Pre-existing parasympathetic dominance seems to cause persistent heart rate slowing after 6 months of fingolimod treatment in patients with multiple sclerosis.

PURPOSE: Vagomimetic fingolimod effects cause heart rate (HR) slowing upon treatment initiation but wear off with sphingosine-1-phosphate receptor downregulation. Yet, prolonged HR slowing may persist after months of fingolimod treatment. We evaluated whether cardiovascular autonomic modulation differs before and 6 months after fingolimod initiation between patients with RRMS with and without initially prolonged HR slowing upon fingolimod initiation. METHODS: In 34 patients with RRMS, we monitored RR intervals (RRI) and blood pressure (BP), at rest and upon standing up before fingolimod initiation. Six hours and 6 months after fingolimod initiation, we repeated recordings at rest. At the three time points, we calculated autonomic parameters, including RRI standard deviation (RRI-SD), RRI-total-powers, RMSSD, RRI high-frequency [HF] powers, RRI and BP low-frequency (LF) powers, and baroreflex sensitivity (BRS). Between and among patients with and without prolonged HR slowing upon fingolimod initiation, we compared all parameters assessed at the three time points (analysis of variance [ANOVA] with post hoc testing; significance: p < 0.05). RESULTS: Six hours after fingolimod initiation, all patients had decreased HRs but increased RRIs, RRI-SDs, RMSSDs, RRI-HF-powers, RRI-total-powers, and BRS; 11 patients had prolonged HR slowing. Before fingolimod initiation, these 11 patients did not decrease parasympathetic RMSSDs and RRI-HF-powers upon standing up. After 6 months, all parameters had reapproached pretreatment values but the 11 patients with prolonged HR slowing had lower HRs while the other 23 patients had lower parasympathetic RMSSDs and RRI-HF-powers, and BRS than before fingolimod initiation. CONCLUSION: Our patients with prolonged HR slowing upon fingolimod initiation could not downregulate cardiovagal modulation upon standing up even before fingolimod initiation, and 6 months after fingolimod initiation still had more parasympathetic effect on HR while cardiovagal modulation and BRS were attenuated in the other 23 patients. Pre-existing parasympathetic predominance may cause prolonged HR slowing upon fingolimod initiation.

Impact of surgical aortic valve replacement and transcatheter aortic valve implantation on cardiovascular and cerebrovascular controls: A pilot study.

Surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) are options in severe aortic valve stenosis (AVS). Cardiovascular (CV) and cerebrovascular (CBV) control markers, derived from variability of heart period, systolic arterial pressure, mean cerebral blood velocity and mean arterial pressure, were acquired in 19 AVS patients (age: 76.8 ± 3.1 yrs, eight males) scheduled for SAVR and in 19 AVS patients (age: 79.9 + 6.5 yrs, 11 males) scheduled for TAVI before (PRE) and after intervention (POST, <7 days). Left ventricular function was preserved in both groups. Patients were studied at supine resting (REST) and during active standing (STAND). We found that: (i) both SAVR and TAVI groups featured a weak pre-procedure CV control; (ii) TAVI ensured better CV control; (iii) cerebral autoregulation was working in PRE in both SAVR and TAVI groups; (iv) SAVR and TAVI had no impact on the CBV control; (v) regardless of group, CV and CBV control markers were not influenced by STAND in POST. Even though the post-procedure preservation of both CV and CBV controls in TAVI group might lead to privilege this procedure in patients at higher risk, the missing response to STAND suggests that this advantage could be insignificant.

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 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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

Evaluación de la frecuencia cardiaca durante la bipedestación activa inicial en pacientes que padecen síncope vasovagal / Evaluation of the heart rate during initial active standing in patients with vasovagal syncope

Introducción: El síncope vasovagal es la causa más frecuente de pérdida breve de la conciencia, en su etiopatogenia se reporta una disfunción autonómica que puede ponerse de manifiesto en la bipedestación activa inmediata. Objetivo: Comparar la dinámica de los cambios de la frecuencia cardíaca durante la bipedestación activa inmediata, de pacientes que padecen síncope vasovagal y sujetos controles. Métodos: Se evaluaron 132 sujetos supuestamente sanos (grupo A) entre 18 y 25 años y 156 pacientes con síncopes vasovagales; fueron divididos por su respuesta ante la bipedestación prolongada, negativa 111 (grupo B) y positiva 45 (grupo C). Se registró la actividad electrocardiográfica en decúbito supino y al inicio de la bipedestación activa, se obtuvo las secuencias de intervalos RR. Se comparó la frecuencia cardíaca en los 3 grupos, con 22 indicadores (posicionales, temporales, ordinales y relacionales, promedio y de la velocidad de los cambios). Resultados: No hubo diferencias en los indicadores promedio, sin embargo, algunos que evalúan la velocidad del cambio inicial, fueron significativamente menores en el grupo A comparado con B y C (p < 0,05), mientras que los que evalúan la velocidad de recuperación, fueron significativamente menores en el grupo C comparado con A y B. Conclusión: La dinámica de los cambios de frecuencia, permitió encontrar indicadores que pueden considerarse posibles predictores de una respuesta cardiovascular inadecuada en pacientes con síncope vasovagal(AU)

Introduction: Vasovagal syncope is the most frequent cause of brief loss of consciousness, in its etiopathogenesis an autonomic dysfunction is reported that can be manifested in immediate active standing. Objective: To compare the dynamics of heart rate changes during immediate active standing of patients suffering from vasovagal syncope with control subjects. Methods: 132 supposedly healthy subjects (group A) between 18 and 25 years old and 156 patients with vasovagal syncope were evaluated, which were divided by their response to prolonged standing, negative 111 (group B) and positive 45 (group C). Electrocardiographic activity was recorded in the supine position and at the beginning of active standing, the sequences of RR intervals were obtained. The heart rate was compared in the 3 groups, using 22 indicators (positional, temporal, ordinal and relational, average and of the speed of changes). Results: Differences were not found in the average indicators in the analyzed period, however, some that evaluate the speed of the initial change were significantly lower in group A compared to B and C (p < 0.05), while others that evaluate the speed recovery rates were significantly lower in group C compared to A and B. This allows to characterize, compare and differentiate the groups studied during the complex and rapid interactions that occur in the change of position. Conclusion: The dynamic of frequency changes, allowed to find indicators, which can be considered as possible predictors of an inadequate cardiovascular response in patients with vasovagal syncope(AU)

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.