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J Am Coll Cardiol, 2001; 37:386-391
© 2001 by the American College of Cardiology Foundation
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CLINICAL STUDY: HEART FAILURE

A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study

Van Cheng, BS*, Radmila Kazanagra, MD*, Alex Garcia, LVN*, Leslie Lenert, MD* {dagger}, Padma Krishnaswamy, MD*, Nancy Gardetto, NP*, Paul Clopton, BS* and Alan Maisel, MD, FACC* {dagger}

* Division of Cardiology, Veteran’s Affairs Medical Center, San Diego, California, USA
{dagger} Department of Medicine, University of California, San Diego, California, USA

Manuscript received April 27, 2000; revised manuscript received September 20, 2000, accepted October 26, 2000.

Reprint requests and correspondence: Dr. Alan Maisel, VAMC Cardiology 111-A, 3350 La Jolla Village Drive, San Diego, California 921161
amaisel{at}ucsd.edu


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
OBJECTIVES

The goal of this study was to determine if B-type natriuretic peptide (BNP) levels predict outcomes of patients admitted with decompensated heart failure.

BACKGROUND

Treatment of decompensated congestive heart failure (CHF) has often been based on titration of drugs to relieve patient’s symptoms, a case that could be made for attempting to also treat neurohormonal abnormalities. Because BNP reflects both elevated left ventricular pressure as well as neurohormonal modulation, we hypothesized that BNP might be useful in assessing outcomes in patients admitted with decompensated CHF.

METHODS

We followed 72 patients admitted with decompensated New York Heart Association class III to IV CHF, measuring daily BNP levels. We then determined the association between initial BNP measurement and the predischarge or premoribund BNP measurement and subsequent adverse outcomes (death and 30-day readmission).

RESULTS

Of the 72 patients admitted with decompensated CHF, 22 end points occurred (death: n = 13, readmission: n = 9). In these patients, BNP levels increased during hospitalization (mean increase, 233 pg/ml, p < 0.001). In patients without end points, BNP decreased (mean decrease 215 pg/ml). Univariate analysis revealed that the last measured BNP was strongly associated with the combined end point. In patients surviving hospitalization, BNP discharge concentrations were strong predictors of subsequent readmission (area under the receiver operator curve of 0.73).

CONCLUSIONS

In patients admitted with decompensated CHF, changes in BNP levels during treatment are strong predictors for mortality and early readmission. The results suggest that BNP levels might be used successfully to guide treatment of patients admitted for decompensated CHF.

Abbreviations and Acronyms
  BNP = B-type natriuretic peptide
  CHF = congestive heart failure
  LV = left ventricle, left ventricular
  NYHA = New York Heart Association
  SEM = standard error of the mean

Heart failure is the leading cause of hospital admission among patients over the age of 65 years and accounts for 3% of the total national health care budget, 70% of which comes from hospitalization (1). Despite advances in treatment, patients admitted with decompensated heart failure have significant hospital mortality and early readmission rates (1–4). This stems, in part, from the fact that there are no reliable indicators of the adequacy of treatment (5,6).

B-type natriuretic peptide (BNP) is a cardiac neurohormone secreted from membrane granules in the cardiac ventricles as a response to ventricular volume expansion and pressure overload (7–9). B-type natriuretic peptide levels have been shown to be elevated in patients with symptomatic left ventricular (LV) dysfunction and correlate to LV filling pressure, New York Heart Association (NYHA) classification and prognosis (10–12). Falling BNP levels reflect beneficial treatment but, until recently, had the same pitfalls of measurement as other neurohormones and cytokines (13–15).

Using a recently developed rapid BNP assay (Biosite Diagnostics, San Diego, California), we asked whether BNP levels might be useful in assessing therapeutic responses in patients admitted with decompensated congestive heart failure (CHF). To test this hypothesis, we observed the relationship between BNP measurements performed during hospitalization and serious adverse outcomes.


