Classification of De novo post-operative and persistent atrial fibrillation using multi-channel ECG recordings

Atrial fibrillation (AF) is the most sustained arrhythmia in the heart and also the most common complication developed after cardiac surgery. Due to its progressive nature, timely detection of AF is important. Currently, physicians use a surface electrocardiogram (ECG) for AF diagnosis. However, when the patient develops AF, its various development stages are not distinguishable for cardiologists based on visual inspection of the surface ECG signals. Therefore, severity detection of AF could start from differentiating between short-lasting AF and long-lasting AF. Here, de novo post-operative AF (POAF) is a good model for short-lasting AF while long-lasting AF can be represented by persistent AF. Therefore, we address in this paper a binary severity detection of AF for two specific types of AF. We focus on the differentiation of these two types as de novo POAF is the first time that a patient develops AF. Hence, comparing its development to a more severe stage of AF (e.g., persistent AF) could be beneficial in unveiling the electrical changes in the atrium. To the best of our knowledge, this is the first paper that aims to differentiate these different AF stages. We propose a method that consists of three sets of discriminative features based on fundamentally different aspects of the multi-channel ECG data, namely based on the analysis of RR intervals, a greyscale image representation of the vectorcardiogram, and the frequency domain representation of the ECG. Due to the nature of AF, these features are able to capture both morphological and rhythmic changes in the ECGs. Our classification system consists of a random forest classifier, after a feature selection stage using the ReliefF method. The detection efficiency is tested on 151 patients using 5-fold cross-validation. We achieved 89.07% accuracy in the classification of de novo POAF and persistent AF. The results show that the features are discriminative to reveal the severity of AF. Moreover, inspection of the most important features sheds light on the different characteristics of de novo post-operative and persistent AF.</p

Study on the non-linear metrics contribution to estimate atrial fibrillation organization from the surface electrocardiogram

