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Despite significant advances in drug‐based and device‐based therapies, heart failure remains a major and growing public health problem associated with substantial disability, frequent hospitalizations, and high economic costs. Keeping patients well and out of the hospital has become a major focus of heart failure disease management. Achieving and maintaining such stability in heart failure patients requires a holistic approach, which includes at least the management of the underlying heart disease, the management of comorbidities and the social and psychological aspects of the disease, and the management of haemodynamic/fluid status. In this regard, accurate assessment of elevated ventricular filling pressures or volume overload, that is, haemodynamic or pulmonary congestion, respectively, before the onset of worsening heart failure symptoms represents an important management strategy. Unfortunately, conventional methods for assessing congestion, such as physical examination and monitoring of symptoms and daily weights, are insensitive markers of worsening heart failure. Assessment tools that directly measure congestion, accurately and in absolute terms, provide more actionable information that enables the application of treatment algorithms designed to restore patient stability, in a variety of clinical settings. Two such assessment tools, implantable haemodynamic monitors and remote dielectric sensing (ReDS), meet the prerequisites for useful heart failure management tools, by providing accurate, absolute, and actionable measures of congestion, to guide patient management. This review focuses on the use of such technologies, across the spectrum of heart failure treatment settings. Clinical data are presented that support the broad use of pulmonary artery pressure‐guided and/or ReDS‐guided heart failure management in heart failure patients with reduced and preserved left ventricular ejection fraction.

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients. The authors acknowledge the Heart Failure Association of the European Society of Cardiology for organizing the meeting during which this topic was discussed. The authors acknowledge T.J. for her expert review of the manuscript, and W.G. S., PharmD (Campbell University College of Pharmacy and Health Sciences), supported by the Heart Failure Association of the European Society of Cardiology for contributions to content development, writing, and editing the manuscript. J.M., C.M. and F.P. performed their expert review of the paper on behalf of Acute Cardiovascular Care Association of the European Society of Cardiology. J.B. and T.T. were supported by the Deutsche Forschungsgemeinschaft, Clinical Research Group 311 (KFO 311) '(Pre-)terminal heart and lung failure: unloading and repair' (DFG; TP1 and TP11). Harjola, VP (corresponding author), Helsinki Univ Hosp, Dept Emergency Med & Serv, Div Emergency Med, PL 340, Helsinki 00029, Finland. veli-pekka.harjola@hus.fi

Aims Concentrations of insulin‐like growth factor binding protein‐7 (IGFBP7) have been linked to abnormal cardiac structure and function in patients with chronic heart failure (HF), but cardiovascular correlates of the biomarker in patients with more acute presentations are lacking. We aimed to determine the relationship between IGFBP7 concentrations and cardiac structure and to evaluate the impact of IGFBP7 on the diagnosis of acute HF among patients with acute dyspnoea. Methods and results In this pre‐specified subgroup analysis of the International Collaborative of N‐terminal pro‐B‐type Natriuretic Peptide Re‐evaluation of Acute Diagnostic Cut‐Offs in the Emergency Department (ICON‐RELOADED) study, we included 271 patients with and without acute HF. All patients presented to an emergency department with acute dyspnoea, had blood samples for IGFBP7 measurement, and detailed echocardiographic evaluation. Higher IGFBP7 concentrations were associated with numerous cardiac abnormalities, including increased left atrial volume index (LAVi; r = 0.49, P

Objective To determine the utility of a highly sensitive troponin assay when utilized in the emergency department.Methods The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician’s clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible.Trial registration ClinicalTrials.gov Identifier NCT00880802

Background The BinaxNOW coronavirus disease 2019 (COVID‐19) Ag Card test (Abbott Diagnostics Scarborough, Inc.) is a lateral flow immunochromatographic point‐of‐care test for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleocapsid protein antigen. It provides results from nasal swabs in 15 minutes. Our purpose was to determine its sensitivity and specificity for a COVID‐19 diagnosis. Methods Eligible patients had symptoms of COVID‐19 or suspected exposure. After consent, 2 nasal swabs were collected; 1 was tested using the Abbott RealTime SARS‐CoV‐2 (ie, the gold standard polymerase chain reaction test) and the second run on the BinaxNOW point of care platform by emergency department staff. Results From July 20 to October 28, 2020, 767 patients were enrolled, of which 735 had evaluable samples. Their mean (SD) age was 46.8 (16.6) years, and 422 (57.4%) were women. A total of 623 (84.8%) patients had COVID‐19 symptoms, most commonly shortness of breath (n = 404; 55.0%), cough (n = 314; 42.7%), and fever (n = 253; 34.4%). Although 460 (62.6%) had symptoms ≤7 days, the mean (SD) time since symptom onset was 8.1 (14.0) days. Positive tests occurred in 173 (23.5%) and 141 (19.2%) with the gold standard versus BinaxNOW test, respectively. Those with symptoms >2 weeks had a positive test rate roughly half of those with earlier presentations. In patients with symptoms ≤7 days, the sensitivity, specificity, and negative and positive predictive values for the BinaxNOW test were 84.6%, 98.5%, 94.9%, and 95.2%, respectively. Conclusions The BinaxNOW point‐of‐care test has good sensitivity and excellent specificity for the detection of COVID‐19. We recommend using the BinasNOW for patients with symptoms up to 2 weeks.

