Autonomic dysfunction after mild acute ischemic stroke and six months after: a prospective observational cohort study.

INTRODUCTION: Autonomic dysfunction is prevalent in ischemic stroke patients and associated with a worse clinical outcome. We aimed to evaluate autonomic dysfunction over time and the tolerability of the head-up tilt table test in an acute stroke setting to optimize patient care. PATIENTS AND METHOD: In a prospective observational cohort study, patients were consecutively recruited from an acute stroke unit. The patients underwent heart rate and blood pressure analysis during the Valsalva maneuver, deep breathing, active standing, and head-up tilt table test if active standing was tolerated. In addition, heart rate variability and catecholamines were measured. All tests were performed within seven days after index ischemic stroke and repeated at six months follow-up. RESULTS: The cohort was comprised of 91 acute stroke patients, mean (SD) age 66 (11) years, median (IQR) initial National Institute of Health Stroke Scale 2 (1-4) and modified Ranking Scale 2 (1-3). The head-up tilt table test revealed 7 patients (10%) with orthostatic hypotension. The examination was terminated before it was completed in 15%, but none developed neurological symptoms. In the acute state the prevalence of autonomic dysfunction varied between 10-100% depending on the test. No changes were found in presence and severity of autonomic dysfunction over time. CONCLUSION: In this cohort study of patients with mild stroke, autonomic dysfunction was highly prevalent and persisted six months after index stroke. Head-up tilt table test may be used in patients who tolerate active standing. Autonomic dysfunction should be recognized and handled in the early phase after stroke.

Orthostatic hypotension in dementia with Lewy bodies: a meta-analysis of prospective studies.

PURPOSE: Orthostatic hypotension (OH), one of the supportive clinical features in the diagnosis of dementia with Lewy bodies (DLB), is a significant problem in advanced age because of its severe negative consequences. The aim of this meta-analysis was to investigate the prevalence and risk of OH in patients with DLB. METHODS: The indexes and databases cited to identify relevant studies were PubMed, ScienceDirect, Cochrane, and Web of Science. The keywords for the search were "Lewy body dementia" and "autonomic dysfunction" or "dysautonomia" or "postural hypotension" or "orthostatic hypotension." English-language articles published from January 1990 to April 2022 were searched. The Newcastle-Ottawa scale was applied to evaluate the quality of the studies. Odds ratios (OR) and risk ratios (RR) were extracted with 95% confidence intervals (CI) and combined using the random effects model after logarithmic transformation. The prevalence in the patients with DLB was also combined using the random effects model. RESULTS: Eighteen studies (10 case controls and 8 case series) were included to evaluate the prevalence of OH in patients with DLB. Higher rates of OH were found to be associated with DLB (OR 7.71, 95% CI 4.42, 13.44; p < 0.001), and 50.8% of 662 patients had OH. CONCLUSION: DLB increased the risk of OH by 3.62- to 7.71-fold compared to healthy controls. Therefore, it will be useful to evaluate postural blood pressure changes in the follow-up and treatment of patients with DLB.

The baroreceptor reflex brought to life outside the classroom - an e-learning based asynchronous laboratory class using a non-supervised modified Active Standing Test.

BACKGROUND: E-learning based laboratory classes can replace or enhance in-classroom laboratories. They typically offer temporal flexibility, self-determined learning speed, repeatability and do not require supervision or face-to-face contact. The aim of this feasibility study was to investigate whether the established in-classroom laboratory class on the baroreceptor reflex (BRR) can be transformed into a new e-learning based asynchronous laboratory class for untrained, non-supervised students without medical equipment. The BRR is a fundamental cardiovascular process which is regularly visualized in physiology during in-classroom laboratories by a student-performed Active Standing Test (AST). During this voluntary provocation of orthostatic stress, the BRR reliably causes a solid rise in heart rate (HR) and a stabilization or even increase in blood pressure (BP). METHODS: The conventional AST was modified by omission of BP measurements which would require medical devices and was embedded into a framework of interactive digital material allowing independent student performance. With specific adaptions, this instrument was implemented to 1st and 2nd year curricula of human medicine, dental medicine, midwifery and pharmacy. An audience response system was used to collect the students' data on HR, epidemiology, technical problems, satisfaction and orthostatic symptoms. As primary outcome, we investigated the students' correct performance of the modified AST regarding textbook conformity of the HR data. Secondary outcomes included technical feasibility, the students' satisfaction and consistency of HR data within predefined subgroups (e.g., gender, curricula). Descriptive statistics are reported. RESULTS: The class was completed by 217 students (mean age: 23 ± 8 [SD], 81% female, 19% male). Mean reported rise of HR during standing was ~ 20 bpm (~ 30%) which is highly concordant to textbooks. Reported feasibility (~ 80% negated any technical issues) and students' satisfaction (4.4 on 5-point Likert-scale) were high. The HR data were consistent within the subgroups. CONCLUSION: This study demonstrates that the highly relevant BRR can be successfully addressed in an e-learning based asynchronous laboratory class implementing a non-supervised AST restricted to HR measurements embedded in digital material. The robust HR response and the adjustable complexity allow an application to different healthcare-related curricula. This class, therefore, provides a broad audience access to a fundamental concept of cardiovascular physiology.

Monitoring the Evolution of Asynchrony between Mean Arterial Pressure and Mean Cerebral Blood Flow via Cross-Entropy Methods.

Cerebrovascular control is carried out by multiple nonlinear mechanisms imposing a certain degree of coupling between mean arterial pressure (MAP) and mean cerebral blood flow (MCBF). We explored the ability of two nonlinear tools in the information domain, namely cross-approximate entropy (CApEn) and cross-sample entropy (CSampEn), to assess the degree of asynchrony between the spontaneous fluctuations of MAP and MCBF. CApEn and CSampEn were computed as a function of the translation time. The analysis was carried out in 23 subjects undergoing recordings at rest in supine position (REST) and during active standing (STAND), before and after surgical aortic valve replacement (SAVR). We found that at REST the degree of asynchrony raised, and the rate of increase in asynchrony with the translation time decreased after SAVR. These results are likely the consequence of the limited variability of MAP observed after surgery at REST, more than the consequence of a modified cerebrovascular control, given that the observed differences disappeared during STAND. CApEn and CSampEn can be utilized fruitfully in the context of the evaluation of cerebrovascular control via the noninvasive acquisition of the spontaneous MAP and MCBF variability.

Cerebral Blood Oxygenation Changes in Juvenile Patients with Delayed Orthostatic Hypotension During an Active Standing Test.

Delayed orthostatic hypotension (OH) is a minor subset of orthostatic dysregulation (OD). Cerebral blood oxygenation in juvenile patients with delayed OH has not been studied. We investigated the bilateral changes in cerebral oxygenation in the prefrontal cortex during an active standing test in 23 juvenile patients with delayed OH using near-infrared spectroscopy (NIRS). We measured the oxy-Hb, deoxy-Hb, and total-Hb during the active standing test. Four observations were made during the test: t1 in a resting supine position, t2 when maintaining blood pressure, and the remaining two (t3, t4) during hypotension. The concentration of oxy-Hb significantly decreased prior to satisfying the diagnostic criteria of delayed OH after standing and did not change thereafter. The concentration of deoxy-Hb increased gradually during the measurement periods. In addition, total-Hb increased from t2 to t3. There was no significant difference in the change in each Hb parameter between the left and right cerebral hemispheres. Our results indicate that NIRS parameters are more sensitive than blood pressure for the interpretation of cerebral autoregulation in juvenile patients with delayed OH.

Association between Mean Heart Rate and Recurrence Quantification Analysis of Heart Rate Variability in End-Stage Renal Disease.

