Europace

Europace 2004 6(6):590-601; doi:10.1016/j.eupc.2004.08.005
© 2004 by European Society of Cardiology

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (22) Request Permissions Disclaimer Google Scholar Articles by Pachon M, J. C. Articles by Jatene, A. D. Search for Related Content PubMed PubMed Citation Articles by Pachon M, J. C. Articles by Jatene, A. D. Social Bookmarking          What's this?

A new treatment for atrial fibrillation based on spectral analysis to guide the catheter RF-ablation

Jose C. Pachon M^*, Enrique I. Pachon M, Juan C. Pachon M, Tasso J. Lobo, Maria Z. Pachon, Remy N. A. Vargas, Denilda Q. V. Pachon, Francisco J. Lopez M and Adib D. Jatene

Dante Pazzanese Cardiology Institute and Sao Paulo Heart Hospital, Pacemaker and Arrhythmias Acoce, 515/31, Indianopolis, 04075023 Sao Paulo, SP, Brazil

Manuscript submitted 7 August 2004. Accepted after revision 12 August 2004.

^*Corresponding author. Tel./fax: +55 11 50514646. E-mail address: jcpachon{at}hotmail.com (J.C. Pachon M).

	Abstract

Top Abstract Introduction Background Objectives Method Results Discussion and comments Conclusions References

 
BACKGROUND: By studying the spectrum of atrial potentials by fast Fourier transform (FFT) we have found two types of atrial muscle: the compact (CM) and the fibrillar (FM) myocardium. The former presents normal in-phase conduction inferring a great number of cellular connections, long-lasting refractoriness and leftward FFT-shift. The latter shows anisotropic out-of-phase conduction, fewer cellular connections, short refractoriness and a segmented right-FFT-shift. The compact is the normal predominant muscle and the fibrillar is different and may be neural input, vein insertion, interatrial (1A) septum, left atrial (LA) roof, etc. or pathological tissue, being so by loss of cellular connections this is a possible mechanism for conversion of compact into fibrillar-like myocardium. During atrial fibrillation (AF), clusters of FM (AF nests) present higher frequencies than any surrounding tissue.

PURPOSE: The purpose was to describe a new method for paroxysmal AF RF-ablation targeting AF nests.

METHOD: Forty patients, six control and 34 having idiopathic drug-refractory paroxysmal or persistent AF were studied and treated. Two catheters were placed in the LA by transseptal approach. RF (30–40 J/60–70 °C) was applied to all sites outside the pulmonary veins (PV) presenting right-FFT-shift (AF nests).

RESULTS: Numerous AF nests were found in 34/34 AF patients and only in 1/6 controls (only in this case it was possible to induce AF despite an absence of AF history). The main FM sites were: LA roof, LA septum, close to the insertion of the superior PV, near the insertion of the inferior PV, LA posterior wall, RA near the superior vena cava insertion, RA lateral and anterior wall and the right IA septum. Ablation of all AF nests near PV insertions resulted in 35 PV isolations. After 9.9 ± 5 months only two AF patients presented relapse of a different AF form (coarse AF) which was very well controlled with medication previously ineffective. The AF was more frequent as the ratio FM/CM increased.

CONCLUSIONS: The RF-ablation of AF nests decreasing the fibrillar/compact myocardium ratio eliminated 94% of the paroxysmal AF in patients in the FU of 9.9 ± 5 months. The AF nests may be easily identified by spectral analysis and seem to be the real AF substrate. Paroxysmal AF may be cured or controlled by applying RF in several places outside the PV and, thereby, avoiding PV stenosis.

Key Words: fibrillation, atrium, veins, catheter ablation, electrophysiology, spectral mapping

	Introduction

Top Abstract Introduction Background Objectives Method Results Discussion and comments Conclusions References

 
In about 90% of people the atrial myocardium may be found in the pulmonary vein both with circular and longitudinal bundles. The landmark work of Haïssaguerre et al. established that these muscular fascicles cause atrial premature beats, very fast atrial tachycardias and finally atrial fibrillation [1] (AF). This very important discovery prompted the emergence of several techniques that comprise modern AF catheter ablation therapy ^[2–^7] based on focal, segmental ablation or encircling pulmonary vein isolation ^[8–^13].

Despite these very well accepted techniques some questions remain to be answered:

1. Pulmonary vein ectopic beats or tachycardias, together with atrial anatomical barriers may explain the atrial tachycardias but they are insufficient to explain the maintenance of AF in most of cases;
   
2. Regardless of its being rare, AF has been observed without pulmonary vein participation;
   
3. It is definitely accepted that pulmonary vein premature beats are the most frequent AF triggers [1,14–18]. However, the substrate is poorly understood. Why do pulmonary vein ectopic premature beats cause AF in some patients while in others they may persist throughout life without causing any additional arrhythmia? Why may young people without any apparent cardiopathy have lone AF? How can many severely diseased atria survive without AF?
   

These questions suggest the presence of a consistent AF substrate apart from pulmonary vein triggers, which is common to both sick and apparently normal hearts.

