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Competing Interests: Conflict of interest The authors declare they have no conflict of interest.

Background: We aimed to identify the target of deprescribing, i.e. the 24-hour SBP increase needed to achieve the greatest reduction of SBP drops., Method: Forty hypertensive patients (mean age 73.6 ± 9.3 years, 26 females) with reflex syncope and SBP drops on a screening ABPM were advised to withdraw or to reduce their therapy. The study objective was the reduction of SBP drops <90 mmHg and <100 mmHg on a second ABPM performed within 3 months., Results: Out of a total of 98 drugs taken during ABPM 1, 44 were withdrawn, 16 had a dose reduction and 38 remained unchanged at the time of ABPM 2. 24-hour SBP increased from 119.7 ± 10.1 mmHg to 129.4 ± 13.2 mmHg during ABPM2. Total disappearance of daytime SBP drops <100 mmHg was achieved in 20 (50 %) patients who had 24-hour SBP of 134±13 mmHg and an increase from ABPM 1 of 12 (IQR 5-20) mmHg. Compared with the 20 patients who had persistence of drops, these patients had a greater reduction of the number of hypotensive drugs (67 % versus 19 %, p = 0.002) and a greater rate of withdrawals (62 % versus 29 %, p = 0.003)., Conclusion: In hypertensive patients with reflex syncope, an increase of 12 mmHg and an absolute value of 24-hour SBP of 134 mmHg appear to represent the optimal goals aimed to prevent SBP drops. Drugs withdrawal, rather than simply dose reduction, is mostly required to achieve the above target., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Syncope is a symptom that poses an important diagnostic and therapeutic challenge, and generates significant cost for the healthcare system. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated beneficial cardiovascular effects, but their possible effects on incident syncope have not been fully investigated. This study compared the effects of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) on new-onset syncope., Methods and Results: This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus (T2DM) patients treated with SGLT2i or DPP4i between 1 January 2015 and 31 December 2020, in Hong Kong, China. The outcomes were hospitalization of new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were applied to evaluate the association between SGLT2i and DPP4i with incident syncope and mortality. After matching, a total of 37 502 patients with T2DM were included (18 751 SGLT2i users vs. 18 751 DPP4i users). During a median follow-up of 5.56 years, 907 patients were hospitalized for new-onset syncope (2.41%), and 2346 patients died from any cause (6.26%), among which 471 deaths (1.26%) were associated with cardiovascular causes. Compared with DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope [HR 0.49; 95% confidence interval (CI) 0.41-0.57; P < 0.001], 65% lower risk of cardiovascular mortality (HR 0.35; 95% CI 0.26-0.46; P < 0.001), and a 70% lower risk of all-cause mortality (HR 0.30; 95% CI 0.26-0.34; P < 0.001) in the fully adjusted model. Similar associations with syncope were observed for dapagliflozin (HR 0.70; 95% CI 0.58-0.85; P < 0.001), canagliflozin (HR 0.48; 95% CI 0.36-0.63; P < 0.001), and ertugliflozin (HR 0.45; 95% CI 0.30-0.68; P < 0.001), but were attenuated for empagliflozin (HR 0.79; 95% CI 0.59-1.05; P = 0.100) after adjusting for potential confounders. The subgroup analyses suggested that, compared with DPP4i, SGLT2i was associated with a significantly decreased risk of incident syncope among T2DM patients, regardless of gender, age, glucose control status, Charlson comorbidity index, and the association remained constant amongst those with common cardiovascular drugs and most antidiabetic drugs at baseline., Conclusion: Compared with DPP4i, SGLT2i was associated with a significantly lower risk of new-onset syncope in patients with T2DM, regardless of gender, age, degree of glycaemic control, and comorbidity burden., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To evaluate Epileptic drop attacks (EDAs) treatment options among pediatric neurologists in Saudi Arabia (SA) and to develop a recommendation scheme for the management of EDAs in SA. Epileptic drop attacks are one of the most pharmaco-resistant epileptic seizures. The different approaches to EDA treatment are influenced by a variety of factors, including pharmaceutical availability, costs, side effects, treating physicians' experience and personal preferences., Methods: This cross-sectional study was conducted online. A structured questionnaire that aimed to measure the therapeutic options for patients with EDA was electronically distributed to pediatric neurologists across SA. It contained 21 questions, and the data were collected in Excel sheets and analyzed., Results: Our study included a cohort of 71 pediatric neurologists from SA, of which male doctors represented 60%. Most of the participating pediatric neurologists had more than 10 years of experience in the field. We found that 77% of the included pediatric neurologists used valproic acid as a first-line drug in patients with EDA. Further, in the different case scenarios provided to participants, levetiracetam, clobazam, topiramate, and rufinamide were included in the initial management protocol for EDA., Conclusion: The majority of pediatric neurologists in Saudi Arabia chose valproic acid and/or levetiracetam as the first line of treatment for EDA. These results highlight the need for an evidence-based clinical guidelines to treat EDA., (Copyright: © Neurosciences.)

Background: Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data., Methods and Findings: This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out., Conclusions: Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sheppard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Purpose: Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials of antihypertensive therapy. In this systematic review and meta-analysis, we sought to determine whether the association of antihypertensive therapy and adverse events (e.g. falls, syncope), differed among trials that included or excluded patients with orthostatic hypotension., Methods: We performed a systematic review and meta-analysis of randomised controlled trials comparing blood pressure lowering medications to placebo, or different blood pressure targets on falls or syncope outcomes and cardiovascular events. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall in subgroups of trials that excluded patients with orthostatic hypotension and trials that did not exclude patients with orthostatic hypotension, and tested P for interaction. The primary outcome was fall events., Results: 46 trials were included, of which 18 trials excluded orthostatic hypotension and 28 trials did not. The incidence of hypotension was significantly lower in trials that excluded participants with orthostatic hypotension (1.3% versus 6.2%, P < 0.001) but not incidences of falls (4.8% versus 8.8%; P = 0.40) or syncope (1.5% versus 1.8%; P = 0.67). Antihypertensive therapy was not associated with an increased risk of falls in trials that excluded (OR 1.00, 95% CI; 0.89-1.13) or included (OR 1.02, 95% CI; 0.88-1.18) participants with orthostatic hypotension (P for interaction = 0.90)., Conclusions: The exclusion of patients with orthostatic hypotension does not appear to affect the relative risk estimates for falls and syncope in antihypertensive trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Purpose: In clinical studies, rivaroxaban treatment has been associated with increased incidence of syncope not related to bleeding, anemia, or stroke. The study objective was to evaluate the occurrence of dizziness and/or syncope not related to bleeding, anemia, or stroke in patients treated with direct oral anticoagulants (DOACs)., Methods: A retrospective, observational, comparative study of adult patients diagnosed with atrial fibrillation and treated with DOACs was conducted using digital retrieval of medical records. Primary outcomes were an emergency department (ED) visit or hospitalization due to syncope, fall, or dizziness. Cases related to bleeding, anemia, or stroke were excluded. Separate examination of a sample of records validated the data., Findings: Of 6467 eligible patients, 256 (4%) were hospitalized or referred to the ED due to fall, syncope, or dizziness during a mean observation period of 20.1 months. After multivariate regression analysis, statistically independent risk factors were found to be age (hazard ratio [HR] = 1.04, P < 0.0001) and benzodiazepine use (HR = 1.33, P = 0.03). No statistically significant difference was found among the different DOAC types regarding the primary outcome (apixaban and rivaroxaban HR = 0.97, P = 0.85; dabigatran and rivaroxaban HR = 1.2, P = 0.386)., Implications: The study results failed to confirm the claimed association between the use of a DOAC and syncopal symptoms unrelated to bleeding, anemia, or stroke in this relatively large Israeli patient population. Age and benzodiazepine treatment were significant independent risk factors of these events., Competing Interests: DECLARATION OF INTEREST None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: We aimed to describe the clinical characteristics, underlying causes and outcomes of syncope in patients with transthyretin amyloid cardiomyopathy (ATTR-CM)., Methods: The clinical profile and underlying causes of syncopal episodes were reviewed in a cohort of 128 patients with ATTR-CM enrolled from January 2018 to June 2020 in a prospective multicentre registry in 7 hospitals of Galicia (Spain). After enrollment, patients were followed during a median period of 520 days. The effect of syncope on all-cause mortality was assessed by means of multivariate Cox´s regression., Results: Thirty (23.4%) patients had a history of previous syncope as a clinical antecedent before being enrolled in the prospective phase of the registry, and 4 (3.1%) experienced a first episode of syncope thereafter. The estimated incidence density rate of syncope during the prospective follow-up period after registry enrollment was 71.9 episodes per 1000 patients-year (95% Confidence Interval (CI) 32.8-111.1). The estimated overall prevalence of syncope was 26.6% (95% CI 18.9%-34.2%). Cardiac arrhythmias (n = 11, 32.3%), structural diseases of the heart or great vessels (n = 5, 14.7%), a neurally mediated reflex (n = 6, 17.6%), and orthostatic hypotension (n = 4, 11.8%) were identified as probable underlying causes of syncope; in 8 (23.6%) patients, syncope remained unexplained. Patients with syncope had increased non-adjusted all-cause mortality than patients without it (univariate hazard-ratio 3.37; 95% CI 1.43-7.94). When other independent predictors of survival were added to the survival model, this association was no longer statistically significant (multivariate hazard-ratio 1.81, 95% CI 0.67-4.84)., Conclusions: Syncope is frequent in patients with ATTR-CM. This study could not demonstrate an independent association between syncope and mortality in those individuals. Abbreviations: ATTR-CM: Transthyretin amyloid cardiomyopathy; CI: Confidence Interval; HF: Heart Failure; HR: Hazard Ratio; IQR: Interquartile rank; LVEF: Left Ventricular Ejection Fraction; NTproBNP: N-terminal pro-brain natriuretic peptide; SD: Standard Deviation; 99m Tc-DPD: technetium-99m-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid.

