Catheter ablation is a curative therapeutic approach for atrial fibrillation (AF). Ablation of rotational sources based on basket catheter measurements has been proposed as a promising approach in patients with persistent AF to complement pulmonary vein isolation. However, clinically reported success rates are equivocal calling for a mechanistic investigation under controlled conditions. We present a computational framework to benchmark ablation strategies considering the whole cycle from excitation propagation to electrogram acquisition and processing to virtual therapy. Fibrillation was induced in a patient-specific 3D volumetric model of the left atrium, which was homogeneously remodelled to sustain reentry. The resulting extracellular potential field was sampled using models of grid catheters as well as realistically deformed basket catheters considering the specific atrial anatomy. Virtual electrograms were processed to compute phase singularity density maps to target rotor tips with up to three circular ablations. Stable rotors were successfully induced in different regions of the homogeneously remodelled atrium showing that rotors are not constrained to unique anatomical structures or locations. Phase singularity density maps correctly identified and located the rotors (deviation < 10 mm) based on catheter recordings only for sufficient resolution (inter-electrode distance = 3 mm) and proximity to the wall (< 10 mm). Targeting rotor sites with ablation did not stop reentries in the homogeneously remodelled atria independent from lesion size (1-7 mm radius), from linearly connecting lesions with anatomical obstacles, and from the number of rotors targeted sequentially (up to 3). Our results show that phase maps derived from intracardiac electrograms can be a powerful tool to map atrial activation patterns, yet they can also be misleading due to inaccurate localization of rotor tips depending on electrode resolution and distance to the wall. This should be considered to avoid ablating regions that are in fact free of rotor sources of AF. In our experience, ablation of rotor sites was not successful to stop fibrillation. Our comprehensive simulation framework provides the means to holistically benchmark ablation strategies in silico under consideration of all steps invol
L. A. Unger, M. Rottmann, G. Seemann, and O. Dössel. Detecting phase singularities and rotor center trajectories based on the Hilbert transform of intraatrial electrograms in an atrial voxel model. In Current Directions in Biomedical Engineering, vol. 1(1) , pp. 38-41, 2015
This work aimed at the detection of rotor centers within the atrial cavity during atrial fibrillation on the basis of phase singularities. A voxel based method was established which employs the Hilbert transform and the phase of unipolar electrograms. The method provides a 3D overview of phase singularities at the endocardial surface and within the blood volume. Mapping those phase singularities from the inside of the atria at the endocardium yielded rotor center trajectories.We discuss the results for an unstable and a more stable rotor. The side length of the areas covered by the trajectories varied from 1.5mm to 10 mm. These results are important for cardiologists who target rotors with RF ablation in order to cure atrial fibrillation.
Acquiring adequate mapping data in patients with atrial fibrillation is still one of the main obstacles in the treatment of this atrial arrhythmia. Due to the lack of catheters with both a panoramic field of view and sufficient electrode density for simultaneous mapping, electrophysiologists are forced to fall back on sequential mapping techniques. But, because activation patterns change rapidly during atrial fibrillation, they cannot be mapped sequentially. We propose that mapping tissue properties which are time independent, in contrast, allows a sequential approach. Here, we use the shortest measured electrogram cycle length to estimate the effective refractory period of the underlying tissue in a simulation study. Atrial fibrillation was simulated in a spherical model of the left atrium comprised of regions with varied refractory period. We found that the minimal measured electrogram cycle length correlates with the effective refractory period of the underlying tissue if the regions with distinct refractory properties are large enough and if the absolute difference in effective refractory periods is sufficient. This approach is capable of identifying regions of lowered effective refractory period without the need for cardioversion. Those regions are likely to harbor drivers of atrial fibrillation, which emphasizes the necessity of their localization.
Cardiac arrhythmias such as atrial fibrillation occur frequently in industrialized countries. Radiofrequency ablation (RFA) is a standard treatment if drug therapy fails. This minimally invasive surgery aims at stabilizing the heart rhythm on a permanent basis. However, the procedure commonly needs to be repeated because of the high recurrence rate of arrhythmias. Non-transmural lesions as well as gaps within linear lesions are among the main problems during the RFA. The assessment of lesion formation is not adequate in state of the art procedures. Therefore, the aim of this study is to investigate the short-term reversibility of lesions using human electrograms recorded by a high-density mapping system during an electrophysiological study (EPS). A predefined measurement protocol was executed during the EPS in order to create three ablation points in the left atrium. Subsequently, after preprocessing the recorded signals, electrogram (EGM) paths were formed along the endocardial surface of the atrium. By analyzing changes of peak to peak amplitudes of unipolar EGMs before and after ablation, it was possible to distinguish lesion area and healthy myocardium. The peak to peak amplitudes of the EGMs decreased by 40-61% after 30 seconds of ablation. Furthermore, we analyzed the morphological changes of EGMs surrounding the lesion. High-density mapping data showed that not only the tissue, which had direct contact with the catheter tip during the RFA, but also the surrounding tissue was affected. This was demonstrated by low peak to peak amplitudes in large areas with a width of 14 mm around the center of the ablation lesion. After right pulmonary vein isolation, high-density mapping was repeated on the previous lesions. The outer region of RFA-treated tissue appears to recover as opposed to the central core of the ablation point. This observation suggests that the meaningfulness of an immediate remap after ablation during an EPS may lead the physician to false conclusions.
Atrial fibrillation is a common irregular heart rhythm. Until today there is still a need for research to quantify typical signal characteristics of rotors, which can induce atrial fibrillation. In this work, signal characteristics of a stable and a more unstable rotor in a realistic heart model including fiber orientation were analyzed with the following methods: peak-to-peak amplitude, Hilbert phase, approximate entropy and RS-difference. In this simulation model the stable rotor rotated with a cycle length of 145 ms and stayed in an area of 1.5 mm x 3 mm. Another more unstable rotor with a cycle length of 190msmovedinanareaof10mmx4mm. Inadistance of 2 mm to the rotor tip, the peak-to-peak amplitude decreased significantly, whereas the RS-difference and the approximate entropy were maximal. The rotor center trajectories were detected by phase singularity points determined by the Hilbert transform. We showed that more unstable rotors resulted in more amplitude changes over time and also the cycle length differed more. Furthermore, we presented typical activation time patterns of the Lasso catheter centered at the rotor tip and in different distances to the rotor tip. We suggest that cardiologists use a combination of the described methods to determine a rotor tip position in a more robust manner.
Student Theses (2)
L. A. Unger. Substrate Mapping During Atrial Fibrillation - A Combined in Silico and Clinical Test of Concept Study. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Masterarbeit. 2017
Acquiring adequate mapping data in patients with atrial fibrillation (AFib) is one of the main obstacles in the treatment of this arrhythmia. Due to the lack of catheters with both a panoramic field of view and sufficient electrode density for simultaneous mapping, electrophysiologists are forced to fall back on sequential mapping techniques to identify activation patterns. However, this approach is insufficient for rapidly changing patterns as they typically occur during AFib. In contrast to activation time mapping, substrate mapping avoids this drawback by analyzing time independent tissue properties. While most of the existing methods for substrate mapping do not reflect actual tissue properties but certain electrogram features, the results suffer from dependencies on parameters of data analysis or are limited to harmonic signals. Here, we investigate the potential and limitations of measured electrogram cycle lengths to derive information about the effective refractory period of the underlying tissue during sequences of AFib. Following theoretical considerations, areas with decreased effective refractory period are likely to harbor AFib drivers.In a first step, different parametrizations of the Courtemanche-Ramirez-Nattel model with varying ERP served as substrates for bidomain simulations of AFib in a spherical model of the left atrium. Circular regions of deviating effective refractory period with radii between 9 mm and 19 mm were imposed. We found that the minimal measured electrogram cycle length correlates with the effective refractory period of the underlying tissue if the regions with distinct refractory properties are large enough and if the absolute difference in effective refractory periods is significant. Rhythms of high complexity which cause many other mapping approaches to come up against limiting factors favor the here introduced method as statistics profit from the variability in observed events.In a second step, the clinical feasibility of using measured cycle length statistics to conclude on the underlying ERP of the tissue was investigated. Lacking ground truth data providing reliable in vivo information on the ERP of the tissue, final validations of our hypotheses remain due. The 25 % quantile of cycle lengths was used rather than the minimum in favor of improved robustness in clinical application. The cycle length analysis in patient data yielded physiologically reasonable results with locally low gradients but globally differing statistics. Both the in silico and the clinical test of concept study suggested that applying statistical measures such as the 25 % quantile to measured electrogram cycle lengths is capable of revealing information on the effective refractory period of the underlying tissue. This, in turn, is of particular clinical interest, as regions of lowered effective refractory period are likely to harbor AFib drivers.
L. A. Unger. Simulation based Estimation of Parameters for Reentries in Human Atria. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2014