Perspective:

The following are 10 key points regarding the use of natriuretic peptides to guide and monitor heart failure (HF):

1. B-type cardiac natriuretic peptides (B-type natriuretic peptide [BNP] and/N-terminal pro-BNP [NT-proBNP]) are a biochemical signal that reflects the degree of control and/or prognosis, with plasma concentrations reflecting cardiac structure and function (both systolic and diastolic).

2. Response to anti-HF therapy, such as diuretics and vasodilators, are reflected in rapidly apparent parallel changes in plasma BNP/NT-proBNP.

3. During the last 10 years, the hormone-guided hypothesis has been tested in a number of small-to-moderate–sized randomized therapeutic trials that have included more than 2,000 patients.

4. Two meta-analyses of trial summary data have been published. Both found a significant reduction in mortality for biomarker-guided therapy (six trials, n = 1,627, hazard ratio 0.69, 95% confidence interval 0.55-0.86; and eight trials, n = 1,726, relative risk 0.76, 95% confidence interval 0.63-0.91; p = 0.003).

5. Review of these trials indicated that patient age, burden of comorbidity, presence or absence of preserved left ventricular ejection fraction (LVEF), severity of the prognosis, aggressiveness with which adjustment of therapy is pursued, and target peptide concentrations chosen may all be pertinent to the efficacy of peptide-guided therapy.

6. Most trials have demonstrated that younger mean age is associated with better outcomes from hormone-guided treatment. This may be secondary to reduced renal function and failure of the autonomic nervous system to meet changes in blood pressure due to volume- and pressure-lowering multidrug therapy.

7. Variation in study outcomes may partially relate to lack of specific drug escalation algorithms as well as differences in target natriuretic peptide values.

8. The mechanism underlying improved outcomes with hormone guidance is unclear, but may relate to tighter serial optimization (“tailoring”) of therapy rather than overall higher pharmacologic dosing.

9. Hormone-guided therapy appears to preferentially benefit patients with reduced LVEF, with little data supporting a treatment effect in patients with preserved LVEF.

10. Future trials should be adequately powered, should be conducted in patients with reduced EF (<50%) and no more than one significant comorbidity, and should define a peptide target that is age adjusted and no more than twice the upper limit of the reference interval for that age group, with standardized triggers for drug escalation and the escalation algorithm.