   Methods
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Results
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Patients.   Between March 1999 and December 1999, we identified a convenience sample of 72 male Veterans patients between 28 and 102 years old (mean age = 68 ± 1.6 years) who had been admitted for CHF (Table 1). Criteria for inclusion included new-onset CHF confirmed by at least one cardiologist using standard Framingham criteria or exacerbation of previously documented CHF. All patients had to be at least NYHA class III to be included. The initial BNP level had to be drawn within 24 h of admission and within 24 h of discharge or death to be included in the study. Informed consent was obtained from a protocol approved by the UCSD Institutional Review Board. Inability and unwillingness to consent to study participation were the only two criteria for exclusion. During this period, approximately one hundred and ten patients were screened. Failure to enroll patients was due to the inability to consent (refusal or intubation) or that the initial BNP was drawn after the 24 h limit.


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  		Table 1 Patient Characteristics in 72 Patients With Decompensated Congestive Heart Failure

 
Study protocol.   Patients were treated in standard fashion with either oral or intravenous diuretics and vasodilators. Blood was also sampled whenever treatment changes were made or the patient’s condition changed (typically, on a daily basis throughout hospitalization). In patients who died during hospitalization, the last measured BNP concentration was considered the "discharge" BNP measurement. Physicians treating the patients were blinded to the results of BNP measurements.

Because of the small sample size and the low anticipated rate of adverse events, this study used a (prespecified) combined outcome of either death in hospital or death within 30 days after discharge or readmission to the hospital facility for CHF within 30 days. At 30 days, patient records were checked for readmission or death. Events outside facilities were also tracked by medical records, as patients are always transferred to the VA when stable. One hundred percent of patients received complete follow-up at 30 days.

Measurement of BNP plasma levels.   For each BNP measurement, 5 ml of whole blood was collected into tubes containing potassium EDTA (1 mg/ml blood). B-type natriuretic peptide was measured using the Triage B-Type Natriuretic Peptide test (Biosite Diagnostics Inc., San Diego, California). The Triage BNP test is a fluorescence immunoassay for the quantitative determination of BNP in whole blood and plasma specimens. There is a 15 to 20 min turn around time for the assay. When possible, BNP levels were measured in whole blood and processed within 4 h. When this was not possible, samples were spun down, and the plasma was frozen until the sample was analyzed (1 to 2 days), an approach known to produce well-calibrated results with whole blood sample methods.

Statistics.   Comparisons of group means were made using t tests for independent samples. In all cases, comparisons were first computed using raw BNP values and then verified with log-transformed BNP values because the BNP distribution was positively skewed. Both procedures yielded identical results.

To evaluate the association between BNP measurements and the combined outcome, we used logistic regression. We also performed a subgroup analysis looking at the association between surviving discharge BNP concentration and readmission to the hospital. In surviving patients, we also computed a receiver-operated curve to assess whether discharge BNP could be used to distinguish patients who would later be readmitted from patients whose CHF was successfully treated.

The number of subjects was not sufficient to permit a true multivariate analysis of the many predictors; thus, the analyses were conducted in a univariate manner. Each logistic regression involved the entry of a single nominal predictor or a continuous covariate and no other predictors.


   Results
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Discussion
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Patient outcomes and BNP levels.   Patients who died or were readmitted tended to have an increase in their BNP concentration during the course of hospitalization (+239 ± 233 pg/ml); patients who had successful treatment tended to have decreases in their BNP concentration during hospitalization (–216 ± 69 pg/ml) (p < 0.05).

Figure 1 shows the association between BNP concentration, NYHA classification (at admission and discharge) and patient outcome. Patients who had good outcomes tended to be characterized by decreases in both their NYHA class and BNP levels during hospitalization, with final BNP levels of 690 ± 103 pg/ml (Fig. 2, A1 and B1). Figure 2, A2 and B2, shows admission and last measured BNP levels and NYHA classification in those patients who were readmitted within 30 days of discharge. Even though the NYHA class decreased with treatment in this group, there were only minimal decreases in BNP levels during hospitalization, with a mean discharge BNP of 1,506 ± 452 pg/ml. Finally, subjects who died in the hospital (Fig. 2, A3 and B3) had rising BNP levels and little change in symptoms.



