Methods of the PivotaL triAl of the Atellica VTLi point of care emergencY dePartment high sensitivity troponin evalUationS.

BACKGROUND: The Atellica® VTLi point-of-care (POC) High Sensitivity Cardiac Troponin-I (hs-cTnI) assay is intended for use as an aid in the diagnosis of myocardial infarction (MI). Our primary objective is to assess its diagnostic performance in patients presenting with suspected acute coronary syndrome (ACS). METHODS: This prospective observational study will enrol ∼1500 patients at ∼20 U.S. Emergency Departments. After informed consent, adults (>21 years of age) with suspected ACS, and no prior enrollment in this study, will provide a fingerstick and venous blood sample within 2 h of ED presentation, >2 to ≤4 h, and >4 to ≤9 h (max. blood draw = 60 mL). HEART and EDACS scores will be prospectively documented. Patients without the first blood draw may be enrolled if the second draw was obtained. Capillary and venous whole blood will undergo Atellica VTLi assay testing, with remaining venous sample processed to plasma and run. All results will be blinded to the clinical care team. Site operators will undergo a 3-day familiarization period. Quality control testing will be performed daily. At 30 ± 3 days, patient mortality status, major adverse cardiac events, and rehospitalizations will be determined. A clinical endpoint adjudication committee, blinded to hs-cTnI VTLi result, will define the final diagnosis. Sensitivity, specificity, and predictive values will describe the assay performance. RESULTS: We expect study completion within 114 weeks of enrollment of the first patient. CONCLUSIONS: It is anticipated that the Atellica VTLi hs-cTnI assay validation study will define a performance equivalent to lab-based hs-cTnI, with results within ∼8 min at the point of care.

The Influence of Body Mass Index on Clinical Interpretation of Established and Novel Biomarkers in Acute Heart Failure.

BACKGROUND: Body mass index (BMI) is a known confounder for natriuretic peptides, but its influence on other biomarkers is less well described. We investigated whether BMI interacts with biomarkers' association with prognosis in patients with acute heart failure (AHF). METHODS AND RESULTS: B-type natriuretic peptide (BNP), high-sensitivity cardiac troponin I (hs-cTnI), galectin-3, serum neutrophil gelatinase-associated lipocalin (sNGAL), and urine NGAL were measured serially in patients with AHF during hospitalization in the AKINESIS (Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic Heart Failure) study. Cox regression analysis was used to determine the association of biomarkers and their interaction with BMI for 30-day, 90-day and 1-year composite outcomes of death or HF readmission. Among 866 patients, 21.2%, 29.7% and 46.8% had normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) or obese (≥ 30 kg/m2) BMIs on admission, respectively. Admission values of BNP and hs-cTnI were negatively associated with BMI, whereas galectin-3 and sNGAL were positively associated with BMI. Admission BNP and hs-cTnI levels were associated with the composite outcome within 30 days, 90 days and 1 year. Only BNP had a significant interaction with BMI. When BNP was analyzed by BMI category, its association with the composite outcome attenuated at higher BMIs and was no longer significant in obese individuals. Findings were similar when evaluated by the last-measured biomarkers and BMIs. CONCLUSIONS: In patients with AHF, only BNP had a significant interaction with BMI for the outcomes, with its association attenuating as BMI increased; hs-cTnI was prognostic, regardless of BMI.

Implications of worsening renal function before hospitalization for acute heart failure.

AIMS: Kidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF). METHODS AND RESULTS: We evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in-hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One-hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16-1.28, 95% confidence interval [CI] 1.00-1.55) and lower diastolic blood pressure (OR 0.97-0.98, 95% CI 0.96-0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0-2.2). WRF across definitions was not associated with a higher odds of adverse in-hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome. CONCLUSIONS: Admission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in-hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events.

Galectin-3, Acute Kidney Injury and Myocardial Damage in Patients With Acute Heart Failure.

BACKGROUND: Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF). METHODS AND RESULTS: We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death. CONCLUSIONS: In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes.

Diagnostic Accuracy of a Bacterial and Viral Biomarker Point-of-Care Test in the Outpatient Setting.

