Mark J Earley, Richard J Schilling

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266 Eletrophysiology CATHETER AND SURGICAL ABLATION OF ATRIAL FIBRILLATION Take the online multiple hoie questions assoiated with this artile (see page 274) PAROXYSMAL, See end of artile for authors affiliations Correspondene to: Dr Rihard Shilling, Cardiology Researh Department, St Bartholomew s Hospital, Dominion House, 60 Bartholomew Close, London EC1A 7BE, UK; r.shilling@ qmul.a.uk T Mark J Earley, Rihard J Shilling Heart 2006; 92:266 274. doi: 10.1136/hrt.2005.067389 here is inreasing onfusion regarding the results and benefits of atheter and surgial ablation for atrial fibrillation (AF). This is beause of rapidly evolving tehniques and a wide range of opinion regarding its effiay. Just as the balloon and stent enthusiasts of the 1980s were viewed with some suspiion by many dotors treating oronary atheroslerosis, w1 the pratie of urative ablation of AF has been ritially reviewed by ardiologists. w2 w3 This artile aims to demonstrate why an apparently haoti heart rhythm is amenable to ure, ritially review the urrently employed surgial and atheter tehniques, and provide some guidelines as to the appropriate referral of patients for these proedures. PERSISTENT, AND PERMANENT AF AF is usually prefixed by a temporal desriptive term suh as paroxysmal or hroni whih has impliations for the most suitable treatment strategy. A onsensus on nomenlature has now been ahieved 1 in whih an AF event is either the first deteted or a reurrent episode. Paroxysmal AF desribes episodes that terminate spontaneously within seven days. AF is persistent if it lasts longer than seven days or requires ardioversion by any means to restore sinus rhythm. Permanent AF is reserved for when either attempts to ardiovert have failed or not been attempted. MECHANISMS UNDERLYING AF The mehanism of AF is not learly understood. The predominant theory of the 20th entury was that haoti multiple re-entry iruits, following onstantly varying lines of ondution blok, perpetuate AF (fig 1). w4 w5 This onept was hallenged, however, by the observation that in some patients without ardia strutural abnormalities, an ECG pattern of AF an be seen even when there is a definite foal soure suh as a rapidly firing atrial tahyardia emerging from a pulmonary vein (PV). 2 A single wavefront propagating aross the atria is vulnerable to being split and turned by anatomial obstales and by spatial variation in the ondution properties of the atrial myoardium suh that if the fous depolarises rapidly the rest of the atria may not be able to ondut 1:1, thus forming multiple wavefronts. This is desribed as fibrillatory ondution (fig 1). 3 These two mehanisms should not be onsidered as separate entities though. Patients with paroxysmal AF and relatively normal hearts are more likely to have a foal mehanism, in whih the episode only persists as long as the soure of the wavefronts is present. Over time, however, beause of the reurrent tahyardia episodes, remodelling of the atrial tissue (altering both the ondution and strutural properties) will our, suh that the atria dilate and an then maintain multiple re-entry wavefronts without the need for the foal soure. 4 This pathologial progression (remodelling of the atria) is mirrored by the well reognised linial observation that paroxysmal AF beomes permanent, partiularly if untreated. w6 w7 It is also possible that even in patients with permanent AF, foal drivers may sustain AF. Although there is evidene to support this in animal models, 3 there have been little data regarding this in humans. BRINGING ORDER TO CHAOS Curative ablation of AF then has two mehanisti goals: to remove all potential triggers that may initiate or perpetuate AF; and the alteration of the ondution properties of the atria (substrate modifiation) so that AF annot be sustained even when triggered. It is reognised that partiular AF mehanisms may result in a partiular linial substrate and thus allow the proedure to be tailored so that, for example, in paroxysmal AF only isolation of triggers is attempted, whereas in persistent AF additional and more omplex substrate modifiation may be performed. The most ommon soures of triggers are the PVs; however, up to 20% may be non-pv in origin suh as the superior vena ava, oronary sinus, or rista terminalis. 5 The trigger sites are isolated from the rest of the atria by either destroying the musular onnetions that link them to the atria or by reating a ontinuous line of ondution blok in the atria that surrounds and ompletely enloses them.

