Abstract
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.
Original language | English (US) |
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Pages (from-to) | 127-136 |
Number of pages | 10 |
Journal | JACC: Heart Failure |
Volume | 9 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2021 |
Keywords
- ANP
- HFrEF
- cardiac remodeling
- sacubitril/valsartan
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine