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Mapping-guided ablation of pulmonary veins to cure atrial fibrillation
Mapping-Guided Ablation of Pulmonary Veins to Cure Atrial Fibrillation Michel Haı¨ssaguerre, MD, Dipen C. Shah, MD, Pierre Jaı¨s, MD, Me´le`ze Hocini, Teiichi Yamane, MD, Isabel Deisenhofer, MD, Ste´phane Garrigue, MD, and Jacques Cle´menty, MD
MD,
Catheter ablation of triggers inducing paroxysms of atrial fibrillation (AF) is an emerging therapy for this common arrhythmia. In a series of 225 consecutive patients with AF resistant to multiple drugs, 96% presented with triggering foci originating from 1 or multiple pulmonary veins (PV), independently of whether or not the patient had ectopy or structural heart disease. The present article describes the mapping and ablation techniques applicable to individual patients: (1) criteria to define an arrhythmogenic PV; (2) use of provocative maneuvers; and (3) the role of circumferential mapping catheters to provide extent, distribution, and activation of PV muscle as well as monitoring distal PV potentials
(PVP) during ablation. Radiofrequency ablation can be performed by targeting the PVP during sinus rhythm (right PV) or left atrial pacing (left PV) with the procedural endpoint of PVP elimination, which is more effective in predicting a successful outcome than suppression of acute ectopy. Complete elimination of AF is presently obtained in 70% of patients, allowing interruption of arrhythmias and in use anticoagulants. It is anticipated that continued technologic improvements will improve and facilitate this technique of curative treatment of AF. 䊚2000 by Excerpta Medica, Inc. Am J Cardiol 2000;86(suppl):9K–19K
trial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with A an increased risk of stroke, cardiac failure, and mor-
complex lesion patterns was reported in a series of 45 patients with daily paroxysmal AF (mean duration ⫽ 379 min/day).16 The lesions produced linear conduction block in only 4 of a total of 90 lines (5%). Only 4 patients (9%) were arrhythmia-free without drugs, over a follow-up of 36 ⫾ 5 months. Gaı¨ta et al32 and Calkins et al33 reported series of catheter ablation in the right atrium with similar limited results, which worsened after longer follow-up. Ernst et al34 produced complete linear conduction block in 16 of 32 patients (anterior in 12, intercaval in 4) to the extent of producing intra-atrial dissociation after cavotricuspid isthmus ablation in 4. However, 93% of patients—including those with right atrial free-wall isolation— continued to have episodes of ectopic beats and fibrillation pointing to the initiating and driving role of the left atrium. These right atrial procedures were relatively safe, the main risks being the effect on cardiac conduction and the right phrenic nerve. Linear left atrial ablation: Left atrial lines performed through transeptal access were reported by Jaı¨s et al in a series of 44 patients.35 The lines attempted to create a rectangle with the mitral annulus (as its base) on the posterior wall with a gap left in 1 segment to avoid isolation of the posterior left atrium. A complete validated line of block could only be created in 18 patients: 16 required an irrigated tip catheter36,37 whereas only 2 complete lines were created using a conventional tip catheter. Acutely sustained AF (⬎3 min) was rendered noninducible in 70% of patients. However, left atrial flutters appeared secondarily in 31 patients, despite their noninducibility at the end of the session indicating “remodeling” of linear lesions leaving gaps. These secondary left atrial flutters represented a major problem because they needed extensive
tality.1– 4 Catheter techniques for ventricular rate control (atrioventricular junction ablation or modification) have been shown to be effective,5–7 but the persistence of AF and the frequent requirement for a permanent pacemaker have significant disadvantages. Curative therapies are currently being developed both by surgeons and cardiologists based on either modifying the substrate maintaining AF using linear lesions,8 –13 or eliminating the initiating trigger,14 –17 essentially in the pulmonary veins (PV). This article will focus on the mapping techniques involved in—and the advantages and limitations of—ablation of the trigger as a cure of AF.
PRESENT LIMITATIONS OF CATHETER LINEAR ABLATION IN TARGETING THE ATRIAL SUBSTRATE In the early 1990s, high success rates in curing AF were reported using complex surgical atriotomies.18 –22 Experimental studies aiming to emulate them using catheter techniques were then performed but with inconsistent results.23–29 Two case reports in 1994 demonstrated the feasibility of catheter ablation of AF in humans. Lesions restricted to the right atrium were successful for a patient with paroxysmal AF, and a catheter biatrial Maze procedure was performed in a patient with chronic AF.30,31 Linear right atrial ablation: The efficacy of linear ablation limited to the right atrium using increasingly From the Hoˆpital Cardiologique du Haut-Le´veˆque, Bordeaux, France. Address for reprints: Michel Haı¨ssaguerre, MD, Hoˆpital Cardiologique du Haut-Le´veˆque, Avenue de Magellan, 33604 BordeauxPessac, France. ©2000 by Excerpta Medica, Inc. All rights reserved.
0002-9149/00/$ – see front matter PII S0002-9149(00)01186-3
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3-dimensional mapping to reconstruct the circuit, had multiple morphologies, and required repeated sessions to be eliminated. Gaps were encountered at any point of the left atrial lines but most frequently at the bottom of the right superior pulmonary vein mitral line both endocardially and epicardially, requiring additional radiofrequency applications via the coronary sinus. During a follow-up of 24 ⫾ 5 months (after the last session), ablation was successful in 37 patients: 25 were cured without drugs (57%) and 12 with a previously ineffective drug. The achievement of a line of block (and successful focus ablation) was predictive of success. Ernst et al34 performed a circular line surrounding the PV connecting down to the mitral annulus in 13 patients. Postablation mapping showed that no complete line was created and all patients had recurrent AF. Pappone et al38 reported better clinical results using a similar ablation schema although no complete line was achieved as indicated by persistent conduction inside the line encircling the PV. Other studies by Swartz et al, Packer et al, and Maloney et al29,31,39 reported success rates varying 22–75%. All linear ablation procedures in the left atrium were lengthy (mean 10 hours) and associated with significant morbidity, notably pericardial effusion and thromboembolic events. The above experience of catheter ablation targeting the atrial substrate indicates that the left atrium plays the main role, but the technique has presently been suspended because complete lines are difficult to achieve in this chamber. Based on our experience, the ability to achieve complete line of block requires at least the use of irrigated tip catheters delivering sufficient power for transmural lesions in thicker parts of the left atrial wall. In addition, new catheter technologies are needed to optimize lesion characteristics, avoid proarrhythmic discontinuities, and prevent the need for further ablation sessions. Pending such improvements, the current practical curative therapy of paroxysmal AF involves targeting the initiating triggers (Table 1).
ELECTROCARDIOGRAPHIC SPECTRUM OF FOCAL ARRHYTHMIAS In paroxysmal AF, arrhythmogenic foci may represent the sole abnormality in a few patients in whom the focus discharges for long periods (focal AF). More commonly, a short train of focal discharges triggers episodes of AF that subsequently continue independently of the initiating event (focally initiated AF).14,15,17 This terminology is frequently confused with “focal AF” which is supposed to include only the small subset of AF patients in whom the focus discharges for long periods; whereas in actual fact, virtually 100% of paroxysmal AF—with or without ectopy, with or without structural heart disease— have focal origins that can be targeted for ablation. These foci have a characteristically predominant anatomic location in the pulmonary veins, and unusual properties including long conduction time to the left atrium, unpredictable firing, and frequent occurrence of focal 10K THE AMERICAN JOURNAL OF CARDIOLOGY姞
discharges confined within the vein. Rarely, triggers originate from other veins (superior vena cava, ligament of Mashall, coronary sinus) or atrial tissue, notably the posterior left atrium.14,40 – 46 Holter monitoring shows the variable and capricious nature of spontaneous arrhythmias in the same patient and from 1 patient to another: (1) AF without any preceding isolated ectopic, (2) AF preceded by a single ectopic (short–long sequence), and (3) AF preceded by a long phase of bigeminal rhythm or only isolated ectopics or no arrhythmia at all. A single focus can produce different types of atrial arrhythmia. Single discharges manifest as isolated extrasystoles, repetitive discharges with long cycle lengths manifest as an automatic rhythm (sometimes mimicking sinus rhythm, however, with a different P wave), and shorter cycles result in organized monomorphic tachycardia or a pattern of focal “flutter.” At short cycle lengths, an electrocardiographic pattern of focal AF is produced (i.e., a rapid and irregular tachycardia without discrete P waves).15 Sudden variations (up to 350 msec beat to beat) in the cycle length are the most characteristic pattern for a focal mechanism. True intracardiac AF is initiated when the focus abruptly discharges in a very rapid train of impulses with a cycle length of 182 ⫾ 57 msec (330 beats per minute) leading to chaotic atrial activity.17 The source of isolated extrasystoles and AF initiation is identical because initiation is the result of sudden transformation of benign isolated extrasystoles into a “malignant” train of rapid discharges. Intracardiac recordings show that this initial phase of rapid discharges from the PV is followed by an apparently random “fibrillation” pattern of left atrial activation, which is much more suggestive of wandering reentry. During AF, the PV is activated passively; however, focal discharges can occur during AF (contributing to maintenance of AF) and this can be demonstrated by abrupt distal to proximal activation sequences (Figure 1). In patients without apparent isolated ectopy, AF is initiated because discharges from the focus occur only in trains, every train inducing AF. Initiations of common atrial flutter, its degeneration into AF, or its interruption are also frequently the result of PV discharges.47 The first ectopic P wave— whether isolated or initiating AF—is superimposed on the T wave of the previous QRS complex producing a P on T pattern recognizable at first sight. During an ablation procedure, any focus resulting in P on T ectopy is considered a target for ablation, even without documentation of its role in AF initiation. This is because in our early experience, when these foci were spared, most patients had subsequent recurrences of AF originating from the unablated focus and required a new ablation session.