Linear heart rate variability (HRV) indices are dependent on the mean heart rate, which has been demonstrated in different models (from sinoatrial cells to humans). The association between nonlinear HRV indices, including those provided by recurrence plot quantitative analysis (RQA), and the mean heart rate (or the mean cardiac period, also called meanNN) has been scarcely studied. For this purpose, we analyzed RQA indices of five minute-long HRV time series obtained in the supine position and during active standing from 30 healthy subjects and 29 end-stage renal disease (ESRD) patients (before and after hemodialysis). In the supine position, ESRD patients showed shorter meanNN (i.e., faster heart rate) and decreased variability compared to healthy subjects. The healthy subjects responded to active standing by shortening the meanNN and decreasing HRV indices to reach similar values of ESRD patients. Bivariate correlations between all RQA indices and meanNN were significant in healthy subjects and ESRD after hemodialysis and for most RQA indices in ESRD patients before hemodialysis. Multiple linear regression analyses showed that RQA indices were also dependent on the position and the ESRD condition. Then, future studies should consider the association among RQA indices, meanNN, and these other factors for a correct interpretation of HRV.

Autonomic nervous system function in adolescent migraineurs.

BACKGROUND: Migraine is a common and disabling neurological disorder. Studies on the relationship between migraine and the autonomic nervous system (ANS) have been inconclusive. Moreover, pediatric studies are extremely limited. Therefore, the present study investigated interictal ANS function in adolescent migraineurs. METHODS: We studied 21 patients with migraine and 26 healthy controls. Beat-to-beat blood pressure (BP) and heart rate (HR) were non-invasively and continuously measured in the supine and standing positions. ANS function was evaluated on power spectral analysis of HR variability and diastolic BP (DBP) variability. RESULTS: Heart rate and systolic BP were not different between the two groups in either the supine or standing position. DBP did not differ between groups in the standing position, but was significantly higher in migraineurs in the supine position. The vasoconstrictor index was significantly higher in migraineurs. High-frequency (HF) RR interval variability (RR-HF) and the ratio of the low-frequency (LF) to HF component of RR interval variability (RR-LF/HF) were not different between the two groups in both positions. The LF component of DBP variability (DBP-LF) in the supine position was significantly lower in migraineurs, while DBP-LF during standing in migraineurs was significantly higher than in controls. CONCLUSION: Migraineurs have significantly lower sympathetic vasomotor activity in the supine position, while sympathetic vasomotor activity was hyperresponsive during standing.

Pathophysiology of neurally-mediated syncope. / Fisiopatología del síncope neuralmente mediado.

INTRODUCTION: Neurally-mediated syncope (NMS) is defined as a transient loss of consciousness due to an abrupt and intermittent drop in blood pressure (BP). OBJECTIVES: This study describes the putative pathophysiological mechanisms giving rise to NMS, the role of baroreflex (BR), and the interaction of its main haemodynamic variables: heart rate (HR) and BP. DEVELOPMENT: Episodic dysregulation affects control over the haemodynamic variables (HR and BP) mediated by baroreflex mechanisms. During active standing, individuals experience a profound transient drop in systolic BP due to the effect of gravity on the column of blood and probably also because of reflex vasodilation. Abnormalities in the BR in NMS could be due to a more profound drop in BP upon standing, or to delayed or incomplete vasoconstriction resulting from inhibited or delayed sympathetic activity. CONCLUSIONS: Sympathetic hyperactivity is present in patients with NMS at rest and before syncope. During active standing or passive tilting, excessive tachycardia may be followed by bradycardia and profound hypotension. Recovery of systolic BP is delayed or incomplete.

Clinical and endocrine features of orthostatic intolerance detected in patients with long COVID.

Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.

The differences of orthostatic hypotension in patients with Parkinson's disease and multiple system atrophy.

