Barbora Czippelova

Multiscale time irreversibility of heart rate and blood pressure variability during orthostasis

Time irreversibility is a characteristic feature of non-equilibrium, complex systems such as the cardiovascular control mediated by the autonomic nervous system (ANS). Time irreversibility analysis of heart rate variability (HRV) and blood pressure variability (BPV) represents a new approach to assess cardiovascular regulatory mechanisms. The aim of this paper was to assess the changes in HRV and BPV irreversibility during the active orthostatic test (a balance of ANS shifted towards sympathetic predominance) in 28 healthy young subjects. We used three different time irreversibility indices-Portas, Guziks and Ehlers indices (P%, G% and E, respectively) derived from data segments containing 1000 beat-to-beat intervals on four timescales. We observed an increase in the HRV and a decrease in the BPV irreversibility during standing compared to the supine position. The postural change in irreversibility was confirmed by surrogate data analysis. The differences were more evident in G% and E than P% and for higher scale factors. Statistical analysis showed a close relationship between G% and E. Contrary to this, the association between P% and G% and P% and E was not proven. We conclude that time irreversibility of beat-to-beat HRV and BPV is significantly altered during orthostasis, implicating involvement of the autonomous nervous system in its generation.

Causal analysis of short-term cardiovascular variability: state-dependent contribution of feedback and feedforward mechanisms

Baroreflex function is usually assessed from spontaneous oscillations of blood pressure (BP) and cardiac RR interval assuming a unidirectional influence from BP to RR. However, the interaction of BP and RR is bidirectional—RR also influences BP. Novel methods based on the concept of Granger causality were recently developed for separate analysis of feedback (baroreflex) and feedforward (mechanical) interactions between RR and BP. We aimed at assessing the proportion of the two causal directions of the interactions between RR and systolic BP (SBP) oscillations during various conditions, and at comparing causality measures from SBP to RR with baroreflex gain indexes. Arterial BP and ECG signals were noninvasively recorded in 16 young healthy volunteers during supine rest, mental arithmetics, and head-up tilt test, as well as during the combined administration of these stressors. The causal interactions between beat-to-beat RR and SBP signals were analyzed in time, frequency, and information domains. The baroreflex gain was assessed in the frequency domain using non-causal and causal measures of the transfer function from SBP to RR. We found a consistent increase in the baroreflex coupling strength from SBP to RR during head-up tilt, an insensitivity of the coupling strength along the non-baroreflex direction to both stressors, and no significant effect of mental arithmetics on the feedback coupling strength. It indicates that the proportion of causal interactions between SBP and RR significantly varies during different conditions. The increase in the coupling from SBP to RR with tilt was not accompanied by concomitant variations of the transfer function gain, suggesting that causality and gain analyses are complementary and assess different aspects of the baroreflex regulation of heart rate.

Entropy Analysis of RR and QT Interval Variability during Orthostatic and Mental Stress in Healthy Subjects

Autonomic activity affects beat-to-beat variability of heart rate and QT interval. The aim of this study was to explore whether entropy measures are suitable to detect changes in neural outflow to the heart elicited by two different stress paradigms. We recorded short-term ECG in 11 normal subjects during an experimental protocol that involved head-up tilt and mental arithmetic stress and computed sample entropy, cross-sample entropy and causal interactions based on conditional entropy from RR and QT interval time series. Head-up tilt resulted in a significant reduction in sample entropy of RR intervals and cross-sample entropy, while mental arithmetic stress resulted in a significant reduction in coupling directed from RR to QT. In conclusion, measures of entropy are suitable to detect changes in neural outflow to the heart and decoupling of repolarisation variability from heart rate variability elicited by orthostatic or mental arithmetic stress.

