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Background: There is no universally followed protocol for managing Reflex Vasovagal syncope (VVS)., Methods: VVS patients were treated with a 2 step protocol. Step I - counseling, hydration, physiotherapy, and Tadasana Yoga maneuver. Patients with ≥2 VVS recurrences were given step II care - intensification of step I, elastic stockings,and pharmacotherapy. Follow-up included assessment by periodic functional status questionnaires., Results: 157 patients (103 males & 54 females,mean age - 53 ± 20 years & mean LVEF - 62 ± 5%.) experienced 867 total events - 382 syncopal, and 485 near syncopal episodes over 14 ± 9 months. After step I protocol, the mean total, syncopal and near syncopal events declined from 5 ± 7 to 0.3 ± 1.2 (P < 0.0001), 3 ± 2 to 0.1 ± 0.4 (P < 0.0001) and 3 ± 6 to 0.2 ± 1.1 (P < 0.0001) respectively. Twenty (12.7%) patients had 53 event recurrences, 15- syncopal episodes in 7 and 38 near syncope events in 13. After step II, 5 patients had 14 events. At 33 ± 15 months, in 152 patients (96.8%) there were no recurrences and syncope was prevented in all (100%). The median total, syncopal and near syncopal events declined from 3 to 0,(p < 0.001) 2 to 0 (p < 0.001) and 1 to 0 (p < 0.001) respectively. There was an improvement in all the 3 quality of life parameters., Conclusion: We demonstrate a simple and effective protocol that can be universally adopted to prevent VVS recurrences,with improvement in quality of life., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 ± 0.59 vs. 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., (© 2024 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Catheter-based neuromodulation of intrinsic cardiac autonomic nervous system is increasingly being used to improve outcomes in patients with vasovagal syncope and bradyarrhythmias caused by vagal overactivity. However, there is still no consensus for patient selection, technical steps, and procedural end points. This review takes the reader on a practical exploration of neuromodulation for bradyarrhythmias, concentrating on the critical aspects of proper patient selection, evidence-based insights, and anatomic intricacies within the intrinsic cardiac autonomic nervous system. Also discussed are different mapping techniques and outcome measures. Future directions to optimize the utilization of this technique in clinical practice are highlighted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The mechanism of vasovagal syncope (VVS) is multifaceted and involves a delicate balance within the autonomic nervous system (ANS). This review delves into the complex interplay between the ANS and VVS, elucidating the pivotal role that autonomic imbalance plays in the pathophysiology of this condition. Through a comprehensive exploration of the sympathetic and parasympathetic branches of the ANS, this review provides insights into the mechanisms that underlie VVS. In addition, this article discusses established and emerging research on the management of VVS., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

To determine whether young women who have experienced typical vasovagal syncope (tVVS) have altered autonomic response parameters, based on a battery of autonomic tests and maneuvers. Notably, previous studies including small cohorts and a partial list of tests yielded conflicting results. A total of 91 otherwise healthy women were included and divided according to those who had experienced tVVS (39 patients) or not (52 patients). Heart rate variability was evaluated at rest, under strict conditions, during 5 min of standing and during a deep breathing test. Response to Valsalva maneuver and Ewing maneuver were also quantified and compared. Both groups had similar clinical characteristics at baseline. No significant differences were found between the two groups in any of the autonomic parameters evaluated. Autonomic responses in young women who experienced typical vasovagal syncope at baseline were indistinguishable from those who did not. Thus, using non-tilt test autonomic screening tests does not seem to provide diagnostic benefits, and may not be useful in predicting recurrence in this patient population., (© 2024. The Author(s).)

Purpose: The goal of this manuscript was to review the biological and clinical evidence that serotonin neurotransmission might play an important role in the  physiology and treatment of vasovagal syncope., Methods: The authors reviewed PubMed and handsearches of secondary sources for papers related to the Bezold-Jarisch reflex and serotonin, the plausible involvement of the Bezold-Jarisch reflex in vasovagal syncope, and three lines of clinical evidence involving serotonin and the syncope., Results: The Bezold-Jarisch reflex was first described following the infusion of veratrum alkaloids into animals in the 19th century. The reflex is triggered by serotonin stimulation chemoreceptors and mechanoreceptors in the the left ventricle. The afferent component of the reflex is carried by unmyelinated type C vagal nerve fibers, which results in parasympathetic efferent stimulation that causes bradycardia. The similarity of the combination of hypotension and bradycardia in the Bezold-Jarisch reflex and in vasovagal syncope led to the suggestion that the reflex was the cause of the syndrome.  Three lines of evidence implicate the serotonin 5HT3 receptors in the heart in the reflex. There is genetic and physiologic evidence for the serotonin 5HT1A and 5HT3 receptors and the serotonin reuptake transporter (SERT). Acute blockade of SERT induces vasovagal syncope in humans undergoing head-up tilt table testing, and SERT inhibition reduces hypotension and bradycardia during spinal anaesthesia. Finally, three randomized clinical trials of SERT inhibitors uniformly reported that they significantly reduce the likelihood of vasovagal syncope recurrences., Conclusion: Multiple lines of evidence implicate serotonin neurotransmission in the cause of vasovagal syncope., (© 2024. Springer-Verlag GmbH Germany.)

Objective: Syncope is a transient loss of consciousness resulting from cerebral hypoperfusion. Vasovagal syncope (VVS) is a form of orthostatic intolerance (OI). Its clinical signs such as dizziness and hypotension may mimic symptoms of adrenal insufficiency. The objective of this study was to evaluate the adrenal gland function in patients with vasovagal syncope after stimulation with synthetic adrenocorticotropic hormone (ACTH)., Design: Case-control study on patients with VVS and healthy controls., Methods: The study involved 42 participants, including 27 patients diagnosed with VVS using the head-up tilt test and 15 healthy individuals with no history of syncope or any orthostatic symptoms. Serum cortisol and aldosterone concentrations were measured under basal conditions and at 30 and 60 min after intramuscular ACTH stimulation., Results: Patients with VVS had significantly higher cortisol levels at baseline (441 ± 143 vs. 331 ± 84.7 nmol/L, p = 0.01), at 30 min (802 ± 143 vs. 686 ± 105 nmol/L, p = 0.01) and at 60 min (931 ± 141 nmol/L vs. 793 ± 147 nmol/L, p = 0.001) after ACTH administration (Synacthen 250 μg). Plasma aldosterone increased after ACTH stimulation, but did not show significant differences among groups. Furthermore, there was also no significant correlation between cortisol levels and blood pressure or heart rate., Conclusion: Patients diagnosed with VVS have higher cortisol levels both at baseline and after ACTH stimulation. This finding indicates that individuals with VVS have higher adrenocortical activity potentially as a response to the orthostatic stress induced by syncope, which acts as a stressful stimulus on the autonomic nervous system., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The compensatory mechanisms supporting cerebral perfusion throughout head-up tilt (HUT) in patients with vasovagal syncope (VVS) remain unclear. We tested the hypothesis that increased cerebrovascular compliance (Ci) and decreased cerebrovascular resistance (CVR) support cerebral blood velocity (CBV) during pre-syncope in VVS., Methods: Finger arterial blood pressure (ABP) and right middle cerebral artery blood velocity (CBV) were recorded in 15 individuals diagnosed with VVS (n = 11 female, mean age: 40 ± 16 years, mean body mass index: 24.9 ± 4.0 kg/m 2 ) at supine rest and during HUT (80 degree angle). Individual ABP and CBV waveforms during VVS were input into a modified Windkessel model to calculate Ci and ohmic CVR. Gosling's pulsatility index (Pi; pulse amplitude/mean CBV) was calculated., Results: Diastolic ABP, systolic ABP, mean ABP (72 ± 11 to 51 ± 12 mmHg), and CVR decreased progressively during presyncope (all P ≤ 0.04). As expected, systolic CBV was sustained (all P ≥ 0.29) while diastolic and mean CBV (51 ± 13 to 38 ± 13 mmHg) fell during presyncope (all P ≤ 0.04). Both Ci and Pi increased during presyncope (128 ± 97 and 60 ± 41%, respectively; all P ≤ 0.049) and were positively correlated (R 2  = 0.79, P < 0.01). Increased Ci contributed to changes in mean CBV (P < 0.01) but decreased CVR did not (P = 0.28)., Conclusions: These data provide evidence that Ci increases during presyncope in patients with VVS and is likely involved in the maintenance of systolic CBV during a fall in diastolic CBV. However, this regulation is not sufficient to preserve CBV in the presence of such extreme and progressive reductions in ABP., (© 2024. Springer-Verlag GmbH Germany.)

Aims: Cardioneuroablation (CNA) is a catheter-based intervention for recurrent vasovagal syncope (VVS) that consists in the modulation of the parasympathetic cardiac autonomic nervous system. This survey aims to provide a comprehensive overview of current CNA utilization in Europe., Methods and Results: A total of 202 participants from 40 different countries replied to the survey. Half of the respondents have performed a CNA during the last 12 months, reflecting that it is considered a treatment option of a subset of patients. Seventy-one per cent of respondents adopt an approach targeting ganglionated plexuses (GPs) systematically in both the right atrium (RA) and left atrium (LA). The second most common strategy (16%) involves LA GP ablation only after no response following RA ablation. The procedural endpoint is frequently an increase in heart rate. Ganglionated plexus localization predominantly relies on an anatomical approach (90%) and electrogram analysis (59%). Less utilized methods include pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Post-CNA, anticoagulation or antiplatelet therapy is prescribed, with only 11% of the respondents discharging patients without such medication. Cardioneuroablation is perceived as effective (80% of respondents) and safe (71% estimated <1% rate of procedure-related complications). Half view CNA emerging as a first-line therapy in the near future., Conclusion: This survey offers a snapshot of the current implementation of CNA in Europe. The results show high expectations for the future of CNA, but important heterogeneity exists regarding indications, procedural workflow, and endpoints of CNA. Ongoing efforts are essential to standardize procedural protocols and peri-procedural patient management., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

There is a perceived need to express concisely the advice of guidelines in the context of consideration of invasive management of highly symptomatic vasovagal syncope. In response to this need the table is presented as a checklist and the text adds explanation and details. It is anticipated that this will prove to be of value for clinicians., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardioneuroablation (CNA) targets the intrinsic cardiac autonomic nervous system ganglionated plexi located in the peri-atrial epicardial fat. There is increasing interest in CNA as a treatment of vasovagal syncope (VVS), despite no randomized clinical trial (RCT) data., Objective: The purpose of this study was to poll the opinion on CNA) for VVS., Methods: A REDCap (Research Electronic Data Capture) survey was administered to international physicians treating patients with VVS on their opinion about patient selection criteria, ablation approach, RCT design, and most appropriate end points for CNA procedures., Results: The survey was completed by 118 physicians; 86% were cardiac electrophysiologists. The majority of respondents (79%) would consider referring a patient with refractory VVS for CNA, and 27% have performed CNA for VVS themselves. Most felt patient selection should require a head-up tilt test with a cardioinhibitory response (67%) and suggest a minimum age of 18 years with a median of 3 (interquartile range 2-5) episodes in the past year. There were differences in patient selection between physicians who have performed CNA themselves and those who have not. The majority felt that the ablation strategy should include both atria (70%) with an anatomical approach in combination with autonomic stimulation (85%). Performing a sham procedure in the control arm was supported by 56% of respondents, providing equipoise in RCT design. The preferred primary outcome was freedom from syncope within 1 year of follow-up., Conclusion: There is widespread support for well-designed RCTs to confirm the hypothesized clinical benefit of CNA, provide data to guide the risk-benefit equations during patient selection, and appropriately estimate the placebo effect., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Head up Tilt-table Test (HUTT) is a practical examination of the most common type of pediatrics syncope. The electrocardiographic (ECG) changes during this test, show the autonomic defects that cause neuraly-mediated syncope in response to tilting process., Methods: All pediatric syncope patients referred to our center in a 1-year period, were included in the study. HUTT was performed and patients were classified into two groups of Negative and Positive HUTT results, and the latter group was subclassified as three subgroups of "vasodepressor", "cardioinhibitory" and "mixed type" responses to HUTT. QT and corrected QT (QTc) dispersion was measured by the baseline standard 12-lead ECG obtained before HUTT., Results: Eighty-six patients with a mean age of 12.19 ± 5.34 were included. Patients with positive HUTT were significantly younger and male gender was more prevalent in this group. Mean QT dispersion was significantly higher in patients with positive HUTT result and also in patients with mixed response to HUTT compared to isolated vasodepressor response. Duration of QTc interval did not change between different study groups. Reciever-Operating-Characteristic (ROC) analysis showed that QT dispersion higher than 32 ms is a significant predictor of positive HUTT result (with 92% sensitivity and 98% specificity) and values higher than 40 ms can predict the mixed type of response to HUTT (with 84% sensitivity and 63% specificity)., Conclusions: Baseline myocardial repolarization disparity significantly correlates with susceptibility to symptomatic vasovagal syncope. This pathology seems to play its role mainly via excessive vagotonic response to sympathetic activation during HUTT process (known as cardioinhibitory response)., (© 2021 Wiley Periodicals LLC.)

