Novel Approaches to ECG-Based Modeling and Characterization of Atrial Fibrillation

This thesis deals with signal processing algorithms for analysis of the electrocardiogram (ECG) during atrial fibrillation (AF). Such analysis can be used for diagnosing patients, and for monitoring and predicting their response to various treatment. The thesis comprises an introduction and five papers describing methods for ECG-based modeling and characterization of AF. Paper I--IV deal with methods for characterization of the atrial activity, whereas Paper V deals with modeling of the ventricular response, both problems with the assumption that AF is present. In Paper I, a number of measures characterizing the atrial activity in the ECG, obtained using time-frequency analysis as well as nonlinear methods, are evaluated for their ability to predict spontaneous termination of AF. The AF frequency, i.e, the repetition rate of the atrial fibrillatory waves of the ECG, proved to be a significant factor for discrimination between terminating and non-terminating AF. Noise is a common problem in ECG signals, particularly in long-term ambulatory recordings. Hence, robust algorithms for analysis and characterization are required. In Paper II, a robust method for tracking the AF frequency in noisy signals is presented. The method is based on a hidden Markov model (HMM), which takes the harmonic pattern of the atrial activity into account. Using the HMM-based method, the average RMS error of the frequency estimates at high noise levels was significantly lower compared to existing methods. In Paper III, the HMM-based method is employed for analysis of 24-h ambulatory ECG signals in order to explore circadian variation in AF frequency. Circadian variations reflect autonomic modulation; attenuation or absence of such variations may help to diagnose patients. Methods based on curve fitting, autocorrelation, and joint variation, respectively, are employed to quantify circadian variations, showing that it is present in most patients with long-standing persistent AF, although the short-term variation is considerable. In Paper IV, 24-h ambulatory ECG recordings with paroxysmal and persistent AF are analyzed using an entropy-based method for characterization of the atrial activity. Short segments are classified based on these measures, showing that it is feasible to distinguish between patient with paroxysmal and persistent AF from 10-s ECGs; the average classification rate was above 95%. The ventricular response during AF is mainly determined by the AV nodal blocking of atrial impulses. In Paper V, a new model-based approach for analysis of the ventricular response during AF is proposed. The model integrates physiological properties of the AV node and the atrial fibrillatory rate; the model parameters can be estimated from ECG signals. Results show that ventricular response is sufficiently represented by the estimated model in a majority of the recordings; in 85.7% of the analyzed 30-min segments the model fit was considered accurate, and that changes of AV nodal properties caused by autonomic modulation could be tracked through the estimated model parameters. In summary, the work within this thesis contributes with new methods for non-invasive analysis of AF, which can be used to tailor and evaluate different strategies for AF treatment

Relationship between body surface potential maps and atrial electrograms in patients with atrial fibrillation

PhD ThesisAtrial fibrillation (AF) is the most common cardiac arrhythmia. It is distinguished by fibrillating or trembling of the atrial muscle instead of normal contraction. Patients in AF have a much higher risk of stroke. AF is often driven by the left atrium (LA) and the diagnosis of AF is normally made from lead V1 in a 12-lead electrocardiogram (ECG). However, lead V1 is dominated by right atrial activity due to its proximal location to the right atrium (RA). Consequently it is not well understood how electrical activity from the LA contributes to the ECG. Studies of the AF mechanisms from the LA are typically based on invasive recording techniques. From a clinical point of view it is highly desirable to have an alternative, non-invasive characterisation of AF. The aim of this study was to investigate how the LA electrical activity was expressed on the body surface, and if it could be observed preferentially in different sites on the body surface. For this purpose, electrical activity of the heart from 20 patients in AF were recorded simultaneously using 64-lead body surface potential mapping (BSPM) and bipolar 10-electrode catheters located in the LA and coronary sinus (CS). Established AF characteristics such as amplitude, dominant frequency (DF) and spectral concentration (SC) were estimated and analysed. Furthermore, two novel AF characteristics (intracardiac DF power distribution, and body surface spectral peak type) were proposed to investigate the relationship between the BSPM and electrogram (EGM) recordings. The results showed that although in individual patients there were body surface sites that preferentially represented the AF characteristics estimated from the LA, those sites were not consistent across all patients. It was found that the left atrial activity could be detected in all body surface sites such that all sites had a dominant or non-dominant spectral peak corresponding to EGM DF. However, overall the results suggested that body surface site 22 (close to lead V1) was more closely representative of the CS activity, and site 49 (close to the posterior lower central right) was more closely representative of the left atrial activity. There was evidence of more accurate estimation of AF characteristics using additional electrodes to lead V1

Spatial Characterization and Estimation of Intracardiac Propagation Patterns During Atrial Fibrillation

This doctoral thesis is in the field of biomedical signal processing with focus on methods for the analysis of atrial fibrillation (AF). Paper I of the present thesis addresses the challenge of extracting spatial properties of AF from body surface signals. Different parameters are extracted to estimate the preferred direction of atrial activation and the complexity of the atrial activation pattern. In addition, the relation of the spatial properties to AF organization, which is quantified by AF frequency, is evaluated. While no significant correlation between the preferred direction of atrial activation and AF frequency could be observed, the complexity of the atrial activation pattern was found to increase with AF frequency. The remaining three papers deal with the analysis of the propagation of the electrical activity in the atria during AF based on intracardiac signals. In Paper II, a time-domain method to quantify propagation patterns along a linear catheter based on the detected atrial activation times is developed. Taking aspects on intra-atrial signal organization into account, the detected activation times are combined into wavefronts, and parameters related to the consistency of the wavefronts over time and the activation order along the catheter are extracted. Furthermore, the potential relationship of the extracted parameters to established measures from body surface signals is investigated. While the degree of wavefront consistency was not reflected by the applied body surface measures, AF frequency could distinguish between recordings with different degrees of intra-atrial signal organization. This supports the role of AF frequency as an organization measure of AF. In Paper III, a novel method to analyze intracardiac propagation patterns based on causality analysis in the frequency domain is introduced. In particular, the approach is based on the partial directed coherence (PDC), which evaluates directional coupling between multiple signals in the frequency domain. The potential of the method is illustrated with simulation scenarios based on a detailed ionic model of the human atrial cell as well as with real data recordings, selected to present typical propagation mechanisms and recording situations in atrial tachyarrhythmias. For simulated data, the PDC is correctly reflecting the direction of coupling and thus the propagation between all recording sites. For real data, clear propagation patterns are identified which agree with previous clinical observations. Thus, the results illustrate the ability of the novel approach to identify propagation patterns from intracardiac signals during AF which can provide important information about the underlying AF mechanisms, potentially improving the planning and outcome of ablation. However, spurious couplings over long distances can be observed when analyzing real data comprised by a large number of simultaneously recorded signals, which gives room for further improvement of the method. The derivation of the PDC is entirely based on the fit of a multivariate autoregressive (MVAR) model, commonly estimated by the least-squares (LS) method. In Paper IV, the adaptive group least absolute selection and shrinkage operator (LASSO) is introduced in order to avoid overfitting of the MVAR model and to incorporate prior information such as sparsity of the solution. The sparsity can be motivated by the observation that direct couplings over longer distances are likely to be zero during AF; an information which has been further incorporated by proposing distance-adaptive group LASSO. In simulations, adaptive and distance-adaptive group LASSO are found to be superior to LS estimation in terms of both detection and estimation accuracy. In addition, the results of both simulations and real data analysis indicate that further improvements can be achieved when the distance between the recording sites is known or can be estimated. This further promotes the PDC as a method for analysis of AF propagation patterns, which may contribute to a better understanding of AF mechanisms as well as improved AF treatment

Bottom-up design of artificial neural network for single-lead electrocardiogram beat and rhythm classification

Performance improvement in computerized Electrocardiogram (ECG) classification is vital to improve reliability in this life-saving technology. The non-linearly overlapping nature of the ECG classification task prevents the statistical and the syntactic procedures from reaching the maximum performance. A new approach, a neural network-based classification scheme, has been implemented in clinical ECG problems with much success. The focus, however, has been on narrow clinical problem domains and the implementations lacked engineering precision. An optimal utilization of frequency information was missing. This dissertation attempts to improve the accuracy of neural network-based single-lead (lead-II) ECG beat and rhythm classification. A bottom-up approach defined in terms of perfecting individual sub-systems to improve the over all system performance is used. Sub-systems include pre-processing, QRS detection and fiducial point estimations, feature calculations, and pattern classification. Inaccuracies in time-domain fiducial point estimations are overcome with the derivation of features in the frequency domain. Feature extraction in frequency domain is based on a spectral estimation technique (combination of simulation and subtraction of a normal beat). Auto-regressive spectral estimation methods yield a highly sensitive spectrum, providing several local features with information on beat classes like flutter, fibrillation, and noise. A total of 27 features, including 16 in time domain and 11 in frequency domain are calculated. The entire data and problem are divided into four major groups, each group with inter-related beat classes. Classification of each group into related sub-classes is performed using smaller feed-forward neural networks. Input feature sub-set and the structure of each network are optimized using an iterative process. Optimal implementations of feed-forward neural networks provide high accuracy in beat classification. Associated neural networks are used for the more deterministic rhythm-classification task. An accuracy of more than 85% is achieved for all 13 classes included in this study. The system shows a graceful degradation in performance with increasing noise, as a result of the noise consideration in the design of every sub-system. Results indicate a neural network-based bottom-up design of single-lead ECG classification is able to provide very high accuracy, even in the presence of noise, flutter, and fibrillation

Automated algorithm-driven methods of localising drivers of persistent atrial fibrillation using atrial fibrillation cycle length and atrial fibrillation voltage

The assessment of atrial fibrillation cycle length has played a role in the development of atrial fibrillation ablation by pulmonary vein isolation (PVI) and has also been used to assess response to ablation. Areas of rapid rotational activity in the left atrium have been implied to act as drivers of persistent atrial fibrillation and several methods have been developed to identify these potential drivers. Unprocessed atrial fibrillation electrograms show large variation in cycle length and signal amplitude. Current methods of localising driver regions rely on complex pattern recognition and subjective assessment of operators. The main hypotheses of this thesis were as follows: 1) a technique can be developed to ascertain a clinically relevant, dominant cycle length for any AF segment, 2) the automated technique, can be used to map rapid and regular activity in the left atrium, 3) a patient-tailored definition of rapid activity and low AF voltage, calculated based on patient-specific parameters is feasible; 4) paired with automated low voltage substrate analysis, dominant cycle length analysis is able to provide a framework for localising drivers of AF that is objective, transparent and requires no complex pattern recognition of subjective judgement. To test the hypotheses, a technique was developed based on manual annotation of real-world AF electrograms that was able to ascertain cycle length independent of missing segments or variable cycle length or signal amplitude. Following this, an automated algorithm was validated to determine dominant cycle length. In the following chapter, the nature of AF cycle length was investigated by investigating the patterns of rapid activity with extended AF segments and the concept of patient-tailored definitions of rapid activity was introduced. In the subsequent analysis, the effect of PVI was examined on AF voltage and the AF cycle length, focusing on rapid and regular areas and low voltage zones, and their changes. The last chapter utilised the accumulated information to test the sensitivity and specificity of a percentile-based, patient-tailored approach to low AF voltage and to present an objective, automated method of localising rapid and regular areas within low voltage zones within the left atrium. In summary, it is feasible to assess and locate rapid and regular areas, and localise low voltage zones in persistent AF with a completely automated algorithm, and patient-tailored definitions of low voltage rapid AF activity are a preferable alternative to absolute cut offs.Open Acces

Blind Source Separation for the Processing of Contact-Less Biosignals

(Spatio-temporale) Blind Source Separation (BSS) eignet sich für die Verarbeitung von Multikanal-Messungen im Bereich der kontaktlosen Biosignalerfassung. Ziel der BSS ist dabei die Trennung von (z.B. kardialen) Nutzsignalen und Störsignalen typisch für die kontaktlosen Messtechniken. Das Potential der BSS kann praktisch nur ausgeschöpft werden, wenn (1) ein geeignetes BSS-Modell verwendet wird, welches der Komplexität der Multikanal-Messung gerecht wird und (2) die unbestimmte Permutation unter den BSS-Ausgangssignalen gelöst wird, d.h. das Nutzsignal praktisch automatisiert identifiziert werden kann. Die vorliegende Arbeit entwirft ein Framework, mit dessen Hilfe die Effizienz von BSS-Algorithmen im Kontext des kamera-basierten Photoplethysmogramms bewertet werden kann. Empfehlungen zur Auswahl bestimmter Algorithmen im Zusammenhang mit spezifischen Signal-Charakteristiken werden abgeleitet. Außerdem werden im Rahmen der Arbeit Konzepte für die automatisierte Kanalauswahl nach BSS im Bereich der kontaktlosen Messung des Elektrokardiogramms entwickelt und bewertet. Neuartige Algorithmen basierend auf Sparse Coding erwiesen sich dabei als besonders effizient im Vergleich zu Standard-Methoden.(Spatio-temporal) Blind Source Separation (BSS) provides a large potential to process distorted multichannel biosignal measurements in the context of novel contact-less recording techniques for separating distortions from the cardiac signal of interest. This potential can only be practically utilized (1) if a BSS model is applied that matches the complexity of the measurement, i.e. the signal mixture and (2) if permutation indeterminacy is solved among the BSS output components, i.e the component of interest can be practically selected. The present work, first, designs a framework to assess the efficacy of BSS algorithms in the context of the camera-based photoplethysmogram (cbPPG) and characterizes multiple BSS algorithms, accordingly. Algorithm selection recommendations for certain mixture characteristics are derived. Second, the present work develops and evaluates concepts to solve permutation indeterminacy for BSS outputs of contact-less electrocardiogram (ECG) recordings. The novel approach based on sparse coding is shown to outperform the existing concepts of higher order moments and frequency-domain features

Characterization, Classification, and Genesis of Seismocardiographic Signals

Seismocardiographic (SCG) signals are the acoustic and vibration induced by cardiac activity measured non-invasively at the chest surface. These signals may offer a method for diagnosing and monitoring heart function. Successful classification of SCG signals in health and disease depends on accurate signal characterization and feature extraction. In this study, SCG signal features were extracted in the time, frequency, and time-frequency domains. Different methods for estimating time-frequency features of SCG were investigated. Results suggested that the polynomial chirplet transform outperformed wavelet and short time Fourier transforms. Many factors may contribute to increasing intrasubject SCG variability including subject posture and respiratory phase. In this study, the effect of respiration on SCG signal variability was investigated. Results suggested that SCG waveforms can vary with lung volume, respiratory flow direction, or a combination of these criteria. SCG events were classified into groups belonging to these different respiration phases using classifiers, including artificial neural networks, support vector machines, and random forest. Categorizing SCG events into different groups containing similar events allows more accurate estimation of SCG features. SCG feature points were also identified from simultaneous measurements of SCG and other well-known physiologic signals including electrocardiography, phonocardiography, and echocardiography. Future work may use this information to get more insights into the genesis of SCG

Feasibility of improving risk stratification in the inherited cardiac conditions

Fatal ventricular arrhythmias can occur in patients with Hypertrophic Cardiomyopathy, Brugada Syndrome and rarely in patients with normal cardiac investigations. Despite very different pathogeneses, we hypothesised that a common electrophysiological substrate precipitates these arrhythmias and could be used as a marker for risk stratification. In Chapter 3 of this thesis, we found that fewer than half the cardiac arrest survivors with Brugada Syndrome would have been offered prophylactic defibrillators based on current risk scoring, highlighting the need for better risk stratification. Our group previously used a commercially available 252-electrode vest which constructs ventricular electrograms onto a CT image of the heart to show exercise related differences in high-risk patients. In Chapter 4, we applied this method to Brugada patients, but could not reproduce prior results. Further investigation revealed periodic changes in activation patterns after exercise that could explain this discrepancy. An alternative matrix approach was developed to overcome this problem. Exercise induced conduction heterogeneity differentiated Brugada patients from unaffected controls, but not those surviving cardiac arrest. However, if considered alongside spontaneous type 1 ECG and syncope, inducible conduction heterogeneity markedly improved identification of Brugada cardiac arrest survivors. In Chapter 5 the method was shown to differentiate idiopathic ventricular fibrillation patients from those fully recovered from acute ischaemic cardiac arrest, implying a permanent electrophysiological abnormality. In Chapter 8, we showed prolonged mean local activation times and activation-recovery intervals in hypertrophic cardiomyopathy cardiac arrest survivors compared to those without previous ventricular arrhythmia. These metrics were combined into both logistic regression and support vector machine models to strongly differentiate the groups. We concluded that electrophysiological changes could identify cardiac arrest survivors in various cardiac conditions, but a single factor common pathway was not established. Prospective studies are required to determine if using these parameters could enhance current risk stratification for sudden death.Open Acces