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Background: For emergency department (ED) patients with syncope, cardiac troponin can identify acute coronary syndrome (ACS) and prognosticate for 30-day serious adverse events. However, it is unclear if serial testing improves diagnostic yield and prognostication., Methods: This was a secondary analysis of data from two prospective studies conducted to develop the Canadian Syncope Risk Score. Adults (age ≥ 16 years) with syncope were enrolled, and patient characteristics, vital signs, physician diagnostic impression, electrocardiogram and troponin results, and adjudicated 30-day serious adverse event were collected. The primary outcome was the detection of a serious adverse event within 30 days of ED disposition. The secondary outcome was comparison of ED length of stay among patients with single versus serial troponin measurements., Results: 4996 patients [mean age 64.5 (SD 18.8) years, 52.2% male] were included: 4397 (89.8%) with single troponin [232 (5.3%) with serious adverse event in the ED and 203 (4.6%) after ED disposition]; 499 (10.2%) patients with > 1 troponin measurement [39 (7.8%) with serious adverse event in ED and 60 (12.0%) after ED disposition]. Among those with serial measurements, 10 patients (2.0%) had a rise from below to above the 99th percentile threshold, of whom 4 patients (0.8%) suffered serious adverse event: two with arrhythmias diagnosed on electrocardiogram, one with ACS and one suffered respiratory failure. Nine patients (1.8%) had Canadian Syncope Risk Score risk reclassification based on serial measurement, and none suffered 30-day serious adverse event. Median ED length of stay was significantly longer for patients with serial testing (5.6 vs. 3.8 h, p < 0.001)., Conclusions: The initial troponin measurement was sufficient for serious adverse event detection and in-ED risk stratification. Serial troponin testing does not improve the diagnostic yield or prognostication and should be reserved for patients with ongoing symptoms or electrocardiogram findings suggestive of cardiac ischemia., (© 2024. The Author(s), under exclusive licence to the Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Background: Thiazide diuretics are a mainstay in the management of hypertension and often associated with dyselectrolytemias. We investigated the prevalence of and risk factors for hyponatremia and hypokalemia in thiazide users, substance-specific differences, and the association of thiazides with syncope and falls., Methods: In this cross-sectional analysis all patients admitted to an interdisciplinary emergency department in Switzerland between January 1, 2017, and December 31, 2018, with measurements of serum sodium and potassium were included. Data regarding serum electrolytes and creatinine were analyzed to classify for dysnatremias, dyskalemias, and acute kidney injury. Chart reviews were performed to screen for syncope or falls., Results: A total of 1604 patients (7.9%) took thiazides. Acute kidney injury was significantly more common in thiazide users (22.1 vs 7%, P < .0001). Hyponatremia (22.1 vs 9.8%, P < .0001) and hypokalemia (19 vs 11%, P < .0001) were more frequent with thiazides. Thiazide use together with higher age and female sex were independent predictors of hyponatremia and hypokalemia. A dose-dependent effect was found for electrolyte disorders, and there was a variance in risk between the investigated substances with chlorthalidone bearing the highest and hydrochlorothiazide the lowest risk. Patients taking thiazide diuretics had significantly more episodes of syncope and falls., Conclusions: Thiazide use is a clear risk factor for hyponatremia and hypokalemia. The effect appears to be dose-dependent and highly variable depending on the substance. Syncope and falls seem to be causally related to thiazide use. Especially in patients who are elderly, female, and prone to falls, the use of thiazide diuretics should be thoroughly questioned., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The objective of this study is to evaluate the diagnostic accuracy of high-sensitivity (hs) troponin I to predict cardiac origin after syncope. The secondary objective is to determine the causes of elevated troponin., Procedure: Were included hospitalized patients with syncope/near syncope diagnosed in ED. The diagnostic accuracy to predict cardiac origin was evaluated and compared to the "high risk" group, defined by the 2018 European Society of Cardiology guidelines., Results: A total of 163 patients were enrolled, 26% had a cardiac origin. Positive troponin I hs predict a cardiac origin with a sensitivity of 31%, a specificity of 80%, positive predictive value of 35% and negative value of 77%. These diagnostic performances are not discriminating and lower than the ESC classification. A positive troponine I hs level is associated with 5 times more cardiac failure during the hospitalization., Conclusion: A positive troponin I hs level after syncope/near syncope is not predictive of cardiac origin. It appears to be an early marker of ventricular remodeling in heart failure., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: The objective of this study was to assess the value of prehospital measurement of lactate level in blood for diagnosis of seizures in cases of transient loss of consciousness., Methods: Between March 2018 and September 2019, prehospital lactate was measured with a point-of-care device by the emergency medical services in an area serving a population of 900 000. A total of 383 cases of transient loss of consciousness were identified and categorized as tonic-clonic seizure (TCS), other seizure, syncope, or other cause, according to the final diagnosis in the electronic medical records system. Receiver operating characteristic curve analyses were used to identify the optimal lactate cut-off., Results: A total of 383 cases were included (135 TCS, 42 other seizure, 163 syncope, and 43 other causes). The median lactate level in TCS was 7.0 mmol/L, compared to a median of 2.0 mmol/L in all other cases (P < .001). The area under the curve (AUC) of TCS vs nonepileptic causes was 0.87 (95% confidence interval [CI] 0.83-0.91). The optimal cut-off (Youden index, 67.8%) was 4.75 mmol/L, with 79% sensitivity (95% CI 71-85) and 89% specificity (95% CI 85-93) for TCS., Significance: Prehospital lactate can be a valuable tool for identifying seizures in transient loss of consciousness. For acceptable specificity, a higher cut-off than that previously demonstrated for hospital-based measurements must be used when values obtained close to the time of the event are interpreted., (© 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Studies have reported that natriuretic peptides provide prognostic information for emergency department (ED) syncope., Objective: To evaluate whether adding N -terminal pro-B-type natriuretic peptide (NT-proBNP) to the Canadian Syncope Risk Score (CSRS) improves prediction of 30-day serious adverse events (SAEs)., Design: Prospective cohort study., Setting: 6 EDs in 2 Canadian provinces., Participants: 1452 adult ED patients with syncope., Intervention: Serum NT-proBNP was measured locally at 1 site and batch processed at a central laboratory from other sites. The concentrations were not available to treating physicians or for adjudication of outcomes., Measurements: An adjudicated composite outcome of 30-day SAEs, including death and cardiac (arrhythmic and nonarrhythmic) and noncardiac events., Results: Of 1452 patients enrolled, 152 (10.5% [95% CI, 9.0% to 12.1%]) had 30-day SAEs, 57 (3.9%) of which were identified after the index ED disposition. Serum NT-proBNP concentrations were significantly higher among patients with SAEs than those without them (median, 626.5 ng/L vs. 81 ng/L; P < 0.001). Adding NT-proBNP values to the CSRS did not significantly improve prognostication (c-statistic, 0.89 and 0.90; P  = 0.12 for difference), regardless of SAE subgroup or whether the SAE was identified after the index ED visit. The net reclassification index shows that NT-proBNP would have correctly reclassified 3% of patients with SAEs at the expense of incorrectly reclassifying 2% of patients without SAEs., Limitations: Our study was powered to detect a 3% difference in the area under the curve. The heterogeneity of outcomes and robust baseline discrimination by the CSRS will make improvements challenging., Conclusion: Although serum NT-proBNP concentrations were generally much higher among ED patients with syncope who had a 30-day SAE, this blood test added little new information to the CSRS. Routine use of NT-proBNP for ED syncope prognostication is not recommended., Primary Funding Source: Physicians' Services Incorporated Foundation, Canadian Institutes of Health Research, and The Ottawa Hospital Academic Medical Organization.

