Ablatio n o f Atrial Fibrillatio n Eduardo B. Saad, M D , N assir F. M arrouche, M D , and Andrea N atale, M D Address D epartment of Cardiovascular Medicine, The Cleveland Clinic Foundation, D esk F15, 9500 Euclid Avenue, Cleveland, O H 44122, USA. E-mail: natalea@ ccf.org Current Cardiology Reports 2002, 4:379–387 Current Science Inc. ISSN 1523-3782 Copyright © 2002 by Current Science Inc. Associated with significant morbidity and mortality, atrial fibrillation is one of the most common cardiac rhythm disorders. Cure of this arrhythmia has been elusive over the years, despite development of different antiarrhythmic drugs and advances in the understanding of its pathophysiology. Initial experience with catheter ablation procedures based on the creation of linear lesions in both atria has been disappointing, but has led to the key obser vation that focal triggers localized in the pulmonary veins are responsible for initiation of atrial fibrillation, and thus are suitable targets for catheter ablation. W ith advances in technology and larger experience, it has become clear that electrical isolation of all four pulmonar y veins from the left atrium provides the higher cure rates. H owever, the procedure is still operator dependent and is associated with a small but significant risk of pulmonary vein stenosis. Further simplification of the isolation techniques and refinement in the catheter design will allow more widespread use of this procedure and higher success rate. Intro ductio n Atrial fibrillatio n ( AF) is a co m m o n and recurrent cardiac arrhythmia asso ciated with increased mo rbidity and mo rtality [1,2], despite therapy with currently available antiarrhythmic drugs. Even the best available medical therapy is asso ciated with a 50% to 60% annual success rate in m aintaining sinus rhythm [3]. Furtherm o re, side effects and pro arrhythmia are majo r co ncerns o ver the lo ng term. Radio frequency catheter ablatio n ( RFA) o f the atrio ventricular ( AV) no de and pacemaker implantatio n is an effective fo rm o f rate co ntro l [4], but atrial systo le is no t resto red and thro mbo embo lic co mplicatio ns are no t affected, thus requiring co ntinuo us antico agulatio n. In the past decade, the success rates repo rted with the surgical Maze enco uraged the develo pm ent o f catheterbased techniques to duplicate this pro cedure in a less invasive fashio n. By creating linear lesio ns in either the right and/ o r left atrial ( LA) chambers, the substrate respo nsible fo r m aintaining AF wo uld b e m o d ified and no lo nger capable o f suppo rting intra-atrial re-entries [5–8]. Ho wever, so o n it b ecam e clear that no t o nly were tho se pro cedures extrem ely challenging and tim e co nsum ing, but also asso ciated with significant m o rb idity and co m plicatio n rates. Mo reo ver, these investigatio ns fo und that linear lesio ns were o ften arrhythm o genic due to gaps in the lines, giving rise to flutter circuits. Recent advances in understanding the patho physio lo gy o f AF initiatio n have led to a no vel appro ach to catheter ab latio n o f this arrhythm ia. The reco gnitio n that AF is initiated and/ o r m aintained by rapidly discharging fo ci b ro ught ab o ut the co ncep t o f fo cal o rigin o f AF, thus m aking it m o re am enab le to m apping and RFA. In this paper we review the current co ncepts and m anagem ent strategies fo r ablatio n o f fo cal AF. Fo cal Initiatio n o f Atrial Fibrillatio n Mapping and ablatio n o f AF with linear lesio ns created an ideal milieu to disclo se that paro xysms o f AF frequently had a stereo typed mo de o f initiatio n, in the fo rm o f iso lated o r m ultiple fo cal discharges, traced in nearly all patients to sleeves o f atrial myo cardium encasing the pulmo nary veins ( PVs) [9,10••]. These seminal o bservatio ns paved the way to targeted mapping and ablatio n o f AF. In paro xysm al AF, arrhythm o genic fo ci m ay represent the so le abno rmality and be respo nsible no t o nly fo r initiatio n but also fo r m aintenance o f AF. Mo re co m m o nly, a sho rt train o f fo cal discharges triggers episo des o f AF that co ntinue independently o f the initiating event. These fo ci, as m entio ned, have a predo m inant anato m ic lo catio n in the PVs and unusual pro perties such as lo ng co nductio n tim es to the LA, unpredictable firing and frequent o ccurrence o f co ncealed d