ObjectiveTo develop an ECG-based tool for rapid risk assessment of a cardiac cause of syncope in patients ≥40 years.MethodsIn a prospective international multicentre study, 2007 patients ≥40 years presenting with syncope were recruited in the emergency department (ED) of participating centres ranging from large university hospitals to smaller rural hospitals in eight countries from May 2010 to July 2017. 12-Lead ECG recordings were obtained at ED presentation following the syncopal event. The primary diagnostic outcome, a cardiac cause of syncope, was centrally adjudicated by two independent cardiologists using all available clinical information including 12-month follow-up. ECG predictors for a cardiac cause of syncope were identified using penalised backward selection and a continuous-scale likelihood was calculated based on regression analysis coefficients. Findings were validated in an independent US multicentre cohort including 2269 patients.ResultsIn the derivation cohort, a cardiac cause of syncope was adjudicated in 267 patients (16%). Seven ECG criteria were identified as predictors for this outcome: heart rate and QTc-interval (continuous predictors), rhythm, atrioventricular block, ST-segment depression, bundle branch block and ventricular extrasystole/non-sustained ventricular tachycardia (categorical predictors). Diagnostic accuracy of these combined predictors for a cardiac cause of syncope was high (area under the curve 0.80, 95% CI 0.77 to 0.83). Overall, 138 patients (8%) were rapidly triaged towards rule-out and 181 patients (11%) towards rule-in of a cardiac cause of syncope. External validation showed similar performance.ConclusionIn patients ≥40 years with a syncopal event, a combination of seven ECG criteria enabled rapid assessment of the likelihood that syncope was due to a cardiac cause.Trial registration numberNCT01548352 (BASEL IX), NCT01802398 (SRS study).

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, post-concussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging, because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large scale (n = 5,000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for one year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

Summary Pulmonary embolism (PE) is the most feared clinical presentation of venous thromboembolism (VTE). Patients with PE have traditionally been treated in hospital; however, many are at low risk of adverse outcomes and current guidelines suggest outpatient treatment as an option. Outpatient treatment of PE offers several advantages, including reduced risk of hospital‐acquired conditions and potential cost savings. Despite this, patients with low‐risk PE are still frequently hospitalized for treatment. This narrative review summarizes current guideline recommendations for the identification of patients with low‐risk PE who are potentially suitable for outpatient treatment, using prognostic assessment tools (e.g. the Pulmonary Embolism Severity Index [PESI] and simplified PESI) and clinical exclusion criteria (e.g. Hestia criteria) alone or in combination with additional cardiac assessments. Treatment options are discussed along with recommendations for the follow‐up of patients managed in the non‐hospital environment. The available data on outpatient treatment of PE are summarized, including details on patient selection, anticoagulant choice, and short‐term outcomes in each study. Accumulating evidence suggests that outcomes in patients with low‐risk PE treated as outpatients are at least as good as, if not better than, those of patients treated in the hospital. With mounting pressures on health care systems worldwide, increasing the proportion of patients with PE treated as outpatients has the potential to reduce health care burdens associated with VTE.

Hyperkalaemia is a common electrolyte abnormality and can cause life-threatening cardiac arrhythmia. Even though it is common in patients with diabetes, heart failure, and kidney disease, there is poor consensus over its definition and wide variability in its treatment. Medications used to treat hyperkalaemia in the emergent setting do not have robust efficacy and safety data to guide treatment leading to mismanagement due to poor choice of some agents or inappropriate dosing of others. Moreover, the medications used in the emergent setting are at best temporizing measures, with dialysis being the definitive treatment. New and old k binder therapies provide means to excrete potassium, but their roles are unclear in the emergent setting. Electrocardiograms are the corner stones of hyperkalaemia management; however, recent studies show that they might manifest abnormalities infrequently, even in severe hyperkalaemia, thus questioning their role. With an aging population and a rise in rates of heart and kidney failure, hyperkalaemia is on the rise, and there is a need, now more than ever, to understand the efficacy and safety of the current medications and to develop newer ones.

Objective Natriuretic peptides are useful diagnostic and prognostic markers in patients presenting to the emergency department (ED) with acute shortness of breath. However, B‐type natriuretic peptide (BNP) level represents a single snapshot in time, while changes relative to a patient's baseline may be useful in risk stratification. We aimed to define the variation of BNP levels between chronic stable and acute decompensated heart failure (ADHF) that is associated with significant clinical outcomes. Methods We performed a retrospective cohort chart review study of chronic heart failure (HF) patients followed in an outpatient clinic from 2010 to 2013. Inclusion criteria were available hospital and clinic BNP levels and at least 1 year of follow‐up care. ADHF was defined as a hospital admission for acute HF. Dry BNP was defined as its concentration after >3 months of optimal treatment and no variations in New York Heart Association class. Dry BNP was compared to the BNP at a subsequent ED visit that was associated with hospitalization because of ADHF. Results Overall, 253 patients were included. Their median (interquartile range [IQR]) dry BNP was 191(83–450) pg/mL. There were 67 ADHF admissions, occurring 15 ± 15 months after patient's dry BNP was established. At subsequent ED admission, the median (IQR) BNP was 1505 (72–2620) pg/mL. Patients requiring inpatient admission had a BNP ∼250% higher than their stable BNP (404 vs 164 pg/mL, p

