Zuzana Lazarova

Reduced short-term complexity of heart rate and blood pressure dynamics in patients with diabetes mellitus type 1: multiscale entropy analysis

Multiscale entropy (MSE) analysis provides information about complexity on various time scales. The aim of this study was to test whether MSE is able to detect autonomic dysregulation in young patients with diabetes mellitus (DM). We analyzed heart rate (HR) oscillations, systolic (SBP) and diastolic blood pressure (DBP) signals in 14 patients with DM type 1 and 14 age- and sex-matched healthy controls. SampEn values (scales 1-10) and linear measures were computed. HR: among the linear measures of heart rate variability significant differences between groups were only found for RMSSD (p = 0.043). MSE was significantly reduced on scales 2 and 3 in DM (p = 0.023 and 0.010, respectively). SBP and DBP: no significant differences were detected with linear measures. In contrast, MSE analysis revealed significantly lower SampEn values in DM on scale 3 (p = 0.039 for SBP; p = 0.015 for DBP). No significant correlations were found between MSE and linear measures. In conclusion, MSE analysis of HR, SBP and DBP oscillations is able to detect subtle abnormalities in cardiovascular control in young patients with DM and is independent of standard linear measures.

Recurrences in heart rate dynamics are changed in patients with diabetes mellitus.

Detection of subclinical autonomic dysfunction in patients with diabetes mellitus (DM) is of vital importance for risk stratification and subsequent management. Heart rate variability (HRV) analysis is a sensitive tool for assessment of cardiovascular autonomic dysfunction. As the heart is controlled by non‐linear deterministic system, the non‐linear dynamics measures should be preferred. Recurrence plot (RP) is able to analyse recurrences within system dynamics. The aim of the study was to detect heart rate dysregulation in DM by RP and to ascertain which of the recurrence quantification analysis (RQA) measures are changed in patients with DM compared to control group. We analysed HRV recordings from 17 young patients with type 1 DM and 17 healthy matched control subjects. RQA was performed on RPs with a fixed value of recurrence points percentage. From RQA measures based on diagonal lines, we have found higher percentage of determinism in DM group (P = 0·038). Trapping time measure was also higher in DM (P = 0·022). RQA revealed changes in dynamics recurrences with reduced complexity of heart rate control in young diabetic patients. As RQA parameters are independent of overall HRV, parameters of RP should be used together with linear HRV parameters for better description of heart rate dysregulation in patients with diabetics.

Baroreflex analysis in diabetes mellitus: linear and nonlinear approaches

The aim of our study was to employ novel nonlinear synchronization approaches as a tool to detect baroreflex impairment in young patients with subclinical autonomic dysfunction in Type 1 diabetes mellitus (DM) and compare them to standard linear baroreflex sensitivity (BRS) methods. We recorded beat-to-beat pulse interval (PI) and systolic blood pressure (SBP) in 14 DM patients and 14 matched healthy controls. We computed the information domain synchronization index (IDSI), cross-multiscale entropy, joint symbolic dynamics, information-based similarity index (IBSI) in addition to time domain and spectral measures of BRS. This multi parametric analysis showed that baroreflex gain is well-preserved, but the time delay within the baroreflex loop is significantly increased in patients with DM. Further, the level of similarity between blood pressure and heart rate fluctuations was significantly reduced in DM. In conclusion, baroreflex function in young DM patients is changed. The quantification of nonlinear similarity and baroreflex delay in addition to baroreflex gain may provide an improved diagnostic tool for detection of subclinical autonomic dysfunction in DM.

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.

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.

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.

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.

Causal coherence analysis of cardiovascular variables in obese preadolescents and adolescents

Obesity during adulthood has been associated with cardiovascular disease, but its adverse effects during adolescence are less well established. The aim of this study was to probe cardiovascular control in obese adolescence by studying causal coherence between cardiovascular variables. Sixty minutes of resting ECG and finger blood pressure were recorded in 19 obese and 19 non-obese subjects in the supine position to measure pair-wise spectral coherence in the low frequency band between heart rate, systolic and diastolic blood pressure, pulse pressure, total peripheral resistance and left ventricular ejection time. We observed that causal coherences in {systolic blood pressure → total peripheral resistance} and {left ventricular ejection time → systolic blood pressure} directions were significantly decreased in obese preadolescents and adolescents when compared to the healthy control group, despite the lack of difference in the magnitude of oscillations of cardiovascular variables. In conclusion, causal coherence analysis of cardiovascular variables may give new insight into cardiovascular dysregulation in young obese subjects.