Deceleration Capacity--A Novel Measure for Autonomic Nervous System in Patients with Vasovagal Syncope on Tilt-table Testing

This study was to investigate the changes of autonomic nerve function and hemodynamics in patients with vasovagal syncope(VVS) during head-up tilt-table testing(HUT). HUT was performed in 68 patients with unexplained syncope and 18 healthy subjects served as control group. According to whether bradycardia, hypotension or both took place during the onset of syncope, the patients were divided during the test into three subgroups: vasodepressor syncope(VD), cardioinhibitory syncope(CI) and mixed syncope(MX) subgroups. Heart rate, blood pressure, heart rate variability(HRV), and deceleration capacity(DC) were continuously analyzed during HUT. For all the subjects with positive responses, the normalized low frequency(LFn) and the LF/HF ratio markedly decreased whereas normalized high frequency(HFn) increased when syncope occurred. Syncopal period also caused more significant increase in the power of the DC in positive groups. These changes were more exaggerated compared to controls. All the patients were indicative of a sympathetic surge in the presence of withdrawal vagal activity before syncope and a sympathetic inhibition with a vagal predominance at the syncopal stage by the frequency-domain analysis of HRV. With the measurements of DC, a decreased vagal tone before syncope stage and a vagal activation at the syncopal stage were observed. The vagal tone was higher in subjects showing cardioinhibitory responses at the syncopal stage. DC may provide an alternative method to understand the autonomic profile of VVS patients.

Evaluation of cilazapril in vasovagal syncope treatment

Objective: to evaluate cilazapril in vasovagal syncope treatment. Method: eighty\|six cases of VVS patients found positive in TTT tilt were medicated with 2.5 mg cilazapril daily for three months and followed up by TTT. Results: seven cases quit due to cough or unexplained reason; 79 VVS patients had no more fainting spells; 75.95% of TTT results of patients changed to negative after 3 months therapy. The before and after cilazapril treatment average blood pressures (taken in lying position) were 121/73 mm Hg (1 mm Hg= 0.133kPa) and 120/76 mm Hg respectively ( P > 0.05); and mean heart rates were 68.63±12.37/min and 70.13±13.15/min respectively with no significant changes ( P > 0.05). Conclusion: Cilazapril was effective in treatment of VVS; did not affect normal blood pressure and heart rate; was safe; and had little side effect.

Predictive Value of Blood Pressure,Heart Rate,and Blood Pressure/Heart Rate Ratio in a Chinese Subpopulation with Vasovagal Syncope

Objective:The head-up tilt test(HUTT)is widely used but is time-consuming and not cost-effective to evaluate patients with vasovagal syncope(VVS).The present study aims to verify the hypothesis that ambulatory blood pressure(BP)monitoring(ABPM)and the simplistic tilt test may be potential alternatives to the HUTT.Methods:The study consecutively enrolled 360 patients who underwent the HUTT to evaluate VVS.BP),heart rate(HR),and BP/HR ratios derived from ABPM and the simplistic tilt test were evaluated to predict the presence,pattern,and stage of syncope during the HUTT.Results:Mixed response was the commonest pattern,and syncope occurred frequently with infusion of isoproterenol at a rate of 3μg/min.During the simplistic tilt test,the cardioinhibitory group had higher tilted BP/HR ratios than the vasodepressor group,while the vasodepressor group had a faster tilted HR and a larger HR difference than the cardioinhibitory group.The higher the BP/HR ratio in the tilted position,the higher the isoproterenol dosage needed to induce a positive response.During ABPM,BP/HR ratios were signifi cantly higher in the cardioinhibitory group than in the vasodepressor group.The higher the ABPM-derived BP,the higher the dosage of isoproterenol needed to induce syncope.There were signifi cant correlations in BP/HR ratios between ABPM and the supine position in the vasodepressor group,while signifi cant correlation was found only for the diastolic BP/HR ratio between ABPM and the tilted position in the cardioinhibitory group.The mixed pattern shared correlative features of the other two patterns.Conclusion:ABPM and the simplistic tilt test might be used as promising alternatives to the HUTT in VVS evaluation in clinical settings.

