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(Circulation. 1997;95:572-576.)
© 1997 American Heart Association, Inc.

Articles

A Focal Source of Atrial Fibrillation Treated by Discrete Radiofrequency Ablation

Pierre Jais, MD; Michel Haissaguerre, MD; Dipen C. Shah, MD; Salah Chouairi, MD; Laurent Gencel, MD; Meleze Hocini, MD; Jacques Clementy, MD

the Hopital Cardiologique du Haut-Leveque, Bordeaux-Pessac, France.

Correspondence to Dr Pierre Jais, Hopital Cardiologique du Haut-Leveque, Ave de Magellan, 33604 Bordeaux-Pessac, France.

	Abstract

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Background Atrial fibrillation is usually thought to be due to multiple circulating reentrant wavelets. From previous studies, a focal mechanism is considered to be very unlikely. In this report, focal atrial fibrillation is defined on an ECG pattern of atrial fibrillation and later demonstrated to be due to a focal source.

Methods and Results Nine patients (five men and four women; age, 38±7 years) with paroxysmal focal atrial fibrillation are reported here. All were free of structural heart disease and had frequent episodes of atrial fibrillation despite the use of a mean of 4±2 antiarrhythmic drugs. Atrial fibrillation was associated with runs of irregular atrial tachycardia or monomorphic extrasystoles. The electrophysiological study demonstrated that all the atrial arrhythmias were due to the same focus firing irregularly and exhibiting a consistent and centrifugal pattern of activation. Three foci were found to be located in the right atrium, two near the sinus node and one in the ostium of the coronary sinus. Six others were located in the left atrium at the ostium of the right pulmonary veins (n=5) and at the ostium of the left superior pulmonary vein (n=1). All atrial arrhythmias were successfully treated by use of a mean of 4±4 radiofrequency pulses.

Conclusions In some patients, the surface ECG pattern of atrial fibrillation is due to a focal rapidly firing source of activity that can be eliminated by discrete radiofrequency energy applications.

Key Words: fibrillation • catheter ablation • tachycardia • arrhythmia

	Introduction

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Atrial fibrillation is the most common supraventricular arrhythmia. Its diagnosis is based on a surface ECG showing the absence of P waves and a chaotic and irregular baseline. Typically, AF is believed to result from the simultaneous existence of multiple migratory reentrant wave fronts of activation in both atria.^{1 2 3} This is the rationale for curative therapy by surgical atriotomies^{4 5 6} or catheter-mediated ablation lines.^{7 8 9 10} A focal mechanism is considered to be very unlikely on the basis of experimental studies^{3 11} and surgical human mapping data.^{12 13} However, we report here nine patients with paroxysmal AF produced by a focal source from among a cohort referred for resistant paroxysmal AF. In the present report, focal AF is defined on the basis of an ECG pattern of AF demonstrated to be due to a focal source firing very rapidly. We use the term "focus" to indicate a localized source of activation without specific knowledge of the underlying mechanism.

	Methods

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Study Population
The study population included nine patients with symptomatic drug refractory AF (Table 1), four women and five men (age, 38±7 years). One of these patients has been described earlier.¹⁴ The analysis of available 12-lead ECGs showed in all patients tracings typical of sustained AF in five but only in runs in four patients. All patients had also extrasystoles or irregular atrial tachycardia with discrete monomorphic P waves. This phenomenon occurred often in patients taking antiarrhythmic drugs but also occurred spontaneously.

View this table: [in this window] [in a new window]   Table 1. Clinical Characteristics of Patients

Electrophysiological Study
Antiarrhythmic drugs except for amiodarone were discontinued for at least five half-lives. One quadripolar diagnostic catheter (Bard) was positioned in the right lateral atrium for incremental or programmed atrial stimulation. Conventional ablation catheters (Cordis-Webster) or, in some cases, woven Dacron multielectrode catheters (Bard Electrophysiology) were used to map the earliest activation time. If the ectopic P wave appeared negative or isoelectric in lead 1, earliest activity was recorded in the distal coronary sinus during tachycardia, or no favorable site for ablation was encountered in the RA, mapping of the LA was performed by the retrograde aortic approach, a permeable foramen ovale, or transeptal puncture. Bipolar electrograms were recorded, along with unfiltered unipolar electrograms, at a filter setting of 30 to 500 Hz at a gain of 5 to 10 cm/mV. Stimuli were twice the diastolic threshold and 2 ms long. If the arrhythmia did not spontaneously manifest during electrophysiological study or was not sustained enough, pacing (incremental, programmed, or burst), isoproterenol infusion, or both were used. A focal source of activation was confirmed by a consistent and centrifugal pattern of activation during atrial arrhythmias and by their elimination with a localized application of RF energy (Fig 1). Centrifugal activation was demonstrated by multielectrode mapping in some patients (Fig 1) and by sequential mapping (with respect to a reference ECG) in the remaining patients.