Importance: Acute respiratory infections (ARIs) account for most outpatient visits. Discriminating bacterial vs viral etiology is a diagnostic challenge with therapeutic implications. Objective: To investigate whether FebriDx, a rapid, point-of-care immunoassay, can differentiate bacterial- from viral-associated host immune response in ARI through measurement of myxovirus resistance protein A (MxA) and C-reactive protein (CRP) from finger-stick blood. Design, Setting, and Participants: This diagnostic study enrolled adults and children who were symptomatic for ARI and individuals in a control group who were asymptomatic between October 2019 and April 2021. Included participants were a convenience sample of patients in outpatient settings (ie, emergency department, urgent care, and primary care) who were symptomatic, aged 1 year or older, and had suspected ARI and fever within 72 hours. Individuals with immunocompromised state and recent vaccine, antibiotics, stroke, surgery, major burn, or myocardial infarction were excluded. Of 1685 individuals assessed for eligibility, 259 individuals declined participation, 718 individuals were excluded, and 708 individuals were enrolled (520 patients with ARI, 170 patients without ARI, and 18 individuals who dropped out). Exposures: Bacterial and viral immunoassay testing was performed using finger-stick blood. Results were read at 10 minutes, and treating clinicians and adjudicators were blinded to results. Main Outcomes and Measures: Bacterial- or viral-associated systemic host response to an ARI as determined by a predefined comparator algorithm with adjudication classified infection etiology. Results: Among 520 participants with ARI (230 male patients [44.2%] and 290 female patients [55.8%]; mean [SD] age, 35.3 [17.7] years), 24 participants with missing laboratory information were classified as unknown (4.6%). Among 496 participants with a final diagnosis, 73 individuals (14.7%) were classified as having a bacterial-associated response, 296 individuals (59.7%) as having a viral-associated response, and 127 individuals (25.6%) as negative by the reference standard. The bacterial and viral test correctly classified 68 of 73 bacterial infections, demonstrating a sensitivity of 93.2% (95% CI, 84.9%-97.0%), specificity of 374 of 423 participants (88.4% [95% CI, 85.0%-91.1%]), positive predictive value (PPV) of 68 of 117 participants (58.1% [95% CI, 49.1%-66.7%), and negative predictive value (NPV) of 374 of 379 participants (98.7% [95% CI, 96.9%-99.4%]).The test correctly classified 208 of 296 viral infections, for a sensitivity of 70.3% (95% CI, 64.8%-75.2%), a specificity of 176 of 200 participants (88.0% [95% CI, 82.8%-91.8%]), a PPV of 208 of 232 participants (89.7% [95% CI, 85.1%-92.9%]), and an NPV of 176 of 264 participants (66.7% [95% CI, 60.8%-72.1%]). Conclusions and Relevance: In this study, a rapid diagnostic test demonstrated diagnostic performance that may inform clinicians when assessing for bacterial or viral etiology of ARI symptoms.

Decongestion, kidney injury and prognosis in patients with acute heart failure.

BACKGROUND: In patients with acute heart failure (AHF), the development of worsening renal function with appropriate decongestion is thought to be a benign functional change and not associated with poor prognosis. We investigated whether the benefit of decongestion outweighs the risk of concurrent kidney tubular damage and leads to better outcomes. METHODS: We retrospectively analyzed data from the AKINESIS study, which enrolled AHF patients requiring intravenous diuretic therapy. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and B-type natriuretic peptide (BNP) were serially measured during the hospitalization. Decongestion was defined as ≥30% BNP decrease at discharge compared to admission. Univariable and multivariable Cox models were assessed for one-year mortality. RESULTS: Among 736 patients, 53% had ≥30% BNP decrease at discharge. Levels of uNGAL and BNP at each collection time point had positive but weak correlations (r ≤ 0.133). Patients without decongestion and with higher discharge uNGAL values had worse one-year mortality, while those with decongestion had better outcomes regardless of uNGAL values (p for interaction 0.018). This interaction was also significant when the change in BNP was analyzed as a continuous variable (p < 0.001). Although higher peak and discharge uNGAL were associated with mortality in univariable analysis, only ≥30% BNP decrease was a significant predictor after multivariable adjustment. CONCLUSIONS: Among AHF patients treated with diuretic therapy, decongestion was generally not associated with kidney tubular damage assessed by uNGAL. Kidney tubular damage with adequate decongestion does not impact outcomes; however, kidney injury without adequate decongestion is associated with a worse prognosis.