Background: Subclinical hyperthyroidism is defined by a subnormal serum thyroidstimulating hormone (TSH) level with normal free thyroxine (FT4) and free triiodothyronine (FT3) levels. Its prevalence varies from 0.6% to 16% in the elderly and can increase to 20% in patients receiving thyroid hormone replacement therapy. Thyroid disease and/or replacement therapy are frequently associated with cardiovascular involvement., Cases Presentation: We report three clinical cases of patients with initial subclinical hyperthyroidism and cardiological manifestations, including supraventricular and ventricular extrasystoles, prolapse of the mitral valve with severe regurgitation, higher mean heart rate and deterioration of the arrhythmias on arrhythmogenic dysplasia substrate., Conclusion: We discuss the role of appropriate and early correction of thyroid dysfunction in improving cardiological manifestations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Generalized tonic-clonic seizures (GTCS), syncope, and psychogenic nonepileptic seizures (PNES) are common emergent neurological conditions that cause transient disturbances of consciousness; however, it is sometimes difficult to distinguish them., Objective: This study aimed to explore the value of serum uric acid levels in differentiating among GTCS, syncope, and PNES by analyzing serum uric acid levels in patients with GTCS, syncope, and PNES., Methods: A total of 391 patients were retrospectively analyzed. Venous blood was drawn from the patients within 20 min of their arrival to the emergency department; serum uric acid levels were measured using the uricase method., Results: Serum uric acid levels and the percentage of patients with elevated uric acid (elevation percentage) were significantly higher in the group with GTCS (n = 179) than in the groups with syncope (n = 156) (p < 0.001) and PNES (n = 56) (p < 0.001). The result remained the same when the serum uric acid level of male or female patients in the group with GTCS were compared separately with that in the other two groups (all p < 0.001). In the group with GTCS, both the serum uric acid level (p < 0.001) and elevation percentage (p < 0.05) were significantly higher in males than in females. The receiver operating characteristics (ROC) analysis in male patients yielded a serum uric acid value of 428.50 μmol/L with a sensitivity of 0.78 and a specificity of 0.99 as the optimal cutoff value to distinguish GTCS from other events. In female patients, a cutoff value of 338.00 μmol/L had a sensitivity of 0.69 and a specificity of 0.91 to distinguish GTCS from other events. For the group with GTCS, the period of time between the onset of seizure and serum uric acid levels dropping to normal were analyzed in 40 patients. The duration was 44.56 ± 11.46 h for males (n = 23) and 40.37 ± 9.78 h for females (n = 17) with no significant difference (p = 0.325)., Conclusion: Serum uric acid levels provided certain clinical value for the differentiation of GTCS, syncope, and PNES; however, this requires verification in prospective studies with larger sample sizes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.)

Objectives: An estimated 1.2 million annual emergency department (ED) visits for syncope/near syncope occur in the United States. Cardiac biomarkers are frequently obtained during the ED evaluation, but the prognostic value of index high-sensitivity troponin (hscTnT) and natriuretic peptide (NT-proBNP) are unclear. The objective of this study was to determine if hscTnT and NT-proBNP drawn in the ED are independently associated with 30-day death/serious cardiac outcomes in adult patients presenting with syncope., Methods: A prespecified secondary analysis of a prospective, observational trial enrolling participants ≥ age 60 presenting with syncope, at 11 United States hospitals, was conducted between April 2013 and September 2016. Exclusions included seizure, stroke, transient ischemic attack, trauma, intoxication, hypoglycemia, persistent confusion, mechanical/electrical invention, prior enrollment, or predicted poor follow-up. Within 3 hours of consent, hscTnT and NT-proBNP were collected and later analyzed centrally using Roche Elecsys Gen 5 STAT and 2010 Cobas, respectively. Primary outcome was combined 30-day all-cause mortality and serious cardiac events. Adjusting for illness severity, using multivariate logistic regression analysis, variations between primary outcome and biomarkers were estimated, adjusting absolute risk associated with ranges of biomarkers using Bayesian Markov Chain Monte Carlo methods., Results: The cohort included 3,392 patients; 367 (10.8%) experienced the primary outcome. Adjusted absolute risk for the primary outcome increased with hscTnT and NT-proBNP levels. HscTnT levels ≤ 5 ng/L were associated with a 4% (95% confidence interval [CI] = 3%-5%) outcome risk, and hscTnT > 50 ng/L, a 29% (95% CI = 26%-33%) risk. NT-proBNP levels ≤ 125 ng/L were associated with a 4% (95% CI = 4%-5%) risk, and NT-proBNP > 2,000 ng/L a 29% (95% CI = 25%-32%) risk. Likelihood ratios and predictive values demonstrated similar results. Sensitivity analyses excluding ED index serious outcomes demonstrated similar findings., Conclusions: hscTnT and NT-proBNP are independent predictors of 30-day death and serious outcomes in older ED patients presenting with syncope., (© 2019 by the Society for Academic Emergency Medicine.)

The role of serum troponin testing in patients presenting to the ED after syncope is unclear. The aim of this systematic review was to examine the practice and utility of troponin testing among patients presenting to the ED after syncope. We conducted a search of MEDLINE, Embase, Cochrane Library, Web of Science and Scopus databases from 1990 to February 2017 using keyword and subject headings for syncope and troponin testing. Design and results of the included studies are extracted. Studies were assessed for heterogeneity and the pooled proportion of measured troponin and positive troponin result described. There were nine studies included for analysis. Significant statistical heterogeneity among studies was observed (P < 0.001). Using the random effects model, the pooled proportion of patients presenting to the ED after syncope who had troponin measured was 0.64 (95% CI 0.46-0.82). Among patients who had been troponin tested, the pooled proportion who had a positive result was 0.19 (95% CI 0.13-0.26). Variability among reported outcomes prevented further meta-analysis. Troponin testing was commonly performed for the assessment of patients with syncope with a substantial proportion returning positive results. The correlation between raised troponin and patient outcomes was not adequately reported. It is possible that an elevated troponin may indicate serious illness, rather than myocardial damage alone., (© 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.)

Background: We aimed to compare current syncope risk stratification scores and propose a new more feasible and easy-to-use one., Methods: In this prospective cohort study, we enrolled all patients (≥18 years) with chief complaint of syncope if they were not eligible for admission in terms of high-risk features. San Francisco Syncope Rule, Osservatorio Epidemiologico sulla Sincope nel Lazio, and risk stratification of syncope in the emergency department scores were compared in our population., Results: Overall, 356 patients (mean age: 44.5 years, 46.3% male) were followed for 3 months. Serious adverse events occurred in 26 (7.3%) patients including 4 deaths. Odds ratio for adverse events was 6.8 [95% confidence interval (CI), 2.8-16.1; P < 0.001; area under the curve (AUC): 66.3], 7.7 (95% CI, 3.2-18; P < 0.001; AUC: 72.8), and 18 (95% CI, 7.1-45.4; P < 0.001; AUC: 70.8) when considering San Francisco Syncope Rule, Osservatorio Epidemiologico sulla Sincope nel Lazio, and risk stratification of syncope in the emergency department scores as the predicting tools, respectively. We proposed a relatively more feasible risk score (presenting symptoms, history of cardiovascular diseases, ejection fraction <50%, and predefined electrocardiography abnormalities). According to this syncope score, odds ratio for occurring adverse events was 20.9 (95% CI, 8.4-52; P < 0.001; AUC: 79.8)., Conclusions: The 3 syncope risk scores could somehow predict 3-month adverse events. We found more feasible indicators that could predict serious events better. It suits well for emergency department.

Rationale: Carotid sinus hypersensitivity (CSH) is traditionally classified into 3 subgroups: cardioinhibitory, vasodepressor, and mixed subtypes. However, the underlying mechanism of CSH in head and neck cancer is controversial. Several pathological mechanisms of CSH have been proposed: atherosclerotic noncompliance, sternocleidomastoid proprioceptive denervation, and generalized autonomic dysfunction., Patient Concerns: We reported a 75-year-old man who had recurrent syncope attacks secondary to hypotension and reduced plasma norepinephrine (NE) levels. CSH was suspected when carotid massage induced syncope-like symptom., Diagnoses: Nasopharynx carcinoma with regional lymph node involvement and CSH., Interventions: On admission, dopamine was administered to maintain the blood pressure. When NE deficiency was confirmed, intravenous NE combined with oral midodrine replaced the dopamine treatment., Outcomes: The syncopal episodes completely resolved with periodic occurrence of hypertension., Lessons: Our case suggests a potential role of carotid sinus in regulating the release of NE in adrenal gland and that the monitoring of catecholamine level is recommended in the CSH cases either from head and neck tumors or other mechanical manipulation of carotid sinus.

Neuroendocrine syncope is a newly proposed term to embody both syncope of reflex and adenosine-related etiology. Recent publications on tilt testing have revealed the presence of a hypotensive tendency in some patients, even in the face of severe cardioinhibition. This new understanding may allow better selection of older reflex syncope patients, documented by ECG loop recorder, for successful pacing where tilt testing is ideally negative for a good result in terms of few syncope recurrences and prompts a less aggressive management policy when hypotensive medication is required. Furthermore, plasma adenosine levels not only define a new group of patients who have low adenosine and will respond well to cardiac pacing but also, by assessing adenosine receptor affinity, offer a possible explanation for vasodepression accompanying severe cardioinhibition. The question of the timing of loss of consciousness in reflex syncope needs to be addressed because, if consciousness is lost before asystole, pacing is likely to be ineffective., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Laboratory parameters can help in the differential diagnostics of acute episodes of transient loss of consciousness. Especially serum lactate and serum creatine kinase (CK) levels may provide valuable hints to distinguish generalized tonic-clonic seizures (GTCS) from syncope., Material and Methods: Serum lactate levels at admission and CK levels 10-48 h after the episodes that led to admission were compared between patients with GTCS (n = 30) and those with syncope (n = 15). In addition, sensitivity and specificity of lactate and CK as diagnostic markers for syncope and GTCS were determined., Results: The serum lactate and serum CK levels were significantly increased in patients with GTCS as compared to syncope patients (serum lactate: p < 0.001; CK: p < 0.005). The area under the curve (AUC) for serum lactate as an indicator for GTCS was 0.94 (95% confidence interval [CI] 0.88-1.0). For CK the receiver operating characteristics (ROC) analysis produced an AUC of only 0.77 (95% CI: 0.63-0.9)., Conclusion: The determination of the lactate value as point-of-care diagnostics appears to be highly relevant in the rapid clarification of unclear episodes with transient loss of consciousness. The CK level at follow-up is also suitable for distinguishing GTCS from syncope but is inferior to the serum lactate value.

Concentrations of serum creatine kinase (CK) and serum lactate are frequently measured to help differentiate between generalized tonic-clonic seizures (GTCS) and syncope. The aim of this prospective cohort study was to systematically compare these two markers. The primary outcome is the measurement of serum lactate and CK in blood samples drawn within 2 h of the event in patients admitted with either a GTCS (n = 49) or a syncope (n = 36). Furthermore, the specificity and sensitivity of serum lactate and CK are determined as diagnostic markers in distinguishing between GTCS and syncope. GTCS patients have significantly higher serum lactate levels compared to syncope patients (p < 0.001). In contrast, CK does not differ between groups at admission. Regarding the first hour after the seizure, we identify a cut-off for serum lactate of 2.45 mmol/l for diagnosing GTCS as the cause of an impairment of consciousness with a sensitivity of 0.94 and a specificity of 0.93 (AUC: 0.97; 95% CI 0.94-1.0). In the second hour after the event, the ROC analysis yields similar results (AUC: 0.94; 95% CI 0.85-1.0). Serum lactate is a sensitive and specific diagnostic marker to discriminate GTCS from syncope and is superior to CK early after admission to the emergency department.

Background: The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional-pro-A-type natriuretic peptide (MRproANP), C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin., Methods and Results: We prospectively enrolled unselected patients presenting with syncope to the emergency department (ED) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1-year follow-up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MRproANP, C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes ( P <0.001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76-0.84), 0.69 (95% CI, 0.64-0.74), 0.58 (95% CI, 0.52-0.63), and 0.68 (95% CI, 0.63-0.73), respectively. In conjunction with the ED probability (0.86; 95% CI, 0.82-0.90), MRproANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87-0.93), which was significantly higher than for the ED probability alone ( P =0.003). An algorithm to rule out cardiac syncope combining an MRproANP level of <77 pmol/L and an ED probability of <20% had a sensitivity and a negative predictive value of 99%., Conclusions: The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01548352., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antiarrhythmic effects, possibly via modulation of the cardiac ion channels. Nevertheless, it is unknown whether low serum levels of n-3 PUFAs are risk factors for ventricular fibrillation in patients with Brugada syndrome (BrS). We retrospectively reviewed data from 62 men with BrS and evaluated their serum levels of EPA and DHA, and the risk factors for sudden cardiac death, including a history of cardiogenic syncope. Nineteen patients had a history of cardiogenic syncope, and their EPA and DHA levels were significantly lower than those of the patients without syncope. Multivariate logistic regression analysis revealed that low EPA and DHA levels were associated with the incidence of syncope. The receiver-operator characteristic curve showed the area under the curves of EPA and DHA for history of syncope were 0.84 and 0.72, respectively. In conclusion, low levels of EPA and DHA are risk factors for cardiogenic syncope in patients with BrS, which suggests that n-3 PUFAs play important roles in preventing ventricular fibrillation in BrS.