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  		Figure 1 B-type natriuretic peptide levels and NYHA classification before and after treatment in relation to end points or no end points (successful treatment). Each value represents mean ± SEM and is analyzed by analysis of variance. BNP = B-type natriuretic peptide; NYHA = New York Heart Association.

 


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  		Figure 2 The relation between end points and rising versus falling BNP levels during treatment. Values are given as percentages and analyzed by chi-square analysis. BNP = B-type natriuretic peptide (p < 0.001).

 
Figure 2 shows a significant association between end points and rising versus falling BNP levels (p < 0.001). Patients with falling BNP levels during treatment had only a 16% end point rate.

Defining a potential target discharge BNP level.   Table 2 shows univariate logistic regression to predict combined end points (death or readmission) or readmission for both discrete and continuous variables. The only historical variable that significantly predicted outcomes was a previous hospitalization of CHF (p = 0.05). B-type natriuretic peptide levels and admission NYHA classification were both strong predictors of combined end points, as well as being strong predictors of 30-day readmission subsequent outcome. Although both admission BNP levels and the change in BNP levels over the period of hospitalization were significant predictors of outcome, the last measured BNP level was the single variable that was most strongly associated with patients experiencing one of the prespecified end points. The mean BNP concentration was significantly greater in patients experiencing end points (1,801 ± 273 pg/ml standard error of the mean [SEM] vs. 690 ± 103 pg/ml SEM) than in patients with successful treatment of CHF (p < 0.001).


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  		Table 2 Univariate Predictors of End Points

 
In examining the subgroup of patients surviving to discharge, although NYHA classification was the most significant predictor (p = 0.0002) of readmission, discharge BNP was also associated with readmission within 30 days (p = 0.02). The receiver operator curve, shown in Figure 3, illustrates the sensitivity and specificity of BNP measurements at discharge in discriminating patients who will require readmission in 30 days from those successfully treated for their CHF. Potential discrete cut points are labeled. The area under the receiver operator curve was 0.72, indicating fair to good discriminatory power. The area under the curve (C-statistic) for all end points (death and readmission) was 0.84.



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  		Figure 3 Receiver operating characteristic curves for patients with decompensated congestive heart failure compares the sensitivity and specificity of BNP measurements to 30-day readmission rates. Discrete cut-points are labeled. The AUC (C-statistic) was 0.72 for readmission. Sensitivity, specificity, positive and negative predictive values and accuracy are recorded for each cut-point of the receiver operating characteristic curve. AUC = area under the curve; BNP = B-type natriuretic peptide.

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
Congestive heart failure is characterized by complicated cardiorenal, hemodynamic and neurohormonal alterations (16,17). Although patients who are admitted to the hospital with decompensated heart failure often have improvement in symptoms with the various treatment modalities available, there has been no good way to evaluate the long-term effects of the short-term treatment. Indeed, in-hospital mortality and readmission rates for patients with CHF are extremely high (3,4). The conventional tests for cardiac function take time and often do not correlate with symptomatic changes in the patient’s conditions. A simple and reliable method to assess therapeutic efficacy ("a digitalis level") in patients being treated for decompensated CHF is lacking (6).

The fact that increased levels of vasoconstrictor neurohumoral factors such as norepinephrine, renin and endothelin-1 have been found to be significant prognostic predictors in CHF suggests an important role of these vasoconstrictors in the pathogenesis of CHF (18–21). Although they are antagonizing, these vasoconstrictors have led to improvements in cardiac function (22,23); the use of these markers as monitors of therapy is impractical, in large part due to difficult assay characteristics, general instability of markers and wide-ranging, often overlapping values (24,25).