ischarges ( co nfined to the veins) . Firings fro m these so urces characteristically have very sho rt co upling intervals and the ecto pic P wave usually is hidden in the T wave. Rarely, triggers o riginate fro m o ther so urces as the superio r vena cava, ligam ent o f Marshall, co ro nary sinus and o ther atrial structures [11•,12–15]. A single fo cus can pro duce different types o f arrhythmias, manifesting as iso lated beats, repetitive rapid ( mimicking atrial tachycardia o r flutter) , o r slo w ( m im icking sinus rhythm , b ut with a different P-wave m o rpho lo gy) discharges and as a rapid and irregular tachycardia witho ut a discernible P wave [9]. This fo rm m ay pro duce chao tic atrial activity leading to AF. The so urce o f iso lated extrasysto les and AF initiatio n is identical, initiatio n being the 380 Diagno sis and Treatment o f Arrhythmias result o f sudden transfo rm atio n o f b enign extrasysto les into a train o f rapid discharges. Mapping Techniques Mainly, two different strategies have been develo ped to eliminate PV triggers: fo cal ablatio n targeting single o r multiple fo ci in the arrhythmo genic PV o r electrical iso latio n o f the PVs by circumferential o r segmental RFA lesio ns. Fo cal Ablatio n Initial investigatio ns o n RFA relied o n targeting the ecto py respo nsible fo r precipitating AF [16••,17–19]. An arrhythmo genic PV is defined as o ne that gives rise to spo ntaneo us discharges, single o r multiple, with o r witho ut co nductio n to the LA [10••]. Multipo lar catheters are used to lo ngitudinally map the vein, pro ximally ( o stial) to distal. During sinus rhythm , do uble po tentials are reco rded in the PVs. The first o ne is a lo w-frequency farfield po tential reflecting atrial activatio n, whereas the latest po tentials are highfrequency spikes reflecting activatio n o f m uscular bands extending in the PVs fro m the LA ( pulmo nary vein po tential [PVP]) . Separatio n between these po tentials in the leftsided veins can frequently be appreciated o nly with either left appendage o r distal co ro nary sinus pacing. During ecto pic beats a reversal o f the abo ve activatio n seq uence is o b served , with the PVP p reced ing LA activatio n. A single ecto py with such activatio n seq uence is eno ugh to define an arrhythmo genic vein. Rarely an o stial o rigin m ay pro duce the sam e activatio n pattern as during sinus and mask as a no n-PV ecto py. Inductio n o f atrial ecto py and/ o r AF is required with this appro ach, which pro ved to be an impo rtant limitatio n because in up to 30% patients no sufficient ecto py can be induced to allow precise mapping. Firing fro m these so urces is co m m o nly interm ittent unless very high do ses o f iso pro tereno l ( up to 20 µg/ m in) [20] are given to m axim ize chances o f inducing ecto pies. Multiple cardio versio ns are freq uently req uired during the pro cedure, as sustained episo des o f AF are induced o r recur with the first PV ecto py. It is also uncertain weather the appro priate pro cedural endpo ints are the eliminatio n o f premature beats, the inability to induce AF o r b o th. Furtherm o re, 1) ab latio n o f m o re than o ne PV is freq uently req uired in m o st patients and recurrences can arise either fro m veins no t previo usly targeted o r fro m mo re pro ximal sites within the ablated veins; 2) the co mplex PV anato my renders mapping difficult; and 3) ablatio n within the PVs increases the risk o f steno sis Electrical Iso latio n o f the Pulmo nary Veins An alternative strategy has been co nsidered, which fo cuses at elim inating the critical co nnectio ns b etween the sub strate and triggers irrespective o f o ngo ing trigger activity. Multipo lar circular m apping catheters have beco m e avail- able that facilitate identificatio n o f the m uscular co nnectio ns between the PVs and the LA aro und the entire vein circumference. This allo ws do cumentatio n o f the distributio n and extent o f the PV muscle sleeves by the number o f bipo les sho wing sharp PVPs during sinus rhythm ( Fig. 1) . A feature that m akes circular m apping attractive is the reco gnitio n that discrete fascicles o f atrial m uscle m ay be respo nsible fo r co nnecting electrically the PVs to the LA. The distributio n o f these m uscle sleeves can be identified by earlier activatio n o n o ne o f the bipo les o f the circular catheter, co rrespo nding to a vein segm ent. This early sites can be targeted and few discrete RFA lesio ns may be all that is required to iso late the vein. In o ur experience, this is a co mmo n finding in the inferio r PVs. Th is ap p ro ach h as th e ad van tages o f p ro vid in g a unifo rm endpo int fo r RFA and permitting ablatio n during sinus rhythm, avo iding lengthy mapping o f AF initiatio ns and simplifying the pro cedure. Ablatio n Strategies As discussed abo ve, RFA can be perfo rm ed at the earliest activatio n site ( fo cal ablatio n) o r at the o stial exit in the PV-LA jun ctio n ( segm en tal RFA) . Alth o ugh w ith th e fo rm er, elim inatio n o f the triggers can be achieved with a smaller number o f lesio ns, this appro ach requires meticulo us and tim e-co nsum ing m apping o f freq uent ecto pies and/ o r AF initiatio ns [16••,21–23]. Also , fo cal ab latio n assisted by lo ngitudinal m apping is asso ciated with high in cid en ce o f late recurren ce [ 2 4 •] , an d m ay carry an increased risk o f po st RFA PV steno sis [25]. Mo re recently, fo cal ab latio n o f AF triggers has b een attem pted with a no nco ntact m apping system that relays o n virtual electro grams derived fro m a mathematic mo del b ased o n the inverse Laplace’s eq uatio n to identify the atrial tissue resp o n sib le fo r AF [ 2 6 ] . Th is ap p ro ach , altho ugh appealing, has been used in a limited number o f patients and has no t been tho ro ughly validated. Indeed, because o f the o rientatio n o f and distance to the PV o stia, the system m ay no t pro vide adequate reso lutio n to m ap these structures. In additio n, deplo yment o f this large mapping to o l in the LA may result in increased risk o f co mplicatio ns, d ifficult m anip ulatio n o f o ther catheters, and increased chance o f generating mechanical ecto pies, directing ablatio n to no nrelevant areas. Presently, iso latio n o f the PV tissue fro m the LA is the treatment strategy mo re co mmo nly used in practice. Iso latio n has been achieved with different to o ls, including electro an ato m ic m ap p in g, ultraso un d en ergy d elivered circum ferentially thro ugh a b allo o n catheter, and RFA guided by circular mapping. Each o f these appro aches has advantages and disadvantages. In o ur experience, RFA at the atrial-veno us junctio n frequently needs nearly circumferential ablatio n to achieve iso latio n. It seems to be asso ciated with a lower risk o f inducing PV steno sis, and it may have the advantage o f abo lishing all Ablatio n o f Atrial Fibrillatio n • Saad et al. 381 Figure 1. Bipolar electrogram recordings from a 10-pole circular mapping catheter (L1–L10) placed at the ostium of a right pulmonary vein. Mapping during sinus rhythm records the left atrial activation (A) immediately preceding the sharp PV potentials (PV), demonstrating earliest conduction in the segments corresponding to electrodes 1-2 and 9-10. After delivery of two radiofrequency lesions close to electrodes 9-10 and 8-9 (B) a change in the activation sequence of the PV potentials is observed, suggesting the presence of discrete muscular connections. After one additional lesion is delivered close to electrodes 1-2, isolation is completed (C) and entrance block is shown by the absence of PV potentials. CS—coronary sinus; ESO—esophageal recording; HRA—high right atrial. 382 Diagno sis and Treatment o f Arrhythmias Figure 2. Circumferential mapping-guided ablation of the pulmonary veins (PVs). The left panel depicts a schematic demonstration of a circular catheter placed at the ostium of a PV. This catheter records local PV activation around the circumference of the vein and serves as a fluoroscopic landmark for radiofrequency ablation. The right panel shows the fluoroscopic view of the circular catheter (open arrow ) around the ostium of the right inferior PV during catheter ablation (ABL). The solid arrow points to the intracardiac echo probe situated in the right atrium. CS—coronary sinus catheter. po tential fo ci related to the PV structures. In this regard, the circular mapping technique appears to facilitate ablatio n by providing a useful electro physio lo gic and fluo ro sco pic target ( Fig. 2) . Ab o ve all, arrhythm o genic PVs can b e readily identified with few ecto pies o r even reco gnized by finding co ncealed premature co ntractio ns in sinus rhythm. Emerging Ro le o f Pulmo nary Vein