High-sensitivity cardiac troponin (hs-cTn) assays have different analytic characteristics.The goal of this study was to quantify differences between assays for common analytical benchmarks and to determine whether they may result in differences in the management of patients with suspected acute coronary syndrome (ACS).The authors included patients with suspected ACS enrolled in the ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) I and II trials, with blood samples taken at emergency department presentation (ROMICAT-I and -II) or at 2 and 4 h thereafter (ROMICAT-II). hs-cTn concentrations were measured using 3 assays (Roche Diagnostics, Elecsys 2010 platform; Abbott Diagnostics, ARCHITECT i2000SR; Siemens Diagnostics, HsVista). Per blood sample, we determined concordance across analytic benchmarks (limit of detection [LOD]/LOD-99th percentile/99th percentile). Per-patient, the authors determined concordance of management recommendations (rule-out/observe/rule-in) per the 0/2-h algorithm, and their association with diagnostic test findings (coronary artery stenosis50% on coronary computed tomography angiography or inducible ischemia on perfusion imaging) and ACS.Among 1,027 samples from 624 patients (52.8 ± 10.0 years; 39.4% women), samples were classified as LOD (56.3% vs. 10.4% vs. 41.2%; p 0.001), LOD-99th percentile (36.5% vs. 83.5% vs. 52.6; p 0.001),99th percentile (7.2% vs. 6.0% vs. 6.2%) by Roche, Abbott, and Siemens, respectively. A total of 37.4% (n = 384 of 1,027) of blood samples were classified into the same analytical benchmark category, with low concordance across benchmarks (LOD 11.1%; LOD-99th percentile 29.3%;99th percentile 43.6%). Serial samples were available in 242 patients (40.1% women; mean age: 52.8 ± 8.0 years). The concordance of management recommendations across assays was 74.8% (n = 181 of 242) considering serial hs-cTn measurements. Of patients who were recommended to discharge, 19.6% to 21.1% had positive diagnostic test findings and 2.8% to 4.3% had ACS at presentation.Caregivers should be aware that there are significant differences between hs-cTn assays in stratifying individual samples and patients with intermediate likelihood of ACS according to analytical benchmarks that may result in different management recommendations. (Rule Out Myocardial Infarction by Computer Assisted Tomography [ROMICAT]; NCT00990262) (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).

Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the United States (n = 13) and Europe (n = 3)., Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the United States (n = 13) and Europe (n = 3). First, on testing of 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true-positive and 97.2% true-negative results. Second, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC positive and PCR/ESI-MS negative, 4.3%; BC positive and PCR/ESI-MS positive, 10.3%; BC negative and PCR/ESI-MS positive, 15.3%; and BC negative and PCR/ESI-MS negative, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and Candida species, 83%. The specificities were >94% for all individual species. Patients who had received prior antimicrobial medications (n = 603) had significantly higher PCR/ESI-MS positivity rates than patients without prior antimicrobial treatment—31% versus 22% (P

Background Hospitalization for low‐risk pulmonary embolism (PE) is common, expensive, and of questionable benefit. Objective The objective was to determine if low‐risk PE patients discharged from the emergency department (ED) on rivaroxaban require fewer hospital days compared to standard of care (SOC). Methods Multicenter, open‐label randomized trial in low‐risk PE defined by Hestia criteria. Adult subjects were randomized to early ED discharge on rivaroxaban or SOC. Primary outcome was total number of initial hospital hours, plus hours of hospitalization for bleeding or venous thromboembolism (VTE), 30 days after randomization. A 90‐day composite safety endpoint was defined as major bleeding, clinically relevant nonmajor bleeding, and mortality. Results Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of –28.8 hours (95% confidence interval [CI] = –42.55 to –15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = –46.97 to –3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = –0.18 to 0.19). Total costs were $1,496 for early discharge and $4,234 for SOC, with a median difference of $2,496 (95% CI = –$2,999 to –$2,151). Conclusions Low‐risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days.

Acute ischemic stroke affects over 800,000 US adults annually, with hundreds of thousands more experiencing a transient ischemic attack. Emergent evaluation, prompt acute treatment, and identification of stroke or TIA (transient ischemic attack) etiology for specific secondary prevention are critical for decreasing further morbidity and mortality of cerebrovascular disease. The Biomarkers of Acute Stroke Etiology (BASE) study is a multicenter observational study to identify serum markers defining the etiology of acute ischemic stroke. Observational trial of patients presenting to the hospital within 24h of stroke onset. Blood samples are collected at arrival, 24, and 48h later, and RNA gene expression is utilized to identify stroke etiology marker candidates. The BASE study began January 2014. At the time of writing, there are 22 recruiting sites. Enrollment is ongoing, expected to hit 1000 patients by March 2017. The BASE study could potentially aid in focusing the initial diagnostic evaluation to determine stroke etiology, with more rapidly initiated targeted evaluations and secondary prevention strategies.Clinical Trial Registration Clinicaltrials.gov NCT02014896 https://clinicaltrials.gov/ct2/show/NCT02014896?term=biomarkers+of+acute+stroke+etiology&rank=1.

Aims This study aimed to systematically identify and summarise all risk scores evaluated in the emergency department setting to stratify acute heart failure patients. Methods and results A systematic review of PubMed and Web of Science was conducted including all multicentre studies reporting the use of risk predictive models in emergency department acute heart failure patients. Exclusion criteria were: (a) non-original articles; (b) prognostic models without predictive purposes; and (c) risk models without consecutive patient inclusion or exclusively tested in patients admitted to a hospital ward. We identified 28 studies reporting findings on 19 scores: 13 were originally derived in the emergency department (eight exclusively using acute heart failure patients), and six in emergency department and hospitalised patients. The outcome most frequently predicted was 30-day mortality. The performance of the scores tended to be higher for outcomes occurring closer to the index acute heart failure event. The eight scores developed using acute heart failure patients only in the emergency department contained between 4–13 predictors (age, oxygen saturation and creatinine/urea included in six scores). Five scores (Emergency Heart Failure Mortality Risk Grade, Emergency Heart Failure Mortality Risk Grade 30 Day mortality ST depression, Epidemiology of Acute Heart Failure in Emergency department 3 Day, Acute Heart Failure Risk Score, and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) have been externally validated in the same country, and two (Emergency Heart Failure Mortality Risk Grade and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) further internationally validated. The c-statistic for Emergency Heart Failure Mortality Risk Grade to predict seven-day mortality was between 0.74–0.81 and for Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure to predict 30-day mortality was 0.80–0.84. Conclusions There are several scales for risk stratification of emergency department acute heart failure patients. Two of them are accurate, have been adequately validated and may be useful in clinical decision-making in the emergency department i.e. about whether to admit or discharge.

