Search

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.

Vasovagal syncope (VVS) (or neurocardiogenic syncope) is a common clinical condition that is challenging to both physicians and patients alike. Severe episodes of recurrent syncope can result in physical injury as well as psychological distress. This article provides a brief overview of current management strategies and a detailed overview of therapeutic modalities such as closed loop stimulation (CLS) and cardioneuroablation (CNA).

The impact of cardioneuroablation (CNA) on ventricular repolarization by using corrected QT interval (QTc) measurements has been recently demonstrated. The effects of cardiac pacing (CP) on ventricular repolarization have not been studied in patients with vasovagal syncope (VVS). We sought to compare ventricular repolarization effects of CNA (group 1) with CP (group 2) in patients with VVS.We enrolled 69 patients with age 38 ± 13 years (53.6% male), n = 47 in group 1 and n = 22 in group 2. Clinical diagnosis of cardioinhibitory type was supported by cardiac monitoring or tilt testing. QTc was calculated at baseline (time-1), at 24 h after ablation (time-2), and at 9-12 months (time-3) in the follow-up.In the group 1, from time-1 to time-2, a significant shortening in QTcFredericia (from 403 ± 27 to 382 ± 27 ms, p0.0001), QTcFramingham (from 402 ± 27 to 384 ± 27 ms, p0.0001), and QTcHodges (from 405 ± 26 to 388 ± 24 ms, p0.0001) was observed which remained lower than baseline in time-3 (373 ± 29, 376 ± 27, and 378 ± 27 ms, respectively). Although the difference between measurements in time-1 and time-2 was not statistically significant for QTcBazett, a significant shortening was detected between time-1 and time-3 (from 408 ± 30 to 394 ± 33, p = 0.005). In the group 2, there was no time-based changes on QTc measurements. In the linear mixed model analysis, the longitudinal reduction tendency in the QTcFredericia and QTcFramingham was more pronounced in group 1.Our results demonstrate that CNA reduces QTc levels through neuromodulation effect whereas CP has no effect on ventricular repolarization in patients with VVS.

Background The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. Methods In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. Conclusion The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Background: Severe blood donor adverse events are rare, but due to their rarity studying them can be difficult. To get an accurate estimate of their frequency and rate in the donor population it may be necessary to combine donation data across countries. Study Design and Methods: International blood collection organizations (BCOs) provided data on rare/severe donor reactions as well as denominator information for their donor populations from 2015 to 2017. Donor reactions were classified using standardized definitions. Results: BCOs from six countries provided reaction data for more than 22 million donations. A total of 480 rare reactions were reported of which 76.7% were imputed as definite and 11% probable. Rates of rare reactions were higher in females and first-time donors. Systemic rare reactions were the most common reaction type, accounting for over three quarters of reactions reported. Of systemic reactions, vasovagal reactions with loss of consciousness and injury or off-site (n = 350) made up the majority and occurred 1.53 per 100,000 donations. For the 22.3% that were localized reactions, the majority of these were cellulitis (n = 71, 0.31 per 100,000 donations) followed by deep venous thrombosis (n = 21, 0.09 per 100,000 donations). Conclusion: Pulling together data from multiple BCOs across countries allows for a better understanding of rare reactions, such as vasovagal reaction with injury or cellulitis, and for generating a reliable incidence rate for air embolism or compartment syndrome. However, gaps remain due to missing elements such as unknown donor status or location of reaction.

Aims Vasovagal syncope (VVS) is the most common type of syncope and is usually considered a benign disorder. The potential for injury is worrisome but the likelihood is unknown. We aimed to determine the proportion of patients injured due to VVS. Methods and results A systematic search of studies published until August 2020 was performed in multiple medical and nursing databases. Included studies had data on the proportion of patients with injury due to VVS prior to study enrolment. Random effects methods were used. Twenty-three studies having 3593 patients met inclusion criteria. Patients were diagnosed clinically with VVS, and 82% had >2 syncopal episodes before enrolment. Tilt test was positive in 60% and 14 studies reported comorbidities (32.6% hypertensive). The weighted mean injury rate was 33.5% [95% confidence interval (CI): 27.3–40.5%]. The likelihood of injury correlated with population age (r = 0.4, P = 0.05), but not with sex, positive tilt test, or hypertension. The injury rates were 25.7% (95% CI: 19.1–32.8%) in studies with younger patients (mean age ≤50 years, n = 1803) and 43.4% (95% CI: 34.9–52.3%) in studies with older patients (P = 0.002). Nine studies reported major injuries; with a weighted mean rate of major injuries of 13.9% (95% CI: 9.5–19.8%). Conclusion Injuries due to syncope are frequent, occurring in 33% of patients with VVS. The risk of major injuries is substantial. Older patients are at higher risk. Clinicians should be aware of the risk of injuries when providing care and advice to patients with VVS.