Background: The differential diagnosis of generalized tonic-clonic seizures (GTCS), psychogenic nonepileptic seizures (PNES), and syncope constitutes a major challenge. Misdiagnosis rates up to 20 to 30% are reported in the literature., Purpose: To assess the clinical utility of serum lactate levels for differentiation of GTCS, PNES, and syncope based on gender differences., Methods: Data from 270 patients were evaluated retrospectively. Only patients ≥18 years old with the final diagnosis of GTCS, PNES, or syncope in their chart were recruited. Serum lactate levels were measured in the first 2h of the index event., Results: Serum lactate levels in patients with GTCS (n=157) were significantly higher than in the patients with PNES (n=25) (p<0.001) and syncope (n=88) (p<0.001). When compared with the females, serum lactate levels in patients with GTCS were significantly higher in the male subgroup (p=0.004). In male patients the ROC analysis yielded a serum lactate value of 2.43mmol/l with a sensitivity of 0.85 and a specificity of 0.88 as the optimal cut-off value to distinguish GTCS from other events. The ROC analysis for the AUC yielded a high estimate of 0.94 (95% confidence interval: 0.91-0.98). When a cut-off value of 2.43mmol/l was chosen for the females, which was an optimal value for male patients, the specificity was 0.85, however, the sensitivity was 0.64., Conclusion: We propose that serum lactate level when measured in the first 2h after the index event has a high clinical utility in the differential diagnosis of GTCS, PNES, and syncope. With concomitant clinical signs and physical examination findings besides neuroimaging and EEG, elevated levels of lactate should be taken into account when evaluating a patient with impaired consciousness. On the other hand, the suggested cut-off value 2.43mmol/l might not have a discriminative effect between GTCS, PNES, and syncope in female patients. This finding should be verified in a prospectively designed study with a larger patient population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine if serum cardiac troponin I (cTnI) concentration distinguishes between cardiogenic syncope and collapsing dogs presenting with either generalized epileptic seizures (both with and without cardiac disease) or vasovagal syncope., Animals: Seventy-nine prospectively recruited dogs, grouped according to aetiology of collapse: generalized epileptic seizures (group E), cardiogenic syncope (group C), dogs with both epileptic seizures and cardiac disease (group B), vasovagal syncope (group V) or unclassified (group U)., Methods: Most patients had ECG (n = 78), echocardiography (n = 78) and BP measurement (n = 74) performed. Dogs with a history of intoxications, trauma, evidence of metabolic disorders or renal insufficiency (based on serum creatinine concentrations >150 μmol/L and urine specific gravity <1.030) were excluded. Serum cTnI concentrations were measured and compared between groups using non-parametric statistical methods. Multivariable regression analysis investigated factors associated with cTnI. Receiver operator characteristic curve analysis examined whether cTnI could identify cardiogenic syncope., Results: Median cTnI concentrations were higher in group C than E (cTnI: 0.165 [0.02-27.41] vs. 0.03 [0.01-1.92] ng/mL; p<0.05). Regression analysis found that serum cTnI concentrations decreased with increasing time from collapse (p=0.015) and increased with increasing creatinine concentration (p=0.028). Serum cTnI diagnosed cardiogenic syncope with a sensitivity of 75% and specificity of 80%., Conclusions: Serum cTnI concentrations were significantly different between groups C and E. However, due to the overlap in cTnI concentrations between groups cTnI, measurement in an individual is not optimally discriminatory to differentiate cardiogenic syncope from collapse with generalized epileptic seizures (both with and without cardiac disease) or vasovagal syncope., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: The diagnostic classification of disorders of consciousness is often challenging, particularly the distinction between epileptic and non-epileptic seizures. The aim of the study was to examine serum lactate as a diagnostic marker of transient loss of consciousness., Method: Serum lactate levels in blood samples drawn within 2h of the event were compared retrospectively between patients with generalized tonic-clonic seizures (n=195) and patients with other seizures (syncopes [n=52], psychogenic non-epileptic seizures [n=17], and complex focal seizures [n=37]), respectively., Results: Serum lactate in patients with generalized tonic-clonic seizures was significantly (p<0.001, Mann-Whitney-U test) increased in comparison to other forms of seizure incidences. The area under the ROC-curve was 0.94 (95% CI 0.91-0.96). For a cut-off concentration of 2.45mmol/l, the sensitivity was 0.88 and the specificity 0.87., Conclusions: Serum lactate levels in the acute diagnosis were an excellent biomarker for the discrimination of generalized seizures from psychogenic non-epileptic and syncopal events, corroborating its importance for the standard work-up of acute disturbances of consciousness., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Compliance with Ethical Standards Prior Presentations The case presented here was presented as a Clinical Vignette Unknown at the Southern Society of General Internal Medicine, New Orleans, February 20–22, 2014. The clinical information and case discussion closely reflect the topics discussed. The case description was modified slightly for instructional purposes. Conflicts of Interest The authors declare that they do not have a conflict of interest. Disclosures The opinions expressed in this article are those of the authors alone and do not reflect the views of the Department of Veterans Affairs.

Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI., (Copyright © 2016 the American Physiological Society.)

Objective: To determine the value of bedside heart-type fatty acid binding protein in diagnosis of cardiac syncope in patients presenting with syncope or presyncope., Methods: The prospective study was conducted at Ankara Numune Training and Research Hospital, Ankara, Turkey, between September 1, 2010, and January 1, 2011, and comprised patients aged over 18 years who presented with syncope or presyncope. Patients presenting to emergency department within 4 hours of syncope or presyncope underwent a bedside heart-type fatty acid binding protein test measurement. SPSS 16 was used for statistical analysis., Results: Of the 100 patients evaluated, 22(22%) were diagnosed with cardiac syncope. Of them, 13(59.1%) patients had a positive and 9(40.9%) had a negative heart-type fatty acid binding protein result. Consequently, the test result was 12.64 times more positive in patients with cardiac syncope compared to those without., Conclusions: Bedside heart-type fatty acid binding protein, particularly at early phase of myocardial injury, reduces diagnostic and therapeutic uncertainity of cardiac origin in syncope patients.

Objectives: Orthostatic hypotension has been linked with increased mortality and cardiovascular morbidity; however, the underlying mechanisms are still unknown. The aim of the study was to assess markers of coagulability in patients with and without orthostatic hypotension who suffered transient loss of consciousness., Methods: A total of 233 consecutive patients more than 15 years old, with unexplained transient loss of consciousness, underwent head-up tilt test (HUT, Italian protocol). Blood samples were collected during supine rest before and at 3 min of 70° HUT for determination of fibrinogen, von Willebrand factor antigen (vWF:Ag) and activity (vWF:GP1bA), factor VIII (FVIII:C), lupus anticoagulant, and functional activated protein C-resistance. Orthostatic hypotension was defined as persistent decrease in SBP and/or DBP of more than 20/10 mmHg or SBP lower than 90 mmHg during passive HUT., Results: One hundred and seventy-eight patients (81 men, 45.5%) not treated with vitamin-K antagonists were analyzed. Those with orthostatic hypotension (n = 49) were older [61 ± 18 vs. 47 ± 21 years (mean ± SD), P < 0.001], had increased, Fviii: C-supine (1.2 ± 0.39 vs. 1.0 ± 0.35, P = 0.001), FVIII:C-standing (1.2 ± 0.36 vs. 1.0 ± 0.34, P = 0.001), vWF:Ag-supine (1.5 ± 0.66 vs. 1.1 ± 0.44, P < 0.001), vWF:Ag-standing (1.5 ± 0.67 vs. 1.1 ± 0.46, P < 0.001), vWF:GP1bA-supine (1.5 ± 0.73 vs. 1.1 ± 0.42, P < 0.001), vWF:GP1bA-standing (1.5 ± 0.75 vs. 1.1 ± 0.42 P < 0.001), fibrinogen-standing (2.9 ± 0.53 vs. 2.7 ± 0.61, P = 0.03) but not fibrinogen-supine (2.8 ± 0.54 vs. 2.7 ± 0.61, P = 0.078) compared with patients without orthostatic hypotension. However, after adjustment for age, sex, and comorbidity, only vWF:Ag and vWF:GP1bA levels remained significantly increased in orthostatic hypotension patients., Conclusion: Concentration of vWF is elevated in patients with orthostatic hypotension who suffered a syncopal event. This observation may be helpful in understanding the increased risk of cardiovascular events in orthostatic hypotension.

