- Email: [email protected]
More evidence for bedside BNP in heart failure assessment
P.R. Kalra, A.D. Struthers / International Journal of Cardiology 86 (2002) 149 – 152 [3] 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;82:1724–9. [4] Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 1992;20:248–54. [5] Cowie MR, Struthers AD, Wood DA et al. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet 1997;350:1349–53. [6] Richards AM, Nicholls MG, Yandle TG et al. Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction. The Christchurch Cardioendocrine Research Group. Heart 1999;81:114–20. [7] Murdoch DR, Byrne J, Morton JJ et al. Brain natriuretic peptide is stable in whole blood and can be measured using a simple rapid assay: implications for clinical practice. Heart 1997;78:594–7. [8] Cheng V, Kazanagra R, Garcia A 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;37:386–91. [9] Van den Broek SA, Van Veldhuisen DJ, de Graeff PA, Landsman ML, Hillege H, Lie KI. Comparison between New York Heart Association classification and peak oxygen consumption in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1992;70:359–63.
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[10] Dao Q, Krishnaswamy P, Kazanegra R et al. Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol 2001;37:379–85. [11] Omland T, Aakvaag A, Bonarjee VV 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;93:1963–9. [12] Van Veldhuisen DJ, Genth-Zotz S, Brouwer J et al. High-versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril. J Am Coll Cardiol 1998;32:1811–8. [13] Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 2000;355:1126–30. [14] Maeda K, Tsutamoto T, Wada A et al. High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure. J Am Coll Cardiol 2000;36:1587–93. [15] Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 1993;88:107–15. [16] Swedberg K, Kjekshus J, Snapinn S. Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I. Eur Heart J 1999;20:136–9.
Editorial Comment
More evidence for bedside BNP in heart failure assessment a, b Paul R. Kalra *, Allan D. Struthers a
Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6 LY, UK b Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK Received 4 July 2002; accepted 23 July 2002
Abstract The central role of neurohormones, including brain natriuretic peptide (BNP), in the pathophysiology of heart failure is now firmly established. Plasma levels of BNP are elevated in patients with chronic heart failure (CHF); there is now the prospect of plasma BNP being used in diagnosing heart failure, in assessing prognosis and even in tailoring therapy in CHF. Despite the increasing wealth of evidence supporting clinical BNP assessment, it is not yet used in everyday clinical practice. A major
*Corresponding author. Tel.: 144-20-7351-8513; fax: 144-20-7351-8733. E-mail address: [email protected] (P.R. Kalra). 0167-5273 / 02 / $ – see front matter 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 02 )00410-2
150
P.R. Kalra, A.D. Struthers / International Journal of Cardiology 86 (2002) 149 – 152
limitation has been the complexity and hence relative inaccessibility of earlier assays. New developments in BNP assay methodology should improve things. In this issue of the Journal, Tjeerdsma et al. provide data that support the use of a rapid bedside (Triage BNP Test, Biosite Diagnostics) BNP test in the assessment of stable patients with CHF in an outpatient setting. The assay is performed using a portable kit and a result can be obtained within 20 minutes. In this study a BNP level of ,20 pmol / L had a negative predictive value of 95% and a positive predictive value of 85% for the diagnosis of left ventricular systolic dysfunction. Many heart failure patients remain unidentified or misdiagnosed. In those correctly diagnosed, a wide discrepancy in the provision of care is encountered. The development of assays, including rapid bedside kits, has made the assessment of plasma BNP a clinical reality. It is hoped that the incorporation of routine BNP testing in the diagnosis and treatment of CHF will help to improve morbidity and mortality. 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Brain natriuretic peptide; Chronic heart failure
The central role of neurohormones, including the natriuretic peptides, in the pathophysiology of heart failure is now firmly established [1]. Produced by the myocardium, atrial (ANP) and brain natriuretic peptide (BNP) contribute to the maintenance of circulatory homeostasis via potent vasodilatory actions, together with promoting natriuresis and diuresis [2,3]. Plasma levels of both ANP and BNP are elevated in patients with chronic heart failure (CHF), which has led to the prospect of plasma BNP being used in diagnosing heart failure, in assessing prognosis and even in tailoring therapy in CHF. Determination of plasma BNP is a valuable aid in the assessment of patients with possible heart failure, and has recently been incorporated into the European Society of Cardiology guidelines for the diagnosis and treatment of CHF [4]. A BNP level within the normal range has a high negative predictive value for the diagnosis of CHF [5]. This has led to the suggestion that plasma BNP can be a useful screening tool; a value in normal range virtually excludes the diagnosis of CHF (in untreated patients), whereas an abnormal value can be used to select those individuals who warrant further evaluation with resource limited investigations such as echocardiography [6]. Plasma BNP is also an independent prognostic indicator in CHF, post-myocardial infarction and in apparently healthy individuals, selected by advanced age (summarized in Ref. [2]). BNP appears to be a better predictor of prognosis than ANP in CHF, and this presumably reflects the close relationship between its production and ventricular wall stress. In light of this relationship it has been suggested that plasma BNP levels could be used as a guide to
