Tone entropy analysis of foetal heart rate variability

Development of the foetal autonomic nervous system can be indirectly understood by looking at the changes in beat to beat variability in foetal heart rates. This study presents Tone-Entropy (T-E) analysis of foetal heart rate variability (HRV) at multiple lags (1–8) to understand the influence of gestational ages (early and late) on the development of the foetal autonomic nervous system (ANS). The analysis was based on foetal electrocardiograms (FECGs) of 46 healthy foetuses of 20–32 weeks (early group) and 22 foetuses of 35–41 weeks (late group). Tone represents sympatho-vagal balance and entropy the total autonomic activities. Results show that tone increases and entropy decreases at all lags for the late foetus group. On the other hand, tone decreases and entropy increases at lags 1–4 in the early foetus group. Increasing tone in late foetuses might represent significant maturation of sympathetic nervous systems because foetuses approaching to delivery period need increased sympathetic activity. T-E could be quantitative clinical index to determine the early foetuses from late ones on the basis of maturation of autonomic nervous system

Physiological time-series investigations of cardiovascular regulation in healthy young adults during physical exercise.

Physiological parameters may be recorded non-invasively to gain information on cardiovascular function which can then characterise populations with various pathologies. Physical exercise produces specific autonomic nervous system (ANS) changes. There has been no comprehensive profiling of cardiovascular function during exercise or simultaneous characterisation of the influence of exercise on cardiac ventricular function and electrical activity. This work aims to address that, using a combination of physiological parameters. Between-lead agreement for ambulatory electrocardiographic (EGG) depolarisation-repolarisation (QT) interval was quantified during rest and exercise. In contrast to cardiac interval (RR) data, between-lead bias and limits of agreement for QT interval data should be quantified when reporting results from an ambulatory EGG system and between-gender QT differences should also be accounted for. EGG electrode location appears to significantly affect QT-RR hysteresis, the shortening of the post-exercise QT interval relative to that at similar heart rates during exercise or pre-exercise rest, further emphasising the need for standardisation of EGG electrode placement. Sample entropy (SampEn) measures data complexity. Few studies have compared SampEn of RR data (SampEn-RR) during exercise, whilst none have examined SampEn for the corresponding QT interval (SampEn-QT). Fractal analysis assesses data correlation and scaling structures. Detrended fluctuation analysis (DFA) provides a scaling exponent (a) which describes these properties. This has not been quantified for RR interval data during post-exercise recovery and has not been reported for QT interval data. Differences in a magnitudes for RR and QT data suggest that these quantities have different fractal properties. Exercise perturbs the resting QT-RR relationship via hysteresis. The QT variability index (QTVI) quantifies the relative autonomic influence on the atrial and ventricular myocardium during rest and exercise. QTVI is a consistent measure of cardiac ventricular function and as such appears to be a more useful index than other parameters based on RR or QT interval alone

Pulse Rate Variability for the Assessment of Cardiovascular Changes

Pulse rate variability (PRV) describes the way pulse rate changes through time and is measured from pulsatile signals such as the photoplethysmogram (PPG). It has been proposed as a surrogate for heart rate variability (HRV). Nonetheless, the relationship between these variables is not entirely clear, probably due to both physiological and technical aspects involved in the extraction of PRV. Moreover, the effects of cardiovascular changes on PRV have not been elucidated. In this thesis, four studies were performed to (1) determine the best combination of some technical aspects for the extraction of PRV from PPG signals; (2) evaluate the relationship between PRV and HRV under different cardiovascular conditions; and (3) explore the effects of cardiovascular changes on PRV. First, PRV extraction gave lower errors when (1) signals were acquired for at least 120 s with a 256 Hz sampling rate and filtered with lower low cut-off frequencies and elliptic, equiripple or Parks-McClellan filter; (2) cardiac cycles were determined using the D2max algorithm and the a fiducial points; and (3) the Fast Fourier Transform was applied to obtain frequency spectra. Secondly, the relationship between HRV and PRV was found to be affected by cold exposure and changes in blood pressure, while PRV was found to be different at different body sites. Finally, PRV was affected by haemodynamic changes, such as target flow, stroke rate and blood pressure, both in an in-vitro model and in-vivo data. Additionally, PRV was found to be a potential tool for the estimation of blood pressure, with errors as low as 1:54 ± 0:17 mmHg, 1:07 ± 0:06 mmHg and 1:22 ± 0:09 mmHg for the estimation of systolic, diastolic and mean arterial pressure. Although more studies are needed to fully understand PRV and its clinical potential, PRV should not be regarded as the same as HRV, and it could be consider as a potential valuable biomarker for cardiovascular health

Novel Approaches to Pervasive and Remote Sensing in Cardiovascular Disease Assessment

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, responsible for 45% of all deaths. Nevertheless, their mortality is decreasing in the last decade due to better prevention, diagnosis, and treatment resources. An important medical instrument for the latter processes is the Electrocardiogram (ECG). The ECG is a versatile technique used worldwide for its ease of use, low cost, and accessibility, having evolved from devices that filled up a room, to small patches or wrist- worn devices. Such evolution allowed for more pervasive and near-continuous recordings. The analysis of an ECG allows for studying the functioning of other physiological systems of the body. One such is the Autonomic Nervous System (ANS), responsible for controlling key bodily functions. The ANS can be studied by analyzing the characteristic inter-beat variations, known as Heart Rate Variability (HRV). Leveraging this relation, a pilot study was developed, where HRV was used to quantify the contribution of the ANS in modulating cardioprotection offered by an experimental medical procedure called Remote Ischemic Conditioning (RIC), offering a more objective perspective. To record an ECG, electrodes are responsible for converting the ion-propagated action potential to electrons, needed to record it. They are produced from different materials, including metal, carbon-based, or polymers. Also, they can be divided into wet (if an elec- trolyte gel is used) or dry (if no added electrolyte is used). Electrodes can be positioned either inside the body (in-the-person), attached to the skin (on-the-body), or embedded in daily life objects (off-the-person), with the latter allowing for more pervasive recordings. To this effect, a novel mobile acquisition device for recording ECG rhythm strips was developed, where polymer-based embedded electrodes are used to record ECG signals similar to a medical-grade device. One drawback of off-the-person solutions is the increased noise, mainly caused by the intermittent contact with the recording surfaces. A new signal quality metric was developed based on delayed phase mapping, a technique that maps time series to a two-dimensional space, which is then used to classify a segment into good or noisy. Two different approaches were developed, one using a popular image descriptor, the Hu image moments; and the other using a Convolutional Neural Network, both with promising results for their usage as signal quality index classifiers.As doenças cardiovasculares (DCVs) são a principal causa de morte no mundo, res- ponsáveis por 45% de todas estas. No entanto, a sua mortalidade tem vindo a diminuir na última década, devido a melhores recursos na prevenção, diagnóstico e tratamento. Um instrumento médico importante para estes recursos é o Eletrocardiograma (ECG). O ECG é uma técnica versátil utilizada em todo o mundo pela sua facilidade de uso, baixo custo e acessibilidade, tendo evoluído de dispositivos que ocupavam uma sala inteira para pequenos adesivos ou dispositivos de pulso. Tal evolução permitiu aquisições mais pervasivas e quase contínuas. A análise de um ECG permite estudar o funcionamento de outros sistemas fisiológi- cos do corpo. Um deles é o Sistema Nervoso Autônomo (SNA), responsável por controlar as principais funções corporais. O SNA pode ser estudado analisando as variações inter- batidas, conhecidas como Variabilidade da Frequência Cardíaca (VFC). Aproveitando essa relação, foi desenvolvido um estudo piloto, onde a VFC foi utilizada para quantificar a contribuição do SNA na modulação da cardioproteção oferecida por um procedimento mé- dico experimental, denominado Condicionamento Isquêmico Remoto (CIR), oferecendo uma perspectiva mais objetiva. Na aquisição de um ECG, os elétrodos são os responsáveis por converter o potencial de ação propagado por iões em eletrões, necessários para a sua recolha. Estes podem ser produzidos a partir de diferentes materiais, incluindo metal, à base de carbono ou polímeros. Além disso, os elétrodos podem ser classificados em húmidos (se for usado um gel eletrolítico) ou secos (se não for usado um eletrólito adicional). Os elétrodos podem ser posicionados dentro do corpo (dentro-da-pessoa), colocados em contacto com a pele (na-pessoa) ou embutidos em objetos da vida quotidiana (fora-da-pessoa), sendo que este último permite gravações mais pervasivas . Para este efeito, foi desenvolvido um novo dispositivo de aquisição móvel para gravar sinal de ECG, onde elétrodos embutidos à base de polímeros são usados para recolher sinais de ECG semelhantes a um dispositivo de grau médico. Uma desvantagem das soluções onde os elétrodos estão embutidos é o aumento do ruído, causado principalmente pelo contato intermitente com as superfícies de aquisição. Uma nova métrica de qualidade de sinal foi desenvolvida com base no mapeamento de fase atrasada, uma técnica que mapeia séries temporais para um espaço bidimensional, que é então usado para classificar um segmento em bom ou ruidoso. Duas abordagens diferentes foram desenvolvidas, uma usando um popular descritor de imagem, e outra utilizando uma Rede Neural Convolucional, com resultados promissores para o seu uso como classificadores de qualidade de sinal

Cardiovascular autonomic control after spinal cord injury: Comprehensive investigations into classification and care

Over 86,000 Canadians live with the consequences of a spinal cord injury (SCI). Injury to spinal autonomic pathways can lead to profound cardiovascular autonomic dysfunction. Key areas of concern identified by individuals living with SCI relate to continence and cardiovascular dysfunction. Conditions that result from autonomic dysfunction, such as autonomic dysreflexia (sudden extreme hypertension) are of particular concern. This thesis examined the cardiovascular autonomic consequences of SCI and their relationship to bowel care, the most potent stimulus for dysreflexia, and a key factor that negatively impacts quality of life after SCI. To assess cardiovascular autonomic control, first a quantitative marker of autonomic dysfunction following SCI had to be identified. In Aim 1 (Chapter 3), cardiovascular dysfunction during, and beyond, the first year of injury (n=63) was assessed using a novel quantitative non-invasive marker of cardiovascular autonomic control. From here, a randomized double-blind placebo-controlled crossover clinical trial to determine the effect of topical afferent blockade (lidocaine) on dysreflexia severity during bowel care was conducted (n=13). Aim 2 (Chapter 4) provides evidence that, contrary to current clinical guidelines, topical lidocaine prolongs bowel care, worsens dysreflexia, and increases cardiovascular symptoms. Despite bowel care concerns, past research shows that individuals do not change bowel care practices, highlighting knowledge translation gaps concerning evidence-based bowel management strategies. To address this, in Aim 3 (Chapter 5), semi-structured interviews (n=13) were used to examine the barriers and facilitators to changing bowel care. The largest influences on changing bowel care and potentially relevant intervention options were identified. Finally, during dysreflexia profound sympathetic stimulation may increase risk for cardiac arrhythmia. Aim 4 (Chapter 6) evaluated susceptibility to arrhythmia in a rodent-model of SCI, the impact of the sympathomimetic drug dobutamine on arrhythmia risk, and the potential mitigating effect of exercise training. SCI increased susceptibility to cardiac arrhythmia, with dobutamine further increasing susceptibility in high-level SCI. Exercise training ameliorated markers of arrhythmia risk during dobutamine. The research conducted in this thesis uses a translational and patient-orientated approach to bridge the gap between physiological understanding and meaningful improvement in the clinical setting for individuals living with cardiovascular and continence implications of SCI

Autonomic function in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory condition with poorly understood pathophysiology and increased cardiovascular risk. The mechanisms for increased cardiovascular risk are not fully known, however one novel mechanism explored in this thesis is autonomic nervous system (ANS) dysfunction. The thesis comprises of: a systematic literature review; two case-control studies (n=30 RA patients, n=34 controls; a longitudinal case-study (n=1 RA patient); a cohort study (n=112 RA patients); and a randomised placebo controlled crossover study (n=10 healthy controls). The work presented in this thesis demonstrates that ANS dysfunction is prevalent in ~60 % of RA patients and characterised by heightened sympathetic outflow to the peripheral vasculature (determined by muscle sympathetic nerve activity using microneurography), depressed baroreflex control of heart rate (determined using the modified Oxford technique), depressed heart rate variability and heightened vascular responses to stressors (cold pressor test and mental stress). Inflammation was associated with ANS dysfunction, and may well contribute to the increased cardiovascular risk seen in RA. Further studies are required to: confirm these findings; determine whether therapeutic strategies to restore ANS function improve prognosis in RA; and further explore the precise mechanisms by which inflammatory cytokines may influence ANS function in health and disease