Figure 1 A shemati view of the interior surfae of the right (blue) and left (pink) atria. The white arrows represent wavefronts of eletrial depolarisation. (A) An etopi fous (asterisk) from within the left superior pulmonary vein generates repetitive wavefronts at a high frequeny. The rest of the atrial myoardium annot propagate these wavefronts uniformly beause of the heterogeneity of its ondution properties and anatomial obstales. The zigzag lines represent slowed ondution and the red line ondution blok. The wavefronts are onsequently broken down into multiple wavefronts whih manifest as atrial fibrillation on the ECG. If the foal trigger stops firing the fibrillation will terminate. (B) Multiple wavelet re-entry. The wavefronts are turned and split by olliding with the anatomial strutures (fixed blok) and other wavefronts (funtional blok). The number of wavefronts is determined by the size and ondution properties of the atria. These wavefronts self propagate and are not dependent on a foal trigger. There are two approahes to substrate modifiation. Firstly, it an be ahieved by reating transmural linear lesions that onnet two anatomial strutures and form barriers to ondution, thus interrupting the re-entry iruits that perpetuate AF. The alternative approah (also known as atrial debulking) is to redue the amount of atrial tissue available to form re-entry wavefronts, either by enlosing and isolating large areas of atrial tissue (typially done around the PVs) or to ablate widely all over the atria thus reduing the amount of viable tissue. A possible downside to substrate modifiation is the redution in the ontratile potential of the atria whih may prevent reovery of mehanial funtion. CLINICAL OBJECTIVES OF ABLATION OF AF It is important to remember what the linial objetives are when treating AF in this invasive way with its potential risks. The main goals are to abolish or redue symptoms, to improve left ventriular funtion by restoring both eletrial and mehanial atrial systole, and finally to redue the risk of stroke. Evidene from large multientre trials have shown us that the suess rates of onventional treatments for restoring and maintaining sinus rhythm are low and that attempts to restore sinus rhythm may do more harm than good, partiularly if antioagulation is not presribed appropriately. 6 7 Unfortunately these data do not help us deide whether a strategy of restoring and maintaining sinus rhythm is a worthwhile one and to date there is no evidene that treatment of AF by ablation improves mortality, although there are unontrolled data suggesting that this may be the ase. 8 Therefore, asymptomati patients should not be offered urative ablation of AF, exept in the ase of those patients undergoing ardia surgery who may benefit from surgial ablation of their AF as an adjuntive proedure. There is also evidene that patients with heart failure have signifiant improvements in left ventriular funtion following suessful atheter ablation of AF. This result is not explained by better ventriular rate ontrol and is partiularly notable if they do not have another ause for their impaired ardia funtion (for example, ishaemi heart disease). 9 SURGICAL ABLATION The Maze proedure Cardia surgeons were the pioneers of urative ablation of AF, and in 1992 Cox s Maze-III proedure evolved from five years aumulated worldwide surgial experiene and arefully onduted animal and human mapping studies. 10 Initially the lesions were reated by a ut and sew method through a median sternotomy. This has the huge advantage of introduing lesions under diret vision in whih the transmurality of the lesions is ertain and therefore the mehanisti goals desribed above are definitely ahieved. As a onsequene this tehnique is extremely effetive, with maintenane of sinus rhythm reported by Cox at greater than 97% w8 w9 and at 84.9% in a systemati review of 1553 patients in all published series up to 2004. 11 In addition both left atrial (LA) mehanial funtion w8 w10 w11 and left ventriular funtion have been shown to improve. w12 Another important feature of the surgial approah is the removal or losure of the LA appendage whih leads to a very low operative (0.5%) and follow up stroke rate (0.3% at 12 11 w13 years in one study). Limitations of the surgial Maze If the prevalene of AF is so high and the Maze III is so effetive, why has it not been widely embraed by ardia surgeons? In its original form the operation was tehnially hallenging with Cox himself desribing its diffiulty as being 9.5 on a sale to 10. w14 As a result few entres in the world have been able to repliate the original Cox results. In addition there is a mortality and morbidity assoiated with the proedure whih may be too high for the treatment of an arrhythmia onsidered by many (albeit wrongly) to be benign. From the large series the 30 day mortality rates vary from 0 7.2% (mean 2.1%); however, many of these deaths have ourred in patients undergoing onomitant surgery. 11 Other ompliations are sinus node dysfuntion with requirement for permanent paing (5.8%), bleeding aused by the multiple inisions (4.9%), and stroke (0.5%). 11 Newer tehniques of surgial ablation The key to the suess of any atheter or surgial ablation of AF is the orret hoie of lesions (as desribed above) and the prodution of transmural lesions (fig 2). 12 w15 w16 To make AF surgery more attrative, partiularly as a stand alone proedure, tehniques have developed allowing it to beome minimally invasive and redue the length of the proedure. Progress has been made on two fronts. Firstly, there has been a searh for the minimum lesion set needed to ahieve the mehanisti goals desribed above. The Maze-III proedure was designed to interrupt all possible reentry iruits that ould exist in AF and it remains the gold 267

268 Figure 2 A shemati view of the posterior aspet of the left and right atria demonstrating a typial lesion set for surgial ablation of AF as an adjunt to mitral valve surgery at our institution. This is based upon that used by Sie et al. w51 Irrigated radiofrequeny ablation an be delivered by a bipolar lamp or endoardially using a monopolar pen. The mitral valve (MV), triuspid valve (TV), oronary sinus (CS), superior vena ava (SVC), inferior vena ava (IVC), and left (LAA) and right (RAA) atrial appendages are labelled. The four pulmonary veins are visible on the left atrium. The blak hathed lines are inisions and the white lines ablation lesions. (A) The pulmonary veins are isolated as ipsilateral pairs by applying the lamp epiardially. The LA is entered via an inision adjaent to the posterior intra atrial groove. (B) This line of ondution blok is extended by ablation to reah the left pulmonary veins. The LAA is exised and a line of ablation extended from it to the left pulmonary vein line. (C) A line of ablation extends from the left pulmonary veins to the MV annulus. The right atrium is entered via a lateral inision. (D) A line is extended from this inision superiorly to the SVC and (E G) lines to the IVC, CS, and TV to produe ondution blok in the TV IVC isthmus. standard; however, it appears the LA is usually the soure of AF wavefronts with the right atrium as a bystander. w17 19 It is not surprising then that similar results have been found for ablation in the LA only, ompared to ablation performed in both atria. 11 A lesion set that isolates all pulmonary veins, a line that links the isolated PV line to the mitral valve annulus (and ideally enirles the oronary sinus at that point) and a right atrial line aross the triuspid valve inferior vena ava isthmus may be suffiient on its own to give high suess rates in most patients. Cox has desribed this as the Minimaze. w14 Lesion sets limited to just isolating the PVs w15 w20 are not effetive for permanent AF. Seondly, new energy soures for ablation have been developed as an alternative to ut and sew. Cryoablation and radiofrequeny are the most ommon, whih use hand held probes applied endoardially by diret vision. Alternatively, lamp devies hold the atrial wall between two jaws, either using small inisions in the atria or by surrounding the PV antrum epiardially, and deliver radiofrequeny energy to produe a omplete lesion. w20 Newer energy soures suh as laser, mirowave, w21 and ultrasound have the potential to produe transmural lesions even when applied epiardially. A further development from this is the use of a limited thorai inision and thorasopially guided proedure. w22 The inevitable goal is the development of a losed hest, robotially assisted proedure performed on the beating heart. w23 As is the ase with atheter ablation studies, the variety of surgial tehniques, the heterogeneity of the patients treated, and the different antiarrhythmi regimens make omparing studies diffiult. However, a omprehensive review of 2279 patients who underwent these newer surgial methods found 78.3% maintenane of sinus rhythm at follow up with an operative mortality of 4.2% 11 ; 98.4% of these operations were performed alongside other ardia surgery, predominantly mitral valve surgery. Meta-analysis of surgial AF ablation Figure 3 Eletrial isolation of the left superior pulmonary vein. A fluorosopi image of the heart viewed in the anterior posterior projetion. The pulmonary vein atheter (PV) has 14 eletrodes in a spiral and is positioned in the left superior pulmonary vein reording the eletrograms inside the vein. The ablation atheter (MAP) is at the ostium of the vein where it joins the left atrium. Through this atheter radiofrequeny energy is delivered to ablate the onnetions between the left atrium and pulmonary vein until eletrial isolation of a pulmonary vein is ahieved. A atheter is also seen in the oronary sinus (CS) whih an be used to pae to separate the pulmonary vein potential form the far field left atrial potential. studies reveals that the results are very similar regardless of the tehnique used. CATHETER ABLATION The potential for atheter ablation of AF was awakened by the disovery that etopi atrial ativation emerging from

Figure 4 Eletrial isolation of the left superior pulmonary vein. The surfae and intraardia eletrograms reorded during ablation at the ostium of the left superior pulmonary vein. The signals shown are (from top to bottom); the surfae ECG leads (I and V1, green), ablation atheter (Map, white), the oronary sinus (CS, pink) and the pulmonary vein atheter (PV, yellow). A double potential is reorded on some of the bipoles of the PV atheter (marked by yellow arrows). The first potential is the far field left atrial signal and the seond the loal PV potential. From the fifth sinus beat onwards the loal PV potential disappears indiating the vein has beome eletrially isolated from the rest of the left atrium. pulmonary veins ould trigger AF and that ablation of these sites prevents reurrene of AF in previously highly symptomati patients. 2 There has been an exponential growth in the number of atheter AF ablations performed sine then. w24 Isolation of the triggers The PVs are the predominant soure of triggers and the minimum atheter ablation proedure involves isolating them from the rest of the atria. Potential non-pv triggers an also be isolated at the same proedure if they are spontaneously ative. 