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Brain natriuretic peptide assays may make it easier
Heart failure is an increasingly important problem
for primary care physicians in most healthcare systems in developed
countries. The condition is almost as common as diabetes mellitus in
older adults, occurring in at least 2% of the adult population and
rising to 3% in those aged over 75 years.
1 2
Although
the incidence of most cardiovascular diseases has declined over the
past 20 years, the incidence of heart failure has continued to rise,
due in part to the fact that more people are surviving after acute myocardial infarctions and also to the increasing number of elderly people.3
Symptomatic heart failure has a major impact on patients and
healthcare systems: it has a worse prognosis than breast cancer or
prostate cancer and is second only to stroke in terms of healthcare costs.4 Heart failure costs the United States over $8bn
(£5bn) each year, and 5% of all admissions in the United Kingdom
involve some degree of heart failure.5 In addition
to high mortality, patients with heart failure also have morbidity from
symptoms such as dyspnoea and fatigue.6
Accurate and early diagnosis is important since angiotensin
converting enzyme inhibitors improve both morbidity and mortality in
all grades of symptomatic heart failure caused by left ventricular systolic dysfunction and can delay or prevent progression to
symptomatic heart failure. More recently, research has shown the
prognostic benefits of treatment with Unfortunately, most patients with suspected heart failure and
preserved systolic function cannot be classed as having the elusively
categorised diastolic heart failure. In this issue of the
BMJ, Caruana et al (p 215) report that of 159 patients referred to hospital with suspected heart failure, 109 had
preserved ventricular function; on further investigation, however, only
seven of these patients did not have an alternative explanation for
their symptoms of "heart failure," such as obesity, respiratory
disease, or myocardial ischaemia.8
To positively establish a diagnosis of heart failure in primary care,
most patients must be referred for cardiac imaging. A recent survey of
a random sample of primary care physicians across six European
countries reported only 5% (Netherlands) to 37% (United Kingdom) of
general practitioners had direct access to
echocardiography.9 This poor access is partially due to a
lack of trained staff to run clinics and partially to concerns that
providing primary care physicians with direct access would result in
inappropriate use (although a trial of open
access echocardiography found only 12% of referrals to be
"inappropriate").10
Are there alternatives to echocardiography in primary care? A
normal electrocardiogram usually excludes left ventricular
dysfunction.11 However, changes may be subtle and primary
care physicians' lack of skill in interpreting electrocardiograms may
mean that referral for specialist opinion is still required.
A potential diagnostic aid in primary care is the assessment of
patients by measuring plasma concentrations of brain natriuretic peptide. However, data on the validity of brain natriuretic peptide are
conflicting. Brain natriuretic peptide testing had a sensitivity of
97%, a specificity of 84%, a positive predictive value of 70%, and a
negative predictive value of 98% in 106 patients with symptoms of
recent onset who were referred to a rapid access heart failure clinic.12 Similar predictive performance for the peptide
was reported both in patients with confirmed left ventricular systolic dysfunction (the commonest cause of heart failure) in a population of
1653 adults aged between 25 and 75 years who were screened in Glasgow,
an area with high rates of cardiovascular disease,13 and
in another paper in the BMJ in which 155 patients aged over 75 were screened in primary care.14 However, these studies
were small, and a study of 134 patients who were stable after a
myocardial infarction found that brain natriuretic peptide could not
predict the presence of mild to moderate left ventricular systolic
dysfunction compared with normal function (McClure SJ et al, 20th
Congress of the European Society of Cardiology, Vienna, 1998). For 126 patients in general practice who were referred to an echocardiography clinic, in another recent paper in the BMJ, there was only a
small diagnostic advantage in adding brain natriuretic peptide to
standard investigations of electrocardiography and chest
radiographs, although 1 in 7 patients was given a false negative
diagnosis.15 However, these latter findings contrast with
a negative predictive value of 98% reported in an accompanying paper
on brain natriuretic peptide that appeared in the same
issue.14
So which data are correct? Obviously, more research is needed before
brain natriuretic peptide becomes a routine assay. The most likely
initial application will be in triaging symptomatic adults for
echocardiography on the basis of a positive test; a negative result is
likely to exclude a diagnosis of heart failure. The assay's
performance characteristics are likely to preclude its use in screening
healthy populations because of the lower positive predictive value of
the test. A comparatively high prior probability of heart failure in
certain groups at risk (those who have had heart attacks or who have
hypertension or diabetes) may make selective screening in these
populations worthy of further study. It is possible that brain
natriuretic peptide could be used to guide treatment analogous to the
use of glycated haemoglobin in the follow up of patients with
diabetes.16
Primary care physicians need structured approaches to diagnosing
heart failure; these approaches should involve stratifying patients
into risk groups and assessing them with objective tests. In many
cases, there is no immediate alternative to echocardiography to confirm
the diagnosis and determine the aetiology. However, the brain
natriuretic peptide assay holds an exciting potential to determine who
should be listed for echocardiography, with the possibility that it can
aid in treatment and predicting prognosis.
