Introduction
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).
Hypothesis
Longitudinal change in ANP concentration following initiation of S/V is associated
with reverse cardiac remodeling.
Methods
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.
Results
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.
Conclusions
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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Identification
Copyright
© 2020 Published by Elsevier Inc.