Imaging Periprocedural imaging Recently, intracardiac echo cardio graphy ( IE) has beco me a useful im po rtant to o l fo r electro physio lo gic pro cedures [27•,28]. Two types o f catheters are currently available, a mechanically ro tating single crystal pro be, which pro vides limited penetratio n, and a single plane phase array pro be, which utilizes multiple transducers and pro vides a wedgeshap ed im age sim ilar to that o f transeso p hageal echo cardio graphy ( TEE) . The latter o ffers Do ppler flo w info rmatio n and imaging o f distant chambers. When applied to AF ab latio n, IE has m any po tential ad van tages o ver fluo ro sco py as an im agin g m o d ality [29,30]. It pro vides a detailed an accurate definitio n o f intracardiac structures. By pro viding a clear and direct visualizatio n o f the interatrial septum and fo ssa o valis, it greatly facilitates transseptal puncture and po tentially decreases co mplicatio ns [31,32]. Accurate catheter po sitio ning and tissue co ntact are key to successful and safe ablatio n o f the PV o stia. IE allo ws direct visualizatio n o f the atrio -veno us junctio n, and therefo re is very useful in co nfirming accurate placement o f the Figure 3. Intracardiac echocardiogram using a phase array probe located in the right atrium during AF ablation. Visualization of the circular mapping catheter (Map) inside the left pulmonary vein (LPV). Note that there is a common ostium for the left superior and inferior PVs. The atrial septum and the atrial cavities are clearly visualized. The mapping catheter is subsequently positioned at the ostium to guide ablation. AF—atrial fibrillation; LA—left atrium; RA—right atrium. circular mapping catheter at the PV o stium. Electro de migratio n during ablatio n is readily apparent and can avo id lesio n delivery inside the veins. Impo rtantly, detectio n o f pericardial effusio n befo re it beco m es hem o dynam ically significant allows pro mpt interventio n. Figure 3 shows an example o f IE imaging during circumferential mapping o f the PVs. Visualizatio n o f m icro bubbles during RFA is ano ther impo rtant feature o f IE. It is a marker o f tissue heating and it Ablatio n o f Atrial Fibrillatio n • Saad et al. 383 may use this info rmatio n to better select the to o ls to be used. Also , a prepro cedure assessment is valuable fo r subsequent analysis o f po st RFA co mplicatio ns (Fig. 4) and their co rrelatio n with sym p to m s. Because no sup erio rity has b een proven, the metho d o f cho ice sho uld be based o n the institutio n’s experience and availability. In o ur institutio n, despite the presence o f sym pto m s we ro utinely perfo rm spiral CT 3 m o nths after the pro cedure to evaluate the PV anato my, and use the results to triage patients to o ther investigatio ns and treatment o ptio ns. Patients sho wing 70% o r higher degrees o f narro wing are co nsidered fo r ballo o n dilatatio n. In tho se with mild and mo derate steno sis ( < 70% ) repeat spiral CTs are perfo rmed up to 1 year po st-RFA to exclude lesio n pro gressio n. O utco mes Figure 4. Spiral computed tomography performed 3 months after radiofrequency ablation of the PVs. Both left and right inferior pulmonary veins are clearly depicted. There is a severe stenosis (circle) at the proximal segment of the left inferior PV. LIPV—left inferior pulmonary vein; RIPV—right inferior pulmonary vein. presence is an early marker o f po tential co agulum fo rmatio n. It pro vides an alternative to tem perature and im pedance mo nito ring during RFA, as it can be used fo r accurate power titratio n. In o ur experience, two types o f bubble patterns are seen: bubbles limited to the area aro und the ablatio n catheter, reflecting appro priate lesio n fo rmatio n, and a shower o f dense bubbles extending to the LA cavity and reflecting tissue overheating. Dense generatio n o f bubbles appears to precede impedance elevatio n by a few seco nds. Ro utine use o f IE to titrate radio frequency energy is a pro mising to o l to decrease embo lic co mplicatio ns and PV steno sis. Pre- and Postprocedural imaging of the pulmonary veins With the reco gnitio n o f the co mplex and variable anato my o f the LA and PVs [33], as well as the po ssible develo pment o f PV steno sis after RFA, imaging metho ds capable o f functio nal and m o rpho lo gic analysis o f the PVs have gained impo rtance. TEE is a widely