Skip Navigation

European Journal of Heart Failure 2004 6(3):335-341; doi:10.1016/j.ejheart.2004.01.002
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Kirk, V.
Right arrow Articles by Nielsen, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kirk, V.
Right arrow Articles by Nielsen, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2004 European Society of Cardiology

N-terminal proBNP and mortality in hospitalised patients with heart failure and preserved vs. reduced systolic function: data from the prospective Copenhagen Hospital Heart Failure Study (CHHF)

V. Kirka,*, M. Baya, J. Parnerc, K. Krogsgaardc, T.M. Herzogd, S. Boesgaardb, C. Hassagerb, O.W. Nielsenb, J. Aldershvileb and H. Nielsena

a Department of Medicine, Amager Hospital Copenhagen, Denmark
b Medical Department B, Division of Cardiology Rigshospitalet, Copenhagen, Denmark
c Clinical Research Unit, Hvidovre Hospital Denmark
d Roche, Copenhagen, Denmark

* Corresponding author. Present address: Faeroevej 40, DK-2800 Lyngby, Denmark. Tel.: +45-48244444 E-mail address: v.kirk{at}dadlnet.dk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Preserved systolic function among heart failure patients is a common finding, a fact that has only recently been fully appreciated. The aim of the present study was to examine the value of NT-proBNP to predict mortality in relation to established risk factors among consecutively hospitalised heart failure patients and secondly to characterise patients in relation to preserved and reduced systolic function.

Material: At the time of admission 2230 consecutively hospitalised patients had their cardiac status evaluated through determinations of NT-proBNP, echocardiography, clinical examination and medical history. Follow-up was performed 1 year later in all patients.

Results: 161 patients fulfilled strict diagnostic criteria for heart failure (HF). In this subgroup of patients 1-year mortality was approximately 30% and significantly higher as compared to the remaining non-heart failure population (approx. 16%). Using univariate analysis left ventricular ejection fraction (LVEF), New York Heart Association classification (NYHA) and plasma levels of NT-proBNP all predicted mortality independently. However, regardless of systolic function, age and NYHA class, risk-stratification was provided by measurements of NT-proBNP. Having measured plasma levels of NT-proBNP, LVEF did not provide any additional prognostic information on mortality among heart failure patients (multivariate analysis).

Conclusion: The results show that independent of LVEF, measurements of NT-proBNP add additional prognostic information. It is concluded that NT-proBNP is a strong predictor of 1-year mortality in consecutively hospitalised patients with heart failure with preserved as well as reduced systolic function.

Key Words: Heart failure • Prognosis • Natriuretic peptides

Received December 17, 2003; Accepted January 9, 2004


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Heart failure is a clinical syndrome primarily affecting the elderly [1–5]. Preserved systolic function among heart failure patients is a common finding, a fact that has only recently been fully appreciated. Various studies have found approximately 50% of heart failure patients to have normal ejection fractions [6–8]. Some studies have shown similar mortality rates and readmission rates among heart failure patients with preserved systolic function as compared to heart failure patients with systolic dysfunction [9–12], while others describe a more benign prognosis for patients with preserved systolic function [13–16]. Survival data from 5491 patients admitted for new or worsening heart failure showed patients with preserved systolic function to be older, more frequently female, and to have less evidence of ischemia as compared to patients with systolic dysfunction [15]. Low LVEF, age, male gender and diabetes are well-established prognostic predictors among heart failure patients [15]. The predictive value of these markers may change though when natriuretic peptides are included for analysis.