The management of syncope is clinically important for heart failure (HF) patients. We herein describe a case on the efficacy of disopyramide for refractory syncope in HF with preserved ejection fraction (HFpEF). An 82-year-old man was hospitalized for respiratory distress and lower limb edema and was subsequently diagnosed with HFpEF. The use of diuretics improved HF symptoms; however, on day 10 after hospitalization, a rapid decrease in blood pressure and transient loss of consciousness developed. After neurologic examination, he was diagnosed with pure autonomic failure. Although he was administered midodrine 8 mg/d, fludrocortisone 0.1 mg/d, and droxidopa 300 mg/d, syncope was observed once a day on average. According to the Holter electrocardiogram, the patient's heart rate and coefficient of variation of R-R intervals (CVRR) during the day were unstable. In addition, high frequency power (parasympathetic nerve activity) was significantly higher than low frequency power (both sympathetic and parasympathetic nerves activity), suggesting that the parasympathetic nerves may have been highly active while the sympathetic nerves would have been blocked. On day 29, a pharmacist proposed disopyramide 300 mg/d, which blocks parasympathetic nerves and improves neural-mediated syncope, to the attending doctor. After the initiation of disopyramide, transient loss of consciousness was not observed. Furthermore, the diurnal variation in the heart rate and CVRR completely disappeared. In conclusion, disopyramide would be effective for refractory syncope in patients with HFpEF, and the Holter electrocardiogram may be a useful tool for the assessment of drug efficacy by pharmacists.

Free-floating right-heart thrombus (FFRHT) in the context of a pulmonary embolism (PE) is a rare but serious encounter with no guidelines addressing its management. We performed a systematic review and meta-analysis addressing prevalence, clinical behavior, and outcomes of FFRHT associated with PE. Among the included 397 patients with FFRHT and PE, dyspnea was the main presenting symptom (73.3%). Obstructive shock was documented in 48.9% of cases. Treatment with thrombolytic therapy, surgical thrombectomy, and percutaneous thrombectomy was documented in 43.8%, 32.7%, and 6.5% of patients, respectively. The overall mortality rate was 20.4%. Syncope ( p : 0.027), chest pain ( p : 0.006), and obstructive shock ( p : 0.037) were significantly associated with mortality. Use of thrombolytic therapy was significantly associated with survival ( p : 0.008). A multivariate logistic regression model to determine mortality predictors revealed that syncope (OR: 1.97, 95% CI: 1.06-3.65, p : 0.03), and obstructive shock (OR: 2.23, 95% CI: 1.20-4.14, p : 0.01) were associated with increased death odds. Treatment with thrombolytic therapy (OR: 0.22, 95% CI: 0.086-0.57, p : 0.002) or surgical thrombectomy (OR: 0.35, 95% CI: 0.137-0.9, p : 0.03) were associated with reduced death odds. Meta-analysis of observational studies revealed a pooled prevalence of FFRHT among all PE cases of 8.1%, and overall mortality of 23%. Although uncommon, the presence of FFRHT in the context of PE is associated with high obstructive shock and mortality rates. Favorable survival odds are observed with thrombolytic therapy and surgical thrombectomy. Data are derived from case reports and observational studies. Clinical trials elucidating these findings are needed.

A 17-year-old woman presented with transient consciousness impairment attack and convulsion after bathing and prolonged standing since age 12. EEG showed WHAM ( wake, high amplitude, anterior, male) type of phantom spikes that usually carry the high risk of epilepsy at age 13. At age 17, EEG wise generalized spike and wave complex was recorded once, and head-up tilt test was positive. She was carefully observed without antiepileptic drugs since convulsive syncope due to neurally mediated syncope was most likely. During the follow-up period, she had eventually unprovoked generalized tonic-clonic seizures (convulsive seizure) twice and thus she was started with antiepileptic drug with success. Although both convulsive syncope and convulsive seizure differ in nature and effects on quality of life, in this patient, the latter occurred later and both occurs together. It is important to distinguish them by means of the degree of convulsion and EEG finding.

Competing Interests: Carlos Fritzsche erhielt in den letzten 3 Jahren Vortragshonorare von MSD und GILEAD, sowie Reisekostenunterstützung von GILEAD. Für Elisa Schilling und Femke Böhmer liegen keine Konflikte vor.