Objective: To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT)., Methods: Inclusion criteria for VVS were a history of VVS and tilt-induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, "convex," or decelerated, "concave"; (2) the time from head-up tilt to when BP reached one-half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations., Results: We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19-98 sec) than in VVS (median 1571 sec, IQR 1381-1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%., Interpretation: These new hemodynamic criteria reliably differentiate cOH from VVS., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

We investigated circulatory dynamics in patients with vasodepressor type neurally mediated syncope (VT-NMS) by performing high-resolution Holter electrocardiography and a correlation analysis of changes in adenylate cyclase activity, blood pressure, and pulse during the head-up tilt test. Holter electrocardiography was performed for 30 patients. Adenylate cyclase activity was evaluated in lymphocytes from blood samples taken at rest and during the head-up tilt test. There was no change in autonomic nerve fluctuation during electrocardiography in VT-NMS patients, but our results showed a significant difference in blood pressure and adenylate cyclase activity between VT-NMS patients and healthy volunteers; the systolic blood pressure of VT-NMS patients decreased after 5 min, while at 10 min, the adenylate cyclase activity was the highest (0.53%) and the systolic blood pressure was the lowest (111.8 mm Hg). Pulse rates increased after 10 min. VT-NMS patients showed higher blood pressure, pulse rate, and adenylate cyclase activity during the tilt test than did healthy volunteers. In patients with syncope, standing for longer than 10 minutes may increase the risk of VT-NMS. From our results, we consider it likely that high systolic blood pressure and adenylate cyclase activity at rest cause fainting in VT-NMS patients. Our findings may be helpful for identifying individuals with a high risk of developing NMS in the healthy population., Competing Interests: The authors have declared that no competing interests exist.

[Figure: see text].

Background: There are several strategies to reduce donor reactions. We report donor participation and reaction rates before and after implementing multiple measures at Canadian Blood Services., Study Design and Methods: We introduced a structured program of 500 mL of water and a salty snack pre-donation and applied muscle tension (AMT) during donation. Donors were not deferred for out of range blood pressure (BP); however, BP was measured in first time donors. Time on the donation chair post-donation was decreased from 5 to 2 min for repeat donors. We assessed participation rates using our quarterly survey of 10,000 recent donors. We extracted vasovagal reactions with loss of consciousness (LOC) from our operational database and compared pre-implementation (Oct 12,018-March 31,2019) and post-implementation (Oct 12,019-March 31,2020) periods., Results: Survey response rates varied from 11% to 16%. The percentage of donors who drank the water and ate the salty snack increased from 58% to 82% and 44% to 70% over 4 quarters; those performing AMT increased from 24% to 41%. Reactions decreased from 19.07 per 10,000 (744 reactions in 390,123 donations) to 14.04 per 10,000 (537 in 382,382 donations) (p < .0001). No first-time donors with high BP (n = 684) but 5 with low BP (n = 718) had reactions, CI were very large., Conclusions: Achieving optimal participation was challenging. After implementation of a donor wellness initiative based on best practice, rates of vasovagal reactions with LOC decreased by 25%. A larger dataset is necessary to assess the safety contribution of BP deferrals when other mitigation measures are in place., (© 2021 AABB.)

It is commonly reported that vasovagal syncope (VVS) is more frequent in women. Presently, this issue has never been investigated. The purpose of this review was to evaluate, through an extensive review of the literature, whether women are really more affected by VVS than men. The gender distribution was investigated in individuals with classical and nonclassical VVS. The database PubMed was searched using the terms 'syncope', 'vasovagal syncope', 'neurally mediated syncope' and 'tilt testing'. Twelve studies dealing with classical and 75 with nonclassical VVS were eligible. In the individuals with classical (N = 1861) and nonclassical VVS (N = 9696), a trend towards a greater percentage of women emerged (P = 0.14 and 0.07, respectively). In the total population with VVS (N = 11 557), the percentage of women was significantly higher than that of men (58 versus 42%, P = 0.03). Most of the individuals were young or middle-aged. In 84% of the studies, the percentage of women was greater than that of men. A separate analysis was carried out in older VVS patients (≥60 years) and only two studies were eligible to be evaluated. Considering that almost all the studies were carried out in the western nations, where the number of men and women is almost superimposable until the age of 65 years and a bias by gender has never been reported in the management of VVS, these data strongly suggest that young and middle-aged women are more affected by VVS than their male counterparts. At present, data are too scant to draw a definitive conclusion in older VVS patients., (Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.)

While many of the cardiac limitations to exercise performance are now well-characterized, extracardiac limitations to exercise performance have been less well recognized but are nevertheless important. We propose that abnormalities of cardiac preload reserve represents an under-recognized but common cause of exercise limitations. We further propose that mechanistic links exist between conditions as seemingly disparate as heart failure with preserved ejection fraction, nonalcoholic fatty liver disease, and pelvic venous compression/obstruction syndromes (eg, May-Thurner). We conclude that extracardiac abnormalities of preload reserve serve as a major pathophysiologic mechanism underlying these and other disease states.

Background: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation, the vagal denervation by radiofrequency ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after cardioneuroablation. Additionally, it intends to investigate the arrhythmias behavior after cardioneuroablation., Methods: Prospective longitudinal study with intrapatient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to cardioneuroablation, 49 (59%) male, 47.3±17 years old, having vagal paroxysmal atrial fibrillation 58 (70%) or neurocardiogenic syncope 25 (30%), New York Heart Association class0.05) suggesting that the reinnervation has halted. There was also an important reduction in all bradyarrhythmias and tachyarrhythmias pre-cardioneuroablation versus post-cardioneuroablation ( P <0.01)., Conclusions: There is an important and significant vagal and sympathetic denervation after 2 years of cardioneuroablation with a significant reduction in bradyarrhythmia and tachyarrhythmia in the whole group. There were no complications.

Background: Increased parasympathetic activity is thought to play important roles in syncope events of patients with vasovagal syncope (VVS). However, direct measurements of the vagal control are difficult. The novel deceleration capacity (DC) of heart rate measure has been used to characterize the vagal modulation. This study aimed to assess vagal control in patients with VVS and evaluate the diagnostic value of the DC in VVS., Methods: Altogether, 161 consecutive patients with VVS (43±15 years; 62 males) were enrolled. Tilt table test was positive in 101 and negative in 60 patients. Sixty-five healthy subjects were enrolled as controls. DC and heart rate variability in 24-hour ECG, echocardiogram, and biochemical examinations were compared between the syncope and control groups., Results: DC was significantly higher in the syncope group than in the control group (9.6±3.3 versus 6.5±2.0 ms, P <0.001). DC was similarly increased in patients with VVS with a positive and negative tilt table test (9.7±3.5 and 9.4±2.9 ms, P =0.614). In multivariable logistic regression analyses, DC was independently associated with syncope (odds ratio=1.518 [95% CI, 1.301-1.770]; P =0.0001). For the prediction of syncope, the area under curve analysis showed similar values when comparing single DC and combined DC with other risk factors ( P =0.1147). From the receiver operator characteristic curves for syncope discrimination, the optimal cutoff value for the DC was 7.12 ms., Conclusions: DC>7.5 ms may serve as a good tool to monitor cardiac vagal activity and discriminate VVS, particularly in those with negative tilt table test.

