Perspective:

The European Society of Cardiology (ESC) outlined principles for the application of natriuretic peptide levels to care for patients with heart failure. The following are 10 points to remember:

1. While B-type natriuretic peptide (BNP) is expressed mostly in the atria of normal hearts, its production is upregulated in high wall stress states (e.g., heart failure and renal failure), promoting diuresis, natriuresis, vasodilation, and renin-angiotensin-aldosterone system (RAAS) antagonism.

2. PreproBNP is cleaved to form proBNP. This is then cleaved into BNP (biologically active) and N-terminal (NT)-proBNP (biologically inactive). Patients with heart failure often have high concentrations of relatively inactive glycosylated proBNP which cannot be converted to active BNP—the so-called ‘natriuretic peptide paradox.’

3. BNP is cleared via endopeptidases, clearance receptors, and renally. NT-proBNP is cleared passively by high blood flow organs (i.e., liver and kidney). Renal dysfunction leads to elevation of both peptides. NT-proBNP levels are higher in general due to a longer half-life.

4. Natriuretic peptides are neither heart failure nor heart disease specific.

5. Because the intrapatient natriuretic peptide’s biological variability is 30-50%, large changes must occur within patients for them to be deemed clinically important (>30% change). Thus, frequent blood sampling during acute management is not recommended.

6. Natriuretic peptide levels may not be elevated despite acute hemodynamic compromise and pulmonary congestion in those with preserved ejection fraction, constrictive pericarditis, and acute mitral regurgitation.

7. Both BNP and NT-proBNP have reduced sensitivity in severe obesity.

8. In the setting of normal renal function and body mass index, a BNP <100 ng/L and NT-proBNP <300 ng/L makes the diagnosis of heart failure less likely. Similarly, a BNP level >500 ng/L makes a heart failure diagnosis in the correct clinical setting more likely.

9. Natriuretic peptide measurements on admission can provide risk stratification and predict short- and long-term mortality. A BNP that reduces >30% from admission at the time of discharge is associated with improved survival.

10. Natriuretic peptide measurements can be prognostic in the setting of several nonheart failure-related conditions such as acute pulmonary embolism, acute coronary syndrome, and acute lung injury.