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Observational Study
. 2022 Apr;9(2):1160-1166.
doi: 10.1002/ehf2.13787. Epub 2022 Jan 18.

Soluble neprilysin and survival in critically ill patients

Max Lenz  1   2 , Konstantin A Krychtiuk  1   2 , Mira Brekalo  1 , Dominik F Draxler  1 , Noemi Pavo  1 , Christian Hengstenberg  1 , Kurt Huber  2   3 , Martin Hülsmann  1 , Gottfried Heinz  1 , Johann Wojta  1   2   4 , Walter S Speidl  1
Affiliations
Observational Study

Soluble neprilysin and survival in critically ill patients

Max Lenz et al. ESC Heart Fail. 2022 Apr.

Abstract

Background: Critically ill patients admitted to an intensive care unit (ICU) exhibit a high mortality rate irrespective of the initial cause of hospitalization. Neprilysin, a neutral endopeptidase degrading an array of vasoactive peptides became a drug target within the treatment of heart failure with reduced ejection fraction. The aim of this study was to analyse whether circulating levels of neprilysin at ICU admission are associated with 30 day mortality.

Methods and results: In this single-centre prospective observational study, 222 consecutive patients admitted to a tertiary ICU at a university hospital were included. Blood was drawn at admission and soluble neprilysin levels were measured using ELISA. In the total cohort, soluble neprilysin levels did not differ according to survival status after 30 days as well as type of admission. However, in patients after surgery or heart valve intervention, 30 day survivors exhibited significantly lower circulating neprilysin levels as compared to those who died within 30 days (660.2, IQR: 156.4-2512.5 pg/mL vs. 6532.6, IQR: 1840.1-10 000.0 pg/mL; P = 0.02). Soluble neprilysin predicted mortality independently from age, gender, and commonly used scores of risk-prediction (EuroSCORE II, STS-score, and SAPS II score). Additionally, soluble neprilysin was markedly elevated in patients with sepsis and septic shock (P < 0.05).

Conclusion: At the time of ICU admission, circulating levels of neprilysin independently predicted 30 day mortality in patients following cardiac surgery or heart valve intervention, but not in critically ill medical patients. Furthermore, patients suffering from sepsis and septic shock displayed significantly increased circulating neprilysin levels.

Keywords: 30 day mortality; Critical care; ICU; Neprilysin; Soluble neprilysin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Neprilysin levels at admission to the intensive care unit. Soluble neprilysin levels of medical vs. surgical and valve intervention patients, at time of admission to the intensive care unit (A); levels of neprilysin in patients after cardiac surgery or heart valve intervention (B); neprilysin levels in medical patients according to primary diagnosis (C); *P < 0.05.
Figure 2
Figure 2
Neprilysin levels and 30 day survival. Serum levels of neprilysin in 30 day survivors and non‐survivors in the total cohort (A), in patients that were admitted due to cardiac surgery or heart valve intervention (B) and medical patients (C); *P < 0.05.
Figure 3
Figure 3
Survival according to neprilysin levels above or below the median. Survival according to neprilysin levels above (red line) or below (blue line) the median in the total cohort (A), in patients that were admitted due to cardiac surgery or heart valve intervention (B) and in medical patients (C).
See this image and copyright information in PMC

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