5 PV isolation is the usual proedure performed for symptomati paroxysmal AF. Initial attempts were made to identify from whih PV the triggers were arising and ablate the ulprits only. It was then reognised, however, that AF may have multiple triggers of whih many will be silent during the ablation proedure; onsequently the urrent approah aims to ablate all PVs. Two main tehniques that have been developed for total PV isolation and their relative merits are among the most ontroversial issues of invasive arrhythmia management. The Bordeaux group pioneered destroying the onnetions of the PV to the LA also known as segmental ostial ablation. 2 13 Via two transseptal puntures an ablation atheter and PV mapping atheter are introdued into the LA. The PV atheter is an adjustable irumferential atheter whih is positioned at the ostia of eah of the veins and allows ativation mapping of the PV. For the left sided PVs it an be diffiult to distinguish between the potentials of the PV and those of the immediately adjaent musular LA appendage. This an be overome by paing either from the distal oronary sinus or the LA appendage, whih then separates the two potentials by advaning the LA appendage signal. If the patient is in sinus rhythm the tehnique is to identify from the PV atheter at whih segment the PV ativates initially. The ablation atheter is moved to this site and positioned 1 m proximal to the PV LA juntion. Energy is delivered at this site until the signal reorded at the ablation signal is attenuated or the ativation pattern in the PV hanges. This proess is repeated, moving the ablation atheter to new sites until one of two end points is reahed; either abolition of all PV potentials (figs 3 and 4) or the PV potentials beome dissoiated from the rest of the LA. Ablation of the PV an also be performed during AF with the end point as abolition of all signals. w25 w26 The outomes of segmental ostial isolation are exellent (51 100% freedom from AF); however, the methods and reporting of observational studies have varied greatly (table 1). The alternative strategy is to reate a ontinuous line of ablation in the LA that surrounds and ompletely enloses the PVs in ipsilateral pairs also known as wide area irumferential ablation. Plaement of multiple lesions as a ontiguous line in suh a omplex three dimensional struture is muh easier if a non-fluorosopi guidane system is utilised. These make use of magneti fields (Carto), low amplitude eletrial fields (Ensite NavX), or a nonontat mapping balloon array (Ensite Array). They all enable atheters to be viewed without fluorosopy and enable onstrution of a omputer generated model of the LA onto whih anatomial strutures and ablation lesions an be superimposed (fig 5). The tehnique as originally desribed is an empiri anatomi one with no attempt made to demonstrate that the PVs are eletrially isolated. In one study using an end point of voltage redution to, 1mV within a oalesent line of ablation around the pulmonary veins, 45% of PVs remained eletrially onneted to the LA. w27 Despite this being ontrary to our understanding of AF mehanisms, it has delivered exellent results with 80% freedom from AF (table 1). 14 269

270 Table 1 Results of peer reviewed observational studies of paroxysmal AF ablation Serious ompliation rateà (%) Use of antiarrhythmi drugs for quoted suess* (%) Repeat proedures for quoted suess (%) How SR assessed Strutural heart disease (%) Tehnology used Follow up (months) Mean (SD) Type of AF (%) Study Patients (n) SR (%) Segmental ostial isolation of 4 pulmonary veins 8 (5) 100 paroxysmal 19 Cirular PV atheter 54 Symptoms & Holter reordings 0 4.4 75 51 7.6 (4.4) 92 paroxysmal. Haissaguerre et al 90 71 2000 w28 4 mm RFA Fluorosopy only Deisenhofer et al 56 Cirular PV atheter 40 Repeated 7 day Holters Not learly stated 10.7 2003 w52 8 persistent 4 mm RFA Fluorosopy only 24 Cirular PV atheter 0 Holter reordings Not learly stated 3.5 4 mm, 8 mm and ooled RFA Event reorder onsidered if symptomati Fluorosopy only Reurrenes,3 weeks ignored Marrouhe et al 211 79 100 4 (2) 10 (3) 54 paroxysmal, 2002 w53 16 persistent, 30 permanent 46 Cirular PV atheter 0 Event reorders 38 7.7 Cryoablation Fluorosopy only Tse et al 2003 w54 52 56 12 (6) 87 paroxysmal, 13 persistent 7 Cirular PV atheter 9 Event reorder if symptomati 0 1.4 4 mm RFA Fluorosopy only 4.9 (2.6) 83 paroxysmal, 17 persistent Oral et al 2002 w34 70 71 paroxysmal, 25 persistent 17 Cirular PV atheter 49 Not stated 0 0.7 Cooled RFA Fluorosopy only Male et al 2002 w45 136 66 8.8 (5.3) 90 paroxysmal, 10 persistent 14 Eletroanatomial mapping Not stated Monthly Holter monitoring 5 0.8 RFA (size not stated) Wide area irumferene ablation of pulmonary veins Pappone et al 42 Eletroanatomial mapping Not stated Daily trans telephoni monitoring Not learly stated 0.7 8 mm RFA Monthly Holter monitoring Reurrenes,6 weeks ignored 2001 14 29 permanent 251 80 10.4 (4.5) 71 paroxysmal, Pappone et al 280 76 Not stated 66 paroxysmal, 2004 w31 34 permanent 0 0 2 Cirular PV atheters 22 Transtelephoni monitoring for Cooled RFA asymptomati patients and regular Eletroanatomial mapping Holter monitoring 44 Cirular PV atheter 0 Transtelephoni monitoring and Combination of wide area irumferential ablation and isolation of PV atheter Ouyang et al 2004 17 41 95 6 (1) 100% paroxysmal Not learly stated 0` Not stated regular 48 Holter monitoring Reurrenes,2 months ignored 8 mm RFA Eletroanatomial mapping Intraardia eho 15.8 (7.8) 39% paroxysmal, 61 non-paroxysmal Verma et al 2005 18 700 86 paroxysmal, 73 nonparoxysmal *Vaughn-Williams group 1 and 3 only. ÀDeath, stroke, tamponade, arterial venous fistula needing repair, pulmonary embolism, phreni nerve palsy, or >1 pulmonary vein stenosis.50% (or ausing symptoms). `All patients started on sotalol, propafenone, fleainide, or dofetilide for first 2 months then all stopped. AF, atrial fibrillation; PV, pulmonary vein; RFA, radiofrequeny ablation; SR, sinus rhythm.