Decongestion discriminates risk for one-year mortality in patients with improving renal function in acute heart failure.

AIMS: Improving renal function (IRF) is paradoxically associated with worse outcomes in acute heart failure (AHF), but outcomes may differ based on response to decongestion. We explored if the relationship of IRF with mortality in hospitalized AHF patients differs based on successful decongestion. METHODS AND RESULTS: We evaluated 760 AHF patients from AKINESIS for the relationship between IRF, change in B-type natriuretic peptide (BNP), and 1-year mortality. IRF was defined as a ≥20% increase in estimated glomerular filtration rate (eGFR) relative to admission. Adequate decongestion was defined as a ≥40% decrease in last measured BNP relative to admission. IRF occurred in 22% of patients who had a mean age of 69 years, 58% were men, 72% were white, and median admission eGFR was 49 mL/min/1.73 m2 . IRF patients had more severe heart failure reflected by lower admission eGFR, higher blood urea nitrogen, lower systolic blood pressure, lower sodium, and higher use of inotropes. IRF patients had higher 1-year mortality (25%) than non-IRF patients (15%) (P < 0.01). However, this relationship differed by BNP trajectory (P-interaction = 0.03). When stratified by BNP change, non-IRF patients and IRF patients with decreasing BNP had lower 1-year mortality than either non-IRF and IRF patients without decreasing BNP. However, in multivariate analysis, IRF was not associated with mortality [adjusted hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.7-1.5] while BNP was (adjusted HR 0.5, 95% CI 0.3-0.7). When IRF was evaluated as transiently occurring or persisting at discharge, again only BNP change was significantly associated with mortality. CONCLUSION: Improving renal function is associated with mortality in AHF but not independent of other variables and congestion status. Achieving adequate decongestion, as reflected by lower BNP, in AHF is more strongly associated with mortality than IRF.

Relation of Decongestion and Time to Diuretics to Biomarker Changes and Outcomes in Acute Heart Failure.

Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multiorgan dysfunction, and 1-year composite end point of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase-associated lipocalin, and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease ≥ 30% compared with admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine neutrophil gelatinase-associated lipocalin, and lower incidence of the composite end point. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite end point (p = 0.006 and p = 0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis.

Potential Utility of Cardiorenal Biomarkers for Prediction and Prognostication of Worsening Renal Function in Acute Heart Failure.

BACKGROUND: Multiple different pathophysiologic processes can contribute to worsening renal function (WRF) in acute heart failure. METHODS AND RESULTS: We retrospectively analyzed 787 patients with acute heart failure for the relationship between changes in serum creatinine and biomarkers including brain natriuretic peptide, high sensitivity cardiac troponin I, galectin 3, serum neutrophil gelatinase-associated lipocalin, and urine neutrophil gelatinase-associated lipocalin. WRF was defined as an increase of greater than or equal to 0.3 mg/dL or 50% in creatinine within first 5 days of hospitalization. WRF was observed in 25% of patients. Changes in biomarkers and creatinine were poorly correlated (r ≤ 0.21) and no biomarker predicted WRF better than creatinine. In the multivariable Cox analysis, brain natriuretic peptide and high sensitivity cardiac troponin I, but not WRF, were significantly associated with the 1-year composite of death or heart failure hospitalization. WRF with an increasing urine neutrophil gelatinase-associated lipocalin predicted an increased risk of heart failure hospitalization. CONCLUSIONS: Biomarkers were not able to predict WRF better than creatinine. The 1-year outcomes were associated with biomarkers of cardiac stress and injury but not with WRF, whereas a kidney injury biomarker may prognosticate WRF for heart failure hospitalization.

The Impact of a Concierge Medicine Model on Door to Doctor Time and Patient Flow in an Urban Emergency Department.

