Head-up Tilt Research Articles

Awareness of postural orthostatic tachycardia syndrome is required in adolescent syncope.

We investigated head-up tilt test (HUTT) results across age-groups in syncope/presyncope patients to establish pediatric postural orthostatic tachycardia syndrome (POTS) characteristics. We retrospectively reviewed syncope patients' medical records. Adolescents were defined as 10 to 19 years old, adults as 20 to 59 years old, and older individuals as ≥60 years old. From HUTT results, we determined POTS prevalence and differences among the age-groups. We included 147 adolescents, 269 adults, and 123 older patients. Seventy (13.0%) patients (61.4% females; median age: 20 [17-25] years) were diagnosed with POTS. The syndrome was more prevalent among adolescents (33 [22.4%]) than adults (37 [13.8%]), and was absent among older individuals. Affected adolescents had significantly lower resting diastolic blood pressure (DBP) and heart rate (HR), and converted to maximum HR more rapidly than adolescents without the syndrome during the passive phase. Adolescents with POTS demonstrated several unique characteristics compared to adults with and adolescents without this syndrome. POTS may be underrecognized among syncope and presyncope patients, among which 22.4% of adolescents were diagnosed with the syndrome. POTS should be considered when evaluating syncope patients.

Improved health-related quality of life after cardioneuroablation in patients with vasovagal syncope.

As the most common cause of syncope, vasovagal syncope (VVS) is mediated by parasympathetic overactivity and/or sympathetic withdrawal. Although catheter ablation of ganglionated plexi or cardioneuroablation has been used to treat VVS, its role in quality of life (QoL) has not been formally evaluated. The aim of this study was to demonstrate if this novel treatment results in improvement QoL of patients with VVS. Twenty-seven consecutive patients (age: 34 ± 14years, 51.8% male) with dominant cardioinhibitory type VVS were prospectively enrolled in the study. After confirmation of > 3s asystole on head-up tilt testing (HUT), all patients underwent cardioneuroablation. ECGs were obtained prior to procedure and at 12-month follow-up visit. HUTs were repeated 1month after cardioneuroablation procedures. QoL was assessed with the use of SF-36, EQ-5D, and EQ VAS questionnaires. ECG, HUT, and QoL data were available in all patients. At 12-month follow-up, heart rate on rest ECG significantly increased (from 74 ± 15 to 84 ± 14bpm, p = 0.003). Repeated HUTs were negative in 23 (85.1%) patients. All of 27 patients remained free of syncope. QoL assessed by SF-36 score significantly improved in postprocedural follow-up (92 ± 9 and 96 ± 11, p = 0.016). Similarly, significant improvements in mobility, self-care, and usual activity domains of EQ-5D were observed (mean scores of 3.0 ± 1.5 and 2.1 ± 1.3, p < 0.001; 1.3 ± 0.9 and 1.2 ± 0.6, p = 0.041; 1.7 ± 1.0 and 1.4 ± 0.8 respectively). EQ-VAS score also improved significantly (39 ± 24 to 77 ± 18, p < 0.001). Our findings suggest that cardioneuroablation may be associated with intermediate term improvement in QoL in patients with VVS.

Short-term virtual reality simulation of the effects of space station colour and microgravity and lunar gravity on cognitive task performance and emotion

This study implemented a short-term virtual reality examination of the impacts of environmental colour and posture changes (to simulate microgravity and lunar gravity) on cognitive task performance and emotions. In a standard posture change laboratory study, sixty participants performed a simple cognitive task battery (finding A's test and number comparison test) and an emotional state questionnaire within nine different colour scenes while using three postures (normal sitting (SP), −12° head-down bed (HD) and 9.6° head-up tilt bed (HU)). The results showed that in all colour scenes, the HD posture significantly reduced the participants' task performance and level of positive emotions. There was also some variability in task performance and emotional reaction by scene colour. Overall, the study adds to our understanding of how environmental and postural factors impact on cognition and emotion.

Abstract 12760: Microvascular Endothelial Dysfunction in Postural Orthostatic Tachycardia Syndrome Associated With Post-Acute Sequelae of COVID-19

Introduction: Post-acute sequelae of COVID-19 (PASC) is a novel clinical syndrome. We have previously reported that PASC patients can develop postural orthostatic tachycardia syndrome (POTS) and that COVID-19 induce microvascular endothelial dysfunction in acutely ill, hospitalized patients, that persist up to four months post discharge. Whether microvascular endothelial dysfunction contributes to POTS pathophysiology in PASC remains unclear. Hypothesis: Patients with PACS combined with POTS have impaired microvascular endothelial function. Methods: PASC patients (n=44) with mild SARS-CoV-2 infection (not hospitalized) were recruited from the post-COVID multidisciplinary clinic at Karolinska University Hospital. PASC diagnosis was based on the WHO PASC criteria. POTS was diagnosed in 21 patients (PASC + POTS) while 23 had a negative head-up tilt test (PASC - POTS). Age- and gender-matched healthy subjects (n=15) served as controls. Microvascular endothelial function was quantified as reactive hyperemia index (RHI) determined from the changes in pulse amplitude tonometry before and after a 5 min episode of arterial occlusion. Stress-perfusion cardiac magnetic resonance imaging (cMRI) with adenosine was performed in a subset of patients. Results: Mean age was 42±11 years and 95 % were women among PACS patients. Time from COVID-19 symptom onset to study inclusion was 18±3 months. RHI was significantly lower in PASC + POTS than in healthy controls and PASC - POTS (Figure 1). The prevalence of cardiac microvascular dysfunction on cMRI did not differ between the PASC groups (8% in PASC + POTS vs. 13% in PASC - POTS, p=1.00). All subjects with microvascular dysfunction on cMRI except one had a RHI below the cutoff (1.67) indicating microvascular dysfunction. Conclusions: Microvascular endothelial dysfunction is common in patients with PACS-associated POTS and may cause stress-induced myocardial ischemia up to 18 months after a mild primary infection.

Abstract 12737: Baseline Carotid Sinus Massage in the Supine Position Predicts Outcome of Head Up Tilt Table Testing: Potential for Abbreviating the Tilt Table Test Protocol

Introduction: Carotid sinus massage (CSM) has been used to evaluate carotid sinus hypersensitivity. Its role in evaluating a vasodepressor response has not been well studied. CSM can also result in a vasodepressor response in the absence of significant bradycardia. Its role in predicting the subsequent outcome of head-up tilt testing (HUT) is not well defined. Hypothesis: A vasodepressor response elicited with baseline carotid sinus massage (CSM) may predict the subsequent outcome of HUT. Methods: In this prospective study Consecutive patients with a history suggestive of a reflex neurocardiogenic etiology underwent HUT. Patients underwent HUT testing using a standard protocol, including baseline CSM in the supine posture followed by HUT testing at 60 degrees for 30 minutes. If negative, a repeat of CSM was performed in the upright posture. Then, isoproterenol was infused in incremental dose 1 to 3 mcg/minute. Results: 25 patients (20 females and 5 males) with a mean age of 52.87±6.77 years underwent HUT. 5 out of 25 (20%) patients had a positive tilt result for a vasodepressor response. 4 of these 5 patients had a significant vasodepressor response (symptomatic hypotension BP drop less than 30 mmHg) without significant bradycardia (HR less than 50 BPM) during CSM in the supine posture. Of these patients, 3 patients became positive during HUT and 1 patient became positive during isoproterenol infusion. The positive predictive value was 0.8. Sensitivity was 67%. 20 out of 25 (80%) patients had a negative tilt result for a vasodepressor response despite protocol completion. 18 of these 20 patients had no drop in BP during CSM and no significant bradycardia. The negative predictive value was 0.9. The specificity was 94.74%. 2 of these patients had a negative response on CSM but a borderline response at HUT with borderline symptoms with the isoproterenol. These 2 had a transient drop in BP when CSM was repeated at the end of 30 minutes during the head-up position. Conclusions: In this population of patients, a negative CSM in the supine posture predicted a subsequent negative Tilt test. Baseline CSM can be performed at the bedside and may obviate the need for full tilt table testing even for patients with a clinical diagnosis of reflex syncope (vasodepressor).