Background The incidence of vasovagal syncope (VVS) precipitated by medical procedures such as blood donation is quoted as between 0.13% and 4.17%. Vasovagal events have been observed to occur following cast removal at our paediatric orthopaedic clinic; however, there is no available information in the existing literature regarding incidence or risk factors. This study aims to identify the incidence and demographic traits of patients experiencing syncopal events following cast removal. Methods Over a 12-month period, paediatric patients experiencing a syncopal or pre-syncopal event during an outpatient appointment for cast removal were prospectively enrolled into the study. Basic demographic data were recorded, as well as injury and procedure details and a description of the event. Statistical analysis as well as calculation of incidence of vasovagal events were performed. Results A total of 6078 patients presented for cast removal in the 12-month period. Twenty syncopal or pre-syncopal events were recorded. Incidence was calculated as 0.32%. Mean patient age was 10.8 years. Male : female ratio was 2.3:1. Mean body mass index (BMI) was 20.08, with a trend for higher prevalence of males under the 50th BMI percentile-for-age. The mean time post-injury was 31.4 days. Ninety-five percent of patients were being treated for an upper limb injury and 30% had injuries that had been treated surgically. There were no associated secondary complications or injuries. Conclusions Incidence of VVS following cast removal is comparable to the values quoted in literature for other medical procedures. Demographic data of our cohort suggested that those who experienced VVS were predominantly young males of lower-than-average BMI.

Sighing is a common symptom in children and adolescents. In this study, we explored the clinical characteristics and hemodynamic responses to head-up tilt test (HUTT) in children and adolescents with unexplained sighing.One hundred ninety-two children and adolescents complaining of unexplained sighing were enrolled as study group after excluding chest wall, lung, heart diseases, and psychogenic disorders. Sixty-nine healthy individuals were enrolled as control group. All the subjects underwent HUTT.Nitroglycerin-stimulated HUTT positive rate was higher in the study group than the control group (24.0% vs 10.1%, P = 0.014). In total, 32.3% of patients with sighing had positive responses to HUTT, which was higher than that of healthy individuals (32.3% vs 15.9%, P = 0.009). Among 62 cases with positive responses to HUTT in the study group, 48 cases were vasoinhibitory type vasovagal syncope (VVS), 5 cases were mixed type VVS, 3 cases were cardioinhibitory type VVS, 5 cases were postural tachycardia syndrome, and one case was orthostatic hypertension. Sighing patients with positive responses to HUTT had female dominance (54.8% vs39.2%, P = 0.045), older mean age (9.6 ± 2.8 vs 8.1 ± 2.7 years old, P = 0.001), higher basic systolic blood pressure (104.8 ± 10.4 vs 101.1 ± 9.9 mmHg, P = 0.019), and higher diastolic blood pressure (66.0 ± 7.5 vs 62.9 ± 9.2 mmHg, P = 0.021) compared with those of negative responses. CONCLUSIONS : Nearly one-third of children and adolescents with unexplained sighing had positive responses to HUTT, demonstrating that sighing was related to dysfunction of the autonomic nervous system. Elder female patients with higher systolic and diastolic blood pressure were more likely to have positive responses to HUTT.

Background:Vasovagal syncope is the most common cause of syncope in childhood and its treatment is not at a satisfactory level yet. We aimed to investigate patients who were diagnosed with vasovagal syncope, did not benefit from conventional treatment, received midodrine treatment, and to evaluate their response to midodrine treatment.Methods:Files of 24 patients who were diagnosed with recurrent vasovagal syncope, did not benefit from non-pharmacological treatments, and received midodrine treatment during June 2017–October 2019 were retrospectively analysed.Results:In total, 24 patients received a treatment dose of midodrine at 5 mg/day (2.5 mg BID) included in the study. The mean number of syncope was 5.75 ± 2.67 prior to treatment. Following treatment, the mean number of syncope was 0.42 ± 0.89. It was observed that syncope episodes did not recur in 17 patients, but it recurred in 4 out of 7 patients in the first 3 months of the treatment and did not recur in the following months. The episodes improved in two patients with an increase in the treatment dose, but the syncope episodes continued in only one patient.Conclusion:It was concluded that midodrine treatment was effective and safe in adolescents with recurrent vasovagal syncope.