INTRODUCTION: Emergency Department (ED) crowding negatively impacts patient outcomes, patient satisfaction, and patient safety. One solution involves introducing a Concierge Physician (CP) whose sole purpose is to provide a brief initial assessment (BIA) and aid patient navigation through the ED. The goal of this study was to quantify the impact of a CP on patient flow dynamics in an urban ED setting. METHODS: We performed a retrospective observational cohort study in an urban academic ED over a 6-month period. Initially, the CP was present in the treatment area during weekdays; during the last half of the observation period, an additional CP was added to the waiting room on weekends. We identified four major milestones in the ED visit with regards to patient throughput. Adult patients presenting to the ED with a triage level of Urgent (ESI 3) were analyzed for this study. Data were stratified based on the patient's ultimate disposition (admitted or discharged) and presented as means with predictive analysis. RESULTS: Between August 2016 and January 2017, the ED evaluated 42,397 adult patients. Of those, 26,976 (64%) were triage level Urgent (3). Of the level 3 patients, 10,279 (38%) received a BIA from a CP. Patients evaluated by a CP were seen approximately 30 mins faster (40% reduction in Door to Doctor time), but stayed 30 mins longer in the ED on average, because the medical decision-making process took >1 hr longer when the patient was initially evaluated by a CP. CONCLUSION: Adapting a concierge medicine model to rapidly evaluate patients resulted in a dramatically reduced Door to Doctor time, but an increase in overall time spent in the ED. This discrepancy was a direct result of the delay in physician disposition.

Short-term prognostic implications of serum and urine neutrophil gelatinase-associated lipocalin in acute heart failure: findings from the AKINESIS study.

AIMS: Kidney impairment has been associated with worse outcomes in acute heart failure (AHF), although recent studies challenge this association. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker of kidney tubular injury. Its prognostic role in AHF has not been evaluated in large cohorts. The present study aimed to determine if serum NGAL (sNGAL) or urine NGAL (uNGAL) is superior to creatinine for predicting short-term outcomes in AHF. METHODS AND RESULTS: The study was conducted in an international, multicentre, prospective cohort consisting of 927 patients with AHF. Admission and peak values of sNGAL, uNGAL and uNGAL/urine creatinine (uCr) ratio were compared to admission and peak serum creatinine (sCr). The composite endpoints were death, initiation of renal replacement therapy, heart failure (HF) readmission and any emergent HF-related outpatient visit within 30 and 60 days, respectively. The mean age of the cohort was 69 years and 62% were male. The median length of stay was 6 days. The composite endpoint occurred in 106 patients and 154 patients within 30 and 60 days, respectively. Serum NGAL was more predictive than uNGAL and the uNGAL/uCr ratio but was not superior to sCr [area under the curve: admission sNGAL 0.61, 95% confidence interval (CI) 0.55-0.67, and 0.59, 95% CI 0.54-0.65; peak sNGAL: 0.60, 95% CI 0.54-0.66, and 0.57, 95% CI 0.52-0.63; admission sCr: 0.60, 95% CI 0.54-0.64, and 0.59, 95% CI 0.53-0.64; peak sCr: 0.61, 95% CI 0.55-0.67, and 0.59, 95% CI 0.54-0.64, at 30 and 60 days, respectively]. NGAL was not predictive of the composite endpoint in multivariate analysis. CONCLUSIONS: Serum NGAL outperformed uNGAL but neither was superior to admission or peak sCr for predicting adverse events.

B-type natriuretic peptide trend predicts clinical significance of worsening renal function in acute heart failure.