	Background

Top Abstract Introduction Background Objectives Method Results Discussion and comments Conclusions References

 
Fourier transform
Joseph Fourier (1768–1830) was a French mathematician who discovered that practically any wave could be represented as a sum of sinus waves (frequency spectrum). In general, in electrophysiology the waves are displayed on a time basis (time domain). The Fourier transform is a mathematical tool that allows the visualization of the frequency spectrum (the frequencies of sinus waveforms whose sum makes the original wave) of any wave (frequency domain). Nowadays, there is a simplified method to carry out Fourier transforms called "Fast Fourier Transform" or FFT. Therefore, it can be said that while the EKG enables us "to see", the FFT enables us "to hear" the P–QRS complexes. By applying the FFT to the endocardial signals we can study frequencies of up to 500 Hz depending on the filters applied during the recordings. As a rule, in the myocardium, the more organized the conduction, the narrower the frequency spectrum of the signal, Fig. 1 (2A).

View larger version (19K): [in this window] [in a new window]   Figure 1 Comparison of the spectral analysis of the left atrium endocardial potentials (1A and 1B) showing in A the "compact" and in B the "fibrillar" myocardium (posterior wall and left atrial roof, respectively). It can be observed that the "compact" presents one fundamental frequency (2A) and higher power than the "fibrillar", which presents at least three prominent frequencies (one fundamental and two important harmonics, 2B). Although in the time domain (1A and 1B) the endocardial potentials are similar there is significant difference in the FFT-spectral analysis (frequency domain, 2A and 2B).

 
Seeking the AF substrate
Aiming at studying the atrial myocardial electrical features, we have used spectral analysis through the fast Fourier transforms (FFT), thus going beyond the time domain to the frequency domain of the atrial potentials. For this purpose, we have developed a software programme that works with a 32 channel-polygraph, permitting us to obtain the FFT of the endocardial signals. By using this tool, we have found two types of atrial myocardium: the first that we have called "compact", works like one isolated cell—the classical myocardial behaviour. It presents homogeneous, fast conduction with all cells working in-phase and normal refractory periods. The FFT of these tissue potentials presents a well-defined shape with one high power fundamental frequency and fast uniformly decreasing harmonics. In Fig. 1 (2A) it may be observed that most frequencies are distributed to the left. On the other hand, the second type of myocardium that we have called "fibrillar" is similar to a group of nerve cells. It is characterized by relatively independent fascicles with heterogeneous and out-of-phase conduction. It has a short refractory period allowing faster activation rate than the surrounding myocardium. The FFT of these tissue potentials shows low power fragmented and heterogeneous profile suggesting that it represents a bundle of distinct cells. Besides its fundamental frequency, it has a greater number of irregular harmonics of high amplitude and wide distribution. The relatively high amplitude of these signals with high frequency causes a "right-shifting" of the FFT, Fig. 1 (2B). Fortunately, the "fibrillar" myocardium is clustered in small areas that we have named "AF nests".

	Objectives

Top Abstract Introduction Background Objectives Method Results Discussion and comments Conclusions References

 
These observations made us hypothesize that the "fibrillar myocardium" niches—the "AF nests"—could be the real AF substrate depicting a new approach to cure the arrhythmia apart from targeting the triggers. Therefore, the goal of this study was to describe a new technique for AF catheter RF-ablation based on the elimination of "AF nests".

	Method

Top Abstract Introduction Background Objectives Method Results Discussion and comments Conclusions References

 
Patient characteristics
Forty patients were studied. They were 34 highly symptomatic patients with long duration drug-refractory AF, paroxysmal [19] in 20 (59%) and persistent [19] in 14 (41%) with very frequent episodes (from two episodes a month to incessant), mean age of 53.9 ± 12 years (ranging from 22 to 70), 8 (24%) females and 26 (74%) males, and six controls (34.5 ± 6 years) who had no AF history but underwent general left atrial electrophysiological assessment. There was no significant heart disease in any patient: mean ejection fraction = 0.63 ± 8 and mean left atrium size = 41.1 ± 7 mm. Mitral regurgitation was mild in 16 (47%) and moderate in 5 (14.7%) patients. Twelve cases (35.3%) had a history of mild to moderate arterial hypertension. There was no significant coronary disease or dilated cardiomyopathy. All patients were taking high doses of amiodarone (21), sotalol (19), other beta blockers (10), propafenone (12), quinidine (7), disopyramide (8) either alone or in combination (two or three drugs). Seventeen patients were under regular warfarin use keeping the mean prothrombin time at 2.1 ± 0.3 INR. Twelve patients were taking 100 mg of aspirin a day. None of these cases had had a history of a thromboembolic episode. Eight patients had diabetes mellitus controlled by oral anti-diabetic drugs.

Electrophysiological and ablation procedures
Before the procedure, all AF patients were studied by magnetic resonance in order to evaluate pulmonary vein anatomy. All cases presenting risk factors like hypertension, diabetes or mild atrial dilatation were treated with warfarin for 1 month replaced by subcutaneous low molecular weight heparin two days before the ablation. All patients provided written informed consent. The procedure was performed under general anaesthesia.

The heart rate, oximetry, blood pressure, plethysmography, peripheral perfusion, capnography and respiratory gases were monitored. Brain functions were monitored by direct measurement of the awareness level keeping the Bi-spectral index between 40 and 50 (BIS Aspect A-1000), and through cerebral oximetry measured by frontal infra-red spectroscopy (NIRS-Cerebral Oximeter Somanetics-INVOS) targeting the sRO₂ 75% from the pre-induction levels. A complete trans-oesophageal echocardiogram was performed seeking thrombus or "spontaneous contrast" before the transseptal and electrophysiological catheterization. In eight cases (21%) that were in AF at the time, a transthoracic cardioversion (biphasic 30–100 J) was performed, restoring sinus rhythm. Four electrophysiological catheters were placed (coronary sinus, His bundle, right atrium and right ventricle) through subclavian and femoral venous punctures, to permit a conventional electrophysiological study. Finally, one spiral lead St. Jude Supreme (14 cases) and one EPT Blazer 7F (EP Technologies, Inc.) (34 cases) were placed in the left atrium, through a patent oval foramen in two patients and through transseptal puncture in 32 patients, by using two introducers DAIG SL-1 and SL-2 8F. Systemic anticoagulation was achieved with intravenous 5–10,000 IU heparin and with additional 1000 IU according to the coagulation activated time. The electrophysiological mapping was accomplished with a 32 channel-polygraph TEB-32 with special software for spectral analysis (Pachón-TEB2002) and the graphical software ScopeDSP Iowegian-USA 3.6a and SigView-1.9.

The study began at the endocardial surface of the left atrium near the left pulmonary vein insertions, with the ablation of all the potentials that presented right-Fourier-shift (AF nests) during sinus rhythm and during pacing of the distal coronary sinus. The same procedure was repeated for the left atrial roof, for the left atrial wall near the right pulmonary vein insertions, for the left atrial posterior wall and, finally, for the left surface of the interatrial septum. A similar procedure was repeated for the right atrium eliminating all AF nests, taking special care to avoid lesions in the sinus and AV nodes. Ablations were performed with the Thermo-Controlled Biotronik MDS ablator with 30–40 J for 15–20 s, at 60 or 70 °C. In each AF nest, RF was applied only in order to shift the FFT toward the left by eliminating the harmonics, Fig. 6. The spiral catheter was used only for checking the frequently occurring pulmonary vein isolation during the ablation of the AF nests. Electrical venous isolation was not intended. The procedure was suspended as soon as no more AF nests could be found. Oral anticoagulation was maintained for 3 months.

Statistical analysis
Continuous variables were expressed as mean ± one SD and were compared by Student's t test. A P 0.05 indicated statistical significance.

	Results

Top Abstract Introduction Background Objectives Method Results Discussion and comments Conclusions References

 
Spectral analysis of the compact and fibrillar myocardium
The compact myocardium presented a homogeneous spectrum with a fundamental frequency ranging between 50 and 75 Hz (mean 59.6 ± 11.4 Hz), Fig. 1 (2A). Most AF nests (fibrillar myocardium) presented a fractionated spectrum with 3–6 significant components (mean 3.6 ± 0.8), Fig. 1 (2B). The fundamental frequency ranged from 15 to 87 Hz (mean of 34.8 ± 18.1 Hz) with the first most significant harmonic between 38 and 137 Hz (mean of 81.1 ± 27.3 Hz). The remaining harmonics presented mean frequencies of 174.2 and 252.8 Hz, respectively. After ablation, the fibrillar myocardium showed remarkable reduction of the harmonics but only moderate reduction in the amplitude of the fundamental frequency, resulting in a left frequency shift, with the final spectral curve being similar to that of compact myocardium, Fig. 6.

AF nests
In the control group no typical AF nests were found except in one patient. AF induction was possible only in this case despite having no history of spontaneous AF. In the PAF group AF nests were very frequent in all cases. They were treated by a mean of 40.9 ± 11.8 (range 18–61) ablations. AF nests were 9.7 times more frequent in the left than in the right atrium. They were located mainly in the following places:

1. Left atrial endocardium:
   
   1. Near the left superior pulmonary vein insertion in 31 (91.1%) and near the inferior in 23 (67.6%) patients;
      
   2. Near the right superior pulmonary vein in 30 (88.2%) and near the inferior in 18 (52.9%) patients;
      
   3. Left atrial roof in all patients (100%);
      
   4. Left surface of the interatrial septum in 31 (91.1%) patients;
      
   5. Left atrial posterior wall in 20 (58.8%) patients;
      
   
   
2. Right atrial endocardium:
   
   1. Right surface of the interatrial septum in 15 (44.1%) patients;
      
   2. Right lateral wall and crista terminalis in 16 (47%) patients;
      
   3. Right atrial wall near the insertion of the vena cavae (except the sinus node area) in 21 (61.7%) patients.
      
   
   

Non-intentional electrical isolation of 35 pulmonary veins, six superior and three inferior vena cava was observed during the ablation of AF nests near the venous insertion.

At ablation, two atypical left atrial flutters were observed, one case was abolished by RF application and the other reverted by cardioversion. Another three cases of atypical flutter were observed on the first and second post-ablation days and were treated with intravenous amiodarone (2) and external cardioversion. Finally, a different kind of AF was also observed in six cases in the first week of post-ablation, which was coarse with larger "f" waves and at a lower rate than the AF before ablation. They were treated with low doses of amiodarone for one to three days. All these arrhythmias were not observed after the healing phase.

The mean follow-up was 9.9 ± 5 months. After the healing phase, 32 paroxysmal or persistent AF patients are in sinus rhythm with no episode of AF (94.1%). Only two patients presented AF relapse (5.9%) responsive to previously ineffective medication. Holter monitoring was performed in 28 patients. The most significant finding was the presence of frequent atrial premature beats in six patients and rare atrial premature beats in 26 patients. Furthermore, very short episodes of non-sustained atrial tachycardia were observed in five cases. Despite the very low significance of the arrhythmias, 14 (41.1%) patients are taking low doses of previously ineffective antiarrhythmic drugs (amiodarone 100 mg/day [12], sotalol 40–80 mg/day [7]) for palpitations and/or blood pressure control. Two pericardial effusions occurred in cases with difficult transseptal punctures due to anatomical variation, one resolved and the other required pericardial drainage. No other complications were observed. The mean fluoroscopy time, including the transseptal puncture, was 44.1 ± 11.2 min.

	Discussion and comments

Top Abstract Introduction Background Objectives Method Results Discussion and comments Conclusions References

 
In this study, using spectral analysis through the fast Fourier transform (FFT), it was possible to identify clearly two kinds of atrial myocardium with very important electrophysiological differences, which we have called compact and fibrillar, Fig. 1. The former, normal and predominant, shows a homogeneous spectral shape around the fundamental frequency, Fig. 1 (2A). In contrast, the latter shows a lower amplitude, segmented and heterogeneous spectrum, Fig. 1 (2B). Since the harmonics are gathered in two to five groups of relatively high amplitude, the fibrillar myocardium is characterized by a right-shift of the spectrum. The FFT allows us to conclude that the fibrillar myocardium may be composed of several myocardium strands with few lateral connections, presenting dispersion of the conduction speed.

Thanks to the connexins, the compact myocardium—which is the predominant pattern—we infer to be composed of tightly connected cells, Table 1. This very well organized structure works as a single cell due to the intercalated discs. Its conduction is homogeneous with a predominant wave front, and in absence of barriers presents similar speed in any direction (isotropy), Fig. 2 (1A). As a rule, the resulting potential is fast, bi or triphasic, Fig. 2 (1B). The cells work in-phase, reacting in an organized sequence that results in a uniform spectral pattern, Fig. 2 (1C). The fibrillar myocardium is much less frequent and is located in some specific regions in the atrial wall (AF nests), Table 1. Apparently, it is more primitive, and seems to have transitional features between neural, vascular and atrial tissue. In contrast to the compact, it functions as a group of loosely connected cells. Probably, lateral connections are scarce favouring longitudinal conduction speed over transverse (anisotropy), and heterogeneous wave front conduction. High-speed filaments are adjacent to others of less speed, Fig. 2 (1B), resulting in out-of-phase conduction and a polyphasic potential, Fig. 2 (2B). The spectrum of this tissue is typically very fractioned, suggesting that it composed of relatively independent fascicles. We infer it has much less connexins than the compact tissue, Fig. 2 (2C). The electrophysiological features of this tissue permit the highest response rate of cardiac cells and probably being the substrate for AF maintenance.

View larger version (28K): [in this window] [in a new window]   Figure 2 Diagram of the activation wave in the "compact" (1) and "fibrillar" (2) myocardium. In the former, the activation moves forward in a homogeneous way, with all cells in-phase (1A). The endocardial potential usually shows bi or triphasic shape (1B, time domain). The study in the frequency domain (FFT) shows a homogeneous profile around one fundamental frequency (1C, frequency domain). Conversely, the "fibrillar" myocardium works similarly to many cell groups. The wave front is irregular because of out-of-phase activation between several strands of cells (2A). In the time domain, this generally results in a polyphasic wave (2B), and in the frequency domain it shows less amplitude and a heterogeneous profile with the fundamental frequency followed by a variable number of harmonics grouped in large segments.

 

View this table: [in this window] [in a new window]   Table 1 Comparison of the electrophysiological and spectral properties of the "compact" and "fibrillar" myocardium

 
Location of the compact and fibrillar myocardium
By means of spectral analysis, the narrow areas of fibrillar myocardium—AF nests—can easily be found. Although there was significant variation among patients, these places were usually found in the atrial wall near the pulmonary vein insertions, more often close to the superior veins or even frequently. Frequently it was inside them. A very interesting aspect was the large number of AF nests in the roof of the left atrium, Fig. 1 (1B) in all patients. Another place with great prevalence of AF nests was the interatrial septum, Fig. 3, associated with a dilatation in one patient and a small aneurysm in another. AF nests were found over the whole left surface of the interatrial septum, but were less frequent on the right. This finding raises the possibility that distension of the atrial myocardium converted the compact into fibrillar myocardium, perhaps by detaching inter-cellular connections. This phenomenon could explain one acquired origin of fibrillar myocardium, caused by the stretching and/or degeneration of compact tissue. Less frequent AF nests were found in the right atrium. The more commonly involved places were the junction of superior vena cava and right atrium, the right surface of the interatrial septum in the posterior area and near the fossa ovalis and the crista terminalis. An essential trait is that both the sinus and the AV node areas present frequency spectra very similar to the fibrillar myocardium (due to their nervous connections) demanding special attention to avoid damage.

View larger version (22K): [in this window] [in a new window]   Figure 3 Upper strip: left atrial potential recording (distal coronary sinus, LA-DCS). The second and third strips were obtained from the right atrium, RA (in the second strip the lead is positioned at one "AF nest" on the right side of the interatrial septum in the posterior region; in the third strip the lead is positioned on the RA free wall). The lower strip shows the standard V2 lead. AF was induced with atrial-programmed stimulation in the right atrium. In this case the highest activation rate is observed in the right atrial "AF nest". The very fast and successive activations pointed out by arrows are typical of tissues that present very short refractory periods, out-of-phase conduction, reflection and micro-reentry. Comparing the "fibrillar" myocardium (second strip, "AF nest") with the "compact" (third strip, normal RA free wall) the number of activations can be seen to be higher in the former.