Background: The role of hormones in reduced orthostatic tolerance following long-term immobilization remains uncertain. We have previously shown that plasma concentrations of adrenomedullin and galanin, two peptides with vasodepressor properties, rise significantly during orthostatic challenge. We tested the hypothesis that bedrest immobilization increases the rise in adrenomedullin and galanin during orthostatic challenge leading to presyncope., Materials and Methods: We measured baseline (supine), presyncope and recovery (10 min postpresyncope, supine) levels of adrenomedullin and galanin in 8 healthy men, before and after 21 days of -6° head-down bed rest (HDBR). Presyncope was elicited using a combined head-up tilt and graded lower body negative pressure protocol. Orthostatic tolerance was defined as the time taken from the commencement of head-up tilt to the development of presyncope., Results: Orthostatic tolerance time after HDBR reduced by 8·36 ± 5·39 min (P = 0·0032). HDBR increased plasma adrenomedullin concentration to orthostatic challenge (P = 0·0367). Compared to pre-HDBR, a significant rise in post-HDBR presyncopal (P < 0·001) and recovery adrenomedullin concentration (P < 0·01) was demonstrated. In contrast, we observed no change in pre- and post-HDBR galanin levels to orthostatic challenge., Conclusions: Bedrest immobilization appears to affect adrenomedullin levels in that greater increases in adrenomedullin occur at presyncope following bedrest immobilization. Due to its peripheral vasculature hypotensive effect, the greater levels of adrenomedullin at presyncope following bedrest immobilization may have contributed to the reduced orthostatic capacity postbedrest., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

Introduction: Syncope and palpitations as the only initial manifestations of myotonic dystrophy type 1 (MD1) due to a CTG expansion of 50-100 repeats have not been reported., Case Report: In a 55-year-old female with a family history of MD1 and a personal history of a single syncope, palpitations, and hyperCKemia, 70 CTG repeats were detected in the DMPK gene. Her brother had presented atypical clinical, electromyographic, and muscle biopsy features since the age of 35 but had been diagnosed with MD1 after he later developed typical distal myotonia. He died suddenly during an episode of syncope at the age of 53. A sister with clinical myotonia died suddenly during sleep at the age of 45 and a second sister with quadriparesis died from complications of intestinal rupture at age 52. A third sister committed suicide at age 40 after developing recurrent syncopes, while a fourth sister had hyperCKemia and foot-extensor weakness. The mother of these five affected children died suddenly from myocardial rupture., Conclusions: MD1 with <100 CTG repeats may exclusively manifest cardiologically. Family screening for MD1 is important even in asymptomatic patients. MD1 may initially manifest without typical features, while muscle biopsy may be misleading and indicate glycogenosis. Close cardiac follow-up is important if MD1 manifests cardiologically to prevent syncope or sudden cardiac death., (Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Objective: We examined the diagnostic and predictive value of high-sensitivity cardiac troponin T (cTnThs) in patients with syncope., Methods: We performed an analysis of consecutive patients with syncope presenting to the emergency department. The primary end point was the accuracy to diagnose a cardiac syncope. In addition, the study explored the prognostic relevance of cTnThs in patients with cardiac and noncardiac syncope., Results: A total of 360 patients were enrolled (median age, 70.5 years; male, 55.8%; 23.9% aged >80 years). Cardiac syncope was present in 22% of patients, reflex syncope was present in 40% of patients, syncope due to orthostatic hypotension was present in 20% of patients, and unexplained syncope was present in 17.5% of patients. A total of 148 patients (41%) had cTnThs levels above the 99% confidence interval (CI) (cutoff point). The diagnostic accuracy for cTnThs levels to determine the diagnosis of cardiac syncope was quantified by the area under the curve (0.77; CI, 0.72-0.83; P < .001). A comparable area under the curve (0.78; CI, 0.73-0.83; P < .001) was obtained for the predictive value of cTnThs levels within 30 days: Patients with increased cTnThs levels had a 52% likelihood for adverse events, patients with cTnThs levels below the cutoff point had a low risk (negative predictive value, 83.5%). Increased cTnThs levels indicate adverse prognosis in patients with noncardiac causes of syncope, but not in patients with cardiac syncope being a risk factor for adverse outcome by itself., Conclusions: Patients with syncope presenting to the emergency department have a high proportion of life-threatening conditions. cTnThs levels show a limited diagnostic and predictive accuracy for the identification of patients with syncope at high risk., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Central hypovolemia elevates hemostatic activity which is essential for preventing exsanguination after trauma, but platelet activation to central hypovolemia has not been described. We hypothesized that central hypovolemia induced by lower body negative pressure (LBNP) activates platelets. Eight healthy subjects were exposed to progressive central hypovolemia by LBNP until presyncope. At baseline and 5 min after presyncope, hemostatic activity of venous blood was evaluated by flow cytometry, thrombelastography, and plasma markers of coagulation and fibrinolysis. Cell counts were also determined. Flow cytometry revealed that LBNP increased mean fluorescence intensity of PAC-1 by 1959±455 units (P<0.001) and percent of fluorescence-positive platelets by 27±18%-points (P = 0.013). Thrombelastography demonstrated that coagulation was accelerated (R-time decreased by 0.8±0.4 min (P = 0.001)) and that clot lysis increased (LY60 by 6.0±5.8%-points (P = 0.034)). Plasma coagulation factor VIII and von Willebrand factor ristocetin cofactor activity increased (P = 0.011 and P = 0.024, respectively), demonstrating increased coagulation activity, while von Willebrand factor antigen was unchanged. Plasma protein C activity and tissue-type plasminogen activator increased (P = 0.007 and P = 0.017, respectively), and D-dimer increased by 0.03±0.02 mg l(-1) (P = 0.031), demonstrating increased fibrinolytic activity. Plasma prothrombin time and activated partial thromboplastin time were unchanged. Platelet count increased by 15±13% (P = 0.014) and red blood cells by 9±4% (P = 0.002). In humans, LBNP-induced presyncope activates platelets, as evidenced by increased exposure of active glycoprotein IIb/IIIa, accelerates coagulation. LBNP activates fibrinolysis, similar to hemorrhage, but does not alter coagulation screening tests, such as prothrombin time and activated partial thromboplastin time. LBNP results in increased platelet counts, but also in hemoconcentration.

Purpose: The aim of this study was to assess the clinical significance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in the differentiation of patients with cardiac and reflex syncope., Methods: The study included a group of 100 patients (56 women, 44 men), aged 18-77 years (mean 52.6 ± 16.7), with a history of reflex (group I) or cardiac syncope (group II). Diagnosis of syncope was performed according to the European Society of Cardiology (ESC) guidelines. In all patients, the concentration of NT-proBNP was measured., Results: The assessment of NT-proBNP concentrations showed significantly higher concentrations in group II than in group I (448.7 ± 212.2 vs. 68.2 ± 64.1 pg/ml, P<0.0001). The receiver operating characteristic (ROC) curve analysis revealed that the concentration of NT-proBNP at 210.5 pg/ml may be a useful cut-off point which allows the prediction of cardiac syncope with 98 % specificity, 94 % sensitivity, and 94 % negative predictive value. In patients with cardiac arrhythmias and conduction abnormalities, the concentrations of NT-proBNP were higher in comparison to those without such disorders., Conclusions: The concentration of NT-proBNP is useful in the diagnosis of syncope and may initially guide the diagnostic process. The NT-proBNP value exceeding 200 pg/ml seems to be the most rational in determining cardiac syncope.

