Copyright © 2003 by the European Society of Cardiology.
Clinical research
N-terminal pro-brain natriuretic peptide
A new gold standard in predicting mortality in patients with advanced heart failure
a The Scottish Cardiopulmonary Transplant Unit, Glasgow Royal Infirmary, Glasgow, UK
b Department of Cardiology, University of Glasgow, Glasgow, UK
* Correspondence to: Dr R. S. Gardner, Department of Cardiology, University of Glasgow, 10 Alexandra Parade, Glasgow G31 2ER, UK. Tel: +44 141 211 4689; Fax: +44 141 211 4950
E-mail address: rsgardner{at}doctors.org.uk
Received 19 February 2003; revised 1 July 2003; accepted 9 July 2003
Abstract
Aims The selection of patients for cardiac transplantation (CTx) is notoriously difficult and traditionally involves clinical assessment and an assimilation of markers of the severity of CHF such as the left ventricular ejection fraction (LVEF), maximum oxygen uptake (peak VO2) and more recently, composite scoring systems e.g. the heart failure survival score (HFSS). Brain natriuretic peptide (BNP) is well established as an independent predictor of prognosis in mild to moderate chronic heart failure (CHF). However, the prognostic ability of NT-proBNP in advanced heart failure is unknown and no studies have compared NT-proBNP to standard clinical markers used in the selection of patients for transplantation. The purpose of this study was to examine the prognostic ability of NT-proBNP in advanced heart failure and compare it to that of the LVEF, peak VO2and the HFSS.
Methods and results We prospectively studied 142 consecutive patients with advanced CHF referred for consideration of CTx. Plasma for NT-proBNP analysis was sampled and patients followed up for a median of 374 days. The primary endpoint of all-cause mortality was reached in 20 (14.1%) patients and the combined secondary endpoint of all-cause mortality or urgent CTx was reached in 24 (16.9%) patients. An NT-proBNP concentration above the median was the only independent predictor of all cause mortality (
2=6.03, P=0.01) and the combined endpoint of all cause mortality or urgent CTx (2=12.68, P=0.0004). LVEF, VO2and HFSS were not independently predictive of mortality or need for urgent cardiac transplantation in this study.
Conclusion A single measurement of NT-proBNP in patients with advanced CHF, can help to identify patients at highest risk of death, and is a better prognostic marker than the LVEF, VO2or HFSS.
Key Words: BNP • Brain natriuretic peptide • Prognosis • Chronic heart failure • Cardiac transplantation • Mortality
Despite recent advances in medical therapy, the mortality of advanced chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) remains high. Although donor organ availability restricts its use, cardiac transplantation (CTx) remains an option for those patients with advanced CHF who do not respond to medical therapy.
The selection of patients for CTx is notoriously difficult and traditionally involves clinical assessment and an assimilation of markers of the severity of CHF such as the LVEF and peak VO2. Previous studies have shown that those with a peak VO2
14ml/kg/min benefit in terms of prognosis from transplantation.1–3More recently, many centres have applied a composite scoring system developed by Aaronson et al.4to predict those who will benefit from transplantation: the heart failure survival score (HFSS).
However, each of these methods has limitations. Patients with severe CHF often cannot achieve a true peak VO2due to leg fatigue, angina or general debilitation. Also, it is well known that an echocardiographic determination of LVEF can only be obtained in 70–85% of patients5and an accurate and reproducible determination of LVEF relies on the availability of radionuclide ventriculography. For these reasons, as well as the limited number of patients who were treated with beta-blockers or spironolactone during the development and validation of the HFSS, an ideal method of deciding who will benefit from transplantation has yet to be found. There would therefore be considerable interest in a biochemical marker, which could simplify this process.
Brain natriuretic peptide (BNP) is well known to be increased in both asymptomatic and symptomatic LVSD6,7and increases in proportion to the severity of chronic heart failure.8It also independently predicts morbidity and mortality in asymptomatic LVSD9and in mild-moderate CHF.10–12In addition, BNP has also been shown to be a strong, independent predictor of sudden death in patients with CHF.13Similarly, the N-terminal portion of pro-brain natriuretic peptide (NT-proBNP) has been shown to be an independent marker of mortality or decompensated heart failure after myocardial infarction14or in those with chronic LV dysfunction of an ischaemic aetiology.11However, to date, there are no published data on the prognostic ability of NT-proBNP in patients with advanced heart failure of any aetiology, and no studies have examined its potential role in patient selection for cardiac transplantation.
The aims of this study were firstly to evaluate the prognostic value of NT-proBNP in patients with advanced heart failure referred for consideration of cardiac transplantation, and secondly to compare the prognostic ability of NT-proBNP to that of the HFSS, and its individual component parameters.
2.1. Patient selection
We recruited 142 consecutive patients with advanced heart failure referred to the Scottish Cardiopulmonary Transplant Unit for cardiac transplant assessment between April 2001 and December 2002. Patients with chronic heart failure secondary to left ventricular systolic dysfunction (LVEF35% by radionuclide ventriculography) in New York Heart Association functional class II–IV were included. No patients fulfilled the exclusion criteria of age less than 16 years, pregnancy or known concurrent malignancy. The local research ethics committee approved the study protocol and all patients gave written informed consent. The study complies with the Declaration of Helsinki.
At baseline screening, patients had a full medical history taken, clinical examination performed and NYHA class assigned. All patients had an LVEF measured by RNVG and, where possible, a progressive exercise test to quantify their peak VO2. A baseline HFSS was calculated for each patient. Patients were followed up every 3 months or more frequently as required.
*Measurement of HFSS:4
 |
 |
 |
 |
 |
 |
 |
 |
2.2. Measurement of NT-proBNP plasma levels
Blood samples were collected in ethylenediamine-tetraacetic acid-containing tubes. The samples were then spun at 3000rpm for 10min at 0°C. The plasma was then extracted and frozen in aliquots at –70°C until analysis. NT-proBNP was measured using a chemiluminsecent immunoassay kit (Röche Diagnostics) on an Elecsys 2010 analyser. The clinicians involved with the patients’ care were blinded to the NT-proBNP values obtained.
2.3. Follow-up
The primary end point was all-cause mortality. The secondary endpoint was all-cause mortality or urgent transplantation. Urgent transplantation is considered in suitable inotrope dependent patients with end-stage heart failure who have an anticipated life expectancy of less than 1 week. Patients were followed up until the endpoints were reached or 31st January 2003. The median follow-up was 374 days (range=1 to 660). No patients were lost to follow-up.
2.4. Statistical analysis
All data analysis was performed using the Statistical Package for Social Sciences (SPSS 9.0) software (SPSS Inc., Chicago, Illinois). Normally distributed, continuous data, unless otherwise stated, are expressed as mean values (±SD). Non-normally distributed continuous data are expressed as medians [25th and 75th percentile].
Cumulative univariate adverse event rates were compared by use of 2tests with risk ratios and 95% confidence intervals quoted. Kaplan–Meier survival curves were calculated with the data dichotomized at the mean or median values for each parameter as appropriate. The mean values of clinical variables for patients with and without the primary or secondary endpoints were compared by the use of independent t-tests and median values by the Mann–Whitney U-test.
To compare the predictive value of NT-proBNP, LVEF, peak VO2and the HFSS, receiver operating characteristic (ROC) analysis was performed and the area under the curves calculated.15To identify predictors of death, Cox proportional hazards analysis was used and variables achieving P<0.10 on univariate analysis were then tested in a stepwise (forward) multiple Cox regression survival model to determine the independent predictors of both the primary and secondary endpoints. A P<0.05 was considered statistically significant.
The baseline clinical and demographic features of the patients are described in Table 1. The population was predominantly male (82.4%). Over 85% of patients were in NYHA classes III and IV, the mean LVEF was 14.9% and the mean peak VO2was 11.8ml/kg/min. The NT-proBNP values were skewed with the median concentration being 1490 [511–3887] pg/ml.
|
Of the 142 patients, 20 (14.1%) reached the primary endpoint of death (16.7% 1-year mortality) and 4 (2.1%) were urgently transplanted. The secondary endpoint of death or urgent CTx occurred in 24 (16.9%). A further 17 patients (12%) were transplanted during the study, but these subjects were considered survivors.
3.1. Markers of prognosis in advanced heart failure
Table 2shows the relative risk ratios of various traditional and potential prognostic markers in CHF dichotomized about their median values. The only significant univariate predictor of all cause mortality was an NT-proBNP level above the median value (RR=5.0 [1.6–15.9], P=0.006)-out of 20 deaths, 16 (80%) had an NT-proBNP concentration above the median, compared with four deaths below the median level.
|
The significant univariate predictors of the secondary endpoint of all cause mortality or urgent cardiac transplantation were a RVEF, HFSS and serum sodium below the median and an NT-proBNP level above the median. Most notably, 83% of patients who reached the combined endpoint had an NT-proBNP level above the median value.