N-Terminal proBrain Natriuretic Peptide (NT-proBNP) belongs to a family of natriuretic peptides primarily secreted from the heart in response to an increase in wall tension [17–19]. In heart failure patients, post-myocardial infarction patients (post-MI) and patients with acute coronary syndrome Atrial Natriuretic Peptide (ANP), the amino-terminal fragment of proANP (NT-proANP) and Brain Natriuretic Peptide (BNP) have all been used as predictors of mortality [20–25]. Plasma levels of BNP have been shown to be elevated in patients with poor left ventricular function with and without symptoms [26]. The inactive amino-terminal fragment of BNP (NT-proBNP) is elevated in patients with hypertension and EF below 45% irrespective of their functional class [27] and a previous study has shown NT-proBNP to be a prognostic marker among post-MI patients [28]. NT-proBNP is more stable and has a slower plasma clearance than BNP making it a more suitable peptide for assays [19].

One study has found plasma levels of BNP to be elevated in heart failure patients with preserved systolic function admitted due to acute dyspnoea as compared to out-patients suffering the same disease. Patients with heart failure and reduced systolic function had even higher plasma levels of BNP [29]. So far, there have been no studies of the prognostic value of NT-proBNP in hospitalised patients with heart failure in relation to preserved and reduced systolic function.

The aim of the present study was to evaluate the prognostic value of plasma levels of NT-proBNP in relation to established risk factors among consecutively hospitalised heart failure patients and secondly to characterise heart failure patients in relation to preserved and reduced systolic function.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Patients and methods
During April 1st 1998 and March 31st 1999 all patients above the age of 40, admitted to Amager Hospital, a general city hospital in the Copenhagen area, were invited to take part in the study. In the inclusion period a total of 3644 eligible patients were admitted to the hospital. Four hundred and eight patients (11%) were excluded due to: (1) discharge within 24 h after admittance (N=155); (2) death before inclusion (N=56); (3) mental or physical status not allowing examination (N=68); and (4) refusing to give consent (N=129). The remaining 3236 (89%) patients gave written informed consent, among which 13 patients (aortic stenosis=6, pericardial effusion=7) were excluded due to echocardiographic findings showing a need for acute intervention. Of the patients included in the study after June 1st, 2230 (80%) had blood samples collected and these patients comprise the study population in the present study. Among these, echocardiographic measurements of left ventricular function could not be satisfactory performed in 37 (2%).

At inclusion all patients had a standardised medical history taken with reference to former heart, lung or liver diseases, diabetes, lipid status and present medication. The interview also concerned daily alcohol consumption and smoking habit in addition to specific heart-related symptoms such as orthopnea, dyspnea at night, dyspnea at rest or when walking at pace, oedema of the lower extremities, tiredness and weight loss due to diuretics. All patients had a medical examination focusing on heart failure. Blood-samples for later analysis of NT-proBNP were taken in the morning, the day after admission. Echocardiography was performed within 24 h of admission. Additionally, patients were classified according to the New York Heart Association classification. After discharge all files were evaluated, and diagnosis at discharge, laboratory results and medication at discharge were noted.

Vital status of patients (100%) was established 1 year after discharge using national registers. Death certificates or hospital files were evaluated for all the patients who had died.

Physicians treating the patients were blinded to the results obtained in the study. The study was approved by the ethical committee of the city of Copenhagen.

2.2. Heart failure
The European Society of Cardiology (ESC) defines heart failure as a syndrome consisting of symptoms such as dyspnea or fluid retention in coexistence with objective abnormal cardiac findings [30]. We evaluated the prognostic value of NT-proBNP in heart failure patients diagnosed by the ESC heart failure criteria.

HF: Patients were diagnosed as having heart failure if the following three criteria were fulfilled: (1) appropriate symptoms (shortness of breath, fatigue at rest or during exercise); (2) clinical signs of fluid retention (central and/or peripheral); and (3) abnormal echocardiographic findings. Echocardiographic measurements were considered abnormal if any of the following were present: dys-synergy, systolic dysfunction with EF≤45%, posterior wall thickness or inter-ventricular-septum thickness >11 mm, left atrium >45 mm, left ventricular diastolic diameter >58/62 mm (female/male), mitral-septal-separation >10 mm, aortic stenosis with a peak gradient >50 mmHg.