AIMS: In acute heart failure (AHF), relationships between changes in B-type natriuretic peptide (BNP) and worsening renal function (WRF) and its prognostic implications have not been fully determined. We investigated the relationship between WRF and a decrease in BNP with in-hospital and 1-year mortality in AHF. METHODS AND RESULTS: The Acute Kidney Injury NGAL Evaluation of Symptomatic heart faIlure Study (AKINESIS) was a prospective, international, multicentre study of AHF patients. Severe WRF (sWRF) was a sustained increase of ≥44.2 µmol/L (0.5 mg/dL) or ≥50% in creatinine, non-severe WRF (nsWRF) was a non-sustained increase of ≥26.5 µmol/L (0.3 mg/dL) or ≥50% in creatinine, and WRF with clinical deterioration was nsWRF with renal replacement therapy, inotrope use, or mechanical ventilation. Decreased BNP was defined as a ≥30% reduction in the last measured BNP compared to admission BNP. Among 814 patients, the incidence of WRF was not different between patients with or without decreased BNP (nsWRF: 33% vs. 31%, P = 0.549; sWRF: 11% vs. 9%, P = 0.551; WRF with clinical deterioration: 8% vs. 10%, P = 0.425). Decreased BNP was associated with better in-hospital and 1-year mortality regardless of WRF, while WRF was associated with worse outcomes only in patients without decreased BNP. In multivariate Cox regression analysis, decreased BNP, sWRF, and WRF with clinical deterioration were significantly associated with 1-year mortality. CONCLUSIONS: Decreased BNP was associated with better in-hospital and long-term outcomes. WRF was only associated with adverse outcomes in patients without decreased BNP.

Utility of Urine Neutrophil Gelatinase-Associated Lipocalin for Worsening Renal Function during Hospitalization for Acute Heart Failure: Primary Findings of the Urine N-gal Acute Kidney Injury N-gal Evaluation of Symptomatic Heart Failure Study (AKINESIS).

BACKGROUND: Worsening renal function (WRF) during acute heart failure (AHF) occurs frequently and has been associated with adverse outcomes, though this association has been questioned. WRF is now evaluated by function and injury. We evaluated whether urine neutrophil gelatinase-associated lipocalin (uNGAL) is superior to creatinine for prediction and prognosis of WRF in patients with AHF. METHODS AND RESULTS: We performed a multicenter, international, prospective cohort of patients with AHF requiring IV diuretics. The primary outcome was whether uNGAL predicted development of WRF, defined as a sustained increase in creatinine of 0.5 mg/dL or ≥50% above first value or initiation of renal replacement therapy, within the first 5 days. The main secondary outcome was a composite of in-hospital adverse events. We enrolled 927 patients (mean 68.5 years of age, 62% men). The primary outcome occurred in 72 patients (7.8%). The first, peak and the ratio of uNGAL to urine creatinine (area under curves (AUC) ≤ 0.613) did not have diagnostic utility over the first creatinine (AUC 0.662). There were 235 adverse events in 144 patients. uNGAL did not predict (AUCs ≤ 0.647) adverse clinical events better than creatinine (AUC 0.695). CONCLUSIONS: uNGAL was not superior to creatinine for predicting WRF or adverse in-hospital outcomes and cannot be recommended for WRF in AHF.

Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study.

OBJECTIVES: To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States. DESIGN: Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol. SETTING: Thirteen U.S.-based emergency departments and ICUs. PATIENTS: Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department, other wards, or directly from out of hospital were included. INTERVENTIONS: Procalcitonin was measured daily over the first 5 days. MEASUREMENTS AND MAIN RESULTS: The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80% from baseline to day 4 and 28-day mortality using Cox proportional hazards regression. Among 858 enrolled patients, 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis. The 28-day all-cause mortality was two-fold higher when procalcitonin did not show a decrease of more than 80% from baseline to day 4 (20% vs 10%; p = 0.001). This was confirmed as an independent predictor in Cox regression analysis (hazard ratio, 1.97 [95% CI, 1.18-3.30; p < 0.009]) after adjusting for demographics, Acute Physiology and Chronic Health Evaluation II, ICU residence on day 4, sepsis syndrome severity, antibiotic administration time, and other relevant confounders. CONCLUSIONS: Results of this large, prospective multicenter U.S. study indicate that inability to decrease procalcitonin by more than 80% is a significant independent predictor of mortality and may aid in sepsis care.

Renal Function and Scaled Troponin in Patients Presenting to the Emergency Department with Symptoms of Myocardial Infarction.