Background: Ganglionated plexus (GP) ablation is used to treat atrial fibrillation (AF) and vasovagal syncope (VVS). However, the comparative effects of GP ablation in treating paroxysmal atrial fibrillation (PAF) and VVS have not been well studied., Objective: The purpose of this study was to investigate the effects of intensive GP ablation on PAF and VVS., Methods: PAF and VVS patients were enrolled in this study. Pulmonary vein isolation (PVI) was performed in the PAF group, and additional ablation was performed at GP sites. Anatomic ablation of left atrial GPs was performed in the VVS group. The primary endpoint was freedom from AF or other sustained atrial tachycardia and syncope recurrence., Results: A total of 195 patients were enrolled: 146 patients with PAF, including eight patients with combined VVS (PAF group), and 49 patients with VVS (VVS group). Vasovagal response (VR) was achieved in 78 (53.4%) patients in the PAF group and 48 patients (98.0%) in the VVS group (P < .05). During the 17.8 ± 10.5 (range, 3-42) month follow-up, 126 (86.3%) patients were free of AF in the PAF group, and 45 (91.8%) patients in the VVS group had no syncope recurrence and significantly improved symptoms., Conclusions: Anatomically guided intensive GP ablation showed efficient clinical outcomes for both groups of patients. Compared with PAF patients, VVS patients had more VR during ablation in the left atrium. Furthermore, VR during ablation indicated a better prognosis in PAF patients., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Objective: To develop an orthostatic intolerance symptom scoring system to assess orthostatic intolerance and then to compare the symptom score among different head-up tilt test responses., Methods: 272 subjects (5-18 years) presenting with orthostatic intolerance symptoms finished questionnaire and head-up tilt test. According to head-up tilt test hemodynamic responses, the subjects were divided into head-up tilt test negative, vasovagal syncope, and postural tachycardia syndrome groups., Results: We built up a symptom score according to the frequency of dizziness, headache, blurred vision, palpitations, chest discomfort, gastrointestinal symptoms, profuse perspiration, and syncope. The median score in postural tachycardia syndrome subjects was highest. A score of 2.5 for predicting vasovagal syncope yielded a sensitivity of 75.0% and specificity of 50.3%, a score of 5.5 for predicting postural tachycardia syndrome yielded a sensitivity of 69.7% and specificity of 72.0%. Furthermore, the median score in postural tachycardia syndrome subjects was significantly higher than that in head-up tilt test negative subjects with heart rate increment of 30-39 beats/min ( P < .01)., Conclusions: This suggests that the symptom score has some predictive value in head-up tilt test results, which can be served as a preliminary assessment instrument.

Background and Aim: Vasovagal syncope (VVS) in children and adolescents is a common disorder. There may be an internal relationship between creatine kinase (CK) and its isoenzymes (CKMB) and syncope. The aim of this study was to evaluate the changes of CK and CKMB in children and adolescents with VVS., Methods and Results: The VVS group included 218 patients (93 male and 125 female). The control group included 129 healthy children (78 male and 51 female). Serum CK and CKMB levels were estimated. We founded ①Serum CK and CK-MB levels decreased in VVS group than that in control group (P < 0.05). ②The CK levels of female were significantly lower than those of male in VVS group (P < 0.05). ③Serum level of CK-MB were in negative correlation with age, height, weight, BMI whereas in positively correlation with HR. ④CK was effected by CK-MB (β = 0.147, P = 0.037) while CK-MB was independently influenced by age (β = -0.203, P = 0.002) and DBP (β = 0.171, P = 0.011). ⑤Both CK and CK-MB significantly influenced on VVS occurrence after adjusting for the effects of gender, age, height, weight, BMI and HR., Conclusion: The serum CK and CKMB levels decrease in children and adolescents with VVS. CK and CK-MB are the independent protective factors with VVS., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Single-chamber leadless pacemakers (LPs) have been shown to be an effective alternative to conventional transvenous pacemakers (CTPs), but their benefit in the context of cardioinhibitory vasovagal syncope (CI-VVS) is unknown., Objective: The purpose of this study was to evaluate the safety and efficacy of LP compared with dual-chamber CTP for CI-VVS., Methods: We conducted a multicenter, retrospective study comparing patients who received LP or dual-chamber CTP for drug-refractory CI-VVS. CI-VVS was diagnosed clinically and supported by cardiac monitoring and head-up tilt table testing. The primary efficacy endpoint was freedom from syncope during follow-up. Secondary endpoints included device efficacy and safety estimated by device-related major and minor adverse events (AEs)., Results: Seventy-two patients (24 LP, 48 CTP; age 32 ± 5.5 years; 90% female; syncope frequency 7.6 ± 3.4 per year) were included. At 1 year, 91% of patients (22/24) in the LP group and 94% of patients (43/48) in the CTP group met the primary efficacy endpoint (P = .7). Device efficacy endpoint was met in 92% of the LP group and 98% of the CTP group (P = .2). Early major AEs occurred in 2 of 24 in the LP group and 3 of 48 in the CTP group (P = .4). Late major AEs occurred in 0 of 24 in the LP group and 2 of 48 in the CTP group (P = 1)., Conclusion: In patients with CI-VVS, single-chamber LP demonstrated equivalent efficacy in reducing syncopal events compared to dual-chamber CTP, with a similar safety profile., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Rationale: Assessing the relative contributions of cardioinhibition and vasodepression to the blood pressure (BP) decrease in tilt-induced vasovagal syncope requires methods that reflect BP physiology accurately., Objective: To assess the relative contributions of cardioinhibition and vasodepression to tilt-induced vasovagal syncope using novel methods., Methods and Results: We studied the parameters determining BP, that is, stroke volume (SV), heart rate (HR), and total peripheral resistance (TPR), in 163 patients with tilt-induced vasovagal syncope documented by continuous ECG and video EEG monitoring. We defined the beginning of cardioinhibition as the start of an HR decrease (HR) before syncope and used logarithms of SV, HR, and TPR ratios to quantify the multiplicative relation BP=SV·HR·TPR. We defined 3 stages before syncope and 2 after it based on direction changes of these parameters. The earliest BP decrease occurred 9 minutes before syncope. Cardioinhibition was observed in 91% of patients at a median time of 58 seconds before syncope. At that time, SV had a strong negative effect on BP, TPR a lesser negative effect, while HR had increased (all P <0.001). At the onset of cardioinhibition, the median HR was at 98 bpm higher than baseline. Cardioinhibition thus initially only represented a reduction of the corrective HR increase but was nonetheless accompanied by an immediate acceleration of the ongoing BP decrease. At syncope, SV and HR contributed similarly to the BP decrease ( P <0.001), while TPR did not affect BP., Conclusions: The novel methods allowed the relative effects of SV, HR, and TPR on BP to be assessed separately, although all act together. The 2 major factors lowering BP in tilt-induced vasovagal syncope were reduced SV and cardioinhibition. We suggest that the term vasodepression in reflex syncope should not be limited to reduced arterial vasoconstriction, reflected in TPR, but should also encompass venous pooling, reflected in SV.