 
AF substrate
Our main purpose was to find and abolish the AF substrate without creating lines of block. In this sense, the following observations suggest that fibrillar myocardium and AF nests are the real AF substrate:

In this series, the more frequent the AF episodes, the more numerous the AF nests, found in 34/34 AF patients (100%) and only in 1/6 of the control group (16.7%).

Nearly all PAF patients (94.1%) were cured or very well controlled with low antiarrhythmic drug doses after ablation of all AF nests that could be treated.

In two cases AF could only be induced in the right atrium, the left remaining in secondary tachycardia (limited by its refractory period) after the treatment of all the left atrial "AF nests".

It was also observed that during AF the AF nests presented activation rates higher than any surrounding atrial myocardium. In Fig. 3, it may be clearly observed that the AF nest presents the highest frequency and the most out-of-phase and disorganized activation. The shortest interval between the two consecutive near-fields shows that the refractory period of the AF nest is much shorter than that of the compact myocardium. These data match with the findings of Haïssaguerre et al. [20] who have demonstrated the very short refractory period of muscular pulmonary vein sleeves (less than 100 ms). Oral et al. have reported AF ablation during arrhythmia by seeking the fastest activation rate [21] in the pulmonary veins sleeves (probably fibrillar myocardium inside the veins). We have observed similar behaviour of the AF nests in the atrial wall. It is possible that very early premature beats originating in the pulmonary veins [1] or in the atrial wall enter the AF nests, are multiplied by reflection, micro-reentry or mainly by "electrical resonance" and serve to maintain AF by feedback among several of them. The elimination of AF nests or the isolation by creating lines of block [22–24,8] makes the maintenance of AF more difficult.

It has been shown that patients who have undergone pulmonary vein isolation present AF control in spite of atrio-pulmonary vein conduction recovering (in up to 70% of cases). In other cases there has been observed AF recurrence despite complete atrio-venous electrical block, suggesting that in some cases the AF treatment may not be totally dependent on complete pulmonary veins isolation.

In this series, many AF nests were observed near the pulmonary veins insertions. Conventional RF over these areas, aiming at encircling or segmental isolation of pulmonary veins [8], ablating great amount of compact and fibrillar myocardium, decreases the number of AF nests. In these cases AF control may have been obtained also by AF nest elimination. This effect may be more significant in cases undergoing multiple procedures.

In one patient AF was caused by numerous AF nests located in the interatrial septum, which had remarkable dilatation. The ablation of these points was enough to cure the arrhythmia.

In five control patients we did not find AF nests and could not manage to induce AF with atrial stimulation. However, in one control patient (a 22-year-old man) presenting AF nests, sustained AF was induced despite having no AF history.

Simplifying the identification of "AF nests"
Studying a large number of AF nests by using the Fourier transform we have developed a simplified spectral analysis by filtering the RF-catheter signal in three channels of the conventional polygraph—30–500 Hz in the first, 100–500 Hz in the second and 300–500 Hz in the third, Fig. 4. We have observed that AF nests tend to present relatively delayed high amplitude signals in the third channel with characteristic polyphasic high frequency potentials in the second and third channels. Typically, the third channel potential lasts more than 30 ms when measured from the beginning of the complex in the first channel, Fig. 4 (3B).

View larger version (23K): [in this window] [in a new window]   Figure 4 Atrial potentials recorded in the time domain (1, 2 and 3) and in the frequency domain (4) from the left atrium. A: "compact" myocardium in LA-interatrial septum; B: "fibrillar" myocardium from the LA roof. Spectral analysis shows very different profiles, with a homogenous "compact" spectrum (A4) versus a "right shifted" and coarsely segmented "fibrillar" spectrum (B4), despite the similar and polyphasic conventional filtered atrial potentials (A1 and B1). The great difference appears in high frequency channels 2 and 3, which shows high fractioned complexes in the "fibrillar" myocardium ("AF nest"), B2 and B3. Therefore, time domain with high frequency filters may be used to map the "fibrillar" myocardium that must be ablated.

 
"AF nest" ablation
The location and the treatment of AF nests were accomplished with the same catheter. The spiral catheter, placed in pulmonary veins, was used to demonstrate that the elimination of AF nests near the pulmonary veins resulted in the isolation of many veins, Fig. 5. This fact suggests that the natural muscular fibres dispersion in the atrium–vein transition probably favours the appearance of fibrillar myocardium.

View larger version (53K): [in this window] [in a new window]   Figure 5 On the left: recording of the electrical activity of an "AF nest" in the left interatrial septum, close to the LA roof, before (A) and after RF-ablation (B). The As and Bs are, respectively, the spectral analysis of the A and B potentials obtained by FFT. The five identified channels in the PV are connected from the five dipoles of a spiral lead, placed inside the initial portion of the same pulmonary vein. A vein potential of great amplitude is observed in 1–2, 3–4, and 5–6 (*) dipoles. After RF-ablation of the "AF nest" in the left atrial wall, outside the pulmonary vein, we can observe (on the right) the electrical "isolation" of the vein with disappearance of the vein potentials. The "AF nest" lost about 50% of its spectral power and there was almost complete disappearance of signals above 100 Hz from the "AF nest" (Bs). In that way, from the spectral point of view, the RF converts the "fibrillar" myocardium into being "compact-like". On the right: radiological road-mapping during spectral AF ablation showing the RF-catheter in one "AF nest" in the left interatrial septum, therefore outside the pulmonary vein. TEE: transoesophageal echocardiographical probe; CS: coronary sinus; LSPV: left superior pulmonary vein; IA Punction: transseptal puncture; RA and RV: right atrium and ventricle.

