Division of Cardiology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR
* Correspondence to: Professor John E Sanderson, Department of Medicine and Therapeutics, 9th Fl Clinical Science Bldg, Prince of Wales Hospital, Hong Kong, SAR. Tel.: +852 2632 2064; fax: +852 2637 2396 (E-mail: jesanderson{at}cuhk.edu.hk).
This editorial refers to "Comparison of echocardiography and plasma B-type natriuretic peptide for monitoring the response to treatment in acute heart failure" by A. Gackowski et al. on
page 1788
No-one would question the value of echocardiography for the initial assessment of patients with heart failure and it is now a mandatory investigation. Not only can the cause be frequently correctly identified, but important prognostic information can also be gleaned. In particular, the restrictive filling pattern seen with the Doppler mitral inflow velocities is recognized to be associated with a poor prognosis, especially if it does not normalize with initial treatment.1 The restrictive filling pattern is also associated with higher atrial natriuretic peptide (ANP) and brain natriuretic peptide levels (BNP) and both peptides correlate inversely with ejection fraction, and positively with pulmonary artery pressure.2
Although BNP is secreted by both atrial and ventricular tissue, in heart failure there is upregulation of ventricular production which is more important for BNP than ANP and circulating BNP levels are consistently elevated in untreated heart failure compared to normals. In response to changes in stretch, such as would occur with treatment, the changes in circulating peptide levels are more rapid for ANP than BNP.
Nevertheless, BNP has been shown to be a powerful prognostic marker in both chronic and acute heart failure independent of standard echocardiographic parameters.3,4 What is not so clear is the value of BNP for the diagnosis of heart failure or for the monitoring of treatment. It would be marvellous to have a quick blood test for assessing the heart failure patient and which could be used for adjusting the treatment to suit the individual, similar to the blood sugar for monitoring diabetes or the cholesterol level for treating hyperlipidaemia. But does BNP match up to this requirement? Many studies have suggested that BNP may be useful for the diagnosis of heart failure and the evaluation of the breathless patient. But there is still debate about what is the best cut-off point and there are specificity problems; for example, many elderly patients with renal failure and hypertension will have high BNP, but these are the very patients in whom the diagnosis of heart failure can be difficult and therefore the role of BNP for diagnosis has been questioned.5 But, since BNP is a robust marker of prognosis in epidemiological studies, it seems only logical that it might be useful for the monitoring of therapy. However, the biological variations of BNP are sufficiently great that large differences in values are required before any real trend can be confidently assumed.
Despite the large number of publications documenting the relationship between BNP, cardiac function and prognosis there has been few studies on its use for monitoring therapy although this is obviously an attractive proposition that has been floated for a long time. Previously in a small study Troughton et al., evaluated NT-proBNP guided therapy.6 The group assigned to NT-proBNP based therapy received higher doses of ACE-inhibitors and diuretics and the probability of a first heart failure event or mortality was lower. However, it could reasonably be argued that physicians should titrate the dose of drugs to the recommended levels in all patients in any case and BNP results are no more than a tap on the shoulder and a gentle reminder to increase doses; surely an expensive way to ensure optimum therapy. Furthermore, in the chronic ambulatory care situation, Tang et al., have found that patients with stable systolic heart failure have a wide range of plasma BNP levels and in 21% of symptomatic individuals the levels were below the diagnostic level.7 It is not clear how physicians should react to such a BNP result.
However, in the acute situation, serial measurements of BNP could be more useful and possibly more so than repeat echocardiography for assessing progress. In this issue of the Journal, Gackowski and colleagues8 report a study where they have compared the value of Doppler echocardiography and BNP for acute management, and showed that BNP measured on admission after 24 h and at day 7 can add incremental prognostic value, after taking clinical factors and standard Doppler echocardiography performed at the same time intervals into account. Those patients in whom the BNP did not fall by >10% by day 2 or with a plasma BNP >300 pg/ml at day 7 had a worse outcome during a 60-day follow-up. In this study the majority of patients had "systolic" heart failure (72% had an LVEF<45%) and very few had ß-blocker therapy started during the initial admission. It is therefore not clear if these results also apply to the larger group with heart failure and a "normal" LV ejection fraction (so-called Diastolic heart failure). In many hospitals, ß-blockers would be started earlier while the patient is still in the ward. But the effect of ß-blockers on BNP levels is variable; in the early stages they cause an elevation in BNP and ANP, although over the long-term the levels usually decline.9
Furthermore the newer Tissue Doppler-based parameters, such as annular velocities, were not included in the assessment. The peak early diastolic annular velocity is also a powerful predictor of mortality in many cardiovascular conditions10 including heart failure and provides incremental value to standard echocardiographic measurements. Since the ratio E/Em is more closely related to left ventricular filling pressures than deceleration time or the restrictive filling pattern, it may be a more useful and quick measurement to make. The decision whether to do repeat Doppler-echo studies or BNP measurements instead, therefore, may not be so clear cut as might appear from the study of Gackowski et al., 8 if these newer tissue Doppler techniques are used.
Although the jury is still out on whether serial measurements of BNP are justified for monitoring in the outpatient ambulatory care environment, in the acute care situation, if the BNP has been used to confirm the diagnosis on admission, then a repeat BNP performed at least 24 h later may have some value and in some hospitals may be easier to perform than repeat echocardiography. However, what the physician should do if the BNP values do not fall after admission is unclear as presumably such sick patients will already be receiving maximum therapy. The only upshot may be to try to optimise the diuretic dosage if this has not already been done. This is the hub of the problem in deciding the therapeutic value and clinical relevance of BNP assays. Gackowski et al.,8 do not address the question whether knowledge of the BNP results can influence management significantly in a positive way as they have assessed only the prognostic value of the test.
At best, BNP testing may provide better titration of the diuretic dose, allow earlier discharge when the BNP levels do fall satisfactorily, and identify those patients who should have more intensive therapy (if it is possible) and closer observation. But all patients deserve optimal therapy with the standard proven medications of ß-blockers with complete blockade of the reninangiotensinaldosterone system titrated to the doses used in the major clinical trials. This can be achieved in the majority without a BNP measurement or repeat echocardiography.
Although BNP is clearly related to prognosis and may be helpful for the initial diagnosis of heart failure, larger clinical studies are needed before we can be certain that routine measurement of BNP either in hospital or the clinic will influence the management in any significant manner or make any difference to the eventual outcome. Individualising treatment based on BNP is an attractive hypothesis but which remains unproved.
Footnotes
doi:10.1016/j.ehj.2004.07.038
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References
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