Background and Purpose: Optimal secondary prevention for patients with embolic stroke of undetermined source (ESUS) remains unknown. We aimed to assess whether high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with major vascular events and whether hs-cTnT may identify patients who benefit from anticoagulation following ESUS. Methods: Data were obtained from the biomarker substudy of the NAVIGATE ESUS trial, a randomized controlled trial testing the efficacy of rivaroxaban versus aspirin for secondary stroke prevention in ESUS. Patients were dichotomized at the hs-cTnT upper reference limit (14 ng/L, Gen V, Roche Diagnostics). Cox proportional hazard models were computed to explore the association between hs-cTnT, the combined cardiovascular end point (recurrent stroke, myocardial infarction, systemic embolism, cardiovascular death), and recurrent ischemic stroke. Results: Among 1337 patients enrolled at 111 participating centers in 18 countries (mean age 67±9 years, 61% male), hs-cTnT was detectable in 95% and at/above the upper reference limit in 21%. During a median follow-up of 11 months, the combined cardiovascular end point occurred in 68 patients (5.0%/y, rivaroxaban 28 events, aspirin 40 events; hazard ratio, 0.67 [95% CI, 0.41–1.1]), and recurrent ischemic stroke occurred in 50 patients (4.0%/y, rivaroxaban 16 events, aspirin 34 events, hazard ratio 0.45 [95% CI, 0.25–0.81]). Annualized combined cardiovascular end point rates were 8.2% (9.5% rivaroxaban, 7.0% aspirin) for those above hs-cTnT upper reference limit and 4.8% (3.1% rivaroxaban, 6.6% aspirin) below with a significant treatment modification ( P =0.04). Annualized ischemic stroke rates were 4.7% above hs-cTnT upper reference limit and 3.9% below, with no suggestion of an interaction between hs-cTnT and treatment ( P =0.3). Conclusions: In patients with ESUS, hs-cTnT was associated with increased cardiovascular event rates. While fewer recurrent strokes occurred in patients receiving rivaroxaban, outcomes were not stratified by hs-cTn results. Our findings support using hs-cTnT for cardiovascular risk stratification but not for decision-making regarding anticoagulation therapy in patients with ESUS. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02313909.

Purpose To review the mechanisms of action, expected efficacy and side effects of strategies to control hyperkalemia in acutely ill patients. Methods We searched MEDLINE and EMBASE for relevant papers published in English between Jan 1, 1938, and July 1, 2018, in accordance with the PRISMA Statement using the following terms: “hyperkalemia,” “intensive care,” “acute kidney injury,” “acute kidney failure,” “hyperkalemia treatment,” “renal replacement therapy,” “dialysis,” “sodium bicarbonate,” “emergency,” “acute.” Reports from within the past 10 years were selected preferentially, together with highly relevant older publications. Results Hyperkalemia is a potentially life-threatening electrolyte abnormality and may cause cardiac electrophysiological disturbances in the acutely ill patient. Frequently used therapies for hyperkalemia may, however, also be associated with morbidity. Therapeutics may include the simultaneous administration of insulin and glucose (associated with frequent dysglycemic complications), β-2 agonists (associated with potential cardiac ischemia and arrhythmias), hypertonic sodium bicarbonate infusion in the acidotic patient (representing a large hypertonic sodium load) and renal replacement therapy (effective but invasive). Potassium-lowering drugs can cause rapid decrease in serum potassium level leading to cardiac hyperexcitability and rhythm disorders. Conclusions Treatment of hyperkalemia should not only focus on the ability of specific therapies to lower serum potassium level but also on their potential side effects. Tailoring treatment to the patient condition and situation may limit the risks. Electronic supplementary material The online version of this article (10.1186/s13613-019-0509-8) contains supplementary material, which is available to authorized users.

Lung ultrasound is a useful tool for the assessment of patients with both acute and chronic heart failure, but the use of different image acquisition methods, inconsistent reporting of the technique employed and variable quantification of 'B-lines,' have all made it difficult to compare published reports. We therefore need to ensure that future studies utilizing lung ultrasound in the assessment of heart failure adopt a standardized approach to reporting the quantification of pulmonary congestion. Strategies to improve patient care by use of lung ultrasound in the assessment of heart failure have been difficult to develop. In the present document, key aspects of standardization are discussed, including equipment used, number of chest zones assessed, the method of quantifying B-lines, the presence and timing of additional investigations (e.g. natriuretic peptides and echocardiography) and the impact of therapy. This consensus report includes a checklist to provide standardization in the preparation, review and analysis of manuscripts. This will serve as a guide for investigators and clinicians and enhance the quality and transparency of lung ultrasound research.