Table 3describes the mean and median values of various clinical parameters, including the LVEF, peak VO2, HFSS, and NT-proBNP, in survivors, non-survivors and in those who died or were urgently transplanted. The median NT-proBNP level in patients who died was 3052pg/ml, compared to that of survivors of 1222pg/ml (P<0.001) and the median NT-proBNP level in patients who died or required urgent transplantation was 5518pg/ml, compared to that of survivors of 1177pg/ml (P<0.001).
|
The area under the curve on ROC analysis for NT-proBNP, the LVEF, peak VO2and HFSS, for the prediction of the primary and secondary endpoints are shown inFig. 1and Fig. 2. The greatest area under the curve for both endpoints was NT-proBNP (AUC=0.738 and 0.786, respectively).
|
|
Multiple Cox proportional hazards regression analysis was performed using the above univariate predictors (systolic BP, serum sodium, Peak VO2, HFSS and RVEF) and repeated to force the LVEF into the model. The analysis was first performed with variables dichotomized about their median value and then repeated using continuous variables with identical results. NT-proBNP remained the only independent predictor of all cause mortality (
2=6.03, P=0.01). For the combined endpoint of all-cause mortality or urgent cardiac transplantation, the only independent predictor was again an NT-proBNP value above the median (2=12.68, P=0.0004). LVEF, Peak VO2and HFSS were not independently predictive of mortality or need for urgent transplantation. Kaplan–Meier survival curves for all-cause mortality are depicted in Fig. 3for the variables most commonly associated with a poor outcome in advanced heart failure (LVEF, Peak VO2and HFSS), as well as NT-proBNP. The only predictor of all-cause mortality was an NT-proBNP above the median value (log rank statistic=10.99, P=0.0009). Kaplan–Meier survival curves for all-cause mortality and urgent transplantation are shown in Fig. 4for the same variables. The predictors of mortality or urgent CTx were LVEF (log rank statistic=5.92, P=0.015) and NT-proBNP (log rank statistic=15.36, P=0.0001).Fig. 5shows poorer outcome associated with increasing NT-proBNP concentrations represented as quartiles (log rank statistic=12.7 (P=0.005) for all-cause mortality and 21.22 (P=0.0001) for all-cause mortality and urgent transplantation).
|
|
|
4. Discussion
This study first of all confirms the poor prognosis associated with advanced heart failure; in the cohort, 14.1% of patients died in the median follow up period of 374 days and 16.9% either did not survive or were urgently transplanted. The 1-year mortality rate of 16.7% is in keeping with mortality rates reported in a recent trial of beta-adrenoreceptor antagonists in advanced heart failure-the COPERNICUS Study16—where the annual mortality rates were 18.5% in the placebo group and 11.4% in the carvedilol treated group. The truly advanced nature of the LVSD in this transplant referral population is also highlighted by the fact that 85% of patients were either in NYHA Classes III or IV, and the mean LVEF was 14.9% and the mean peak VO2 was 11.8ml/kg/min.
Our study has also demonstrated for the first time that NT-proBNP concentrations are independent markers of both mortality and death or urgent transplantation in patients with advanced heart failure referred for consideration of cardiac transplantation. As such, this work confirms previous research which has demonstrated that an increased BNP concentration is associated with a poorer survival rate in patients with CHF due to systolic dysfunction in NHYA Classes II and II,8in minimally symptomatic LVD9and indeed, in the general population.7Interestingly Pacher's group have also very recentlydemonstrated that BNP is a predictor of sudden death in heart failure.13Our study was not sufficiently powered to comment on the mode of death in this heart failure population and we have restricted our analyses to all cause mortality. Atrial natriuretic peptide (ANP) has also been shown to be an independent predictor of mortality in a cohort of patients referred for further hospital assessment of their heart failure. However, in that study only 38% of patients were in NYHA Classes III/IV compared to 85% in this work and the mean LVEF was 27% and mean peak VO217.1ml/kg/min indicating they were not as severe a group of patients.17
This study also extends our current knowledge of the prognostic power of NT-proBNP into the advanced heart failure arena. Richards et al. have shown that NT-proBNP is an independent predictor of both adverse prognosis and the development of heart failure after myocardial infarction14and in patients with CHF of ischaemic aetiology.11In contrast, our study includes patients with both ischaemic and dilated cardiomyopathies. Stanek et al. have recently reported that NT-proBNP (as well as BNP) is an independent predictor of prognosis in 91 patients with advanced LV dysfunction.18However, the work described here is in a more severe group than in Stanek's paper, where 86% of subjects were in NHYA Class II. Interestingly Zugck et al. have also published on a cohort of 408 patients referred for out-patient or in-patient hospital assessment of heart failure19and shown that NT-proBNP was an independent predictor of cardiac events (hospitalization for heart failure or cardiovascular death) in the total cohort but not in the subgroup receiving beta-blocker therapy. In contrast, in this study, NT-proBNP predicted a poor outcome independent of treatment. In addition, once again Zugck's observations were in a cohort with less severe CHF; the mean NHYA was 2.3 compared with 3.0 in this work and the mean LVEF and peak VO2 levels were 22% and 14.9ml/kg/min.
The usefulness of the traditional markers of the severity of heart failure in predicting prognosis in this cohort of patient is worthy of discussion. We did not find either the LVEF, peak VO2, RVEF, serum sodium, or systolic blood pressure to be independent predictors of death. This may of course be due to the relatively small numbers of deaths or insufficient length of follow up to date. Alternatively, the explanation may lie in the severity of the patient population referred-with amean LVEF of 14.9±7.1% and a mean peak VO2of 11.8±3.6ml/kg/min. We may have insufficient spread of these parameters to allow adequate discrimination to be seen. However, this reflects the real life situation of trying to predict prognosis in a transplant referral setting as opposed to a more heterogeneous heart failure population. NT-proBNP was clearly able to assign a poor survival with far greater power.
Because of the difficulties in trying to predict an adverse outcome in advanced heart failure by relying on single parameters of severity, the HFSS has been developed to try and predict more reliably those who will have a definite survival advantage from cardiac transplantation. This is the first study to our knowledge to compare NT-proBNP concentrations with the HFSS in terms of their usefulness in assigning a poorer survival. NT-proBNP emerged as the superior modality, indeed it was the only independent predictor of all-cause mortality or the combine endpoint of all-cause mortality and urgent transplantation in our study. With the one year mortality rate post transplantation being in the region of 15–20%,20it is of vital importance to try and select those for the procedure whose mortality rate exceeds this. Of note in this group of patients the mortality rate at our median follow-up of 374 days was 22.5% in those with a NT-proBNP concentration greater than the median value, compared to 5.6% in those with an NT-proBNP concentration less than the median value, and 80% of the deaths and 83% of the secondary endpoints occurred in this group with an NT-proBNP above the median level for the cohort.
This study has demonstrated for the first time that NT-proBNP may well have significant potential in helping to decide which of our advanced heart failure patients may benefit from the scarce resource of a cardiac transplant. Much work still needs to be done in greater numbers of patients referred in for cardiac transplantation to help identify how this test could fit in clinically. In particular we need to know if a certain concentration of NT-proBNP at referral would be useful or whether a value that is rising or failing to fall with optimization of heart failure therapy would be superior. It is likely that BNP would produce similar results. However, NT-proBNP may be a more useful marker of prognosis than BNP especially if future treatment with intravenous BNP or neutralendopeptidase inhibition (which could interfere with the measurement of BNP, but not NT-proBNP) becomeroutinely used in clinical practice. Bigger studies are therefore needed to compare NT-proBNP and BNP in terms of their prognostic potential in this patient group, and to determine if we can use these natriuretic peptides in isolation and, if not, which clinical, invasive and non-invasive parameters would be useful to use in combination with them.
Although there are differences in the absolute concentrations of BNP21and NT-proBNP between normal men and women, as far as we are aware, there are no inter-gender differences in the prognostic power of NT-proBNP in CHF patients; however, our numbers are too small to test for this formally. Similarly, BNP and NT-proBNP concentrations are also higher in patients with significant renal impairment. However, in this cohort of patients the median creatinine was 120µmol/l [interquartile range 100–140]. The absence of significant renal impairment in our cohort presumably reflects the fact that renal dysfunction is a relative contra-indication for subsequent cardiac transplantation.
In this study plasma was taken for NT-proBNP analysis on first contact with each patient, before any changes in therapy were made. Whilst adjustments to therapy may well influence both outcome and the NT-proBNP concentration, in this paper we are only addressing the hypothesis that an increased baseline NT-proBNP concentration would be predictive of an adverse outcome.
As the natriuretic peptides and in particular BNP and NT-proBNP are coming into clinical use for the diagnosis of heart failure and rapid assays are now available, it is tantalizing to think that we now may well have a simple, non-invasive marker of the severity of heart failure to help unravel the complex problem of whom to refer for cardiac transplantation.
Acknowledgments
We would like to acknowledge the help and support of Dr Roger Carter PhD, Dr Bill Martin PhD, Dr JJ Morton PhD, and the patients and staff of the Scottish Cardiopulmonary Transplant Unit. We would also like to acknowledge the financial assistance of the British Heart Foundation.
References
- Mancini DM, Eisen H, Kussmaul W et al. Value of peak exercise consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation. 1991;83:778–786.
[Abstract/Free Full Text] - Mancini D, LeJemtel T, Aaronson K. Peak VO2: a simple yet enduring standard. Circulation. 2000;101(10):1080–1082.
[Free Full Text] - Pardaens K, Van CJ, Vanhaecke J et al. Peak oxygen uptake better predicts outcome than submaximal respiratory data in heart transplant candidates. Circulation. 2000;101(10):1152–1157.
[Abstract/Free Full Text] - Aaronson KD, Schwartz JS, Chen TM et al. Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. Circulation. 1997;95:2660–2667.