[Background] The European Syncope Guidelines (ESG) recommend the use of Head-up tilt test (HUT) in case of suspicion of vasovagal syncope (VVS) or orthostatic hypotensive syncope (OHS) after an adequate initial inconclusive evaluation. We report a single center experience in the scenario of suspected VVS or OHS, who underwent HUT in patients referred to a Syncope Clinic after ruling out high-risk causes., [Methods] We prospectively and consecutively included all syncopal patients that were referred for HUT, by their attending physician after performing a series of diagnostic tests to rule out cardiac etiology. The clinical history and diagnostic tests performed were reviewed prior to HUT. Patients were pre-classified according to the recommendations from the ESG as; VVS, OHS or Syncope of Unknown Etiology (SUE)., [Results] We studied 1058 patients, 558 (52.7%) males, mean age 46.5 ± 20.1 yr. There were no gender differences in age, risk factors, previous heart diseases, ECG findings or number of previous tests. Based on the ESG criteria a significant number of diagnostic tests were probably unnecessarily performed. HUT was positive in 609 patients (57.5%). The rate of positive HUT according to pre-classification was significantly different among groups: 60% VVS, 46.1% OHS and 54.3% SUE (p = 0.037). Combining ESG recommendations and HUT results of the 1058 resulted in 762 (72%) diagnosed as VVS, 89 (8.4%) as OHS and 207 (19.5%) as SUE., [Conclusions] Appropriate application of ESG recommendations combined with HUT, identified 81% of patients with non-cardiogenic syncope, potentially avoiding a significant number of unnecessary diagnostic tests.

Vasovagal syncope (VVS) is well-known to occur in patients undergoing phlebotomy, however, there have been no large-scale studies of the incidence of VVS in the blood collection room. The aim of our present retrospective study was to investigate the conditions of phlebotomy and determine the incidence/factors predisposing to the development of VVS. We investigated 677,956 phlebotomies performed in outpatients in the blood collection room, to explore factors predisposing to the development of VVS. Our analysis revealed an overall incidence of VVS of 0.004% and suggested that use of more than 5 blood collection tubes and a waiting time of more than 15 min were associated with a higher risk of VVS. The odds ratios of these factors were 8.10 (95% CI 3.76–17.50) and 3.69 (95% CI 0.87–15.60), respectively. This is the large-scale study to analyze factors of the development of VVS in the blood collection room, and according to our results, use of a large number of blood collection tubes and a prolonged waiting time for phlebotomy may be risk factors for the development of VVS.

Ablation of ganglionated plexuses (GPs) is a relatively new technique in patients with vasovagal syncope. Due to individual variation of GP settlement, reproducible GP detection methods are needed to during electrophysiologic study. In the present case, fractionation mapping software of Ensite system was tested to detect localization of GPs and first compared with previously validated fractionated electrograms based strategy.

Aims Syncope can lead to injuries. We determined the frequency, severity, and predictors of injuries due to syncope in cohorts of syncope patients. Methods and results Participants were enrolled in the POST2 (fludrocortisone) and POST4 (midodrine) vasovagal syncope (VVS) randomized trials, and POST3 enrolled patients with bifascicular block and syncope. Injury was defined as minor (bruising, abrasions), moderate (lacerations), and severe (fractures, burns, joint pain), and recorded up to 1 year after enrolment. A total of 459 patients (median 39 years) were analysed. There were 710 faints occurred in 186 patients during a 1-year follow-up. Fully 56/186 (30%) of patients were injured with syncope (12% of overall group). There were 102 injuries associated with the 710 faints (14%), of which 19% were moderate or severe injuries. Neither patient age, sex, nor the presence of prodromal symptoms associated with injury-free survival. Patients with bifascicular block were more prone to injury (relative risk 1.98, P = 0.018). Patients with ≥4 faints in the prior year had more injuries than those with fewer faints (relative risk 2.97, P Conclusion Injuries are frequent in syncope patients, but only 4% of injuries were severe. None of age, sex, and prodromal symptoms associate with injury.

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.

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 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.

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.

Cardioneuroablation (CNA) is an endocardial ablation technique aiming to prevent the autonomic imbalance occurring in vasovagal syncope (VVS). A 46-year-old female was referred to our center for pacemaker implantation due to recurrent syncopal episodes despite conventional treatments. A 22-s asystole was detected on head-up tilt testing. After a discussion with the patient and her family, we decided to perform CNA. Positive response was confirmed, and procedural endpoints were defined using pre-procedural atropine response test. Ganglionated plexus (GP) sites were detected and ablated by using fractionated electrogram (FE)-based strategy. During baseline electrophysiological study, AA and PR intervals were calculated as 810 ms and 164 ms, respectively. Based on our ablation order, radiofrequency ablation (RFA) was started from the left inferior and left superior GPs, respectively. A significant vagal response with sinus pauses and atrioventricular (AV) block was detected during RFA. Ablation of the right superior GP caused a significant increase of sinus rate with continuing AV block. After completion of ablation on the right superior and inferior GPs, PR interval was still 164 ms although AA interval decreased to 640 ms. After RFA on the posteromedial left GP which provides mainly vagal innervation of AV node, PR interval and cycle length of sinus node were detected as 134 ms and 540 ms, respectively. Selective parasympathetic innervation principles of the sinus node and AV node were previously demonstrated. We described a case of successful parasympathetic denervation of the sinus node and AV nodes using CNA.

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.

Vasovagal syncope is the most common cause for loss of consciousness. The need for treatment of this condition is warranted by impaired quality of life and a risk of trauma due to the fall. At present, there are no medications with proven preventive effectiveness for vasovagal syncope as demonstrated by large randomized, placebo-controlled studies. At the same time, information about the pathogenesis of vasovagal reaction and provoking factors allows effective use of non-drug methods (such as patient education, physical exercise, maneuvers) in the management of patients with vasovagal syncope.

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.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.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).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.

Vasovagal syncope (VVS) occurs in40% 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.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.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, P0.001). 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).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.

Background. The direction of changes in hemodynamic parameters during the tilt test (TT) nin individuals with history of vasovagal syncope (VVS) is a subject of discussion. Objective: to study changes of volume-impedance hemodynamic indicators in the process of tilt test in somatically healthy young men with history of VVS. Materials and methods. A total of 102 men aged 18–30 years were divided into 4 groups, taking into account the specific features of fainting history and response to TT. Persons of group 1 (n=14) had history of VVS and positive response to TT (syncope). Subjects of group 2 (n=14) had history of VVS and a pattern of postural tachycardia without fainting during TT. Persons of group 3 (n=42) had history of VVS and negative response to TT. Subjects of group 4 (n=32) had no history of VVS and negative response to TT. During TT, we studied dynamics of some indicators, including cardiac output (CO) and total peripheral vascular resistance (TPVR). Results. In individuals of all groups in the initial horizontal phase of TT values of CO and TPVR corresponded to the norm. Subjects of group 1 had significantly lower CO compared with subjects of groups 2, 3, 4 (p0.05). Conclusions. In tilt-positive and tilt-negative subjects with history of VVS, standardized postural stress leads to unidirectional changes in cardiac output, but to multidirectional changes in total peripheral vascular resistance.

Vasovagal syncope (VVS) is a clinical condition related to bradycardia (cardioinhibitory response) and/or hypotension (vasodepressor response), likely mediated by parasympathetic overactivity and sympathetic withdrawal. Although clinical presentation is usually related to a self-limited event, frequent episodes or events without prodrome might be debilitating. There are limited medical therapies proven effective in randomized clinical trials. In patients not responsive to standard therapy, permanent pacemaker therapy may be suggested. However, the role of cardiac pacing for the prevention of syncope recurrences remains controversial due to difficulties to exclude potential role of the vasodepressor component during the episode.

Aim The benefit of cardiac pacing in patients with severe recurrent reflex syncope and asystole induced by tilt testing has not been established. The usefulness of tilt-table test to select candidates for cardiac pacing is controversial. Methods and results We randomly assigned patients aged 40 years or older who had at least two episodes of unpredictable severe reflex syncope during the last year and a tilt-induced syncope with an asystolic pause longer than 3 s, to receive either an active (pacing ON; 63 patients) or an inactive (pacing OFF; 64 patients) dual-chamber pacemaker with closed loop stimulation (CLS). The primary endpoint was the time to first recurrence of syncope. Patients and independent outcome assessors were blinded to the assigned treatment. After a median follow-up of 11.2 months, syncope occurred in significantly fewer patients in the pacing group than in the control group [10 (16%) vs. 34 (53%); hazard ratio, 0.23; P = 0.00005]. The estimated syncope recurrence rate at 1 year was 19% (pacing) and 53% (control) and at 2 years, 22% (pacing) and 68% (control). A combined endpoint of syncope or presyncope occurred in significantly fewer patients in the pacing group [23 (37%) vs. 40 (63%); hazard ratio, 0.44; P = 0.002]. Minor device-related adverse events were reported in five patients (4%). Conclusion In patients aged 40 years or older, affected by severe recurrent reflex syncope and tilt-induced asystole, dual-chamber pacemaker with CLS is highly effective in reducing the recurrences of syncope. Our findings support the inclusion of tilt testing as a useful method to select candidates for cardiac pacing. Study registration ClinicalTrials.gov identifier NCT02324920, Eudamed number CIV-05-013546., Graphical Abstract

(Wilmshurst P, Clamp M. Impaired consciousness when scuba diving associated with vasovagal syncope. Diving and Hyperbaric Medicine. 2020 December 20;50(4):421–423. doi: 10.28920/dhm50.4.421-423. PMID: 33325026.) Introduction: Drowning is likely to result from impairment of consciousness when scuba diving. Causes include toxic effects of breathing gas, including nitrogen narcosis and oxygen toxicity, and arterial gas embolism. Methods: Review of the medical records of scuba divers who had impaired consciousness underwater that could not be attributed to toxic effects of breathing gas or arterial gas embolism. Results: Four scuba divers had episodes of impaired consciousness when at shallow depths (8−18 m) underwater. The descriptions of the episodes were very similar. Three had histories of recurrent episodes of vasovagal syncope on land. Conclusions: Absence of other causes for their impaired consciousness underwater leads to the conclusion that the probable cause was vasovagal syncope.