Objective Introduction of target specific anticoagulants and recent guidelines encourage outpatient management of low risk patients with venous thromboembolism. We describe hospital admission rates over time for patients presenting to US emergency departments (EDs) with deep vein thrombosis (DVT) and pulmonary embolism (PE) and estimate the proportion of low-risk PE patients who could potentially be managed as outpatients. Methods We performed a structured analysis of the National Hospital Ambulatory Medical Care Survey (a nationally representative weighted sampling of US ED visits) database for the years 2006-2010 including all adult patients with a primary diagnosis of DVT or PE. Simplified pulmonary embolus scoring index (sPESI) scores were determined in patients with PE to identify low risk patients. Results There were an estimated 652,000 and 394,000 ED visits for DVT and PE over the 5-year period (0.17%). Mean (SE) age was 59 (1.3), 50% were female, and 40% were > 65 years. Admission rates for DVT and PE were 52% and 90% respectively with no significant changes over time. In patients with DVT, predictors for admission were age (odds ratio, 1.03 per year of age [95% confidence interval, 1.01 to 1.05]) and race (odds ratio, 4.1 [95% confidence interval, 0.9 to 19.8] for Hispanics and 2.9 [1.2 to 7.4] for Blacks). Of all ED patients with PE, 51% were low risk based on sPESI scores. Conclusion Admission rates for DVT and PE have remained high and unchanged, especially with PE, minorities, and in older patients. Based on sPESI scores, up to half of PE patients might be eligible for early discharge or outpatient therapy.

Background We aimed to compare the diagnostic accuracy of the Alere Triage Cardio3 Tropinin I (TnI) assay (Alere, Inc., USA) and the PathFast cTnI-II (Mitsubishi Chemical Medience Corporation, Japan) against the central laboratory assay Singulex Erenna TnI assay (Singulex, USA). Methods Using the Markers in the Diagnosis of Acute Coronary Syndromes (MIDAS) study population, we evaluated the ability of three different assays to identify patients with acute myocardial infarction (AMI). The MIDAS dataset, described elsewhere, is a prospective multicenter dataset of emergency department (ED) patients with suspected acute coronary syndrome (ACS) and a planned objective myocardial perfusion evaluation. Myocardial infarction (MI) was diagnosed by central adjudication. Results The C-statistic with 95% confidence intervals (CI) for diagnosing MI by using a common population (n=241) was 0.95 (0.91-0.99), 0.95 (0.91-0.99), and 0.93 (0.89-0.97) for the Triage, Singulex, and PathFast assays, respectively. Of samples with detectable troponin, the absolute values had high Pearson (R(P)) and Spearman (R(S)) correlations and were R(P)=0.94 and R(S)=0.94 for Triage vs Singulex, R(P)=0.93 and R(S)=0.85 for Triage vs PathFast, and R(P)=0.89 and R(S)=0.73 for PathFast vs Singulex. Conclusions In a single comparative population of ED patients with suspected ACS, the Triage Cardio3 TnI, PathFast, and Singulex TnI assays provided similar diagnostic performance for MI.

Aims It is unknown whether cardiac syncope, and possibly also other syncope aetiologies exhibit circadian, weekly, seasonal, and temperature-dependent patterns. Methods and results We prospectively recorded the exact time, date, and outside temperature of syncope of patients >40 years old presenting with syncope to the emergency department in a diagnostic multicentre study. Two independent cardiologists/emergency physicians adjudicated the final diagnosis based on all information becoming available during clinical work-up including 1-year follow-up. Among 1230 patients, the adjudicated aetiology was cardiac in 14.6%, reflex in 39.2%, orthostatic in 25.7%, other non-cardiac in 9.7%, and unknown in 10.8% of patients. All syncope aetiologies occurred much more frequently during the day when compared with the night (P 40 years old display circadian, weekly, seasonal, and temperature-dependent patterns. Unfortunately, these patterns do not allow to reliably differentiate cardiac syncope from other aetiologies.

BACKGROUND The early diagnosis of urgent abdominal pain (UAP) is challenging. Most causes of UAP are associated with extensive inflammation. Therefore, we hypothesized that quantifying inflammation using interleukin-6 and/or procalcitonin would provide incremental value in the emergency diagnosis of UAP. METHODS This was an investigator-initiated prospective, multicenter diagnostic study enrolling patients presenting to the emergency department (ED) with acute abdominal pain. Clinical judgment of the treating physician regarding the presence of UAP was quantified using a visual analog scale after initial clinical and physician-directed laboratory assessment, and again after imaging. Two independent specialists adjudicated the final diagnosis and the classification as UAP (life-threatening, needing urgent surgery and/or hospitalization for acute medical reasons) using all information including histology and follow-up. Interleukin-6 and procalcitonin were measured blinded in a central laboratory. RESULTS UAP was adjudicated in 376 of 1038 (36%) patients. Diagnostic accuracy for UAP was higher for interleukin-6 [area under the ROC curve (AUC), 0.80; 95% CI, 0.77–0.82] vs procalcitonin (AUC, 0.65; 95% CI, 0.62–0.68) and clinical judgment (AUC, 0.69; 95% CI, 0.65–0.72; both P < 0.001). Combined assessment of interleukin-6 and clinical judgment increased the AUC at presentation to 0.83 (95% CI, 0.80–0.85) and after imaging to 0.87 (95% CI, 0.84–0.89) and improved the correct identification of patients with and without UAP (net improvement in mean predicted probability: presentation, +19%; after imaging, +15%; P < 0.001). Decision curve analysis documented incremental value across the full range of pretest probabilities. A clinical judgment/interleukin-6 algorithm ruled out UAP with a sensitivity of 97% and ruled in UAP with a specificity of 93%. CONCLUSIONS Interleukin-6 significantly improves the early diagnosis of UAP in the ED.