[EN] Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia, characterized by an uncoordinated atrial electrical activation, thus causing the atria to be unable to pump blood effectively. The prevalence of AF is expected to increase significantly in the next decades as the population ages. However, both the knowledge and the treatment of this arrhythmia still have to experiment a significant progress. Previous studies have reported that AF organization, which can be defined as the repetitiveness degree of the atrial activity pattern, correlates with the arrhythmia status as well as with the therapy outcome. Thus, estimating AF organization from surface electrocardiographic (ECG) recordings constitutes a very interesting approach because ECG recordings are easy and cheap to obtain. The objective of this doctoral thesis is to assess the use of a variety of nonlinear indices in the estimation of AF organization from single-lead noninvasive ECG recordings. Apart from the most common noninvasive AF organization estimators, such as Sample Entropy (SampEn) and the dominant atrial frequency (DAF), the following nonlinear indices have been studied: Fuzzy Entropy, Spectral Entropy, Lempel-Ziv Complexity and Hurst Exponents. Moreover, since the presence of noise and ventricular residuals affects the performance of nonlinear methods, the application of a strategy aimed at reducing these nuisances has been evaluated. Therefore, the application of these metrics over the atrial activity fundamental waveform, named the main atrial wave (MAW), has been proposed. In this doctoral thesis, the following scenarios involving AF organization have been considered: the prediction of paroxysmal AF spontaneous termination, the study of the earlier signs anticipating AF termination and the classification between paroxysmal and persistent AF from short ECG recordings. Firstly, the performance of the studied metrics discriminating events related to AF organization was tested making use of a reference database aimed at predicting AF spontaneous termination. In this study, most of the proposed indices provided higher accuracy than traditional AF organization estimators. Accuracy values higher than 90% were obtained with several indices. In particular, the generalized Hurst exponents of order 1 and 2, H(1) and H(2), achieved outstanding results, thus being selected for later studies in this thesis. Furthermore, the computation of H(2) depends on two critical parameters, namely, the analyzed interval length (L) and the maximum search window for self-similarities (tau). Hence, a study with 660 combinations on these two parameters was performed, together with the sampling frequency (fs) of the recording, in order to obtain their optimal combination in computing AF organization. On the other hand, previous works analyzing the spontaneous termination of AF have been only focused on the last 2 minutes preceding the termination. In contrast, a different scenario considering longer recordings to detect the earlier signs anticipating paroxysmal AF termination has been analyzed for the first time in this thesis. H(2) was selected for the study because of its highest accuracy in AF termination prediction. Additionally, the DAF and SampEn were also computed as references. Through this study it has been corroborated that AF organization only varies significantly within the last 3 minutes before spontaneous termination. As a consequence, the early prediction of paroxysmal AF spontaneous termination does not seem feasible through the current signal analysis tools. Finally, H(2) was applied in the classification between paroxysmal and persistent AF from short ECG recordings, achieving a higher diagnostic accuracy than DAF and SampEn. This result suggests that the analysis of ambulatory ECG recordings through H(2) could be a future alternative to the use of Holter ECG recordings in the classification between paroxysmal and persistent AF.[ES] La fibrilación auricular (FA) es la arritmia más frecuente y se caracteriza por una actividad auricular descoordinada, que impide que las aurículas bombeen sangre de manera eficaz. Se espera que la prevalencia de la FA aumente significativamente en las próximas décadas debido al envejecimiento de la población. Sin embargo, tanto el conocimiento relativo a esta arritmia como su tratamiento son todavía mejorables. Estudios previos han relacionado la organización de la FA, que se puede definir como el grado de repetitividad de la actividad auricular, con el estado de la arritmia o su respuesta al tratamiento. Además, la estimación de la organización de la FA a partir de registros electrocardiográficos (ECG) de superficie resulta especialmente interesante porque su obtención es sencilla y barata. El objetivo de esta tesis doctoral es evaluar el uso de distintos índices no lineales para estimar la organización de la FA a partir del ECG. Además de los estimadores no invasivos de organización más comunes, como la entropía muestral (SampEn) y la frecuencia auricular dominante (DAF), se han estudiado los siguientes métodos no lineales: la entropía borrosa, la entropía espectral, la complejidad Lempel-Ziv y los exponentes de Hurst. Además, se ha estudiado el uso de una estrategia destinada a la reducción del ruido y los residuos de actividad ventricular para mejorar el desempeño de métodos no lineales. Así, los índices estudiados también se han aplicado sobre la forma de onda fundamental de la actividad auricular, conocida como la onda auricular principal (MAW). Se han considerado los siguientes escenarios relacionados con la organización de la FA: la predicción de la terminación espontánea de la FA paroxística, el estudio de los primeros indicios de terminación espontánea de la FA y la clasificación entre FA paroxística y FA persistente a partir de registros ECG de corta duración. Primero, se estudió la capacidad de los índices estudiados para distinguir eventos relacionados con la organización de