Natriuretic Peptides for Managing Other Conditions
A detailed overview of other conditions where natriuretic peptides have been shown to be beneficial is beyond the scope of this review, but a very short overview is provided. Both BNP and NT-proBNP have repeatedly been shown to be very useful in differential diagnosis of acute dyspnoea, both in the emergency department and in outpatient settings, mainly to exclude HF if levels are normal. This is also recognised in guidelines as class I indication.2,41 The prognostic value not only in chronic HF, but also in many other cardiac and non-cardiac conditions is beyond any doubt. However, knowing the prognosis does not necessarily mean knowing how to improve it, unless prospectively tested and this is only the case for chronic HF, as well as for more appropriate diagnosis in acute HF with faster and more relevant therapeutic intervention.49 Additionally, BNP levels may help in screening patients at risk for HF to aid earlier and more efficacious intervention with improved outcome, as shown in the STOP-HF trial.50 Additionally, the PONTIAC trial suggest that the diabetes patient with elevated NT-proBNP levels could profit from more intensive medical therapy (ACE-inhibitors and beta-blockers), also resulting in fewer HF events.51 These two studies show the potential of measuring natriuretic peptides in outpatient care beyond therapy guidance in chronic HF, but additional studies are needed to confirm the findings and to better define which patients profit most from natriuretic peptide measurements.
Biomarkers Other than Natriuretic Peptides
Biomarkers other than natriuretic peptides have not been prospectively tested to guide therapy in HF or to prevent HF. A huge number of biomarkers has shown to be of prognostic value, but few have clinical implications in cardiac diseases.52 In chronic HF, two biomarkers, soluble sST2 and galectin-3, have been particularly proposed as being useful in selection of patients most likely to benefit from specific interventions. Both fulfil requirements that make them attractive to guide therapy as already discussed above for natriuretic peptides. In particular, prognostic value of sST2 may be complementary to BNP/NT-proBNP,53 or possibly may be superior to BNP/NT-proBNP when serially measured.54 Moreover, they represent different pathophysiological pathways (sST2 from interleukin family, inflammation, fibrosis and remodelling; galactin-3 activates fibroblasts, fibrosis, inflammation) from natriuretic peptides and are largely independent of them, which might indicate that they can also independently add to clinical decision making. Importantly, both markers have shown some interaction with therapy response in HF. Thus, galectin-3 might predict lack of treatment response to statins in HF.55 However, similar potential interaction with MRA therapy response was not found in HF.56 A relationship between sST2 levels and the effect of eplerenone in post-MI patients with reduced LVEF was found,57 thus, sST2 predicted reverse remodelling, which could be attenuated in patients receiving eplerenone. Likewise, a high dose of beta-blockade was found to be particularly useful in patients with high sST2 levels.58 Although promising, it is important to note that these were all post-hoc analyses investigating only a single time-point of biomarker measurement and are, at best, hypothesis-generating. Prospective studies investigating specific interventions based on these biomarker levels must be done before they can be incorporated into clinical practice. Given the time required before natriuretic peptide-guided therapy in chronic HF may be implemented into clinical practice, there is still a long way to go with these new biomarkers, but it may be hoped that studies testing these new biomarkers are planned more cooperatively and on a larger scale at an early stage.