C. Nagel, G. Luongo, L. Azzolin, S. Schuler, O. Dössel, and A. Loewe. Non-Invasive and Quantitative Estimation of Left Atrial Fibrosis Based on P Waves of the 12-Lead ECG—A Large-Scale Computational Study Covering Anatomical Variability. In Journal of Clinical Medicine, vol. 10(8) , pp. 1797, 2021
The arrhythmogenesis of atrial fibrillation is associated with the presence of fibrotic atrial tissue. Not only fibrosis but also physiological anatomical variability of the atria and the thorax reflect in altered morphology of the P wave in the 12-lead electrocardiogram (ECG). Distinguishing between the effects on the P wave induced by local atrial substrate changes and those caused by healthy anatomical variations is important to gauge the potential of the 12-lead ECG as a non-invasive and cost-effective tool for the early detection of fibrotic atrial cardiomyopathy to stratify atrial fibrillation propensity. In this work, we realized 54,000 combinations of different atria and thorax geometries from statistical shape models capturing anatomical variability in the general population. For each atrial model, 10 different volume fractions (0-45%) were defined as fibrotic. Electrophysiological simulations in sinus rhythm were conducted for each model combination and the respective 12-lead ECGs were computed. P wave features (duration, amplitude, dispersion, terminal force in V1) were extracted and compared between the healthy and the diseased model cohorts. All investigated feature values systematically in- or decreased with the left atrial volume fraction covered by fibrotic tissue, however value ranges overlapped between the healthy and the diseased cohort. Using all extracted P wave features as input values, the amount of the fibrotic left atrial volume fraction was estimated by a neural network with an absolute root mean square error of 8.78%. Our simulation results suggest that although all investigated P wave features highly vary for different anatomical properties, the combination of these features can contribute to non-invasively estimate the volume fraction of atrial fibrosis using ECG-based machine learning approaches.
C. Nagel, S. Schuler, O. Dössel, and A. Loewe. A bi-atrial statistical shape model for large-scale in silico studies of human atria: model development and application to ECG simulations. In Medical Image Analysis, vol. 74, pp. 102210, 2021
Large-scale electrophysiological simulations to obtain electrocardiograms (ECG) carry the potential to pro- duce extensive datasets for training of machine learning classifiers to, e.g., discriminate between different cardiac pathologies. The adoption of simulations for these purposes is limited due to a lack of ready-to- use models covering atrial anatomical variability. We built a bi-atrial statistical shape model (SSM) of the endocardial wall based on 47 segmented human CT and MRI datasets using Gaussian process morphable models. Generalization, specificity, and compact- ness metrics were evaluated. The SSM was applied to simulate atrial ECGs in 100 random volumetric instances. The first eigenmode of our SSM reflects a change of the total volume of both atria, the second the asym- metry between left vs. right atrial volume, the third a change in the prominence of the atrial appendages. The SSM is capable of generalizing well to unseen geometries and 95% of the total shape variance is cov- ered by its first 24 eigenvectors. The P waves in the 12-lead ECG of 100 random instances showed a duration of 109 . 7 ±12 . 2 ms in accordance with large cohort studies. The novel bi-atrial SSM itself as well as 100 exemplary instances with rule-based augmentation of atrial wall thickness, fiber orientation, inter-atrial bridges and tags for anatomical structures have been made publicly available. This novel, openly available bi-atrial SSM can in future be employed to generate large sets of realistic atrial geometries as a basis for in silico big data approaches.
The electrocardiogram (ECG) is a standard cost-efficient and non-invasive tool for the early detection of various cardiac diseases. Quantifying different timing and amplitude features of and in between the single ECG waveforms can reveal important information about the underlying (dys-)function of the heart. Determining these features requires the detection of fiducial points that mark the on- and offset as well as the peak of each ECG waveform (P wave, QRS complex, T wave). Manually setting these points is time-consuming and requires a physician’s expert knowledge. Therefore, the highly modular ECGdeli toolbox for MATLAB was developed, which is capable of filtering clinically recorded 12-lead ECG signals and detecting the fiducial points, also called delineation. It is one of the few open toolboxes offering ECG delineation for P waves, T Waves and QRS complexes. The algorithms provided were evaluated with the QT database, an ECG database comprising 105 signals with fiducial points annotated by clinicians. The median difference between the fiducial points set by the boundary detection algorithm and the clinical annotations serving as a ground truth is less than 4 samples (16 ms) for the P wave and the QRS complex markers.
Computer modeling of the electrophysiology of the heart has undergone significant progress. A healthy heart can be modeled starting from the ion channels via the spread of a depolarization wave on a realistic geometry of the human heart up to the potentials on the body surface and the ECG. Research is advancing regarding modeling diseases of the heart. This article reviews progress in calculating and analyzing the corresponding electrocardiogram (ECG) from simulated depolarization and repolarization waves. First, we describe modeling of the P-wave, the QRS complex and the T-wave of a healthy heart. Then, both the modeling and the corresponding ECGs of several important diseases and arrhythmias are delineated: ischemia and infarction, ectopic beats and extrasystoles, ventricular tachycardia, bundle branch blocks, atrial tachycardia, flutter and fibrillation, genetic diseases and channelopathies, imbalance of electrolytes and drug-induced changes. Finally, we outline the potential impact of computer modeling on ECG interpretation. Computer modeling can contribute to a better comprehension of the relation between features in the ECG and the underlying cardiac condition and disease. It can pave the way for a quantitative analysis of the ECG and can support the cardiologist in identifying events or non-invasively localizing diseased areas. Finally, it can deliver very large databases of reliably labeled ECGs as training data for machine learning.
Conference Contributions (6)
C. Nagel, O. Dössel, and A. Loewe. Sensitivity and Generalization of a Neural Network for Estimating Left Atrial Fibrotic Volume Fractions from the 12-lead ECG. In Current Directions in Biomedical Engineering, vol. 7(2) , pp. 307-310, 2021
Clinical and computational studies highlighted the role of atrial anatomy for atrial fibrillation vulnerability. However, personalized computational models are often generated from electroanatomical maps, which might lack important anatomical structures like the appendages, or from imaging data which are potentially affected by segmentation uncertainty. A bi-atrial statistical shape model (SSM) covering relevant structures for electrophysiological simulations was shown to cover atrial shape variability. We hypothesized that it could, therefore, also be used to infer the shape of missing structures and deliver ready-to-use models to assess atrial fibrillation vulnerability in silico. We implemented a highly automatized pipeline to generate a personalized computational model by fitting the SSM to the clinically acquired geometries. We applied our framework to a geometry coming from an electroanatomical map and one derived from magnetic resonance images (MRI). Only landmarks belonging to the left atrium and no information from the right atrium were used in the fitting process. The left atrium surface-to-surface distance between electroanatomical map and a fitted instance of the SSM was 2.26+-1.95 mm. The distance between MRI segmentation and SSM was 2.07+-1.56 mm and 3.59+-2.84 mm in the left and right atrium, respectively. Our semi-automatic pipeline provides ready-to-use personalized computational models representing the original anatomy well by fitting a SSM. We were able to infer the shape of the right atrium even in the case of using information only from the left atrium.