 
The RF was applied outside the pulmonary vein in pulses of 30–40 J for 15–20 s, with the temperature limited to 60 or 70 °C (depending on the proximity of the pulmonary veins). The purpose was to eliminate or significantly attenuate the high frequency AF nest potentials in the third channel. The low frequency presents only a mild amplitude reduction, left shifting the resulting spectrum towards the normal shape. The Fourier transform shows that, after ablation, the large number of segmented harmonics above 80 Hz from AF nests is greatly reduced or eliminated with the fundamental frequency being less affected. As a result, partial RF-ablation of the fibrillar myocardium tends to convert its spectrum into that of the compact, Fig. 6.

View larger version (20K): [in this window] [in a new window]   Figure 6 Spectral analysis, using Fourier transform (FFT), of the "compact" myocardium (A) and "AF nest" potentials found in the left atrium roof before (B) and after RF-ablation (C). The RF blunts more significantly in frequencies above 80 Hz, rendering the spectrum of the "AF nest" similar to that of the "compact" myocardium.

 
AF nests and the pathophysiology of the AF
Stimulating the atrium with progressively higher rates we have found a very interesting difference in the compact and fibrillar myocardium behaviour. The former resists the frequency increase without electrical disorganization ("Bystander Behaviour"—the passive state), Fig. 3 (RA), in contrast to the fibrillar which presents cyclic high frequency disorganization ("Resonant Behaviour"—the active state), Fig. 7. The "Resonant Behaviour" is a repetitive and decremental electrical activity, similar to an energized "tuning-fork". In this study it was observed that maintenance of the AF needs at least one AF nest all the time in the "resonant" state or several cyclic AF nests, out-of-phase oscillating from the "bystander" to the "resonant" state. In this way, when one AF nest is in the "passive state" (bystander) it is activated by another AF nest that is in the "active state" (resonant). AF only spontaneously reverts when for a brief moment all the AF nests coincide in the "bystander" condition. This pathophysiological understanding has allowed us to ablate AF during the arrhythmia. In this case we have sought "resonant" areas and after ablating several areas we have converted AF to sinus rhythm.

View larger version (25K): [in this window] [in a new window]   Figure 7 Dual state behaviour commonly observed in the AF nest during AF. The "on" is the "active state" (resonant behaviour featured by repetitive, disorganized and decremental responses—baseline not well defined). The "off" is the "passive state" (bystander behaviour—in this moment the AF nest only awaits external stimulation—baseline well defined). If there are at least two AF nests switching these states in out-of-phase AF is maintained because when one is passive it is stimulated by the other active nest. However, if there is a coincidence of the bystander state of all the AF nests AF ceases.

 
Positive aspects of this methodology

1. This method allows AF ablation with an apparently high probability of cure or control without seeking pulmonary vein premature beats. Besides being less time-consuming, it seems to be highly effective, regardless of the erratic presence of pulmonary ectopic activity [25];
   
2. Ablation outside pulmonary veins avoids the risk of pulmonary stenosis;
   
3. Use of short pulses of RF avoids destruction of large amounts of tissue aiming at shifting the spectrum (Fig. 6)—and avoiding lines of block reduces lesions, decreases perforation and pericardial tamponade risks and minimizes thromboembolic hazard, as well as iatrogenic arrhythmia caused by incomplete lines of block;
   
4. The procedure duration and cost were also reduced, since additional mapping procedures like electroanatomic and venous transverse mapping were not necessary;
   
5. As AF induction and cardioversion are not performed, complications and myocardial damage are less likely to occur;
   
6. The total or partial treatment of the substrate has eliminated the arrhythmia, even when triggers persist or appear;
   
7. This initial experience, despite being in the learning curve and without use of navigation-aids, is showing very good results;
   
8. The need for only one catheter decreases risks and costs;
   
9. Although it was not tested in this series, this methodology using the spectral analysis has great potential for ablation during AF;
   
10. Finally, this new methodology identifies and defines a new concept of the AF substrate and pathophysiology.
    

Limitations

1. The whole atrial endocardium needs to be scrutinized. It will be improved in the future by using computer aided mapping. Incomplete mapping may leave some AF nests predisposing to arrhythmia relapses;
   
2. Despite the fact that simplified mapping is possible, currently no device is commercially available which is dedicated to this kind of application;
   
3. In this series, the value of this technique for ablation of AF during arrhythmia was not assessed;
   
4. In some cases triggers may persist in being the origin of occasional symptoms although AF has been ablated.
   

	Conclusions

Top Abstract Introduction Background Objectives Method Results Discussion and comments Conclusions References

 
In this study a new technique for curative radiofrequency AF ablation is described based on a concept and on demonstration of the compact and fibrillar myocardium, the latter forming AF nests. It was observed that the atrial wall is a blend of these two kinds of muscle. Strong evidence that the fibrillar myocardium could be the real AF substrate was found. It could be congenital (atrium–vein transition or myocardium–nervous system transition) or acquired (poorly connected cells due to degeneration, stretching or by other processes) and can be found in several parts of the atrial wall and entering the pulmonary veins. The greater the fibrillar/compact myocardium ratio, greater is the frequency and propensity to AF. This tissue, which seems to have intermediate features between nerve and myocardium can be easily identified and mapped by spectral analysis and phase study. Computerised fast Fourier transform (FFT) was used for this purpose. Elimination or inactivation of AF nests by low amount of catheter RF applications has allowed PAF cure in 94% and clinical control in 100% of cases, regardless of the removal of triggers or isolation of pulmonary veins. The procedure is accomplished by transseptal puncture and requires only one catheter for ablation and mapping. RF is applied outside the pulmonary veins, avoiding risk of stenosis. The patient should be in sinus rhythm. However, the spectral analysis technique may have potential to localize the application targets—AF nests—even during arrhythmia. Taking great care in the transseptal puncture and RF-ablation, the complication rate is minimized.

