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.

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.

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.

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.

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury.

INTRODUCTION: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01209169.

The association between self-reported exercise intensity and acute coronary syndrome in emergency department chest pain patients.

BACKGROUND: Regular exercise is thought to be protective against coronary artery disease. As a result, some physicians believe that the likelihood of acute coronary syndrome (ACS) in patients with acute chest pain is reduced in those who exercise regularly. We studied the association between self-reported frequency of exercising and the likelihood of ACS in patients presenting to the Emergency Department (ED) with chest pain. METHODS: A multi-center prospective, descriptive, cohort study design was used in ED patients to determine whether the risk of ACS was reduced in patients who self-reported regular exercise. RESULTS: There were 1093 patients enrolled. Median (interquartile range) age was 57 (48-67) years; 506 (45.7%) were female. ACS was diagnosed in 248 (22.7%) patients. Patients who did not exercise at least monthly were more likely to be diagnosed with ACS than those who did (129/466 [27.7%] vs. 119/627 [19.0%]; odds ratio 1.63, 95% CI 1.23-2.17). After adjusting for age, gender, body mass index, smoking, and prior history, limited exercise was still associated with ACS (adjusted odds ratio 1.52, 95% CI 1.10-2.10). There was no apparent association between frequency and intensity of exercise and risk of ACS. CONCLUSION: Although self-reported frequency of exercise was significantly associated with a decrease in ACS in ED patients with chest pain, it should not be used to exclude ACS in symptomatic ED patients.

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.

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.

Diagnostic accuracy of a point-of-care troponin I assay for acute myocardial infarction within 3 hours after presentation in early presenters to the emergency department with chest pain.

BACKGROUND: Guidelines recommend that serial cardiac marker testing to rule out acute myocardial infarction (AMI) be performed for 8 to 12 hours after symptom onset. We aim to determine the diagnostic accuracy of a contemporary point-of-care (POC) troponin I (TnI) assay within 3 hours for patients presenting within 8 hours of symptom onset. METHODS: The MIDAS study collected blood from patients presenting with suspected acute coronary syndrome at presentation and at 90 minutes, 3 hours, and 6 hours in whom the emergency physician planned an objective cardiac ischemia evaluation. Criterion standard diagnoses were adjudicated by experienced clinicians using all available medical records per American Heart Association/American College of Cardiology criteria. Reviewers were blinded to the investigational marker, Cardio3 TnI POC. The Cardio3 TnI reference value was defined as >0.05 ng/mL. Measures of diagnostic accuracy are presented with 95% CI. RESULTS: A total of 858 of 1107 patients met the inclusion criteria. The study cohort had 476 men (55.5%) with median age of 57.0 years (interquartile range 48.0-67.0 years). Median time from symptom onset to initial blood draw was 3.9 hours (interquartile range 2.7-5.2 hours). Acute myocardial infarction was diagnosed in 82 patients (9.6%). The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio over 3 hours were 84.1, 93.4, 12.8, and 0.17, respectively. There was no significant improvement in diagnostic accuracy associated with adding 6-hour serial testing to the 3-hour sample. CONCLUSION: In suspected patients with acute coronary syndrome presenting to the emergency department within 8 hours of symptom onset, 3 hours of serial testing with the Cardio3 TnI POC platform provides similar diagnostic accuracy for AMI as longer periods.

History of symptom triggers in patients presenting to the emergency department for asthma.

OBJECTIVES: Understanding triggers is important for managing asthma particularly for patients who seek emergency department (ED) care for exacerbations. The objectives of this analysis were to delineate self-reported triggers in ED patients and to assess associations between triggers and asthma knowledge, severity, and quality of life. METHODS: At the time of an ED visit, 296 patients were asked what were their usual asthma triggers based on a checklist of 25 potential items, and what they thought specifically precipitated their current ED visit. Using standardized scales, patients also were asked about asthma knowledge, severity, and quality of life. RESULTS: The mean age was 44 years and 72% were women. Patients cited a mean of 12 triggers; most patients had diverse triggers spanning respiratory infections, environmental irritants, emotions, allergens, weather, and exercise. Patients with more triggers were more likely to be women (odds ratio (OR) = 2.0, confidence interval (CI) = 1.3, 3.2, p = .002), obese (OR = 1.7, CI = 1.1, 2.5, p = .01), and to not have a smoking history (OR = 1.9, CI = 1.3, 2.9, p = .001). There were no associations between number of triggers and current age, age at diagnosis, education, socioeconomic status, or race/ethnicity. Patients who cited more triggers had more frequent flares (OR = 1.1, CI = 1.1, 1.2, p < .0001), worse quality of life scores (OR 1.6, CI = 1.1, 2.4, p = .02), and were more likely to have been previously hospitalized for asthma (OR = 1.9, CI = 1.3, 2.9, p = .003) and to have previously required oral corticosteroids (OR = 2.9, CI = 1.6, 5.1, p = .003). There was little clustering of specific triggers according to the variables we considered except for more frequent animal allergy in patients diagnosed at a younger age (OR = 2.8, CI = 1.7, 4.5, p < .0001) and worse quality of life in patients citing emotional stress as a trigger (OR = 2.5, CI = 1.5, 4.0, p = .0002). Patients attributed their current ED visit to multiple precipitants, particularly respiratory infections and weather, and these were concordant with what they reported were known triggers. CONCLUSIONS: Patients presenting to the ED for asthma reported multiple triggers spanning diverse classes of precipitants and having more triggers was associated with worse clinical status. ED patients should be instructed that although it may not be possible to eliminate all triggers, mitigating even some triggers can be helpful.