MAPPING TECHNIQUES
Candidates for trigger mapping and ablation:
Whereas the initial patients were selected based on the occurrence of frequent ectopy to allow mapping,16,17,40,42 the selection is now neither based on ectopy number nor on structural heart disease. In total,
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TABLE 1 Risk/Benefit Analysis of Curative Approaches for Atrial Fibrillation Approach
Advantages
Limitations
● Mapping required, notably for non-PV foci ● Inconsistent firing/ induction ● Multiplicity of foci ● Anatomic approach ● Inability to achieve (no prior mapping linear block with required) conventional catheter ● Higher morbidity
Risks
Trigger ablation ● Accessible using conventional catheters ● No proarrhythmic effect of ablation
● Stenosis/thrombosis of PV ● Damage to surrounding tissue
Linear ablation in the LA
● Pericardial effusion ● Thromboembolic event ● Damage to surrounding tissue ● Proarrhythmic effects
LA ⫽ left atrium; PV ⫽ pulmonary vein.
FIGURE 1. Focal discharges during atrial fibrillation (AF). A multielectrode catheter placed inside right inferior (RI) pulmonary vein (PV) shows synchronous venous activation during AF. A train of 3 impulses (arrows) with a mean cycle length of 170 msec originates near the electrode and produces a distal (Dist) to proximal (Prox) activation sequence, thereby contributing to the maintenance of fibrillation. LA ⴝ left atrium; RA ⴝ right atrium.
225 patients were investigated and all had frequent drug-resistant AF with a mean daily duration of 447 ⫾ 449 minutes (0 –1,440). The broad range of age (25– 82 years), AF clinical profiles, and right or left heart disease covered the great majority of clinical situations encountered in practice. We found that 96% of triggering foci originated from a total of 475 arrhythmogenic PV (mean 2.1 PV per patient) with 74% of patients having ⬎1 arrhythmogenic PV. Therefore, there are no criteria for selecting (or excluding) candidates for AF ablation, although the present technical difficulties prompt us to favor multi-drug resistant AF. Catheter techniques: Different catheter techniques can be used for PV mapping. In patients with frequent ectopics and nonsustained AF, a single catheter can be introduced in the right atrium and then into the left atrium for vein-by-vein mapping. In most patients, few ectopics were observed and we straightaway performed a transseptal catheterization to introduce 2 roving ablation catheters with different curve sizes (Cordis–Webster yellow and blue) into the left atrium.
In the beginning, they are placed in the 2 superior PV and on recording some ectopics moved into the inferior PV. Few P on T ectopics or AF initiations are necessary using this method to identify the arrhythmogenic PV(s). Ectopics with a long coupling interval observed during PV mapping are usually mechanically induced and are a target for ablation only if they have been clinically documented (matching morphology of the P wave using a 12-lead electrocardiograph or Holter) or shown to trigger AF. Some authors advocate introducing 3 or 4 diagnostic catheters to simultaneously map multiple PV; however, this has no significant advantage in terms of time because these nonsteerable catheters are difficult to position in the inferior PV or at the bottom of the superior PVs and cannot be used for ablation. Definition of an arrhythmogenic PV: An arrhythmogenic PV is defined as a PV (extending from the ostium to its tributaries) that gives rise to spontaneous discharges—single or multiple and with or without conduction to the left atrium.17 During sinus rhythm, A SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART
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FIGURE 2. Near- and farfield pulmonary vein potential (PVP). The third beat is an ectopic producing a distal to proximal and pulmonary vein potential (PVP)–atrial sequence, thus defining the arrhythmogenicity of left superior PV (LSPV). At high amplifications (1 cm ⴝ 0.1 mV), PVPs originating from the LSPV are recorded simultaneously in the left inferior PV (LIPV) as well as through lower amplitude slower (lower dv/dt) farfield deflection (asterisk). Note that the sequence of activation remains from distal to proximal in both veins, suggesting the electrotonic origin of the LIPV deflections.
double or multiple potentials are recorded in sequence from the proximal to the distal PV; synchronous with the first (right PVs) or second (left PVs) half of the P wave. The first potential is low in frequency (farfield) reflecting activation of the adjacent left atrium; an additional early (synchronous with the P wave onset) potential emanating from the adjacent right atrium is recorded from the right superior PV anterior wall. The latest potentials are high frequency spikes indicating local activation of muscular bands extending into the PV from the left atrium (PV potential [PVP]). The ostial PVP may be concealed in the left PVs in contrast to the right PVs because of the superimposed (fusing) left atrial potential during sinus rhythm requiring pacing of the distal coronary sinus or left atrial appendage (when distal coronary sinus cannot be reached) for their separation.48 During ectopy from within an arrhythmogenic PV, there is a reversal of the activation sequence, proceeding from the distal to the proximal bipole with the PVP preceding the left atrial potential. A single ectopic producing a PVP–atrial sequence is sufficient to define an arrhythmogenic PV (Figure 2). Rarely, ectopy originates from the ostium, thus producing early local activation and an unchanged sequence (proximal to distal) within the vein. The source of ectopy marked by the earliest PVP is often discrete in contrast to the intravenous course and atrial exit where a synchronous PVP with a later timing (up to 160 msec) can be recorded in wide sectors. A lower amplitude farfield PVP (⬍ 0.1 mV) can also be recorded from a neigh12K THE AMERICAN JOURNAL OF CARDIOLOGY姞
boring PV trunk: for instance, a farfield left inferior PVP reflecting a sharp PVP originating actually from the left superior PV bottom (Figure 2). During ectopy, orthodromic and antidromic conduction can also be recorded in different parts of the same vein (indicating 2 independent atriovenous fascicles) so that recording late activity (with an orthodromic left atrial–PVP sequence) in 1 sector of the PV during ectopy does not exclude an origin in another part of the same vein, particularly after an initial ablation. The conduction time to the left atrium is typically long and exhibits decremental conduction with increasing prematurity (Figure 3). Ectopics closely coupled to the previous sinus beat are not conducted to the left atrium (i.e., confined within the vein) and documented in 42–70% of arrhythmogenic PVs—a figure that varies depending on the particular vein.48 Such ectopic PVPs are usually synchronous to the local ventricular electrogram and distinguished from it by intermittent occurrence or disappearance with atrial pacing (Figure 3). A slightly longer coupling interval—5–10 msec—is sufficient to allow conduction to the left atrium,17 thus, even “concealed” ectopy is equally indicative of an arrhythmogenic pulmonary vein. Multiplicity of foci from the same PV: Multielectrode catheters allowing simultaneous mapping of the complete venous perimeter are capable of documenting multiple foci from the same vein as well as the distribution and extent of PV muscle coverage. We explored 20 patients using a circumferential PV catheter
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FIGURE 3. (Top) Increase in the pulmonary vein potential (PVP)– ostial conduction time with shortening of the coupling interval (spike to spike) to the sinus beat. The PVP coupled <165 msec are nonconducted. (Bottom) Electrocardiograph illustration in the right superior pulmonary vein. A first ectopic discharge (Star) after the second sinus beat with a coupling interval of 160 msec is confined to the vein. An ectopic discharge with a coupling interval of 170 msec is conducted to the left atrium.
equipped with 10 electrodes and a deflectable shaft (Lasso, Biosense Webster). Local electrograms were acquired simultaneously during sinus rhythm, ectopy, or AF onset, either spontaneously or induced by provocative maneuvers. Changes in the site of earliest activation (source) and intra-PV activation as documented by the remaining electrodes, were compared during different initiations with the catheter in a stable position in the arrhythmogenic PV. During isolated ectopy, the earliest and/or intra-PV activation was identical in 76% and different in 24%. The earliest activity was sometimes restricted to a single bipole corresponding to a discrete PV fascicle. During repetitive ectopy and/or AF, initiation from varying sources, and/or with distinct activation patterns were noted in 45%, indicating multiple foci in the same PV. The multiplicity of foci correlated with the extent of muscle coverage. Provocation of ectopy: Provocative maneuvers are frequently required to elicit ectopy when the arrhythmia did not spontaneously develop during electrophysiologic study. Different clinical profiles are en-
countered: One end of the spectrum is the uncommon patient with frequent spontaneous ectopy and short episodes of AF in whom mapping is simple; the other end consists of patients with few or no ectopy and long-lasting AF in whom provocative maneuvers induce AF requiring cardioversion—frequently multiple. In patients developing sustained AF, all provocative maneuvers are suspended as soon as the arrhythmogenic PVs are identified on the basis of a single or a few ectopy/AF initiations. After ablation, provocative maneuvers are repeated in a progressively more aggressive fashion using higher doses of isoproterenol and higher pacing rates. Several maneuvers can be successful in eliciting ectopy from the same focus while different foci in the same patient can exhibit varying sensitivity. They are performed in the following order: (1) vagal maneuvers, effective in 2–10% depending on the arrhythmogenic PV, (2) pauses after cessation of pacing in 7–10%, (3) isoproterenol in 20 – 44%, (4) combination in 10 –17%, and (5) adenosine triphosphate or saline solution infusions anecdotally. AF reinitiation is A SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART
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FIGURE 4. Examples of late and distinct pulmonary vein potential during sinus rhythm in patients with atrial fibrillation and without inducible ectopy. LIPV ⴝ left inferior pulmonary vein; LSPV ⴝ left superior pulmonary vein.
observed in 30% of cases after cardioversion. In 10% of the studies, we cannot record a single ectopy or AF initiation, and ablation is performed at the ostia of PV displaying distinct and late PV potentials—a finding not seen in control patients without AF—and continued until their complete abolition (Figure 4).
