State of the Art: Catheter Ablation of Atrial Fibrillation

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FEATURED REVIEW

State of the Art: Catheter Ablation of Atrial FibrillationMATTHEW WRIGHT, M.B.B.S., PH.D., MICHEL HAISSAGUERRE, M.D.,

SEBASTIEN KNECHT, M.D., SEIICHIRO MATSUO, M.D.,MARK D. O’NEILL, M.B., B.CH., D. PHIL., ISABELLE NAULT, M.D.,

NICOLAS LELLOUCHE, M.D., MELEZE HOCINI, M.D.,FREDERIC SACHER, M.D., and PIERRE JAIS, M.D.

From the Hopital Cardiologique du Haut-Leveque and the Universite Victor Segalen Bordeaux II, Bordeaux, France

State of the Art: Catheter Ablation of AF. Curative treatment of atrial fibrillation with catheterablation is now a legitimate option for a large number of patients. In the last decade a tremendous amounthas been discovered about this fascinating arrhythmia, yet there is still much that is understood. A numberof different ablation strategies have been used including pulmonary vein isolation, targeting of fractionatedelectrograms, compartmentalising the atria with linear lesions and various combinations and modifica-tions of these lesion sets. The optimal ablation strategy for both paroxysmal and long-lasting persistentatrial fibrillation is unknown. In this review the possible mechanisms underlying atrial fibrillation areexamined along with the current catheter ablation techniques used in the treatment atrial fibrillation.(J Cardiovasc Electrophysiol, Vol. 19, pp. 583-592, June 2008.)

atrial fibrillation, atrial tachycardia, mapping, complex fractionation, macroreentry, focal sources

Introduction

Atrial fibrillation (AF) is the most common cardiacarrhythmia, responsible for approximately one-third of allhospital admissions with a cardiac rhythm disturbance.1 Itis responsible for an increased risk of stroke, heart failure,and all-cause mortality.2,3 The vast improvement in resultsof catheter ablation, compared with pharmacological treat-ment4 over the last decade, means that catheter ablation canbe considered early in the management of patients. Yet thereis room for improvement before this can be the initial treat-ment of choice, particularly in the case of chronic AF. Wherehave we been, where are we at, and where are we going?

Mechanisms

Multiple Wavelet Hypothesis

Catheter ablation of AF has been successful even withouta complete understanding of the mechanisms underlying thefibrillatory process. The multiple wavelet hypothesis, pro-posed by Moe,5 with supportive/contributory experimental

Sebastien Knecht is supported by the Belgian Foundation for CardiacSurgery.

Mark D. O’Neill is supported by the British Heart Foundation.

Address for correspondence: Matthew Wright, M.B.B.S., Ph.D., Service deRythmologie, Hopital Cardiologique du Haut-Leveque, Avenue de Mag-ellan, 33604 Bordeaux-Pessac, France. Fax: 33-5-57-65-65-09; E-mail:[email protected]

Manuscript received 28 February 2008; Revised manuscript received 6March 2008; Accepted for publication 10 March 2008.

doi: 10.1111/j.1540-8167.2008.01187.x

work by Alessie,6 was the predominant hypothesis prior tothe late 1990s, and was the premise on which Cox’s Mazeprocedure was developed. The developments of surgical ab-lation of AF culminated in the Maze III,7 which incorporatesfour lesion sets: (i) encirclement of the pulmonary veins; (ii)a lesion joining the circumferential PV lesion to the mitralannulus with amputation of the left atrial appendage; (iii)a circumferential lesion in the coronary sinus; (iv) ablationof the right atrium. Although catheter ablation approachesbased on the early surgical approaches were tried by a num-ber of groups, the success rate was disappointing, with anunacceptable high complication rate.8,9

Focal Source Hypothesis

The observation that AF could be triggered from ectopicsoriginating from the pulmonary veins,10 with ablation at thesource of the ectopy eliminating AF, changed the empha-sis of catheter ablation away from linear lesions compart-mentalizing the atria to treating focal sources. Although fo-cal sources, incorporating automaticity and/or local reentry,have been implicated in both atria,11-13 the majority residewithin the left atrium, which is consistent with a dominantrole for the left atrium in human AF. As catheter ablationhas progressed from treating patients with paroxysmal AF tolong-lasting persistent AF, the importance of treating the leftatrial substrate has become apparent. The interesting obser-vation that multiple-point ablation (targeting sites of complexelectrograms), without creating lines of block, actually im-proves the success rate in treating persistent AF does notintrinsically support a multiple-wavelet mechanism, as pointablation should increase the number of anchoring points forwavelets, thus worsening AF.

