Inflammatory Biomarkers and Clinical Judgment in the Emergency Diagnosis of Urgent Abdominal Pain.

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.

Indications and practical approach to non-invasive ventilation in acute heart failure.

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.

Presenting phenotypes of acute heart failure patients in the ED: Identification and implications.

BACKGROUND: There is little known about the baseline hemodynamic (HD) profiles (beyond pulse/blood pressure) of patients presenting to the Emergency department (ED) with acute heart failure (AHF). Assessing these baseline parameters could help differentiate underlying HD phenotypes which could be used to develop specific phenotypic specific approaches to patient care. METHODS: Patients with suspected AHF were enrolled in the PREMIUM (Prognostic Hemodynamic Profiling in the Acutely Ill Emergency Department Patient) multinational registry and continuous HD monitoring was initiated on ED presentation using noninvasive finger cuff technology (Nexfin, BMEYE, Edwards Lifesciences, Irvine, California). Individuals with clinically suspected and later confirmed AHF were included in this analysis and initial 15minute averages for available HD parameters were calculated. K-means clustering was performed to identify out of 23 HD variables a set that provided the greatest level of inter-cluster discrimination and intra-cluster cohesions. RESULTS: A total of 127 patients had confirmed AHF. The final model, using mean normalized patient baseline HD values was able to differentiate these individuals into 3 distinct phenotypes. Cluster 1: normal cardiac index (CCI) and systemic vascular resistance index (SVRI); cluster 2: very low CI and markedly increased SVRI: and cluster 3: low CI and an elevated SVRI. These clusters were not differentiated using clinically available ED information. CONCLUSIONS: Three distinct clusters were defined using novel noninvasive presenting HD monitoring technology in this cohort of ED AHF patients. Further studies are needed to determine whether phenotypic specific therapies based on these clusters can improve outcomes.

Hemodynamic characteristics of suspected stroke in the emergency department.

BACKGROUND: Systemic hemodynamic characteristics of patients with suspected acute ischemic stroke are poorly described. The objective of this study was to identify baseline hemodynamic characteristics of emergency department (ED) patients with suspected acute stroke. METHODS: This was a planned analysis of the stroke cohort from a multicenter registry of hemodynamic profiling of ED patients. The registry prospectively collected non-invasive hemodynamic measurements of patients with suspicion for acute stroke within 12h of symptom onset. K-means cluster analysis identified hemodynamic phenotypes of all suspected stroke patients, and we performed univariate hemodynamic comparisons based on final diagnoses. RESULTS: There were 72 patients with suspected acute stroke, of whom 38 (53%) had a final diagnosis of ischemic stroke, 10 (14%) had hemorrhagic stroke, and 24 (33%) had transient ischemic attack (TIA). Analysis defined three phenotypic clusters based on low or normal cardiac index (CI) and normal or high systemic vascular resistance index (SVRI). Patients with TIA had lower mean CI (2.3L/min/m2) compared to hemorrhagic or ischemic stroke patients (p<0.01). CONCLUSIONS: The study demonstrates the feasibility of defining hemodynamic phenotypes of ED patients with suspected stroke.

Presenting hemodynamic phenotypes in ED patients with confirmed sepsis.

OBJECTIVES: To derive distinct clusters of septic emergency department (ED) patients based on their presenting noninvasive hemodynamic (HD) measurements and to determine if any clinical parameters could identify these groups. METHODS: Prospective, observational, convenience study of individuals with confirmed systemic infection. Presenting, pretreatment noninvasive HD parameters were compiled using Nexfin (Bmeye/Edwards LifeSciences) from 127 cases. Based on normalized parameters, k-means clustering was performed to identify a set of variables providing the greatest level of intercluster discrimination and intracluster cohesion. RESULTS: Our best HD clustering model used 2 parameters: the cardiac index (CI [L/min per square meter]) and systemic vascular resistance index (SVRI [dynes·s/cm5 per square meter]). Using this model, 3 different patient clusters were identified. Cluster 1 had high CI with normal SVRI (CI, 4.03 ± 0.61; SVRI, 1655.20 ± 348.08); cluster 2 low CI with increased vascular tone (CI, 2.50 ± 0.50; SVRI, 2600.83 ± 576.81); and cluster 3 very low CI with markedly elevated SVRI (CI, 1.37 ± 0.81; SVRI, 5951.49 ± 1480.16). Cluster 1 patients had the lowest 30-day overall mortality. Among clinically relevant variables available during the initial patient evaluation in the ED age, heart rate and temperature were significantly different across the 3 clusters. CONCLUSIONS: Emergency department patients with confirmed sepsis had 3 distinct cluster groupings based on their presenting noninvasively derived CI and SVRI. Further clinical studies evaluating the effect of early cluster-specific therapeutic interventions are needed to determine if there are outcome benefits of ED HD phenotyping in these patients.