optimise therapy and that they might prove to be superior to clinical assessment (with its inherent difficulties) in patients with CHF. Troughton et al. [7] compared conventional drug therapy intensified to reduce plasma BNP levels to within normal range against therapy directed by standard clinical assessment in patients with symptomatic CHF (n569). Fewer cardiovascular events (death, hospital admission or heart failure decompensation) were seen in the BNP guided therapy group when compared to the clinical group. Although the therapeutic algorithm was relatively complicated and beta-blocker use low, this represents an exciting development and may in future help to standardize the delivery of care given to CHF patients by heart failure specialists and other healthcare professionals. Despite the increasing wealth of evidence supporting clinical BNP assessment, it is not yet incorporated into everyday practice within primary or secondary care, or even in many specialist heart failure clinics. A major limitation in the clinical utilisation of BNP has been the complexity and hence relative inaccessibility of the earlier assays. Whilst readily applicable to batch testing of samples in research studies, radioimmunoassays take 2–3 days to perform. If results are to be of optimum clinical usefulness they are needed as soon after sampling as possible. For an average district hospital laboratory this may equate to a maximum of several samples per day, which at least for a radioimmunoassay, will significantly increase the absolute cost per sample. New developments in BNP assay methodology should improve things. Firstly, new bedside quick tests for BNP are now available which give rapid
P.R. Kalra, A.D. Struthers / International Journal of Cardiology 86 (2002) 149 – 152
results, akin to BM stix in diabetes. Secondly, recent evidence also suggests that the addition of aprotinin (a protease inhibitor) to the EDTA tube used for blood collection, and immediate processing and freezing of the plasma sample is not necessary [8], implying that the peptides are somewhat more stable than initially anticipated. This will certainly contribute to the generalized applicability of these tests. A diagnostic test that could be used by primary and secondary care professionals whilst evaluating a patient with potential CHF, prior to the implementation of treatment (e.g. diuretics) would be of major value. For prognostic assessment and tailored therapy, an immediate, accurate and reliable result is equally desirable. In this issue of the journal, Tjeerdsma et al. [9] provide data that support the use of a rapid bedside (Triage BNP Test, Biosite Diagnostics) BNP test in the assessment of stable patients with CHF (n578) in an outpatient setting. The assay is performed using a portable kit and a result can be obtained within 20 min. Whole blood (i.e. without the need for aprotinin) is added to the sample port on a test device (cartridge), which is then inserted into the portable meter. The BNP level, assessed by a fluorescent immunoassay, is automatically displayed on the screen without the need for any further manipulation. As expected the bedside test was highly correlated with a conventional, validated immunoradiometric assay. At higher BNP levels (.200 pmol / l) the correlation was less strong, and there were minor discrepancies in this range of markedly abnormal values but these are unlikely to be of major clinical importance. A BNP level of ,20 pmol / l had a negative predictive value of 95% and a positive predictive value of 85% for the diagnosis of left ventricular systolic dysfunction. Indeed the sensitivity and specificity of BNP for the detection of left ventricular systolic dysfunction in this paper were as good as 91 and 92%, respectively. This was perhaps even better than anticipated given the fact that patients were stable and receiving conventional heart failure therapy, which may itself lower the BNP level. BNP assessed by the bedside technique was also strongly related to other conventional markers of heart failure severity / prognosis, including peak oxygen consumption and ejection fraction. Other investigators have also demonstrated the utility of this test
151
in the acute assessment of patients presenting to the emergency room [10]. It is unlikely that BNP assessment will completely negate the need for other validated methods of assessment for CHF patients. A complimentary role is more realistic. Further studies are required to determine whether serial measurements of BNP in an individual can be used to optimize the use of expensive and even less accessible tests such as cardiopulmonary exercise testing (and even echocardiography). In the United Kingdom cardiopulmonary exercise testing remains restricted to highly specialized centres and therefore appropriate targeting of individuals and subsequent timing of evaluation is essential. Many patients with CHF remain unidentified or misdiagnosed, and therefore do not receive appropriate evidence based therapy. In those correctly diagnosed, a wide discrepancy in the provision of care is encountered. Improved communication and dissemination of information between primary and secondary care, the utilization of heart failure specialist nurses, and better access to diagnostic tests are all required. The development of new assays, including rapid bedside test kits, has made the assessment of plasma BNP a clinical reality. It is hoped that the incorporation of routine BNP testing in the diagnosis and treatment of CHF will help to improve the bleak prognosis of a condition that affects at least 10 million Europeans.
