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Objective: We hypothesised that biomarkers representing different pathophysiological pathways of atherosclerosis namely growth differentiation factor 15 (GDF-15), N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT) could enhance cardiovascular risk prediction in patients with type 2 diabetes mellitus., Methods: This is a prospective study in 746 patients with type 2 diabetes mellitus, who were followed up for 60 months. The primary endpoint was defined as unplanned hospitalisation for cardiovascular disease or death. The prognostic performance of the biomarkers of interest (GDF-15 in comparison with NT-proBNP and hs-TnT) was evaluated in univariate as well as in stepwise Cox regression models. HRs are presented per standard unit increase., Results: The primary endpoint was registered in 171 patients (22.9%). In univariate Cox regression models, GDF-15 as well as hs-TnT provided significant prognostic information. Even after adjusting for established cardiovascular risk factors, GDF-15, hs-TnT and NT-proBNP remained strong independent predictors of the endpoint (logGDF-15: HR 1.37, p<0.01, CI 1.12 to 1.68; loghs-TnT: HR 1.43, p<0.01, CI 1.13 to 1.1.82; logNT-proBNP: HR 1.45, p<0.01, CI 1.26 to 1.66). The number of elevated markers showed a strong complementarity to predict future long-term risk. Adding hs-TnT and GDF-15 to a zero model already including NT-proBNP led to a net reclassification improvement (NRI) of 33.6% (CI 16.0% to 50.8%, NRI for patients with event: 11.1% CI -4.7% to 26.6%, for patients without event: 22.5% CI 13.6% to 30.5%)., Conclusions: GDF-15 and hs-TnT are strong independent cardiovascular biomarkers augmenting the predictive value of NT-proBNP in patients with diabetes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: Patients with cancer may display elevated levels of B-type natriuretic peptide (BNP) and high-sensitive troponin T (hsTnT) without clinical manifestation of cardiac disease. This study aimed to evaluate circulating cardiovascular hormones and hsTnT and their association with mortality in cancer., Methods: We prospectively enrolled 555 consecutive patients with a primary diagnosis of cancer and without prior cardiotoxic anticancer therapy. N-terminal pro BNP (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), copeptin, hsTnT, proinflammatory markers interleukin 6 (IL-6) and C reactive protein (CRP), and cytokines serum amyloid A (SAA), haptoglobin and fibronectin were measured. All-cause mortality was defined as primary endpoint., Results: During a median follow-up of 25 (IQR 16-31) months, 186 (34%) patients died. All cardiovascular hormones and hsTnT levels rose with tumour stage progression. All markers were significant predictors of mortality with HRs per IQR of 1.54 (95% CI 1.24 to 1.90, p<0.001) for NT-proBNP, 1.40 (95% CI 1.10 to 1.79, p<0.01) for MR-proANP, 1.31 (95% CI 1.19 to 1.44, p<0.001) for MR-proADM, 1.21 (95% CI 1.14 to 1.30, p<0.001) for CT-proET-1, 1.22 (95% CI 1.04 to 1.42, p=0.014) for copeptin and 1.21 (95% CI 1.13 to 1.32, p<0.001) for hsTnT, independent of age, gender, tumour entity and stage, and presence of cardiac comorbidities. NT-proBNP, MR-proANP, MR-proADM and hsTnT displayed a significant correlation with IL-6 and CRP., Conclusions: Circulating levels of cardiovascular peptides like NT-proBNP, MR-proANP, MR-proADM, CT-pro-ET-1 and hsTnT were elevated in an unselected population of patients with cancer prior to induction of any cardiotoxic anticancer therapy. The aforementioned markers and copeptin were strongly related to all-cause mortality, suggesting the presence of subclinical functional and morphological myocardial damage directly linked to disease progression., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide (NT-proBNP)., Background: Few clinical trials have successfully demonstrated the prevention of cardiac events in patients with diabetes. One reason for this might be an inaccurate selection of patients. NT-proBNP has not been assessed in this context., Methods: A total of 300 patients with type 2 diabetes, elevated NT-proBNP (>125 pg/ml) but free of cardiac disease were randomized. The "control" group was cared for at 4 diabetes care units; the "intensified" group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system (RAS) antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after 