[Abstract/Free Full Text] - McDonagh TA, Morrison CE, Lawrence A et al. Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population. Lancet. 1997;350:829–833.[CrossRef][Web of Science][Medline]
- Lerman A, Gibbons RJ, Rodeheffer RJ et al. Circulating N-terminal atrial natriuretic peptide as a marker for symptomless left-ventricular dysfunction. Lancet. 1993;341:1105–1109.[CrossRef][Web of Science][Medline]
- McDonagh TA, Cunningham AD, Morrison CE et al. Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population. Heart. 2001;86:21–26.
[Abstract/Free Full Text] - Tsutamoto T, Wada A, Maeda K et al. Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure — Prognostic role of brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction. Circulation. 1997;96:509–516.
[Abstract/Free Full Text] - Tsutamoto T, Wada A, Maeda K et al. Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction-Comparison with plasma angiotensin II and endothelin-1. Eur Heart J. 1999;20:1799–1807.
[Abstract/Free Full Text] - Hüllsmann M, Berger R, Sturm B et al. Prediction of outcome by neurohumoral activation, the six-minute walk test and the Minnesota Living with Heart Failure Questionnaire in an outpatient cohort with congestive heart failure. Eur Heart J. 2002;23:886–891.
[Abstract/Free Full Text] - Richards AM, Doughty R, Nicholls MG et al. Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. J Am Coll Cardiol. 2001;37(7):1781–1787.
[Abstract/Free Full Text] - Koglin J, Pehlivanli S, Schwaiblmair M et al. Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure. J Am Coll Cardiol. 2001;38(7):1934–1941.
[Abstract/Free Full Text] - Berger R, Hülsmann M, Strecker K et al. B-type natriuretic peptide predicts sudden death in patients with chronic heart failure. Circulation. 2002;105:2392–2397.
[Abstract/Free Full Text] - Richards AM, Nicholls G, Yandle TG et al. Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: New neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. Circulation. 1998;97:1921–1929.
[Abstract/Free Full Text] - Hanley JA, McNeill BJ. The meaning and use of the area under a receiver operator characteristic (ROC) curve. Radiology. 1982;143:29–36.
[Abstract/Free Full Text] - Packer M, Coats AJ, Fowler MB et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344(22):1651–1658.
[Abstract/Free Full Text] - Pousset F, Isnard R, Lechat P et al. Prognostic value of plasma endothelin-1 in patients with chronic heart failure. Eur Heart J. 1997;18:254–258.
[Abstract/Free Full Text] - Stanek B, Frey B, Hulsmann M et al. Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction. J Am Coll Cardiol. 2001;38(2):436–442.
[Abstract/Free Full Text] - Zugck C, Haunstetter A, Kruger C et al. Impact of Beta-blocker treatment on the prognostic value of currently used risk predictors in congestive heart failure. J Am Coll Cardiol. 2002;39:1615–1622.
[Abstract/Free Full Text] - Hosenpud JD, Bennet LE, Keck BM et al. ISHLT Registry Report: The registry of the International Society for Heart and Lung Transplantation: Seventeenth Official Report-2000. J Heart Lung Transplant. 2000;19:909–931.[CrossRef][Web of Science][Medline]
- Redfield MM, Rodeheffer RJ, Jacobsen SJ et al. Plasma brain natriuretic peptide concentration: Impact of age and gender. J Am Coll Cardiol. 2002;40:976–982.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Bollerslev, T. Rosen, C. L. Mollerup, J. Nordenstrom, M. Baranowski, C. Franco, Y. Pernow, G. A. Isaksen, K. Godang, T. Ueland, et al. Effect of Surgery on Cardiovascular Risk Factors in Mild Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2255 - 2261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kubanek, K. M. Goode, V. Lanska, A. L. Clark, and J. G.F. Cleland The prognostic value of repeated measurement of N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure due to left ventricular systolic dysfunction Eur J Heart Fail, April 1, 2009; 11(4): 367 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wedel, J. J.V. McMurray, M. Lindberg, J. Wikstrand, J. G.F. Cleland, J. H. Cornel, P. Dunselman, A. Hjalmarson, J. Kjekshus, M. Komajda, et al. Predictors of fatal and non-fatal outcomes in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA): incremental value of apolipoprotein A-1, high-sensitivity C-reactive peptide and N-terminal pro B-type natriuretic peptide Eur J Heart Fail, March 1, 2009; 11(3): 281 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Krum Role of renin in heart failure and therapeutic potential of direct renin inhibition Journal of Renin-Angiotensin-Aldosterone System, September 1, 2008; 9(3): 177 - 180. [PDF]
|
|
|
|
|
|