584 Journal of Cardiovascular Electrophysiology Vol. 19, No. 6, June 2008

Catheter Ablation

Catheter ablation of AF is now a realistic therapeutic op-tion across a broad spectrum of patients from patients withparoxysmal AF to those with long-lasting persistent AF,14

including patients with moderate-to-severe left ventricularimpairment.15,16 Indeed, there is evidence to suggest thatrestoration and maintenance of sinus rhythm by catheter ab-lation may lead to improved outcomes in these patients.16,17

In our center, we accept patients for catheter ablation ifthey have symptomatic paroxysmal AF and have failed atleast one antiarrhythmic drug. Patients with long-lasting per-sistent atrial fibrillation are considered for ablation if they aresymptomatic and have failed treatment with more than oneconventional antiarrhythmic drug, electrical cardioversion,or both. In nearly half of patients with long-lasting persistentAF, a second procedure is necessary to maintain sinus rhythm,and there are no absolute exclusion criteria nor is there a pre-determined limit to the number of procedures performed perpatient. In light of the increasing body of evidence to supporta safe and effective role for catheter ablation in patients withboth atrial fibrillation and heart failure,16,18 we offer ablationto patients with atrial fibrillation, echocardiographic evidenceof left ventricular dysfunction, New York Heart Associationheart failure symptoms of grade II or more, and the absenceof an alternative explanation for their cardiac dysfunction.

Paroxysmal Atrial Fibrillation

Pulmonary vein isolation, whether ostial or antral, is thecornerstone in treatment for paroxysmal AF. Electrical iso-lation of all pulmonary veins is the endpoint of ablation, andthis objective measure of pulmonary vein disconnection iseasy to confirm and results in maintenance of sinus rhythmin between 60% and 85% of patients.19,20 The difficulty ishow to improve on this. Although most of the clinical re-currences associated with this procedure are due to lesionrecovery, this does not account for all recurrences.21-23

The role of additional substrate modification in parox-ysmal AF is controversial. Strategies based on targeting ofcomplex fractionated atrial electrograms (CFAE) result inmaintenance of sinus rhythm in a mixed population of pa-tients with both paroxysmal and long-lasting persistent AF in76% of patients with a single procedure, without necessarilyachieving pulmonary vein isolation. A majority of lesions inpatients with paroxysmal AF, however, were located aroundthe pulmonary veins. The addition of linear lesions (a roofline connecting the left and right superior pulmonary veins,and/or a mitral line connecting the mitral annulus to the in-ferior pulmonary vein) to pulmonary vein isolation improvessuccess rates from 69% to 91% at 18-month follow-up.24,25

The question that is not yet fully answered is how to deter-mine which patients require substrate modification in addi-tion to pulmonary vein isolation during the index procedure.Noninducibility of AF can be used as an endpoint in paroxys-mal AF and the subsequent need for substrate modification,yet this may lead to an overtreatment, that is, excessive abla-tion, in some patients.26-28 An alternative option is to performsubstrate modification during a second procedure in patientswith recurrent AF despite proven pulmonary vein isolation.

Long-Lasting Persistent Atrial Fibrillation

The mechanisms underlying long-lasting persistent AFare more complex and multifactorial. Many early studies

of pulmonary vein isolation (PVI) included patients withboth paroxysmal and long-lasting persistent AF, universallydemonstrating a much lower freedom of recurrent AF in pa-tients with long-lasting persistent AF. With circumferentialpulmonary vein ablation using an electroanatomic mappingtechnique, freedom from AF was reported in 85% of pa-tients with paroxysmal AF and 68% of those with chronicAF.29 A further study, also using a circumferential mappingcatheter-guided approach, reported an even lower freedomfrom recurrent AF in persistent (22%) versus paroxysmal(70%) AF, despite achieving electrical isolation in 94% oftargeted veins.30 Using a basket catheter to achieve a 100%rate of PV isolation, freedom from AF was demonstrated in70% of patients with paroxysmal but in only 44% of patientswith persistent AF,31 further confirming that extension of thetechnique of PVI alone from patients with paroxysmal tolong-lasting persistent AF was inadequate.

