Vasovagal Syncope Patients Research Articles

A higher peak heart rate during head-up tilt test predicts the therapeutic efficacy of metoprolol in vasovagal syncope

BackgroundAlthough beta blockers, such as metoprolol, have been widely used in the management of vasovagal syncope (VVS), their efficacy remains debated, with larger studies showing limited benefit. Identifying patient-specific characteristics that predict a positive response to metoprolol could optimize its use. This study aims to investigate the key factors that may determine which VVS patients are suitable candidates for metoprolol treatment.MethodsThis retrospective study was conducted at a single center. Patients diagnosed with VVS and treated with metoprolol for a minimum of three months were included. A 50% reduction in syncope symptom score (SS) after three months of metoprolol treatment was used to define metoprolol responders, while those who did not achieve this reduction were classified as non-responders. After a three-month follow-up, patients were divided into two groups: responders and non-responders. Baseline data—including age, gender, comorbidities, laboratory tests, and the type of VVS—were analyzed for each patient. Changes in heart rate (HR) and blood pressure during the head-up tilt test (HUTT) were also evaluated between the two groups. Logistic regression analysis was performed to identify potential predictors of metoprolol response, and receiver operating characteristic (ROC) curve analysis was used to assess the value of these predictors in selecting potential responders.ResultsA total of 168 VVS patients were enrolled between January 2016 and December 2020. Of these, 100 patients responded positively to metoprolol, while 68 did not. No significant differences in baseline characteristics or HUTT results were observed between the two groups (p > 0.05). However, responders exhibited a significantly higher peak HR compared to non-responders during the HUTT (120.13 ± 19.33 vs. 106.60 ± 22.32, p < 0.001). The increase in HR was also more pronounced in responders (0.60 ± 0.23 vs. 0.41 ± 0.25, p < 0.001). Additionally, HR variability was significantly greater in responders than in non-responders (16.18 ± 5.51 vs. 12.61 ± 5.50, p < 0.001).ConclusionHigher peak HR, larger increases in HR, and greater HR variability during the HUTT may serve as reliable predictors of a positive response to metoprolol in patients with VVS.

Normal baseline cardiac autonomic function and increased pupillary parasympathetic tone in patients with vasovagal syncope.

It is controversial whether people with vasovagal syncope (VVS) have abnormal autonomic responses at baseline and whether specific diagnostic manoeuvres have a diagnostic value. We investigated whether the pupillary light reflex and cardiac autonomic tests can be used to identify autonomic dysfunction in volunteers with a medical history of VVS. The study groups included 128 healthy volunteers, of whom 31 reported a history of typical VVS. The right pupil was evaluated using an automated, commercial infra-red pupillometer under strict conditions. In addition to miosis and mydriasis kinetics, pupil diameters were measured. Heart rate variability at rest and heart rate changes to standing were quantified with high-resolution electrocardiography and designated software. The demographic and clinical characteristics of both groups were statistically similar. Average constriction velocity (ACV) was significantly higher in VVS patients following a univariate analysis (3.83 ± 0.59vs. 3.56 ± 0.73 mm/s, p = 0.042) and after correcting for potential confounders (p = 0.049). All other pupillometric and heart rate indices were comparable between groups. Patients with a history of VVS depict pupillary parasympathetic overactivity in response to light stimuli, manifested as increased ACV. The prognostic implications of this finding and the significance of using this simple clinical tool to identify patients who are at risk for developing frequent episodes of VVS or physical injuries following a syncope merits further study.

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

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. Metoprolol-treated VVS patients were recruited. The median duration of therapy was threemonths. 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. 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. A novel nomogram based on age and MPV can predict the therapeutic benefits of metoprolol in children with VVS.

Cardioneuroablation for the management of patients with recurrent vasovagal syncope and symptomatic bradyarrhythmias: the CNA-FWRD Registry.

Cardioneuroablation has been emerging as a potential treatment alternative in appropriately selected patients with cardioinhibitory vasovagal syncope (VVS) and functional AV block (AVB). However the majority of available evidence has been derived from retrospective cohort studies performed by experienced operators. The Cardioneuroablation for the Management of Patients with Recurrent Vasovagal Syncope and Symptomatic Bradyarrhythmias (CNA-FWRD) Registry is a multicenter prospective registry with cross-over design evaluating acute and long-term outcomes of VVS and AVB patients treated by conservative therapy and CNA. The study is a prospective observational registry with cross-over design for analysis of outcomes between a control group (i.e., behavioral and medical therapy only) and intervention group (Cardioneuroablation). Primary and secondary outcomes will only be assessed after enrollment in the registry. The follow-up period will be 3years after enrollment. There remains a lack of prospective multicentered data for long-term outcomes comparing conservative therapy to radiofrequency CNA procedures particularly for key outcomes including recurrence of syncope, AV block, durable impact of disruption of the autonomic nervous system, and long-term complications after CNA. The CNA-FWRD registry has the potential to help fill this information gap.

Plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine

BackgroundOrthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine.MethodsPlasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis.ResultsA total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05).ConclusionsThe levels of choline-related metabolites and glutamate–related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance.

Brain MRI and EEG overemployment in patients with vasovagal syncope: results from a tertiary syncope unit

BackgroundThe diagnosis of vasovagal syncope (VVS) is mainly based on history-taking and physical examination. However, brain Magnetic Resonance Imaging (MRI) and Electroencephalogram (EEG) are commonly used in the diagnostic course of VVS, despite not being indicated in the guidelines. This study aims to find the possible associated factors with the administration of brain MRI and EEG in patients with VVS.MethodsPatients with a diagnosis of VVS from 2017 to 2022 were included. Several demographic and syncope features were recorded. The association of these was assessed with undergoing MRI, EEG, and either MRI or EEG. Univariate and multivariable logistic regression models were also used to calculate odds ratios (OR) and 95% confidence intervals (CI).ResultsA total of 1882 patients with VVS were analyzed, among which 810 underwent MRI (43.04%), 985 underwent EEG (52.34%), and 1166 underwent MRI or EEG (61.96%). Head trauma (OR 1.38, 95% CI 1.06 to 1.80), previous neurologist visit (OR 6.28, 95% CI 4.24 to 9.64), and gaze disturbance during syncope (OR 1.75, 95% CI 1.13 to 2.78) were all positively associated to the performance of brain MRI/EEG. Similar results were found for urinary incontinence (OR 2.415, 95% CI 1.494 to 4.055), amnesia (OR 1.421, 95% CI 1.053 to 1.930), headache after syncope (OR 1.321, 95% CI 1.046 to 1.672), and tonic-clonic movements in head-up tilt table test (OR 1.501, 95% CI 1.087 to 2.093). However, male sex (OR 0.655, 95% CI 0.535 to 0.800) and chest pain before syncope (OR 0.628, 95% CI 0.459 to 0.860) had significant negative associations with performing brain MRI/EEG.ConclusionBased on our findings, performing MRI or EEG was common among VVS patients while it is not indicated in the majority of cases. This should be taken into consideration to prevent inappropriate MRI/EEG when there is a typical history compatible with VVS.

Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study

Serum uric acid (UA) level has been proven to be related to several cardiovascular and metabolic diseases. In the present study, we examined if baseline serum UA level could predict the therapeutic efficacy of midodrine hydrochloride on vasovagal syncope (VVS) in children. The pediatric VVS patients who received midodrine hydrochloride from November 2008 to October 2022 were enrolled. After a median treatment duration of 3 months, the therapeutic effect was evaluated. According to the patients’ responses to midodrine hydrochloride, which was determined by the recurrence of syncope, they were divided into effective and ineffective groups. The baseline variables were explored using univariable and multivariate logistic analysis. The predictive efficacy was assessed by receiver operating characteristic curve (ROC), precision-recall curve (PR), Hosmer–Lemeshow test, calibration curve, and decision curve analysis (DCA). Totally, 53 participants were included in the study. Among the 51 patients who were successfully followed up, 29 (56.9%) responded to midodrine hydrochloride (effective group), and the other 22 (43.1%) failed to respond to midodrine hydrochloride (ineffective group). The participants in effective group had lower baseline serum UA level than those in ineffective group (276.5 ± 73 μmol/L vs. 332.7 ± 56 μmol/L, p = 0.004). Multivariable logistic analysis showed that serum UA was associated with the therapeutic response (odds ratio (OR): 0.985, 95% confidence interval (CI): 0.974–0.997, p = 0.01). ROC analysis indicated that using baseline serum UA < 299 μmol/L as a threshold value yielded a sensitivity of 77.3% and a specificity of 79.3% in predicting the treatment response to midodrine hydrochloride. The area under the PR curve was 0.833. Hosmer–Lemeshow test yielded a p value of 0.58, and calibration plot indicated that the model was well-fitted. DCA demonstrated that treatment decision depending on the baseline serum UA level resulted in a favorable net benefit. Conclusion: This pilot study suggested that the baseline serum UA level could be taken as a predictor of therapeutic effect of midodrine hydrochloride on VVS in children.What is Known:• Empirical and unselected use of midodrine hydrochloride has an unfavorable therapeutic effect on VVS in children. Serum uric acid (UA) is closely linked to cardiovascular events.What is New:• A low baseline serum UA level successfully predicts the therapeutic effectiveness of midodrine hydrochloride on VVS in children.