O. Oldenburg, A. Schmidt, B. Lamp, T. Bitter, B. G. Muntean, C. Langer, and D. Horstkotte Adaptive servoventilation improves cardiac function in patients with chronic heart failure and Cheyne-Stokes respiration Eur J Heart Fail, June 1, 2008; 10(6): 581 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Pascual-Figal, M. Domingo, T. Casas, I. Gich, J. Ordonez-Llanos, P. Martinez, J. Cinca, M. Valdes, J. L. Januzzi, and A. Bayes-Genis Usefulness of clinical and NT-proBNP monitoring for prognostic guidance in destabilized heart failure outpatients Eur. Heart J., April 2, 2008; 29(8): 1011 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pfister, H. Diedrichs, A. Schiedermair, S. Rosenkranz, M. Hellmich, E. Erdmann, and C. A. Schneider Prognostic impact of NT-proBNP and renal function in comparison to contemporary multi-marker risk scores in heart failure patients Eur J Heart Fail, March 1, 2008; 10(3): 315 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Gardner, K. S. Chong, E. O'Meara, A. Jardine, I. Ford, and T. A. McDonagh Renal dysfunction, as measured by the modification of diet in renal disease equations, and outcome in patients with advanced heart failure Eur. Heart J., December 2, 2007; 28(24): 3027 - 3033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Jeger, A. M. Lowe, C. E. Buller, M. E. Pfisterer, V. Dzavik, J. G. Webb, J. S. Hochman, U. P. Jorde, and for the SHOCK Investigators Hemodynamic Parameters Are Prognostically Important in Cardiogenic Shock But Similar Following Early Revascularization or Initial Medical Stabilization: A Report From the SHOCK Trial Chest, December 1, 2007; 132(6): 1794 - 1803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lajer, L. Tarnow, A. Jorsal, and H.-H. Parving Polymorphisms in the B-type natriuretic peptide (BNP) gene are associated with NT-proBNP levels but not with diabetic nephropathy or mortality in type 1 diabetic patients Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3235 - 3239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Duckelmann, F. Mittermayer, D. G. Haider, J. Altenberger, J. Eichinger, and M. Wolzt Asymmetric Dimethylarginine Enhances Cardiovascular Risk Prediction in Patients With Chronic Heart Failure Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 2037 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Metra, S. Nodari, G. Parrinello, C. Specchia, L. Brentana, P. Rocca, F. Fracassi, T. Bordonali, P. Milani, R. Danesi, et al. The role of plasma biomarkers in acute heart failure. Serial changes and independent prognostic value of NT-proBNP and cardiac troponin-T Eur J Heart Fail, August 1, 2007; 9(8): 776 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.H. Wilson Tang, G. S. Francis, D. A. Morrow, L. K. Newby, C. P. Cannon, R. L. Jesse, A. B. Storrow, R. H. Christenson, COMMITTEE MEMBERS, R. H. Christenson, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure Circulation, July 31, 2007; 116(5): e99 - e109. [Full Text] [PDF]
|
|
|
|
|
|
F. M. Fruhwald, A. Fahrleitner-Pammer, R. Berger, F. Leyva, N. Freemantle, E. Erdmann, D. Gras, L. Kappenberger, L. Tavazzi, J.-C. Daubert, et al. Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony Eur. Heart J., July 1, 2007; 28(13): 1592 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Luthje, D. Vollmann, T. Drescher, P. Schott, D. Zenker, G. Hasenfuss, and C. Unterberg Intrathoracic impedance monitoring to detect chronic heart failure deterioration: Relationship to changes in NT-proBNP Eur J Heart Fail, June 1, 2007; 9(6-7): 716 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Marz, B. Tiran, U. Seelhorst, B. Wellnitz, J. Bauersachs, B. R. Winkelmann, and B. O. Boehm N-Terminal Pro-B-Type Natriuretic Peptide Predicts Total and Cardiovascular Mortality in Individuals with or without Stable Coronary Artery Disease: The Ludwigshafen Risk and Cardiovascular Health Study Clin. Chem., June 1, 2007; 53(6): 1075 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Jourdain, G. Jondeau, F. Funck, P. Gueffet, A. Le Helloco, E. Donal, J. F. Aupetit, M. C. Aumont, M. Galinier, J. C. Eicher, et al. Plasma Brain Natriuretic Peptide-Guided Therapy to Improve Outcome in Heart Failure: The STARS-BNP Multicenter Study J. Am. Coll. Cardiol., April 24, 2007; 49(16): 1733 - 1739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Gardner, K. S. Chong, J. J. Morton, and T. A. McDonagh A change in N-terminal pro-brain natriuretic peptide is predictive of outcome in patients with advanced heart failure Eur J Heart Fail, March 1, 2007; 9(3): 266 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sakhuja, S. Green, E. M. Oestreicher, P. M. Sluss, E. Lee-Lewandrowski, K. B. Lewandrowski, and J. L. Januzzi Jr. Amino-Terminal Pro-Brain Natriuretic Peptide, Brain Natriuretic Peptide, and Troponin