Postural orthostatic tachycardia syndrome (POTS) is estimated to impact millions of people each year. However, there is no established gold standard for its treatment. Bupropion is a norepinephrine and a dopamine reuptake inhibitor and has been implicated as a potential treatment for POTS. We performed a non-randomized retrospective chart review on 47 patients with POTS with statistical analysis evaluating for significant findings including reduced orthostasis and improvement of symptoms with the use of bupropion. Bupropion was not associated with a statistically significant improvement in orthostatic vitals but there was an overall reduction in reported syncope. While the use of bupropion does not show a statistically significant impact on orthostatic vitals in patients with POTS, it did show a degree of improvement in syncope and as such might be useful in patients with syncope-predominant POTS., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Paraganglioma of the bladder is a rare tumour accounting for less than 0.06% of all urinary bladder tumours and has varied presentations. It may present with clinical symptoms of phaeochromocytoma, may be non-functioning and asymptomatic or may present with haematuria. Hence, paragangliomas are occasionally misdiagnosed, and this results in unanticipated intraoperative hypertensive crisis. We present the case of a 44-year-old woman with urinary bladder paraganglioma who presented with young onset hypertension, recurrent micturition syncope with prior history of coronary artery disease and stroke. She was stabilised preoperatively with alpha blocking agents and subsequently underwent successful transurethral resection of the same., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients affected by syncope without or with very short (≤5 s) prodrome with normal heart and normal ECG have been seen to present low plasma adenosine levels. We investigated whether chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, results in clinical benefit., Methods: In a consecutive case-series of 16 patients (mean age 47 ± 25 years, 9 females) who had ECG documentation of asystolic syncope, we compared the incidence of syncopal recurrence during a period without and a period with tailored theophylline therapy., Results: During a median of 60 months before ECG documentation of the index episode, the patients had a median of 2 syncopes per year. During the 6 months of the study phase without therapy, the patients had a median of 2.6 syncopes per year, p = 0.63. During the 23 months of the study phase with theophylline, the patients had a median of 0.4 syncopes per year, p = 0.005 vs history and p = 0.005 vs no therapy. In the 13 patients who had an implantable loop recorder during both study phases, the incidence of asystolic episodes > 3 s decreased from 9.6 per year to 1.1 per year, p = 0.0007. During theophylline treatment, syncope recurred in 1/5 (20%) patients who had an idiopathic atrioventricular block as the index event versus 9/11 (81%) patients who had a sinus arrest, p = 0.005., Conclusion: Theophylline is effective in reducing syncopal burden in patients with syncope without prodromes with normal heart and normal ECG. Its efficacy is greater in those with idiopathic atrioventricular block., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: The aims of the present study are to investigate the variations in clinical features, including medical history, hearing function, vestibular function, and degree of endolymphatic hydrops (EH), in Meniere's disease (MD) patients with and without drop attacks (DAs), and to examine the efficacy of intratympanic gentamicin (ITG) treatment in alleviating DAs., Methods: In total, 177 unilateral definite MD patients, including 16 patients with DAs and 161 patients without DAs, were enrolled. The results of hearing test, vestibular-evoked myogenic potentials (VEMPs), and magnetic resonance imaging (MRI) were analyzed. Thirteen patients with DAs received a single ITG treatment and were followed up., Results: The disease course of MD in the DA group was significantly longer than that in the control group (p = 0.007). MD patients with DAs had significantly greater hearing loss and worse EH than MD patients without DAs (p < 0.05). However, there was no between-group difference in vestibular function. In the study, 92.31% of refractory definite MD patients with DAs achieved satisfactory control of DAs after ITG treatment., Conclusions: MD patients with DAs tend to suffer from severe hearing loss and a significant degree of EH in the inner ear. However, the vestibular function of MD patients with DAs may not be completely abolished, but be sensitive to stimulating signals. ITG treatment, which helps to decrease vestibular sensitivity, was an effective treatment to control DAs.

There have been over 80 documented cases of swallow syncope-a rare form of reflex or neurally mediated syncope-with most cases associated with an underlying esophageal disorder. Here, we describe the first reported case of swallow syncope or presyncope caused by an infectious esophagitis. Our 65-year-old patient initially developed dysphagia, odynophagia, and presyncope with swallowing. This lead to nutrition and medication avoidance behavior, which was followed by the development of diabetic ketoacidosis. The diagnosis of swallow presyncope was confirmed with a provocative swallow study demonstrating 8 s sinus arrest, and an underlying cause of Candida esophagitis was found by upper endoscopy. Symptoms completely resolved after treatment with micafungin.

