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Objectives The objectives were to reassess use of amino-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations for diagnosis and prognosis of acute heart failure (HF) in patients with acute dyspnea. Background NT-proBNP facilitates diagnosis, prognosis, and treatment in patients with suspected or proven acute HF. As demographics of such patients are changing, previous diagnostic NT-proBNP thresholds may need updating. Additionally, value of in-hospital NT-proBNP prognostic monitoring for HF is less understood. Methods In a prospective, multicenter study in the United States and Canada, patients presenting to emergency departments with acute dyspnea were enrolled, with demographic, medication, imaging, and clinical course information collected. NT-proBNP analysis will be performed using the Roche Diagnostics Elecsys proBNPII immunoassay in blood samples obtained at baseline and at discharge (if hospitalized). Primary end points include positive predictive value of previously established age-stratified NT-proBNP thresholds for the adjudicated diagnosis of acute HF and its negative predictive value to exclude acute HF. Secondary end points include sensitivity, specificity, and positive and negative likelihood ratios for acute HF and, among those with HF, the prognostic value of baseline and predischarge NT-proBNP for adjudicated clinical end points (including all-cause death and hospitalization) at 30 and 180 days. Results A total of 1,461 dyspneic subjects have been enrolled and are eligible for analysis. Follow-up for clinical outcome is ongoing. Conclusions The International Collaborative of N-terminal pro–B-type Natriuretic Peptide Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department study offers a contemporary opportunity to understand best diagnostic cutoff points for NT-proBNP in acute HF and validate in-hospital monitoring of HF using NT-proBNP.

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.MIDAS was an 18-center prospective study enrolling suspected ACS emergency department patients who presented8 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.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.Myeloperoxidase has insufficient accuracy for decision making in patients with suspected ACS.

Background B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNP ≥100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis. Methods The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results. Results Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively ( P Conclusions Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP ≥54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNP ≥170 pg/mL) could be used to increase specificity.

Objectives The study purpose was to examine “gray zone” B-type natriuretic peptide (BNP) levels (100-500 pg/mL) in terms of associated clinical factors, perceived severity, and outcomes in patients with established congestive heart failure (CHF). Background Although gray zone BNP levels may have diagnostic ambiguity, the implications of these levels in patients with an established diagnosis of CHF have not been examined. Methods REDHOT was a national prospective study in which 464 patients seen in the emergency department with dyspnea had BNP levels drawn. Entrance criteria included a BNP >100 pg/mL; however, physicians were blinded to the actual BNP level. Patients were followed up for 90 days. Results Thirty-three percent had gray zone BNP levels. There was no difference in perceived New York Heart Association class ( P = .32) or admission rates ( P = .76) between the gray zone and non–gray zone groups; 62% of patients with a gray zone BNP were identified as class III or IV CHF. Despite this perceived severity, the 90-day event rate was lower in the gray zone group (19.2% vs 32.9%, respectively, P = .002). Although patients in the gray zone had more symptoms of concomitant pulmonary disease, multivariate analysis could not demonstrate any variable that worsened the prognosis of patients with a gray zone BNP level. Conclusions In patients with established CHF, those with gray zone BNP levels have a better prognosis than those with non–gray zone levels despite being perceived by physicians as having New York Heart Association class III or IV CHF.

B-type natriuretic peptide (BNP) is secreted from the cardiac ventricles in response to increased wall tension.The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea and had BNP measured with a point-of-care assay upon arrival. The gold standard for congestive heart failure (CHF) was adjudicated by two independent cardiologists, blinded to BNP results, who reviewed all clinical data and standardized scores. The current study explores the effect of these variables on BNP decision statistics as well as the impact that changing cutoffs might have on the cost-effectiveness of diagnostic decisions that use BNP information.Significant differences in CHF rates were found on the basis of age (P.001) and racial group (P =.020) but not sex (P =.424). BNP levels increased with increasing age (P.001). To evaluate potential differences in the diagnostic utility of BNP levels as a function of demographic variables, separate receiver operating characteristic curves were performed. BNP was a stronger predictor in younger subjects than in older subjects and slightly weaker for female patients than for male patients (area under the curve = 0.918 and 0.870, respectively). An even smaller difference was noted between the white and black racial groups (area under the curve = 0.888 and 0.903, respectively). The differences in specificity as a function of age are larger than other differences in specificity or sensitivity. When logistic regression was used in a multivariate approach to combine the demographic variables with BNP information in the prediction of CHF, only BNP contributed significantly to the prediction of acute CHF. When the model was expanded to include terms for the interaction of each of the demographic variables with log(10) BNP, a significant interaction was found for sex. Since the relative consequences of false-positives and false-negatives are unlikely to be equivalent, the BNP cut-points that would be selected based on the current data as a function of relative costs are presented. Sharply rising consequences are seen for BNP cut-points100 pg/mL.If one assumes that failing to treat cases of CHF is worse than treating negative cases, then relatively low BNP cut-points (eg, not100 pg/mL) should be used in patients presenting to the Emergency Department with a chief complaint of dyspnea, regardless of age, sex, or ethnicity.

B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNPor = 100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis.The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results.Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively (P.05 for all comparisons except 35 vs 25). B-type natriuretic peptide cut-points to maintain 90% sensitivity for a HF diagnosis were 170 pg/mL for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL in severely/morbidly obese patients.Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNPor = 54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNPor = 170 pg/mL) could be used to increase specificity.

We evaluated whether recent cocaine use alters the specificity of CK-MB, myoglobin, and cardiac troponin I for acute myocardial infarction (AMI) in patients who are seen in the emergency department for chest pain. Patients60 years old with potential myocardial ischemia underwent a standardized history and physical examination and routine CK-MB assays every 8 to 12 hours and had study serum obtained at presentation for CK-MB, myoglobin, and cardiac troponin I immunoassays, as well as benzoylecgonine, cocaine's main metabolite. We enrolled 97 patients, 19 (20%) of whom had recent used cocaine. Patients with and without cocaine use were similar with regards to sex, race, renal and muscular disease, diabetes, family history, and hypertension and rate of AMI (12% vs 11%, p = 1.0). In patients without MI, the mean myoglobin level was higher in cocaine users than noncocaine users (179 vs 74 ng/ml; Mann-Whitney p = 0.003), but the mean values were similar for CK-MB (2.2 vs 2.1 ng/ml; Mann-Whitney p = 0.58) and for cardiac troponin-I (0.02 vs 0.02 ng/ml; Mann-Whitney p = 0.87). The specificities of the markers in patients with and without cocaine use were as follows: cardiac troponin I, 94% vs 94%, (p = 1.0); CK-MB, 75% vs 88% (p = 0.24); and myoglobin, 50% vs 82%, (p = 0.02), respectively. Our data demonstrate that the specificity of myoglobin was altered by recent cocaine use. The specificity of CK-MB was affected less and the specificity of cardiac troponin I was not affected by recent cocaine use.

The impact of regulatory requirements, which require central adjudication for the diagnosis of acute myocardial infarction (AMI) in cardiac biomarker studies, is unclear. We determined the impact of local (at the site of subject enrollment) versus central adjudication of AMI on final diagnosis.This is a retrospective analysis of data from the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study, an 18-center prospective study of patients with suspected acute coronary syndromes, with enrollment from December 19, 2006, to September 20, 2007. Local adjudication of AMI was performed by a single site investigator at each center following the protocol-specified definition and according to the year 2000 definition of AMI, which based cardiac troponin (cTn) elevation on local cut points for each of the 13 different assays. After completion of the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study primary analysis and to evaluate a new troponin assay, a Food and Drug Administration-mandated central adjudication was performed by 3 investigators at different institutions. This adjudication used the 2007 Universal Definition of AMI, which differs by use of the manufacturer's 99th percentile cTn cut point. We describe the outcome of this process and compare it with the local adjudication. Central adjudicators were not blinded to local adjudications. For central adjudication, discrepant diagnoses were resolved by consensus. Local versus central cTn cut points differed for 6 assays. Both definitions required a rise and/or fall of cTn. Discrepant cases were reviewed by the lead author. Difficult cases were defined as having a difference between local and central adjudication, an elevated cTn with a temporal rise and fall, and a negative or absent risk stratification test. Statistics were by χ(2), κ, and logistic regression.Of 1,107 patients enrolled, 11 had indeterminate central adjudication, leaving 1,096 for analysis. In spite of high agreement across central versus local adjudicators, κ = 0.79 (95% CI [0.73, 0.85]), AMI was diagnosed more often by central adjudication, 134 (12.2%) versus 104 (9.5%), with 44 local diagnoses (4%) changed from non-AMI to AMI (n = 37) or AMI to non-AMI (n = 7) (P.001). These 44 represented 34% (95% CI 26%-42%) of 141 cases in which either central or local adjudication was AMI. Of diagnoses changed to AMI, 3 reasons contributed approximately one-third each: the local use of a non-99th percentile cTn cutoff (32%), the possibility of human error (34%), and difficult cases (34%).Despite an acceptable κ, over a third of patients with a diagnosis of AMI were not assigned that diagnosis by both sets of adjudicators. This supports the importance of 1 standard method for diagnosis of AMI.

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.