The vasodilator neurohumoral natriuretic peptide family may be better candidates for neurohumoral profiling in CHF (26). In particular, BNP has drawn recent interest in its ability to match the decompensated state of circulatory congestion (13,14,27–31).

B-type natriuretic peptide is a 32-aa polypeptide containing a 17-aa ring structure common to all natriuretic peptides (32,33). The source of plasma BNP is cardiac ventricles, which suggests that it may be a more sensitive and specific indicator of ventricular disorders than other natriuretic peptides (6,7,34). Tsutamoto et al. (34) found that plasma BNP was more useful than ANP or norepinephrine for assessing the mortality in patients with chronic CHF and that plasma levels of BNP provided prognostic information independent of other variables previously associated with a poor prognosis.

Although extensive guidelines have been published on the outpatient management of patients with CHF or asymptomatic LV dysfunction (35), few guidelines address appropriate management during the period of inpatient hospitalization (the phase of care that contributes highly to morbidity and cost). This is the first study that specifically examines outcomes of patients admitted for decompensated CHF using BNP levels drawn throughout hospitalization. Our data suggest that rapid testing of BNP may someday be used to tailor treatment of patients admitted with decompensated heart failure.

Patients whose discharge BNP level fell below 1,220 pg/ml with treatment in the hospital had a reasonable likelihood of leaving the hospital in good condition and not being readmitted within the following 30 days. A final BNP level ≤430 pg/ml had a strong negative predictive value for readmission. This level is similar to that seen in a group of 200 patients with LV dysfunction on echocardiography with no previous diagnosis of CHF (36). This level also correlates to NYHA classification of approximately class II to III ([37] and personal observation).

Why is plasma BNP a useful predictor of decompensated CHF outcome?.   B-type natriuretic peptide is a truly ventricular hormone. There is a direct relationship between ventricular wall stress and secretion of BNP (28). B-type natriuretic peptide responds to changes in LV filling pressure (28,29). The nucleic acid sequence of the BNP gene contains the destabilizing sequence "tatttat," which suggests that turnover of BNP messenger RNA is high and that BNP is synthesized in bursts (38–40). Cheung et al. (41) has suggested that BNP level reflects long-term intravascular volume status rather than momentary volume. Our data agree more with Tsutamoto and others (34,42), whose data suggest that BNP is the emergency hormone that responds immediately to ventricular overload.

Study limitations.   This was an observational study conducted using a prospective retrospective design in a convenience sample of male patients. As such, the data must be interpreted with caution. Because of the small sample size, multivariate analysis was not performed. Regression studies present the fit of parameters to observed data rather than the predictive performance.

Point-of-care testing and tailored treatment for decompensated heart failure—is there a future?.   The correlation between the drop in BNP level and the patient’s improvement in symptoms (and subsequent outcome) suggests that BNP guided treatment might make "tailored therapy" more effective and, in some cases, might reduce the need for invasive hemodynamic monitoring in selected patients. Although there has not been sufficient testing of the value of plasma protein measurements for tailoring therapy of CHF once the patient has been discharged (43), several research groups have recently reported data suggesting that BNP measurements may be useful in the adjustment of medications in heart failure (43–46).

In conclusion, the data presented in previously published papers, when combined with the results of this study, suggest that point-of-care testing of BNP may be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. Future studies should examine the feasibility and outcomes of BNP-directed therapy of CHF using point-of-care measurements.


   Acknowledgments
 
The authors would like to thank the physicians and nursing staff working at the VA Medical Center for their cooperation and support.


   Footnotes
 
Supported, in part, by an unrestricted grant from Biosite Diagnostics, San Diego, California.


