Atrial Natriuretic Peptide and Treatment With Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction.

Journal Article (Journal Article)

OBJECTIVES: This study sought to assess associations between longitudinal change in atrial natriuretic peptide (ANP) and reverse cardiac remodeling following initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: Neprilysin inhibition results in an increase of several vasoactive peptides that may mediate the beneficial effects of sacubitril/valsartan, including ANP. METHODS: In a prospective study of initiation and titration of sacubitril/valsartan in patients with HFrEF, blood was collected at scheduled time points into tubes containing protease inhibitors. This pre-specified exploratory analysis included patients in whom ANP was measured at baseline and serially through 12 months of treatment. RESULTS: Among 144 participants (mean age: 64.5 years; left ventricular ejection fraction: 30.8%), following initiation of sacubitril/valsartan, there was an early and significant increase in ANP, with the majority of rise from 99 pg/ml at baseline to 156 pg/ml at day 14 (p < 0.001). There was a further trend toward a second increase from day 30 to day 45 (p = 0.07). At maximal rise, ANP had doubled. In longitudinal analyses, early rise in ANP was followed by a subsequent increase in urinary cycle guanosine monophosphate. Larger early increase in ANP was associated with larger later improvements in left ventricular ejection fraction and left atrial volume index (p < 0.001 for both). CONCLUSIONS: Concentrations of ANP doubled after initiation of sacubitril/valsartan in patients with HFrEF. Larger early increases in ANP were associated with a greater magnitude of subsequent reverse cardiac remodeling. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

Full Text

Duke Authors

Cited Authors

  • Murphy, SP; Prescott, MF; Camacho, A; Iyer, SR; Maisel, AS; Felker, GM; Butler, J; Piña, IL; Ibrahim, NE; Abbas, C; Burnett, JC; Solomon, SD; Januzzi, JL

Published Date

  • February 2021

Published In

Volume / Issue

  • 9 / 2

Start / End Page

  • 127 - 136

PubMed ID

  • 33189632

Electronic International Standard Serial Number (EISSN)

  • 2213-1787

Digital Object Identifier (DOI)

  • 10.1016/j.jchf.2020.09.013


  • eng

Conference Location

  • United States