Risk of Electrolyte Disorders, Syncope, and Falls in Patients Taking Thiazide Diuretics: Results of a Cross-Sectional Study.

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.

Prehospital lactate levels in blood as a seizure biomarker: A multi-center observational study.

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.

[Diagnostic value of high-sensitivity troponin I to predict cardiac causes after syncope/near syncope in emergency department]. / La troponine I hypersensible comme marqueur diagnostique d'un(e) malaise/syncope d'origine cardiaque au service d'accueil des urgences adultes.

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.

Does N-Terminal Pro-B-Type Natriuretic Peptide Improve the Risk Stratification of Emergency Department Patients With Syncope?

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.

Role of Subclinical Iatrogenic Hyperthyroidism in the Setting of Heart Disease and Arrhythmic Burden.

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.

The value of serum uric acid levels to differentiate causes of transient loss of consciousness.

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 ±â€¯11.46 h for males (n = 23) and 40.37 ±â€¯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.

Efficacy of theophylline in patients with syncope without prodromes with normal heart and normal ECG.

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 ±â€¯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.

Do High-sensitivity Troponin and Natriuretic Peptide Predict Death or Serious Cardiac Outcomes After Syncope?

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.

Review article: Utility of troponin after syncope: A systematic review and meta-analysis.

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.

Syncope and hypotension associated with carotid sinus hypersensitivity in a patient with nasopharyngeal carcinoma: A case report.

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.

A New Feasible Syncope Risk Score Appropriate for Emergency Department: A Prospective Cohort Study.

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.

[Laboratory diagnostics in transient loss of consciousness : Serum lactate compared to serum creatine kinase as diagnostic indicator for generalized tonic-clonic seizures]. / Labordiagnostik bei transienten Bewusstseinsstörungen : Serumlaktatwert im Vergleich zur Serumkreatinkinase als diagnostischer Indikator für generalisierte tonisch-klonische Anfälle.

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.

Emerging concepts in diagnosis and treatment of syncope by pacing.

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.

Early postictal serum lactate concentrations are superior to serum creatine kinase concentrations in distinguishing generalized tonic-clonic seizures from syncopes.

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.

Low Serum Levels of Eicosapentaenoic Acid and Docosahexaenoic Acid are Risk Factors for Cardiogenic Syncope in Patients with Brugada Syndrome.

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.

Clinical utility of serum lactate levels for differential diagnosis of generalized tonic-clonic seizures from psychogenic nonepileptic seizures and syncope.

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.

Prohormones in the Early Diagnosis of Cardiac Syncope.

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.

Serum cardiac troponin I in canine syncope and seizures.

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.

Lactate as a diagnostic marker in transient loss of consciousness.

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.