   References
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 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Stevenson LW, Braunwald E. Recognition and management of patients with heart failure. Goldman L, Braunwald E. Primary Cardiology. Philadelphia, PA: W.B. Saunders; 1998. p. 310–329
  2. Drumholtz HM, Chen YT, Wan Y, Vaccarino V, Radford MF, Horowitz RI. Predictors of readmission among elderly survivors of admission with heart failure. Am Heart J. 2000;139:72–77[Medline]
  3. Rich MW, Freedland KE. Effect of DRGs on three-month readmission rate of geriatric patients with heart failure. Am J Pub Health. 1988;78:680–682[Abstract/Free Full Text]
  4. Vinson JM, Rich MW, Sperry JC, Shah AS, McNamara T. Early readmission of elderly patients with heart failure. J Am Geriatr Soc. 1990;38:1290–1295[Medline]
  5. Adams KF. Post-hoc subgroup analysis and the truth of a clinical trial. Am Heart J. 1998;136:751–758[CrossRef][Medline]
  6. Struthers AD. Prospects for using a blood sample in the diagnosis of heart failure. Q J Med. 1995;88:303–306
  7. Nagagawa O, Ogawa Y, Itoh H, Suga S, Komatsu Y, Kishimoto I. Rapid transcriptional activation and early mRNA turnover of BNP in cardiocyte hypertrophy: evidence for BNP as an "emergency" cardiac hormone against ventricular overload. J Clin Invest. 1995;96:1280–1287[Medline]
  8. Yoshimura M, Yasue H, Okamura K, et al. Different secretion pattern of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart failure. Circulation. 1993;87:464–469[Abstract/Free Full Text]
  9. Nakao K, Ogawa Y, Suga S, Imura H. Molecular biology and biochemistry of the natriuretic peptide system. J Hypertens. 1992;10:907–912[Medline]
  10. Maeda K, Takayoshi T, Wada A, Hisanaga T, Kinoshita M. Plasma brain natriuretic peptide as a biochemical marker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction. Am Heart J. 1998;135:825–832[CrossRef][Medline]
  11. Clerico A, Iervasi G, Chicca M, et al. Circulating levels of cardiac natriuretic peptides (ANP and BNP) measured by highly sensitive and specific immunoradiometric assays in normal subjects and in patients with different degrees of heart failure. J Endocrinol Invest. 1998;21:170–179[Medline]
  12. Wallen T, Landahl S, Hedner T, Nako K, Saito Y. Brain natriuretic peptide predicts mortality in the elderly. Heart. 1997;77:264–267[Abstract/Free Full Text]
  13. Daggubati S, Parks JR, Overton RM, Cintron G, Schocken DD, Vesely DL. Adrenomedullin, endothelin, neuropeptide Y, atrial, brain and C-natriuretic prohormone peptides compared as early heart failure indicators. Cardiovasc Res. 1997;36:246–255[Abstract/Free Full Text]
  14. Richards AM, Nicholls MG, Yandle TG, et al. Plasma n-terminal probrain natriuretic peptide and adrenomedullin. Circulation. 1998;77:1921–1929
  15. Murdoch DR, Byrne J, Morten JJ. Brain natriuretic peptide is stable in whole blood and can be measured using a simple rapid assay: implications for clinical practice. Heart. 1997;78:594–597[Abstract/Free Full Text]
  16. Mann DL. Mechanisms and models of heart failure: a combinatorial approach. Circulation. 1999;100:999–1008[Free Full Text]
  17. Grantham JA, Burnett JC Jr. BNP: increasing importance in the pathophysiology and diagnosis of congestive heart failure. Circulation. 1997;96:388–390
  18. Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure: a substudy of the studies of left ventricular dysfunction (SOLVD). Circulation. 1990;82:1724–1729[Abstract/Free Full Text]
  19. Remes J, Tikkanen I, Fyhrquist F, Ryoarala K. Neuroendocrine activity in untreated heart failure. Br Heart J. 1991;65:249–255[Abstract/Free Full Text]
  20. Consensus Trial Study GroupSwedberg K, Eneroth P, Kjekshus J, Wilhelmsen L. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. Circulation. 1990;82:1730–1736[Abstract/Free Full Text]
  21. Tsutamoto T, Hisanaga T, Fukai D, et al. Prognostic value of plasma intercellular adhesion molecule-1 and endothelin-1 concentration in patients with chronic congestive heart failure. Am J Cardiol. 1995;76:803–808[CrossRef][Medline]
  22. SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med. 1991;325:293–302[Abstract]
  23. Bristow MR, Gilbert EM, Abraham WT, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation. 1996;94:2807–2816[Abstract/Free Full Text]
