Biomarker Guided Therapy in Chronic Heart Failure

Abstract

Although the first study on biomarker-guided therapy of chronic heart failure (HF) was published 15 years ago, 1 there is still no real proof of the superiority of this approach as compared with standard therapy.The guidelines of the European Society of Cardiology simply state that:"several RCTs that evaluated natriuretic peptide-guided treatment (intensifying treatment in order to lower peptide levels) have given conflicting results. It is uncertain whether outcome is better using this approach than by simply optimising treatment according to guidelines". Apart from being markers of function of different organs, biomarkers, mainly natriuretic peptides, are considered useful only for excluding HF and as prognostic markers.2 However, several metaanalyses, 3-6 including a very recent one based on individual patientdata (IPD), 7 have found that natriuretic peptide-guided therapy may reduce both mortality and HF related hospitalisations. However, one recent systematic review was less positive and concluded that current evidence does not support the use of B-type naturiuretic peptide (BNP) and N-terminal pro (NT-pro)BNP. to guide HF therapy.8 This review addresses current evidence of natriuretic peptide-guided therapy and discusses potential reasons why this approach needs further investigation. Moreover, it will give short insight into other emerging biomarkers that are promising for therapy guidance in chronic HF. Natriuretic Peptide Guided Heart Failure TherapyLevels of natriuretic peptides, other than BNP and the N-terminal residual of its pro-hormone NT-proBNP, have little or no clinical role in HF, at least in Europe and the US. Other biomarkers have not yet been sufficiently studied in guiding chronic therapy. Therefore, this review focuses largely on these two peptides. In order to understand the concept of natriuretic peptide-guided therapy in chronic HF several aspects are important, as summarised in a recent review.9 Thus, HF is a very costly chronic disease (around 2 % of the total healthcare budget spent for HF) with increasing prevalence (at present there about 10 million HF patients in Europe).10 Prognosis remains poor despite significant advances in therapy 11,12 and to some extent, this is related to the insufficient use of available treatment in HF.13,14 Achieving optimal therapy seems to be extremely difficult and additional markers to identify those patients in most need may be helpful. Natriuretic peptides may be very useful in this as they are strong prognostic markers across the whole spectrum of HF, particularly in the chronic stage 15 and seem to change relatively little if patients are clinically stable. 16 More importantly, natriuretic peptides change over time in parallel with change in prognosis 17,18 and treatment of chronic HF influences plasma levels of natriuretic peptides. Thus, loop diuretics, angiotensin-converting enzyme (ACE)-inhibitors, angiotensin-II receptor blockers (ARB) and mineralocorticoid receptor antagonists (MRA), as well as cardiac resynchronisation therapy (CRT), ...