2 years., Results: At baseline, the mean age of the patients was 67.5 ± 9 years, duration of diabetes was 15 ± 12 years, 37% were male, HbA1c was 7 ± 1.1%, blood pressure was 151 ± 22 mm Hg, heart rate was 72 ± 11 beats/min, median NT-proBNP was 265.5 pg/ml (interquartile range: 180.8 to 401.8 pg/ml). After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups (p < 0.0001). Blood pressure was significantly reduced in both (p < 0.05); heart rate was only reduced in the intensified group (p = 0.004). A significant reduction of the primary endpoint (hazard ratio: 0.351; 95% confidence interval: 0.127 to 0.975, p = 0.044) was visible in the intensified group. The same was true for other endpoints: all-cause hospitalization, unplanned cardiovascular hospitalizations/death (p < 0.05 for all)., Conclusions: Accelerated up-titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [PONTIAC]; NCT00562952)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Accurate risk prediction is important for an adequate management of heart failure (HF) patients. We assessed the incremental prognostic ability of a multi-biomarker approach in advanced HF., Methods: In 349 patients with advanced HF (median 75 years, 66% male) we investigated the incremental prognostic value of 12 novel biomarkers involved in different pathophysiological pathways including inflammation, immunological activation, oxidative stress, cell growth, remodeling, angiogenesis and apoptosis., Results: During a median follow-up of 4.9 years 55.9% of patients died. Using multivariable Cox regression and bootstrap variable-selection age, chronic obstructive pulmonary disease, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the following 5 novel biomarkers were retained in the best mortality prediction model: the chemokine fractalkine, the angiogenic and mitogenic hepatocyte growth factor (HGF), the growth differentiation factor 15 (GDF-15) influencing cardiac remodeling and apoptosis, and the 2 pro-apoptotic molecules soluble apoptosis-stimulating fragment (sFAS) and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). This multi-biomarker score had strong discriminatory power for 5-year mortality (area under the Receiver Operating Characteristic curve [AUC]=0.81) and improved risk prediction beyond the prognostic power of a comprehensive conventional risk score including known clinical predictors and NT-proBNP (AUC=0.77). Net reclassification confirmed a significant improvement of individual risk prediction (p=0.003)., Conclusions: Risk prediction by a multi-biomarker score is superior to a conventional risk score including clinical parameters and NT-proBNP. Additional predictive information from different biological pathways reflects the multisystemic character of HF., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Cardiac transplantation represents the best procedure to improve long-term clinical outcome in advanced chronic heart failure (CHF), if pre-selection criteria are sufficient to outweigh the risk of the failing heart over the risk of transplantation. Although the cornerstone of success, risk assessment in heart transplant candidates is still under-investigated. Amino terminal pro B-type natriuretic peptide (NT-proBNP) is regarded as the best predictor of outcome in CHF, and the Seattle Heart Failure Score (SHFS), including clinical markers, is widely used if NT-proBNP is unavailable., Methods: The present study assessed the predictive value for all-cause death of the SHFS in CHF patients and compared it with NT-proBNP in a multivariate model including established baseline parameters known to predict survival., Results: A total of 429 patients receiving stable HF-specific pharmacotherapy were included and monitored for 53.4 ± 20.6 months. Of these, 133 patients (31%) died during follow-up. Several established predictors of death on univariate analysis proved significant for the total study cohort. Systolic pulmonary arterial pressure (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.02-1.05); p < 0.001, Wald 15.1), logNT-proBNP (HR, 1.51; 95% CI, 1.22-1.86; p < 0.001, Wald 14.9), and the SHFS (HR, 0.99; 95% CI, 0.99-1.00; p < 0.001, Wald 12.6) remained within the stepwise multivariate Cox regression model as independent predictors of all-cause death. Receiver operating characteristic curve analysis revealed an area under the curve of 0.802 