Objectives The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI). Background The rapid and reliable exclusion of AMI is a ...major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress may be useful in this setting. Methods In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, we measured levels of copeptin at presentation, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists using all available data. Results The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses (median 20.8 pmol/l vs. 6.0 pmol/l, p < 0.001). The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p < 0.001). A copeptin level <14 pmol/l in combination with a troponin T ≤0.01 μg/l correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%. Conclusions The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients. (Advantageous Predictors of Acute Coronary Syndromes Evaluation APACE; NCT00470587 )
We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score ...for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible.
Myeloperoxidase (MPO) is a biomarker of inflammation and oxidative stress produced by neutrophils, monocytes, and endothelial cells. Concentrations of MPO predict mortality in patients with chronic ...heart failure. This study sought to investigate the diagnostic accuracy and prognostic value of MPO in patients with acute heart failure (AHF).
We prospectively enrolled 667 patients presenting to the emergency department with dyspnea and observed them for 1 year. MPO and B-type natriuretic peptide (BNP) were measured at presentation. Two independent cardiologists adjudicated final discharge diagnoses.
MPO concentrations were similar in patients with AHF (n = 377, median 139 pmol/L) and patients with noncardiac causes of dyspnea (n = 290, median 150 pmol/L, P = 0.26). The diagnostic accuracy of MPO for AHF was limited area under the ROC curve (AUC) 0.53 and inferior to that of BNP (AUC 0.95, P < 0.001). In patients with AHF, MPO concentrations above the lowest tertile (MPO >99 pmol/L) were associated with significantly increased 1-year mortality (hazard ratio 1.58, P = 0.02). The combination of MPO (< or = 99 vs >99 pmol/L) and BNP (median of < or = 847 vs >847 ng/L) improved the prediction of 1-year mortality (hazard ratio 2.80 for both variables increased vs both low, P < 0.001). After adjustment for cardiovascular risk factors in multivariable Cox proportional hazard analysis, increases in MPO contributed significantly toward the prediction of 1-year mortality (hazard ratio 1.51, P = 0.045).
MPO is an independent predictor of 1-year mortality in AHF, is additive to BNP, and could be helpful in identifying patients with a favorable prognosis despite increased BNP concentrations.
Monitoring treatment efficacy and assessing outcome by serial measurements of natriuretic peptides in acute decompensated heart failure (ADHF) patients may help to improve outcome.
This was a ...prospective multi-center study of 171 consecutive patients (mean age 80 73-85 years) presenting to the emergency department with ADHF. Measurement of BNP and NT-proBNP was performed at presentation, 24 hours, 48 hours and at discharge. The primary endpoint was one-year all-cause mortality; secondary endpoints were 30-days all-cause mortality and one-year heart failure (HF) readmission.
During one-year follow-up, a total of 60 (35%) patients died. BNP and NT-proBNP levels were higher in non-survivors at all time points (all P < 0.001). In survivors, treatment reduced BNP and NT-proBNP levels by more than 50% (P < 0.001), while in non-survivors treatment did not lower BNP and NT-proBNP levels. The area under the ROC curve (AUC) for the prediction of one-year mortality increased during the course of hospitalization for BNP (AUC presentation: 0.67; AUC 24 h: 0.77; AUC 48 h: 0.78; AUC discharge: 0.78) and NT-proBNP (AUC presentation: 0.67; AUC 24 h: 0.73; AUC 48 h: 0.75; AUC discharge: 0.77). In multivariate analysis, BNP at 24 h (1.02 1.01-1.04, P = 0.003), 48 h (1.04 1.02-1.06, P < 0.001) and discharge (1.02 1.01-1.03, P < 0.001) independently predicted one-year mortality, while only pre-discharge NT-proBNP was predictive (1.07 1.01-1.13, P = 0.016). Comparable results could be obtained for the secondary endpoint 30-days mortality but not for one-year HF readmissions.
BNP and NT-proBNP reliably predict one-year mortality in patients with ADHF. Prognostic accuracy of both biomarker increases during the course of hospitalization. In survivors BNP levels decline more rapidly than NT-proBNP levels and thus seem to allow earlier assessment of treatment efficacy. Ability to predict one-year HF readmission was poor for BNP and NT-proBNP.
ClinicalTrials.gov identifier: NCT00514384.
The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and ...specific marker of AKI.
A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification.
Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P<0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P<0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P=0.04) in multivariable regression analysis.
Plasma NGAL levels do not adequately predict AKI in patients with AHF.
Delayed recognition of sepsis and inappropriate initial antibiotic therapy are associated with increased mortality and morbidity. The early detection of the causative organism in sepsis is an unmet ...clinical need. A novel multiplex real-time polymerase chain reaction (MRT-PCR) (SeptiFast®) technique may provide the microbiological diagnosis within six hours.
We assessed the diagnostic accuracy of blood cultures and MRT-PCR in a comparative diagnostic cohort study in 110 consecutive adult patients presenting to the emergency department (ED) with suspected sepsis.
We collected 205 corresponding PCR samples and blood culture (BC) pairs from the 110 patients. There was moderate to high concordance between PCR and BC with 181 (88%) matching and 24 (12%) mismatching samples. The diagnostic accuracy of MRT-PCR in detecting sepsis and its causative organism was comparable to that of BCs. The additional use of MRT-PCR significantly reduced the time to microbiological diagnosis as compared to the use of conventional microbiological methods alone (mean time gained 3.9 hours, range 0-66 hours, p <0.001).
Diagnostic accuracy of BCs and MRT-PCR in the early diagnosis of sepsis and its causative organism in the ED are comparable. However, MRT-PCR reduces the time to microbiological diagnosis. Whether a more rapid detection of the organism by MRT-PCR could improve the outcome of patients has to be assessed in large prospective randomised trials.
Background Obesity may reduce diagnostic accuracy of B-type natriuretic peptide (BNP) and affect long-term outcome. Methods This study evaluated patients included in the BASEL study (N = 452). We ...compared BNP levels in patients with (n = 86) and without (n = 366) obesity (body mass index <30 and >30 kg/m2 ) and determined sensitivities and specificities of BNP in both patient groups by receiver-operating characteristic analysis. Impact of BNP measurements on patient management and outcome in obesity, as well as 360-day mortality, was assessed. Results The BNP levels were lower in obese patients (172 pg/mL interquartile range 31-515 vs 306 interquartile range 75-1,040). The optimal BNP cut-point to detect heart failure was 182 pg/mL in obese patients and 298 pg/mL nonobese patients. Obese patients had lower in-hospital mortality (3.5% vs 8.5%, P = .045) and 360-day mortality (15% vs 30%, P = .001). In obese patients, the determination of BNP levels reduced time to initiation of the appropriate treatment (96 ± 98 vs 176 ± 230, P < .05) without impacting other end points. Conclusions Adjustment of BNP values in the assessment of obese patients presenting with acute dyspnea seems necessary to improve diagnostic accuracy and patient management. Obese patients had half the short- and long-term mortality of nonobese patients, independent of their final discharge diagnosis.
Abstract Background Cardiopulmonary exercise testing is the method of choice for the differentiation of exercise intolerance. This study sought to assess the utility of B-type natriuretic peptide ...(BNP) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) for the identification of a cardiocirculatory exercise limitation. Methods In 162 patients undergoing cardiopulmonary exercise testing, rest and peak exercise BNP and NT-proBNP levels were measured. In 94 patients fulfilling criteria for appropriate effort and sufficient diagnostic certainty, the accuracy of BNP and NT-proBNP for the prediction of a cardiocirculatory limitation, as assessed based on clinical and exercise testing data, was determined. Results A cardiocirculatory limitation was identified in 27 (29%) patients. Median (interquartile range) resting BNP 162 (45-415) vs 39 (19-94) vs 24 (15-46) pg/mL; P <.001 and NT-proBNP 506 (129-1167) vs 77 (35-237) vs 34 (19-77) pg/mL; P <.001 were higher in patients with cardiocirculatory as compared with those with pulmonary limitation (n = 28) and those without cardiocirculatory or pulmonary limitation (n = 39). The area under the receiver operator characteristics curve for BNP and NT-proBNP to identify a cardiocirculatory limitation was 0.79 and 0.84, respectively ( P = .15 for comparison of the curves). Sensitivity and specificity of the optimal BNP cutoff of 85 pg/mL were 63% and 84%, respectively. Sensitivity and specificity of the optimal NT-proBNP cutoff of 223 pg/mL were 74% and 85%, respectively. Peak exercise biomarkers were not more accurate than resting levels. Conclusions Among patients referred for cardiopulmonary exercise testing for evaluation of unexplained exercise intolerance, BNP and NT-proBNP were similarly useful to identify those with a cardiocirculatory limitation.
