Differences in heart rate responses to upright posture are associated with variations in the high-frequency power of heart rate variability.

High resting heart rate is a cardiovascular risk factor, but limited data exist on the underlying hemodynamics and reproducibility of supine-to-upright increase in heart rate. We recorded noninvasive hemodynamics in 574 volunteers [age, 44.9 yr; body mass index (BMI), 26.4 kg/m2; 49% male] during passive head-up tilt (HUT) using whole body impedance cardiography and radial artery tonometry. Heart rate regulation was evaluated using heart rate variability (HRV) analyses. Comparisons were made between quartiles of supine-to-upright heart rate changes, in which heart rate at rest ranged 62.6-64.8 beats/min (P = 0.285). The average upright increases in heart rate in the quartiles 1-4 were 4.7, 9.9, 13.5, and 21.0 beats/min, respectively (P < 0.0001). No differences were observed in the low-frequency power of HRV, whether in the supine or upright position, or in the high-frequency power of HRV in the supine position. Upright high-frequency power of HRV was highest in quartile 1 with lowest upright heart rate and lowest in quartile 4 with highest upright heart rate. Mean systolic blood pressure before and during HUT (126 vs. 108 mmHg) and the increase in systemic vascular resistance during HUT (650 vs. 173 dyn·s/cm5/m2) were highest in quartile 1 and lowest in quartile 4. The increases in heart rate during HUT on three separate occasions several weeks apart were highly reproducible (r = 0.682) among 215 participants. To conclude, supine-to-upright increase in heart rate is a reproducible phenotype with underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. As heart rate at rest influences prognosis, future research should elucidate the prognostic significance of these phenotypic differences.NEW & NOTEWORTHY Subjects with similar supine heart rates are characterized by variable increases in heart rate during upright posture. Individual heart rate increases in response to upright posture are highly reproducible as hemodynamic phenotypes and present underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. These results indicate that resting heart rate obtained in the supine position alone is not an optimal means of classifying people into groups with differences in cardiovascular function.

Adult vasovagal syncope with abdominal pain diagnosed by head-up tilt combined with transcranial doppler: a preliminary study.

BACKGROUND: Syncope is a common condition that increases the risk of injury and reduces the quality of life. Abdominal pain as a precursor to vasovagal syncope (VVS) in adults is rarely reported and is often misdiagnosed.​. METHODS: We present three adult patients with VVS and presyncopal abdominal pain diagnosed by synchronous multimodal detection (transcranial Doppler [TCD] with head-up tilt [HUT]) and discuss the relevant literature. RESULTS: Case 1: A 52-year-old man presented with recurrent decreased consciousness preceded by six months of abdominal pain. Physical examinations were unremarkable. Dynamic electrocardiography, echocardiography, head and neck computed tomography angiography, magnetic resonance imaging (MRI), and video electroencephalogram showed no abnormalities. Case 2: A 57-year-old woman presented with recurrent syncope for 30 + years, accompanied by abdominal pain. Physical examination, electroencephalography, and MRI showed no abnormalities. Echocardiography showed large right-to-left shunts. Case 3: A 30-year-old woman presented with recurrent syncope for 10 + years, with abdominal pain as a precursor. Physical examination, laboratory analysis, head computed tomography, electrocardiography, and echocardiography showed no abnormalities. Syncope secondary to abdominal pain was reproduced during HUT. Further, HUT revealed vasovagal syncope, and synchronous TCD showed decreased cerebral blood flow; the final diagnosis was VVS in all cases. CONCLUSIONS: Abdominal pain may be a precursor of VVS in adults, and our findings enrich the clinical phenotypic spectrum of VVS. Prompt recognition of syncopal precursors is important to prevent incidents and assist in treatment decision-making. Abdominal pain in VVS may be a sign of sympathetic overdrive. Synchronous multimodal detection can help in diagnosing VVS and understanding hemodynamic mechanisms.

The triggers of situational syncope do not influence the head-up tilt test response and prognosis.

AIMS: The study evaluated the positivity rate, haemodynamic responses, and prognosis in terms of syncopal recurrence among patients with situational syncope (SS) stratified according to the underlying situational triggers. METHODS AND RESULTS: We retrospectively evaluated all consecutive patients with SS who underwent nitroglycerine (NTG)-potentiated head-up tilt test (HUTT) at Syncope Unit of the University of Campania 'Luigi Vanvitelli'-Monaldi Hospital from 1 March 2017 to 1 May 2023. All patients were followed for at least one year. The study population was divided according to the underlying triggers (micturition, swallow, defaecation, cough/sneeze, post-exercise). Two hundred thirty-six SS patients (mean age 50 ± 19.3 years; male 63.1%) were enrolled; among them, the situational trigger was micturition in 109 patients (46.2%); swallow in 32 (13.6%) patients; defaecation in 35 (14.8%) patients; post-exercise in 41 (17.4%) patients; and cough/sneeze in 17 (7.2%) patients. There were no significant differences in baseline clinical characteristics and HUTT responses between different situational triggers. The Kaplan-Meier analysis did not show a statistically different rate of syncope recurrence across patients stratified by baseline situational triggers (log-rank P = 0.21). CONCLUSION: Situational syncope appears to be a homogenous syndrome, and different triggers do not impact the HUTT response or syncope recurrence at 1 year.

Classification of vasovagal syncope from physiological signals on tilt table testing.

BACKGROUND: The diagnostic test for vasovagal syncope (VVS), the most common cause of syncope is head-up tilt test (HUTT) assessment. During the test, subjects experienced clinical symptoms such as nausea, sweating, pallor, the feeling of palpitations, being on the verge of passing out, and fainting. The study's goal is to develop an algorithm to classify VVS patients based on physiological signals blood pressure (BP) and electrocardiography (ECG) obtained from the HUTT. METHODS: After 10 min of supine rest, the subject was tilted at a 70-degree angle on a tilt table for approximately a total of 35 min. 400 µg of glyceryl trinitrate (GTN) was administered sublingually after the first 20 min and monitoring continued for another 15 min. Mean imputation and K-nearest neighbors (KNN) imputation approaches to handle missing values. Next, feature selection techniques were implemented, including genetic algorithm, recursive feature elimination, and feature importance, to determine the crucial features. The Mann-Whitney U test was then performed to determine the statistical difference between two groups. Patients with VVS are categorized via machine learning models including Support Vector Machine (SVM), Gaussian Naïve Bayes (GNB), Multinomial Naïve Bayes (MNB), KNN, Logistic Regression (LR), and Random Forest (RF). The developed model is interpreted using an explainable artificial intelligence (XAI) model known as partial dependence plot. RESULTS: A total of 137 subjects aged between 9 and 93 years were recruited for this study, 54 experienced clinical symptoms were considered positive tests, while the remaining 83 tested negative. Optimal results were obtained by combining the KNN imputation technique and three tilting features with SVM with 90.5% accuracy, 87.0% sensitivity, 92.7% specificity, 88.6% precision, 87.8% F1 score, and 95.4% ROC (receiver operating characteristics) AUC (area under curve). CONCLUSIONS: The proposed algorithm effectively classifies VVS patients with over 90% accuracy. However, the study was confined to a small sample size. More clinical datasets are required to ensure that our approach is generalizable.

Relationship between hemodynamic type and syncopal symptoms in pediatric vasovagal syncope.

Vasovagal syncope (VVS) is a clinically common neurally mediated syncope. The relationship between different hemodynamic types of VVS and clinical syncopal symptoms has not been reported. The purpose of this research is to explore relationship between hemodynamic types and syncopal symptoms in pediatric VVS. Two thousand five hundred thirteen patients diagnosed with VVS at the age of 3-18 years, average age was 11.76 ± 2.83 years, including 1124 males and 1389 females, due to unexplained syncope and pre-syncope from single-center of January 2001 to December 2021 were retrospectively analyzed. Subjects were divided into two groups according to the presence or absence of syncopal symptoms: syncope group (1262 cases) and pre-syncope group (1251 cases). (1) Baseline characteristics: age, height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) increased in the syncope group compared with the pre-syncope group; the composition ratio of females was more than that of males in the syncope group; and the composition ratio of VVS-cardioinhibited (VVS-CI) and VVS-mixed (VVS-M) was more in the syncope group than that of the pre-syncope group (all P < 0.05). (2) Univariate analysis: age, height, weight, SBP, DBP, female, VVS-CI, and VVS-M were potential risk factors for the presence of syncopal symptoms (all P < 0.05). (3) Multivariate analysis: VVS-CI and VVS-M were independent risk factors for the presence of syncopal symptoms, with an increased probability of 203% and 175%, respectively, compared to VVS-vasoinhibited (VVS-VI) (all P < 0.01). CONCLUSION: The hemodynamic type of pediatric VVS is closely related to the syncopal symptoms. WHAT IS KNOWN: • There are varying probabilities of syncopal episodes in different hemodynamic types of VVS, and there is a lack of research to assess the comparative risk of syncope in children with different hemodynamic types of VVS. WHAT IS NEW: • The probability in presence of syncopal symptoms varies greatly between different hemodynamic types of VVS. • VVS-CI and VVS-M had a 203% and 175% increased risk in presence of syncopal symptoms compared with VVS-VI, respectively.

