liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Focal atrial tachycardia: Insights concerning the arrhythmogenic substrate based on analysis of intracardiac electrograms and inflammatory markers
Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Focal atrial tachycardias are tachycardias characterized by a radial spread of activation from a discrete area of the atrial myocardium. They account for 10-15% of supraventricular tachycardias and are generally poorly responsive to pharmacological treatment. The pathophysiologic substrate of these arrhythmias remains poorly understood. Computational studies suggest that a certain degree of intercellular uncoupling and anisotropy are important prerequisites for the development of focal arrhythmias. The anisotropy and intercellular uncoupling could promote focal arrhythmias by minimizing the suppressive effect of the surrounding atrial muscle on the pacemaking process in the focus. This hypothesis would be in agreement with the fact that fractionated electrograms, a marker of anisotropy and reduced intercellular coupling, are often recorded at the site of earliest activated site. Reduced intercellular coupling could be induced by factors enhancing the amount of intracardiac connective tissue, such as advancing age or cardiac disease states. Indeed, focal inflammatory processes have been reported in atrial specimens resected from patients with focal tachycardia undergoing arrhythmia surgery.

Methods: In a group of patients with paroxysmal and permanent atrial fibrillation we sought to assess whether there is a link between inflammation and the occurrence of atrial arrhythmia. We therefore analyzed different inflammatory markers (C-reactive protein and interleukin-6 and 8) in the systemic and pulmonary circulation as well as in the heart in these patients. In addition, we assessed the extent of intercellular uncoupling in the vicinity of tachycardia origin in patients with focal atrial tachycardia. We also assessed the impact of electrogram fractionation on the method of activation time determination, by comparing different methods for estimating activation time with regard to the appearance of the resultant activation maps and the location of the foci. We also assessed the observer variability in the estimation of activation time during mapping of these tachycardias.

Results: There was no evidence of elevated circulatory levels of inflammatory markers in patients with paroxysmal atrial fibrillation. However, patients with permanent atrial fibrillation had increased levels of inflammatory markers (interleukin-8) in the systemic circulation but not in the pulmonary circulation or in the heart. In patients with focal atrial tachycardia, a higher degree of electrogram fractionation existed in the region surrounding the earliest activation site and activated within the first 15 ms as compared with the remaining atrium. Moreover, within this region, from the periphery towards the earliest activated site, there was a gradual increase in electrogram fractionation as well as a gradual decrease in the peak-to-peak voltage. When comparing different methods for estimating local activation time we found that different methods can generate activation maps with different appearances and foci with different locations. However, regardless of the method of activation time determination, the foci tend to cluster within relatively large areas of low-amplitude fractionated electrograms. In addition we found significant observer variability in the estimation of the local activation time.

Conclusion: Patients with paroxysmal atrial fibrillation (and probably focal atrial tachycardia) do not have elevated levels of inflammatory markers. The increased levels of interleukin-8 in the systemic circulation suggest a link between long-lasting arrhythmia and inflammation. A relatively wide area of increased electrogram fractionation exists around the site of origin of focal atrial tachycardia. These findings suggest a sizeable atrial region with particular electrophysiological proprieties and raise the possibility of an anatomical substrate of the tachycardia. Increased electrogram fractionation can impact the process of activation determination, as suggested by the fact that different methods compute foci with different locations. In addition, there is significant observer variability in the estimation of local activation time in these patient.

Place, publisher, year, edition, pages
Linköp: Linköping University Electronic Press , 2009. , 96 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1148
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-20461ISBN: 978-91-7393-556-2 (print)OAI: oai:DiVA.org:liu-20461DiVA: diva2:234582
Public defence
2009-09-04, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Opponent
Note
Article II and III are the same article while article III is linked to the corrected article and article II to the original article.Available from: 2009-09-09 Created: 2009-09-09 Last updated: 2010-02-25Bibliographically approved
List of papers
1. Source of inflammatory markers in patients with atrial fibrillation
Open this publication in new window or tab >>Source of inflammatory markers in patients with atrial fibrillation
Show others...
2008 (English)In: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, ISSN 1532-2092, Vol. 10, no 7, 848-853 p.Article in journal (Refereed) Published
Abstract [en]

AIMS: Elevated levels of C-reactive protein and other inflammatory markers have been reported in some patients with atrial fibrillation (AF). Whether this finding is related to AF per se or to other conditions remains unclear. In addition, the source of inflammatory markers is unknown. Therefore, in the present study, we sought to assess the extent and the source of inflammation in patients with AF and no other concomitant heart or inflammatory conditions.

METHODS AND RESULTS: The study group consisted of 29 patients referred for radiofrequency catheter ablation: 10 patients with paroxysmal AF, 8 patients with permanent AF, and 10 control patients with Wolf-Parkinson-White (WPW) syndrome and no evidence of AF (mean age 54 +/- 11 vs. 57 +/- 13 vs. 43 +/- 16). No patient had structural heart diseases or inflammatory conditions. High-sensitive C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were assessed in blood samples from the femoral vein, right atrium, coronary sinus, and the left and right upper pulmonary veins. All samples were collected before ablation. Compared with controls and patients with paroxysmal AF, patients with permanent AF had higher plasma levels of IL-8 in the samples from the femoral vein, right atrium, and coronary sinus, but not in the samples from the pulmonary veins (median values in the femoral vein: 2.58 vs. 2.97 vs. 4.66 pg/mL, P = 0.003; right atrium: 2.30 vs. 3.06 vs. 3.93 pg/mL, P = 0.013; coronary sinus: 2.85 vs. 3.15 vs. 4.07, P = 0.016). A high-degree correlation existed between the IL-8 levels in these samples (correlation coefficient between 0.929 and 0.976, P < 0.05). No differences in the C-reactive protein and IL-6 levels were noted between the three groups of patients.

CONCLUSION: The normal levels of C-reactive protein and IL-6, along with the elevated levels of IL-8 in patients with permanent AF but not in those with paroxysmal AF, suggest a link between a low-grade inflammatory reaction and long-lasting AF. The elevated IL-8 levels in the peripheral blood, right atrium, and coronary sinus but not in the pulmonary veins suggest a possible source of inflammation in the systemic circulation.

Keyword
Atrial fibrillation, Inflammation, Catheter ablation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20458 (URN)10.1093/europace/eun111 (DOI)18523031 (PubMedID)
Available from: 2009-09-09 Created: 2009-09-09 Last updated: 2013-12-17Bibliographically approved
2. Corrigendum for: Focal atrial tachycardia: increased electrogram fractionation in the vicinity of the earliest activation site. In Europace (ISSN 1099-5129), vol 10, issue 11, pg 1357
Open this publication in new window or tab >>Corrigendum for: Focal atrial tachycardia: increased electrogram fractionation in the vicinity of the earliest activation site. In Europace (ISSN 1099-5129), vol 10, issue 11, pg 1357
2008 (English)In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 10, no 11, 1357-1357 p.Article in journal (Other academic) Published
Abstract [en]

P values of P < 0.0001 should have been given in the abstractfor the increase within the region activated during the first15 ms of both the incidence of bipolar electrograms with multiplenegative deflections and of the incidence of unipolar electrogramswith multiple negative deflections.

In the section ‘Characteristics of electrograms in theregion surrounding the earliest activation site and in the remainingatrium’ the P value for bipolar voltage should be P <0.0001, not P < 0001. In the same section the P value forthe decrease of unipolar and bipolar peak-to-peak voltage shouldbe P < 0.0001, not P < 0001.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16116 (URN)10.1093/europace/eun290 (DOI)
Available from: 2009-01-08 Created: 2009-01-07 Last updated: 2017-12-14Bibliographically approved
3. Corrigendum for: Focal atrial tachycardia: increased electrogram fractionation in the vicinity of the earliest activation site. In Europace (ISSN 1099-5129), vol 10, issue 11, pg 1357
Open this publication in new window or tab >>Corrigendum for: Focal atrial tachycardia: increased electrogram fractionation in the vicinity of the earliest activation site. In Europace (ISSN 1099-5129), vol 10, issue 11, pg 1357
2008 (English)In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 10, no 11, 1357-1357 p.Article in journal (Other academic) Published
Abstract [en]

P values of P < 0.0001 should have been given in the abstractfor the increase within the region activated during the first15 ms of both the incidence of bipolar electrograms with multiplenegative deflections and of the incidence of unipolar electrogramswith multiple negative deflections.

In the section ‘Characteristics of electrograms in theregion surrounding the earliest activation site and in the remainingatrium’ the P value for bipolar voltage should be P <0.0001, not P < 0001. In the same section the P value forthe decrease of unipolar and bipolar peak-to-peak voltage shouldbe P < 0.0001, not P < 0001.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16116 (URN)10.1093/europace/eun290 (DOI)
Available from: 2009-01-08 Created: 2009-01-07 Last updated: 2017-12-14Bibliographically approved
4. Activation mapping of focal atrial tachycardia: the impact of the method for estimating activation time
Open this publication in new window or tab >>Activation mapping of focal atrial tachycardia: the impact of the method for estimating activation time
2009 (English)In: Journal of interventional cardiac electrophysiology (Print), ISSN 1383-875X, E-ISSN 1572-8595, Vol. 26, no 3, 169-180 p.Article in journal (Refereed) Published
Abstract [en]

Purpose

Different methods can be used to estimate activation time during the mapping of focal atrial tachycardia. The present study aimed to compare activation maps generated by three widely used methods of determining activation time.

Methods

Fourteen patients (mean age 48 ± 17 years) with focal atrial tachycardia were investigated. Mapping was performed with the CARTO system. All patients underwent successful ablation. Local activation time was successively defined as the peak amplitude (Bi-peak), the steepest downslope (Bi-dslope), and the onset (Bi-on) of the bipolar electrograms.

Results

The three methods of activation time determination were highly correlated with one another but generated foci with different locations. The distances between the foci generated by the different methods were 4.36 ± 4.91 mm (Bi-peak–Bi-dslope), 7.21 ± 5.11 mm (Bi-peak–Bi-on), and 7.21 ± 5.87 mm (Bi-dslope–Bi-on) (p = 0.26). Also, the three methods generated foci with different diameters: 3.13 ± 2.17 mm for Bi-peak, 2.81 ± 0.78 for Bi-dslope, and 2.54 ± 0.14 mm for Bi-on (p = 0.60). However, the foci tended to cluster within relatively wide regions of low-amplitude fractionated electrograms. The surface of these regions was 3.81 ± 2.34 cm2 (Bi-peak), 3.38 ± 2.12 cm2 (Bi-dslope), and 4.76 ± 3.01 cm2 (Bi-on) (p = 0.34).

Conclusion

The three methods of activation time determination, although highly correlated with one another, may generate foci of different sizes and in different locations. However, the foci tend to cluster within relatively large areas of low-amplitude fractionated electrograms. These findings suggest a sizeable atrial region with particular electrophysiological proprieties and raise the possibility of an anatomical substrate of the tachycardia. During mapping, this region can be roughly delineated by all three methods of activation time estimation. However, details concerning the activation pattern within the region and the location of the focus vary among the methods.

Place, publisher, year, edition, pages
Springer, 2009
Keyword
Tachycardia, mapping, catheter ablation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20459 (URN)10.1007/s10840-009-9437-0 (DOI)000272848800004 ()
Note

Presented in part at the American Heart Association Scientific Sessions 2008, New Orleans, LA, USA, November 8–12, 2008

Available from: 2009-09-09 Created: 2009-09-09 Last updated: 2017-12-13Bibliographically approved
5. Electroanatomic Mapping of Focal Atrial Tachycardia: Reproducibility ofActivation Time Measurement and Focus Localization
Open this publication in new window or tab >>Electroanatomic Mapping of Focal Atrial Tachycardia: Reproducibility ofActivation Time Measurement and Focus Localization
2010 (English)Article in journal (Other academic) Submitted
Abstract [en]

Background: Different algorithms of estimating local activation time (LAT) can be usedduring the mapping of focal atrial tachycardia (FAT).

Objective: The impact of these algorithms on the reproducibility of LAT measurementand the location of the focus.

Methods: Fifteen patients (48 ± 17 yrs) with FAT were studied. Three independentobservers reviewed 1438 bipolar electrograms and successively assigned the LAT on thepeak amplitude (Bi-peak), the steepest downslope (Bi-dslope), and the onset (Bi-on) ofthe electrograms. The reproducibility of LAT measurement was estimated.

Results: The mean interobserver absolute differences in LAT for the three algorithmswere 1.47 ± 2.75 ms (Bi-peak) vs. 2.15 ± 3.89 ms (Bi-dslope) vs. 2.87 ± 3.47 (Bi-on) (p <0.0001). The corresponding intraobserver differences were 2.29 ± 3.74 ms (Bi-peak) vs2.47 ± 4.17 ms (Bi-dslope) vs 3.16 ± 4.49 ms (Bi-on) (p < 0.0001). The interobserverdifferences in the location of the focus were 3.57 ± 3.81 mm (Bi-peak) vs 5.47 ± 4.98mm (Bi-dslope) vs 6.57 ± 6.94 mm (Bi-on) (p = 0.03), with differences of up to 13 mm(Bi-peak), 16 mm (Bi-dslope), and 25 mm (Bi-on). However, regardless of the method ofLAT determination, the foci computed by the three observers clustered within regions oflow-amplitude fractionated electrograms.

Conclusions: Significant observer variability exists among the three algorithms, whichtend to compute different LAT and foci with different locations. However, the foci aresituated in regions of low voltage fractionated electrograms.

Keyword
Ectopic atrial tachycardia; catheter ablation; atrial electrogram
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20460 (URN)
Available from: 2009-09-09 Created: 2009-09-09 Last updated: 2013-12-17Bibliographically approved

Open Access in DiVA

Focal atrial tachycardia(768 kB)392 downloads
File information
File name FULLTEXT01.pdfFile size 768 kBChecksum SHA-512
b5465a9a3476f73fd30e5d22b23fbdbe9f91248108fed51ab1b0bd42690fbe0b8dc66ab0d74d9989e6a20a4f0b958454345e29a115394ccd1625347dd23eeeee
Type fulltextMimetype application/pdf
Cover(297 kB)31 downloads
File information
File name COVER01.pdfFile size 297 kBChecksum SHA-512
49318abc269cba5a60407c6601cc3d39e9928826a02572493576df62bbd052c3a53f10cdd73b6bbbddefabffe9653db6ef9ce343d3e2fc4277b25bd7071d3249
Type coverMimetype application/pdf

Authority records BETA

Liuba, Ioan

Search in DiVA

By author/editor
Liuba, Ioan
By organisation
Cardiology Faculty of Health SciencesDepartment of Cardiology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 392 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 982 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf