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Circulation. 1996;93:960-968

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(Circulation. 1996;93:960-968.)
© 1996 American Heart Association, Inc.


Articles

Heterogeneity of Retrograde Fast-Pathway Conduction Pattern in Patients With Atrioventricular Nodal Reentry Tachycardia

Observations by Use of Simultaneous Multisite Catheter Mapping of Koch's Triangle

Frederic Anselme, MD; Bruce Hook, MD; Kevin Monahan, MD; Joost Frederiks, MD; David Callans, MD; Marco Zardini, MD; Laurence M. Epstein, MD; Joseph Zebede, MD; Mark E. Josephson, MD

From Harvard-Thorndike Institute of Electrophysiology, Cardiology Division, Beth Israel Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Mark E. Josephson, MD, Cardiovascular Division, Beth Israel Hospital, 330 Brookline Ave, Boston, MA 02215.


*    Abstract
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*Abstract
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Background Selective ablation of either the fast or the slow pathway resulting in cure of AV nodal reentry tachycardia (AVNRT) has led to the concept that these pathways are discrete, anatomically defined structures. We hypothesized that if a discrete retrograde fast pathway exists, it should be possible to record a single focus of early atrial activation near the apex of Koch's triangle, with sequential spread of depolarization to the rest of the atria.

Methods and Results We evaluated 46 patients (33 women, 13 men; mean age, 45±17 years) undergoing electrophysiology study and catheter ablation for typical AVNRT. Retrograde atrial activation during AVNRT (337±43 ms) and ventricular pacing at a similar cycle length (352±51 ms) was recorded in the region of Koch's triangle with a decapolar catheter in the His bundle position, a multipolar catheter in the coronary sinus, and a deflectable quadripolar catheter along the tricuspid annulus anterior to the coronary sinus ostium. Earliest atrial activation was recorded at the apex of the triangle of Koch in 38 patients during ventricular pacing and in 43 patients during AVNRT. A broad wave front of atrial activation was recorded in 17 patients during ventricular pacing and in 26 patients during AVNRT. During AVNRT, only 2 patients had a single early site with focal and sequential activation along the tendon of Todaro. There was concordance in the pattern of atrial activation between ventricular pacing and AVNRT in only 21 of 46 patients.

Conclusions Retrograde atrial activation over the fast pathway is heterogeneous within Koch's triangle and the coronary sinus, both for the entire population and for individual patients during different modes of activation. These data do not support the concept of an anatomically discrete retrograde fast pathway.


Key Words: tachycardia • atrioventricular node • reentry


*    Introduction
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up arrowAbstract
*Introduction
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The success of catheter ablation in curing AV nodal reentry tachycardia (AVNRT) is now well established.1 2 3 4 5 6 7 8 9 10 11 Techniques for selective ablation of either the fast5 7 8 11 or the slow1 2 3 4 8 9 10 11 pathway have been reported, and spatial separation of successful ablation sites has fostered the concept that the fast and slow pathways are discrete anatomic structures.

Evidence exists, however, that a simplistic construct of anatomically defined pathways is not correct. Successful ablation of the fast pathway has been reported with use of a posterior approach, and slow-pathway conduction has been eliminated with ablation at anterior sites.2 11 Furthermore, histological studies have not confirmed the presence of discrete fast and slow AV nodal pathways. The posterior and anterior "inputs" into the region of the compact AV node are composed of a heterogeneous mixture of working myocardial cells and transitional cells.12 13 The manner in which atrial cells are coupled to these transitional cells is unknown. In fact, electrophysiological and anatomic correlates of rabbit and dog AV junction suggest that transitional cells enter the compact node.14 15 Thus, although the overall success rate for cure of AVNRT by either approach is beyond question, a precise anatomic and physiological correlation to explain the mechanism of the tachycardia is lacking.

The purpose of the present study was to gain further insight into the details of retrograde fast-pathway conduction in patients with typical AVNRT by use of simultaneous multisite catheter mapping of Koch's triangle and adjacent coronary sinus. We hypothesized that if a discrete retrograde fast pathway exists, it should be possible to record a single focus of early atrial activation with sequential spread to the rest of the atria. In contrast, variability in the site of earliest retrograde atrial activation and discordance in atrial activation during AVNRT and ventricular pacing would suggest the presence of a functionally determined circuit with multiple and heterogeneous potential pathways of retrograde conduction.


