Skip Navigation


Europace Advance Access originally published online on July 28, 2008
Europace 2008 10(10):1195-1204; doi:10.1093/europace/eun192
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
10/10/1195    most recent
eun192v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Liuba, I.
Right arrow Articles by Walfridsson, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liuba, I.
Right arrow Articles by Walfridsson, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Electrophysiology

Focal atrial tachycardia: increased electrogram fractionation in the vicinity of the earliest activation site{dagger}

Ioan Liuba* and Håkan Walfridsson

Department of Cardiology, University Hospital Linköping, 581 85 Linköping, Sweden

Manuscript submitted 9 March 2008. Accepted after revision 4 July 2008.

* Corresponding author. Tel: +46-73-84 86 292; fax: +46 13 222171. E-mail address: ioan.liuba{at}imv.liu.se


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Limitations of the study
 Conclusions
 Future directions
 Funding
 References
 
Aims: Fractionated electrograms are often noted during mapping of focal atrial tachycardia (FAT). This finding suggests poor cell-to-cell coupling, which is thought to be an important prerequisite in the process of ectopic impulse initiation and propagation. The purpose of the present study was to assess the electrogram fractionation in the vicinity of the earliest activation site and in the remaining atrium in these patients.

Methods and results: Thirteen patients with FAT (age 48 ± 17 years) who underwent catheter ablation were investigated. Mapping was performed with the CARTO system. Electrogram fractionation was assessed on the basis of the number of negative deflections, both in the region surrounding the earliest activation site and in the remaining atrium. Unipolar and bipolar peak-to-peak voltage and bipolar electrogram duration were also studied. All patients underwent successful radiofrequency ablation. A higher degree of electrogram fractionation existed in the region surrounding the earliest activation site and activated within the first 15 ms when compared with the remaining atrium (incidence of bipolar electrograms with multiple negative deflections: 88 vs. 79%, P < 0.0001; incidence of unipolar electrograms with multiple negative deflections: 56 vs. 43%, P = 0.0001). The peak-to-peak voltage in the region activated within the first 15 ms was less than that in the remaining atrium (bipolar voltage: 1.33 ± 0.99 vs. 1.61 ± 1.11 mV, P < 0.001; unipolar voltage: 1.75 ± 0.92 vs. 1.95 ± 1.11 mV, P = 0.0188). There were no significant differences in bipolar electrogram duration. Within the region activated during the first 15 ms, from the periphery to the earliest activation site, there was a gradual increase in electrogram fractionation (incidence of bipolar electrograms with multiple negative deflections gradually increasing from 82 to 100% and incidence of unipolar electrograms with multiple negative deflections increasing from 56 to 90%), as well as a gradual decrease in peak-to-peak voltage (bipolar voltage gradually decreasing from 1.47 ± 1.06 to 0.89 ± 0.54 mV, P < 0.0001; unipolar voltage gradually decreasing from 1.89 ± 0.94 to 1.30 ± 0.63 mV, P < 0.0001). Irregular, closely spaced isochrones were also noted in the region activated during the first 15 ms. The area of this region was 4.88 ± 3.59 cm2.

Conclusion: Increased electrogram fractionation exists within a relatively wide region around the tachycardia origin when compared with the remaining atrium. Moreover, this region is electrically heterogeneous, as suggested by the fact that the degree of electrogram fractionation increases gradually whereas the electrogram voltage decreases gradually towards the earliest activation site. These findings suggest that a non-discrete atrial region with gradually changing electrophysiological properties may underlie the substrate of FAT.

Key Words: Focal atrial tachycardia, Mapping, Electrogram, Fractionation


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Limitations of the study
 Conclusions
 Future directions
 Funding
 References
 
Focal atrial tachycardia (FAT) accounts for 5–17% of all supraventricular tachycardias observed in the clinical electrophysiology laboratory.1Go,2Go The underlying mechanism of this arrhythmia is highly complex, requiring both the initiation of ectopic activity in the focus and its propagation out to surrounding myocardium.3Go These processes are dependent on the size of the focus and on the magnitude of electrical coupling within the focus and between the focus and the surrounding cardiac tissue.4Go,5Go Experimental studies and computer simulations have shown that factors augmenting inter-cellular uncoupling and electrical anisotropy favour the development of focal arrhythmias.5Go,6Go In line with these observations, microelectrode recordings of atrial specimens resected from patients with FAT have shown marked inter-cellular uncoupling in the region surrounding the tachycardia origin.7Go