Introduction: Lymphoma of parapharyngeal space (PPS) is a rare condition. The clinical presentations may vary and often masquerades as infection or an inflammatory condition. A misdiagnosis will lead to a delay in treatment of the disease. Due to the complex anatomy of PPS, any attributed pressure from masses can lead to a life-threatening event such as cardiac syncope., Case Report: We report a rare case of PPS B-cell non-Hodgkin lymphoma with superimposed Tuberculosis (TB) and fungal infection that presents with several episodes of syncope and hemodynamic depression., Discussion: The clinical entities in PPS lesions syncope and its associated syndromes, pathophysiology, and differential diagnosis together with possible managements are further discussed.

Objective: An artificial liver support system (ALSS) is an effective therapy for patients with severe liver injury. A vasovagal reaction (VVR) is a common complication in various treatment settings but has not been reported previously in ALSS., Methods: This study retrospectively evaluated patients who suffered an ALSS-related VRR between January 2018 and June 2019. We collected data from VVR episodes including onset time, duration, changes in heart rate (HR) and blood pressure (BP), and drug treatment., Results: Among 637 patients who underwent ALSS treatment, 18 were included in the study. The incidence of VVR was approximately 2.82%. These patients were characterized by a rapid decrease in BP or HR with associated symptoms such as chest distress, nausea, and vomiting. The majority of patients (78%) suffered a VVR during their first ALSS treatment. Sixteen patients (89%) had associated symptoms after treatment began. Sixteen patients (89%) received human albumin or Ringer's solution. Atropine was used in 11 patients (61%). The symptoms were relieved within 20 min in 15 patients and over 20 min in 3 patients., Conclusions: A VVR is a rare complication in patients with severe liver injury undergoing ALSS treatment. Low BP and HR are the main characteristics of a VVR., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Shanshan Ma et al.)

Background: Vasovagal syncope (VVS) significantly reduces quality of life, yet lacks effective medical therapies. Pharmacological norepinephrine transporter (NET) inhibition increases synaptic norepinephrine reuptake, which may be able to prevent hypotension, bradycardia, and syncope., Objective: The objective of this systematic review was to evaluate the ability of 3 NET inhibitors-reboxetine, sibutramine, and atomoxetine-to prevent head-up tilt-induced vasovagal outcomes in healthy participants and patients with VVS., Methods: Relevant studies were identified from Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature without language restriction from database inception to August 2019. All randomized controlled trials comparing the benefit of a NET inhibitor vs placebo in adult populations were selected for review and meta-analysis., Results: Four studies (101 participants) met inclusion criteria. The mean study size was 25 (range 11-56) participants. NET inhibition reduced the likelihood of vasovagal reactions marked by hypotension and bradycardia in healthy participants during head-up tilt testing (relative risk 0.15; 95% confidence interval 0.04-0.52; P = .003). This relative risk reduction also occurred in patients with VVS during head-up tilt when given atomoxetine (relative risk 0.49; 95% confidence interval 0.28-0.86; P = .01). This was achieved through heart rate compensation with NET inhibition toward the end of tilt testing (106 ± 32 beats/min vs 60 ± 22 beats/min; P < .001), which in turn preserved cardiac output and mean arterial pressure (71 ± 20 mm Hg vs 43 ± 13 mm Hg; P < .001) in the absence of significantly increased systemic vascular resistance., Conclusion: NET inhibition prevents severe vasovagal reactions and syncope induced by head-up tilt testing in both healthy participants and patients with VVS. Pharmacological NET inhibition is a promising potential treatment of recurrent syncope., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Vasovagal syncope (VVS) is a common cause of recurrent syncope. Nevertheless, the exact hemodynamic mechanism has not been elucidated. Pulse wave analysis (PWA) is widely used to evaluate vascular properties, as it reflects the condition of the entire arterial system., Hypothesis: Cardiovascular autonomic modulation may influence the hemodynamic mechanism and result in different vascular properties between VVS patients and healthy individuals., Methods: We enrolled consecutive patients diagnosed with VVS on head-up tilt testing from January 2014 to August 2019. Healthy subjects were enrolled as the control group. We performed PWA on all participants. Using propensity score matching, we assembled a study population with similar baseline characteristics and compared hemodynamic parameters., Results: A total of 111 VVS patients (43 ± 18 years, 72 females) and 475 healthy control subjects (48 ± 13 years, 192 females) were enrolled. Compared to the healthy control subjects, the VVS patients had a higher augmentation index (AIx) adjusted to a heart rate of 75 beats per minute (AIx@HR75, 20.5 ± 13.1% vs 16.7 ± 11.9%, P = .003). After 1:1 matched comparison (111 matched control), VVS patients consistently showed higher AIx@HR75 (20.5 ± 13.1% vs 16.7 ± 12.9%, P = .02) than the matched control group. According to age distribution, VVS patients showed significantly higher AIx@HR75 (10.6 ± 11.7% vs 2.5 ± 11.1%, P = .01) in a young age (15-33 years) group., Conclusions: VVS patients had greater arterial stiffness than healthy subjects. This is one of the plausible mechanisms of the pathophysiology of VVS., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