for logNT-proBNP and 0.762 for the SHFS., Conclusions: NT-proBNP is a more potent marker to identify patients at the highest risk. If the NT-proBNP measurement is unavailable, the SHFS may serve as an adequate clinical surrogate to predict all-cause death., (Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiovascular events are the most relevant events in patients with diabetes mellitus. We aimed to compare the predictive values of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the state-of-the-art marker, albuminuria, for cardiac events in diabetic patients., Methods: In this prospective observational study we recruited 1071 patients with diabetes mellitus. NT-proBNP and albuminuria ⊟ defined as a urinary albumin/creatinine ratio >30 mg/g were measured at baseline. Patients were followed during a mean observation period of 33.1 months. A total of 103 patients reached the defined endpoint (unplanned hospitalization due to a cardiac event or death)., Results: The mean duration of diabetes was 15 ± 12 years and the mean HbA(1c) was 7.5 ± 3.1%. At baseline, 23.7% of the patients presented with albuminuria and 36.6% had plasma NT-proBNP values >125 pg/ml. Multiple Cox regression analysis including age, gender, duration of diabetes HbA(1c), albuminuria, and lnNT-proBNP revealed that lnNT-proBNP (hazard ratio 2.314; 95% CI 1.914-2.798, p < 0.001) was a better predictor than albuminuria (HR 1.544; 95% CI 1.007-2.368, p = 0.047) or age (HR 1.030; 95% CI 1.008-1.053, p = 0.007). Calculating different Cox-models with (A) albuminuria, (B) NT-proBNP, or (C) both in the model revealed that the C-index was best if NT-proBNP was entered in the model (C-index for A 0.735, for B 0.809, and for C 0.786). Kaplan-Meier analysis demonstrated that albuminuria does not add substantial information if NT-proBNP is entered into the model., Conclusion: NT-proBNP was superior to albuminuria for predicting cardiac events.

Background: Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes., Methods: In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded., Results: The median duration of diabetes was 11 ± 10.35 years. Patients were in the mean 60 ± 13 years old and mean HbA(1c) was 62 ± 13 mmol/mol (7.8 ± 3.3%). At baseline, mean uric acid was 321.2 ± 101.1 μmol/l (range 101.1-743.5 μmol/l), median N-terminal pro-B-type natriuretic peptide was 92 ± 412 pg/ml and median urinary albumin to creatinine ratio was 8 ± 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide (r = 0.237, P < 0.001) and urinary albumin:creatinine ratio (r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model., Conclusion: Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro-B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Background: In primary care, identification of patients who are at risk of major adverse events is of great importance. At the same time identifying individuals who are at very low risk and do not need further diagnostic workup and therapy is also important and may help to correctly allocate scarce healthcare resources., Aim: This study evaluated amino-terminal pro B-natriuretic peptide (NT-proBNP) as a risk marker in primary care patients with hypertension, diabetes, clinically suspected heart failure (HF), history of coronary artery disease or myocardial infarction., Methods and Results: A prospective observational study was conducted in 1203 primary care patients. The primary endpoint, time to all-cause hospitalisation, was reached in 282 (24%) individuals within 12 months. Of all variables analysed, only NT-proBNP (HR 1.001 [1.000-1.001], p < 0.001) and age (HR 1.018 [1.007-1.028], p = 0.001) were of independent predictive value in a stepwise Cox regression analysis regarding all-cause hospitalisation. Neither systolic dysfunction nor signs and symptoms of HF added independent information to predict outcome. The negative predictive value (NPV) increased depending on the specificity of the endpoint (NPV was 86% for all-cause, 98% for cardiac and 100% for HF-related hospitalisation for 125 pg/ml). Positive predictive value and NPV were superior for NT-proBNP compared to clinical signs and symptoms of HF at every cut-point between 100 and 500 pg/ml., Conclusion: NT-proBNP levels predicted clinical events in primary care patients at risk. NPVs were excellent in this high risk population, proving NT-proBNP measurement a safe diagnostic tool.