2.3. Echocardiography
Echocardiography was performed by one of the investigators (V.K. or M.B.), with the patient in the left lateral position if possible, using a Hewlett Packard, Image Point; model M2410A. Left ventricular ejection fraction was calculated through M-mode analysis if no dys-synergy [31], and in the presence of dys-synergy wall motion index (WMI) was used [32]. Inter-observer variation in the evaluation of ejection fraction was 4%, r=0.95; N=12.

2.4. Analysis of NT-proBNP
EDTA-containing blood-tubes were immediately placed on ice, centrifuged at 4 °C, and plasma was stored at –80 °C until analysis [33]. All blood samples were taken between 08.00 and 10.00 h. Plasma levels of NT-proBNP were measured by an ELISA/2-step sandwich assay using streptavidin coated microtitre plates (Roche, Basel) [34], an assay where sample extraction steps are not required. This assay has no detectable cross reactivity to BNP, ANP, NT-proANP or Urodilatin. Inter-assay variance: 10%, intra-assay variance: 3%, recovery: 104–112% as reported by manufacturer. The present study used an earlier generation assay (ELISA method; microtiter plate) and the conversion factor from the present assay to the commercially available Roche Elecsys proBNP assay is: NT-proBNP (ELISA, pmol/L)=NT-proBNP (Elecsys, pmol/L)*2.7, (information from Roche Diagnostics). To convert pmol/L to pg/ml multiply pmol/L by 8.457.

2.5. Statistics
For normal distributed variables value are expressed as mean±S.E.M. Other continuous variables are given as median and range. Differences in mean between groups were compared using a t-test and differences in median by use of Mann–Whitney's U-test. Survival beyond hospitalisation was evaluated using the Kaplan–Meier estimator and differences in survival between groups investigated by use of log-rank tests. Differences in proportions were compared using a {chi}2-test.

Assessing the effect of predictors on survival at 12-months was performed using a multivariate logistic regression model. Survival status was chosen as dependent variable while the set of predictors were age, gender, EF, ln(NT-proBNP) and NYHA-classification. EF was divided into three groups: 0–20%, 21–40% and 41% and above, NYHA-classification into groups of 0–4. Log-linearity of age and ln(NT-proBNP) on the odds-ratio as well as their interaction was investigated using generalised additive models [35]. In addition, all lower order interactions were investigated and separate analyses were conducted on the HF patients. P-values below 0.05 were considered statistically significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Heart failure
A total of 2230 patients (41% males) had blood samples drawn. Using the ESC-criteria 161 patients (7.2%) were classified as having heart failure. Patients with heart failure were older, had lower ejection fraction and higher plasma NT-proBNP levels as compared to patients without heart failure (Table 1).


View this table:
[in this window]
[in a new window]

  		Table 1 Characteristics of patients with and without heart failure

 
Seventy-five patients (46%) were admitted due to an acute coronary episode, the rest being admitted due to other reasons, including surgical ones. Among patients with heart failure 50% had systolic dysfunction (81/161). Patients with systolic dysfunction had significantly higher plasma levels of NT-proBNP as compared to patients with preserved systolic function (Table 2; P<0.001). In addition, systolic dysfunction was associated with more ischemic heart disease (P<0.05), a higher proportion of chest X-rays with congestion or pulmonary oedema (P<0.04), and mitral valve abnormalities (P<0.006). There was no difference in age, pulmonary rales, aortic valve abnormalities, oedemas of the lower extremities, dyspnoea or mortality rate between patients with preserved and reduced systolic function.


View this table:
[in this window]
[in a new window]

  		Table 2 Characteristics of heart failure patients with systolic dysfunction and preserved systolic function

 
One-year mortality was significantly higher among heart failure patients as compared to patients without heart failure (HF: 31.5% vs. 17.6%; P<0.0001) (Table 1). Within the heart failure group there were significantly higher plasma levels of NT-proBNP in patients who died, compared to patients still alive after 1 year (P<0.001) (Table 3). In the total population of 2230, a significant association between lower ejection fraction and higher mortality was found (P<0.001). HF-patients who died had a higher NYHA-classification, regardless of whether this was due to systolic heart failure or not (data not shown).