Abstract 15677: Comprehensive Physiological Phenotyping Reveals Deconditioning Among Individuals With Long-COVID-19

Introduction: Post-acute COVID-19 sequalae (PASC) is a poorly understood constellation of symptoms that persist or emerge following the post-viral convalescent period. We sought to comprehensively evaluate cardiac and autonomic function and deconditioning as possible contributors to PASC associated fatigue. Methods: Thirty individuals with PASC (20F:10M; 41±11yrs; 137-730 days post-infection) prospectively underwent measures of autonomic function (heart rate [HR] and muscle sympathetic nerve activity [MSNA] response to passive head-up tilt 60° [HUT]); cardiac function (echocardiogram); arrhythmia burden (24-hour Holter monitor); exercise capacity (cardiopulmonary exercise test); hemoglobin and inflammatory biomarkers (CRP, troponin, IL-6, TNFα, IL-10). Participants were stratified by ongoing fatigue and symptoms of breathlessness (SOB+ or SOB-). Individuals with pre-existing conditions associated with fatigue were excluded. Results: Sixteen individuals (53%) reported breathlessness. Other common symptoms were palpitations (n=9; 30%) and light-headedness (n=5; 17%). Exercise capacity normalised for age and gender was lower in breathless subjects (SOB+) than in non-breathless subjects (SOB-); 70±11% vs 85±15%, p =0.004. The SOB+ group tended to have a blunted MSNA response to HUT when compared to SOB- ( p =0.06), with similar prevalence of postural orthostatic tachycardia (SOB+ n=5 vs SOB- n=5). Echocardiography revealed that global longitudinal strain trended higher in the SOB+ group compared with SOB- ( p= 0.075), with similar prevalence of participants who fulfilled diastolic dysfunction criteria (SOB+ 5 vs SOB- 4). There were no significant sustained arrhythmias on 24-hour Holter monitoring. Hemoglobin, troponin and cytokines were all similar (p&gt;0.05), but CRP was higher in the breathless group ( p =0.016). Conclusions: This is the first comprehensive phenotyping of PASC with ongoing fatigue and breathlessness. We found that these symptoms were associated with reduced exercise capacity but without any associated cardiac impairment, arrhythmias, or autonomic dysfunction. These findings suggest that deconditioning may contribute to the pathophysiology of PASC.

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±8yrs., 5 males) at rest in supine position (REST) and during 60° head-up tilt (HUT) and in 19 patients (age: 64±8yrs., 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.

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.

Cerebrovascular regulation in patients with vasovagal syncope and autonomic failure due to familial amyloidotic polyneuropathy.

While there is strong evidence for autonomic involvement in cerebrovascular function acutely, long-term role of autonomic nervous system in cerebrovascular function has been controversial. We assessed autoregulation in 10 healthy individuals, nine patients with vasovagal syncope (VVS), and nine with Familial Amyloidotic Polyneuropathy (FAP), in response to head-up tilt test (HUTT). Arterial blood pressure heart rate, cardiac output, and bilateral cerebral blood flow velocity (CBFV) at the M1 segment of middle cerebral artery (transcranial Doppler ultrasound) were recorded during supine rest and 70° HUTT. Autoregulation was quantified using a validated nonlinear and nonparametric approach based on projection pursuit regression. Plasma adrenaline and noradrenaline were also measured at rest and during HUTT. During supine rest and HUTT, plasma noradrenaline content was lower in FAP patients. During HUTT, VVS patients had a hyperadrenergic status; CBFV decreased in all groups, which was greater in FAP patients (p<0.01). Healthy controls responded to HUTT with a reduction in CBFV responses to increases (p=0.01) and decreases (p<0.01) in arterial pressure without any change in the range or effectiveness of autoregulation. VVS patients responded to HUTT with a reduction in falling (p=0.02), but not rising slope (p=0.40). Autoregulatory range (p<0.01) and effectiveness increased (p=0.09), consistent with the rapid increase in levels of catecholamines. In FAP patients, the level of increase in range of autoregulation was significantly related to the magnitude of increase in plasma noradrenaline in response to HUTT (R2=0.26, p=0.05). Autonomic dysfunction affects the cerebral autoregulatory response orthostatic to challenge.