	References

Top Abstract Introduction Background Objectives Method Results Discussion and comments Conclusions References

 
[1] Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339: 659–666.[Abstract/Free Full Text]

[2] Haïssaguerre M, Jaïs P, Shah DC, Garrigue S, Takahashi A, Lavergne T, et al. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Circulation 2000; 101: 1409–1417.[Abstract/Free Full Text]

[3] Jaïs P, Haïssaguerre M, Shah DC, et al. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation 1997; 95: 572–576.[Abstract/Free Full Text]

[4] Seshadri N, Marrouche NF, Wilber D, Packer D, Natale A. Pulmonary vein isolation for treatment of atrial fibrillation: recent updates. Pacing Clin Electrophysiol 2003; 26: 1636–1640.[CrossRef][Medline]

[5] Sanders P, Morton JB, Deen VR, Davidson NC, Sparks PB, Vohra JK, et al. Immediate and long-term results of radiofrequency ablation of pulmonary vein ectopy for cure of paroxysmal atrial fibrillation using a focal approach. Intern Med J 2002; 32: 202–207.[CrossRef][Medline]

[6] Tada H, Oral H, Wasmer K, Greenstein R, Pelosi F Jr, Knight BP, et al. Pulmonary vein isolation: comparison of bipolar and unipolar electrograms at successful and unsuccessful ostial ablation sites. J Cardiovasc Electrophysiol 2002; 13: 13–19.[CrossRef][Web of Science][Medline]

[7] Rocha Neto AC, Farias RL, de Paola AA. Treatment of atrial fibrillation with radiofrequency ablation and simultaneous multipolar mapping of the pulmonary veins. Arq Bras Cardiol 2001; 77: 407–428.[Medline]

[8] Pappone C, Rosanio S, Oreto G, Tocchi M, Gugliotta F, Vicedomini G, et al. Circumferential radiofrequency ablation of pulmonary vein ostia: a new anatomic approach for curing atrial fibrillation. Circulation 2000; 102: 2619–2628.[Abstract/Free Full Text]

[9] Macle L, Jaïs P, Scavee C, Weerasooriya R, Hocini M, Shah DC, et al. Pulmonary vein disconnection using the LocaLisa three-dimensional nonfluoroscopic catheter imaging system. J Cardiovasc Electrophysiol 2003; 14: 693–697.[Web of Science][Medline]

[10] Pappone C, Rosanio S, Augello G, Gallus G, Vicedomini G, Mazzone P, et al. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol 2003; 42: 185–197.[Abstract/Free Full Text]

[11] Pappone C. Atrial fibrillation—a curable condition? Eur Heart J 2002; 23: 558–566.[Abstract/Free Full Text]

[12] Marchlinski FE, Callans D, Dixit S, Gerstenfeld EP, Rho R, Ren JF, et al. Efficacy and safety of targeted focal ablation versus PV isolation assisted by magnetic electroanatomic mapping. J Cardiovasc Electrophysiol 2003; 14: 358–365.[CrossRef][Web of Science][Medline]

[13] Morady F. Treatment of paroxysmal atrial fibrillation by pulmonary vein isolation. Circ J 2003; 67: 567–571.[CrossRef][Web of Science][Medline]

[14] Chen SA, Hsieh MH, Tai CT, Tsai CF, Prakash VS, Yu WC, et al. Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation. Circulation 1999; 100: 1879–1886.[Abstract/Free Full Text]

[15] Natale A. Radiofrequency ablation of the pulmonary veins: can it stop atrial fibrillation at its source? Cleve Clin J Med 2001; 68: 21–24.

[16] Horlitz M, Schley P, Shin DI, Muller M, Sause A, Krolls W, et al. Catheter ablation of ectopic atrial tachycardia by electrical pulmonary vein disconnection. Z Kardiol 2003; 92: 193–199.[Medline]

[17] Chen YJ, Chen SA, Chang MS, Lin CI. Arrhythmogenic activity of cardiac muscle in pulmonary veins of the dog: implication for the genesis of atrial fibrillation. Cardiovasc Res 2000; 48: 265–273.[Abstract/Free Full Text]

[18] Asenjo R, Morris R, Oyarzun R, Dussaillant G, Ortiz M, Nicola M, et al. Focal atrial fibrillation. Clinical characteristic and results of radiofrequency ablation. Rev Med Chil 2002; 130: 482–494.[Medline]

[19] Fuster V, Rydén LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. J Am Coll Cardiol 2001; 38: 1231–1266.[Free Full Text]

[20] Jaïs P, Hocini M, Macle L, Choi KJ, Deisenhofer I, Weerasooriya R, et al. Distinctive electrophysiological properties of pulmonary veins in patients with atrial fibrillation. Circulation 2002; 106: 2479–2485.[Abstract/Free Full Text]