Introduction: Among implantable cardioverter-defibrillator (ICD) patients, a substantial proportion of syncopes are due to fast ventricular tachycardias (FVTs). In the experimental models of ventricular tachycardias, the arterial vasoconstriction plays an important role in recovering the arterial pressure. Since beta-blockers increase vascular resistance, we hypothesized that beta-blockers could reduce the occurrence of syncope due to FVTs. Our objective was to determine the relationship between the beta-blocker therapy and the incidence of syncope in FVT (cycle length [CL] 250-320 ms) occurring in ICD patients. Slow VTs were excluded because of the lack of symptoms and VF episodes because of the small number., Methods and Results: In this multicenter study, 226 patients (LVEF 31 ± 10%) with single-chamber ICDs were followed. FVT programming was standardized, including antitachycardia pacing (ATP) as initial therapy. Symptoms were correlated with ICD-stored episode data of FVTs. The beta-blocker therapy was determined at each FVT presentation. We analyzed 289 FVTs (CL 291 ± 21 ms; 77% under beta-blockers; median of the duration:8 s) occurring consecutively in 52 ICD patients. The frequency of FVT-related syncope was 22 (7.6%). Beta-blockers were associated with a lower heart rate preceding FVT (85 ± 22 vs. 94 ± 23 bpm; p = 0.009), a higher ATP effectiveness (86 vs. 57%; p < 0.001), a lower duration of episodes (8 [2] vs. 10 [14] s; p < 0.001), and a lower incidence of FVT-related syncope (4.5 vs. 18%; p < 0.001). By logistic regression, a FVT > 8 s (OR = 21; p = 0.003) and the beta-blocker therapy (OR = 0.3; p = 0.012) were found as independent predictors of syncope., Conclusion: Among ICD patients with left ventricular dysfunction, beta-blockers are associated with a lower incidence of FVT-related syncope.

Benign hereditary chorea (BHC) is a rare autosomal dominant disease that is characterized by non-progressive chorea with early-childhood-onset, congenital hypothyroidism, and neonatal respiratory distress. Although tetrabenazine and levodopa are partly effective for chorea and drop attacks in some patients, there is no standard treatment option. We herein describe a childhood case of BHC that presented with l-thyroxine-responsive drop attacks. A genetic analysis revealed an interstitial deletion that included two enhancer regions of NKX2-1, providing genetic confirmation of BHC. This is the first report to inform the connection between thyroid function and drop attacks in BHC. Moreover, our findings identify l-thyroxine as a therapeutic option for the management of drop attacks in BHC., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Anaphylaxis is a life-threatening allergic reaction. Several studies reported different anaphylactic reactions according to the causative substances. However, a comparison of anaphylaxis for each cause has not been done. This study was conducted to identify common causes of anaphylaxis, characteristics of anaphylactic reaction for each cause and to analyze the factors related to the severity of the reaction., Methods: Medical records of patients who visited the emergency room of Ewha Womans University Mokdong Hospital from March 2003 to April 2016 and diagnosed with anaphylactic shock were retrospectively reviewed. We compared the clinical features of anaphylaxis according to the cause. In addition, the severity of anaphylaxis was analyzed and contributing factors for severe anaphylaxis were reviewed., Results: A total of 199 patients with anaphylaxis were analyzed. Food was the most common cause (49.7%), followed by drug reaction (36.2%), bee venom (10.1%), and unknown cause (4.0%). Cardiovascular symptoms of syncope and hypotension were more common in drug-induced anaphylaxis. The incidence of severe anaphylaxis was the highest in anaphylaxis due to drugs (54.2%). Urticaria and other skin symptoms were significantly more common in food-induced anaphylaxis. Risk factors for severe anaphylaxis included older age, male, and drug-induced one. Epinephrine treatment of anaphylaxis was done for 69.7% and 56.9% of patients with food-induced and drug-induced anaphylaxis, respectively., Conclusions: More severe anaphylaxis developed with drug treatment and in males. Low rate of epinephrine prescription was also observed. Male patients with drug induced anaphylaxis should be paid more attention., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: To compare the efficacy of intratympanic gentamicin injection (ITG) on vertigo control, drop attacks, and functional level in Menière's disease patients with and without a history of migraine., Patients: Menière's disease patients (patients with migraine and age- and sex-matched control patients without migraine) treated from 2002 to 2012 who failed medical management and received ITG, with a minimum 2-year follow up., Intervention: ITG., Main Outcome Measures: Vertigo control, drop attack prevalence, and change in functional level., Results: Twenty-eight Menière's disease patients were included in this study (14 with migraine and 14 matched patients without migraine). There were three men and 11 women in each groups, with a mean age of 53 ± 8.9 years. Baseline characteristics (Menière's stage, vertigo frequency, drop attack prevalence, and functional level) before ITG were not significantly different between the two groups. Two years after ITG, 71% of Menière's disease with migraine patients and 78% of Menière's disease without migraine patients had class A, B, or C vertigo control (p > 0.999). Change in prevalence of drop attacks (43-7% versus 50-0%, respectively) was also similar (p > 0.999). However, significantly fewer vertigo control class A, B, and C migraine patients achieved functional level 1 or 2 (40%) compared with non-migraine patients (91%) (p = 0.007)., Conclusions: Although ITG appears equally effective in treating vertigo and drop attacks in Menière's disease with and without migraine, patients with migraine derive significantly less benefit in terms of functional improvement.

Background: Ventricular tachycardia is a life threatening cardiac arrhythmia. It needs management with defibrillation, without which, immediate death may occur., Case Presentation: A 66 year old black African patient with a 2 year history of hypertension was admitted to the emergency department of the Buea Regional hospital, a semi-urban setting in Cameroon, after presenting with syncope while in church. The wife described a similar episode 2 weeks prior without any further evaluation. Upon arrival at the emergency, patient had regained consciousness but lethargic, tachypneic and diaphoretic. The blood pressure was 85/61 mmHg; the pulse was 219/min, weak and thready. He had cold extremities. A 12 lead electrocardiogram performed showed a sustained monomorphic ventricular tachycardia at 230/min. He was administered six tablets of amiodarone, oxygen by nasal cannula and intravenous fluids. No electrical cardioversion was attempted due to the non availability of a defibrillator. Outcome was fatal with death of the patient 30 min after his arrival to the emergency., Conclusion: Our health facilities should be well equipped for resuscitative measures by adopting Advanced Cardiac Life Support as cardiovascular diseases are becoming more frequent in our settings.

The pro-arrhythmic triggers in Brugada and early repolarization syndromes (BrS, ERS) have not been analyzed systematically except for case reports. We clinically investigated the circumstances which precede/predispose to arrhythmic events in these syndromes during long-term follow-up. A detailed history from the patients/witnesses was taken to investigate the antecedent events in the last few hours that preceded syncope/ventricular fibrillation (VF); medical records, ECG and blood test from the emergency room (ER) were reviewed. 19 patients that fulfilled the investigation criteria were followed up for 71 ± 49 months (34-190 months). Prior to the event (syncope/VF), the patients were partaking different activities in the following decreasing order; drinking alcoholic beverage, having meal, and getting up from sleep, exercise. 3 patients reported mental/physical stress prior to the event and 2 patients developed VF several days after starting oral steroid for treatment of bronchial asthma. In the ER, elevated J-wave amplitude (0.27 ± 0.15 mV) was found with 58 % of the patients having hypokalemia. After electrolyte correction and cessation of steroids, the following day plasma K + (4.2 ± 0.3 mEq/L, P < 0.001) was significantly increased and J-wave amplitude (0.13 ± 0.1 mV, P < 0.001) was remarkably reduced. Three patients were kept on oral spironolactone/potassium supplements. During follow-up for 71 ± 49 (34-190) months, among 4 patients with VF recurrence, one patient developed VF after taking oral steroid. In ERS and BrS, hypokalemia and corticosteroid therapy add substantial pro-arrhythmic effects, but potentially treatable. Stopping steroid therapy and avoiding hypokalemia had excellent long-term outcome.

Drop attack (DA) associated with Ménière's disease (MD) and delayed endolymphatic hydrops (DEH) is not common and may cause life-threatening clinical problems. The intratympanic dexamethasone (ITD) is one of primary treatments for MD or DEH. Our study investigated the effect of ITD on the DA associated with endolymphatic hydrops (EH).We retrospectively reviewed 10 patients with MD- and DEH-associated DA between January 2009 and December 2013 in Outpatient Department of Otolaryngology, Union Hospital, Wuhan, China. Among them, 7 patients (5 cases with MD, 2 cases of DEH) received ITD (4 times, on weekly basis). Further repeated ITD courses or intratympanic gentamicin (ITG) were given if the vertigo was not satisfactorily controlled. The number of DA and status of vertigo control after intratympanic injection were evaluated. After a follow-up study lasting from 19 to 35 months, DA in 5 cases (71.4%) disappeared after initial ITD course. In 2 cases, DA was altogether controlled after an additional intratympanic injection (repeated ITD or/and ITG).This study showed that ITD promises to be a first-line conservative treatment for MD- or DEH-related DA since the steroid possesses no inner-ear toxicity. Furthermore, for MD- or DEH-related DA refractory to ITD, ITG can be an effective alternative., Competing Interests: The authors have no conflicts of interest to disclose.

Foreign body granulomatosis is a rare complication of intravenous injection of pulverized oral prescription tablets. We present the case of an active duty male who was ultimately diagnosed with foreign body granulomatosis caused by the crushing and intravenous injection of acetaminophen with oxycodone (Percocet). The 24-year-old patient initially presented with multiple syncopal episodes, hemoptysis and hypoxia. The patient presentation and imaging findings involved in foreign body granulomatosis can mimic many pulmonary disorders and can be widely variable. Diagnosis is made following lung biopsy. The disease has irreversible effects and patients usually have a progressive decline in pulmonary function. Treatment is supportive although lung transplantation may be beneficial in patients with end-stage lung disease. Pulmonary foreign body granulomatosis should be considered in patients presenting with unexplained hypoxia and imaging consistent with diffuse micronodular disease., (Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.)

