Concomitant evaluation of cardiovascular and cerebrovascular controls via Geweke spectral causality to assess the propensity to postural syncope.

The evaluation of propensity to postural syncope necessitates the concomitant characterization of the cardiovascular and cerebrovascular controls and a method capable of disentangling closed loop relationships and decomposing causal links in the frequency domain. We applied Geweke spectral causality (GSC) to assess cardiovascular control from heart period and systolic arterial pressure variability and cerebrovascular regulation from mean arterial pressure and mean cerebral blood velocity variability in 13 control subjects and 13 individuals prone to develop orthostatic syncope. Analysis was made at rest in supine position and during head-up tilt at 60°, well before observing presyncope signs. Two different linear model structures were compared, namely bivariate autoregressive and bivariate dynamic adjustment classes. We found that (i) GSC markers did not depend on the model structure; (ii) the concomitant assessment of cardiovascular and cerebrovascular controls was useful for a deeper comprehension of postural disturbances; (iii) orthostatic syncope appeared to be favored by the loss of a coordinated behavior between the baroreflex feedback and mechanical feedforward pathway in the frequency band typical of the baroreflex functioning during the postural challenge, and by a weak cerebral autoregulation as revealed by the increased strength of the pressure-to-flow link in the respiratory band. GSC applied to spontaneous cardiovascular and cerebrovascular oscillations is a promising tool for describing and monitoring disturbances associated with posture modification.

On the Different Abilities of Cross-Sample Entropy and K-Nearest-Neighbor Cross-Unpredictability in Assessing Dynamic Cardiorespiratory and Cerebrovascular Interactions.

Nonlinear markers of coupling strength are often utilized to typify cardiorespiratory and cerebrovascular regulations. The computation of these indices requires techniques describing nonlinear interactions between respiration (R) and heart period (HP) and between mean arterial pressure (MAP) and mean cerebral blood velocity (MCBv). We compared two model-free methods for the assessment of dynamic HP-R and MCBv-MAP interactions, namely the cross-sample entropy (CSampEn) and k-nearest-neighbor cross-unpredictability (KNNCUP). Comparison was carried out first over simulations generated by linear and nonlinear unidirectional causal, bidirectional linear causal, and lag-zero linear noncausal models, and then over experimental data acquired from 19 subjects at supine rest during spontaneous breathing and controlled respiration at 10, 15, and 20 breaths·minute-1 as well as from 13 subjects at supine rest and during 60° head-up tilt. Linear markers were computed for comparison. We found that: (i) over simulations, CSampEn and KNNCUP exhibit different abilities in evaluating coupling strength; (ii) KNNCUP is more reliable than CSampEn when interactions occur according to a causal structure, while performances are similar in noncausal models; (iii) in healthy subjects, KNNCUP is more powerful in characterizing cardiorespiratory and cerebrovascular variability interactions than CSampEn and linear markers. We recommend KNNCUP for quantifying cardiorespiratory and cerebrovascular coupling.

Yield of overnight pulse oximetry in screening commercial drivers for obstructive sleep apnea.

PURPOSE: To assess the efficacy of overnight pulse oximetry in screening male commercial drivers (CDs) for obstructive sleep apnea (OSA). METHODS: Consecutive male CDs undergoing their annual scheduled occupational health visit were enrolled from ten transportation facilities. All subjects underwent a home sleep apnea test (HSAT) to determine the Respiratory Event Index (REI). Oxygen desaturation indices (ODIs) below the 3% and 4% thresholds were computed using the built-in HSAT pulse oximeter. We then assessed the association between ODI values and the presence of OSA (defined as an REI ≥ 5 events/hour) as well as moderate to severe OSA (REI ≥ 15 events/hour). RESULTS: Of 331 CDs recruited, 278 (84%) completed the study protocol and 53 subjects were excluded due to inadequate HSAT quality. The included and excluded subjects were comparable in demographics and clinical characteristics. The included CDs had a median age of 49 years (interquartile range (IQR) = 15 years) and a median body mass index of 27 kg/m2 (IQR = 5 kg/m2). One hundred ninety-nine (72%) CDs had OSA, of which 48 (17%) were with moderate OSA and 45 (16%) with severe OSA. The ODI3 and ODI4 receiving operating characteristic curve value were 0.95 for predicting OSA and 0.98-0.96 for predicting moderate to severe OSA. CONCLUSION: Overnight oxygen oximetry may be an effective means to screen CDs for OSA.

Comparing Cross-Sample Entropy and K-Nearest-Neighbor Cross-Predictability Approaches for the Evaluation of Cardiorespiratory and Cerebrovascular Dynamic Interactions.

Quantification of the cardiorespiratory and cerebrovascular couplings is a relevant clinical issue given that their changes are considered signs of pathological status. The inherent nonlinearity of mechanisms underlying cardiorespiratory and cerebrovascular links requires nonlinear tools for their reliable evaluation. In the present study we compare two nonlinear methods for the assessment of coupling strength between two time series, namely cross-sample entropy (CSampEn) and k-nearest-neighbor cross-predictability (KNNCP). CSampEn uses a strategy that fixes the pattern length, while KNNCP optimizes the pattern length to maximize cross-predictability. CSampEn and KNNCP were applied to the beat-to-beat series of heart period (HP) and respiration (R) during a controlled breathing protocol with the aim at assessing cardiorespiratory coupling and to the beat-to-beat series of mean cerebral blood flow (MCBF) and mean arterial pressure (MAP) during an orthostatic stressor with the aim at evaluating cerebrovascular coupling. Although both the methods have the possibility to quantify the degree of HP-R and MCBF-MAP association, they exhibited different statistical power and even diverse trends in response to the considered physiological challenges. CSampEn and KNNCP are not interchangeable and should be utilized in association more than in alternative for the quantification of the HP-R and MCBF-MAP coupling strength. Clinical Relevance - This study proves that cross-entropy and cross-predictability might lead to different conclusions about cardiorespiratory and cerebrovascular couplings.

Spectral decomposition of cerebrovascular and cardiovascular interactions in patients prone to postural syncope and healthy controls.

We present a framework for the linear parametric analysis of pairwise interactions in bivariate time series in the time and frequency domains, which allows the evaluation of total, causal and instantaneous interactions and connects time- and frequency-domain measures. The framework is applied to physiological time series to investigate the cerebrovascular regulation from the variability of mean cerebral blood flow velocity (CBFV) and mean arterial pressure (MAP), and the cardiovascular regulation from the variability of heart period (HP) and systolic arterial pressure (SAP). We analyze time series acquired at rest and during the early and late phase of head-up tilt in subjects developing orthostatic syncope in response to prolonged postural stress, and in healthy controls. The spectral measures of total, causal and instantaneous coupling between HP and SAP, and between MAP and CBFV, are averaged in the low-frequency band of the spectrum to focus on specific rhythms, and over all frequencies to get time-domain measures. The analysis of cardiovascular interactions indicates that postural stress induces baroreflex involvement, and its prolongation induces baroreflex dysregulation in syncope subjects. The analysis of cerebrovascular interactions indicates that the postural stress enhances the total coupling between MAP and CBFV, and challenges cerebral autoregulation in syncope subjects, while the strong sympathetic activation elicited by prolonged postural stress in healthy controls may determine an increased coupling from CBFV to MAP during late tilt. These results document that the combination of time-domain and spectral measures allows us to obtain an integrated view of cardiovascular and cerebrovascular regulation in healthy and diseased subjects.

Exploring metrics for the characterization of the cerebral autoregulation during head-up tilt and propofol general anesthesia.

Techniques grounded on the simultaneous utilization of Tiecks' second order differential equations and spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV), recorded from middle cerebral arteries through a transcranial Doppler device, provide a characterization of cerebral autoregulation (CA) via the autoregulation index (ARI). These methods exploit two metrics for comparing the measured MCBFV series with the version predicted by Tiecks' model: normalized mean square prediction error (NMSPE) and normalized correlation ρ. The aim of this study is to assess the two metrics for ARI computation in 13 healthy subjects (age: 27 ± 8 yrs., 5 males) at rest in supine position (REST) and during 60° head-up tilt (HUT) and in 19 patients (age: 64 ± 8 yrs., all males), scheduled for coronary artery bypass grafting, before (PRE) and after (POST) propofol general anesthesia induction. Analyses were carried out over the original MAP and MCBFV pairs and surrogate unmatched couples built individually via time-shifting procedure. We found that: i) NMSPE and ρ metrics exhibited similar performances in passing individual surrogate test; ii) the two metrics could lead to different ARI estimates; iii) CA was not different during HUT or POST compared to baseline and this conclusion held regardless of the technique and metric for ARI estimation. Results suggest a limited impact of the sympathetic control on CA.

Poor performance of screening questionnaires for obstructive sleep apnea in male commercial drivers.

PURPOSE: Screening commercial drivers (CDs) for obstructive sleep apnea (OSA) reduces the risk of motor vehicle accidents. We evaluated the accuracy of standard OSA questionnaires in a cohort of CDs. STUDY DESIGN AND METHODS: We enrolled consecutive male CDs at 10 discrete transportation companies during their yearly scheduled occupational health visit. The CDs had their anthropometric measures taken; completed the Berlin, STOP, STOP-BANG, OSAS-TTI, SACS, EUROSAS, and ARES questionnaires; and underwent a home sleep apnea test (HSAT) for the determination of their respiratory events index (REI). We assessed the questionnaires' ability to predict OSA (REI ≥ 5 events/h) and moderate-to-severe OSA (REI ≥ 15 events/h). RESULTS: Among 315 CDs recruited, 243 (77%) completed the study protocol, while 72 subjects were excluded for inadequate HSAT quality. The demographics and clinical data were comparable in both the included and excluded subjects. The included CDs had a median age of 50 years (interquartile range (IQR) 25-70) and a mean body mass index of 27 ± 4 kg/m2. One hundred and seventy-one subjects (71%) had OSA, and 68 (28%) had moderate-to-severe OSA. A receiver operating characteristic curve of the questionnaires were 0.51-0.71 for predicting OSA and 0.51-0.66 for moderate-to-severe OSA. The STOP-BANG questionnaire had an unsatisfactory positive predictive value, while all of the other questionnaires had an inadequate negative predictive value. CONCLUSIONS: Standard OSA questionnaires are not suited for screening among CDs. The use of the HSAT could provide an objective evaluation of for OSA in this special population.

Dynamic cerebrovascular autoregulation in patients prone to postural syncope: Comparison of techniques assessing the autoregulation index from spontaneous variability series.

Three approaches to the assessment of cerebrovascular autoregulation (CA) via the computation of the autoregulation index (ARI) from spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV) were applied: 1) a time domain method (TDM); 2) a nonparametric method (nonPM); 3) a parametric method (PM). Performances were tested over matched and surrogate unmatched pairs. Data were analyzed at supine resting (REST) and during the early phase of 60° head-up tilt (TILT) in 13 subjects with previous history of postural syncope (SYNC, age: 28 ± 9 yrs.; 5 males) and 13 control individuals (noSYNC, age: 27 ± 8 yrs.; 5 males). Analysis was completed by computing autonomic markers from heart period (HP) and systolic arterial pressure (SAP) variability series via spectral approach. HP and SAP spectral indexes suggested that noSYNC and SYNC groups exhibited different autonomic responses to TILT. ARI analysis indicated that: i) all methods have a sufficient statistical power to separate matched from unmatched pairs with the exception of nonPM applied to impulse response; ii) ARI estimates derived from different methods might be uncorrelated and, even when correlated, might exhibit a significant bias; iii) orthostatic stressor did not induce any evident ARI change in either noSYNC or SYNC individuals; iv) this conclusion held regardless of the method. Methods for the ARI estimation from spontaneous variability provide different ARIs but none indicate that noSYNC and SYNC subjects have different dynamic component of CA.

Categorizing the Role of Respiration in Cardiovascular and Cerebrovascular Variability Interactions.

OBJECTIVE: Respiration disturbs cardiovascular and cerebrovascular controls but its role is not fully elucidated. METHODS: Respiration can be classified as a confounder if its observation reduces the strength of the causal relationship from source to target. Respiration is a suppressor if the opposite situation holds. We prove that a confounding/suppression (C/S) test can be accomplished by evaluating the sign of net redundancy/synergy balance in the predictability framework based on multivariate autoregressive modelling. In addition, we suggest that, under the hypothesis of Gaussian processes, the C/S test can be given in the transfer entropy decomposition framework as well. Experimental protocols: We applied the C/S test to variability series of respiratory movements, heart period, systolic arterial pressure, mean arterial pressure, and mean cerebral blood flow recorded in 17 pathological individuals (age: 64±8 yrs; 17 males) before and after induction of propofol-based general anesthesia prior to coronary artery bypass grafting, and in 13 healthy subjects (age: 27±8 yrs; 5 males) at rest in supine position and during head-up tilt with a table inclination of 60°. RESULTS: Respiration behaved systematically as a confounder for cardiovascular and cerebrovascular controls. In addition, its role was affected by propofol-based general anesthesia but not by a postural stimulus of limited intensity. CONCLUSION: The C/S test can be fruitfully exploited to categorize the role of respiration over causal variability interactions. SIGNIFICANCE: The application of the C/S test could favor the comprehension of the role of respiration in cardiovascular and cerebrovascular regulations.

An Empirical Mode Decomposition Approach to Assess the Strength of Heart Period-Systolic Arterial Pressure Variability Interactions.

This work proposes an empirical mode decomposition (EMD) method to assess the strength of the interactions between heart period (HP) and systolic arterial pressure (SAP) variability. EMD was exploited to decompose the original series (OR) into its first, and fastest, intrinsic mode function (IMF1) and the residual (RES) computed by subtracting the IMF1 from OR. EMD procedure was applied to both HP and SAP variability series. Then, the cross correlation function (CCF) was computed over OR, IMF1 and RES series derived from HP and SAP variability in 13 healthy subjects (age 27±8 yrs, 5 males) at rest in supine position (REST) and during head-up tilt (TILT). The first CCF maximum at negative time lags and the first CCF minimum at positive time lags were taken respectively as indexes of the coupling along the feedback baroreflex and feedforward mechanical arms of HP-SAP closed-loop control. Results showed that the coupling strength is increased during TILT on both arms and this result holds on REST. At REST the coupling along both arms was stronger when computed over IMF1 because interactions were mainly governed by respiration. This result was not observed during TILT possibly due to the reduced importance of respiration compared to other mechanisms acting at slower time scales. The proposed method allowed the investigation of the strength of HP-SAP variability interactions according to the time scales of the physiological mechanisms.The proposed EMD-based method allows the quantification of the strength of the HP-SAP closed-loop variability interactions according to the different time scales of respiration and slower baroreflex-mediated reflexes.

Strength and Latency of the HP-SAP Closed Loop Variability Interactions in Subjects Prone to Develop Postural Syncope.

The coupling and latency between heart period (HP) and systolic arterial pressure (SAP) variability can be investigated along the two arms of the HP-SAP closed loop, namely along the baroreflex feedback from SAP to HP, and along the feedforward pathway from HP to SAP. This study investigates the HP-SAP closed loop variability interactions through cross-correlation function (CCF). Coupling strength and delay between HP and SAP variability series were monitored in 13 subjects prone to develop orthostatic syncope (SYNC, 28±9 yrs, 5 males) and in 13 subjects with no history of postural syncope (noSYNC, age: 27±8 yrs, 5 males). Analysis was carried out at rest in supine position (REST) and during head-up tilt (TILT) at 60 degrees. The null hypothesis of HP-SAP uncoupling was tested through a surrogate analysis associating the HP series of a subject with a SAP sequence of a different one. Results showed that during TILT the coupling strength increased along the baroreflex and latency augmented along the mechanical feedforward pathway exclusively in noSYNC subjects. Finally, closed loop HP-SAP interactions were detected in about one third of subjects and the situation of full uncoupling was rarely found. CCF analysis was found to be a straightforward and easily applicable method to investigate HP-SAP control deserving a direct comparison with more sophisticated signal processing tools assessing causality.

Cerebrovascular and cardiovascular variability interactions investigated through conditional joint transfer entropy in subjects prone to postural syncope.

OBJECTIVE: A model-based conditional transfer entropy approach was exploited to quantify the information transfer in cerebrovascular (CBV) and cardiovascular (CV) systems in subjects prone to develop postural syncope. APPROACH: Spontaneous beat-to-beat variations of mean cerebral blood flow velocity (MCBFV) derived from a transcranial Doppler device, heart period (HP) derived from surface electrocardiogram, mean arterial pressure (MAP) and systolic arterial pressure (SAP) derived from finger plethysmographic arterial pressure device were monitored at rest in supine position (REST) and during 60° head-up tilt (TILT) in 13 individuals (age mean ± standard deviation: 28 ± 9 years, min-max range: 18-44 years, 5 males) with a history of recurrent episodes of syncope (SYNC) and in 13 age- and gender-matched controls (NonSYNC). Respiration (R) obtained from a thoracic belt was acquired as well and considered as a conditioning signal in transfer entropy assessment. Synchronous sequences of 250 consecutive MCBFV, HP, MAP, SAP and R values were utilized to estimate the information genuinely transferred from MAP to MCBFV (i.e. disambiguated from R influences) and vice versa. Analogous indexes were computed from SAP to HP and vice versa. Traditional time and frequency domain analyses were carried out as well. MAIN RESULTS: SYNC subjects showed an increased genuine information transfer from MAP to MCBFV during TILT, while they did not exhibit the expected rise of the genuine information transfer from SAP to HP. SIGNIFICANCE: We conclude that SYNC individuals featured an impaired cerebral autoregulation visible during TILT and were unable to activate cardiac baroreflex to cope with the postural challenge. Traditional frequency domain markers based on transfer function modulus, phase and coherence functions were less powerful or less specific in typifying the CBV and CV controls of SYNC individuals. Conditional transfer entropy approach can identify the impairment of CBV and CV controls and provide specific clues to identify subjects prone to develop postural syncope.

The importance of polysomnography in the evaluation of prolonged disorders of consciousness: sleep recordings more adequately correlate than stimulus-related evoked potentials with patients' clinical status.

OBJECTIVES: The aim of our study was to evaluate the importance of sleep recordings and stimulus-related evoked potentials (EPs) in patients with prolonged disorders of consciousness (DOCs) by correlating neurophysiologic variables with clinical evaluation obtained using specific standardized scales. METHODS: There were 27 vegetative state (VS) and 5 minimally conscious state (MCS) patients who were evaluated from a clinical and neurophysiologic perspective. Clinical evaluation included the Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS), and Glasgow Coma Scale (GCS). Neurophysiologic evaluation included 24-h polysomnography (PSG), somatosensory EPs (SEPs), brainstem auditory EPs (BAEPs), and visual EPs (VEPs). RESULTS: Patients with preservation of each single sleep element (sleep-wake cycle, sleep spindles, K-complexes, and rapid eye movement [REM] sleep) always showed better clinical scores compared to those who did not have preservation. Statistical significance was only achieved for REM sleep. In 7 patients PSG showed the presence of all considered sleep elements, and they had a CRS-R score of 8.29±1.38. In contrast, 25 patients who lacked one or more of the sleep elements had a CRS-R score of 4.84±1.46 (P<.05). Our multivariate analysis clarified that concurrent presence of sleep spindles and REM sleep were associated with a much higher CRS-R score (positive interaction, P<.0001). On the other hand, no significant associations were found between EPs and CRS-R scores. CONCLUSIONS: PSG recordings have proved to be a reliable tool in the neurophysiologic assessment of patients with prolonged DOCs, correlating more adequately than EPs with the clinical evaluation and the level of consciousness. The main contribution to higher clinical scores was determined by the concomitant presence of REM sleep and sleep spindles. PSG recordings may be considered inexpensive, noninvasive, and easy-to-perform examinations to provide supplementary information in patients with prolonged DOCs.

Investigating the mechanisms of cardiovascular and cerebrovascular regulation in orthostatic syncope through an information decomposition strategy.

Some previous evidence suggests that postural related syncope is associated with defective mechanisms of cerebrovascular (CB) and cardiovascular (CV) control. We characterized the information processing in short-term CB regulation, from the variability of mean cerebral blood flow velocity (CBFV) and mean arterial pressure (AP), and in CV regulation, from the variability of heart period (HP) and systolic AP (SAP), in ten young subjects developing orthostatic syncope in response to prolonged head-up tilt testing. We exploited a novel information-theoretic approach that decomposes the information associated with a variability series into three amounts: the information stored in the series, the information transferred to the series from another series, and the information unexplained by the knowledge of both series. With this approach we were able to show that, compared with the first minutes after head-up tilt, in the period preceding the syncope event (i) the information stored in CBFV variability decreased significantly while the information transferred to CBFV from AP variability increased significantly; (ii) the information storage of HP was kept high but the information transferred to HP from SAP variability decreased significantly. These patterns of information processing suggest that presyncope occurs with a loss both of CB regulation, described by the reduced ability of CBFV of buffering AP fluctuations, and of CV regulation, described by the reduced baroreflex modulation from SAP to HP. We believe that the utilization of tools from the field of information dynamics may give an integrated view of the mechanisms of CB and CV regulation in normal and diseased states, and also provide a deeper understanding of findings revealed by more traditional techniques.