ABLATION TECHNIQUES Radiofrequency ablation can be performed distally at the site of earliest spike activity (source), along its intravenous course, or at its ostial exit into the left atrium with similar efficacy. Ablation at the source requires a meticulous and time-consuming mapping of frequent enough ectopics/AF initiations,16,40,42 which is infrequently encountered. There is a risk of later recurrence from other foci in the same vein.48 Distal ablation close to PV branching increases the difficulties of performing venous angioplasty, stenting, or surgery in the case of stenosis.50 On the other hand, although the substrate toward the ostium is wider, proximal ablation has a lower risk of inducing significant stenosis and the advantage of isolating all potential foci into the vein. Above all, the arrhythmogenic PVs can be identified readily with few ectopics and then proximal ablation is performed to the local PV muscle during sinus rhythm with the endpoint of PVP elimination. The endpoint of complete atriovenous disconnection is more effective in predicting a successful outcome (without drug) than the endpoint of acute ectopy suppression.48 This result is somewhat similar to flutter ablation in which isthmus block provides a better long-term result than flutter interruption. When there are multiple ar14K THE AMERICAN JOURNAL OF CARDIOLOGY姞
rhythmogenic PVs, the PV producing the most repetitive ectopy and/or inducing AF is first targeted; radiofrequency energy is then delivered in a second PV after angiographic verification of unchanged potency of the first one. Extent and distribution of PV muscle: A circumferential PV catheter allows an instantaneous assessment of the extent of muscle coverage by the number of bipoles showing sharp PVPs during sinus rhythm. At the atrial margin of the ostia, PVPs are usually present circumferentially (all bipoles display PVP) whereas inside the PV, potentials cover only varying parts of the perimeter with a different circumferential distribution for each PV in the following order: left superior, right superior, left inferior; and a gradual reduction in their width from proximal to distal. In the proximal part of the vein (where ablation is performed), synchronous PVP activation in a sector indicates wide fascicles, which will require multiple contiguous radiofrequency applications for a progressive elimination of all PV muscle. In contrast, limited PVP sites (1 or 2 bipoles) or sequential PVP activation (cascade pattern) indicates limited fascicles, which can be abruptly eliminated by discrete radiofrequency applications. Ablation during sinus rhythm: Sequential radiofrequency applications are delivered within the first ostial centimeter targeting the PVP during sinus rhythm or left atrial pacing (for left PVs) with the endpoint of eliminating (or dissociating) all distal PVPs.48,49 This is achieved with variable radiofrequency applications ranging from a discrete area (notably in the inferior
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FIGURE 5. Partial left inferior pulmonary vein (LIPV) disconnection. Multielectrode mapping in the proximal left inferior pulmonary vein (LIPV) after ostial (ost) radiofrequency ablation demonstrates persistent atriovenous conduction in a discrete part of the vein circumference (bipole 9 –10) while there is a dissociated potential in the major remaining part of the circumference (electrodes 3 to 7). This activation pattern indicates the presence of 1 discrete connection from the atria to the vein susceptible to cause recurrence of atrial fibrillation. Furthermore, pacing from inside the vein will not capture the left atrium (falsely suggesting atriovenous block) unless the pacing stimulus involves the area explored by the bipole 9 –10. RSPV ⴝ right superior pulmonary vein.
veins) to a circumferential ablation (notably in the left superior PV). The use of 2 conventional catheters with differing curve radii allows the operator to reach the complete perimeter of all veins. Practically, the circumferential PV catheter, which initially indicated the areas to be targeted, can then be pushed distally during ostial radiofrequency ablation to monitor disappearance or activation change of the distal PVP, permitting the optimal dosing of radiofrequency energy. Furthermore, we verify through the ablation catheter that each radiofrequency application is delivered at a site showing sharp PVPs, and once this activity has been abolished or become farfield, the ablation catheter is displaced to another point. Usually, radiofrequency ablation progressively delays PVPs before their abrupt abolition; whereas in 15% of cases, PVP is still seen as an automatic dissociated rhythm (Figures 5 and 6). The incidence of dissociation is higher in the superior (22%) than in the inferior (8%) PV. Dissociated PVP in one part of the vein while conduction is present in another part is unusual (Figure 5). Dissociated repetitive discharges were observed in 5 patients. In patients with frequent ectopics, sequential radiofrequency applications produce a progressive decrease of repetitive and isolated ectopics sometimes after a transient exacerbation of arrhythmia. Persistent ectopics are often due to a residual PV fascicle requiring careful mapping of the venous perimeter searching for a continuum of atrial–PVP (gap-like) electrogram.49 A local radiofrequency application results in abrupt disappearance of local and distal PVP. When the PV is
disconnected, persistent ectopics may sometimes be due to discharges from the atrial edge of the same ostium (proximal to the ablation lesion) or foci from other PV or atrial tissue. Ablation during AF: When several cardioversions have been performed to interrupt AF but with prompt recurrence, ostial ablation can be performed during AF while still monitoring the distal PVP (Figure 7). In this situation, ostial PVP are difficult to differentiate from left atrial potentials so that ablation is performed anatomically around the PV perimeter.48 After return in sinus rhythm (spontaneous or after infusion of antiarrhythmic drugs: amiodarone and/or flecainide), additional ablation is performed targeting the remaining PVP if necessary.
EFFICACY Long-term elimination of AF paroxysms is strongly associated with disappearance of the distal PVP whereas persistence (immediately after ablation) or recovery of the PVP is associated with a high risk of arrhythmia recurrence. Total PV disconnection is corroborated by the inability to capture the left atrium by pacing from the PV. However, a limited PV fascicle may not be captured by venous pacing, making circumferential PV mapping a more reliable technique (Figure 5). In patients with recurrent AF, repeat mapping shows that recurrent ectopy may originate from: (1) within a previously targeted PV, related to persistent or recovered PV potentials—a remaining PV fascicle small enough to be ablated by a single radiofreA SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART
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FIGURE 6. Progressive ablation of left superior pulmonary vein (LSPV) posterior wall. A multielectrode circular catheter placed 1 cm inside LSPV exhibits sharp and delayed (terminal) potentials in bipoles 1–7 during pacing from the left atrial appendage. It indicates the presence of pulmonary vein muscle in the posterior wall of the vein. Proximal radiofrequency ablation at the level of the vein ostium delays these potentials (middle panel) before finally eliminating them (extreme right).
quency application can be sufficient to produce AF; (2) a nontargeted PV; (3) combination of the above; (4) the PV ostium instead of inside the vein; and (5) non-PV sites. This explains the frequent need for multiple ablation sessions but is nevertheless encouraging because it indicates a significant margin for improvement with better ablation techniques applied at the index procedure. Different ablation catheters are being developed to cauterize a wider substrate with each application. It includes supple electrodes conforming to part of the venous perimeter (selected by prior mapping) or devices expanded into the vein orifices to “anatomically” perform circumferential lesions. Complete elimination of AF without drug is observed in 70% of our patients, allowing interruption of anticoagulant treatment. However, these patients may have residual P on T ectopics, which—in contrast to before ablation—are isolated and unable to discharge in trains so as to initiate AF. The success rate decreases with the number of arrhythmogenic PV—from 93% in patients with a single arrhythmogenic PV, to 73 and 55% when ⱖ2 PV are involved— because of difficulties in consistently eliminating the PVP. A 16K THE AMERICAN JOURNAL OF CARDIOLOGY姞
single PV is significantly associated with younger age, fewer AF and smaller atrial dimensions whereas multiple arrhythmogenic PV are associated with older patients having a longer history of AF, more frequent episodes, and larger atrial dimensions. Most of the “unsuccessfully treated” patients are significantly improved. Chen et al42 reported an 86% success rate in 79 patients who had short episodes of AF (daily duration 28 ⫾ 30 min). Multiple PV was found in only 44% and their procedural endpoint was acute ectopy suppression without relying on PVP mapping.45
SAFETY: RISK OF PV STENOSIS PV stenosis, defined as a diameter reduction ⱖ50%, was observed in 9 patients (2% of PV ablated) the mean gradient was 4 ⫾ 2 mm Hg and no patient had pulmonary hypertension. Only 2 patients had symptoms: 1 because of PV thrombosis, and the other because 2 PV were stenosed requiring balloon angioplasty for relieving symptoms. Importantly, PV stenosis occurred acutely (immediately at the end of ablation) and few changes were observed later. The left inferior PV, a distal ablation site (close to PV branch-
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FIGURE 7. (Top) A slow regular dissociated local potential is recorded from the left superior pulmonary vein (LSPV) during atrial fibrillation (AF). This vein was ablated during AF. (Bottom) After ablation in both the RSPV and LSPV, a potential is dissociated from sinus rhythm. dist ⴝ distal.
ing) and the use of radiofrequency power reaching 45–50 watts were factors predictive of stenosis.48 –50 Without limitation of radiofrequency power, some authors reported up to 42% of distal PV stenosis as indicated by a significant PV flow acceleration; quadruple stenoses requiring angioplasty were also observed.42,50 In our experience, with a present limitation of radiofrequency power ⬍30 watts (10 –20 watts often sufficient in the inferior veins), a single PV stenosis occurs at the ostia although a longer-term follow-up is probably necessary. This limited power was associated with low “achieved” temperature in the PV (average: 42°C), owing to the local high cooling blood flow similar to the functioning of the irrigated tip catheter, and considerably decreased the incidence of extracardiac damage (coughing due to bronchial irritation or vagal excitation). Other potential risks of left atrial ablation procedures are less specific, including hemopericardium (1%), thromboembolic events (1%), or catheterization side effects.