Background: Risk stratification in patients with type 3 long-QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of β-blocker therapy has not been studied previously in a large LQT3 population., Methods: The study population included 406 LQT3 patients with 51 sodium channel mutations; 391 patients were known to be event free during the first year of life and were the focus of our study. Clinical, electrocardiographic, and genetic parameters were acquired for patients from 7 participating LQT3 registries. Cox regression analysis was used to evaluate the independent contribution of clinical, genetic, and therapeutic factors to the first occurrence of time-dependent cardiac events (CEs) from age 1 to 41 years., Results: Of the 391 patients, 118 (41 males, 77 females) patients (30%) experienced at least 1 CE (syncope, aborted cardiac arrest, or long-QT syndrome-related sudden death), and 24 (20%) suffered from LQT3-related aborted cardiac arrest/sudden death. The risk of a first CE was directly related to the degree of QTc prolongation. Cox regression analysis revealed that time-dependent β-blocker therapy was associated with an 83% reduction in CEs in females (P=0.015) but not in males (who had many fewer events), with a significant sex × β-blocker interaction (P=0.04). Each 10-ms increase in QTc duration up to 500 ms was associated with a 19% increase in CEs. Prior syncope doubled the risk for life-threatening events (P<0.02)., Conclusions: Prolonged QTc and syncope predispose patients with LQT3 to life-threatening CEs. However, β-blocker therapy reduces this risk in females; efficacy in males could not be determined conclusively because of the low number of events., Competing Interests: Disclosures: Dr. Wilde serves on the scientific advisory board of Lilanova. Dr. Ackerman is a consultant for Boston Scientific, Gilead Sciences, Medtronic, and St. Jude Medical. Dr. Ackerman and Mayo Clinic receive royalties from Transgenomic for their FAMILION-LQTS and FAMILION-CPVT genetic tests. None of these entities provided financial support for this study. The other authors report no conflicts., (© 2016 American Heart Association, Inc.)

A 73-year-old woman who had hypertension developed a slight fever and general malaise with laboratory-proven hepatic dysfunction as well as frequent syncopal attacks 3 months before admission to our hospital. One month later, she developed urinary retention and distal limb numbness. Upon admission, her neurological examination showed reduced limb tendon reflexes, glove and stocking-type numbness, and diminished senses of touch, temperature, pain, and distal leg vibration and position. Serum cytomegalovirus (CMV) IgM antibody and CMV IgG antibody were elevated on admission, and both decreased thereafter, confirming CMV infection. No serum anti-ganglioside antibody was detected. Cerebrospinal fluid revealed a mild pleocytosis and elevated proteins. Compound muscle action potential (CMAP) amplitudes of the tibial and peroneal nerve were slightly reduced. Sensory nerve action potential (SNAP) amplitudes of the median and ulnar nerves were reduced, and sural SNAP was not evoked. Systolic blood pressure dropped 48 mmHg when the patient assumed a standing position from a supine one, demonstrating orthostatic hypotension, and a cold pressor test was abnormal, both indicating an obvious hypofunction of the sympathetic nerve. The postganglionic autonomic nerve appeared to be damaged because the accumulation of [(123)I] meta-iodobenzylguanidine was reduced on myocardial scintigraphy. These findings combined together led us to make a diagnosis of subacute autonomic and sensory neuropathy associated with CMV infection in this case. Following an eventless administration of oral fludrocortisones, intravenous immuno-globulin (IVIg) was given after one month of the hospitalization with a remarkable reduction of the syncope. This case is instructive in two points. One is that there may be a couple of months with syncope alone before the sensory disturbance appearance, and the other is that IVIg may be considerably effective for the patient-annoying syncopes. To our knowledge, this is the first report of subacute autonomic and sensory neuropathy caused by CMV infection.

Background: Syncope may develop in 9-35% of patients with pulmonary embolism (PE). Despite its severity and importance, the prognostic value of syncope in PE is unclear. We aimed to assess the value of syncope in patients with high-to-intermediate risk PE., Methods: A total of 117 patients (62 males and 55 females, median age 51,86 ± 13,4 years) were enrolled into the study. According to the presence of syncope at the onset of PE, all patients were divided into two groups: the syncope group (SG) comprised 35 patients (48.8 ± 15.5 years, male 54.3%) who experienced at least one syncopal episode. The remaining 82 patients (53.4 ± 12.6 years, male 42.7%) without syncope comprised the control group (CG)., Results: The main predisposing risk factors of PE were the same except fewer recurrent episodes of PE (8.5 vs. 24.5% in patients from SG (p=0.048). Clinical probability of PE according to the Revised Geneva and Wells scores was high almost in every second patient in both groups (p=NS). There were twice as many patients with a high risk of fatal outcome among patients with syncope in comparison with CG patients (45.7 vs. 25.6%, respectively, p=0.032). Massive PE on computed tomography scans was found again significantly more frequently in patients with syncope (60 vs. 39%, p=0.036). The vast majority (60%) of patients with a history of syncope were treated by thrombolytic therapy (21/35) vs. only 29% of patients without syncopal events (24/82; p=0.001). In-hospital mortality was higher in patients with syncope than the control group (14.2 vs. 8.5%, p=NS)., Conclusions: The history of syncope in patients with suspected PE should be considered as a possible criterion of high risk of fatal complications of in-hospital period due to frequent embolism of the pulmonary trunk and its main branches. The use of thrombolytic therapy showed a tendency in improving outcomes., (© The European Society of Cardiology 2014.)