The Changes of Baroreflex Sensitivity During Head-up Tilt Test and Its Clinical Significance in the Patients with Vasovagal Syncope

Objective To study thechanges of baroreflex sensitivity (BRS) during head - up tilt test (HUT) in patients with vasovagal syncope (VS), and to examine the relationship between baroreflex sensitivity and neurohormonal factors. Furthermore, to investigate the effects of the changes of BRS on VS. Methods Forty - two patients with unexplained syncope (Among the 42 patients, there were 22 patients with positive HUT and 20 patients with negative HUT respectively) and 20 healthy volunteers (with negative HUT) underwent passive head - up tilt testing, Ante-cubital vein blood samples were taken before and after HUT, or at syncope. The fasting plasma endothelin , serum nitric oxide (NO), serum NE were measured, the BRS was assessed on the basis of the linear regression slope the RR interval versus systolic arterial blood pressure during the increment in blood pressure after intravenous administration of phenylephrine. Results (1) During the syncope, the BRS significantly reduced in HUT(+) group than baseline. At the end of tilt, the level of plasma ET, serum NO in patients with positive HUT significantly increased compared with baseline or normal controls, and the plasma concentration of NE also had the trend of increase. (2) By multiple regression analysis, a significant negative correlation was found between baroreceptor sensitivity and the plasma ET, NO at the end of HUT in patients with positive HUT, but there was no relationship between BRS and NE. Conclusions During the syncope occure, the BRS in patients with VS decreased significantly compared with normal controls. The abnormal plasma ET, NO concen-tration might contribute to the mechanism of VS.

Age and mean platelet volume-based nomogram for predicting the therapeutic efficacy of metoprolol in Chinese pediatric patients with vasovagal syncope

Background Vasovagal syncope(VVS)is the most common type of orthostatic intolerance in children.We investigated whether platelet-related factors related to treatment efficacy in children suffering from VVS treated with metoprolol.Methods Metoprolol-treated VVS patients were recruited.The median duration of therapy was three months.Patients were followed and divided into two groups,treament-effective group and treatment-ineffective group.Logistic and least absolute shrinkage selection operator regressions were used to examine treatment outcome variables.Receiver-operating characteristic(ROC)curves,precision-recall(PR)curves,calibration plots,and decision curve analyses were used to evaluate the nomogram model.Results Among the 72 patients who complete the follow-up,treatment-effective group and treatment-ineffective group included 42(58.3%)and 30(41.7%)cases,respectively.The patients in the treatment-effective group exhibited higher mean platelet volume(MPV)[(11.0±1.0)fl vs.(9.8±1.0)fl,P<0.01]and platelet distribution width[12.7%(12.3%,14.3%)vs.11.3%(10.2%,12.2%),P<0.01]than those in the treatment-ineffective group.The sex ratio was significantly different(P=0.046).A fit model comprising age[odds ratio(OR)=0.766,95%confidence interval(CI)=0.594-0.987]and MPV(OR=5.613,95%CI=2.297-13.711)might predict therapeutic efficacy.The area under the curve of the ROC and PR curves was computed to be 0.85 and 0.9,respectively.The P value of the Hosmer-Lemeshow test was 0.27.The decision curve analysis confirmed that managing children with VVS based on the predictive model led to a net advantage ranging from 0.01 to 0.58.The nomogram is convenient for clinical applications.Conclusion A novel nomogram based on age and MPV can predict the therapeutic benefits of metoprolol in children with VVS.

Pathophysiology and Individualized Management of Vasovagal Syncope and Postural Tachycardia Syndrome in Children and Adolescents:An Update

Vasovagal syncope(VVS) and postural tachycardia syndrome(POTS) are the main forms of orthostatic intolerance in pediatrics and both are underlying causes of neurally-mediated syncope.In recent years,increasing attention has been paid to the management of VVS and POTS in children and adolescents.A number of potential mechanisms are involved in their pathophysiology,but the leading cause of symptoms varies among patients.A few studies thus have focused on the individualized treatment of VVS or POTS based on selected hemodynamic parameters or biomarkers that can predict the therapeutic effect of certain therapies and improve their effectiveness.This review summarizes the latest developments in individualized treatment of VVS and POTS in children and indicates directions for further research in this field.

Advance in the understanding of vasovagal syncope in children and adolescents

Background Vasovagal syncope(VVS)accounts for 60-80% of cases of neurally mediated syncope.VVS results from acute orthostatic intolerance and recurrent syncopal attacks,which can seriously affect an individual's quality of life.In addition,some children even experience trauma during attacks.Therefore,it is particularly important to clarify the pathogenesis of VVS.The aim of our study is to reveal the latest research progress of VVS.Data sources Literature that involved the pathogenesis of VVS were selected from Cochrane Library(1990-2019),EMBASE(1991-2019)and PubMed(1968-2019)databases.Results Hypovolemia,autonomic dysfunction,vasomotor dysfunction,baroreceptor reflex abnormalities,endothelial dys-function,serotonin surges,and gut microbiota were involved in the underlying mechanism of VVS.Conclusions VVS is not always a benign prognosis.Various aspects were involved in its pathogenesis.Bezold-Jarish reflex,dysfunction of the autonomic nervous system,genetic factors and so on played important roles in VVS;however,the mecha-nism remains unclear.

