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B-type natriuretic peptide: a new diagnostic tool for congestive heart failure |
Summary
B-type natriuretic peptide is released from the ventricle of patients with heart failure. High concentrations help to distinguish heart failure from other causes of dyspnoea. The test is sensitive in congestive heart failure but it cannot distinguish if the dysfunction is diastolic or systolic. B-type natriuretic peptide is not used as a routine test in Australia, but if it becomes available it may be helpful in ruling out the diagnosis of congestive heart failure. It is also being investigated as a screening tool for heart disease in the community.
Key words: echocardiography, dyspnoea, screening.
(Aust Prescr 2003;26:64-5)
Introduction
The diagnosis of congestive heart failure rests on three elements. These aresuitable signs and symptoms, objective evidence of ventricular dysfunction,and response to treatment. While the diagnosis is generally clear when thepatient has obvious clinical or radiological pulmonary oedema, it can be difficultto make when the condition is less advanced or the patient has comorbiditiessuch as lung disease. The Framingham criteria are a way of scoring symptomsand clinical signs, but cannot be regarded as giving a definitive diagnosisof congestive heart failure. In one recent study the Framingham criteria werecompared with the diagnosis made by two cardiologists with access to echocardiographicresults for 1586 acutely dyspnoeic patients presenting to emergency wards.The criteria and the final diagnosis were concordant in only 73% of patients.1 Improvedways of detecting congestive heart failure would therefore be of great clinicalbenefit.
Objective evidence of ventricular dysfunction is currently obtained from echocardiography,catheter studies, or nuclear medicine studies. Catheter studies and nuclearmedicine are invasive, quite expensive and not widely available. Echocardiographyis more widely available, however it still requires waiting for, and travelto, an appointment. This can be a problem for the frail aged or patients inrural areas. Detection of ventricular dysfunction by a simple blood test wouldtherefore be a very attractive alternative.
Physiology
Four neurohormonal systems are activated by ventricular dysfunction. Theseare the sympathetic nervous system, the renin-angiotensin-aldosterone system,the endothelin pathway, and the natriuretic peptides. All these systems maintainsystemic tissue perfusion and the first three also maintain blood pressure,which is advantageous in the short term but deleterious to the heart in thelong term.
The natriuretic peptides produce diuresis, natriuresis and vasodilatation.These effects reduce the load on the heart, and work in opposition to the renin-aldosteronesystem and the sympathetic nervous system. Although natriuretic peptides areincreased in heart failure, their effects are overwhelmed by the activatedrenin-angiotensin-aldosterone system and sympathetic nervous system. Threepeptides have been identified:
– A (or atrial) natriuretic peptide is secreted by the atrium in responseto dilatation
– B natriuretic peptide (BNP, originally called 'brain natriuretic peptide'as it was found in the brains of pigs) is produced by the ventricle in responseto increased end diastolic pressure or volume
– C natriuretic peptide is produced widely by endothelial cells in responseto shearing stresses.
B-type natriuretic peptide
When stimulated by stress or stretch, ventricular myocytes activate transcriptionof the relevant gene and produce a 108 amino acid peptide (Pro BNP). Beforeexcretion by the myocyte this peptide is cleaved to produce an inactive 76amino acid N-terminal fragment and the C-terminal 32 amino acid with hormonalactivity (BNP).2 Plasmahalf-life of BNP in vivo is 18 to 22 minutesso concentration promptly reflects changes in cardiac status.
Available assays measure either the inactive N-terminal fragment or the active32 amino acid peptide. There are currently several assays available that donot give directly comparable results. Individual laboratory reference rangesshould therefore be used.
