Head-up Tilt Test Research Articles

Diagnosing Neurally Mediated Syncope Using Classification Techniques.

Syncope is a medical condition resulting in the spontaneous transient loss of consciousness and postural tone with spontaneous recovery. The diagnosis of syncope is a challenging task, as similar types of symptoms are observed in seizures, vertigo, stroke, coma, etc. The advent of Healthcare 4.0, which facilitates the usage of artificial intelligence and big data, has been widely used for diagnosing various diseases based on past historical data. In this paper, classification-based machine learning is used to diagnose syncope based on data collected through a head-up tilt test carried out in a purely clinical setting. This work is concerned with the use of classification techniques for diagnosing neurally mediated syncope triggered by a number of neurocardiogenic or cardiac-related factors. Experimental results show the effectiveness of using classification-based machine learning techniques for an early diagnosis and proactive treatment of neurally mediated syncope.

Adenosine plasma levels and adenosine receptor levels determine the outcome of adenosine test and head-up tilt test in syncopal patients with a normal heart

Abstract Background/Introduction The neurohumoral profile underlying the manifestation of reflex syncope remains incompletely understood. Adenosine plasma (ADP) and adenosine receptor (ADR) levels may differentiate the outcomes of head-up tilt table test (HUTT) and adenosine test (ADT) but their role in the diagnostic evaluation of patients with syncope has yet to be determined. Purpose We sought to assess the ADP and ADR levels in patients without structural heart disease who underwent HUTT and ADT tests as part of the diagnostic workup of syncope. We specifically investigated differences in the outcomes of the HUTT and ADT tests as well as to the ADP levels during HUTT. Methods HUTT and ADT were performed as per the standard protocols. ADT was considered positive in the event of asystole >6 seconds or heart block for >10 seconds after intravenous Adenosine 0.15 mg/kg administration in the supine position. ADP levels were assessed at three timepoints during the HUTT: at baseline (supine), immediately after bed tilt and, in cases of a positive HUTT, at the time of syncope. Patients were categorized in quintiles of very low, low, intermediate, high and very high baseline ADP levels. We also assessed the A2A ADR levels of monocytes. Results We prospectively analyzed 124 patients (71 women, age 46.78±21.01 years). ADT was positive in 12.9% of patients and HUTT in 44.4% of patients. Patients with very low baseline ADP levels (lowest quintile) more frequently presented with a positive ADT (odds ratio [OR] 4.08, 95% Confidence Interval [CI] 1.40 to 13.13, p<0.05). Baseline ADP did not differ between patients with positive and negative HUTT. However, patients with vasodepressor response to HUTT exhibited increase in ADP from baseline to bed tilt (0.33±1.03 vs. 0.42±1.14 ppm/Um/L, p<0.05) and in syncope (0.70±1.89, P<0.05), while no difference was noted in patients with cardioinhibitory or mixed response. Patients with positive ADT and negative HUTT had higher ADR levels (221.5±88.56 MFI) as compared to patients with negative ADT and positive HUTT (59.78±83.65 MFI, p<0.05) and to patients with positive ADT and HUTT (33.29±35.77 MFI, p<0.05). Within patients with positive HUTT, those with onset of syncope in the Isoprenaline provocation phase (>20 min) had lower ADR levels (80.88±238.98 vs 89.43±96.08 MFI, p<0.05). Conclusion(s) Baseline ADP levels are related to the outcome of ADT while an ADP increase immediately after bed tilt and in syncope is evident in vasodepressor response to HUTT. Higher ADR levels are related to positive ADT and negative HUTT. Lower ADR levels are associated with more delayed onset of syncope during HUTT. ADP and ADR levels warrant further investigation as they may characterize a subset of patients with specific responses to ADT and HUTT and may be implicated in the pathophysiology of reflex syncope. Funding Acknowledgement Type of funding sources: None.

Support Vector Machine-Based Classification of Vasovagal Syncope Using Head-Up Tilt Test.