Time to seeking emergency department care for asthma: self-management, clinical features at presentation, and hospitalization.

OBJECTIVES: Understanding the events preceding emergency department (ED) asthma visits can guide patient education regarding managing exacerbations and seeking timely care. The objectives of this analysis were to assess time to seeking ED care, self-management of asthma exacerbations, and clinical status on presentation. METHODS: A total of 296 patients was grouped according to time to seeking ED care: ≤1 day (22%), 2-5 days (44%), and >5 days (34%) and was compared for clinical and psychosocial characteristics. Asthma severity at presentation was obtained from patient report with the Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ) and from physicians' ratings using decision to hospitalize as an indicator of worse status. RESULTS. Mean age was 44 years, 72% were women, 10% had been in the ED in the prior week, and 28% came to the ED by ambulance. Patients who waited longer were more likely to be older, have more depressive symptoms, and have been in the ED in the prior week. They also were more likely to have taken more medications, but they were not more likely to have visited or consulted their outpatient physicians. Patients who waited longer reported worse ACQ (p < .0001) and AQLQ (p = .0002) scores and were more likely to be hospitalized for the current exacerbation (odds ratio 1.9, 95% CI 1.1, 3.2, p = .03). CONCLUSIONS: Patients who waited longer to come to the ED had worse asthma on presentation, had more functional limitations, and were more likely to be hospitalized. The ability to gauge severity of exacerbations and the use of the ED in a timely manner are important but often overlooked are self-management skills that patients should be taught.

Improving patient flow in acute coronary syndromes in the face of hospital crowding.

BACKGROUND: The current paradigm for the evaluation of patients with suspected acute coronary syndromes (ACS) in the emergency department (ED) is focused on the identification of patients with active underlying coronary disease. The majority of patients evaluated in the ED setting do not have active underlying cardiac disease. OBJECTIVE: To measure the effect of bedside point-of-care (POC) cardiac biomarker testing on telemetry unit admissions from the ED. Furthermore, to evaluate the effect telemetry admissions have on ED length of stay (LOS) and overall hospital LOS. METHODS: Primary data were collected over two 6-month periods in an urban teaching hospital ED. This was an observational cohort study conducted pre- and post-availability of a POC testing platform for cardiac biomarkers. Major measures included number of overall telemetry admissions, ED LOS, hospital LOS, and disposition. Patients were followed at 30 days for significant cardiac events, repeat ED visit or admission, and death. RESULTS: In the post-implementation period there was a 30% (95% confidence interval [CI] 36-44%) reduction in admissions to telemetry with a 33% (95% CI 26-39%) reduction in ED LOS and a 20% (95% CI 7-34%) reduction in hospital LOS. There was a 62% reduction in overall mortality between the pre-implementation period and the post-implementation period (p=0.001). CONCLUSION: The focused use of a rapid cardiac disposition protocol can dramatically impact resource utilization, expedite patient flow, and improve short-term outcomes for patients with suspected ACS.

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.

Myeloperoxidase in the diagnosis of acute coronary syndromes: the importance of spectrum.