Background: Prior studies of admitted geriatric syncope patients suggest that diagnostic tests affect management < 5% of the time; whether this is true among all emergency department (ED) patients with syncope remains unclear., Objectives: To determine the diagnostic yield of routine testing in the hospital or after ED discharge among patients presenting to an ED with syncope., Methods: A prospective, observational, cohort study of consecutive ED patients aged ≥ 18 years presenting with syncope was conducted. The four most commonly utilized tests (echocardiography, telemetry, ambulatory electrocardiography monitoring, and troponin) were studied. Interobserver agreement as to whether test results determined the etiology of the syncope was measured using kappa (κ) values., Results: Of 570 patients with syncope, 73 patients (8%; 95% confidence interval 7-10%) had studies that were diagnostic. One hundred fifty (26%) had echocardiography, with 33 (22%) demonstrating a likely etiology of the syncopal event, such as critical valvular disease or significantly depressed left ventricular function (κ = 0.75). On hospitalization, 330 (58%) patients were placed on telemetry, and 19 (3%) had worrisome dysrhythmias (κ = 0.66). There were 317 (55%) patients who had troponin levels drawn, of whom 19 (3%) had positive results (κ = 1); 56 (10%) patients were discharged with monitoring, with significant findings in only 2 (0.4%) patients (κ = 0.65)., Conclusion: Although routine testing is prevalent in ED patients with syncope, the diagnostic yield is relatively low. Nevertheless, some testing, particularly echocardiography, may yield critical findings. Current efforts to reduce the cost of medical care by eliminating nondiagnostic medical testing and increasing emphasis on practicing evidence-based medicine argue for more discriminate testing when evaluating syncope., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This review summarizes evidence in humans for an association between hyperventilation (HV)-induced hypocapnia and a reduction in cerebral perfusion leading to syncope defined as transient loss of consciousness (TLOC). The cerebral vasculature is sensitive to changes in both the arterial carbon dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2 the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced cardiac output brain perfusion becomes jeopardized. Whether, in patients with cardiovascular disease and/or defect, cerebral blood flow cerebral control HV-induced hypocapnia elicits cerebral hypoperfusion, leading to TLOC, remains to be established.

B-type natriuretic peptides (BNPs) have been investigated as biomarkers for risk stratification of patients with syncope. Their concentration can be influenced by age and co-morbidities. In the present study, we compared the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels within 6 hours in patients with vasovagal and arrhythmic syncope to determine whether this change can predict arrhythmic syncope. Using a case-control design, 33 patients were enrolled. Of the 33 patients, 18 with arrhythmic syncope, as they underwent controlled ventricular tachycardia or ventricular fibrillation (VF) during device safety testing of an implantable cardioverter defibrillator implantation or battery replacement, were compared with 15 patients, who during a tilt-table test were diagnosed with vasovagal syncope (VS). For each patient, a blood sample for NT-proBNP evaluation was collected at baseline and 6 hours after the episode of ventricular tachycardia, VF, or VS. We calculated the percentage of increase in the 6-hour NT-proBNP concentration between the 2 groups using nonparametric techniques. We also calculated the area under a receiver operating characteristic curve with the 95% confidence intervals. The 6-hour change in the NT-proBNP concentrations between patients who had had an episode of ventricular tachycardia or VF and patients with VS was significantly different, with a median increase of 32% in the ventricular tachycardia or VF group versus 5% in the VS group (p <0.01). The area under a receiver operating characteristic curve to predict arrhythmic syncope was 0.8 (95% confidence interval 0.65 to 0.95). In conclusion, the results of the present study suggest that a 6-hour NT-proBNP increase might be able to predict arrhythmic syncope. Future work is needed to confirm these findings in undifferentiated emergency department patients who present with syncope., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Syncope is a transient loss of consciousness, which is the result of global brain hypoperfusion, characterized by rapid onset, short duration, and spontaneous complete resolution. Syncope is a common clinical problem due to its complex, multi-causal etiology, not completely understood pathogenesis and potential complications. Diagnosis of syncope is often associated with the implementation of many medical tests. In the recent years, the role of determining the concentration of NT-proBNP in the differential diagnosis of syncope has been highlighted. Aims of the study was analysis of NT-proBNP concentrations in patients with cardiogenic syncope in comparison to patients with neurogenic syncope and determination of the threshold value of NT-proBNP to differentiate cardiac and neurogenic syncope and to determine its sensitivity and specificity. The study included 160 pts (64 man, 96 women), aged 18 - 77 yrs (mean age 50,6) with a reflex syncope (group I) or cardiac syncope (group II). To determine the etiology of syncope, collected were: medical history for symptoms and circumstances of the syncope, measurements of blood pressure, resting ECG recording, cardiac echocardiography, and the concentration of NT-proBNP levels. Results: the group I included 80 pts (29 men, 51 women), aged 18 - 72 yrs (mean age 41.2). Group II included 80 pts (35 man, 45 women), aged 38 - 77 yrs (mean age 62.1). The assessment of concentrations of NT-proBNP showed significantly higher levels in group II than group I (467.6 +/- 227.4 vs 64.1 +/- 59.1; p <0.0001). In patients with arrhythmias and conduction abnormalities, the levels of NT-proBNP were higher in comparison to those without such disorders (364 +/- 249 vs. 171 +/- 209 pg/ml, p < 0.001). It was found that the concentration of NT-proBNP at 230.6 pg/ml might be a cut-off point that allows the prediction of cardiogenic cause of syncope with 96% specificity, 92% sensitivity and 93% negative predictive value. Conclusions: 1. The concentration of peptide NT-proBNP patients with reflex syncope. 2. It was shown that the cut off concentration of the NT-proBNP equal 230.6 pg/ml is characterized by the high sensitivity, specificity, and negative predictive value in determining the etiology of syncope.

Orthostatic dysregulation (OD) has been classified into subtypes by heart rate and blood pressure; however, the hemodynamics of brains have not yet been revealed. Therefore, we investigated changes in cerebral blood flow and oxygenation during an active standing test to clarify the pathophysiology of two subtypes: postural tachycardia syndrome (POTS) and neurally mediated syncope (NMS). We studied 31 children (15 boys, 16 girls; mean age, 14.0 ± 1.7 years) who presented with OD at the Department of Pediatrics and Child Health, Nihon University School of Medicine between 2009 and 2011. OD was diagnosed using the Japanese clinical guidelines for juvenile orthostatic dysregulation. After a 10-min resting period in the supine position, patients were asked to quickly stand up and keep upright for 10 min. Cerebral blood flow and cerebral oxygenation were measured using transcranial Doppler sonography and near-infrared spectroscopy. POTS showed a significant decrease of oxy-Hb and resistance index (RI), suggesting transient ischemia with maintainable cerebral autoregulation. NMS showed a decrease of oxy-Hb and an increase of RI, suggesting ischemia and impairment of autoregulation.

Syncope and orthostatic intolerance (OI) are common clinical syndromes often requiring medical attention. The former is defined as transient loss of consciousness and postural tone due to self-limited cerebral hypoperfusion, while the latter consists of inappropriate cardiovascular responses to upright posture such as occur with orthostatic hypotension (OH) or postural orthostatic tachycardia syndrome. The most frequent causes of syncope and OI are conditions that temporarily disrupt essential moment-to-moment interaction between the autonomic nervous system and cardiovascular system. In this regard, many neuropeptides (NPs) or peptide hormones (PH) exert cardioactive effects that might contribute to the pathophysiology of certain forms of syncope or OI. To date, the principal peptides that have been studied in this context are: atrial and B-type-neuropeptides, adrenomedullin, endothelin-1 (ET-1), galanin, and vasopressin. While definitive conclusions cannot yet be drawn, the intrinsic vasoconstrictor ET-1 appears to be elevated in OH, presumably to compensate for vasodilation and hypotension of other etiologies. As such elevated ET-1 may become a marker for OH. Further, elevated NT-proBNP may play a role in causing vasodilation and hypotension in some forms of OH of previously unknown cause, and may be a marker in other patients of a cardiovascular cause of syncope and OI. In the end, the study of the role of NPs and PHs in syncope and OI syndromes is at an early stage, and considerable further future effort is needed.