Simple SummarySyncope is a medical condition triggered by short-lived interruption of the oxygen supply to the brain, which may result in free fall or accidents. The diagnosis of syncope is a challenging task, as various other states of altered consciousness present with the same symptoms as syncope. This work uses historical medical data for the diagnosis of syncope using sophisticated computing solutions. The experimental results prove the effectiveness of the approach, leading to the proactive prediction of syncope.Syncope is the medical condition of loss of consciousness triggered by the momentary cessation of blood flow to the brain. Machine learning techniques have been established to be very effective way to address such problems, where a class label is predicted for given input data. This work presents a Support Vector Machine (SVM) based classification of neuro-mediated syncope evaluated using train–test–split and K-fold cross-validation methods using the patient’s physiological data collected through the Head-up Tilt Test in pure clinical settings. The performance of the model has been analyzed over standard statistical performance indices. The experimental results prove the effectiveness of using SVM-based classification for the proactive diagnosis of syncope.

Association of folate and vitamin B12 deficiency with vasovagal syncope: a case-control study

Abstract Background Studies demonstrated an association between vitamin B12 deficiency and vasovagal syncope (VVS) in pediatric patients. Moreover, some evidence suggested a pathophysiological role of plasma catecholamines elevation in VVS, which can arise from folate or vitamin B12 deficiency in terms of biochemical pathways. Purpose We aimed to evaluate the association of folate and vitamin B12 deficiency with VVS in adults. Methods In this case-control study, adult patients (18–70 years of age) with the diagnosis of VVS based on history and physical examination (2018 ESC guidelines) who underwent a head-up tilt test (HUTT) were included as the case group. The control group comprised age- and sex-matched individuals who participated in a population-based cohort study. The most important exclusion criteria were taking vitamin B12 or folate supplements, carbamazepine and phenobarbital, and a history of bariatric surgeries. Plasma levels of vitamin B12, folate, homocysteine, and thyroid-stimulating hormone (TSH), a possible confounder, were measured by Abbott Diagnostics chemiluminescence kits. We compared categorical variables and continuous variables by Chi-square and t-test, respectively. Logistic regression models were employed for adjusting for possible confounders, including age, sex, and TSH. Results From February 2020 to February 2021, we screened 157 patients with VVS, of whom 44 patients were included. After matching for age and sex, 44 healthy individuals without a history of syncope were examined as the control group. The mean age was 37.9 years in both groups, with 23 women (52.3%) in each group. Baseline characteristics were comparable across the study groups. There were no significant differences between serum levels of vitamin B12, folate, homocysteine, and TSH, as well as the prevalence of deficiency of folate and vitamin B12 between case and control groups (Table 1), even after adjusting for confounding variables. Serum levels of vitamin B12 were remarkably lower in patients with a lifetime syncopal episodes of ≥3 compared to patients with <3 lifetime attacks (Table 2, P=0.042). This correlation remained statistically significant after adjusting for possible confounders, including age, sex, and TSH by the logistic regression model (P=0.032). Conclusions In this study, we found that there is no significant difference between the prevalence of folate and vitamin B12 deficiency and serum levels of these vitamins in adult patients with VVS and healthy individuals; however, serum vitamin B12 was significantly lower in patients with recurrent VVS compared to patients with a lower burden of syncopal episodes. Future studies with larger sample sizes are recommended in the recurrent VVS subgroup. Therapeutic implications of these findings should be investigated in randomized-controlled trials. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Iran National Science Foundation Table 1Table 2

Comparison of the sit-up test and head-up tilt test for assessing blood pressure and hemodynamic responses in healthy young individuals.

The sit-up test is used to assess orthostatic hypotension, without the use of a tilt table, in populations who are unable to stand. The primary objective of this study was to determine the differences in blood pressure and hemodynamic responses between the sit-up and head-up tilt tests. The secondary objective was to determine the hemodynamic responses related to changes in blood pressure during each test. Nineteen healthy volunteers (nine males, aged 24.3 ± 2.4 years) underwent the sit-up and head-up tilt tests. Systolic and diastolic blood pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were measured. The increase in systolic blood pressure (15 ± 9 vs. 8 ± 8 mmHg) was greater, while the increase in heart rate (8 ± 5 vs. 12 ± 8 bpm) and reduction in stroke volume (-17 ± 10 vs. -21 ± 10 ml) were smaller during the sit-up test than during the head-up tilt test (P < 0.05). Additionally, the increases in blood pressure variables were significantly associated with the increase in total peripheral resistance (P < 0.05), but not with changes in other hemodynamic variables in both tests. Although the magnitudes of changes in systolic blood pressure, heart rate, and stroke volume differed between the tests, the hemodynamic variable related to changes in blood pressure was the same for both tests. These results may contribute to the clinical application of the sit-up test for identifying the presence and hemodynamic mechanisms of orthostatic hypotension.

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.

Intravenous cyclophosphamide treatment for systemic lupus erythematosus with severe autonomic disorders confirmed by head-up tilt table test: A case series.

Autonomic disorders are common in patients with systemic lupus erythematosus (SLE), but the therapeutic strategy and methods for evaluating the effects of therapy have not been established. We describe the three cases of SLE patients who developed severe autonomic disorders as demonstrated by the head-up tilt table test (HUT). All three patients were treated by intensive immunosuppressive treatments including intravenous cyclophosphamide (IVCY); their HUT results all became negative. Our cases suggest that IVCY treatment can be a good therapeutic option for severe autonomic disorders in SLE patients. The HUT is a useful objective method for the diagnosis of and the evaluation of longitudinal therapeutic effects on autonomic disorders in SLE patients with orthostatic intolerance.

Plasma neurofilament light chain level and orthostatic hypotension in early Parkinson's disease.

To delineate the impact of non-motor markers (REM sleep behavior disorder (RBD), orthostatic hypotension (OH), cardiac sympathetic denervation, hyposmia) on neuronal injury in early-stage Parkinson's disease (PD), we measured the plasma neurofilament light chain (NFL) level of PD patients and evaluated its relationship with these markers. The study population comprised a cohort of 77 patients with PD and 54 controls. OH was assessed using 5-min head-up tilt-table test. Other clinical parameters such as RBD, Unified Parkinson's Disease Rating Scale (UPDRS), cognition, Cross-Cultural Smell Identification Test (CCSIT), white matter hyperintensity (WMH), cardiac metaiodobenzylguanidine (MIBG) and striatal dopamine transporter (DAT) uptake were assessed. Plasma NFL levels were measured using Simoa platform. During mean 24.8months of follow-up, 70 patients remained PD, 5 patients converted to Parkinson-plus syndrome (P + converter), and 2 were lost to follow-up. NFL level did not differ between PD and control groups (age-adjusted means 10.40pg/mL vs 9.51pg/mL, p = 0.151), but PD patients with OH (median 15.31pg/mL) had higher levels compared with those without OH (median 9.2pg/mL, p = 0.008), as well as the control group (median 9.7pg/mL, p = 0.002). P + converter group had the highest plasma NFL level (38.17pg/mL, p < 0.001). In a multiple regression analysis, OH, age, and disease duration independently correlated with plasma NFL level. This finding adds biomarker-based evidence for poor clinical outcomes associated with OH in patients with PD.

Maybe angiotensin II is getting on our nerves, and the role of exercise.

Maybe angiotensin II is getting on our nerves, and the role of exercise.

Quantitative Complexity Theory Used in the Prediction of Head-Up Tilt Testing Outcome.

Background Head-up tilt testing (HUTT), a well-established tool in the diagnosis of vasovagal syncope, is time-consuming, and every provoked vasovagal reaction may result in consolidating the reflex mechanism. Therefore, identification of parameters that could shorten the duration of HUTT and prevent fainting is desirable. Quantitative complexity theory (QCT) may provide holistic information on the cardiovascular reaction in HUTT. The aim of the present article was to evaluate the prognostic value of complexity in comparison with traditional haemodynamic parameters (HR and BP) in predicting the HUTT outcome. Methods Eighty-one healthy volunteers (74 men; mean age: 37.8 years) were included in this retrospective analysis of data collected within the project realized in Department of Cardiology and Internal Diseases, Military Institute of Medicine between January 2012 and October 2014. The subjects underwent HUTT, with beat-to-beat haemodynamic monitoring with a Niccomo™. The chosen haemodynamic parameters (including BP, HR, stroke volume, cardiac output, systemic vascular resistance) have been used in complexity analysis. Results HUTT was positive in 54 (66.7%) study participants. The values of complexity were already higher in fainting subjects than those were in nonfainting ones 300 s before HUTT termination (HUTT_end), with a significant upward trend starting 150 s before (pre)syncope. An area under the curve (AUC) over 0.700 was observed for complexity from 120 s before HUTT_end, with a sensitivity of 63% and specificity of 78% at this time point. The prognostic value of complexity was superior to that of the HR and mean arterial pressure (MAP). Conclusions Complexity has been shown to be a sensitive marker of cardiovascular haemodynamic response to orthostatic stress and proved to be superior over HR and BP in predicting HUTT outcomes.

Comparison of the Active Sitting Test and Head-Up Tilt Test for Diagnosis of Postural Tachycardia Syndrome in Children and Adolescents.

Objectives: We aimed to compare the hemodynamic responses to the active sitting test with the passive head-up tilt test (HUTT) in children and adolescents with postural tachycardia syndrome (POTS). We hypothesized that sitting tachycardia was also present in POTS patients during sitting.Materials and methods: We tested 30 POTS patients and 31 control subjects (mean age = 12 years, range = 9–16 years) who underwent both active sitting test and HUTT successively. We measured the heart rate (HR) and blood pressure (BP) during each test.Results: For both POTS patients and control subjects, the HUTT produced significantly larger HR and BP increases from 3 to 10 min of postural change than did the sitting test. Moreover, POTS patients with excessive orthostatic tachycardia during the HUTT also had significantly larger increases in HR at all test intervals during the sitting test than did the control subjects. A maximum increase in HR ≥ 22 bpm within 10 min of the sitting test was likely suggested to predict orthostatic tachycardia, yielding a sensitivity and specificity of 83.3 and 83.9%, respectively. Only six of 30 POTS patients (20%) reached the 40-bpm criterion during the sitting test, and no one complained of sitting intolerance symptoms.Conclusions: We have shown that POTS patients also have sitting tachycardia when changing from a supine position to a sitting position. We believe that the active sitting test is a reasonable alternative maneuver in assessing POTS in population groups that cannot tolerate the standing test or HUTT.

Clinical Significance of the Head-Up Tilt Test in Improving Prognosis in Patients with Possible Neurally Mediated Syncope.

Simple SummarySeveral diseases can cause syncope, which is commonly known as fainting; however, syncope triggered by a reflex mechanism, also termed neurally mediated syncope (NMS), is one of the most common forms. While NMS is considered a benign disease, it can cause critical clinical events, such as severe trauma due to syncope. The head-up tilt test (HUTT) is one of the modalities for the diagnosis of NMS. The clinical significance of HUTT in the prognosis of NMS, such as recurrence rate of syncope and mortality, are still to be elucidated. This research aimed to clarify the value of HUTT for the diagnosis of NMS, and to investigate the prognosis of patients with NMS by analyzing the data of 101 patients with syncope and their close long-term (four years at the longest) follow-up. Furthermore, as insertable cardiac monitors (ICMs) are considered effective in patients with syncope, this study also aimed to evaluate the usefulness of ICM in patients with negative HUTT results. Finally, our research contributes to the improvement of the clinical management for patients with syncope.Syncope is commonly encountered in daily clinical practice. Depending on its etiology (benign or life-threatening conditions or environmental triggers), syncope can be neurally mediated (reflex), cardiac, or orthostatic. Furthermore, neurologic disease can cause symptoms that mimic syncope. However, there is limited research on neurally mediated syncope (NMS), which is considered a benign disorder, and close follow-ups are rarely performed. NMS can cause serious clinical events, including severe trauma and car accidents. The head-up tilt test (HUTT) is the gold standard for diagnosing NMS; however, its clinical significance remains unknown, and its relevance to NMS prognosis requires further research. This retrospective study aimed to assess the clinical significance of the HUTT for NMS. We reviewed the charts of 101 patients who underwent HUTT at Tokai University Hospital in Japan between January 2016 and March 2019. During the HUTT, 72 patients (69.2%) experienced syncope. Patients were followed up for 886.1 ± 457.7 days (interquartile range: 518–1293 days). The syncope recurrence rate was 16.9%; however, no significant difference was observed between the two groups (HUTT positive vs. negative) (13.8% vs. 18.1%, p = 0.772). Four of 29 (13.9%) and two of 72 (2.8%) patients in the negative and positive HUTT groups, respectively, experienced cardiac events (p = 0.019). Negative HUTT results may assist in anticipating unexpected clinical events within a few years. A negative HUTT result may allow us to reconsider the NMS diagnosis based on clinical information. Close outpatient follow-up of patients with negative HUTT results is warranted.

