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.

Prognosis is worse with elevated cardiac troponin in nonacute coronary syndrome compared with acute coronary syndrome.

BACKGROUND: Cardiac troponin (cTn) can be elevated in many patients presenting to the emergency department (ED) with chest pain but without a diagnosis of acute coronary syndrome (ACS). We compared the prognostic significance of cTn in these different populations. METHODS: We retrospectively analyzed the CHOPIN study, which enrolled patients who presented to the ED with chest pain. Patients were grouped as ACS, non-ACS cardiovascular disease, noncardiac chest pain and chest pain not otherwise specified (NOS). We examined the prognostic ability of cTnI for the clinical endpoints of mortality and major adverse cardiovascular event (MACE; a composite of acute myocardial infarction, unstable angina, revascularization, reinfarction, and congestive heart failure and stroke) at 180-day follow-up. RESULTS: Among 1982 patients analyzed, 14% had ACS, 21% had non-ACS cardiovascular disease, 31% had a noncardiac diagnosis and 34% had chest pain NOS. cTnI elevation above the 99th percentile was observed in 52, 18, 6 and 7% in these groups, respectively. cTnI elevation was associated with mortality and MACE, and their relationships were more prominent in noncardiac diagnosis and chest pain NOS than in ACS and non-ACS cardiovascular diagnoses for mortality, and in non-ACS patients than in ACS patients for MACE (hazard ratio for doubling of cTnI 1.85, 2.05, 8.26 and 4.14, respectively; P for interaction 0.011 for mortality; 1.04, 1.23, 1.54 and 1.42, respectively; P for interaction <0.001 for MACE). CONCLUSION: In patients presenting to the ED with chest pain, cTnI elevation was associated with a worse prognosis in non-ACS patients than in ACS patients.

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.

Utility of COVID-19 antigen testing in the emergency department.

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

Suture Granuloma Diagnosed and Treated With Bedside Ultrasound.

BACKGROUND: Emergency physicians frequently evaluate patients with postoperative wound issues. The differential is broad, but obviously includes postoperative site infections. We present a case where a suspected postoperative abscess was evaluated with bedside ultrasound prior to incision and drainage. Suture material was recognized, shifting our approach to treatment of the lesion. CASE REPORT: A 24-year-old female patient presented with pain, swelling, and drainage from a left lower quadrant abdominal wound that had been present since undergoing a laparoscopic appendectomy 1 year prior. A computed tomography scan was performed, which was negative for foreign bodies. Prior to incision and drainage, a bedside ultrasound was performed to evaluate the lesion, which was notable for sonographic findings consistent with suture material. Suture granuloma was diagnosed, and ultrasound was then used to successfully guide retrieval of the suture. To our knowledge, this is the first published case where ultrasound was used to both diagnose and dynamically remove the offending suture material. We briefly discuss suture granulomas, their sonographic appearance, and management. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians frequently perform ultrasound on suspected abscesses prior to incision and drainage and should be aware of the sonographic appearance of suture material as it would change management if present. If a suture granuloma is suspected due to swelling at a postoperative site, ultrasound use should be strongly considered for evaluation.

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.

CODE BLUE-19: Proposal to Mitigate COVID-19 Transmission in the Emergency Department for Out-of-hospital Cardiac Arrest.

Resuscitation of cardiac arrest in coronavirus disease 2019 (COVID-19) patients places the healthcare staff at higher risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unfortunately, COVID-19 status is unknown in most patients presenting to the emergency department (ED), and therefore special attention must be given to protect the healthcare staff along with the other patients. This is particularly true for out-of-hospital cardiac arrest patients who are transported to the ED. Based on the current data available on transmissibility of SARS-CoV-2, we have proposed a protocolized approach to out-of-hospital cardiac arrests to limit risk of transmission.

Age-adjusted and Expanded Lactate Thresholds as Predictors of All-Cause Mortality in the Emergency Department.

INTRODUCTION: While numerous studies have found emergency department (ED) lactate levels to be associated with increased in-hospital mortality, little information is available on the role age plays in this association. This study investigates whether age is a necessary variable to consider when using lactate levels as a marker of prognosis and a guide for management decisions in the ED. METHODS: This was a retrospective cohort study in an urban, tertiary-care teaching hospital. A total of 13,506 lactate levels were obtained over a 4.5-year period. All adult patients who had a lactate level obtained by the treating provider in the ED were screened for inclusion. The main outcome measure was in-hospital mortality using age-adjusted cohorts and expanded lactate thresholds with secondary outcomes comparing mortality based on the primary clinical impression. RESULTS: Of the 8796 patients in this analysis, there were 474 (5.4%) deaths. Mortality rates increased with both increasing lactate levels and increasing age. For all ages, mortality rates increased from 2.8% in the less than 2.0 millimoles per liter (mmol/L) lactate level, to 5.6% in the 2.0-2.9 mmol/L lactate level, to 8.0% in the 3.0-3.9 mmol/L lactate level, to 13.9% in the 4.0-4.9 mmol/L lactate level, to 13.7% in the 5.0-5.9 mmol/L lactate level, and to 39.1% in the 6.0 mmol/L or greater lactate level (p <0.0001). Survivors, regardless of age, had a mean lactate level <2.0 whereas non-survivors had mean lactate levels of 6.5, 4.5, and 3.7 mmol/L for age cohorts 18-39, 40-64, and ≥ 65 years, respectively. CONCLUSION: Our findings suggest that although lactate levels can be used as a prognostic tool to risk stratify ED patients, the traditional lactate level thresholds may need to be adjusted to account for varying risk based on age and clinical impressions.