ABLATION OF PV IN CHRONIC AF Although the role of foci is probably less in chronic AF compared with the substrate, 2 studies reported the mode of reinitiation of chronic AF after cardioversion and the efficacy of ablating these foci of reinitiation.
Lau et al44 performed mapping of AF reinitiation in 32 patients with chronic AF (mean 13 months) and identified a PV focus in 4 patients. A 2-center study included 15 patients, 7 with structural heart disease, persistent for 5 ⫾ 4 months.49 In all patients, cardioversion was followed by documentation of P on T atrial ectopy and/or early recurrence, which allowed mapping of the reinitiating trigger. A total of 32 arrhythmogenic PVs and 2 atrial foci (left septum and left appendage) were identified. No PV stenosis was noted either acutely or at repeated follow-up angiography. In total, 8 patients (55%) were in stable sinus rhythm without antiarrhythmic drugs with a follow-up of 11 ⫾ 8 months, and anticoagulants were interrupted in 7. The successful outcome was associated with PVP elimination. A larger group and longer follow-up is needed to further investigate the role of trigger ablation in curative therapy for chronic AF, but these results are supported by those of limited antiarrhythmic surgery around the PV by Sueda et al51 or Melo et al.52
INDICATIONS In view of the difficulties in producing effective lesions in multiple PV, ablation of arrhythmogenic PV is presently indicated in multidrug resistant, symptomA SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART
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atic patients with paroxysmal AF. In such patients, the risks associated with persistent AF (notably 1–3% thromboembolic events per year with increased mortality) and the risks of antiarrhythmic and anticoagulant drugs appear to outweigh those of the ablation procedure, and it is our opinion that this curative approach is clearly superior to atrioventricular junction ablation. A history of thromboembolic phenomena or tachycardia-mediated heart failure, as evidence of AF morbidity, further supports the indication for the procedure. It is anticipated that continued technologic developments will optimize and facilitate these techniques. Ultimately it may become a widespread procedure, provided that further studies demonstrate a favorable risk/benefit ratio, notably, maintained improvement of symptoms, better survival, and decreased risk of thromboembolic events compared with alternative treatments. Acknowledgment: The authors wish to express their appreciation for the secretarial assistance of Joe¨lle Bassibey.
1. Feinberg WM, Blackshear JL, Laupacis A. Prevalence, age distribution, and
gender of patients with atrial fibrillation: analysis and implications. Arch Intern Med 1995;155:469 – 473. 2. Kopecky SL, Gersh BJ, McGoon MD, Whisnant JP, Holmes DR Jr, Ilstrup DM, Frye RL. The natural history of lone atrial fibrillation: a population-based study over three decades. N Engl J Med 1987;317:669 – 674. 3. Prystowsky EN, Benson DW, Fuster V. Management of patients with atrial fibrillation: a statement for healthcare professionals from the subcommittee on electrocardiography and electrophysiology, American Heart Association. Circulation 1996;93:1262–1277. 4. Le´vy S, Breithardt G, Campbell RWF, Camm AJ, Daubert JC, Allessie M, Aliot E, Capucci A, Cosio F, Crijns H, et al. Atrial fibrillation: current knowledge and recommendations for management. Eur Heart J 1998;19:1294 –1320. 5. Scheinman MM, Morady F, Hess DS, Gonzalez R. Catheter-induced ablation of atrioventricular junction to control refractory supraventricular arrhythmias. JAMA 1982;248:855– 861. 6. Langberg JJ, Chin M, Schamp DJ. Ablation of the atrioventricular junction with radiofrequency current energy using a new electrode catheter. Am J Cardiol 1991;67:142–147. 7. Williamson BD, Man KC, Daoud E, Niebauer M, Strickberger SA, Morady F. Radiofrequency catheter modification of atrioventricular conduction to control the ventricular rate during atrial fibrillation. N Engl J Med 1994;331:910 –917. 8. Garrey WE. The nature of fibrillatory contraction of the heart: its relation to tissue mass and form. Am J Physiol 1914;33:397– 414. 9. Moe GK, Rheinboldt WC, Abildskov JA. A computer model of atrial fibrillation. Am Heart J 1964;67:200 –220. 10. Konings KTS, Kirschhof CJHJ, Smeets JRLM, Wellens HJJ, Penn O, Allessie MA. High-density mapping of electrically induced atrial fibrillation in humans. Circulation 1994;89:1665–1680. 11. Allessie MA, Rensma PL, Brugada J, Smeets JLRM, Penn O, Kirchhof CJHJ. Pathophysiology of atrial fibrillation. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia: WB Saunders, 1990: 548 –559. 12. Ortiz J, Niwano S, Abe H, Rudy Y, Johnson NJ, Waldo AL. Mapping the conversion of atrial flutter to atrial fibrillation and atrial fibrillation to atrial flutter: insights into mechanism. Circ Res 1994;74:882– 894. 13. Wang Z, Feng J, Nattel S. Idiopathic atrial fibrillation in dogs: electrophysiologic determinants and mechanisms of antiarrhythmic action of flecainide. J Am Coll Cardiol 1995;26:277–326. 14. Haı¨ssaguerre M, Marcus FI, Fischer B, Cle´menty J. Radiofrequency catheter ablation in unusual mechanisms of atrial fibrillation: report of 3 cases. J Cardiovasc Electrophysiol 1994;5:743–751. 15. Jaı¨s P, Haı¨ssaguerre M, Shah DC, Chouairi S, Gencel L, Hocini M, Cle´menty J. A focal source of atrial fibrillation treated by discrete radio frequency ablation. Circulation 1997;95:572–576. 16. Haı¨ssaguerre M, Jaı¨s P, Shah DC, Gencel L, Pradeau V, Garrigue S, Chouairi S, Hocini M, Le Me´tayer P, Roudaut R, Cle´menty J. Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 1996;7:1132–1144. 17. Haı¨ssaguerre M, Jaı¨s P, Shah DC, Takahashi A, Hocini M, Quiniou G,
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Garrigue S, Le Mouroux A, Le Me´tayer P, Cle´menty J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659 – 666. 18. Cox JL, Canavan TE, Schuessler RB. The surgical treatment of atrial fibrillation II: intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and fibrillation. J Thorac Cardiovasc Surg 1991;101:406 – 426. 19. Cox JL, Boineau JP, Schuessler RB, Kater KM, Lappas DG. Five year experience with the Maze procedure for atrial fibrillation. Ann Thorac Surg 1993;56:814 – 824. 20. Defauw JJ, Guiraudon GM, Van Hemel NM, Vermeulen FE, Kingma JH, de Bakker JM. Surgical therapy of paroxysmal atrial fibrillation with the corridor operation. Ann Thorac Surg 1992;53:564 –571. 21. Shyu KG, Cheng JJ, Chen JJ. Recovery of atrial function after atrial compartment operation for chronic atrial fibrillation in mitral valve disease. J Am Coll Cardiol 1994;24:392–398. 22. Kosakai Y, Kawaguchi AT, Isobe F. Modified Maze procedure for patients with atrial fibrillation undergoing simultaneous open-heart surgery. Circulation 1995;92(suppl II):II-359 –II-364. 23. Avitall B, Hare J, Mughal K. Ablation of atrial fibrillation in a dog model. J Am Coll Cardiol 1994;484:276A. 24. Elvan A, Pride HP, Eble JN, Zipes DP. Radiofrequency catheter ablation of the atria reduces inducibility and duration of atrial fibrillation in dogs. Circulation 1995;91:2235–2244. 25. Morillo CA, Klein GJ, Jones DL. Chronic rapid atrial pacing: structural, functional and electrophysiologic characteristics of a new model of sustained atrial fibrillation. Circulation 1995;91:1588 –1595. 26. Olgin J, Kalman JM, Maguire M. Electrophysiologic effects of long linear atrial lesions placed under intracardiac echo guidance. Circulation 1997;96: 2715–2721. 27. Tondo C, Scherlag BJ, Otomo K, Antz M, Patterson E, Arruda M, Jackman WM, Lazzara R. Critical atrial site for ablation of pacing-induced atrial fibrillation in the normal dog heart. J Cardiovasc Electrophysiol 1997;8:1255–1265. 28. Haines DE, McRury IA. Linear atrial ablation in a canine model of chronic atrial fibrillation. Circulation 1997;96:2715–2721. 29. Packer DL, Johnson SB, Pederson B, Hauck J. The utility of non-contact mapping in identifying and rectifying discontinuity-mediated atrial proarrhythmia accompanying linear lesion creation. PACE Pacing Clin Electrophysiol 1998;21: 867. 30. Haı¨ssaguerre M, Gencel L, Fischer B, Le Me´tayer P, Poquet F, Marcus FI, Cle´menty J. Successful catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol 1994;5:1045–1052. 31. Swartz JF, Pellersels G, Silvers J. A catheter-based curative approach to atrial fibrillation in humans. Circulation 1994;90:I-335. 