View larger version (40K): [in this window] [in a new window]   Figure 1. Top left, Centrifugal activation mapped with a multielectrode catheter in the LA during an irregular atrial tachycardia. Note the divergent activation front moving away from bipole 5-6 (arrows) and the striking changes in cycle length (300 to 180 ms) with a maintained activation pattern. Top right, LA endocardial activation in patient 4 during a significantly faster atrial tachycardia (demonstrated by endocardial mapping but not shown here). Note the short cycle length of 150 ms and the concomitant and resultant surface ECG features of AF. Bottom, During the same continuing arrhythmia in patient 4, discrete RF applications at the ostium of the right superior pulmonary vein restored sinus rhythm promptly. Paper speed was 100 mm/s; surface ECG leads were I, II, III, AVR, AVL, and AVF.

Ablation Procedure
The ablation site was chosen on the basis of the earliest bipolar activity relative to a stable atrial electrogram reference during AF. If the rate was slow enough to allow P-wave identification on the surface ECG, the earliest bipolar activity relative to the P-wave onset associated with a sharp negative unipolar deflection was targeted. RF energy was applied with a HAT 200 (Osypka Gmbh), Medtronic (Atakr), or Stockert (Cordis) generator delivering a 500- to 550-kHz sine wave output between the distal electrode of the ablation catheter and the 110-cm² cutaneous patch electrode placed over the left scapula. A temperature setting of 60°C to 70°C was used. RF energy was delivered for 60 to 90 seconds at each apparently successful ablation site or otherwise for 20 seconds. Procedural success was defined as the definitive interruption of the tachycardia after RF delivery and the inability to reinduce it with pacing and/or isoproterenol infusion (if inducible at baseline).

Postablation Management
After the ablation procedure, subcutaneous low-molecular-weight heparinate was administered in a dose of 2500 U once a day. A clinically successful outcome was demonstrated by Holter recording and telemetry during the 5 days after the procedure. Late follow-up consisted of visits to the hospital of the referring physician and 24-hour Holter recording.

	Results

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Mapping during different types of atrial arrhythmias showed that they were due to the same focus firing irregularly with striking and abrupt changes in atrial cycle length. Eight patients also had isolated extrasystoles that exhibited the same activation pattern as the tachycardias. Long cycle lengths were responsible for the organized monomorphic tachycardia, whereas the shortest cycle lengths between 160 and 130 ms resulted in an ECG pattern of AF. In most patients, the atrial activity during AF was organized (suggesting type I AF),¹² but in some instances, paroxysms of typical AF (with chaotic and changing endocardial activation) were noted to be triggered by such bursts of irregular atrial tachycardia. In one patient (patient 2), a localized area around the coronary sinus exhibited disorganized activity (type III),¹² whereas the remaining of the RA was consistently activated from the focus. Mapping was performed during AF in two patients, during irregular atrial tachycardia in five patients, and during runs of extrasystoles in two patients. In the patients mapped during recurrent extrasystoles, both isoproterenol infusion and pacing maneuvers were unable to induce more sustained tachycardias. The mapping was then performed on extrasystoles exhibiting the same morphology of P waves and activation patterns as during atrial tachycardia.

Three foci were found to be located in the RA: two near the sinus node and one in the ostium of the coronary sinus. Six others were found in the LA: one at the junction between the right superior and inferior pulmonary veins and four at the ostium of the right superior pulmonary veins. The last one was successfully ablated at the ostium of the left superior pulmonary vein. A specific phenomenon was observed during mapping of right pulmonary vein ostial foci. During organized tachycardia, the P wave was positive in lead 1-2-3, which led us to begin the mapping in the RA, followed by LA mapping because of unsuccessful attempts (n=2) or lack of good criteria for ablation (n=3). In all five patients, we found that the atrial electrogram in the region in which the posterior RA is adjacent to the right pulmonary veins region in the LA was made up of two components: one resulting from RA activity and the other from LA activity. The sharper and higher potential represented the local activity, whereas the slower and smaller potential reflected far-field activity of the other atrium (Fig 2). In sinus rhythm in the LA, there was an initial low component and a second sharp component, whereas in tachycardia originating from the LA, the sequence was reversed, with the sharpest potential becoming the first one and preceding the onset of the ectopic P wave by up to 80 ms. During mapping of such a tachycardia in the posterior RA, an initial slow component was noted at this location that falsely suggested a favorable site of ablation (Fig 2). The ablation was successful only in the LA.