available metho d and can pro vide PV flo w measurements. An increase in flo w is a surro gate o f a narrowed lumen. In a series o f patients undergo ing fo cal ablatio n TEE sho wed high incidences o f PV steno sis. Ho wever, the co rrelatio n between flo w velo city and degree o f steno sis has no t been carefully evaluated. Spiral co m puted to m o graphy ( CT) , electro n-beam CT and magnetic reso nance imaging ( MRI) [34–36] are excellent no ninvasive metho ds fo r visualizing the PVs. They co uld be helpful befo re PV iso latio n, as they can precisely delineate the PV anato my and its variatio ns ( eg, co mmo n o stium, right middle lo be branch) . In this way, the o perato r can be aware o f po tential technical difficulties during the pro cedure and Repo rted success rates varied, in part due to differences in patient selectio n and the different strategies used. In the past 2 years a shift to ward a mo re anato mically based pro cedure has o ccurred, thus avo iding lengthy m apping and need fo r AF initiatio ns. In such case, ablatio n aims at iso latio n o f o ne o r all PVs. The initial experience with AF m apping and fo cal PV ab latio n invo lved 45 patients and sho wed that 94% o f ecto p ies resp o nsib le fo r AF initiatio n had a PV o rigin [10••]. Acute pro cedural success was o btained in 80% o f patients. Mo st patients had RFA o f a single vein and two o r three pro cedures were required to achieve cure in 62% o f patients at 8 mo nths fo llo w-up. Sim ilarly, Chen et al. [ 1 6 ••] rep o rted that 8 8 % o f ecto pies initiating AF were fro m the PVs, and that fo cal ablatio n was acutely successful in eliminating 95% o f fo ci. Ab o ut 56% o f patients had a single vein ab lated. After 6 m o nths o f fo llo w-up, 86% o f 79 patients that had PV fo cal ablatio n was free o f recurrences witho ut antiarrhythm ic drugs. These results required a repeated RFA in abo ut 10% o f patients, and evidence o f PV steno sis was present in abo ut 42% o f the veins targeted, as assessed by increased flo w velo city measured by TEE. Mo re recently, Haissaguerre et al. [ 3 7 ••] used the circular m ap p ing techniq ue to ab o lish the PVPs fro m arrhythm o genic PVs in 70 patients. RFA was perfo rm ed pro ximally in the vein, as dictated by stability o f the circular catheter. Successful PV disco nnectio n was achieved in 97% o f targeted PVs, but AF recurrence was no ted in 44% o f p atients. Co m p lete elim inatio n o f AF witho ut antiarrhythm ic therapy was o btained in 73% o f patients, but ap p ro xim ately 40% req uired two RFA p ro ced ures. The initiating trigger was m apped to a previo usly ablated PV that reco vered in 62% o f these patients. Pappo ne et al. [38] used an alternative strategy based o n the use o f no nfluo ro sco pic electro anato mic mapping to em pirically create circum ferential lesio ns aro und all the PVs in 26 patients, irrespective o f demo nstrable firing. RFA lesio ns were targeted to the vein o stia as defined by the 384 Diagno sis and Treatment o f Arrhythmias T able 1. Summary of the results of AF radiofrequency ablation guided by circumferential mapping according to types of catheters used 4-mm tip catheter Patients, n Age, y Structural heart disease, % Fluoroscopy time, min Procedure time, h Lesions per PV, n/min per PV Follow up, mo Recurrence rate, % Severe stenosis, % (> 7 0 %) 48 53 ± 13 19 110 ± 40 5.5 ± 3 15 ± 3 (10 ± 2) 12 ± 3 23† 2 8-mm tip catheter 25 55 ± 8 20 51 ± 8* 3.1 ± 0.8* 5 ± 2 (3 ± 1) 8± 4 0 0 Cooled-tip catheter 191 54 ± 11 17 80 ± 23*† 4.5 ± 1* 10 ± 4 (4 ± 2) 8 ± 4*† 15† 1.5 AF— atrial fibrillation; n— absolute number; PV— pulmonary vein. * P < 0.05 vs 4-mm tip † P < 0.05 vs 8-mm tip m apping system , which m ay no t be accurate. Despite the sm all num b er o f p atients, they rep o rted a 62% rate o f eliminatio n o f AF witho ut drug therapy. In o ur lab o rato ry, em p iric iso latio n o f b o th up p er PVs was attem pted with the sam e no nfluo ro sco pic threedim ensio nal m apping system in 71 patients [39•]. After a m ean fo llo w up o f 29 m o nths, 80% o f tho se patients in sinus rhythm o ff medicatio ns had the upper PVs, and the left inferio r PV effectively iso lated, whereas o nly 17% o f tho se remaining in AF actually had the veins iso lated. O verall, iso latio n co uld be achieved in o nly 31% o f the targeted PVs, pro ving the technical difficulties o