Characteristics of deceleration capacity and deceleration runs in vasovagal syncope.

Increased vagal activity plays a prominent role in vasovagal syncope (VVS). The aim of this study was to characterize vagal function in VVS by evaluating the heart rate (HR) deceleration capacity (DC) and the HR deceleration runs (DRs) in patients with VVS between attacks. A total of 188 consecutive VVS patients were enrolled in the study, of whom 129 had positive head-up tilt test (HUTT); 132 healthy participants were enrolled as controls. DC, DRs (DR2, i.e., episodes of 2 consecutive beat-to-beat HR decelerations), and the sum of DR8-10 (very long DR [VLDR]) were calculated using 24-h electrograms. Clinical characteristics, DC, and DRs were compared among syncope groups and controls. Patients with VVS had higher DC (10.63 ± 2.1 vs. 6.58 ± 1.7ms; P < 0.001) and lower minimum HR and DR6-10 than controls. No significant differences in DC or DR6-10 were found between the patients with positive and those with negative HUTT results. In multivariate logistic regression analysis, minimum HR ≥ 40bpm (odds ratio [OR] 0.408, 95% confidence interval [CI] 0.167-0.989; P = 0.048), daytime DC ≥ 7.37ms (OR 3.040, 95% CI 1.220-7.576; P = 0.013), and VLDR ≥ 0.046% (OR 0.306, 95% CI 0.138-0.679; P = 0.004) were demonstrated to be risk factors significantly associated with VVS. Compared to healthy controls, patients with VVS demonstrated distinct HR deceleration profiles between attacks, including overall higher DC and lower DR6-10.

Cerebral Oxygenation Responses to Standing in Young Patients with Vasovagal Syncope.

Vasovagal syncope (VVS) is common in young adults and is attributed to cerebral hypoperfusion. However, during active stand (AS) testing, only peripheral and not cerebral hemodynamic responses are measured. We sought to determine whether cerebral oxygenation responses to an AS test were altered in young VVS patients when compared to the young healthy controls. A sample of young healthy adults and consecutive VVS patients attending a Falls and Syncope unit was recruited. Continuous beat-to-beat blood pressure (BP), heart rate, near-infrared spectroscopy (NIRS)-derived tissue saturation index (TSI), and changes in concentration of oxygenated/deoxygenated Δ[O2Hb]/Δ[HHb] hemoglobin were measured. BP and NIRS-derived features included nadir, peak, overshoot, trough, recovery rate, normalized recovery rate, and steady-state. Multivariate linear regression was used to adjust for confounders and BP. In total, 13 controls and 27 VVS patients were recruited. While no significant differences were observed in the TSI and Δ[O2Hb], there was a significantly smaller Δ[HHb] peak-to-trough and faster Δ[HHb] recovery rate in VVS patients, independent of BP. A higher BP steady-state was observed in patients but did not remain significant after multiple comparison correction. Young VVS patients demonstrated a similar cerebral circulatory response with signs of altered peripheral circulation with respect to the controls, potentially due to a hyper-reactive autonomic nervous system. This study sets the grounds for future investigations to understand the role of cerebral regulation during standing in VVS.

Association between vitamin D deficiency and vasovagal syncope: A systematic review and meta-analysis.

Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have investigated vitamin D levels in VVS patients. In this systematic review and meta-analysis, we aim to review these studies to find possible associations between vitamin D deficiency and vitamin D levels with VVS. International databases including Scopus, Web of Science, PubMed, and Embase were searched with keywords related to "vasovagal syncope" and "vitamin D." Studies were screened and the data were extracted from them. Random-effect meta-analysis was conducted to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for vitamin D levels in comparison to VVS patients and controls. Also, VVS occurrence was measured and the odds ratio (OR) and 95% CI were calculated for comparison of vitamin D deficient cases and nondeficient individuals. Six studies were included with 954 cases investigated. Meta-analysis showed that patients with VVS had significantly lower vitamin D serum levels in comparison to non-VVS cases (SMD -1.05, 95% CI -1.54 to -0.57, p-value < .01). Moreover, VVS occurrence was higher in vitaminD-deficient individuals (OR 5.43, 95% CI 2.40 to 12.27, p-value < .01). Our findings which show lower vitamin D levels in VVS patients can have clinical implications in order for clinicians to pay attention to this when approaching VVS. Further randomized controlled trials are certainly warranted to assess the role of vitamin D supplementation in individuals with VVS.

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

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. 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. 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. 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.

Risk factors associated with malignant vasovagal syncope in children

Objective: To analyze the clinical characteristics and risk factors of malignant vasovagal syncope (VVS) in children. Methods: This was a case-control study. The data of 368 VVS patients who were treated in the Department of Cardiology, Children's Hospital, Capital Institute of Pediatrics from June 2017 to December 2021 was collected and analyzed. They were divided into malignant VVS group and non-malignant VVS group according to the presence of sinus arrest, and then their demographic characteristics were compared. The children with malignant VVS and complete clinical information were recruited into the case group and were matched by age and sex (1∶4 ratio) with non-malignant VVS patients during the same period.Their clinical characteristics and lab tests were compared. Independent sample t test, Mann Whitney U or χ2 test was used for comparison between groups.Logistic regression was used to analyze the risk factors for malignant VVS in children. Results: Eleven malignant VVS and 342 non-malignant VVS met the inclusion and exclusion critera. Eleven malignant VVS and 44 non-malignant children were recruited in the case-control study. Ten patients of the 11 malignant VVS had a cardiac arrest occurring at 35 (28, 35) minutes of the head-up tilt test, and the duration of sinus arrest was (9±5) s. One patient had syncope occurring while waiting for drawing blood, and the duration of sinus arrest was 3.4 s. The children with malignant vasovagal syncope were younger than non-malignant VVS patients (9 (7, 10) vs. 12 (10, 14) years old, P<0.05), and had higher mean corpuscular hemoglobin concentration (MCHC) and standard deviation of the mean cardiac cycle over 5-minute period within 24 hours ((347±9) vs. (340±8) g/L, (124±9) vs. (113±28) ms, both P<0.05). Logistic regression analysis showed that MCHC was an independent risk factor for malignant VVS in pediatric patients (OR=1.13, 95%CI 1.02-1.26, P=0.024). Conclusions: The onset age of malignant VVS was younger, with no other special clinical manifestations. MCHC was an independent risk factor for malignant VVS.

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

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

Anxiety and Depression as Risk Factors for Vasovagal Syncope and Potential Treatment Targets: A Systematic Review.

Vasovagal syncope (VVS) is a transient, sudden loss of consciousness followed by complete resolution, usually due to a paradoxical autonomic reaction that results in hypotension and/or bradycardia. In this study, we assessed the correlation between VVS and a patient's psychiatric status, as well as if this association could be a target in the treatment of those patients. We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the available literature using the following databases: PubMed, Google Scholar, and ScienceDirect, with last access on July 21, 2022. The search resulted in 1691 articles, and inclusion and exclusion criteria were applied to nine remaining articles, all of which were accepted after using the quality assessment tools, four observationaland four randomized controlled trials (RCTs). Four of the included studies assessed the correlation among vasovagal syncope, psychosocial impairment, and quality of life. We found a consistent correlation among VVS, psychosocial impairment, and quality of life (QoL), meaning that VVS patients usually have some degree of psychosocial impairment, especially in the form of anxiety and depression, and a poorer QoL in comparison to their healthy counterparts. The use of psychotherapy and antidepressants was proven to be effective in VVS in RCTs, but further evidence is needed.

