistent AF. Among patients with a CHADS2 score of zero, a thrombus was identified in ≤0.3% of patients and >5% of patients with a CHADS2 score of two or greater.

There is wide variation among the Task Force Members concerning use of TEE prior to AF ablation. Approximately 50% of Task Force Members perform a TEE in all patients undergoing AF ablation regardless of presenting rhythm and CHADS2 or CHA2DS2VASc score. Another 20% of the writing group only performs a TEE if a patient presents in AF of unknown duration or more than 48 hours' duration and has not been systemically anticoagulated for at least four weeks. The remaining one-third of Task Force Members employs clinical judgment and decides on a case-by-case basis whether to perform a TEE. For example, if a patient presents in sinus rhythm, has a normal LA size, and a CHADS2 or CHA2DS2VASc score of zero, many members of the Task Force would not obtain a TEE regardless of preprocedure anticoagulation. But if a patient has had AF for >48 hours, a TEE would be obtained. Conversely, a TEE would be obtained in a patient with longstanding persistent AF with a CHADS2 score greater than two and a large LA even if the patient has been therapeutically anticoagulated for four weeks or longer. Although there is no consensus among the Task Force as to whether a TEE should be performed in the subset of patients who have received four weeks of systemic anticoagulation, many in the group perform TEEs in all patients undergoing AF ablation.

Systemic Anticoagulation Prior to AF Ablation

Many patients who are undergoing AF ablation have an elevated CHADS2 or CHA2DS2VASc score or are in persistent AF prior to ablation and are therefore systemically anticoagulated with warfarin or with a direct thrombin or Factor Xa inhibitor.392–396

There are two strategies that have been used for patients who have been anticoagulated with warfarin. Historically, patients would have their warfarin discontinued, and they would be “bridged” with intravenous or low molecular weight heparin prior to and following the ablation procedure. Although widely adopted throughout the world, it was recognized that this approach resulted in a high incidence of bleeding complications, especially at the site of vascular access.386–388,397 This has resulted in a new trend towards performing AF ablation procedures in patients who are continuously therapeutically anticoagulated with warfarin.388,394,398–403 In the event of persistent bleeding or cardiac tamponade protamine is administered to reverse heparin. Fresh frozen plasma, prothrombin complex concentrates (PCC: Factors II, VII, IX, and X), or recombinant activated factor VII (rFVIIa) can be administered for reversal of warfarin.404 This strategy has proved to be safe and effective and is now adopted by approximately 50% of Task Force members.

Another emerging anticoagulation strategy involves the use of a thrombin inhibitor (dabigatran), or Factor Xa inhibitor (rivaroxaban, apixaban) for systemic anticoagulation of patients with AF. The predictable pharmacological profile of these new agents allows us to use these drugs without the need for routine coagulation monitoring. Clinical experience with these new anticoagulation agents in association with an AF ablation procedure at the present time is limited.405

Intracardiac Ultrasound and CT to Screen for Left Atrial Thrombus

Intracardiac echocardiography and CT scanning are commonly employed prior to or during AF ablation procedures. Several studies have investigated whether these modalities can be used to screen for left atrial thrombi, with the hope of obviating the need for a screening TEE in high risk patients. Unfortunately, these studies have reported conflicting data. Whereas some studies have demonstrated that each of these modalities has reduced sensitivity in the detection of left atrial thrombi as compared with standard TEE,406,407 other studies have reported that CT scanning can identify left atrial appendage thrombi with good sensitivity but moderate specificity.408 Consistent with these findings, the members of this Task Force do not recommend that ICE or CT imaging be used to screen for LA thrombi in patients who are at high risk of stroke, and TEE is warranted. Some members of the Task Force advocate that ICE, while not a substitute for TEE in high risk patients, may be of value in lower risk patients for distinguishing spontaneous echo contrast versus true thrombus.

