Postural Syncope Research Articles

‘Normal’ blood pressure: too good to be true? Case series on postural syncope and the ‘white-coat’ effect

‘Normal’ blood pressure: too good to be true? Case series on postural syncope and the ‘white-coat’ effect

A Ten-Year Experience With Midodrine for Postural Orthostatic Tachycardia Syndrome and Neurocardiogenic Syncope

A Ten-Year Experience With Midodrine for Postural Orthostatic Tachycardia Syndrome and Neurocardiogenic Syncope

Spectrum of Autonomic Nervous System Impairment in Sjögren Syndrome.

To describe the spectrum of autonomic dysfunction in a uniformly evaluated cohort of patients with Sjögren syndrome. A series of 13 patients underwent a comprehensive evaluation for suspected autonomic impairment, including a neurological examination, autonomic testing, and laboratory studies. A diagnosis of Sjögren syndrome was established as the cause of autonomic dysfunction in all. Clinical features, findings on autonomic testing, and laboratory results are described. All patients in this series reported postural lightheadedness and syncope or near-syncope. Autonomic testing confirmed the presence of orthostatic hypotension on tilt-table testing in 5 patients and an excessive postural tachycardia and/or hypertensive response in 8 patients. Only 2 of the patients with orthostatic hypotension had a significant sensory neuropathy. Symptoms suggestive of gastrointestinal and genitourinary impairment were seen in nearly all patients, with abnormal motility testing (most frequently esophageal dysmotility) in 5 of 6 patients who underwent formal testing. Patients in this series treated with immune-modulating therapy experienced significant improvement. A diagnosis of Sjögren syndrome should be aggressively pursued in patients with signs and symptoms suggestive of autonomic nervous system impairment. Although the spectrum of adrenergic failure is variable, ranging from orthostatic hypotension to an excessive postural tachycardia, most patients do have symptoms of more generalized autonomic failure. Patients who were treated with immune-modulating therapy did improve.

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

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

Postural Heart Rate Changes in Young Patients With Vasovagal Syncope.

Recurrent postural vasovagal syncope (VVS) is caused by transient cerebral hypoperfusion from episodic hypotension and bradycardia; diagnosis is made by medical history. VVS contrasts with postural tachycardia syndrome (POTS), defined by chronic daily symptoms of orthostatic intolerance with excessive upright tachycardia without hypotension. POTS has recently been conflated with VVS when excessive tachycardia is succeeded by hypotension during tilt testing. We hypothesize that excessive tachycardia preceding hypotension and bradycardia is part of the vasovagal response during tilt testing of patients with VVS. We prospectively performed head-up tilt (HUT) testing on patients with recurrent VVS (n = 47, 17.9 ± 1.1 y), who fainted at least 3 times within the last year, and control subjects (n = 15, 17.1 ± 1.0 y), from age and BMI-matched volunteers and measured blood pressure, heart rate (HR), cardiac output, total peripheral resistance, and end tidal carbon dioxide. Baseline parameters were the same in both groups. HR (supine versus 5 and 10 minutes HUT) significantly increased in control (65 ± 2.6 vs 83 ± 3.6 vs 85 ± 3.7, P < .001) and patients with VVS (69 ± 1.6 vs 103 ± 2.3 vs 109 ± 2.4, P < .001). HUT in controls maximally increased HR by 20.3 ± 2.9 beats per minute; the increase in patients with VVS of 39.8 ± 2.1 beats per minute was significantly greater (P < .001). An increase in HR of ≥40 beats per minute by 5 and 10 minutes or before faint with HUT, occurred in 26% and 44% of patients with VVS, respectively, but not in controls. Orthostasis in VVS is accompanied by large increases in HR that should not be construed as POTS.

Benign Joint Hypermobility Minimally Impacts Autonomic Abnormalities in Pediatric Subjects with Chronic Functional Pain Disorders

To determine if children with benign joint hypermobility (BJH) syndrome and chronic functional pain disorders have more autonomic dysfunction. Retrospective chart review study of pediatric patients seen in the pediatric neurogastroenterology and autonomic clinic who underwent autonomic testing and had either a Beighton score of ≥6 and met Brighton criteria for BJH (with BJH) or a score of ≤2 (no BJH). Twenty-one female subjects (10 without BJH) met inclusion criteria; 64% of BJH had diagnosis confirmed by genetics consultation. We evaluated for postural tachycardia syndrome, syncope, orthostatic intolerance, and orthostatic hypotension. None of these diagnoses, as well as baseline heart rate, peak heart rate in first 10 minutes of head up tilt (P = .35 and P = .61, respectively), and sudomotor index (suggestive of autonomic neuropathy) (P = .58), showed differences between the groups. Age of onset of symptoms was also similar (P = .61) (BJH vs without BJH: median [range]:15.6 years [12.9-17.5] vs 15.4 years [11.1-18.2]). There was no difference between groups in complaints of migraine, chronic nausea, chronic fatigue, lightheadedness, dizziness, fainting >3 times/lifetime, delayed onset of sleep, irritable bowel syndrome, dyspepsia, abdominal migraine, functional abdominal pain, constipation, or fibromyalgia. Children with chronic functional pain disorders and BJH have autonomic testing findings and comorbid features compared with a similar cohort of subjects without BJH, suggesting that BJH is not the driver of the autonomic and comorbid disorders.

Autonomic Testing in Women with Chronic Pelvic Pain

We determined whether abnormal autonomic nervous system innervation of the bladder underlies IC (interstitial cystitis)/BPS (bladder pain syndrome) differently than other chronic pelvic pain. In this institutional review board approved protocol 39 healthy controls and 134 subjects were enrolled, including 36 with IC/BPS, 14 with myofascial pelvic pain and 42 with IC/BPS plus myofascial pelvic pain. Three subjects were excluded from study. Autonomic nervous system evaluations included deep breathing, the Valsalva maneuver, and the tilt table and sudomotor tests. The latter evaluates autonomic neuropathy. A modified validated composite autonomic laboratory score was applied. Median age in the IC/BPS group was 47.5 years (range 21 to 78), greater than in healthy controls (34 years, range 20 to 75, p = 0.006), the myofascial pelvic pain group (33 years, range 22 to 56, p = 0.004) and the IC/BPS plus myofascial pelvic pain group (38 years, range 18 to 64, p = 0.03). Body mass index did not significantly differ but the myofascial pelvic pain and IC/BPS plus myofascial pelvic pain groups had a higher body mass index than healthy controls (p = 0.05 and 0.03, respectively). Cardiovascular and adrenergic indexes did not differ. The tilt table test showed more orthostatic intolerance in all chronic pelvic pain groups. Tilt table test diagnoses (orthostatic hypotension, postural tachycardia syndrome and reflex syncope) were rare. Baseline heart rate was higher in all chronic pelvic pain groups (p = 0.004). Compared to healthy controls all myofascial pelvic pain groups showed significantly more clear-cut autonomic neuropathy, defined as a sweat score of 3 or greater (vs IC/BPS plus myofascial pelvic pain p = 0.007 and vs myofascial pelvic pain p = 0.03). Some chronic pelvic pain types show autonomic neuropathy and some show vagal withdrawal. In all types orthostatic intolerance likely reflects central sensitization and perhaps catastrophizing. Some of these findings suggest novel therapeutic targets.

Abstract P633: Low Serum Vitamin D is Associated with Greater Impairment in Autonomic Function upon Head Up Tilt in Children with Orthostatic Intolerance

In previous work we identified a group of children (n = 48) between the ages of 10-18 years whose diagnostic workup for chronic nausea unexplained by conventional diagnostic tests revealed that 60% had underlying cardiovascular instability (n = 30) presenting as orthostatic intolerance (OI). The OI could be sub-classified based on head up tilt (HUT) testing into three groups: Postural Orthostatic Tachycardia Syndrome (POTS), orthostatic hypotension (OH) and syncope. Children with OI in all three groups had a greater reduction in autonomic control upon HUT manifested as greater loss of baroreflex sensitivity (BRS) and heart rate variability (HRV) and higher norepinephrine levels compared to those in the non OI group. Vitamin D deficiency is associated with impaired vascular responses to vasoconstrictors and alterations in autonomic control mechanisms in adults. In this study we sought to determine if vitamin D level is lower in these pediatric OI subjects and if it correlates with the hemodynamic responses to tilt. Serum 25(OH)D tended to be lower in OI vs non OI (18.6 ± 0.7 ng/ml, n = 25, vs 22.2 ± 2.4 ng/ml, n = 15; p = 0.16). Most importantly 25(OH)D showed a high positive correlation with supine measures of BRS (seq ALL, R = 0.51, p = 0.05), HRV (rMSSD, R = 0.44, p = 0.02) only in the OI group and there was a trend for a negative correlation with sympathovagal balance ( LF/HF ratio: R =-0.35, p = 0.08). Low 25(OH)D correlated with greater loss of both BRS (R = 0.51, p = 0.01) and HRV (R = 0.44, p = 0.05) upon HUT. These findings support the concept that low vitamin D may contribute to impaired responses to tilt in OI subjects. Further work is needed to evaluate if vitamin D supplementation will improve the vascular and hemodynamic responses to tilt and help improve the OI symptoms. Our goal is to provide a safer therapeutic alternative for the treatment of OI in children.

Extended Granger causality: a new tool to identify the structure of physiological networks

Granger causality (GC) is a very popular tool for assessing the presence of directional interactions between two time series of a multivariate data set. In its original formulation, GC does not account for zero-lag correlations possibly existing between the observed time series. In the present study we compare the GC with a novel measure, termed extended GC (eGC), able to capture instantaneous causal relationships. We present a two-step procedure for the practical estimation of eGC based on first detecting the existence of zero-lag correlations, and then assigning them to one of the two possible causal directions using pairwise measures of non-Gaussianity. The proposed method was validated in a simulation study, showing that the estimation procedure based on the extended representation overcomes the limits of the classic computation of GC, correctly detecting the presence and direction of zero-lag interactions and providing a meaningful causal interpretation based on the eGC. Then, GC and eGC were computed on the physiological variability series of heart period (HP), mean arterial pressure (AP) and cerebral blood flow velocity (FV) in ten subjects with postural related syncope (PRS), during different epochs of an head-up tilt test protocol. We found that both measures reflect the baroreflex impairment and the loss of cerebral autoregulation during pre-syncope. Furthermore, eGC analysis suggests that fast, within-beat effects between AP and FV variability contribute substantially to the mutual regulation of these physiological variables, and may play an important role in the impairment of cerebrovascular regulation associated with PRS.

Prothèse trachéobronchique dans le syndrome de Mounier-Kuhn : nouvelles perspectives

Mounier-Kuhn syndrome or tracheobronchomegaly is a rare congenital condition, the management of which is complex. We report the case of a patient who was treated with interventional endoscopy. We describe the case of a 74-year-old man with a diagnosis of tracheobronchomegaly who was admitted in 2003 with a background of deteriorating respiratory status and the occurrence of postural syncope. He initially received a tracheobronchial silicone Y prosthesis, extended with metal prostheses at the tracheal and bronchial level. This arrangement remained stable until 2011. He then began to develop episodes of asphyxia related to posterior dislocation of the tracheobronchial prosthesis, after breakage of the metallic mesh tracheal prosthesis. A new tracheobronchial prosthesis Y was then placed, custom-made from a 3D model of the airways. This was clinically and functionally effective. This case describes the management of a patient with Mounier-Kuhn syndrome by interventional bronchoscopy, with the adaptation of prosthetic materials, on an individual basis, to the anatomy of the patient's airway.

Conditional symbolic analysis detects nonlinear influences of respiration on cardiovascular control in humans.

We propose a symbolic analysis framework for the quantitative characterization of complex dynamical systems. It allows the description of the time course of a single variable, the assessment of joint interactions and an analysis triggered by a conditioning input. The framework was applied to spontaneous variability of heart period (HP), systolic arterial pressure (SAP) and integrated muscle sympathetic nerve activity (MSNA) with the aim of characterizing cardiovascular control and nonlinear influences of respiration at rest in supine position, during orthostatic challenge induced by 80° head-up tilt (TILT) and about 3 min before evoked pre-syncope signs (PRESY). The approach detected (i) the exaggerated sympathetic modulation and vagal withdrawal from HP variability and the increased presence of fast MSNA variability components during PRESY compared with TILT; (ii) the increase of the SAP-HP coordination occurring at slow temporal scales and a decrease of that occurring at faster time scales during PRESY compared with TILT; (iii) the reduction of the coordination between fast MSNA and SAP patterns during TILT and PRESY; (iv) the nonlinear influences of respiration leading to an increased likelihood to observe the abovementioned findings during expiration compared with inspiration one. The framework provided simple, quantitative indexes able to distinguish experimental conditions characterized by different states of the autonomic nervous system and to detect the early signs of a life threatening situation such as postural syncope.

Tu2006 Internet-Delivered Cognitive Behavior Therapy for Adolescents With Functional Gastrointestinal Disorders: A Pilot Study

the association with foregut symptoms. Methods: We conducted a retrospective review of the medical notes and electronic patient records for all children diagnosed with JHS (Beighton score >4/9) referred to the syncope service based at Hammersmith Hospital. The study period was June 2011 to October 2013. Cardiovascular autonomic function was evaluated using the tilt table test. Results: A total of 53 children were recruited with a median age range of 15.2 yrs (range 8.1yrs-18.7 yrs). The gender distribution was 28 females (53%) and 25 males (47%). All patients had autonomic nervous system-related symptoms including postural dizziness or syncope (53%), palpitations (40%), migraine (25%) and chest pain (19%). Of the 53 JHS patients with autonomic symptoms, 48 (91%) patients had GI-related symptoms. 45 (85%) of these patients had confirmed cardiovascular autonomic dysfunction on tilt testing. All these patients also complained of foregut symptoms, predominantly nausea and bloating. Summary: Foregut dysfunction was a co-morbid presentation in all JHS patients with cardiovascular dysautonomia. Conclusion: Children with JHS presenting with foregut symptoms are likely to have associated cardiovascular autonomic dysfunction. Recognition of these symptoms by paediatricians is important as formal evaluation and treatment of the dysautonomia may improve the quality of life for these patients. Further studies are required to evaluate the objective improvement of GI symptoms following treatment for dysautonomia.

Sympathetic Nervous System Moves Toward Center Stage in Cardiovascular Medicine

In 1664, the first anatomically correct depiction of the sympathetic nervous system came from Thomas Willis and his circle of London anatomists,1 included in The Anatomy of the Brain and Nerves , 1664 (Figure 1). This, the first work dedicated completely to the nervous system, also described the arterial loops at the base of the brain, which we now know as the Circle of Willis.1 Christopher Wren, an anatomist member of the group, was the principal illustrator1 before being asked by the City Fathers to turn his talents to town planning, architecture, and cathedral building after the 1666 Great Fire of London. Figure 1. An illustration of the human sympathetic nerves of the neck and thorax, from The Anatomy of the Brain and Sympathetic Nerves , published in 1664 by Thomas Willis and reproduced in Soul Made Flesh .1 Almost 2 centuries later, subsequent microscopic examination demonstrated that blood vessel walls were densely innervated, leading Stelling in 18402 to correctly conclude that these vasomotor fibers were in fact sympathetic nerves that were carried from the central nervous system to the blood vessels. In the mid-19th century, celebrated European physiologists, including Brown-Sequard, Waller, and Bernard,2 built on these observations, demonstrating vasoconstriction with electrical stimulation of the cut nerves and vasodilatation on nerve section, which indicated that the sympathetic fibers exerted a tonic, vasoconstrictor influence. The pressor nerves had gained recognition. Identification of the sympathetic neurotransmitter proved to be difficult. Claims for epinephrine3,4 and the hypothetical sympathins I and E confused the picture. Ulf von Euler compared bioassay responses of epinephrine, norepinephrine, and dihydroxy norephedrine with those of cattle splenic nerve extract, by testing blood pressure (BP) responses in the anesthetized cat and contractile responses in the isolated pregnant rabbit uterus, to definitively demonstrate the …

Tilt angles and positive response of head-up tilt test in children with orthostatic intolerance

This study aimed at examining three tilt angle-based positive responses and the time to positive response in a head-up tilt test for children with orthostatic intolerance, and the psychological fear experienced at the three angles during head-up tilt test. A total of 174 children, including 76 boys and 98 girls, aged from 4 to 18 years old (mean 11.3±2.8 years old), with unexplained syncope, were randomly divided into three groups, to undergo head-up tilt test at the angles of 60°, 70° and 80°, respectively. The diagnostic rates and times were analysed, and Wong-Baker face pain rating scale was used to access the children's psychological fear. There were no significant differences in diagnostic rates of postural orthostatic tachycardia syndrome and vasovagal syncope at different tilt angles during the head-up tilt test (p>0.05). There was a significant difference, however, in the psychological fear at different tilt angles utilising the Kruskal-Wallis test (χ2=36.398, p<0.01). It was mildest at tilt angle 60° utilising the Kolmogorov-Smirnov test (p<0.01). A positive rank correlation was found between the psychological fear and the degree of tilt angle (r(s)=0.445, p<0.01). Positive response appearance time was 15.1±14.0 minutes at 60° for vasovagal syncope children. There was no significant difference in the time to positive response, at different tilt angles during the head-up tilt test for vasovagal syncope or for postural orthostatic tachycardia syndrome. Hence, it is suggested that a tilt angle of 60° and head-up tilt test time of 45 minutes should be suitable for children with vasovagal syncope.

Disruption of phase synchronization between blood pressure and muscle sympathetic nerve activity in postural vasovagal syncope

Withdrawal of muscle sympathetic nerve activity (MSNA) may not be necessary for the precipitous fall of peripheral arterial resistance and arterial pressure (AP) during vasovagal syncope (VVS). We tested the hypothesis that the MSNA-AP baroreflex entrainment is disrupted before VVS regardless of MSNA withdrawal using the phase synchronization between blood pressure and MSNA during head-up tilt (HUT) to measure reflex coupling. We studied eight VVS subjects and eight healthy control subjects. Heart rate, AP, and MSNA were measured during supine baseline and at early, mid, late, and syncope stages of HUT. Phase synchronization indexes, measuring time-dependent differences between MSNA and AP phases, were computed. Directionality indexes, indicating the influence of AP on MSNA (neural arc) and MSNA on AP (peripheral arc), were computed. Heart rate was greater in VVS compared with control subjects during early, mid, and late stages of HUT and significantly declined at syncope (P = 0.04). AP significantly decreased during mid, late, and syncope stages of tilt in VVS subjects only (P = 0.001). MSNA was not significantly different between groups during HUT (P = 0.700). However, the phase synchronization index significantly decreased during mid and late stages in VVS subjects but not in control subjects (P < .001). In addition, the neural arc was significantly affected more than the peripheral arc before syncope. In conclusion, VVS is accompanied by a loss of the synchronous AP-MSNA relationship with or without a loss in MSNA at faint. This provides insight into the mechanisms behind the loss of vasoconstriction and drop in AP independent of MSNA at the time of vasovagal faint.

Common Syndromes of Orthostatic Intolerance

The autonomic nervous system, adequate blood volume, and intact skeletal and respiratory muscle pumps are essential components for rapid cardiovascular adjustments to upright posture (orthostasis). Patients lacking sufficient blood volume or having defective sympathetic adrenergic vasoconstriction develop orthostatic hypotension (OH), prohibiting effective upright activities. OH is one form of orthostatic intolerance (OI) defined by signs, such as hypotension, and symptoms, such as lightheadedness, that occur when upright and are relieved by recumbence. Mild OI is commonly experienced during intercurrent illnesses and when standing up rapidly. The latter is denoted "initial OH" and represents a normal cardiovascular adjustment to the blood volume shifts during standing. Some people experience episodic acute OI, such as postural vasovagal syncope (fainting), or chronic OI, such as postural tachycardia syndrome, which can significantly reduce quality of life. The lifetime incidence of ≥1 fainting episodes is ∼40%. For the most part, these episodes are benign and self-limited, although frequent syncope episodes can be debilitating, and injury may occur from sudden falls. In this article, mechanisms for OI having components of adrenergic hypofunction, adrenergic hyperfunction, hyperpnea, and regional blood volume redistribution are discussed. Therapeutic strategies to cope with OI are proposed.

The dark knight of syncope: the urologist!

I would like to congratulate Juul-Möller et al. 1 on their contributions to the SYNCOPE Symposium, reported in your Journal. The above authors stress the different aspects of this variegated syndrome and the various approaches according to specific causes. In particular, they state that the main aetiology of syncope consists of neurocardiogenic reflexes, autonomic disorders (such as orthostatic hypotension), primary cardiovascular diseases or a combination of these, identifying within the healthcare system various specialists not only involved in the management process, but also in some cases directly responsible for the onset of symptoms: from general practitioners to cardiologists to internists, there are several physicians guilty of having prescribed drugs causing syncope, a time-limited circulatory disorder resulting in loss of consciousness and spontaneous recovery. Nevertheless, none of the papers focusing on this syndrome mention the fact that a specialist may be guilty and responsible for several ‘crimes’ through drug prescriptions – a ‘dark knight’ whose responsibilities are often overshadowed: the Urologist! Evaluating male patients with common symptoms of the lower urinary tract (e.g. dysuria, nocturia, urinary frequency, etc.), urologists may diagnose prostate enlargement due to benign hypertrophy (BPH). For patients with storage and voiding symptoms, the most common first-line medical treatment is alpha-adrenoceptor antagonists: starting from the evidence of the high concentration of alpha-receptors in the prostate gland, prostatic urethra and bladder neck, alpha-antagonists are used to cause significant relaxation of prostate and bladder smooth muscle, with consequent improvement of urinary stream hesitancy and attenuation of frequency. Because of the presence of alpha-adrenergic receptors, mainly in smooth muscle and also in the walls of blood vessels, the action of alpha-blockers may have a hypotensive effect, due to the generalized relaxation of blood vessels. Although the latest alpha-adrenoceptor antagonists used to treat BPH are super-selective and directed only against alpha-1-adrenoceptors, located mainly at the level of the bladder neck/prostate and not in blood vessel walls, many patients treated with drugs such as Tamsulosin, Terazosin, Alfuzosin or Doxazosin undergo adverse events related to alpha-blockers, such as dizziness, headache, asthenia, somnolence, postural hypotension and … syncope! 2. As reported in one of the largest studies on the treatment of BPH with alpha-blockers (3047 patients), the most common adverse events that occurred more frequently in men treated with Doxazosin than in the placebo group (P < 0.005) were dizziness, postural hypotension and asthenia, with percentages of up to 5%; because of these symptoms, about 25% of patients discontinued the treatment 3. In other studies on other alpha-blockers, the similar incidence of these side effects has been reported, highlighting the severe impact of postural hypotension on patient safety 4 and on quality of life 5. As the prevalence rate of lower urinary tract symptoms has been reported to increase with age, from 2.7% among 45–49-year-old men to 24% at age 80, the incidence of postural hypotension and syncope of 2–5% (according to various reports in the literature 6) due to alpha-blockers for BPH treatment must be counted among the most frequent causes. No conflict of interest to declare. I declare that all material in this assignment is my own work and does not involve plagiarism. I have no conflicts of interest to disclose.

Loss of muscle sympathetic nerve activity and blood pressure phase synchronization in postural vasovagal syncope

Withdrawal of muscle sympathetic nerve activity (MSNA) may not be necessary for the precipitous fall of peripheral arterial resistance and blood pressure (BP) during vasovagal syncope (VVS). We tested the hypothesis that the MSNA‐BP baroreflex entrainment is disrupted prior to VVS regardless if MSNA is withdrawn. We measured phase synchronization during 70° head‐up tilt (HUT) in 14 individuals including 8 VVS and 6 healthy control (C). Heart rate (HR), BP and MSNA were measured during supine baseline and at early, mid, and late stages of HUT. The phase synchronization index (PhSI), the rate of change of MSNA phase with BP phase (neural arc) and that of BP with MSNA (peripheral arc) were computed. During HUT, HR was greater in VVS compared to C (time × group; p=.04). BP did not change during the early stage, but significantly decreased during mid and late stages in VVS only (time × group; p=.001). MSNA was not different between groups during HUT (time × group; p=.700). However, PhSI significantly decreased during mid and late stages in VVS but not C (time × group; p&lt;.001) indicating breakdown of MSNA‐BP phase locking, and therefore interaction, in VVS. In addition, the neural arc was significantly affected more than the peripheral arc prior to syncope. This provides a mechanism for the loss of vasoconstriction and drop in BP independent of late sympathetic nerve activity at the time of vasovagal faint. Supported by NIH (HL‐074873).

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

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

Update on the theory and management of orthostatic intolerance and related syndromes in adolescents and children

Orthostasis means standing upright. One speaks of orthostatic intolerance (OI) when signs, such as hypotension, and symptoms, such as lightheadedness, occur when upright and are relieved by recumbence. The experience of transient mild OI is part of daily life. ‘Initial orthostatic hypotension’ on rapid standing is a normal form of OI. However, other people experience OI that seriously interferes with quality of life. These include episodic acute OI, in the form of postural vasovagal syncope, and chronic OI, in the form of postural tachycardia syndrome. Less common is neurogenic orthostatic hypotension, which is an aspect of autonomic failure. Normal orthostatic physiology and potential mechanisms for OI are discussed, including forms of sympathetic hypofunction, forms of sympathetic hyperfunction and OI that results from regional blood volume redistribution. General and specific treatment options are proposed.