Background: Although the request for D-dimer is widespread in emergency departments (EDs), the causes of elevation and their relationship with D-dimer levels in patients with diagnostic values are uncertain., Methods: In this retrospective investigation, the study population consisted of all patients who visited our large urban ED in the year 2012, for whom a D-dimer test was requested for excluding or diagnosing venous thromboembolism (VTE). Only patients with D-dimer values >243ng/mL were included, regardless of their pre-test clinical probability for VTE., Results: The final study population consisted of 1647 patients. A significant positive correlation was found between age and D-dimer. Infection was the most frequent diagnosis (15.6%), followed by VTE (12.1%), syncope (9.4%), heart failure (8.9%), trauma (8.2%) and cancer (5.8%). D-dimer was higher in patients with VTE than in those with other diagnoses (2541ng/mL vs 1030ng/mL; p<0.001). The frequency of VTE gradually increased from patients with values <1000ng/mL to those with D-dimer >3000ng/mL (4.1 vs 26.7%; p<0.001). As compared with D-dimer values <1000ng/mL, the Odds Ratio for VTE was 8.5 for values >3000ng/mL., Conclusions: These results show that D-dimer lacks specificity for diagnosing VTE, especially in elderly patients admitted to the ED with significant co-morbidities. In older patients, elevated values (>1000ng/mL) are more frequently associated with VTE, so the use of higher cut-offs may be advantageous., (© 2013.)

In competitive apnea divers, the nutritional demands may be essentially different from those of, for example, endurance athletes, where energy resources need to be maximised for successful performance. In competitive apnea, the goal is instead to limit metabolism, as the length of the sustainable apneic period will depend to a great extent on minimising oxygen consumption. Many but not all elite divers fast before performing static apnea in competition. This may increase oxygen consumption as mainly lipid stores are metabolised but could also have beneficial effects on apneic duration. Our aim was to determine the effect of over-night fasting on apnea performance. Six female and seven male divers performed a series of three apneas after eating and fasting, respectively. The series consisted of two 2-min apneas spaced by 3 min rest and, after 5 min rest, one maximal effort apnea. Apneas were performed at supine rest and preceded by normal respiration and maximal inspiration. Mean (± SD) time since eating was 13 h (± 2 h 43 min) for the fasting and 1 h 34 min (± 33 min) for the eating condition (P < 0.001). Mean blood glucose was 5.1 (± 0.4) mmol/L after fasting and 5.9 (± 0.7) mmol/L after eating (P<0.01). Lung volumes were similar in both conditions (NS). For the 2-min apneas, nadir SaO2 during fasting was 95 (± 1)% and 92 (± 2)% (P < 0.001) on eating and ETCO2 was lower in the fasting condition (P < 0.01) while heart rate (HR) during apnea was 74 (± 10) bpm for fasting and 80 (± 10) bpm for eating conditions (P < 0.01). Maximal apnea durations were 4 min 41 s (± 43 s) during fasting and 3 min 51 s (± 37 s) after eating (P < 0.001), and time without respiratory contractions was 31 s (25%) longer after fasting (P < 0.01). At maximal apnea termination, SaO2 and ETCO2 were similar in both conditions (NS) and apneic HR was 63 (± 9) bpm for fasting and 70 (± 10) bpm for eating (P < 0.01). The 22% longer apnea duration after fasting with analogous end apnea SaO2 levels suggests that fasting is beneficial for static apnea performance in elite divers, likely via metabolism-limiting mechanisms. The oxygen-conserving effect of the more pronounced diving response and possibly other metabolism-limiting mechanisms related to fasting apparently outweigh the enhanced oxygen consumption caused by lipid metabolism.

Objectives: This study sought to investigate the clinical and laboratory findings of patients affected by sudden-onset syncope without prodromes who had a normal heart and normal electrocardiogram., Background: The pathophysiology of syncope in these patients is uncertain., Methods: We compared the clinical and laboratory findings of 15 patients with sudden-onset syncope without prodromes who had a normal heart and normal electrocardiogram (the study group) with those of 31 patients with established vasovagal syncope (VVS)., Results: The patients in the study group were older than those with VVS (age 61 ± 12 years vs. 46 ± 17 years) and had a history of fewer episodes of syncope (median of 2 [interquartile range [IQR]: 1 to 2.5] vs. 9 [IQR: 4 to 15] years) that were of more recent onset (median of 1 [IQR: 0 to 1] vs. 10.5 [IQR: 3.3 to 27] years). The study group had lower median baseline adenosine plasmatic levels than the VVS group (0.25 μmol/l [95% confidence interval: 0.10 to 1.51] vs. 0.85 μmol/l [95% confidence interval: 0.32 to 2.80]). On receiver-operating characteristic curve analysis, the adenosine plasmatic level of ≤0.36 best discriminated between groups, displaying 73% sensitivity and 93% specificity. Tilt table testing was more frequently positive in patients with VVS than in the study group (74% vs. 33%). A similarly high positivity rate of adenosine/adenosine triphosphate testing was found in both groups., Conclusions: Common clinical features and a low adenosine plasmatic level define a distinct form of syncope, distinguish it from VVS, and suggest a causal role of the adenosine pathway., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Syncope is associated with poor prognosis in patients with pulmonary hypertension. Atrial septostomy improves cardiac index and functional class in appropriately selected patients with pulmonary hypertension, and has been shown to improve syncope. One of the major challenges to its effectiveness is maintaining septostomy patency. We report the case of percutaneous deployment of a modified peripheral stent to create an atrial septostomy in a man with severe pulmonary hypertension and syncope, initially intolerant of medical therapy., Procedures: Percutaneous butterfly stent deployment across the interatrial septum using intracardiac echocardiography and fluoroscopy., Findings: The patient improved in all clinical parameters (BNP, six-minute walk test, dyspnoea score), and was subsequently able to tolerate targeted pulmonary hypertension therapies., Principal Conclusions: Atrial septostomy using butterfly stents to maintain patency may play a role in the treatment of patients with advanced pulmonary hypertension who do not respond to targeted therapy., (Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Aim: This study was designed to evaluate the diagnostic value of B-type natriuretic peptide (BNP) in syncope in children and adolescents., Methods: Serum BNP concentration was measured by electrochemiluminescence assay in 62 consecutive children and adolescents hospitalized for syncope., Results: Of the 62 children and adolescents hospitalized for syncope, 39 had noncardiac syncope, of whom 37 (59.7%) had autonomic-mediated reflex syncope and two (3.2%) had syncope of unknown cause. Twenty-three patients (37.1%) had cardiac syncope: 11 of these had cardiac arrhythmias and 12 had structural cardiac/cardiopulmonary disease. Patients with cardiac syncope had significantly higher serum BNP than those with non-cardiac syncope (958.78 ± 2443.41 pg/mL vs 31.05 ± 22.64 pg/mL, p < 0.05). Logistic multivariate regression analysis revealed that urinary incontinence during syncopal episodes, ECG abnormalities and increased serum BNP levels were independent predictors of cardiac syncope. At a cut-off value of 40.65 pg/mL, serum BNP was associated with significant risk of a cardiac cause of syncope, with sensitivity of 73.9% and specificity of 70.0% for distinguishing cardiac syncope from noncardiac syncope., Conclusion: Serum BNP was helpful in differentiating cardiac syncope from noncardiac syncope in children and adolescents., (©2013 The Author(s)/Acta Paediatrica ©2013 Foundation Acta Paediatrica.)