The effects of ALDH2 Glu487Lys polymorphism on vasovagal syncope patients undergoing head-up tilt test supplemented with sublingual nitroglycerin

Background and objectiveHead-up tilt test (HUTT) is clinically advantageous for diagnosing patients with vasovagal syncope (VVS). Nitroglycerin is mainly used as a stimulant during HUTT, and mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in the metabolism of nitroglycerin (NTG). ALDH2 Glu487Lys polymorphism (ALDH2 rs671) is the most common variant in the East Asian population. This study aimed to assess the effects of ALDH2 rs671 on VVS patients undergoing HUTT supplemented with sublingual NTG (HUTT-NTG). MethodsPatients with recurrent VVS (at least 2 times) who were admitted to the syncope center of our hospital were enrolled. All VVS patients have undergone HUTT. The polymorphism of Glu487Lys gene of ALDH2 was measured by the DNA Microarray Chip Method. The results of HUTT-NTG of VVS patients with different ALDH2 genotypes were compared and their hemodynamic characteristics were assessed.ResultsA total of 199 VVS patients were enrolled, including 101 patients in the ALDH2*1/*1 group and 98 patients in the ALDH2*2 group. Among patients undergoing HUTT-NTG, 70.3% of patients in the ALDH2*1/*1 group and 68.4% of patients in the ALDH2*2 group were positive, and the difference between the two groups was not statistically significant (P = 0.77). The proportions of VASIS I, VASIS II, and VASIS III were 40.6%, 8.9%, and 20.8% in the ALDH2*1/*1 group, respectively, and the corresponding proportions in the ALDH2*2 group were 36.7%, 11.2%, and 20.4%, respectively. There was no statistically significant difference between the two groups (P = 0.91). The hemodynamic characteristics of different genotypes in VVS patients undergoing HUTT-NTG were compared, and no statistically significant difference was found. The median time of syncopal episode occurred after NTG administration in the ALDH2*1/*1 group was 6 min (interquartile range [IQR]: 5.0–9.0), and it was 6.0 min in the ALDH2*2 group (IQR: 4.25–8.0, P = 0.64).ConclusionALDH2 Glu487Lys polymorphism did not affect the outcome of VVS patients undergoing HUTT-NTG, and no significant change in the hemodynamic characteristics of different genotypes was found.

331 THE USE OF BODY MASS INDEX IN PREDICTING ORTHOSTATIC HYPOTENSION IN OLDER ADULTS

Abstract Background The presence of Orthostatic Hypotension (OH) is known to be associated with an increased mortality risk. Previous Irish research has shown that elevated Body Mass Index (BMI) may be protective against OH, with overweight and obese patients having significantly smaller Systolic Blood Pressure (SBP) drops during Head-Up-Tilt (HUT) Testing. Methods Demographics, including age, height and weight, were obtained retrospectively from all head up tilt testing performed in a tertiary Irish hospital between 2000 and 2021. All incomplete records were excluded. A total of 4,717 patients were analysed. Linear regression models were used to examine the relationship between BMI and change in tilt SBP. Results 2,089 males and 2,628 females over the age of 60 years old were examined. The mean age is 77 years ± 7.8 (S.D.), with majority (51.5%) of the cohort overweight or obese. 69.7% of individuals demonstrated OH. The mean change in tilt SBP was –7mmHg in the underweight and healthy weight group, and –10mmHg in the overweight or obese group. The linear regression model established that BMI significantly predicted a change in tilt SBP (beta=0.394, 95% CI: 0.235 to 0.554, p&amp;lt;0.001), but remains a poor predictive variable (R2=0.004) for this cohort. This correlation was similar for both genders (male: r=0.08, female: r=0.07). Conclusion Our findings confirmed a correlation between BMI and its predictive impact on OH in older adults. Future studies should explore targeted populations with multivariate analysis, taking into consideration age and gender, to reduce the heterogeneity of data.