The addition of left atrial substrate modification usingelectrogram-based or linear ablation considerably improvesthe outcomes in patients with long-lasting persistent AF.32 Inone randomized study, the addition of left atrial linear lesions(left atrial roof line and a mitral isthmus line) improved theoutcome in patients at 16-month follow-up from 20% withPVI alone to 69% with PVI and substrate modification. Thiswas despite evidence of bidirectional block in only 44% ofpatients with a roof line and 72% with a mitral isthmus line.32

The incremental benefit of substrate modification (PVI andleft atrial linear lesions with bidirectional block) was alsoseen in a population of patients with heart failure, with 69%of patients being in sinus rhythm, off all antiarrhythmic med-ication at 1 year.16

In the above approaches, the endpoint is a technical end-point, that is, completion of PVI or linear block; but the pro-cedure is terminated by DC or pharmacological cardioversionin 55% to 90% of cases. In contrast to paroxysmal AF, wherenoninducibility of AF can be achieved in most patients,25,33,34

the same is not true in long-lasting persistent AF as AF/AT isconsistently inducible in the large majority of patients at theend of the index procedure.35

When termination of AF by radiofrequency ablation isused as an endpoint, a better clinical outcome is achieved.36 Inwork from our group (see below), sinus rhythm was restoredby catheter ablation in 85% of patients with long-lasting per-sistent, usually via an intermediate step of one or more ATsand without the use of concomitant antiarrhythmic drugs.36

Patients in whom sinus rhythm was restored during the indexprocedure, the long-term (over 2 years) freedom from AFwas considerably greater (recurrence of AF in only 5%) thanthose in whom sinus rhythm was not restored (recurrence ofAF in 39%).36 We believe that termination of AF by ablationalone is the endpoint against which the procedural outcomeof all AF ablation techniques should be measured.

Targets for Catheter Ablation

Pulmonary Vein Isolation

The technique of PVI is similar for paroxysmal AF andlong-lasting persistent AF. Pulmonary vein isolation is cur-rently performed as the initial ablation step in all patients withlong-lasting persistent AF in our laboratory.20,37 Althoughisolation restricted to veins identified as “arrhythmogenic”has been advocated by others,38 uniform isolation of all pul-monary veins identified is routinely performed and confirmed

Wright et al. State of the Art: Catheter Ablation of AF 585

using a circumferential mapping catheter positioned at the ve-nous ostium. Veins are isolated individually or as ipsilateralpairs in accordance with the venous anatomy and operator’spreference. Confirmed isolation is critical, as the electricallyinactive tissue enclosed within the ablation lesions serves asan anchor for the roof and mitral isthmus lines that may benecessary, should AF persist.

Complex Fractionated Atrial Electrograms

The HRA/EHRA/ECAS expert consensus document oncatheter and surgical ablation of AF15 suggests that ar-eas with CFAEs potentially represent AF substrate sites.Complex fractionated atrial electrograms are defined aselectrograms displaying more than two deflections that arefractionated or have a short cycle length <120 ms,39 in itsmaximal form giving continuous electrical activity.40 Themechanisms underlying such fractionated potentials includelocal slow conduction and anistropy.41,42 The behavior of ar-eas of CFAE is critically dependent on both the directionof wavefront progression43 and its cycle length, or the pre-maturity of the extrastimulus. For CFAE-based ablation, theendpoint that has been used is electrogram abatement, or abo-lition of fractionation with organization of atrial electrogramsat the site, or conversion to sinus rhythm.17,39,44

The problem with targeting fractionation is differentiatingactive from passive fractionation. In practice, there is diffusefractionation in persistent AF when there is a short AFCL,while more limited fractionation occurs in paroxysmal AFdue to the longer AFCL.