  24. Murdoch DR, Byrne J, Morten JJ. Brain natriuretic peptide is stable in whole blood and can be measured using a simple rapid assay: implications for clinical practice. Heart. 1997;78:594–597[Abstract/Free Full Text]
  25. Klinge R, Hystad M, Kjekshus J, et al. An experimental study of cardiac natriuretic peptides as markers of development of CHF. Scand J Clin Lab Invest. 1998;58:683–689[CrossRef][Medline]
  26. Grantham JA, Borgeson DD, Burnett JC. BNP: pathophysiological and potential therapeutic roles in acute congestive heart failure. Am J Physiol. 1997;92:R1077–R1083
  27. Luchner A, Stevens TL, Borgeson DD, et al. Differential atrial and ventricular expression of myocardial BNP during evolution of heart failure: 46th Annual Scientific Session of the American College of Cardiology. Am J Physiol 1998;274:H1684–9.
  28. Maeda K, Tsutamoto T, Wada A, et al. High level of plasma BNP at discharge is an independent risk factor for mortality and morbidity in patients with congestive heart failure (abstr). J Am Coll Cardiol 1999;33 Suppl A:192A.
  29. Muders F, Kromer EP, Griese DP, et al. Evaluation of plasma natriuretic peptides as markers for left ventricular dysfunction. Am Heart J 1997;134:442–9.
  30. Nagaya N, Nishikimi T, Goto Y, et al. Plasma brain natriuretic peptide is a marker for the prediction of progressive ventricular remodeling after acute myocardial infarction. Am Heart J. 1998;135:21–28[CrossRef][Medline]
  31. Naruse H, Ischii J, Mori Y, et al. Early risk stratification using cardiac troponin T and brain natriuretic peptide in patients with congestive heart failure. (abstr)J Card Failure. 1999;(Suppl 2):134
  32. Stein BC, Levin RI. Natriuretic peptides: physiology therapeutic potential and risk stratification in ischemic heart disease. Am Heart J. 1998;135:914–923[CrossRef][Medline]
  33. Cheung BMY, Kumana CR. Natriuretic peptides—relevance in cardiac disease. J Am Med Assoc. 1998;280:1983–1984[Free Full Text]
  34. Tsutamoto T, Wada A, Maeda K, et al. Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction. Circulation. 1997;96:509–516[Abstract/Free Full Text]
  35. ACC/AHA Task Force. ACC/AHA task force report: guidelines for the evaluation and management of heart failure. Circulation. 1995;92:276–284
  36. Koon J, Hope J, Garcia A, et al. A rapid bedside test for brain natriuretic peptide accurately predicts cardiac function in patients referred for echocardiography. (abstr)J Invest Med. 2000;48:56A
  37. Sandberg SM, Chen HH, Stevens TL, et al. Superiority of brain natriuretic peptide in assessing efficacy of therapy to improve symptoms of congestive heart failure in the outpatient setting (abstr). J Am Coll Cardiol 1999;193A:1140–15.
  38. Porter JG, Arestem A, Palasi T, Scarborough RM, Lewicki JA, Seilhamer JJ. Cloning of cDNA encoding porcine brain natriuretic peptide. J Biol Chem. 1989;264:6689–6692[Abstract/Free Full Text]
  39. Sudoh T, Maekawa K, Kojima M, Minamino N, Kangawa K, Matsuo H. Cloning and sequence analysis of cDNA encoding—a precursor for human brain natriuretic peptide. Biochem Biophy Res Commun. 1989;159:1427–1434[CrossRef][Medline]
  40. Seilhamer JJ, Arestem A, Miller JA, et al. Human and canine gene homologs of porcine brain natriuretic peptide. Biochem Biophy Res Commun. 1989;165:650–658[CrossRef][Medline]
  41. Cheung B, Kumana CR. Natriuretic peptides—relevance in cardiovascular disease. J Am Med Assoc. 1998;289:1983–1984
  42. Hama N, Itoh H, Shirakami G, et al. Rapid ventricular activation of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation. 1995;92:1558–1564[Abstract/Free Full Text]
  43. Poole-Wilson PA. Tailored treatment for heart failure: an emerging concept. Am Heart J. 1999;138:1005–1006[CrossRef][Medline]
  44. Australia-New Zealand Heart Failure GroupRichardson AM, Doughty R, Nicholls MG, et al. Neurohumoral predictors of benefit from carvedilol in ischemic left ventricular dysfunction. Circulation. 1999;99:786–797[Abstract/Free Full Text]
  45. Murdoch DR, McDonaugh TA, Byrne J, et al. Titration of vasodilator therapy in chronic heart failure according to plasma brain natriuretic peptide concentration: randomized comparison of the hemodynamic and neuroendocrine effects of tailored versus empirical therapy. Am Heart J. 1999;138:1126–1132[CrossRef][Medline]
  46. Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma amino terminal brain natriuretic peptide (N-BNP) concentrations. Lancet. 2000;355:1126–1130[CrossRef][Medline]