Objectives: The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope., Design and Setting: An observational study was conducted including 255 patients (mean age 60 years, range 15-93; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head-up tilt test including carotid sinus massage, and nitroglycerin provocation if indicated. Using logistic regression, we explored the associations between specific diagnoses of syncope and resting levels of circulating biomarkers: C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1 precursor fragment (CT-proET-1), midregional fragments of pro-atrial natriuretic peptide (MR-proANP) and pro-adrenomedullin (MR-proADM)., Results: A total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS), 85 (33%) with orthostatic hypotension (OH) and 47 (18%) with carotid sinus hypersensitivity (CSH); in addition, 74 (29%) patients had more than one diagnosis. Thirty-five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS was highest in the first quartile of MR-proANP [Q1 vs. Q4: odds ratio (OR) 5.57, 95% confidence interval (CI) 1.86-16.74; P < 0.001] and CT-proET-1 (OR 7.17, 95% CI 2.43-21.13; P < 0.001). By contrast, the probability of OH was highest in the fourth quartile of CT-proET-1 (Q4 vs. Q1: OR 8.66, 95% CI 2.49-30.17; P < 0.001). Furthermore, CSH was most frequently observed in the first quartile of MR-proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.62-26.62; P = 0.008) among those over 60 years of age, whereas the cardioinhibitory reflex was strongly associated with low CT-proET-1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97-696.6; P < 0.001). Moreover, in patients with VVS, a high concentration of CT-proET-1 was predictive of OH (OR per 1 SD 2.4, 95% CI 1.15-5.02; P = 0.02), whereas low CT-proET-1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.25-0.70; P = 0.001)., Conclusions: The levels of MR-proANP and CT-proET-1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks., (© 2013 The Association for the Publication of the Journal of Internal Medicine.)

Syncope from sustained orthostasis results from cerebral hypoperfusion associated with reductions in arterial pressure at the level of the brain (BPMCA) and reductions in arterial CO2 as reflected by end-tidal values (PetCO2). It was hypothesized that reductions in PetCO2 increase cerebrovascular tone before a drop in BPMCA that ultimately leads to syncope. Twelve men (21-42 yr of age) completed an orthostatic tolerance test consisting of head-up tilt and progressive lower body negative pressure to presyncope, before and after completing 5 days of continuous head-down bed rest (HDBR). Cerebral blood velocity (CBFV), BPMCA, and PetCO2 were continuously recorded throughout the test. Cerebrovascular indicators, cerebrovascular resistance, critical closing pressure (CrCP), and resistance area product (RAP), were calculated. Comparing from supine baseline to 6-10 min after the start of tilt, there were reductions in CBFV, PetCO2, BPMCA, and CrCP, an increase in RAP, and no change in cerebrovascular resistance index. Over the final 15 min before syncope in the pre-HDBR tests, CBFV and CrCP were significantly related to changes in PetCO2 (r = 0.69 ± 0.17 and r = 0.63 ± 0.20, respectively), and BPMCA, which was not reduced until the last minute of the test, was correlated with a reduction in RAP (r = 0.91 ± 0.09). Post-HDBR, tilt tolerance was markedly reduced, and changes in CBFV were dominated by a greater reduction in BPMCA with no relationships to PetCO2. Therefore, pre-HDBR, changes in PetCO2 with orthostasis contributed to increases in cerebrovascular tone and reductions in CBFV during the progression toward syncope, whereas, after 5 days of HDBR, orthostatic responses were dominated by changes in BPMCA.

The contribution of sweating to heat stress-induced reductions in haemorrhagic tolerance is not known. This study tested the hypothesis that fluid loss due to sweating contributes to reductions in simulated haemorrhagic tolerance in conditions of heat stress. Eight subjects (35 ± 8 years old; 77 ± 5 kg) underwent a normothermic time control and two heat stress trials (randomized). The two heat stress trials were as follows: (i) with slow intravenous infusion of lactated Ringer solution sufficient to offset sweat loss (IV trial); or (ii) without intravenous infusion (dehydration; DEH trial). Haemorrhage was simulated via progressive lower-body negative pressure (LBNP) to presyncope after core body (intestinal) temperature was raised by ~1.5 °C using a water-perfused suit or a normothermic time control period. The LBNP tolerance was quantified via a cumulative stress index. Middle cerebral artery blood velocity (transcranial Doppler) and mean blood pressure (Finometer®) were measured continuously. Relative changes in plasma volume were calculated from haematocrit and haemoglobin. Increases in core body temperature and sweat loss (~1.6% body mass deficit) were similar (P > 0.05) between heat stress trials. Slow intravenous infusion (1.2 ± 0.3 litres) prevented heat-induced reductions in plasma volume (IV trial, -0.6 ± 6.1%; and DEH trial, -6.6 ± 5.1%; P = 0.01). Intravenous infusion improved LBNP tolerance (632 ± 64 mmHg min) by ~20% when compared with the DEH trial (407 ± 117 mmHg min; P = 0.01), yet tolerance remained 44% lower in the IV trial relative to the time control normothermic trial (1138 ± 183 mmHg min; P < 0.01). These data indicate that although sweat-induced dehydration impairs simulated haemorrhagic tolerance, this impairment is secondary to the negative impact of heat stress itself.

Background: Jugular venous reflux (JVR) has been reported to cause cough syncope via retrograde-transmitted venous hypertension and consequently decreased cerebral blood flow (CBF). Unmatched frequencies of JVR and cough syncope led us to postulate that there should be additional factors combined with JVR to exaggerate CBF decrement during cough, leading to syncope. The present pilot study tested the hypothesis that JVR, in addition to an increased level of plasma endothelin-1 (ET-1), a potent vasoconstrictor, is involved in the pathophysiology of cough syncope., Methods: Seventeen patients with cough syncope or pre-syncope (Mean[SD] = 74.63(12.37) years; 15 males) and 51 age/gender-matched controls received color-coded duplex ultrasonography for JVR determination and plasma ET-1 level measurements., Results: Multivariate logistic analysis showed that the presence of both-side JVR (odds ratio [OR] = 10.77, 95% confident interval [CI] = 2.40-48.35, p = 0.0019) and plasma ET-1 > 3.43 pg/ml (OR = 14.57, 95% CI = 2.95-71.59, p = 0.001) were independently associated with the presence of cough syncope/ pre-syncope respectively. There was less incidence of cough syncope/ pre-syncope in subjects with the absence of both-side JVR and a plasma ET-1 ≦3.43 pg/ml. Presence of both side JVR and plasma ET-1 level of > 3.43 pg/ml, increased risk for cough syncope/pre-syncope (p < 0.001)., Conclusions: JVR and higher plasma levels of ET-1 are associated with cough syncope/ pre-syncope. Although sample size of this study was small, we showed a synergistic effect between JVR and plasma ET-1 levels on the occurrence of cough syncope/pre-syncope. Future studies should confirm our pilot findings.

Aims: To assess whether plasma troponin concentration measured by a sensitive assay can predict 1-month and 1-year serious outcome, or all-cause death in patients presenting with syncope to the emergency department (ED)., Methods: Prospective cohort study of admitted adult patients presenting to the ED after an episode of syncope who had plasma troponin measured 12 h after syncope using the ARCHITECT STAT sensitive troponin I assay (Abbott Diagnostics). Primary endpoints were the composite endpoint of serious outcome or all-cause death at 1 month and 1 year., Results: Between 1 March 2007 and 22 July 2008, 338 of 528 patients admitted from the ED with syncope had plasma troponin concentrations determined. Troponin concentrations were above the limit of detection in 261 (77%) patients. Patients numbering 120 (36%) had a troponin concentration ≥0.03 ng/ml (99th percentile of normal reference population), and 66 (20%) had concentrations ≥0.05 ng/ml (local diagnostic threshold for myocardial infarction). The proportion of patients with a composite serious outcome increased across patients stratified into quintiles based on peak troponin concentration at 1 month (0%, 9%, 13%, 26%, 70%) and at 1 year (10%, 22%, 26%, 52%, 85%)., Conclusions: The majority of patients admitted from the ED with syncope have detectable plasma troponin concentrations. Peak troponin concentration was associated with increasing risk of serious outcome and death, and this risk increases with higher troponin concentrations. Troponin may have a future role in the risk stratification of patients with syncope.