Falls are a common adverse event (AE) in general hospital admissions and in the epilepsy monitoring unit (EMU) and can cause serious physical injury for patients; however, fall prevention policies widely vary between epilepsy centers. Patient safety, including minimizing AEs, such as falls, continue to be a major goal of quality improvement in the EMU. The bathroom area in an EMU is highly prone for falls due to the need for patient privacy. Syncope is a physiologic non-epileptic event with high prevalence in general population and is a potential cause for fall. It is also reported in people diagnosed with epilepsy. We report a case of vasovagal syncope (VVS) associated with injury in a young female during long-term video EEG recording in our EMU facility. We also briefly address concerns for identifying patients at risk for syncope and its prevention. A multidisciplinary team including EEG technologists can play a vital role in educating patients and caretakers about the risk factors of syncopal fall and its preventive measures.

Objective: To determine the level of serotonin in patients of vasovagal syncope and postural tachycardia syndrome after head-up tilt test. Method: The cross-sectional analytical study was conducted at the Islamic International Medical College and the Department of Electrophysiology, Armed Forces Institute of Cardiology, Rawalpindi, from April 2017 to March 2018. Group A comprised cases of vasovagal syncope, group B had patients of postural tachycardia syndrome, and group C had healthy controls. Cases were chosen on the basis of history, episodes of syncope and findings of head-up tilt test. After the test, blood samples were taken for hormonal analysis of serotonin using enzyme-linked immunosorbent assay. Data was analysed using SPSS 21. Results: Of the 80 subjects, 35(43.8%) were in group A, 35(43.8%) in group B and 10(12.4%) in group C. Mean serotonin value in group A was 918.39±380.16nM, in group B it was 1188.70±449.55nM., while in control group C the mean value was 771.40±376.14nM (p

Aims Syncope without prodromes in subjects with normal heart and normal electrocardiogram (ECG) is classified as non-classical neurally mediated syncope and is characterized by low adenosine plasma levels (APLs) and frequent asystolic syncope. We assessed the efficacy of theophylline, a non-selective adenosine receptor antagonist, in preventing syncopal events. Methods and results Participants received an implantable cardiac monitor, underwent APL measurement, and received oral theophylline at maximum tolerated dose (starting dose 300 mg b.i.d.). They were compared with a historical cohort of untreated patients with implantable cardiac monitor who had the same inclusion criteria and were balanced with the propensity score (PS) method as regard age, sex, lifetime syncopal episodes, APL, and antihypertensive drugs. Primary endpoint was time to first syncopal recurrence at 24 months. There were 76 patients in the theophylline group and 58 in the control group. Syncope recurred in 25 (33%) patients in the theophylline group and in 27 (47%) patients in the control group, with an estimated 2-year recurrence rate of 33% and 60%, respectively, and a hazard ratio of 0.53 [95% confidence interval (CI), 0.30–0.95; P = 0.034]. Most of the benefit of theophylline is derived from reduction of syncope due to asystolic atrioventricular (AV) block (hazard ratio of 0.13; 95% CI, 0.03–0.58; P = 0.008). Thirty (39%) patients discontinued theophylline after a median of 6.4 (interquartile range 1.7–13.8) months due to side effects. Conclusion Theophylline was effective in preventing recurrences in patients with syncope without prodromes, normal heart, and normal ECG. The benefit was greater in patients with syncope due to asystolic AV block. ClinicalTrials.gov Identifier NCT03803215.

Background Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope. Objective To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions. Design Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481). Setting 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom. Patients Patients with recurrent vasovagal syncope and no serious comorbid conditions. Intervention Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months. Measurements The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up. Results The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups. Limitation Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center. Conclusion Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden. Primary funding source The Canadian Institutes of Health Research.

Vasovagal syncope (VVS) has a high prevalence in the general population and is associated with potential complications. There is limited information on the possible association between venous capacitance (VC) and venous return (VR), important determinants of preload and VVS. Since the tilt test was reported to yield a high rate of false positive results, the aim of this study was to evaluate whether abnormal VC and VR at baseline could predispose individuals to VVS. To this end, 88 young, healthy volunteers were recruited and classified to 26 (29.5%) who experienced typical VVS and 62 (70.5%) who did not. VC and VR were evaluated with a commercial device and plethysmography applied to the elevated legs. Maximum venous outflow (MVO), segmental venous capacitance (SVC) and MVO/SVC ratio were calculated and averaged. No significant differences between MVO (5.0±0.5 vs 5.6±0.8, p>0.05), SVC (6.0±0.5 vs 6.3±0.8, p>0.05) or MVO/SVC ratio (0.83±0.02 vs 0.86±0.03, p>0.05) were observed for the non-VVS and VVS volunteers, respectively. There was a significant association between a higher MVO and SVC values and a larger decrease in diastolic blood pressure with standing, although correlations were weak (R2=0.0582 and 0.0681, respectively). In conclusion, at baseline, VC and VR are not impaired in healthy volunteers with a history of VVS. It remains unknown if similar results would be found in patients with cardiovascular comorbidities. Also, the sensitivity of VC and VR evaluations to identify a predisposition for VVS following physiological provocations merits further study.

Background:Recent studies confirm the role of B vitamins deficiency and hyperhomocysteinaemia in the development of dysautonomia that has been considered to be the main factor in vasovagal syncope development. The aim of the study was to investigate serum pyridoxine, folate, cobalamin, and homocysteine levels in children presenting with vasovagal syncope and to analyse the correlation between them and main clinical parameters of syncope.Methods:We studied 40 children, ages 8–17 years with a history of vasovagal syncope and 24 healthy volunteers. The serum pyridoxine, folate, cobalamin, and homocysteine levels were measured by a quantitative sandwich enzyme immunoassay technique using a commercial kit (Monobind, USA). Twenty-four-hour Holter monitoring and 24-hour ambulatory blood pressure monitoring were conducted for all participated patients.Results:Serum pyridoxine (9.42 ± 4.87, 16.11 ± 5.53 µg/L) and cobalamin (307.48 ± 95.50, 447.28 ± 108.85 ng/L) levels were reasonably low (p < 0.05) in patients with vasovagal syncope. Although there was no significant change in folate levels between syncope and healthy children (4.00 ± 1.34, 4.71 ± 1.73 µg/L; p = 0.20), we detected low folate-level association with longer duration of syncope (r = −0.42) and post syncope (r = −0.43) symptoms (p < 0.05). Finally, there was increased serum homocysteine level (13.55 ± 5.03, 7.81 ± 1.71 µmol/L; p < 0.05) in patients with vasovagal syncope. It was positively correlated with the average PQ interval (r = 0.35, p < 0.05) and average QTc interval (r = 0.49, p < 0.05).Conclusions:The results suggested that pyridoxine, folate, cobalamin, and homocysteine may be involved in the pathogenesis of vasovagal syncope. This might provide a new approach for effective treatment of paediatric vasovagal syncope, requiring further study.

This study aims to determine the impact of yoga as an adjunct to standard therapy versus standard therapy alone on the symptomatic burden in patients with recurrent vasovagal syncope (VVS).There is a significant reduction in the quality of life (QoL) of patients with recurrent VVS. Existing management therapies have been largely ineffective. Recent trials have demonstrated the efficacy of yoga in diseases with autonomic imbalance, suggesting its possible utility in VVS.Patients with recurrent VVS were randomized to receive either a specialized yoga training program in addition to current guideline-based therapy (intervention arm, group 1) or current guideline-based therapy alone (control arm, group 2). The primary outcome was a composite of the number of episodes of syncope and presyncope at 12 months. Secondary outcomes included QoL assessment by World Health Organization Quality of Life Brief Field questionnaire (WHOQoL-BREF) scores and Syncope Functional Status Questionnaire scores at 12 months, head up tilt test, and heart rate variability at 6 weeks.A total of 55 patients underwent randomization. The mean number of syncopal or presyncopal events at 12 months was 0.7 ± 0.7 in the intervention arm compared to 2.52 ± 1.93 in the control arm (P0.01). In the intervention arm, 13 (43.3%) patients remained free of events versus 4 (16.0%) patients in the control arm (P = 0.02). QoL at 12 months showed significant improvement of all Syncope Functional Status Questionnaire scores and 2 domains of WHOQoL-BREF scores (P0.05).Yoga as adjunctive therapy is superior to standard therapy alone in reducing the symptomatic burden and improving QoL in patients with recurrent VVS.

BACKGROUND All studies of vasovagal syncope (VVS) after blood donation have been performed with civilian donors. We hypothesized that military donors have a lower incidence of VVS and a particular set of predisposing factors. STUDY DESIGN AND METHODS Retrospective case-control study matching every case of VVS seen from 2011 to 2019 with two controls without VVS from the same blood drive. We used the odds ratio (OR) and its 95% confidence interval (CI), estimated by multivariate logistic regression, to identify independent predictors of VVS. RESULTS There were 105 episodes of VVS among 65.481 whole blood donations (0.15%). VVS was more frequent among donors from military academies than from other military units (0.37% vs. 0.10%, p

It is well known that the autonomic nervous system (ANS) is a major contributor in etiopathogenesis of vasovagal syncope (VVS). Catheter based neuromodulation (CNA) of the intrinsic cardiac ANS has evolved rapidly from being an experimental unproven procedure to its current status as an increasingly performed ablation procedure in many major hospitals worldwide. The present review aims to bring the anatomical elements of intrinsic cardiac ANS and clinical application of intrinsic cardiac neuromodulation together, by reviewing anatomical terminologies and clinical data, in order to provide a practical assistance to the electrophysiology community.