BACKGROUND: Cardiac troponins are often found to be elevated in patients with renal dysfunction, even in the absence of acute myocardial injury. The objective of this report was to characterize the scaled troponin values and proportion of adjudicated acute myocardial infarction (AMI) among patients with and without renal dysfunction. METHODS: The data was from a multicenter prospective study including patients presenting to the emergency department with symptoms of AMI. Troponin measurements were standardized across various assays by calculating the observed results as multiples of the assay-specific 99th percentile upper limit of normal. Patients with an estimated glomerular filtration rate (eGFR; calculated by the Chronic Kidney Disease Epidemiology Collaboration formula) <60 mL/min/1.73 m2 were considered to have renal dysfunction. RESULTS: Of 430 included patients, 249 (58%) were male and 181 (42%) were female, with a mean age of 55.9 ± 12.3 and 57.3 ± 12.8 years, respectively. Eighty-seven (20.2%) had renal dysfunction. The proportions of patients with at least one scaled troponin value above the 99th percentile cut-off point among patients with and without renal dysfunction were 40 (45.9%) and 81 (23.6%) respectively (p < 0.001). The proportions of patients with an adjudicated diagnosis of AMI among those with and without renal dysfunction were 20.7 and 18.7%, respectively (p = 0.67). Using scaled troponins, by the second test there was >5X and by the third test >15X separation in the excursion of troponin among those with AMI compared to those without. CONCLUSIONS: One or more elevated troponin values are common in those with renal dysfunction. Scaled troponins for eGFR groups were similar, indicating that the use of this interpretative technique is applicable in discerning AMI for those with and without renal dysfunction.

Interpretation of positive troponin results among patients with and without myocardial infarction.

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.

Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury During Acute Heart Failure Hospitalizations: The AKINESIS Study.

BACKGROUND: Worsening renal function (WRF) often occurs during acute heart failure (AHF) and can portend adverse outcomes; therefore, early identification may help mitigate risk. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel renal biomarker that may predict WRF in certain disorders, but its value in AHF is unknown. OBJECTIVES: This study sought to determine whether NGAL is superior to creatinine for prediction and/or prognosis of WRF in hospitalized patients with AHF treated with intravenous diuretic agents. METHODS: This was a multicenter, prospective cohort study enrolling patients presenting with AHF requiring intravenous diuretic agents. The primary outcome was whether plasma NGAL could predict the development of WRF, defined as a sustained increase in plasma creatinine of 0.5 mg/dl or ≥50% above first value or initiation of acute renal-replacement therapy, within the first 5 days of hospitalization. The main secondary outcome was in-hospital adverse events. RESULTS: We enrolled 927 subjects (mean age, 68.5 years; 62% men). The primary outcome occurred in 72 subjects (7.8%). Peak NGAL was more predictive than the first NGAL, but neither added significant diagnostic utility over the first creatinine (areas under the curve: 0.656, 0.647, and 0.652, respectively). There were 235 adverse events in 144 subjects. The first NGAL was a better predictor than peak NGAL, but similar to the first creatinine (areas under the curve: 0.691, 0.653, and 0.686, respectively). In a post hoc analysis of subjects with an estimated glomerular filtration rate <60 ml/min/1.73 m(2), a first NGAL <150 ng/ml indicated a low likelihood of adverse events. CONCLUSIONS: Plasma NGAL was not superior to creatinine for the prediction of WRF or adverse in-hospital outcomes. The use of plasma NGAL to diagnose acute kidney injury in AHF cannot be recommended at this time. (Acute Kidney Injury Neutrophil Gelatinase-Associated Lipocalin [N-GAL] Evaluation of Symptomatic Heart Failure Study [AKINESIS]; NCT01291836).

Can a Point-of-Care Troponin I Assay be as Good as a Central Laboratory Assay? A MIDAS Investigation.

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.

Cardiac Output Monitoring Managing Intravenous Therapy (COMMIT) to Treat Emergency Department Patients with Sepsis.