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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.
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 Eur Heart JHome page
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.
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 J Am Coll CardiolHome page
G. C. Fonarow, W. F. Peacock, C. O. Phillips, M. M. Givertz, M. Lopatin, and for the ADHERE Scientific Advisory Committee and I
Admission B-Type Natriuretic Peptide Levels and In-Hospital Mortality in Acute Decompensated Heart Failure
J. Am. Coll. Cardiol., May 15, 2007; 49(19): 1943 - 1950.
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 Anesth. Analg.Home page
M. Cannesson, C. Bionda, B. Gostoli, O. Raisky, S. di Filippo, D. Bompard, C. Vedrinne, R. Rousson, J. Ninet, J. Neidecker, et al.
Time Course and Prognostic Value of Plasma B-type Natriuretic Peptide Concentration in Neonates Undergoing the Arterial Switch Operation
Anesth. Analg., May 1, 2007; 104(5): 1059 - 1065.
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 J Am Coll CardiolHome page
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.
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 EuropaceHome page
B. Naegeli, D. J. Kurz, D. Koller, E. Straumann, M. Furrer, D. Maurer, E. Minder, and O. Bertel
Single-chamber ventricular pacing increases markers of left ventricular dysfunction compared with dual-chamber pacing
Europace, March 1, 2007; 9(3): 194 - 199.
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 Eur J EchocardiogrHome page
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.
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 J. Am. Soc. Nephrol.Home page
A. Y.-M. Wang, C. W.-K. Lam, C.-M. Yu, M. Wang, I. H.-S. Chan, Y. Zhang, S.-F. Lui, and J. E. Sanderson
N-Terminal Pro-Brain Natriuretic Peptide: An Independent Risk Predictor of Cardiovascular Congestion, Mortality, and Adverse Cardiovascular Outcomes in Chronic Peritoneal Dialysis Patients
J. Am. Soc. Nephrol., January 1, 2007; 18(1): 321 - 330.
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 Br J AnaesthHome page
A. Mekontso-Dessap, L. Tual, M. Kirsch, G. D'Honneur, D. Loisance, L. Brochard, and J.-L. Teboul
B-type natriuretic peptide to assess haemodynamic status after cardiac surgery
Br. J. Anaesth., December 1, 2006; 97(6): 777 - 782.
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 J Am Coll CardiolHome page
M. Christ, K. Laule-Kilian, W. Hochholzer, T. Klima, T. Breidthardt, A. P. Perruchoud, and C. Mueller
Gender-Specific Risk Stratification With B-Type Natriuretic Peptide Levels in Patients With Acute Dyspnea: Insights From the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation Study
J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1808 - 1812.
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 CirculationHome page
J. F. Price, A. K. Thomas, M. Grenier, B. W. Eidem, E. O. Smith, S. W. Denfield, J. A. Towbin, and W. J. Dreyer
B-Type Natriuretic Peptide Predicts Adverse Cardiovascular Events in Pediatric Outpatients With Chronic Left Ventricular Systolic Dysfunction