The pathophysiology of vasovagal syncope (VVS) is reviewed, focusing on hemodynamic aspects. Much more is known about orthostatic than about emotional VVS, probably because the former can be studied using a tilt table test (TTT). Recent advances made it possible to quantify the relative contributions of the three factors that control blood pressure: heart rate (HR), stroke volume (SV) and total peripheral resistance (TPR). Orthostatic VVS starts with venous pooling, reflected in a decrease of SV. This is followed by cardioinhibition (CI), which is a decrease of HR that accelerates the ongoing decrease of BP, making the start of CI a literal as well as fundamental turning point. The role of hormonal and other humoral factors, respiration and of psychological influences is reviewed in short, leading to the conclusion that a multidisciplinary approach to the study of the pathophysiology of VVS may yield new insights.

INTRODUCTION The Sudden Cardiac Death-Screening of Risk FactOrS survey included a 12-lead electrocardiogram (ECG) plus a digital-based questionnaire and aimed to screen for warning signs of diseases that may course with sudden cardiac death in children and young adults. We aimed to estimate the prevalence of unexplained syncope (US) and characterize its high-risk features and predictors in this cohort. METHODS AND RESULTS We determined the most probable etiology of transient loss of consciousness (TLOC) episodes based on clinical criteria. US was an exclusion diagnosis and we analyzed its potential clinical and ECG predictors. Among 11 878 individuals, with a mean age of 21 ± 6 (range 6-40) years old, the cumulative incidence of TLOC was 26.5%, 76.2% corresponding to females. Reflex syncope was present in 66.4%, orthostatic hypotension in 8.2%, and 14.8% of the individuals had US. Unexplained syncope was independently associated with age

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 one-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 32ms is a significant predictor of positive HUTT result (with 92% sensitivity and 98% specificity) and values higher than 40ms 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). This article is protected by copyright. All rights reserved.

We report the first case of syncope with a documented asystole in a child triggered by hair grooming. No pathological findings were found, and a 15 s asystole event was recorded in an ambulatory 24 h electrocardiogram while her mother was combing her hair. Syncope by hair grooming is an infrequent type, reported in 162 patients. It is more prevalent in females (84.6% vs. 15.4%) with a mean age in the range of 8.9–12.3 years. The diagnostic is based on clinical history and the most frequent complementary examination is the electrocardiogram. No significant arrythmias or epileptic events have been reported.

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.

Background Frequent syncope is linked to poorer health-related quality of life (HRQoL). Recurrent syncope has been observed to reduce in all groups after seeing a syncope expert and enrolling in a clinical trial. It is unknown if HRQoL improves with this reduction in syncope recurrence. Objectives We examined the change in HRQoL over time in vasovagal syncope (VVS) patients seen by a syncope expert and enrolled in a trial. We also explored whether change differed with treatment or the frequency of fainting during follow up. Methods The Short Form Health Survey (SF36) was completed at baseline (BL), 6 m, and 12 m post-enrollment by VVS patients in the 1st and 2nd Prevention of Syncope Trials, which were multi-centered, randomized, placebo-controlled trials of metoprolol (POST) and fludrocortisone (POST2). Differences in HRQoL at BL, 6 m, and 12 m were analyzed and compared by faints in follow-up and randomization group. Results Complete study data were available for 143 VVS patients (40 ± 17 years, 62% F). Over 12 months, patients reported improvement in all SF36 dimensions except for bodily pain. Post hoc analyses indicated that differences first occurred between BL and 6 m for all but general health. Fainting in follow-up or drug randomization group did not diminish the improvements. The baseline syncope burden was not different whether patients' HRQoL improved or not. Conclusion HRQoL of VVS patients improves over time after enrolling in a clinical trial, even with recurrent faints or randomization to placebo. Improvements may result from alternative factors, such as interaction with experts or patient adjustment.

A previous study of electroencephalography (EEG) changes with syncope led to a finding that some young patients develop prolonged periods of tilt-induced hypotension, but they do not lose consciousness. The present study aim was to compare patterns of hemodynamic changes, measures of duration, and sweating between these patients and patients with tilt-induced vasovagal syncope.In an observational study, qualitative changes in hemodynamic parameters were compared between patients with prolonged hypotension (n = 30) and with syncope (n = 30). To demonstrate that periods of hypotension far-exceed the typical presyncope period, several parameters were used to compare the durations of events between groups. Differences in sweating patterns were explored.Parallels in hemodynamic changes were present in both groups suggesting similar vasovagal mechanisms. Patients with prolonged hypotension had longer durations of hypotension (165 ± 44 versus 57 ± 13 s, p 0.001), diminished cardiac output (109 ± 38 versus 32 ± 9 s, p 0.001), and EEG slowing (85 ± 31 versus 9 ± 4 s, p 0.001) compared to patients with syncope. While all patients generated an increase in sweat rate, those with hypotension only developed a robust sweat response that always preceded the plateau in hypotension compared to 14 (47%) patients with syncope who developed an increase in sweating prior to syncope, p 0.001.Similarities are present among hemodynamic changes with prolonged hypotension and with tilt-induced vasovagal syncope, suggesting a possible vasovagal mechanism for prolonged hypotension. If true, understanding why some individuals develop a vasovagal response that does not culminate in rapid syncope may help to elucidate the physiologic underpinnings of the vasovagal reflex.

