Page 13 - Biomarkers for risk stratification and guidance in heart failure

Chapter 1
In 2000, a small pilot study was published suggesting that guiding HF management by aiming for a target NT-proBNP level may improve outcome34. In this study, the investigators aimed to achieve NT-proBNP levels of 200 pmol/l (1,700 pg/ml) or lower. Such a low target value is difficult to achieve in many patients with established HF. Several other randomized trials evaluated the clinical value of such low and absolute (NT-pro)BNP target levels in HF.35-39 These studies failed to show an overall reduction in mortality. However, two of these studies demonstrated a significant improvement by natriuretic peptide-guided therapy in patients aged 75 years or less.35,36
The low (NT-pro) BNP target level was achieved only in a minority of patients, ranging from 33% to less then 50%.36,38 Although the target (NT-pro) BNP level was not achieved in the majority of patients randomized to (NT-pro)BNP-guided therapy, most of these patients received intensified treatment. These studies therefore show that a more generalized intensification of HF therapy might be beneficial in the specific subgroups. However, it was not addressed whether serial assessment of NT-proBNP enables to select patients at risk for increased morbidity and mortality. It is well known that in many HF patients, NT-proBNP levels never normalize, whereas these patients still remain clinically stable over years. This suggests that introducing a patient's individualized target level may allow selection of those HF patients most likely to progress towards events. Such an individual target level could be defined as the lowest level at hospital discharge or at 2 weeks follow-up after admission because of acute HF. However, the prognostic value of such an individualized target value has not yet been assessed. Furthermore, it is unclear whether knowledge of such an individual target level can reduce morbidity and mortality in HF patients.
Guided therapy of heart failure: applicable to all patients?
As mentioned before, the two trials demonstrating a mortality reduction by natriuretic peptide-guided treatment did so only in patients at the age of 75 or less.35,36 Therefore, it seems that not every patient profits from natriuretic peptide- guided treatment of HF. Question remains if older age itself is a limiting factor, or that age associated comorbidities like renal failure, hypertension and COPD cause natriuretic peptide-guided therapy to fail. Furthermore, etiology of heart failure differs between younger and older patients with HF: in elderly patients, HF with preserved ejection fraction (HFpEF) is more common.40 HFpEF has a different etiologic background compared with HF with reduced ejection fraction (HFrEF).41
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