Prognostic value and kinetics of soluble neprilysin in acute heart failure. a pilot study.

1. Antoni Bayes-Genis MD, PhD, FESC
No Conflicts of Interest
Prognostic Value and Kinetics of Soluble Neprilysin
in Acute Heart Failure.
A Pilot Study
Antoni Bayes-Genis, Jaume Barallat, Domingo Pascual, Julio Nuñez,
Gema Miñana, Jesús Sánchez-Mas, Amparo Galan, Juan Sanchis,
Elisabet Zamora, María Teresa Pérez-Martínez, Josep Lupón

2. sNEP in chronic HF
Bayes-Genis A et al. J Am Coll Cardiol 2015;65:

3. Objectives and Endpoints
Objectives: To examine the prognostic value of sNEP in acute
HF (AHF) and sNEP kinetics during hospital
admission.
Primary endpoints: CV death or HF hospitalizations at short-term (2
month)
CV death or HF hospitalizations at long-term (1.8 ± 1.2
years)

4. Patients and methods
Patients: 350 patients (mean age 72.6±10.7 years) admitted
for AHF were consecutively included in the study. 3 Centers:
Badalona, Murcia and Valencia.
In a subgroup of patients sNEP was measured both at
admission and discharge (n=92).
Human NEP: modified sandwich immunoassay (HUMAN NEP/CD10
Aviscera Biosciences, Lot No. 20112070). Intra- and inter-
assay coefficients of variation were 3.7% and 8.9%.
Stats: Cox regression analyses including sNEP with age as a
covariate and multivariable Cox regression analyses were
performed

5. Total Cohort
N= 350
Age, yr 72.6 ± 10.7
Female, n (%) 186 (53.1)
Ischemic etiology of HF, n (%) 132 (37.7)
LVEF, in % 46.6 ± 16.2
Creatinine, mg/dl 1.26 ± 0.6
Hemoglobin, g/dl 12.2 ± 2.1
NT-proBNP ng/l 3953 (1988–8155)
Neprilysin, ng/ml 0.67 (0.37-1.29)
sNEP in acute HF: cohort characteristics

6. HR 1.59 (95%CI 1.16-2.19),
p=0.004
HR 1.87 (95%CI 1.11-3.16),
p=0.02
0,0
Combined endpoint – 60 days Combined endpoint – long-term
Primary Endpoints
60 composite endpoints 158 composite endpoints

7. Multivariable Cox regression analyses: age, sex, ischemic etiology of HF, left
ventricular ejection fraction, hemoglobin, creatinine and NTproBNP,
At 2 months: sNEP: HR 1.22, 95% CI 0.97-1.53, p=0.09
At long term, even including treatment into the model (BB, ACEI, MRAs):
sNEP: HR 1.21, 95% CI 1.04-1.40, p=0.01
NTproBNP: HR 1.19, 95% CI 0.96-1.47, p=0.12
Results
N= 92: sNEP- admission: 0.70ng/mL
sNEP- discharge: 0.52 ng/mL
P=0.006
Dynamic sNEP changes during hospital admission

8. Conclusions
This pilot multicentre study suggests that admission sNEP levels are
associated with short- and long-term outcomes in AHF, and that sNEP
concentrations are dynamic during hospital admission.
These preliminary data may argue in favour of NEP inhibitor use in AHF.
TRANSLATIONAL OUTLOOK:
Prospective trials are needed to assess whether NEP inhibition based on
measurements of plasma NEP levels in patients with AHF is clinically useful
Bayes-Genis A et al. JACC HF 2015 In Press; ePub Online May 22