032| Volume 26, ISSUE 10, SUPPLEMENT , S15, October 2020

Atrial Natriuretic Peptide Mediates Reverse Cardiac Remodeling During Treatment with Sacubitril/Valsartan in Patients with Heart Failure with Reduced Ejection Fraction


      Sacubitril/valsartan (S/V) promotes reverse cardiac remodeling in patients with HFrEF. Neprilysin inhibition results in increase of several vasoactive peptides that may mediate effects of S/V, however its effects on atrial natriuretic peptide (ANP) are largely unknown. Effects of ANP are mediated by cyclic guanosine monophosphate (cGMP).


      Longitudinal change in ANP concentration following initiation of S/V is associated with reverse cardiac remodeling.


      Within a prospective open-label study of initiation and titration of S/V in patients with HFrEF, this pre-specified sub-study included patients in whom ANP was measured from samples collected in protease inhibitors to minimize its degradation. Concentrations of ANP and cGMP were measured at baseline and serially through 12 months of treatment. Echocardiographic assessment of LVEF and left atrial volume index (LAVi) was performed at baseline, 6 and 12 months.


      Among 144 participants (mean age 64.5 years; LVEF 30.8%), median ANP concentration at baseline was 102 pg/mL. Following initiation of S/V, ANP increased steeply and consistently during the first 2 months, with a significant increase in log-transformed ANP concentration at Day 14 (from 4.60 pg/mL to 5.05 pg/mL; Δ = 0.453; P <.001; 95% CI: 0.273-0.632) and a second increase that approached statistical significance at Day 45 compared to Day 30 (Δ = 0.147, P =.071; 95% CI: -0.006, 0.30; Figure 1). Early changes in ANP were reflected in later change of urinary cGMP. Larger early increases in ANP were associated with larger later gains in LVEF and reduction in LAVi (P <.001 for both). Latent class analysis revealed 5 groups with different rates and magnitudes of ANP and cGMP change over time, however improvement in LVEF and LAVi after S/V initiation was similar between groups.


      Concentrations of ANP increase substantially after initiation of S/V in patients with HFrEF. Larger early increases in ANP after S/V initiation were associated with greater magnitude of reverse cardiac remodeling (PROVE-HF; NCT02887183).
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