T for Prediction of Mortality in Acute Heart Failure Clin. Chem., March 1, 2007; 53(3): 412 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H H Feringa, O. Schouten, M. Dunkelgrun, J. J Bax, E. Boersma, A. Elhendy, R. de Jonge, S. E Karagiannis, R. Vidakovic, and D. Poldermans Plasma N-terminal pro-B-type natriuretic peptide as long-term prognostic marker after major vascular surgery Heart, February 1, 2007; 93(2): 226 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schou, F. Gustafsson, A. Kjaer, and P. R. Hildebrandt Long-term clinical variation of NT-proBNP in stable chronic heart failure patients Eur. Heart J., January 11, 2007; (2007) ehl449v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bibbins-Domingo, R. Gupta, B. Na, A. H. B. Wu, N. B. Schiller, and M. A. Whooley N-Terminal Fragment of the Prohormone Brain-Type Natriuretic Peptide (NT-proBNP), Cardiovascular Events, and Mortality in Patients With Stable Coronary Heart Disease JAMA, January 10, 2007; 297(2): 169 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Scardovi, C. Coletta, N. Aspromonte, S. Perna, M. Greggi, P. D'Errigo, A. Sestili, and V. Ceci Brain natriuretic peptide plasma level is a reliable indicator of advanced diastolic dysfunction in patients with chronic heart failure Eur J Echocardiogr, January 1, 2007; 8(1): 30 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kubanek, I. Malek, J. Bytesnik, P. Fridl, L. Riedlbauchova, L. Karasova, V. Lanska, and J. Kautzner Decrease in plasma B-type natriuretic peptide early after initiation of cardiac resynchronization therapy predicts clinical improvement at 12 months Eur J Heart Fail, December 1, 2006; 8(8): 832 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Roig Usefulness of neurohormonal markers in the diagnosis and prognosis of heart failure Eur. Heart J. Suppl., September 1, 2006; 8(suppl_E): E12 - E17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rienstra, I. C. Van Gelder, M. P. Van den Berg, F. Boomsma, and D. J. Van Veldhuisen Natriuretic peptides in patients with atrial fibrillation and advanced chronic heart failure: determinants and prognostic value of (NT-)ANP and (NT-pro)BNP Europace, July 1, 2006; 8(7): 482 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Chong, R. S. Gardner, J. J. Morton, E. A. Ashley, and T. A. McDonagh Plasma concentrations of the novel peptide apelin are decreased in patients with chronic heart failure Eur J Heart Fail, June 1, 2006; 8(4): 355 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Gardner, T. A. McDonagh, M. MacDonald, H. J. Dargie, A. J. Murday, and M. C. Petrie Who needs a heart transplant? Eur. Heart J., April 1, 2006; 27(7): 770 - 772. [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Januzzi Jr, R. Sakhuja, M. O'Donoghue, A. L. Baggish, S. Anwaruddin, C. U. Chae, R. Cameron, D. G. Krauser, R. Tung, C. A. Camargo Jr, et al. Utility of amino-terminal pro-brain natriuretic Peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department. Arch Intern Med, February 13, 2006; 166(3): 315 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Januzzi, R. van Kimmenade, J. Lainchbury, A. Bayes-Genis, J. Ordonez-Llanos, M. Santalo-Bel, Y. M. Pinto, and M. Richards NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: The International Collaborative of NT-proBNP Study Eur. Heart J., February 1, 2006; 27(3): 330 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O'Meara, K. S. Chong, R. S. Gardner, A. G. Jardine, J. B. Neilly, and T. A. McDonagh The Modification of Diet in Renal Disease (MDRD) equations provide valid estimations of glomerular filtration rates in patients with advanced heart failure Eur J Heart Fail, January 1, 2006; 8(1): 63 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R S Gardner, K S Chong, A J Murday, J J Morton, and T A McDonagh N-terminal brain natriuretic peptide is predictive of death after cardiac transplantation Heart, January 1, 2006; 92(1): 121 - 123. [Full Text] [PDF]
|
|
|
|
|
|
J. De Sutter, D. De Bacquer, S. Cuypers, J. Delanghe, M. De Buyzere, M. Kornitzer, and G. De Backer Plasma N-terminal pro-brain natriuretic peptide concentration predicts coronary events in men at work: a report from the BELSTRESS study Eur. Heart J., December 2, 2005; 26(24): 2644 - 2649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Unterberg, L. Luthje, J. Szych, D. Vollmann, G. Hasenfuss, and S. Andreas Atrial overdrive pacing compared to CPAP in patients with obstructive sleep apnoea syndrome Eur. Heart J., December 1, 2005; 26(23): 2568 - 2575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schou, M. K. Dalsgaard, O. Clemmesen, E. A. Dawson, C. C. Yoshiga, H. B. Nielsen, F. Gustafsson, P. R. Hildebrandt, and