View larger version (53K): [in this window] [in a new window]   Figure 2. Data on patient 5. A, B, and C, Different atrial arrhythmias observed in the same patient: three monomorphic extrasystoles with short and very long (third star) coupling intervals (A), a monomorphic and a very irregular atrial tachycardia with well discernible P waves of similar morphology (B), and the same monomorphic and irregular atrial tachycardia shown in the beginning of this tracing (C). At the end of the recording, the intrinsic rate of the focus is high enough to give an ECG pattern of a coarse AF. Mapping of the RA was performed first, and earliest bipolar activity was recorded in the posterior high RA by use of a multielectrode catheter positioned vertically along the border of the right side of the heart as shown in the radiograph (D). After six unsuccessful RF attempts in this area, LA mapping was performed. Earlier bipolar activity was found just behind the previous RA region, in the right superior pulmonary vein area. This is the position of the quadripolar ablation catheter shown in D, placed just inside the right superior pulmonary vein via the retrograde aortic approach. E, Analysis of RA and LA activity. The timing of the earliest (arrows) component of each electrogram is the same, but the RA activity is slow and small in amplitude (far-field activity), whereas the LA activity is sharp and of higher amplitude, representing local activity. The first RF pulse delivered at this site successfully ablated all the atrial arrhythmias for this patient. Abbreviations as in Fig 1. SIT Dst indicates distal bipole of the ablation catheter; UNI Dst, unfiltered unipolar electrogram from the tip of the ablation catheter; OD Prx B7-B8 and OD B5-B6, two adjacent bipoles from the multielectrode catheter in the RA.

All patients were treated with a mean of 4±4 RF pulses. One patient had a clinically documented recurrence 7 days after an initially successful procedure. She underwent a definitively successful second ablation procedure 10 days after the first attempt. During a mean follow-up of 10±10 months, neither atrial tachycardia nor AF recurred (Table 2).

View this table: [in this window] [in a new window]   Table 2. Data Related to Ablation

	Discussion

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This study demonstrates that in some patients the surface ECG pattern of AF is due to a focal rapidly firing source of activity that can be eliminated by discrete RF energy applications. These patients have a distinctive clinical profile and ECG characteristics that are suggestive of the diagnosis.

In the early experimental studies, AF was produced by either rapid atrial pacing and vagal stimulation^{10 11} or local application of aconitine.¹⁵ Both models resulted in a similar pattern of AF. However, aconitine-induced AF was initiated and perpetuated from the same focus, whereas cholinergic AF was perpetuated as long as vagal stimulation was maintained but remained independent of the event that started it. Recent studies have developed the concept that AF is due to multiple simultaneous reentrant wavelets^{11 12 13} without identifying possible spontaneous triggers. In a few reports, some focal sources of activation have been identified¹² but have been attributed to epicardial breakthrough but only as solitary events. Repetitive focal responses have never been observed in humans. In the present study, a subset of the patients referred to us for paroxysmal AF have provided data consistent with a focal source of activation, in contrast to the currently accepted concept of the basis of clinical AF. The term "AF" as used here refers to a medical definition based on a surface ECG rather than on chaotic intracardiac atrial activity. These patients showed organized endocardial atrial activity despite short cycle lengths (up to 130 ms) in contrast to activation patterns recorded during typical paroxysmal AF.¹⁶ Thus, the surface ECG pattern of AF was attributed to a rapid and irregular focal atrial tachycardia on the basis of the following data. First, AF and atrial tachycardia were clinically observed before ablation with a similar clinical presentation, usually runs of atrial activity interrupted by a few sinus beats several times a day.¹⁴ Second, endocardial mapping during AF showed an organized though rapid atrial rhythm with a centrifugal and consistent pattern of activation, similar to data obtained during atrial tachycardia. The difference between both forms of the same basic arrhythmia was dependent on the intrinsic rate of the focus. Third, ablation of the focus eliminated the atrial arrhythmias, and no AF was inducible after ablation despite rapid atrial stimulation in seven of the nine patients. The mechanism underlying the focal arrhythmia could not be specified. However, both the abrupt and frequent changes in atrial activity and the noninducibility of arrhythmia plead against reentrant circuits and favor abnormal automaticity or triggered activity.

Such a focal AF has not been identified by previous studies. There may be multiple reasons for this. Previous mapping studies have usually been epicardial and limited to the anterolateral free wall of the RA and LA, whereas most of the foci reported in the present study are located near the ostia of great vessels. The time windows used for mapping also were probably too short to record a very intermittent phenomenon. Finally, animal models of AF may not be relevant to human pathology.

Conclusions
For catheter ablation, it is important to designate focal-source AF because limited RF applications will be able to cure these patients. In our experience, the most relevant clinical information leading to suspicion of focal-source AF is the association with episodes of monomorphic irregular atrial tachycardia or extrasystoles, particularly in young patients without structural heart disease. This observation must lead to an early electrophysiological study at the time of spontaneous episodes of tachycardia, thereby allowing mapping and successful ablation of the focus.

	Selected Abbreviations and Acronyms

 

AF = atrial fibrillation LA = left atrium/left atrial RA = right atrium/right atrial RF = radiofrequency

Received August 12, 1996; revision received October 23, 1996; accepted October 24, 1996.

	References

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