[21] Oral H, Knight BP, Ozaydin M, Chugh A, Lai SW, Scharf C, et al. Segmental ostial ablation to isolate the pulmonary veins during atrial fibrillation: feasibility and mechanistic insights. Circulation 2002; 106: 1256–1262.[Abstract/Free Full Text]

[22] Cox JL, Ad N, Palazzo T, Fitzpatrick S, Suyderhoud JP, DeGroot KW, et al. The maze-III procedure combined with valve surgery. Semin Thorac Cardiovasc Surg 2000; 12: 53–55.[Medline]

[23] Sueda T, Nagata H, Orihashi K, Morita S, Okada K, Sueshiro M, et al. Efficacy of a simple left atrial procedure for chronic atrial fibrillation in mitral valve operations. Ann Thorac Surg 1997; 63: 1070–1075.[Abstract/Free Full Text]

[24] Jatene MB, Marcial MB, Tarasoutchi F, Cardoso RA, Pomerantzeff P, Jatene AD. Influence of the maze procedure on the treatment of rheumatic atrial fibrillation—evaluation of rhythm control and clinical outcome in a comparative study. Eur J Cardiothorac Surg 2000; 17: 117–124.[Abstract/Free Full Text]

[25] Adragao P, Cavaco D, Aguiar C, Palos J, Morgado F, Ribeiras R, et al. Ablation of pulmonary vein foci for the treatment of atrial fibrillation; percutaneous electroanatomical guided approach. Europace 2002; 4: 391–399.[Abstract/Free Full Text]

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				H. Oral, A. Chugh, K. Yoshida, J. F. Sarrazin, M. Kuhne, T. Crawford, N. Chalfoun, D. Wells, W. Boonyapisit, S. Veerareddy, et al. A randomized assessment of the incremental role of ablation of complex fractionated atrial electrograms after antral pulmonary vein isolation for long-lasting persistent atrial fibrillation. J. Am. Coll. Cardiol., March 3, 2009; 53(9): 782 - 789. [Abstract] [Full Text] [PDF]

				A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, P. Clopton, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, J. D. Knoke, W. Y.W. Lew, J. A.C. Lima, et al. Highlights of the year in JACC 2007. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 490 - 512. [Full Text] [PDF]

				D. G. Katritsis and A. J. Camm Catheter ablation of atrial fibrillation: do we know what we are doing? Europace, November 1, 2007; 9(11): 1002 - 1005. [Full Text] [PDF]

				H. Oral and F. Morady Autonomic Innervation, Atrial Electrogram Morphology, and Atrial Fibrillation J. Am. Coll. Cardiol., October 2, 2007; 50(14): 1332 - 1334. [Full Text] [PDF]

				N. Lellouche, E. Buch, A. Celigoj, C. Siegerman, D. Cesario, C. De Diego, A. Mahajan, N. G. Boyle, I. Wiener, A. Garfinkel, et al. Functional Characterization of Atrial Electrograms in Sinus Rhythm Delineates Sites of Parasympathetic Innervation in Patients With Paroxysmal Atrial Fibrillation J. Am. Coll. Cardiol., October 2, 2007; 50(14): 1324 - 1331. [Abstract] [Full Text] [PDF]

				H. Oral, A. Chugh, E. Good, A. Wimmer, S. Dey, N. Gadeela, S. Sankaran, T. Crawford, J. F. Sarrazin, M. Kuhne, et al. Radiofrequency Catheter Ablation of Chronic Atrial Fibrillation Guided by Complex Electrograms Circulation, May 22, 2007; 115(20): 2606 - 2612. [Abstract] [Full Text] [PDF]

				T. H. Everett IV, E. E. Wilson, S. Verheule, J. M. Guerra, S. Foreman, and J. E. Olgin Structural atrial remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in canine models of structural and electrical atrial remodeling Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2911 - H2923. [Abstract] [Full Text] [PDF]

				K. Lemola, M. Ting, P. Gupta, J. N. Anker, A. Chugh, E. Good, S. Reich, D. Tschopp, P. Igic, D. Elmouchi, et al. Effects of Two Different Catheter Ablation Techniques on Spectral Characteristics of Atrial Fibrillation J. Am. Coll. Cardiol., July 18, 2006; 48(2): 340 - 348. [Abstract] [Full Text] [PDF]

				J. C. Pachon M, E. I. Pachon M, J. C. Pachon M, T. J. Lobo, M. Z. Pachon, R. N.A. Vargas, and A. D. Jatene "Cardioneuroablation" - new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation Europace, January 1, 2005; 7(1): 1 - 13. [Abstract] [Full Text] [PDF]

				G. Mönnig, J. Wessling, K. U. Juergens, P. Milberg, M. Ribbing, R. Fischbach, J. Wiekowski, Gün. Breithardt, and L. Eckardt Further evidence of a close anatomical relation between the oesophagus and pulmonary veins Europace, January 1, 2005; 7(6): 540 - 545. [Abstract] [Full Text] [PDF]

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (22) Request Permissions Disclaimer Google Scholar Articles by Pachon M, J. C. Articles by Jatene, A. D. Search for Related Content PubMed PubMed Citation Articles by Pachon M, J. C. Articles by Jatene, A. D. Social Bookmarking          What's this?

Online ISSN 1532-2092 - Print ISSN 1099-5129

Copyright © 2009 European Heart Rhythm Association of the European Society of Cardiology (ESC)

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics