Head-up Tilt Test Research Articles

Evaluation of autonomic nervous system functions by using tilt table test and heart rate variability in epileptic children

Objective: The value of head-up tilt test (HUTT) for differential diagnosis of epilepsy and the autonomic nervous system functions in
 epileptic children using heart rate variability (HRV) are studied.
 Patients and Methods: The study group consisted of 16 children with idiopatic/criptogenic epilepsy and 12 controls. Heart rate, PR
 interval, corrected QT (QTc) interval, QT and QTc dispersion were calculated using 12-lead electrocardiogram (ECG), HRV analysis
 was performed using the Holter recordings obtained both during HUTT and throughout the day. Time domain parameters, standard
 deviation of all RR intervals (SDNN), the standard deviation of mean NN intervals in five-minutes recording (SDANN), mean standard
 deviation of NN intervals in five-minutes recordings (SDNNi), root mean square of successive differences (RMSSD), count divided
 by the total number of all NN intervals (pNN50) and frequency domain parameters low frequency (LF), high frequency (HF), lowfrequency/
 high-frequency ratio (LF/HF) were calculated in both and compared between the two groups.
 Results: Head-up tilt test was positive in 4 epileptic children (25%), none of controls were positive. The heart rate of the patients were
 higher than the controls (p=0.015). LF/HF ratio in 24-hour Holter recordings, were significantly lower (1.13±0.6, 1.83±0.7 respectively,
 p=0.002); the SDANN during HUTT (28.7±20.2, 18.2 ± 19.9 respectively, p=0.024) were significantly higher in the patients than the
 controls.
 Conclusion: Head-up tilt test positivity is frequent in epileptic children, and cannot be used in differential diagnosis. HRV calculated
 both from 24 hour Holter recordings and Holter recordings under orthostatic stress were impaired in favour of parasympathetic
 system in epileptic children.

Post-acute sequelae of SARS-CoV-2 syndrome presenting as postural orthostatic tachycardia syndrome.

The novel SARS-CoV-2 emerged in 2019, and the global COVID-19 pandemic continues into 2022. It has been known that a subset of patients develops chronic, debilitating symptoms after otherwise complete recovery from acute infection of COVID-19. Multiple terms have been used to describe this constellation of symptoms, including long COVID, long-haul COVID, and postacute sequelae of SARS-CoV-2 syndrome (PASC). PASC is broadly defined as a wide range of new, returning, or ongoing symptoms at least four weeks after infection. Those patients are often seen in emergency departments after acute COVID-19 infection, but their symptoms are not adequately managed because the underlying pathophysiology of PASC is not well understood. Among patients with PASC, postural orthostatic tachycardic syndrome (POTS) has been increasingly recognized. POTS is one of the most common forms of autonomic dysfunction and defined by a sustained orthostatic tachycardia during active standing or head-up tilt test in the absence of orthostatic hypotension or other cardiopulmonary diseases. Because POTS is a treatable condition, it is important to recognize POTS among PASC patients. Herein, we reviewed the current literature on POTS and dysautonomia in PASC in order to better understand the overlap and distinction between these pathologies.

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

IntroductionAutonomic 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 methodIn 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.ResultsThe 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.ConclusionIn 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.

The clinical presentation of syncope influences the head-up tilt test responses

Little is still known about the positivity rate of nitroglycerin (NTG) potentiated head-up tilt test (HUTT) according to the history-based clinical features of syncope. The study aimed to compare the HUTT positivity rate and type of responses in patients with classical and non-classical vasovagal syncope (VVS). We retrospectively evaluated all consecutive patients who underwent NTG-potentiated HUTT for VVS. The study population was dichotomized into classical and non-classical VVS. A total of 1285 VVS patients (45± 19.1 years; 49.6% male) were enrolled: 627 (48.8%) had a history of classical VVS and 658 (51.2%) of non-classical VVS. HUTT was positive in 866 (67.4%) patients. The positivity rate was significantly higher in patients with classical compared to those with non-classical VVS (81.5% vs 54%; P< 0.0001). Cardioinhibitory response showed similar total positivity rate (27.6% vs 31%; P= 0.17), but higher relative prevalence among positive tests (57.7% vs 33.9%, P< 0.0001) in patients with non-classical VVS. At multivariable analysis, classical reflex syncope, male sex, history of traumatic syncope and use of diuretics were independent predictors of HUTT positivity. The clinical presentation of syncope influences the overall HUTT positivity rate and the type of responses. Cardioinhibitory response and traumatic syncope are more likely in patients with non-classical VVS.

Cardiovascular reflex tests detect autonomic dysfunction in symptomatic and pre-symptomatic subjects with hereditary transthyretin amyloidosis.

Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages. All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison. Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001). Autonomic dysfunctions are frequent in subjectswith ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.

Cardiovascular reactivity to stress in long-term yoga practitioners.

Bhramari Pranayama yogic breathing is a very simple exercise of voluntary breathing which mitigates stress reactivity through autonomic modulation of heart rate. To study the effects of long-term practice of the yoga breathing exercise on cardiovascular reactivity to head-up tilt (HUT) test. All the participants were subjected to a 10-item yoga questionnaire. Based on Likert scale scoring, 32 subjects (group I) were selected as long-term yogic breathing practitioners, and autonomic function tests using heart rate variability (HRV) and a provocative stress test and HUT test were conducted. Cardiovascular parameters obtained were compared with controls who had never been engaged in any form of yoga (group II). A highly significant decrease in values of both high (HF) and low frequency (LF) variables was observed in group II as compared to group I. However, a highly significant rise in LF/HF has been observed in group I compared to group I (P = 0.004), further indicating a greater withdrawal of vagal tone during the HUT test and also during recovery (P = 0.001). The results and discussion of HRV analysis during provocative tests concluded that autonomic imbalance was present in the subjects who were not exposed to any form of yoga. Thus, it is advisable to practice yoga in any form regularly to mitigate the early onset of autonomic dysfunction.

Vagal cross-sectional area correlates with parasympathetic dysfunction in Parkinson's disease.

The aim of this prospective study was to investigate autonomic function in Parkinson's disease with a multidimensional approach including clinical evaluation tools, head-up tilt test and morphological studies of the vagus nerve. Head-up tilt test parameters including high frequency power of the heart frequency interval, the ratio of low frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval) to the high frequency and low frequency power of systolic blood pressure were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively, in 80 patients with Parkinson's disease. We examined the cross-sectional area of the vagus nerves bilaterally using nerve ultrasound and compared mean values with a control group of healthy subjects (n = 40) as well as patients with chronic inflammatory demyelinating polyneuropathy (n = 76). The cross-sectional area of right/left vagus nerve of Parkinson's patients was significantly lower compared to the right/left vagus nerve of the control group and of chronic demyelinating polyneuropathy patients. Furthermore, the cross-sectional area of the right vagus nerve was significantly larger from the one of the left vagus nerve for all groups. Based on tilt test, 43 patients (disease duration 7 ± 5, age at evaluation 71 ± 9, Hoehn and Yahr score 2.8 ± 8) were diagnosed with autonomic dysfunction (orthostatic hypertension n = 11, chronotropic incompetence n = 31, postural orthostatic tachycardia syndrome n = 1). Patients with orthostatic hypotension showed significantly higher Unified Parkinson's Disease Rating Scale-III values than those with chronotropic incompetence. The cross-sectional area of the vagus nerve correlated inversely with heart rate in rest and supine position and positively with tilt test parameters representing parasympathetic modulation through vagal activity [high frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval)] at rest. We demonstrate for the first time that morphological characteristics of the vagus nerve correlate with parameters of parasympathetic function from the spectral analysis of cardiovascular parameters in tilt test for Parkinson's patients. This correlation reveals the impact of the atrophy of vagal atrophy for autonomic function in Parkinson's disease. Nerve ultrasound of the vagus nerve could potentially be used as an adjunct to tilt table examination to diagnose autonomic dysfunction.

1011 HETEROGENEOUS ARRHYTHMIC PHENOTYPE IN A CASE OF LEFT VENTRICULAR NON COMPACTION CARDIOMYOPATHY

Abstract A young 47 years old female patient was hospitalized in our department for recurrent traumatic syncopal episodes in order to undergo Head Up Tilt Test and Electrophysiology Study (EPS). Her ECG was normal and also transthoracic echocardiography didn't show pathological findings. 24 hour Holter ECG recording showed a short run of polymorphic ventricular tachycardia. Regarding familiar history her mother had died at a young age of sudden death. Head-up tilt test resulted negative for induced-syncope. During hospitalization the patient complained onset of malaise rapidly exiting in syncope: telemetry showed two pauses of 3.8 and 5.1 sec respectively, due to paroxysmal III degree atrio-ventricular block. The day after, the patient underwent electrophysiological study. During programmed ventricular stimulation from RV apex with train and V extrastimolous S1 300 S2 220 induction of syncopal ventricular fibrillation was observed, promptly treated with external DC shock. Cardiac MRI was performed showing diagnostic signs of Left Ventricular non-Compaction Cardiomyopathy. Considering the history of traumatic syncope the patient underwent dual chamber ICD implantation and was discharged. No clinical events in a 6 month follow-up. Genetical analysis was performed and we are waiting for the results. The term left ventricular non-compaction (LVNC) identifies a cardiomyopathy, characterized by intrauterine arrest of the compaction process of the ventricular myocardium during the end of the fourth week, thus leading to the development of prominent trabeculae of the left ventricle, deep intertrabecular recesses and a ventricular wall divider into two different layers of myocardium, the first compact, the other not. This nosological entity is difficult to classify (the European Society of Cardiology considers it as not classifiable among other cardiomyopathies, unlike the American Heart Association) mostly from the point of view of clinical implications, often unpredictable. In fact, we may have completely asymptomatic forms, which, according to some authors, should be considered as normal and completely benign variants, and various manifestations, in which the lack of compaction represents a morphological trait shared by phenotypically distinct forms of cardiomyopathy, such as hypertrophic, dilated and restrictive. LVNC carries an increased risk of ventricular dysfunction resulting in chronic heart failure, thromboembolic events and especially arrhythmic, often ventricular and life-threatening manifestations. A large spectrum of arrhythmias has been observed in patients with non-compact ventricles: in particular, supraventricular and ventricular tachycardias, Wolff-Parkinson-White (WPW) syndrome, but also bradyarrhythmias, which include sinus bradycardia, Sick Sinus Syndrome and various degrees of atrioventricular block, up to complete block. Ventricular tachycardias, including those that progress to ventricular fibrillation, occur in 38–47% of adult patients with LVNC, hence sudden death is often the cause of clinical presentation. Seen the features of the pathology, early diagnosis and family clinical evaluation are necessary aspects in patient management.

Changes in Dynamic Stability of Cardiovascular Time Series by Local Largest Lyapunov Exponent in the Time-Frequency Domain in Vasovagal Syncope

Orthostatic stress via a head-up tilt test (HUTT) has been clinically used to rule out vasovagal syncope (VVS), which is generated by an inappropriate autonomic nervous system (ANS) regulation. VVS has been evaluated mainly by hemodynamic variables and linear analysis of heart rate variability. In this study, the estimation of the local largest Lyapunov exponent (LLE[Formula: see text] was used to assess the predictability of the beat-to-beat interval (BBI), systolic (SBP), and diastolic blood pressure (DBP) times series to analyze in a nonlinear and time-varying fashion the impact of HUTT on ANS regulation in young females, healthy and patients with VVS. The estimation of LLEL of the time series was achieved in both the original domain (full-band) and narrow-band signals by the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN). Results pointed out that during the orthostatic phase (OPH), the VVS patients showed: (1) significantly higher predictability (less complexity) of the BBI time series, i.e., significant altered cardiac vagal modulation, (2) less predictability of SBP variability suggesting altered sympathetic modulation to the vasculature, and (3) LLEL in conjunction with CEEMDAN evidenced an impairment of cardiovascular autonomic control.