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

BACKGROUND: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. METHODS: Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. RESULTS: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI. CONCLUSIONS: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.

Echocardiographic assessment of insulin-like growth factor binding protein-7 and early identification of acute heart failure.

AIMS: Concentrations of insulin-like growth factor binding protein-7 (IGFBP7) have been linked to abnormal cardiac structure and function in patients with chronic heart failure (HF), but cardiovascular correlates of the biomarker in patients with more acute presentations are lacking. We aimed to determine the relationship between IGFBP7 concentrations and cardiac structure and to evaluate the impact of IGFBP7 on the diagnosis of acute HF among patients with acute dyspnoea. METHODS AND RESULTS: In this pre-specified subgroup analysis of the International Collaborative of N-terminal pro-B-type Natriuretic Peptide Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) study, we included 271 patients with and without acute HF. All patients presented to an emergency department with acute dyspnoea, had blood samples for IGFBP7 measurement, and detailed echocardiographic evaluation. Higher IGFBP7 concentrations were associated with numerous cardiac abnormalities, including increased left atrial volume index (LAVi; r = 0.49, P < 0.001), lower left ventricular ejection fraction (r = -0.27, P < 0.001), lower right ventricular fractional area change (r = -0.31, P < 0.001), and higher tissue Doppler E/e' ratio (r = 0.44, P < 0.001). In multivariable linear regression analyses, increased LAVi (P = 0.01), lower estimated glomerular filtration rate (P = 0.008), higher body mass index (P = 0.001), diabetes (P = 0.009), and higher concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP, P = 0.02) were independently associated with higher IGFBP7 concentrations regardless of other variables. Furthermore, IGFBP7 (odds ratio = 12.08, 95% confidence interval 2.42-60.15, P = 0.02) was found to be independently associated with the diagnosis of acute HF in the multivariable logistic regression analysis. CONCLUSIONS: Among acute dyspnoeic patients with and without acute HF, increased IGFBP7 concentrations are associated with a range of cardiac structure and function abnormalities. Independent association with increased LAVi suggests elevated left ventricular filling pressure is an important trigger for IGFBP7 expression and release. IGFBP7 may enhance the diagnosis of acute HF.

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.

Implications of culture collection after the first antimicrobial dose in septic emergency department patients.

BACKGROUND: Previous research has illustrated the importance of collection of microbiologic cultures prior to first antimicrobial dose (FAD) in septic patients to avoid sterilization of pathogens and thus allowing confirmation of infection, identification of pathogen(s), and de-escalation of antimicrobial therapy. There is currently a lack of literature characterizing the implications and clinical courses of patients who have cultures collected after FAD. METHODS: In this single-center, retrospective chart review of 163 sepsis cases in the emergency department, the primary outcome was positive-cultures from appropriate sources. Secondary outcomes included time to FAD (TFAD); ICU and hospital lengths of stay (LOS); rate of antibiotic restart; secondary infection rate; readmission; and mortality. Cases were divided based on culture timing relative to FAD: culture-first (CF) or antimicrobial-first (AF) cohorts. RESULTS: Cultures were more frequently positive in the CF cohort vs. AF cohort overall (80.4% vs. 46.7%, p < 0.005). TFAD was greater in the CF cohort (202 min vs. 153 min, p = 0.036) and these cases trended toward shorter ICU and hospital LOS (6.8 days vs. 8.4 days, p = 0.122; 11.5 days vs. 13.5 days, p = 0.218). Antibiotic restart was less frequent in the CF cohort (10.7% vs. 17.8%, p < 0.005). C. difficile infection and mortality trended toward lower incidence in the CF cohort, and readmission rates were similar. CONCLUSIONS: Sepsis patients who have cultures obtained after FAD (represented in the AF cohort) had less positive-cultures, shorter TFAD, a trend toward longer ICU and hospital LOS, and perhaps higher risk of C. difficile infection, and mortality.

Copeptin to rule out myocardial infarction in Blacks versus Caucasians.

BACKGROUND: Copeptin in combination with troponin has been shown to have incremental value for the early rule-out of myocardial infarction, but its performance in Black patients specifically has never been examined. In light of a potential for wider use, data on copeptin in different relevant cohorts are needed. This is the first study to determine whether copeptin is equally effective at ruling out myocardial infarction in Black and Caucasian races. METHODS: This analysis of the CHOPIN trial included 792 Black and 1075 Caucasian patients who presented to the emergency department with chest pain and had troponin-I and copeptin levels drawn. RESULTS: One hundred and forty-nine patients were diagnosed with myocardial infarction (54 Black and 95 Caucasian). The negative predictive value of copeptin at a cut-off of 14 pmol/l (as in the CHOPIN study) for myocardial infarction was higher in Blacks (98.0%, 95% confidence interval (CI) 96.2-99.1%) than Caucasians (94.1%, 95% CI 92.1-95.7%). The sensitivity at 14 pmol/l was higher in Blacks (83.3%, 95% CI 70.7-92.1%) than Caucasians (53.7%, 95% CI 43.2-64.0%). After controlling for age, hypertension, heart failure, chronic kidney disease and body mass index in a logistic regression model, the interaction term had a P value of 0.03. A cut-off of 6 pmol/l showed similar sensitivity in Caucasians as 14 pmol/l in Blacks. CONCLUSIONS: This is the first study to identify a difference in the performance of copeptin to rule out myocardial infarction between Blacks and Caucasians, with increased negative predictive value and sensitivity in the Black population at a cut-off of 14 pmol/l. This also holds true for non-ST-segment elevation myocardial infarction and, although numbers were small, similar trends exist in the normal troponin population. This may have significant implications for early rule-out strategies using copeptin.