University of Birmingham, Edgebaston Birmingham P15 2TT
(F.D.R.Hobbs{at}bham.ac.uk)
blockers in heart failure
caused by left ventricular systolic dysfunction. Unfortunately, heart failure is difficult to diagnose accurately on clinical grounds. Only
26% of patients with suspected heart failure referred to a rapid
access clinic for echocardiography had the diagnosis confirmed after
investigation. Clinical diagnosis by hospital physicians is just as
poor.7
| 1. | McDonagh TA, Morrison CE, Lawrence A, Ford I, Tunstall-Pedoe H, McMurray JJV, et al. Symptomatic and asymptomatic left ventricular systolic dysfunction in an urban population. Lancet 1997; 350: 829-833[CrossRef][Medline]. |
| 2. | Cowie MR, Mosterd A, Wood DA. The epidemiology of heart failure. Eur Heart J 1997; 18: 208-225. |
| 3. |
Brown A, Cleland JGF.
Influence of pattern of concomitant disease on patterns of hospitalisation in patients with heart failure discharged from Scottish hospitals in 1995.
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1998;
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| 6. | Davis RC, Hobbs FDR, Kenkre JE, Roalfe AK, McLeod S, Hare R, et al. Quality of life in heart failure and other conditions. J Am Coll Cardiol 1999; 33(2(A)): 265 |
| 7. |
Clarke KW, Gray D, Hampton JR.
Evidence of inadequate investigation and treatment of patients with heart failure.
Br Heart J
1994;
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584-587 |
| 8. |
Caruana L, Petrie MC, Davie AP, McMurray JJV.
Do patients with suspected heart failure and preserved left ventricular systolic function suffer from "diastolic heart failure" or from misdiagnosis? A prospective descriptive study.
BMJ
2000;
321:
215-218 |
| 9. | Hobbs FDR, Wilson S, Jones MI, Tobias RS, Allen TF, Fletcher M. European survey (EuroHF) of primary care physician perceptions and practice in heart failure diagnosis and management. Eur Heart J 2000 (in press). |
| 10. |
Francis CM, Caruana L, Klerney PL, Love M, Sutherland GR, Starkey IR, et al.
Open access echocardiography in management of heart failure in the community.
BMJ
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310:
634-636 |
| 11. |
Davie AP, Francis CM, Love MP, Caruana L, Starkey IR, Shaw TRD, et al.
Value of the electrocardiogram in identifying heart failure due to left ventricular systolic dysfunction.
BMJ
1996;
312:
222 |
| 12. | Cowie MR, Struthers AD, Wood DA, Coates AJS, Thompson SG, Poole-Wilson PA, et al. Value of natriuretic peptides in assessment with patients with possible new heart failure in primary care. Lancet 1997; 350: 1349-1353[CrossRef][Medline]. |
| 13. | McDonagh TA, Robb SD, Murdoch DR, Morton JJ, Ford I, Morrison C, et al. Biochemical detection of left ventricular systolic dysfunction. Lancet 1998:9-13 |
| 14. |
Smith H, Pickering RM, Struthers A, Simpson I, Mant D.
Biochemical diagnosis of ventricular dysfunction in elderly patients in general practice: observational study.
BMJ
2000;
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906-908 |
| 15. |
Landray MJ, Lehman R, Arnold I.
Measuring brain natriuretic peptide in suspected left ventricular systolic dysfunction in general practice: cross-sectional study.
BMJ
2000;
320:
985-986 |
| 16. | Murdoch DR, McDonagh TA, Bryne J. Titration of vasodilator therapy in chronic heart failure according to plasma brain natriuretic peptide concentration: randomised comparison of haemodynamic and neuroendocrine effects of tailored versus empirical therapy. Am Heart J 1999; 138: 1126-1132[CrossRef][Medline]. |
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