OBJECTIVE: Fluid responsiveness is proposed as a physiology-based method to titrate fluid therapy based on preload dependence. The objectives of this study were to determine if a fluid responsiveness protocol would decrease progression of organ dysfunction, and a fluid responsiveness protocol would facilitate a more aggressive resuscitation. METHODS: Prospective, 10-center, randomized interventional trial. INCLUSION CRITERIA: suspected sepsis and lactate 2.0 to 4.0 mmol/L. Exclusion criteria (abbreviated): systolic blood pressure more than 90 mmHg, and contraindication to aggressive fluid resuscitation. INTERVENTION: fluid responsiveness protocol using Non-Invasive Cardiac Output Monitor (NICOM) to assess for fluid responsiveness (>10% increase in stroke volume in response to 5 mL/kg fluid bolus) with balance of a liter given in responsive patients. CONTROL: standard clinical care. OUTCOMES: primary-change in Sepsis-related Organ Failure Assessment (SOFA) score at least 1 over 72 h; secondary-fluids administered. Trial was initially powered at 600 patients, but stopped early due to a change in sponsor's funding priorities. RESULTS: Sixty-four patients were enrolled with 32 in the treatment arm. There were no significant differences between arms in age, comorbidities, baseline vital signs, or SOFA scores (P > 0.05 for all). Comparing treatment versus Standard of Care-there was no difference in proportion of increase in SOFA score of at least 1 point (30% vs. 33%) (note bene underpowered, P = 1.0) or mean preprotocol fluids 1,050 mL (95% confidence interval [CI]: 786-1,314) vs. 1,031 mL (95% CI: 741-1,325) (P = 0.93); however, treatment patients received more fluids during the protocol (2,633 mL [95% CI: 2,264-3,001] vs. 1,002 mL [95% CI: 707-1,298]) (P < 0.001). CONCLUSIONS: In this study of a "preshock" population, there was no change in progression of organ dysfunction with a fluid responsiveness protocol. A noninvasive fluid responsiveness protocol did facilitate delivery of an increased volume of fluid. Additional properly powered and enrolled outcomes studies are needed.

Comparing an Unstructured Risk Stratification to Published Guidelines in Acute Coronary Syndromes.

INTRODUCTION: Guidelines are designed to encompass the needs of the majority of patients with a particular condition. The American Heart Association (AHA) in conjunction with the American College of Cardiology (ACC) and the American College of Emergency Physicians (ACEP) developed risk stratification guidelines to aid physicians with accurate and efficient diagnosis and management of patients with acute coronary syndrome (ACS). While useful in a primary care setting, in the unique environment of an emergency department (ED), the feasibility of incorporating guidelines into clinical workflow remains in question. We aim to compare emergency physicians' (EP) clinical risk stratification ability to AHA/ACC/ACEP guidelines for ACS, and assessed each for accuracy in predicting ACS. METHODS: We conducted a prospective observational cohort study in an urban teaching hospital ED. All patients presenting to the ED with chest pain who were evaluated for ACS had two risk stratification scores assigned: one by the treating physician based on clinical evaluation and the other by the AHA/ACC/ACEP guideline aforementioned. The patient's ACS risk stratification classified by the EP was compared to AHA/ACC/ACEP guidelines. Patients were contacted at 30 days following the index ED visit to determine all cause mortality, unscheduled hospital/ED revisits, and objective cardiac testing performed. RESULTS: We enrolled 641 patients presenting for evaluation by 21 different EPs. There was a difference between the physician's clinical assessment used in the ED, and the AHA/ACC/ACEP task force guidelines. EPs were more likely to assess patients as low risk (40%), while AHA/ACC/ACEP guidelines were more likely to classify patients as intermediate (45%) or high (45%) risk. Of the 119 (19%) patients deemed high risk by EP evaluation, 38 (32%) were diagnosed with ACS. AHA/ACC/ACEP guidelines classified only 57 (9%) patients low risk with 56 (98%) of those patients diagnosed with no ACS. CONCLUSION: In the ED, physicians are more efficient at correctly placing patients with underlying ACS into a high-risk category. A small percentage of patients were considered low risk when applying AHA/ACC/ACEP guidelines, which demonstrates how clinical insight is often required to make an efficient assessment of cardiac risk and established criteria may be overly conservative when applied to an acute care population.