Background: Multiple system atrophy (MSA) and Parkinson's disease (PD) have similar clinical presentations in their early stages. Orthostatic hypotension (OH) is a common autonomic dysfunction associated with MSA and PD. Heart rate (HR) and systolic blood pressure (SBP) changes are measured in response to the active standing test, which is widely used to screen for cardiovascular autonomic function. Objectives and methods: Overall, 255 patients (67 MSA, 188 PD) underwent continuous beat-to-beat non-invasive BP monitoring and active standing test. The total standing time was 10 min, and the BP differences between both groups were compared to determine whether the ΔHR/ΔSBP can differentiate both conditions. Results: Classical orthostatic hypotension (COH) (52%) and initial OH (19%) were most common in MSA and PD, respectively. MSA had a higher HR (75.0 ± 9.7 vs. 71.0 ± 10.7, P = 0.008) than PD in the supine position. SBP (135.70 ± 15.68 mmHg vs. 127.31 ± 15.14 mmHg, P = 0.106), diastolic BP (78.45 ± 12.36 mmHg vs. 67.15 ± 13.39 mmHg, P = 0.009) and HR (73.94 ± 8.39 bpm vs. 71.08 ± 13.52 bpm, P = 0.389) at baseline were higher in MSA-COH than in PD-COH. After adjusting for age and disease duration, the ΔHR/ΔSBP-10 min significantly discriminated MSA-COH from PD-COH (P = 0.031). An ΔHR/ΔSBP-10 min of 0.517 showed a sensitivity of 67% and specificity of 84% (AUC = 0.77, 95% CI: 0.63-0.91). Conclusion: The SBP, diastolic BP, and HR were higher in the supine position; however, ΔHR and ΔSBP were lower after standing in MSA patients than in PD patients. The ΔHR/ΔSBP-10 min discriminated between MSA-COH and PD-COH with quiet acceptable accuracy.

Evaluation of cardiovascular and cerebrovascular control mechanisms in postural orthostatic tachycardia syndrome via conditional transfer entropy: the impact of the respiratory signal type.

Objective.Closed loop cardiovascular (CV) and cerebrovascular (CBV) variability interactions are assessed via transfer entropy (TE) from systolic arterial pressure (SAP) to heart period (HP) and vice versa and from mean arterial pressure (MAP) to mean cerebral blood velocity (MCBv) and vice versa. This analysis is exploited to assess the efficiency of baroreflex and cerebral autoregulation. This study aims at characterizing CV and CBV controls in postural orthostatic tachycardiac syndrome (POTS) subjects experiencing exaggerated sympathetic response during orthostatic challenge via unconditional TE and TE conditioned on respiratory activity (R).Approach.In 18 healthy controls (age: 28 ± 13 yrs; 5 males, 13 females) and 15 POTS individuals (age: 29 ± 11 yrs; 3 males, 12 females) we acquired beat-to-beat variability of HP, SAP, MAP and MCBv and twoRsignals, namely respiratory chest movement (RCM) and capnogram (CAP). Recordings were made at sitting rest and during active standing (STAND). TE was computed via vector autoregressive approach.Main results.We found that: (i) when assessing CV interactions, the increase of the TE from SAP to HP during STAND, indicating baroreflex activation, is detected solely when conditioning on RCM; (ii) when assessing CBV interactions, the impact ofRon the TE computation is negligible; (iii) POTS shows baroreflex impairment during STAND; (iv) POTS exhibits a normal CBV response to STAND.Significance.TE is useful for detecting the impairment of specific regulatory mechanisms in POTS. Moreover, using differentRsignals highlights the sensitivity of CV and CBV controls to specificRaspects.

The degree of engagement of cardiac and sympathetic arms of the baroreflex does not depend on the absolute value and sign of arterial pressure variations.