*    Methods
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Study Population
The study population included 46 patients undergoing electrophysiology study and catheter ablation for typical AVNRT. AVNRT was defined by previously published standard criteria.16 17 18 19 20 There were 33 women and 13 men, with a mean age of 45±17 years. Forty-two patients had no identifiable structural heart disease, 3 had coronary artery disease, and 1 had dilated cardiomyopathy. One patient had mild hypertension. All studies were performed in the postabsorptive state after all antiarrhythmic medications had been stopped for at least five half-lives. Informed written consent was obtained from each patient before the study in accordance with institutional guidelines.

Atrial Recording Sites
Transvenous intracardiac multielectrode catheters were positioned as follows: Quadripolar catheters with 5-mm interelectrode distance were positioned in the high right atrium and the right ventricle. A decapolar catheter with 2-mm interelectrode distance was placed across the tricuspid valve and positioned to obtain the largest His bundle deflection in the distal electrode pair, and the remaining electrodes were positioned in contact with the atrium along the tendon of Todaro (His bundle electrogram [HBE] catheter). Efforts were made to ensure that atrial potentials could be recorded from each bipolar pair during sinus rhythm, ventricular pacing, and AVNRT. A hexapolar, octapolar, or decapolar catheter with 5-mm interelectrode distance was placed in the coronary sinus with the proximal electrode at the ostium. A steerable quadripolar catheter (interelectrode distance, 2/5/2 mm) was positioned along the tricuspid annulus approximately at the level of the coronary sinus ostium. The ratio of atrial:ventricular electrogram amplitude recorded from the distal electrode pair during sinus rhythm at this site was <1 for all patients. The positioning of this catheter was not dictated by the presence of slow-pathway potential, nor was it necessarily at the site of subsequent successful ablation. Rather, this position was chosen anatomically to standardize the recording site for the entire study population. The distance between the proximal HBE recording electrodes and the closest electrodes on the catheter in the posterior triangle of Koch ranged from 1 to 3 cm, with an average of 2 cm. Data were analyzed from the five HBE bipolar pairs, the distal slow-pathway electrode pair, and the coronary sinus bipolar pair that recorded the earliest atrial electrogram. A schematic diagram of the recording sites relative to Koch's triangle is presented in Fig 1Down.



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Figure 1. Schematic of the recording sites relative to the triangle of Koch in a right anterior oblique view. The five sequential His bundle recording sites are shown traversing the tendon of Todaro. Recordings from the base of Koch's triangle were provided by the coronary sinus catheter and the deflectable catheter in the so-called slow-pathway region. CS os indicates coronary sinus ostium; HBE, His bundle electrogram (d, distal; p, proximal); and SP, the so-called slow-pathway area at the base of the Koch's triangle.

Measurement of Atrial Activation
Bipolar electrograms were filtered at 40 to 400 Hz. An analog to digital sampling rate of 1000 Hz was applied before digital storage and analysis. Ventricular pacing was performed at twice diastolic threshold with a programmable stimulator (Bloom Assoc). Measurements of atrial activation were made at a sweep speed of 200 mm/s by use of electronic calipers on a digital electrophysiology recording system in 32 patients; in the remaining 14 patients, analog signals sampled at 4000 Hz were analyzed by handheld calipers. Atrial activation was recorded during ventricular pacing and AVNRT at similar cycle lengths in each patient. Recordings were performed first during AVNRT and immediately thereafter during ventricular pacing to avoid changes in autonomic tone. In those patients who required isoproterenol and/or atropine for initiation of sustained AVNRT, measurements of atrial activation were made in close temporal proximity after these agents had been administered.

Measurements were made with the onset of the atrial electrogram. There was no difference in the qualitative patterns of retrograde atrial activation when the largest deflection that crossed the isoelectric baseline was used. When atrial and ventricular activation occurred simultaneously, single or double ventricular premature depolarizations were delivered to separate the individual components (Fig 2Down). Care was taken to ensure that the ventricular premature depolarization did not affect the tachycardia circuit.



