I. Extensive experimental and clinical data suggest that certain electrical and structural changes develop in the atria of patients with atrial fibrillation (AF). These alterations are commonly referred as atrial remodeling and are considered to play a crucial role in the self-perpetuation of this arrhythmia.
a. A hallmark of LA structural remodeling is the LA dilatation which is a predictor for progression to chronic AF and therapeutic failure as well. However, AF is associated not only with LA enlargement but also with asymmetrical changes in the left atrial geometry.
b. Furthermore, the electrical remodeling is characterized by slower and asynchronous inter- and intra-atrial conduction that also contributes to the maintenance of AF. Some studies suggested a role of the conduction block in the Bachmann’s bundle, connecting the right and left atrium, in the AF pathophysiology and LA remodeling.
II. Echocardiography and especially the tissue Doppler method can provide additional insight into the nature of the LA remodeling, because it allows the characterization of the intrinsic LA velocities.
a. Using pulsed-wave tissue Doppler (PW-TDI) is possible to measure the interval from the onset of the surface P wave to the A´ velocity at the lateral mitral annulus as a representation of the total interatrial conduction time (TACT). In number of studies, it was demonstrated that prolonged TACT was associated with new-onset AF, AF after open heart surgery, and AF recurrences after electrical cardioversion and catheter ablation.
b. An important limitation of the previous studies is that TACT has never been validated by direct measurements of the true electrical conduction in the LA. Moreover, it was assumed that the activation of the lateral MA must be the latest LA activation site.
III. In this study, we sought to evaluate the feasibility of the PW-TDI as a simple and quick method to evaluate the LA asynchrony. For the purpose, we measured the time intervals from the onset of P-wave to the A´ (P-A´) in PW-TDI at 4 different left atrial sites next to mitral annulus (septal, lateral, anterior and inferior) in patients referred for electrophysiological study and catheter ablation because of atrial fibrillation or other arrhythmias.
a. The differences between the longest and shortest P-A´ (DLS-PA´), as well as the standard deviation (SD-4PA´) of all 4 values were calculated as indexes for LA asynchrony. Importantly, LA asynchrony in patients with AF was compared with a matched control group of patients without history of AF.
b. Moreover, the TACT was validated by comparing it with the actual electrical activation of the left atrium measured directly in the coronary sinus. For this purpose, the intervals between the onset of the P-wave and the local LA activation at the distal electrode pair of a catheter inserted in the coronary sinus were measured.
c. Having in mind the ovoid LA shape and asymmetrical changes in LA geometry observed in patients with AF, we hypothesized that the lateral mitral annulus may not always be the latest activation spot. Therefore, we sought to determine the latest LA activation site exhibiting the longest P-A´ interval, as well as to describe the sequence of LA activation in AF patients and non-AF controls.
IV. One hundred and thirty patients with AF (AF group) and 70 patients without a history of AF (non-AF control group) were examined prospectively using PW-TDI.
a. Both groups were matched for the baseline characteristics, including LA diameter. The P-A´ interval measured with PW-TDI at the lateral LA showed a strong, positive, linear correlation with the P-A activation at the distal poles of the CS catheter at the lateral MA: Pearson r=0.708; P=0.0001.
b. Asynchrony in the AF group was more pronounced in comparison to the non-AF control group. Patients in the AF group had longer DLS-PA´ as compared to controls: 37±16 msec. vs. 28±13 msec.; P=0.0001, as well as bigger SD-4PA´: 17±7 msec. vs. 13±5 msec.; P=0.0001.
c. Furthermore, distinct patterns of LA activation were observed. Most AF patients (86.5%) showed an upward LA activation with inferior LA breakthrough, whereas the non-AF controls exhibited mostly a downward LA activation (65.5%), spreading from LA roof downwards.
d. ROC analysis revealed that P-A´ at anterior LA successfully discriminated patients with AF from the non-AF controls (AUC 0.85, P<0.0001). A cut off value for P-A´ anterior > 55 msec. discriminated between AF patients and controls with 85% sensitivity; 81% specificity; positive predictive value of 0.898, and negative predictive value of 0.707.
V. In conclusion, PW-TDI can be reliably used to assess the LA asynchrony. Patients with atrial fibrillation showed greater LA asynchrony in PW-TDI independently from the LA dimensions. For the first time, we described that LA activation showed 3 distinct patterns with the upward LA activation being the most frequently observed in patients with AF. Patients with AF demonstrated a prolonged P-A´ activation time at the anterior left atrium. P-A´ at anterior LA > 55 msec. discriminates between patients with AF and non-AF controls with high sensitivity and specificity. This method can be useful to identity patients at risk for occurrence of new-onset atrial fibrillation, as well as to assess the severity of the LA remodeling in order to improve the selection of patients for catheter ablation.:Table of Contents
1 Background 5
1.1 Mechanisms of initiation and perpetuation of atrial fibrillation 5
1.2 Left atrial remodeling in atrial fibrillation 7
1.3 Echocardiographic assessment of left atrial remodeling 8
1.4 Pathophysiology of interatrial conduction in atrial fibrillation 10
2 Objectives and methods 11
2.1 Study objectives 11
2.2 Methods 11
2.2.1 Echocardiography 13
2.2.2 Electrophysiological study 15
2.2.3 Statistical methods 16
3 Publication 17
4 Discussion 26
5 Limitations 30
6 Conclusion 31
7 Synopsis 32
8 References 36
9 Selbstständigkeitserklärung 47
10 Curriculum vitae and list of publications 48
11 Danksagung /Acknowledgments 56
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:16692 |
| Date | 02 November 2017 |
| Creators | Dinov, Borislav |
| Contributors | Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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