Could Orthostatic Stress Responses Predict Acute Mountain Sickness Susceptibility Prior to High Altitude Travel? A Pilot Study.

Bellovary, Bryanne N., Andrew D. Wells, Zachary J. Fennel, Jeremy B. Ducharme, Jonathan M. Houck, Trevor J. Mayschak, Ann L. Gibson, Scott N. Drum, and Christine M. Mermier. Could orthostatic stress responses predict acute mountain sickness susceptibility before high altitude travel? A pilot study. High Alt Med Biol. 24:19-26, 2023. Purpose: This study assessed head-up tilt (HUT) responses in relation to acute mountain sickness (AMS)-susceptibility during hypoxic exposure. Materials and Methods: Fifteen participants completed three lab visits: (1) protocol familiarization and cycle maximal oxygen consumption (VO2max) test; (2) HUT test consisting of supine rest for 20 minutes followed by 70° tilting for ≤40 minutes; and (3) 6 hours of hypobaric hypoxic exposure (4,572 m) where participants performed two 30-minute cycling bouts separated by 1 hour at a 50% VO2max workload within the first 3 hours and rested when not exercising. During HUT, systolic blood pressure (SBP), diastolic blood pressure, heart rate (HR), and variability (blood pressure variability [BPV] and HR variability [HRV]) were measured continuously. The AMS scores were determined after 6 hours of exposure. Correlations determined relationships between HUT cardiovascular responses and AMS scores. Repeated-measures analysis of variance (ANOVA) assessed differences between those with and without AMS symptoms during HUT. Results: Higher AMS scores correlated with greater change in SBP variability (r = 0.52, p = 0.048) and blunted changes in HRV (root mean square of successive differences between normal heartbeats r = 0.81, p = 0.001, percentage of adjacent normal sinus intervals that differ by more than 50 milliseconds [pNN50] r = 0.87, p < 0.001) during HUT. A pNN50 interaction (p = 0.02) suggested elevated cardiac sympathetic activity at baseline and a blunted increase in cardiac sympathetic influence throughout HUT in those with AMS (pNN50 baseline: AMS = 26.2% ± 15.3%, no AMS = 51.0% ± 13.5%; first 3 minutes into HUT: AMS = 17.2% ± 19.1%, no AMS = 17.1% ± 10.9%; end of HUT: AMS = 6.2% ± 9.1%, no AMS 11.0% ± 10.0%). Conclusions: The results suggest autonomic responses via HUT differ in AMS-susceptible individuals. Changes in HRV and BPV during HUT may be a promising predictive measurement for AMS-susceptibility, but further research is needed for confirmation.

L’hypotension orthostatique : mise au point sur une pathologie fréquente parfois méconnue

Orthostatic hypotension is a frequent pathology especially in older adults and inhospital patients. Prevalence is increasing with age, and is about 30% of patients older than 65 years. Orthostatic hypotension is defined as a fall in blood pressure of at least 20 mmHg systolic or 10 mmHg diastolic when standing or during head-up tilt testing. Orthostatic hypotension is significantly associated with several adverse outcomes such as falls, neurodegenerative disease, cardiovascular outcomes (such as stroke or heart failure), and mortality. Different mechanisms may be involved in pathogeny especially medications. Etiological work up will evaluate cardiac response when standing. Neurogenic orthostatic hypotension is characterized by a cardiovascular autonomic failure due to central or peripheral nervous system disorders. Non-neurogenic orthostatic hypotension is primarily caused by hypovolemia. Therapeutic management is based on non-pharmacological therapies, especially legs venous compression, even if evidence for effectiveness is lacking. Pharmacological therapies may be necessary for neurogenic orthostatic hypotension.

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.

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.

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 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.

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.

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.