Acknowledgements P.R. Kalra is supported by the British Heart Foundation. Wessex Heartbeat and the Waring Trust have previously supported P.R. Kalra.
References [1] Coats AJS. The importance and complexity of neurohumeral overactivity in chronic heart failure. Int J Cardiol 2000;73:13–4. [2] Kalra PR, Anker SD, Coats AJS. Water and sodium regulation in chronic heart failure: the role of natriuretic peptides and vasopressin. Cardiovasc Res 2001;51:495–509. [3] Lang CC, Choy AM, Struthers AD. Atrial and brain natriuretic peptides: a dual natriuretic peptide system potentially involved in circulatory homeostasis. Clin Sci (Lond) 1992;83:519–27.
152
P.R. Kalra, A.D. Struthers / International Journal of Cardiology 86 (2002) 149 – 152
[4] Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology, Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001;22:1527–60. [5] Cowie MR, Struthers AD, Wood DA et al. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet 1997;350:1349–53. [6] Struthers AD. How to use natriuretic peptide levels for diagnosis and prognosis. Eur Heart J 1999;20:1374–5. [7] Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma
aminoterminal natriuretic peptide (N-BNP) concentrations. Lancet 2000;355:1126–30. [8] Buckley MG, Marcus NJ, Yacoub MH. Cardiac peptide stability, aprotinin and room temperature: importance for assessing cardiac function in clinical practice. Clin Sci (Lond) 1999;97:689–95. [9] Tjeerdsma MD, de Boer RA, Boomsma F et al. Rapid bedside measurement of brain natriuretic peptide in patients with chronic heart failure. Int J Cardiol 2002;86:141–7. [10] Dao Q, Krishnaswamy P, Kazanegra R et al. Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol 2001;37:379–85.
149
[10] Dao Q, Krishnaswamy P, Kazanegra R et al. Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol 2001;37:379–85. [11] Omland T, Aakvaag A, Bonarjee VV 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;93:1963–9. [12] Van Veldhuisen DJ, Genth-Zotz S, Brouwer J et al. High-versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril. J Am Coll Cardiol 1998;32:1811–8. [13] Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 2000;355:1126–30. [14] Maeda K, Tsutamoto T, Wada A et al. High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure. J Am Coll Cardiol 2000;36:1587–93. [15] Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 1993;88:107–15. [16] Swedberg K, Kjekshus J, Snapinn S. Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I. Eur Heart J 1999;20:136–9.
Editorial Comment
More evidence for bedside BNP in heart failure assessment a, b Paul R. Kalra *, Allan D. Struthers a
Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6 LY, UK b Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK Received 4 July 2002; accepted 23 July 2002
Abstract The central role of neurohormones, including brain natriuretic peptide (BNP), in the pathophysiology of heart failure is now firmly established. Plasma levels of BNP are elevated in patients with chronic heart failure (CHF); there is now the prospect of plasma BNP being used in diagnosing heart failure, in assessing prognosis and even in tailoring therapy in CHF. Despite the increasing wealth of evidence supporting clinical BNP assessment, it is not yet used in everyday clinical practice. A major
*Corresponding author. Tel.: 144-20-7351-8513; fax: 144-20-7351-8733. E-mail address: [email protected] (P.R. Kalra). 0167-5273 / 02 / $ – see front matter 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 02 )00410-2
150
P.R. Kalra, A.D. Struthers / International Journal of Cardiology 86 (2002) 149 – 152
limitation has been the complexity and hence relative inaccessibility of earlier assays. New developments in BNP assay methodology should improve things. In this issue of the Journal, Tjeerdsma et al. provide data that support the use of a rapid bedside (Triage BNP Test, Biosite Diagnostics) BNP test in the assessment of stable patients with CHF in an outpatient setting. The assay is performed using a portable kit and a result can be obtained within 20 minutes. In this study a BNP level of ,20 pmol / L had a negative predictive value of 95% and a positive predictive value of 85% for the diagnosis of left ventricular systolic dysfunction. Many heart failure patients remain unidentified or misdiagnosed. In those correctly diagnosed, a wide discrepancy in the provision of care is encountered. The development of assays, including rapid bedside kits, has made the assessment of plasma BNP a clinical reality. It is hoped that the incorporation of routine BNP testing in the diagnosis and treatment of CHF will help to improve morbidity and mortality. 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Brain natriuretic peptide; Chronic heart failure
The central role of neurohormones, including the natriuretic peptides, in the pathophysiology of heart failure is now firmly established [1]. Produced by the myocardium, atrial (ANP) and brain natriuretic peptide (BNP) contribute to the maintenance of circulatory homeostasis via potent vasodilatory actions, together with promoting natriuresis and diuresis [2,3]. Plasma levels of both ANP and BNP are elevated in patients with chronic heart failure (CHF), which has led to the prospect of plasma BNP being used in diagnosing heart failure, in assessing prognosis and even in tailoring therapy in CHF. Determination of plasma BNP is a valuable aid in the assessment of patients with possible heart failure, and has recently been incorporated into the European Society of Cardiology guidelines for the diagnosis and treatment of CHF [4]. A BNP level within the normal range has a high negative predictive value for the diagnosis of CHF [5]. This has led to the suggestion that plasma BNP can be a useful screening tool; a value in normal range virtually excludes the diagnosis of CHF (in untreated patients), whereas an abnormal value can be used to select those individuals who warrant further evaluation with resource limited investigations such as echocardiography [6]. Plasma BNP is also an independent prognostic indicator in CHF, post-myocardial infarction and in apparently healthy individuals, selected by advanced age (summarized in Ref. [2]). BNP appears to be a better predictor of prognosis than ANP in CHF, and this presumably reflects the close relationship between its production and ventricular wall stress. In light of this relationship it has been suggested that plasma BNP levels could be used as a guide to
optimise therapy and that they might prove to be superior to clinical assessment (with its inherent difficulties) in patients with CHF. Troughton et al. [7] compared conventional drug therapy intensified to reduce plasma BNP levels to within normal range against therapy directed by standard clinical assessment in patients with symptomatic CHF (n569). Fewer cardiovascular events (death, hospital admission or heart failure decompensation) were seen in the BNP guided therapy group when compared to the clinical group. Although the therapeutic algorithm was relatively complicated and beta-blocker use low, this represents an exciting development and may in future help to standardize the delivery of care given to CHF patients by heart failure specialists and other healthcare professionals. Despite the increasing wealth of evidence supporting clinical BNP assessment, it is not yet incorporated into everyday practice within primary or secondary care, or even in many specialist heart failure clinics. A major limitation in the clinical utilisation of BNP has been the complexity and hence relative inaccessibility of the earlier assays. Whilst readily applicable to batch testing of samples in research studies, radioimmunoassays take 2–3 days to perform. If results are to be of optimum clinical usefulness they are needed as soon after sampling as possible. For an average district hospital laboratory this may equate to a maximum of several samples per day, which at least for a radioimmunoassay, will significantly increase the absolute cost per sample. New developments in BNP assay methodology should improve things. Firstly, new bedside quick tests for BNP are now available which give rapid