Nademanee was the first to target exclusively CFAE inboth the left and right atrium in patients with PAF and per-sistent AF, with maintenance of sinus rhythm of 91% at 1year, with an average of 1.2 procedures per patient.39 In alarge cohort of patients with both PAF and long-lasting per-sistent AF, the longer term success rate is equally as impres-sive, with 81% of patients maintaining sinus rhythm, with amean follow-up of over 2 years and an average of 1.7 pro-cedures per patient. In patients with long-lasting persistentAF, the long-term success rate was 71%, as monitored bysymptoms and annual Holter monitoring.17 There is, how-ever, a discrepancy in results between different groups usinga defractionation only strategy. In a study by another group,CFAE-based ablation resulted in only 33% of patients beingin sinus rhythm without antiarrhythmic medication at a meanof 14 months follow-up, rising to only 57% when a repeatablation was performed.44

We performed a prospective study comprising 40 consec-utive patients undergoing sequential ablation for long-lastingAF (duration of persistent AF: median 12 months, range 1–84months) to assess if there were any features of fractionatedelectrograms that could be predictive of AF termination ormodification. Electrograms were characterized by (i) the du-ration of continuous electrical activity, (ii) bipolar voltage,(iii) dominant frequency, (iv) “fractionation index,” (v) lo-cal cycle length, and (vi) presence of a temporal gradientof activation. AF was terminated by electrogram-based leftatrial/coronary sinus ablation in 29 patients (73%) after tar-geting a total of 171 regions. Electrogram characteristics atfavorable ablation sites, defined as those associated with AFtermination (29 regions) or modification (a ≥5 ms increasein AF cycle length, 43 regions) were compared with those ofunfavorable sites. In favorable ablation sites, the duration ofcontinuous electrical activity was significantly greater (me-

dian 78% [first quartile 45%; third quartile 90%] vs 55%[25%; 85%]), and a temporal gradient of activation was morecommonly observed (22% vs 10%). Electrogram voltage, cy-cle length, fractionation index, and dominant frequency werenot found to be associated with AF modification or termina-tion.

Linear Lesions

Linear ablation, whether in combination with other abla-tion targets or not, alters the substrate for AF by both defrag-mentation and when complete electrical block is achieved bydisrupting large macroreentrant circuits capable of sustainingAF. A number of studies have demonstrated that the additionof linear lesions to pulmonary vein isolation improves out-comes. Circumferential PV ablation and adjunctive roof andmitral isthmus ablation significantly reduced the AF burdenat 12-month follow-up among patients with persistent AF asmeasured by 7-day Holter.45 In a prospective study of patientswith persistent AF with a follow-up of 15 months, 69% of pa-tients were in sinus rhythm who underwent pulmonary veinisolation plus ablation at the roof and mitral isthmus in com-parison with only 20% of patients who underwent pulmonaryvein isolation alone.32 In a further prospective comparison,catheter ablation at the mitral isthmus, in addition to pul-monary vein isolation, increased freedom from paroxysmalAF at 1 year from 69% to 87%.46

Autonomic Targets

Macroreentrant tachycardias that occur at follow-up arefrequently associated with gaps in linear lesions, either dueto lesion recovery or an initial incomplete line.47,48 That lin-ear lesions are useful in persistent AF, despite the potentialproarrhythmic effect, suggests that their benefit is not solelyrelated to disrupting macroreentry. Both the left atrial roofline and the mitral isthmus line inadvertently incorporate thelocations of known vagal ganglia, with the highest densityof cardiac autonomic nerves occurring within 5 mm of theLA-PV junction.49 Although it is feasible to map and locateindividual vagal ganglia50 with high-frequency stimulation,this is not routinely performed in clinical practice, nor mayit be necessary, given the overlap between the PV ostia andthe vagal ganglia.

The autonomic nervous system is known to play a rolein the generation of AF, with increased sympathetic andparasympathetic activity preceding pulmonary vein firing,and shortening the atrial refractory period.51 In patients withdrug refractory paroxysmal AF, the abolition of evoked vagalresponses seen during circumferential PV ablation rendered99% of patients free of AF at 12 months, compared with 85%in those in whom vagal responses could not be evoked.52 Cur-rently, however, we cannot differentiate whether an indepen-dent effect of ablation at sites of ganglionic plexi is due to aneural effect compared to the effect on local atrial tissue.

Right Atrium

Early work by several groups9,53 investigated the utility ofright atrial linear lesions with or without additional left atriallinear lesions54 with only modest success in patients with ei-ther paroxysmal or persistent AF. This does not mean, how-ever, that the right atrium does not contribute to AF. Spectralanalysis during AF shows an important contribution fromthe right atrium.55 In addition to left atrial focal activationwith fibrillatory conduction, right atrial focal and reentrant


Figure 1. The effect of ablation on atrial fibrillation cycle length. In the stepwise approach, the effect of each ablation step on AFCL is monitored. In thelefthand panel, where all patients had AF terminated in the LA, the change in AFCL measured from the LAA is mirrored by a similar change in AFCL asmeasured from the RAA. In the righthand panel, the slowing of AFCL in the LAA is not mirrored in the RAA. In the patients illustrated on the righthandpanel, right atrial ablation terminated persistent AF. AFCL = atrial fibrillation cycle length; Base = baseline AFCL; CL = cycle length; INF LA = inferiorleft atrium; LA = left atrium; LAA = left atrial appendage; Mitral = mitral isthmus line; PVI = pulmonary vein isolation; RA = right atrium; RAA = rightatrial appendage; Roof = line joining the two superior venous ostia.

activity has also been demonstrated during intraoperativehigh-density epicardial mapping of patients with long-lastingpersistent AF.56 There is accumulating evidence that in asubset of patients, possibly up to 20% of patients with long-lasting persistent AF,57,58 the right atrium is critical in themaintenance of AF. In 80 patients with persistent or perma-nent AF, linear right atrial ablation has been reported to im-prove the outcome when performed in addition to circumfer-ential pulmonary vein ablation with mitral and cavotricuspidisthmus ablation.58 In this study, AF terminated during abla-tion of the left atrium in 19 patients and during right atriumablation (following left atrial ablation) in 24 patients.

The targets for ablation in the right atrium are similar tothose in the left atrium, that is, regions displaying rapid orcomplex activity. The superior vena cava is only targetedwhen there is distal to proximal activation of the mappingcatheter, with the distal electrode in the superior vena cava,or when there is high frequency activity suggestive of thepresence of an arrhythmogenic source in this vessel. Caremust be taken to avoid phrenic nerve and sinus node injuryduring ablation in this region.59 In our laboratory, all patientsundergo ablation of the cavotricuspid isthmus. Importantly,the subset of patients in whom AF terminates in the rightatrium can be predicted by the AFCL as measured in theright atrium, compared with the left atrium, with the AFCLbeing significantly shorter in the right atrium (Fig. 1).

Stepwise Approach

The stepwise approach in which several strategies arecombined (pulmonary vein isolation, targeting of fraction-ated potentials, and linear lesions) has resulted in unprece-dented success in maintaining sinus rhythm in the mediumterm with recovery of atrial mechanical function48,60-62 inpatients with long-lasting persistent AF. The endpoint of ab-lation is restoration of sinus rhythm, which normally occursvia one or more intermediate ATs,48 with PVI and integrityof linear lesions being confirmed or completed by further ab-lation as necessary following restoration of sinus rhythm.36

With this approach, termination of AF occurred in 87%,62

resulting in freedom from sinus rhythm at 1 year of 95%.48

Importantly, the order of ablation targets (pulmonary veins,

CFAE, coronary sinus, and linear lesions) has been shown tobe irrelevant, suggesting that all of the targets contributed tothe maintenance of AF.63

The regions targeted are the pulmonary veins, fractionatedalong the inferior left atrium/coronary sinus interface, leftatrial tissue incorporating all regions of the chamber wherefractionation remains, followed linear ablation at the roofand mitral isthmus, and ablation within the right atrium andsuperior vena cava when necessary.62 Structures outside theleft atrium are targeted on a discretionary basis following anassessment of their relative contribution to fibrillation. Eachregion is targeted in sequence and the impact of ablationupon the global fibrillatory process assessed both before andafter ablation by measurement of AF cycle length (AFCL) ata site remote from the ablation target. Ablation is typicallyaccompanied by a cumulative increase in the AFCL priorto termination of AF by conversion either directly to sinusrhythm or to an AT, which is then mapped conventionally andablated.