WOS: 000432489900040, PubMed: 29525076, Background: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. Aims: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. Methods: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Results: Mean age was 66.9 +/- 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. Conclusions: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research., Bayer AGBayer AG; Janssen Research and Development; Canadian Stroke Prevention Intervention Network, Grant support: Sponsored by Bayer AG and Janssen Research and Development; partial funding for the Biomarker, Genetics, Gene Expression Substudy from the Canadian Stroke Prevention Intervention Network.

To assess the effects of non-invasive ventilation (NIV) in emergency department (ED) patients with acute heart failure (AHF) on short term outcomes.Patients from the EAHFE Registry (a multicenter, observational, multipurpose, cohort-designed database including consecutive AHF patients in 41 Spanish EDs) were grouped based on NIV treatment (NIV+ and NIV-groups). Using propensity score (PS) methodology, we identified two subgroups of patients matched by 38 covariates and compared regarding 30-day survival (primary outcome). Interaction was investigated for age, sex, ischemic cardiomyopathy, chronic obstructive pulmonary disease, AHF precipitated by an acute coronary syndrome (ACS), AHF classified as hypertensive or acute pulmonary edema (APE), and systolic blood pressure (SBP). Secondary outcomes were intensive care unit (ICU) admission; mechanical ventilation; in-hospital, 3-day and 7-day mortality; and prolonged hospitalization (7 days).Of 11,152 patients from the EAHFE (age (SD): 80 (10) years; 55.5% women), 718 (6.4%) were NIV+ and had a higher 30-day mortality (HR = 2.229; 95%CI = 1.861-2.670) (p 0.001). PS matching provided 2 groups of 490 patients each with no significant differences in 30-day mortality (HR = 1.239; 95%CI = 0.905-1.696) (p = 0.182). Interaction analysis suggested a worse effect of NIV on elderly patients (85 years, p 0.001), AHF associated with ACS (p = 0.045), and SBP 100 mmHg (p 0.001). No significant differences were found in the secondary endpoints except for more prolonged hospitalizations in NIV+ patients (OR = 1.445; 95%CI = 1.122-1.862) (p = 0.004).The use of NIV to treat AHF in ED is not associated with improved mortality outcomes and should be cautious in old patients and those with ACS and hypotension.

Introduction: Hypertensive emergency has a high mortality risk and the treatment goal is to quickly lower blood pressure with intravenous (IV) medications. Characteristics that are associated with non-response to IV antihypertensives have not been identified. The objective is to identify patient characteristics associated with resistance to IV antihypertensives. Methods: This was a subanalysis of patients enrolled in the previously described comparative effectiveness trial of IV nicardipine vs. labetalol use in the emergency department (CLUE) study, a randomized trial of nicardipine vs. labetalol. Non-responders were defined as those patients who did not achieve target systolic blood pressure (SBP), as set by the treating physician, within thirty minutes of IV antihypertensive medication, +/- 20mmHg. Stepwise logistic regression was used to identify covariates associated with the measurement outcomes. Results: CLUE enrolled 226 patients, 52.7% female, 76.4% black, mean age of 52.6±14.6 years, of whom 110 were treated with nicardipine and 116 with labetalol. The median (IQR) initial systolic blood pressure was 211mmHg (198, 226), 210 (200, 230), and 211mmHg (198, 226), for the total, non-responder, and responder cohorts, respectively (p-value=0.65, 95% CI [-5.8-11.3]). Twenty-nine were non-responders, 9 in the nicardipine and 20 in the labetalol group. In univariate analysis, several symptoms suggestive of end organ damage were associated with non-response. After multiple variable logistic regression (AUC = 0.72), treatment with labetalol (OR 2.7, 95% CI [1.1-6.7]), history of stroke (OR 5.4, 95% CI [1.6-18.5]), and being male (OR 3.3, 95% CI [1.4-8.1]) were associated with failure to achieve target blood pressure. Conclusion: Male gender and history of previous stroke are associated with difficult to control blood pressure. [West J Emerg Med. 2015;16(2):276–283.]

To compare short-term outcomes after an episode of acute heart failure (AHF) in patients with reduced and preserved ejection fractions (HFrEF, 49%; respectively) according to their destinations after emergency department (ED) care. Methods and results: This secondary analysis of the EAHFE Registry (consecutive AHF patients diagnosed in 41 Spanish EDs) investigated 30-day all-cause mortality, in-hospital all-cause mortality, prolonged hospitalisation (> 7 days), and 30-day post-discharge ED revisit due to AHF, all-cause death, and combined endpoint (ED revisit/death) in 5829 patients with echocardiographically documented HFrEF and HfpEF (HFrEF/HFpEF: 1,442/4,387). Adjusted ratios were calculated for patients admitted to internal medicine (IM), short stay unit (SSU), and discharged from the ED without hospitalisation (DEDWH) and compared with those admitted to cardiology. For HFrEF, the only significant differences were lower in-hospital mortality (OR = 0.26; 95% CI 0.08-0.81; p = 0.021) and prolonged hospitalisation (OR = 0.07; 95% CI 0.04-0.13; p