View this table:
[in this window]
[in a new window]

  		Table 3 Characteristics of heart failure patients. Relation between plasma levels of NT-proBNP at admission and vital status at 12 months

 
3.2. NT-proBNP and mortality
Logarithmic transformation of NT-proBNP data was found to approximate a normal distribution. Plasma levels of NT-proBNP increased with age and were significantly higher in patients who died as compared to patients still alive at 12 month (Table 3).

Mean values of the logarithmic transformation of NT-proBNP divided patients into two equally sized groups. Approximately 50% of patients in the group with NT-proBNP levels above mean died within 1 year. In addition the highest plasma levels of NT-proBNP identified patients with a very poor short-term prognosis as illustrated by the steep initial decrease in survival curves among patients in the group with values above the mean (Fig. 1).


Figure 1
View larger version (18K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Kaplan–Meier survival curves for patients with heart failure. Patients are divided into 2 groups according to mean plasma levels of ln(NT-proBNP). Each line represents 12 month mortality. A significant difference between the two survival curves was found (P<0.0007).

 
On univariate analysis LVEF, NYHA-classification and plasma levels of NT-proBNP all predicted mortality in the total population (data not shown). However, in the heart failure population, mortality was similar in patients with preserved or decreased systolic function (Fig. 2 and Table 3).


Figure 2
View larger version (13K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Kaplan–Meier survival curves for patients with heart failure and preserved vs. reduced systolic function. Patients are divided into 2 groups according to LVEF. Each line represents 12 month mortality. No significant difference between the two survival curves was found.

 
In the heart failure population, the probability of death within 12 months after admission was predicted by plasma levels of NT-proBNP (Fig. 3), in patients with systolic dysfunction as well as in patients with preserved systolic function.


Figure 3
View larger version (8K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Mortality in patients with heart failure and reduced as well as preserved systolic function in relation to plasma levels of NT-proBNP.

 
Multivariate analysis using EF, NYHA-classification, sex, age and ln(NT-proBNP) demonstrated a highly significant predictive value of NT-proBNP on mortality among patients with HF. In this group of patients ln(NT-proBNP) was a strong predictor of mortality with an OR per unit of 1.66 (95% CI: 1.25–2.2). Other variables had no additional predictive value.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
The major finding of this study is that NT-proBNP is a strong prognostic predictor of mortality regardless of systolic function, NYHA class, age or sex in patients with symptoms and objective signs of heart failure on admission. Preserved systolic function comprised 50% of heart failure cases. Despite higher LVEF, higher plasma levels of NT-proBNP and lower frequency of ischemic disease, patients with heart failure and preserved systolic dysfunction had a similar mortality to patients with reduced systolic function.

Heart failure patients in this study reflected a broad group of consecutively hospitalised patients screened for heart failure using echocardiography and objective examination no matter the reason for admission or prior heart failure status.

4.1. Other studies
Heart failure may be difficult to diagnose, and within the heart failure population good prognostic tools are important to improve treatment in patients with a high mortality. The natriuretic peptides can be used as prognostic tools in this group of patients. In patients with acute myocardial infarction plasma levels of NT-proBNP was found to be predictive of 2-year mortality [22]. Furthermore, NT-proBNP appeared to be a better predictor of death than ANP and BNP, which in smaller studies [20,22–25,36,37] have been shown to carry prognostic information in patients with heart failure or a previous myocardial infarction. Finally, Tsutamoto et al. [23] found that plasma BNP was a better prognostic marker in chronic heart failure patients than both ANP and norepinephrine. BNP is predictive of death as well as new ischemic events and worsening of heart failure in patients admitted to hospital due to acute coronary syndrome [21].

