Abstract:

Diseases caused by alterations of ionic concentrations are frequently observed challenges and play an important role in clinical practice. The clinically established method for the diagnosis of electrolyte concentration imbalance is blood tests. A rapid and non-invasive point-of-care method is yet needed. The electrocardiogram (ECG) could meet this need and becomes an established diagnostic tool allowing home monitoring of the electrolyte concentration also by wearable devices. In this review, we present the current state of potassium and calcium concentration monitoring using the ECG and summarize results from previous work. Selected clinical studies are presented, supporting or questioning the use of the ECG for the monitoring of electrolyte concentration imbalances. Differences in the findings from automatic monitoring studies are discussed, and current studies utilizing machine learning are presented demonstrating the potential of the deep learning approach. Furthermore, we demonstrate the potential of computational modeling approaches to gain insight into the mechanisms of relevant clinical findings and as a tool to obtain synthetic data for methodical improvements in monitoring approaches.

Abstract:

End-stage chronic kidney disease (CKD) patients are facing a 30% rise for the risk of lethal cardiac events (LCE) compared to non-CKD patients. At the same time, these patients undergoing dialysis experience shifts in the potassium concentrations. The increased risk of LCE paired with the concentration changes suggest a connection between LCE and concentration disbalances. To prove this link, a continuous monitoring device for the ionic concentrations, e.g. the ECG, is needed. In this work, we want to answer if an optimised signal processing chain can improve the result quantify the influence of a disbalanced training dataset on the final estimation result. The study was performed on a dataset consisting of 12-lead ECGs recorded during dialysis sessions of 32 patients. We selected three features to find a mapping from ECG features to [K+]o: T-wave ascending slope, T-wave descending slope and T-wave amplitude. A polynomial model of 3rd order was used to reconstruct the concentrations from these features. We solved a regularised weighted least squares problem with a weighting matrix dependent on the frequency of each concentration in the dataset (frequent concentration weighted less). By doing so, we tried to generate a model being suitable for the whole range of the concentrations.With weighting, errors are increasing for the whole dataset. For the data partition with [K+]o<5 mmol/l, errors are increasing, for [K+]o≥5 mmol/l, errors are decreasing. However, and apart from the exact reconstruction results, we can conclude that a model being valid for all patients and not only the majority, needs to be learned with a more homogeneous dataset. This can be achieved by leaving out data points or by weighting the errors during the model fitting. With increasing weighting, we increase the performance on the part of the [K+]o that are less frequent which was desired in our case.

Abstract:

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

Abstract:

Atrial fibrillation (AF) is the most common type of arrhythmia encountered in clinical practice but its maintaining mechanisms remain elusive. Over the last years, various theories have been proposed to target AF mechanisms. Recently, there has been an increasing interest in understanding how spiral waves and rotors sustain AF and how they might be therapeutic targets for catheter-based ablation. Phase mapping has recently been used as a robust method to characterize the spatiotemporal variability of electrical activities. In this study, we propose an independent approach for basket catheter electrogram (EGM) processing to detect rotors in AF. An improved version of the sinusoidal recomposition method for the local activation timings (LATs) has been developed and 3D phase maps have been reconstructed. An algorithm able to detect stable and meandering rotors on the left atrium (LA) surface was then developed. This workflow has been validated on synthetic EGMs and in silico showing excellent results. On in vivo data, we found 4.0±3.4 and 4.6±5.0 localized and meandering rotors with a persistence in time: 303.2 ±58.2ms and 302.3±52.0ms respectively.

Abstract:

Atrial fibrillation (AF) ablation guided by basket catheter mapping has shown to be beneficial. Yet, the initial excitement is mitigated by a growing skepticism due to the difficulty in verifying the protocol in multicenter studies. Overall, the underlying assumptions of rotor ablation require further verification. The aim of this study was therefore to test such hypotheses by using computational modeling. The 3D left atrial geometry of an AF patient was segmented from a pre-operative MR scan. Atrial activation was simulated on the 3D anatomy using the monodomain approach and a variant of the Courtemanche action potential model. Ablated tissue was assigned zero conductivity. Reentry was successfully initialized by applying a single suitably delayed extra stimulus. Unipolar electrograms were computed at the simulated electrode positions. The final dataset was generated by varying location of reentry and catheter position within the LA. The effect of inter-electrode distance and distance to the atrial wall was studied in relation to the ability to recover rotor trajectory, as computed by a novel algorithm described here. The effect of rotor ablation was also assessed.