A 38-year-old woman presented with a history of recurrent episodes of transient loss of consciousness (TLOC) with seizure-like activity and post-TLOC left sided paresis. Electroencephalogram and MRI of the brain were normal, and events were not controlled by anti-convulsant therapy. Tilt testing produced reflex mixed pattern vasovagal syncope, with exact symptom reproduction, including bilateral upper and lower limb myoclonic movements and post-TLOC left hemiparesis that persisted for 27 min. A witness for the tilt event confirmed reproduction of patients 'typical' TLOC event. Syncope is the most frequent cause of TLOC. Myoclonic movements during syncope are not uncommon and can be misdiagnosed as epilepsy. It is rare to experience paresis after syncope, which in this case, lead to misdiagnosis and unnecessary anti-convulsant treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Introduction: Suspension syndrome describes a potentially life-threatening event during passive suspension on a rope. The pathophysiological mechanism is not fully understood; however, the most widespread hypothesis assumes blood pools in the lower extremities, prompting a reduction in cardiac preload and cardiac output and leading to tissue hypoperfusion, loss of consciousness, and death. The aim of this study was to assess venous pooling by ultrasound in simulated suspension syndrome using human subjects., Methods: In this trial, 20 healthy volunteers were suspended in a sit harness for a maximum of 60 min with and without preceding exercise. Venous pooling was assessed by measuring the diameter of the superficial femoral vein (SFV) with ultrasound at baseline in supine and standing positions as well as during and after suspension., Results: SFV diameter increased and blood flow became progressively sluggish. In 30% of the tests, near syncope occurred. However, SFV diameter did not differ between subjects with and without near syncope., Conclusions: Free hanging in a harness leads to rapid venous pooling in the lower limbs. The most important measure to prevent suspension syndrome might be constant movement of the legs., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Most of the research on vasovagal reactions has focused on the contributions of cardiovascular activity to the development of symptoms. However, other research suggests that additional mechanisms like hyperventilation may contribute to the process. The goal of the present investigation was to examine the influences of cardiovascular and respiratory variables on vasovagal symptoms., Methods: This study was part of a randomized controlled trial investigating the effects of behavioral techniques on the prevention of vasovagal reactions in blood donors. Data from the no-treatment control group were analyzed. The final sample was composed of 160 college and university students. Observational and self-report measures of symptoms were obtained. Physiological variables were measured mainly using respiratory capnometry., Results: Although respiration rate remained stable throughout donation, change in end-tidal carbon dioxide was associated with requiring treatment for a reaction during donation (odds ratio = 0.57, 95% confidence interval [CI] = 0.41 to 0.79, p = .001) and self-reported symptoms measured in the postdonation period using the Blood Donation Reactions Inventory (β = -0.152, 95% CI = -0.28 to -0.02, t = -2.32, p = .022). Individuals with higher levels of predonation anxiety displayed larger decreases in end-tidal carbon dioxide throughout the procedure (F(2,236) = 3.64, p = .043, ηp = 0.030). Blood Donation Reactions Inventory scores were related to changes in systolic (β = -0.022, 95% CI = -0.04 to -0.004, t = -2.39, p = .019) and diastolic blood pressure (β = -0.038, 95% CI = -0.06 to -0.02, t = -4.03, p < .001)., Conclusions: Although the vasovagal reaction has traditionally been viewed as a primarily cardiovascular event, the present results suggest that hyperventilation also plays a role in the development of vasovagal symptoms.

The role of pacing in vasovagal syncope (VVS) is considered from a physiological basis. Most VVS patients lose consciousness due to hypotension before severe bradycardia/asystole occurs. Patients who benefit from dual-chamber pacing typically are older with highly symptomatic, late-onset, frequent and severe syncope with short/no prodrome and documented severe cardioinhibition. Tilt testing is of value in patients with recurrent unexplained syncope to identify important hypotensive susceptibility stemming from reduced venous return and stroke volume (SV). A negative tilt test in vasovagal patients with spontaneous asystole documented by an implantable/insertable loop recorder is associated with lower syncope recurrence rates after pacemaker implantation. Pacing may be more effective if triggered by sensor detection of a parameter changing earlier in the reflex than bradycardia when SV may still be relatively preserved. In this regard, detection of right ventricular impedance offers promise. Conservatism is recommended, limiting pacing in VVS to a small subset of symptomatic older patients with clearly documented cardioinhibition and paying particular attention to the timing of loss of consciousness in relation to asystole/bradycardia. Understanding VVS physiology permits application of well-timed, appropriate pacing that yields benefit for highly symptomatic patients., (Copyright © 2020 Heart Rhythm Society. All rights reserved.)

Purpose: Although the underlying mechanisms of reflex syncope remain under debate, there is evidence that it results from decreased cardiac output related to splanchnic blood pooling or a fall in systemic vascular resistance. The aim was to evaluate the response of cerebrovascular and autonomic variables to passive orthostatic challenge in adult patients with different mechanisms leading to reflex syncope., Methods: The study included 30 subjects (66% women, mean age 34 ± 14 years) who suffered a hemodynamic collapse during a drug-free head-up tilt test. They were categorized into three groups according to their hemodynamic cardiovascular response during the head-up tilt test: (1) reduced cardiac output (patients, n = 10), (2) reduced systemic vascular resistance (patients, n = 10), and (3) reduced cardiac output and systemic vascular resistance, (reduced cardiac output reduced systemic vascular resistance patients, n = 10). Cardiovascular and cerebrovascular dynamics, as well as autonomic variables, were noninvasively assessed during the head-up tilt test and median values were calculated at baseline and throughout the three phases of the tilt., Results: At baseline, the reduced systemic vascular resistance group had lower cardiac output and higher total peripheral resistance index and a sustained increase of heart rate throughout the head-up tilt test in comparison to the other groups. Cerebrovascular dynamics and autonomic variables showed no difference among groups throughout the test. Compared with baseline, these variables had similar percentual change during the orthostatic challenge., Conclusions: Although different cardiovascular hemodynamic mechanisms of reflex syncope exist in adult patients, cerebrovascular hypoperfusion and autonomic modulation occur to a similar extent.

The physiological principles underlying pacemaker treatment in patients with vasovagal syncope have never been reviewed. Current knowledge suggests that pacing the right heart is unlikely to correct blood pressure during a vasovagal reaction. In adults, the reason for this is that stroke volume is dictated by central blood volume contained in the cardiopulmonary vessels within the chest (ie, left ventricular preload). Preceding posture-triggered vasovagal syncope, there is a significant fall in central blood volume and therefore in stroke volume and cardiac output long before the onset of bradycardia. This explains why high rate cardiac pacing does not improve cardiac output or blood pressure during presyncope. Contradictory results between physiological theory and trial evidence underlying pacemaker treatment at present cannot be explained. Placebo effects during pacing for vasovagal syncope should be considered. More work is needed to solve the dilemma., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Upright posture reduces venous return, stroke volume, and cardiac output (CO) while causing reflex sinus rate (heart rate [HR]) increase. Yet, in inappropriate sinus tachycardia (IST), postural tachycardia syndrome (POTS), and vasovagal syncope (VVS), symptomatic excessive HR occurs. We hypothesized that CO reaches maximum as function of HR in all., Methods: We recruited 12 healthy controls, 9 IST, 30 VVS, and 30 POTS patients (13-23years) selected randomly by disorder not by HR, each fulfilled appropriate diagnostic criteria. Subjects were instrumented for electrocardiography, beat-to-beat blood pressure, respiratory rate, CO-Modelflow algorithm, and central blood volume from impedance cardiography; 10-minute data were collected supine; subjects were tilted head-up for ≤10 minutes. We computed phase differences, ΔΦ, between fluctuations of HR (ΔHR) and CO (ΔCO) tabulating data when phases were synchronized, determined by a squared nonlinear phase synchronization index >0.5, describing extent/validity of CO/HR coupling. We graphed results supine, 1-minute post-tilt-up, mid-tilt, and pre-tilt-down using polar coordinates (HR-radius, ΔΦ-angle) plotting cos(ΔΦ) versus HR to determine if transition HR exists at which in-phase shifts to antiphase above which CO decreases when HR further increases., Results: At baseline HR, diastolic and mean arterial pressures in IST and POTS were higher versus controls. Upright HR increased most in POTS then IST and VVS, with diverse changes in CO, SVR, and central blood volume. Each patient grouping was separately and collectively analyzed for HR change showing transition from in-phase to anti-phase (ΔΦ) as HR increased: HR transition =115±6 (IST), 123±8 (POTS), 124±7 (VVS), P =ns. Controls never reached transitional HR., Conclusions: Excessive HR independently and equivalently reduces upright CO, in IST, POTS, and VVS.