Figure 5 The non-fluorosopi atheter navigation systems used for atheter ablation of AF. A reonstruted geometry of the left atrium is visualised from the posterior perspetive as indiated by the human torso. (A) Ensite Navx uses eletrial fields to loate the atheters. Four pulmonary veins are learly visible and a diagnosti deapolar atheter positioned in the oronary sinus is also visible. (B) Ensite Array (non-ontat mapping) uses eletrial signals to loate the atheters. Four pulmonary veins are visible and the brown markers are lesions of radiofrequeny ablation. (C) Carto (eletroanatomial mapping) uses magneti fields to loate the ablation atheter. The oloured ylinders represent the pulmonary veins. The olour depits the timing of the atrial eletrograms reorded; in this ase the earliest ativation (red) is the result of a right upper pulmonary vein tahyardia. (D) Cartomerge integrates a three dimensional omputed tomographi reonstrution of the patient s left atrium into the Carto geometry giving muh greater anatomial definition than seen in (C). The mapping atheter an be seen in the entre of the image. The blue markers represent lesions of radiofrequeny ablation. The advantage of segmental ostial isolation is that a definite, measurable eletrophysiologial end point is ahieved. There is onfliting evidene from observational studies that isolation of the PVs is both a preditor of, w28 and not neessary for, w29 a suessful outome. Even randomised ontrolled trials whih have ompared the two tehniques Risks and benefits of atheter ablation Suess 60 90% depending on paroxysmal versus permanent AF Suess rate redued in permanent AF in patients with longstanding AF (. 5 years) Many patients (approximately 40%) (partiularly permanent AF) will need more than one proedure to ahieve drug-free sinus rhythm Serious ompliation rate 2% the most ommon is periardial tamponade then stroke (approximately 0.5 1%) have had opposite results. 15 16 What is lear, however, is that wide area irumferential ablation virtually eliminates the risk of PV stenosis at the ost of an inidene of maroreentrant atrial tahyardias as high as 24%, w30 although this may be redued by the addition of linear lesions on the posterior wall of the LA. w31 A tehnique that ombines the merits of these rival strategies is to both perform wide area irumferential ablation and hek for PV isolation using a irular mapping atheter. Suh a tehnique attaks all the possible mehanisms of paroxysmal AF PV triggers, miroreentry in the PV antrum, and denervation of the parasympatheti inputs surrounding the PVs. Freedom from paroxysmal AF is high using this tehnique (86 17 18 95%). Substrate modifiation It is lear from observational studies that PV isolation alone is not as effetive for patients with persistent or permanent rather than paroxysmal AF, w32 34 whih is onsistent with 271

272 the urrent understanding of the mehanisms desribed above. Initial attempts at delivering long lines of radiofrequeny ablation aimed at mimiking the lines of the surgial Maze, although suessful, led to high ompliation rates. w35 w36 Delivering lines to the right atrium only is safe but of low effiay, partiularly in permanent AF. w37 39 Ablation of the avotriuspid isthmus, however, is a simple adjuntive proedure to ablation in the LA, that may redue the inidene of typial atrial flutter. w40 Substrate modifiation of the LA has evolved as eletrophysiologists have beome omfortable ablating around the PVs. The simplest approah of ablating around the PVs (wide area irumferential ablation) exludes a large area of the LA whih is then not available to support AF. Following this proedure Pappone reported 68% freedom from permanent 14 18 AF and Verma 73% from non-paroxysmal AF. Further improvements have required a strategy loser to the surgial Maze that is, lines to onnet the ipsilateral pairs of the PVs and a line to link the left pulmonary vein to the mitral valve annulus, whih an be desribed as the atheter Maze. Suh w31 w41 lines further improve the outomes of paroxysmal AF and have produed good results for permanent AF ablation as well. w42 It is lear that produing lines with proven transmural ondution blok leads to a smaller reurrene of AF; however, ahieving this is tehnially hallenging and requires long, arduous proedures. 