NT-proBNP is an excellent predictor of adverse events in patients with diabetes mellitus. Due to an aging population it is of interest to determine whether NT-proBNP can predict cardiac events with equal precision in subgroups with different ages. 1395 outpatients with diabetes mellitus were recruited for this prospective observational study. NT-proBNP, renal function, lipid status and other demographic variables were measured at baseline. The cohort was divided into three groups: Group I (609 patients under 60 years of age), group II (634 patients ranging from 60-75) and group III (152 patients older than 75). Patients were followed during a mean observation period of 11 months, 75 patients reached the defined endpoint, which was unplanned hospitalization due to a cardiac event. Mean age was 60 ± 30 years, mean HbA(1c) was 7.6% and mean NT-proBNP was 242 ± 437 pg/ml. In a multiple Cox regression model, age (hazard ratio (HR) 11.18, p < 0.01) and the absence of a cardiac disease (HR 0.49, p < 0.01) were important variables for short-term prognosis. The addition of the logarithm of NT-proBNP provided independent prognostic information (HR 1.81 p < 0.01) and significantly increased the explained variance of the model (χ(2 )= 22.93; d.f. = 1; p < 0.01). More importantly, the predictive power of this model was similar in different age-groups. The prognostic information of NT-proBNP was not influenced by age and this biomarker remained a reliable predictor of short-term cardiac events in patients with diabetes mellitus aged 75 years or older.

Objectives: This study was designed to investigate whether the addition of N-terminal pro-B-type natriuretic peptide-guided, intensive patient management (BM) to multidisciplinary care (MC) improves outcome in patients following hospitalization due to heart failure (HF)., Background: Patients hospitalized due to HF experience frequent rehospitalizations and high mortality., Methods: Patients hospitalized due to HF were randomized to BM, MC, or usual care (UC). Multidisciplinary care included 2 consultations from an HF specialist who provided therapeutic recommendations and home care by a specialized HF nurse. In addition, BM included intensified up-titration of medication by HF specialists in high-risk patients. NT-proBNP was used to define the level of risk and to monitor wall stress. This monitoring allowed for anticipation of cardiac decompensation and adjustment of medication in advance., Results: A total of 278 patients were randomized in 8 Viennese hospitals. After 12 months, the BM group had the highest proportion of antineurohormonal triple-therapy (difference among all groups). Accordingly, BM reduced days of HF hospitalization (488 days) compared with the hospitalization for the MC (1,254 days) and UC (1,588 days) groups (p < 0.0001; significant differences among all groups). Using Kaplan-Meier analysis, the first HF rehospitalization (28%) was lower in the BM versus MC groups (40%; p = 0.06) and the MC versus UC groups (61%; p = 0.01). Moreover, the combined end point of death or HF rehospitalization was lower in the BM (37%) than in the MC group (50%; p < 0.05) and in the MC than in the UC group (65%; p = 0.04). Death rate was similar between the BM (22%) and MC groups (22%), but was lower compared with the UC group (39%; vs. BM: p < 0.02; vs. MC: p < 0.02)., Conclusions: Compared with MC alone, additional BM improves clinical outcome in patients after HF hospitalization. (BNP Guided Care in Addition to Multidisciplinary Care; NCT00355017).

Aims: The Cardiac Resynchronization in Heart Failure (CARE-HF) study showed that cardiac resynchronization therapy (CRT) reduces mortality in HF patients with markers of dyssynchrony. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) might predict which patients benefit most from CRT. We evaluated whether the prognostic value of NT-proBNP was influenced by CRT and the effects of CRT stratified according to NT-proBNP., Methods and Results: A total of 813 patients were enrolled in CARE-HF. Baseline log-transformed NT-proBNP independently predicted all-cause mortality, sudden death, and death from pump failure. In a multivariable model including log-transformed NT-proBNP, assignment to CRT remained independently associated with better prognosis without evidence of interaction. Stratifying patients according to the median NT-proBNP and to CRT treatment allocation, all-cause mortality was 12% if or= median + CRT, and 51% if >or= median + control group. There was no evidence of a difference in the relative effect of CRT across different values of NT-proBNP., Conclusion: NT-proBNP retains its prognostic value in HF patients with CRT. Deploying CRT before the patients have reached end-stage HF may maximize the benefit of treatment.