In the clinical electrophysiology laboratory, local inter-cellular uncoupling and increased anisotropy are suggested by the recording of fractionated electrograms.8Go Indeed, some investigators have reported multicomponent, low-voltage electrograms at the site of successful ablation in patients with FAT.9Go However, a more detailed assessment of the degree of electrogram fractionation in the vicinity of tachycardia origin has not been performed. Conceivably, such data might provide information concerning the substrate of the tachycardia, provided that increased anisotropy and electrical uncoupling are indeed important prerequisites for the mechanism of FAT. Therefore, the purpose of the present study was to assess, in a group of patients with FAT, the characteristics of electrograms and the degree of electrogram fractionation in the region surrounding the earliest activation site.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Limitations of the study
 Conclusions
 Future directions
 Funding
 References
 
Study population
Thirteen patients (three men, mean age 48 ± 17 years; Table 1), who underwent catheter ablation of FAT in our institution, were retrospectively studied. The mean duration of symptoms was 9 ± 11 years. No patient had undergone previous catheter ablation. One patient had combined aortic valve and coronary artery disease, whereas no evidence of structural heart disease was found in the remaining 12 patients. All anti-arrhythmic drugs were discontinued more than five half-lives prior to ablation.


View this table:
[in this window]
[in a new window]

  		Table 1 Clinical and electrophysiological characteristics of study population

 
Mapping and ablation
Mapping and ablation were guided by the CARTO electro-anatomic mapping system (Biosense Webster, Diamond Bar, CA, USA). An 8 Fr quadripolar catheter with a 3.5 mm distal tip electrode was used for mapping and ablation (Navistar Thermocool, Biosense Webster). Bipolar electrograms were recorded between the tip electrode and the ring electrode (electrode spacing 2 mm). Unipolar electrograms from the tip electrode were also recorded. Electrograms were filtered at 30–400 Hz (bipolar electrograms) and 0.05–400 Hz (unipolar electrograms). Bipolar electrograms recorded from the coronary sinus or right atrial appendage were used as time reference to determine the local activation time.

Mapping of the entire atrium was performed initially. Care was taken to ensure stable catheter position during mapping. Electrograms with large beat-to-beat variation in morphology at individual locations were discarded. A focal mechanism was suggested by a radial spread of activation from the discrete region of atrial myocardium. Detailed mapping was then carried out around the site of earliest activation, followed by radiofrequency ablation.

Analysis of electrograms
Local activation time was assigned on the steepest downslope of the unipolar electrograms. Electrograms were displayed at a sweep speed of 100–200 mm/s and at a gain of 0.67 mV/cm (bipolar electrograms) and 1 mV/cm (unipolar electrograms). The analysis of bipolar electrograms included the assessment of the number of negative deflections, peak-to-peak voltage, and duration (Figure 1). An electrogram deflection was defined as a positive or negative deflection of at least 0.07 mV (the baseline noise limit of the CARTO system in our laboratory), consistently recorded during a time window of 2 s. Electrogram fractionation was assessed on the basis of the number of the negative deflections.10Go,11Go In this respect, bipolar electrograms were categorized as electrograms with 1, 2, and ≥3 negative deflections, and the incidence of these electrograms was compared among different atrial regions. Peak-to-peak voltage was measured automatically between the positive and negative peaks. The measurements were adjusted manually whenever necessary. The duration of electrograms was measured with onscreen calipers between the onset and the end of electrograms. The onset of electrogram was defined as the instant of the earliest electrical activity deviating from the baseline at an angle of at least 45°.12Go The end of electrogram was defined as the instant when the last deflection returned to the baseline.


Figure 1
View larger version (12K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 1 Electrogram analysis. From top to bottom are lead II, the bipolar electrogram (RF1-2), and the unipolar electrogram (RF1) recorded by the mapping catheter. Digits indicate electrogram deflections. Vertical and horizontal dashed lines indicate bipolar electrogram duration and bipolar peak-to-peak voltage, respectively.

 
The analysis of unipolar electrograms consisted of the assessment of the number of negative deflections and peak-to-peak voltage. As in the case of bipolar signals, unipolar electrogram fractionation was assessed on the basis of the number of negative deflections.10Go,11Go Only deflections ≥0.1 mV were counted.13Go Unipolar electrograms were categorized as electrograms with 1, 2, and ≥3 negative deflections, and the incidence of different types of electrograms was compared among different atrial regions. The peak-to-peak voltage was measured automatically (and adjusted manually when necessary) between the positive and negative peak excursions of electrogram.

Atrial regions studied
Isochronal maps with isochrones drawn at 5, 10, and 15 ms intervals, respectively, were studied. The shell of the atrium was thus segmented into small atrial regions delimited by two consecutive isochrones. The characteristics of electrograms were compared among these regions.

Statistical analysis
Continuous data are expressed as mean ± SD, except for figures where they are expressed as mean ± SEM. Normally distributed parameters were compared with the Student’s t-test or one-way analysis of variance followed by Tukey’s post hoc test. Unipolar peak-to-peak voltage and bipolar peak-to-peak voltage were non-normally distributed and were therefore compared using the Kruskal–Wallis test. Differences in the number of electrogram deflections were assessed with the {chi}2 test. A P-value less than 0.05 was considered statistically significant. The analysis was carried out with JMP software version 5.1.1 (SAS Institute Inc., Cary, NC, USA) and Statview software version 5.0 (SAS Institute Inc.).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Limitations of the study
 Conclusions
 Future directions
 Funding
 References
 
All patients underwent successful ablation. The mean cycle length of tachycardia was 411 ± 64 ms (range 320–580). There were 13 foci: five at the crista terminalis, two in the inter-atrial septum, five at the tricuspid annulus, and one in the anterior left atrial wall. The mean procedure time was 209 ± 94 min, and the mean fluoroscopy time was 15 ± 11 min.

Characteristics of electrograms in the entire atrium
A total of 1205 bipolar and 1021 unipolar electrograms were suitable for analysis (77 ± 61 bipolar electrograms per patient and 72 ± 63 unipolar electrograms per patient, respectively). In one patient (Patient 4), some unipolar electrograms were partially hidden within the terminal portion of the ventricular electrograms; therefore we decided to analyse no unipolar electrograms in this patient. All electrograms were recorded prior to ablation. Electrogram characteristics are detailed in Table 2.


View this table:
[in this window]
[in a new window]

  		Table 2 Characteristics of electrograms

 
Characteristics of electrograms in the region surrounding the earliest activation site and in the remaining atrium
The region surrounding the earliest activation site and activated during the first 15 ms consisted of electrograms with greater degree of fractionation and with lower peak-to-peak voltage than the remaining atrium. Thus, the incidence of bipolar electrograms with multiple negative deflections was 88% (58% electrograms with 2 negative deflections and 30% electrograms with ≥3 negative deflections) in the region activated during the first 15 ms vs. 79% (58% electrograms with 2 negative deflections and 21% electrograms with ≥3 negative deflections) in the remaining atrium (P < 0.0001). The incidence of unipolar electrograms with multiple negative deflections in the same regions was 56% (41% electrograms with 2 negative deflections and 15% electrograms with ≥3 negative deflections) vs. 43% (34% electrograms with 2 negative deflections and 9% electrograms with ≥3 negative deflections) (P = 0.0001). The bipolar voltage was 1.33 ± 0.99 mV in the region activated within the first 15 ms vs. 1.61 ± 1.11 mV in the remaining atrium (P < 0001), whereas the unipolar voltage in these regions was 1.75 ± 0.92 vs. 1.95 ± 1.11 mV (P = 0.0188). In both regions, the incidence of electrograms with 2 negative deflections was greater than that of electrograms with ≥3 negative deflections. The bipolar electrogram duration did not differ significantly between the two atrial regions (49.53 ± 12.46 vs. 48.56 ± 10.98 ms, P = 0.1800).

When studying the entire population of electrograms, within the region activated during the first 15 ms we noticed a consistent gradient in both the number of negative deflections and the peak-to-peak voltage. Specifically, the incidence of both unipolar and bipolar electrograms with multiple negative deflections increased progressively (P < 0.0001), whereas the unipolar and bipolar peak-to- peak voltage decreased progressively (P < 0001) from the region activated between 10 and 15 ms to the earliest activation site (Table 3 and Figure 2). The maximum incidence of unipolar and bipolar electrograms with multiple negative deflections and the minimum value of the peak-to-peak voltage were reached in the region activated between 0 and 5 ms and at the earliest activation site.


Figure 2
View larger version (40K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 2 (A and B) Incidence of unipolar and bipolar electrograms with one, two, and three or more negative defections in the earliest activation site (focus), in the regions activated between 0 and 5 ms (region 0–5 ms), 5 and 10 ms (region 5–10 ms), and 10 and 15 ms (region 10–15 ms), respectively, and in the remaining atrium. The incidence of electrograms with 1 negative deflection decreased gradually, whereas the incidence of electrograms with 2 and ≥3 negative deflections increased gradually towards the earliest activation site. (C and D) Bipolar and unipolar voltage in the same atrial regions. Bipolar voltage decreases gradually towards the earliest activation site.

 


View this table:
[in this window]
[in a new window]

  		Table 3 Characteristics of electrograms in different atrial regions

 
The surface of the region activated within the first 15 ms was 4.88 ± 3.59 cm2 (range 0.9–12.5 cm2).

Activation pattern in the region surrounding the earliest activation site
The activation pattern in the region activated within the first 15 ms was visually analysed on isochronal maps. Irregular isochrones suggestive of anisotropic conduction were found in this region. Two examples are shown in Figure 3: panel A depicts the isochronal map during tachycardia originating from the right atrial septum. The isochrones drawn at 5, 10, and 15 ms are highly irregular and closely spaced in the vertical axis than in the horizontal axis, suggesting pronounced anisotropy, with slower conduction in the vertical than in the transversal axis. Panel B presents an isochronal map during a tachycardia originating from the anterior left atrial wall. Isochrones at 5, 10, and 15 ms are irregular and more crowded along the transversal axis than along the vertical axis, again suggesting anisotropy and directional differences in conduction velocity.


Figure 3
View larger version (21K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 3 Isochronal activation maps during focal atrial tachycardia originating from the right inter-atrial septum (A, right atrium viewed in left lateral projection) and in the anterior left atrial wall, respectively (B, left atrium viewed in antero-posterior projection). Isochrone lines were plotted at 5 ms intervals. The following regions are shown: region activated between 0 and 5 ms, coloured in red; region activated between 5 and 10 ms, coloured in green; region activated between 10 and 15 ms, coloured in blue. The remaining atrium is depicted in violet. Irregular, closely aligned isochrones in the vertical (upper map) and in the horizontal directions (lower map), respectively, suggest anisotropic conduction in the region surrounding the point of earliest activation. This is concordant with the increased incidence of electrograms with multiple negative deflections in this region, as showed in the insets. The bipolar and unipolar peak-to-peak voltage decreased towards the region activated between 0 and 5 ms and the earliest activation site. Blue rings indicate the tricuspid and mitral rings; red dot indicates a site where a His-bundle potential was recorded; tubular icons represent the pulmonary veins; yellow dots mark the points of earliest activation.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Limitations of the study
 Conclusions
 Future directions
 Funding
 References
 
The present study aimed at assessing the characteristics of bipolar and unipolar electrograms and the degree of electrogram fractionation in patients with FAT. The main results are: (i) the region surrounding the earliest activation site and generally activated within the first 15 ms was characterized by a higher degree of electrogram fractionation and a lower peak-to-peak voltage than the remaining atrium; this pattern was noted for both unipolar and bipolar electrograms and (ii) within this region, the degree of electrogram fractionation increased gradually, whereas the peak-to-peak voltage decreased gradually towards the earliest activation site.

The pattern of bipolar electrogram fractionation in the region surrounding the earliest activation site was similar to that of unipolar electrogram fractionation. This fact suggests a real fractionation due to the local electrical activation, rather than artifactual findings secondary to the directional sensitivity of the bipolar electrograms.14Go

Spach and Dolber15Go showed that fractionated extracellular waveforms are the result of asynchronous activation of adjacent, poorly coupled myocardial fibres separated by ingrowths of connective tissue septa. Given the fact that the amplitude of electrograms is related to the mass of the activated cardiac tissue, a larger amount of connective tissue along with less amount of myocardial fibres would result in lower electrogram voltage.15Go,16Go Electrical activation of such a medium is anisotropic, as reflected by irregular and closely aligned isochrones on the activation map. In view of these data, the higher degree of electrogram fractionation and the lower electrogram voltage in the region surrounding the earliest activation site when compared with the remaining atrium could suggest a higher degree of cell-to-cell uncoupling within the former region, thereby supporting the concept that inter-cellular uncoupling may play a role in the development of FAT. Moreover, computational studies showed that inter-cellular uncoupling can augment local dispersion of action potential duration,17Go which could also contribute to electrogram fractionation.18Go,19Go

One can speculate on the significance of increased connective tissue expression as a possible cause of impaired inter-cellular coupling in patients with FAT. Such conditions are naturally present in regions such as the crista terminalis or the pulmonary veins:20Go–22Go two of the most frequent sources of focal arrhythmias.23Go These conditions could be further augmented by some pathological states.24Go–27Go Indeed, inflammatory infiltrates and increased connective tissue have been observed in atrial specimens resected from patients with FAT undergoing surgical ablation.28Go–30Go Fromer et al.31Go reported two patients with no evidence of structural heart disease, in whom intra-operative mapping showed that tachycardias originated from well-defined areas of fractionated electrograms. Histological examination of these areas revealed focal atrial myocarditis, whereas examination of ventricular endomyocardial biopsies showed no abnormalities. These findings suggest that focal structural and electrical changes secondary to occult cardiomyopathic processes confined to the atria could underlie the substrate of FAT. Possibly, these changes would enhance and remodel the naturally present poor inter-cellular coupling in atrial regions that already contain cells with latent pacemaking capabilities such as the crista terminalis or the region of the pulmonary veins. This process could release the pacemaker cells from the inhibitory hyperpolarizing effects from the surrounding myocardium, thereby favouring focal arrhythmias.5Go

When studying the entire electrogram population recorded from our patients, within the region surrounding the earliest activation we noticed a gradient in both electrogram fractionation and peak-to-peak voltage of both bipolar and unipolar electrograms. The highest degree of electrogram fractionation and the lowest peak-to-peak voltage were encountered at the earliest activation site and in the region activated during the first 15 ms. From this region, the number of negative deflections decreased gradually, whereas the voltage increased gradually towards the remaining atrium. These data suggest a heterogeneous substrate with gradually changing electrophysiological proprieties.

The exact electrophysiological mechanism of tachycardias in this study remains unclear (i.e. automaticity, triggered activity, or micro-re-entry). However, the findings of the present study could be compatible with both automaticity and re-entry.

Thus, the concept of gradually changing electrical proprieties around tachycardia origin reminds of the sinoatrial node. It has been shown that due to a larger amount of connective tissue and a particular cell orientation, the inter-cellular coupling within the node is poorer than in the rest of the atrium.5Go,32Go This is an important feature, because it will protect the pacemaker cells against the inhibiting hyperpolarizing influences from the surrounding atrial myocardium, thus allowing the pacemaking process within the node.5Go,32Go From the central part of the node, which harbours the leading pacemaker site, there is a gradual transition in cell morphology and membrane electrical proprieties in all directions towards the periphery of the node.32Go–34Go This is another important feature for the proper function of the node, allowing the node to provide sufficient current to drive the much larger mass of atrial myocardium.6Go,35Go Corroborating these data with the findings of the present study, one can speculate that an ectopic focus, just like the sinus node, is an entity with complex architecture and electrophysiology. The point of earliest activation might act as the leading pacemaker site in the case of the sinus node. The poorer inter-cellular coupling in the area surrounding the earliest activation site compared with the rest of the atrium, as suggested by the differences in the degree of electrogram fractionation, reminds of the poorer inter-cellular coupling within the sinus node compared with the working atrial myocardium. As in the case of sinus node, this feature could be important for the pacemaking process. Furthermore, the gradual change in electrical proprieties within the area surrounding the earliest activation site, as suggested by the gradual change in the degree of electrogram fractionation and peak-to-peak voltage, could be necessary for the propagation of the excitation to the atrial musculature. In this respect, it is noteworthy that some focal ventricular tachycardias occurring immediately after successful defibrillatory shocks have been reported to origin in areas with large gradients in local electrical proprieties.36Go

Computational studies show that local heterogeneity in electrophysiological proprieties and cell-to-cell coupling are associated with increased dispersion in action potential duration and susceptibility to re-entry.17Go,37Go One could therefore speculate that the varying electrophysiological proprieties and inter-cellular coupling in the region surrounding the earliest activation site, as suggested by the electrogram characteristics in this region, could provide a substrate not only for automaticity but also for functional re-entry. In this case, the higher degree of electrogram fractionation and the lower voltage encountered in the central part of this region could indicate a discrete area of depressed electrical activity, which might serve as the pivot point around which the activation wave rotates. The participation of triggered activity in the mechanism of the tachycardias in this study and its relationship with the above-mentioned pattern of electrogram fractionation remain unclear.

In conclusion, the results of the present study seem to be consistent with the concept that the area encircling the point of earliest activation and generally activated within the first 15 ms may play an important role in the process of focal activity. In this case, the size of this region (up to 12.5 cm2 in this study) would suggest that the substrate of FAT is, in fact, a sizeable region with complex, gradually changing electrophysiological proprieties and not just a point-like area, as commonly regarded.38Go


   Limitations of the study
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Limitations of the study
Conclusions
 Future directions
 Funding
 References
 
In the present study, mapping was performed with the CARTO system. Electrograms were recorded with the Navistar catheter (3.5 mm tip electrode and 2 mm inter-electrode distance), and were filtered at 30–400 Hz (bipolar signals) and 0.05–400 Hz (unipolar signals). Given the fact that the configuration of electrograms is dependent on the catheter type and the recording technique,39Go electrogram characteristics found in the present study may not be applicable to electrograms recorded in other circumstances Secondly, it should be acknowledged that we studied a relatively small number of patients; therefore, these results have to be confirmed in larger studies. Finally, we analysed FAT originating mainly at four atrial regions: crista terminalis, tricuspid annulus, inter-atrial septum, and anterior left atrial wall. Therefore, it remains unclear whether the findings could be extended to tachycardias originating from other atrial regions.


   Conclusions
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Limitations of the study
 Conclusions
Future directions
 Funding
 References
 
The present study confirms previous observations with regard to increased electrogram fractionation in the region surrounding the point of earliest activation. This region could be relatively large (up to several square centimetres), and electrogram fractionation increases gradually towards the point of earliest activation. These findings suggest that a sizeable atrial region with gradually changing electrophysiological proprieties could underlie the substrate of FAT.


   Future directions
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Limitations of the study
 Conclusions
 Future directions
Funding
 References
 
The present study raises the question of whether the differences in electrogram characteristics between the region surrounding the earliest activation site and the remaining atrium would be noted not only during tachycardia but also during sinus rhythm. This would confirm the existence of an anatomical substrate for FAT. Therefore, studies comparing electrogram characteristics during tachycardia and sinus rhythm are warranted. Preliminary data from two of our patients (Patients 11 and 13, Figure 4), who underwent mapping both during tachycardia and during sinus rhythm, suggest that this hypothesis may indeed be true.

Conflict of interest: none declared.


Figure 4
Figure 4
View larger version (61K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 4 Electrogram characteristics in Patients 11 and 13. These patients underwent mapping during sinus rhythm within the same ablation procedure. Patient 11 underwent sinus mapping before the ablation, whereas Patient 13 underwent sinus mapping after the ablation; in the latter patient, all electrograms recorded within 5 mm around the ablation points were discarded in order to avoid the inclusion of signals affected by the ablation. In these patients, we compared electrogram parameters during tachycardia and during sinus rhythm. (A) Electrogram characteristics during tachycardia in the region around the focus (region activated during the first 15 ms) and in the remaining atrium. (B) Electrogram characteristics during sinus rhythm in the same regions. During tachycardia, the peak-to-peak voltage in the region around the focus is less than the peak-to-peak voltage in the remaining atrium. In addition, a higher incidence of electrograms with multiple negative deflections exits in the former region when compared with the later one. A similar pattern exists during sinus rhythm. These data indicate that the differences in electrogram characteristics between the atrial region harbouring the focus and the remaining atrium are not dependent on the heart rhythm and heart frequency, thereby supporting the hypothesis concerning an underlying anatomic substrate for focal atrial tachycardia.

 

   Funding
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Limitations of the study
 Conclusions
 Future directions
 Funding
References
 
This work was supported by a grant from Biosense Webster Scandinavia and Carldavid Jonsson Research Foundation.


   Footnotes
 
{dagger} Presented in part at Cardiorhythm, 2–4 February 2007, Hong Kong and at the 13th World Congress in Pacing and Electrophysiology, 2–6 December 2007, Rome, Italy. Back


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Limitations of the study
 Conclusions
 Future directions
 Funding
 References
 
[1] Klersy C, Chimeti M, Marangoni E, Comelli M, Salerno A. Factors that predict spontaneous remission of ectopic atrial tachycardia. Eur Heart J (1993) 14:1654–6.[Abstract/Free Full Text]

[2] Wharton M, Shenasa H, Barold H, Simons G, Vergara I. Ablation of atrial tachycardia in adults. In: Radiofrequency Catheter Ablation of Cardiac Arrhythmias: Basic Concepts and Clinical Applications—Huang SKS, Wilber DJ, eds. (2000) New York: Futura Publishing. 139–63.

[3] Wang YG, Kumar R, Wagner MB, Wilders R, Golod DA, Goolsby WN, et al. Electrical interactions between a real ventricular cell and an anisotropic two-dimensional sheet of model cells. Am J Physiol Heart Circ Physiol (2000) 278:H452–60.[Abstract/Free Full Text]

[4] Joyner RW, Wang YG, Wilders R, Golod DA, Wagner MB, Kumar R, et al. A spontaneously active focus drives a model atrial sheet more easily than a model ventricular sheet. Am J Physiol Heart Circ Physiol (2000) 279:H752–63.[Abstract/Free Full Text]

[5] Wilders R, Wagner MB, Golod DA, Kumar R, Wang YG, Goolsby WN, et al. Effects of anisotropy on the development of cardiac arrhythmias associated with focal activity. Pflugers Arch (2000) 441:301–12.[CrossRef][Web of Science][Medline]

[6] Joyner RW, Wilders R, Wagner MB. Propagation of pacemaker activity. Med Biol Eng Comput (2007) 45:177–87.[CrossRef][Web of Science][Medline]

[7] de Bakker JM, Hauer RN, Bakker PF, Becker AE, Janse MJ, Robles de Medina EO. Abnormal automaticity as mechanism of atrial tachycardia in the human heart—electrophysiologic histologic correlation: a case report. J Cardiovasc Electrophysiol (1994) 5:335–44.[Web of Science][Medline]

[8] Gardner PI, Ursell PC, Fenoglio JJ, Wit AL. Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts. Circ Res (1985) 72:596–611.

[9] Roberts-Thomson KC, Kistler PM, Kalman JM. Atrial tachycardia: mechanisms, diagnosis and management. Curr Probl Cardiol (2005) 30:529–73.[CrossRef][Web of Science][Medline]

[10] de Groot NM, Shalji MJ. Fragmented, long-duration, low amplitude electrograms characterize the origin of focal atrial tachycardia. J Cardiovasc Electrophysiol (2006) 17:1086–92.[CrossRef][Web of Science][Medline]

[11] Konings KTS, Smeets JLRM, Penn OC, Wellens HJJ, Allessie MA. Configuration of unipolar atrial electrograms during electrically induced atrial fibrillation in humans. Circulation (1997) 95:1231–41.[Abstract/Free Full Text]

[12] Paul T, Moak JP, Morris C, Garson A. Epicardial mapping: how to measure local activation? Pacing Clin Electrophysiol (1990) 13:285–92.[CrossRef][Medline]

[13] Villacastin J, Almendral J, Arenal A, Castellano NP, Gonzalez S, Ortiz M, et al. Usefulness of unipolar electrograms to detect isthmus block after radiofrequency ablation of typical atrial flutter. Circulation (2000) 102:3080–5.[Abstract/Free Full Text]

[14] Ndrepepa G, Caref EB, Yin H, el-Sherif N, Restivo M. Activation time determination by high-resolution unipolar and bipolar extracellular electrograms in the canine heart. J Cardiovasc Electrophysiol (1995) 6:174–88.[Web of Science][Medline]

[15] Spach MS, Dolber PC. Relating extracellular potentials and their derivatives to anisotropic propagation at a microscopic level in human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age. Circ Res (1986) 58:356–71.[Abstract/Free Full Text]

[16] Brunckhorst CB, Stevenson WG, Jackman WM, Kuck KH, Soejima K, Nakagawa H, et al. Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction. Eur Heart J (2002) 23:1131–8.[Abstract/Free Full Text]

[17] Lesh MD, Pring M, Spear JF. Cellular uncoupling can unmask dispersion of action potential duration in ventricular myocardium. A computer modeling study. Circ Res (1989) 65:1426–40.[Abstract/Free Full Text]

[18] Tai CT, Chen SA, Tzeng JW, Kuo BI, Ding YA, Chang MS, et al. Prolonged fractionation of paced right atrial electrograms in patients with atrial flutter and fibrillation. J Am Coll Cardiol (2001) 37:1651–7.[Abstract/Free Full Text]

[19] Li H, Hare J, Mughal K, Krum D, Biehl M, Deshpande S, et al. Distribution of atrial electrogram types during atrial fibrillation: effect of rapid atrial pacing and intercaval junction ablation. J Am Coll Cardiol (1996) 27:1713–21.[Abstract]

[20] Sanchez-Quintana D, Anderson RH, Cabrera JA, Climent V, Martin R, Farre J, et al. The terminal crest: morphological features relevant to electrophysiology. Heart (2002) 88:406–11.[Abstract/Free Full Text]

[21] Arora R, Kadish A. Fundamentals in cardiac mapping. In: Catheter Ablation of Cardiac Arrhythmias—Huang SKS, Wood MA, eds. (2006) 112. Philadelphia: Elsevier.

[22] Ho S, Cabrera J, Tran V, Farre J, Anderson R, Sanchez-Quintana D. Architecture of the pulmonary veins: relevance to radiofrequency ablation. Heart (2001) 86:265–70.[Abstract/Free Full Text]

[23] Lesh MD, Kalman JM, Karch MR. Use of intracardiac echocardiography during electrophysiologic evaluation and therapy of atrial arrhythmias. J Cardiovasc Electrophysiol (1998) 9:S40–7.[Web of Science][Medline]

[24] Pandit SV, Jalife J. Aging and atrial fibrillation research: where we are and where we should go. Heart Rhythm (2007) 4:186–7.[CrossRef][Web of Science][Medline]

[25] Anyukhovsky EP, Sosunov EA, Plotnikov A, Gainullin RZ, Jhang JS, Marboe CC, et al. Cellular electrophysiologic properties of old canine atria provide a substrate for arrhythmogenesis. Cardiovasc Res (2002) 54:462–9.[Abstract/Free Full Text]

[26] Matsuyama TA, Inoue S, Kobayashi Y, Sakai T, Saito T, Katagiri T, et al. Anatomical diversity and age-related histological changes in the human right atrial posterolateral wall. Europace (2004) 6:307–15.[Abstract/Free Full Text]

[27] Becker AE. How structurally normal are human atria in patients with atrial fibrillation? Heart Rhythm (2004) 1:627–31.[CrossRef][Web of Science][Medline]

[28] Josephson ME, Spear JF, Harken AH, Horowitz LN, Dorio RJ. Surgical excision of automatic atrial tachycardia: anatomic and electrophysiologic correlates. Am Heart J (1982) 104:1076–85.[CrossRef][Web of Science][Medline]

[29] Wyndham CR, Arnsdorf MF, Levitsky S, Smith TC, Dhingra RC, Denes P, et al. Successful surgical excision of focal paroxysmal atrial tachycardia. Observations in vivo and in vitro. Circulation (1980) 62:1365–72.[Abstract/Free Full Text]

[30] Moro C, Rufilanchas JJ, Tamargo J, Novo L, Martinez J. Evidence of abnormal automaticity and triggering activity in incessant ectopic atrial tachycardia. Am Heart J (1988) 116:550–2.[CrossRef][Web of Science][Medline]

[31] Fromer M, Genton C, Schlaepfer J, Goy JJ, Kappenberger L. Is there an isolated arrhythmogenic right atrial myocarditis? Eur Heart J (1990) 11:566–71.[Abstract/Free Full Text]

[32] Boyett MR, Honjo H, Kodama I. The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc Res (2000) 47:658–87.[Abstract/Free Full Text]

[33] Boyett MR, Dobrzynski H, Lancaster MK, Jones SA, Honjo H, Kodama I. Sophisticated architecture is required for the sinoatrial node to perform its normal pacemaker function. J Cardiovasc Electrophysiol (2003) 14:104–6.[CrossRef][Web of Science][Medline]

[34] Kodama I, Boyett MR. Regional differences in the electrical activity of the rabbit sinus node. Pflugers Arch (1985) 404:214–26.[CrossRef][Web of Science][Medline]

[35] Joyner RW, van Capelle FJ. Propagation through electrically coupled cells: how a small SA node drives a large atrium? Biophys J (1986) 50:1157–64.[Web of Science][Medline]

[36] Wharton JM, Wolf PD, Smith WM, Chen PS, Frazier DW, Yabe S, et al. Cardiac potential and potential gradient fields generated by single, combined, and sequential shocks during ventricular defibrillation. Circulation (1992) 85:1510–23.[Abstract/Free Full Text]

[37] Clayton RH, Holden AV. Dispersion of cardiac action potential duration and the initiation of re-entry: a computational study. Biomed Eng Online (2005) 4:11.[CrossRef][Medline]

[38] Singarayar S, Kalman JM. Focal atrial tachycardia: is it yet time for a new paradigm? J Cardiovasc Electrophysiol (2004) 15:1394–5.[CrossRef][Web of Science][Medline]

[39] Josephson ME. Catheter and surgical ablation in the therapy of arrhythmias. In: Clinical Cardiac Electrophysiology: Techniques and Interpretations (2002) 3rd ed. Philadelphia: Lippincott Williams, & Wilkins. 751.


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



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
10/10/1195    most recent
eun192v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Liuba, I.
Right arrow Articles by Walfridsson, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liuba, I.
Right arrow Articles by Walfridsson, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?