In the Breathing Not Properly trial plasma levels of BNP were significantly lower in patients with heart failure due to preserved compared to reduced systolic function as in the present study [29]. However, BNP was not able to accurately differentiate preserved from reduced systolic function, thus, a measurement of ejection fraction would still be required to guide management and confirm the diagnosis. Their data suggested that BNP would be highly accurate for the diagnosis of systolic HF, but unfortunately perform less well for heart failure with preserved systolic function. Our findings indicate that NT-proBNP can be used as a prognostic indicator in patients with both acute and chronic heart failure, whether or not it is due to LV systolic dysfunction.

The high 1-year mortality rate of 31% is partly a reflection of the great age of patients in the present study and it is consistent with mortality rates found in other studies evaluating mortality in older patients with heart failure [31]. Pernenkil et al. [9] investigated heart failure patients with a mean age similar to the patients in the present study and found a 1-year mortality of 28% among those with normal ejection fraction and a 38% 1-year mortality among patients with abnormal LV ejection fraction.

The Kaplan–Meier survival curves showed a steep initial slope suggesting that a high level of NT-proBNP may indicate a poor short-term prognosis, as has been described for NT-proANP [38,39]. At present, it is not known whether NT-proBNP carries more information on prognosis than NT-proANP or whether a combination of the two is more informative.

Other studies have shown ejection fraction to be an important prognostic tool [40,41]. This is consistent with the univariate findings in this study regarding ejection fraction. However, results from the multivariate analysis showed the prognostic value of LVEF to disappear when NT-proBNP is included, suggesting that prognosis among heart failure patients is more accurately determined using plasma levels of NT-proBNP rather than LVEF. Similar findings have been reported for NT-proANP [38]. Importantly, recent data suggest that mortality may be reduced in patients showing a decline in NT-proBNP or BNP during medical treatment [42].

4.2. Limitations
The diagnosis of heart failure was coherent with the criteria as defined by the ESC. However, these criteria may be limited in the sense that symptoms of signs of heart failure may be non-specific as milder abnormalities demonstrated by echocardiography. However, the median value of NT-proBNP and mortality were higher in patients with heart failure and preserved as well as reduced systolic function. This suggests that the patients did indeed have a significant cardiac abnormality.

In the present study patients were consecutively examined with a very low drop out rate, which illustrates the daily clinical practice in a general city hospital. The results show that NT-proBNP adds independent prognostic information on mortality beyond EF, NYHA-classification age and sex in consecutively admitted patients with heart failure. It is concluded that high levels of NT-proBNP in patients with heart failure are associated with a very high 1-year mortality.