32. Gaı¨ta F, Riccardi R, Calo L, Scaglione M, Garberoglio L, Antolini R, Kirchner M, Lamberti F, Richiardi E. Atrial mapping and radiofrequency catheter ablation in patients with idiopathic atrial fibrillation. Circulation 1998;97:2136 – 2145. 33. Calkins H, Hall J, Ellenbogen K, Walcott G, Sherman M, Bowe W, Simpson J, Castellano T, Kay GN. A new system for catheter ablation of atrial fibrillation. Am J Cardiol 1999;83(suppl):227D–236D. 34. Ernst S, Schlu¨ter M, Ouyang F, Khanedani A, Cappato R, Hebe J, Wolkmer M, Antz M, Kuck KH. Modification of the substrate for maintenance of idiopathic human atrial fibrillation. Circulation 1999;100:2085–2092. 35. Jaı¨s P, Shah DC, Haı¨ssaguerre M, Takahashi A, Lavergne T, Hocini M, Garrigue S, Barold SS, Le Me´tayer P, Cle´menty J. Efficacy and safety of septal and left atrial linear ablation for atrial fibrillation. Am J Cardiol 1999;84(suppl 9A):139R–146R. 36. Lavergne T, Jaı¨s P, Haı¨ssaguerre M, Bruszewski W, Bruneval P, Cle´menty J. Evaluation of a single passage RF ablation line in animal atria using an irrigated tip catheter (abstract). Circulation 1997;96(suppl I):I-259. 37. Jaı¨s P, Haı¨ssaguerre M, Shah DC, Takahashi A, Hocini M, Lavergne T, Lafitte S, Le Mouroux A, Fischer B, Cle´menty J. Successful irrigated tip catheter ablation of atrial flutter resistant to conventional radio frequency ablation. Circulation 1998;98:835– 838. 38. Pappone C, Oreto G, Lamberti F. Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system. Circulation 1999;100:1203–1208. 39. Maloney JD, Milner L, Barold SS, Czerska B, Markel M. Two-staged biatrial linear and focal ablation to restore sinus rhythm in patients with refractory chronic atrial fibrillation: procedure experience and follow-up beyond one year. PACE Pacing Clin Electrophysiol 1998;21:2527–2532. 40. Wharton JM, Vergara I, Shander G. Identificaton and ablation of focal mechanisms of atrial fibrillation (abstract). Circulation 1998;98:18. 41. Chen SA, Tai CT, Yu WC. Right atrial focal atrial fibrillation: electrophysiologic characteristics and radiofrequency catheter ablation. J Cardiovasc Electrophysiol 1999;10:328 –335. 42. Chen SA, Hsieh MH, Tai CT. Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiologic characteristics, pharmacological responses, and effects of radio frequency ablation. Circulation 1999;100:1879 –1886. 43. Hwang C, Karagueuzian HS, Chen PS. Idiopathic paroxysmal atrial fibrillation induced by a focal discharge mechanism in the left superior pulmonary vein: possible roles of the ligament of Marshall. J Cardiovasc Electrophysiol 1999;10: 636 – 648.
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44. Lau CP, Tse HF, Ayers GM. Defibrillation-guided radio frequency ablation
of atrial fibrillation secondary to an atrial focus. J Am Coll Cardiol 1999;33: 1217–1226. 45. Chen SA, Tai CT, Tsai CF, Hsieh MH, Ding YA, Chang MS. Radiofrequency catheter ablation of atrial fibrillation initiated by pulmonary vein ectopic beats. J Cardiovasc Electrophysiol 2000;11:218 –227. 46. Tsai CF, Tai CT, Hsieh MH. Paroxysmal atrial fibrillation initiated by ectopic beats originating in the superior vena cava: electrophysiologic findings and radio frequency ablation results. Circulation 2000 (in press). 47. Shah DC, Haı¨ssaguerre M, Jaı¨s P, Takahashi A, Cle´menty J. Atrial flutter: contemporary electrophysiology and catheter ablation. PACE Pacing Clin Electrophysiol 1999;22:344 –359. 48. Haı¨ssaguerre M, Jaı¨s P, Shah DC, Garrigue S, Takahashi A, Lavergne T, Hocini M, Peng JT, Roudaut R, Cle´menty J. Electrophysiological end point for
catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Circulation 2000;101:1409 –1417. 49. Haı¨ssaguerre M, Jaı¨s P, Shah DC, Arentz T, Kalusche D, Takahashi A, Garrigue S, Hocini M, Peng JT, Cle´menty J. Catheter ablation of chronic atrial fibrillation targeting the reinitiating triggers. J Cardiovasc Electrophysiol 2000; 11:2–10. 50. Robbins IM, Colvin EV, Doyle TP, Kemp WE, Loyd JE, McMahon WS, Kay N. Pulmonary vein stenosis after catheter ablation of atrial fibrillation. Circulation 1998;98:1769 –1775. 51. Sueda T, Nagata H, Khirkata H. Simple left atrial procedure for chronic atrial fibrillation associated with mitral valve disease. Ann Thorac Surg 1996;62:1796 – 1800. 52. Melo JQ, Neves J, Adragao P. When and how to report results of surgery on atrial fibrillation. Eur J Cardiothorac Surg 1997;12:739 –745.
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MD,
Catheter ablation of triggers inducing paroxysms of atrial fibrillation (AF) is an emerging therapy for this common arrhythmia. In a series of 225 consecutive patients with AF resistant to multiple drugs, 96% presented with triggering foci originating from 1 or multiple pulmonary veins (PV), independently of whether or not the patient had ectopy or structural heart disease. The present article describes the mapping and ablation techniques applicable to individual patients: (1) criteria to define an arrhythmogenic PV; (2) use of provocative maneuvers; and (3) the role of circumferential mapping catheters to provide extent, distribution, and activation of PV muscle as well as monitoring distal PV potentials
(PVP) during ablation. Radiofrequency ablation can be performed by targeting the PVP during sinus rhythm (right PV) or left atrial pacing (left PV) with the procedural endpoint of PVP elimination, which is more effective in predicting a successful outcome than suppression of acute ectopy. Complete elimination of AF is presently obtained in 70% of patients, allowing interruption of arrhythmias and in use anticoagulants. It is anticipated that continued technologic improvements will improve and facilitate this technique of curative treatment of AF. 䊚2000 by Excerpta Medica, Inc. Am J Cardiol 2000;86(suppl):9K–19K
trial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with A an increased risk of stroke, cardiac failure, and mor-
complex lesion patterns was reported in a series of 45 patients with daily paroxysmal AF (mean duration ⫽ 379 min/day).16 The lesions produced linear conduction block in only 4 of a total of 90 lines (5%). Only 4 patients (9%) were arrhythmia-free without drugs, over a follow-up of 36 ⫾ 5 months. Gaı¨ta et al32 and Calkins et al33 reported series of catheter ablation in the right atrium with similar limited results, which worsened after longer follow-up. Ernst et al34 produced complete linear conduction block in 16 of 32 patients (anterior in 12, intercaval in 4) to the extent of producing intra-atrial dissociation after cavotricuspid isthmus ablation in 4. However, 93% of patients—including those with right atrial free-wall isolation— continued to have episodes of ectopic beats and fibrillation pointing to the initiating and driving role of the left atrium. These right atrial procedures were relatively safe, the main risks being the effect on cardiac conduction and the right phrenic nerve. Linear left atrial ablation: Left atrial lines performed through transeptal access were reported by Jaı¨s et al in a series of 44 patients.35 The lines attempted to create a rectangle with the mitral annulus (as its base) on the posterior wall with a gap left in 1 segment to avoid isolation of the posterior left atrium. A complete validated line of block could only be created in 18 patients: 16 required an irrigated tip catheter36,37 whereas only 2 complete lines were created using a conventional tip catheter. Acutely sustained AF (⬎3 min) was rendered noninducible in 70% of patients. However, left atrial flutters appeared secondarily in 31 patients, despite their noninducibility at the end of the session indicating “remodeling” of linear lesions leaving gaps. These secondary left atrial flutters represented a major problem because they needed extensive
tality.1– 4 Catheter techniques for ventricular rate control (atrioventricular junction ablation or modification) have been shown to be effective,5–7 but the persistence of AF and the frequent requirement for a permanent pacemaker have significant disadvantages. Curative therapies are currently being developed both by surgeons and cardiologists based on either modifying the substrate maintaining AF using linear lesions,8 –13 or eliminating the initiating trigger,14 –17 essentially in the pulmonary veins (PV). This article will focus on the mapping techniques involved in—and the advantages and limitations of—ablation of the trigger as a cure of AF.
PRESENT LIMITATIONS OF CATHETER LINEAR ABLATION IN TARGETING THE ATRIAL SUBSTRATE In the early 1990s, high success rates in curing AF were reported using complex surgical atriotomies.18 –22 Experimental studies aiming to emulate them using catheter techniques were then performed but with inconsistent results.23–29 Two case reports in 1994 demonstrated the feasibility of catheter ablation of AF in humans. Lesions restricted to the right atrium were successful for a patient with paroxysmal AF, and a catheter biatrial Maze procedure was performed in a patient with chronic AF.30,31 Linear right atrial ablation: The efficacy of linear ablation limited to the right atrium using increasingly From the Hoˆpital Cardiologique du Haut-Le´veˆque, Bordeaux, France. Address for reprints: Michel Haı¨ssaguerre, MD, Hoˆpital Cardiologique du Haut-Le´veˆque, Avenue de Magellan, 33604 BordeauxPessac, France. ©2000 by Excerpta Medica, Inc. All rights reserved.
0002-9149/00/$ – see front matter PII S0002-9149(00)01186-3
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3-dimensional mapping to reconstruct the circuit, had multiple morphologies, and required repeated sessions to be eliminated. Gaps were encountered at any point of the left atrial lines but most frequently at the bottom of the right superior pulmonary vein mitral line both endocardially and epicardially, requiring additional radiofrequency applications via the coronary sinus. During a follow-up of 24 ⫾ 5 months (after the last session), ablation was successful in 37 patients: 25 were cured without drugs (57%) and 12 with a previously ineffective drug. The achievement of a line of block (and successful focus ablation) was predictive of success. Ernst et al34 performed a circular line surrounding the PV connecting down to the mitral annulus in 13 patients. Postablation mapping showed that no complete line was created and all patients had recurrent AF. Pappone et al38 reported better clinical results using a similar ablation schema although no complete line was achieved as indicated by persistent conduction inside the line encircling the PV. Other studies by Swartz et al, Packer et al, and Maloney et al29,31,39 reported success rates varying 22–75%. All linear ablation procedures in the left atrium were lengthy (mean 10 hours) and associated with significant morbidity, notably pericardial effusion and thromboembolic events. The above experience of catheter ablation targeting the atrial substrate indicates that the left atrium plays the main role, but the technique has presently been suspended because complete lines are difficult to achieve in this chamber. Based on our experience, the ability to achieve complete line of block requires at least the use of irrigated tip catheters delivering sufficient power for transmural lesions in thicker parts of the left atrial wall. In addition, new catheter technologies are needed to optimize lesion characteristics, avoid proarrhythmic discontinuities, and prevent the need for further ablation sessions. Pending such improvements, the current practical curative therapy of paroxysmal AF involves targeting the initiating triggers (Table 1).
ELECTROCARDIOGRAPHIC SPECTRUM OF FOCAL ARRHYTHMIAS In paroxysmal AF, arrhythmogenic foci may represent the sole abnormality in a few patients in whom the focus discharges for long periods (focal AF). More commonly, a short train of focal discharges triggers episodes of AF that subsequently continue independently of the initiating event (focally initiated AF).14,15,17 This terminology is frequently confused with “focal AF” which is supposed to include only the small subset of AF patients in whom the focus discharges for long periods; whereas in actual fact, virtually 100% of paroxysmal AF—with or without ectopy, with or without structural heart disease— have focal origins that can be targeted for ablation. These foci have a characteristically predominant anatomic location in the pulmonary veins, and unusual properties including long conduction time to the left atrium, unpredictable firing, and frequent occurrence of focal 10K THE AMERICAN JOURNAL OF CARDIOLOGY姞
discharges confined within the vein. Rarely, triggers originate from other veins (superior vena cava, ligament of Mashall, coronary sinus) or atrial tissue, notably the posterior left atrium.14,40 – 46 Holter monitoring shows the variable and capricious nature of spontaneous arrhythmias in the same patient and from 1 patient to another: (1) AF without any preceding isolated ectopic, (2) AF preceded by a single ectopic (short–long sequence), and (3) AF preceded by a long phase of bigeminal rhythm or only isolated ectopics or no arrhythmia at all. A single focus can produce different types of atrial arrhythmia. Single discharges manifest as isolated extrasystoles, repetitive discharges with long cycle lengths manifest as an automatic rhythm (sometimes mimicking sinus rhythm, however, with a different P wave), and shorter cycles result in organized monomorphic tachycardia or a pattern of focal “flutter.” At short cycle lengths, an electrocardiographic pattern of focal AF is produced (i.e., a rapid and irregular tachycardia without discrete P waves).15 Sudden variations (up to 350 msec beat to beat) in the cycle length are the most characteristic pattern for a focal mechanism. True intracardiac AF is initiated when the focus abruptly discharges in a very rapid train of impulses with a cycle length of 182 ⫾ 57 msec (330 beats per minute) leading to chaotic atrial activity.17 The source of isolated extrasystoles and AF initiation is identical because initiation is the result of sudden transformation of benign isolated extrasystoles into a “malignant” train of rapid discharges. Intracardiac recordings show that this initial phase of rapid discharges from the PV is followed by an apparently random “fibrillation” pattern of left atrial activation, which is much more suggestive of wandering reentry. During AF, the PV is activated passively; however, focal discharges can occur during AF (contributing to maintenance of AF) and this can be demonstrated by abrupt distal to proximal activation sequences (Figure 1). In patients without apparent isolated ectopy, AF is initiated because discharges from the focus occur only in trains, every train inducing AF. Initiations of common atrial flutter, its degeneration into AF, or its interruption are also frequently the result of PV discharges.47 The first ectopic P wave— whether isolated or initiating AF—is superimposed on the T wave of the previous QRS complex producing a P on T pattern recognizable at first sight. During an ablation procedure, any focus resulting in P on T ectopy is considered a target for ablation, even without documentation of its role in AF initiation. This is because in our early experience, when these foci were spared, most patients had subsequent recurrences of AF originating from the unablated focus and required a new ablation session.
MAPPING TECHNIQUES
Candidates for trigger mapping and ablation:
Whereas the initial patients were selected based on the occurrence of frequent ectopy to allow mapping,16,17,40,42 the selection is now neither based on ectopy number nor on structural heart disease. In total,
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TABLE 1 Risk/Benefit Analysis of Curative Approaches for Atrial Fibrillation Approach
Advantages
Limitations
● Mapping required, notably for non-PV foci ● Inconsistent firing/ induction ● Multiplicity of foci ● Anatomic approach ● Inability to achieve (no prior mapping linear block with required) conventional catheter ● Higher morbidity
Risks
Trigger ablation ● Accessible using conventional catheters ● No proarrhythmic effect of ablation
● Stenosis/thrombosis of PV ● Damage to surrounding tissue
Linear ablation in the LA
● Pericardial effusion ● Thromboembolic event ● Damage to surrounding tissue ● Proarrhythmic effects
LA ⫽ left atrium; PV ⫽ pulmonary vein.
FIGURE 1. Focal discharges during atrial fibrillation (AF). A multielectrode catheter placed inside right inferior (RI) pulmonary vein (PV) shows synchronous venous activation during AF. A train of 3 impulses (arrows) with a mean cycle length of 170 msec originates near the electrode and produces a distal (Dist) to proximal (Prox) activation sequence, thereby contributing to the maintenance of fibrillation. LA ⴝ left atrium; RA ⴝ right atrium.
225 patients were investigated and all had frequent drug-resistant AF with a mean daily duration of 447 ⫾ 449 minutes (0 –1,440). The broad range of age (25– 82 years), AF clinical profiles, and right or left heart disease covered the great majority of clinical situations encountered in practice. We found that 96% of triggering foci originated from a total of 475 arrhythmogenic PV (mean 2.1 PV per patient) with 74% of patients having ⬎1 arrhythmogenic PV. Therefore, there are no criteria for selecting (or excluding) candidates for AF ablation, although the present technical difficulties prompt us to favor multi-drug resistant AF. Catheter techniques: Different catheter techniques can be used for PV mapping. In patients with frequent ectopics and nonsustained AF, a single catheter can be introduced in the right atrium and then into the left atrium for vein-by-vein mapping. In most patients, few ectopics were observed and we straightaway performed a transseptal catheterization to introduce 2 roving ablation catheters with different curve sizes (Cordis–Webster yellow and blue) into the left atrium.