N. H. Secher Kidneys extract BNP and NT-proBNP in healthy young men J Appl Physiol, November 1, 2005; 99(5): 1676 - 1680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Manios, E. M. Kallergis, E. M. Kanoupakis, H. E. Mavrakis, D. C. Kambouraki, D. A. Arfanakis, and P. E. Vardas Amino-Terminal Pro-Brain Natriuretic Peptide Predicts Ventricular Arrhythmogenesis in Patients With Ischemic Cardiomyopathy and Implantable Cardioverter-Defibrillators Chest, October 1, 2005; 128(4): 2604 - 2610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S G Williams, L L Ng, R J O'Brien, D Barker, Y-F Li, and L-B Tan Safe use of brain natriuretic protein to rule out the diagnosis of heart failure depends on the selection of cut off value Heart, August 1, 2005; 91(8): 1090 - 1091. [Full Text] [PDF]
|
|
|
|
|
|
E. Stanton, M. Hansen, H. C. Wijeysundera, P. Kupchak, C. Hall, J. L. Rouleau, and On behalf of the PRAISE-2 study investigators A direct comparison of the natriuretic peptides and their relationship to survival in chronic heart failure of a presumed non-ischaemic origin Eur J Heart Fail, June 1, 2005; 7(4): 557 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. V. Potapov, F. Hennig, F. D. Wagner, H.-D. Volk, R. Sodian, H. Hausmann, H. B. Lehmkuhl, and R. Hetzer Natriuretic peptides and E-selectin as predictors of acute deterioration in patients with inotrope-dependent heart failure Eur. J. Cardiothorac. Surg., May 1, 2005; 27(5): 899 - 905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A Doust, E. Pietrzak, A. Dobson, and P. Glasziou How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review BMJ, March 19, 2005; 330(7492): 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Gardner, V. Chong, I. Morton, and T. A. McDonagh N-terminal brain natriuretic peptide is a more powerful predictor of mortality than endothelin-1, adrenomedullin and tumour necrosis factor-{alpha} in patients referred for consideration of cardiac transplantation Eur J Heart Fail, March 2, 2005; 7(2): 253 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kragelund, B. Gronning, L. Kober, P. Hildebrandt, and R. Steffensen N-Terminal Pro-B-Type Natriuretic Peptide and Long-Term Mortality in Stable Coronary Heart Disease N. Engl. J. Med., February 17, 2005; 352(7): 666 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Goetze, J. F. Rehfeld, R. Videbaek, L. Friis-Hansen, and J. Kastrup B-type natriuretic peptide and its precursor in cardiac venous blood from failing hearts Eur J Heart Fail, January 1, 2005; 7(1): 69 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sliwa, G. R. Norton, N. Kone, G. Candy, J. Kachope, A. J. Woodiwiss, C. Libhaber, P. Sareli, and R. Essop Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure J. Am. Coll. Cardiol., November 2, 2004; 44(9): 1825 - 1830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bettencourt, A. Azevedo, J. Pimenta, F. Frioes, S. Ferreira, and A. Ferreira N-Terminal-Pro-Brain Natriuretic Peptide Predicts Outcome After Hospital Discharge in Heart Failure Patients Circulation, October 12, 2004; 110(15): 2168 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gackowski, R. Isnard, J.-L. Golmard, F. Pousset, A. Carayon, G. Montalescot, J.-S. Hulot, D. Thomas, W. Piwowarska, and M. Komajda Comparison of echocardiography and plasma B-type natriuretic peptide for monitoring the response to treatment in acute heart failure Eur. Heart J., October 2, 2004; 25(20): 1788 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Larsen and K. Dickstein BNP in acute coronary syndromes: the heart expresses its suffering Eur. Heart J., August 1, 2004; 25(15): 1284 - 1286. [Full Text] [PDF]
|
|
|
|
|
|
F.X Kleber, P Waurick, and M Winterhalter CPET in heart failure Eur. Heart J. Suppl., August 1, 2004; 6(suppl_D): D1 - D4. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M R Cowie B type natriuretic peptide testing: where are we now? Heart, July 1, 2004; 90(7): 725 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Januzzi, A. S. Maisel, R. W. Troughton, A. M. Richards, T. G. Yandle, M. G. Nicholls, T. Nishikimi, H. Matsuoka, and M. Packer Routine Measurement of Natriuretic Peptide to Guide the Diagnosis and Management of Chronic Heart Failure * Response Circulation, June 29, 2004; 109(25): e325 - e326. [Full Text] [PDF]
|
|
|
|
|
|
P. Hildebrandt, M. Boesen, M. Olsen, K. Wachtell, and B. Groenning N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis Eur J Heart Fail, March 15, 2004; 6(3): 313 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bettencourt NT-proBNP and BNP: biomarkers for heart failure management Eur J Heart Fail, March 15, 2004; 6(3): 359 - 363. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||