Hyperadrenergic Orthostatic Hypotension With Pure Peripheral Sympathetic Denervation Associated With Sjogren’s Syndrome

Hyperadrenergic orthostatic hypertension (hyper OH), defined as OH with elevated levels of upright plasma norepinephrine (NE), is assumed to be a clinical expression of peripheral sympathetic denervation (PSD). Primary Sjogren’s syndrome (pSS) is an autoimmune disease that not only affects the exocrine glands but also develops autonomic neuropathy with PSD. We present a hyper OH with PSD possibly associated with pSS and successfully treated with intravenous immunoglobulin (IVIg). The case was a 60-year-old man who developed recurrent syncope on rapid standing from a sitting position. Head-up tilt test and NE infusion test showed hyper OH with PSD. This case report raises the possible associations between hyper OH and autonomic neuropathy as pSS developed.

Abstract P192: Orthostatic Tolerance Before And After 60 Days Of Strict Head Down Tilt Bedrest With And Without Daily Artificial Gravity Training

Background: Orthostatic intolerance occurs after space flight, immobilization and in patients with autonomic diseases, so there is a need for more effective countermeasures. We hypothesized that daily artificial gravity elicited through short-arm centrifugation attenuates plasma volume loss and orthostatic intolerance following 60 days of HDTBR, which models cardiovascular responses to weightlessness. Methods: We studied 24 healthy persons (8 women, 33.4±9.3 yr, 24.3±2.1 kg/m2) exposed to 60d HDTBR. Subjects were assigned to 30 min/d continuous short arm centrifugation (cAG), 6x5 min short arm centrifugation (iAG), or a control group (ctr, no countermeasures). Head-up tilt testing (15 min of 80°) followed by incremental lower body negative pressure (-10 mmHg every 3 min) until presyncope was performed before and at the end of HDTBR. Plasma volume was measured (CO rebreathing) 12-2 days before and after 56d of HDTBR. Stroke volume was measured by cMRI. Norepinephrine, epinephrine, aldosterone, and renine plasma levels were measured before and after HDTBR. Results: Time to presyncope decreased in all groups following bedrest (ctr: 22:56 min pre and 9:35 min post, cAG 15:34 min pre and 10:11 min post; iAG 14:56 min pre and 10:00 min post, p&lt;0.001). The significant interaction (p=0.025) between bedrest and intervention was explained by greater baseline orthostatic tolerance time in the ctr. AG Data was pooled analysis. The reduction in stroke volume (ctr, pre: 93±19 ml, HDTBR: 69±13 ml, AG, pre: 88±20 ml, HDTBR: 67±17 ml) and plasma volume was similar (ctr, pre: 4155±1085 ml, HDTBR: 3855±1087 ml, AG, pre: 4114±1250 ml, HDTBR: 3674± 1313 ml). Catechols and aldosterone did not change significantly during bedrest. The increase in renine was similar between groups (ctr pre: 18±12 mE/L, HDTBR: 21±8 mE/L, AG pre: 21±10 mE/L, HDTBR: 31±12 mE/L). Conclusions: 30 min daily AG didn’t prevent a reduction in orthostatic tolerance following 60d HDTBR. Whether numerically smaller reductions in orthostatic tolerance in the AG groups indicate efficacy or result from baseline differences can’t be ascertained. A stronger AG stimulus or combination with other countermeasures might be required to maintain orthostatic tolerance and to attenuate the volume reduction.

Delirium and abnormal autonomic nervous system response to head-up tilt testing.

Delirium is a common condition with poorly understood pathophysiology. Various theories have been proposed including that delirious patients have reduced cerebral blood flow. We hypothesised that patients with delirium could have abnormal autonomic nervous system function, as assessed by tilt table testing, which would explain the alteration in blood flow. A prospective cohort study of medical inpatients aged 65years and older was undertaken. Delirium was assessed using DRS-R98 and DSM-IV criteria. Beat-to-beat blood pressure (BP) was recorded during tilt testing. Differences in BP changes between the two groups (those with delirium and those without) were explored. The association between severity of delirium and magnitude of BP changes was also examined. 64 participants were recruited during hospitalisation. 29 completed follow-up Head-Up Tilt testing. The mean age of participants was 80.8years (SD 6.2years). The control group (n=12) had a median decrease in systolic BP of 17.5mmHg (IQR 20.75). The delirium group (n=17) had a median decrease in systolic BP of 1mmHg (IQR 38.5), p=0.04. As delirium severity scores increased, systolic BP change during tilting also increased (rs=0.42, p=0.03). Participants in the delirium group showed different BP responses to tilt test which may represent abnormal sympathetic response. This would be consistent with other features of delirium such as treatment response to centrally acting alpha-2 blockers. Equity of access to research for older, frail and delirious cohorts is essential but feasibility and acceptability needs to be optimised and factored into study design.

Heart rate variability and heart rate turbulence in patients with vasovagal syncope.

Aim The autonomic nervous system plays an important role in the pathogenesis of vasovagal syncope, but studies on the effect of basal autonomic tone have found confusing results. The aim of this study was to investigate the effect of basal autonomic functions, as assessed by heart rate variability (HRV) and heart rate turbulence (HRT), in patients with vasovagal syncope.Material and methods Patients who underwent head-up tilt test (HUTT) due to unexplained syncope and who had a 24 hr Holter ECG recording in the same period were retrospectively analyzed. Patients with diabetes, a history of myocardial infarction, heart failure, orthostatic hypotension, atrial fibrillation, or use of vasoactive drugs, such as beta blockers, were excluded from the study. 161 patients who met these criteria were included in the study. Time domain HRV parameters from Holter ECG recordings and HRT parameters from patients with sufficient number of ventricular premature contractions were measured.Results The age of the patients varied from 16 to 75 yrs (mean: 44.8±18.5 yrs). HUTT results of 60 (37.2 %) patients were evaluated as positive. There were no significant differences in the basal demographic, clinical, or laboratory findings of the tilt-positive and tilt-negative patient groups. Likewise, there were no significant differences between the time domain HRV parameters and HRT parameters of both groups.Conclusion HRV and HRT parameters reflecting basal autonomic function were not different between HUTT positive and HUTT negative patient groups. These findings suggest that basal autonomic functions have no effect on vasovagal syncope pathogenesis.

Characteristics of blood proteome changes in hemorrhagic syndrome after head-up tilt test during 21-day Dry Immersion

The effect of the rapid redistribution of blood during head-up tilt tests in 21-day Dry Immersion suddenly became relevant in connection with the occurrence of mild hemorrhagic syndrome in the study participants. It became necessary to analyze the processes of occurrence of hemorrhagic syndrome as orthostatic and congestive purpura. The aim of this work was to study the features of the proteomic response of the human body to the rapid redistribution of blood during head-up tilt tests during 21-day immersion, which led to stagnant and orthostatic purpura. According to the results of examination of 10 healthy male volunteers aged 23–34 years after head-up tilt tests, pitting edema and local petechial hemorrhages in the soft tissues of the legs and feet were observed. Proteomic analysis of the samples was carried out by high performance liquid chromatography with tandem mass spectrometry. For bioinformatic analysis, the software packages Perseus, ANDSystem were used. From reliably different (p-value <0.05) proteins, proteins directly related to injury and changes in vascular permeability were determined. Сhanges in the levels of plasminogen, fibronectin, other factors of coagulation and fibrinolysis, activation of the complement system, changes in the coagulation cascade and concentrations of plasminogen and its activators (kallikrein, etc.), increased content of fibrinolysis products were revealed. A panel of proteins indicating changes in plasmin-antiplasmin, fibrinogen-soluble fibrin-monomeric complexes and other systems is identified. The obtained data are of scientific and practical interest in the direction of stratification of the risk of secondary hemosiderosis and evaluation of new treatment methods aimed at reducing reperfusion damage to soft tissues and parenchymal organs.