Predictive value of plasma proenkephalin and neutrophil gelatinase-associated lipocalin in acute kidney injury and mortality in cardiogenic shock.

BACKGROUND: Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock. RESULTS: P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71-150) pmol/mL and 138 (84-214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1-4.4, p = 0.03] and 2.8 [95% CI 1.2-6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK24h > 105.7 pmol/L and P-NGAL24h > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1-10.7, p < 0.001) and 5.2 (95% CI 2.8-9.8, p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock. CONCLUSIONS: High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality. TRIAL REGISTRATION: NCT01374867 at www.clinicaltrials.gov , registered 16 Jun 2011-retrospectively registered.

Risk stratification scores for patients with acute heart failure in the Emergency Department: A systematic review.

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.

Expert consensus document: Reporting checklist for quantification of pulmonary congestion by lung ultrasound in heart failure.

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.

Emergency department perspectives on B-type natriuretic peptide utility.

In the emergency department (ED), patients do not present with a diagnosis. Rather they manifest a symptom for which the physician must determine the most probable cause. It is the sorting of possibly acutely fatal diagnoses that is unique to the practice of emergency medicine. Unfortunately, the historically available rapid diagnostic tools lack both sensitivity and specificity. This creates risk for the acutely ill patient in whom either a delayed or erroneous diagnosis can be associated with a startling increase in mortality. B-type natriuretic peptide (BNP) assessment in the ED is a valuable adjunct for increasing the accuracy of the initial clinical impression. This allows early outcome-improving interventions to proceed with greater certainty. Finally, as a prognostic marker indicative of illness severity, knowledge of BNP levels can improve the accuracy of disposition decisions.

Usefulness of serial assessment of natriuretic peptides in the emergency department for patients with acute decompensated heart failure.

The value of natriuretic peptides, both B-type natriuretic peptide (BNP) and N-terminal prohormone brain natriuretic peptide (NTproBNP), for determining diagnosis, severity, and prognosis of emergency department (ED) patients with acute decompensated heart failure (ADHF) has been well documented. Emerging data support the hypothesis that repeated natriuretic peptide determinations in the acute phase of ADHF may assist in confirming the diagnosis, monitoring drug therapy, and evaluating the adequacy of patient stabilization. Data from the authors' group demonstrate that in patients admitted to the ED for acute dyspnea, serial NTproBNP measurement at admission and 4, 12, and 24 hours later was useful in confirming the diagnosis of ADHF compared with patients with chronic obstructive pulmonary disease. Moreover, in the same patients receiving intensive intravenous diuretic therapy, there was a progressive reduction of NTproBNP blood levels from hospitalization to discharge (P<.001), accompanied by clinical improvement and stabilization of heart failure. More recently, the authors also demonstrated that in ADHF patients improving with diuretics, a progressive reduction in BNP levels was observed, starting 24 hours after ED admission and continuing until discharge. Comparing BNP and NTproBNP, there was a significant correlation between NTproBNP and BNP levels but not between NTproBNP's and BNP's percent variation compared with baseline. In ADHF, serial ED measurements of BNP are useful for monitoring the effects of treatment. A reduction in BNP from admission to discharge is indicative of clinical improvement.

Natriuretic peptides in acute coronary syndromes: prognostic value and clinical implications.

Levels of natriuretic peptides, including B-type natriuretic peptide and N-terminal prohormone brain natriuretic peptide, are strong independent predictors of prognosis in acute coronary syndrome (ACS). They are associated with short- and long-term mortality and with the risk of new-onset heart failure, above and beyond the conventional risk factors. Myocardial ischemia and ventricular wall stress are triggers for the release of natriuretic peptides, and although the latter are associated with the severity of the underlying coronary artery disease, they fail to predict recurrent nonfatal ACS. In conclusion, natriuretic peptide values may improve risk stratification in ACS when used in addition to troponin levels and other prognostic markers, but more data are needed to define their role in ACS therapy.

Frequency and Prognostic Significance of Abnormal Liver Function Tests in Patients With Cardiogenic Shock.