Diagnosis and treatment of recurrent syncope in a middle-aged women.

A 50-year-old female patient, presented with repeated syncope for more than 2 years. Prior assessments were conducted at different hospitals, but no definite abnormalities were found. The patient's fear and anxiety about possible future attacks were escalating. Through a Head-up tilt test, the cause was finally identified as vasovagal syncope. Following a 5-min administration of nitroglycerin, the patient reported palpitations, nausea, and deep, rapid breathing. The electrocardiogram initially showed a first-degree atrioventricular block, progressing swiftly to a second-degree type I atrioventricular block-high atrioventricular block. Immediate intervention was undertaken, but blood pressure was not instantly ascertainable, coinciding with an abrupt loss of consciousness. Subsequent electrocardiographic findings included paroxysmal third-degree atrioventricular block, sinus arrest, and complete cardiac arrest, prompting the initiation of external cardiac compressions. The longest recorded ventricular arrest approximated 15 s, with sinus rhythm resuming post 10 s of cardiac compressions and the patient regaining consciousness. The patient underwent vagal ablation and no longer experienced syncope.

Short-duration head-up tilt test potentiated with sublingual nitroglycerin in suspected vasovagal syncope: the fast Italian protocol.

BACKGROUND: The traditional nitroglycerin (NTG) head-up tilt test (HUTT) is time-consuming and the test duration is a barrier to widespread utilization in clinical practice. It was hypothesized that a short-duration protocol is not inferior to the traditional protocol regarding the positivity rate and has a similar distribution of hemodynamic response. METHODS AND RESULTS: Patients undergoing HUTT were randomized 1:1 to a 10 min passive phase plus a 10 min 0.3 mg NTG if the passive phase was negative (Fast) or to a 20 min passive phase plus a 15 min 0.3 mg NTG if the passive phase was negative (Traditional). A sample size of 277 patients for each group achieved 80% power to detect an expected difference of 0% with a non-inferiority margin of -10% using a one-sided t-test and assuming a significant level alpha of 0.025. A total of 554 consecutive patients (mean age 46.6 ± 19.3 years, 47.6% males) undergoing HUTT for suspected vasovagal syncope were randomly assigned to the Fast (n = 277) or Traditional (n = 277) protocol. A positive response was defined as the induction of syncope in presence of hypotension/bradycardia, and was observed in 167 (60.3%) patients with Fast and in 162 (58.5%) patients with the Traditional protocol. There was a trend of lesser vasodepressor response (14.8% Fast vs. 20.6% Traditional) which was significant during the passive phase (P = 0.01). CONCLUSION: The diagnostic value of the Fast HUTT protocol is similar to that of the Traditional protocol and therefore the Fast protocol can be used instead of the Traditional protocol.

Relationship between syncopal symptoms and head-up tilt test modes.