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Figure 2. Use of ventricular premature depolarization (VPD) in revealing retrograde atrial activation pattern during AV nodal reentry tachycardia in patient 1. Surface leads II and V1 are shown along with intracardiac recordings from the high right atrium (HRA), His bundle region (HBEd through HBEp), coronary sinus (CSp through CSd), slow-pathway region (SPd and SPp), and right ventricular apex (RVA). The tachycardia cycle length is 360 ms. The VPD does not affect the subsequent tachycardia cycle. Note that the CSp atrial electrogram occurs before the HBEp atrial electrogram, thus defining a second atrial breakthrough. A indicates atrial depolarization; HBE, His bundle electrogram; d, distal; and p, proximal.

The site of earliest atrial activation was recorded during AVNRT and during ventricular pacing for each patient. This site was assigned a reference time of zero, and the timing of all other sites was measured relative to this.

To characterize the pattern of atrial activation, the following categories were defined along the His bundle catheter: (1) sequential wave front: earliest atrial activation at one or two adjacent bipole pairs with sequential spread to the remaining electrode pairs; (2) broad wave front: three or more adjacent bipolar pairs of the HBE catheter within 5 ms.

Over the entire Koch's triangle, the following categories were defined: (1) multiple early sites: (a) two or more activation times along the HBE catheter within 5 ms separated by two later sites, and (b) one or more sites on the HBE catheter and any other catheter within 5 ms; (2) single early site: sites that did not fulfill criteria for multiple early sites.

For each patient, the site of earliest atrial activation as well as the qualitative pattern of atrial activation over the Koch's triangle was compared during ventricular pacing and AVNRT.

To ensure the reproducibility of the measurement, tracings were analyzed in a blinded manner three times by two different investigators 2 weeks apart. The retrograde atrial activation sequence was assessed by use of at least three beats with stable cycle length. Although differences in the absolute timing of atrial electrograms could differ up to 10 ms, qualitative assessment of relative atrial activation did not vary between investigators.


*    Results
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Activation times at each site and the qualitative patterns of atrial activation during both ventricular pacing and tachycardia are shown in Table 1Down.


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Table 1. Patient Data

Sites of Earliest Atrial Activation
The sites of earliest atrial activation during ventricular pacing and AVNRT are summarized in Fig 3Down.



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Figure 3. Sites of earliest atrial activation. This diagram shows the number of patients according to their earliest atrial site of activation during ventricular pacing (VP) and AV nodal reentry tachycardia (AVNRT) in the entire population. HBE indicates His bundle catheter recording in which we defined five different types of earliest atrial activation site (earliest electrograms between 0 and 5 ms) (d/2, pair of electrodes distal and/or number 2; 2+3, pair of electrodes numbers 2 and 3; 3, pair of electrodes number 3; Broad, broad wave front of atrial activation, defined as three or more adjacent electrograms within 5 ms; d+p, earliest atrial activation simultaneous in the distal and proximal pairs of HBE electrodes); CS, coronary sinus recording; SP, recording of the so-called slow-pathway area at the base of the Koch's triangle; and Multiple, multiple earliest atrial activation between 0 and 5 ms (H-CS, earliest activation simultaneous in the HBE catheter and in the CS catheter; H-SP, earliest activation simultaneous in the HBE catheter and at the base of the Koch's triangle; H-CS-SP, earliest activation simultaneous in the HBE catheter, in the CS catheter, and at the base of the Koch's triangle).

During Ventricular Pacing
Earliest atrial activation was recorded in one of the two distal HBE electrode pairs in 38 patients (82.6%), whereas activation in the remaining 8 patients was distributed evenly over the other recording sites. Multiple sites of earliest atrial activation were recorded in 10 patients (21.7%). Earliest atrial activation was simultaneous in the coronary sinus and in the HBE in 2 patients; in the coronary sinus, in the HBE, and at the base of the triangle of Koch in 4 patients; and in the HBE and at the base of the triangle of Koch in 4 patients (Fig 4Down). In 1 patient, the earliest atrial activation was recorded at the base of the triangle of Koch.