The technique has the strength of integrating effective as-pects of different but inflexible ablation schema to offer anindividualized ablation strategy. The benefit of this integra-tion of anatomic and electrophysiologic information is an un-precedented level of termination of chronic AF by catheterablation.48,62

The Use of AFCL as a Monitoring Tool

Experimental mapping studies have shown that the AFCLis correlated with local refractory periods,16 shortens withmaintenance of AF,64 and prolongs progressively or immedi-ately before arrhythmia termination by drugs.65 We have pre-viously shown that there is a progressive increase in AFCLmeasured in the coronary sinus following PVI66 in patientsin whom AF is terminated by catheter ablation. Furthermore,with increasing left atrial ablation, a gradual prolongationof the AFCL is seen,58 with the largest increments occur-ring after ablation of the pulmonary vein/left atrial junction,inferior left atrium/coronary sinus interface, and left atrialappendage.48,58 Once an AFCL in the region of 180 ms to200 ms has been achieved, AF terminates either by conver-sion directly to sinus rhythm or, in the majority of cases, to


Figure 2. Parallel prolongation of AFCL with termination in the left atrium recording from an individual, illustrating the effect that ablation has on AFCL,which is used as a monitoring tool. At baseline, the AFCL in the left atrium is 160 ms and in the right atrium it is 171 ms; following pulmonary vein isolationand roof line ablation, this increases to 191 ms and 198 ms, respectively. After further electrogram-based ablation, the AFCL prolongs to 212 ms in theleft atrium and 217 ms in the right atrium. With further ablation in the left atrium, the patients convert to an atrial tachycardia, which can then be mappedconventionally. AFCL = atrial fibrillation cycle length; CS = coronary sinus; LAA = left atrial appendage; D = distal; P= proximal; RAA = right atrialappendage.

an atrial tachycardia (AT), which is then mapped and ablatedconventionally (Fig. 2). In about 80% of patients, there is aparallel prolongation in the AFCL measured from both theleft and the right atrium indicating that the left atrium wasdriving the right atrium. In 20% of patients the prolongationin AFCL, measured from the left atrial appendage, is not mir-rored in the right atrium (right atrial cycle length shorter thanthe left), and ablation within the right atrium terminates AF,indicating that in these patients the right atrium was drivingthe left atrium at this time.57

Electromechanical Effects of Stepwise Ablation

A potential concern regarding ablation of long-lastingpersistent AF is the amount of atrial ablation required toterminate AF and for long-term maintenance of sinus rhythm.In a study that evaluated the effect of stepwise ablation by us-ing an electroanatomical voltage map to assess areas of scarand low-voltage, these areas accounted for 31% and 32% ofthe total LA surface area, respectively. The ablated pulmonaryvein region represented majority of the scar burden, account-ing for approximately two-thirds of the ablated area.61 Mostimportantly, there was recovery of atrial mechanical func-tion, and this is in patients who had very dysfunctional atrialfunction prior to ablation, being in AF.

The Future

Atrial Tachycardia: The Second Front

Although catheter ablation of long-lasting persistent AFis successful at treating AF, many patients have recurrenceswith regular ATs, which can be either macroreentry, or focal.With stepwise ablation, 40% of patients have a recurrencewith a regular tachycardia within 3 months.48 These tachy-cardias represent the second front of AF ablation.

In patients who have undergone an AF ablation, PV re-conduction is the main cause of AT.67 Therefore, PV isolationshould be systematically checked as the first step in the ATmapping process. The next step is to exclude macroreentryaround the mitral annulus or utilizing the roof by sequentialmapping around the mitral annulus for the former and theanterior and posterior walls for the latter, with confirmationwith entrainment maneuvers. If macroreentry as a mecha-nism is eliminated, the next step is to map the atria to find aregion with centrifugal activation. Whilst these tachycardiashave been previously thought to be “focal,” we have foundthat a majority of so-called focal ATs are actually due to smalllocalized reentry (Figs. 3 and 4).