Cardiac sympathetic burden reflects Parkinson disease burden, regardless of high or low orthostatic blood pressure changes

Reduced uptake of 123I-meta-iodobenzylguanidine (123I-MIBG) and orthostatic hypotension (OH) are independently associated with worse clinical outcomes of Parkinson’s disease (PD). However, their interactive influence on PD has not been studied. The role of 123I-MIBG myocardial uptake, as a biomarker of PD severity, was investigated, conditional on the mediating effects of OH. A total of 227 PD patients were enrolled. Their motor and nonmotor aspects were assessed with standardized tools. Global disease burden was estimated by averaging the scaled z-scores of the assessment tools. Every patient went through 123I-MIBG scan, and OH was evaluated with the head-up tilt-test. The mediating role of orthostatic blood pressure changes (ΔBP) on the association between cardiac sympathetic denervation and disease burden was investigated. Low heart-to-mediastinum (H/M) ratio with less than 1.78 was seen in 69.6% of the patient population, and 22.9% of patients had OH. Low H/M ratio was associated with OH, and these patients had worse disease burden than subjects with normal 123I-MIBG uptake (global composite z-score: normal 123I-MIBG vs. abnormal 123I-MIBG; −0.3 ± 0.5 vs. 0.1 ± 0.7; p < 0.001). The mediation models, controlled for age and disease duration, revealed that the delayed H/M ratio and global composite score were negatively associated, irrespective of orthostatic ΔBP. Adverse relationship between cardiac sympathetic denervation and disease burden was shown without any interference from orthostatic blood pressure fluctuations. This result suggested that extracranial cardiac markers might reflect disease burden, regardless of labile blood pressure influence.

Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy.

Background:Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.Methods:This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics.Results:A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = −2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = −2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039–1.387, P = 0.013).Conclusions:Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.

The impact of atrial mechanical function on age-dependent presentation of neurocardiogenic syncope.

BackgroundThe contribution of atrial and ventricular function in neurocardiogenic syncope (NCS) pathophysiology is elusive.HypothesisWe assessed the influence of echocardiographic properties to the age of presentation and NCS recurrences.MethodsWe assigned 124 patients with symptoms suggesting NCS, to those with syncope initiation at age <35 (group A, n = 56) and >35 years (group B, n = 68). Echocardiographic indices were measured before head‐up tilt test (HUTT).ResultsA total of 55 had positive HUTT (44%) with a trend favoring group A (p = .08). Group A exhibited lower left atrial (LA) volume index (17 ± 6 vs. 22 ± 11 ml/m2, p = .015), higher LA ejection fraction (69 ± 10 vs. 63 ± 11%, p = .008), LA peak strain (reservoir phase 41 ± 13 vs. 31 ± 14%, p = .001, contraction phase 27 ± 11 vs. 15 ± 10%, p < .001) and LA peak strain rate (reservoir phase 1.83 ± 1.04 vs. 1.36 ± 0.96 1/s, p = .012, conduit phase 2.36 ± 1.25 vs. 1.36 ± 0.78 1/s, p = .001). Group A showed smaller minimum right atrial (RA) volume, better RA systolic function, superior left ventricular diastolic indices, and lower filling pressures. Group A patients were more likely to have >3 recurrences (82.0% vs. 50.1%, p < .05).ConclusionsPatients with younger age of NCS onset and more syncopal recurrences manifest smaller LA and RA dimensions with distinct patterns of systolic and diastolic function and better LA reservoir and contraction properties. These findings may indicate an increased susceptibility to preload reduction, thereby triggering the NCS mechanism.