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Figure 4. Example of concordance in retrograde atrial activation sequence between ventricular pacing and AV nodal reentry tachycardia in patient 12. A, During ventricular pacing at a cycle length of 400 ms, earliest atrial depolarization was observed in the distal His bundle electrogram (HBE) with a sequential activation along this catheter. Coronary sinus (CS) region and the base of Koch's triangle (SP) were depolarized later. Single-sequential pattern was assigned. B, During tachycardia at a cycle length of 350 ms, a double ventricular premature depolarization was introduced without affecting the AV nodal circuit to better determine the location of the atrial electrogram. The atrium was depolarized in the same way as during ventricular pacing with a single early breakthrough at the apex of the triangle of Koch and a sequential activation to the rest of the triangle. d indicates distal; p, proximal; HRA, high right atrium; A, atrial depolarization; and H, His bundle.

During AVNRT
Earliest atrial activation was recorded in one of the two distal HBE electrode pairs in the majority of patients (40 of 46; 87%). However, multiple sites of earliest atrial depolarization were found in 8 patients (17.4%), and in 2 patients, the earliest site was in the coronary sinus or at the base of the triangle of Koch (Fig 3Up).

In only 18 (39.1%) of the 46 patients, the earliest atrial site of activation was identical during ventricular pacing and typical AVNRT.

Pattern of Atrial Activation
During Ventricular Pacing
Twenty-nine patients demonstrated a sequential pattern in the HBE catheter, whereas a broad wave front was recorded in 17 patients. Fifteen patients (32.6%) had only a single early site of atrial activation, and 31 patients (67.4%) demonstrated multiple sites of early breakthrough in the area of the triangle of Koch.

During AVNRT
Twenty patients had a sequential pattern and 26 patients had a broad wave front of activation. Fifteen patients (32.6%) showed early activity at a single site, and 31 patients (67.4%) had multiple early breakthrough sites recorded over the area of the triangle of Koch.

Only 21 patients (45.7%) demonstrated concordance in the qualitative pattern of atrial activation within Koch's triangle during both AVNRT and ventricular pacing. Representative intracardiac recordings from 2 patients with discordant patterns and from 1 patient with a concordant pattern of retrograde atrial activation between AVNRT and ventricular pacing are presented in Figs 4, 5, and 6.

Table 2Down summarizes the qualitative patterns of atrial activation during ventricular pacing and AVNRT. Note that the pattern of a single early site with sequential activation along the HBE catheter was seen in only six patients during ventricular pacing and in two patients during AVNRT.


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Table 2. Pattern of Retrograde Atrial Activation (Number of Patients)


*    Discussion
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*Discussion
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The major finding of this study is that fast retrograde atrial activation is heterogeneous within the area of Koch's triangle in patients with AVNRT both during tachycardia and during ventricular pacing. We hypothesized that if the retrograde fast pathway is an anatomically discrete structure similar to an accessory pathway, then atrial activation should demonstrate a single early site with focal and sequential spread proceeding from the apex of Koch's triangle to posterior atrial sites. Our results showed, however, that this type of pattern was rare (ventricular pacing=6 patients, AVNRT=2 patients). In fact, multiple sites of early breakthrough in the triangle of Koch as well as a broad wave front of activation in the His bundle catheter were frequent (31 and 17 patients during ventricular pacing, 31 and 26 patients during AVNRT, respectively). Since discordance in the retrograde atrial activation sequence was present between ventricular pacing and AVNRT, the retrograde fast pathway appears to be not only variable in different patients but also dynamic for each individual.

Previous Studies
Early studies on retrograde atrial activation during ventricular pacing and typical AVNRT were performed with use of bipolar recordings of the right atrial septum, high lateral right atrium, and "proximal" and "distal" coronary sinus (neither of which was specifically localized or standardized). Retrograde activation measured in a small number of patients revealed that the right atrial septum was the earliest site of retrograde atrial activation and preceded activation of the "proximal" coronary sinus and high lateral right atrium.21 22 The sequence of retrograde atrial activation was further characterized by Sung et al23 in seven patients with dual AV nodal pathways during ventricular pacing and typical AVNRT. Earliest atrial activation was recorded at the apex of the triangle of Koch in all of the patients.

Recently, McGuire et al24 reported results of intraoperative high-resolution mapping of Koch's triangle in patients with AVNRT. These investigators used a plaque with 60 unipolar electrodes to record atrial activation in the region surrounding the AV node in 13 patients undergoing surgery for AVNRT. In 9 patients with typical AVNRT in whom atrial activation was recorded during ventricular pacing, a single site of earliest activation was seen in 7 patients. In 1 patient, however, almost the entire area of Koch's triangle was activated simultaneously. In 2 patients, dual sites of earliest atrial activation were observed. Recordings made during AVNRT demonstrated earliest breakthrough anteriorly at the apex of Koch's triangle in 9 of 10 patients.

Current Results
Our series demonstrated that multiple sites of earliest atrial activation were present in 21.7% of patients during ventricular pacing and in 17.4% of patients during typical AVNRT, with only 39.1% concordance in the site of earliest activation. We defined multiple sites of early breakthrough to describe a pattern in which atrial depolarization at the coronary sinus or slow-pathway region was recorded too early to have been a consequence of sequential activation from the apex of the triangle of Koch. By this definition, multiple sites of early breakthrough were recorded in two thirds of patients during both ventricular pacing and AVNRT. Moreover, a broad wave front of HBE activation was recorded in 37% and 56.5% of patients during ventricular pacing and AVNRT, respectively. Concordance in the pattern of activation was present in only 45.7% of the patients.

Several factors may explain the discrepancies between previous studies and our results. Previous series that used catheter mapping were limited by the small number of recording sites used.21 22 23 Therefore, the possibility of multiple areas of breakthrough could not be excluded. In the McGuire series,24 the use of unipolar recordings may have confounded results by the detection of far-field signals. Even though they did not specifically address secondary breakthrough sites, they did note qualitative differences in retrograde conduction in different patients, similar to our findings. Furthermore, earliest retrograde atrial activation was recorded over 6 mm or more (simultaneous in three poles 3 mm apart) in several patients who showed intracardiac recordings of typical AVNRT.24 This corresponds to our definition of a broad wave front of activation and supports the presence of heterogeneity of fast retrograde conduction. The isochrons drawn from such maps demonstrate anisotropic propagation, not a sequential loop of activation.

Many investigators have emphasized the importance of slow-pathway potentials in localizing the anatomic site of the slow pathway.1 3 Although it has been theorized that these potentials represent activation of a structurally discrete pathway of slow conduction, recent observations contradict this hypothesis. Josephson25 reported that in 30% of patients, ablation at sites just above the coronary sinus in the posterior triangle, an area in which slow-pathway potentials were often recorded, resulted in elimination of fast-pathway conduction. McGuire et al26 demonstrated a similar area over which slow-pathway potentials could be recorded in dogs. These potentials represented far-field potentials from the atrial septum and deeper local potentials from transitional cells close to the tricuspid annulus and did not correspond to a well-defined area of slow conduction. Our results provide confirmation as to the heterogeneity of conduction properties at sites in the posterior aspect of the Koch's triangle and may further undermine the significance of high-frequency potentials recorded at these sites as specific electrophysiological markers.

Clinical Implication
Despite extensive experience in radio frequency ablation of AVNRT during the past several years, many clinical observations relating to fast- and slow-pathway conduction remain unexplained. Complete heart block complicates up to 1% of cases1 2 3 4 when the slow pathway is targeted and up to 2% to 10% of cases when the fast pathway is targeted.7 27 28 Elimination of fast-pathway conduction has been reported at posterior sites of ablation,25 and complete heart block can complicate cases in which ablation is performed distant from the compact AV node.1 2 3 4 These observations are difficult to reconcile with a model of AVNRT in which distinct pathways of conduction exist in anatomically determined sites. Our results emphasize the anatomic heterogeneity and potentially dynamic properties of retrograde AV nodal conduction and stand in contrast to a strictly anatomically determined model. This complexity may underlie the unexpected outcomes observed during AVNRT radiofrequency ablation.