212 FATIGUE EXPERIENCED BY ADULTS WITH LONG-COVID WAS NOT ASSOCIATED WITH AN EMG-DERIVED MUSCLE FATIGUE INDEX

Abstract Background One of the most prominent challenges of the COVID-19 pandemic is the emergence of the post-COVID-19 syndrome or ‘long-COVID’ following the acute phase of the viral infection. With a plethora of debilitating symptoms across many physiological systems, the pathophysiology of long-COVID remains elusive and subject of intense research efforts. Adults with long COVID are often affected by prolonged fatigue, which could be linked to neuromuscular function impairment. We hypothesised that there might be a correlation between subjective fatigue and an Electromyograph(EMG)-derived muscle fatigue index in adults with long-COVID. Methods As part of a neuro-cardiovascular instability assessment protocol, participants were asked to squeeze the thigh muscles as hard as possible for ten seconds during both supine resting and after active and passive standing (head-up tilt) tests. Surface EMG was used to capture on each leg the physiological activity of the vastus lateralis and rectus femoris during the squeezes, from which the muscle fatigue index was computed based on both the mean and median frequencies of each 10-second maximum prompted muscle contraction. Using two-sided Spearman correlation coefficients, we examined the associations between the muscle fatigue indices and self-reported fatigue measured by the Chalder Fatigue Scale (CFQ). Results 108 participants were included, 77 female and 31 male, with a mean age of 46 (range 25-78) years, 22% of whom were hospitalised in the acute phase of SARS-CoV-2 infection. Strong intercorrelations were found between the muscle fatigue indices derived from the mean and median frequencies of thigh muscle contractions. However, no significant correlations were detected between the muscle fatigue indices and CFQ scores. Conclusion Self-reported fatigue as measured by the CFQ was not associated with an EMG-derived muscle fatigue index in this long-COVID cohort.

Effects of short-term hypercaloric nutrition on orthostatic tolerance in healthy individuals: a randomized controlled crossover study

Reduced-caloric intake lowers blood pressure through sympathetic inhibition, and worsens orthostatic tolerance within days. Conversely, hypercaloric nutrition augments sympathetic activity and blood pressure. Because dietary interventions could be applied in patients with syncope, we tested the hypothesis that short-term hypercaloric dieting improves orthostatic tolerance. In a randomized crossover trial, 20 healthy individuals (7 women, 26.7 ± 8 years, 22.6 ± 2 kg/m2) followed a 4-day hypercaloric (25% increase of energy intake by fat) or normocaloric nutritional plan, with a washout period of at least 23 days between interventions. We then performed head-up tilt table testing with incremental lower body negative pressure while recording beat-by-beat blood pressure and heart rate. The primary endpoint was orthostatic tolerance defined as time to presyncope. Time to presyncope during combined head-up tilt and lower body negative pressure did not differ between hypercaloric and normocaloric dieting (median 23.19 versus 23.04 min, ratio of median 1.01, 95% CI of ratio 0.5–1.9). Heart rate, blood pressure, heart rate variability, and blood pressure variability in the supine position and during orthostatic testing did not differ between interventions. We conclude that 4 days of moderate hypercaloric nutrition does not significantly improve orthostatic tolerance in healthy individuals. Nevertheless, given the important interaction between energy balance and cardiovascular autonomic control in the brain, caloric intake deserves more attention as a potential contributor and treatment target for orthostatic intolerance.

Syncopal patients without prodromes exhibit a diverse pattern of adenosine release during head-up tilt test

Abstract Background/Introduction In a significant proportion of patients with neurally-mediated syncope (NMS), the mechanism of syncope remains largely undetermined. Adenosine has been proposed as a central humoral factor in various forms of NMS: high Adenosine Plasma Levels (ADP) are encountered in patients with vasovagal syncope (VVS), low ADP in non-prodromes syncope (NPS), while ADP in patients with situational syncope SS are less well determined. Purpose We sought to assess ADP in patients with different clinical forms of syncope, with an emphasis on the presence or absence of prodromal symptoms, as well as the relation between ADP and the outcomes of Head-Up Tilt Table Test (HUTT) and Adenosine test (ADT). Methods Patients with different clinical types of NMS (n=124), i.e., VVS, NPS, or SS, were investigated using a standard protocol including HUTT and ADT. During HUTT, ADP was measured in the supine position, at table tilting, and in syncope. Results Baseline ADP did not differ among groups. ADP at syncope were higher in NPS compared to VVS (1.55±1.29 vs 0.16±0.05 μM, p=0.03) and SS (0.15±0.05 μM, p=0.02). In NPS, ADP increased from the supine position to the time of syncope (0.47±0.25 to 1.55±1.29 μM, p=0.04). In VVS, ADP increased only from the supine to the tilt position (0.23±0.04 to 0.35±0.10 μMu, p=0.02), while in SS ADP did not change in any stage of HUTT. SS was associated with cardioinhibitory HUTT (OR 3.40, 95% CI 1.05 to 9.56, p=0.04) and positive ADT (OR 4.22, 95% CI 1.47 to 11.46, p=0.012). Conclusion(s) A distinct pattern of ADP increase is noted during HUTT in NPS, suggesting that an excessive increase of ADP may play the key role in triggering this type of clinical presentation of syncope independently of the baseline ADP. Cardioinhibition prevails in patients with SS without clear adenosine involvement. Such observations contribute to an enhanced understanding of the pathophysiology of different clinical forms of syncope which may offer the possibility to tailor the management approach appropriately. Funding Acknowledgement Type of funding sources: None.

Arterial compliance and its dynamics in obese adolescents.

Arterial compliance (AC) decrease with aging is accelerated by factors associated with the progression of atherosclerotic process, including obesity. Prevalence of obesity increases not only in adult population but also in children and adolescents. The results of studies characterizing the effect of obesity on AC (often indirectly estimated by pulse wave velocity (PWV)) are contradictory. Considering the limitations of previously applied methods and the need to interpret AC values in the context of potential confounders or during various physiological states, the aim of this study was to compare AC of control and obese adolescents during four different physiological states: supine rest, head-up tilt (HUT), supine recovery and mental arithmetic (MA). AC was assessed by the method based on two-element Windkessel model as the ratio of a time constant t characterizing diastolic blood pressure decay and total peripheral resistance (TPR). In total, fifty healthy and normotensive subjects (40 females, 10 males, age 17.5 years (SD=1.1 years)) were examined - 25 obese and 25 age- and sex-matched control subjects. We observed significantly increased AC values during all phases in obese group. An increase in AC was also preserved after controlling for blood pressure influence. These results were confirmed using PWV based AC estimation. Interestingly, AC decreased similarly during stress phases (HUT, MA) in both groups. Lastly, TPR was decreased throughout the study protocol in obese subjects. In conclusion, AC is increased in young obese subjects consistently during various physiological states. Furthermore, changes of physiological states evoke similar response of AC in both groups indicating preserved autonomic control of elastic arteries. A decreased TPR in obese subjects points towards the influence of different maturation state of the arterial tree and/or changes in vasomotion possibly counterbalancing acceleration of atherosclerosis process.

Input for baroreflex analysis: which blood pressure signal should be used?

The baroreflex (BR) is an important physiological regulatory mechanism which reacts to blood pressure perturbations with reflex changes of target variables such as the heart period (electrocardiogram derived RR interval) or the peripheral vascular resistance (PVR). Evaluation of cardiac chronotropic (RR as a target variable) and vascular resistance (target PVR) BR arms was in previous studies mainly based on the use of the spontaneous variability of the systolic or diastolic blood pressure (SBP, DBP), respectively, as the input signals. The use of other blood pressure measures such as the mean blood pressure (MBP) as an input signal for BR analysis is still under investigation. Making the assumption that the strength of coupling along the BR indicates the more appropriate input signal for baroreflex analysis, we employ partial spectral decomposition to assess in the frequency domain the causal coupling from SBP, MBP or DBP to RR or PVR. Noninvasive beat-to-beat recording of RR, SBP, MBP and DBP and PVR was performed in 39 and 36 volunteers in whom orthostatic and cognitive loads were evoked respectively through head-up tilt and mental arithmetic task. At rest, the MBP was most tightly coupled with RR, in contrast to the analysis of the vascular resistance BR arm where the results showed similar importance of all blood pressure input signals. During orthostasis, the increased importance of SBP as the input signal for BR analysis along the cardiac chronotropic arm was demonstrated. In addition, the gain from MBP to RR was more sensitive to physiological state changes compared to gains with SBP or DBP signal as inputs. We conclude that the coupling strength depends not only on the analysed baroreflex arm but also on the selection of the input blood pressure signal and the physiological state. The MBP signal should be more frequently used for the cardiac baroreflex analysis.

Patients with POTS fear that data on abnormal haemodynamic physiology have been ignored

Norcliffe-Kaufmann et al.1 recently reported that patients with postural orthostatic tachycardia syndrome (POTS) had an exaggerated anticipatory heart rate (HR) increase in the 30 s prior to head-up tilt (HUT). Based largely on these findings, the authors conclude that patients with POTS suffer from a ‘fear-conditioning behavioural response’ to the thought of standing, and that POTS is a ‘functional psychogenic disorder’ that would best be treated by mental health professionals. Their basic finding is of potential interest; unfortunately their conclusions ignore limitations in their participant selection, methodological approach, and prior research into POTS pathophysiology, and they illustrate their lack of knowledge of psychiatric diagnosis and care. A major study limitation is the choice to compare POTS patients with a healthy control group. In a previous report,2 participants with POTS scored higher on the anxiety sensitivity index than healthy control participants, but scores were not significantly different compared to the general population.2 Patients with chronic illness have elevated depression, anxiety and health anxiety scores compared to healthy controls.3 Consequently, Norcliffe-Kaufmann et al.1 should have chosen a control group with chronic illness but without an orthostatic disorder. Without this control group, the study finding of exaggerated anticipatory tachycardia to a tilt stimulus may simply reflect elevated somatic anxiety due to chronic illness.

Clinical autonomic nervous system laboratories in Europe: A joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies: A joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies.

Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p= 0.021). This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.

An atrioventricular node model incorporating autonomic tone.

The response to atrial fibrillation (AF) treatment is differing widely among patients, and a better understanding of the factors that contribute to these differences is needed. One important factor may be differences in the autonomic nervous system (ANS) activity. The atrioventricular (AV) node plays an important role during AF in modulating heart rate. To study the effect of the ANS-induced activity on the AV nodal function in AF, mathematical modelling is a valuable tool. In this study, we present an extended AV node model that incorporates changes in autonomic tone. The extension was guided by a distribution-based sensitivity analysis and incorporates the ANS-induced changes in the refractoriness and conduction delay. Simulated RR series from the extended model driven by atrial impulse series obtained from clinical tilt test data were qualitatively evaluated against clinical RR series in terms of heart rate, RR series variability and RR series irregularity. The changes to the RR series characteristics during head-down tilt were replicated by a 10% decrease in conduction delay, while the changes during head-up tilt were replicated by a 5% decrease in the refractory period and a 10% decrease in the conduction delay. We demonstrate that the model extension is needed to replicate ANS-induced changes during tilt, indicating that the changes in RR series characteristics could not be explained by changes in atrial activity alone.

Baroreflex sensitivity predicts therapeutic effects of metoprolol on pediatric postural orthostatic tachycardia syndrome.

ObjectiveTo determine if the baseline baroreflex sensitivity (BRS) could be a useful predictor for the metoprolol therapeutic efficacy on postural orthostatic tachycardia syndrome (POTS) in children.MethodsIn this retrospective case-control study, 54 children suffering from POTS treated with metoprolol were recruited from the pediatric department of Peking University First Hospital. After 2–3 months of metoprolol treatment, all subjects were divided into responders and non-responders based on whether the symptom score (SS) was decreased by over 50% after metoprolol treatment at the follow-up. The baseline demographic parameters and the supine BRS during the head-up tilt test (HUTT) obtained by Finapres Medical System (FMS) were compared between the two groups. The value of BRS to predict the effectiveness of POTS was analyzed by a receiver-operating characteristic (ROC) curve.ResultsThe age, sex, height, weight, body mass index (BMI), course of the disease, baseline SS, medication time, metoprolol dose, and follow-up time of the subjects were not statistically different between the responders and non-responders (P > 0.05). The decline in symptom scores (ΔSS) of the responders was more obvious than that of the non-responders (P < 0.01). The supine BRS, BRS at maximum HR, supine heart rate (HR), and maximum HR were different between responders and non-responders (P < 0.01, P = 0.022, P < 0.01, P = 0.047). The binary multivariable analysis showed that baseline supine BRS was significantly associated with the response to metoprolol therapy [OR: 2.079, 95% CI: (1.077, 4.015), P = 0.029]. According to the ROC curve, the area under the curve (AUC) of baseline BRS was 0.912 (95% CI, 0.840–0.984), with a cut-off value of 8.045 ms/mmHg, yielding a sensitivity and specificity of 75.8% and 95.2%, respectively, in predicting the effectiveness of POTS.ConclusionThe baseline supine BRS level > 8.045 ms/mmHg can predict a good therapeutic response to metoprolol and the results would assist in guiding the individualized β-adrenoceptor blocker use in pediatric patients suffering from POTS.