12 w43 w44 In addition gaps in these lines may promote maroreentrant (left) atrial tahyardia. Table 2 Compliation Compliations of atheter ablation Inidene w24 How to minimise risk Stroke/transient 1% Warfarin substituted for lexane during ishaemi attak perioperative period Preoperative transoesophageal ehoardiography Heparin infusion to maintain ativated lotting time.300 s throughout ase Heparin saline irrigated ablation atheters Transseptal sheaths in right side of heart when possible Fastidious tehnique when removing/ exhanging atheters Tamponade 1.2% Competeny in transseptal punture Intraardia eho to monitor mirobubbles and venting (indiating potential avitation of lesion) Competeny in emergeny periardial aspiration Rapid aess to ardiothorai surgial assistane.50% pulmonary vein stenosis Atriooesophageal fistula 1.3% Ablation on atrial aspet of LA-PV juntion or outside vein Low power (20 30 W) radiofrequeny ablation near PV Cryoablation auses less PV stenosis but longer proedure Symptoms non-speifi therefore need low suspiion to investigate Few ases worldwide LA, left atrium; PV, pulmonary vein. Where possible avoid lesions in posterior LA Redued power (20 30 W) if ablating at posterior LA Fluorosopi loation of oesophagus using probe Figure 6 A ontrast enhaned magneti resonane image of the left atrium (LA) showing a severe ostial stenosis of the left superior pulmonary vein. The body of the left atrium is viewed in the anteroposterior (AP) projetion. The right superior and inferior pulmonary veins are visible and the arrow indiates the stenosis. This patient was asymptomati; however, redued perfusion to the left lung was demonstrated by a VQ san and a suessful balloon angioplasty of this vessel was performed. A novel approah has been the ablation of all frationated eletrograms in the right and left atrium, with the hypothesis being that these are onsistent sites where fibrillating wavefronts turn or split. By ablating these areas the propagating random wavefronts are progressively restrited until the atria an no longer support AF. Nademanee demonstrated 70% freedom from AF following a single proedure for permanent AF patients. 19 In another study it was shown that in addition to wide area irumferential ablation, targeting frationated potentials redued intraoperative induibilty of AF from 90% to 40%. w41 It is not lear from either of these studies though whether the suess of this tehnique is related simply to debulking myoardium or to targeting the ritially positioned frationated eletrograms. Compliations of atheter ablation For the 9000 patients reported in the worldwide survey of AF ablation there was a mortality of 0.05% and an overall ompliation rate of 5.9%. w24 Some of the largest interventional entres, however, did not ontribute to this study and published single entre studies report the inidene of 14 17 w45 ompliations at, 1% for paroxysmal AF (table 1). When linear ablation is attempted a higher rate is expeted. 12 Ablation of atrial fibrillation (AF): key points Who to refer for onsideration of AF ablation Patients experiening symptomati AF who have failed onventional treatment for example, antiarrhythmi drugs and/or ardioversion (for atheter ablation) Patients with AF undergoing ardiothorai surgery for other reasons (for surgial ablation) A less proven indiation is AF assoiated with heart failure It is important that patients are fully ounselled as to the risks of ablation and are prepared to take them Who not to refer for AF ablation Patients wishing to ome off antioagulation there is still no randomised ontrolled data demonstrating that patient s stroke risk is redued by ablation Patients hoping that ompliations and death assoiated with AF will be avoided

Stroke and periardial tamponade are understandable risks of a proedure that involves multiple transseptal puntures and the delivery of radiofrequeny energy within the systemi irulation. These an be minimised though by good tehnique and training (table 2). Iatrogeni PV stenosis is a linial ondition that beame apparent as a result of delivering too muh energy within the PVs. Symptoms of progressive dyspnoea, ough, and haemoptysis, however, are insidious and an be wrongly diagnosed as respiratory pathology. Remarkably patients are usually asymptomati unless more than a single PV is oluded or severely stenosed (fig 6). w46 Although it an be suessfully treated by angioplasty, w47 it is best avoided (table 2). The development of an atrio-oesophageal fistula is a very rare but lethal ompliation. Presentation is with periarditis, sepsis (suspeted endoarditis), or massive haemotemesis. w48 Even prompt surgial intervention may not be life saving and therefore this ompliation must be avoided (table 2). Who to refer for atheter ablation One of the diffiulties with ounselling patients regarding AF ablation is that the published studies are very diffiult to ompare and interpret beause they vary in the proportion of patients with persistent or permanent AF, prevalene of strutural heart disease, the length of follow up, how sinus rhythm is assessed, the use of antiarrhythmi drugs, and the need for repeat proedures. Studies often emerge from single entres with polarised views on the mehanisms of AF and the best tehnique of ablation. The reader should be aware of suh bias and it is often easier to reommend to patients that they ask the results of an individual entre when they are assessed for AF ablation before they make a final deision as to how they wish to proeed. We have given a summary of the results that most good high volume entres are likely to ahieve as a guide (table 1). CONCLUSION For many patients with a previously untreatable heart rhythm, ablation has dramatially improved their symptoms by restoring and maintaining sinus rhythm. The rapid development of these treatments has made this an exiting time to be involved in ardia eletrophysiology. Despite this we annot be sure that atheter or surgial ablation offers any advantages over any other form of treatment as there have been only three small randomised ontrolled trials omparing 20 w49 w50 surgial or atheter ablation to onventional therapy. This is primarily beause ablation is used most often in patients who have already failed onventional treatment. There is therefore still a need for well onduted multientre randomised ontrolled trials using standardised and verifiable riteria of inlusion, proedure, and follow up. This would give us a better idea of the impat that ablation may have on patients mortality and morbidity, most important of whih is the risk of stroke. Additional referenes appear on the Heart website http:// /supplemental ACKNOWLEDGEMENTS Dr Domini Abrams ontributed the original artwork for fig 1 and 2.... Authors affiliations M J Earley, Manhester Heart Centre, Manhester Royal Infirmary, Manhester, UK R J Shilling, St Bartholomew s Hospital, London, UK In ompliane with EBAC/EACCME guidelines, all authors partiipating in Eduation in Heart have dislosed potential onflits of interest that might ause a bias in the artile REFERENCES 1 Levy S, Camm AJ, Saksena S, et al. International onsensus on nomenlature and lassifiation of atrial fibrillation: a ollaborative projet of the working group on arrhythmias and the working group of ardia paing of the European Soiety of Cardiology and the North Amerian Soiety of Paing and Eletrophysiology. J Cardiovas Eletrophysiol 2003;14:443 5. This is an important onsensus for standardising the terms we use to desribe the temporal aspet of atrial fibrillation that is, paroxysmal, persistent, and permanent. 2 Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by etopi beats originating in the pulmonary veins. N Engl J Med 1998;339:659 66. A landmark paper that ignited the urrent enthusiasm for atheter ablation of AF. An observational study of 45 patients where areful mapping of the atria revealed that runs of atria tahyardia from pulmonary veins triggered paroxysms of AF and that ablation of these foi redued the inidene of AF episodes. 3 Jalife J, Berenfeld O, Mansour M. Mother rotors and fibrillatory ondution: a mehanism of atrial fibrillation. Cardiovas Res 2002;54:204 16. A review by the hief proponent of the onept that high frequeny reentry iruits drive AF. 4 Wijffels MC, Kirhhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation. A study in awake hronially instrumented goats. Cirulation 1995;92:1954 68. A landmark experiment supporting the onept of remodelling of the eletrial properties of the atria aused by AF. 5 Chen SA, Tai CT. Catheter ablation of atrial fibrillation originating from the non-pulmonary vein foi. J Cardiovas Eletrophysiol 2005;16:229 32. Not all foi driving paroxysmal AF are from the pulmonary veins and this review explains the approah to ablation of alternative foi. 6 The AFFIRM Investigators. A omparison of rate ontrol and rhythm ontrol in atrial fibrillation. N Engl J Med 2002;347:1825 33. 7 Van Gelder IC, Hagens VE, Bosker HA, et al. A omparison of rate ontrol and rhythm ontrol in patients with reurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834 40. These two studies have generated a great deal of debate regarding whether restoration of sinus rhythm is a worthwhile goal for patients with AF. Their most important messages, however, are that antiarrhythmi drugs are toxi and proarrhythmi and that antioagulation with warfarin is the ornerstone of AF management. Only very few patients had AF ablation. 8 Pappone C, Rosanio S, Augello G, et al. Mortality, morbidity, and quality of life after irumferential pulmonary vein ablation for atrial fibrillation: outomes from a ontrolled nonrandomized long-term study. J Am Coll Cardiol 2003;42:185 97. Carlo Pappone has performed by far the greatest number of AF ablations worldwide using his tehnique of wide area irumferential ablation. Although non-randomised, this study highlights the superiority of this approah in his hands. 9 Hsu LF, Jais P, Sanders P, et al. Catheter ablation for atrial fibrillation in ongestive heart failure. N Engl J Med 2004;351:2373 83. This is another very important study from Bordeaux, whih shows that suessful ablation of AF improves left ventriular funtion in heart failure patients. 10 Cox JL. Cardia surgery for arrhythmias. Paing Clin Eletrophysiol 2004;27:266 82. Cox is the pioneer of ardia surgery to treat AF and in this review overs the history and evolution of the Maze proedure. 