Background In nonvalvular atrial fibrillation (NVAF), rivaroxaban is used to prevent stroke and systemic embolism. Objective To evaluate major bleeding (MB) in NVAF patients treated with rivaroxaban in a real-world clinical setting. Methods From January 1, 2013, to March 31, 2014, US Department of Defense electronic health care records were queried to describe MB rates and demographics. Major bleeding was identified using a validated algorithm. Results Of 27 467 patients receiving rivaroxaban, 496 MB events occurred in 478 patients, an incidence of 2.86 per 100 person-years (95% confidence interval: 2.61-3.13). The MB patients were older, mean (SD) age of 78.4 (7.7) vs 75.7 (9.7) years, compared with non-MB patients. Patients with MB had higher rates of hypertension (95.6% vs 75.8%), coronary artery disease (64.2% vs 36.7%), heart failure (48.5% vs 23.7%), and renal disease (38.7% vs 16.7%). Of MB patients, 63.2% were taking 20 mg, 32.2% 15 mg, and 4.6% 10 mg of rivaroxaban. Four percent of MB patients took warfarin within the prior 30 days. Major bleeding was most commonly gastrointestinal (88.5%) or intracranial (7.5%). Although 46.7% of MB patients received a transfusion, none had sufficient evidence of receiving any type of clotting factor. Fourteen died during their MB hospitalization, yielding a fatal bleeding incidence rate of 0.08 per 100 person-years (95% confidence interval: 0.05-0.14). Mean age at death was 82.4 years. Conclusions In this large observational study, the MB rate was generally consistent with the registration trial results, and fatal bleeds were rare.

In acute heart failure (AHF) syndromes significant respiratory failure (RF) is essentially seen in patients with acute cardiogenic pulmonary oedema (ACPE) or cardiogenic shock (CS). Non-invasive ventilation (NIV), the application of positive intrathoracic pressure through an interface, has shown to be useful in the treatment of moderate to severe RF in several scenarios. There are two main modalities of NIV: continuous positive airway pressure (CPAP) and pressure support ventilation (NIPSV) with positive end expiratory pressure. Appropriate equipment and experience is needed for NIPSV, whereas CPAP may be administered without a ventilator, not requiring special training. Both modalities have shown to be effective in ACPE, by a reduction of respiratory distress and the endotracheal intubation rate compared to conventional oxygen therapy, but the impact on mortality is less conclusive. Non-invasive ventilation is also indicated in patients with AHF associated to pulmonary disease and may be considered, after haemodynamic stabilization, in some patients with CS. There are no differences in the outcomes in the studies comparing both techniques, but CPAP is a simpler technique that may be preferred in low-equipped areas like the pre-hospital setting, while NIPSV may be preferable in patients with significant hypercapnia. The new modality 'high-flow nasal cannula' seems promising in cases of AHF with less severe RF. The correct selection of patients and interfaces, early application of the technique, the achievement of a good synchrony between patients and the ventilator avoiding excessive leakage, close monitoring, proactive management, and in some cases mild sedation, may warrant the success of the technique.

BackgroundNearly 5 million emergency department (ED) visits for head injury occur each year in the United States, of which

Background Dyspnea is the most common presenting symptom in patients with acute heart failure (AHF), but is difficult to quantify as a research measure. The URGENT Dyspnea study compared 3 scales: (1) 10 cm VAS, (2) 5-point Likert, and (3) a 7-point Likert (both VAS and 5-point Likert were recorded in the upright and supine positions). However, the minimal clinically important difference (MCID) to patients has not been well established. Methods We performed a secondary analysis from URGENT Dyspnea, an observational, multi-center study of AHF patients enrolled within 1 h of first physician assessment in the ED. Using the anchor-based method to determine the MCID, a one-category change in the 7-point Likert was used as the criterion standard (‘minimally improved or worse’). The main outcome measures were the change in visual analog scale (VAS) and 5-point Likert scale from baseline to 6-h assessment relative to a 1-category change response in the 7-point Likert scale (‘minimally worse’, ‘no change’, or ‘minimally better’). Results Of the 776 patients enrolled, 491 had a final diagnosis of AHF with responses at both time points. A 10.5 mm (SD 1.6 mm) change in VAS was the MCID for improvement in the upright position, and 14.5 mm (SD 2.0 mm) in the supine position. However, there was no MCID for worsening, as few patients reported worse dyspnea. There was also no significant MCID for the 5-point Likert scale. Conclusion A 10.5 mm change is the MCID for improvement in dyspnea over 6 h in ED patients with AHF.

Background Hospitalization and early anticoagulation therapy remain standard care for patients who present to the emergency department (ED) with pulmonary embolism (PE). For PEs discovered incidentally, however, optimal therapeutic strategies are less clear—and all the more so when the patient has cancer, which is associated with a hypercoagulable state that exacerbates the threat of PE. Methods We conducted a retrospective review of a historical cohort of patients with cancer and incidental PE who were referred for assessment to the ED in an institution whose standard of care is outpatient treatment of selected patients and use of low-molecular-weight heparin for anticoagulation. Eligible patients had received a diagnosis of incidental PE upon routine contrast enhanced chest CT for cancer staging. Survival data was collected at 30 days and 90 days from the date of ED presentation and at the end of the study. Results We identified 193 patients, 135 (70%) of whom were discharged and 58 (30%) of whom were admitted to the hospital. The 30-day survival rate was 92% overall, 99% for the discharged patients and 76% for admitted patients. Almost all (189 patients, 98%) commenced anticoagulation therapy in the ED; 170 (90%) of these received low-molecular-weight heparin. Patients with saddle pulmonary artery incidental PEs were more likely to die within 30 days (43%) than were those with main or lobar (11%), segmental (6%), or subsegmental (5%) incidental PEs. In multivariate analysis, Charlson comorbidity index (age unadjusted), hypoxemia, and incidental PE location (P = 0.004, relative risk 33.5 (95% CI 3.1–357.4, comparing saddle versus subsegmental PE) were significantly associated with 30-day survival. Age, comorbidity, race, cancer stage, tachycardia, hypoxemia, and incidental PE location were significantly associated with hospital admission. Conclusions Selected cancer patients presenting to the ED with incidental PE can be treated with low-molecular-weight heparin anticoagulation and safely discharged. Avoidance of unnecessary hospitalization may decrease in-hospital infections and death, reduce healthcare costs, and improve patient quality of life. Because the natural history and optimal management of this condition is not well described, information supporting the creation of straightforward evidence-based practice guidelines for ED teams treating this specialized patient population is needed.

Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI).Purpose: To estimate the ability of a single hs-cTnT concentration below the limit of detection (Data Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016).Study Selection: Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization.Data Extraction: Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements Data Synthesis: Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died.Limitation: Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies.Conclusion: A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome.Primary Funding Source: Emergency Care Foundation.

Background Guidelines suggest observation stays are appropriate for pulmonary embolism (PE) patients at low-risk for early mortality. We sought to assess agreement between United States (US) observation management of PE and claims-based and clinical risk stratification criteria. Methods Using US Premier data from 11/2012 to 3/2015, we identified adult observation stay patients with a primary diagnosis of PE, ≥1 PE diagnostic test claim and evidence of PE treatment. The proportion of patients at high-risk was assessed using the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) equation and high-risk characteristics (age > 80 years, heart failure, chronic lung disease, renal or liver disease, high-risk for bleeding, cancer or need for thrombolysis/embolectomy). Results We identified 1633 PE patients managed through an observation stay. Despite their observation status, IMPACT classified 46.4% as high-risk for early mortality and 33.3% had ≥1 high-risk characteristic. Co-morbid heart failure, renal or liver disease, high-risk for major bleeding, cancer and hemodynamic instability were low (each 80 years-of-age and 19.4% had chronic lung disease. Conclusion Many PE patients selected for management in observation stay units appeared to have clinical characteristics suggestive of higher-risk for mortality based upon published claims-based and clinical risk stratification criteria.

Measuring cardiac troponins is integral to diagnosing acute myocardial infarction (AMI); however, troponins may be elevated without AMI, and the use of multiple different assays confounds comparisons. We considered characteristics and serial troponin values in emergency department chest pain patients with and without AMI to interpret troponin excursions. We compared serial troponin in 124 AMI and non-AMI patients from the observational Performance of Triage Cardiac Markers in the Clinical Setting (PEARL) study who presented with chest pain and had at least one troponin value exceeding the 99th percentile of normal. Because 8 assays were used during data collection, we employed a method of scaling the troponin value to the corresponding assay's 99th percentile upper reference limit to standardize the results. In 81 AMI patients, 96% had elevated troponin at the first test following initial elevation, compared to 73% of the 43 non-AMI patients (P < 0.001). Scaling troponin to the 99th percentile of normal yielded a median value that was 4.8 [2.2, 14.1] times higher than the 99th percentile cutpoint among AMI patients, compared to 2.3 [1.5, 6.5] times higher among non-AMI patients (P = 0.04). The rise in serial scaled troponin values distinguished the AMI patients. Scaling to the 99th percentile was useful for comparing troponin when different assays were utilized.

D-dimer testing is important to aid in the exclusion of venous thromboembolic events (VTEs), including deep venous thrombosis and pulmonary embolism, and it may be used to evaluate suspected aortic dissection. D-dimer is produced upon activation of the coagulation system with the generation and subsequent degradation of cross-linked fibrin by plasmin. Many different assays for D-dimer testing are currently used in routine care. However, these tests are neither standardized nor harmonized. Consequently, only clinically validated assays and assay specific decision limits should be used for routine testing. For the exclusion of pulmonary embolism/deep vein thrombosis, age-adjusted cut-offs are recommend. Clinicians must be aware of the validated use of their hospital's D-dimer assay to avoid inappropriate use of this biomarker in routine care.

The purpose of this article is to review the clinical efficacy and safety of nitrates in acute heart failure (AHF) by examining various trials on nitrates in AHF. Management of AHF can be challenging due to the lack of objective clinical evidence guiding optimal management. There have been many articles suggesting that, despite a benefit, nitrates are underused in clinical practice. Nitrates, when appropriately dosed, have a favourable effect on symptoms, blood pressure, intubation rates, mortality and other parameters.

Objective To compare health service cost and length of stay between a traditional and an accelerated diagnostic approach to assess acute coronary syndromes (ACS) among patients who presented to the emergency department (ED) of a large tertiary hospital in Australia. - Design, setting and participants This historically controlled study analysed data collected from two independent patient cohorts presenting to the ED with potential ACS. The first cohort of 938 patients was recruited in 2008–2010, and these patients were assessed using the traditional diagnostic approach detailed in the national guideline. The second cohort of 921 patients was recruited in 2011–2013 and was assessed with the accelerated diagnostic approach named the Brisbane protocol. The Brisbane protocol applied early serial troponin testing for patients at 0 and 2 h after presentation to ED, in comparison with 0 and 6 h testing in traditional assessment process. The Brisbane protocol also defined a low-risk group of patients in whom no objective testing was performed. A decision tree model was used to compare the expected cost and length of stay in hospital between two approaches. Probabilistic sensitivity analysis was used to account for model uncertainty. - Results Compared with the traditional diagnostic approach, the Brisbane protocol was associated with reduced expected cost of $1229 (95% CI −$1266 to $5122) and reduced expected length of stay of 26 h (95% CI −14 to 136 h). The Brisbane protocol allowed physicians to discharge a higher proportion of low-risk and intermediate-risk patients from ED within 4 h (72% vs 51%). Results from sensitivity analysis suggested the Brisbane protocol had a high chance of being cost-saving and time-saving. - Conclusions This study provides some evidence of cost savings from a decision to adopt the Brisbane protocol. Benefits would arise for the hospital and for patients and their families.