Cardiogenic shock (CS) is a cardiac emergency often leading to multiple organ failure and death. Assessing organ dysfunction and appropriate risk stratification are central for the optimal management of these patients. The purpose of this study was to assess the prevalence of abnormal liver function tests (LFTs), as well as early changes of LFTs and their impact on outcome in CS. We measured LFTs in 178 patients in CS from serial blood samples taken at 0 hours, 12 hours, and 24 hours. The associations of LFT abnormalities and their early changes with all-cause 90-day mortality were estimated using Fisher's exact test and Cox proportional hazards regression analysis. Baseline alanine aminotransferase (ALT) was abnormal in 58% of the patients, more frequently in nonsurvivors. Abnormalities in other LFTs analyzed (alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin) were not associated with short-term mortality. An increase in ALT of >20% within 24 hours (ΔALT>+20%) was observed in 24% of patients. ΔALT>+20% was associated with a more than 2-fold increase in mortality compared with those with stable or decreasing ALT (70% and 28%, p <0.001). Multivariable regression analysis showed that ΔALT>+20% was associated with increased 90-day mortality independent of other known risk factors. In conclusion, an increase in ALT in the initial phase was seen in 1/4 of patients in CS and was independently associated with 90-day mortality. This finding suggests that serial ALT measurements should be incorporated in the clinical assessment of patients in CS.

European Society of Cardiology-Acute Cardiovascular Care Association Position paper on acute heart failure: A call for interdisciplinary care.

Acute heart failure (AHF) continues to have unacceptably high rates of mortality and morbidity. This position paper highlights the need for more intense interdisciplinary cooperation as one key element to overcome the challenges associated with fragmentation in the care of AHF patients. Additional aspects discussed include the importance of early diagnosis and treatment, options for initial treatment, referral bias as a potential cause for treatment preferences among experts, considerable uncertainty regarding patient disposition, the diagnosis of accompanying acute myocardial infarction, the need for antibiotic therapy, as well as assessment of intravascular volume status.

Disposition of emergency department patients diagnosed with acute heart failure: an international emergency medicine perspective.

Many patients with acute heart failure are initially managed in emergency departments (EDs) worldwide. Although some require hospitalization for further management, it is likely that a sizeable proportion could be safely discharged either directly from the ED or after a more extended period of management in an observation-type unit. Identification of low-risk patients who are safe for such an approach to management continues to be a global unmet need. This is driven in part by a lack of clarity on postdischarge outcomes for lower risk patients and a nonexistent consensus on what may be acceptable event rates. The current paper reviews previous studies carried out on patients directly discharged from the ED, suggests a general disposition algorithm and focuses on discharge metrics, which are based on both evidence and expert opinion. In addition, we propose that the following variables be considered for future determination of acceptable event rates: (a) baseline characteristics and risk status of the patient; (b) access to follow-up;

Emergency department use of galectin-3.

Emergency medicine represents a unique practice environment where diagnostic accuracy, treatment, and critical disposition decisions must occur in a time-sensitive environment intolerant of both errors and inefficiency. These pressures can make an accurate heart failure diagnosis challenging, as it must be predominately based on clinical findings. Although accuracy is improved by natriuretic peptide testing, at some point in the clinical course a disposition is required regardless of diagnostic certainty. Disposition options range widely from expensive and highly specialized intensive care unit admissions to low-tech/low-cost observation management or even discharge directly to home. In this vein, success is predicated on matching patient needs to available resources while minimizing the untimely discharge that results in a return visit to the emergency room. Thus, the role of the emergency physician is to predict the future based on limited objective data. Biomarkers may aid in this task, and the newly available galectin-3 assay may be of particular utility. Elevated galectin-3, reflective of myocardial fibrosis and inflammation, is associated with increased risk of short-term death and the necessity for 30-day rehospitalization. The availability of accurate risk stratification tools for predicting the probability of rehospitalization or death could guide in the matching of resource-intensive heart failure disease management efforts to the higher risk cohort, while simultaneously identifying lower risk candidates for successful observation unit or outpatient management. This article reviews the potential utility of galectin-3 measurement for use in emergency department decision making.

Noninvasive hemodynamic monitoring in emergency patients with suspected heart failure, sepsis and stroke: the PREMIUM registry.

INTRODUCTION: Noninvasive hemodynamic (HD) assessments in the emergency department (ED) might assist in the diagnosis, therapeutic plan development and risk stratification of acutely ill patients. This multinational observational study was designed to initiate noninvasive HD measurements prior to any ED patient therapeutic interventions and broadly evaluate them for potential diagnostic, therapeutic and predictive value. METHODS: We enrolled patients with suspected acute heart failure (AHF), sepsis or stroke. Continuous noninvasive HD monitoring was begun using the Nexfin finger cuff device (Edwards LifeSciences, BMEYE, Amsterdam, Netherlands). Beat-to-beat HD measurements were averaged for the initial 15 minutes, prior to therapeutic intervention. We performed suspected disease group comparisons and evaluated HD predictors of 30-day mortality. RESULTS: Of 510 patients enrolled: 185 (36%) AHF, 194 (38%) sepsis and 131 (26%) stroke. HD variables were significantly different (p<0.05) amongst the groups. Cardiac output and index and stroke volume index (SVI) were highest in sepsis (6.5, 3.5, 36), followed by stroke (5.5, 2.7, 35.8), and lowest in AHF (5.4, 2.7, 33.6). The in-group HD standard deviations and ranges measurements were large, indicating heterogeneous underlying HD profiles. Presenting SVI predicted 30-day mortality for all groups. CONCLUSION: Presenting ED noninvasive HD data has not been previously reported in any large patient population. Our data suggest a potential role for early noninvasive HD assessments aiding in diagnosing of patients, individualizing therapy based on each person's unique HD values and predicting 30-day mortality. Further studies and analyses are needed to determine how HD assessments should be best used in the ED.

Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox.

OBJECTIVES: This study sought to define the relationship between body mass index (BMI) and mortality in heart failure (HF) across the world and to identify specific groups in whom BMI may differentially mediate risk. BACKGROUND: Obesity is associated with incident HF, but it is paradoxically associated with better prognosis during chronic HF. METHODS: We studied 6,142 patients with acute decompensated HF from 12 prospective observational cohorts followed-up across 4 continents. Primary outcome was all-cause mortality. Cox proportional hazards models and net reclassification index described associations of BMI with all-cause mortality. RESULTS: Normal-weight patients (BMI 18.5 to 25 kg/m(2)) were older with more advanced HF and lower cardiometabolic risk. Despite worldwide heterogeneity in clinical features across obesity categories, a higher BMI remained associated with decreased 30-day and 1-year mortality (11% decrease at 30 days; 9% decrease at 1 year per 5 kg/m(2); p < 0.05), after adjustment for clinical risk. The BMI obtained at index admission provided effective 1-year risk reclassification beyond current markers of clinical risk (net reclassification index 0.119, p < 0.001). Notably, the "protective" association of BMI with mortality was confined to persons with older age (>75 years; hazard ratio [HR]: 0.82; p = 0.006), decreased cardiac function (ejection fraction <50%; HR: 0.85; p < 0.001), no diabetes (HR: 0.86; p < 0.001), and de novo HF (HR: 0.89; p = 0.004). CONCLUSIONS: A lower BMI is associated with age, disease severity, and a higher risk of death in acute decompensated HF. The "obesity paradox" is confined to older persons, with decreased cardiac function, less cardiometabolic illness, and recent-onset HF, suggesting that aging, HF severity/chronicity, and metabolism may explain the obesity paradox.

Incremental value of biomarkers to clinical variables for mortality prediction in acutely decompensated heart failure: the Multinational Observational Cohort on Acute Heart Failure (MOCA) study.

AIM: This study aims to evaluate the incremental value of plasma biomarkers to traditional clinical variables for risk stratification of 30-day and one-year mortality in acutely decompensated heart failure (ADHF). METHODS AND RESULTS: Through an international collaborative network, individual patient data on 5306 patients hospitalized for ADHF were collected. The all-cause mortality rate was 11.7% at 30 days and 32.9% at one year. The clinical prediction model (age, gender, blood pressure on admission, estimated glomerular filtration rate <60 mL/min/1.73 m(2), sodium and hemoglobin levels, and heart rate) had a c-statistic of 0.74 for 30-day mortality and 0.73 for one-year mortality. Several biomarkers measured at presentation improved risk stratification when added to the clinical model. At 30 days, the net reclassification improvement (NRI) was 28.7% for mid-regional adrenomedullin (MR-proADM; p<0.001) and 25.5% for soluble (s)ST2 (p<0.001). At one year, sST2 (NRI 10.3%), MR-proADM (NRI 9.1%), amino-terminal pro-B-type natriuretic peptide (NT-proBNP; NRI 9.1%), mid-regional proatrial natriuretic peptide (MR-proANP; NRI 7.4%), B-type natriuretic peptide (NRI 5.5%) and C-reactive protein (CRP; NRI 5.3%) reclassified patients with ADHF (p<0.05 for all). CRP also markedly improved risk stratification of patients with ADHF as a dual biomarker combination with MR-proADM (NRI 36.8% [p<0.001] for death at 30 days) or with sST2 (NRI 20.3%; [p<0.001] for one-year mortality). CONCLUSION: In this study, biomarkers provided incremental value for risk stratification of ADHF patients. Biomarkers such as sST2, MR-proADM, natriuretic peptides and CRP, reflecting different pathophysiologic pathways, add prognostic value to clinical risk factors for predicting both short-term and one-year mortality in ADHF.

Association between elevated blood glucose and outcome in acute heart failure: results from an international observational cohort.

OBJECTIVE: The aim of this analysis was to assess the association between elevated blood glucose level and mortality in acute heart failure (AHF). BACKGROUND: Elevated blood glucose has been reported to be prognostically meaningful in patients with cardiac diagnoses, such as coronary artery disease. The short-term prognostic impact of hyperglycemia in AHF is unknown, however. METHODS: In a multinational cohort of AHF, we examined the ability of blood glucose concentrations at presentation to predict all-cause mortality by 30 days. Fully adjusted models for prognosis included a previous diagnosis of diabetes mellitus as a covariate. RESULTS: A total of 6,212 subjects with AHF (mean age, 72 years; 52.5% male) were studied; the median blood glucose concentration on arrival at the hospital was 7.5 mmol/l (135 mg/dl), and 41% had a previous diagnosis of diabetes mellitus (DM). After 30 days, 618 patients (10%) had died. Compared with survivors, decedents had significantly higher median blood glucose concentrations (8.9 mmol/l vs. 7.4 mmol/l; p < 0.0001). In the fully adjusted model, an elevated blood glucose level was an independent predictor of 30-day mortality in AHF (odds ratio: 2.19; 95% confidence interval: 1.69 to 2.83; p < 0.001). The risk associated with an elevated blood glucose level appeared consistent across all subgroups of patients, including patients with preserved (hazard ratio: 5.41; 95% confidence interval: 2.44 to 12.0; p < 0.0001) and impaired systolic function (hazard ratio: 2.37; 95% confidence interval: 1.57 to 3.59; p < 0.0001). Furthermore, in reclassification analyses, elevated blood glucose added significant prognostic information to clinical parameters alone (4.4% net reclassification improvement; p = 0.01). CONCLUSIONS: Among patients with AHF, blood glucose concentrations at presentation are powerfully prognostic for 30-day mortality, independent of a diagnosis of diabetes mellitus or other clinical variables. Because blood glucose is easily modifiable, it may represent a valid target for therapeutic intervention.

Short-term mortality risk in emergency department acute heart failure.

OBJECTIVES: Few tools exist that provide objective accurate prediction of short-term mortality risk in patients presenting with acute heart failure (AHF). The purpose was to describe the accuracy of several biomarkers for predicting short-term death rates in patients diagnosed with AHF in the emergency department (ED). METHODS: The Biomarkers in ACute Heart failure (BACH) trial was a prospective, 15-center, international study of patients presenting to the ED with nontraumatic dyspnea. Clinicians were blinded to all investigational markers, except troponin and natriuretic peptides, which used the local hospital reference range. For this secondary analysis, a core lab was used for all markers except troponin. This study evaluated patients diagnosed with AHF by the on-site emergency physician (EP). RESULTS: In the 1,641 BACH patients, 466 (28.4%) had an ED diagnosis of AHF, of whom 411 (88.2%) had a final diagnosis of AHF. In the ED-diagnosed HF patients, 59% were male, 69% had a HF history, and 19 (4.1%) died within 14 days of their ED visit. The area under the curve (AUC) for the 14-day mortality receiver operating characteristic (ROC) curve was 0.484 for brain natriuretic peptide (BNP), 0.586 for N-terminal pro-B-type natriuretic peptide (NT-proBNP), 0.755 for troponin (I or T), 0.742 for adrenomedullin (MR-proADM), and 0.803 for copeptin. In combination, MR-proADM and copeptin had the best 14-day mortality prediction (AUC = 0.818), versus all other markers. CONCLUSIONS: MR-proADM and copeptin, alone or in combination, may provide superior short-term mortality prediction compared to natriuretic peptides and troponin. Presented results are explorative due to the limited number of events, but validation in larger trials seems promising.