Can Vitamin B12 Deficiency Really Cause Vasovagal Syncope? Retrospective Analysis of 469 Pediatric Vasovagal Syncope Cases

Objective: Syncope is a frequent reason for referral to pediatric cardiology clinics. Vitamin B12 deficiency is frequently diagnosed in pediatric patients. In this study, we determined the frequency of vitamin B12 deficiency in pediatric vasovagal syncope (VVS). Methods: This study was designed retrospectively. VVS patients were identified from the hospital registry system with ICD code ‘R55, syncope, and fainting’. The frequency of VVS and vitamin B12 levels of the patients were evaluated. Below 200 ng/L was considered vitamin B12 deficiency. Results: Eight hundred twelve patients were identified with ICD code R55, syncope, and fainting’ in pediatric cardiology hospital records. Two hundred sixteen patients were excluded from the study due to insufficient hospital records. Four hundred and sixty-nine patients were diagnosed with VVS. One hundred and seventy-three patients were excluded from the study because of non-available vitamin B12 level. Ninety-six patients had epileptic sezure/suspected VVS, 28 patients had psychogenic syncope and 3 patients had cardiac syncope. Demographic characteristics, hemoglobin and vitamin B12 levels, and the frequency of vitamin B12 deficiency were similar in the patient and control groups (p&gt;0.05). Two hundred and sixty-four patients had normal vitamin B12 level, whereas 32 patients were diagnosed with vitamin B12 deficiency. Fifty-six patients who had normal vitamin B12 levels experienced frequent VVS and 6 patients with vitamin B12 deficiency experienced frequent VVS (21.2% vs 23.0%, p&gt;0.05). Conclusion: Although VVS can cause serious concern in patients and families, it is unlikely to be a serious underlying disease. Vitamin B12 deficiency was not found at a high rate in this disease as in other studies.

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

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

Cerebrovascular regulation in patients with vasovagal syncope and autonomic failure due to familial amyloidotic polyneuropathy.

While there is strong evidence for autonomic involvement in cerebrovascular function acutely, long-term role of autonomic nervous system in cerebrovascular function has been controversial. We assessed autoregulation in 10 healthy individuals, nine patients with vasovagal syncope (VVS), and nine with Familial Amyloidotic Polyneuropathy (FAP), in response to head-up tilt test (HUTT). Arterial blood pressure heart rate, cardiac output, and bilateral cerebral blood flow velocity (CBFV) at the M1 segment of middle cerebral artery (transcranial Doppler ultrasound) were recorded during supine rest and 70° HUTT. Autoregulation was quantified using a validated nonlinear and nonparametric approach based on projection pursuit regression. Plasma adrenaline and noradrenaline were also measured at rest and during HUTT. During supine rest and HUTT, plasma noradrenaline content was lower in FAP patients. During HUTT, VVS patients had a hyperadrenergic status; CBFV decreased in all groups, which was greater in FAP patients (p<0.01). Healthy controls responded to HUTT with a reduction in CBFV responses to increases (p=0.01) and decreases (p<0.01) in arterial pressure without any change in the range or effectiveness of autoregulation. VVS patients responded to HUTT with a reduction in falling (p=0.02), but not rising slope (p=0.40). Autoregulatory range (p<0.01) and effectiveness increased (p=0.09), consistent with the rapid increase in levels of catecholamines. In FAP patients, the level of increase in range of autoregulation was significantly related to the magnitude of increase in plasma noradrenaline in response to HUTT (R2=0.26, p=0.05). Autonomic dysfunction affects the cerebral autoregulatory response orthostatic to challenge.

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

Background and objectiveHead-up tilt test (HUTT) is clinically advantageous for diagnosing patients with vasovagal syncope (VVS). Nitroglycerin is mainly used as a stimulant during HUTT, and mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in the metabolism of nitroglycerin (NTG). ALDH2 Glu487Lys polymorphism (ALDH2 rs671) is the most common variant in the East Asian population. This study aimed to assess the effects of ALDH2 rs671 on VVS patients undergoing HUTT supplemented with sublingual NTG (HUTT-NTG). MethodsPatients with recurrent VVS (at least 2 times) who were admitted to the syncope center of our hospital were enrolled. All VVS patients have undergone HUTT. The polymorphism of Glu487Lys gene of ALDH2 was measured by the DNA Microarray Chip Method. The results of HUTT-NTG of VVS patients with different ALDH2 genotypes were compared and their hemodynamic characteristics were assessed.ResultsA total of 199 VVS patients were enrolled, including 101 patients in the ALDH2*1/*1 group and 98 patients in the ALDH2*2 group. Among patients undergoing HUTT-NTG, 70.3% of patients in the ALDH2*1/*1 group and 68.4% of patients in the ALDH2*2 group were positive, and the difference between the two groups was not statistically significant (P = 0.77). The proportions of VASIS I, VASIS II, and VASIS III were 40.6%, 8.9%, and 20.8% in the ALDH2*1/*1 group, respectively, and the corresponding proportions in the ALDH2*2 group were 36.7%, 11.2%, and 20.4%, respectively. There was no statistically significant difference between the two groups (P = 0.91). The hemodynamic characteristics of different genotypes in VVS patients undergoing HUTT-NTG were compared, and no statistically significant difference was found. The median time of syncopal episode occurred after NTG administration in the ALDH2*1/*1 group was 6 min (interquartile range [IQR]: 5.0–9.0), and it was 6.0 min in the ALDH2*2 group (IQR: 4.25–8.0, P = 0.64).ConclusionALDH2 Glu487Lys polymorphism did not affect the outcome of VVS patients undergoing HUTT-NTG, and no significant change in the hemodynamic characteristics of different genotypes was found.

Plasma human growth cytokines in children with vasovagal syncope.

PurposeThe study was designed to investigate the profile of plasma human growth cytokines in pediatric vasovagal syncope (VVS).Materials and methodsIn the discovery set of the study, plasma human growth cytokines were measured using a Quantiboby Human Growth Factor Array in 24 VVS children and 12 healthy controls. Scatter and principal component analysis (PCA) diagrams were used to describe the samples, an unsupervised hierarchical clustering analysis was used to categorize the samples. Subsequently, the cytokines obtained from the screening assays were verified with a suspension cytokine array in the validation set of the study including 53 VVS children and 24 controls. Finally, the factors associated with pediatric VVS and the predictive value for the diagnosis of VVS were determined.ResultsIn the discovery study, the differential protein screening revealed that the plasma hepatocyte growth factor (HGF), transforming growth factor b1 (TGF-b1), insulin-like growth factor binding protein (IGFBP)-4, and IGFBP-1 in children suffering from VVS were higher than those of the controls (all adjust P- value < 0.05). However, the plasma IGFBP-6, epidermal growth factor (EGF), and IGFBP-3 in pediatric VVS were lower than those of the controls (all adjust P- value < 0.01). Meanwhile, the changes of 7 differential proteins were analyzed by volcano plot. Unsupervised hierarchical cluster analysis demonstrated that patients in the VVS group could be successfully distinguished from controls based on the plasma level of seven differential proteins. Further validation experiments showed that VVS patients had significantly higher plasma concentrations of HGF, IGFBP-1, and IGFBP-6, but lower plasma concentrations of EGF and IGFBP-3 than controls. The logistics regression model showed that increased plasma concentration of HGF and IGFBP-1 and decreased plasma concentration of EGF were correlated with the development of pediatric VVS. ROC curve analysis showed that the abovementioned 3 proteins were useful for assisting the diagnosis of VVS.ConclusionPlasma human growth cytokine profiling changed in pediatric VVS. Elevated plasma concentrations of HGF and IGFBP-1, and decreased EGF were associated factors in the development of pediatric VVS. The abovementioned three proteins are helpful for the diagnosis of pediatric VVS.

Calcitonin gene-related peptide predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope.

The vasoconstriction agent midodrine hydrochloride is a vital treatment for pediatric patients diagnosed with vasovagal syncope (VVS), although the efficacy is variable. This study was designed to explore the value of calcitonin gene-related peptide (CGRP) in predicting the effect of midodrine hydrochloride treatment upon VVS patients. In total, 55 children diagnosed with VVS were treated with midodrine hydrochloride for 3 months. Therapeutic response was evaluated using a symptom score system. CGRP levels were significantly higher in VVS patients (68.700 ± 6.460) than in control subjects (43.400 ± 5.810; t = 18.207, P < 0.001) and symptom scores correlated positively with CGRP concentrations (r = 0.779, P < 0.001). Patients treated with midodrine hydrochloride showed a significant reduction in symptom scores [4 (0, 6.5) vs. 1 (1, 2); z = –6.481; P < 0.001]. However, the value of plasma CGRP were potently elevated in the positive-response subjects than in the negative-response subjects (70.080 ± 5.040) vs. (61.150 ± 3.090); t = 5.817; P < 0.001). The area under the ROC curve showed that the value of CGRP for predicting the therapeutic response to midodrine hydrochloride was 0.946 (95% CI: 0.879–0.997, P < 0.001). With high sensitivity (97.7%) and specificity (83.3%), CGRP predicted the therapeutic response to midodrine hydrochloride (cut-off value, 62.56 pg/ml). In conclusion, CGRP can be used to predict the effect of midodrine hydrochloride administration in VVS patients.