P.R. Kalra, A.D. Struthers / International Journal of Cardiology 86 (2002) 149 – 152
results, akin to BM stix in diabetes. Secondly, recent evidence also suggests that the addition of aprotinin (a protease inhibitor) to the EDTA tube used for blood collection, and immediate processing and freezing of the plasma sample is not necessary [8], implying that the peptides are somewhat more stable than initially anticipated. This will certainly contribute to the generalized applicability of these tests. A diagnostic test that could be used by primary and secondary care professionals whilst evaluating a patient with potential CHF, prior to the implementation of treatment (e.g. diuretics) would be of major value. For prognostic assessment and tailored therapy, an immediate, accurate and reliable result is equally desirable. In this issue of the journal, Tjeerdsma et al. [9] provide data that support the use of a rapid bedside (Triage BNP Test, Biosite Diagnostics) BNP test in the assessment of stable patients with CHF (n578) in an outpatient setting. The assay is performed using a portable kit and a result can be obtained within 20 min. Whole blood (i.e. without the need for aprotinin) is added to the sample port on a test device (cartridge), which is then inserted into the portable meter. The BNP level, assessed by a fluorescent immunoassay, is automatically displayed on the screen without the need for any further manipulation. As expected the bedside test was highly correlated with a conventional, validated immunoradiometric assay. At higher BNP levels (.200 pmol / l) the correlation was less strong, and there were minor discrepancies in this range of markedly abnormal values but these are unlikely to be of major clinical importance. A BNP level of ,20 pmol / l had a negative predictive value of 95% and a positive predictive value of 85% for the diagnosis of left ventricular systolic dysfunction. Indeed the sensitivity and specificity of BNP for the detection of left ventricular systolic dysfunction in this paper were as good as 91 and 92%, respectively. This was perhaps even better than anticipated given the fact that patients were stable and receiving conventional heart failure therapy, which may itself lower the BNP level. BNP assessed by the bedside technique was also strongly related to other conventional markers of heart failure severity / prognosis, including peak oxygen consumption and ejection fraction. Other investigators have also demonstrated the utility of this test
151
in the acute assessment of patients presenting to the emergency room [10]. It is unlikely that BNP assessment will completely negate the need for other validated methods of assessment for CHF patients. A complimentary role is more realistic. Further studies are required to determine whether serial measurements of BNP in an individual can be used to optimize the use of expensive and even less accessible tests such as cardiopulmonary exercise testing (and even echocardiography). In the United Kingdom cardiopulmonary exercise testing remains restricted to highly specialized centres and therefore appropriate targeting of individuals and subsequent timing of evaluation is essential. Many patients with CHF remain unidentified or misdiagnosed, and therefore do not receive appropriate evidence based therapy. In those correctly diagnosed, a wide discrepancy in the provision of care is encountered. Improved communication and dissemination of information between primary and secondary care, the utilization of heart failure specialist nurses, and better access to diagnostic tests are all required. The development of new assays, including rapid bedside test kits, has made the assessment of plasma BNP a clinical reality. It is hoped that the incorporation of routine BNP testing in the diagnosis and treatment of CHF will help to improve the bleak prognosis of a condition that affects at least 10 million Europeans.
Acknowledgements P.R. Kalra is supported by the British Heart Foundation. Wessex Heartbeat and the Waring Trust have previously supported P.R. Kalra.
References [1] Coats AJS. The importance and complexity of neurohumeral overactivity in chronic heart failure. Int J Cardiol 2000;73:13–4. [2] Kalra PR, Anker SD, Coats AJS. Water and sodium regulation in chronic heart failure: the role of natriuretic peptides and vasopressin. Cardiovasc Res 2001;51:495–509. [3] Lang CC, Choy AM, Struthers AD. Atrial and brain natriuretic peptides: a dual natriuretic peptide system potentially involved in circulatory homeostasis. Clin Sci (Lond) 1992;83:519–27.
152
P.R. Kalra, A.D. Struthers / International Journal of Cardiology 86 (2002) 149 – 152
[4] Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology, Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001;22:1527–60. [5] Cowie MR, Struthers AD, Wood DA et al. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet 1997;350:1349–53. [6] Struthers AD. How to use natriuretic peptide levels for diagnosis and prognosis. Eur Heart J 1999;20:1374–5. [7] Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma
aminoterminal natriuretic peptide (N-BNP) concentrations. Lancet 2000;355:1126–30. [8] Buckley MG, Marcus NJ, Yacoub MH. Cardiac peptide stability, aprotinin and room temperature: importance for assessing cardiac function in clinical practice. Clin Sci (Lond) 1999;97:689–95. [9] Tjeerdsma MD, de Boer RA, Boomsma F et al. Rapid bedside measurement of brain natriuretic peptide in patients with chronic heart failure. Int J Cardiol 2002;86:141–7. [10] Dao Q, Krishnaswamy P, Kazanegra R et al. Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol 2001;37:379–85.