Cost-effectiveness of diagnostic approaches to vasovagal syncope in children and adolescents in China： a health economic analysis

Background Syncope is a common clinical problem with multiple causes. Vasovagal syncope （VVS） is by far the most frequent cause of syncope in children and adolescents. The traditional diagnostic approach to VVS of children and adolescents is based on a series of tests to exclude all other causes, which is complex and time and medical resource consuming. Attempts have been made to develop a new cost-effective diagnostic approach to avoid these problems. This study aimed to compare the economic effectiveness and diagnostic value of the traditional diagnostic approach to VVS of children with a new diagnostic approach. Methods One hundred and eighteen children diagnosed as VVS were divided into two groups according to the different diagnostic approaches. The diagnostic value of the two diagnostic approaches was then analyzed. Meanwhile, the costs of hospitalization, diagnostic testing and hospital stay were determined. Data were evaluated by the cost-minimization analysis. Results The diagnostic value of the new diagnostic approach was similar to that of the traditional diagnostic approach （56.57% vs. 53.91%, P=0.697）. However, the cost of hospitalization per patient by the new diagnostic approach was （1507.08±144.63） Yuan （RMB） which was less than that of the traditional diagnostic approach （2603.64±2.08.19） Yuan. The costs of diagnostic tests per patient by the new diagnostic approach was （1256.04±109.14） Yuan and by the traditional approach （2175.22±153.32） Yuan. Conclusion Compared to the traditional diagnostic approach to diagnose VVS in children and adolescents, the new diagnostic approach is of a good economic value, and it should be popularized in clinical practice.

Plasma Neuropeptide Y Levels in Vasovagal Syncope in Children

Background： Vasovagal syncope （VVS） is the most common cause of syncope in children. Neuropeptide Y （NPY） plays an important role in the regulation of blood pressure （BP）, as well as myocardial contractility. This study aimed to explore the role of plasma NPY in VVS in children. Methods： Fifty-six children who were diagnosed with VVS （VVS group） using head-up tilt test （HUT） and 31 healthy children who were selected as controls （control group） were enrolled. Plasma NPY concentrations were detected. The independent t-test was used to compare the data of the VVS group with those of the control group. The changes in plasma NPY levels in the VVS group during the HUT, as well as hemodynamic parameters, such as heart rate （HR）, BP, total peripheral vascular resistance （TPVR）, and cardiac output （CO）, were evaluated using the paired t-test. Furthermore, the correlations between plasma NPY levels and hemodynamic parameters were analyzed using bivariate correlation analysis. Results： The BP, HR, and plasma NPY （0.34 ± 0.12 pg/ml vs. 0.46 ± 0.13 pg/ml） levels in the supine position were statistically low in the VVS group compared to levels in the control group （all P 〈 0.05）. Plasma NPY levels were positively correlated with the HR （Pearson, R = 0.395, P 〈 0.001） and diastolic BP （Pearson, R = 0.311, P = 0.003） when patients were in the supine position. When patients in the VVS group were in the supine position, elevated TPVR （4.6 ± 3.7 mmHg·min-1·L-1 vs. 2.5 ± 1.0 mmHg·min-1·L-1, respectively, P 〈 0.001;1 mmHg = 0.133 kPa） and reduced CO （1.0 ± 0.7 L/min vs. 2.4 ± 1.3 L/min, respectively, P 〈 0.001） were observed in the positive-response period compared with baseline values. The plasma NPY levels were positively correlated with TPVR （Spearman, R = 0.294, P = 0.028） but negatively correlated with CO in the positive-response period during HUT （Spearman, R = -0.318, P = 0.017）. Conclusions： Plasma NPY may contribute to the pathogenesis of VVS by increasing the TPVR and decreasing the CO during orthostatic regulation.

Body mass index is a promising predictor of response to oral rehydration saline in children with vasovagal syncope

Background:Vasovagal syncope(VVS)greatly impairs quality of life.The therapeutic efficacy of oral rehydration saline(ORS)for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease.Body mass index(BMI)was demonstrated to reflect blood volume to a certain extent.Therefore,the present study explored the capability of BMI to predict the therapeutic response of children with VVS to ORS treatment.Methods:Seventy-four children with VVS who visited the Syncope Unit of Pediatrics at Peking University First Hospital from November 2010 to June 2019 receiving ORS treatment were enrolled for this retrospective case-control study.A comparison of demographic,clinical,and hemodynamic characteristics was performed between responders and non-responders.The correlation between baseline BMI and response time was analyzed.To determine the value of baseline BMI in predicting the therapeutic efficacy of ORS in children with VVS,a receiver operating characteristic curve analysis was performed.Results:Fifty-two children were identified as responders,and the remaining 22 children were identified as non-responders.The baseline BMI of the responders was much lower than that of the non-responders(16.4[15.5,17.8]kg/m2vs.20.7±3.6 kg/m2,P<0.001),and baseline BMI was positively correlated with response time in the head-up tilt test after adjusting for sex(r=0.256,95%confidence interval[CI]:0.067-0.439,P=0.029).The area under the receiver operating characteristic curve of baseline BMI was 0.818(95%CI:0.704-0.932,P<0.001),and an optimal cut-off value of 18.9 kg/m2 yielded a sensitivity of 83%and a specificity of 73%to predict the efficacy of ORS in VVS.Conclusion:Prior to treatment,baseline BMI is a promising predictor of response to ORS in children with VVS.

Age and Sex Distribution of Patients with Vasovagal Syncope Undergoing Head-up Tilt Table Test: 7-Year Audit

To investigate age and sex distribution of vasovagal syncope （VVS） patients undergoing head-up tilt table test （HUTT） at a tertiary hospital. The details of syncope patients who underwent HUTT at our department of cardiac function from January 2004 to December 2010 were reviewed. Of the 1 799 patients who underwent the HUTT, 854 tested positive, of which 558 （65.3%） were women, which were more than the women in the negative group （450, 47.6%） （p〈0.05）. VVS patients showed a bimodal age distribution between 11 and 20 years of age and in the fourth decade. In almost all age groups, mixed response was the highest compared with vasodepressor and cardioinhibitory. VVS patients who underwent HUTT indicate bimodal distribution peaking before the second decade and the fourth decade. The incidence of females was twice that of males before the sixth decade, and old age occupies a small percentage of VVS with no other comorbidities.

Minimal Vasovagal Dysautonomia in Patients with Rare or Unique Syncope

Introduction: It is common to find people sent to perform a Head Up Tilt Test (HUT) who suffered a single syncope, or syncopes that occur during certain periods and never appear again. We wonder how these people are different from those who have never had syncope. Methods: We found 300 patients who suffered only one (unique) or a maximum of 5 vasovagal syncopes during their life. And their HUT was positive for vasovagal dysautonomia. We compared them, with 120 healthy volunteers who have never had syncope. We try to explain how some constitutional predisposing factors act in these patients, and are associated with environmental triggers to precipitate the syncope. Results: We found differences between cases and controls in predisposing factors such as: heredity, joint hypermobility, baroreflex failure, venous compliance and some neurological diseases. Then an environmental factor acts as a trigger for syncope: prolonged standing, stress, pain and emotions, dehydration, use of certain drugs, abundant food. Conclusions: There are people with minimally expressed vasovagal dysautonomia who have an organic predisposition to present vasovagal syncopes (heredity, joint hypermobility, baroreflex failure, venous compliance, some neurological diseases, etc.). But this predisposition is not enough by itself to produce syncopes. One or more environmental factors must be added, acting as a trigger that would be the reason why these episodes are so infrequent.

Syncope Beginning in People Over 50 Years Old—Experience in 52 Cases

It is not common to start suffering from syncopes after age 50. They are mainly male patients who present causes other than vasovagal syncope, which predominates at an early age. Orthostatic hypotension is the predominant causal factor, which is attributed in many cases to advanced age, metabolic, cardiovascular or neurological diseases, to failure of baroreflexes, all of the above may be associated with the use of hypotensive drugs alone or in combination with psychotropic drugs. Furthermore, causes such as carotid sinus syncope, postprandial syncope and situational syncope become more frequent. Therefore, as people age, they present a favorable pathological terrain for the production of syncope. The older you are, the more likely you are to start with syncope. Finding the definitive diagnosis for their syncopes can be difficult, given the multiplicity of interacting factors. Their study is more exhaustive and requires a good anamnesis, knowing the drugs used by the patient, concomitant diseases and careful surveillance to get closer to the diagnosis.

Serious response during tilt-table test in elderly and its prophylactic management

Objective: To evaluate the serious response during tilt-table test (TTT) and its prophylactic management. Method: Seventy-six elderly patients were tested at a tilt angle of 70 degrees for a maximum of 45 min and then subjected to isoprotere- nol-provocative tilt testing. ECG and blood pressure were monitored during the test and patients were kept at normal saline con- dition through a peripheral intravenous duct. Results: Fifty-one of 76 patients were defined as positive including 23 having serious response; 6 of the 23 patients had arteriosclerosis involving internal carotid arteries and 7 cases had bradycardia, two of which were associated with II°-I A-V block and the others with chronic atrial fibrillation. The serious response consisted of cardiac arrest for more than 5 s (6 cases), or serious bradycardia for more than 1 min (7 cases) or serious hypotension for more than 1 min (10 cases). Those with serious response were managed by returning to supine position, thus driving up legs and intravenous atropine, CPR (2 cases with cardiac arrest) and needing oxygen supplementation (11 cases). Only 2 hypotension patients recovered gradually by 10 min after emergency management, while others recovered rapidly with no complications. Conclusion: Although non-invasive, TTT may result in serious response, especially in elderly. Therefore proper patient selection, control of isoproterenol infusion and close observation of vital signs are decisive for a safe consequence.