Objective.The percentages of cardiac and sympathetic baroreflex patterns detected via baroreflex sequence (SEQ) technique from spontaneous variability of heart period (HP) and systolic arterial pressure (SAP) and of muscle nerve sympathetic activity (MSNA) burst rate and diastolic arterial pressure (DAP) are utilized to assess the level of the baroreflex engagement. The cardiac baroreflex patterns can be distinguished in those featuring both HP and SAP increases (cSEQ++) and decreases (cSEQ--), while the sympathetic baroreflex patterns in those featuring a MSNA burst rate decrease and a DAP increase (sSEQ+-) and vice versa (sSEQ-+). The present study aims to assess the modifications of the involvement of the cardiac and sympathetic arms of the baroreflex with age and postural stimulus intensity.Approach.We monitored the percentages of cSEQ++ (%cSEQ++) and cSEQ-- (%cSEQ--) in 100 healthy subjects (age: 21-70 years, 54 males, 46 females), divided into five sex-balanced groups consisting of 20 subjects in each decade at rest in supine position and during active standing (STAND). We evaluated %cSEQ++, %cSEQ--, and the percentages of sSEQ+- (%sSEQ+-) and sSEQ-+ (%sSEQ-+) in 12 young healthy subjects (age 23 ± 2 years, 3 females, 9 males) undergoing incremental head-up tilt.Main results.We found that: (i) %cSEQ++ and %cSEQ-- decreased with age and increased with STAND and postural stimulus intensity; (ii) %sSEQ+- and %sSEQ-+ augmented with postural challenge magnitude; (iii) the level of cardiac and sympathetic baroreflex engagement did not depend on either the absolute value of arterial pressure or the direction of its changes.Significance.This study stresses the limited ability of the cardiac and sympathetic arms of the baroreflex in controlling absolute arterial pressure values and the equivalent ability of both positive and negative arterial pressure changes in soliciting them.

The Effect of Epipharyngeal Abrasive Therapy (EAT) on the Baroreceptor Reflex (BR).

Introduction Epipharyngeal Abrasive Therapy (EAT) has been used as a treatment for chronic epipharyngitis, and although autonomic nerve stimulation has been pointed out as one of the mechanisms by which EAT produces therapeutic effects, there have been few reports examining this mechanism of action. This study investigated the effects of repeated EAT on autonomic nervous system activity in chronic epipharyngitis patients over time, using heart rate variability analysis. In addition, we conducted a loading test using the active standing test (AS test) to examine the effects of EAT on the baroreceptor reflex (BR). Subjects and methods A retrospective study was conducted on 39 patients who visited our clinic between July 2017 and November 2019 and underwent autonomic function tests with a diagnosis of chronic nasopharyngeal inflammation. The subjects were divided into two groups: the improvement group and the invariant group for comparison. Electrocardiographic recordings and blood pressure measurements were made under the stress of the AS test. Heart rate, high-frequency (HF) component, low-frequency (LF) component, and Coefficient of Variation on R-R interval were evaluated as indices of autonomic function. Component coefficient of variance high frequency was used as an index of parasympathetic function. ccvLF/ccvHF ratio was calculated by dividing the component coefficient of variance low frequency by ccvHF. The AS test was conducted in phase 1 in the initial resting sitting position, in phase 2 in the standing position, in phase 3 in the standing and holding the standing position, and in phase 4 in the seated and holding the sitting position. Systolic blood pressure, mean arterial pressure, and diastolic blood pressure were obtained in each phase. A paired t-test was used to compare the improved and invariant groups before and after treatment. The post-treatment comparison between the improved group and the invariant group was performed by unpaired t-test. Variation of the evaluation index over time was evaluated by repeated measures ANOVA. Multiple comparisons were corrected by the Bonferroni method. Results The EAT showed that parasympathetic activity was significantly suppressed in the improvement group, while the AS test showed significant fluctuations over time for the improvement and invariant groups. The interaction between the time course and the two factors in the improvement and invariant groups was not statistically evident. Although no significant difference was found, the improvement group showed a tendency to suppress parasympathetic activity and a tendency to stimulate sympathetic activity compared to the invariant group. Blood pressure in the improvement group showed a tendency to decrease. Conclusions EAT was found to suppress parasympathetic activity over time, and the AS test did not reveal an interaction effect of EAT on BR. However, there was a trend toward suppression of parasympathetic activity and stimulation of sympathetic activity in the improved group compared to the invariant group. Blood pressure in the improved group tended to decrease. It is possible that EAT may have a positive effect on autonomic neuropathy symptoms such as orthostatic dysregulation (OD), postural orthostatic tachycardia syndrome (POTS), etc. by stimulating the BRs. It is thought that the autonomic nervous system stimulating action and the immune system stimulating action act synergistically to express the therapeutic effect of EAT.