Intra Procedural Anticoagulation

Optimal anticoagulation using heparin with close attention to maintain therapeutic dosing during the procedure is important. One recommendation of the Task Force (Table 4) is that heparin should be administered prior to or immediately following transseptal puncture during AF ablation procedures and adjusted to achieve and maintain a target ACT (activated clotting time) of 300 to 400 seconds. This recommendation reflects the well-established observation that thrombi can form on the transseptal sheath and/or electrode catheter almost immediately after crossing the septum and that early heparinization substantially decreases this risk.318,381–384,409–411 More than 50% of the Task Force Members give heparin prior to the transseptal puncture. A heparin loading dose should be administered initially followed by a standard heparin infusion. Although no scientific data exist to guide the frequency with which ACT levels be monitored, the consensus of the writing group was that an ACT level should be checked at 10–15-minute intervals until therapeutic anticoagulation is achieved and then at 15–30-minute intervals for the duration of the procedure. The heparin dose should be adjusted to maintain an ACT of at least 300–350 seconds throughout the procedure. Approximately one-third of the Task Force uses a target ACT of 350 seconds, especially in patients with spontaneous echo contrast or significant atrial enlargement.402,407,411 It is also recommended that heparinized saline be infused continuously through each transseptal sheath to further reduce the risk of thrombi.383 The risk of systemic embolization of thrombus formed on a sheath may be reduced by withdrawing the sheath to the right atrium once a catheter is positioned in the LA. Heparin infusion can be discontinued once all catheters are removed from the LA, and the sheaths removed from the groin when the ACT is less than 200–250 seconds. Alternatively, the heparin effect can be reversed with protamine.412 This approach is used by approximately 50% of Task Force members. Controlled data to support either of these recommendations are lacking, and other practices may be as valid as the specific suggestions outlined above.

Post-Procedural Anticoagulation

The atria are often stunned after RF ablation as following direct current (DC) cardioversion. Optimal anticoagulation post ablation can help prevent thrombus formation. After removal of all sheaths, warfarin should be reinitiated within 4–6 h and low-molecular weight heparin (LMWH) (enoxaparin 0.5–1.0 mg/kg twice daily) or intravenous heparin should be used as a bridge to resumption of international normalized ratio (INR) 2.0–3.0. Alternatively, a direct thrombin or Factor Xa inhibitor can be administered following ablation.392,393,395,396 If warfarin was not interrupted before ablation, use of LMWH can be avoided; continue warfarin maintaining INR 2.0–3.0. Another consensus recommendation from this Task Force (Table 4) is that systemic anticoagulation with warfarin or with a direct thrombin or Factor Xa inhibitor is recommended for all patients for at least two months following an AF ablation procedure. Although a single center reported data suggesting that selected low-risk patients with CHADS2 scores of zero or one can safely be discharged following left atrial ablation procedure on aspirin alone, this approach has not been adopted into widespread clinical practice.413 Other Consensus Recommendations of this Task Force that pertain to post-procedure anticoagulation strategies are: (1) decisions regarding the use of systemic anticoagulation more than two months following ablation should be based on the patient's risk factors for stroke and not on the presence or type of AF, (2) discontinuation of systemic anticoagulation therapy post ablation is not recommended in patients who are at high risk of stroke as estimated by currently recommended schemes (CHADS2 or CHA2DS2VASc), and (3) patients who are at increased risk for stroke in whom discontinuation of systemic anticoagulation is being considered should undergo some type of continuous ECG monitoring to screen for asymptomatic AF/AFL and AT. In considering these Consensus Recommendations, it is worth commenting that some patients who are at increased risk of stroke are highly motivated to stop systemic anticoagulation and are willing to accept an increased risk of stroke. It is for these patients that we recommend that some type of continuous monitoring be performed to screen for silent AF at regular intervals as long as they remain off systemic anticoagulation. This complex and controversial topic is discussed in more detail in Section 7.10.

Less information is available concerning the optimal approaches to anticoagulation following surgical ablation of AF. Many variables need to be considered including whether the patient underwent ligation of their left atrial appendage as well as the patients' stroke risk profile. The surgical members of this Task Force recommend that anticoagulation should be continued after surgical ablation of AF for several months due to the relatively high incidence of early atrial tachyarrhythmias that occur following surgical AF ablation procedures. Anticoagulation is often discontinued on a case by case basis after documentation of the absence of symptomatic or asymptomatic atrial arrhythmias on follow-up ECG monitoring. A post-operative echocardiogram is commonly obtained to rule out atrial stasis or thrombus prior to discontinuation of anticoagulation.