To explore the value of the acceleration index as a predictor of therapeutic response to orthostatic training in children with vasovagal syncope (VVS).Thirty-three children with VVS were recruited and treated with orthostatic training. The therapeutic response of each patient was evaluated after 3 months of treatment. A Pearson correlation was calculated between the acceleration index and the severity of VVS. The value of the acceleration index in predicting the therapeutic response to orthostatic training was assessed by analysis of the receiver operating characteristic curve.Among the 33 children with VVS, 20 were found to be responders and the remaining were nonresponders. The mean acceleration index was significantly lower in responders compared with nonresponders (21.10 ± 6.61 vs 31.36 ± 9.00; P = .001) and it was negatively correlated with positive response time in the head-up tilt test, with systolic blood pressure and with diastolic blood pressure at positive response time in the head-up tilt test (P .05). The receiver operating characteristic curve for the predictive value of the acceleration index showed that the area under the curve was 0.827 (95% CI, 0.676-0.978; P = .002), and a cutoff value of the acceleration index of 26.77 yielded a sensitivity of 85.0% and a specificity of 69.2%.The acceleration index may be useful for predicting the efficacy of orthostatic training on VVS in children.

A proportion of patients with vasovagal syncope (VVS) experience recurrence despite appropriate management. Closed loop stimulation (CLS) pacing is a promising treatment for a subgroup of patients with cardioinhibitory response on head-up tilt table test (HUTT). Nonetheless, its efficacy remains uncertain. We sought to assess the efficacy of CLS pacing in patients with cardioinhibitory VVS. We searched PubMed, Google Scholar, and the Cochrane Central Register of controlled trials for relevant studies (last search date April 23, 2018). Data were pooled using the Mantel-Haenszel fixed-effects model. For cohort studies, we used a Freeman-Tukey transformation to calculate the weighted summary proportion. Primary outcomes are syncope and presyncope. Eight studies were included in the final analyses (two single-blinded and one double-blinded RCT, two prospective observational studies, and three retrospective observational studies). Two hundred ninety-one patients included, with an average age of 57 years. Quality of evidence is moderate. Use of CLS pacing was associated with reduced risk of syncope (OR 0.08; 95% CI 0.03–0.18; I2 32%) and presyncope (OR 0.34; 95% CI 0.18–0.63; I2 0.00%). Using proportion meta-analysis, the summary estimate of the proportion of cases that developed syncope during CLS pacing was similar between RCTs and prospective studies (3.2% and 3.1%), respectively. This is much lower than the rate of recurrence in the control arm of RCTs at 33.7%. Sensitivity analyses yielded similar results. CLS pacing is beneficial for patients with recurrent vasovagal syncope who demonstrate a cardioinhibitory response on HUTT.

Background Syncope is a symptom associated with a wide range of pathological conditions, ranging from benign to life threatening. The most frequent is the reflex syncope that may be challenging to treat because of the complex and partially unknown pathophysiological mechanism that has to be addressed by the chosen therapy. Areas of uncertainty Head-up tilt testing is so far the only clinical test able to reproduce reflex syncope, but its diagnostic yield has been recently redefined. A new mechanism such as adenosine-sensitive syncope and idiopathic atrioventricular block have been recently described, and the appropriate therapy is not yet established. There is uncertainty on the efficacy of theophylline and on the use of cardiac pacing in these patients. Data sources Clinical trial published data and position paper from the main expert groups on fludrocortisone, midodrine, etilefrine, beta-blockers, and cardiac pacing as useful therapies for patients affected by reflex syncope. Therapeutic advances Theophylline proved in observational trials to be efficient in preventing reflex syncope recurrences in patients with documented spontaneous paroxysmal conduction disorders comparable to cardiac pacing in a subgroup of patients. Reboxetine and sibutramine may elicit a significant pressor and tachycardic effect able to delay the onset of symptoms during head-up tilt testing. Droxidopa has short-term effects on improving the symptoms because of orthostatic hypotension. Cardiac pacing is effective in preventing reflex syncope recurrences with best results when the indication for pacemaker implantation was based on the documentation of bradycardia or asystole during the spontaneous event by a cardiac monitor. External compression using elastic bandage or compressive stockings is able to prevent the decrease in blood pressure in patients with orthostatic hypotension. Conclusions The optimal management of the complex diagnostic and therapeutic options can be achieved following a standardized and evidence-based approach to the patient with syncope.