f PV iso latio n witho ut circular m apping and em phasizing the im po rtant ro le o f co mplete iso latio n fo r o ptimal results. In additio n, PV steno sis was detected by spiral CT in 36% o f patients, 10% o f who m had severe steno sis, co nfirming the inability o f electro anato mic navigatio n to accurately guide RFA to the vein o stia. O f no te, 20% o f patients develo ped LA flutter po stRFA, and m apping revealed extensive areas o f electrically silent areas ( scar tissue) , raising the po ssibility that AF represents o ne o f the m anifestatio ns o f an o ngo ing atrial myo pathy, which co uld also result in o ther atrial arrhythmias. Fo llo wing the same ratio nale, O ral et al. [40] described their experience in 70 patients using empiric circular mapp ing-guid ed o stial RFA. The left sup erio r, left inferio r, and right superio r PVs were successfully iso lated in 94% o f patients, whereas the right lo wer PV was iso lated in o nly 20 patients. After 5 mo nths o f fo llo w-up, 70% o f patients presenting with paro xysm al AF were free fro m recurrent AF. O nly 22% o f tho se with persistent AF were arrhythmia free, but the num ber o f patients was very sm all. These results suggest that iso latio n o f all PVs may indeed be necessary to maximize chances o f cure. O ur present appro ach co nsists o f iso latio n o f all PVs guided by circular mapping and IE in every patient referred fo r RFA. In the first 264 patients treated with this technique, we o b served recurrence in ab o ut 15% to 23% o f them ( depending o n the type o f catheter utilized) ( Table 1) , irrespective o f AF duratio n o r LA size. O verall, chro nic cure was achieved o n 94% , 90% , and 89% o f patients with paro xysmal, persistent, and permanent fo rms o f AF, respectively. In o ur series, iso latio n o f all fo ur pulmo nary veins has been effective even in patients with severe left ventricular dysfunctio n [41], which was present in abo ut 10% o f patients. An alternative appro ach to PV iso latio n includes the use o f a b allo o n ultraso und ab latio n system [42•]. This co nsists o f a saline-filled ballo o n with a centrally lo cated ultraso und transducer. O nce the ballo o n is inflated within the PVs, energy is delivered sim ultaneo usly to the entire vein circum ference. This appro ach has the advantage o f being less o perato r-dependent than circular mapping, and it appears to be asso ciated with a very lo w risk o f PV steno sis. Ho wever, the initial o ver-the-wire design was difficult to deplo y in the inferio r PVs, as well as at the o stia. In additio n, an eccentric o rientatio n o f the transducer within the vein was frequently o bserved, and resulted in ineffective energy delivery to certain PV segm ents. Because o f these lim itatio ns, o nly abo ut 40% o f the patients treated with this system had AF co ntro lled after the pro cedure. Co mplicatio ns Pulm o nary vein steno sis ( Fig. 4) is a well-kno wn co m plicatio n o f AF RFA and co uld have severe co nseq uences when m ultiple veins are invo lved. Its exact incidence is unkno wn, as it has no t been co nsistently assessed. Vario us m eth o d s are availab le to m ake th e d iagn o sis. Flo w measurements with TEE [16••,23], and PV visualizatio n by MRI [43], spiral, and electro n beam CT have been repo rted. We have recently repo rted o ur experience with D o ppler flo w measurements using IE befo re and immediately after PV iso latio n [44]. So far, acute changes did no t co rrelate with subsequent develo pm ent o f chro nic steno sis. Ho wever, we did no t have any case with flo w higher than 1.5 m sec. It is co nceivable that high flo w velo cities co uld be used as an indicatio n that PV RFA has to be abando ned. The risk o f PV steno sis appears to be higher fo r the distal versus the o stial ablatio n sites and co uld be related to Ablatio n o f Atrial Fibrillatio n • Saad et al. the radio frequency po wer setting. Indeed, o stial iso latio n is asso ciated with a significant reductio n in the incidence o f steno sis, when co mpared with ablatio n within the PVs. This co uld reflect the thickness o f the PV o stium and lack o f smo o th muscle cells in that regio n, which co ld respo nd with scarring and co ntractio n after therm al injury. The rep o rted incid ence o f PV steno sis has ranged b etween 3% and 42% [23,24•,25,39•,45] and co uld reflect the ap p ro ach