In a study involving 74 consecutive patients who under-went catheter ablation for persistent AF, the mechanism ofsubsequent AT (total 142) observed during/after AF ablationwas mapped using activation sequence and PPI mapping andthen ablated. Mechanisms of AT were defined as macroreen-try (perimitral, roof dependent, or peritricuspid) or focal ac-cording to the HRS/ESC nomenclature. Focal AT was definedas the origin of atrial wavefront from a discrete source withcentrifugal activation of the rest of the atrium. Ninety-sevenpercent (138 of 142) of ATs were successfully mapped. Therewere 61 macroreentry ATs (28 perimitral, 17 roof dependent,and 16 peritricuspid) and 77 “focal” ATs. Of these, a newdistinct mechanism, localized reentry, was identified in 57that was neither macroreentry nor focal. Localized reentrywas demonstrated by (1) electrograms covering all the cyclelength of AT within an area <2 cm, (2) PPI <30 ms at thesite, and (3) an identifiable zone of slow conduction. Durationof radiofrequency to terminate arrhythmia was significantlyshorter for localized reentry (27 ± 23 seconds), comparedwith macroreentry AT (303 ± 374 seconds P < 0.0001) andsimilar to focal AT (35 ± 25 seconds). Thus, localized reen-try where the focus is not a point but an area constitutes an


Figure 3. Mapping focal sources during atrial tachycardia-differing perspectives dependent upon the mapping system. Upper panel. Using the multipolepentaray catheter, discrete electrograms with a consistent activation sequence are seen. When the catheter is placed near the left superior pulmonary vein,activation in all spines appears on time, with the reference catheter in the coronary sinus, on the bottom of the trace. As the catheter is moved progressivelytoward the source, activation becomes progressively earlier in spine D, indicating the direction of activation. In the septum there is a dramatic changeof mapping through the pentaray catheter, switching from relatively synchronous activation to complex activation, spanning all the cycle length when thecatheter is placed directly above the small localized source. This source is likely due to small localized reentry, as confirmed by entrainment mapping. In thelower panel, the electroanatomical map from this patient gives a different perspective. The earliest activation can be seen to come from the inferior septum;but, in fact, considerable postprocessing was necessary to achieve a map, such as the one demonstrated, as it is difficult to assign temporal information tothe signals seen in the upper panel, when the mapping catheter is directly above the source. The multiple electrograms at the source have been assigned asingle, earliest, timepoint. Ablation at the source location restored sinus rhythm within 10 seconds (righthand panel). This example demonstrates that withouta global perspective, given by the multipole catheter, point by point activation mapping would be extremely difficult.

important mechanism of AT in the context of AF ablation.The circuit is contained within an area of 2 cm and includesa small isthmus of slow conduction that can be easily inter-rupted with ablation.

Electrophysiologic Targets and Mapping of AF

Although an exclusive CFAE-based approach and the step-wise approach, with their respective endpoints, are effective,as of yet there is no mapping tool that has been shown to beclinically effective in determining active from passive areasof activation. This has led to the use of dominant frequency

(DF) analysis to try and determine the areas with the highestfrequency of activation. In one study using spectral analy-sis of 3-D electroanatomic maps, ablation of areas with thehighest DF did result in prolongation of AFCL and resultedin termination of AF in 87% of patients with paroxysmalAF.55 In patients with long-lasting persistent AF, the sites ofhighest dominant frequency were located throughout the leftatrium with some sites in the right atrium, compared withpatients with paroxysmal AF where the sites were predom-inantly located around the pulmonary veins, consistent withwhat we have learned through catheter ablation. There are anumber of caveats, however, with this approach. There were


Figure 4. Localized temporal gradient. Inthis example, a source is located in the in-ferior left atrium. As the mapping catheter isbrought to the periphery there is an activationgradient between the two bipoles; as the map-ping catheter is placed across the source, thegradient becomes more pronounced, suggest-ing that the catheter is across two parts of asmall localized circuit, or rotor, that may becapable of sustaining AF.