   Acknowledgements
 
This study was supported by unrestricted research grants from AstraZeneca, Denmark and from Roche, Switzerland.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Kannel W.B., Ho K., Thom T. Changing epidemiological features of cardiac failure. Brit Heart J (1994) 72:S3–S9.[Free Full Text]
  2. Lauer M.S., Evans J.C., Levy D. Prognostic implications of subclinical left ventricular dilatation and systolic dysfunction in men free of overt cardiovascular disease (the Framingham Heart Study). Am J Cardiol (1992) 70:1180–1184.[CrossRef][Web of Science][Medline]
  3. McKee P.A., Castelli W.P., McNamara P.M., Kannel W.B. The natural history of congestive heart failure: the Framingham study. N Engl J Med (1971) 285:1441–1446.[Web of Science][Medline]
  4. Schocken D.D., Arrieta M.I., Leaverton P.E., Ross E.A. Prevalence and mortality rate of congestive heart failure in the United States. J Am Coll Cardiol (1992) 20:301–306.[Abstract]
  5. Schocken D.D. Epidemiology and risk factors for heart failure in the elderly. Clin Geriatr Med (2000) 16:407–418.[CrossRef][Web of Science][Medline]
  6. McDonagh T.A., Morrison C.E., Lawrence A., Ford I., Tunstall-Pedoe H., McMurray J.J., et al. Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population. Lancet (1997) 350:829–833.[CrossRef][Web of Science][Medline]
  7. McDonagh T.A. Asymptomatic left ventricular dysfunction in the community. Curr Cardiol Rep (2000) 2:470–474.[Medline]
  8. McMurray J.V., McDonagh T.A., Davie A.P., Cleland J.G., Francis C.M., Morrison C. Should we screen for asymptomatic left ventricular dysfunction to prevent heart failure? Eur Heart J (1998) 19:842–846.[Web of Science][Medline]
  9. Pernenkil R., Vilson J.M., Shah A.S., Beckham V., Wittenberg C., Rich M.W. Course and prognosis in patients > or =70 years of age with congestive heart failure and normal vs. abnormal left ventricular ejection fraction. Am J Cardiol (1997) 79:216–219.[CrossRef][Web of Science][Medline]
  10. Vasan R., Larson M., Benjamin E., Evans J., Reis C., Levy D. Congestive heart failure in subjects with normal vs. reduced left ventricular fraction: prevalence and mortality in a population-based cohort. J Am Coll Cardiol (1999) 33:1948–1955.[Abstract/Free Full Text]
  11. Senni M., Tribouillowy C.M., Rodenheffer R.J., Jacobsen S.J., Evans J.M., Bailey K.R. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation (1991) 98:2282–2289.
  12. Kupari M., Lindroos M., Iivanainen A.M., Heikkila J., Tilvis R. Congestive heart failure in old age: prevalence, mechanisms and 4-year prognosis in the Helsinki Ageing Study. J Intern Med (1997) 241:387–394.[CrossRef][Web of Science][Medline]
  13. Vasan R., Benjamin E., Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol (1995) 26:1565–1574.[Abstract]
  14. Cohn J., Johnson G. Heart failure with normal ejection fraction: the V-HeFT study. Circulation (1990) 81(Suppl_III):III48–III53. the Veterans Administration Cooperative Study Group.[Medline]
  15. Gustafsson F, Torp-Pedersen C, Brendorp B, Seibæk M, Burchardt H, Køber L, for the DIAMOND study. Long-term survival in patients hospitalised with congestive heart failure: relation to preserved and reduced left ventricular systolic function. Eur Heart J (2003);24:863–70.
  16. Smith G.L., Masoudi F.A., Vaccarino V., Radford M.J., Krumholz H.M. Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. J Am Coll Cardiol (2003) 41:1510–1518.[Abstract/Free Full Text]
  17. Chen H.H., Burnett J.C. Jr. The natriuretic peptides in heart failure: diagnostic and therapeutic potentials. Proc Assoc Am Phys (1999) 111:406–416.[Web of Science][Medline]
  18. Hobbs F.D. The scale of heart failure: diagnosis and management issues for primary care. Heart (1999) 82(Suppl 4):IV8–IV10.[Medline]
  19. Levin E.R., Gardner D.G., Samson W.K. Natriuretic peptides. N Engl J Med (1998) 339:321–328.[Free Full Text]
  20. Arad M., Elazar E., Shotan A., Klein R., Rabinowitz B. Brain and atrial natriuretic peptides in patients with ischemic heart disease with and without heart failure. Cardiology (1996) 87:12–17.[Web of Science][Medline]
  21. de Lemos J.A., Morrow D.A., Bentley J.H., Omland T., Sabatine M.S., McCabe C.H., et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med (2001) 345:1014–1021.[Abstract/Free Full Text]
  22. Omland T., Aakvaag A., Bonarjee V.V., Caidahl K., Lie R.T., Nilsen D.W., et al. Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide. Circulation (1996) 93:1963–1969.[Abstract/Free Full Text]
  23. Tsutamoto T., Wada A., Maeda K., Hisanaga T., Mabuchi N., Hayashi M., 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]
  24. Wallen T., Landahl S., Hedner T., Hall C., Saito Y., Nakao K. Atrial natriuretic peptides predict mortality in the elderly. J Intern Med (1997) 241:269–275.[CrossRef][Web of Science][Medline]