utilized d uring RFA and the co nsistent p o stpro cedure assessment o f PV steno sis. It is impo rtant to reco gnize that mo st patients with PV steno sis have no sym pto m s, especially when a m o derate degree o f steno sis is present and a single vein draining a single lung lo be is invo lved. With severe steno sis, typical sympto ms include exertio nal dyspnea, lung co nso lidatio n, hem o ptysis, persistent co ugh, and chest pain. Given the no nspecific nature o f these sym pto m s, it is no t surprising that many patients are initially treated fo r o ther co nditio ns such as pneum o nia and pulm o nary em bo lism befo re the co rrect diagno sis is made. In o ur experience, acute flo w assessm ent after o stial iso latio n never sho wed evidence o f severe ( > 70% ) narro wing. Chro nic evaluatio n with sp iral CT d em o nstrated chro nic severe steno sis in less than 2% o f patients who had o stial iso latio n, as co m pared with 14% o f tho se who had d istal iso latio n. The incid ence o f m o d erate and severe steno sis appeared to be reduced by the o perato r experience and the assistance o f IE imaging. O ther im p o rtant co m p licatio ns o f AF RFA includ e embo lic events, mo stly peripro cedural, and cardiac perfo ratio n. Even if small, the risk o f these co mplicatio ns needs to be weighted against the po tential benefits o f the pro cedure. Indicatio ns Given the co mplexity and the difficulties in ablating multiple PVs, AF RFA is currently reserved to drug-refracto ry, sym pto m atic patients. Po tential candidates are generally yo ung patients [46] with either very sym pto m atic AF o r experiencing severe drug side effects. Ho wever, PV ab latio n is increasingly p erfo rm ed in patients with persistent and permanent fo rms o f AF, and in patients with structural heart disease. In o ur series, results were very similar in all gro ups o f patients when iso latio n o f all PVs was achieved. We recently assessed the perfo rmance o f different catheter techno lo gies fo r PV iso latio n. When co m pared with the co nventio nal 4 -m m tip , 8 -m m tip , and co o led -tip were asso ciated with significantly sho rter fluo ro sco py and pro cedure tim es, as well as with a reduced AF recurrence ( Table 1) . It is po ssible that mo re effective ablatio n o f the pro ximal po rtio n o f the PV sleeves may be respo nsible fo r the better success seen with these catheters. A newer iteratio n o f b allo o n ultraso und catheters is being develo ped. Sim ilarly, ballo o n based system s using laser and cryo ablatio n are being designed and sho uld enter clinical investigatio n so o n. Circular catheters thro ugh which either radio frequency o r cryo lesio ns can be delivered are also b eing tested , and m ay facilitate iso latio n o f the PVs. Co nclusio ns New insights in the patho physio lo gy o f AF have led to impo rtant advances in the management o f this arrhythmia. The co ncept o f a fo cal o rigin in the PVs paved the way to catheter based pro cedures designed to iso late the PVs by transecting the m uscular sleeves that co nnect the veins to the left atrium. Alb eit still in develo pm ent, PV o stial iso latio n using the circular m apping technique is a pro m ising appro ach to cure AF, irrespective o f the duratio n o r the presence o f structural heart disease. Future refinem ents in catheter techno lo gy sho uld m ake the pro cedure easier and less dependent o n the o perato r skills and experience. The po ssibility o f curing AF represents a m ajo r breakthro ugh in invasive card iac electro p hysio lo gy. Current anato m ically based RFA strategies are very pro m ising, and pro bably fo rm the basis fo r further refinem ents. The years to co m e will ho p efully b ring ad vances that will p lace ablatio n as the m ainstay fo rm o f therapy fo r AF. References and Reco mmended Reading Papers o f particular interest, published recently, have been highlighted as: • O f impo rtance •• O f majo r impo rtance 1. Future Expectatio ns It is expected that with further advances in techno lo gy and simplificatio n o f the techniques, AF RFA will beco me a widespread pro cedure that co uld reduce the mo rbidity and co sts asso ciated with AF m anagem ent. Evidence is m o unting that this pro cedure can significantly impro ve quality o f life sco res in the sho rt term [47]. 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