11 Khargi K, Hutten BA, Lemke B, et al. Surgial treatment of atrial fibrillation; a systemati review. Eur J Cardiothora Surg 2005;27:258 65. This is a omprehensive review of all the observational studies to date of surgial treatment of AF, omparing ut and sew methods with those using newer ablation energy soures to reate lines of ondution blok. 12 Ernst S, Ouyang F, Lober F, et al. Catheter-indued linear lesions in the left atrium in patients with atrial fibrillation: an eletroanatomi study. J Am Coll Cardiol 2003;42:1271 82. This observational study of 84 patients demonstrated that prodution of long omplete lines of ondution blok are more effetive in preventing reurrene of AF; however, they are very diffiult to ahieve and lead to a high rate of ompliations. 13 Hoini M, Sanders P, Jais P, et al. Tehniques for urative treatment of atrial fibrillation. J Cardiovas Eletrophysiol 2004;15:1467 71. This reviews in detail the approah of segmental ostial isolation to disonnet eletrially the pulmonary veins. 14 Pappone C, Oreto G, Rosanio S, et al. Atrial eletroanatomi remodeling after irumferential radiofrequeny pulmonary vein ablation: effiay of an anatomi approah in a large ohort of patients with atrial fibrillation. Cirulation 2001;104:2539 44. This study was the first large study (251 patients) of wide area irumferential ablation establishing that it was effetive and a rival to pulmonary vein isolation. 273

274 15 Karh MR, Zrenner B, Deisenhofer I, et al. Freedom from atrial tahyarrhythmias after atheter ablation of atrial fibrillation: a randomized omparison between 2 urrent ablation strategies. Cirulation 2005;111:2875 80. 16 Oral H, Sharf C, Chugh A, et al. Catheter ablation for paroxysmal atrial fibrillation: segmental pulmonary vein ostial ablation versus left atrial ablation. Cirulation 2003;108:2355 60. These two randomised studies have attempted to ompare the two major strategies to atheter ablation of AF; however, they have produed ontraditory results and the debate ontinues. 17 Ouyang F, Bansh D, Ernst S, et al. Complete isolation of left atrium surrounding the pulmonary veins. New insights from the double-lasso tehnique in paroxysmal atrial fibrillation. Cirulation 2004;110:2090 6. 18 Verma A, Wazni OM, Marrouhe NF, et al. Pre-existent left atrial sarring in patients undergoing pulmonary vein antrum isolation: an independent preditor of proedural failure. J Am Coll Cardiol 2005;45:285 92. These two observational studies are the best results published so far for atheter ablation of AF with ure rates of 90% for paroxysmal AF. They both use a tehnique of eletrial isolation of the pulmonary veins inside a wide line of ablation that also enloses the surrounding atrial tissue. MULTIPLE CHOICE QUESTIONS Eduation in Heart Interative (/mis/eduation.shtml) 19 Nademanee K, MKenzie J, Kosar E, et al. A new approah for atheter ablation of atrial fibrillation: mapping of the eletrophysiologi substrate. JAm Coll Cardiol 2004;43:2044 53. This observational study has taught us a radially different approah to AF ablation that appears to be effetive that is, ablation of frationated eletrograms found in the atria. It is not lear why it is so effetive. 20 Wazni OM, Marrouhe NF, Martin DO, et al. Radiofrequeny ablation vs antiarrhythmi drugs as first-line treatment of symptomati atrial fibrillation: a randomized trial. JAMA 2005;293:2634 40. Although small (70 patients), to date this is the only randomised study omparing medial treatment and atheter ablation to manage AF. It demonstrated that ablation leads to fewer symptomati reurrenes, less hospitalisation and improved quality of life. Additional referenes appear on the Heart website http:///supplemental There are six multiple hoie questions assoiated with eah Eduation in Heart artile (these questions have been written by the authors of the artiles). Eah artile is submitted to EBAC (European Board for Areditation in Cardiology; www.eba-me.org) for 1 hour of external CPD redit. How to find the MCQs: Clik on the Online Learning: [Take interative ourse] link on the table of ontents for the issue online or on the Eduation in Heart olletion (/gi/olletion/heart_eduation). Free aess: This link will take you to the BMJ Publishing Group s online learning website. Your Heart Online user name and password will be reognised by this website. As a Heart subsriber you have free aess to these MCQs but you must register on the site so you an trak your learning ativity and reeive redit for ompleted ourses. How to get aess: If you have not yet ativated your Heart Online aess, please do so by visiting http://www.bmjjournals.om/gi/ativate/basi and entering your six digit (all numeri) ustomer number (found above your address label with your print opy). If you have any trouble ativating or using the site please ontat subsriptions@bmjgroup.om Case based Heart: You might also be interested in the interative ases published in assoiation with Heart (http://pd.bmjjournals.om/gi/hierarhy/pd_node;cbh)