  25. Wallen T., Landahl S., Hedner T., Nakao K., Saito Y. Brain natriuretic peptide predicts mortality in the elderly. Heart (1997) 77:264–267.[Abstract/Free Full Text]
  26. McDonagh T.A., Robb S.D., Murdoch D.R., Morton J.J., Ford I., Morrison C.E., et al. Biochemical detection of left-ventricular systolic dysfunction. Lancet (1998) 351:9–13.[CrossRef][Web of Science][Medline]
  27. Hunt P.J., Richards A.M., Nicholls M.G., Yandle T.G., Doughty R.N., Espiner E.A. Immunoreactive amino-terminal pro-brain natriuretic peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol (Oxf) (1997) 47:287–296.[CrossRef][Medline]
  28. Richards A.M., Nicholls M.G., Yandle T.G., Frampton C., Espiner E.A., Turner J.G., 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]
  29. Maisel A.S., McCord J., Nowak R.M., Hollander E., Wu A.H., Duc P. Bedside B-type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction: results from the Breathing Not Properly (BNP) multinational study. J Am Coll Cardiol (2003) 41:2010–2017.[Abstract/Free Full Text]
  30. The task force on heart failure of the European society of cardiology. Guidelines for the diagnosis of heart failure. Eur Heart J 1955;16:741–51.
  31. Teichholz L.E., Kreulen T., Herman M.V., Gorlin R. Problems in echocardiographis volume determination: echocardiographic–angiographis correlations in the presence or absence of asynergy. Am J Cardiol (1976) 37:7–11.[CrossRef][Web of Science][Medline]
  32. Berning J., Rokkedal Nielsen J., Launbjerg J., Fogh J., Mickley H., Andersen P.E. Rapid estimation on left ventricular ejection fraction in acute myocardial infarction by echocardiographic wall motion analysis. Cardiology (1992) 80:257–266.[Web of Science][Medline]
  33. Gobinet-Georges A., Valli N., Filliatre H., Dubernet M.F., Dedeystere O., Bordenave L. Stability of brain natriuretic peptide (BNP) in human whole blood and plasma. Clin Chem Lab Med (2000) 38:519–523.[CrossRef][Web of Science][Medline]
  34. Karl J., Borgya A., Gallusser A., Huber E., Krueger K., Rollinger W., et al. Development of a novel, N-terminal-proBNP (NT-proBNP) assay with a low detection limit. Scand J Clin Lab Invest Suppl (1999) 230:177–181.[Medline]
  35. Hastie T.J., Tibshirani R.J. Generalised additive models (1990) London: Chapmann and Hall.
  36. Cheng V., Kazanagra R., Garcia A., Lenert L., Krishnaswamy P., Gardetto N., et al. A Rapid Bedside Test for B-Type Peptide Predicts Treatment outcomes in Patients Admitted for Decompensated Heart Failure: a Pilot Study. J Am Coll Cardiol (2001) 37:386–391.[Abstract/Free Full Text]
  37. Wang R., Mouliswar M., Denman S., Kleban M. Mortality of the institutionalized old-old hospitalized with congestive heart failure. Arch Intern Med (1998) 158:2464–2468.[Abstract/Free Full Text]
  38. Dickstein K., Abrahamsen S., Aarsland T. Plasma N-terminal Atrial natriuretic peptide predicts hospitalisation in patients with heart failure. Scand Cardiovasc J (1998) 32:361–364.[CrossRef][Web of Science][Medline]
  39. Hall C., Rouleau J.L., Moye L., de Chanplain J., Bichet D., Klein M., et al. N-terminal proatrial natriuretic factor. An independent predictor of long-term prognosis after myocardial infarction. Circulation (1994) 89:1934–1942.[Abstract/Free Full Text]
  40. Gadsboll N., Hoilund-Carlsen P.F., Madsen E.B., Marving J., Pedersen A., Lonborg-Jensen H., et al. Right and left ventricular ejection fraction: relation to 1-year prognosis in acute myocardial infarction. Eur Heart J (1987) 8:1201–1209.[Abstract/Free Full Text]
  41. Madsen B.K., Hansen J.F., Stokholm K.H., Brons J., Husum D., Mortensen L.S. Chronic congestive heart failure. Description and survival of 190 consecutive patients with a diagnosis of chronic congestive heart failure based on clinical signs and symptoms. Eur Heart J (1994) 15:303–310.[Abstract/Free Full Text]
  42. Troughton R.W., Frampton C.M., Yandle T.G., Espiner E.A., Nicholls M.G., Richards A.M. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet (2000) 355:1126–1130.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur J Heart FailHome page
J. B. Somaratne, C. Berry, J. J.V. McMurray, K. K. Poppe, R. N. Doughty, and G. A. Whalley
The prognostic significance of heart failure with preserved left ventricular ejection fraction: a literature-based meta-analysis
Eur J Heart Fail, September 1, 2009; 11(9): 855 - 862.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
T. Kumler, G. H. Gislason, V. Kirk, M. Bay, O. W. Nielsen, L. Kober, and C. Torp-Pedersen
Accuracy of a heart failure diagnosis in administrative registers
Eur J Heart Fail, July 1, 2008; 10(7): 658 - 660.
[Abstract] [Full Text] [PDF]