The rapid and reliable diagnosis of acute myocardial infarction is a major unmet clinical need.
We conducted a multicenter study to examine the diagnostic accuracy of new, sensitive cardiac troponin ...assays performed on blood samples obtained in the emergency department from 718 consecutive patients who presented with symptoms suggestive of acute myocardial infarction. Cardiac troponin levels were determined in a blinded fashion with the use of four sensitive assays (Abbott-Architect Troponin I, Roche High-Sensitive Troponin T, Roche Troponin I, and Siemens Troponin I Ultra) and a standard assay (Roche Troponin T). The final diagnosis was adjudicated by two independent cardiologists.
Acute myocardial infarction was the adjudicated final diagnosis in 123 patients (17%). The diagnostic accuracy of measurements obtained at presentation, as quantified by the area under the receiver-operating-characteristic curve (AUC), was significantly higher with the four sensitive cardiac troponin assays than with the standard assay (AUC for Abbott-Architect Troponin I, 0.96; 95% confidence interval CI, 0.94 to 0.98; for Roche High-Sensitive Troponin T, 0.96; 95% CI, 0.94 to 0.98; for Roche Troponin I, 0.95; 95% CI, 0.92 to 0.97; and for Siemens Troponin I Ultra, 0.96; 95% CI, 0.94 to 0.98; vs. AUC for the standard assay, 0.90; 95% CI, 0.86 to 0.94). Among patients who presented within 3 hours after the onset of chest pain, the AUCs were 0.93 (95% CI, 0.88 to 0.99), 0.92 (95% CI, 0.87 to 0.97), 0.92 (95% CI, 0.86 to 0.99), and 0.94 (95% CI, 0.90 to 0.98) for the sensitive assays, respectively, and 0.76 (95% CI, 0.64 to 0.88) for the standard assay. We did not assess the effect of the sensitive troponin assays on clinical management.
The diagnostic performance of sensitive cardiac troponin assays is excellent, and these assays can substantially improve the early diagnosis of acute myocardial infarction, particularly in patients with a recent onset of chest pain. (ClinicalTrials.gov number, NCT00470587.)
Abstract Background Uric acid was shown to predict outcome in patients with stable chronic heart failure. Its impact in patients admitted in the Emergency Department with acute dyspnea, however, ...remains unknown. Methods We prospectively investigated the diagnostic and prognostic value of uric acid in 743 unselected patients presenting to the Emergency Department with acute dyspnea. Results Uric acid at admission was higher in patients with acute decompensated heart failure (51% of the cohort) as compared with patients with noncardiac causes of dyspnea (median, 447 μmol/L vs 340 μmol/L, P <.001). The area under the receiver operating characteristic curve for the accuracy to detect acute decompensated heart failure was inferior for uric acid (0.70) than for B-type natriuretic peptide (area under the receiver operating characteristic curve 0.91, P <.001). Patients in the highest uric acid tertile more often required admission to the hospital (92% vs 74% in the first tertile, P <.001) and had higher in-hospital mortality (13% vs 4% in the first tertile, P <.001). Cumulative 24-month mortality rates were 28% in the first, 31% in the second, and 50% in the third tertile ( P <.001). After adjustment in multivariable Cox proportional hazard analysis, uric acid predicted 24-month mortality independently of B-type natriuretic peptide ( P = .003). Conclusions Our study first shows that uric acid, measured at Emergency Department admission or hospital discharge, is a powerful predictor of long-term outcome in dyspneic patients.
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