In the beginning, they are placed in the 2 superior PV and on recording some ectopics moved into the inferior PV. Few P on T ectopics or AF initiations are necessary using this method to identify the arrhythmogenic PV(s). Ectopics with a long coupling interval observed during PV mapping are usually mechanically induced and are a target for ablation only if they have been clinically documented (matching morphology of the P wave using a 12-lead electrocardiograph or Holter) or shown to trigger AF. Some authors advocate introducing 3 or 4 diagnostic catheters to simultaneously map multiple PV; however, this has no significant advantage in terms of time because these nonsteerable catheters are difficult to position in the inferior PV or at the bottom of the superior PVs and cannot be used for ablation. Definition of an arrhythmogenic PV: An arrhythmogenic PV is defined as a PV (extending from the ostium to its tributaries) that gives rise to spontaneous discharges—single or multiple and with or without conduction to the left atrium.17 During sinus rhythm, A SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART
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FIGURE 2. Near- and farfield pulmonary vein potential (PVP). The third beat is an ectopic producing a distal to proximal and pulmonary vein potential (PVP)–atrial sequence, thus defining the arrhythmogenicity of left superior PV (LSPV). At high amplifications (1 cm ⴝ 0.1 mV), PVPs originating from the LSPV are recorded simultaneously in the left inferior PV (LIPV) as well as through lower amplitude slower (lower dv/dt) farfield deflection (asterisk). Note that the sequence of activation remains from distal to proximal in both veins, suggesting the electrotonic origin of the LIPV deflections.
double or multiple potentials are recorded in sequence from the proximal to the distal PV; synchronous with the first (right PVs) or second (left PVs) half of the P wave. The first potential is low in frequency (farfield) reflecting activation of the adjacent left atrium; an additional early (synchronous with the P wave onset) potential emanating from the adjacent right atrium is recorded from the right superior PV anterior wall. The latest potentials are high frequency spikes indicating local activation of muscular bands extending into the PV from the left atrium (PV potential [PVP]). The ostial PVP may be concealed in the left PVs in contrast to the right PVs because of the superimposed (fusing) left atrial potential during sinus rhythm requiring pacing of the distal coronary sinus or left atrial appendage (when distal coronary sinus cannot be reached) for their separation.48 During ectopy from within an arrhythmogenic PV, there is a reversal of the activation sequence, proceeding from the distal to the proximal bipole with the PVP preceding the left atrial potential. A single ectopic producing a PVP–atrial sequence is sufficient to define an arrhythmogenic PV (Figure 2). Rarely, ectopy originates from the ostium, thus producing early local activation and an unchanged sequence (proximal to distal) within the vein. The source of ectopy marked by the earliest PVP is often discrete in contrast to the intravenous course and atrial exit where a synchronous PVP with a later timing (up to 160 msec) can be recorded in wide sectors. A lower amplitude farfield PVP (⬍ 0.1 mV) can also be recorded from a neigh12K THE AMERICAN JOURNAL OF CARDIOLOGY姞
boring PV trunk: for instance, a farfield left inferior PVP reflecting a sharp PVP originating actually from the left superior PV bottom (Figure 2). During ectopy, orthodromic and antidromic conduction can also be recorded in different parts of the same vein (indicating 2 independent atriovenous fascicles) so that recording late activity (with an orthodromic left atrial–PVP sequence) in 1 sector of the PV during ectopy does not exclude an origin in another part of the same vein, particularly after an initial ablation. The conduction time to the left atrium is typically long and exhibits decremental conduction with increasing prematurity (Figure 3). Ectopics closely coupled to the previous sinus beat are not conducted to the left atrium (i.e., confined within the vein) and documented in 42–70% of arrhythmogenic PVs—a figure that varies depending on the particular vein.48 Such ectopic PVPs are usually synchronous to the local ventricular electrogram and distinguished from it by intermittent occurrence or disappearance with atrial pacing (Figure 3). A slightly longer coupling interval—5–10 msec—is sufficient to allow conduction to the left atrium,17 thus, even “concealed” ectopy is equally indicative of an arrhythmogenic pulmonary vein. Multiplicity of foci from the same PV: Multielectrode catheters allowing simultaneous mapping of the complete venous perimeter are capable of documenting multiple foci from the same vein as well as the distribution and extent of PV muscle coverage. We explored 20 patients using a circumferential PV catheter
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FIGURE 3. (Top) Increase in the pulmonary vein potential (PVP)– ostial conduction time with shortening of the coupling interval (spike to spike) to the sinus beat. The PVP coupled <165 msec are nonconducted. (Bottom) Electrocardiograph illustration in the right superior pulmonary vein. A first ectopic discharge (Star) after the second sinus beat with a coupling interval of 160 msec is confined to the vein. An ectopic discharge with a coupling interval of 170 msec is conducted to the left atrium.
equipped with 10 electrodes and a deflectable shaft (Lasso, Biosense Webster). Local electrograms were acquired simultaneously during sinus rhythm, ectopy, or AF onset, either spontaneously or induced by provocative maneuvers. Changes in the site of earliest activation (source) and intra-PV activation as documented by the remaining electrodes, were compared during different initiations with the catheter in a stable position in the arrhythmogenic PV. During isolated ectopy, the earliest and/or intra-PV activation was identical in 76% and different in 24%. The earliest activity was sometimes restricted to a single bipole corresponding to a discrete PV fascicle. During repetitive ectopy and/or AF, initiation from varying sources, and/or with distinct activation patterns were noted in 45%, indicating multiple foci in the same PV. The multiplicity of foci correlated with the extent of muscle coverage. Provocation of ectopy: Provocative maneuvers are frequently required to elicit ectopy when the arrhythmia did not spontaneously develop during electrophysiologic study. Different clinical profiles are en-
countered: One end of the spectrum is the uncommon patient with frequent spontaneous ectopy and short episodes of AF in whom mapping is simple; the other end consists of patients with few or no ectopy and long-lasting AF in whom provocative maneuvers induce AF requiring cardioversion—frequently multiple. In patients developing sustained AF, all provocative maneuvers are suspended as soon as the arrhythmogenic PVs are identified on the basis of a single or a few ectopy/AF initiations. After ablation, provocative maneuvers are repeated in a progressively more aggressive fashion using higher doses of isoproterenol and higher pacing rates. Several maneuvers can be successful in eliciting ectopy from the same focus while different foci in the same patient can exhibit varying sensitivity. They are performed in the following order: (1) vagal maneuvers, effective in 2–10% depending on the arrhythmogenic PV, (2) pauses after cessation of pacing in 7–10%, (3) isoproterenol in 20 – 44%, (4) combination in 10 –17%, and (5) adenosine triphosphate or saline solution infusions anecdotally. AF reinitiation is A SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART
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FIGURE 4. Examples of late and distinct pulmonary vein potential during sinus rhythm in patients with atrial fibrillation and without inducible ectopy. LIPV ⴝ left inferior pulmonary vein; LSPV ⴝ left superior pulmonary vein.
observed in 30% of cases after cardioversion. In 10% of the studies, we cannot record a single ectopy or AF initiation, and ablation is performed at the ostia of PV displaying distinct and late PV potentials—a finding not seen in control patients without AF—and continued until their complete abolition (Figure 4).
ABLATION TECHNIQUES Radiofrequency ablation can be performed distally at the site of earliest spike activity (source), along its intravenous course, or at its ostial exit into the left atrium with similar efficacy. Ablation at the source requires a meticulous and time-consuming mapping of frequent enough ectopics/AF initiations,16,40,42 which is infrequently encountered. There is a risk of later recurrence from other foci in the same vein.48 Distal ablation close to PV branching increases the difficulties of performing venous angioplasty, stenting, or surgery in the case of stenosis.50 On the other hand, although the substrate toward the ostium is wider, proximal ablation has a lower risk of inducing significant stenosis and the advantage of isolating all potential foci into the vein. Above all, the arrhythmogenic PVs can be identified readily with few ectopics and then proximal ablation is performed to the local PV muscle during sinus rhythm with the endpoint of PVP elimination. The endpoint of complete atriovenous disconnection is more effective in predicting a successful outcome (without drug) than the endpoint of acute ectopy suppression.48 This result is somewhat similar to flutter ablation in which isthmus block provides a better long-term result than flutter interruption. When there are multiple ar14K THE AMERICAN JOURNAL OF CARDIOLOGY姞
rhythmogenic PVs, the PV producing the most repetitive ectopy and/or inducing AF is first targeted; radiofrequency energy is then delivered in a second PV after angiographic verification of unchanged potency of the first one. Extent and distribution of PV muscle: A circumferential PV catheter allows an instantaneous assessment of the extent of muscle coverage by the number of bipoles showing sharp PVPs during sinus rhythm. At the atrial margin of the ostia, PVPs are usually present circumferentially (all bipoles display PVP) whereas inside the PV, potentials cover only varying parts of the perimeter with a different circumferential distribution for each PV in the following order: left superior, right superior, left inferior; and a gradual reduction in their width from proximal to distal. In the proximal part of the vein (where ablation is performed), synchronous PVP activation in a sector indicates wide fascicles, which will require multiple contiguous radiofrequency applications for a progressive elimination of all PV muscle. In contrast, limited PVP sites (1 or 2 bipoles) or sequential PVP activation (cascade pattern) indicates limited fascicles, which can be abruptly eliminated by discrete radiofrequency applications. Ablation during sinus rhythm: Sequential radiofrequency applications are delivered within the first ostial centimeter targeting the PVP during sinus rhythm or left atrial pacing (for left PVs) with the endpoint of eliminating (or dissociating) all distal PVPs.48,49 This is achieved with variable radiofrequency applications ranging from a discrete area (notably in the inferior
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FIGURE 5. Partial left inferior pulmonary vein (LIPV) disconnection. Multielectrode mapping in the proximal left inferior pulmonary vein (LIPV) after ostial (ost) radiofrequency ablation demonstrates persistent atriovenous conduction in a discrete part of the vein circumference (bipole 9 –10) while there is a dissociated potential in the major remaining part of the circumference (electrodes 3 to 7). This activation pattern indicates the presence of 1 discrete connection from the atria to the vein susceptible to cause recurrence of atrial fibrillation. Furthermore, pacing from inside the vein will not capture the left atrium (falsely suggesting atriovenous block) unless the pacing stimulus involves the area explored by the bipole 9 –10. RSPV ⴝ right superior pulmonary vein.