BACKGROUND: Myeloperoxidase (MPO) is proposed for risk stratification in patients with suspected acute coronary syndromes (ACSs). We determined if MPO has diagnostic value in patients being evaluated for ACS. METHOD: MIDAS was an 18-center prospective study enrolling suspected ACS emergency department patients who presented <8 hours after symptom onset and in whom serial cardiac markers and objective cardiac perfusion testing were planned. Blinded MPO (Biosite, Inc, San Diego, CA) and troponin I (Triage Cardio 3; Biosite, Inc) were drawn at arrival, and Troponin I (TnI) was measured at 90, 180, and 360 minutes. Final diagnoses were adjudicated by the local investigator blinded to study assay. RESULTS: Of 1,018 patients, 54% were male, 26% black, with a mean age of 58 ± 13 years. Diagnoses were ACS in 288 (23%) and noncardiac chest pain (NCCP) in 788 (77%). Of patients with ACS, 94 (9.2%) had a myocardial infarction (MI) at presentation (69 non-ST-elevation MI, 25 ST-elevation MI), and 136 had unstable angina. Using a cutpoint of 210 ng/mL to provide 90% specificity, MPO had a sensitivity of 0.18; negative predictive value, 0.69; positive predictive value, 0.47; negative likelihood ratio, 0.91; and a positive likelihood ratio of 1.83 to differentiate ACS and NCCP. Because of the large overlap of quartiles, MPO was not clinically useful to predict serial TnI changes. The C statistics ± 95% CI for MPO differentiating ACS from NCCP and for AMI versus NCCP were 0.629 ± 0.04 and 0.666 ± 0.06, respectively. CONCLUSIONS: Myeloperoxidase has insufficient accuracy for decision making in patients with suspected ACS.

A randomized controlled trial of self-management education for asthma patients in the emergency department.

STUDY OBJECTIVE: Patients using the emergency department (ED) for asthma may benefit from self-management education. Our goal is to test an educational intervention in 296 asthma ED patients. METHODS: This was a randomized controlled trial with concealed allocation. Controls received instruction from an asthma knowledge test, peak flowmeter training, and asthma brochures. Intervention patients received these plus a self-management workbook, a behavioral contract, inhaler training, and telephone reinforcements. The main outcome was change in Asthma Quality of Life Questionnaire (AQLQ) score at 8 weeks (a change of 1.5 is a marked clinically important difference). Secondary outcomes were repeated ED visits and change in AQLQ scores at 4, 12, and 16 weeks and 1 year. RESULTS: Mean age of patients was 44 years, and 93% had the 8-week follow-up. Enrollment AQLQ scores were comparable and increased at 8 weeks by more than a marked clinically important difference in both groups. For controls, the change in score was 1.95 (95% confidence interval [CI] 1.74 to 2.16; P<.001), for intervention patients the change in score was 1.83 (95% CI 1.64 to 2.03; P<.001), and the difference between groups was 0.11 (95% CI -0.17 to 0.40; P=.43). Patients who improved more (ie, change was above the group mean) were more likely to be high school graduates (odds ratio=1.9; 95% CI 1.0 to 3.8), previous or current smokers at enrollment (odds ratio=2.2; 95% CI 1.3 to 3.5), and to have been admitted to the hospital from the ED (odds ratio=1.7; 95% CI 1.0 to 2.8). Similar variables were associated with AQLQ outcomes in hierarchic analyses during 16 weeks. Repeated ED visits occurred for 12% of patients at 8 weeks and in multivariate analysis were associated with no hospitalization for the index ED visit, difficult access to outpatient care, and previous ED visits. Fewer patients (16%) had an ED visit at 12 weeks compared with a similar time before enrollment (36%). CONCLUSION: Patients in both groups had marked sustained improvements in clinical status 16 weeks after an ED visit for asthma. A self-management education intervention delivered in the ED and reinforced by telephone was successfully implemented, with high retention rates, but did not provide incremental benefit for quality of life and short-term repeated ED visit outcomes.

Estimating the clinical impact of bringing a multimarker cardiac panel to the bedside in the ED.

OBJECTIVES: We examined the use of point-of-care (POC) testing of cardiac biomarkers against standard core laboratory testing to determine the time-savings and estimate a cost-benefit ratio at our institution. METHODS: We prospectively enrolled 151 patients presenting to the emergency department undergoing evaluation for acute coronary syndrome and conducted both central laboratory troponin T (TnT) testing at baseline and 6 hours as well as POC assays of creatine kinase MB, troponin I (TnI), and myoglobin at baseline and 2 hours. Sensitivity/specificity was calculated to measure the ability of the POC-accelerated pathway to identify enzyme elevations at rates parallel to our core laboratory. The time-savings were calculated as the difference between the median of the current protocol and the accelerated POC pathway. RESULTS: Troponin T tests were elevated in 12 patients, which were all detected by the accelerated pathway yielding a relative sensitivity of 100%. Time-saving between the accelerated pathway and core laboratory showed a saving of 390 minutes (6.5 hours). The accelerated POC pathway would have benefited 60% (95% confidence interval [CI], 52%-68%) of our patients with an estimated cost of $7.40 (95% CI, $6.40-$8.70) per direct patient care hour saved. CONCLUSION: Our data suggest that the use of an accelerated cardiac POC pathway could have dramatically impacted the care provided to a large percentage of our patients at a minimal cost per direct patient care hour saved.

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.