Anesthesia/Sedation During Ablation

Patients undergoing catheter ablation of AF are required to lie motionless on the procedure table for several hours. Repeated stimuli from ablation are sometimes painful. For these reasons, most patients are treated with conscious sedation or general anesthesia. The choice of approach is determined by the institutional preference and also by assessment of the patient's suitability for conscious sedation. General anesthesia is generally employed for patients at risk of airway obstruction, those with a history of sleep apnea, and also those at increased risk of pulmonary edema. General anesthesia may also be employed electively in healthy patients in order to improve patient tolerance of the procedure. Anesthesia or analgesia needs to be administered by well-trained and experienced individuals with monitoring of heart rate, non-invasive or arterial line blood pressure, and oxygen saturation.414 Guidelines for assessing levels of anesthesia and training requirements for administration of intravenous sedation during procedures have been developed by the American Society of Anesthesiologists and may be found on their website.415 Deep sedation has evolved as a third sedation alternative for catheter ablation of AF. This strategy can achieve a painless deep sedation without the need for intubation and general anesthesia. In a prospective study in 650 consecutive patients, the goal of keeping the patient in deep sedation while maintaining spontaneous ventilation and cardiovascular hemodynamic stability was accomplished.416 In that study, the sedation was administered by a trained nurse under the supervision of the electrophysiologist. More recently, general anesthesia with jet ventilation has been used at a number of centers who feel that it allows less respiratory motion and higher catheter stability.417,418 Among Task Force Members, approximately 50% routinely employ general anesthesia for all their AF ablation procedures. It is important to recognize that the approach to sedation and anesthesia will differ in different hospital settings and countries.

Esophageal Monitoring

A rare but potentially devastating complication of AF ablation is injury to the esophagus with the possible outcome of atrial esophageal fistula or esophageal perforation leading to mediastinal infection, stroke, and/or death.419,420 Another complication that is thought to be related to thermal injury to the peri-esophageal vagal plexus is gastroparesis.421 More information concerning the incidence, presentation, and management of these complications is presented in section 9.

Because of the severe consequences of an atrial esophageal fistula, it is important to attempt to avoid this complication. At the present time, a number of different approaches are being employed to prevent this complication. These approaches include: (1) modifying energy delivery, (2) visualizing the esophagus and using “abstinence,” (3) esophageal thermal monitoring, and (4) active protection of the esophagus. The first of these, modifying energy delivery, is the most common practice. When using open irrigated RF energy in the posterior LA, it is common to decrease power delivery to less than 25 W. However, even this lower level of power may damage the esophagus if either the duration of ablation is prolonged or the catheter–tissue contact force is significant, such as when a deflectable sheath is being employed. Another strategy that has been employed is to move the ablation catheter every 10 to 20 seconds on the posterior wall; however, the effect of these strategies on long-term durability of electrical PVI is not fully defined. Some operators employ light conscious sedation and use pain as an assay for potential esophageal injury; however, there are conflicting data on the specificity of this approach. There also are a number of reports of using an alternative energy source such as cryoenergy when close to the esophagus in an effort to minimize injury. While there have not been any reports of an atrial esophageal fistula or peri-esophageal vagal plexus injury with cryoablation, one study reported the presence of esophageal ulceration in a subset of patients.422 There are also data that other heat-based energy sources such as ultrasound energy can damage the esophagus.282 The second strategy is to visualize the esophagus and use “abstinence” either by designing the ablation lesions to avoid the esophagus, using lower power, and moving more quickly when over the esophagus, or employing cryoenergy when lesions over the esophagus are required. The location of the esophagus can be “visualized” using a variety of approaches, including multidetector computerized tomography,423 topographic tagging of the esophageal position with an electroanatomical mapping system,424,425 barium paste,426,427 and ICE.428,429 A third strategy involves use of luminal esophageal temperature monitoring to identify potentially dangerous heating of the esophagus.430–432 Importantly, since the esophagus is broad, the lateral position of the temperature probe or mapping electrode may not align with the ablation electrode, and the operator may have a false impression of safety. Although there is general agreement among those operators who employ temperature probes that an increase in esophageal temperature should trigger interruption of RF energy delivery, there is no consensus as to what degree of temperature elevation should trigger RF termination. A final strategy is to protect the esophagus with active cooling or displacement.433–435

Although each of these four approaches is variously adopted by different ablation centers, each remains largely unproven due to the rarity of an atrial esophageal fistula as a complication. Among the Task Force Members, 75% decrease RF power when ab