Early increase and subsequent decrease in mature BNP and early decrease and continued decrease in proBNP after sacubitril/valsartan may relate to left ventricular reverse remodeling in heart failure
Authors: Miyamoto S , Nishikimi T , Nakagawa Y 
Published: October 2024

Abstract

Background
Current BNP assays measure not only mature BNP (BNP1-32) but also precursor proBNP. Previous studies have shown that the change in BNP after sacubitril/valsartan (Sac/Val) treatment is not consistent. The reason for this may be due to the fact that the immunoreactivity of BNP consists of mature BNP and proBNP and neprilysin degrades only mature BNP but not proBNP.

Purpose
This study assessed changes in mature BNP, proBNP, total BNP (= mature BNP + proBNP) before and 2 and 12 weeks after administration of Sac/Val in heart failure (HF).

Methods
We measured mature BNP, proBNP, and total BNP levels by our developed immunoassay, NT-proBNP and ANP by conventional assay and left ventricular (LV) remodeling indices by echocargdioraphy in 34 HF patients before, 2, and 12 weeks (wk) after Sac/Val treatment. 34 HF patients were divided into two groups. Group D (n=20) was defined as the group whose mature BNP at 12wk was lower than the baseline. Whereas Group I (n=14) was defined as the group whose mature BNP at 12wk was higher than the baseline.

Results
In all patients, total BNP did not change after 2wk or 12wk compared to baseline. ProBNP decreased after 2wk and tended to decrease after 12wk (p=0.07). Whereas there was no change inmature BNP after 2wk or 12wk (Table 1). In group D, total BNP did not change at 2wk, but decreased after 12wk. Mature BNP did not change at 2wk, but decreased after 12wk. ProBNP decreased at 2wk and further decreased at 12wk. In contrast, in group I total BNP did not change at 2wk, but increased at 12wk. ProBNP did not change after 2wk or 12wk compared to baseline. Mature BNP increased after 2wk and further increased after 12wk. Thus, a decrease in both proBNP and mature BNP contributed to the decrease in total BNP in group D, while the increase in total BNP in group I was mainly due to the increase in mature BNP. Correlation coefficient and p value between total BNP, proBNP, mature BNP, NT-proBNP and ANP at baseline, 2wk and 12wk are shown in Table 2. A close correlation was observed between BNP molecular forms. NT-proBNP decreased and ANP increased after Sac/Val administration; however, there was a modest correlation between the two peptides. There were no significant differences in LV ejection fraction (LVEF: %), end-diastolic volume index (LVEDVI: ml/m²) or end-systolic volume index (LVESVI: ml/m²) between two groups at baseline or at 12 wk; however, the delta (at 12 wk – pretreatment) LVEDVI, and LVESVI significantly improved in group D compared with group I (-9.3±11.3 vs. 3.7±10.1, p&lt;0.01; -8.2±13.5 vs. 2.7±8.9, p&lt;0.01, respectively).

Conclusion
These results suggest that total BNP appears to be unchanged after Sac/Val administration, but its components, proBNP and mature BNP, are altered; reverse cardiac remodeling may relate to decrease of mature BNP and proBNP; and the closely correlated natriuretic peptide molecules, regardless of the degradation by neprilysin, may be regulated in the same direction.