Basic cardiovascular variability signals: mutual directed interactions explored in the information domain

The study of short-term cardiovascular interactions is classically performed through the bivariate analysis of the interactions between the beat-to-beat variability of heart period (RR interval from the ECG) and systolic blood pressure (SBP). Recent progress in the development of multivariate time series analysis methods is making it possible to explore how directed interactions between two signals change in the context of networks including other coupled signals. Exploiting these advances, the present study aims at assessing directional cardiovascular interactions among the basic variability signals of RR, SBP and diastolic blood pressure (DBP), using an approach which allows direct comparison between bivariate and multivariate coupling measures. To this end, we compute information-theoretic measures of the strength and delay of causal interactions between RR, SBP and DBP using both bivariate and trivariate (conditioned) formulations in a group of healthy subjects in a resting state and during stress conditions induced by head-up tilt (HUT) and mental arithmetics (MA). We find that bivariate measures better quantify the overall (direct  +  indirect) information transferred between variables, while trivariate measures better reflect the existence and delay of directed interactions. The main physiological results are: (i) the detection during supine rest of strong interactions along the pathway RR  →  DBP  →  SBP, reflecting marked Windkessel and/or Frank-Starling effects; (ii) the finding of relatively weak baroreflex effects SBP  →  RR at rest; (iii) the invariance of cardiovascular interactions during MA, and the emergence of stronger and faster SBP  →  RR interactions, as well as of weaker RR  →  DBP interactions, during HUT. These findings support the importance of investigating cardiovascular interactions from a network perspective, and suggest the usefulness of directed information measures to assess physiological mechanisms and track their changes across different physiological states.

Cardiovascular control during orthostatic and mental stress: Conditional entropy based analysis

The aim of this study was to characterize the changes in cardiovascular dynamics as a result of orthostatic and mental stress and their combination by linear and information domain analysis of heart rate and blood pressure oscillations. We recorded beat-to-beat RR intervals and systolic blood pressure values in 16 volunteers during mental arithmetics task and head-up tilt test and their simultaneous administration. The analysis included spectral measures and quantification of cardiovascular signals complexity and their mutual causal coupling. Our results demonstrated that orthostatic and mental stress challenges - despite similar heart rate and blood pressure changes - evoked different effects on cardiovascular control system. The novel conditional entropy based measures were sensitive to detect differences in heart rate and blood pressure dynamics responses evoked by mental stress in different body positions.

Time irreversibility of heart rate oscillations in newborns – Does it reflect system nonlinearity?

Abstract The aim of our research was to find out if the time irreversibility as a sign of specific class of nonlinear dynamics is present even in the newborns heart rate oscillations. Multiscale irreversibility indices (Portas index P %, Guzik index G % and Ehlers index E ) of the heart rate signals were computed in 20 healthy neonates. The presence of system nonlinearity was assessed by surrogate data analysis. The results of our analysis revealed asymmetrical nature of heart rate oscillations present in the majority of neonatal heart rate recordings. Moreover, time irreversibility index P % was able to detect shift of sympathovagal balance toward sympathetic dominance in newborns. Our findings support the concept of nonlinearity as a universal feature of the biological control system even in the early stage of the system maturation. This finding supports the application of nonlinear methods to heart rate variability analysis.

Heart rate and blood pressure control in obesity – how to detect early dysregulation?

Obesity is accompanied by many severe complications including various cardiovascular disorders. An impairment of cardiovascular control by autonomic nervous system could be one of the possible links between obesity and cardiovascular complications development. The aim of this study was to compare spontaneous heart rate and systolic blood pressure oscillations reflecting cardiovascular autonomic control of young obese subjects with normal control subjects by linear and nonlinear methods and to find sensitive markers of early autonomic dysregulation. Continuous recordings of beat‐to‐beat systolic blood pressure and RR intervals from ECG were obtained from 40 obese subjects (25 female, age 14·2 [13·1–16·1] (median [interquartile range]) years) and gender and age matched non‐obese control subjects. In addition to linear measures (time and frequency domain), we performed recurrence quantification analysis (RQA) and multiscale entropy analysis for both signals. While no significant differences in heart rate and systolic blood pressure dynamics were detected by linear measures and MSE, analysis of recurrence plots from RR intervals time series showed significant differences – indices trapping time and maximal length of vertical from RQA were significantly higher in obese compared to control group. We conclude that heart rate and blood pressure control by autonomic nervous system in young obese subjects is relatively well preserved. However, novel RQA‐related measures are able to detect early subtle abnormalities in cardiac autonomic control in obese subjects indicating decreased signal complexity.

Towards understanding the complexity of cardiovascular oscillations: Insights from information theory

Cardiovascular complexity is a feature of healthy physiological regulation, which stems from the simultaneous activity of several cardiovascular reflexes and other non-reflex physiological mechanisms. It is manifested in the rich dynamics characterizing the spontaneous heart rate and blood pressure variability (HRV and BPV). The present study faces the challenge of disclosing the origin of short-term HRV and BPV from the statistical perspective offered by information theory. To dissect the physiological mechanisms giving rise to cardiovascular complexity in different conditions, measures of predictive information, information storage, information transfer and information modification were applied to the beat-to-beat variability of heart period (HP), systolic arterial pressure (SAP) and respiratory volume signal recorded non-invasively in 61 healthy young subjects at supine rest and during head-up tilt (HUT) and mental arithmetics (MA). Information decomposition enabled to assess simultaneously several expected and newly inferred physiological phenomena, including: (i) the decreased complexity of HP during HUT and the increased complexity of SAP during MA; (ii) the suppressed cardiorespiratory information transfer, related to weakened respiratory sinus arrhythmia, under both challenges; (iii) the altered balance of the information transferred along the two arms of the cardiovascular loop during HUT, with larger baroreflex involvement and smaller feedforward mechanical effects; and (iv) an increased importance of direct respiratory effects on SAP during HUT, and on both HP and SAP during MA. We demonstrate that a decomposition of the information contained in cardiovascular oscillations can reveal subtle changes in system dynamics and improve our understanding of the complexity changes during physiological challenges.

Univariate and multivariate conditional entropy measures for the characterization of short-term cardiovascular complexity under physiological stress

OBJECTIVE A defining feature of physiological systems under the neuroautonomic regulation is their dynamical complexity. The most common approach to assess physiological complexity from short-term recordings, i.e. to compute the rate of entropy generation of an individual system by means of measures of conditional entropy (CE), does not consider that complexity may change when the investigated system is part of a network of physiological interactions. This study aims at extending the concept of short-term complexity towards the perspective of network physiology, defining multivariate CE measures whereby multiple physiological processes are accounted for in the computation of entropy rates. APPROACH Univariate and multivariate CE measures are computed using state-of-the-art methods for entropy estimation and applied to time series of heart period (H), systolic (S) and diastolic (D) arterial pressure, and respiration (R) variability measured in healthy subjects monitored in a resting state and during conditions of postural and mental stress. MAIN RESULTS Compared with the traditional univariate metric of short-term complexity, multivariate measures provide additional information with plausible physiological interpretation, such as (i) the dampening of respiratory sinus arrhythmia and activation of the baroreflex control during postural stress; (ii) the increased complexity of heart period and blood pressure variability during mental stress, reflecting the effect of respiratory influences and upper cortical centers; (iii) the strong influence of D on S, mediated by left ventricular ejection fraction and vascular properties; (iv) the role of H in reducing the complexity of D, related to cardiac run-off effects; and (v) the unidirectional role of R in influencing cardiovascular variability. SIGNIFICANCE Our results document the importance of employing a network perspective in the evaluation of the short-term complexity of cardiovascular and respiratory dynamics across different physiological states.

The role of respiration in the cardiovascular response to orthostatic and mental stress

The objective of this study was to determine the response of heart rate and blood pressure variability (respiratory sinus arrhythmia, baroreflex sensitivity) to orthostatic and mental stress, focusing on causality and the mediating effect of respiration. Seventy-seven healthy young volunteers (46 women, 31 men) aged 18.4 ± 2.7 yr underwent an experimental protocol comprising supine rest, 45° head-up tilt, recovery, and a mental arithmetic task. Heart rate variability and blood pressure variability were analyzed in the time and frequency domain and modeled as a multivariate autoregressive process where the respiratory volume signal acted as an external driver. During head-up tilt, tidal volume increased while respiratory rate decreased. During mental stress, breathing rate increased and tidal volume was elevated slightly. Respiratory sinus arrhythmia decreased during both interventions. Baroreflex function was preserved during orthostasis but was decreased during mental stress. While sex differences were not observed during baseline conditions, cardiovascular response to orthostatic stress and respiratory response to mental stress was more prominent in men compared with women. The respiratory response to the mental arithmetic tasks was more prominent in men despite a significantly higher subjectively perceived stress level in women. In conclusion, respiration shows a distinct response to orthostatic versus mental stress, mediating cardiovascular variability; it needs to be considered for correct interpretation of heart rate and blood pressure phenomena.