OBJECTIVE: Head-up tilt test (HUTT) is an important tool in the diagnosis of pediatric vasovagal syncope. This research will explore the relationship between syncopal symptoms and HUTT modes in pediatric vasovagal syncope. METHODS: A retrospective analysis was performed on the clinical data of 2513 children aged 3-18 years, who were diagnosed with vasovagal syncope, from Jan. 2001 to Dec. 2021 due to unexplained syncope or pre-syncope. The average age was 11.76 ± 2.83 years, including 1124 males and 1389 females. The patients were divided into the basic head-up tilt test (BHUT) group (596 patients) and the sublingual nitroglycerine head-up tilt test (SNHUT) group (1917 patients) according to the mode of positive HUTT at the time of confirmed pediatric vasovagal syncope. RESULTS: (1) Baseline characteristics: Age, height, weight, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and composition ratio of syncope at baseline status were higher in the BHUT group than in the SNHUT group (all P < 0.05). (2) Univariate analysis: Age, height, weight, HR, SBP, DBP, and syncope were potential risk factors for BHUT positive (all P < 0.05). (3) Multivariate analysis: syncope was an independent risk factor for BHUT positive, with a probability increase of 121% compared to pre-syncope (P<0.001). CONCLUSION: The probability of BHUT positivity was significantly higher than SNHUT in pediatric vasovagal syncope with previous syncopal episodes.

Adverse childhood experiences are associated with altered cardiovascular reactivity to head-up tilt in young adults.

Adverse childhood experiences (ACEs) are associated with greater prevalence of cardiovascular disease and altered acute stress reactivity. The current study investigated the effect of ACEs on hemodynamic and autonomic responses to orthostatic stress imposed by 60° head-up tilt (HUT) in young adults. Two-hundred twenty-six healthy young adults (age = 22.6 ± 1.5 yr; n = 116 females) without cardiovascular disease participated and had complete data. Participants underwent supine blood pressure (BP), R-R interval (RRI), cardiac output (CO), total peripheral resistance (TPR), and cardiovagal baroreflex sensitivity (cvBRS) testing followed by a transition to 60° HUT where measures were reassessed. Childhood adversity exposures were assessed based on categorical exposure and nonexposure to childhood household dysfunction and maltreatment, and <4 and ≥4 types of ACEs. Significantly greater increases in SBP (P < 0.05), DBP, MAP, and TPR (P < 0.01; all) following 60° HUT were observed in individuals with ≥4 compared with those with <4 types of ACEs. Attenuated decreases in RRI and cvBRS were observed in those with ≥4 types of ACEs (P < 0.05). Experiencing ≥4 types of ACEs was associated with augmented BP and TPR reactivity and a blunted decrease in cvBRS in response to 60° HUT in young adults. Results suggest that a reduced vagal response to orthostatic stress is present in those who have experienced ≥4 types of ACEs that may promote autonomic dysfunction. Future research examining the sympathetic and vagal baroreflex branches is warranted.

Differential regulation of sympathetic neural burst frequency and amplitude throughout normal pregnancy: a longitudinal study.

Sympathetic activation is a hallmark of pregnancy. However, longitudinal assessments of muscle sympathetic nerve activity (MSNA) in pregnancy are scarce and have primarily focused on burst occurrence (frequency) at rest, despite burst strength (amplitude) representing distinct characteristics of sympathetic outflow. Thus, we assessed MSNA burst amplitude distributions in healthy women to determine the impact of normal pregnancy on neural discharge patterns in response to orthostatic stress. Twenty-six women were studied longitudinally during pre-, early- (4-8 wk of gestation), and late (32-36 wk) pregnancy, as well as postpartum (6-10 wk after delivery). MSNA, blood pressure (BP), and heart rate (HR) were measured in the supine posture and during graded head-up tilt (30° and 60° HUT). Mean and median MSNA burst amplitudes were used to characterize burst amplitude distribution. In late pregnancy, women demonstrated smaller increases in HR (P < 0.001) during 60° HUT and larger increases in systolic BP (P = 0.043) throughout orthostasis, compared with prepregnancy. The increase in MSNA burst frequency during late- relative to prepregnancy (Late: Δ14[10] vs. Pre: Δ21[9] bursts/min; P = 0.001) was smaller during 60° HUT, whereas increases in burst incidence were smaller in late- relative to prepregnancy throughout orthostasis (P = 0.009). Nonetheless, median burst amplitude was smaller throughout orthostasis in late compared with prepregnancy (P = 0.038). Thus, while supine MSNA burst frequency was greater in late pregnancy, increases in burst frequency and strength during orthostasis were attenuated. These smaller, orthostatically induced MSNA increases may reflect natural adaptions of pregnancy serving to prevent sympathetic hyper-reactivity that is common in pathological states.

Prevalence of asystole during tilt test-induced vasovagal syncope may depend on test methodology.

This review addresses tilt-testing methodology by searching the literature which reports timing of asystole and loss of consciousness (LOC). Despite the Italian protocol being the most widely adopted, its stipulations are not always followed to the letter of the European Society of Cardiology guidelines. The discrepancies permit reassessment of the incidence of asystole when tilt-down is early, impending syncope, compared with late, established LOC. Asystole is uncommon with early tilt down and diminishes with increasing age. However, if LOC is established as test-end, asystole is more common, and it is age-independent. Thus, the implications are that asystole is commonly under-diagnosed by early tilt-down. The prevalence of asystolic responses observed using the Italian protocol with a rigorous tilt down time is numerically close to that observed during spontaneous attacks by electrocardiogram loop recorder. Recently, tilt-testing has been questioned as to its validity but, in selection of pacemaker therapy in older highly symptomatic vasovagal syncope patients, the occurrence of asystole has been shown to be an effective guide for treatment. The use of head-up tilt test as an indication for cardiac pacing therapy requires pursuing the test until complete LOC. This review offers explanations for the findings and their applicability to practice. A novel interpretation is offered to explain why pacing induced earlier may combat vasodepression by raising the heart rate when sufficient blood remains in the heart.

Definitive aetiology of unexplained syncope after cardiovascular autonomic tests in a tertiary syncope unit.

AIMS: Syncope is a common condition with many possible causes, ranging from benign to life-threatening aetiologies. Establishing a diagnosis can be difficult, and specialized syncope units, using cardiovascular autonomic tests (CATs), including a head-up tilt test, can increase the diagnostic yield. However, up to one-fifth of examined patients have inconclusive CAT results. The aim of the present study was to investigate the predictive value of history, and clinical findings for unexplained syncope after CAT and characterize the group with negative results. METHODS AND RESULTS: Consecutive syncope patients [n = 2663, 61% women, median age 52 (32-69) years] were evaluated and CAT explained aetiology of syncope in 79% of cases, whereas 21% remained unexplained. Predictors of negative CAT were older age at first syncope (+8% higher odds per 10-year increment, P = 0.042), higher supine heart rate (HR; +12% per 10 b.p.m.; P = 0.003), absence of prodromes (+48%; P < 0.001), hypertension (+45%; P = 0.003), diabetes (+82%; P < 0.001), heart failure (+98%; P = 0.014), and coronary artery disease (+51%; P = 0.027). Compared with vasovagal syncope, patients with negative CAT were older, reported more often the absence of prodromes, and had a higher burden of cardiovascular comorbidities. CONCLUSION: A cardiovascular autonomic test established the cause of syncope in 79% of patients evaluated in a syncope unit. Syncope without prodromes and cardiovascular comorbidities were significant predictors of failure to reveal an aetiology from assessment by CAT. These are known risk factors for cardiac syncope and patients with inconclusive CAT warrant further investigation.

A cross-sectional nationwide survey of guideline based syncope units in the Netherlands: the SU-19 score-a novel validation for best practices.

AIMS: We aimed to identify all syncope units (SUs) in the Netherlands and assess the extent to which these SUs fulfil the essential requirements outlined by the consensus statements of the European Heart Rhythm Association and the European Society of Cardiology syncope guidelines. For this, we developed the SU-19 score, a novel guideline based validation tool for best practice. METHODS AND RESULTS: All outpatient clinics of cardiology, neurology, and internal medicine in the Netherlands were screened for presence of any form of structured specialized syncope care. If present, these were included as SUs and requested to complete a questionnaire regarding syncope care. We assessed all SUs using the SU-19 score regarding structure (3 points), available tests (12 points), and initial evaluation (4 points). Twenty SUs were identified in the Netherlands, both academic (5/20) and non-academic hospitals (15/20), 17/20 reported multidisciplinary involvement during initial evaluation. In 19/20, neurology, cardiology, or both were responsible for the syncope management. Non-physicians were involved performing the head-up tilt test (44%) and initial evaluation (40%). The mean SU-19 score was 18.0 ± 1.1, 45% achieved the maximum score of 19 points. Variations were observed in protocols for active standing test, carotid sinus massage, and head-up tilt test. CONCLUSION: There is a network of 20 SUs in the Netherlands. Forty-five per cent fully met the SU-19 score (mean 18.0 ± 1.1). Slight variety existed in protocols for autonomic function tests. Neurology and cardiology were mostly involved in syncope management. Non-physicians play an important role in syncope care.