la FA mediante el análisis de una base de datos de referencia para la predicción de su terminación espontánea. La mayoría de los índices propuestos consiguieron una mayor precisión que los estimadores tradicionales de organización. Así, varios de los índices obtuvieron una precisión superior al 90% en la predicción de la terminación espontánea de la FA. En particular, los exponentes de Hurst generalizados de orden 1 y 2, H(1) y H(2), lograron los mejores resultados de clasificación. Puesto que el cálculo de H(2) depende de dos parámetros críticos, la longitud del intervalo analizado (L) y el tamaño máximo de la ventana donde buscar similitudes (tau), se llevó a cabo un estudio con 660 combinaciones de esos dos parámetros junto con la frecuencia de muestreo (fs) del registro para determinar el uso óptimo de este índice. Por otra parte, los trabajos previos que han estudiado la terminación espontánea de la FA se han centrado en los últimos 2 minutos antes de la terminación. Por contra, en esta tesis doctoral se han estudiado por primera vez registros de mayor duración para detectar los primeros indicios de la terminación de la FA. Para ello, se eligió el uso de H(2) por su alta precisión en la predicción de la terminación de la FA. Además, la DAF y SampEn se calcularon como referencias. En este estudio se ha comprobado que la organización de la FA solamente presenta variaciones significativas en los últimos 3 minutos antes de su terminación espontánea. Por ello, la predicción temprana de la terminación no parece posible con los medios actuales de análisis de la señal. Por último, se aplicó H(2) para clasificar entre FA paroxística y FA persistente a partir de ECGs de corta duración, obteniendo una mayor precisión diagnóstica que la DAF y SampEn. Este resultado sugiere que el análisis de ECGs ambulatorios por medio de H(2) puede ser en el futuro una alte[CA] La fibril·lació auricular (FA) és l'arítmia més freqüent i es caracteritza per una activitat auricular descoordinada, que impedix que les aurícules bomben sang de manera eficaç. S'espera que la prevalença de la FA augmente significativament en les pròximes dècades a causa de l'envelliment de la població. No obstant això, tant el coneixement relatiu a esta arítmia com el seu tractament són encara millorables. Estudis previs han relacionat l'organització de la FA, que es pot definir com el grau de repetitivitat de l'activitat auricular, amb l'estat de l'arítmia o la seua resposta al tractament. A més, l'estimació de l'organització de la FA a partir de registres electrocardiogràfics (ECG) de superfície resulta especialment interessant perquè la seua obtenció és senzilla i barata. L'objectiu d'esta tesi doctoral és avaluar l'ús de distints índexs no lineals en l'estimació de l'organització de la FA a partir de l'ECG de superfície. A més dels estimadors no invasius d'organització més comuns, com l'entropia mostral (SampEn) i la freqüència auricular dominant (DAF), s'han estudiat els següents mètodes no lineals: l'entropia borrosa, l'entropia espectral, la complexitat Lempel-Ziv i els exponents de Hurst. A més, s'ha estudiat l'ús d'una estratègia destinada a la reducció del soroll i els residus d'activitat ventricular per a millorar la seua capacitat d'estimar l'organització. Així, doncs, els índexs estudiats també s'han aplicat sobre la forma d'onda fonamental de l'activitat auricular, coneguda com l'onda auricular principal (MAW). S'han considerat els següents escenaris relacionats amb l'organització de la FA: la predicció de la terminació espontània de la FA paroxística, l'estudi dels primers indicis de terminació espontània de la FA i la classificació entre FA paroxística i FA persistent a partir de registres ECG de curta duració. Primer, es va estudiar la capacitat dels índexs estudiats per a distingir esdeveniments relacionats amb l'organització de la FA per mitjà de l'anàlisi d'una base de dades de referència per a la predicció de la seua terminació espontània. La majoria dels índexs proposats van aconseguir una major precisió que els estimadors tradicionals d'organització de la FA. Així, alguns dels índexs van obtindre una precisió superior al 90% en la predicció de la terminació espontània de la FA. En particular, els exponents de Hurst generalitzats d'orde 1 i 2, H(1) i H(2), van aconseguir els millors resultats de classificació. Com el càlcul de H(2) depén de dos paràmetres crítics, la longitud de l'interval analitzat (L) i la grandària màxima de la finestra on buscar similituds (tau), es va dur a terme un estudi amb 660 combinacions d'eixos dos paràmetres junt amb la freqüència de mostratge (fs) del registre per a determinar la combinació òptima de valors per a estimar l'organització de la FA. D'altra banda, els treballs previs que han estudiat la terminació espontània de la FA s'han centrat en els últims 2 minuts abans de la terminació. Per contra, en esta tesi doctoral s'han estudiat per primera vegada registres de major duració amb l'objectiu de detectar els primers indicis de la terminació de la FA. Es va triar l'ús de H(2) per a este estudi per la seua alta precisió en la predicció de la terminació de la FA. A més, la DAF i SampEn es van calcular com a referències. En este estudi s'ha comprovat que l'organització de la FA només presenta variacions significatives en els últims 3 minuts abans de la seua terminació espontània. Per això, la predicció primerenca de la terminació no pareix possible amb els mitjans actuals d'anàlisi del senyal. Finalment, es va aplicar H(2) per a classificar entre FA paroxística i FA persistent a partir d'ECGs de curta duració, obtenint una millor precisió diagnòstica que amb la DAF i SampEn. Este resultat suggerix que l'anàlisi d'ECGs ambulatoris per mitjà de H(2) pot ser en eJulián Seguí, M. (2015). Study on the non-linear metrics contribution to estimate atrial fibrillation organization from the surface electrocardiogram [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/56150TESI