Breath-holding spells are a common childhood disorder that typically present before 12 months of age. Whereas most cases are benign, some patients have very severe cases associated with bradycardia that can progress from asystole to syncope and seizures. Treatment studies have implicated the use of several therapies, such as oral iron, fluoxetine, and pacemaker implantation. This is a retrospective study of patients treated with glycopyrrolate for pallid breath-holding spells. Clinical data from 4 patients referred to pediatric cardiology who saw therapeutic benefit from treatment using glycopyrrolate were reviewed to evaluate for clinical response to the drug. Two twin patients, whose symptoms began at 5 months of age, experienced a decrease in breath-holding frequency after 1 month. A patient diagnosed at 7 months of age experienced a decrease in frequency of spells. A patient diagnosed at 10 months of age reported cessation of syncope shortly after initiation of glycopyrrolate and complete resolution of breath-holding spells during prolonged treatment. This case study of 4 patients with pallid breath-holding offers evidence that glycopyrrolate may be beneficial in treating breath-holding spells and has a safer side-effect profile than pacemaker implantation., (Copyright © 2015 by the American Academy of Pediatrics.)

Objective: Symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) can be disabling. Midodrine has been proposed in the management of patients with these conditions but its impact on patient important outcomes remains uncertain. We performed a systematic review to evaluate the efficacy and safety of midodrine in patients with SOH and RRS., Methods: We searched multiple electronic databases without language restriction from their inception to June 2013. We included randomized controlled trials of patients with SOH or RRS that compared treatment with midodrine against a control and reported data on patient important outcomes. We graded the quality of evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach., Results: Eleven trials involving 593 patients were included in this review. Three studies addressed health-related quality of life in patients with RRS, showing improvement with midodrine: risk difference 14% (95% confidence interval [CI] -3.5 to 31.6), very low confidence. Seven studies addressed symptom improvement and provided poolable data showing improvement with midodrine in patients with SOH: risk difference 32.8% (95% CI 13.5-48), low confidence; and RRS: risk difference 63.3% (95% CI 47.6-68.2), very low confidence. Five studies reported syncope recurrence in patients with RRS showing improvement with midodrine: risk difference 37% (95% CI 20.8%-47.4%), moderate confidence. The most frequent side effects in the midodrine arm were pilomotor reactions (33.6%, risk ratio 4.58 [95% CI 2.03-10.37])., Conclusions: Evidence warranting low/moderate confidence suggests that midodrine improves clinical important outcomes in patients with SOH and RRS., (© 2014 American Academy of Neurology.)

Objectives/hypothesis: Vertigo attacks in most cases of Meniere's disease (MD) are successfully treated with lifestyle changes and medication. However, approximately 6% of patients with MD develop drop attacks (DAs), a potentially life-threatening condition. Traditional treatment for DAs has been surgical labyrinthectomy. The objective of this study was to assess the effectiveness of intratympanic gentamicin for DAs in patients with MD., Study Design: Retrospective charts review., Methods: All charts were reviewed from Meniere DA patients at our hospital during the 10-year period from 2002 to 2012 who had been treated with intratympanic gentamicin and had been followed for at least 1 year afterward., Results: Twenty-four ears fulfilled inclusion criteria. The time for manifestation of DAs varied from 1 to 20 years after diagnosis (mean 10 years). A total of 83.3% of ears with intractable MD and DA achieved complete symptom control of DAs after the first intratympanic gentamicin cycle and 95.8% after the further injections. Among patients with no DA recurrence by the end of the study follow-up, the symptom-free interval varied from 12 to 120 months (mean: 43.5 months). All 15 patients with ≥ 24 months follow-up were still free of DAs. Elevated or absent vestibular evoked myogenic potential thresholds were more common in DA than in contralateral ears, and hearing loss was not a major complication of the treatment., Conclusion: Intratympanic gentamicin treatment appears to be a long-lasting and effective treatment for MD with DAs., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

We report a case of a patient with recurrent syncope and paroxysmal atrial fibrillation whose clinical status greatly improved after a period of orthostatic training. The potential efficacy of this non-pharmacological measure in modulating the autonomic tone is discussed below., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The repeated syncopes in case of head and neck cancer are a complication rarely described in the literature. They occur when the tumor invade the carotid sinus or the afferent fibers of the glossopharyngeal nerve. We report the case of a 62-year-old man presented episodes of syncope synchronous of a recurrent hypopharyngeal tumor scheduled for chemotherapy and gastrostomy. A computerized tomography showed a voluminous tumor expanded to the carotid and parapharyngeal spaces. After treatment by isporenaline chlorhydrate in intensive care unit, a pacemaker was implanted to prevent syncopes and allowed the beginning of the chemotherapy., (Copyright © 2014. Published by Elsevier SAS.)