Of all the neurohormones, BNP is the best candidate for use as a diagnostictest. When BNP rises it tends to go very high, which gives it good discriminatorypower in separating ventricular causes of dyspnoea from other causes. In oneseries of patients presenting to an emergency ward with shortness of breath,those without heart failure had a mean BNP concentration of 38 pg/mL whilein those with heart failure it averaged 1076 pg/mL. 3 Four studies (totalling1994 patients) have compared the test performance of BNP with the diagnosisof congestive heart failure made by echocardiographyand consideration of all clinical details.1,3,4,5 Theresults show BNP has a sensitivity of 90-97% and a specificity of 76-92%.There have also been four studies(totalling 6109 people) which investigatedusing BNP to screen for pre-clinical heart disease in the community.6,7,8,9 Threeof these studies showed good test performance with sensitivities ranging from77% to 100% and specificities from 70% to 96%. Recent results9 contradictthese findings and show sensitivity in detecting any left ventricular systolicdysfunction of only 53% in men and 26% in women. For moderate to severe leftventricular systolic dysfunction these values are 65% and 80%, well below thosefound in the other studies. This suggests that although BNP shows good testperformance in acutely sick hospital patients it is less accurate in the detectionof ventricular dysfunction in asymptomatic individuals. Only two of the studies (involving 232 patients) investigated the use of BNPas a diagnostic tool for suspected congestive heart failure in general practice.Further research is needed to validate the test in the milder spectrum of diseaseseen in general practice. One such study is currently under way in Newcastle,New South Wales. Congestive heart failure can be due to either systolic or diastolic ventriculardysfunction. While there are guidelines10 anda wealth of good evidence from randomised controlled trials on the managementof systolic dysfunction, there is scant evidence on how to manage diastolicfailure. BNP is increased in both systolic and diastolic dysfunction so manypatients will still need echocardiography in order to plan therapy. The valueof the test may eventually be in its capacity to rule out heart failure asa cause of a patient's illness. BNP has been shown to be a powerful predictor of prognosis in patients withheart failure. A high concentration is associated with a poor prognosis. Somecentres are therefore using BNP concentrations to guide therapy, however thisusage is still experimental. E-mail: ben.ewald@newcastle.edu.au References 1. Maisel A, Krishnaswamy P, Nowak RM, McCord J, HollanderJE, Duc P. Rapid measurement of B-type natriuretic peptide in the emergencydiagnosis of heart failure. N Engl J Med 2002;347:161-7. 2. Clerico A, Del Ry S, Giannessi D. Measurement of cardiacnatriuretic hormones (atrial natriuretic peptide, brain natriuretic peptide,and related peptides) in clinical practice: the need for a new generation ofimmunoassay methods. Clin Chem 2000;46:1529-34. 3. Dao Q, Krishnaswamy P, Kazanegra R, Harrison A, AmirnovinR, Lenert L, et al. Utility of B-type natriuretic peptide in the diagnosisof congestive heart failure in an urgent-care setting. J Am Coll Cardiol 2001;37:379-85. 4. Davis M, Espiner E, Richards G, Billings J, Town I,Neill A, et al. Plasma brain natriuretic peptide in assessment of acute dyspnoea.Lancet 1994;343:440-4. 5. Cowie MR, Struthers AD, Wood DA, Coats AJS, ThompsonSG, Poole-Wilson PA, et al. Value of natriuretic peptides in assessment ofpatients with possible new heart failure in primary care. Lancet 1997;350:1349-53. 6. McDonagh TA, Robb SD, Murdoch DR, Morton JJ, Ford I,Morrison CE, et al. Biochemical detection of left-ventricular systolic dysfunction.Lancet 1998;351:9-13. 7. Hobbs FDR, Davis RC, Roalfe AK, Hare R, Davies MK,Kenkre JE. Reliability of N-terminal pro-brain natriuretic peptide assay indiagnosis of heart failure: cohort study in representative and high risk communitypopulations. Br Med J 2002;324:1498-500. 8. Nakamura M, Endo H, Nasu M, Arakawa N, Segawa T, HiramoriK. Value of plasma B type natriuretic peptide measurement for heart diseasescreening in a Japanese population. Heart 2002;87:131-5. 9. Vasan RS, Benjamin EJ, Larson MG, Leip EP, Wang TJ,Wilson PWF, et al. Plasma natriuretic peptides for community screening forleft ventricular hypertrophy and systolic dysfunction. The Framingham heartstudy. JAMA 2002;288:1252-9. 10. Krum H, National Heart Foundation of Australia andCardiac Society of Australia & New Zealand Chronic Heart Failure ClinicalPractice Guidelines Writing Panel. Guidelines for management of patients withchronic heart failure in Australia. Med J Aust 2001;174:459-66. Dr Ewald's research into BNP is funded by the HunterMedical Research Institute.
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