Circulating levels of B-type natriuretic peptide (BNP) and NH(2)-terminal-proBNP (NT-proBNP) increase in response to volume overload and help in the differential diagnosis of acute heart failure. Elevated plasma BNP levels are observed also in sepsis and do not always correspond to left ventricular dysfunction. Here, we investigated plasma NT-proBNP fluctuations in response to human bacterial endotoxinemia, an experimental model of systemic infection and inflammation. Escherichia coli endotoxin (LPS) (2 ng/kg) was administered to 10 healthy volunteers in a randomized, placebo-controlled, cross-over design. Plasma NT-proBNP, C-reactive protein (CRP), COOH terminal pro-endothelin-1 (CT-proET-1), and midregional-pro-adrenomedullin (MR-proADM) were measured at hourly intervals for 6 h. LPS administration induced a continuous increase in plasma NT-proBNP that reached peak values after 6 h (40.7 +/- 7.9 vs. 16.1 +/- 3.2 pg/ml in placebo days, mean +/- SE; P = 0.023). The profile of changes in NT-proBNP correlated to changes in body temperature (P < 0.001), heart rate (P = 0.005), CRP (P < 0.001), and CT-proET-1 (P = 0.008), but not to blood pressure values. Our results demonstrate that plasma NT-proBNP increases in a model of systemic infection/inflammation in healthy men with normal heart function. This finding emphasizes the necessity to consider concomitant infections when interpreting elevated circulating NT-proBNP concentrations.

Aims: This study evaluated the predictive value of NT-proBNP for patients with diabetes mellitus and compared the prognostic aptitude of this neurohumoral marker to traditional markers of cardiovascular events., Methods and Results: A prospective observational study was conducted in 631 diabetic patients. The composite endpoint consisted of unplanned hospitalization for cardiovascular events or death within the observation period of 12 months. Of all variables analysed (age, gender, history of hypertension, ischaemic heart disease/any cardiac disease, smoking, duration of diabetes, body mass index, blood pressure, New York Heart Association-class, Dyspnoea score, Minnesota Living with Heart Failure Questionnaire, LDL-cholesterol, HbA(1c), creatinine, glomerular filtration rate), the logarithm of NT-proBNP gave the most potent information in a stepwise Cox regression analysis (P < 0.0001). Bootstrapping with 500 samples supports this result in 95% samples. The negative predictive value of a normal value (<125 pg/mL) of NT-proBNP for short-term cardiovascular events in diabetic patients is 98%., Conclusion: We have demonstrated a strong and independent correlation between NT-proBNP and short-term prognosis of cardiovascular events for patients with diabetes mellitus. With a high negative predictive value it can identify individuals who are not at intermediate risk for cardiovascular events. NT-proBNP proved to be of higher predictive value than traditional cardiovascular markers, in this unselected cohort.

Background: We evaluated the prognostic value of sequential NT-proBNP values in ambulatory heart failure patients after discharge, investigating whether the current value or the recent percent change is more important., Methods and Results: In 166 patients, NT-proBNP was measured at discharge from heart failure hospitalisation and three months later. The combined endpoint of death or heart failure rehospitalisation was evaluated after a maximum of 18 months or at follow-up closure. During a mean observation time of 14+/-4 months, 63 patients (38%) reached the endpoint. In multiple Cox analysis, NT-proBNP three months after discharge (NT-proBNP-3Mo) and NT-proBNP percent change (NT-proBNP-%change) were the only independent predictors of the endpoint among various clinical and laboratory variables. After definition of a high- (n=83, 57% endpoints) and a low-NT-proBNP patient subgroup (n=83, 19% endpoints) according to the median NT-proBNP-3Mo (1751 pg/ml), NT-proBNP-%change was the strongest predictor in the high-NT-proBNP subgroup. In the low-NT-proBNP subgroup, NT-proBNP-3Mo was the only independent predictor., Conclusions: In ambulatory heart failure patients, the prognostic value of sequential NT-proBNP measurements depends on the magnitude of the current NT-proBNP value. Recent percent changes in NT-proBNP provide important prognostic information in patients with high NT-proBNP but not in patients with low NT-proBNP.