veins) to a circumferential ablation (notably in the left superior PV). The use of 2 conventional catheters with differing curve radii allows the operator to reach the complete perimeter of all veins. Practically, the circumferential PV catheter, which initially indicated the areas to be targeted, can then be pushed distally during ostial radiofrequency ablation to monitor disappearance or activation change of the distal PVP, permitting the optimal dosing of radiofrequency energy. Furthermore, we verify through the ablation catheter that each radiofrequency application is delivered at a site showing sharp PVPs, and once this activity has been abolished or become farfield, the ablation catheter is displaced to another point. Usually, radiofrequency ablation progressively delays PVPs before their abrupt abolition; whereas in 15% of cases, PVP is still seen as an automatic dissociated rhythm (Figures 5 and 6). The incidence of dissociation is higher in the superior (22%) than in the inferior (8%) PV. Dissociated PVP in one part of the vein while conduction is present in another part is unusual (Figure 5). Dissociated repetitive discharges were observed in 5 patients. In patients with frequent ectopics, sequential radiofrequency applications produce a progressive decrease of repetitive and isolated ectopics sometimes after a transient exacerbation of arrhythmia. Persistent ectopics are often due to a residual PV fascicle requiring careful mapping of the venous perimeter searching for a continuum of atrial–PVP (gap-like) electrogram.49 A local radiofrequency application results in abrupt disappearance of local and distal PVP. When the PV is
disconnected, persistent ectopics may sometimes be due to discharges from the atrial edge of the same ostium (proximal to the ablation lesion) or foci from other PV or atrial tissue. Ablation during AF: When several cardioversions have been performed to interrupt AF but with prompt recurrence, ostial ablation can be performed during AF while still monitoring the distal PVP (Figure 7). In this situation, ostial PVP are difficult to differentiate from left atrial potentials so that ablation is performed anatomically around the PV perimeter.48 After return in sinus rhythm (spontaneous or after infusion of antiarrhythmic drugs: amiodarone and/or flecainide), additional ablation is performed targeting the remaining PVP if necessary.
EFFICACY Long-term elimination of AF paroxysms is strongly associated with disappearance of the distal PVP whereas persistence (immediately after ablation) or recovery of the PVP is associated with a high risk of arrhythmia recurrence. Total PV disconnection is corroborated by the inability to capture the left atrium by pacing from the PV. However, a limited PV fascicle may not be captured by venous pacing, making circumferential PV mapping a more reliable technique (Figure 5). In patients with recurrent AF, repeat mapping shows that recurrent ectopy may originate from: (1) within a previously targeted PV, related to persistent or recovered PV potentials—a remaining PV fascicle small enough to be ablated by a single radiofreA SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART
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FIGURE 6. Progressive ablation of left superior pulmonary vein (LSPV) posterior wall. A multielectrode circular catheter placed 1 cm inside LSPV exhibits sharp and delayed (terminal) potentials in bipoles 1–7 during pacing from the left atrial appendage. It indicates the presence of pulmonary vein muscle in the posterior wall of the vein. Proximal radiofrequency ablation at the level of the vein ostium delays these potentials (middle panel) before finally eliminating them (extreme right).
quency application can be sufficient to produce AF; (2) a nontargeted PV; (3) combination of the above; (4) the PV ostium instead of inside the vein; and (5) non-PV sites. This explains the frequent need for multiple ablation sessions but is nevertheless encouraging because it indicates a significant margin for improvement with better ablation techniques applied at the index procedure. Different ablation catheters are being developed to cauterize a wider substrate with each application. It includes supple electrodes conforming to part of the venous perimeter (selected by prior mapping) or devices expanded into the vein orifices to “anatomically” perform circumferential lesions. Complete elimination of AF without drug is observed in 70% of our patients, allowing interruption of anticoagulant treatment. However, these patients may have residual P on T ectopics, which—in contrast to before ablation—are isolated and unable to discharge in trains so as to initiate AF. The success rate decreases with the number of arrhythmogenic PV—from 93% in patients with a single arrhythmogenic PV, to 73 and 55% when ⱖ2 PV are involved— because of difficulties in consistently eliminating the PVP. A 16K THE AMERICAN JOURNAL OF CARDIOLOGY姞
single PV is significantly associated with younger age, fewer AF and smaller atrial dimensions whereas multiple arrhythmogenic PV are associated with older patients having a longer history of AF, more frequent episodes, and larger atrial dimensions. Most of the “unsuccessfully treated” patients are significantly improved. Chen et al42 reported an 86% success rate in 79 patients who had short episodes of AF (daily duration 28 ⫾ 30 min). Multiple PV was found in only 44% and their procedural endpoint was acute ectopy suppression without relying on PVP mapping.45
SAFETY: RISK OF PV STENOSIS PV stenosis, defined as a diameter reduction ⱖ50%, was observed in 9 patients (2% of PV ablated) the mean gradient was 4 ⫾ 2 mm Hg and no patient had pulmonary hypertension. Only 2 patients had symptoms: 1 because of PV thrombosis, and the other because 2 PV were stenosed requiring balloon angioplasty for relieving symptoms. Importantly, PV stenosis occurred acutely (immediately at the end of ablation) and few changes were observed later. The left inferior PV, a distal ablation site (close to PV branch-
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FIGURE 7. (Top) A slow regular dissociated local potential is recorded from the left superior pulmonary vein (LSPV) during atrial fibrillation (AF). This vein was ablated during AF. (Bottom) After ablation in both the RSPV and LSPV, a potential is dissociated from sinus rhythm. dist ⴝ distal.
ing) and the use of radiofrequency power reaching 45–50 watts were factors predictive of stenosis.48 –50 Without limitation of radiofrequency power, some authors reported up to 42% of distal PV stenosis as indicated by a significant PV flow acceleration; quadruple stenoses requiring angioplasty were also observed.42,50 In our experience, with a present limitation of radiofrequency power ⬍30 watts (10 –20 watts often sufficient in the inferior veins), a single PV stenosis occurs at the ostia although a longer-term follow-up is probably necessary. This limited power was associated with low “achieved” temperature in the PV (average: 42°C), owing to the local high cooling blood flow similar to the functioning of the irrigated tip catheter, and considerably decreased the incidence of extracardiac damage (coughing due to bronchial irritation or vagal excitation). Other potential risks of left atrial ablation procedures are less specific, including hemopericardium (1%), thromboembolic events (1%), or catheterization side effects.
ABLATION OF PV IN CHRONIC AF Although the role of foci is probably less in chronic AF compared with the substrate, 2 studies reported the mode of reinitiation of chronic AF after cardioversion and the efficacy of ablating these foci of reinitiation.
Lau et al44 performed mapping of AF reinitiation in 32 patients with chronic AF (mean 13 months) and identified a PV focus in 4 patients. A 2-center study included 15 patients, 7 with structural heart disease, persistent for 5 ⫾ 4 months.49 In all patients, cardioversion was followed by documentation of P on T atrial ectopy and/or early recurrence, which allowed mapping of the reinitiating trigger. A total of 32 arrhythmogenic PVs and 2 atrial foci (left septum and left appendage) were identified. No PV stenosis was noted either acutely or at repeated follow-up angiography. In total, 8 patients (55%) were in stable sinus rhythm without antiarrhythmic drugs with a follow-up of 11 ⫾ 8 months, and anticoagulants were interrupted in 7. The successful outcome was associated with PVP elimination. A larger group and longer follow-up is needed to further investigate the role of trigger ablation in curative therapy for chronic AF, but these results are supported by those of limited antiarrhythmic surgery around the PV by Sueda et al51 or Melo et al.52
INDICATIONS In view of the difficulties in producing effective lesions in multiple PV, ablation of arrhythmogenic PV is presently indicated in multidrug resistant, symptomA SYMPOSIUM: ELECTRICAL THERAPIES FOR THE HEART
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atic patients with paroxysmal AF. In such patients, the risks associated with persistent AF (notably 1–3% thromboembolic events per year with increased mortality) and the risks of antiarrhythmic and anticoagulant drugs appear to outweigh those of the ablation procedure, and it is our opinion that this curative approach is clearly superior to atrioventricular junction ablation. A history of thromboembolic phenomena or tachycardia-mediated heart failure, as evidence of AF morbidity, further supports the indication for the procedure. It is anticipated that continued technologic developments will optimize and facilitate these techniques. Ultimately it may become a widespread procedure, provided that further studies demonstrate a favorable risk/benefit ratio, notably, maintained improvement of symptoms, better survival, and decreased risk of thromboembolic events compared with alternative treatments. Acknowledgment: The authors wish to express their appreciation for the secretarial assistance of Joe¨lle Bassibey.
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