Home page
 HeartHome page
C. Raphael, C. Briscoe, J. Davies, Z. Ian Whinnett, C. Manisty, R. Sutton, J. Mayet, and D. P Francis
Limitations of the New York Heart Association functional classification system and self-reported walking distances in chronic heart failure
Heart, April 1, 2007; 93(4): 476 - 482.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
F. Bursi, S. A. Weston, M. M. Redfield, S. J. Jacobsen, S. Pakhomov, V. T. Nkomo, R. A. Meverden, and V. L. Roger
Systolic and diastolic heart failure in the community.
JAMA, November 8, 2006; 296(18): 2209 - 2216.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
T. E. Owan, D. O. Hodge, R. M. Herges, S. J. Jacobsen, V. L. Roger, and M. M. Redfield
Trends in prevalence and outcome of heart failure with preserved ejection fraction.
N. Engl. J. Med., July 20, 2006; 355(3): 251 - 259.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
A. A. Chen, M. J. Wood, D. G. Krauser, A. L. Baggish, R. Tung, S. Anwaruddin, M. H. Picard, and J. L. Januzzi
NT-proBNP levels, echocardiographic findings, and outcomes in breathless patients: results from the ProBNP Investigation of Dyspnoea in the Emergency Department (PRIDE) echocardiographic substudy
Eur. Heart J., April 1, 2006; 27(7): 839 - 845.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
G. I.W. Galasko, A. Lahiri, S. C. Barnes, P. Collinson, and R. Senior
What is the normal range for N-terminal pro-brain natriuretic peptide? How well does this normal range screen for cardiovascular disease?
Eur. Heart J., November 1, 2005; 26(21): 2269 - 2276.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
J. J. Thune, C. Carlsen, P. Buch, M. Seibaek, H. Burchardt, C. Torp-Pedersen, L. Kober, and on behalf of the DIAMOND investigators
Different prognostic impact of systolic function in patients with heart failure and/or acute myocardial infarction
Eur J Heart Fail, August 1, 2005; 7(5): 852 - 858.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
M. Weber, R. Arnold, M. Rau, A. Elsaesser, R. Brandt, V. Mitrovic, and C. Hamm
Relation of N-terminal pro B-type natriuretic peptide to progression of aortic valve disease
Eur. Heart J., May 2, 2005; 26(10): 1023 - 1030.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Kirk, V.
Right arrow Articles by Nielsen, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kirk, V.
Right arrow Articles by Nielsen, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?