Left atrial function evaluation by 2D speckle-tracking echocardiography in patients with vasovagal syncope.

OBJECTIVES: Evidence indicates left atrial (LA) involvement in vasovagal syncope (VVS). The LA regulates left ventricular filling during the cardiac cycle. We aimed to assess LA function in patients with VVS by 2D speckle-tracking echocardiography. METHODS: Sixty-nine consecutive patients with VVS were recruited. Based on the head-up tilt test (HUTT) results, the study population was divided into two groups: HUTT+ (n = 45) and HUTT- (n = 24). Fifty-one consecutive subjects were enrolled as the control group. LA myocardial deformation parameters were measured by 2D speckle-tracking echocardiography to evaluate LA function. RESULTS: Maximal, minimal, and pre-P LA volumes were lower in patients with VVS. Strain and strain rate during reservoir, conduit, and contraction phases in VVS patients with HUTT+ or HUTT- were not statistically significantly different from those in the control group. Additionally, the volumetric parameters of LA function showed no difference in statistical significance between the three study groups. CONCLUSIONS: While LA phasic function was not different between the two groups of VVS patients with HUTT+ or HUTT- and the control group, LA size during the three LA phases was smaller in patients with VVS.

Effects of posture changes on dynamic cerebral autoregulation during early pregnancy in women with obesity and/or sleep apnea.

The incidence of syncope during orthostasis increases in early human pregnancy, which may be associated with cerebral blood flow (CBF) dysregulation in the upright posture. In addition, obesity and/or sleep apnea per se may influence CBF regulation due to their detrimental impacts on cerebrovascular function. However, it is unknown whether early pregnant women with obesity and/or sleep apnea could have impaired CBF regulation in the supine position and whether this impairment would be further exacerbated in the upright posture. Dynamic cerebral autoregulation (CA) was evaluated using transfer function analysis in 33 women during early pregnancy (13 with obesity, 8 with sleep apnea, 12 with normal weight) and 15 age-matched nonpregnant women during supine rest. Pregnant women also underwent a graded head-up tilt (30° and 60° for 6 min each). We found that pregnant women with obesity or sleep apnea had a higher transfer function low-frequency gain compared with nonpregnant women in the supine position (P = 0.026 and 0.009, respectively) but not normal-weight pregnant women (P = 0.945). Conversely, the transfer function low-frequency phase in all pregnancy groups decreased during head-up tilt (P = 0.001), but the phase was not different among pregnant groups (P = 0.180). These results suggest that both obesity and sleep apnea may have a detrimental effect on dynamic CA in the supine position during early pregnancy. CBF may be more vulnerable to spontaneous blood pressure fluctuations in early pregnant women during orthostatic stress compared with supine rest due to less efficient dynamic CA, regardless of obesity and/or sleep apnea.

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

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

Early and late-onset syncope: insight into mechanisms.

AIMS: Unexplained syncope is an important clinical challenge. The influence of age at first syncope on the final syncope diagnosis is not well studied. METHODS AND RESULTS: Consecutive head-up tilt patients (n = 1928) evaluated for unexplained syncope were stratified into age groups <30, 30-59, and ≥60 years based on age at first syncope. Clinical characteristics and final syncope diagnosis were analysed in relation to age at first syncope and age at investigation. The age at first syncope had a bimodal distribution with peaks at 15 and 70 years. Prodromes (64 vs. 26%, P < 0.001) and vasovagal syncope (VVS, 59 vs. 19%, P < 0.001) were more common in early-onset (<30 years) compared with late-onset (≥60 years) syncope. Orthostatic hypotension (OH, 3 vs. 23%, P < 0.001), carotid sinus syndrome (CSS, 0.6 vs. 9%, P < 0.001), and complex syncope (>1 concurrent diagnosis; 14 vs. 26%, P < 0.001) were more common in late-onset syncope. In patients aged ≥60 years, 12% had early-onset and 70% had late-onset syncope; older age at first syncope was associated with higher odds of OH (+31% per 10-year increase, P < 0.001) and CSS (+26%, P = 0.004). Younger age at first syncope was associated with the presence of prodromes (+23%, P < 0.001) and the diagnoses of VVS (+22%, P < 0.001) and complex syncope (+9%, P = 0.018). CONCLUSION: In patients with unexplained syncope, first-ever syncope incidence has a bimodal lifetime pattern with peaks at 15 and 70 years. The majority of older patients present only recent syncope; OH and CSS are more common in this group. In patients with early-onset syncope, prodromes, VVS, and complex syncope are more common.

On the Different Abilities of Cross-Sample Entropy and K-Nearest-Neighbor Cross-Unpredictability in Assessing Dynamic Cardiorespiratory and Cerebrovascular Interactions.

Nonlinear markers of coupling strength are often utilized to typify cardiorespiratory and cerebrovascular regulations. The computation of these indices requires techniques describing nonlinear interactions between respiration (R) and heart period (HP) and between mean arterial pressure (MAP) and mean cerebral blood velocity (MCBv). We compared two model-free methods for the assessment of dynamic HP-R and MCBv-MAP interactions, namely the cross-sample entropy (CSampEn) and k-nearest-neighbor cross-unpredictability (KNNCUP). Comparison was carried out first over simulations generated by linear and nonlinear unidirectional causal, bidirectional linear causal, and lag-zero linear noncausal models, and then over experimental data acquired from 19 subjects at supine rest during spontaneous breathing and controlled respiration at 10, 15, and 20 breaths·minute-1 as well as from 13 subjects at supine rest and during 60° head-up tilt. Linear markers were computed for comparison. We found that: (i) over simulations, CSampEn and KNNCUP exhibit different abilities in evaluating coupling strength; (ii) KNNCUP is more reliable than CSampEn when interactions occur according to a causal structure, while performances are similar in noncausal models; (iii) in healthy subjects, KNNCUP is more powerful in characterizing cardiorespiratory and cerebrovascular variability interactions than CSampEn and linear markers. We recommend KNNCUP for quantifying cardiorespiratory and cerebrovascular coupling.

Systems analysis of the mechanisms governing the cardiovascular response to changes in posture and in peripheral demand during exercise.

Blood flows and pressures throughout the human cardiovascular system are regulated in response to various dynamic perturbations, such as changes to peripheral demands in exercise, rapid changes in posture, or loss of blood from hemorrhage, via the coordinated action of the heart, the vasculature, and autonomic reflexes. To assess how the systemic and pulmonary arterial and venous circulation, the heart, and the baroreflex work together to effect the whole-body responses to these perturbations, we integrated an anatomically-based large-vessel arterial tree model with the TriSeg heart model, models capturing nonlinear characteristics of the large and small veins, and baroreflex-mediated regulation of vascular tone and cardiac chronotropy and inotropy. The model was identified by matching data from the Valsalva maneuver (VM), exercise, and head-up tilt (HUT). Thirty-one parameters were optimized using a custom parameter-fitting tool chain, resulting in an unique, high-fidelity whole-body human cardiovascular systems model. Because the model captures the effects of exercise and posture changes, it can be used to simulate numerous clinical assessments, such as HUT, the VM, and cardiopulmonary exercise stress testing. The model can also be applied as a framework for representing and simulating individual patients and pathologies. Moreover, it can serve as a framework for integrating multi-scale organ-level models, such as for the heart or the kidneys, into a whole-body model. Here, the model is used to analyze the relative importance of chronotropic, inotropic, and peripheral vascular contributions to the whole-body cardiovascular response to exercise. It is predicted that in normal physiological conditions chronotropy and inotropy make roughly equal contributions to increasing cardiac output and cardiac power output during exercise. Under upright exercise conditions, the nonlinear pressure-volume relationship of the large veins and sympathetic-mediated venous vasoconstriction are both required to maintain preload to achieve physiological exercise levels. The developed modeling framework is built using the open Modelica modeling language and is freely distributed.

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

BACKGROUND AND OBJECTIVE: Head-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).  METHODS: Patients 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. RESULTS: A 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). CONCLUSION: ALDH2 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.