Study Limitations
Subtle degrees of catheter movement between AVNRT and ventricular pacing protocols potentially could have affected the comparison of results. However, to minimize this possibility, frequent fluoroscopic images and review of electrogram characteristics were obtained, with concurrence of stability by two observers. Slight repositioning was occasionally necessary and was guided by stored fluoroscopic images and electrogram morphology.

We systematically introduced ventricular premature depolarizations during AVNRT to advance the ventricular electrogram and to fully expose the atrial electrogram. The absolute timing of the atrial electrogram could vary by up to 10 ms between the different investigators during the different measurements. However, the qualitative assessment of the relative atrial activation and the pattern assigned did not differ.

Although retrograde atrial activation during ventricular pacing and during typical AVNRT were analyzed at cycle lengths that were as similar as possible, these cycle lengths were not identical for all the patients. However, conduction over the fast pathway was ensured through analysis of the retrograde ventriculoatrial conduction curves.

Conclusions
Successful cure of AVNRT is now possible in nearly all patients. However, the mechanism of the tachycardia is still not fully understood. Whereas a single radiofrequency lesion may cure the tachycardia, retrograde AV nodal conduction is highly complex. The analogy of retrograde AV nodal conduction to accessory pathway conduction appears to be overly simplistic. Our data and those of other investigators have shown that retrograde atrial activation is heterogeneous and not fully determined by discrete anatomic pathways. We believe that these data are most consistent with a subatrial reentrant circuit (which may be temporally "fixed" during the tachycardia) with variable propagation to the atrium due to heterogeneous nodal-atrial coupling. Further studies are needed to better define the determinants of this variability in retrograde AV nodal conduction.




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Figure 6. Second example of discordance between right ventricular outflow tract (RVOT) pacing and tachycardia (patient 21). A, During ventricular pacing, earliest atrial activation is observed in the distal HBE catheter with a sequential depolarization along this catheter. The posterior triangle of Koch (SP) and the CS ostium are depolarized later. The pattern of atrial activation sequence is a single site of early breakthrough with sequential activation of the His bundle region. B, During AV nodal reentry tachycardia, double ventricular premature depolarizations are introduced to advance the ventricular activation without affecting the tachycardia cycle. Simultaneous atrial depolarization is seen in the entire HBE catheter. The same atrial activation sequence is seen in the HBE catheter on the last spontaneous beat of the tracing. Compared with ventricular pacing, the SP area and the entire CS are activated earlier. The atrial activation pattern is defined as a single early site of breakthrough with broad activation of the His bundle region. Abbreviations as in Fig 4Up.


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Table 1B. Continued


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Figure 5. Example of discordance in retrograde atrial activation sequence during right ventricular pacing and typical AV nodal reentry tachycardia (AVNRT) in patient 22. A, During pacing, earliest atrial activation is seen in the distal His bundle electrogram recording (HBEd) with sequential spread proximally along the HBE catheter. A second site of early activation is observed in the "slow pathway" region, 27 ms before the HBE proximal (HBEp) depolarization. The pattern of atrial activation is defined as multiple breakthroughs with sequential activation of the HBE catheter (M-Se). B, During AVNRT, atrial activation was determined by use of a single ventricular premature depolarization to advance ventricular activation. Earliest atrial depolarization is almost simultaneous in the entire HBE catheter, indicating a broad wave front of activation. The rest of the Koch's triangle is depolarized sequentially. The pattern of atrial activation during AVNRT is defined as a single breakthrough with a broad wave front of activation in the HBE catheter. RVA indicates right ventricular apex; other abbreviations as in Fig 4Up.


*    Acknowledgments
 
Dr Anselme was supported by a grant from La Federation Francaise de Cardiologie. The authors gratefully acknowledge the excellent technical assistance of Philippa Beswick and the active participation of Panos Papageorgiou, Noel Boyle, and Claudio Schuger.

Received June 23, 1995; revision received October 11, 1995; accepted October 16, 1995.


*    References
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up arrowAbstract
up arrowIntroduction
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up arrowResults
up arrowDiscussion
*References
 

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