Increased multimorbidity is associated with impaired cerebral and peripheral hemodynamic stabilization during active standing.

BACKGROUND: Age-related morbidities and frailty are associated with impaired blood pressure (BP) and heart rate (HR) recovery after standing. Here we investigate how multimorbidity affects cerebral and peripheral hemodynamics during standing in a large sample of older patients. METHODS: Patients were recruited from a national Falls and Syncope Unit. They underwent an active stand test (5-10 min lying +3 min standing) with monitoring of continuous BP, HR, total peripheral resistance (TPR), stroke volume (SV), and a near-infrared spectroscopy (NIRS) derived cerebral tissue saturation index (TSI). A multimorbidity count was derived from a 26-item list of conditions. Features derived from the signals included: nadir, overshoot, value at 30 s, steady-state and recovery rate. Robust linear regression was used to assess the association between multimorbidity, TSI and peripheral hemodynamics while correcting for covariates. A p-value <0.05 was considered statistically significant. RESULTS: Multimorbidity was associated with poorer recovery of TSI at 30 s after standing (ß: -0.15, CI:[-0.25-0.06], p = 0.009) independent of all peripheral hemodynamics. Impaired diastolic BP (DBP) recovery at 30s (ß:-1.34, CI:[-2.29-0.40], p = 0.032), DBP steady-state (ß:-1.18, CI:[-2.04-0.32], p = 0.032), TPR overshoot-to-nadir difference (ß:-0.041, CI:[-0.070-0.013], p = 0.045), and SV at 30s (ß:1.30, CI:[0.45 2.15], p = 0.027) were also associated with increasing multimorbidity. After sex stratification, only females demonstrated impaired TSI with multimorbidity at overshoot (ß: -0.19, CI: [-0.32 -0.07], p = 0.009), 30 s (ß: -0.22 [-0.35-0.10], p = 0.005) and steady-state (ß: -0.20, CI:[-0.35-0.04], p = 0.023), independent of peripheral hemodynamics. CONCLUSIONS: Transient cerebral oxygenation and peripheral hemodynamic responses are impaired with multimorbidity (frailty) in older patients, particularly in females. This study demonstrates the feasibility of using NIRS in this clinical context and may inform the development of clinical management strategies targeting both cerebral oxygenation and blood pressure impairments in patients with faints and falls.

Association of the Heart Rate Variability Response to Active Standing with the Severity of Calcific Aortic Valve Disease: Novel Insights of a Neurocardiovascular Pathology.

The aim of this work was to obtain insights of the participation of the autonomic nervous system in different stages of calcific aortic valve disease (CAVD) by heart rate variability (HRV) analysis. Studying subjects with no valve impairments and CAVD patients, we also sought to quantify the independent contribution or explanatory capacity of the aortic valve echocardiographic parameters involved in the HRV changes caused by active standing using hierarchical partitioning models to consider other variables or potential confounders. We detected smaller adjustments of the cardiac autonomic response at active standing caused specifically by the aortic valve deterioration. The highest association (i.e., the highest percentage of independent exploratory capacity) was found between the aortic valve area and the active standing changes in the short-term HRV scaling exponent α1 (4.591%). The valve's maximum pressure gradient echocardiographic parameter was present in most models assessed (in six out of eight models of HRV indices that included a valve parameter as an independent variable). Overall, our study provides insights with a wider perspective to explore and consider CAVD as a neurocardiovascular pathology. This pathology involves autonomic-driven compensatory mechanisms that seem generated by the aortic valve deterioration.

Recurrence Quantitative Analysis of Wavelet-Based Surrogate Data for Nonlinearity Testing in Heart Rate Variability.

Exploring the presence of nonlinearity through surrogate data testing provides insights into the nature of physical and biological systems like those obtained from heart rate variability (HRV). Short-term HRV time series are of great clinical interest to study autonomic impairments manifested in chronic diseases such as the end stage renal disease (ESRD) and the response of patients to treatment with hemodialysis (HD). In contrast to Iterative Amplitude Adjusted Fourier Transform (IAAFT), the Pinned Wavelet Iterative Amplitude Adjusted Fourier Transform (PWIAAFT) surrogates preserve nonstationary behavior in time series, a common characteristic of HRV. We aimed to test synthetic data and HRV time series for the existence of nonlinearity. Recurrence Quantitative Analysis (RQA) indices were used as discriminative statistics in IAAFT and PWIAAFT surrogates of linear stationary and nonstationary processes. HRV time series of healthy subjects and 29 ESRD patients before and after HD were tested in this setting during an active standing test. Contrary to PWIAAFT, linear nonstationary time series may be erroneously regarded as nonlinear according to the IAAFT surrogates. Here, a lower proportion of HRV time series was classified as nonlinear with PWIAAFT, compared to IAAFT, confirming that the nonstationarity condition influences the testing of nonlinear behavior in HRV. A contribution of nonlinearity was found in the HRV data of healthy individuals. A lower proportion of nonlinear time series was also found in ESRD patients, but statistical significance was not found. Although this proportion tends to be lower in ESRD patients, as much as 60% of time series proved to be nonlinear in healthy subjects. Given the important contribution of nonlinearity in HRV data, a nonlinear point of view is required to achieve a broader understanding of cardiovascular physiology.

Skin sympathetic nerve activity in patients with chronic orthostatic intolerance.

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by the development of tachycardia and other symptoms when assuming an upright body position. OBJECTIVE: The purpose of this study was to test the hypothesis that skin sympathetic nerve activity (SKNA) bursts are specific symptomatic biomarkers in patients with chronic OI. METHODS: We used an electrocardiogram monitor with a built-in triaxial accelerometer to simultaneously record SKNA and posture in ambulatory participants. Study 1 compared chronic OI (14 women and 2 men; mean age 35 ± 10 years) with reference control participants (14 women; mean age 31 ± 6 years). Study 2 included 17 participants with chronic OI (15 women and 2 men; mean age 39 ± 12 years) not yet treated with ivabradine, pyridostigmine, or ß-blockers. RESULTS: In study 1, there were 124 episodes (8 ± 4 per participant) of postural changes, with 11 episodes (8.9%) associated with symptoms. In comparison, 0 of 104 postural changes (7 ± 3 per participant) in controls were symptomatic (P = .0011). In participants with chronic OI, the SKNA bursts associated with symptoms had higher burst frequencies, longer burst durations, and larger mean burst areas than did bursts during asymptomatic periods. However, SKNA bursts and tachycardia were asymptomatic in controls. We analyzed 110 symptomatic episodes in study 2 (6 ± 5 per participant). Among them, 98 (89.1%) followed at least 1 SKNA burst. In comparison, only 41 (37.3%) had heart rate exceed 100 beats/min 1 minute before symptom onset (P < .0001). CONCLUSION: SKNA bursts are a highly specific, albeit insensitive, symptomatic biomarker for chronic OI.

Cardiac Autonomic Response to Active Standing in Calcific Aortic Valve Stenosis.

Aortic stenosis is a progressive heart valve disorder characterized by calcification of the leaflets. Heart rate variability (HRV) analysis has been proposed for assessing the heart response to autonomic activity, which is documented to be altered in different cardiac diseases. The objective of the study was to evaluate changes of HRV in patients with aortic stenosis by an active standing challenge. Twenty-two volunteers without alterations in the aortic valve (NAV) and twenty-five patients diagnosed with moderate and severe calcific aortic valve stenosis (AVS) participated in this cross-sectional study. Ten minute electrocardiograms were performed in a supine position and in active standing positions afterwards, to obtain temporal, spectral, and scaling HRV indices: mean value of all NN intervals (meanNN), low-frequency (LF) and high-frequency (HF) bands spectral power, and the short-term scaling indices (α1 and αsign1). The AVS group showed higher values of LF, LF/HF and αsign1 compared with the NAV group at supine position. These patients also expressed smaller changes in meanNN, LF, HF, LF/HF, α1, and αsign1 between positions. In conclusion, we confirmed from short-term recordings that patients with moderate and severe calcific AVS have a decreased cardiac parasympathetic supine response and that the dynamic of heart rate fluctuations is modified compared to NAV subjects, but we also evidenced that they manifest reduced autonomic adjustments caused by the active standing challenge.

Dynamical interaction between heart rate and blood pressure of end-stage renal disease patients evaluated by cross recurrence plot diagonal analysis.

The assessment of spontaneous variability of blood pressure and heart rate is based on specific physiological hypotheses about dynamic features, for example, the baroreflex modulation of heart rate over time in daily life. Usually, arterial baroreflex control of heart rate is explored without delays between blood pressure and heart rate data points, within a narrow range of values, excluding the analysis of saturation regions or low-threshold changes. In this work, we examine the dynamic interactions between systolic blood pressure (SBP) and interbeat interval (IBI), in 15-min length time series and for the first time using the analysis of diagonals derived from a cross-recurrence plots in healthy persons and end-stage renal disease (ESRD) patients. We found that ESRD patients have stronger intermittent dynamical interactions between IBI and SBP, but they lose most of the dynamical interactions. Although healthy subjects exhibit a continuously changing order of precedence between IBI and SBP at different lags, ESRD patients preserve this changing order of precedence only for lags >0 beats.NEW & NOTEWORTHY This study is the first to compare the time-variant pattern of systolic blood pressure (SBP) and interbeat interval (IBI) coupling between ESRD patients and healthy volunteers through the analysis of diagonal in cross-recurrence plots, and in the face of an orthostatic challenge. Our results demonstrated alternant interactions on the order of precedence (IBI → SBP or SBP→ IBI) at different time delays. This pattern is different in resting position and during active standing for the two groups studied, and interestingly, some association patterns are lost in ESRD patients. These patterns of alternant interactions on the order of precedence could be related to autonomic neural activities and cardiovascular synchronization at different scales both in time and space. This could reflect physiological adaptive flexibility of cardiovascular regulation. Losing some association patterns in ESRD may be the result of chronic adjustments of many physiological mechanisms (including chronic sympathetic hyperactivity), which could increase cardiovascular vulnerability to hemodynamic challenges.

Orthostatic Headache in Children Including Postural Tachycardia Syndrome and Orthostatic Hypotension: A Near-Infrared Spectroscopy Study.

BACKGROUND AND AIM: Although head and/or neck pain attributed to orthostatic hypotension is included in international guidelines, its mechanisms and relevance remain unknown. This study examined the term's relevance and aimed to elucidate the associated clinical features. METHODS: An active stand test was performed to evaluate fluctuations in systemic and cerebral circulation in children and adolescents reporting complaints in the absence of a confirmed organic disorder. The subjects were categorized based on orthostatic headache presence/absence, and their characteristics and test results were compared. RESULTS: Postural tachycardia syndrome was observed in 50.0% of children with, and 55.1% without, orthostatic headache. For orthostatic hypotension, the respective values were 31.3% and 30.6%. A history of migraine was more prevalent in children with orthostatic headaches (64.1% vs. 28.6%; p < 0.01). The observed decrease in the cerebral oxygenated hemoglobin level was larger in children with orthostatic headaches (Left: 6.3 (3.2-9.4) vs. 4.1 (0.8-6.1); p < 0.01, Right: 5.3 (3.1-8.6) vs. 4.0 (0.8-5.9); p < 0.01). CONCLUSION: Fluctuations in cerebral blood flow were associated with orthostatic headaches in children, suggesting that the headaches are due to impaired intracranial homeostasis. As orthostatic headache can have multiple causes, the term "head and/or neck pain attributed to orthostatic (postural) hypotension" should be replaced with a more inclusive term.