similar numbers of high DF sites that did not result in termi-nation when ablated as those that did, and the temporal spatialstability of these areas is not fully understood. The mainlimitation of this technique currently is that the very ar-eas that are of most interest to decipher, such as CFAE,are just the areas where frequency analysis has technicaldifficulties.68-70

In some cases, AF is “organized,” that is, atrial activitydisplays consistent activation sequences as a sort of inter-mediate step between AF and AT. In our laboratory, among80 patients undergoing catheter ablation for long-lasting per-sistent AF using the stepwise approach, AF could be termi-nated in 69 (82%), while AF could not be terminated by abla-tion alone in the remainder.71 Of the 69 successfully ablatedpatients, AF termination occurred during regional ablationfollowing the stepwise approach in 50 (72%). In the remain-ing 19 patients (28%), ablation targeting discrete anatomicsites was necessary to achieve termination. These sites werepreferentially located to the coronary sinus, the base of the leftatrial appendage, and the interatrial septum and were found todisplay a nonspecific range of preablation electrogram mor-phologies, suggesting different underlying arrhythmia mech-anisms despite anatomic similarities. Some of the potentialelectrophysiological mechanisms underlying the electrogrammorphologies shown in Figure 3 have been previously char-acterized using high-density contact mapping.72 Centrifugalactivation spreads radially from a single site of earliest ac-tivity (Fig. 3); a small local reentrant source (or “rotor”) isprobably represented by a temporal gradient between two

closely spaced bipoles of a conventional mapping catheter(Fig. 4).72

Ablation at these sources has been shown to prolong AFcycle length, change activation sequence, and terminate AFin patients with paroxysmal and persistent AF organized byprior ablation.56,62 More importantly, failure to recognize thecontribution of these discrete sites to the fibrillatory processwill result in failure to terminate AF (Fig. 5).

Technical Improvements

Given the current limitations, how are we going to improveon current practice? The two major areas for improvementare improved mapping tools to allow identification of theactive substrate from passive substrate and improved ablationtechnologies.

One of the most active areas of development has beenthe development of different catheters and alternative en-ergy sources to radiofrequency energy. When radiofrequencycatheters were initially developed, the arrhythmias that werebeing treated required point ablation, for example, accessorypathways and AVNRT. For AF, the lesions that are made withthese catheters are encircling lesions around the pulmonaryveins, ablating relatively large areas of fractionated activityand producing linear lesions. There are a number of balloon-based catheters that have been developed using a variety ofenergy sources, for example, high intensity focused ultra-sound73 and cryothermal balloons.74 Currently, only limiteddata are available on the efficacy and safety profile of such


Figure 5. A focal source maintaining AF. In this case, a gentleman hadpersistent AF. Ablation at the site giving centrifugal activation, from theanterior LA, resulted in termination of AF. Despite the patient being in sinusrhythm, the focal source is continually firing (within an island created byRF applications). This patient is currently free of AF, off all antiarrhythmicdrugs for 7 years. This case is evidence for a focal source maintaining AF,and explains why even extensive nonmapping-guided ablation may fail.

catheters. One of the major limitations of any balloon-basedtechnology is the variation in pulmonary venous anatomy,both in size of the veins and the presence of common os-tia. Although preprocedural imaging could potentially alertthe physician to patients with unsuitable anatomy,75 a furtherproblem is that balloon-based catheters are very specific topulmonary vein isolation;76 and that although appropriate forPAF, the need for several different catheters in persistent AF,and thus increased cost, limits their applicability.

Another area of development is remote navigation, andpresently two main systems are in clinical use. The potentialbenefits of remote navigation include improved catheter sta-bility and precision, integration with 3-D mapping systems,and reduction in radiation exposure to the operator. The twosystems that have been developed for clinical use are theremote magnetic navigation system by Stereotaxis and theremote robotic navigation system by Hansen.77

Conclusions

Although all forms of AF can now be effectively treatedwith catheter ablation, the main barrier to overcome is toidentify areas that actively participate in the AF process forany one individual so as to minimize ablation. When we canidentify these areas, there is hope that we will truly under-stand the processes involved in AF and perform an effectiveindividual cure.

References

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State of the Art: Catheter Ablation of Atrial Fibrillation

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