Novel approaches for quantitative electrogram analysis for rotor identification: Implications for ablation in patients with atrial fibrillation

University of Minnesota Ph.D. dissertation. May 2017. Major: Biomedical Engineering. Advisor: Elena Tolkacheva. 1 computer file (PDF); xxviii, 349 pages + 4 audio/video filesAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia that causes stroke affecting more than 2.3 million people in the US. Catheter ablation with pulmonary vein isolation (PVI) to terminate AF is successful for paroxysmal AF but suffers limitations with persistent AF patients as current mapping methods cannot identify AF active substrates outside of PVI region. Recent evidences in the mechanistic understating of AF pathophysiology suggest that ectopic activity, localized re-entrant circuit with fibrillatory propagation and multiple circuit re-entries may all be involved in human AF. Accordingly, the hypothesis that rotor is an underlying AF mechanism is compatible with both the presence of focal discharges and multiple wavelets. Rotors are stable electrical sources which have characteristic spiral waves like appearance with a pivot point surrounded by peripheral region. Targeted ablation at the rotor pivot points in several animal studies have demonstrated efficacy in terminating AF. The objective of this dissertation was to develop robust spatiotemporal mapping techniques that can fully capture the intrinsic dynamics of the non-stationary time series intracardiac electrogram signal to accurately identify the rotor pivot zones that may cause and maintain AF. In this thesis, four time domain approaches namely multiscale entropy (MSE) recurrence period density entropy (RPDE), kurtosis and intrinsic mode function (IMF) complexity index and one frequency domain approach namely multiscale frequency (MSF) was proposed and developed for accurate identification of rotor pivot points. The novel approaches were validated using optical mapping data with induced ventricular arrhythmia in ex-vivo isolated rabbit heart with single, double and meandering rotors (including numerically simulated data). The results demonstrated the efficacy of the novel approaches in accurate identification of rotor pivot point. The chaotic nature of rotor pivot point resulted in higher complexity measured by MSE, RPDE, kurtosis, IMF and MSF compared to the stable rotor periphery that enabled its accurate identification. Additionally, the feasibility of using conventional catheter mapping system to generate patient specific 3D maps for intraprocedural guidance for catheter ablation using these novel approaches was demonstrated with 1055 intracardiac electrograms obtained from both atria’s in a persistent AF patient. Notably, the 3D maps did not provide any clinically significant information on rotor pivot point identification or the presence of rotors themselves. Validation of these novel approaches is required in large datasets with paroxysmal and persistent AF patients to evaluate their clinical utility in rotor identification as potential targets for AF ablation

Autonomic nervous system biomarkers from multi-modal and model-based signal processing in mental health and illness

Esta tesis se centra en técnicas de procesado multimodal y basado en modelos de señales para derivar parámetros fisiológicos, es decir, biomarcadores, relacionados con el sistema nervioso autónomo (ANS). El desarrollo de nuevos métodos para derivar biomarcadores de ANS no invasivos en la salud y la enfermedad mental ofrece la posibilidad de mejorar la evaluación del estrés y la monitorización de la depresión. Para este fin, el presente documento se estructura en tres partes principales. En la Parte I, se proporciona unaintroducción a la salud y la enfermedad mental (Cap. 1). Además, se presenta un marco teórico para investigar la etiología de los trastornos mentales y el papel del estrés en la enfermedad mental (Cap. 2). También se destaca la importancia de los biomarcadores no invasivos para la evaluación del ANS, prestando especial atención en la depresión clínica (Cap. 3, 4). En la Parte II, se proporciona el marco metodológico para derivar biomarcadores del ANS. Las técnicas de procesado de señales incluyen el análisis conjunto de la variabilidad del rítmo cardíaco (HRV) y la señal respiratoria (Cap. 6), técnicas novedosas para derivar la señal respiratoria del electrocardiograma (ECG) (Cap. 7) y un análisis robusto que se basa en modelar la forma de ondas del pulso del fotopletismograma (PPG) (Ch. 8). En la Parte III, los biomarcadores del ANS se evalúan en la quantificacióndel estrés (Cap. 9) y en la monitorización de la depresión (Ch. 10).Parte I: La salud mental no solo está relacionada con ese estado positivo de bienestar, en el que un individuo puede enfrentar a las situaciones estresantes de la vida, sino también con la ausencia de enfermedad mental. La enfermedad o trastorno mental se puede definir como un trastorno emocional, cognitivo o conductual que causa un deterioro funcional sustancial en una o más actividades importantes de la vida. Los trastornos mentales más comunes, que muchas veces coexisten, son la ansiedad y el trastorno depresivo mayor (MDD). La enfermedad mental tiene un impacto negativo en la calidad de vida, ya que se asocia con pérdidas considerables en la salud y el funcionamiento, y aumenta ignificativamente el riesgo de una persona de padecer enfermedades ardiovasculares.Un instigador común que subyace a la comorbilidad entre el MDD, la patologíacardiovascular y la ansiedad es el estrés mental. El estrés es común en nuestra vida de rítmo rapido e influye en nuestra salud mental. A corto plazo, ANS controla la respuesta cardiovascular a estímulos estresantes. La regulación de parámetros fisiológicos, como el rítmo cardíaco, la frecuencia respiratoria y la presión arterial, permite que el organismo responda a cambios repentinos en el entorno. Sin embargo, la adaptación fisiológica a un fenómeno ambiental que ocurre regularmente altera los sistemas biológicos involucrados en la respuesta al estrés. Las alteraciones neurobiológicas en el cerebro pueden alterar lafunción del ANS. La disfunción del ANS y los cambios cerebrales estructurales tienen un impacto negativo en los procesos cognitivos, emocionales y conductuales, lo que conduce al desarrollo de una enfermedad mental.Parte II: El desarrollo de métodos novedosos para derivar biomarcadores del ANS no invasivos ofrece la posibilidad de mejorar la evaluacón del estrés en individuos sanos y la disfunción del ANS en pacientes con MDD. El análisis conjunto de varias bioseñales (enfoquemultimodal) permite la cuantificación de interacciones entre sistemas biológicos asociados con ANS, mientras que el modelado de bioseãles y el análisis posterior de los parámetros del modelo (enfoque basado en modelos) permite la cuantificación robusta de cambios en mecanismos fisiológicos relacionados con el ANS. Un método novedoso, quetiene en cuenta los fenómenos de acoplo de fase y frecuencia entre la respiración y las señales de HRV para evaluar el acoplo cardiorrespiratorio no lineal cuadrático se propone en el Cap. 6.3. En el Cap. 7 se proponen nuevas técnicas paramejorar lamonitorización de la respiración. En el Cap. 8, para aumentar la robustez de algunas medidas morfológicas que reflejan cambios en el tonno arterial, se considera el modelado del pulso PPG como una onda principal superpuesta con varias ondas reflejadas.Parte III: Los biomarcadores del ANS se evalúan en la cuantificación de diferentes tipos de estrés, ya sea fisiológico o psicológico, en individuos sanos, y luego, en la monitorización de la depresión. En presencia de estrés mental (Cap. 9.1), inducido por tareas cognitivas, los sujetos sanos muestran un incremento en la frecuencia respiratoria y un mayor número de interacciones no lineales entre la respiración y la seãl de HRV. Esto podría estar asociado con una activación simpática, pero también con una respiración menos regular. En presencia de estrés hemodinámico (Cap. 9.2), inducido por un cambio postural, los sujetos sanos muestran una reducción en el acoplo cardiorrespiratoriono lineal cuadrático, que podría estar relacionado con una retracción vagal. En presencia de estrés térmico (Cap. 9.3), inducido por la exposición a emperaturas ambientales elevadas, los sujetos sanos muestran un aumento del equilibrio simpatovagal. Esto demuestra que los biomarcadores ANS son capaces de evaluar diferentes tipos de estrés y pueden explorarse más en el contexto de la monitorización de la depresión. En el Cap. 10, se evalúan las diferencias en la función del ANS entre elMDD y los sujetos sanos durante un protocolo de estrés mental, no solo con los valores brutos de los biomarcadores del ANS, sino también con los índices de reactividad autónoma, que reflejan la capacidad deun individuo para afrontar con una situación desafiante. Los resultados muestran que la depresión se asocia con un desequilibrio autonómico, que se caracteriza por una mayor actividad simpática y una reducción de la distensibilidad arterial. Los índices de reactividad autónoma cuantificados por cambios, entre etapas de estrés y de recuperación, en los sustitutos de la rigidez arterial, como la pérdida de amplitud de PPG en las ondas reflejadas, muestran el mejor rendimiento en términos de correlación con el grado de la depresión, con un coeficiente de correlación r = −0.5. La correlación negativa implicaque un mayor grado de depresión se asocia con una disminución de la reactividadautónoma. El poder discriminativo de los biomarcadores del ANS se aprecia también por su alto rendimiento diagnóstico para clasificar a los sujetos como MDD o sanos, con una precisión de 80.0%. Por lo tanto, se puede concluir que los biomarcadores del ANS pueden usarse para evaluar el estrés y que la distensibilidad arterial deteriorada podría constituir un biomarcador de salud mental útil en el seguimiento de la depresión.This dissertation is focused on multi-modal and model-based signal processing techniques for deriving physiological parameters, i.e. biomarkers, related to the autonomic nervous system (ANS). The development of novel approaches for deriving noninvasive ANS biomarkers in mental health and illness offers the possibility to improve the assessment of stress and the monitoring of depression. For this purpose, the present document is structured in three main parts. In Part I, an introduction to mental health and illness is provided (Ch. 1). Moreover, a theoretical framework for investigating the etiology of mental disorders and the role of stress in mental illness is presented (Ch. 2). The importance of noninvasive biomarkers for ANS assessment, paying particular attention in clinical depression, is also highlighted (Ch. 3, 4). In Part II, themethodological framework for deriving ANS biomarkers is provided. Signal processing techniques include the joint analysis of heart rate variability (HRV) and respiratory signals (Ch. 6), novel techniques for deriving the respiratory signal from electrocardiogram (ECG) (Ch. 7), and a robust photoplethysmogram(PPG)waveform analysis based on amodel-based approach (Ch. 8). In Part III, ANS biomarkers are evaluated in stress assessment (Ch. 9) and in the monitoring of depression (Ch. 10). Part I:Mental health is not only related to that positive state ofwell-being, inwhich an individual can cope with the normal stresses of life, but also to the absence of mental illness. Mental illness or disorder can be defined as an emotional, cognitive, or behavioural disturbance that causes substantial functional impairment in one or more major life activities. The most common mental disorders, which are often co-occurring, are anxiety and major depressive disorder (MDD). Mental illness has a negative impact on the quality of life, since it is associated with considerable losses in health and functioning, and increases significantly a person’s risk for cardiovascular diseases. A common instigator underlying the co-morbidity between MDD, cardiovascular pathology, and anxiety is mental stress. Stress is common in our fast-paced society and strongly influences our mental health. In the short term, ANS controls the cardiovascular response to stressful stimuli. Regulation of physiological parameters, such as heart rate, respiratory rate, and blood pressure, allows the organism to respond to sudden changes in the environment. However, physiological adaptation to a regularly occurring environmental phenomenon alters biological systems involved in stress response. Neurobiological alterations in the brain can disrupt the function of the ANS. ANS dysfunction and structural brain changes have a negative impact on cognitive, emotional, and behavioral processes, thereby leading to development of mental illness. Part II: The development of novel approaches for deriving noninvasive ANS biomarkers offers the possibility to improve the assessment of stress in healthy individuals and ANS dysfunction in MDD patients. Joint analysis of various biosignals (multi-modal approach) allows for the quantification of interactions among biological systems associated with ANS, while the modeling of biosignals and subsequent analysis of the model’s parameters (model-based approach) allows for the robust quantification of changes in physiological mechanisms related to the ANS. A novel method, which takes into account both phase and frequency locking phenomena between respiration and HRV signals, for assessing quadratic nonlinear cardiorespiratory coupling is proposed in Ch. 6.3. Novel techniques for improving the monitoring of respiration are proposed in Ch. 7. In Ch. 8, to increase the robustness for some morphological measurements reflecting arterial tone changes, the modeling of the PPG pulse as amain wave superposed with several reflected waves is considered. Part III: ANS biomarkers are evaluated in the assessment of different types of stress, either physiological or psychological, in healthy individuals, and then, in the monitoring of depression. In the presence of mental stress (Ch. 9.1), induced by cognitive tasks, healthy subjects show an increment in the respiratory rate and higher number of nonlinear interactions between respiration and HRV signal, which might be associated with a sympathetic activation, but also with a less regular breathing. In the presence of hemodynamic stress (Ch. 9.2), induced by a postural change, healthy subjects show a reduction in strength of the quadratic nonlinear cardiorespiratory coupling, whichmight be related to a vagal withdrawal. In the presence of heat stress (Ch. 9.3), induced by exposure to elevated environmental temperatures, healthy subjects show an increased sympathovagal balance. This demonstrates that ANS biomarkers are able to assess different types of stress and they can be further explored in the context of depression monitoring. In Ch. 10, differences in ANS function between MDD and healthy subjects during a mental stress protocol are assessed, not only with the raw values of ANS biomarkers but also with autonomic reactivity indices, which reflect the ability of an individual to copewith a challenging situation. Results show that depression is associated with autonomic imbalance, characterized by increased sympathetic activity and reduced arterial compliance. Autonomic reactivity indices quantified by changes, from stress to recovery, in arterial stiffness surrogates, such as the PPG amplitude loss in wave reflections, show the best performance in terms of correlation with depression severity, yielding to correlation coefficient r = −0.5. The negative correlation implies that a higher degree of depression is associated with a decreased autonomic reactivity. The discriminative power of ANS biomarkers is supported by their high diagnostic performance for classifying subjects as having MDD or not, yielding to accuracy of 80.0%. Therefore, it can be concluded that ANS biomarkers can be used for assessing stress and that impaired arterial compliance might constitute a biomarker of mental health useful in the monitoring of depression.<br /

ECG-derived respiratory rate in atrial fibrillation

Objective: The present study addresses the problem of estimating the respiratory rate from the morphological ECG variations in the presence of atrial fibrillatory waves (f-waves). The significance of performing f-wave suppression before respiratory rate estimation is investigated. Methods: The performance of a novel approach to ECG-derived respiration, named “slope range” (SR) and designed particularly for operation in atrial fibrillation (AF), is compared to that of two well-known methods based on either R-wave angle (RA) or QRS loop rotation angle (LA). A novel rule is proposed for spectral peak selection in respiratory rate estimation. The suppression of f-waves is accomplished using signal- and noise-dependent QRS weighted averaging. The performance evaluation embraces real as well as simulated ECG signals acquired from patients with persistent AF; the estimation error of the respiratory rate is determined for both types of signals. Results: Using real ECG signals and reference respiratory signals, rate estimation without f-wave suppression resulted in a median error of 0.015±0.021 Hz and 0.019±0.025 Hz for SR and RA, respectively, whereas LA with f-wave suppression resulted in 0.034±0.039 Hz. Using simulated signals, the results also demonstrate that f-wave suppression is superfluous for SR and RA, whereas it is essential for LA. Conclusion: The results show that SR offers the best performance as well as computational simplicity since f-wave suppression is not needed. Significance: The respiratory rate can be robustly estimated from the ECG in the presence of AF

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

Personalised Signal Processing for Cortical and Cardiac Applications

Biomedical signals reflect alterations in human physiological parameters in both healthy and pathological conditions. Their inherent variability over time and across individuals reduces the reproducibility of results and utility of biomedical signals. Personalisation of signal processing schemes by including parameters associated with the sources of inter-session and inter-subject variability can promote the usability of biomedical signals for larger cohorts. This thesis explores strategies for personalising signal processing techniques for the assessment of cortical and cardiac electrophysiological phenomena. A sensorimotor rhythm-based brain-computer interface (BCI) exploits changes in electroencephalogram (EEG) during motor imagery tasks and can establish a direct communication link between the brain and a computer, which may augment motor performance. Dealing with the variability inherent in EEG signals is not trivial and yet to be understood comprehensively to deliver BCI technology for practical use. A waveletbased signal processing method has been applied to model inter-subject associative source activations, leading to a more generalised BCI design. Intracardiac electrograms (EGM) are important for mapping electrical activation across the heart. Multiple variables, including bipolar vector orientation relative to the wave propagation vector, inter-electrode spacing, impact EGM recording. In this thesis, intracardiac EGM recorded with a customised array of electrodes were analysed to assess the impact of bipolar vector orientation and inter-electrode spacing on atrial fibrillation mapping. A novel spatial filtering method has been proposed to reduce the measurement uncertainty due to bipolar vector orientation. Besides, an independent component analysis-based filtering has been proposed as a potential preprocessing method for eliminating ventricular far-field artefact.Thesis (MPhil) -- University of Adelaide, School of Electrical & Electronic Engineering, 202

Reflex syncope : an integrative physiological approach

Síncope, a forma mais comum de perda temporária de consciência é responsável por até 5% das idas aos serviços de emergência e até 3% dos internamentos hospitalares. É um problema médico frequente, com múltiplos gatilhos, incapacitante, potencialmente perigoso e desafiante em termos diagnósticos e terapêuticos. Assim, é necessária uma anamnese detalhada para primeiro estabelecer a natureza da perda de consciência, mas, após o diagnóstico, as medidas terapêuticas existentes são pouco eficazes. Embora a fisiopatologia da síncope vasovagal ainda não tenha sido completamente esclarecida, alguns mecanismos subjacentes foram já desvendados. Em última análise, a síncope depende de uma falha transitória na perfusão cerebral pelo que qualquer factor que afecte a circulação sanguínea cerebral pode determinar a ocorrência de síncope. Assim, o objectivo do presente estudo é caracterizar o impacto hemodinâmico e autonómico nos mecanismos subjacentes à síncope reflexa, para melhorar o diagnóstico, o prognóstico e a qualidade de vida dos doentes e dos seus cuidadores. Para isso, desenhámos e implementámos novas ferramentas matemáticas e computacionais que permitem uma avaliação autonómica e hemodinâmica integrada, de forma a aprofundar a compreensão do seu envolvimento nos mecanismos de síncope reflexa. Além disso, refinando a precisão do diagnóstico, a sensibilidade e a especificidade do teste de mesa de inclinação (“tilt test”), estabelecemos uma ferramenta preditiva do episódio iminente de síncope. Isso permitiu-nos estabelecer alternativas de tratamento eficazes e personalizadas para os doentes refractários às opções convencionais, sob a forma de um programa de treino de ortostatismo (“tilt training”), contribuindo para o aumento da sua qualidade de vida e para a redução dos custos directos e indirectos da sua assistência médica. Assim, num estudo verdadeiramente multidisciplinar envolvendo doentes com síncope reflexa refractária à terapêutica, conseguimos demonstrar uma assincronia funcional das respostas reflexas autonómicas e hemodinâmicas, expressas por um desajuste temporal entre o débito cardíaco e as adaptações de resistência total periférica, uma resposta baroreflexa atrasada e um desequilíbrio incremental do tónus autonómico que, em conjunto, poderão resultar de uma disfunção do sistema nervoso autónomo que se traduz por uma reserva simpática diminuída. Igualmente, desenhámos, testámos e implementámos uma plataforma computacional e respectivo software associado - a plataforma FisioSinal –incluindo novas formas, mais dinâmicas, de avaliação integrada autonómica e hemodinâmica, que levaram ao desenvolvimento de algoritmos preditivos para a estratificação de doentes com síncope. Além disso, na aplicação dessas ferramentas, comprovámos a eficácia de um tratamento não invasivo, não disruptivo e integrado, focado na neuromodulação das variáveis autonómicas e cardiovasculares envolvidas nos mecanismos de síncope. Esta terapêutica complementar levou a um aumento substancial da qualidade de vida dos doentes e à abolição dos eventos sincopais na grande maioria dos doentes envolvidos. Em conclusão, o nosso trabalho contribuiu para preencher a lacuna entre a melhor informação científica disponível e sua aplicação na prática clínica, sustentando-se nos três pilares da medicina translacional: investigação básica, clínica e comunidade.Syncope, the most common form of transient loss of consciousness, accounts for up to 5% of emergency room visits and up to 3% of hospital admissions. It is a frequent medical problem with multiple triggers, potentially dangerous, incapacitating, and challenging to diagnose. Therefore, a detailed clinical history is needed first to establish the nature of the loss of consciousness. However, after diagnosis, the therapeutic measures available are still very poor. Although the exact pathophysiology of vasovagal syncope remains to be clarified, some underlying mechanisms have been unveiled, dependent not only on the cause of syncope but also on age and various other factors that affect clinical presentation. Ultimately, syncope depends on a failure of the circulation to perfuse the brain, so any factor affecting blood circulation may determine syncope occurrence. Thus, the purpose of the present study is to understand the impact of the hemodynamic and autonomic functions on reflex syncope mechanisms to improve patients diagnose, prognosis and general quality of life. Bearing that in mind, we designed and implemented new mathematical and computational tools for autonomic and hemodynamic evaluation, in order to deepen the understanding of their involvement in reflex syncope mechanisms. Furthermore, by refining the diagnostic accuracy, sensitivity and specificity of the head-up tilt-table test, we established a predictive tool for the impending syncopal episode. This allowed us to establish effective and personalised treatment alternatives to patient’s refractory to conventional options, contributing to their increase in the quality of life and a reduction of health care and associated costs. In accordance, in a truly multidisciplinary study involving reflex syncope patients, we were able to show an elemental functional asynchrony of hemodynamic and autonomic reflex responses, expressed through a temporal mismatch between cardiac output and total peripheral resistance adaptations, a deferred baroreflex response and an unbalanced, but incremental, autonomic tone, all contributing to autonomic dysfunction, translated into a decreased sympathetic reserve. Through the design, testing and implementation of a computational platform and the associated software - FisioSinal platform -, we developed novel and dynamic ways of autonomic and hemodynamic evaluation, whose data lead to the development of predictive algorithms for syncope patients’risk stratification. Furthermore, through the application of these tools, we showed the effectiveness of a non-invasive, non-disruptive and integrated treatment, focusing on neuromodulation of the autonomic and cardiovascular variables involved in the syncope mechanisms, leading to a substantial increase of quality of life and the abolishment of syncopal events in a vast majority of the enrolled patients. In conclusion, our work contributed to fill the gap between the best available scientific information and its application in the clinical practice by tackling the three pillars of translational medicine: bench-side, bedside and community

The Application of Computer Techniques to ECG Interpretation

This book presents some of the latest available information on automated ECG analysis written by many of the leading researchers in the field. It contains a historical introduction, an outline of the latest international standards for signal processing and communications and then an exciting variety of studies on electrophysiological modelling, ECG Imaging, artificial intelligence applied to resting and ambulatory ECGs, body surface mapping, big data in ECG based prediction, enhanced reliability of patient monitoring, and atrial abnormalities on the ECG. It provides an extremely valuable contribution to the field