Objectives: Natriuretic peptides emerged during recent years as potent prognostic markers in patients with heart failure and acute myocardial infarction. In addition, natriuretic peptides show strong predictive value in patients with pulmonary embolism, sepsis, renal failure, and shock. The present study tests the prognostic information of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in an unselected cohort of critically ill patients., Design: Prospective, observational study., Setting: A tertiary intensive care unit in a university hospital., Patients: A total of 289 consecutive patients admitted to the intensive care unit during a 16-month period with the following data: age 64 +/- 14 yrs, male n = 191, Simplified Acute Physiology Score II of 52 +/- 24, mechanical ventilation n = 180 (62%), vasopressors n = 179 (62%), renal failure n = 24 (8%)., Interventions: None., Measurements and Main Results: Plasma NT-pro-BNP samples (Roche Diagnostics) were obtained on intensive care unit admission. Data are given as median [range]. Intensive care unit survivors had significantly lower NT-pro-BNP values compared with intensive care unit nonsurvivors (3394 [24-35,000] vs. 6776 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). Hospital survivors were characterized by significantly lower NT-pro-BNP values (2656 [24-35,000] vs. 8390 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). NT-pro-BNP levels were not significantly different in patients with primary cardiac diagnosis compared with those with a noncardiac admission diagnosis (4794 [26-35,000], n = 202 vs. 3349 [24-35,000], n = 87, cardiac vs. noncardiac, respectively, p = .28). In a logistic regression model, Simplified Acute Physiology Score II and NT-pro-BNP were independently associated with hospital survival (chi = 35.6, p = .0001 and chi = 11.3, p = .0008, Simplified Acute Physiology Score II and NT-pro-BNP, respectively). Areas under the receiver operating characteristic curves of NT-pro-BNP and Simplified Acute Physiology Score II were not statistically significant different regarding the prediction of outcome., Conclusions: NT-pro-BNP on admission is an independent prognostic marker of outcome in an unselected cohort of critically ill patients. A single measurement of NT-pro-BNP might facilitate triage of emergency and intensive care unit patients.

Background: The aim of the present study was to demonstrate the capability of B-type natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) as prognostic markers in patients with dyspnoea as a chief complaint., Methods: BNP and NT-proBNP plasma concentrations were obtained from 251 short of breath patients presenting to the emergency department of a tertiary care hospital. Patients with acute coronary syndromes or trauma were excluded. The endpoint was defined as all-cause mortality, and the study participants were followed up for 365 days from the time they attended the emergency department., Results: Of the 251 patients, 62 died and 189 stayed alive during follow-up. In the present study, optimal cut off levels for the prediction of survival were 454 ng/L for BNP, and 2060 ng/L for NT-proBNP. Mortality was higher in patients with baseline BNP and NT-proBNP concentrations above these cut off levels (log rank p<0.001; hazard ratios, 0.325 and 0.357, respectively). In multivariate Cox proportional-hazards regression analyses, elevated BNP/NT-proBNP, low systolic blood pressure, and renal dysfunction were predictors of mortality even when the baseline diagnosis of acute destabilized heart failure was factored into the model., Conclusions: Both BNP and NT-proBNP measures obtained from short of breath patients presenting to an emergency department may be predictive of one-year all-cause mortality independently of the baseline diagnosis of acute destabilized heart failure.