Background: Cardiogenic syncope in Brugada syndrome (BrS) increases the risk of major events. Nevertheless, clinical differentiation between cardiogenic and vasovagal syncope can be challenging. We characterized the long-term incidence of major events in a large cohort of BrS patients who presented with syncope., Methods: From a total of 474 patients, syncope was the initial manifestation in 135 (28.5%) individuals (43.9 ± 13.9 years, 71.1% male). The syncope was classified prospectively as cardiogenic, vasovagal, or undefined if unclear characteristics were present. Clinical, electrocardiographic, genetic, and electrophysiologic features were analyzed. Cardiogenic syncope, sustained ventricular arrhythmias, and sudden death were considered major events in follow-up., Results: In 66 patients (48.9%), the syncope was cardiogenic; in 51 (37.8%), vasovagal and in 18 (13.3%); undefined. The electrophysiology study (EPS) inducibility was more frequent in patients with cardiogenic syncope and absent in all patients with undefined syncope (28 [53.8%] vs 5 [12.2%] vs 0 [0%]; P < .01). During follow-up (7.7 ± 5.6 years), only patients with cardiogenic syncope presented major events (16 [11.9%]). Among patients with inducible EPS, 7 (21.2%) presented major events (P = .04). The negative predictive value of the EPS for major events was 92.4%. The incidence rate of major events was 2.6% person-year. Parameters associated with major events included cardiogenic syncope (hazard ratio [HR] 6.3; 95% CI 1.1-10.4; P = .05), spontaneous type 1 electrocardiogram (HR 3.7; 95% CI 1.3-10.5; P = .01), and inducible EPS (HR 2.8; 95% CI 1.1-8.8; P = .05)., Conclusions: An accurate syncope classification is crucial in BrS patients for risk stratification. In patients with syncope of unclear characteristics, the EPS may be helpful to prevent unnecessary implantable cardioverter defibrillators., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Syncope is a sudden but reversible brief loss of consciousness secondary to an acute reduction of cerebral perfusion. Reflex syncope denotes neurologically mediated syncope, which includes vasovagal, carotid sinus syndrome, and other situational syncope. The most frequent form of syncope is vasovagal, which is triggered by emotional stress or prolonged standing, and may be diagnosed with the tilt table test. A thorough investigation of syncope is necessary as serious cardiovascular disorders may also be a cause. A tilt table test is a widely used tool utilized by clinicians to diagnose vasovagal syncope and is sometimes augmented with isoproterenol, a β-sympathomimetic that acts on the heart. This report seeks to explain a case of a 48-year-old previously healthy woman who experienced inferior wall ST elevations during tilt table test supplemented with isoproterenol. There is reason to believe that the results of this patient's tilt table test were due to vasovagal syncope in conjunction with right coronary artery vasospasm.

Background: Vasovagal syncope (VVS) occurs in > 40% of individuals at least once in their lifetime. Sex-dependent differences in presentation and outcomes are not understood. We sought to determine differences in clinical presentation, treatment modalities, and outcomes of VVS between men and women., Methods: Data were collected as part of the Prevention of Syncope Trials (POST) I and II, 2 multicenter, placebo-controlled, randomized trials testing the effectiveness of metoprolol and fludrocortisone, respectively. Data regarding clinical presentation, outcomes, and time to first syncope event after randomization were compared., Results: Of the 418 patients (280 women and 138 men), women were younger at the time of first syncope event (21 vs 26 years P = 0.002) and had a lower baseline systolic blood pressure (117 vs 124 mm Hg, P < 0.001). Response to heat as a trigger for syncope was more common in women (68% vs 48%, P = 0.011). Clinical presentation in women consisted more commonly of feeling warm, having seizures, and experiencing more postsyncope fatigue (68% vs 54%, P = 0.048; 10% vs 2.7%, P = 0.045; 75% vs 59%, P = 0.017, respectively). Women were more likely to experience recurrent syncope after adjustment for prerandomization syncope burden and randomization assignment (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P = 0.012)., Conclusion: Clinical presentation and provocative factors of VVS differ between men and women, as do recurrent events. Recognition of these differences may help target therapy specifically in men and women., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Vasovagal reflex is the most common type of syncope but its etiology is not fully elucidated. Venous return and cardiac output are key in hemodynamic control. The aim of the study was to assess cardiovascular biomarkers and echocardiographic measures at rest and during hypovolemia in women with and without a history of vasovagal syncope., Methods: Fourteen women (aged 18-30) suffering from recurrent vasovagal syncope and 15 age-matched healthy women were included. Graded lower body negative pressure (LBNP) was used to create central hypovolemic stress until signs of presyncope occurred. Echocardiography was applied at rest and throughout LBNP. Cardiovascular biomarkers: copeptin, mid-regional proadrenomedullin, mid-regional pro-ANP, C-terminal proendothelin-1, and plasma norepinephrine were measured both at rest and throughout graded hypovolemia to presyncope., Results: Women prone to vasovagal syncope presented with a narrower right ventricle (RV) (29 ± 1 vs 32 ± 1 mm, P < .05), smaller left atrium (36 ± 2 vs 47 ± 3 cm 3 , P < .01) and lower cardiac output at rest (3.1 ± 0.2 vs 3.7 ± 0.2 L/min, P < .05) and during graded hypovolemia (P < .05). Copeptin was elevated at rest (4.3 ± 0.8 vs 2.5 ± 0.2 pmol/L, P < .05) and increased more in women with vasovagal syncope during progression of LBNP (P < .01). At rest, lower C-terminal proendothelin-1 (35 ± 5 vs 46 ± 2 pmol/L, P < .05) and higher norepinephrine levels (1.1 ± 0.1 vs 0.8 ± 0.1 nmol/L, P < .01) were seen in women with vasovagal syncope., Conclusion: Women prone to vasovagal syncope demonstrate reduced cardiac preload, lower cardiac output, as well as increased release of vasopressin in rest and during hypovolemic challenge. The results emphasize the importance of venous return and cardiac output in the pathogenesis of vasovagal syncope., (© 2019 Wiley Periodicals, Inc.)

Background: The study was prompted by our observation that some patients with neurally mediated syncope (NMS) have an isolated QRS complex, of very low voltage (≤0.3 mV cutoff), in 1 of the frontal leads on the 12-lead electrocardiogram., Objective: To prospectively evaluate whether the presence of isolated very low voltage (VLV) predicts recurrence of NMS., Methods: We included 205 patients (aged 50 ± 17 years) with a median of 3 syncopal episodes. Tilt testing was performed in all patients and was positive in 87 (42%). The patients were followed for a median of 14 months., Results: VLV in frontal leads was present in 92 patients (45%). During the follow-up period 60 patients experienced recurrence of syncope. The actuarial total syncope recurrence rate at 1 year was 32% (95% confidence interval [CI 23%-44%) in patients with isolated VLV in frontal plane leads, and 14% (95% CI 8%-24%) in patients without VLV (log-rank test P < .0001). The significant relationship between the presence of isolated VLV in the frontal leads and syncope recurrence was retained in Cox multivariate analysis that included the history of presyncope and syncope as well as the left ventricular end-diastolic diameter. The presence of isolated VLV in frontal leads was associated with a 3-fold increase of the risk of recurrent syncope., Conclusions: Isolated very low QRS voltage in the frontal leads predicts recurrence of NMS independent of clinical factors that predict recurrence of syncope in such patients. This phenomenon may help generate new diagnostic tools and insights into the pathogenesis of NMS., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: A number of patients with neurally mediated syncope (NMS) have isolated QRS complexes of very low voltage (≤0.3 mV) in the frontal plane leads on the 12-lead electrocardiogram (ECG)., Hypothesis: The aim of this study was to assess the importance of QRS voltage in predicting response to tilt-table testing (TTT) in patients with suspected NMS., Methods: We included 216 patients (age: 49 ± 20 years, 103 men) with suspected NMS who had either a positive or negative response to TTT (n = 91 TTT+, and n = 125 TTT-). The QRS voltage was measured in mV on 12-lead ECGs performed within 3 days of the TTT. The lowest QRS voltage (QRSmin), as well as the voltage in each of the 12 leads was also determined., Results: Very low voltage (QRSmin  ≤ 0.3 mV) in the frontal leads was significantly more prevalent in the TTT+ group than in the TTT- group (74 vs 22%, respectively; P  < .001). Patients in the TTT+ group had significantly lower QRSmin when compared to patients in the TTT- group. QRSmin predicted a positive tilt-table test in a multivariate model that also included patient gender, height, history of presyncope, QRS duration, and left ventricular end-diastolic diameter indexed to height. ROC analysis showed that QRSmin of ≥0.3 mV discriminated between TTT+ and TTT- patients with a sensitivity of 78% and specificity of 68%., Conclusion: Isolated very low QRS voltage in the frontal leads predicts a positive response to TTT in patients with suspected NMS., (© 2019 Wiley Periodicals, Inc.)

Aims: There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope., Methods and Results: Vasovagal syncope patients were given two doses of study drug [randomized to atomoxetine 40 mg (n = 27) or matched placebo (n = 29)] 12 h apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate (HR), blood pressure (BP), and cardiac haemodynamics were recorded using non-invasive techniques and stroke volume modelling. Patients were 35 ± 14 years (73% female) with medians of 12 lifetime and 3 prior year faints. Fewer subjects fainted with atomoxetine than with placebo [10/29 vs. 19/27; P = 0.003; risk ratio 0.49 (confidence interval 0.28-0.86)], but equal numbers of patients developed presyncope or syncope (23/29 vs. 21/27). Of patients who developed only presyncope, 87% (13/15) had received atomoxetine. Patients with syncope had lower nadir mean arterial pressure than subjects with only presyncope (39 ± 18 vs. 69 ± 18 mmHg, P < 0.0001), and this was due to lower trough HRs in subjects with syncope (67 ± 30 vs. 103 ± 32 b.p.m., P = 0.006) and insignificantly lower cardiac index (2.20 ± 1.36 vs. 2.84 ± 1.05 L/min/m2, P = 0.075). There were no significant differences in stroke volume index (32 ± 6 vs. 35 ± 5 mL/m2, P = 0.29) or systemic vascular resistance index (2156 ± 602 vs. 1790 ± 793 dynes*s/cm5*m2, P = 0.72)., Conclusion: Norepinephrine transporter inhibition significantly decreased the risk of tilt-induced syncope in VVS subjects, mainly by blunting reflex bradycardia, thereby preventing final falls in cardiac index and BP., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background and Objectives : Vasovagal syncope (VVS) is the most common cause of syncope and has multiple pathophysiological mechanisms. Asymmetric dimethylarginine (ADMA) is the major inhibitor of nitric oxide (NO). In this study, we aimed to investigate the relationship between plasma ADMA levels and syncope during the head-up tilt (HUT) test. Materials and Methods : Overall, 97 patients were included in this study. They were above 18 years of age and were admitted to our clinic with the complaint of at least one episode of syncope consistent with VVS. The HUT test was performed in all patients. Patients were divided into the following two groups based on the HUT test results: group 1 included 57 patients with a positive HUT test and group 2 included 35 patients with a negative HUT test. Blood samples were taken before and immediately after the HUT test to measure ADMA levels. Results : No significant intergroup differences were observed concerning gender and age (female gender 68% vs 60%; mean age 24.85 ± 4.01 vs 25.62 ± 3.54 years, respectively, for groups 1 and 2). ADMA values were similar between groups 1 and 2 before the HUT test [ADMA of 958 (544-1418) vs 951 (519-1269); p = 0.794]. In the negative HUT group, no significant differences were observed in ADMA levels before and after the HUT test [ADMA of 951 (519-1269) vs 951 (519-1566); p = 0.764]. However, in the positive HUT group, ADMA levels were significantly decreased following the HUT test [pretest ADMA of 958 (544-1418) vs post-test ADMA of 115 (67-198); p < 0.001]. Conclusion : ADMA levels significantly decreased after the HUT test in patients with VVS., Competing Interests: The authors have no conflict of interests to disclose.