Circulation, September 5, 2006; 114(10): 1063 - 1069.
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S.-C. Huang, E.-T. Wu, W.-J. Ko, L.-P. Lai, J. Hsu, C.-I. Chang, I.-S. Chiu, S.-S. Wang, M.-H. Wu, F.-Y. Lin, et al.
Clinical Implication of Blood Levels of B-Type Natriuretic Peptide in Pediatric Patients on Mechanical Circulatory Support
Ann. Thorac. Surg., June 1, 2006; 81(6): 2267 - 2272.
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 HeartHome page
M. Weber and C. Hamm
Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine.
Heart, June 1, 2006; 92(6): 843 - 849.
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 J Am Coll CardiolHome page
A. Hirashiki, H. Izawa, F. Somura, K. Obata, T. Kato, T. Nishizawa, A. Yamada, H. Asano, S. Ohshima, A. Noda, et al.
Prognostic Value of Pacing-Induced Mechanical Alternans in Patients With Mild-to-Moderate Idiopathic Dilated Cardiomyopathy in Sinus Rhythm
J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1382 - 1389.
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 HeartHome page
G A Wright and A D Struthers
Natriuretic peptides as a prognostic marker and therapeutic target in heart failure
Heart, February 1, 2006; 92(2): 149 - 151.
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 J Am Coll CardiolHome page
M. Richards, M. G. Nicholls, E. A. Espiner, J. G. Lainchbury, R. W. Troughton, J. Elliott, C. M. Frampton, I. G. Crozier, T. G. Yandle, R. Doughty, et al.
Comparison of B-Type Natriuretic Peptides for Assessment of Cardiac Function and Prognosis in Stable Ischemic Heart Disease
J. Am. Coll. Cardiol., January 3, 2006; 47(1): 52 - 60.
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P. G. Steg, L. Joubin, J. McCord, W. T. Abraham, J. E. Hollander, T. Omland, F. Mentre, P. A. McCullough, A. S. Maisel, and for the Breathing Not Properly Multinational Study
B-Type Natriuretic Peptide and Echocardiographic Determination of Ejection Fraction in the Diagnosis of Congestive Heart Failure in Patients With Acute Dyspnea
Chest, July 1, 2005; 128(1): 21 - 29.
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 Eur Heart JHome page
D. Adlam, P. Silcocks, and N. Sparrow
Using BNP to develop a risk score for heart failure in primary care
Eur. Heart J., June 1, 2005; 26(11): 1086 - 1093.
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 CirculationHome page
D. Detaint, D. Messika-Zeitoun, J.-F. Avierinos, C. Scott, H. Chen, J. C. Burnett Jr, and M. Enriquez-Sarano
B-Type Natriuretic Peptide in Organic Mitral Regurgitation: Determinants and Impact on Outcome
Circulation, May 10, 2005; 111(18): 2391 - 2397.
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 AM J HOSP PALLIAT CAREHome page
M. P. Davis, N. M. Albert, and J. B. Young
Palliation of heart failure
American Journal of Hospice and Palliative Medicine, May 1, 2005; 22(3): 211 - 222.
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 Eur Heart J SupplHome page
M. Gheorghiade and F. Zannad
Modern management of acute heart failure syndromes
Eur. Heart J. Suppl., April 1, 2005; 7(suppl_B): B3 - B7.
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