Background: The aim of the present study was to assess the utility of amino-terminal pro-A-type natriuretic peptide (NT-proANP) measurements for the emergency diagnosis of acute destabilized heart failure (HF), using a novel sandwich immunoassay covering midregional epitopes (MR-proANP)., Methods: The retrospective analysis comprised 251 consecutive patients presenting to the emergency department of a tertiary care hospital with dyspnea as a chief complaint. The diagnosis of acute destabilized HF was based on the Framingham score for HF plus echocardiographic evidence of systolic or diastolic dysfunction. A commercially available immunoluminometric assay was used for measurement of MR-proANP plasma concentrations., Results: Median MR-proANP plasma concentrations were significantly higher in patients with dyspnea attributable to acute destabilized HF (338 pmol/L; n = 137) than in patients with dyspnea attributable to other reasons (98 pmol/L; n = 114; P <0.001). The area under the curve for MR-proANP was 0.876 (SE = 0.022; 95% confidence interval, 0.829-0.914), and the cutoff concentration with the highest diagnostic accuracy was 169 pmol/L (sensitivity, 89%; specificity, 76%; diagnostic accuracy, 83%). In the setting evaluated, diagnostic information obtained by MR-proANP measurements was similar to that obtained with B-type natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) measurements., Conclusions: MR-proANP measurements may be useful as an aid in the diagnosis of acute destabilized HF in short-of-breath patients presenting to an emergency department. The diagnostic value of MR-proANP appears to be comparable to that of BNP and NT-proBNP.

Aims: N-ANP, N-BNP and BNP are proven to be excellent markers for diagnosis and the prediction of outcome in heart failure patients. Published studies on this subject differ in respect of their design and are therefore difficult to compare. The EuroHeart Failure Survey was undertaken to evaluate the drug prescription rate; the cohort of this survey best reflects clinical practice. The purpose of the present study was to compare the three hormones in clinical practice for the purpose of diagnosis and the prediction of outcome. Attention was focused on patients with normal values and the implications of these on survival., Methods and Results: Of 341 patients recruited in the Austrian centers of the survey, blood samples for the determination of N-ANP, N-BNP and BNP were taken from 112 patients. Mortality within the observation period was defined as the endpoint. Normal levels of the hormones were found in 5% of cases for N-ANP, 25% for N-BNP and 30% for BNP. The mortality of patients with normal values was low (0%, 3% and 6%, respectively) and occurred late (after more than 23 months). Above-median levels of all three hormones resulted in a comparable mortality (51% survival for N-ANP, 50% for BNP and 49% for N-BNP)., Conclusions: In a clinical setting, the risk stratification for outcome is similar for N-ANP, N-BNP and BNP. More importantly, all hormones are reliable parameters to diagnose CHF using normal values as a cut-point. However, N-ANP appears to be more sensitive than BNP or N-BNP.

Background: The prognostic value of natriuretic peptides in aortic stenosis (AS) remains unknown., Methods and Results: B-type natriuretic peptide (BNP), N-terminal BNP (NtBNP), and N-terminal atrial natriuretic peptide (NtANP) were determined in 130 patients with severe AS (mean age, 70+/-12 years; mean gradient, 64+/-21 mm Hg; valve area, 0.64+/-0.15 cm2) who were followed up for 377+/-150 days. Natriuretic peptides increased with NYHA class and with decreasing ejection fraction (EF). Even asymptomatic patients frequently had elevated neurohormones. Asymptomatic patients who developed symptoms during follow-up had higher BNP and NtBNP levels at entry compared with those remaining asymptomatic (median for NtBNP, 131 pmol/L [interquartile range, 50 to 202 pmol/L] versus 31 pmol/L [range, 19 to 56 pmol/L]; P<0.001). Symptom-free survival at 3, 6, 9, and 12 months for patients with NtBNP <80 versus > or =80 pmol/L was 100%, 88+/-7%, 88+/-7%, and 69+/-13% compared with 92+/-8%, 58+/-14%, 35+/-15%, and 18+/-15%, respectively (P<0.001). Seventy-nine patients eventually underwent surgery because of symptoms. Considering preoperative neurohormone levels, age, NYHA class, aortic valve area, EF, and presence of coronary artery disease, we found that neurohormones, EF, and NYHA class predicted survival; neurohormones predicted postoperative symptomatic status; and neurohormones and preoperative EF predicted postoperative EF. However, by multivariate analysis, NtBNP was the only independent predictor of outcome., Conclusions: In severe AS, natriuretic peptides provide important prognostic information beyond clinical and echocardiographic evaluation. NtBNP independently predicts symptom-free survival, and preoperative NtBNP independently predicts postoperative outcome with regard to survival, symptomatic status, and left ventricular function. Thus, neurohormones may gain particular importance for timing of surgery in asymptomatic severe AS.